Applying the iterative methodology for dimensionality reduction/feature selection using categorical gradient boosted trees, as it has been defined in and has been successfully applied on similar datasets in and , on a dataset consisted of 12708 gene expressions coming from 5052 individuals from 105 studies, we classify whether a person has acute myeloid leukaemia (AML) or is healthy. A CatBoost model on a dataset with reduced dimensions of 72 genes reached a ROC-AUC score of 0.9973 using ten fold cross validation (10CV) and ROC-AUC: 0.9988 on an inference dataset. We further investigate the options of using less genes that potentially could be used in clinical practise and genes than have not been associated to AML yet, or to blood cancer in general. On the same folds of the 10CV and on the same inference dataset the performance of the tuned CatBoost models show that it could be the case that not all genes with an association to AML have been found yet and 19 genes could be enough to predict AML: CatBoost63 (ROC-AUC: 0.9941, Test: 0.9942), CatBoost19: (ROC-AUC: 0.9946, Test: 0.9941) and CatBoost15: (ROC-AUC: 0.9922, Test: 0.9900). In addition, our results verify that a gene diagnostic test for AML could be possible in the future as well as further research is needed on these 15 genes that it could lead to new and better drugs.

Urinary tract infections (UTIs) are among the most common bacterial infections in community and hospital settings. Infections of the urinary system can range from pyelonephritis to urethritis. Acute renal infections encompass entities such as acute pyelonephritis, acute focal bacterial nephritis, renal and perinephric abscesses, emphysematous pyelonephritis, and pyonephrosis,while xanthogranulomatous pyelonephritis is a chronic granulomatous inflammatory condition that affects the kidneys. The diagnosis of UTIs predominantly relies on clinical assessment and confirmation through abnormal laboratory results. Therefore, routine medical imaging is typically reserved for complicated cases, aiming to identify contributing factors such as renal calculi, determine the type of infection, and evaluate the extent of the infection and its associated complications. Furthermore, imaging has become crucial for radiologists during interventional procedures in the treatment of pyonephrosis and renal abscesses. Traditional imaging tools, like abdominal X-rays, are vital for identifying renal calculi and gas shadows in emphysematous pyelonephritis, while ultrasonography emerges as an excellent modality for assessing urinary infections in emergency scenarios, pregnancy, and paediatric cases. Contrast-enhanced computed tomography (CECT) or non-contrast computed tomography (NCCT) is the imaging method of choice in the most complex situations, allowing for precise assessment of the disease burden. Current MRI sequences yield promising results in specific scenarios, such as pregnancy and paediatric subjects, where minimising radiation exposure is a concern. This article focuses on elucidating the essential radiological modalities and their distinctive features in the context of renal infections, offering valuable guidance to microbiologists and physicians.

Mesoporous silica nanoparticles (MSNs) can be used as carrier materials for the controlled release of pesticides while reducing their negative environmental impact. In this study, we screened an active ingredient, p-cymene (PC), with an excellent inhibitory effect on rice bacterial blight. Subsequently, the PC was successfully loaded onto MSNs via physisorption(PC@MSNs). PC@MSNs, characterized by a regular spherical shape, smooth surface, and an MSN average size of 262.9 nm, achieved an 8.6 % drug loading capacity. The release kinetics of the PC from the PC@MSNs demonstrated a sustained release (288 h) pattern influenced by drug diffusion. The efficacy of the PC@MSNs against Xanthomonas oryzae pv. Oryzae paralleled those of PC. Acute toxicity assays re-vealed that the PC@MSNs were less toxic to aquatic life (LC50=257.867 mg/L) and that the formu-lation showed no adverse effects on rice seedling growth. In summary, these results suggest that PC@MSNs can broaden PC's application scope in managing rice diseases.

Bronchiolitis is an acute viral infection of the lower respiratory tract that affects infants and young children. Respiratory syncytial virus (RSV) is the most common causative agent, however other viruses can be the reason of the disease. We retrospectively reviewed the clinical features of infants aged less than 12 months referred to our Pediatric Units of Chivasso, Cirié and Ivrea for acute bronchiolitis requiring hospitalization over two consecutive bronchiolitis seasons. Patient-, disease- and treatment related variables were analyzed in this retrospective study. We were able to show how with the high flow oxygen support (HFNC) only a very low number of children (8 out of 192) need to be trasferred to our HUB referral centers. The probability of success were 96% for all patients and 93% for RSV vs. 98% for non-RSV patients (P=NS). Factor associated to failure of treatment were age below 1 months and the failure of HFNC. The wide and increasing use of HFNC in pediatric inpatients improved management of bronchiolitis in Spoke hospitals, reducing transfer to a Hub hospital provided with Intensive Care Units.

Endovascular therapy (EVT) has revolutionized the management of acute ischaemic strokes with large vessel occlusion, with emerging evidence suggesting its benefit also in large infarct core volume strokes. In the last 2 years, 4 randomised controlled trials have been published on this topic - RES-CUE-Japan-LIMIT, ANGEL-ASPECT, SELECT2 and TENSION, with overall results showing that EVT improves functional and neurological outcomes compared to medical management alone. This review seeks to summarise the recent evidence presented by these 4 trials and highlight some of the limitations of our current understanding on this topic.

AML is a highly aggressive and heterogeneous form of hematological cancer. Proteomics-based stratification of patients into more refined subgroups may contribute to a more precise characterization of the patient-derived AML cells. Here, we reanalyzed liquid chromatography-tandem mass spectrometry (LC-MS/MS) generated proteomic and phosphoproteomic data from 26 chemoresistant/relapse (RELAPSE) and 15 relapse-free (REL_FREE) AML patients. We considered not only the RELAPSE and REL_FREE characteristics but also integrated the French-American-British (FAB) classification, along with considering the presence of nucleophosmin 1 (NPM1) mutation and cytogenetically normal AML. We found a significant number of differentially enriched proteins (911) and phosphoproteins (257) between the various FAB subtypes in RELAPSE patients. Patients with the myeloblastic M1/M2 subtype showed higher levels of RNA processing-related routes and lower levels of signaling related to terms like translation and degranulation, when compared to the M4/M5 subtype. Moreover, we found that high abundance of proteins associated to mitochondrial translation and oxidative phosphorylation, particularly observed in the RELAPSE M4/M5 NPM1 mutated subgroup, distinguishes relapsing from non-relapsing AML patient cells with the FAB subtype M4/M5. Thus, the discovery of subtype-specific biomarkers through proteomic profiling may complement the existing classification system for AML and potentially aid in selecting personalized treatment strategies for individual patients.

Background and Objectives: The severity of acute pancreatitis (AP) is graded as mild (MAP), moderately severe (MSAP), and severe (SAP) according to the revised Atlanta Classification. Determining the severity of AP is the main goal in the early time of AP. The aim of this study was to compare laboratory parameters or indices including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and neutrophil-creatinine index (NCI) at admission for predicting severity of AP. Materials and Methods: In this retrospective study, the data from patients who admitted with diagnosis of AP between January 2018 and December 2021 were collected. Laboratory parameters and indices including NLR, PLR and NCI were compared in the discrimination of AP severity groups. Results: A total of 421 patients [MAP group (n=213), MSAP group (n=158) and SAP group (n=50)] were included. WBC count, neutrophil count, hematocrit, CRP, BUN, creatinine, NLR and NCI were significant parameters to discriminate AP subgroups. The AUROC analysis for discriminating MSAP from MAP showed that WBC (AUC: 0.723, 95% CI: 0.674-0.768, p<0.001), hematocrit (AUC: 0.566, 95% CI: 0.514-0.607, p=0.032), NLR (AUC: 0.649, 95% CI: 0.598-0.698, p< 0.001) and NCI (AUC: 0.749, 95% CI: 0.701-0.792, p<0.001) were statistically significant parameters. Similarly, AUCs to discriminate SAP from MSAP were (AUC: 0.649, 95% CI: 0.579-0.713, p < 0.001) for WBC, (AUC: 0.703, 95% CI: 0.621-0.785, p< 0.001) for BUN, (AUC: 0.602, 95% CI: 0.532-0.669, p=0.029) for CRP and (AUC: 0.742, 95% CI: 0.676-0.800, p<0.001) for NCI. Logistic regression analyses indicated that NCI was the only parameter to discriminate MSAP form MAP (OR: 1.119, 95% CI: 1.015-1.235, p=0.023) and SAP from MSAP (OR: 1.113, 95% CI: 1.042-1.888, p = 0.001). Conclusions: The present study enabled the identification of neutrophil-creatinine index as a new prognostic tool for the assessment AP severity at hospital admission.

Vascular inflammation is recognized as the primary trigger of acute coronary syndrome (ACS). However, current noninvasive methods are not capable of accurately detecting coronary inflammation. Epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT), in addition to their role as an energy reserve system, have been found to contribute to the development and progression of coronary artery calcifica-tion, inflammation, and plaque vulnerability. They also participate in the vascular re-sponse during ischemia, sympathetic stimuli, and arrhythmia. As a result, the evalua-tion of EAT and PCAT using imaging techniques such as computed tomography (CT), cardiac magnetic resonance (CMR), and nuclear imaging has gained significant atten-tion. PCAT-CT attenuation, which measures the average CT attenuation in Hounsfield units (HU) of the adipose tissue, reflects adipocyte differentiation/size and leukocyte infiltration. It is emerging as a marker of tissue inflammation and has shown prognos-tic value in coronary artery disease (CAD), being associated with plaque development, vulnerability, and rupture. In patients with acute myocardial infarction (AMI), an in-flammatory pericoronary microenvironment promoted by dysfunctional EAT/PCAT has been demonstrated, and more recently, it has been associated with plaque rupture in non-ST-segment elevation myocardial infarction (NSTEMI). Endothelial dysfunc-tion, known for its detrimental effects on coronary vessels and its association with plaque progression, is bidirectionally linked to PCAT. PCAT modulates the secretory profile of endothelial cells in response to inflammation and also plays a crucial role in regulating vascular tone in the coronary district. Consequently, dysregulated PCAT has been hypothesized to contribute to type 2 myocardial infarction with non-obstructive coronary arteries (MINOCA) and coronary vasculitis. Recently, quan-titative measures of EAT derived from coronary CT angiography (CCTA) have been included in artificial intelligence (AI) models for cardiovascular risk stratification. These models have shown incremental utility in predicting major adverse cardiovas-cular events (MACE) compared to plaque characteristics alone. Therefore, the analysis of PCAT and EAT, particularly through PCAT-CT attenuation, appears to be a safe, valuable, and sufficiently specific noninvasive method for accurately identifying cor-onary inflammation and subsequent high-risk plaque. These findings have been sup-ported by biopsy and in vivo evidence. Although speculative, these pieces of evidence open the door to a fascinating new strategy in cardiovascular risk stratification. The incorporation of PCAT and EAT analysis, mainly through PCAT-CT attenuation, could potentially lead to improved risk stratification and guide early targeted primary pre-vention and intensive secondary prevention in patients at higher risk of cardiac events.

The discovery of microRNAs and their role in disease today represents a substantial breakthrough that has inspired and propagating research on microRNAs as targets for diagnosis and therapy. Cardiovascular disease is an area where the limitations of early diagnosis and conventional pharmacotherapy are evident and deserve attention. Thus microRNA-based drugs have substantial potential for development. Research and its application can progress considerably as witnessed in preclinical and clinical trials. The use of miRNAs remains experimental at the time of writing but has a promising role in the diagnosis and prognosis of a variety of acute coronary syndrome presentations. Its use, alone or in combination with currently available biomarkers, could be adopted soon, especially if diagnostic ambiguity exists. In this review, we explore the current state of knowledge about microRNAs as potential targets for diagnosis and therapy in the cardiovascular system. We report recent improvements in the acknowledgment and characterization of microRNAs focusing on clinical translation. The new dares and outlooks toward clinical application are discussed.

Leukemia is a cancer of the bone marrow, a spongy tissue that secretes into the bones and serves as the site for the production of blood cells. One of the most prevalent kinds of leukemia in adults is acute myeloid leukemia (AML). Leukemia has non-specific signs and symptoms that are also similar to those of other interpersonal illnesses. The only way to accurately diagnose leukemia is by manually examining a stained blood smear or bone marrow aspirate under the microscope. However, this approach takes more time and is less precise. This paper describes a method for the automatic recognition and classification of AML in blood smears. Classification techniques include decision trees, logistic regression, support vector machines, and naive bayes.

Purpose: Oxidative stress is responsible for over seventy five diseases and other harmful cytological challenges including cancer, type 2 diabetes mellitus, lipid peroxidation, distortion of cell membrane integrity, shortening of telomerase among others. Antioxidant potency of any plant is a very positive remedy to the debilitating effects of prooxidants and oxidants. The study was aimed at investigating the antioxidant potency of methanol extract of Pentaclethra macrophylla stem bark- in vitro and in vivo. Methods: Different phytochemicals were determined using standard methods. Nitric oxide, 1, 1-diphenyl-2- picrylhydrazyl (DPPH) radical scavenging activity, total antioxidant capacity and ferric reducing/anti-radical power were used to investigate the in vitro antioxidant activity. Catalase assay, superoxide dismutase, malondialdehyde and glutathione peroxidase were used to determine the in vivo antioxidant efficacy using six groups of five rats. Results: The result showed various quantities of phytochemicals, including antioxidant phytochemicals-flavonoids, tannins and total phenolics. The in vitro assay showed that 250 μg/ml of extract had the highest percentage inhibition of DPPH radical (93.93%). The 125 μg/ml had the highest scavenging activity of nitric oxide radical (49.47%) while 250μg/ml showed the least with 41.73%. Other methods showed various degrees of activity. The in vivo antioxidant showed that the principal mechanism of antioxidant activity is by modulating the iron-dependent catalase activity. Conclusion: Pentaclethra macrophylla has both in vitro and in vivo antioxidant activities and therefore is useful in ameliorating the debilitating effects of oxidants.

Objectives: The aim of this study is to evaluate some mechanisms of the immune response of people infected with SARS-CoV-2 in both acute infection and early and late convalescence phases. Methods: This is a cohort study of 70 cases of COVID-19, confirmed by RT-PCR, followed up to 60 days. Plasma Samples and clinical data were. Viral load, blood count, indicators inflammation were the parameters evaluated. Cellular immune response was evaluated by flow cytometry and Luminex immunoassays. Results: In the severe group, hypertension was the only reported comorbidity. Non severe patients have activated memory naive CD4+ T cells. Critically ill patients have central memory CD4+ T cell activation. Severe COVIS-19 patients have both central memory TCD8+ T cells and activated effector TCD8+ cells. Non-severe COVID-19 cases showed an increase in IL1β, IL-6, IL-10 and TNF and severely ill patients had higher levels of the cytokines IL-6, IL-10 and CXCL8.Conclusion: The present work showed that different cellular responses are observed according to the COVID-19 severity in patients from Brazil an epicenter the pandemic in South America. Also, we notice that some cytokines can be used as predictive markers for the disease outcome, possibility implementation of strategies effective by health managers.

