The increasing concern regarding climate change continues to motivate research in the Arctic. Within the delicate cycle of the cryosphere, leads are an important kinematic feature that regulates heat balances and gaseous exchanges in the Arctic. Therefore, it is necessary to quantify the genesis of leads over time to identify when and where changes are occurring. The use of learning techniques is one such tool that is used to identify the characteristics of seasonal ice variability. This paper utilizes the Sentinel-1 RADAR imagery with a support vector machine learning scheme through Google Earth Engine to classify lead types in the Beaufort Sea.

Small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) have recently been grouped as lung neuroendocrine carcinomas (NECs). Because these lung NECs are clinically malignant and their treatment strategies differ from those of non-SCLC, the quality of diagnosis has a significant prognostic impact. The diagnosis of LCNEC requires positive immunohistochemical staining with chromogranin A, synaptophysin, and CD56, along with morphological diagnosis, and insulinoma-associated protein 1 (INSM1) has been proposed as an additional marker but sometimes experience difficulty in making the diagnosis. We investigated Musashi-1 as a novel immunohistochemical marker in 42 patients with SCLCs and 44 with LCNECs who underwent lung resection between 1998 and 2020 at our institution. We found Musashi-1 expression in 41 (98%) of 42 SCLCs and 40 (90%) of 44 LCNECs. These findings were similar to CD56 expression and superior to synaptophysin, chromogranin A, and INSM1. Musashi-1 also tended to show more diffuse and intense staining, especially in LCNEC, with more cases staining >10% than any other existing markers (Musashi-1, 77%; INSM1, 45%; chromogranin A, 34%; synaptophysin, 41%; and CD56, 66%). In conclusion, we identified Musashi-1 as a novel immunohistochemical staining marker to aid in the diagnosis of lung NEC.

Background: Implantation of an endovascular device disrupts the homeostatic CD31:CD31 interactions among quiescent endothelial cells, platelets, and circulating leukocytes. The aim of this study was to mask endovascu-lar stents with peptides imitating CD31, to mimic the device's surface to resemble that of a healthy vascular endothelium. Methods: Peptide design relied on established trans-homophilic sequences found within domains 1 and 2 of CD31. Subsequently, synthetic peptides were immobilized onto flat CoCr and nitinol discs and their impact on the primary human arterial endothelial cell phenotype was evaluated in vitro. Following this, clinical-grade CoCr and nitinol endovascular devices were coated with one of the peptides that demonstrated the capability to induce a pro-physiologic endothelial phenotype, implanted in the arteries of rabbits, and compared to un-coated controls. Results: Membrane-distal CD31 domains 1 and 2 peptides exhibited a distinct capability to foster a healthy endothelial phenotype in vitro. By day 7 post-aortic implantation, CoCr stents were evenly covered by whole-some endothelial cells, devoid of thrombo-inflammatory signs, in contrast to both bare metal and drug-eluting stents. At day 60, nitinol-coated flow diverters demonstrated enhanced performance in comparison to the control groups for excluding experimental carotid aneurysms, facilitating the formation of a seamless "neo-arterial" wall. Conclusion: Membrane-distal CD31 biomimetic peptides effectively camouflage the device surface, prevent-ing local reactions and promoting rapid and seamless endovascular integration.

Phosphorus (P) is an essential plant macronutrient; however, its availability is often limited in soils. Plants have evolved complex mechanisms for efficient phosphate (Pi) absorption, which are responsive to changes in external and internal Pi concentration, and orchestrated through local and systemic responses. To explore these systemic Pi responses, here, we identified AtMYB44 as a phloem-mobile mRNA, an Arabidopsis homolog of Cucumis sativus MYB44, that is responsive to the Pi-starvation stress. qRT-PCR assays revealed that AtMYB44 was up-regulated and expressed in both shoot and root in response to Pi-starvation stress. The atmyb44 mutant displayed higher shoot and root biomass, compared to wild-type plants, under Pi-starvation conditions. Interestingly, the expression of PHOSPHATE TRANSPORTER1;2 (PHT1;2) and PHT1;4 was enhanced in atmyb44 in response to a Pi-starvation treatment. A split-root assay showed that AtMYB44 expression was systemically regulated, under Pi-starvation conditions and, in atmyb44, systemic controls on PHT1;2 and PHT1;4 expression were moderately disrupted. Heterografting assays confirmed graft transmission of AtMYB44 transcripts, and PHT1;2 and PHT1;4 expression was decreased in heterografted atmyb44 rootstocks. Taken together, our findings support the hypothesis that mobile AtMYB44 mRNA serves as a long-distance Pi response signal, which negatively regulates Pi transport and utilization in Arabidopsis.

Irrigation is one of key agricultural management practices of crop cultivation in the world. Irrigation practice is traceable on satellite image. Most irrigated area mapping methods were developed based on time series of NDVI or back scatter coefficient within the growing season. However, it found the winter irrigation out of growing season is also dominating in north China. This kind of irrigation aims to increase the soil moisture for coping with spring drought, and also reduce the wind erosion with the wet soil in the field surface as the strong wind happens in spring. This study developed a remote sensing-based classification approach to identify irrigated fields with Radom Forest algorithm out of growing season. The results showed that the mean of the highest accuracies of 7 RF models was 94.9% and the mean of the averaged accuracies of 7 RF models was 94.1%; the overall accuracy for all 7 outputs was in the range of 86.8-92.5%, Kappa in the range of 84.0-91.0% and F-1 score in the range of 82.1-90.1%. These results showed that the classification was acceptable and not over performed as the accuracies of all classified images were lower than the models. This study also found that irrigation started to apply in early November and irrigated fields were increased and suspended in December and January due to freeze. The newly irrigated fields were found again in March and April when the temperature goes up above zero degree. The area of irrigated fields in the study area were increasing over time with sizes of 98.6, 166.9, 208.0, 292.8, 538.0, 623.1, 653.8 km2 from December to April, accounting for 6.1%, 10.4%, 12.9%, 18.2%, 33.4%, 38.7%, and 40.6% of the total irrigatable land in the study area, respectively.

The restriction of normal blood flow is the cause of many diseases including stroke and coronary artery diseases. To study the consequences of vessel blockade, previous models mainly focused on major arteries and have been well studied. However, the sequela from interruption of capillary vessels by microemboli was less well characterized. In this study, we exploited polystyrene microspheres as a mimicry of microemboli and found that microspheres of this size can be trapped in capillary vessels of all organs without causing apparent acute morbidities of the host. Interestingly, we accidentally found significantly increased recruitment of monocyte to the brain vasculature expressing low levels of Ly6C expression, but not to other organs. Further study revealed the spleen is the major origin of the recruited monocyte. Most importantly, VCAM-1 which is constitutively expressed on mouse brain vasculature orchestrates the recruitment of monocyte. Blockade of VCAM-1 in mice can substantially reduce monocyte recruitment. Interestingly, monocytes get activated through TNF- signaling which likely happens in the spleen instead of the brain. Collectively, we found a unique monocyte recruitment strategy in the brain comparing to other orangs, in response to capillary blockade induced by polystyrene microspheres.

Vessel co-option correlates with resistance against anti-angiogenic agents and chemotherapy in colorectal cancer liver metastasis (CRCLM). We previously identified higher intensity of neutrophils in the tumour microenvironment of vessel co-opting CRCLM lesions compared to their angiogenic counterparts. Herein, we demonstrated that over 50% of the neutrophils in vessel co-opting lesions are expressing pro-apoptotic markers including cleaved caspase-3 and poly (ADP-ribose) polymerase-1 (PARP-1). Our previous publications suggested upregulation of transforming growth factor-beta (TGFβ1) in the microenvironment of vessel co-option CRCLM. Therefore, we examined the effect of TGFβ1 on the expression of cleaved caspase-3 and PARP-1 in neutrophils in vitro. Significantly, we noticed the upregulation of pro-apoptotic markers upon exposure to TGFβ1. This finding might pave the way to determine the role of neutrophils in developing vessel co-option in CRCLM in the future.

Introduction Currently, the increase in the percentage of obese people observed along with the development of civilization, reaching the level of a global pandemic, has forced the search for methods of effective and permanent obesity treatment. Obesity is a multifactorial disease, it coexists with many disease entities and requires multidisciplinary treatment. Obesity leads to metabolic changes in the form of metabolic syndrome, which includes, among others, atherogenic dyslipidemia. The proven relationship between dyslipidemia and cardiovascular risk enforces the need to effectively improve the lipid profile of obese patients. Laparoscopic sleeve gastrectomy is a method of surgical treatment of morbid obesity which improves bariatric and metabolic parameters. The aim of the study was to assess the effectiveness of laparoscopic sleeve gastrectomy (LSG) in improving lipid profile parameters in 1-year follow-up. Material and Methods Bariatric parameters of 196 patients who underwent laparoscopic sleeve gastrectomy as well as lipid profile of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-NDL, and triglycerides (TG) in 1-year observation were analyzed. Results Improvements in bariatric parameters were observed in patients after LSG. Total cholesterol, low-density lipoprotein (LDL), triglycerides and non-HDL levels decrease were observed along with the increase of high-density lipoprotein (HDL) cholesterol level. Conclusions Sleeve gastrectomy is an effective method of treating obesity and improving the lipid profile in obese patients.

The human immunodeficiency virus 1 (HIV-1) viral protease (PR) is one of the most studied viral enzymes, and approval of drugs targeting its catalytic activity opened the door to the develop-ment of highly active antiretroviral therapy (HAART). Despite the fact that its crucial role in viri-on maturation is well characterized, an increasing body of research is starting to focus on its abil-ity to cleave host cell proteins, based on recent advances in proteomics and genomics technologies. Such findings are apparently in contrast with the dogma of HIV-1 PR activity being restricted to the interior of nascent virions, and suggest catalytic activity within the host cell environment. Given the limited amount of PR present in the virion at the time of infection, it is tempting to specu-late that such events mainly occur during viral late gene expression, mediated by newly synthe-sized Gag-Pol polyprotein precursors, rather than at a very early stage of infection, before pro-viral integration. Among cellular targets of HIV-1 PR, three major clusters can be identified: pro-teins involved in viral and cellular translation, those controlling cell survival, and restriction fac-tors responsible for innate/intrinsic antiviral responses. Indeed, by cleaving host cell translation initiation factors HIV-1 PR can impair cap-dependent translation, thus promoting IRES-mediated translation of late viral transcripts and viral production, while by targeting several apoptotic fac-tors it modulates cell survival, thus promoting immune evasion and viral dissemination. Addi-tionally, HIV-1 PR counteracts restriction factors incorporated in the virion that would otherwise interfere with nascent virus vitality. Thus, HIV-1 PR appears to modulate host cell function at dif-ferent times and locations during its life cycle, to ensure efficient viral persistency and propaga-tion. This kind of PR-mediated host cell modulation is found in a plethora of different viruses and HIV-1 is no exception, and although we are far from having a complete picture, it is clear that the PR has a multifaceted role in interfering with host machineries to better suit viral replication, and is a field that needs to be explored further.

