Cationic Antimicrobial Peptides (AMPs), also called Host Defence Peptides have established antimicrobial and anticancer activities. Conjugation of an AMP to a bioactive molecule with complementary activity can address some of the clinical limitations of the peptide candidate. This approach has been particularly applied in antimicrobial applications of AMPs, but remains relatively less explored in the generation of anticancer candidates. Herein, two usnic acid derivatives, based on hydrazinothiazole and benzylidenefuranone pharmacophore moieties, respectively, have been conjugated to L-K6, a lysine/leucine rich AMP, through a new pyrazole ligation intrinsically driven by the cargo molecule. Both components, the usnic acid derivative and the peptide, are selectively active against cancer cells, by targeting the human DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) and through DNA damage, respectively. The two conjugates, based on a hydrazone linkage, exhibited pleiotropic effects, ranging from, overall, reduction of the activity from the parent drugs to their conservation or even enhancement. Notably, the conjugates retain some anti-TDP1 activity and display intermediate, or even higher, cytotoxicities against glioblastoma cells, compared to their individual components.

Background and objectives: Chronic Kidney Disease and Mineral Bone Disorders (CKD-MBD) are frequently associated with an increased risk of both Vascular Calcifications (VCs) and bone fractures (BFs). The complex pathogenesis of VCs and BFs involves various factors such as calcium overload, phosphate imbalance, and secondary hyperparathyroidism. Key players, such as the vitamin K-dependent proteins (VKDPs) matrix Gla protein (MGP) and osteocalcin (BGP), have pivotal roles both for VCs and BFs. The Vitamin K Italian (VIKI) dialysis study, highlighted that hemodialysis patients treated with calcimimetics had higher levels of total BGP and MGP as compared to those untreated, suggesting a potential protective effect of these drugs on BFs and VCs, beyond the beneficial effect to reduce PTH levels. Methods: ETERNITY-ITA is a multi-center, comparative effectiveness, observational, longitudinal study that will enroll 160 hemodialysis patients (80 patients treated with Etelcalcetide and 80 age and sex-matched patients treated with Calcitriol or vitamin D analogs). Nephrologists will tailor the target dose of Etelcalcetide on individual level to achieve the KDIGO PTH target. In the Etelcalcetide-treated group, the addition of calcitriol will be allowed when required by clinical practice (for correction of hypocalcemia). Conclusion: The study will evaluate the real-world effect of Etelcalcetide on VKDP levels, such as BGP and MGP, at 3, 9, and 18 months from baseline. The resulting preservation of vascular and bone health will be assessed for the first time by examining aortic and iliac artery calcifications and vertebral fractures, respectively. Keywords: bone fractures; etecalcetide; hemodialysis; vascular calcification; vitamin K

Sarcoglycanopathies are among the most frequent and severe autosomal recessive forms of limb-girdle muscular dystrophies /LGMD/ with childhood onset. Mutations in , , and sarcoglycan genes lead to various kinds of LGMD. We present the clinical variability of LGMD 2C/R5 among a genetically homogeneous group of 56 patients, belonging to 35 pedigrees. Molecular genetic analysis showed thаt all 57 patients were homozygous for C283Y variant. The muscles of the pelvic girdle and the trunk were early and more severely affected, followed by the the shoulder girdle. Macroglossia, hypertrophy of the calves, scapular winging and lumbar hyperlordosis were common in the ambulatory phase. A great variability in the clinical presentation of LGMD 2C/R5 was observed both intra and interfamilial, despite the same underlying molecular defect. Females demonstrated a relatively milder clinical course, compared to males. Mean CK levels were 20 times above normal values. Muscle CT of MRI showed earlier and more severe involvement of the flexor proximal limb muscles in comparison to the extensor ones.

Vascular impairment, muscle atrophy, and cognitive decline are important age-related conditions that have a significant impact on health. Vascular impairment directly disrupts the flow of blood, leading to the decline of muscle mass associated with aging (sarcopenia) and the decline of neuronal functions (neurodegeneration). Our inadequate understanding of the complex relationships between these conditions impedes precise diagnosis and effective treatment. This review analyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on oxidative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sarcopenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, inflammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can enhance therapeutic strategies and lead to better outcomes for patients. Here, we highlight the intricate relationship among vascular dysfunction, degenerative muscle, and cognitive decline, underscoring the need for multidisciplinary approaches to treatment. Progress in this field can result in improved diagnosis, more potent therapeutic options, and enhanced preventative measures, all of which can contribute to an improved quality of life for the aging population.

In the pursuit of functional foods that promote health, nanoliposomal carriers have been used to enhance the stability and functionality of dairy products such as yogurt, promising therapeutic benefits. This study aimed to evaluate the impact of fucoxanthin-loaded nanoliposomes in yogurt on its antioxidant, physico-chemical, and rheological properties under cold storage (21 days). Fucoxanthin-loaded nanoliposomes were prepared using the ultrasonic film dispersion technique and added at concentrations of 0%, 5% and 10% at the yogurt (Y-C, Y-FXN-5, Y-FXN-10). Homogeneous and uniform nanoliposomes (98.28 nm) were ob-tained, preserving their integrity and functionality, and ensuring prolonged release and bioavailability of fucoxanthin. Y-FXN-10 maintained the highest antioxidant activity according to the DPPH (52.96%), ABTS (97.97%), and FRAP (3.16 mmol ET/g) methods. This formulation exhibited enhanced erythroprotective potential, inhibiting hemolysis, photohemolysis, and heat-induced hemolysis, thereby preventing lipid pe-roxidation. However, viscosity and firmness decreased, affecting the texture and appearance. Sensory properties such as color, flavor, aftertaste, texture, and overall acceptance improved with the 10% fuco-xanthin-enriched yogurt formulation. These results suggest that nanoliposomal are suitable for carries fuco-xanthin, their incorporation into food matrices is key to developing functional foods. Regulatory approvals and consumer perceptions regarding nanotechnology-based products must be addressed, emphasizing their safety and health benefits.

Background: Preserving health and physical fitness is critical to ensure independent living across the lifespan. Lower levels of physical fitness are associated with age-related cognitive decline and a higher prevalence of mild cognitive impairment (MCI). Thus, this study investigates the influence of a six-month dance intervention on selected measures of physical fitness in older adults with MCI. Methods: In this randomized controlled trial 55 patients with MCI were randomized into a sportive dance training (IG; n=26; Age: 70.7 +/- 5.6 years; 62% female) or an inactive control group (CG; n=24; Age: 69.1 +/- 6.8 years; 46% female).The dance group received two 90-minute dance training sessions per week over a duration of six-months, which focused on learning dance movement patterns. During the training sessions, heartrate was measured to control exercise intensity. Physical fitness was assessed using cardiopulmonary exercise testing (CPET), lower limb functional fitness via sit-to-stand test, handgrip strength and heart rate variability (HRV). Results: We observed that the dance intervention preserved the cardiorespiratory fitness as measured by maximal oxygen uptake (VO2max) during CPET, which decreased in the CG. Furthermore, participants in the IG demonstrated increases in leg and handgrip strength although not statistically significant. HRV displayed a nonsignificant decrease following the intervention. Conclusion: The results of this randomized controlled trial suggest that sportive dance training can preserve physical fitness in older adults with MCI. Although improvements in the other parameters were statistically non-significant, likely due to the small sample size, stabilizing muscular fitness and preventing age-related decline in older adults with MCI is important for maintaining functional independence.

Our study aimed to identify predictors for the effectiveness of tumor regression in lung cancer patients undergoing neoadjuvant treatment and cancer resections. Patients admitted between 2016 and 2022 were included in the study. Based on the histology of the tumor, patients were categorized into lung adenocarcinoma group (LUAD), and squamous cell carcinoma group (SQCA). Ninety-five patients with non-small cell lung cancer were included in the study. Fifty-eight (61.1%) and 37 (38.9%) patients were included in the LUAD and SQCA groups, respectively. Nine (9.5%), 56 (58.9%), and 30 (31.6%) patients were categorized with a tumor regression score of I, II, and III respectively. In multivariable analyses, histology of the primary tumor (SQCA), lymph node size in the preoperative CT scan (>1.7cm) and absolute tumor size reduction after neoadjuvant treatment (>2.6 cm) independently predict effectiveness of tumor regression (OR, [95% Confidence interval, p-value] of 6.88 [2.40-19.77, p70 years, extended resection >one lobe, and tumor recurrence or metastasis were identified as significant independent predictors of reduced overall survival. Assessment of tumor size before and after neoadjuvant treatment might help to identify high-risk patients with decreased survival and to improve patient management and care.

Background: The incidence of metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocellular carcinoma (HCC) is increasing annually with a rise in the incidence of obesity and metabolic syndrome. Based on preliminary reports regarding the potential association of HCC and periodontitis, this study aimed to analyze the involvement of periodontal bacteria as well as the oral and intestinal bacterial flora in MASH-related HCC (MASH-HCC). Methods: Forty-one patients with MASH and 19 with MASH-HCC who completed survey questionnaires, underwent periodontal examinations, and subjected to sample collection (saliva, mouth-rinsed water, feces, and peripheral blood) participated in the study. Bayesian network analysis was used to analyze the causation between various factors, including MASH-HCC, examinations, and bacteria. Results: The occupancy rate of the genus Fusobacterium in the intestinal bacterial flora was significantly higher in in the MASH-HCC group than in the MASH group (p = 0.002), whereas that of Butyricicoccus (p = 0.022) and Roseburia (p < 0.05) was significantly lower. Bayesian network analysis revealed the absence of periodontal pathogenic bacteria and enteric bacteria affecting HCC. However, HCC directly affected the periodontal bacterial species Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in the saliva, as well as the genera Lactobacillus, Roseburia, Fusobacterium, Prevotella, Clostridium, Ruminococcus, Trabulsiella, and SMB53 in the intestine. Furthermore, P. gingivalis in the oral cavity directly affected the genera Lactobacillus and Streptococcus in the intestine. Conclusion: MASH-HCC directly affects periodontal pathogenic and intestinal bacteria, and P. gingivalis may affect the intestinal bacteria associated with gastrointestinal cancer.

The mystery phenomenon of fungal bioluminescence has always captivated human curiosity, although more attempts need to be made, particularly to bring the new species to the surface. In this study, we devoted considerable space to the taxonomy of these fungi while discussing their biogeography, evolution, bioluminescence mechanism, and potential ecological roles. We provide a detailed explanation of how these fungi produce light, including the role of the enzyme luciferase and luciferin. We also discussed their applications. Here, we presented an updated list of 122 bioluminescent fungi identified from five distinct evolutionary lineages viz. Armillaria, Eoscyphella, Lucentipes, Mycenoid, and Omphalotus worldwide, mainly in tropical and subtropical areas. The bioluminescent fungi descended from the last common ancestor of the mycenoid and the marasmioid clades of Agaricales, which have been maintained for at least 160 million years of evolution. We highlighted the need for further research to understand the ecological role of bioluminescent fungi. Applying bioluminescent fungi in various areas (e.g., environmental and medicinal) demonstrates their validity.

Approximately 30% of steroid-resistant nephrotic syndromes are attributed to monogenic disorders that involve 27 genes. Mutations in KANK family members have also been linked to nephrotic syndrome; however, the precise mechanism remains elusive. To investigate this, podocyte-specific Kank1 knockout mice were generated to examine phenotypic changes. In the initial assessment under normal conditions, Kank1 knockout mice showed no significant differences in the urinary albumin-creatinine ratio, blood urea nitrogen, serum creatinine levels, or histological features compared to controls. However, following kidney injury with adriamycin, podocyte-specific Kank1 knockout mice exhibited a significantly higher albumin-creatinine ratio and a significantly greater sclerotic index than control mice. Electron microscopy revealed more extensive foot process effacement in the knockout mice than in control mice. In addition, KANK1-deficient human podocytes showed increased detachment and apoptosis following adriamycin exposure. These findings suggest that KANK1 may play a protective role in mitigating podocyte damage under pathological conditions.

World Health Organization recommends adjusting the salt intake as a part of the nine global targets to reduce premature mortality from non-communicable chronic diseases as priority and most cost-effective intervention. In 2006. the main aim of the Croatian Action on Salt and Health was to decrease salt intake for 16% because of its critical intake and consequences on human health. We have organized educative activities for increasing awareness on salt harmfulness, defined food categories of prime interest, collaborate with industries and determine salt intake (24h urine-sodium excretion). It was determined that the proportion of salt in ready-to-eat baked bread should not exceed 1.4%. In the period 2014 –2022, salt in the semi-white bread was reduced 14%, in bakery 22% and in largest meat industry in Croatia 25%. Awareness of the harmfulness of salt on health increased from 65.3% in 2008 to 96.9% in 2023 and salt intake was reduced 15.9%-1.8 grams/day (22.8% men, 11.7% women). In last 18 years a significant decrease in salt intake was achieved in Croatia, awareness of its harmfulness increased, collaboration with food industry established and regulatory documents launched. However, salt intake is still very high underlying the need for continuation of efforts and even stronger activities.

Background/Objectives: Concurrent opioid (OPI) and benzodiazepine (BZD) use may exacerbate falls/fractures risk compared to no use or use alone. Yet, patients may need concurrent OPI-BZD use for co-occurring conditions (e.g., pain and anxiety). Therefore, we examined the association between longitudinal OPI-BZD dosing patterns and subsequent injurious falls risk. Methods: We conducted a retrospective cohort study including non-cancer fee-for-service Medicare beneficiaries initiating OPI and/or BZD in 2016-2018. We identified OPI-BZD use patterns during the 3 months following OPI and/or BZD initiation (i.e., trajectory period) using group-based multi-trajectory models. We estimated time to first injurious fall within 3 months post-trajectory period using inverse-probability-of-treatment-weighted Cox proportional hazards models. Results: Among 622,588 beneficiaries (age≥65=84.6%, female=58.1%, White=82.7%; having injurious falls=0.45%), we identified 13 distinct OPI-BZD trajectories: Group(A):Very-low OPI-only (early discontinuation)(44.9% of the cohort); (B):Low OPI-only (rapid decline)(15.1%); (C):Very-low OPI-only (late discontinuation)(7.7%); (D):Low OPI-only (gradual decline)(4.0%); (E):Moderate OPI-only (rapid decline)(2.3%); (F):Very-low BZD-only (late discontinuation)(11.5%); (G):Low BZD-only (rapid decline)(4.5%); (H):Low BZD-only (stable) (3.1%); (I):Moderate BZD-only (gradual decline)(2.1%); (J):Very-low OPI (rapid decline)/Very-low BZD (late discontinuation)(2.9%); (K):Very-low OPI (rapid decline)/Very-low BZD (increasing)(0.9%); (L):Very-low OPI (stable)/Low BZD (stable)(0.6%); and (M):Low OPI (gradual decline)/Low BZD (gradual decline)(0.6%). Compared with Group(A), 6 trajectories had increased 3-month injurious fall risks: (C): HR, 95%CI=1.78, 1.58-2.01; (D): 2.24, 1.93-2.59; (E): 2.60, 2.18-3.09; (H): 2.02, 1.70-2.40; (L): 2.73, 1.98-3.76; and (M): 1.96, 1.32-2.91. Conclusions: Our findings suggest that 3-month injurious fall risk varied across OPI-BZD trajectories, highlighting the importance of considering both dose and duration when assessing fall risks of OPI-BZD use among older adults.