Prolonged exercise induces acute renal injury; however, the precise mechanism remains unclear. We investigated the effects of neutrophil depletion in male C57BL/6J mice. Male C57BL/6J mice were divided into four groups: sedentary with control antibody, sedentary with antineutrophil antibody, exhaustive exercise with control antibody, and exhaustive exercise with antineutrophil antibody. Antineutrophil (1A8) or control antibody was administered intraperitoneally to the mice prior to their running on a treadmill. Renal histology was assessed 24 h after exhaustive exercise, and the concentration of kidney injury molecule (KIM)-1 was measured using enzyme-linked immunosorbent assay. The expression levels of inflammatory cytokines were measured using quantitative reverse transcriptase-polymerase chain reaction. Furthermore, nicotinamide adenine dinucleotide phosphate oxidase activity and hydrogen peroxide concentration in the kidneys were measured. The pathologic changes were manifested as congested and swollen glomeruli, tubular dilatation, and nuclear infiltration after exhaustive exercise. These changes were suppressed by the administration of the 1A8 antibodies. KIM-1 concentration increased after exhaustive exercise but were reduced by the 1A8 antibodies. Treatment with the 1A8 antibody also decreased exhaustive exercise-induced inflammation and reactive oxygen species levels in the kidney. These results suggest that neutrophils contribute to exercise-induced acute renal injury by regulating inflammation and reactive oxygen species levels.

The traditionally dismal outcome of acute myeloid leukemia (AML) patients carrying the FMS-related tyrosine kinase 3 (FLT3) mutations has been mitigated by the recent introduction into the clinics of tyrosine kinase inhibitors (TKI) such as midostaurin and gilteritinib. The present work summarizes the clinical data that led to the use of gilteritinib in clinical practice. Gilteritinib is a 2nd generation TKI with deeper single-agent activity than 1st generation drugs against both FLT3-ITD and TKD mutations, in human studies. Moreover, the phase I/II dose-escalation, dose-expansion Chrysalis trial showed an acceptable safety profile of gilteritinib (diarrhea, elevated aspartate aminotransferase, febrile neutropenia, anemia, thrombocytopenia, sepsis, and pneumonia) and a 49% overall response rate (ORR) in 191 FLT3-mutated relapsed/refractory (R/R) AML patients. In 2019, the pivotal ADMIRAL trial showed that the median overall survival was significantly longer in patients treated with gilteritinib than among those receiving chemotherapy (9.3 vs 5.6 months, respectively) and the ORR to gilteritinib was 67.6%, outperforming the 25.8% for chemotherapy arm and leading to the license for its clinical use by the US Food and Drug Administration. Since then, several real-world experiences confirmed the positive results in the R/R AML setting. Finally, gilterinib based combinations currently under investigation with several compounds (venetoclax, azacitidine, conventional chemotherapy, etc.) and some practical tips (maintenance after allogeneic transplantation, interaction with antifungal drugs, extramedullary disease, and onset of resistance) will be analyzed in detail in the review.

Abstract: Background: Trauma is the leading cause of morbidity and mortality in young patients, acute surgical conditions cause morbidity and mortality in patients of all ages. Computed tomography scan (CT) assist greatly in the investigation and management of these patients with blunt and penetrating trauma, facilitating early diagnosis and expedites early appropriate treatment of these patients. Acute non-traumatic surgical conditions also mimic non-surgical pathologies and differentiating the two is important because management is different and any delay in surgical intervention results in high morbidity and some may even result in mortality. Method: Literature review of the role of multidetector CT scan (MDCT) in managing acute surgical emergencies and trauma-diagnosis in the trauma patient and patients presenting with acute surgical emergencies. The focus is on the role of the MDCT in the management of these patients. Results highlight that the use of MDCT expedites management of these patients, allowing early surgical intervention and preventing unnecessary surgical interventions where the intervention is not indicated, based on the MDCT results. Conclusion: This paper emphasizes the important role that is played by the MDCT in the management of the above patients.

Background: Primary infection has been questioned as the pathogenetic cause of acute appendicitis. We attempted to identify the bacteria involved, and to investigate if their species, types, or combinations affected the severity of acute appendicitis in children. Methods: Samples from both the appendiceal lumen and the peritoneal cavity of 72 children who underwent appendectomy were collected to perform bacterial culture analysis. The outcomes were studied to see if and how they were associated with the severity of the disease. Regression analysis was performed to identify any risk factors associated with complicated appendicitis. Results: Escherichia coli, Pseudomonas aeruginosa and Streptococcus species were the most common pathogens found in the study population. The same microorganisms, either combined or separate, were the most common in the appendiceal lumen and the peritoneal cavity of patients with complicated appendicitis. Gram-negative bacteria, polymicrobial cultures in the peritoneal fluid and in the appendiceal lumen, were associated with complicated appendicitis. Polymicrobial cultures in the peritoneal cavity presented four times higher risk of complicated appendicitis. Conclusion: Polymicrobial presentation and gram-negative bacteria are associated with complicated appendicitis. Antibiotic regimens should target the combinations of the most frequently identified pathogens, speculating the value of early antipseudomonal intervention.

Biomarkers have become an important tool in the diagnosis and management of cardio renal syndromes (CRS), a complex condition characterized by dysfunction in both the cardiovascular and renal systems. These biomarkers can help identify the presence and severity of CRS, predict its progression and outcomes, and facilitate personalized treatment options. Several biomarkers, including natriuretic peptides, troponins, and inflammatory markers, have been extensively studied in CRS and have shown promising results in improving diagnosis and prognosis. In addition, emerging biomarkers such as kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin offer potential for early detection and intervention of CRS. However, the use of biomarkers in CRS is still in its infancy, and further research is needed to establish their utility in routine clinical practice. This review highlights the role of biomarkers in the diagnosis, prognosis, and management of CRS and discusses their potential as valuable clinical tools for personalized medicine in the future.

Introduction: CT perfusion (CTP) is an alternative tool to assess cerebral hemodynamics in brain trauma. As traumatic acute subdural hematomas (ASH) are severe lesions commonly associated with poor outcome, we aimed to evaluate the brain hemodynamics in this population. Methods: Five patients admitted at the emergency department sustaining traumatic acute subdural hematoma were evaluated. Preoperative CTP was performed immediately after nonenhanced head CT scan. Postoperative CTP was performed in four patients. The outcome was assessed 6 months after surgery using the extended Glasgow Outcome Scale. Results: 4 male and 1 female were evaluated. Mean age was 46y (SD: 8.1). Mean preoperative midline brain shift was 10.1 mm (SD: 1.8). The main mechanism of trauma was falling (four patients). There was a general improvement in cerebral blood flow (CBF) after surgery from 23.9 (SD: 6.1) to 30.7 ml/100g/min, (SD: 5.1) and in mean transit time (MTT) from 7.3 (SD: 1.3) to 5.8s (SD:1.0), although it is not statistically significant (p=0.06 and p=0.06, respectively). There was still a reduction in the cerebral blood volume (CBV) media when compared to the value after surgery, from 2.63 (SD: 1.10) to 2.34 ml/100g (SD: 0.67), which is not statistically significant (p=0.31). Spearman correlation test of postoperative and preoperative CBF ratio with outcome was 0.94 (p=0.054). Only one patient died (three days after surgery). This patient was victim of car crash and had the highest preoperative MTT (9.97 seconds) and CBV (4.51 ml/100 g). Conclusion: Post-operative improvement of hemodynamic CTP parameters may be correlated with outcomes after ASH. Further studies with larger samples are required to confirm this hypothesis.

Searching for bioactive compounds within the huge chemical space is like trying to find a needle in a haystack. Isatin is a unique natural compound which is endowed with different biopertinent activities specially in cancer therapy. Herein, we envisaged that adopting a hybrid strategy of isatin and α,β-unsaturated ketone would afford new chemical entities with strong chemotherapeutic potential. Of interest, compounds 5b and 5g demonstrated significant antiproliferative activities against different cancer genotypes according to NCI assay. Concomitantly, their IC50 against HL-60 cells were 0.38 ± 0.08 and 0.57 ± 0.05, respectively, demonstrating remarkable apoptosis and mod-erate cell cycle arrest at G1 phase. Intriguingly, an impressive safety profile for 5b was reflected by a 37.2 times selectivity against HL-60 over PBMC from a healthy donor. This provoked us to further explore their mechanism of action by in vitro and in silico tools. Conclusively, 5b and 5g stand out as strong chemotherapeutic agents that hold a clinical promise against acute myeloid leukemia.

Despite the recent advances in melanoma therapy, the need for new targets and novel approaches to therapy is urgent. We previously reported melanoma actives that work via binding and downregulating spliceosomal proteins hnRNPH1 and H2 (Palrasu et al., 2019). Given lack of knowledge about side effects of using spliceosomal binders in humans, an acute toxicity study was conducted to evaluate these compounds in mice. Male and female mice were treated with compounds 2155-14 and 2155-18 at 50mg/kg/day via subcutaneous injections and the clinical signs of distress were monitored for 21 days and compared with control mice. Additionally, effect of the leads on blood chemistry, blood cell counts, and organs was evaluated. No significant changes were observed in the mice body weight, blood cell count, blood chemistry, or organs following the compound treatment. The results show that our compounds 2155-14 and 2155-18 are not toxic for the study period of three weeks.

Acute myeloid leukemia (AML) is a hematological malignancy that predominantly affects the elderly. Prognosis declines with age. For those who cannot tolerate intensive chemotherapy, historically established treatment options have been hypomethylating agents (HMAs), low dose cytarabine (LDAC), and best supportive care (BSC). As the standard of care evolves for those unfit for intensive chemotherapy, there is a need to understand established treatment pathways, clinical outcomes and healthcare resource utilization in Canada. The CURRENT study was a retrospective chart review of AML patients not eligible for intensive chemotherapy who initiated first-line treatment between 1 January 2015 and 31 December 2018. Data were collected from 170 Canadian patients treated at six hematology centers, of whom 118 received systemic therapy and 52 received BSC as first-line treatment. Median overall survival was 8.58 months and varied from 2.96 months for BSC to 13.31 months for HMAs. Over 80% of patients had at least one outpatient visit, and 67% of patients receiving systemic therapy and 71% of those receiving BSC had at least one admission to hospital, during their first line of therapy. A total of 96 (81.4%) patients receiving first line systemic therapy and 39 (75.0%) of those receiving first line BSC had at least one red blood cell or platelet transfusion. These findings highlight the unmet need for novel therapies for patients ineligible for intensive chemotherapy.

Urinary tract infections (UTIs) are very frequent in women and can be caused by a range of pathogens. High recurrence rates and increasing antibiotic resistance of uropathogens make UTIs a severe public health problem. d-mannose is a monosaccharide that can inhibit bacterial adhesion to the urothelium after oral intake. Several clinical studies have shown the efficacy of d-mannose in the prevention of recurrent UTI; these also provided limited evidence for the efficacy of d-mannose in acute therapy. A recent prospective, non-interventional study in female patients with acute cystitis reported good success rates for treatment with d-mannose. Here we present data from a post-hoc analysis of this study to compare the cure rate of d-mannose monotherapy with that of antibiotics. The results show that d-mannose is a promising alternative to antibiotics in the treatment of acute uncomplicated UTIs in women.

Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated high rates of response in recurrent B-cell Acute Lymphoblastic Leukemia in children and young adults. Despite this success, a fraction of patients experience relapse after treatment. Relapse is often preceded by recovery of healthy B cells, which suggests loss or dysfunction of CAR T cells in bone marrow. This site is harder to access, and thus is not monitored as frequently as peripheral blood. Understanding the interplay between B cells, leukemic cells and CAR T cells in bone marrow is paramount in ascertaining the causes of lack of response. In this paper, we put forward a mathematical model representing the interaction between constantly renewing B cells, CAR T cells and leukemic cells in the bone marrow. Our model accounts for the maturation dynamics of B cells and incorporates effector and memory CAR T cells. The model provides a plausible description of the dynamics of the various cellular compartments in bone marrow after CAR T infusion. After exploration of the parameter space, we found that the dynamics of CAR T product and disease were independent of the dose injected, initial B-cell load and tumor burden. We also show theoretically the importance of CAR T product attributes in determining therapy outcome, and have studied a variety of possible response scenarios, including second dosage schemes. We conclude by setting out ideas for the refinement of the model.

Background: Disentangling adverse drug reactions from confounders remains a major challenge to assess causality and severity in neonates. Vancomycin and amikacin are perceived as nephrotoxic and often prescribed in neonates. We selected these compounds to assess their impact on creatinine dynamics as sensitive tool to detect a renal impairment signal. Methods: A recently developed dynamical model that characterized serum creatinine concentrations of 217 ELBW neonates (4036 serum creatinine observations) was enhanced with data on individual administration of vancomycin and/or amikacin to identify a potential effect of antibiotic exposure by nonlinear mixed-effects modelling analysis. Results: Of our ELBW patients, 77% were exposed to either vancomycin or amikacin. Antibiotic exposure resulted in transient lower overall creatinine clearance and a modest increase in serum creatinine. Dependency on gestational age was observed in the difference in serum creatinine when exposed to antibiotics during the third week after birth (difference in creatinine for a neonate at 24 weeks gestation decreased with 56% for a 32-week-old neonate). Conclusions: A previously described model on creatinine dynamics was used to explore and quantify the impact amikacin or vancomycin exposure on creatinine dynamics. Such tools can be used to explore minor changes, or compare minor differences between treatment modalities.

AIM: Aim of our study was to evaluate incidence and causative factors for acute kidney injury in gastrointestinal and hepatobiliary surgeries. Material and methods: All the gastrointestinal surgeries performed between April 2018 to March 2020, in our institution have been analysed for acute kidney injury. Acute kidney injury defined according to acute kidney injury network classification. Categorical variables were evaluated by chi square test and continuous variables by Mann Whitney U test. Statistical analysis was done using SPSS version 23. P< 0.05 was considered significant Results: We performed 331 gastrointestinal and hepatobiliary surgery from April 2018 to March 2020. After exclusion 317 patients were included in study population.14 patients (4.4%) were defined as having acute kidney injury according to acute kidney injury network classifications. On univariate analysis acute kidney injury was associated with open surgery (p= 0.002, Intra operative hypotension (p=0.006), CDC grade of surgery (p<0.001), increased used to blood products (p=0.004), higher ASA grade (p<0.0001), increased operative time(p<0.0001). On multivariate logistic regression analysis higher ASA grade (p=0.001) and increased operative time (0.015) independently predicted acute kidney injury. Acute kidney injury was also significantly associated with 90 days mortality. ( p= <0.0001) Conclusion:Post-operative acute kidney injury was associated with significant mortality in gastrointestinal and hepatobiliary surgery. Open surgery, higher CDC grade surgery, more blood products, higher ASA grades, increase operative time predicted acute kidney injury in post operative periods. Higher ASA grades and increased operative time predicted acute kidney injury.

Background: After allogeneic hematopoietic stem cell transplantation (allo-HSCT), acute leukemia relapse is common, and asymmetric bone marrow recurrence hasn’t been reported. Because the anatomical distribution of acute leukemia clones in the bone marrow after allo-HSCT is presumed to be diffuse, bone marrow aspirations are performed in single site. Case presentation: We identified two acute leukemia patients, whose leukemic burden in bilateral bone marrow specimens differed significantly. The first case was a 20-year-old man who was diagnosed with acute myelomonocytic leukemia and received haploidentical allo-HSCT. He had been in complete remission for two years and off immunosuppressive medications for a year, with normal peripheral blood count. Routine bone marrow biopsy of his left posterior iliac bone marrow showed 52% leukemia blasts, while the right side had 0% blasts ten days later. Due to the discordant results, the patient refused further intervention and died of high leukocyte syndrome four months later. The second case was a 23-year-old woman who was diagnosed with acute B lymphoblastic leukemia and received HLA-identical sibling allo-HSCT. Although 62% of blasts were found in her left iliac marrow on day +122, 0 % of blasts were found on a sample obtained from the right iliac crest on day +128. Whole-body 18F-FDG PET/CT scans confirmed that the leukemic infiltration in her bone marrow was asymmetric. Considering the higher leukemic burden on the left, we chose the left posterior iliac crest aspiration for further response evaluation. After chemotherapy combined with donor lymphocyte infusion, she achieved transient hematologic complete remission. She died of septic shock with heart failure at +258 days after allo-HSCT before infusion of anti-CD19 donor chimeric antigen receptor T cells. Conclusions: To our knowledge, these are the first case reports of asymmetric bone marrow infiltration of blasts in acute leukemia patients after allo-HSCT. Bilateral posterior iliac crest aspirations or 18F-FDG-PET/CT scans may help distinguish such distribution. If discordant bone marrow specimens are observed, physicians should restrict future bone marrow studies to the more involved side.