N-of-1 data are unavoidable in zoological medicine. Accordingly, zoological medicine clinicians and investigators need research techniques that can make use of these data. This article reviews two methodologies for using both observational and experimental N-of-1 data: 1) systematic reviews and meta-analyses of case reports and 2) prospective N-of-1 trials. Systematic reviews of case reports and other observational evidence are formal, unbiased summaries of clinical characteristics of a particular disease-taxon combination. They offer advantages to narrative reviews by minimizing omission of relevant articles, thereby reducing the potential for mischaracterization of the literature. Meta-analyses are extensions of systematic reviews that quantitatively synthesize the data from the included articles. While valuable, systematic reviews and meta-analyses of case reports can have limited interpretations due to publication bias and confounding present in their source materials. In contrast to case reports, N-of-1 trials are prospective study designs that allow clinicians to make strong inferences about the effect of an intervention in a particular patient. They are double-blinded, single patient, multi-crossover studies that are of particular value in fields where it is difficult to recruit sufficient patients for conventional randomized control trials (RCTs), such as zoological medicine. Because they require multiple crossover periods, N-of-1 trials are ideal for evaluating short-acting interventions in patients with somewhat stable chronic diseases, such as osteoarthritis. More complex than conventional therapeutic trials, N-of-1 trials require prior consideration of how to achieve blinding, appropriate placebo controls, quantitative primary outcomes, analysis methods, and ethical approval. Aggregation of N-of-1 trials allows estimation of the average treatment effect across the population with fewer participants than a conventional RCT. While systematic reviews and meta-analyses of case reports can be used to synthesize the observational N-of-1 data already in existence, N-of-1 trials offer an exciting way to prospectively generate strong evidence that will be useful for evidence-based decision-making.

Obesity is characterized by chronic low-grade inflammation. Caveolin-1 (CAV1), a structural and functional protein found in adipose tissues (AT), is augmented in obese individuals. We aimed to define the inflammatory mediators that influence CAV1 gene regulation and associated mechanism in obesity. Using subcutaneous AT from 27 (7 lean/20 obese) normoglycemic individuals, in vitro human adipocyte models, and in vivo mice models, we found elevated CAV1 expression in obese AT and a positive correlation between the gene expression of CAV1, tumor necrosis factor alpha (TNF-α), and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). CAV1 gene expression was associated with that of proinflammatory cytokines/chemokines, and their cognate receptor (r ≥ 0.447, p ≤ 0.030) but not with anti-inflammatory markers. CAV1 expression was correlated with CD163, indicating a prospective role for CAV1 in adipose inflammatory microenvironment. Unlike wild-type animals, mice lacking TNF-α exhibited reduced levels of CAV1 mRNA/proteins, which were elevated by administering exogenous TNF-α. Mechanistically, TNF-α induces CAV1 gene transcription by mediating NF-kB binding to its two regulatory elements located in the CAV1 proximal regulatory region. The interplay between CAV1 and TNF-α signaling pathway is interesting and has potential as a target for therapeutic interventions in obesity and metabolic syndromes.

Objective: Type I interferon receptor (IFNAR) signaling contributes to several autoimmune and vascular diseases such as atherosclerosis and stroke. The purpose of this study was to assess the influence of IFNAR1 deficiency on the formation and progression of experimental abdominal aortic aneurysms (AAAs). Methods: AAAs were induced in type I interferon receptor subunit 1 (IFNAR1) deficient and wild type control male mice via intra-infrarenal aortic infusion of porcine pancreatic elastase. Immunostaining for IFNAR1 was evaluated in experimental and clinical aneurysms. The initiation and progression of experimental AAAs was assessed via ultrasound imaging prior to (day 0) and 3-, 7-, and 14-days following elastase infusion. Aneurysmal histopathology was analyzed at sacrifice. Results: Increased aortic medial and adventitial IFNAR1 expression was present in both clinical AAAs harvested at surgery and experimental AAAs. Following AAA initiation, wild type mice experienced progressive, time-dependent infrarenal aortic enlargement. This progression was substantially attenuated in IFNAR1 deficient mice. On histological analyses, medial elastin degradation, smooth muscle cell depletion, leukocyte accumulation and neoangiogenesis were markedly diminished in IFNAR1 deficient as compared to wild type mice. Conclusion: IFNAR1 deficiency limited experimental AAA progression in response to intra-aortic elastase infusion. Combined with clinical observations, these results suggest a regulatory role for IFNAR1 activity in AAA pathogenesis.

In this study, a structural profiling of equid alphaherpesvirus 1 (EHV-1) transcriptome was carried out using next-generation (Illumina) and third-generation (Oxford Nanopore Technologies) sequencing platforms. We annotated the canonical mRNA molecules and their isoforms, including transcript start and end site isoforms, and splice variants. Additionally, a number of putative 5′-truncated mRNAs containing shorter in-frame ORFs were detected. We also demonstrated that EHV-1 produces a high number of non-coding transcripts, including antisense and intergenic RNAs. One of the most remarkable features of the EHV-1 is the generation of abundant fusion transcripts some of which encoding chimeric polypeptides. We observed a higher number of splicing and transcriptional overlaps than in related viruses. Additionally, we found that many upstream genes of tandem gene clusters have their own transcript end sites (TESs) besides the co-terminal TESs, which is rare in other alphaherpesviruses. We show here that the replication origins (OriS and OriL) of the virus are co-localized with promoter sequences and overlap with specific RNA molecules. Furthermore, we discovered a novel non-coding RNA (designated as NOIR) that overlaps the 5′-ends of the longer transcript variants encoded by the two main transactivator genes ORF64 and 65 bracketing the OriL. These all suggest the existence of a central regulatory system which controls the genome-wide transcription and the replication through a mechanism based on the interference between the machineries carrying out the synthesis of DNA and RNA.

Like 18F-FDG, 99mTc-1-thio-D-glucose (99mTc-TG) also binds to GLUT receptors. The aim of this Phase I study was to evaluate the safety, biodistribution and dosimetry of 99mTc-TG. Twelve lym-phoma patients were injected with 729±102 MBq 99mTc-TG. Whole-body planar imaging was per-formed in 10 patients at 2, 4, 6 and 24 h after injection. In all 12 patients SPECT/CT (at 2 h) and SPECT (at 4 and 6 h) imaging was performed. Vital signs and possible side effects were monitored during imaging and up to 7 days after injection. 99mTc-TG injections were well tolerated and no side effects or alterations in blood and urine analyses data were observed. The highest absorbed dose was in the kidneys and urinary bladder wall, followed by the adrenals, prostate, bone mar-row, lungs, myocardium, ovaries, uterus, liver and gall bladder wall. 99mTc-TG SPECT/CT re-vealed foci of high activity uptake in the lymph nodes of all nine patients with known nodal le-sions. Extranodal lesions were detected in all nine cases. In one patient, a lesion in the humerus head, which was not detected by CT, was visualized using 99mTc-TG. Potentially, 99mTc-TG SPECT can be considered as an additional diagnostic method for imaging GLUT receptors in lymphoma patients.

Crescentic glomerulonephritis is a devastating autoimmune disease that without early and properly treat-ment may rapidly progress to end-stage renal disease and death. Current immunosuppressive treatment provided limited efficacy and an important burden of adverse events. Epigenetic drugs are a source of novel therapeutic tools. Among them, bromodomain and extraterminal domain (BET) inhibitors (iBETs) block the interaction between bromodomains and acetylated proteins, including histones and transcription factors. iBETs have demonstrated protective effects on malignancy, inflammatory conditions and experi-mental kidney disease. Recently, Gremlin-1 was proposed as a urinary biomarker of disease progression in human anti-neutrophil cytoplasmic antibody (ANCA)-associated crescentic glomerulonephritis. We have now evaluated whether iBETs regulate Gremlin-1 in experimental anti-glomerular basement membrane nephritis induced by nephrotoxic serum (NTS) in mice, a model of human crescentic glomerulonephritis. In NTS-injected mice, the iBET JQ1 inhibited renal Gremlin-1 overexpression and diminished glomerular damage, including podocyte loss. Chromatin immunoprecipitation assay demonstrated BRD4 enrichment of the Grem-1 gene promoter in injured kidneys, consistent with Gremlin-1 epigenetic regulation. Moreover, JQ1 blocked BRD4 binding and inhibited Grem-1 gene transcription. The beneficial effect of iBETs was also mediated by targeting NOTCH signaling pathway. JQ1 inhibited the gene expression of the NOTCH effec-tors Hes-1 and Hey-1 in NTS-injured kidneys. Our results further support the role for epigenetic drugs, such as iBETs, in the treatment of rapidly progressive crescentic glomerulonephritis.

Phase synchronization is one of the key issues that must be addressed in the bistatic synthetic aperture radar (BiSAR) system. LuTan-1 is an innovative L-band spaceborne BiSAR mission of China. An advanced synchronization scheme is used in the LuTan-1 system. The synchronization pulses are exchanged immediately after the ending time of the radar echo receiving window and before the starting time of the next pulse repetition interval. Therefore, it can not interrupt the normal SAR data acquisition, further improving synchronization frequency and avoiding the data missing effect. In order to accurately monitor system malfunctions and compensate for the phase synchronization errors introduced by hardware system, an innovative internal calibration strategy is designed and employed in the LuTan-1 mission. The test data acquired from the ground validation system of LuTan-1 are used to demonstrate the feasibility of the proposed scheme. The results validate the effectiveness of the proposed scheme and prove the promise for its future application in LuTan-1.

Introduction: Increased oxidative stress, including elevated homocysteine (Hcy) plasma levels, and lowered levels of antioxidants participate in the pathophysiology and progression of chronic kidney disease (CKD). Paraoxonase (PON)1 activity and folic acid are antioxidants which play a role in Hcy metabolism. However, there are no data whether, in CKD, treatment with folic acid improves glomerular filtration rate (GFR) through effects on PON1 activity and Hcy concentrations. Methods: In the current study, we determined PON1 genotypes and activity, Hcy and estimated GFR (eGFR) both before and after treatment with folic acid (5 mg/d) versus no treatment during three consecutive months in 113 outpatients with CKD classified into stages 4, 3b and 3a. Results: PON1 CMPAase and AREase activities were significantly lower in patients allocated to CKD stage 4 as compared with stages 3b and 3a. Treatment with folic acid significantly improved eGFR and increased levels of CMPAase and AREase in patients allocated to classes 4 and 3b, but not 3a. The improvement of eGFR was associated with increased CMPAase and AREase activities, while the latter were associated with increased levels of folic acid. Treatment with folic acid significantly reduced plasma Hcy levels and the Hcy/PON1 activity ratio. The effects of folic acid increasing PON1 activities were not mediated by changes in Hcy. Discussion: Treatment of CKD patients in early/intermediate stages of CKD patients improves oxidative stress by rebalancing the prooxidant (Hcy) / antioxidant (PON1 activities) ratio. Treatment with folic acid significantly improves eGFR and these effects are mediated via increased PON1 activities. Treatment with folic acid in phase G3b and G4 may reduce renal disease progression by enhancing antioxidant defenses.