Opuntia ficus-indica (L.) Mill. belongs to the Cactaceae family and the genus Opuntia; it is a succulent plant that adapts to extreme climatic conditions. The aerial part of the plant consists of the cladodes, morphological changes of branches that appear green, are covered with thorns, and are essential to reduce excessive perspiration of water. The composition of cladodes is very varied, and the main constituents are water, fibers, polysaccharides, proteins, fatty acids, vitamins, sterols, minerals, and polyphenols. Polyphenols are responsible for many beneficial activities for human health, such as antioxidant, anti-inflammatory, antitumor, and nutritional properties. The purpose of this manuscript was to compare the properties of cladodes belonging to the same plant but with different stages of maturity. Relative extracts were tested both in vitro and on a cell line and antioxidant and anti-apoptotic properties were found. The antioxidant activity was tested by the ORAC test, the DPPH test, and the measurement of cellular accumulation of ROS. Anti-apoptotic activity was evaluated by the annexin/PI assay and measurement of caspases 9 and 3 expression. The results obtained have shown that the extracts considered possess antioxidant and anti-apoptotic properties. However, the different stages of maturity of cladodes are essential for the performance of both functions. In addition, important variations have been made in the dissolution of extracts that have brought greater safety in their use. In conclusion, this manuscript provides further information on cladodes of Opuntia ficus-indica, which can be used as adjuvants in many human pathologies.

Hypofunction of the glutamate system in the brain is one of the pathophysiological hypotheses for schizophrenia. Accumulating animal and clinical studies show that sarcosine (N-methylglycine), a glycine transporter-1 inhibitor, is effective for ameliorating the negative and cognitive symptoms of schizophrenia. The aims of the present study were to observe the effects of sarcosine on neuronal activity in the dorsal CA1 (dCA1) hippocampal neurons within an NMDA receptor hypofunction model induced by MK801. We applied in vivo calcium imaging to observe the dynamics of fluorescence from the dCA1 hippocampal neurons when the mice were exploring in an open field. Using this tool, we directly measured and compared neuronal properties between sarcosine-treated and untreated mice. At the same time, the physiological function of the neurons was also quantified by measuring their place fields. Our data demonstrated that MK-801 (0.2 mg/kg) diminished the fluorescence intensity of dCA1 neurons that had been genetically modified with a calcium indicator. MK-801 also significantly increased the correlation coefficient between the fluorescence dynamics of pairs of cells, a feature that may be linked to the symptom of disorganization in human patients with schizophrenia. The spatial correlations of place fields in the mice were impaired by MK-801 as well. Injected sarcosine (500 mg or 1000 mg/kg) significantly alleviated the abovementioned abnormalities. Our data provide evidence to support the use of sarcosine to alleviate symptoms of schizophrenia, especially hippocampus-related functions.

Limited evidence on hepatitis A seroprevalence among HIV-exposed uninfected (HEU) children compared to their HIV infected (HIV) and unexposed uninfected (HUU) counterparts compromises rational vaccine decision-making. This study comprised of a retrospective health facility-based population of children aged 1 month – 12 years. Archival sera were tested for markers of acute (anti-HAV IgM) or past (total anti-HAV) HAV infection. Subgroup analysis was conducted based on HIV exposure or infection status. Of 513 participants, 54% (277) were male and the median age was 10 (IQR: 4 – 25) months. The median maternal age was 29 (IQR: 25 – 34) years. An anti-HAV seropositivity of 95.1% (117/122 [95% CI 90.2-98.4]) was found among those ≤6 months of age, indicative of the rate of transplacental antibody transfer. Among 1–12-year-olds, hepatitis A seroprevalence was 19.3% (37/192 [95% CI 14.1-25.7]), while 1.1% (2/188 [95% CI 0.12-2.76]) had evidence of acute infection. Compared to HIV-exposed subgroups (HIV=60%, 6/10 [95% CI 27.4-86.3] and HEU=45%, 9/20 [95% CI 23.8-68]), hepatitis A seroprevalence among HUU children was low (29.2%, 47/161 [95% CI 22.4-37.0]). Natural immunity among HIV -exposed and -unexposed children in South Africa is insufficient to protect against severe liver complications associated with HAV infection later in adulthood.

The global aging population has experienced rapid growth in recent decades, leading to an increased prevalence of psychiatric disorders, particularly depression, among older adults. Depression in the elderly is often compounded by chronic physical conditions and various psychosocial factors, significantly impacting their quality of life. This paper explores the epidemiology of geriatric depression, highlighting the influence of gender, race, and socio-economic status on its prevalence. The classification and diagnosis of geriatric depressive disorders, based on ICD-11 and DSM-5 criteria, reveal the complexity of managing these conditions in older adults. Personalized Medicine (PM) emerges as a promising approach, focusing on tailoring treatments to the individual’s genetic, clinical, and environmental characteristics. However, the application of PM in this demographic faces challenges, particularly in the context of pharmaceutical forms. The need for age-appropriate drug delivery systems is critical, given the prevalence of polypharmacy and issues such as dysphagia among the elderly. This study emphasizes the importance of developing patient-centric formulations to enhance the effectiveness of personalized therapy in geriatric patients.

Salmonella species are important foodborne pathogens worldwide. Salmonella pathogenicity is associated with multiple virulence factors and enhanced antimicrobial resistance. To determine the molecular characteristics and genetic correlations of Salmonella, 24 strains of Salmonella isolated from different sources (raw poultry, human stool, and food) in the Wenzhou area were investigated to determine the distribution of antimicrobial resistance and virulence determinants using whole-genome sequencing (WGS). Aminoglycoside-resistance genes were detected in all samples. Over half of the samples found antimicrobial resistance genes (ARGs) and point mutations for several clinically frequently used antibiotic, β-lactamases, tetracyclines, and fluoroquinolones. Of these strains, 62.5% were predicted to be multidrug-resistant (MDR). The quinolone-modifying enzyme gene aac(6')-Ib-cr, detected in five samples (S1–S4 and S10), were located on integrons. Analysis of Salmonella pathogenicity island (SPI) profiles suggests that serotypes with close genetic relationships share the same distribution of virulence factors, revealing a link between genotype and SPI profiles. CgMLST analysis indicated that five isolates S14–S18 were closely related to strains originating from the UK, suggesting that they may have been introduced from the UK. Data from this study may enrich the molecular traceability database for Salmonella and provide a basis for effective public health policies.

Clathrate hydrate-based technologies have been considered as promising and sustainable alternatives for the effective management of the climate change risks related to emissions of carbon dioxide, produced by human activities. This work presents a combined experimental and computational investigation of the effects of the operational procedures and characteristics of the experimental configuration, on the phase diagrams of CO2-H2O systems and CO2 hydrates formation, growth and dissociation conditions. The operational modes involved (i) the incremental (step-wise) temperature cycling and (ii) the continuous temperature cycling processes, in the framework of an isochoric pressure search method. Also, two different high pressure PVT configurations were used, of which one encompassed a stirred tank reactor and the other incorporated an autoclave of constant volume with magnetic agitation. The experimental results implied a dependence of the subcooling, (P, T) conditions for hydrate formation and dissociation and thermal stability of the hydrate phase on the applied temperature cycling mode, and the technical features of the utilized PVT configuration. The experimental findings were complemented by a thermodynamic simulation model and other calculation approaches, with the aim to resolve the phase diagrams including the CO2 dissolution over the entire range of the applied (P, T) conditions.

Due to global climate change, cold temperatures have significantly impacted rice production, resulting in reduced yield and quality. In this study, we investigated two traits related to cold tolerance (CT) of 1992 diverse rice accessions at the seedling stage. Geng accessions exhibited higher levels of CT compared to xian accessions, with the GJ-tmp subgroup displaying the strongest CT. However, extreme CT accessions were also identified within the xian subspecies. Through GWAS analysis based on survival rate (SR) and leaf score of cold tolerance (SCT), a total of 30 QTLs associated with CT at the seedling stage were identified, among which four QTLs (qSR3.1a, qSR4.1a, qSR11.1x and qSR12.1a) were found to be important. Furthermore, five candidate genes (LOC_Os03g44760, LOC_Os04g06900, LOC_Os04g07260, LOC_Os11g40610 and LOC_Os12g10710) along with their favorable haplotypes were identified through gene function annotation and haplotype analysis. Pyramiding multiple favorable haplotypes resulted in a significant improvement in CT performance. Subsequently, three selected accessions (CX534, B236, and IRIS_313-8565), carrying different superior alleles for CT, were selected and recommended for molecular breeding for CT using marker-assisted selection (MAS). The findings from this study provide valuable resources for enhancing rice's ability for CT while laying a foundation for future cloning of novel genes involved in conferring CT.

Equine herpesvirus type 1 (EHV-1) causes rhinopneumonitis, abortion and neurological outbreaks (equine herpesvirus myeloencephalopathy, EHM) in horses. EHV-1 also causes lethal encephalitis in laboratory small animals such as mice and hamsters experimentally. EHV-1 ORF76 is a homologue of HSV-1 US9, which is a herpesvirus kinase. Starting with an EHV-1 bacterial artificial chromosome clone of neuropathogenic strain Ab4p (pAb4p BAC), we constructed an ORF76 deletion mutant (Ab4p∆ORF76) by replacing ORF76 with the rpsLneo gene. Deletion of ORF76 had no influence on replication, cell-to-cell spread in cultured cells or replication in primary neuronal cells. In western blots of EHV-1-infected cell lysates, an EHV-1 Us9-specific polyclonal antibody detected multiple bands ranging from 35 to 42-kDa. In a CBA/N1 mouse infection model following intranasal inoculation, the parent and Ab4p∆ORF76 revertant caused the same histopathology in the brain and olfactory bulbs. The parent, Ab4p∆ORF76 and revertant mutant replicated similarly in the olfactory mucosa, although Ab4p∆ORF76 was not transported to the olfactory bulbs and was unable to infect the CNS. These results indicated that the ORF76 (US9) plays an essential role in the anterograde spread EHV-1.

Increasing awareness of the potential health risks associated with microplastics (MPs) presence in the environment has led to significant rise in research focused on these particles over the past few years. This review focuses on research on MPs presence and spread, pathways of exposure and toxicological effects on human health and legal framework related to MP challenges. Several research projects have aimed to assess their potential harm to human health. Toxicological effects have been noticed at high concentrations of MPs, specifically polystyrene, the most widespread typical MP, but only short-term effects have been mostly studied. Significant quantities of consumed MP have been discovered to have diverse detrimental effects, posing a threat to human welfare. The exact concentrations of microplastics that are inhaled and swallowed and then build up in the human body are still not known. Further investigation is necessary to evaluate the impact of MP contamination at minimal concentrations and for prolonged durations.

Background: Ventilatory strategies in acute respiratory distress syndrome patients aim to mitigate the risk of acute lung injury (ALI). However, prolonged utilization of these strategies may precipitate alveolar carbon dioxide elevation and pH reduction. This scoping review endeavors to present extant knowledge concerning hypercapnia effects in experimental models, with or without ALI, specifically focusing on delineating the immunologically mediated pulmonary tissue damage; Methods: A systematic exploration encompassing PubMed, Web of Science, ScienceDirect, Cochrane Reviews, and Scielo databases was undertaken. Articles published between January 1, 2008, and December 31, 2022, were screened for their elucidation of hypercapnia's immunological impact on lung tissue, utilizing experimental or biological models, irrespective of ALI presence; Results: Following duplicate removal and predefined criteria filtering, 30 pertinent articles scrutinizing hypercapnia's influence on pulmonary epithelium were identified. It was observed that hypercapnia induces perturbations in innate immune response gene transcription, mediated via Nuclear Factor-kappa B attenuation. Furthermore, a compromised innate immune response against injurious agents was noted. Concurrently, disruption and subsequent resealing of alveolar epithelial cells were evidenced, primarily through Na/K-ATPase endocytosis, impeding fluid reabsorption at the alveolar epithelium level; Conclusions: In experimental settings, with or without ALI, hypercapnia's immunomediated mechanisms exacerbate innate immune system impairment and disrupt the respiratory epithelium's repair and healing processes.

Groundwater flow and transport models are essential tools for assessing and quantifying the mi-gration of organic contaminants at polluted sites. Uncertainties in the hydrodynamic and transport parameters of the aquifer have a significant effect on model predictions. Uncertainties can be quantified with advanced sensitivity methods such as Sobol’s High Dimensional Model Reduction (HDMR) and Variogram Analysis of Response Surfaces (VARS). Here we present the application of VARS and HDMR to assess the global sensitivities of the outputs of a transient groundwater flow model of the Gállego alluvial aquifer which is located downstream the Sardas landfill in Huesca (Spain). The aquifer is subject to the tidal effects caused by the daily oscillations of the water level in the Sabiñánigo reservoir. Global sensitivities are analysed for hydraulic heads, aquifer/reservoir fluxes, groundwater Darcy velocity and hydraulic head calibration metrics. Input parameters in-clude aquifer hydraulic conductivities and specific storage, aquitard vertical hydraulic conductiv-ities, and boundary inflows and conductances. VARS, HDMR and graphical methods agree to identify the most influential parameters which for most of the outputs are the hydraulic conduc-tivities of the zones closest to the landfill, the vertical hydraulic conductivity of the most permeable zones of the aquitard, and the boundary inflow coming from the landfill. The sensitivity of heads and aquifer/reservoir fluxes with respect to specific storage change with time. The aquifer/reservoir flux when the reservoir level is high shows interactions between specific storage and aquitard conductivity. VARS and HDMR parameter rankings are similar for the most influential parameters. However, there are discrepancies for the less relevant parameters. The efficiency of VARS was demonstrated by achieving stable results with a relatively small number of simulations.

Considering animal welfare, the free-range laying hen farming model is increasingly gaining attention. However, in some countries, large-scale farming still relies on the cage-rearing model, making the focus on the welfare of caged laying hens equally important. To evaluate the health status of caged laying hens, a dataset comprising visible light and thermal infrared images was established for analyses, including morphological, thermographic, comb, and behavioural as-sessments, enabling a comprehensive evaluation of the hens' health, behaviour, and population counts. To address the issue of insufficient data samples in the health detection process for indi-vidual and group hens, a dataset named BClayinghens was constructed containing 61,133 images of visible light and thermal infrared images. The BClayinghens dataset was completed using three types of devices: smartphones, visible light cameras, and infrared thermal cameras. All thermal infrared images correspond to visible light images and have achieved positional alignment through coordinate correction. Additionally, the visible light images were annotated with chicken head labels, obtaining 63,693 chicken head labels, which can be directly used for training deep learning models for chicken head object detection and combined with corresponding thermal infrared data to analyze the temperature of the chicken heads. To enable the constructed deep-learning object detection and recognition models to adapt to different breeding environ-ments, various data enhancement methods such as rotation, shearing, colour enhancement, and noise addition were used for image processing. The BClayinghens dataset is important for ap-plying visible light images and corresponding thermal infrared images in the health detection, behavioural analysis, and counting of caged laying hens under large-scale farming.