Isolated fallopian tube torsions presenting to the emergency department are a very rare cause of childhood acute abdominal pain. Since the diagnosis to be made in the early period is of importance in terms of affecting tubal damage and fertility, it was aimed to evaluate the cases in the light of literature. Materials and Methods: This study included 10 patients under 18 years of age presented to the emergency department with abdominal pain between January 2003 and December 2018. The mean age was 14.5±1.43 years (range: 12-17years). The demographic characteristics, surgical findings, and methods, concomitant pathology results of these patients were retrospectively evaluated. Results: The reason for admitting to the emergency department of 10 patients included in the study was abdominal pain. The mean duration of hospital admission with pain was 4.97 days. The onset of pain was less than 24 hours in 7 patients (70%) and was more than 24 hours in three patients (30%). Of the patients, 9 (90%) had tenderness in the lower abdominal quadrant, 5 (5%) had the defense, and 3 (30%) had a rebound. Nausea, vomiting, and leucocytosis were present in 50% of the cases. Right and left tubal involvement of the cases was equal. Seven (70%) of the isolated tubal torsions were accompanied by paraovarian cysts. Of the patients, 8 (80%) underwent open surgery and 2 (20%) underwent laparoscopic intervention. Detorsion was performed in 5 (50%) and salpingectomy was performed in 5 (50%) cases. Conclusion: Isolated tubal torsion should be considered in children presenting with acute abdominal pain in early adolescence. Early diagnosis is important for the maintenance of fertility.

Idiopathic Pulmonary Fibrosis (IPF) is most common idiopathic interstitial pneumonia. IPF is often seen in elderly men who smoke. Diagnosis of IPF requires integration of a detailed clinical history, specific physical examination, laboratory findings, pulmonary function tests, high-resolution computed tomography (HRCT) of the chest, and histopathology. IPF has a heterogeneous clinical course, from an asymptomatic stable state to progressive respiratory failure or acute exacerbation (AE). AE of IPF has several important differential diagnoses, such as heart failure and volume overload. The International working project proposed new criteria of AE of IPF in 2016 dividing it into triggered and idiopathic AE. On the basis of these criteria, physicians can detect AE of IPF more easily. The recent international IPF guideline emphasized the utility of chest HRCT. In addition, two anti-fibrotic agents have become available. We should attend not only to management of AE, but also to its prevention. The diagnostic process, laboratory findings, typical chest imaging, management and prognosis of AE are comprehensively reviewed.

Long non-coding RNA (lncRNA) aberrant expression have been found in several types of cancer, including acute lymphoblastic leukemia (ALL), but lncRNA mapped in transcribed ultraconserved regions (T-UCRs) are little explored. The T-UCRs uc.112, uc.122, uc.160 and uc.262 were evaluated in pediatric ALL and uc.112 expression was higher in T-ALL compared to patients with B-ALL and in patients with hyperdiploid karyotype. These findings suggest a potential role of this uc.112 in pediatric ALL and emphasize the need for further investigation of T-UCR in pediatric ALL.

In metropolitan regions, which are particularly vulnerable to seismic damage, numerous reinforced concrete (RC) buildings are being constructed. Public safety has been an important consideration to safeguard and protect people, buildings, and infrastructure from the potential effects of earthquakes. The assessment of seismic vulnerability within urban areas encompassed an analysis of both building vulnerability and the scale of seismic hazards prevalent in the locality. This assessment aimed to ascertain the likelihood of building damage resulting from ground motion induced by an earthquake of a specific magnitude. In recent decades, considerable efforts have been made to develop and improve methods for assessing earthquake damage to reinforced concrete (RC) buildings. These efforts included the creation of seismic hazard and seismic risk indices that were used to quantify the potential destruction of individual building components or the entire building. This scholarly review article presents an in-depth analysis and concise summary of the primary techniques (including qualitative or empirical, quantitative, analytical, and experimental test methods) devised for appraising the seismic vulnerability of reinforced concrete frame buildings, pre- and post-earthquake occurrences. It is a valuable reference for policymakers, engineers, researchers, and specialists engaged in earthquake risk mitigation efforts.

After an earthquake, assessing the seismic vulnerability of buildings is essential for prioritizing emergency response, guiding reconstruction, and ensuring public safety. Accurate and timely evaluation of structural damage plays a vital role in mitigating further risks and facilitating in-formed decision-making during disaster recovery. This study investigates the performance of various Generative Artificial Intelligence (GAI) models, developed by different companies with diverse model sizes and context windows, in analysing post-earthquake images. The primary objective was to evaluate the models' effectiveness in classifying structural damage according to the EMS-98 scale (with 5 levels of damage), which ranges from minor damage to total destruction. For masonry buildings, the correct classification rates varied widely across models, from 28.6% to 64.3%, with mean damage grade errors ranging from 0.50 to 0.79. In the case of reinforced concrete buildings, correct classification rates ranged from 37.5% to 75.0%, with mean damage grade errors between 0.50 and 0.88. The use of fine-tuning could probably improve the results substantially. Improving the accuracy of GAI models could significantly reduce the time and resources needed to assess post-earthquake damage, namely when comparing with more traditional approaches. The results achieved thus far demonstrate the promise of GAI models for rapid, automated, and ac-curate damage evaluation, which is critical for expediting decision-making in disaster response scenarios.

(1) Background: although current theories of Post-Traumatic Stress Disorder (PTSD) had focused on depressed mood and intrusion, the mechanism through which depression increases the risk of PTSD remains unclear. Research has concentrated on the hyper-active negative valence system (NVS) (e.g., increased fear and threat responses), but a significant role for hypo-active positive valence system (PVS) (e.g., less neural activation towards rewards) was conceivable. (2) Methods: To investigate the implicit processing in a refugee’s sample, ratings of arousal, dominance, and valence for 60 IAPS pictures (positive, neutral, and negative) were collected from 42 individuals with probable PTSD, and 26 trauma-exposed individuals (M age = 28.49 years, SD = ± 7.78). (3) Results: ANOVAs revealed a main group effect (η2p = 0.379) on arousal, dominance, and valence dimensions, and pictures’ categories (η2p = 0.620). Participants with PTSD responded to unpleasant images with enhanced arousal and lower valence ratings compared with individuals without PTSD. Moreover, arousal ratings were negatively correlated with valence (r = - 0.709, p &lt; 0.01). (4) Conclusions: Our findings supported evidence according to which PTSD origins a state of maladaptive hyperarousal and difficulties in regulating emotions. Positive stimuli are considered less pleasant providing evidence for a complementary involvement of NVS and PVS in PTSD development.

The high flammability and lack of charrability of polystyrene (PS) pose significant limitations on its broader applications. Therefore, there is an urgent need for a straightforward and efficient method for the synthesis of flame-retardant PS, which still poses a considerable challenge. In this study, we present an efficient approach to enhance the flame-retardant properties of PS through direct phosphorylating aromatic C(sp2)-H bonds using commercially available and inexpensive manganese catalyst. A range of phosphonates served as reactive substrates to enable a tunable degree of polymer functionalization. The corresponding phosphorylated PS specimens were determined by means of 1H NMR, 31P NMR, FTIR spectroscopy and GPC. Microscale combustion calorimetry (MCC) tests indicate that this protocol indeed enhances the flame-retardant performance of PS. Moreover, other advantages associated with the incorporation of the phosphonate group have been observed, including improved thermal resistance and wettability. This cost-effective strategy of Mn-catalyzed C-H can also be utilized to directly obtain phosphonate modification of waste foamed PS and styrene acrylonitrile copolymer, providing a new method for the purpose of recycling and upgrading PS plastics.

Frass generated during the production of black soldier fly larvae is taking the interest of scientists and horticultural producers because it is a material from the biotransformation of organic waste, it has several nutrients that can be used by plants, and its recent focus on its biostimulant capacity. The thermal-composting process is a stabilization that improves physical and chemical properties of treated wastes, allowing better performance in plants compared to its fresh state. In this research, thermocomposted frass was evaluated as a germination substrate for kale seeds (Brassica olerasea). To achieve this, it was evaluated the phytotoxicity in different concentrations on the seeds, and seedlings were grown in a germination substrates mixed with 20, 40, 60, 80 and 100% of frass. The treatment with 20% frass showed the highest values of seedling height, stem diameter, number of leaves, length, and width of first true leaf and length and width of cotyledons, reduced the content of phenols and tannins antioxidants but the content of flavonoids increased compared to the control and the rest of mixtures.

After the end of colonial rule in 1997, the Hong Kong education system has been experiencing a policy reform on Senior Secondary Education (NSS) Curriculum commenced in September 2009 aiming to educate students as globalized Hong Kong citizens for the Western. Although previous scholars argued that it is hard to differentiate between domestic values and the Western values in account of curriculum development (Sewpaul, 2007), this study demonstrates an analysis using the dichotomy to investigate how local curriculum, especially in the post-colonial areas, embrace both the Western values and domestic values. Using content analysis on the NSS curriculum guides, this article evaluates the influence of the Western values and Chinese values in the NSS curriculum through investigating: (1) how the Western values and Chinese values was incorporated into the curriculum throughout its development (2) why some values are more significantly highlighted in the curriculum guide. Findings include that more Chinese values are involved in the curriculum documents. This may be because of the upholding of domestic values as a post-colonial city. The Western values which are academically related are greatly incorporated into the local curriculum.

Research indicates that painful experiences can significantly affect the fear of cancer recurrence among cancer survivors, which is a distressing concern that influences both physiological and psychological recovery. Yet, the role of potential factors and mechanisms in these relationships is not fully known. This cross-sectional study aimed to advance our comprehension of the associa-tions between total pain and the fear of recurrence in post-treatment cancer patients by examining two potential mediators: psychological flexibility and mentalization. Three hundred and thirty-five participants (aged 22 to 88, 49.1% female) who had finished their cancer treatment completed self-report assessments of total pain, fear of recurrence, psychological flexibility, and mentalization. The serial mediation analysis showed that all dimensions of total pain were positively related to the fear of recurrence indirectly through psychological flexibility and mentalization, in serial. Additionally, gender moderated these serial mediational effects. In line with the psychological flexibility model, personal capacities to face difficult internal/external problems and interpret one’s behaviour in motivational terms can counterbalance patients’ negative emotions and feelings related to the illness.

Mitochondria are semiautonomous organelles, which are pivotal for the energy metabolism of eukaryotic cells. These organelles contain their own genetic system (mtDNA, mitogenome) that encodes to some structural RNAs and organellar proteins. The biogenesis and function of mitochondria is tightly regulated by nuclear-encoded protein cofactors. The mtDNAs of land plants are characteristically large, with a complex mode of gene organization and expression, in particularly at the post-transcriptional level. To become functional, the primary organellar transcripts undergo extensive maturation steps, which include endo- and exo-nucleolytic cleavage, RNA-base editing, and both ‘cis’- and ‘trans’-splicing events. These essential processing steps rely on the activities of a large set of nuclear-encoded factors. Among these, the RNA helicases serve as key players in organellar (mt-)RNA metabolism. This review summarizes the important roles played by these factors in regulating the highly dynamic processes of transcription, RNA processing, and translation within the mitochondria of land plants. We further discuss recent advancements in understanding how dysregulation of mitochondrial RNA helicases affects the organellar gene expression, respiratory functions, and hence the growth, development and physiology of land plants.

P. palmata is a viable source of nutrients with bioactive properties. The present study determined the potential role of post-extraction ultrasonication on some compositional features and antioxidant properties of resulting extracts after sequential enzymatic/alkaline treatment. No significant difference was detected in terms of protein content and recovery as well as amino acid composition of the extracts. The nitrogen-to-protein conversion factor of 5 was found to be too high for the seaweed and its enzymatic/alkaline extracts. The extracts sonicated by bath for 10 minutes and not sonicated showed the highest and lowest total phenolic contents (p&lt;0.05), respectively. The highest radical scavenging and lowest metal chelating activities were observed for the non-sonicated sample, as evidenced by IC50 values. The extract sonicated by bath for 10 minutes showed the most favorable in vitro antioxidant properties since its radical scavenging was not significantly different from that of not sonicated sample (p&gt;0.05), whereas its metal chelating activity was significantly higher (p&lt;0.05). To conclude, post-extraction ultrasonication by an ultrasonic bath for 10 minutes is recommended to increase phenolic content and improve antioxidant properties of enzymatic-alkaline extracts from P. palmata.

Kiribati is a Pacific Island nation with a widely dispersed population and one of the highest rates of leprosy worldwide. Single dose rifampicin post exposure prophylaxis (SDR-PEP) of leprosy contacts has reduced new case detection rates in controlled trials. In 2018, a SDR-PEP programme was introduced in Kiribati that included screening and chemoprophylaxis of household contacts of leprosy cases both retrospectively (2010-2017) and prospectively (2018 onwards). We conducted a retrospective audit to determine comprehensiveness, timeliness and feasibility of the SDR-PEP programme. Overall, 13,643 household contacts were identified (9,791 in the retrospective and 3,850 in the prospective cohort). In the retrospective cohort, 1,044 (11%) contacts were absent, 403 (4%) were ineligible for SDR and 42 new cases were detected (0.4%) Overall SDR coverage was 84.7%. In the prospective cohort, 164 (4%) contacts were absent, 251 (7%) were ineligible for SDR and 23 new cases were diagnosed (0.6%). Overall, SDR coverage was 88.1%. Across both cohorts, there were a total of 23 SDR refusals. The median time to SDR ad-ministration was 220 days (IQR 162-468) and 120 days (IQR 36-283) for the retrospective and prospective cohorts respectively. SDR was readily accepted in both cohorts. The new case detec-tion rate (0.5%) is consistent with that seen in other studies. Overall SDR coverage in both the retrospective and prospective phases met programmatic expectations.

Post-earthquake fire is considered as a catastrophic secondary disaster to personal and property safety. In this article, an evacuation assessment of a complex rail transit station under the post-earthquake fire for sustainable buildings was conducted from the internal environment and external rescue based on Building Information Modeling (BIM) and Fire Dynamic Simulation (FDS). The internal environment evacuation assessment simulation experiments were conducted in six hypothetical high-risk scenarios. Besides, the external rescue assessment was based on investigation of the route and the rescue time required during different periods of holidays and workdays. The results show that: (1) The influence caused by different size of fire area in the power distribution room is smaller than those in the train at the platform floor. (2) In the case of fire scenarios with the same fire area but different fire locations, the impact on temperature is greater than that on CO concentration in power distribution room. (3) It shows slight differences between single-floor fire and double-floor fire on evacuation of small area fire in power distribu-tion room. Meanwhile, optimized design recommendations are proposed to reduce the risk of emergency evacuation in both internal and external environments of rail transit stations for sustainable future buildings.