In present study, the effect of Inonotus Obliquus extracts used in traditional medicine was investigated on the expression of matrix metalloproteinases-1 (MMP-1) in the normal human dermal fibroblasts. As shown our results, extracts of Inonotus Obliquus decreased MMP1 expression in oxidative stress-exposed normal human dermal fibroblasts. Additionally, Inonotus Obliquus extracts decreased AP-1 transcriptional activity and phospho-JNK in oxidative stress exposed normal human dermal fibroblasts. The results suggest that Inonotus Obliquus extracts decreased MMP1 expression using decreasing AP-1 transcriptional activity and phospho-JNK. Therefore, Inonotus Obliquus extracts has potential to reduce formation of wrinkle and to use as a cosmetic ingredient.

Purinergic receptors are inflammatory mediators activated by extracellular nucleotides released by dying or injured cells. Several studies have described an important role for these receptors in HIV-1 entry, particularly regarding their activity on HIV-1 viral membrane fusion. Several reports identify purinergic receptor antagonists that inhibit HIV-1 membrane fusion; these drugs are suspected to act through antagonizing Env-chemokine receptor interactions. They also appear to abrogate activity of downstream mediators that potentiate activation of the NLRP3 inflammasome pathway. Here we review the literature on purinergic receptors, the drugs that inhibit their function, and the evidence implicating these receptors in HIV-1 entry.

Ulcerative colitis (UC) is a relatively frequent, chronic disease that impacts significantly the patient’s quality of life. Although many therapeutic options are available, additional approaches are needed because many patients either do not respond to current therapies or show significant side effects. Cardiotrophin-1 (CT-1) is a cytokine with potent cytoprotective, anti-inflammatory, and antiapoptotic properties. The purpose of this study was to assess if the administration of CT-1 could reduce colon damage in mice with experimental UC. UC was induced with 5% dextran sulfate sodium (DSS) in the drinking water. Some mice received i.v. dose of CT-1 (200 µg/kg) 2 hours before and 2 and 4 days after DSS administration. Animals were followed during 7 days after DSS. The severity of UC was measured by standard scores. Colon damage was assessed by histology and immunohistochemistry. Inflammatory mediators were measured by Western blot and PCR. CT-1 administration to DSS-treated mice ameliorated both the clinical course (disease activity index), histological damage, inflammation (colon expression of TNF-α, IL-17, IL-10, INF-γ, and iNOS), and apoptosis. Our results suggest that CT-1 administration before UC induction improves the clinical course, tissue damage and inflammation degree in DSS-induced UC in mice.

As lung cancer shows the highest mortality in cancer related death, serum biomarkers are demanded for the lung cancer diagnosis and its treatment. To discover lung cancer protein biomarkers, secreted proteins from primary cultured lung cancer and adjacent normal tissues from patients were subjected to LC/MS-MS proteomic analysis. Quescin sulfhydryl oxidase(QSOX1) was selected as a biomarker candidate from the proteins enriched in the secretion of lung cancer cells. QSOX1levels were higher in 82% (51 of 62 tissues) of lung cancer tissues compared to adjacent normal tissues. Importantly, QSOX1 serum levels were significantly higher in cancer patients (p<0.05, AUC=0.89), when measured by multiple reaction monitoring(MRM). Higher levels of QSOX1 are also uniquely detected in lung cancer tissues among several other solid cancers by immunohistochemistry. QSOX1 knock-downed Lewis lung cancer (LLC) cells was less viable from oxidative stress and had reduced migration and invasion. In addition, LLC mouse models with QSOX1 knock-down also proved that QSOX1 functions in promoting cancer metastasis. In conclusion, QSOX1 might be a lung cancer tissue-derived biomarker and involved in the promotion of lung cancers, and thus can be a therapeutic target for lung cancers.

Predicting how a genetic change affects a given character is a major challenge in biology, and being able to tackle this problem relies on our ability to develop realistic models of gene networks. However, such models are rarely tractable mathematically. In this paper, we propose a mathematical analysis of the sigmoid variant of the Wagner gene-network model. By considering the simplest case, that is, one unique self-regulating gene, we show that numerical simulations are not the only tool available to study such models: theoretical studies can be done too, by mathematical analysis of discrete dynamical systems. It is first shown that the particular sigmoid function can be theoretically investigated. Secondly, we provide an illustration on how to apply such investigations in the case of the dynamical system representing the one self-regulating gene.

: Pearl millet (Pennisetum glaucum L) R. Br) is a subtropical grain and forage crop. It is privileged with several desirable forage attributes. Nevertheless, research on pearl millet is limited especially as a forage crop in the developing countries. Therefore, the objectives of this study were to investigate the field performance and stability of pearl millet genotypes for forage yield across seven environments. The study was conducted in seven environments (combination of locations and seasons) during 2016/2017-2018/2019 seasons. Twenty-five pearl millet genotypes, selected based on forage yield from a core collection of 200 accessions, were arranged in alpha lattice design with three replications. The parameters measured were fresh forage yield, days to flowering, plant height, number of culms m-2, leaf to stem ratio, and stem girth. The combined analysis revealed that environments, genotypes and their interaction had significant effects on all traits studied except the genotypic effect on stem girth. Across the seven environments, four genotypes (G14, G01, G12, and G22) out-yielded the check genotype in fresh matter yield by 20.7, 16.5, 11.0 and 9.8%, respectively. The additive main effects and multiplicative interaction (AMMI) analysis showed that the genotype, environment and their interaction were highly significant (P≤0.001) for fresh matter yield. The results of AMMI Stability Values (ASV) and the genotype selection index (GSI) combined with the AMMI estimate-based selection showed that genotypes G14, G22 and G01 were the most stable and adapted genotypes and were superior to the check genotype. These results indicate that forage pearl millet varieties could be developed directly through evaluation of the wealth available collections or indirectly through hybridization in crop breeding programs.

Maternal obesity and gestational diabetes predispose to metabolic disturbances in the next generation. Moreover, the lactation phase also stands as critical for metabolic programming. Nevertheless, the precise mechanisms originating these changes remain unclear. Here we investigate the consequences of maternal diet lipid-rich diet during gestation and lactation, and its impact on metabolism and behavior in the offspring. Two experimental groups of Wistar female rats were used: a control group (NC) that fed a standard diet during gestation and lactation periods and an overnutrition group that fed a high-fat diet (HF, 60% lipid-rich) during the same phases. Offspring were analyzed at postnatal days 21, 28, and 2 months-old (PD21, PD28, PD60) for metabolic profile (weight, fasting glycemia insulin sensitivity, glucose tolerance) and euthanized for brain collection to evaluate by western blot markers of synaptic dynamics, metabolism and inflammation in the hypothalamus, hippocampus and prefrontal cortex. At 2 months-old, behavioral tests for anxiety, stress, cognition, and food habits were conducted. We observe that female offspring born from HF mothers exhibited increased weight gain and decreased glucose tolerance that attenuates with age. In offspring males, weight gain increased at P21 and worsened with age, while glucose tolerance remained unchanged. Offspring of HF mothers exhibited elevated levels of anxiety and stress during behavioral tests, displaying decreased predisposition for curiosity compared to the NC group. In addition, offspring from mothers with HF showed increased food consumption and a lower tendency towards food-related aggression. We conclude that exposure to HF diet during pregnancy and lactation induces dysmetabolism in the offspring accompanied by heightened stress and anxiety. There was sexual dimorphism in metabolic traits but not behavioral phenotypes.

Cannabis, renowned for its historical medicinal use, harbours various bioactive compounds—cannabinoids, terpenes, and flavonoids. While major cannabinoids like THC and CBD have received extensive scrutiny for their pharmacological properties, emerging evidence underscores the collaborative interactions among these constituents, suggesting a collective therapeutic potential. This comprehensive review explores the intricate relationships and synergies between cannabinoids, terpenes, and flavonoids in cannabis. Cannabinoids, pivotal in cannabis's bioactivity, exhibit well-documented analgesic, anti-inflammatory, and neuroprotective effects. Terpenes, aromatic compounds imbuing distinct flavours, not only contribute to cannabis's sensory profile but also modulate cannabinoid effects through diverse molecular mechanisms. Flavonoids, another cannabis component, demonstrate anti-inflammatory, antioxidant, and neuroprotective properties, particularly relevant to neuroinflammation. The entourage hypothesis posits that combined cannabinoid, terpene, and flavonoid action yields synergistic or additive effects, surpassing individual compound efficacy. Recognizing the nuanced interactions is crucial for unravelling cannabis's complete therapeutic potential. Tailoring treatments based on the holistic composition of cannabis strains allows optimization of therapeutic outcomes while minimizing potential side effects. This review underscores the imperative to delve into the intricate roles of cannabinoids, terpenes, and flavonoids, offering promising prospects for innovative therapeutic interventions and advocating continued research to unlock cannabis's full therapeutic potential within the realm of natural plant-based medicine.

Chimeric antigen receptor and T-cell receptor (CAR-T/TCR) cellular immunotherapies have shown remarkable success in the treatment of some refractory B-cell malignancies, with potential to provide durable clinical response for other types of cancer. In this paper, we look at all available FDA CAR-T/TCR clinical trials for the treatment of cancer, and analyze them with respect to different disease tissues, targeted antigens, products, and originator locations. We found that 627 of 1,007 registered are currently active and of those 273 (44%) originated in China and 280 (45%) in the US. Our analysis suggests that the rapid increase in the number of clinical trials is driven by the development of different CAR-T products that use a similar therapeutic approach. We coin the term bioparallels to describe such products. Our results suggest that one feature of the CAR-T/TCR industry may be a robust response to success and failure of competitor products.

Low levels of physical activity (PA) and sedentarism are associated with the onset of different pathologies and health problems. Regular physical activity has been linked with being beneficial to the health of the general population. Within this framework of analysis, the aim of the present study is to analyse the existing association between the time spent doing physical activity and the expressed motives for doing so, from which the first innovative aspect of the paper emerges: the use of the time spent doing PA as a study variable of the phenomenon. The data analysed come from the latest special Eurobarometer survey about the sport and physical activity done in Europe. Using an exploratory factorial analysis and a structural equations model, we were able to find a six-dimensional factorial model that explains the reasons for doing PA, demonstrating that there is no relationship between the reasons for and time spent doing PA. Therefore, motivation is not a variable that explains the time spent doing PA and another type of variable must be used to explain the phenomenon if PA is to be incentivised.