Background. Respiratory distress syndrome (RDS) is the primary cause of respiratory failure in preterm infants, but it also affects 5-7% of term infants. Dysfunctions in pulmonary surfactant metabolism, resulting from mutations of the lung surfactant genes, are rare diseases, ranging from fatal neonatal RDS to interstitial lung disease, associated with increased morbidity and mortality. This study aims to clarify the clinical significance of ABCA3 variants found in a specific family case, as existing data in the literature is inconsistent. Material and methods: A family case report was conducted; targeted panel genetic testing identified a variant of the SFTPB gene and two variants of ABCA3 genes. Comprehensive research involving a systematic review of PubMed, Google Scholar databases, and genome browsers was used to clarify the pathogenicity of the two ABCA3 variants found in the index patient. Advanced prediction tools were employed to assess the pathogenicity of the two ABCA3 variants, ensuring the validity and reliability of our findings. Results: The index case exhibited fatal neonatal RDS. Genetic testing revealed the presence of the SFTPB p.Val267Ile variant, not previously reported, a benign variant based on family genetic testing and history. Additionally, two ABCA3 gene variants were identified: c.697C>T, not yet reported, and c.838C>T. These variants were found to affect ABCA3 protein function and were likely associated with neonatal RDS. Prediction tools and data from nine other cases in the literature supported this conclusion. Conclusions: Based on in silico predictors, analysis of the presented family, and cases described in the literature, it is reasonable to consider reclassifying the two ABCA3 variants identified in the index case as pathogenic/pathogenic. Reclassification will improve genetic counseling accuracy and facilitate correct diagnosis.

Isolation of new plant-derived lactic acid bacteria (LAB) is highly prioritized in developing novel starter cultures for plant-based fermentation. This study explores the diversity of LAB in Danish flowers and their potential use for plant-based food fermentation. 46 flower samples under 34 genera were collected for LAB isolation. By introducing an enrichment step, in total of 61 LAB strains were isolated and identified by using MALDI-TOF and 16S rRNA sequencing. These strains represent 24 species across 9 genera, predominantly Leuconostoc mesenteroides, Fructobacillus fructosus, Apilactobacillus ozensis, and Apilactobacillus kunkeei. Phenotypic screening for exo-cellular polysaccharide production revealed that 40 strains exhibited sliminess or ropiness on sucrose containing agar plate. HPLC analysis confirmed that all isolates produced exo-cellular polysaccharides containing glucose, fructose or galactose as sugar monomer. Therefore, the strains were glucan, fructan and galactan producers. The suitability of these strains for plant-based fermentations was characterized by using almond, oat and soy milk. The results showed successful acidification in all three types of plant-based matrices but only observed texture development in soy by Leuconostoc, Weissella, Lactococcus, Apilactobacillus, and Fructobacillus. The findings highlight the potential of flower-derived LAB strains for texture development in soy-based dairy alternatives.

Cholesterol homeostasis is pivotal for cellular function. Acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1), also abbreviated as SOAT1, is an enzyme catalyzing the storage of excess cholesterol to cholesteryl esters. ACAT1 is an emerging target to treat diverse diseases including atherosclerosis, cancer, and neurodegenerative diseases. F12511 is a high affinity ACAT1 inhibitor. Previously, we developed a stealth liposome-based nanoparticle to encapsulate F12511 to enhance its delivery to the brain and showed its efficacy in treating a mouse model for Alzheimer’s disease (AD). In this study, we introduce F26, a close derivative of F12511 metabolite in rats. F26 was encapsulated in the same DSPE-PEG2000/phosphatidylcholine (PC) liposome-based nanoparticle system. We employed various in vitro and in vivo methodologies to assess F26's efficacy and toxicity compared to F12511. Results demonstrate that F26 is more effective and durable than F12511 in inhibiting ACAT1, in both mouse embryonic fibroblasts (MEFs) and in multiple mouse tissues including the brain tissues, without exhibiting any overt systemic or neurotoxic effects. This study demonstrates the superior pharmacokinetic and safety profile of F26 in wild-type mice, and suggests its therapeutic potential against various neurodegenerative diseases including AD.

Background: Medication errors often stem from incomplete or incorrect transfer of drug information during reviews. To enhance medication review processes, a collaborative healthcare team, including a pharmacist in the surgical ward, is essential. This study aimed to identify the frequency and the kind of intentional and unintentional discrepancies related to the prescriptions within two surgical wards. Methods: A prospective observational study was conducted among adult patients admitted to two surgical settings. The patients were selected between May 30th and November 30th, 2021. The study followed a three-phase structure: patient selection, medication review to identify discrepancies and DRPs, and the detection of any such issues in the discharge letter. Results: The most frequent types of discrepancies collected were substitutions (60.9%) for the Endocrinological Surgery and omissions for General Surgery (53.4%). In Endocrinological Surgery, 45.9% of cases exhibited class C drug interactions. In General Surgery, class D drug interactions were predominantly observed (54.1%), with 93.3% attributed to drugs carrying an elevated risk of prolonging the QT interval. Conclusions: Frequently, the medication review process is superficially carried out, introducing errors that may adversely affect patient health. This study explores the potential positive impact of involving the clinical pharmacist in identifying and managing discrepancies and DRPs.

Objectives: To compare the effects of high-velocity resistance training to slow-velocity re-sistance training on neuromuscular and functional parameters and to analyze the relationship between changes in walking speed and improvements in neuromuscular parameters following intervetions. Methods: 40 participants were randomly assigned to either a high-speed resistance training group (GHS, n = 18; age = 80.41 ± 10.12 years; BMI = 23.81 ± 3.45 kg/m²) or a low-speed resistance training group (GLS, n = 22; age = 82.89 ± 5.32 years; BMI = 23.81 ± 3.45 kg/m²). Before and after the interventions, gait speed (m/s) was assessed using a 10-minute walking test, and relative maximal force (Relative F max, N/kg) was evaluated during maximal voluntary isometric con-traction of the plantar flexors. From the force-time curve, early (0 – 50 ms) and late (100 – 200 ms) rates of force development (RFD) were extracted from the linear slopes (Δ force / Δ time). Results: Gait speed significantly improved in both groups (p < 0.05). However, the improvement was more pronounced in the GHS compared to the GLS (p < 0.05). Relative Fmax showed a more significant increase in the GLS than in the GHS (p < 0.05). Moreover, a significant 10% increase in early RFD in the GLS and a 20.1% increase in the GHS were observed (p < 0.05). The improvement in early RFD was greater in the GHS (p < 0.05). Additionally, late RFD improved significantly only in the GHS (+20.4%, p < 0.05). Conclusion: High-velocity resistance training appears particularly effective in improving the ability to rapidly generate force, which is essential for many daily activities re-quiring explosive movements and quick responses.

For quantitative determination of honokiol (HNK) and metformin hydrochloride (M-HCl) by HPLC from formulations and from dissolution studies, a QbD approach using three factors - three levels design was implemented to optimize the chromatographic conditions. To study the impact of each variable on the peak area of both compounds and retention time of last compound eluted, the 3D response surface plots were developed. HNK and M-HCl were separated on a Thermoscientific ODS Hypersyl TM (250 x 4.6 mm, 5 μm) column mantained at 30 C, using 0.02 M acetate buffer (pH = 3) / methanol (15 / 85, v / v) as mobile phase with a flow rate of 1 mL/min. The injected volume was 20 L, and the detection wavelengths were 256 nm for HNK and 236 nm for M-HCl. The validation of proposed method showed a linearity range of 4 – 1200 μg/mL for M-HCl (r2 = 0.9992) and 1 – 300 μg/mL for HNK (r2 = 0.9998), good precision (RSD &lt; 2% for both HNK and M-HCl, in intra- and inter-day studies) and accuracy (mean recovery = 100.09% in the range 99.80 – 100.43% for M-HCl and mean recovery = 100.12% in the range 99.70 – 100.38% for HNK). The environmentally friendly nature of the method was confirmed by the evaluation of the method’s greenness. The proposed method was applied for the determination of HNK and M-HCl from oral dosage forms and in dissolution studies.

Blood vessels are essential for maintaining tumor growth, progression, and metastasis, yet the tumor vasculature is under a constant state of remodeling. Since the tumor vasculature is an attractive therapeutic target, there is a need to predict the dynamic changes in intratumoral fluid pressure and velocity which occur across the tumor microenvironment (TME). The goal of this study is to get insight into perfusion anisotropy within lung tumors. To achieve this goal, we used the perfusion marker Hoechst 33342 and vascular endothelial marker CD31 to stain tumor sections from C57BL/6 mice harboring Lewis Lung Carcinoma tumors on their flank. Vasculature, capillary diameter, and permeability distribution were extracted at different time points along the tumor growth curve. A computational model was generated applying a unique modeling approach based on the smeared physical fields (Kojic Transport Model, KTM). KTM predicts spatial and temporal changes in intratumoral pressure and fluid velocity within the growing tumor. Anisotropic perfusion occurs within two domains - capillary and extracellular space. Anisotropy in tumor structure causes nonuniform distribution of pressure and fluid velocity. These results provide insights regarding local vascular distribution for optimal drug dosing and delivery to better predict distribution and duration of retention within the TME.

The objective of this paper was to study the expression pattern of the GLOD4 gene in the testis and its regulatory effect on testicular cells. Currently, the regulated mechanism through are unclear. Here, we explored how GLOD4 functions in goat leydig cells to enhance our understanding of spermatogenesis and improve reproduction in breeding rams. In this study, we demonstrated that the localization of GLOD4 in testicular cells using immunohistochemistry and subcellular localization analyses. Subsequently, we analyzed the GLOD4 expression pattern in 4 age-based groups (0, 6, 12, and 18 months old) using real-time quantitative polymerase chain reaction (qRT‒PCR) and protein blotting. Finally, we performed GLOD4 gene silencing and overexpression studies in testicular cells from goats and explored the effects of GLOD4 on cell proliferation, the cell cycle, steroid hormone secretion and the expression of candidate testosterone hormone-regulated genes. GLOD4 was mainly expressed in testicular leydig cells, and the subcellular localization results showed that the GLOD4 protein was mainly localized in the cytoplasm and nucleus. Silencing of GLOD4 significantly suppressed the mRNA expression levels of the testosterone secretion-related genes CYP11A1, 3β-HSD and CYP17A1 and the mRNA expression levels of cell-cycle related genes CDK6, PCNA, and Cyclin E. Moreover, the cell cycle was blocked at the G2/M phase after GLOD4 silencing, which significantly suppressed testosterone secretion. In contrast, GLOD4 overexpression significantly increased the mRNA expression levels of the testosterone secretion-related genes CYP11A1, 3β-HSD, and CYP17A1 and increased the expression of the cell-cycle related genes CDK6, PCNA, and Cyclin E. Moreover, GLOD4 overexpression promoted the cell cycle from G0/G1 phases to enter the S phase and G2/M phases,promoted the secretion of testosterone. Taken together, our experimental results indicate that GLOD4 may affect the development of cells in Qianbei Ma goats of different ages by influencing the cell cycle, Proliferation and testosterone hormone synthesis. These findings enhance our understanding of the functions of GLOD4 in the cells of goats.

Fish kills in Southeast Asia are frequently associated with harmful algal blooms (HABs) and cause significant ecological and economic impacts. This paper serves as a review of fish kill events with focus on those related to HABs within the region. It examines the causative algal species, known mechanisms of fish mortality, and socio-economic consequences. Fish kills have been reported across multiple countries within Southeast Asia, with notable hotspots in the Philippines, Malaysia, Singapore, Indonesia, and Thailand. The common harmful microalgal species span a diverse group including dinoflagellates (Karenia spp., Karlodinium spp., Margalefidinium polykrikoides, Noctiluca scintillans), raphidophytes (Chattonella spp.), diatoms (Skeletonema spp. and Chaetoceros spp.), and cyanobacteria (Trichodesmium spp.). These microalgae lead to fish kills through mechanisms such as hypoxia, physical gill damage, and ichthyotoxin production. Freshwater fish kills linked to HABs have also been documented for the Philippines, but there is no or limited information for the region. Our review highlights the widespread and recurring nature of fish kills, their impact on fisheries and aquaculture, and challenges in managing and mitigating their effects. There are efforts at enhancing management and mitigation using clay and early-warning systems. However, it is essential to further improve monitoring efforts, the development and deployment of early-warning systems, and viable and holistic mitigation strategies to protect the region’s aquatic resources and dependent communities, especially as aquaculture and coastal development are increasing concurrent with a changing climate that can exacerbate the risks of fish kills and HABs in Southeast Asia.

Background: The study was conducted to investigate if the mRNA vaccine technology could be adapted for the ectothermic vertebrate Atlantic salmon (Salmo salar). The lipid nanoparticle (LNP) technology has been developed and optimized for mRNA vaccines in mammals, stabilizing mRNA and facilitating delivery into cells. However, its utility at the temperature and specific biological environment in ectotherms remains unclear. In addition, it is unknown if modified mRNA containing non-canonical nucleotides can correctly translate in salmonid cells. Methods: We used an mRNA transcript coding for enhanced green fluorescence protein, flanked by the untranslated regions of the hemagglutinin-esterase gene of infectious salmon anemia virus, and a 120-base-long poly(A) tail. The mRNA was generated by in vitro transcription where uridine residues were replaced with N1-methyl-pseudouridines, and then encapsulated in LNPs. Results: When transfected into the salmonid cell line CHH-1, the mRNA-LNP construct induced expression of EGFP. Furthermore, when mRNA-LNPs were injected intramuscularly into salmon, in vivo protein expression was demonstrated by immunohistochemistry. EGFP was observed in cells infiltrating the space between the muscle cells in a focal inflammatory response. Conclusion: The results indicate that the N1-methyl-pseudouridine modified mRNA encapsulated in LNPs can be used to express antigens of interest in salmonid fish.

The growing interest in Kv7.2/7.3 agonists originates from the involvement of these channels in several brain hyperexcitability disorders. In particular, Kv7.2/7.3 mutants have been clearly associated with epileptic encephalopathies (DEE) as well as with a spectrum of focal epilepsy disorders, often associated with developmental plateauing or regression. Nevertheless, there is a lack of available therapeutic options, considering that retigabine, the only molecule used in clinic as broad-spectrum Kv7 agonist, has been withdrawn from the market in the late 2016. This is why several efforts have been made both by both academia and industry in the search for suitable chemotypes acting as Kv7.2/7.3 agonists. In this context, in silico methods have played a major role, since the precise structures of different Kv7 homotetramers have been only recently disclosed. In the present review the computational methods used for the design of Kv.7.2/7.3 small molecule agonists and the underlying medicinal chemistry are discussed in the context of their biological and structure-function properties.