Non-coding RNAs, specifically microRNAs (miRNAs), exhibit altered expression and contribute significantly to the pathological processes observed in numerous diseases, encompassing various types of human cancers. Recent discoveries regarding miRNAs underscore their crucial roles in tumor pathogenesis and their responses to diverse therapeutic interventions. miRNAs are a subset of non-coding RNAs that regulate the expression of a multitude of genes post-transcriptionally and thus are potential diagnostic, prognostic, and predictive biomarkers and have also emerged as potential therapeutics. Because miRNAs are involved in the post-transcriptional regulation of their target mRNAs via repressing gene expression, defects in the miRNA biogenesis pathway and miRNA expression perturb the expression of a multitude of oncogenic or tumor-suppressive target genes that are involved in the pathogenesis of various cancers. As such, numerous miRNAs have been identified to be downregulated or upregulated in many types of cancers functioning as either oncomiRs or oncosuppressor miRs. Moreover, dysregulation of miRNA biogenesis pathways can also change miRNA expression and function in cancer. Profiling deregulated miRNAs in many cancer types has been shown to correlate with disease diagnosis, indicate optimal treatment options, and predict response to a specific therapy. Specific miRNA signatures can track all stages of disease including many cancer types and hold potential as biomarkers and therapeutic targets as well as therapeutics as miRNA mimics and inhibitors (antagomirs). As such, identifying specific miRNAs and mRNAs they regulate in many types of cancer along with downstream pathways can be used as potential therapeutic targets. Because a single miRNA can regulate a pool of targets involved in similar cellular processes and pathways, thereby amplifying the cellular response, this potentially makes miRNAs powerful therapeutics to restore cell functions that are altered as part of a disease phenotype. However, because a single miRNA regulates multiple gene expressions their cellular effects are numerous leading to potential off-target effects. Besides their intended targeting issues, there is a need to reduce the immunogenic reactions and determine the minimal dosing to achieve the desired effect while minimizing side effects. As such, a careful risk evaluation of miRNA therapeutics is needed to minimize off-target effects and to avoid overdosing of miRNA drugs. Furthermore, a limited understanding and validation of the specific roles of miRNAs limits their clinical application. In addition, there are many challenges concerning the delivery, sensitivity, specificity, toxicity, and applicability of the potential utility of miRNAs as therapeutic targets or therapeutics. Thus, future work will warrant if miRNAs can be used as cancer biomarkers as well as therapeutics for clinical application.

This academic article examines the effectiveness of international humanitarian intervention in conflict zones. Humanitarian intervention refers to the use of military, diplomatic, or economic measures by external actors to protect civilians, promote human rights, and alleviate suffering in areas affected by armed conflict. The research employs a comprehensive approach, incorporating content analysis, case study, and historical analysis in its methodology. It explores the key challenges faced by international actors in implementing humanitarian interventions and evaluates their impact on conflict resolution and post-conflict reconstruction. Through this thorough analysis of case studies and scholarly literature, this article contributes to the ongoing debate surrounding the efficacy of international humanitarian intervention.

This paper delves into the essential role of local communities in mitigating climate change in the post-pandemic landscape, with a specific focus on Barangay Acmac, Iligan City, Philippines. Employing a qualitative research approach, the study integrates in-depth literature reviews, informal interviews with participants (B-Part 1 to B-Part 20), meticulous observations, and thematic analysis. The research has uncovered crucial insights, including variations in community climate change awareness that emphasize the necessity of comprehensive education and awareness campaigns. It highlights the significance of community-driven initiatives, adaptation, and resilience as key elements in addressing climate change. Collaborative efforts between local government officials and the community are showcased as effective instruments of climate change mitigation, yet challenges persist, including addressing the perceived powerlessness of some community members. The methodology, participants, and theoretical framework offer a robust foundation for exploring community responses to climate change. Drawing from a diverse theoretical framework, this study presents a comprehensive understanding of the climate change and pandemic intersection. The findings firmly establish that local communities are pivotal players in the global endeavor to mitigate climate change, underscoring the need for collective action, extensive education, and shared responsibility. The post-pandemic era presents a unique opportunity for local communities, policymakers, barangay officials, and residents to champion climate education, foster community-driven initiatives, and empower individuals to enact change at the grassroots level. The collaborative spirit observed in Barangay Acmac in 2022 serves as a model for communities worldwide, offering a blueprint for addressing similar challenges. Overall, this paper concludes with a resounding call to action, advocating for the recognition of local communities as the driving force in climate change mitigation, stressing that the power to combat climate change resides within these communities. The time for action is now, and local communities are the catalysts of this essential mission.

In the ever-evolving landscape of higher education, the shift to hybrid teaching approaches has introduced novel challenges and opportunities for both educators and students. This qualitative study, grounded in a robust theoretical framework, combines in-depth literature reviews, informal interviews, observations, and thematic analysis to explore the multifaceted dynamics of hybrid language learning within a College of Arts and Sciences. By investigating the experiences of twenty students (referred to as 'S-Part 1' to 'S-Part 20'), the research delves into the core theme of 'Teacher-Student Interaction in Higher Education Institutions' and unpacks nine additional themes: 'Adaptability and Resilience,' 'Flexibility and Autonomy,' 'Connectivity Challenges,' 'Feelings of Isolation,' 'Technology Competence,' 'Personalized Learning,' 'Resource Accessibility,' 'Support Mechanisms,' and 'Positive Learning Experiences.' In this study, these themes encapsulate the diverse experiences and challenges encountered by teachers and college students as they navigate the evolving educational landscape. The insights derived from the study are underpinned by a robust theoretical framework and complemented by existing scholarly literature. As we delve into these themes, it becomes evident that they shed light on not only the intricacies of hybrid language learning but also the broader educational context, offering valuable guidance for educators, institutions, students, and researchers. Based on the ample results, recommendations are presented for school administrators, teachers, students, and future researchers to enhance the quality of hybrid teaching and learning, aligning it with the demands of the post-academic era. Overall, this study contributes to the ongoing dialogue on innovative pedagogical strategies and responsive educational environments, underlining the significance of teacher-student interaction in the new normal of higher education.

As the oil industry increasingly turns to unconventional low-permeability and low-porosity reservoirs, precise post-fracture production prediction is a pivotal instrument in investment de-cision-making, formulation of energy policies, and promotion of environmental assessments. Nevertheless, despite extensive research spanning decades, the precise post-fracture production prediction based on logging parameters remains an intricate task. In this study, we gathered ex-tensive logging data and segmented the post-frac gas production during well testing on the first day to enrich the dataset. Nine pipelines were then architected using various techniques of data preprocessing, feature extraction, and advanced machine learning models. Hyperparameter op-timization was executed via the GridsearchCV. To assess the efficacy of diverse models, metrics including the coefficient of determination (R2), standard deviation (SD), and root mean square error (RMSE) were invoked. Among the several pipelines explored, the PS-NN exhibited excellent predictive capability in specific reservoir contexts (an R2 value of 0.94 and an RMSE of 48.15). In essence, integrating machine learning with logging parameters effectively assesses reservoir productivity at multi-meter formation scales. This strategy not only mitigates uncertainties en-demic to reservoir exploration but also equips petroleum engineers with monitoring on reservoir dynamics, thereby facilitating reservoir development. Additionally, this approach provides res-ervoir engineers with an efficient way of reservoir performance oversight.

The measures related to climate change and international technology transfer have been closely intervened as most international environmental instruments, including the United Nations Framework Convention on Climate Change and Kyoto Protocol as well as Paris Agreement which contain the provisions concerning environmentally friendly technology transfer. However, technologies have not been transferred adequately owing to the flaws in the relevant provisions and due to the fact that most technologies are possessed by transnational corporations and other private sectors. In order to undertake the commitment by the governments of developed countries and at the same time, to conform the commercial activities of their respective private sectors to the level of promised international obligation, an uniform international technology transfer agreement needs to be established separately, particularly under the World Trade Organization regime in Post Pairs-Agreement era. This paper first explores the defects and challenges found in provisions related to technology transfer in existing environmental agreements, and examines the possibilities of concluding an international technology transfer agreement both from theoretical and practical perspectives. climate change;environmentally sound technology;international technology transfer;Post Paris-Agreement Era

Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) is an acquired disease with significant morbidity that affects both children and adults. Effective tools to assess functional capacity (FC) are severely lacking which has significant consequences for timely diagnosis, assessments for patient disability benefits and assessing the impact and effectiveness of interventions. In interventional research the inability to assess FC can result in an incomplete assessment of the potential effect of the intervention. Specifically of concern is that if an intervention is effective in reducing symptom load, patients may increase their activity level to reach a pre-intervention symptom load. Thus, if FC is not accurately assessed, beneficial treatment outcomes may be missed. To address this issue, using extensive, repeated patient feedback we have developed a new questionnaire, FUNCAP, to achieve optimal FC assessment in ME/CFS patients. The questionnaire covers eight domains and activity types: A. Personal hygiene / basic functions, B. Walking / movement, C. Being upright, D. Activities in the home, E. Communication, F. Activities outside the home, G. Reactions to light and sound, and H. Concentration. Through five rounds of anonymous web-based surveys and a further test - retest validation round, two versions of the questionnaire were developed; a longer version comprising 55 questions (FUNCAP55) to improve diagnostic and disability benefit/ insurance FC assessments and a shorter version (FUNCAP27) for interventional research and less extensive FC assessments. FUNCAP may also be useful in other conditions where fatigue and PEM is present, such as Long Covid.

The present review aimed to identify through what means neurologic injury can predispose individuals to Post-Traumatic Stress Disorder (PTSD). In recent years, comprehensive studies have helped to clarify which structures in the central nervous system (CNS) that, when damaged, lead to distinct PTSD symptoms–namely dissociative reactions or flashbacks. Our review narrowed its focus to three common neurologic injuries including traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and stroke. Beyond discussing the potential mechanisms by which neurotrauma may lead to PTSD, we summarized our current understanding of the pathophysiology of the disorder and discussed predicted associations between the limbic system and PTSD. In particular, the role of noradrenergic neuromodulatory signaling on the HPA axis as it pertains to fear memory recall needs to be further explored to better understand its effects on limbic structures in PTSD patients. This paper also described how damage to the CNS can alter the function of the limbic system and result in characteristic symptoms of PTSD like intrusive memories and acute psychological distress. Further, our review intended to draw attention to a lack of PTSD prognosis in TBI, SAH, and stroke patients who could benefit from early treatment. PTSD symptoms often compound with pre-existing issues further deteriorating health outcomes for these patients. It is ultimately our goal to clarify the relationship between neurotrauma and PTSD such that earlier diagnoses and appropriate treatment are observed in clinic.

(1) Background: Treatment of male stress incontinence in patients with prostate cancer treated with radical prostatectomy and adjuvant pelvic radiation is a therapeutic challenge. The efficacy and safety of the adjustable trans-obturator male system (ATOMS) in these patients is not well established, despite the general belief that outcomes are worse than in patients without radiation. (2) Methods: Retrospective multicenter study evaluating patients treated with silicone-covered scrotal port (SSP) ATOMS implant after radical prostatectomy and radiotherapy in nine different institutions between 2016 and 2022. The primary endpoint was dry patient rate, defined as pad-test ≤20 mL/day. The secondary endpoints were complication rate (defined using Clavien-Dindo classification), device removal and self-perceived satisfaction using the Patient Global Impression of Improvement (PGI-I) scale. Wilcoxon rank sum test, Fisher’s exact test and logistic regression were performed using stepwise method with a 0.15 entry and 0.1 stay criteria. (3) Results: 223 patients fulfilled criteria for inclusion, 12 (5.4%) had received salvage prostatectomy after radiation and 27 (12.1%) previous devices for stress incontinence. After ATOMS adjustment, 95 patients (42.6%) were dry and 36 (16.1%) had complications of any grade (grade I, n=20; grade II, n=11; grade III, n=5) during the first 3 months postoperatively. At a mean 36 ± 21 months follow-up the device was explanted in 26 (11.7%) patients. Regarding self-perceived satisfaction with the implant, 105 of 125 patients (84%) considered themselves satisfied (PGI-I 1 to 3). In univariate analysis dryness was associated to younger age (p=.06), primary prostatectomy (p=.08), no previous incontinence surgery (p=.02), absence of overactive bladder symptoms (p=.04), absence of bladder neck stricture (p=.001), no need of surgical revision (p=.008) and lower baseline incontinence severity (p=.0003). Multivariate analysis identified absence of surgical revision (p=.018), absence of bladder neck stricture (p=.05), primary prostatectomy (p=.07) and baseline incontinence severity (p&lt;.0001) were independent predictors of dryness. A logistic regression model was proposed and internally validated. (4) Conclusions: ATOMS is an efficacious and safe alternative to treat male incontinence after radical prostatectomy and adjuvant radiotherapy. Factors predictive of dryness are identified in this complex scenario to allow better patient selection.

Landform Evolution Modelling (LEM) provides an avenue for simulating how a landscape may evolve over extended time periods of thousands of years. The CAESAR-Lisflood LEM that includes a hydrologic model (TOPMODEL) and a hydraulic model (Lisflood) can be used to assess the proposed final landform morphology of a mine site by simulating how the mine landform and the landscape would evolve over a 1,000-year period. The accuracy of future simulations depends on the calibration and validation of the model to the past and present events. Calibration and validation of the model involves finding a combination of parameters of the model which when applied and simulated gives model outputs similar to those observed for the real site scenario for corresponding input data. Calibrating the sediment output of the CAESAR-Lisflood model at the catchment level and using it for studying the equilibrium conditions of the landform is an area yet to be explored. Therefore, the aim of this study was to calibrate the CAESAR-Lisflood model and then validate it. To achieve this, the model was run for a rainfall event with a set of parameters, plus discharge and sediment data for the input point of the catchment, to analyze how similar the model output would behave when compared with the discharge and sediment data for the output point of the catchment. The model parameters were then adjusted until the model closely approximate the real site values of the catchment. It was then validated by running the model for a different set of events and checking that the model gave similar results to the real site values. The outcomes demonstrated that while the model can be calibrated to a greater extent for hydrology (discharge output) throughout the year, the sediment output calibration may be slightly improved by having the ability to change parameters to take into account the seasonal vegetation growth during the start and end of the wet season. This study is important for designing and testing post-mining rehabilitated landscape systems that assess hydrology and sediment movement in seasonal biomes.

Informal caregivers are essential in supporting stroke survivors' recovery, but it is unclear whether community interventions can promote healthy eating behaviors and social participation among stroke survivors and their caregivers. The Train-Your-Brain (TYB) program's impact on adherence to national dietary guidelines and social participation among informal caregivers and stroke survivors were assessed in a quasi-experimental study. The TYB program had nine sessions, with one focusing on healthy lifestyle. Participants were prompted to discuss the topics covered, leading to social participation. Dietary habits were assessed using fruits and vegetables consumption questions, while social participation was measured using the Social Impact Measurement Framework. Mann-Whitney U-test and Wilcoxon Signed Rank Test were utilized to analyze the data. Eighteen informal caregivers and 27 stroke survivors participated in the program. Results showed a significant increase in fruit and vegetable intake and social participation in informal caregivers after the program, but there were no significant changes in stroke survivors. Informal caregivers play a crucial role in stroke survivors' lifestyle habits and in encouraging social connections with other stroke survivors. Thus, healthcare professionals should prioritize caregiver support and education to facilitate long-term dietary and social changes that can positively impact stroke survivor's recovery and quality of life.