Multicore magnetic nanoparticles of manganese ferrite were prepared using carboxymethyl-dextran and melamine as agglutinating agents. The nanoparticles prepared using melamine exhibit a flower-shape structure, a saturation magnetization of 6.16 emu/g and good capabilities for magnetic hyperthermia. Magnetoliposome-like structures containing the multicore nanoparticles exhibit sizes in the range 250 – 400 nm. A new antitumor thienopyridine derivative was loaded in these nanocarriers with a high encapsulation efficiency of 98% ± 2.6%. Release profiles in absence and presence of an AMF indicate a transport by diffusion, with a maximum compound release of 31% under the AMF. A sustained and controlled drug release in anticipated from the results, pointing to suitable characteristics of the magnetoliposomes for dual cancer therapy (combined magnetic hyperthermia and chemotherapy).

Long COVID, a name often given to the persistent symptoms following acute SARS-CoV-2 infection, poses a multifaceted challenge for health. This review explores the intrinsic relationship between comorbidities and autoimmune responses in shaping the trajectory of long COVID. Autoantibodies have emerged as significant players in COVID-19 pathophysiology, with implications for disease severity and progression. Studies show immune dysregulation persisting months after infection, marked by activated innate immune cells and high cytokine levels. The presence of autoantibodies against various autoantigens suggests their potential as comorbid factors in long COVID. Additionally, the formation of immune complexes may lead to severe disease progression, highlighting the urgency for early detection and intervention. Furthermore, long COVID is highly linked to cardiovascular complications and neurological symptoms, posing challenges in diagnosis and management. Multidisciplinary approaches, including vaccination, tailored rehabilitation, and pharmacological interventions, are used for mitigating long COVID's burden. However, numerous challenges persist, from evolving diagnostic criteria to addressing the psychosocial impact and predicting disease outcomes. Leveraging AI-based applications holds promise in enhancing patient management and improving our understanding of long COVID. As research continues to unfold, unravelling the complexities of long COVID remains paramount for effective intervention and patient care.

Anastomotic insufficiencies are severe complications of abdominal surgery, often leading to pro-longed hospitalization, serious tissue inflammation, even sepsis and the need for recurrent sur-gery. Current non-surgical treatments such as self-expanding metal stents (SEMS) and endoscopic vacuum therapy (EVT) have limitations, including stent migration or perforation. This review evaluates the effectiveness of the VacStent GITM, a novel medical device combining SEMS and negative-pressure wound therapy in treating gastrointestinal leaks. Data were gathered from four prospective studies and compared with existing treatments. Studies on the VacStent GITM applica-tion demonstrate technical success and competitive closure rates in upper gastrointestinal leaks, with minimal complications reported. Comparative analyses with SEMS and EVT reveal prom-ising and most importantly equally good outcomes while maintaining the possibility for sus-tained enteral nutrition and reducing stent migration risk. The VacStent GITM presents a promis-ing alternative to current non-surgical treatments. Ongoing research aims to validate its efficacy in lower gastrointestinal leaks and establish its role in leak management comprehensively. Fur-ther investigation is necessary to confirm these findings and optimize treatment protocols. Future usages of the VacStent GITM in colonic anastomotic insufficiencies promise an effective approach and might be able to lower the rates of necessary implementations of a stoma.

HIV-1 infection can activate the expression of human endogenous retroviruses (HERVs), particularly HERV-K (HML-2). HIV controllers (HICs) are rare people living with HIV (PLWH) who naturally control HIV-1 replication. The ability of HICs to control the expression of endogenous retroviruses has not been previously addressed. In this study, we measured ERVK-6 RNA expression in PBMCs of HICs (n = 23), antiretroviral (ART)-suppressed subjects (n = 8), and HIV-1-negative (NEG) individuals (n = 10) and correlated the transcript expression of ERVK-6 with multiple HIV-1 restriction factors. Our study reveals that ERVK-6 RNA expression in PBMCs from HICs was significantly downregulated compared with both ART and NEG control groups. Moreover, we detected that ERVK-6 RNA levels in PBMCs across all groups were negatively correlated with the expression levels of p21 and MCPIP1. In our previous study, these two cellular restriction factors were upregulated in HICs compared with control groups. Interestingly, p21 and MCPIP1 limit the activation of macrophages and T cells by downregulating the activity of NF-kB, a transcription factor that stimulates the LTR-driven transcription of HIV-1 and HERV-K proviruses. These findings support that HICs activate innate antiviral mechanisms that may simultaneously downregulate the transcription of both HIV-1 and endogenous retroviruses.

The present paper contains data on the density (ρ), sound velocity (u), specific heat capacity (c_p ) of the mixture of N,N-dimethylformamide + 1-butanol (DMF + BuOH) determined in the entire concentration range of solution and in the temperature range: (293.15–318.15) K. The analysis of thermodynamic functions such as isobaric molar expansion, isentropic and isothermal molar compression, isobaric and isochoric molar heat capacity, as well as their excess functions (〖 E〗_(p,m)^E,〖 K〗_(S,m)^E,〖 K〗_(T,m)^E,〖 C〗_"p,m" ^E,〖 C〗_"V,m" ^E) and also V_m^E was undertaken. The analysis of changes in the physicochemical quantities was based on consideration of the system in an aspect of intermolecular interactions with resulting changes in the mixture structure. The results available in the literature are confusing during the analysis and became the reason for our decision to thoroughly examine the system. What is more, for a system whose components are widely used, there is no information in the literature regarding the heat capacity of the tested mixture, which was also achieved and presented in this publication. The conclusions drawn from so many data allow us to approximate and understand the changes that occur in the structure of the system due to repeatability and consistency of the obtained results

Australian bat lyssavirus (ABLV) is a rhabdovirus that circulates in four species of pteropid bats (ABLVp) and the yellow-bellied sheath-tailed bat (ABLVs) in mainland Australia. In the three confirmed human cases of ABLV, rabies illness preceded fatality. As with rabies virus (RABV), post-exposure prophylaxis (PEP) for potential ABLV infections consists of wound cleansing, ad-ministration of the rabies vaccine and injection of rabies immunoglobulin (RIG) proximal to the wound. Despite the efficacy of PEP, the inaccessibility of human RIG (HRIG) in the developing world and the high immunogenicity of equine RIG (ERIG) has led to consideration of human monoclonal antibodies (hmAbs) as a passive immunization option that offers enhanced safety and specificity. Using a recombinant vesicular stomatitis virus (rVSV) expressing the glycoprotein (G) protein of ABLVs and phage display, we identified two hmAbs, A6 and F11, which completely neutralize ABLVs/ABLVp, and RABV at concentrations ranging from 0.19-3.12 µg/mL and 0.39-6.25 µg/mL respectively. A6 and F11 recognize overlapping epitopes in the lyssavirus G protein, ef-fectively neutralizing phylogroup 1 lyssaviruses, while having little effect on phylogroup 2 and non-grouped diverse lyssaviruses. These results suggest A6 and F11 could be effective therapeutic and diagnostic tools for phylogroup 1 lyssavirus infections.

Studying the multi-function bacterial implications on the natural phytochemicals could be among the best solutions for producing clean-label functional juices. This study aimed to develop a high-quality mulberry juice with enhanced antioxidant capacity through fermentation. The juice was fermented using mono- and co-cultures of Lactobacillus casei (LC), L. plantarum (LP), L. paracasei (LPC), L. acidophilus (LA), and L. helveticus (LH) at different time intervals (24, 48, 72, and 96 h). The total phenolic content (TPC), total flavonoid content (TFC), flavonols, anthocyanins, and proan-thocyanidins were determined, along with the antioxidant activity assays and FTIR analysis. The results revealed significant changes in molecular interactions and functional group presence post-fermentation, indicating microbial incorporation's effect on the juice's functional profile. These changes were attributed to the formation of new compounds during fermentation, such as organic acids, alcohols, glycerol, and phenols, as evidenced by the FTIR spectra. Besides, LC-LA and LC-LPC co-culture treatments yield the most substantial stability in TPC, TFC, and TF after 48 h compared to 24 h and 72 h. After 48 h, the co-cultures of LPC-LH (1265.5 GAE/L) and LPC-LA (1145 GAE/L) were increased the TPC after 48 h than the single cultures. Conclusively, LC-LPC and LP-LPC co-culture fermentation was recommended as a cost-effective method to enhance the an-tioxidant potential and the overall phytochemical capacity of mulberry products. The findings of this study provide valuable insights into the potential of fermented mulberry juice as a functional food with improved health benefits.

We are currently facing a potential ‘polycrisis’, a critical inflection point that requires a whole-of-society response aimed at building collective foresight and preparedness for short-, medium-, and long-term risks. The role of higher education institutions and social stakeholders is decisive to make an impact. This paper depicts the alignment of academia, governance, and industry with the aim to challenge, inspire, and encourage universities to go beyond commodified courses and mere employability, enhance student growth and bind macro-scale measures that lead to a sustainable future. A modest teaching innovation project has served as a transforming lever, with the private sector joining in, to create a platform that reaches more than 50 000 undergraduate students and teaching staff. The resulting structure, rooted in the University’s strategic plan, has served to channel local and regional initiatives, establish effective partnerships with broad social members, raise awareness and promote actions to advance in the pursuit of Sustainable Development Goals. Chronology, materials and methodology, together with a description of the different courses, programmes and actions are provided. The paper concludes with some recommendations for future research, policy and cooperation among stakeholders. Research methodology posted on clinicaltrials.gov under ID NCT04392869, NCT05598944, and NCT05775978.

We are currently facing a potential ‘polycrisis’, a critical inflection point that requires a whole-of-society response aimed at building collective foresight and preparedness for short-, medium-, and long-term risks. The role of higher education institutions and social stakeholders is decisive to make an impact. This paper depicts the alignment of academia, governance, and industry with the aim to challenge, inspire, and encourage universities to go beyond commodified courses and mere employability, enhance student growth and bind macro-scale measures that lead to a sustainable future. A modest teaching innovation project has served as a transforming lever, with the private sector joining in, to create a platform that reaches more than 50 000 undergraduate students and teaching staff. The resulting structure, rooted in the University’s strategic plan, has served to channel local and regional initiatives, establish effective partnerships with broad social members, raise awareness and promote actions to advance in the pursuit of Sustainable Development Goals. Chronology, materials and methodology, together with a description of the different courses, programmes and actions are provided. The paper concludes with some recommendations for future research, policy and cooperation among stakeholders. Research methodology posted on clinicaltrials.gov under ID NCT04392869, NCT05598944, and NCT05775978.