In this study, the mechanical and piezoresistive properties of mortars reinforced with carbon nanotubes (CNTs) and carbon micro fibers (CMFs) are determined. Silica fume as well as a polymer with polyalkylene glycol graft chains were used as dispersant agents for the CNTs and CMFs incorporation into the cement paste. The mechanical properties of the mortar composites were investigated in respect to their flexural and compressive strength. A four-probe method was used for the estimation of their piezoresistive response. The test outcomes revealed that the combination of the dispersant agents along with a low content of CNTs and CMF by weight of cement (bwoc) result in the production of a stronger mortar with enhanced mechanical performance and durability. More specifically, there was an increase in flexural and compressive strength up to 38% and 88%, respectively. Moreover, the piezoresistive response of the reinforced cementitious materials was attributed to the variation of electrical resistivity due to tunneling transport of electrons stemming from two different mechanisms due to the incorporation of the conductive admixtures (CNTs and CMF). This work aims to contribute to the progress acceleration in the field of developing structural materials with self-sensing and electrical actuation related properties.

Nasal high-frequency oscillatory ventilation (nHFOV) has emerged as an effective initial and rescue noninvasive respiratory support mode for preterm infants with respiratory distress syndrome (RDS). Multiple noninvasive respiratory support modes are currently available in Romania, but little is known about nHFOV use in Romanian neonatal intensive care units (NICUs). We aimed to identify the usage extent and clinical application of nHFOV in Romania. A structured web-based questionnaire was designed to find the rate of nHFOV use and knowledge of this new method of noninvasive respiratory support in Romanian level III NICUs. The questionnaire was addressed to the leaders of all level III Romanian NICUs. Using multiple-choice, open-ended, and yes/no questions, we collected information on the NICU’s size, noninvasive respiratory support modes used, nHFOV use, indications, settings, nasal interfaces, secondary effects, and equipment used. Descriptive statistics and comparisons were performed using IBM SPSS Statistics 26.0. A total of 21/23 (91.3%) leaders from level III NICUs (median [IQR] number of beds of 10 [10-17.5]) responded to the survey. The most frequently used noninvasive ventilation modes were CPAP mode on mechanical ventilators (76.2%), followed by NIPPV (76.2%), heated, humidified high flow nasal cannula (HHHFNC) (61.9%), and nHFOV (11/21 units; 52.4%); 5/11 units reported frequent nHFOV use (in 2 or more newborns/month) in both term and preterm infants. The main indications reported for nHFOV use were CPAP failure (90.9%), hypercapnia (81.8%), and bronchopulmonary dysplasia (72.7%). 10/11 units reported setting a mean airway pressure (MAP) equal to the CPAP level plus 1-2 cmH₂O on rescue nHFOV after CPAP failure. Both dedicated equipment (45.5%) and hybrid ventilators (63.6%) were used for nHFOV delivery, with face/nasal masks and short binasal prongs being the most commonly used nasal interfaces (90.9% and 72.7%, respectively). Air leaks at the interface level (90.9%), thick secretions (81.8%), and airway obstruction (63.6%) were the most frequently mentioned adverse effects of nHFOV; none of the units mentioned pneumothorax as an adverse effect. Only 3 of the NICUs had a written protocol for nHFOV use. Initial, minimum, and maximum amplitude and initial and minimum MAP settings used were significantly higher with hybrid ventilators as compared to dedicated equipment (p<0.05). Most units not yet using nHFOV cited lack of equipment, experience, training, or insufficient information and evidence for the clinical use and outcome of nHFOV use in neonates as the main reasons for not implementing this noninvasive respiratory mode. Our survey showed that nHFOV is already used in more than half of the Romanian level III NICUs to support term and preterm infants with respiratory distress despite a lack of consensus regarding indications and settings during nHFOV. A need for training for nHFOV use was identified, and efforts are needed at the national level to develop courses and training sessions, including using simulation workshops, to offer more information on optimal nHFOV use in clinical practice.

(1) Background: This study aims to investigate differences in the perspectives of exercise intensity for resistance exercise of healthcare professionals (HCPs) and adults living with spinal cord injury (SCI) in Asian countries. Also, it verifies the appropriateness of the conventional indicators for resistance exercise intensity in an Asian context; (2) Methods: 121 certified HCPs and 107 adults with SCI participated in a survey conducted in Indonesian, Japanese, Korean and Thai languages. The survey asked what principles are important for prescribing resistance exercise, and if ‘moderate’ and ‘vigorous’ were appropriate terms for indicating an intensity level. Perspective differences were examined between both groups and, further, between countries from a psychosocial perspective; (3) Results: Of the HCPs, 92% perceived that resistance exercise intensity was far more important than frequency, time or type of exercise while frequency (61%) followed by intensity (58%) was perceived as important by respondents with SCI. Only Japanese respondents with SCI agreed with HCP’s perception of intensity. Both HCPs and respondents with SCI showed unfavorable responses on the usage of ‘moderate’ and ‘vigorous’ for describing resistance exercise intensity, especially Japanese HCP and respondents with SCI from Indonesia; (4) Conclusion: Our findings suggest that non-HCPs must improve their perceptions of exercise intensity. Findings also suggest the need for more explicit and user-friendly terms or expressions indicating the level of intensity in a local (Asian) context.

This study investigated the content of macro- and microelements in the lower reaches of the Ob River (Western Siberia). Seasonal sampling was performed over a four-year period (2020-2023) during the main hydrological seasons (winter low water, spring-summer floods, and early fall low water) at three river stations. Suspended and dissolved fractions were separated by filtration through 0.45-micron nitrocellulose filters. The results revealed significant seasonal variations in the elemental content of the Ob River water, associated with changes in catchment inputs, physical and chemical conditions of the aquatic environment, and the amount and composition of incoming suspended sediment. During high water flow events in the Ob River, the concentration of suspended solids increased substantially. These included significant quantities of sparingly soluble hydrolysates such as Al, Ti, Zr, Ga. During the winter period when the Ob River was ice-covered, a 2- to 3-fold rise was observed in the concentration of Na, Mg, Ca, K, Si, Mn. Having accounted for these seasonal variations in water chemistry, we were able to refine our estimates of elemental export to the Arctic Ocean. Compared to estimates from previous studies, we observed with 2.3-fold higher dissolved loads of Mn, 2.1-fold for Zn, 1.6-fold for Fe, and 1.4-fold for Pb.

The Lower Mekong Basin has had extensive hydropower dam development, which changes hydrologic conditions and threatens the exceptional aquatic biodiver-sity. This study quantifies the degree of hydrologic change between pre-impact (1965-1968) and post-impact (2018-2021) peak hydropower development in two major tributaries of the Lower Mekong Basin, the Sekong River with the fewest dams and the Sesan River with the most dams. Both rivers historically supported migratory fishes. We use daily pre- and post-impact data and the Indicators of Hydrologic Alteration framework to evaluate streamflow changes from dam development. We found signifi-cant changes in low and high magnitude flows in the pre- and post-impact periods of dam development. For the Sekong River, minimum flow had large fluctuations that ranged 290% to 412% more than the pre-impact period, while the Sesan River ranged 120% to 160% more than pre-impact. Dry season flows increased by 200±63% on av-erage in the Sekong River, which is caused by releases from upstream dams. Mean-while, Sesan River dry season flows increased by 100±55% on average. This study in-dicates that seasonal flow changes and extreme flow events occurred more frequently in the two basins following dam construction, which may threaten the ecosystem func-tions.

Maternal diet plays a significant role in the fatty acid composition of breast milk. Natural trans fatty acids (TFAs) are generated through the biohydrogenation of unsaturated fatty acids (FAs) in the rumen of animals by bacterial isomerases and are consequently found in milk, dairy products, and meat from ruminant animals. Dietary products such as milk and meat are the primary sources of natural TFAs for humans, derived from rumen fermentations. These peculiar fatty acids hold nutritional significance as they not only lack the detrimental effects on endothelium characteristic of industrially produced trans fat, but also exhibit anti-inflammatory properties. The relationship between the presence in breast milk of eight fatty acids (including natural TFAs trans-vaccenic and conjugated linoleic acid) and maternal diet has been explored, and their abundance has been compared to that of infant formulas. Two cohorts of lactating women participated in this study, originating from a Spanish region adhered to the Southern European Atlantic Diet or Atlantic Diet. While the consumption of conventional meat or dairy products does not seem to increase the abundance of trans fatty acids in breast milk, trans-vaccenic and oleic acid are among the most distinctive features of breast milk fat in mothers consuming naturally improved dairy products, with an improved fatty acid profile. The most significant differences between natural breastfeeding and formula feeding lie in natural trans fatty acids, since formula are notably deficient, while overfortified in alpha-linolenic acid in comparison to breast milk.

Pig farms management is involved in multiple factors such as environmental conditions, animal behavior, weight gaining and others. In all those scenarios, it is fundamental to detect each individual and its development as it grows to reach the shipment phase. Therefore, the objective of this study was to apply an automatic individual pig detection algorithm using Deep Learning Techniques, in frames taken from videos recorded during the weaning phase in real production conditions of small and medium producers in tropical conditions in Colombia. The weaning phase was selected because individual detection in each cage is more difficult due to environmental adaptations that piglets undergo after nursing. Piglets tend to cluster together during this phase, making image processing more challenging compared to the fattening phase, where animals are more isolated. The You Only Look Once (YOLOv7) algorithm and VGG Image Annotator were used to detect individuals in two pens separated by gender. All animal postures, lighting conditions were considered. The Precision, Recall and mAP metrics were used to assess the model performance with different confidence values. A precision of 98.3% in a threshold of 0.9 was reached, Recall of 98.5% in a threshold of 0.85. Data augmentation techniques were important to increase the dataset and to have a more realistic model for individuals’ detection. The method used allowed us to identify all the complete pigs’ bodies under different posture and lighting situations.

Introduction: Gastric cancer (GC) is one of the most common cancers in the world. It is a very aggressive and heterogeneous tumor. GC does not cause symptoms, so it is often diagnosed in an advanced stage and associated with poor prognosis. Despite new treatment options, it still remains a therapeutic problem. An important element determining the method of treatment of locally advanced gastric cancer (LAGC) is the assessment of lymph node metastases in preoperative and postoperative imaging and/or histopathological examination.Aim: The assessment of lymphovascular invasion (LVI) in histopathological examination in patients with LAGC after gastrectomy. The groups of patients were divided into patients who received preoperative chemotherapy, patients without preoperative chemotherapy, and all patients. Additionally, we assessed the correlation between the presence of LVI and the number of lymph nodes collected during gastrectomy.Material and method: We collected patients with histologically confirmed GC after gastrectomy. The collected samples were divided into three subgroups: patients with neoadjuvant chemotherapy (NAC), patients without NAC, and all patients. Histopathological examination assessed the presence of LVI infiltration. We then assessed the correlation between the presence of LVI and the presence of lymph node metastasis in GC. Additionally, we assessed the correlation between LVI and the number of lymph nodes evaluated in patients in each group. The statistical analyses were performed using Statistica v13.3 and Microsoft Excel 2021. The significance limit was set at p<0.05.Results:The presence of LVI strongly correlated with node involvement, and the result was statistically significant in all patients and the group of patients treated with NAC. The difference was not statistically significant in the group not treated by NAC. Additionally, we did not observe a correlation between the presence of LVI and the number of metastatic lymph nodes in GC.Summary and Conclusions: The presence of LVI in a patient with GC indicates a high probability of lymph node metastasis, which should translate into therapeutic procedures. Assessment of LVI may help identify potential patients with lymph node metastases, particularly in patients undergoing endoscopic resection without planned lymphadenectomy. It is advisable to expand research on a larger scale in order to establish clear standards in this area.

Several studies have shown that antibiotics, analgesic – sedative, and antiseizure medications are among the most commonly used medications in preterm and sick neonates. These infants are at high risk of developing nosocomial infections, central nervous system complications, and are exposed to numerous painful/stressful procedures. These severe, potentially life-threatening complications may have serious short- and long-term consequences and should be prevented and/or promptly treated. Previous studies and reviews have revealed significant variability in medications used in neonatal intensive care units (NICUs) worldwide, especially concerning the indications and dosages of first-line medications. This variability indicates the lack of adequate studies regarding the effectiveness and safety of these medications in neonates, especially the preterm ones. Important obstacles contributing to inadequate studies in preterm infants include difficulties in obtaining parental consent, physicians’ unwillingness to recruit preterm infants, the lack of license for use in neonates, and other scientific and ethical concerns. This review is an update on the use of antimicrobials – antifungals, analgesics – sedatives, and antiseizure medications used in neonates, focusing on existing evidence or knowledge gaps regarding their pharmacokinetics, indications, safety, dosage regimen (dose, dosing interval, route of administration), and evidence-based guidelines for the optimal use in neonates.

Wilms tumor (WT), the most prevalent type of renal cancer in children, exhibits overall survival rates exceeding 90%. However, chemotherapy resistance, which occurs in approximately 10% of WT cases, is a major challenge for the treatment of WT, particularly for advanced-stage patients. In this study, we aimed to discover potential mutation markers and drug targets associated with chemotherapy resistance in advanced stage WT. We performed exome sequencing to detect somatic mutations and molecular targets in 43 WT samples, comprising 26 advanced stage WTs, of which 7 cases are chemotherapy-resistant. Our analysis revealed four genes (ALPK2, C16orf96, PRKDC, and SVIL) that correlated with chemotherapy resistance and reduced disease-free survival in ad-vanced-stage WT. Additionally, we identified driver mutations in 55 genes within the chemo-therapy-resistant group, including 14 druggable cancer driver genes. Based on the mutation profile of the resistant WT samples, we propose potential therapeutic strategies involving platinum-based agents, PARP inhibitors, and antibiotic/antineoplastic agents. Our findings provide insights into the genetic landscape of WT and offer potential avenues for targeted treatment, particularly for patients with chemotherapy resistance.

Paratuberculosis, or Johne's disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic granulomatous enteritis affecting both domestic and wild ruminants. The agent was also found in wild mammals such as wild boar (Sus scrofa), however, the role of wild mammals in the epidemiology of MAP is unclear. During the research period, 941 free-ranging wild boar (S. scrofa) legally hunted in two locations in the Centre-eastern region of Portugal were examined. Ninety-seven wild boar exhibited one or more gross lesions and were tested for the presence of Mycobacterium avium subsp. paratuberculosis using acid-fast staining, mycobacterial culture, poly-merase chain reaction (PCR), and histopathological examination. Forty-five animals (46.4%, 95% CI: 36.5-56.3%) were identified as infected, as indicated by positive results in culture and/or PCR. The findings revealed that the most significant risk factor was being a juvenile compared to year-lings and adults (OR = 10.2, 95% CI: 2.2-48.0). Based on our results, 37.9% (n = 11) of the infected animals were considered suitable for human consumption. Our findings offer novel insights into mycobacterial infections in wild boar populations in Portugal and suggest that wild boar could be a source of human infection if zoonotic potential is considered.