Autonomic dysfunction is an increasingly recognised complication in chronic neurological conditions such as Parkinson’s disease , and other medical conditions, including diabetes mellitus, chronic fatigue syndrome, postural tachycardia syndrome with and without Ehlers-Danlos syndrome, fibromyalgia and recently Long Covid. Despite laboratory-based tests to evaluate normal and abnormal autonomic function, there are no home-based tests to record neuro-cardiovascular autonomic responses to common stimuli in daily life that are dependent on the normal functioning of the autonomic nervous system. We have developed an adapted blood pressure/heart Autonomic Profile (aAP) that can be used by an individual independently and repeatedly in a domiciliary setting to determine the physiological and symptomatic response to standing, food, and physical and mental (cognitive, emotional) activities. The aAP aids separating autonomic failure (often irreversible) from autonomic dysfunction. This helps the individual and attending healthcare professional understand the relationship between symptoms and common triggers in daily life and informs on self-management in debilitating conditions such as the postural tachycardia syndrome (PoTS) and Long Covid.

The importance of statistics in biological research is inevitable. The appliance of statistics is the most powerful tool to support the scientific hypothesis and to give credibility to biological research methodology, to interpret convoluted explanations and conclusions based on the research findings. The evidences from literatures point the persistent statistical errors, selection of non-proper statistical test with the consequence of misinterpretation of the scientific results which are published in international journals. One of the most extensively used statistical tests in the field of biology (preclinical and clinical) is analysis of variance (ANOVA). ANOVA test is in place of multiple T-tests to compare the means of more than two groups at a time; and there are some important points which biologists should be aware of them to avoid possible misinterpretation of results with the consequence of wrong conclusion. Accordingly, the aim of the current review is to help biologists to understand the basic concepts of ANOVA test and reach to a more valid interpretation of achieved results.

Here we report the effect of substrate, sonication process, and post-annealing on the structural, morphological, and optical properties of ZnO thin films grown in the presence of isopropyl alcohol (IPA) at temperature 30 – 65 ℃ by successive ionic layer adsorption and reaction (SILAR) method on both soda lime glass (SLG) and Cu foil. The X-ray diffraction (XRD) patterns confirmed the preferential growth thin films along (002) and (101) plane of wurtzite ZnO structure while grown on SLG and Cu foil substrate respectively. Both XRD and Raman spectra confirmed the ZnO and Cu-oxide phases of the deposited films. Scanning electron microscope (SEM) image of the deposited films shows compact and uniformly distributed grains for samples grown without sonication while using IPA at temperature 50 and 65 ℃. The post-annealing treatment improves the crystallinity of the films, further evident by XRD and transmission and reflection results. The estimated optical bandgaps are in the range of 3.37-3.48 eV for as-grown samples. Results revealed that high-quality ZnO thin films could be grown without sonication using IPA dispersant at 50 ℃, which is much lower than the reported results using the SILAR method. This study suggests that in the presence of IPA, the SLG substrate results in better c-axis oriented ZnO thin films than that of DI water, ethylene glycol, propylene glycol at the optimum temperature of 50 ℃. Air-annealing of the samples grown on Cu foils induced the formation of Cu_xO/ZnO junctions which is evident from the characteristic I-V curve including the structural and optical data.

The Ras family of proteins is tethered to the inner leaflet of the cell membranes which play an essential role in signal transduction pathways that promote cellular proliferation, survival, growth, and differentiation. KRas-4B, the most mutated Ras isoform in different cancers, has been under extensive study for more than two decades. Here we have focused our interest on the influence of cholesterol on the orientations that KRas-4B adopts with respect to the plane of the anionic model membranes. How cholesterol in the bilayer might modulate preferences for specific orientation states is far from clear. Herein, after analyzing data from in total 4000 ns-long MD simulations for four KRas-4B systems, properties such as the area per lipid and thickness of the membrane as well as selected radial distribution functions, penetration of different moieties of KRas-4B, and internal conformational fluctuations of flexible moieties in KRas-4B have been calculated. It has been shown that high cholesterol content in the PM favors OS1, exposing the effector-binding loop for signal transduction in the cell from the atomic level. We confirm that high cholesterol in the PM helps KRas-4B mutant stay in its constitutively active state, which suggests that high cholesterol intake can increase mortality and may promote cancer progression for cancer patients. We propose that during the treatment of KRas-4B-related cancers, reducing the cholesterol level in the PM and sustaining cancer progression by controlling the plasma cholesterol intake might be taken into account in anti-cancer therapies.

In this experimental report the biocompatibility of elastomeric scaffold structures made via stereolithography employing table-top 3D printer (Ember, Autodesk) and commercial resin FormLabs Flexible (FormLabs) was studied. The samples were manufactured using standard printing and development protocol, which is known to inherit cytotoxicity due to remaining non-polymerized remaining monomers, despite the polymerized material being fully biocompatible. Additional steps were taken to remedy this problem: the fabricated structures were soaked in isopropanol and methanol for different conditions (temperature, duration) in order to leach out the non-polymerized monomers. Also printed structures were UV exposed to assure maximum polymerization degree of the material. Post-processed structures were seeded with myogenic stem cells and the number of live cells was evaluated as an indicator for the material biocompatibility. The straightforward post-processing protocol enhances the biocompatibility by 7 times after 7 days soaking in isopropanol and methanol and is comparable to control (glass and polystyrene) samples. This proposes the approach as a novel and simple method to be widely applicable for dramatic cytotoxicity reduction of optically 3D printed micro-/nano-scaffolds for biomedical applications.

Clean production of renewable fuels is a great challenge of our scientific community. Iridium complexes have demonstrated a superior catalytic activity in the water oxidation (WO) reaction, which is a crucial step in water splitting process. Herein we have used a defective zirconium MOF with UiO-66 structure as support of a highly active Ir complex based on EDTA with formula [Ir(HEDTA)Cl]Na. The defects are induced by the partial substitution of tereftalic acid with smaller formiate groups. Anchoring of the complex occurs through a post-synthetic exchange of formiate anions, coordinated at the zirconium clusters of the MOF, with the free carboxylate group of the [Ir(HEDTA)Cl]-complex. The modified material was tested as heterogenous catalyst for the WO reaction by using Cerium Ammonium Nitrate as sacrificial agent. Although TOF and TON values are comparable to those of other iridium heterogenized catalysts, the MOF exhibits iridium leaching not limited at the first catalytic run, as usually observed, suggesting a lack of stability of the hybrid system under strong oxidative conditions.

Sustainable agriculture is essential to provide food security for a growing world population without further sacrificing the integrity of the environment. To make progress towards agricultural sustainability we must consider ecological and socioeconomic processes within the agricultural socio-ecosystem and involve stakeholders in the research process. We propose an innovative experimental approach for examining how natural regulation of ecosystems may provide an alternative to increasing external inputs in agriculture while improving the socio-economic welfare of farmers. These “social-ecological experiments” go further to participatory action research by not only involving stakeholders in the research process but also by manipulating simultaneously socioeconomic and ecological processes under real field conditions to give a faster route to sustainability. Social-ecological experiments are undertaken in real field conditions, explicitly involving stakeholders, and help untangle the drivers of social-ecological dynamics under various land management and farming practices. Social-ecological experiments are distinct from adaptive management and scenario-planning approaches as they highlight the interactions between ecological and social processes, manipulate the social and ecological processes shaping the system and show causal links between patterns and processes. As an example, we describe a social-ecological experiment for reducing herbicide use. Social-ecological experiments offer great opportunities for increasing stakeholders’ acceptance of environmental policies implemented through adaptive management. These experiments may help to identify management practices that optimize multiple objectives, deliver a portfolio of ecosystem services and satisfy key stakeholders.

As shown earlier, the algorithmic complexity, like Shannon information and Boltzmann entropy, tends to increase in accordance with the general law of complification. However, the algorithmic complexity of most material systems does not reach its maximum, i.e. chaotic state, due to the various laws of nature that create certain structures. The complexity of such structures is very different from the algorithmic complexity, and we intuitively feel that its maximal value should be somewhere between order and chaos. I propose a formula for calculation such structural complexity, which can be called - structuredness. The structuredness of any material system is determined by structures of three main types: stable, dissipative, and post-dissipative. The latter are defined as stable structures created by dissipative ones, directly or indirectly. Post-dissipative structures, as well as stable, can exist for an unlimited time, but at the micro level only, without energy influx. The appearance of such structures leads to the “ratchet” process, which determines the structuregenesis in non-living and, especially, in living systems. This process allows systems with post-dissipative structures to develop in the direction of maximum structuring due to the gradual accumulation of these structures, even when such structuring contradicts the general law of complification.

Background Lipoprotein(a) [Lp(a)] is a well-established risk factor for incident atherosclerotic cardiovascular (CV) disease. However, evidence regarding its association with recurrent events is limited. To address this gap, we conducted a retrospective analysis of routine clinical data, focusing on patients hospitalized for acute myocardial infarction (AMI) between 2000 and 2022 with available admission Lp(a) results. Methods Patients were stratified into three groups based on their Lp(a) level (≤50 mg/dL, 51–90 mg/dL, and >90 mg/dL). A multivariable-adjusted Cox regression analysis was performed to assess the associations of Lp(a) with recurrent AMI, CV mortality, and all-cause mortality. Results A total of 2248 patients (31.5% women), with a mean age of 64.7 ± 12.2 years, were retrospectively followed until December 31, 2022, or death. The multivariable-adjusted hazard ratios (HRs) for recurrent AMI were 1.01 (p=0.921) for levels 51–90 mg/dL and 1.51 (p=0.013) for levels >90 mg/dL, compared with levels ≤50 mg/dL. The corresponding HRs for CV mortality were 1.13 (p=0.300) and 1.14 (p=0.348), and those for all-cause mortality were 1.09 (p=0.310) and 1.20 (p=0.090), respectively. Stratification by sex and age revealed a significant association of Lp(a) with recurrent AMI only in women aged >65 years, with adjusted HRs of 2.34 (p=0.013) for levels 51–90 mg/dL and 3.94 (p90 mg/dL, compared with levels ≤50 mg/dL. Conclusions We observed a significant association of Lp(a) with recurrent AMI only in patients with Lp(a) levels >90 mg/dL. No associations were found between Lp(a) and CV or all-cause mortality. Notably, the association with recurrent AMI was most pronounced in women aged >65 years.

CNS infiltration (CNS+) leads to serious complications in AML. Cytogenetic and Molecular profile is essential in risk stratification, treatment decisions and envisage prognosis. We utilize the NGS data and cytogenetics as a screening tool, for determining the incidences and specific CNS+ risks, in patients eligible for intrathecal chemotherapy. 52 mutations database per NGS was used for the analysis. 435 newly diagnosed patients underwent frontline induction chemotherapy. 259 (59.5%) patients received LP. The most common molecular mutation in the CNS+ patients were MPN1 (48.3%), FLT3 (22.5%), TET2 (25.8%), RAS / KRAS (25.7%), DMNT3 (19.3%), ASXL1 and (16.1%). Of which 31 patients had confirmed CNS+ disease due to the presence of characteristic markers. CNS+ patients have significantly higher bone marrow blast% (76 vs. 53) (p= 0.0202). WBC count ≥ 100x109/L (OR: 5.614 [2.313-13.626] p=0.0001) in the multivariable analysis, and LDH ≥2ULN (OR: 5.512 [2.176-13.965]; p= 0.0003) in the univariate analysis, revealed higher risk for CNS+. Patients exhibited significantly higher NPM1 mutations (48.4% vs 24.6%, p=0.0053) and 11q23 chromosomal abnormality (12.9% vs 2.19%, p= 0.0139). However, FLT3 by NGS did not predict CNS+ (P=0.1226). CNS+ did not contribute significantly toward CIR (p=0.066), and has no bearing on OS (p=0.9063). Patients presented with either neurological symptoms or accompanied by hyperleukocytosis, elevated LDH, NPM1 positivity or 11q23 abnormality are highly suggestive of CNS+. Therefore, LP is needed to rule-out CNS disease at presentation. NGS did not consistently predict CNS+. A large prospective trial is needed to confirm the results.

Acute Respiratory Distress Syndrome (ARDS) is a severe lung condition with a high mortality rate for which there are no effective therapeutics. The failure of the alveolar-capillary barrier, composed of lung endothelial (EC) and alveolar epithelial (AEC) cells, is a critical factor leading to excessive inflammation and edema characteristics of acute lung injury (ALI). Phosphodiesterases (PDE) are enzymes well-recognized for their roles in regulating endothelial permeability and inflammation. Although PDE inhibitors are used as therapeutics for inflammatory diseases like COPD (chronic obstructive pulmonary disease), their efficacy in treating ARDS has not yet been established. In this study, we investigate the effects of ensifentrine, an FDA-approved novel dual PDE 3/4 inhibitor, on lung endothelial and epithelial dysfunction caused by methicillin-resistant S. aureus (MRSA), a pathogen involved in bacterial ARDS. Human primary lung endothelial cells and alveolar epithelial cell lines (A549 and immortalized AEC) were treated with heat-killed MRSA, and their responses were assessed in the presence or absence of ensifentrine. Ensifentrine given either pre- or post exposure attenuated MRSA-induced increased lung endothelial permeability. VE-cadherin junctions, which serve to stabilize the EC barrier, were disrupted by MRSA; however, ensifentrine effectively prevented this disruption. Pre-treatment with ensifentrine protected against MRSA-induced EC pro-inflammatory signaling by inhibiting the expression of VCAM-1, ICAM-1, and by reducing the IL-6 release. In AEC, MRSA caused upregulation of ICAM-1, activation of NF-kB and production of IL-8, all of which were inhibited by ensifentrine. These results indicate that dual inhibition of phosphodiesterases 3 and 4 by ensifentrine is barrier protective and attenuates MRSA-induced inflammation in both lung endothelial and epithelial cells. The PDE3/4 inhibitor ensifentrine may represent a promising novel strategy for the treatment of ALI.

Background: Despite tremendous advances in medicine, infective endocarditis (IE) continues to be a challenge for physicians due to increasing morbidity and unchanged high mortality. Objectives: Our aim was to evaluate clinical outcomes in patients with IE and to identify predictors of in-hospital mortality. Material and methods: The study was retrospective, single-centered, and included 270 patients diagnosed with IE, for the period 2005-2021 (median age 65 (51–74), man 177 (65.6%). Results: Native IE (NVIE) was found in 180 (66.7%), prosthetic IE (PVIE) in 88 (33.6%) and cardiac device-related IE (CDRIE) in 2 (0.7%), significantly more in the non-survivors group. Healthcare associated IE (HAIE) was 72 (26.7%), the most common pathogen were Staphylococci and the proportion of Gram-negative bacteria (GNB) non-HACEK were significantly higher in non-survivor’s vs survivors (11 (15%) vs 9 (4.5%), p=0.004). Overall, early surgery was performed in 54 (20%) patients, with a significant difference between deceased/alive (3 (4.5%) vs 51 (25.1%, p=0.000). The all-cause in-hospital mortality rate was 24.8% (67). The risk factors identified that increased the risk of death were septic shock (OR – 83 1; 95% CI (17.0-405.2), p=0.000) and acute heart failure (OR –24.6; 95% CI (9.2-65.0), p=0.000). Early surgery (OR – 0.03, 95% CI (0.01-0.16), p=0.000) and low Charlson comorbidity index (OR – 0.85, 95% CI (0.74-0.98, p=0.026) in turn reduce this risk. Conclusion: We found that acute heart failure and septic shock are independent predictors of in-hospital mortality. Low Charlson comorbidity index and early surgery increased survival. Knowing the predictors of death would change the therapeutic approach to a more aggressive one and improve the near and long-term prognosis of patients with IE.