In recent years, weeds is responsible for most of the agricultural yield losses. To deal with this threat, farmers resort to spraying pesticides throughout the field. Such method not only requires huge quantities of herbicides but impact environment and humans health. One way to reduce the cost and environmental impact is to allocate the right doses of herbicide at the right place and at the right time (Precision Agriculture). Nowadays, Unmanned Aerial Vehicle (UAV) is becoming an interesting acquisition system for weeds localization and management due to its ability to obtain the images of the entire agricultural field with a very high spatial resolution and at low cost. Despite the important advances in UAV acquisition systems, automatic weeds detection remains a challenging problem because of its strong similarity with the crops. Recently Deep Learning approach has shown impressive results in different complex classification problem. However, this approach needs a certain amount of training data but, creating large agricultural datasets with pixel-level annotations by expert is an extremely time consuming task. In this paper, we propose a novel fully automatic learning method using Convolutional Neuronal Networks (CNNs) with unsupervised training dataset collection for weeds detection from UAV images. The proposed method consists in three main phases. First we automatically detect the crop lines and using them to identify the interline weeds. In the second phase, interline weeds are used to constitute the training dataset. Finally, we performed CNNs on this dataset to build a model able to detect the crop and weeds in the images. The results obtained are comparable to the traditional supervised training data labeling. The accuracy gaps are 1.5% in the spinach field and 6% in the bean field.

Q-switched laser radiation at wavelengths of 355 nm, 532 nm, and 1064 nm from a Nd: YAG laser was used to generate plasma in laboratory air at the target surface made of compressed nano-silver particles of size 95 ± 10 nm. The emitted resonance spectra from the neutral silver at wavelengths of 327.9 nm and 338.2 nm indicate existence of self-reversal in addition to plasma self-absorption. Both lines were identified in emission spectra at different laser irradiation wavelengths with characteristic dips at the un-shifted central wavelengths. These dips are usually associated with self-reversal. Under similar conditions, plasmas at the corresponding bulk silver target were generated. The recorded emission spectra were compared to those obtained from the nano-material target. The comparisons confirm existence of self-reversal of resonance lines that emerge from plasmas produced at nano-material targets. This work suggests a method for recovery of the spectral line shapes and discusses practical examples. In addition, subsidiary calibration efforts that utilize the Balmer series Hα-line reveal that other Ag I lines at 827.35 nm and 768.7 nm are optically thin under variety of experimental conditions and are well-suited as reference lines for measurement of the laser plasma electron density.

Transcription factors (TFs) and microRNAs (miRNAs) are co-actors in genome-scale decoding and regulatory networks, often targeting common genes. In this paper, we describe the algebraic geometry of both TFs and miRNAs thanks to group theory. In TFs, the generator of the group is a DNA-binding domain while, in miRNAs, the generator is the seed of the sequence. For such a generated (infinite) group $\pi$, we compute the $SL(2,\mathbb{C})$ character variety, where $SL(2,\mathbb{C})$ is simultaneously a \lq space-time' (a Lorentz group) and a \lq quantum' (a spin) group. A noteworthy result of our approach is to recognize that optimal regulation occurs when $\pi$ looks like a free group $F_r$ ($r =1$ to $3$) in the cardinality sequence of its subgroups, a result obtained in our previous papers. A non free group structure features a potential disease. A second noteworthy result is about the structure of the Groebner basis $\mathcal{G}$ of the variety. A surface with simple singularities (like the well known Cayley cubic) within $\mathcal{G}$ is a signature of a potential disease even when $G$ looks like a free group $F_r$ in its structure of subgroups. Our methods apply to groups with a generating sequence made of two to four distinct DNA/RNA bases in $\{A,T/U,G,C\}$. Several human TFs and miRNAs are investigated in detail thanks to our approach.

Since the first reported case of COVID-19 in December 2019, several SARS-CoV-2 variants has evolved and some of them have shown higher transmissibility becoming the prevalent strains. Genomic epidemiological investigations into strains from different time points including the early stages of the pandemic are very crucial for understanding the evolution and transmission patterns. Using whole genome sequences, our study describes the early landscape of SARS-CoV-2 variants in central India retrospectively (including the first known occurrence of SARS-CoV-2 in Madhya Pradesh). We performed amplicon based whole genome sequencing of randomly selected SARS-CoV-2 isolates (n=38) collected between 2020-2022 at state level VRDL, ICMR-NIRTH, Jabalpur from 11899 RT-qPCR positive samples. We observed the presence of five lineages namely B.1, B.1.1, B.1.36.8, B.1.195 and B.6 in 19 genomes from the first wave cases and variants of concern (VOC) lineages i.e. B.1.617.2 (Delta), and BA.2.10 (Omicron) in the second wave cases. There was a shift in mutational pattern of SRAS-CoV-2 strains from the second wave in contrast to the first wave. We have identified five immune escape variants in the S gene: P681R, P681H, L452R, Q57H, and N501Y in the isolates collected during the second wave. Furthermore, these genomes were compared with 2160 complete genome sequences reported from central India that encompass 109 different SARS-CoV-2 lineages. Among them, VOC lineages Delta (28.93%), and Omicron (56.11%) were circulating predominantly in this region. This study provides useful insights into the genetic diversity of SARS-CoV-2 strains over the initial course of the COVID-19 pandemic in central India.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause potentially life-threatening coronavirus disease (COVID-19). COVID-19 is a multisystem disease and is associated with significant respiratory distress, systemic hyper inflammation, vasculitis and multi-organ failures. SARS-CoV-2 causes deterioration of numerous systems with increasing evidence implying that COVID-19 affects endothelium and vascular function. The endothelium is important for preserving vascular tone and homeostasis. The overactivation and dysfunction of endothelial cells are significant outcomes of severity in patients with COVID-19. The Angiopoietin 1/Tie 2 pathway plays an important role in endothelium quiescence and vessel stability. The disruption of Angiopoietins/Tie balance affects vessel contact barrier and leads to vessel leakage, and this in turn causes endothelial dysfunction. Although vascular instability through SARS-CoV-2 is associated with endothelial dysfunction, it is still not understood if the virus affects Angiopoietin/Tie axis directly or via other mechanisms such as cytokine storm and/or immune response associated with the infection. This review provides an overview of the impact SARS-CoV-2 has on endothelial function and more specifically the Angiopoietin/Tie pathway.

The COVID-19 pandemic was declared in March 2020 and is still ongoing. The course of the epidemic remains uncertain, and mutations in the coronavirus, as well as the emergence of new variants of concern, make it possible that there will be periodic surges in the number of cases. Moreover, it is not clear how quickly and to what extent the effectiveness of vaccination will decline as the virus continues to mutate. One possible solution to combat the rapidly mutating coronavirus is the development of pan-coronavirus vaccines that stimulate the production of antibodies against conserved elements of the virus. Another approach could be the creation of safe vaccine platforms that can be rapidly adapted to deliver new, specific antigens in response to viral mutations. Recombinant probiotic microorganisms that can produce viral antigens by inserting specific viral DNA fragments into their genome show promise as a platform and vector for mucosal vaccine antigen delivery. With a well-established safety profile and the ability to transform into vaccine candidates, probiotic bacteria have significant research potential. The authors of this study have developed a convenient and universal technique for inserting the DNA sequences of pathogenic bacteria and viruses into the gene that encodes the pili protein of the probiotic strain E. faecium L3. The paper presents data on the immunogenic properties of two E. faecium L3 vaccine strains, which produce two different fragments of the coronavirus S1 protein, and provides an assessment of the protective efficacy of these oral vaccines against coronavirus infection in Syrian hamsters.

(1) Background: This study aimed to investigate the effect of increased HER-2 expression on tumor-infiltrating lymphocytes (TILs) and determine its impact on the prognosis of colorectal cancer (CRC) patients; (2) Methods: HER-2, CD4, CD8, CD19, LY6G, CD56, CD68, CD11b, and EpCam expression in CRC tissues and adjacent paracancerous tissues were assessed using multiplex fluorescence immunohistochemical staining. The correlation between HER-2 expression and the number of TILs in CRC tissues was analyzed. Kaplan-Meier and Cox proportional hazards models were used to analyze survival outcomes; (3) Results: The expression of HER-2 in tumor tissues was higher than that in paracancerous tissues (1.31 ± 0.45 vs. 0.86 ± 0.20, P < 0.05). Additionally, there was an increase in the numbers of CD4+, CD8+, CD19+, and CD68+ cells in CRC tissues (14.11 ± 1.10 vs. 3.40 ± 0.18, P < 0.005; 0.16 ± 0.12 vs. 0.04 ± 0.04, P < 0.005; 0.71 ± 0.46 vs. 0.25 ± 0.13, P < 0.0005; 0.27 ± 0.24 vs. 0.03 ± 0.11, P < 0.05). The increase in HER-2 expression was positively correlated with an increase in CD4, CD8, and CD19 (p < 0.0001). In HER-2-positive CRC tissues, CD68 expression was increased (0.80 ± 0.55 vs. 0.25 ± 0.22, P < 0.05). In HER-2-upregulated CRC tissues, CD4, CD8, CD19, CD68, CD11b, Ly6G, and CD56 expressions were elevated (0.70 ± 0.37 vs. 0.32 ± 0.17, P = 0.03; 0.22 ± 0.13 vs. 0.09 ± 0.06, P = 0.03; 0.31 ± 0.19 vs. 0.12 ± 0.08, P = 0.02; 1.05 ± 0.62 vs. 0.43 ± 0.21, P < 0.01; 1.34 ± 0.81 vs. 0.53 ± 0.23, P < 0.01; 0.50 ± 0.31 vs. 0.19 ± 0.10, P < 0.01; 1.26 ± 0.74 vs. 0.52 ± 0.24, P < 0.01). Furthermore, increased HER-2 expression is an independent risk factor for recurrence-free survival (RFS) in patients (P < 0.01, HR = 3.421); (4) Conclusions: The increased expression of HER-2 and its relationship with immune cells will provide new insights for immunotherapy in CRC patients.