This aim of this study was to investigate the relationships between lifestyle factors, insulin resistance, and male fertility in 73 men with and without insulin resistance. The participants were divided based on insulin resistance status. Their physical activity, diet, perceived stress, sleep quality, libido level, and the duration of sexual abstinence were assessed on the basis of a number of parameters, including indices proposed by the authors. The results highlighted associations between a number of parameters, i.e., micronutrient and vitamin intake, diet quality, body composition, insulin resistance, and the duration of sexual abstinence, and semen quality, as measured by sperm motility. Significantly, the presence or absence of insulin resistance was linked to male fertility. A multivariate model was developed, incorporating parameters such as the Matsuda index, vitamin intake, and sexual abstinence duration, to predict motility scores. The study underscores the negative impact of modern civilization’s lifestyle choices on male fertility. Notably, vitamin and mineral consumption, especially from antioxidant-rich diets like the Mediterranean diet, emerged as key modifiable factors affecting fertility. Routine diagnostics for insulin resistance in fertility-related interventions is recommended. The study also highlights the importance of considering sexual abstinence duration during semen collection for accurate diagnostic results. Future research should focus on validating the proposed multivariate model and exploring the effects of lifestyle modifications, particularly vitamin supplementation, on fertility outcomes in men, especially in the context of insulin resistance.

This study compared the efficacy of alfaxalone and propofol to induce anesthesia in bitches undergoing an ovariohysterectomy or cesarean sections. 34 healthy and pyometra-affected females were induced with IV propofol administration, 35 healthy and pyometra-affected bitches were induced with the IV administration of alfaxalone. For the cesarean sections, females were induced with propofol (n=14) or alfaxalone (n=14). Maternal physiological parameters (heart rate, blood pressure, temperature) were recorded throughout surgeries; the viability and a modified Apgar score was recorded in the neonates at 5, 60 and 120 minutes after delivery. The use of propofol and alfaxalone did not show relevant differences over parameters assessed, when ovariohysterectomy was performed in healthy bitches or females with pyometra, as well as when cesarean sections were compared; only, a transient tachycardia appeared after alfaxalone administration. However, a higher percentage of bitches needed extra-doses of propofol. Neonatal mortality was similar between both groups, but when alfaxalone was used a higher neonatal viability was observed. Propofol and alfaxalone showed similar efficacy to perform the ovariohysterectomy in all bitches. Both protocols were optimal for cesarean sections, but alfaxalone was associated with a higher neonatal viability and a higher neonatal survival rate.

The COVID-19 pandemic halted progress in global vaccine coverage and disrupted routine childhood vaccination practices worldwide. While there is ample evidence of vaccination declines experienced during the pandemic, it is less clear how low-income countries were affected. We executed a systematic review to synthesize the current literature on impacts to routine childhood vaccinations in low-income countries from January 1, 2020 to February 8, 2023. We collected data using an extraction form on Covidence and assessed the quality of studies included in the review using the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool. Effect estimates for changes in vaccination during the pandemic were reported and summarized. Factors that influenced changes were grouped into descriptive themes. Thirteen studies, encompassing 18 low-income countries and evaluating 15 vaccines at varying doses, were included in the final review. We found that routine childhood vaccinations during the COVID-19 pandemic varied considerably by vaccine type, location, and phase of the pandemic. Nine different themes were identified as factors that influenced changes in vaccination. Documenting past experiences and lessons learned is crucial for informing preparedness efforts in anticipation of future public health emergencies. Failure to effectively address these things in the next public health emergency could result in a recurrence of declining routine childhood vaccinations.

Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccines-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and literature review another 78 patients published from January 2020 to October 2022. Patients were divided into three vaccine groups (viral vector, mRNA and inactivated vaccines) for further analyses. Among 79 patients with COVID-19 vaccines-related CNS IDDs, 49 (62%) cases received viral vector vaccines, 20 (25.3%) received mRNA vaccines and 10 (12.7%) received inactivated vaccines. Twenty-seven cases (34.2%) were confirmed with autoantibodies, including 15 patients (19%) with anti-MOG, 11 (13.9%) with anti-aquaporin 4 (AQP4), and one (1.3%) with both antibodies. Significantly, more males developed CNS IDDs post viral vector vaccines compared to mRNA and inactivated vaccines. Patients receiving mRNA vaccines were older than other groups. Furthermore, mRNA and inactivated vaccines correlated more with anti-AQP4 antibodies, while viral vector vaccines showed higher MOG positivity. The research suggests potential associations between COVID-19 vaccines-related CNS IDDs and gender, age, and autoantibodies, contingent on vaccine types. Protein sequence analysis implies similarities between the S protein and AQP4/MOG. Further studies may elucidate the mechanisms of CNS IDDs, aiding vaccine selection for specific groups.

The paper discusses the mechanism of montmorillonite structure alteration and bentonites properties modification (on the example of samples from clay deposit Taganka, Kazakhstan) due to the thermochemical treatment (treatment with inorganic acid solutions at different temperatures, concentrations and reaction times). With the use of the suit of methods certain processes were distinguished: transformation of montmorillonite structure, which appears in the leaching of interlayer and octahedral cations, protonation of the interlayer and OH groups at octahedral sheets. Changes in the structure of the 2:1 layer of montmorillonite and its interlayer result in significant changes in the properties – reduction of cation exchange capacity and an increase of specific surface area. The results of the work showed that bentonite clays retain a significant portion of its adsorption properties even after the long term and intense thermochemical treatment (6M HNO3, 60°C, 108 hours)

Electronic devices called epiretinal prosthesis are used to restore vision in patients with age-related macular degeneration (AMD) and retinitis pigmentosa (RP), two degenerative retinal illnesses. It functions by stimulating the retina's surviving cells, which then excite the brain to receive visual information from the retina. Epiretinal prosthesis have the flexibility of electrode placement, which enables them to target particular regions of the retina. Furthermore, it enables a high level of spatial resolution, enhancing visual quality. For the purpose of activating retinal cells, it transforms visual input into electrical signals. In general, epiretinal prosthesis are a potential method for helping people with degenerative retinal illnesses regain their vision. Ongoing research aims to increase the effectiveness and safety of these devices.

This study investigates the compressive strength and workability of concrete incorporating coconut shells and bamboo strips as alternative aggregates. The research compares traditional concrete to concrete mixtures with varying percentages of coconut shells and bamboo strips. Specifically, the study examines the effects of adding 10% coconut shell, 10% bamboo strip, and a combination of 5% coconut shell and 5% bamboo strip by volume to the concrete mix, tested in both C20 and C30 grades. To prepare the materials, coconut shells and bamboo strips were first crushed and then sieved. The sieving process retained particles that passed through a 10mm sieve but were retained on a 4.7mm sieve. The primary focus of the experimental tests was on measuring the compressive strength of the resulting concrete mixtures. The findings indicate that concrete incorporating coconut shells showed moderate workability. In contrast, concrete with bamboo strips exhibited lower workability. Regarding compressive strength, the concrete mix containing a combination of 5% coconut shell and 5% bamboo strips demonstrated a reduction in strength compared to the control group of normal concrete. This research highlights the potential of using coconut shells and bamboo strips as sustainable alternatives in concrete construction. While the workability varies between the different materials, the results provide valuable insights into their suitability for specific applications. This encourages further exploration of eco-conscious building practices and the development of sustainable construction materials.

The glucocorticoid receptor alpha (GRα), a pivotal component of the ancient glucocorticoid (GC) signaling system that emerged nearly 450 million years ago, has been instrumental in directing vertebrate evolution and is essential for survival, regulating fertility and fetal development, the function of every organ and circulating cells, metabolism, immune responses, and adaptation to stress. While its anti-inflammatory properties have been recognized since the mid-20th century, GRα’s broader role as the master regulator of homeostatic corrections, particularly in health and critical illness, has only recently been fully appreciated.GRα orchestrates three key phases of homeostatic correction: the Priming Phase, where it rapidly activates early immune responses, mobilizes energy reserves, and prepares the body to mount an immediate defense against various physiological stressors, including infection and injury. During this phase, GRα enhances glucose metabolism, supports mitochondrial function, and facilitates the release of key immune cells to the site of damage, ensuring the body is equipped to handle the initial assault. The Modulatory Phase follows, in which GRα fine-tunes the inflammatory response to prevent excessive tissue damage. By balancing pro- and anti-inflammatory signals, GRα helps contain the immune response, preventing the harmful effects of prolonged inflammation while maintaining immune surveillance. This phase also involves the regulation of oxidative stress, vascular tone, and the preservation of cellular integrity to protect vital organs from injury. Finally, in the Restorative Phase, GRα plays a critical role in resolving inflammation and initiating tissue repair. During this phase, GRα supports cellular regeneration, promotes the clearance of apoptotic cells and debris, and restores anatomical and physiological balance. It aids in rebuilding tissue architecture and returning the neuroendocrine-immune system to its baseline state, ensuring long-term recovery and stability.Throughout these phases, GRα manages complex interactions, including recently discovered co-regulation with pro-inflammatory transcription factors, while also regulating mitochondrial function to ensure bioenergetic and metabolic stability during stress. In critically ill patients, depletion of bioenergetic and micronutrient reserves severely impairs GRα’s capacity to regulate immune responses, heightening the risk of morbidity and mortality.This review, in light of this new understanding, underscores the need to re-evaluate current glucocorticoid (GC) treatment strategies, emphasizing the incorporation of micronutrient support to optimize GRα function across all phases of homeostatic correction. This integrated therapeutic approach has the potential to enhance both immediate immune responses and long-term recovery in critically ill patients, offering a more comprehensive strategy for managing the complex pathobiology of critical illness. Furthermore, this integrative approach could decrease glucocorticoid dose and duration requirements and potential side effects.

Efforts to optimize the design and enhance the efficiency of standing-wave thermoacoustic refrigerators (SWTAR), particularly those with parallel plate stacks, are crucial for achieving rapid and straightforward engineering estimates. This study primarily focuses on optimizing the Coefficient of Performance (COP) by combining the linear thermoacoustic theory (LTT) with the Design of Experiments (DOE) approach. The investigation centers around five key parameters affecting the COP, once the working gas is selected. Then, based on the LLT theory, the COP was estimated numerically, over defined intervals of those five parameters. Moreover, through quantitative and qualitative effect analyses, these five parameters and their interactions are determined. Utilizing a transfer function and surface response analyses based on the COP, the study aims to delineate the best COP value as well as the contribution of the thermoacoustic parameters and their interactions. Furthermore, a comparison between contour and surface responses and several statistical decision approaches applying the Full Factorial Design verify the robustness of the study’s findings. Ultimately, the COP results obtained align with existing literature, underscoring the validity and relevance of the study’s methodologies and conclusions.

In the realm of Lithium-ion batteries, issues like material aging and capacity decline contribute to performance degradation or potential safety hazards. Predicting Remaining Useful Life (RUL) serves as a crucial method to assess the health of batteries, thereby enhancing reliability and safety. Currently hybrid approaches for batteries RUL estimation are prevalence and gained fruitful development. In this paper, a hybrid voting ensembles combining Gradient Boosting, Random Forest and K-Nearest Neighbors is proposed to predict the capacity fade trend and knee point. Finally, extensive experiments are conducted using CALCE CS2 datasets. According to the experimental results, the proposed approach supersedes the single deep learning approach for RUL prediction and the knee point is predicted accurately. Besides prediction purpose, this innovated approach can be also proposed to be integrated into the real-world application for wider usage.

During recent years there is an on-going deployment of 5G base stations for radiofrequency (RF) communication in Sweden as well in many other countries. This is made without investigations on risks to human health and the environment. Since 2016 we have made several measurements of environmental exposure to RF radiation in Stockholm, Sweden, including previous generations and now also 5G. In the current study, performed in October 2023, the broadband meter Narda-550 with the probe EF-1891 was used. It gives results in the root mean square (RMS) mode, thus not peak levels. Both the International Commission on Non-Ionizing Radiation Protection (ICNIRP) and the US Federal Communications Commission (FCC) base their guidelines on RMS levels of RF radiation. Measurements were made in similar city areas as in our previous studies. Results show that the RF radiation has increased substantially. High maximum levels were found at e.g. the Central Railway Station (3 637 191 µW/m2), and popular walking streets such as Mäster Samuelsgatan (11 613 976 µW/m2), and Drottninggatan (5 271 555 µW/m2). The peak values would be much higher. These levels are in the same magnitude or even higher than those measured in homes of persons that rapidly developed symptoms of the microwave syndrome after installation of 5G, usually in combination with 4G+, in the neighborhood. They are also substantially higher than levels that have previously been linked to cancer and the microwave syndrome in studies of people living near base stations and masts from previous generations of telecommunications.

A single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article, and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions. Python, a versatile programming language, holds vast potential for Sentiment Analysis (SA). Leveraging the Requests and TextBlob libraries, we have crafted a user-friendly code that enables Industrial Engineers (IE) and managers, particularly those who are new to Python, to extract and analyze sentiment efficiently. We aim to provide IE/managers in service companies requiring SA capabilities with a simple yet effective Python solution. While machine learning resources like PyTorch/TensorFlow are commonly utilized in SA, offering pre-built algorithms and tools for training, and implementing machine learning models, we sought to exploit Python's versatility by integrating additional web-scraping libraries. Thus, by using a lexicon-based approach, we intend to deliver an informative and practical article. The code in this article is twofold; firstly, it can be easily adapted by IE/managers possessing basic Python skills; secondly, we aim to inspire junior IE/managers to develop their own customized coding solutions tailored to specific organizational needs.

The sustainable development of public open spaces (POS) in suburban areas is crucial to enhancing neighborhood livability, especially in the face of uncontrolled urban sprawl. Therefore, the question was asked: what forms of gathering and recreation places are in suburbs that are subjected to mature urban planning? The research focuses on the Netherlands (Bunnik commune), a country known for its sustainable suburban areas. By conducting field research that involved analyzing physical traces and engaging in non-participatory observation, the study identified and categorized 18 distinct spatial-functional units of POS looking from a top-down design and planning lens. The types of gathering and recreation places identified through top-down development included: estates with recreational areas for neighbors; communal playgrounds; greenery sites by pedestrian routes; social places in central zone; open sports grounds; public allotment gardens; multi-purpose recreational areas at schools, communal facilities generating informal meetings. POS types created as a result of both top-down and bottom-up development were: entrance zones to public facilities with a social value; viewpoints accompanying pedestrian routes; network of green walks for recreation in rural and natural landscapes. Other POS types (resulting from bottom-up development): diner's garden and urban farm.