Background. While selective use of antibiotics for infected pancreatic necrosis (IPN) in acute pan-creatitis (AP) is recommended, studies indicate a high rate of inadequate treatment. Methods. A search of PubMed, Scopus, and Cochrane databases was conducted, focusing on primary research and meta-analyses. Data were categorized based on core concepts, and a narra-tive synthesis was performed. Results. The searches yielded 1016 publications. After assessing 203 full texts and additional sources, 80 studies were included. The answers obtained were: (1) Preventive treatment does not decrease the incidence of IPN or mortality. Given the risks of bacteria resistance and fungal infec-tions, antibiotics should be reserved for highly suspected or confirmed IPN; (2) The diagnosis of IPN not always require microbiological samples, as clinical suspicion or CT signs can suffice. Early di-agnosis and treatment may be improved by using biomarkers such as procalcitonin and novel mi-crobiological methods; (3) When indicated, early initiation of antibiotics of IPN is a key determinant in reducing mortality; (4) Antibiotics with good penetration into pancreatic tissue covering Gram-negative and Gram-positive bacteria should be used. Routine antifungal therapy is not recommended; (5) The step-up approach, including antibiotics, is the standard for IPN manage-ment; (6) Antibiotic duration should be kept to a minimum and should be based on the quality of source control and patient condition. Conclusions. Early antibiotic therapy is essential for the treatment of IPN, but prophylactic anti-biotics are not recommended in AP. High-quality RCTs are required to better understand the role of antibiotics and antifungals in AP management.

Acute myeloid leukemia (AML) is a malignant disease of the blood and bone marrow that is characterized by uncontrolled clonal proliferation of abnormal myeloid progenitor cells. Nucleophosmin 1 (NPM1) gene mutations are the most common genetic abnormality in AML, detectable in blast cells from about one third of adults with AML. AML NPM1mut is recognized as a separate entity in the World Health Organization (WHO) classification of AML. Clinical and survival data suggest that patients with this form of AML often have a more favorable prognosis, which may be due to the immunogenicity created by the mutations in the NPM1 protein. Consequently, AML with NPM1mut can be considered an immunogenic subtype of AML. However, the underlying mechanisms of this immunogenicity and associated favorable survival outcomes need to be further investigated. Immune checkpoint molecules, such as the programmed cell death-1 (PD-1) protein and its ligand, PD-L1, play important roles in leukemogenesis through their maintenance of an immunosuppressive tumor microenvironment. Preclinical trials have shown that the use of PD-1/PD-L1 (PDx) checkpoint inhibitors in solid tumors and lymphoma work best in novel therapy combinations. Patients with NPM1mut AML may be better suited to immunogenic strategies that are based on the inhibition of the immune checkpoint pathway of PDx than patients without this mutation, suggesting the genetic landscape of patients may also inform best practice for the use of PDx inhibitors.

We presented unusual case of double left ventricular false aneurysm complicating late presentation AMI successfully treated with the combination of urgent surgical drainage of tamponade, staged PCI of non-culprit lesion, preventive implantation of ICD-DR, guideline directed heart failure medical therapy and delayed but effective reconstructive operation.

In dermatological practice, disturbances of the skin microbiome are found in various infectious and inflammatory dermatoses featuring one or more skin lesions with loss of tissue, directly exposing skin layers to microbial invasions. Literature data on the incidence of cutaneous-onset sepsis are, however, scarce. This retrospective observational study assessed hospital admissions for primary skin lesions with vs. without bacterial infections and sepsis during 2020-2022 in the largest emergency hospital in NE Romania. Of 509 patients 441 had infected lesions, 78 had sepsis caused by venous ulcers microbial eczema cellulitis, superinfected bullous dermatoses, erysipelas, erythroderma. Cultured samples revealed S. aureus, P. aeruginosa, E. coli, with K. pneumoniae, S. β-hemolytic associated with sepsis even if rarer. Clinical manifestations included ulcerations, erosions, fissures, excoriations, bullae, vesicles, pruritus, tumefaction, edema, fever, chills, pain, adenopathy, mildly altered mental status. Underlying chronic heart failure, atrial fibrillation, anemia, type-1 diabetes mellitus were comorbidities associated with infection and sepsis. Significant associations and risk factors, including their combined effects, are discussed to draw attention to the need for further research and adequate management to prevent sepsis in adult patients of any age presenting with infected skin lesions (especially cellulitis) and comorbidities (especially type 1 diabetes mellitus and anemia).

Keywords: renal replacement therapy. Point-of-Care Ultrasound; intensive care; acute kidney injury; nephrologist.Point of care ultrasonography (POCUS) is gaining heightened significance in critical care settings as it allows for quick decision making at the bedside. While computerized to-mography is still considered the standard imaging modality for many diseases, the risks and delays associated with transferring a critically ill patient out of the Intensive Care Unit (ICU) have prompted physicians to explore alternative tools. Ultrasound guidance has increased safety of invasive procedures in the ICU, such as the placement of vascular catheters and drainage of collections. Ultrasonography is now seen as an extension of the clinical examination, providing quick answers for rapidly deteriorating patients in the ICU. The field of nephrology is increasingly acknowledging the value of diagnostic Point-of-Care Ultrasound (POCUS). By employing multi-organ POCUS, nephrologists can address specific queries arising during the diagnosis and treatment of patients with acute kidney injury. This approach aids in ruling out hydronephrosis and offering immediate information on hemodynamics, thereby consolidating patient data and facilitating the development of personalized treatment strategies.

There is remarkable morphologic and genetic heterogeneity in acute myeloid leukemia (AML). In a small percentage of cases of AML, increased eosinophils and/or basophils are present in the bone marrow and sometimes in the peripheral blood. This is often a puzzling diagnostic situation but also an important finding that requires special investigation. Unique chromosomal rearrangements have been correlated with an increased number of eosinophils and basophils in AML. Identification of the underlying genetic lesion that promotes eosinophilia and basophilia can dramatically change both the prognosis and the treatment of the patient. Thus clinicians must be vigilant in searching for the cause of eosinophilia and/or basophilia in patients with AML, since the different causes may lead to different treatments and survival outcomes. In this article we examine the significance of increased eosinophils and/or basophils in the context of AML, provide guidance that simplifies the differential diagnosis, and prognostic and therapeutic information about specific subtypes of AML associated with eosinophilia and/or basophilia. Evidence supporting personalized (molecularly targeted) therapy for these patients is also presented.

Background: Citicoline, a medical food, lacks proven efficacy for ischemic stroke and has uncertainties around its harms. The continued prescription should be reevaluated given the more robust, high-quality Evidence against that medical food. This essay is based on a recent Cochrane review and uses only one all-cause mortality as the primary outcome. Therefore, the essay should be considered as something other than an updated Cochrane review but like a reflection based on Evidence-based Medicine and Philosophy of Science analysis. Question Research: Why citicoline (a medical food) should not be prescribed to treat people with acute ischemic stroke: The certainty of the Evidence.? Objective: Demonstrate from evidence-based medicine and philosophy of science perspective that citicoline should not be prescribed for acute ischemic stroke due to lack of efficacy and harm uncertainties. Search publications: We searched in PubMed and Cochrane Library from 2020 until 30 October 2023. We, furthermore, used engineering machines Bing and Google Scholar to detect additional papers. Additionally, we also reviewed reference lists of the retrieved publications and review articles and searched the websites of the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA). Selection criteria: We included systematic reviews, meta-analyses, randomized clinical trials, clinical guidelines focused on acute ischemic stroke and comparing citicoline versus placebo or no intervention. We excluded narrative reviews, observational studies and ongoing trials. Data collection and analysis: We identified only new randomized clinical trials and assessed the risk of bias in seven domains. The other eight trials were already included in the mentioned Cochrane review. The systematic reviews with or without meta-analyses were assessed using McMaster University guidelines. We estimated risk ratios (RRs) for that outcome. We measured statistical heterogeneity using the I² statistic. We conducted our analyses using the fixed effect model. We did not use the GRADE approach due to what is shown in a Cochrane review published in 2020 by Martí-Carvajal et al. We used the RevMan 5.4 software from Cochrane Collaboration to conduct the forest plot. We used a Trial Sequential Analysis with Copenhagen Trial Unit Software. We estimated a Bayes factor from the relative risk and 95% confidence interval. Results: We identified only one new RCT (N = 99) reported mortality data and three clinical guidelines. We conducted a new meta-analysis with nine trials (N = 4461) having a high risk of bias and showing little to no difference in mortality between citicoline and placebo (17.1% vs 18.4%; RR 0.94, 95% CI 0.82 to 1.06; I2 = 0%). The Bayes factor was 0.7, indicating weak Evidence for the null over the alternative hypothesis. Trial sequential analysis suggested sufficiency of Evidence for mortality. No guidelines recommend citicoline. Conclusions: This essay reassessed citicoline for acute ischemic stroke after the 2020 Cochrane review. Adding a new RCT further supported the lack of mortality benefit with citicoline. The overall evidence quality could be better. Analyses using evidence-based medicine and philosophy of science approaches do not support prescribing citicoline due to a lack of efficacy substantiation and potential harms.

Although the frequency of myocarditis in the general population is very difficult to accurately determine due to the large number of asymptomatic cases, the incidence of this disease is increasing significantly due to better defined criteria for diagnosis and the development of modern diagnostic method. The multitude of different etiological factors, the diversity of the clinical picture and the variability of the diagnostic findings make this disease often demanding both for the selection of the diagnostic modality and for the proper therapeutic approach. The previously known most common viral etiology of this disease is today overshadowed by new findings based on immune-mediated processes, associated diseases that in their natural course can lead to myocardial involvement, but also the iatrogenic cause of myocarditis due to use of immune checkpoint inhibitors in the treatment of cancer patients. Suspecting that a patient with polymorphic and non-specific clinical signs and symptoms, changes in ECG and echocardiography has myocarditis is the starting point in the diagnostic algorithm. Cardio magnetic resonance imaging is non-invasive diagnostic gold standard for diagnosis and clinical follow-up of thses patients. Endomyocardial biopsy as an invasive method is the diagnostic choice in life-threatening patients with suspicion of fulminant myocarditis where the diagnosis has not yet established or there is no adequate response to the applied therapeutic regimen. The treatment of myocarditis is increasingly demanding and includes conservative methods of treating heart failure, immunomodulatory and immunospressive therapy, methods of mechanical circulatory support and heart transplantation. The goal of developing new diagnostic and therapeutic methods is to reduce mortality from this complex disease, which is still high.

Abstract The hallmark of acute promyelocytic leukemia (APL) is the presence of the characteristic fusion transcript of the promyelocytic leukemia gene with the retinoic acid receptor α gene (PML::RARA), which is a molecular target for all-transretinoic acid (ATRA) and arsenic trioxide (ATO). Therapies with ATRA plus ATO have excellent outcomes in terms of complete remission rate, overall survival, and achievement of a deep and durable molecular response with a very low incidence of relapse. However, although the combination of ATRA and ATO has lower hematologic toxicity than standard chemotherapy, its use is associated with a spectrum of unique toxicities, such as hepatic toxicity, QTc (QT interval corrected) prolongation, neurotoxicity, and differentiation syndrome. Hematologists treating patients with acute promyelocytic leukemia should be aware of possible early-complications of the ATRA plus ATO regimen and aim to balance treatment-related adverse events and efficacy. Careful follow-up of the patient’s clinical course is essential to identify and treat each complication. This study focused on treatment-related complications during induction and consolidations in patients with APL who received ATRA plus ATO. We retrospectively analyzed 26 adult patients diagnosed with APL between 2019 and 2022 at our center to identify the incidence rate, severity and time of onset of short-term non-hematologic adverse events relative to the initiation of the ATRA and ATO regimen. Additionally, we review the existing literature regarding the toxic side effects of ATO in APL and discuss how its most frequent toxicities should be managed. The median follow-up of our patients was 21.5 months (range, 1-48 months) and the most common adverse events were hepatic toxicity (69.2%), infections (46.1%), differentiation syndrome(23%) and QT prolongation (11.5%). All patients experienced at least one adverse event and grade 3 and 4 toxicities occurred in 57.6 % patients; these generally consisted of liver enzyme elevations, QTc prolongation, but also some rare manifestations such as musculoskeletal pain syndrome (1 patient) and ATO-related pancreatitis (1 patient). Most patients developed side-effects during induction. This is the first study about Romanian patients diagnosed with APL. Our results suggest that all treatment-related adverse events, except for differentiation syndrome are manageable, self-limiting and reversible. All patients, except for two (one died during induction and one died during consolidation), were able to complete the treatment consolidation with ATO and ATRA.

A considerable number of infective endocarditis (IE) patients require cardiac surgery with an increased risk for postoperative sepsis. Intraoperative hemoadsorption may diminish the risk of postoperative hyperinflammation with potential economic implications for intensive care unit (ICU) occupation. The present study aimed to theoretically investigate the budget impact of a reduced length of ICU stay in IE patients treated with intraoperative hemoadsorption in the German healthcare system. Data on ICU occupation were extrapolated from a retrospective study on IE patients treated with hemoadsorption. An Excel-based budget impact model was developed to simulate the patient course over the ICU-stay. A base-case scenario without therapy reimbursement and a scenario with full therapy reimbursement were explored. The annual eligible German IE patient population was derived from official German Diagnostic Related Group (DRG) volume data. One-way deterministic sensitivity analysis and bootstrap analysis were performed to evaluate the uncertainty over the model results. Use of intraoperative hemoadsorption resulted in 2,298€ saved per patient in the base-case scenario without therapy reimbursement. Savings increased to 3,804€ per patient in case of full device-specific reimbursement. Deterministic and probabilistic sensitivity analyses confirmed the robustness of savings, with a probability of savings of 99% and 100% in the base-case and full reimbursement scenario, respectively. Intraoperative hemoadsorption in IE patients might have relevant economic benefits related to reduced ICU stay, resulting in improved resource use. Further evaluations in larger prospective cohorts are warranted.

Anastatica hierochuntica L. (Brassicaceae) has been claimed to treat various conditions including complicated childbirth. The principal objective of this research was to provide scientific evidence on the contractile effect of the aqueous and hydroethanolic extracts of the whole plant from A. hierochuntica during labor. Qualitative and quantitative methods helped identify and quantify the phytoconstituents in both extracts. The antioxidant activity was studied using four standard methods. The inhibitory power of the extracts on pro-inflammatory enzymes such as 15-lipoxygenase and phospholipase A2 was determined. The contractile effects of the extracts were evaluated using isolated pregnant mice uteri. Steroids, triterpenoids, flavonoids, tannins, coumarins, and reduced compounds were identified in both extracts. The extracts demonstrated the ability to reduce oxidative stress. The hydroethanolic extract displayed the most significant anti-lipoxygenase activity with an IC50 value of 55.82 ± 1.15 µg/mL. The lethal dose (LD50) of extracts was estimated to be superior to 2000 mg/kg bw. The ability of the samples to produce one cm amplitude of contraction at 50% effective concentrations (EC50) was 1.51 ± 0.08 mg/mL for aqueous extract and 3.57 ± 0.61 mg/mL for hydroethanolic extract. These findings could provide evidence for using Anastatica hierochuntica to augment labor.