Bacteremia and fungemia are significant causes of morbidity and mortality which frequently occur as co-infections with viral respiratory infections including SARS-CoV-2. It was aimed to evaluate the microorganisms isolated from blood cultures of SARS-CoV-2 positive and negative patients and investigate their antimicrobial resistance patterns. A retrospective analysis was performed with the total number of 22,944 blood cultures sent to the laboratory between November 2020 and December 2021. Blood cultures were performed on the BD Bactec automated system. Identification was performed using conventional methods, VITEK-2 and MALDI-TOF MS. Antibacterial/antifungal susceptibility tests were performed according to EUCAST/CLSI recommendations. SARS-CoV-2 tests were performed with RT-PCR. It was detected 1,630 culture positivity belonging to 652 patients. Totally 633 of 652 patients were tested for SARS-CoV-2; 118 (18.6%) were positive and 515 (81.3%) were negative. The bacteria and fungi isolated at the high-est rate in SARS-CoV-2 positive patients were methicillin-resistant coagulase negative staphylococci (MR-CoNS) (21.5%), Escherichia coli (12.4%), Klebsiella pneumoniae (12.4%), Candida albicans (1.65%) and Candida glabrata complex (1.65%); while in negative patients, E. coli (21.3%), MR-CoNS (13.5%), K. pneumoniae (12.05%), C. albicans (2.1%), Candida parapsilosis (1.1%) and Candida tropicalis (0.9%). The fact that the most common isolate was MR-CoNS in SARS-CoV-2 positive patients (p = 0.028); the detection of Acinetobacter baumannii was more frequent (p = 0.001) and the isolation of carbapenem-resistant K. pneumoniae was at a higher rate than in SARS-CoV-2 negative patients; also, the increase in multidrug-resistant strains indicate that healthcare-associated infec-tions should not be disregarded while focusing on the outbreak.

Herein we report the expansion of the chemical space available from the chitin, accessible via the biogenic N-platforms 3A5AF, M4A2C and di-HAF. The biologically active heteroaromatics furo[3,2-d]pyrimidin-4-one and furo[3,2-d]pyrimidin-4-amine can be selectively accessed from 3A5AF and M4A2C, respectively. The chiral pool synthon di-HAF is a viable substrate for the Achmatowicz rearrangement, providing streamlined access to 2-aminosugars possessing a versatile hydroxymethyl group at C5.

The Bcl-2 family plays a crucial role in regulating cell apoptosis, making it an attractive target for cancer therapy. In this study, a series of indole-based compounds, U1-6, were designed, synthesized, and evaluated for their anticancer activity against BCL-2-expressing cancer cell lines. The binding affinity, safety profile, cell cycle arrest, and apoptosis effects of the compounds were tested. The designed compounds exhibited potent inhibitory activity at sub-micromolar IC50 concentrations against MCF-7, MDA-MB-231, and A549 cell lines. Notably, U2 and U3 demonstrated the highest activity, particularly against MCF-7 cells. Respectively, both U2 and U3 showed potential Bcl-2 inhibition activity with IC50 values of 1.2 ± 0.02 and 11.10 ± 0.07 µM using an ELISA binding assay compared to 0.62 ± 0.01 µM for gossypol, employed as positive control. Molecular docking analysis suggested stable interactions of compound U2 at the Bcl-2 binding site through hydrogen bonding, pi-pi stacking, and hydrophobic interactions. Furthermore, U2 demonstrated significant induction of apoptosis and cell cycle arrest at G1/S phase. Importantly, U2 displayed a favorable safety profile on HDF human dermal normal fibroblast cells at 10-fold greater IC50 compared to MDA-MB-231 cells. These findings underscore the therapeutic potential of compound U2 as a Bcl-2 inhibitor and provide insights into its molecular mechanisms of action.

Background: Primary cardiac sarcomas (PCS) are extremely rare malignant tumors involving the heart. Only isolated case reports have been described. There is a paucity of data on the epidemiological characteristics of PCS. This study has the objective of investigating the epidemiologic characteristics, survival outcomes, and independent prognostic factors of PCS. Methods: We enrolled a total of 362 patients with PCS, between 2000 and 2017, by retrieving the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed demographics, clinical characteristics, and overall mortality (OM) as well as cancer-specific mortality (CSM) of PCS. Variables with a p-value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors, with a hazard ratio (HR) of greater than 1 representing adverse prognostic factors. Results: Crude analysis revealed a high OM in age 80+ (HR=5.958, 95% CI 3.357-10.575, p=0), followed by age 60-79 (HR=1.429, 95% CI 1.028-1.986, p=0.033); and PCS with distant metastases (HR=1.888, 95% CI 1.389-2.566, p=0). Patients that underwent surgical resection of the primary tumor and patients with malignant fibrous histiocytomas (HR=0.657, 95% CI 0.455-0.95, p=0.025) had a better OM (HR=0.606, 95% CI 0.465-0.791, p=0). The highest cancer-specific mortality was observed in age 80+ (HR=5.037, 95% CI 2.606-9.736, p=0) and patients with distant metastases (HR=1.953, 95% CI 1.396-2.733, p=0). Patients with malignant fibrous histiocytomas (HR=0.572, 95% CI 0.378-0.865, p=0.008) and those who underwent surgery (HR=0.581, 95% CI 0.436-0.774, p=0) had a lower CSM. Multivariate Cox proportional hazard regression analyses revealed higher OM in the age group 80+ (HR=13.261, 95% CI 5.839-30.119, p=0) and advanced disease with distant metastases (HR=2.013, 95% CI 1.355-2.99, p=0.001). Lower OM was found in patients with rhabdomyosarcoma (HR=0.364, 95% CI 0.154-0.86, p=0.021) and widowed patients (HR=0.506, 95% CI 0.263-0.977, p=0.042). Multivariate Cox proportional hazard regression analyses of CSM also revealed higher mortality in the same groups, and lower mortality in patients with Rhabdomyosarcoma. Conclusion: In this United States population-based retrospective cohort study using the SEER database, we found that cardiac rhabdomyosarcoma was associated with the lowest CSM and OM. Furthermore, as expected, age and advanced disease at diagnosis were independent factors predicting poor prognosis. Surgical resection of the primary tumor showed lower CSM and OM in the crude analysis but when adjusted for covariates in the multivariate analysis, it did not significantly impact the overall mortality or the cancer-specific mortality. These findings allow for treating clinicians to recognize patients that should be referred to palliative/hospice care at the time of diagnosis and avoid any surgical interventions as they did not show any differences in mortality. Surgical resection in patients with poor prognoses should be reserved as a palliative measure rather than an attempt to cure the disease.

SARS-CoV-2 resembles the ancient mythical creature Hydra. Just like with the Hydra, when one head is cut, it is followed by appearance of two more heads, suppression of one SARS-CoV-2 variant causes appearance of newer variants. Unlike Hydra that grows identical heads, newer SARS-CoV-2 variants are usually more infective, which can be observed as time evolution of the virus at hand, which occurs through acquisition of mutations during time. The appearance of new variants is followed by appearance of new COVID-19 pandemic waves. With the appearance of new pandemic waves and determining of sequences, in the scientific community and general public the question is always raised of whether the new variant will be more virulent and more pathogenic. The two variants characterized in this paper, BA.5.2 and BF.7, have caused a pandemic wave during the late 2022. This paper gives full chemical and thermodynamic characterization of the BA.5.2 and BF.7 variants of SARS-CoV-2. Having in mind that Gibbs energy of binding and biosynthesis represent the driving forces for the viral life cycle, based on the calculated thermodynamic properties we can conclude that the newer variants are more infective than earlier ones, but that their pathogenicity has not changed.

The evolution of some epidemics, as influenza, shows common patterns both in different regions and from year to year. On the contrary, epidemics like the novel COVID-19 show quite heterogeneous dynamics and are extremely susceptible to the measures taken to mitigate their spread. In this paper we propose empirical dynamic modeling to predict the evolution of influenza in Spain’s regions. It is a non-parametric method that looks into the past for coincidences with the present to make the forecasts. Here we extend the method to predict the evolution of other epidemics at any other starting territory and we test also this procedure with Spanish COVID-19 data. We finally build influenza and COVID-19 networks to check possible coincidences in the geographical distribution of both diseases. With this, we grasp the uniqueness of the geographical dynamics of COVID-19.

The evolution and the emergence of new mutations of viruses affect their transmissibility and/or pathogenicity features, depending on different evolutionary scenarios of virus adaptation to the host. A typical trade-off scenario of SARS-CoV-2 evolution has been proposed, which leads to the appearance of an Omicron strain with lowered lethality, yet enhanced transmissibility. This direction of evolution might be partly explained by virus adaptation to therapeutic agents and enhanced escape from vaccine-induced and natural immunity formed by other SARS-CoV-2 strains. Omicron’s high mutation rate in the Spike protein, as well as its previously described high genome mutation rate (Kandeel et al., 2021), revealed a gap between it and other SARS-CoV-2 strains, indicating the absence of a transitional evolutionary form to the Omicron strain. Therefore, Omicron has emerged as a new serotype and divergent from the evolutionary lineage of other SARS-CoV-2 strains. Omicron is a rapidly evolving variant of high concern, whose new subvariants continue to manifest. Its further understanding and the further monitoring of key mutations that provide virus immune escape and/or high affinity towards the receptor could be useful for vaccine and therapeutic development in order to control the evolutionary direction of the COVID-19 pandemic.

Since the discovery of the Coronavirus disease 2019 (COVID-19) outbreak, a vast majority of studies have been carried out that confirmed the worst outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with preexisting health conditions, including diabetes, obesity, hypertension, cancer, and cardiovascular diseases. Likewise, diabetes itself is one of the leading causes of global public health concerns that impose a heavy global burden on public health as well as socio-economic development. Both diabetes and SARS-CoV-2 infection have their independent ability to induce the pathogenesis and severity of multi-system organ dysfunction, while the co-existence of these two culprits can accelerate the pathophysiology and magnify the severity of the diseases. However, the exact pathophysiology of multi-system organ failure in diabetic patients after SARS-CoV-2 infection is still obscure. This review summarized the organ-specific possible molecular mechanisms of SARS-CoV-2 and diabetes-induced pathophysiology of several diseases of multiple organs, including the lungs, heart, kidney, brain, eyes, gastrointestinal system, and bones, and subsequent manifestation of multi-system organ failure.

Silicon photonics is emerging as a competitive platform for electronic-photonic integrated circuits (EPICs) at the 2 µm wavelength band where GeSn photodetectors (PDs) have proven to be efficient PDs. Here, we present a comprehensive theoretical study of GeSn vertical p-i-n homojunction waveguide photodetectors (WGPDs) that have a strain-free and defect-free GeSn active layer for 2-µm Si-based EPICs. The use of a narrow-gap GeSn alloy as the active layer can fully cover entire the 2 µm wavelength band. The waveguide structure allows for decoupling the photon-absorbing path and the carrier-collection path, thereby allowing for simultaneous achievement of high-responsivity and high-bandwidth (BW) operation at the 2-µm wavelength band. We present the theoretical models to calculate the carrier saturation velocities, optical absorption coefficient, responsivity, 3-dB bandwidth, zero-bias resistance, and detectivity, and optimize this device structure to achieve highest performance at the 2-µm wavelength band. The results indicate that the performance of the GeSn WGPD has strong dependence on the Sn composition and geometric parameters. The optimally designed GeSn WGPD with 10% Sn concentration can give responsivity of 1.55 A/W, detectivity of 6.12×1010 cmHz½W-1 at 2 µm wavelength, and ~97 GHz BW. Therefore, this optimally designed GeSn WGPD is a potential candidate for silicon photonic EPICs offering high-speed optical communications.