Despite the demonstrated benefits of data monetization initiatives in achieving competitive advantages, many of these efforts struggle to realize their potential. Companies often find it challenging to sustain even initially successful data monetization initiatives due to significant data quality issues. This reflects a disconnect between advancements in data monetization research—spanning digitization, digitalization, and digital transformation—and practical implementation within companies. Consequently, misguided approaches to data monetization are relatively common. A critical prerequisite for successful data monetization is the establishment and maintenance of clean, high-quality data. This study underscores the importance of data quality by conducting an in-depth analysis of Medical Inc., a company engaged in preparing pristine customer master data for advanced customer analytics. The investigation aims to elucidate Medical Inc.’s approach to addressing data cleanliness challenges and to distill a general framework for the customer master data cleansing process. This framework illuminates a relatively unexplored aspect of data monetization supplementing existing literature on digitization, digitalization, and digital transformation.

Modern automotive systems should must satisfy strict reliability requirements. Most of the real vehicle systems and safety-critical networks have complex interconnections. Sensitivities and probabilistic uncertainties of reliability of System with Complex Interconnections (SwCI) can be investigated by the Monte-Carlo Simulation (MCS). The paper focuses on sensitivities and parametrical uncertainties of SwCIs reliability. The proposed method can be used forimplemented in the investigation of uncertainties of SwCIs reliability – in other wordsi.e., for in the determination of critical system elements and to estimateion of the Required Number of Spare Parts (RNSP) of the system, which depends on the probability of allowable spare equipment shortage.

Background: The last-mile delivery phase, the final stage where goods move from a distribution center to customers, is pivotal but faces significant inefficiencies and high costs due to its complexity. Recent advancements in Edge AI or Edge Intelligence (EI) offer promising solutions to these challenges. Methods: This study explores how AI-driven technologies and real-time data processing, combined with EI, can enhance last-mile delivery operations. A thorough literature review was conducted to assess technological advancements, and a Delphi method was used to systematically and empirically assess the impact of EI solutions on both operational efficiency and customer satisfaction. Results: Although EI technologies offer substantial benefits, EU companies are hesitant to adopt these innovations due to high implementation costs. However, firms that have embraced these technologies report significant improvements, including better route optimization, reduced delivery times, and enhanced service reliability. These findings highlight the need for a culture of innovation and the recruitment of experts with advanced qualifications to drive technological advancement in last-mile logistics. Conclusions: The integration of EI represents a significant step towards more efficient, cost-effective, and customer-focused last-mile delivery solutions. Future research should aim to refine these technologies and explore their long-term impacts on the logistics industry.

Climate change and the increasing frequency and severity of drought events pose significant challenges for sustainable agriculture worldwide. Soil microorganisms, both beneficial and pathogenic, play a crucial role in mediating plant-environment interactions and shaping the overall functioning of agroecosystems. This review synthesizes the current knowledge on the contrasting adaptive mechanisms utilized by different groups of plant-soil microorganisms focusing on beneficial and pathogenic bacterial and fungal communities in response to drought and desiccation stresses. The review examines the common survival strategies employed by microbes specifically rhizobacteria and arbuscular mycorrhizal fungi, such as the production of osmoprotectants, altered gene expression, and biofilm formation. It also highlights the distinct adaptive mechanisms of pathogenic versus mutualistic microbes, with pathogens tending to prioritize virulence factors and suppress plant growth, while beneficial microbes enhance plant growth and stress tolerance. Genetic exchange such as horizontal gene transfer (HGT) is identified as a key adaptive mechanism, allowing both pathogenic and non-pathogenic microbes to acquire beneficial traits like stress tolerance and virulence factors. Environmental stressors like drought can promote increased genetic exchange and the spread of pathogenic traits within the soil microbiome. The complex interplay between drought-adapted microbes and their interactions with plants is discussed, emphasizing the need for a deeper understanding of soil microbiome dynamics under climate change. This knowledge can be utilized in sustainable agricultural practices to mitigate the impacts of drought on plant health and productivity. This review provides insights into the divergent survival strategies of soil microorganisms in response to drought and desiccation, for managing the resilience of agroecosystems to climate change.

Background and Aims: Obesity is a pervasive health issue in children. It affects multiple systems in the body including the gastrointestinal tract. Research on obesity-related gastrointestinal diseases has focused mostly on hepatobiliary disorders. However, non-hepatic gastrointestinal diseases such as gastroesophageal reflux, constipation, and functional abdominal pain, though common and debilitating, have not been highlighted in the context of obesity. These entities can downgrade the already compromised lifestyle of obese children. Some of these disorders are more difficult to treat in these children compared to their peers with normal body mass index. Method: We reviewed the available literature on the association between obesity and these three common gastrointestinal disorders. Results: - There appears to be a strong correlation between childhood obesity and constipation and gastroesophageal reflux, and a probable correlation with functional abdominal pain. Conclusion: We suggest that given the available literature, weight management should be an integral part of the management of gastroesophageal reflux, constipation, and functional abdominal pain in obese children. This gains relevance especially because of the recent availability of medications for the treatment of obesity in children.

The rapid growth of the global population is causing a significant increase in waste production, leading to serious environmental and public health challenges. To address these issues, waste management systems are incorporating advanced technologies. Machine learning and computer vision are used to predict waste patterns, optimize collection schedules, and improve sorting accuracy. Deep learning automates the sorting process, provides predictive analytics, and enhances recycling rates. Robotics, combined with AI and computer vision, improves sorting efficiency, while the Internet of Things (IoT) monitors waste levels and optimizes collection routes. Despite these benefits, challenges such as data scarcity, high computational demands, and the need for substantial infrastructure investments must be addressed. This research explores the integration of advanced technologies into waste management and evaluates their effectiveness using waste datasets. It highlights the potential to tackle environmental challenges and lay the groundwork for more intelligent waste management solutions.

To accurately determine the refractive error of the eye, sufficient relaxation of eye accommodation is essential, either through the fogging technique or pharmacological cycloplegia. This study aimed to evaluate the clinical information revealed after cycloplegia and assess how age and non-cycloplegic refractive status influence the classification of eye refractive error. We analyzed the records of 472 non-population-based subjects aged 3–28 years (mean ± SD: 9.1 ± 4.6) who attended a private ophthalmology practice from January 2018 to December 2020. Cycloplegia was induced with one drop of cyclopentolate 1% in each eye, and refraction was measured 30 ± 5 min later using an objective autorefractometer. The average spherical equivalent (SE) difference (mean ± SD) induced by cycloplegia was 0.72 ± 0.73 D, with the highest difference observed in the 3-5 years age group (1.18 ± 0.85 D). Gender had no significant effect on the SE values before or after cycloplegia (p &gt; 0.05). Cycloplegia caused a hyperopic refractive shift in 83% of participants, no shift in 12%, and a myopic refractive shift in 6%. This study highlights the importance of cycloplegia use in children and young adults.

A method for estimating river water surface elevation (WSE) from Landsat imagery using the river inundation area - water surface elevation (RIA-WSE) rating curve constructed from the U.S. Geological Survey Topobathymetric Elevation Model (TEM) data was developed and tested at six gauging stations along the upper Mississippi River. The Otsu's automatic threshold selection algorithm was employed for the image classification and estimation of inundation areas within each pre-defined polygon around each gauging station. In addition to the commonly used green-band based water indices, Landsat 8 and 9 OLI's ultra-blue, blue, and red band-based water indices were also tested in this study, which resulted in twenty different water indices: NDWIv (Normalized Difference Water Index), MNDWI1v and MNDWI2v (Modified Normalized Difference Water Index), AWEIsv (Automatic Water Extraction Index with shadow), and AWEInsv (AWEI without shadow), where v represents the visible light band used in the water index. At each station, about 60-80 Landsat 8 or 9 images during 2013-2023 were used for assessing the performances of the twenty water indices through comparing the estimated WSEs with the measured WSEs. Results showed that the ultra-blue or red band-based AWEIs yielded the most accurate estimations of WSEs among the twenty tested water indices.

Observations of the X-ray binary system Her X-1 by the AstroSat Soft X-ray Telescope 1 (SXT) were carried out in 2020 through 2023 with the goals of measuring X-ray spectrum changes with the 35-day disk rotation phase and measuring eclipses at different 35-day phases. The four multi-day long observations were scheduled during: turn-on to Main High (MH) and MH rise; MH state; Short High (SH) state; and Low State (LS). 35-day phase was determined using monitoring observations with the Swift Burst Alert Telescope (BAT). Nine eclipses were observed at a range of 35-day phases, with at least one eclipse during each observation. Data with dips were separated from data without dips. The variation of X-ray spectral parameters vs. 35-day phase shows the following: eclipse parameters are nearly constant, showing that the scattering corona does not change with 35-day phase; dips show an increase in covering fraction but not column density compared to non-dip data; the 1 keV line normalization indicates an origin in a small region near the continuum emission region, likely the magnetospheric accretion flow from the inner disk onto the neutron star; and the change in blackbody normalization (area) shows that the emission region is much larger than the 1 keV emission region, and consistent with the inner edge of the accretion disk.

The early 2-factor (E2F) family of transcription factors, including E2F1-8, plays a critical role in apoptosis, metabolism, proliferation, and angiogenesis within glioblastoma (GBM). However, the specific functions of E2F transcription factors (E2Fs) and their impact on the malignancy of Bevacizumab (BVZ)-responsive GBM subtypes remain unclear. This study used data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to explore the impact of eight E2F family members on the clinical characteristics of BVZ-responsive GBM subtypes and possible mechanisms of recurrence after BVZ treatment.To predict the possibility of GBM patient survival and progression, we classified and comparedthe expression of E2Fs according to BVZ-responsive subtypes and employed a machine learning method-TreeBagger, one random forest algorithm. Multiple bioinformatics analyses have shown that the significant increased E2F8 post BVZ treatment may enhance the function of angiogenesis and stem cell proliferation, indicating one of the mechanisms of GBM recurrence after treatment. In addition, BVZ treatment in unresponsive GBM patients may potentially worsen disease progression. Our findings suggest that E2F family members play important roles in GBM malignancy and BVZ treatment response, highlighting their potential as prognostic biomarkers and therapeutic targets and recommending precise BVZ treatment for GBM patients.

One of today’s most critical challenges is ensuring a sufficient food production and supply for the ever-expanding global population. Recently, many countries around the world, particularly those in Africa, grapple with severe hunger and food insecurity, frequently exacerbated by escalating global prices, persistent insecurity, and the repercussion of the COVID-19 pandemic. However, this study undertook an extensive review of the prevalence and severity of hunger and food insecurity across diverse countries and regions. The review utilised several metrics, including Global Hunger Index (GHI) scores, Global Food Security index (GFSI) scores, 2023 data (related to two Sustainable Development Goal 2 (SDG2) target) from the Food and Agriculture Organization (FAO), and other pertinent sources to assess the current status of the countries included in this study. The 20 countries with 2023 GHI scores below 5 were collectively ranked from 1 to 20, signifying low hunger levels. However, Central African Republic (CAR) received the lowest ranking at 125 out of 125, with a score of 42.3, indicating an alarming level of hunger. Finland achieved the highest GFSI score of 83.7, with Oman showing the most notable GFSI improvement at +13.8, while Syria experienced a significant decline in GFSI score by -10.5. Over time, many countries, particularly the developed ones, witnessed significant improvement in their GHI and GFSI scores. Meanwhile, most countries in sub-Saharan Africa experienced the most deterioration in their GFSI scores and notable increases in their GHI scores. The review documented the significant progress made by countries and regions in reducing levels of hunger and food insecurity, while highlighting the substantial burden borne by sub-Saharan Africa (SSA) in combating global hunger and food insecurity.

This article argues that philosophy and its influential narrative should take and think "food" - the gastro-world - in order to radically renew itself and develop a gastrocentric view of the world and the future of humanity. It discusses first some of the basic ideas of a gastrocentric understanding of the world, second the adventure of becoming a Terran, and third the daily practice of what I will call "terra madre forming". It tells us this: If there is to be a future of human survival and well-being on Earth, if we are to achieve the goals of sustainable development, then we have a clear agenda for tomorrow with the re-humidification of the soil - madre terra - that nourishes us. What needs to be done is quite simple and down-to-earth: We, each of us, if possible, must participate in the regeneration of the earth. In conclusion, it is time for the Slow Food movement to blossom into a geo-gastro-activism. The future task of this organization is to make itself electable as a political party to support the much-needed transformation of humans into Terrans.

The new unique technology for granulation of metals and nonmetallic melts is presented in the paper. It was created on the newly developed controlled film flow disintegration with rapid cooling of the droplets and solidified granules in amorphous state. Three new phenomena discovered by us created the base for 3 different methods for granulation of metals and nonmetallic melts in a wide range of granules’ sizes. Electromagnetic resonance method allows producing granules of metals in the range of 1 mm and over. The soliton-like vibrational regime is available for production of any granulation material in the range 0.1-1 mm. Moreover, the shockwave regime is applicable for producing particles from 10 micrometers by size. All methods produce particles of the stated size with a narrow distribution by size: deviation from the average size no more than 50%. The other known methods do not produce granules with such high cooling rate, which can realize the amorphous state and cannot regulate size of particles in such bright but narrow range from 10 micrometers to 1-2 mm.

Agricultural activities are the second largest source of greenhouse gas emissions, and carbon emissions from agricultural land use (CEALU) have become a hot issue across the world. However, few scholars explored the impact of agricultural land policies on carbon emissions, such as the High-standard farmland construction(HSFC) in China.Thus，by relying on provincial panel data for China for the period 2005-2017, the effect of the high-standard basic farmland construction policy on carbon emissions from agricultural land use per unit area and its regional differences were quantitatively analyzed using the difference-in-difference (DID) model. The results showed that: 1) China's CEALU per unit area presented a fluctuating upward trend during the period 2005-2017, from 392.58 kg/ha to 457.72 kg/ha, with an average annual growth rate of 1.31%. 2) The high-standard farmland construction(HSFC) policy produced a significant carbon emission reduction effect in agricultural land use, and reduced the CEALU per unit area by 10.80% on average. With the promotion of this policy, its carbon emission reduction effect in agricultural land use presented an overall increasing trend. 3) The carbon emission reduction effect of the high-standard farmland construction policy in agricultural land use was significant in central China, but non-significant in eastern China and western China.

In this work, satellite data from the Clouds and Earth’s Radiant Energy System (CERES) and Moderate Resolution Imaging Spectroradiometer (MODIS) instruments is analyzed to determine how the global absorbed sunlight and global entropy generation rate have changed during the time period from 2002 to 2023. The data is used to test hypotheses derived from the Maximum Power Principle (MPP) and Maximum Entropy Production Principle (MEP) about the evolution of earth’s surface and atmosphere. The results indicate that the amount of absorbed sunlight has increased over the last 20 years but rising surface temperatures have caused the entropy generation rate to remain approximately constant despite that decrease in albedo. The results are simpler to explain using the MPP but do not completely rule out the MEP. Given the acceptance of the MPP or MEP, some extensions and nuances are discussed.