Mild traumatic brain injury (mTBI) or concussion accounts for the bulk of all head injuries and represents a major health concern. Although an mTBI event may not manifest in neurobehavioral impairment, repeated injuries, known as repeated mTBI (rmTBI), can result in a cumulative effect that may progress to long-term cognitive and functional deficits. To date, there is no FDA-approved drug for TBI in general and rmTBI in particular. In previous studies, we have demonstrated the neuroprotective role of mitoquinone (MitoQ), a mitochondrial antioxidant, in an open head injury model and a model of repeated mild TBI (rmTBI) at a chronic time point (30 days). In this work, we set out to assess the neuroprotective potential of MitoQ at acute (3 days) and subacute time points (7 days) post-injury in a controlled cortical impact model of rmTBI. C57BL/6 male mice were injected intraperitoneally with MitoQ (5 mg/kg) one hour after the first mTBI, and three days after the first injury in both the 3-day and 7-day MitoQ + rmTBI subgroups, with an additional injection four days after the second injection in the 7-day group. Cognitive function was evaluated using the Morris water maze (MWM) while gross and fine motor functions were evaluated by the pole climbing, grip strength, and ladder rung tests. Dihydroethidium (DHE) staining was performed to evaluate oxidative stress while qRT-PCR was used to measure the gene expression of different antioxidant enzymes. Also, immunofluorescence staining was performed on brain tissue to assess the degree of microgliosis and astrocytosis. Our results showed that MitoQ conferred significant protection on days 3 and 7 post-injury against fine motor function impairment induced by rmTBI. Moreover, MitoQ enhanced cognitive function and reduced astrogliosis, microgliosis, and levels of oxidative stress on day 7 post-injury. However, antioxidant gene expression generally remained unaffected. In light of our results, MitoQ administration may be considered a preventive approach that helps to alleviate the neurological manifestations associated with rmTBI early before symptoms progress to long-term deficits.

(1) Background: Deep hypothermic circulatory arrest (DHCA) with selective antegrade cerebral perfusion (ACP) is an established cerebral protection technique for the conduction of complex surgical procedures involving the aortic arch. It is controversial if the duration of DHCA is associated with adverse outcome in patients with acute type A aortic dissection (AAAD). Our goal was to investigate whether DHCA time was associated with surgical outcome in patients undergoing a surgical treatment of AAAD. (2) Methods: 410 Patients were divided into two groups concerning the DHCA time less than 60 minutes and equal or longer than 60 minutes. (3) Results: Patients with longer DHCA time were significantly younger (p=0.001). Intraoperatively, complex procedures with aortic arch surgery were more common in patients with longer DHCA time (p&lt;0.001). Accordingly, cardiopulmonary bypass (p&lt;0.001), cross-clamping (p&lt;0.001) and DHCA times (p&lt;0.001) were significantly longer in this group. Postoperatively, only the duration of mechanical ventilation (p&lt;0.001) and the rate of tracheotomy were significantly higher in these patients. 30-day mortality was satisfactory for both groups (p=0.746). (4) Conclusions: Our results showed that improvements in perioperative management including ACP allow a successful performance of surgical treatment of AAAD under DHCA with duration of even longer than 60 minutes.

Acute kidney injury (AKI) is a frequent and critical complication in the clinical setting. In rodents AKI can be prevented effectively through caloric restriction (CR), which has also been shown to increase lifespan in many species. In Caenorhabditis elegans (C. elegans) longevity studies revealed that a marked CR-induced reduction of endocannabinoids may be a key mechanism. Thus, we hypothesized that regulation of endocannabinoids, in particular arachidonoyl ethanolamide (AEA), might also play a role in CR-mediated protection from renal ischemia-reperfusion injury (IRI) in mammals including humans. In male C57Bl6J mice, CR significantly reduced renal IRI and led to a significant decrease of AEA. Supplementation of AEA to near-normal serum concentrations by repetitive intraperitoneal administration in CR mice, however, did not abrogate the protective effect of CR. We also analyzed serum samples taken before and after CR from patients of three different pilot trials of dietary interventions. In contrast to mice and C. elegans, we detected an increase of AEA. We conclude that endocannabinoid levels in mice are modulated by CR, but CR-mediated renal protection does not depend on this effect. Moreover, our results indicate that modulation of endocannabinoids by CR in humans may differ fundamentally from the effects in animal models.

Over the last 20 years, there has been a significant increase in the number of unexplained physiological events (UPEs) reported by pilots of fighter jets across different fleets. The UPEs have resulted in grounding some types of aircraft, loss of airplanes, and even loss of life. Despite considerable research, no single agreed-upon root cause has been found that explains UPEs, and therefore no reliable corrective actions exist. The purpose of this review was to analyze the literature related to other industries in which artificial hyperoxic gas mixes are employed and similar adverse reports have been reported. Based on analysis of the literature, it is hypothesized that UPEs are caused by unlimited delivery of high-dose oxygen in excess of officially approved oxygen schedules in the presence of inadequate airflow rates, at a time when the positive pressure breathing feature of their oxygen regulator system is not used. During flight maneuvers such as climbs, turns, and descents, pulmonary vital capacity is impaired by G-maneuvers and oxygen- and G-induced atelectasis. At the same time, tidal volume is reduced by flight gear, and effective gas exchange is not supported by adequate ventilation. These factors combine to produce hypercarbia, respiratory acidosis, acute respiratory distress syndrome, CO₂ narcosis, and coma. In fact, reports from field data related to incidents in F-18S/H, showing that emergency oxygen did not correct the hypoxia-like symptoms including long-lasting periods of incapacitation and prolonged headaches, lend support to this hypothesis.

The bioherbicidal potential of four essential oils (EOs) from Mediterranean species of Thymus sp. pl.: Thymus algeriensis Boiss. et Reut., T. ciliatus Desf. subspecies coloratus (Boiss. et Reut.) Batt., T. vulgaris L., ecotype Fasano and T. vulgaris L. var. Varico was investigated to identify new sources of biomolecules. In vivo assays were carried out to assess the effect of the EOs on pre and post-emergence of two weed species: Lolium perenne L. and Amaranthus retroflexus L.. Four concentrations of EO emulsions (500, 750, 1000 and 2000 µl/100 mL) were applied. All the EOs expressed an important bioherbicidal activity against the target species. A total inhibition of seed germination was displayed at 2000 µl whereas a potent effec-tiveness was achieved even at 500 µl. On the contrary, for post-emergence experiments, L. perenne showed resistance to the EOs while A. retroflexus was highly sensitive, arguing a selectivity of the EOs. Bioassays were also performed on the model plant Arabidopsis thaliana (L.) Heynh, for a better understanding of the structural modifications induced by the EOs. The root system of EO-treated A. thaliana seedlings was highly damaged.

As Ambeth Ocampo poignantly states, "The past is not dead; it is not even past." In an era where globalization threatens to homogenize distinct cultural identities, the challenge of preserving the rich tapestry of Filipino cultural heritage becomes paramount. This article investigates the dynamic continuum of Filipino cultural identity, shaped by historical influences and contemporary global interactions. It employs theories of cultural hybridity, transnationalism, and identity to examine the interplay between tradition and modernity, revealing how Filipino culture navigates this complex landscape. Through a detailed analysis of traditional practices, modern adaptations, and the impacts of globalization and the COVID-19 pandemic, the study highlights the resilience and adaptability of Filipino cultural expressions. It further explores intergenerational perspectives on cultural preservation, the role of the diaspora in cultural exchange, and the emergence of new cultural forms in urban settings. By evaluating ongoing efforts to celebrate and preserve Filipino heritage, this paper emphasizes the necessity of recognizing both historical roots and contemporary realities. Ultimately, it issues a call to action for a collective commitment to the celebration and preservation of Filipino cultural heritage, underscoring its vital role in fostering identity and community in an increasingly interconnected world.

In this study, the team employed full-scale crash tests to investigate the impact of post-densification technology on the safety performance of separated central median W-beam barriers under low compaction conditions. By precisely simulating the design and construction environment of the central median, the study comprehensively evaluated the barrier's containment, redirection, buffering, and anti-intrusion performances, as well as the deformation of both the barrier and vehicles under various collision scenarios. The results indicate that under low compaction soil conditions, the A-level separated central median barriers reinforced with post-densification technology effectively meet the specified protection requirements. By comparing the influence of soil strength variations on barrier performance under simulated rainfall conditions, it was confirmed that enhancing soil compaction significantly improves soil stability, effectively increases the overall strength and stability of the barriers, reduces deformation, and significantly enhances safety performance. This study not only validates the effectiveness of the reinforcement scheme but also provides new perspectives for the scientific research of safety barriers and offers crucial technical support for the optimal design of road safety protection facilities.

N-methyl-D-aspartate receptors (NMDARs) are the main class of ionotropic receptor for the ex-citatory neurotransmitter glutamate. It plays a crucial role in the permeability of Ca2+ ions and excitatory neurotransmission in the brain. Being heteromeric receptors, they are composed of sev-eral subunits, including two obligatory GluN1 subunits (eight splice variants) and regulatory GluN2 (GluN2A~D) and/or GluN3 (GluN3A~B) subunits. Widely distributed in the brain, they regulate other neurotransmission systems and are therefore involved in essential functions such as synaptic transmission, learning and memory, plasticity, excitotoxicity. The present review will discuss the physiopathological impacts of NMDAR and particularly GluN2A and GluN2B subu-nits in cognitive processes and neurodegenerative diseases (Alzheimer's disease, Huntington's disease, Parkinson's disease). The pharmacology of different NMDAR antagonists and their po-tentialities will be presented. In particular, a focus will be given on fluoroethylnormemantine (FENM), an investigational drug with very promising developments as a tomography radiotracer for NMDARs, an anxiolytic in post-traumatic stress disorder and a neuroprotective agent in Alzheimer's disease.

In recent decades, large-scale forest disturbances such as windthrow and bark beetle infestations have significantly impacted the carbon balance of Earth and forest ecosystems, mainly by altering soil respiration (SR) in addition to decreased gross primary productivity. SR is considered the second highest flux on Earth, emitting 78-98 Gt C yr-1 to the atmosphere, thus contributing to global warming. Post-disturbance development is marked by changes in the size of SR. To investigate the impact of bark beetle (Ips typographus) infestations in mountain spruce forests on SR, we measured SR at infested sites by bark beetles and adjacent undisturbed stands in the High Tatra Mountains (Slovakia). The measurements were conducted during the vegetation period (May-September) in 2016 and 2017, five to six years after the initial attack by bark beetles, at an altitudinal gradient (1100-1400 m a.s.l.). SR varied throughout different months and altitudes, and we observed that SR at infested sites reached higher values (in most cases) than at uninfested stands. Average monthly and altitude SR rates during both vegetation periods showed higher values at infested sites, but not all of them were statistically significant. We observed an insignificant change in SR rate between 2016 and 2017 at both infested and uninfested sites. The highest rates of SR were observed in 2016 from July to August at both infested and undisturbed sites. On the other hand, in 2017 the highest SR rates were observed in June and July at undisturbed sites and from June to August at infested sites. However, yearly SR from May-September at infested sites showed significantly higher rates than uninfested ones in both years. SR showed a decreasing pattern with elevation gain in 2016 at infested sites. However, this pattern was not observed in 2017. Based on our observation and results we postulate that SR rates at infested sites are boosted by needle fall and debris from dead and dying trees, which increases heterotrophic SR and compensates the decrease of autotrophic SR from tree roots. This study provides important insights into the impact of bark beetle infestations on SR and highlights the need for further research on the long-term effects of forest disturbances on carbon cycling.

The success of Toxoplasma gondii (intracellular parasite) host cell invasion relies on the apical complex, a specialized microtubule cytoskeleton structure associated with secretory organelles. The genome encodes three isoforms of both α- and β-tubulin which are altered by specific post-translational modifications (PTMs), changing the biochemical/biophysical proprieties of microtubules, and modulating their interaction with associated proteins. Tubulin PTMs are a powerful and evolutionarily conserved mechanism to generate tubulin diversity, forming a biochemical ‘tubulin code’ that can be ‘read’ by microtubule-interacting factors. The T. gondii tubulin PTMs are: α-tubulin acetylation, α-tubulin detyrosination, Δ5α-tubulin, Δ2α-tubulin, α- and β-tubulin polyglutamylation, and α- and α-tubulin methylation. Tubulin glutamylation is a key candidate to assist microtubule remodeling in Toxoplasma, being involved in the regulation of microtubule stability, dynamics, interaction with motor proteins, and severing enzymes. The correct balance of tubulin glutamylation is achieved by the coordinated action of polyglutamylases and deglutamylating enzymes. In this work we will review and discuss the current knowledge on T. gondii tubulin glutamylation. By in silico identification of mammalian protein orthologs we explored and updated the identification of putative proteins related to glutamylation, contributing to a better understanding of the role of tubulin glutamylation in T. gondii.

In this inclusive review article, the focus is on navigating the dynamic landscape of literature education, particularly the profound pedagogical shifts observed in the aftermath of the pandemic. The article synthesizes global insights, delving into how educators have adapted to hybrid models and embraced digital tools, fundamentally transforming the reading, analysis, and engagement with literary works. Exploring the integration of digital tools in literature education, the review uncovers the transformative impact of technology on traditional pedagogies. It analyzes the challenges and opportunities inherent in adapting literature education to the digital era, emphasizing the need for inclusive practices and adaptability. The article concludes by suggesting future research directions, encompassing AI integration, inclusive practices, cultural variations, long-term effects of hybrid models, and effective pedagogical strategies for technology integration. With a comprehensive approach, this review not only summarizes the current state of literature education but also discusses its implications, offering a holistic understanding of the contemporary educational landscape and setting the stage for future research endeavors.

Post-operative pain is the unpleasant sensory and emotional experience after surgery, its origin being both the inflammatory reaction induced by the surgical trauma on the abdominal wall, and the splanchnic pain, induced by the activation of nociceptors of the viscera, which are highly sensi-tive to distension, ischemia and inflammation. Nowadays, it is well recognized that there is a close relationship between the gut microbiome and pain perception, and that microbiome is highly af-fected by both anaesthesia and surgical manipulation. Thus, efforts to restore the disturbed micro-biome by supplementation with beneficial bacteria, namely probiotics, seems to be effective. In this article the knowledge gained mainly from experimental research on this topic is analyzed, the con-cluding message being that each probiotic strain works in its own way towards pain relief.

Post-harvest handling and ripening techniques have an impact on peach quality and shelf life, which has a big impact on consumer satisfaction and market competitiveness. This review paper examines recent advancements in ripening techniques and post-harvest technologies with the goal of improving peach fruit quality and sustainability. The factors impacting fruit quality after harvest and the physiological changes that occur throughout peach ripening are fully explained. For maintaining peach freshness and reducing losses, novel handling methods like modified atmosphere packaging (MAP) and controlled atmosphere storage (CAS) have been investigated. The study explores the possibilities of nanotechnology applications and low-temperature storage for prolonging shelf life while maintaining texture, flavor, and aroma. Examining the effectiveness and waste reduction potential of automation and mechanization in post-harvest activities. The paper also discusses ethylene-based and non-ethylene-based ripening agents, as well as innovative techniques including gene editing and RNAi technology for controlled and delayed ripening. Analyses are done on how these technologies affect the sensory qualities and nutrient profiles of peaches. The study emphasizes the significance of sustainable practices in the peach industry by focusing on waste reduction, resource efficiency, and circular economy integration. Post-harvest technologies' potential environmental consequences have been taken into consideration and the paper encourages more study and cooperation to increase sustainability.