ABSTRACT Two years after first patients approached the emergency rooms of hospitals in Wuhan becouse of respiratory distress,thousend of SARS-CoV-2 infected persons continue to die every day worldwide.SARS-CoV-2-infected patients undergo a process of dehydration and malnutrition before they develop respiratory problems and approach the emergency room of a hospital.This is,in many cases, the consequence of high fever which causes massive loss of fluids. In addition loss of appetite, is responsible for the deficit of protein intake.Most of the virus-infected patients admitted to the emergency room are therefore hypovolemic and hypoproteinemic and suffer of respiratory distress accompanied by ground grass opacities at CT-scan of the lungs.Critically ill patients are treated following the guidelines for treatment of septic shock but with „conservative“ fluid replacement and administration of diuretics to assure sufficient hourly urine production. The combination of conservative fluid administration with reduced protein content in the enterally administered diet, together with administration of diuretics, has severe hemodynamic consequenses in mostly aged,dehydrated,critically ill patients. Many of them will develop acute kidney injury in the next 24 hours.In most of the cases, patients continue to loose weight by loosing skeletal muscle mass. Ischemic damage in the lung capillaries is responsible for the acute respiratory distreass syndrome (ARDS) and for the hallmark of autoptic findings,diffuse alveolar damage (DAD) characterized by hyaline membrane formation,fluid invasion of the alveoli recruitment of some inflammatory cells and progressive arrest of blood flow in the pulmonary vessels.The consequence is progressive congestion , increase of lung weight and progressive hypoxia (progressive severity of ARDS).Sequestration of blood in the lungs worsen hypovolemia and ischemia in different organs.This is most probably responsible for recruitment of inflammatory cells and for persistance of elevated serum levels of positive acute-phase markers and of hypoalbuminemia. Autoptic studies have been performed mostly in patients who died in the ICU after SARS-CoV-2-infection because of progessive ARDS.In those patients, tubulus epithelium necrosis in the kidney is a frequent finding as it has been the case in the first SARS-CoV-1 pandemic.In the death certification charts, many times weeks after first symptoms have started ,cardiac arrest is the cause of death after respitatory insufficiency.Replacement therapy with sufficient amount of fluid and albumin should be part of the early individualized life-saving supportive measures avoiding mechanical ventilation.

Coronaviruses (CoVs) are a well-known group of viruses in veterinary medicine. We currently know four genera of Coronavirus, alfa, beta, gamma and delta. Wild, farmed and pet animals are infected with CoVs belonging to all four genera. Seven human respiratory coronaviruses have still been identified, four of which cause upper respiratory tract diseases, specifically, the common cold, and the last three that have emerged cause severe acute respiratory syndromes, SARS-CoV-1, MERS-CoV and SARS-CoV-2. In this review we briefly describe animal coronaviruses and what we actually know about SARS-CoV-2 infection in farm and domestic animals.

In humans, coronaviruses can cause infections of the respiratory system, with damage of varying severity depending on the virus examined: ranging from mild or moderate upper respiratory tract diseases, such as the common cold, to pneumonia, severe acute respiratory syndrome, kidney failure and even death. Human coronaviruses known to date, common throughout the world, are seven. The most common - and least harmful - ones were discovered in the 1960s and cause a common cold. Others, more dangerous, were identified in the early 2000s and cause more severe respiratory tract infections. Among these the SARS-CoV, isolated in 2003 and responsible for the Severe Acute Respiratory Syndrome (the so-called SARS), which appeared in China in November 2002, the Coronavirus 2012 (2012-nCoV) cause of the Middle Eastern Respiratory Syndrome from Coronavirus (MERS), which exploded in June 2012 in Saudi Arabia, and actually SARS-CoV-2. On December 31, 2019, a new Coronavirus strain was reported in Wuhan, China, identified as a new Coronavirus beta strain ß-CoV from Group 2B, with a genetic similarity of approximately 70% to SARS-CoV, the virus responsible. of SARS. In the first half of February, the International Committee on Taxonomy of Viruses (ICTV), in charge of the designation and naming of the viruses (i.e., species, genus, family, etc.), thus definitively named the new coronavirus as SARS-CoV-2. This article highlights the main knowledge we have about the biomolecular and pathophysiologic mechanisms of SARS-CoV-2.

The novel coronavirus named by WHO and Coronavirus Study Group (CSG) as SARS-COV-2 is the etiological agent of the newly emerged Coronavirus disease (COVID-19). COVID-19 has become a pandemic threat as the WHO declared it a public health emergency of international concern. Early and precise detection of the virus is important for effective diagnosis and treatment. Various testing kits and assays, including real-time reverse Transcriptase PCR, thermal screening guns, ELISA-based immunoassays, and Point-of-Care (POC), have been implemented or are being explored to detect the virus and/or characterise cellular and antibody responses to the infection. However, these approaches have inherent limitations such as non-specificity, high cost, characterize by long turnaround times for test results, and can be labour intensive. Aptamers, which are single-stranded oligonucleotides, generated artificially by SELEX (Evolution of Ligands by Exponential Enrichment) may offer the capacity to generate high affinity bioprobes for monitoring relevant SARS-COV 2 and COVID-19 biomarkers. This article discusses the prospects of implementing aptasensing technologies for rapid point-of-care detection of SARS-COV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus, is responsible for coronavirus disease 2019 (COVID-19) pandemic of 2020. Experimental evidence suggests that microRNA can mediate an intracellular defence mechanism against some RNA viruses. The purpose of this study was to identify microRNA with predicted binding sites in the SARS-CoV-2 genome, compare these to their microRNA expression profiles in lung epithelial tissue and make inference towards possible roles for microRNA in mitigating coronavirus infection. We hypothesize that high expression of specific coronavirus-targeting microRNA in lung epithelia may protect against infection and viral propagation, conversely low expression may confer susceptibility to infection. We have identified 128 human microRNA with potential to target the SARS-CoV-2 genome, most of which have very low expression in lung epithelia. Six of these 128 microRNA are differentially expressed upon in vitro infection of SARS-CoV-2. Twenty-eight and 23 microRNA also target the SARS-CoV and MERS-CoV, respectively. In addition, 48 and 32 microRNA are commonly identified in two other studies. Further research into identifying bona fide coronavirus targeting microRNA will be useful in understanding the importance of microRNA as cellular defence mechanism against pathogenic coronavirus infections.

A new form of coronavirus called severe acute respiratory disease coronavirus type 2 (SARS-CoV-2) is currently causing a pandemic. A six-month evolutionary history of SARS-CoV-2 is witnessed by characterising the total genome of 821 samples using comparative phylogenomic approaches. Our analyses produced striking inclusive results that may guide scientists/professionals for the past/future of pandemic. Phylogenetic and time estimation analyses suggest the proximate origin of pandemic strain as Guangdong and the origin time as first half of September 2019, not Wuhan and December 2019, respectively. The viral genome experienced a substitution rate similar to other RNA viruses, but it is particularly high in some of the peptides encoding sequences such as leader protein, E gene, orf8, orf10, nsp10, N gene, S gene and M gene and nsp4, while low in nsp11, orf7a, 3C-like proteinase, nsp9, nsp8 and endoRNase. Most strikingly, the divergence rate of amino acid sequences is high proportional to nucleotide divergence. Additionally, specific non-synonymous mutations in nsp3 and nsp6 evolved under positive selection. The exponential growth rate (r), doubling time (Td) and R₀ were estimated to be 47.43 per year, 5.39 days and 2.72, respectively. Comparison of synapomorphies distinguishing the SARS-CoV-2 and the candidate ancestor bat coronavirus indicates that mutation pattern in nsp3 and S gene enabled the new strain to invade human and become a pandemic strain. We arrive at the following main conclusions: (i) six months evolution of viral genome is nearly neutral, (ii) origin of pandemic is not Wuhan and predates formal reports, (iii) although viral population is ongoing an exponential growth, the doubling time is evolving towards shortening, and (iv) divergence rate of total genome is similar to other RNA viruses, but it is prominently high in some genes while low in some others and evolution in these genes should be closely monitored as their protein products intervening to pathogenicity, virulence and immune response.

The Coronavirus Disease 2019 (COVID-19) is a new viral infection caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2). Genomic analyses have revealed that SARS-CoV-2 is related to Pangolin and Bat coronaviruses. In this report, a structural comparison between the Sars-CoV-2 Envelope and Membrane proteins from different human isolates with homologous proteins from closely related viruses is described. The analyses here reported show the high structural similarity of Envelope and Membrane proteins to the counterparts from Pangolin and Bat coronavirus isolates. However, the comparisons have also highlighted structural differences specific of Sars-CoV-2 proteins which may be correlated to the cross-species transmission and/or to the properties of the virus. Structural modelling has been applied to map the variant sites onto the predicted three-dimensional structure of the Envelope and Membrane proteins.

A short review of the important studies was conducted to evaluate the potential of aerosol transmission of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The minimum size of droplets potentially carrying the SARS-CoV-2 was newly estimated and discussed in this review.

The structures of recently discovered primarolides A and B suggest their non-enzymatic formation from a common 2-formylbenzophenone precursor. This hypothesis is based on the experimentally proven facile conversion of pestalone (also a 2-formyl-benzophenone) either into the isomeric lactone pestalalactone or the structurally related isoindolinone pestalachloride A. In a related fashion, the racemic isoindolinone natural product mariline A is supposed to biosynthetically originate from the corresponding keto-aldehyde and an aniline, as experimentally supported by model studies. Due to the close structural relationship with known systems, it appears highly probable that primarolides A and B were generated under the fermentation conditions from a massarinin-related 2-formylbenzophenone (proprimarolide) by reaction either with aniline or a nucleophilic catalyst, respectively. Suberoylanilide hydroxamic acid (SAHA), used as an additive during the fermentation, is supposed to act both as a source of aniline and as a nucleophilic catalyst.

Aim: To perform a descriptive analysis of eating patterns and biophysical conditions of previously diagnosed and currently under treatment individuals from a semi-urban Mayan community of Yucatan, and to contrast them with T2DM therapeutic guidelines. Methods: The present study is derived from a randomized clinical trial conducted at Komchen, Yucatan. Participants’ diagnosed with T2DM were included. A 24-hour dietary recall, anthropometric parameters (weight, visceral fat, height, and waist circumference), biochemical (HbA1c) and clinical (blood pressure) variables were evaluated and compared via hypothesis test with T2DM treatment cut-off points (based on World Health Organization criteria). Results: Anthropometric characteristics differ significantly from the ideal criteria. Obesity prevalence within women with T2DM was 92.9%. Only 21% of the participants were under T2DM control (≤7%). Energy and carbohydrates consumption, significantly exceed therapeutic guidelines, whereas protein, fat, and fiber intake were lower than the recommendations. Conclusions: Komchen’s diet, concomitantly with food characteristics, could be related to glycemic decontrol. There is a disproportion in macronutrients consumption in favor of carbohydrates, probably associated with socioeconomic limitations, food availability, and price. Developing nutritional assistance programs which contemplate cultural and economic factors in this Mayan population must be taken into consideration.