This investigation mainly focused on the microstructural analysis of Al based hybrid metal matrix composites. Aluminium as base metal and reinforced with 2% B4 C, ZrO2 (2%,4%,6%), SiC (4%,8%,12%). Specimens were manufactured by using conventional stir casting technique. Hybrid metal matrix composites were examined by using Scanning electron microscope. This research explained XRD, EDS and Fractography analysis. This investigation shows the reinforced material has given better results in all aspects than pure Al6061 alloy and homogeneous dispersion of particles inside the matrix. Porosity, delamination, cracks, particle distributions were observed through microstructural analysis. Additionally determined the crystal size of pure Aluminium 6061 alloy and hybrid composites.

Photonic sensors are innovative devices that leverage the principles of light-matter interaction to enable precise and efficient detection of various physical parameters. These sensors operate by exploiting the interaction between photons, the fundamental particles of light, and matter. The light propagates through an optical waveguide, and a portion of the electromagnetic field extends beyond the waveguide surface, forming the evanescent field. This evanescent field interacts with the surrounding medium, allowing for highly sensitive detection of changes in the refractive index or properties of nearby substances. The underlying concept involves the modulation of light properties, such as intensity, wavelength, or phase, when it interacts with a target substance or undergoes changes in the surrounding environment. The advancements in photonic sensor technology have paved the way for enhanced sensitivity, selectivity, and miniaturization, making them invaluable tools in diverse industries. The ability to harness light-matter interactions for sensing purposes not only facilitates highly sensitive measurements but also allows for non-intrusive and remote monitoring, contributing to the evolution of smart and connected systems. In this overview, the material platforms and waveguide structures are explored that can make highly sensitive photonic devices applied to gas and biosensing applications.

Three-dimensional (3D) printing technology, also known as additive manufacturing (AM), has emerged as an attractive state-of-the-art tool for precisely fabricating functional materials with complex geometries, championing several advancements in tissue engineering, regenerative medicine, and therapeutics. However, this technology has an untapped potential for biotechnological applications, such as sensor and biosensor development. By exploring these avenues, the scope of 3D printing technology can be expanded and pave the way for groundbreaking innovations in the biotechnology field. Indeed, new printing materials and printers would offer new possibilities for seamlessly incorporating biological functionalities within the growing 3D scaffolds. Herein, we review the extrusion-based 3D printing modalities emphasizing biosensor applications. We highlighted the application of natural, synthetic, and composite biomaterials as 3D-printed soft hydrogels. Emphasis was placed on the approach by which the sensing molecules were introduced during the fabrication process. Finally, the future perspective was provided.

In this paper, we propose an imagined speech-based brain wave pattern recognition using deep learning. Multiple features were extracted concurrently from eight-channel Electroencephalography (EEG) signals. To obtain classifiable EEG data with fewer number of sensors, we placed the EEG sensors on carefully selected spots on the scalp. To decrease the dimensions and complexity of the EEG dataset and to avoid overfitting during the deep learning algorithm, we utilized the wavelet scattering transformation. A low-cost 8-channel EEG headset was used with MATLAB 2023a to acquire the EEG data. The Long-Short Term Memory Recurrent Neural Network (LSTM-RNN) was used to decode the identified EEG signals into four audio commands: Up, Down, Left, and Right. Wavelet scattering transformation was applied to extract the most stable features by passing the EEG dataset through a series of filtration processes. Filtration has been implemented for each individual command in the EEG datasets. The proposed imagined speech-based brain wave pattern recognition approach achieved a 92.50% overall classification accuracy. This accuracy is promising for designing a trustworthy imagined speech-based Brain-Computer Interface (BCI) future real-time systems. For better evaluation of the classification performance, other metrics were considered, and we obtained 92.74%, 92.50% and 92.62% for precision, recall, and F1-score, respectively.

This article analyzes the Franco-Spanish invasion of Vietnam from 1858 to 1860. Research is based on documents such as correspondence, reports, archives and diplomatic treaties as well as monographs from the time France intended to invade Vietnam through missionary activities until the end of the Franco-Spanish invasion. The article focuses on three basic issues that are the causes of the alliance, the evolution of the French and Spanish coalition invasion in Vietnam and its impact on stakeholders. The research results on the Franco-Spanish invasion of Vietnam indicated that the invasion carried out by this alliance was more special than that of the other French coalitions before. The invasion was based on an alliance without any commitment to the interests and responsibilities of the parties. The goals of France and Spain in this invasion were different. That led to conflict between France and Spain during the invasion and the fall of the alliance. France achieved its goal through an invasion that turned Vietnam into a colony, while Spain had barely achieved its desire to have commercial and missionary interests in the area.

In the paper the verification of forecasts of precipitation conditions measured by the standardized precipitation index SPI is presented. For the verification of categorical forecasts a contingency table was used. Standard verification measures were used for the SPI value forecast. The 30 day SPI moved every 10 days by 10 days was calculated in 2013-2015 from April to September on the basis of precipitation data from 35 meteorological stations in Poland. Predictions of the 30 day SPI were created in which precipitation was forecasted in the next 10 days (the SPI 10-day forecast) and 20 days (the SPI 20-day forecast). Both for the 10 and 20 days, the forecasts were skewed towards drier categories at the expense of wet categories. There was a good agreement between observed and 10-day forecast categories of precipitation. Less agreement is obtained for 20-day forecasts – these forecasts evidently “over-dry” the assessment of precipitation anomalies. The 10-day SPI value forecast accuracy is acceptable, whereas for the 20-day forecast is unsatisfactory. Both for the SPI categorical and the SPI value forecast, the 10-day SPI forecast is reliable and the 20-day forecast should be accepted with reservation and used with caution.

Finding a good MIMO system model also major issue in Wireless Communication system. It is facing with so many problem, one of the major problem is finding good system model in terms of capacity and transmitting antenna system. In this paper, we analyze the channel capacity of various MIMO system model with some constant SNR level and outage probability. We establish a novel idea for MIMO system models as consider as 2^N- MIMO system model and find-out change in channel capacity when different transmitting antennas with constant SNR and outage probability. The channel capacity ratio CC_R is presented here on the basis of 2^N- MIMO channel capacity model. Number of transmitted antenna presented in MIMO system is increases is well-known however paper shows change in capacity in simple form.

The aim of this study is to characterize the compound extremes of rainfall and temperature in Côte d’Ivoire. For this purpose, we analyzed the outputs of fourteen (14) climate models from the CORDEX-Africa project. Results show an increase (approximately 4.3°C) of the surface temperature and a decrease (5,90 %) of the mean rainfall in the near (2036-2065) and far futures (2071-2100) over Côte d’Ivoire during January-February-March (JFM) period. The analysis of the compound extremes of wet/warm type highlights an increase in the frequency of this climatic hazard in the northern and central parts of the country during January-March (JFM) season in the near and far futures. The dry/warm mode will increase in the central and southern parts of the country during the near future and in the whole country during the far future. These increase in compound extremes could lead to an increase in droughts and natural disasters over the country and could have a negative impact on socio-economic activities, such as transportation and agricultural production. This work could provide decision support for political decision-makers in formulating future public policies for managing agricultural production, food security, and natural disasters.

Toxicity mechanisms of per- and polyfluoroalkyl substances (PFAS), a chemical class present in diverse ecosystems, are not well characterized in aquatic species. Perfluorooctanesulfonamide (PFOSA, C8H2F17NO2S) is a common precursor of perfluorooctane sulfonic acid (PFOS), a long-chain PFAS. Here, we assessed sub-lethal endpoints related to development, oxidative stress, locomotor activity, and gene expression in zebrafish embryos and larvae following continuous exposure to PFOSA beginning at 6 hours post fertilization (hpf). PFOSA decreased survival in fish treated with 1 µg/L PFOSA, however the effect was modest relative to the controls (difference of 10%). Exposure up to 10 µg/L PFOSA did not affect hatch rate, nor did it induce reactive oxygen species in 7-day-old larvae fish. However, locomotor activity of larval fish treated with 100 µg/L PFOSA was reduced relative to the solvent control. Transcripts related to oxidative stress response and apoptosis were measured and BCL2 associated X, apoptosis regulator (bax), cytochrome c, somatic (cycs), catalase (cat), superoxide dismutase 2 (sod2) were induced with high concentrations of PFOSA. Genes related to neurotoxicity were also measured and transcript levels of acetylcholinesterase (ache), elav-like RNA binding protein 3 (elavl3), growth associated protein 43 (gap43), synapsin II (syn2a), and tubulin 3 (tubb3) levels were all increased in larval fish with higher PFOSA exposure. This study contributes to our knowledge regarding the relative toxicity of PFOSA to fish and contributes data to future risk assessment strategies of these concerning, persistent environmental pollutants.

Cellular senescence is the irreversible growth arrest subsequent to oncogenic mutations, DNA damage or metabolic insult. Senescence is associated with aging and chronic age associated diseases such as cardiovascular disease and diabetes. The involvement of cellular senescence in Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) is not fully understood however, recent studies suggest that such patients have a higher-than-normal level of cellular senescence and accelerated aging. This study aimed to discover key biomarkers of senescence in AKI and CKD patients compared to other chronic ageing diseases as controls. We show that senescence proteins CKAP4 and PTX3 are upregulated in AKI and CKD patients compared with controls with chronic diseases suggesting they may play in a role in overall kidney disease development. Additionally, CKAP4 was found to be differentially expressed in both AKI and CKD when compared to unhealthy controls hence this biomarker could be prognostic senescence biomarker of both AKI and CKD.

Synaptopodin 2-like protein (SYNPO2L) is localized in the sarcomere of cardiomyocytes and is involved in heart morphogenesis. However, the molecular function of SYNPO2L in the heart is not fully understood. We investigated the interaction of SYNPO2L with sarcomeric alpha-actinin and actin filaments in cultured mouse cardiomyocytes. Immunofluorescence studies showed that SYNPO2L colocalized with alpha-actinin and actin filaments at the Z-discs of the sarcomere. Recombinant SYNPO2La or SYNPO2Lb caused bundling of actin filaments in the absence of alpha-actinin and enhanced alpha-actinin-dependent formation of actin bundles. In addition, high-speed atomic force microscopy revealed that SYNPO2La directly bound to alpha-actinin via its globular ends. The interaction between alpha-actinin and SYNPO2La stabilized the two proteins on actin filaments. These results strongly suggest that SYNPO2L cooperates with alpha-actinin during actin bundle formation to facilitate sarcomere formation and maintenance.

The effect of ceria doping of (ZrO2)1-x(Sm2O3)x crystals on their phase composition, microhardness and fracture toughness has been studied. The (ZrO2)0.995-х(Sm2O3)х(СеО2)0.005 crystals (where x = 0.032, 0.037 and 0.04) have been grown using directional melt crystallization in cold skull. The phase composition and structure of the crystals have been studied using X-ray diffraction, TEM and Raman spectroscopy. The mechanical properties such as microhardness and fracture toughness have been studied using Vickers indentation. It has been shown that the (ZrO2)0.995-х(Sm2O3)х(СеО2)0.005 solid solution crystals contain both Се4+ and Се3+ ions. Phase analysis data suggest that СеО2 doping increases the tetragonality degree of the transformable t phase and reduces the tetragonality degree of the non-transformable t' phase as compared to the (ZrO2)1-x(Sm2O3)x crystals. As a result, the t→m phase transition triggered by the indentation-induced stress in the СеО2 doped crystals is more intense and covers greater regions. СеО2 doping of the solid solutions increases the fracture toughness of all the crystals studied whereas the microhardness of the crystals changes but slightly. СеО2 doping of the (ZrO2)1-х(Sm2O3)х solid solutions in the experimental concentration range does not improve the high-temperature phase stability of the crystals and does not prevent high-temperature degradation of their fracture toughness.

Abstract: Endoglin (ENG) is a causative gene of type 1 hereditary hemorrhagic telangiectasia (HHT1). HHT1 patients have arteriovenous malformations (AVMs) in multiple organs, including the brain. In mice, Eng deletion induced by R26RCreER or SM22aCre leads to AVM development in the brain and other organs. We have reported that the severity of brain AVM in mice with activin receptor-like kinase 1 (Alk1, an HHT2 causative gene) mutation is correlated with the number of Alk1 negative endothelial cells (ECs). We hypothesized that increase of Eng negative ECs will enhance AVM severity. To increase EC Eng deletion, we used a codon improved cre (icre), which is more potent in recombination of floxed alleles than the wild type (WT) cre. R26RCreER;Eng^f/f mice that have Rosa promoter driving and tamoxifen (TM) inducible WT cre expression globally and PdgfbiCreER;Eng^f/f that have Pdgfb promoter driving and TM inducible icre expression in ECs were treated with 3 intra-peritoneal injections of TM (2.5 mg/25g of body weight) to delete Eng globally or in the ECs. AAV-VEGF was stereotactically injected into the brain to induce brain focal angiogenesis and brain AVM. We found that iCre caused more Eng deletion in the brain indicated by lower level of Eng proteins (p<0.001) and fewer Eng positive ECs (p=0.01) than mice with WT cre. Mice with iCre mediated Eng deletion have more abnormal vessels (p=0.02), CD68⁺ macrophages (p=0.002), and hemorrhage (p=0.04), and less vascular pericyte and smooth muscle coverage than mice with WT cre. In addition, arteriovenous shunts were detected in the intestines of icre mice, a phenotype that have not been detected in WT cre mice before. RNAseq analysis showed that 8 out of the 10 top upregulated pathways identified by Gene Ontology (GO) analysis are related to the inflammation. Therefore, increase of Eng deletion in ECs exacerbates AVM severity, which is associated with enhanced inflammation. Strategies that can reduce Eng negative ECs could be used to develop new therapies to reduce AVM severity for HHT1 patients.

Abstract Octreotide is the first synthetic peptide hormone, consisted of eight amino acids, that mimics the activity of somatostatin, a natural hormone in the body. During the past decades, advanced instrumentation and crystallographic software established X-ray Powder Diffraction (XRPD) as a valuable tool for extracting structural information of biological macromolecules. The latter was demonstrated by the successful structural determination of octreotide at a remarkably high d-spacing resolution (1.87 Å) (PDB code: 6vc1). This study focuses on the response of octreotide to different humidity levels and temperatures, with a particular focus on the stability of the polycrystalline sample. XRPD measurements were accomplished employing an Anton Paar MHC-trans humidity-temperature chamber installed within a laboratory X’Pert Pro diffractometer (Malvern Panalytical). The chamber is employed to control and maintain precise humidity and temperature levels of samples during XRPD data collection. Pawley analysis of the collected data sets revealed that the octreotide polycrystalline sample is remarkably stable and no structural transitions were observed. The compound retains its orthorhombic symmetry (space group: P212121, a = 18.57744(4) Å, b = 30.17338(6) Å, c = 39.70590(9) Å, d~ 2.35 Å). However, a characteristic structural evolution in terms of lattice parameters and volume of the unit-cell is reported mainly upon controlled relative humidity variation. In addition, an improvement of signal-to-noise ratio in the XRPD data under a cycle of dehydration/rehydration is reported. These results underline the importance of considering the impact of environmental factors, as humidity and temperature, in the context of structure-based drug design, thereby contributing to the development of more effective and stable pharmaceutical products.