The blackening of cut carrots decreases their shelf life and causes severe economic losses but the molecular and metabolic mechanisms that underpin this phenomenon remain poorly characterized. Studies were therefore undertaken to determine the molecular and metabolic causes of the blackening. The susceptibility of blackening was dependent on the period of time that the crop was stored underground prior to harvest. The structure of the cell walls in the black regions was substantially changed compared to the orange regions. The black regions of carrot batons had decreased immunodetection of xyloglucan, HG-pectin, RG-I pectin, galactan and arabinan but had higher levels of lignin and phenolic compounds compared to the orange regions. Transcript profiling analysis revealed that phytohormone signalling processes were activated in the black regions. Transcripts associated with auxin signalling and ethylene-responsive transcription factors were increased in the black regions. In contrast, the levels of transcripts encoding proteins associated with secondary metabolism were decreased in the black regions. These findings implicate ethylene and auxin-related processes in the control of the primary to secondary metabolism shift that results in lignification and cell wall disruption that underpin the blackening process.

A developing energy-saving approach of cold sintering in a pure aqueous medium was applied to the preparation of α-Al2O3 ceramics and performed on spark plasma sintering equipment. The initial γ-Al(OH)3 and γ-AlOOH powders and the cold-sintered ceramics were studied by X-ray diffraction analysis, infrared spectroscopy, thermal analysis, and scanning electron microscopy to reveal the chemical and structural transformations they experienced during the cold sintering. At 450°C and 70 MPa, initial γ-AlOOH transformed into a fragile α-Al2O3 material. Porous α-Al2O3 ceramics with about 60% porosity was obtained after cold sintering of γ-Al(OH)3 in the same conditions combined with subsequent annealing at 1250°C for 3 h. The role of water molecules in the studied processes was considered as the enhancement of structural mobility in the cold-sintered material due to its reversible hydroxylation similar to earlier investigated supercritical water action on the precursors during α-Al2O3 formation. Further improvement of the cold sintering setup and regimens would open prospects in α-Al2O3 ceramics manufacturing by an ecologically benign route.

Over the last few decades, the approach to geological and geomorphological surveys has changed remarkably. The advent of digital tools has allowed significant advances in the acquisition and management of survey data. In this paper, we demonstrate the development and testing of a new and effective digital survey method that allows for the fast acquisition and collaborative storage and management of data and information. This method was tested in collaboration with five universities for the mapping and classification of landslides in 249 survey areas in Central Italy and, more precisely, in the municipalities affected by the 2016 Central Italy Earthquake. Geological and geomorphological surveys were carried out in the field with tablet PCs, GPS, and cameras. The survey project for collecting field data was based on the structure of the Italian Landslide Inventory (IFFI) and the Territorial Resilience Central Apennines Earthquake Reconstruction (ReSTART) projects. The structure of the database and input forms were implemented for these aims. Moreover, the data and information were retrieved and organised in detailed records useful to the administrative entities.

Viruses feature an evolutionary shaped minimal genome that is obligately dependent on the cellular transcription and translation machinery for propagation. To suppress host cell immune responses and ensure efficient replication, viruses employ numerous tactics to favor viral gene expression and protein synthesis. This necessitates a carefully balanced network of virus- and host-encoded components, of which the RNA-based regulatory mechanisms have emerged as particularly interesting albeit insufficiently studied, especially in unicellular organisms. Here, recent advances that further our understanding of RNA-based translation regulation, mainly through post-transcriptional chemical modification of ribonucleosides, codon usage, and (virus-encoded) transfer RNAs, will be discussed in the context of viral infection.

Manual visual inspections typically conducted after an earthquake are high-risk, subjective, and time-consuming. Delays from inspections often exacerbate the social and economic impact of the disaster on affected communities. Rapid and autonomous inspection using images acquired from unmanned aerial vehicles offer the potential to reduce such delays. Indeed, a vast amount of re-search has been conducted toward developing automated vision-based methods to assess the health of infrastructure at the component and structure level. Most proposed methods typically rely on images of the damaged structure, but seldom consider how the images were acquired. To achieve autonomous inspections, methods must be evaluated in a comprehensive end-to-end manner, incorporating both data acquisition and data processing. In this paper, we leverage recent advances in computer generated imagery (CGI) to construct a 3D synthetic environment for simulation of post-earthquake inspections that allows for comprehensive evaluation and valida-tion of autonomous inspection strategies. A critical issue is how to simulate and subsequently render the damage in the structure after an earthquake. To this end, a high-fidelity nonlinear finite element model is incorporated in the synthetic environment to provide a representation of earthquake-induced damage; this finite element model, combined with photo-realistic rendering of the damage, is termed herein a physics-based graphics models (PBGM). The 3D synthetic en-vironment with PBGMs provide a comprehensive end-to-end approach for development and validation of autonomous post-earthquake strategies using UAVs, including: (i) simulation of path planning of virtual UAVs and image capture under different environmental conditions; (ii) au-tomatic labeling of captured images, potentially providing an infinite amount of data for training deep neural networks; (iii) availability of the ground truth damage state from the results of the finite-element simulation; and (iv) direct comparison of different approaches to autonomous as-sessments. Moreover, the synthetic data generated has the potential to be used to augment field datasets. To demonstrate the efficacy of PBGMs, models of reinforced concrete moment-frame buildings with masonry infill walls are examined. The 3D synthetic environment employing PBGMs is shown to provide an effective testbed for development and validation of autonomous vision-based post-earthquake inspections that can serve as an important building block for ad-vancing autonomous data to decision frameworks.

The large production of non-degradable petrol-based plastics has become a major global issue due to its environmental pollution. Biopolymers produced by microorganisms such as polyhydroxyalkanoates (PHAs) are gaining potential as a sustainable alternative, but the high cost associated to their industrial production has been a limiting factor. Post-transcriptional regulation is a key step to control gene expression in changing environments and has been reported to play a major role in numerous cellular processes. However, limited reports are available concerning the regulation of PHA accumulation in bacteria, and many essential regulatory factors still need to be identified. Here, we review studies where the synthesis of PHA has been reported to be regulated at the post-transcriptional level, and we analyze the RNA-mediated networks involved. Finally, we discuss the forthcoming research on riboregulation, synthetic and metabolic engineering which could lead to improved strategies for PHAs synthesis in industrial production, thereby reducing the costs currently associated with this procedure.

The rapid spread of COVID-19 worldwide was accompanied by intense fears, confusion, worries, anger and stress threatening people’s mental health. Unprecedented measures to slow down and prevent the transmission of COVID-19 have had various impacts on the population’s health behaviour and mental health. The main purpose of the present study is to investigate the lockdown’s effects on university students’ mental health in Romania. Based on a cross-sectional design, the survey data were collected from a sample of 722 participants (247 males; M = 21.1 years; SD ± 1.73). A path analysis was performed to verify the hypothesised direct and indirect effects included in the multiple mediation model. The findings showed a positive association between stress and boredom proneness, missing daily social interactions, spending more time on phone conversations and the increasing interest in following news about the pandemic. The path analysis revealed an excellent fit between the proposed multiple mediation model and the sample data. Boredom proneness and missing daily social interactions both affected stress, directly and indirectly, through more time spent on phone conversations. In addition, it was found that the increased interest in following news about the pan-demic mediated the relationship between boredom proneness and perceived stress. In terms of gender differences, our findings revealed that female students experienced significantly higher stress levels than male students, perceived to a greater extent the lack of daily social interactions and spent more time on phone conversations. Overall, the findings further extend the empirical evidence on university students’ mental health in the context of the COVID-19 pandemic. Therefore, universities need to organise support programmes focused on developing university students’ coping strategies to maintain their mental health even in adverse contexts.

Climacteric fruits are characterized by a dramatic increase in autocatalytic ethylene production, which is accompanied by a spike in respiration, at the onset of ripening. The change in the mode of ethylene production from autoinhibitory to auto-stimulatory is known as the system 1 (S1) to system 2 (S2) transition. Existing physiological models explain the basic and overarching genetic, hormonal, and transcriptional regulatory mechanisms governing the S1 to S2 transition of climacteric fruit. However, the links between ethylene and respiration, the two main factors that characterize the respiratory climacteric, have been largely understudied at the molecular level. Results of recent studies indicate that the AOX respiratory pathway may play an important role in mediating cross talk between ethylene response, carbon metabolism, ATP production, and ROS signaling during climacteric ripening. New genomic, metabolic, and epigenetic information sheds light on the interconnectedness of ripening-associated metabolic pathways, necessitating expanding the current, ethylene-centric physiological models. Understanding points at which ripening responses can be manipulated may reveal key, speciesand cultivar-specific targets for regulation of ripening enabling superior strategies for reducing postharvest wastage.

Background: This study investigated the prevalence of worsening problems using Post Stroke Checklist (PSC) at 3, 6, and 12 months post-stroke and their associations with health-related quality of life. Methods: In stroke patients admitted between June 2014 and December 2015, PSC and EuroQol-5Dthree level (EQ-5D-3L) were assessed at post-stroke 3 (n=181), 6 (n=175), and 12months (n=89). The prevalence of worsening problems and its association withEQ-5D-3L at post-stroke 3 and 6months were analyzed. Results: An average of 0.59 (range 0–12), 1.47 (range 0–12), and 1.00 (range 0–10) worsening problems per patient was identified at 3, 6, and 12months after stroke, respectively. The most frequently and continuously identified worsening problems were mood disturbances (reported by 8.8%, 16.0% and13.5% of patients at 3, 6, and 12 months post-stroke, respectively). Worsening mobility was significantly associated with worse EQ-5D index at post-stroke 3 months (β,-0.583; 95% CI, -1.045 to -0.120). The worsening of mobility and communication was significantly associated with worse EQ-5D index at post-stroke 6 months (mobility: β,-0.170; 95% CI, -0.305 to -0.034, communication: β,-0.164; 95% CI, -0.309 to -0.020). Conclusions: PSC may be useful for the detection of various subjective worsening problems during serial clinical follow-up after stroke. Appropriate rehabilitation and management strategy to solve the identified problems could improve the quality of life in stroke survivors.

The prerogative to narrate the experience of marginal identities, particularly ethno-religious ones, appeared only in the post-occupation era in Iraqi fiction. Traditionally, secular Iraqi discourse struggled to openly address “sectarianism” due to the prevalent notion that sectarian identities are mutually exclusive and oppositional to national identity. It is distinctly in post-2003 Iraq—more precisely, since the sectarian violence of 2006–2007 began to cut across class, civil society, and urban identities—that works which consciously refuse to depict normative Iraqi identities with their mainstream formulations become noticeable. We witness this development first in the Western diaspora, where Iraqi novels exhibit a fascination with the ethno-religious culture of the Iraqi margins or subalterns and impart a message of pluralistic secularism. This paper investigates the origins of the taboo that proscribed articulations of ethno-religious subjectivities in 20^th-century Iraqi fiction, and then culls examples of recent diasporic Iraqi novels in which these subjectivities are encoded and amplified in distinct ways. In the diasporic novel, I argue, modern Iraqi intellectuals attain the conceptual and political distance necessary for contending retrospectively with their formative socialization experiences in Iraq. Through a new medium of marginalization—the diasporic experience of the authors themselves—they are equipped with a newfound desire to unmask subcultures in Iraq and to write more effectively about marginal aspects of Iraqi identity inside and outside the country. These new diasporic writings showcase processes of ethnic and religious socialization in the Iraqi public sphere. The result is deconstruction of mainstream Iraqi identity narratives and instrumentalization of marginal identities in a nonviolent struggle against sectarian violence.

Acute myeloid leukemia (AML) is a severe blood cancer in myeloid cells which is found to be developed due to mutation in genes that causes dysregulation in the gene’s expression, affecting the cellular function and signaling pathways. STK24 is a protein belonging to the Germinal Center Kinase III (GCK III) sub-family, found to be related to many intracellular and intercellular processes. In the following study the expression of the gene STK24 is studied using the web-based tool TNM plot, in which the expression is found dysregulated in AML with a significant p-value of 9.76e - 23. In addition to expression analysis, survival analysis is carried out, the dysregulated expression of STK24 is found to be related to lower overall survivable outcome indicated by significant p-value of 1.6e - 05 with median survival for lower expression of the STK24 for 10.7 month time. In the protein-protein interaction analysis, the targeted protein STK24 was found to interact with several proteins, among them some of the proteins which are found to be related to AML pathogenesis are PDCD10, PPP2R1B, STK11, TCP1, STK25, STK26 and STRN3 with combined score between .5 to 1.00. Among the interacting proteins 20 proteins are found to have higher interaction efficiency which is represented in circular format. A correlation study of the target protein STK24 with AML and glutamine metabolism related protein FLT3, NPM1, RUNX1, RARA, IDH1, IDH2, GLS, SLC1A5, GLUD1 and SLC7A11 showed a significant correlation with Pearson’s coefficient r value between -1 to 1 and p-value &lt; 0.05. With the analysis of expression and survival and protein-protein interaction and gene correlation it can be indicated that STK24 may have a role in pathogenesis in AML. But to conclude the study, further expression of the gene STK24 in the AML is needed to prove its correlation with the disease progression and further in vitro and in vivo analysis are needed to be carried out.

The blood-brain barrier (BBB) serves as an interface between the bloodstream and central nervous system. It limits the movement of molecules and immune cells, regulates the entry of nutrients, and removes waste products from the brain. The dysfunction of the BBB has been identified in Parkinson´s disease (PD) but the role of the BBB and endothelial cells (ECs) has not been well studied. LRRK2 G2019S mutation is the most common PD causing mutation with similar pathophysiology than in sporadic cases. How the mutation affects EC function has not been investigated previously in patient’s cells. In the study, we used iPSC-derived ECs from PD patients with the LRRK2 mutation as well as cells from healthy individuals. We report that PD ECs have higher levels of α-synuclein, altered mitochondrial respiration and response to inflammatory exposure, especially to TNFα. In addition, transcriptomic analysis showed upregulation of fatty acid synthesis related pathways in PD ECs and downregulation of lncRNA MEG3, both of which have been associated with PD. Altogether, PD ECs manifest some of the PD related hallmarks and are likely to contribute to the pathogenesis of PD.

This comprehensive analysis aims to offer valuable insights into the safety profiles of these glucocorticoids, facilitating the identification of compounds with potentially reduced adverse effects. This study investigates the toxicity profiles of various glucocorticoids, utilizing predictions from the pKCSM Server. Among the glucocorticoids examined, Dexamethasone, Triamcinolone, Hydrocortisone hemisuccinate, Paramethasone, Fluprednisolone, and Flumethasone emerge as potentially less toxic, displaying favorable scores across diverse parameters such as Max. Tolerated Dose (human, MRT), Oral Rat Acute Toxicity (LD50), and Oral Rat Chronic Toxicity (LOAEL). Notably, Hydrocortisone hemisuccinate and Triamcinolone stand out for their high tolerability capacity based on the Max. Tolerated Dose (human, MRT), suggesting enhanced safety profiles. These findings contribute insights into selecting glucocorticoids with optimal safety and tolerability for potential therapeutic applications.Further research and clinical investigations are warranted to validate and refine these findings, ensuring the responsible and effective use of glucocorticoids in medical practice.