In the world's first pig-to-human cardiac xenotransplant, the elevated levels of porcine cytomeg-alovirus (PCMV) are considered key factors contributing to patient mortality. This has renewed attention to PCMV, a virus widely prevalent in pigs. Currently, there are no effective drugs or vaccines targeting PCMV, and its high detection difficulty poses challenges for prevention and control research. In this study, antiviral small hairpin RNA (shRNA) was selected and inserted into the Rosa26 and miR-17-92 loci of pigs via a CRISPR/Cas9-mediated knock-in strategy. Further in vitro viral challenge experiments demonstrated that these genetically edited pig cells could effec-tively limit PCMV replication. Through this process, we constructed a PCMV-infected cell model, validated partial viral interference sites, enhanced gene knock-in efficiency, performed gene editing at two different gene loci, and ultimately demonstrated that RNA interference (RNAi) technology combined with CRISPR/Cas9 has the potential to generate pig cells with enhanced antiviral infec-tion capabilities. This opens up possibilities for the future production of pig populations with anti-viral functionalities.

SARS-CoV-2 is the Coronavirus responsible for the COVID-19 pandemic. Even though we are no more in a pandemic situation, people are getting infected some of them needing hospitalization, and a few of them die. Methods: We did a retrospective study including 445 patients who accessed the Emergency Section of Policlinico Umberto I, Rome, Italy, where they had routine blood exams. In this study, we concentrated on the complete blood count, creatinine, and azotemia. The data was analyzed using ANOVA, Spearman correlation, and ROC analysis. They were divided into four groups based on their outcome: (1) the emergency group (patients with mild forms who were quickly discharged); (2) the hospital ward group (patients who after admission to the emergency section were hospitalized in a COVID-19 ward); (3) the intensive care unit (ICU) group (patients that after the admission in the emergency section required intensive assistance); (4) the deceased group (patients that after the admission in the emergency section had a fatal outcome). Results: We found significant changes for creatinine, azotemia, hematocrit, mean corpuscular hemoglobin concentration, basophils, monocytes, red blood cell distribution width, hemoglobin, hematocrit, and red blood cell numbers by ANOVA according to their outcomes, particularly for the deceased group. Also, we found outcome correlations for eosinophils, hemoglobin, hematocrit, mean corpuscular hemoglobin concentration, lymphocyte, neutrophil, platelet, and red blood cell number and red blood cell distribution width. Conclusions: This study discloses an association between “classical” routine blood biomarkers and the severity of outcomes in Omicron patients.

This research presents a novel methodology for classifying MRI images into two categories: tumor and non-tumor. The study utilizes a combination of two advanced Convolutional Neural Network (CNN) architectures, VGG16 and ResNet50, to address the challenges in analyzing the complexity and variability of brain MRI scans. The approach begins with a comprehensive preprocessing phase, where the MRI images are enhanced through techniques such as resizing, grayscale conversion, Gaussian blurring, and brain area isolation. Central to the approach is the application of the Multi-verse Optimizer (MVO), a metaheuristic algorithm inspired by theories of the multi-verse in physics. The MVO is utilized to optimize the parameters for data augmentation and to fine-tune the combination of trainable layers within the VGG16 and ResNet50 models. The results of this study indicate a high level of effectiveness of the combined CNN models, significantly enhanced by the MVO, in classifying MRI images. These models show marked improvements in accuracy, precision, and recall, underscoring their potential utility in enhancing brain tumor diagnosis. The paper concludes with an analysis of these findings, emphasizing the importance of this approach in medical imaging and suggesting potential avenues for future research in the area of automated MRI classification.

Microplastics (MP), defined as plastic particles less than 5 mm, pose a significant global environmental threat, particularly in aquatic ecosystems, due to their persistence and potential harmful effects on wildlife and human health. They can absorb persistent organic pollutants (POP) like polycyclic aromatic hydrocarbons (PAH) and polychlorinated biphenyls (PCB), raising concerns about their impact on biota. To elucidate this, the present study employed attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) to analyse the characteristics of MP sourced from commercial cosmetics. It also utilised nematodes, which are widely accepted indicators of environmental change. Indeed, despite the known risks of MP in aquatic habitats, knowledge of their effects on free-living and beneficial nematodes is limited. This study investigated the toxicity of MP on Caenorhabditis elegans and two entomopathogenic nematode species, Steinernema feltiae (the enviroCORE strain SB12[1]) and Steinernema carpocapsae (a commercial strain from e-NEMA) in laboratory bioassays. Nematodes were exposed to various concentrations of MP and other pollutants in controlled settings over 72 to 96 hours. Additionally, high-throughput 18S rDNA sequencing was used to analyse nematode biodiversity in sediments from the River Barrow (RB) in SE Ireland. Results revealed that MP adversely affected nematode survival and community structure, highlighting the ecological risks posed by MP pollution in river sediments and emphasizing the need for further research into the health of benthic ecosystems in Ireland.

Background/Objective: Women treated with large loop excision of the transformation zone (LLETZ) for cervical intraepithelial neoplasia 2-3 (CIN2+) remain at CIN2+ risk for many years. We assessed the role of high-risk human papillomavirus (HR-HPV), surgical margins, and LLETZ characteristics in long-term risk of CIN2+. Methods: A retrospective observational study was performed on 432 women with histological diagnosis of CIN2+ who were treated with LLETZ from 1996 to 2020 and followed-up until October 2021 at Hospital Bellvitge in Barcelona, Spain. Age, surgical margins, 6-month HR-HPV, excision type, and cone volume/dimensions were ana-lyzed in association with follow-up detection of CIN2+. The cumulative probability of follow-up detection of CIN2+ was calculated by Kaplan-Meier and Cox models. Results: CIN2+ was detected in 7.4% of cases, with over 90% found within 5 years post-LLETZ. HR-HPV (HR = 7.36, 95% CI = 3.55-15.26), involved margins (HR = 3.94, 95% CI = 1.68-9.25), uncertain margins (HR = 4.42, 95% CI = 1.55-12.55), and age ≥ 35 years (HR = 2.92, 95% CI = 1.19-7.13) were predictors of follow-up detection of CIN2+. Type 3 excision (p-value = 0.035) and cone length (p-value = 0.010) correlated with clear margins. The negative predictive value (NPV) of both negative HR-HPV post-LLETZ and clear margins was 98.7%. Conclusions: Negative HR-HPV post-LLETZ and clear margins provide stronger reassurance against follow-up detection of CIN2+ than LLETZ characteristics. Larger ex-cisions in older women likely reduced the risk of involved margins. Close surveillance, including repeated HR-HPV testing within the first 5 years post-LLETZ, is crucial.

Background: This study aims to investigate the influence of Body Mass Index (BMI) on the doses received by organs at risk (OAR) during high-dose-rate (HDR) vaginal cuff brachytherapy in pa-tients diagnosed with early-stage endometrial carcinoma. Understanding the relationship be-tween BMI and OAR doses could enhance treatment planning and minimize complications. Methods: We collected brachytherapy data for 242 endometrial cancer patients treated with ad-juvant HDR vaginal cuff brachytherapy. The patients were categorized based on their BMI into normal weight, overweight, and obese groups. Dosimetric data were collected for OARs, includ-ing the bladder, rectum, and sigmoid colon and also for dose fractionation, D90 and the active length of the brachytherapy cylinder. The analysis included comparing the doses received by each organ across different BMI categories using appropriate statistical methods Results: Preliminary findings indicated a significant variation in the doses to OARs correlating with BMI classifications. Obese patients exhibited slightly higher mean doses to the rectum and bladder compared to those with a normal BMI. The statistical analysis demonstrated that as BMI increased, the dose to these organs at risk also tended to increase, suggesting a need for ad-justed treatment planning strategies in this population. Conclusions: Obesity is a key concern in endometrial cancer patients, with higher BMI linked to slightly increased doses to the rectum and sigmoid, though treatment remained homogeneously delivered.Future work should focus on refining dosimetric techniques and exploring strategies to mitigate OAR exposure in patients with higher BMI.

Cervical cancer (CC) remains a significant health issue, especially in low- and middle-income countries (LMICs). While Pap smears are the standard screening method, they have limitations like low sensitivity and subjective interpretation. Liquid-based cytology (LBC) offers improvements but still relies on manual analysis. This study explored the potential of deep learning (DL) for automated cervical cell classification using both Pap smears and LBC samples. A novel image segmentation algorithm was employed to extract single-cell patches for training a ResNet-50 model.The model trained on LBC images achieved remarkably high sensitivity (0.998), specificity (0.997), and accuracy (0.997), outperforming previous CNN models. However, the Pap smear dataset model achieved significantly lower performance (0.694 sensitivity, 0.838 specificity, 0.834 accuracy). This suggests that noisy and poor cell definition in Pap smears pose challenges for automated classification, whereas LBC provides better classifiable cells patches. These findings demonstrate the potential of AI-powered cervical cell classification for improving CC screening, particularly with LBC. The high accuracy and efficiency of DL models combined with effective segmentation can contribute to earlier detection and more timely intervention. Future research should focus on implementing explainable AI models to increase clinician trust and facilitate the adoption of AI-assisted CC screening in LMICs.

In Morocco, cervical cancer is the second most frequent cancer among women and the third in terms of mortality. The Moroccan Health Ministry introduced the Human Papillomavirus vaccine to the national immunization program in October 2022.The study aims to evaluate the knowledge, the satisfaction level, and acceptability of HPV infection and vaccine among Moroccan medical students. We conducted a cross-sectional study from September 2021 to July 2022 among medical students above 5th year across the nine Moroccan medical universities. We shared our questionnaire through Google Forms. The descriptive data analysis was made through Google Forms and excel, and the analytic analysis was made using GraphPad Prism 8.0. We collected 636 answers. The mean age was 24.2 +/- 1.4 years old with a sex ratio (M/F) of 0.5. 3.3% (N=21) were vaccinated against HPV. The HPV infection knowledge mean score was 6.3 +/- 2 /11 (57.2% of good answers) and the vaccine knowledge mean score was 2.0 +/- 1,1 /5 (40% of good answers), with a training satisfaction rate of 7.3 +/- 2.6 /20 (36.5%). 85.8% of the participants (N= 546) were in favor of including the vaccine to the national immunization program. In conclusion, overall Moroccan medical students have an average knowledge of HPV infection and vaccine. The gap in HPV training should be filled especially in the era of the vaccine introduction. The majority of the students agree to make the vaccine mandatory, with superior rates than the other studies.

The accurate detection and assessment of stress play a pivotal role in enhancing individual well-being and healthcare outcomes. Traditional methods of stress detection often grapple with limitations in accuracy and scalability. With the advent of machine learning (ML), the potential to revolutionize stress detection has emerged. This paper presents a comprehensive study on the application of ML algorithms for stress detection, with a focus on physiological and behavioral data analysis. Central to our approach is the integration of SHapley Additive exPlanations (SHAP), an Explainable Artificial Intelligence (XAI) technique, to interpret ML models. SHAP provides a novel lens to understand the impact of individual features in the complex decision-making processes of ML models, thereby enhancing the transparency and reliability of stress predictions. We demonstrate how SHAP not only aids in elucidating model decisions but also contributes to refining the models for greater accuracy. Our results highlight the effectiveness of ML in detecting stress and the pivotal role of XAI in making these models more interpretable and trustworthy. This study underscores the synergy between advanced ML techniques and XAI, paving the way for more nuanced and reliable stress detection methodologies that are essential in diverse settings, from healthcare to workplace environments.

The evaluation of landslide hazard in seismic areas is based on a deterministic analysis to define the stability of the sites. However, deterministic analysis is not able to consider various uncertainties in the analysis process. This paper focuses on the results established by the probabilistic seismic hazard analysis and extends the probabilistic landslide hazard analysis to consider the uncertainties of opposing ground deformations and strength. The work studies the areas between Nibbiano and Sant'Erasmo inhabited centres in the Camerino municipality located in central Italy. The current state of the areas shows dangerous conditions for the building structures. In fact, all constructions present evidence of damage caused by both the 2016 earthquake and slope instability. The studies, carried out through careful geological survey and detailed geophysical investigations, are performed to define the geological, geomorphological and hydrogeological characteristics of the areas and also to run a new analysis aimed to define the material stress-strain behavior. Both inhabited Centers are located on debris deposits with highly variable thicknesses. The key point regards the definition of the depth of unstable mass, its position and its extension. Therefore, this contribution aims to summarize the knowledge of the landslide phenomenon that affected the area, trying to interpret its evolution with new field investigations. Indeed, during the first step, related to the geological and geomorphological detailed surveys, a remarkable geological model was obtained to better interpret the slope dynamics in relation to the structures of this section of the ridge. This model was also confirmed by the geophysical investigations. The study involves a more detailed definition of the landslide perimeter. Indeed, to analyze the phenomenon, it was necessary to study both the local seismic amplification with finite element 2D simulations and the slope stability conditions with finite 3D difference simulation.

Nanostructured polymer dispersed liquid crystals (nano-PDLCs) are transparent and optically isotropic materials, in which submicron-sized liquid crystal (LC) domains are dispersed within a polymer matrix. Nano-PDLCs can induce their birefringence by applying an electric field (E-field) based on reorientation of LC molecules. If nano-PDLCs are utilized as light scattering-less birefringence memory materials, it is necessary to suppress the relaxation of LC molecules orientation after removal of the E-field. We focused on a ferroelectric smectic A (SmA) to suppress the relaxation of LC molecules due to their layered structure and high viscosity. Although nano-PDLCs require a strong E-field to reorient LC molecules due to the anchoring effect on the LC/polymer interface, the required field strength can be reduced by using a ferroelectric smectic A (SmAF) LC with a large dielectric constant. In this study, we fabricated a nano-PDLC by irradiating an ultraviolet light to a mixture comprising of a SmAF LC, photocurable monomers and a photo-initiator and its electro-birefringence effect was evaluated using a polarizing optical microscopy. After removal of an E-field, enhanced memory effect was observed on the sample using SmAFLC comparing to nematic LC based nano-PDLCs. (193 words/ 200 words)

Freeze drying (FD) is a technique used to preserve the bioactive content and flavor of samples. Foods with a short shelf life due to nature have been preserved by FD in recent years. The success of the drying technique is thanks to the high retention ability of the bioactive compounds and the flavor of the sample. However, the high cost and energy consumption of the FD limit its usage in several fields. Freezing, primary drying, and secondary drying, which take place in the same device, are the stages of the FD. In addition, several parameters, including pretreatment, size, temperature, sample species, time, and pressure, affect the FD process. These parameters are controlled to increase the effectiveness of the FD on the samples. Moreover, FD was compared with other drying techniques including hot-air drying, microwave drying, vacuum drying, and solar drying to determine its protective capability. It has also been applied to the valorization of waste products, which is a common problem worldwide. For valorization, microencapsulation and powder production have been achieved by FD. In recent years, studies on the effects and use of the FD on various materials increased, providing new aspects for the future of science and food industry.