Rapid urbanization, increasing population and increased industrialization to cater to demands of the growing population has imposed upon us a huge environmental cost. The significantly deteriorated air quality across the globe is associated with a direct and indirect impact on public health. While associated disorders such as chronic obstructive pulmonary diseases, heart failures are well documented, less is known about the biological basis of the process. We hypothesize that the worsening air quality may likely impact common systemic inflammatory processes, thus driving communicable and non-communicable diseases alike.Receptor mediated entry of particulate matter (PM2.5) results in activation of signaling cascades which culminate in production of inflammatory chemokine and cytokine responses, traversing through the blood mediating impacting not only on other organs but also dysbiosis of microflora. For the purpose of the review we choose tuberculosis (TB) as a model for communicable infectious disease and type 2 diabetes mellitus (T2DM) as a marker for non-communicable disorder. The increasing prevalence of these co-morbidities and the burdening of public health systems justifies this example. However the hypothesis may be applicable to other inflammation driven disorders also.

The problem of quantifying the vulnerability of graphs has received much attention nowadays, especially in the field of computer or communication networks. In a communication network, the vulnerability measures the resistance of the network to disruption of operation after the failure of certain stations or communication links. If we think of a graph as modeling a network, the average lower 2-domination number of a graph is a measure of the graph vulnerability and it is defined by ${\gamma }_{2av}\left(G\right)=\frac{1}{\left|V\left(G\right)\right|}{\sum }_{v\in V\left(G\right)}{\gamma }_{2v}\left(G\right)$, where the lower 2-domination number, denoted by ${\gamma }_{2v}\left(G\right)$, of the graph G relative to v is the minimum cardinality of 2-domination set in G that contains the vertex v. In this paper, the average lower 2-domination number of wheels and some related networks namely gear graph, friendship graph, helm graph and sun flower graph are calculated. Then, we offer an algorithm for computing the 2-domination number and the average lower 2-domination number of any graph G.

Background: Upper respiratory tract infections (URTIs) are a major public health concern due to their high incidence and potential for complications. Pharmacists often serve as the first point of contact for patients with URTIs. This study aims to develop and evaluate the RESP-8 tool to assist pharmacists in determining the need for medical evaluation. Methods: This prospective interventional cohort study was conducted over six months (October 2023 to March 2024) in community pharmacies. Participants included adults aged 18 years and older presenting with URTI symptoms. Pharmacists used the RESP-8 tool, which comprises eight criteria to assess the need for medical referral. Data on medical history, symptom duration, and progression were recorded. The primary outcome was the feasibility of implementing the RESP-8 tool. Secondary outcomes included the accuracy of the tool, the percentage of patients recommended for medical evaluation, and compliance with these recommendations. Results: A total of 64 participants were included, with an average age of 55.7 years. Pharmacists recommended medical evaluation for 75% (48/64) of patients using the RESP-8 tool. Among these, 70.83% (34/48) complied with the recommendation. The tool demonstrated high accuracy in identifying patients needing further medical evaluation, with only two noted errors. All compliant patients received appropriate treatment without complications. The tool was easy to implement, taking less than 5 minutes per patient. Discussion: The RESP-8 tool effectively guided pharmacists in recommending medical evaluations for URTI patients. The high compliance rate indicates patient trust in pharmacists' guidance. While the study's small sample size limits generalizability, the results are promising. Future studies with larger populations are necessary to validate these findings and further refine the tool. Conclusion: The RESP-8 tool shows potential in enhancing pharmacists' ability to make informed decisions about medical referrals for URTIs, ultimately improving patient outcomes and optimizing healthcare resource management.

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.

Objective: We determined, in stable ambulatory heart failure with preserved ejection fraction (HFpEF) subjects and matched controls, the capability of a novel blood based cardiac-specific cBIN1 Score (CS) to diagnose heart failure and prognosticate future hospitalization. Background: Heart failure (HF) poses a costly health care burden worldwide with rising prevalence. Abnormal calcium signaling is intrinsic to HF pathophysiology and correlates with reduced expression of a cardiac membrane scaffolding protein, cardiac bridging integrator 1 (cBIN1). We hypothesize that CS, a numerical score derived from plasma cBIN1 concentration, is a diagnostic and prognostic biomarker of HF. Methods: Plasma cBIN1 is quantified by an ELISA test, and CS is calculated as the natural log of the normalized reciprocal of plasma cBIN1 concentration. We determined CS among 52 clinically stable individuals with HFpEF (LVEF ≥ 50%) (mean age 57 ± 15 years old, 63% men) and 104 age and sex matched volunteers with no known history of HF. We obtained plasma concentrations of NT-proBNP, a marker of volume status, as comparison. Baseline co-morbidities and one year longitudinal clinical information were obtained through electronic medical records. Results: Median CS is 0 (IQR -0.4 – 0.6) in the control cohort and is increased to 1.8 in the HFpEF cohort (IQR 1.5 – 2.3, p < 0.0001). For HFpEF diagnosis, CS has a receiver operating characteristic (ROC) area under the curve (AUC) of 0.94 (95% CI 0.95 – 0.99) and NT-proBNP of 0.89 (95% CI 0.83 – 0.95). Kaplan-Meier analysis of one year cardiovascular hospitalizations reveals that HFpEF patients with CS ≥ 1.8 have a hazard ratio (HR) of 4.0 (95% CI 1.4 – 11.2, p=0.009). Combining CS ≥ 1.8 with NT-proBNP ≥ 300 pg/mL, increases HR to 21.4 (95% CI 2.7 – 171.6, p=0.004). Conclusions: In a cohort of stable ambulatory HF patients with cardiomyopathies of multiple etiologies and preserved ejection fraction, a positive CS correlates with worsening myocardial health and predicts future hospitalization. CS, a marker of cardiac muscle health, provides a novel index to informing the management of stable ambulatory HF patients.

Traditional computer vision techniques aim to extract meaningful information from images but often depend on manual feature engineering, making it difficult to handle complex real-world scenarios. Fractional Calculus (FC), which extends derivatives to non-integer orders, provides a flexible way to model systems with memory effects and long-term dependencies, making it a powerful tool for capturing fractional rates of variation. Recently, Neural Networks (NNs) have demonstrated remarkable capabilities in learning complex patterns directly from raw data, automating computer vision tasks and enhancing performance. Therefore, the use of fractional calculus in neural network-based computer vision is a powerful method to address existing challenges by effectively capturing complex spatial and temporal relationships in images and videos. This paper presents a survey of Fractional Calculus Neural Network-based (FC NN-based) computer vision techniques for denoising, enhancement, object detection, segmentation, restoration, and NN compression. The survey compiles existing FFC NN-based approaches, elucidates underlying concepts, and identifies open questions and research directions. By leveraging FC's properties, FC NN-based approaches offer a novel way to improve the robustness and efficiency of computer vision systems.

Obesity and environmental toxins are risk factors for breast cancer, however there is limited knowledge on how these risk factors interact to promote breast cancer. Acrylamide, a probable carcinogen and obesogen, is a biproduct in foods prevalent in the obesity-inducing Western diet. Acrylamide is metabolized by cytochrome P450 2E1 (CYP2E1) to the genotoxic epoxide, glycidamide, and is associated with increased risk for breast cancer. To investigate how acrylamide and obesity interact to increase breast cancer risk, female mice were fed a low-fat (LFD) or high-fat diet (HFD) and 0.7mM acrylamide-supplemented water or control water. While HFD significantly enhanced weight gain in mice, the addition of acrylamide did not significantly alter body weights compared to respective controls. Mammary epithelial cells from obese, acrylamide-treated mice had increased DNA strand breaks and oxidative DNA damage compared to all other groups. In vitro, glycidamide-treated COMMA-D cells showed significantly increased DNA strand breaks while acrylamide-treated cells demonstrated significantly higher levels of intracellular reactive oxygen species. Knockdown of CYP2E1 rescued the acrylamide-induced oxidative stress. These studies suggest that long-term acrylamide exposure through foods common in the Western diet may enhance DNA damage and CYP2E1-induced generation of oxidative stress in mammary epithelial cells, potentially enhancing obesity-induced breast cancer risk.

Precision medicine (PM), also termed stratified, individualised, targeted or personalised medicine, embraces a rapidly expanding area of research, knowledge, and practice. It brings together two emerging health technologies to deliver better individualised care: the many “-omics” arising from increased capacity to understand the human genome; and “big data” and data analytics including Artificial Intelligence (AI). PM has the potential to transform an individual’s health, moving from population-based disease prevention to more personalised management. There is however a tension between the two, with a real risk that this will exacerbate health inequalities and divert funds and attention from basic healthcare requirements leading to worse health outcomes for many. All areas of medicine should consider how this will affect their practice, with PM now strongly encouraged and supported by government initiatives and research funding. In this review we discuss examples of PM in current practice and its emerging applications in primary care, such as clinical prediction tools that incorporate genomic markers and pharmacogenomic testing. We look towards potential future applications and consider some key questions for PM including evidence of real-world impact, its affordability, the risk of exacerbating health inequalities, and the computational and storage challenges of applying PM technologies at scale.

Beetles are by far one of the most successful and diverse insect species. A part of this success is attributed to their elytra which provide various functions such as protection to their bodies from mechanical forces and the harmful environmental factors. In this study, Stag beetle (Lucanus cervus) elytra were first examined for their overall flexural properties and were observed to have a localized shape retaining snap-through mechanism which could play a crucial role in energy absorption, e.g. during battles and falls from heights. The snap-through mechanism was validated using theoretical calculations and also finite element simulations. Elytra were also characterized to examine their puncture and wear resistance. Our results show that elytra resisted puncture up to a force of 1.8±0.4 N and have puncture resistance compared to that of commercially available puncture resistant gloves. The measured values of modulus and hardness of elytra exocuticle were 10.3±0.8 GPa and 0.7±0.1 GPa. Using the hardness to modulus ratio as an indicator of wear resistance, the estimated value was observed to be in the range of wear resistant biological materials. Thus, our study demonstrates different mechanical properties of the stag beetle elytra which can be explored to design shape retaining bio-inspired composites with enhanced puncture and wear resistance.

From an agricultural perspective, carrots are a significant tap root vegetable crop in the Apiaceae family because of their nutritional value, health advantages, and economic importance. The edible part of a carrot, known as the storage root, contains various beneficial compounds such as carotenoids, anthocyanins, dietary fiber, vitamins, and other nutrients. It has a crucial role in human nutrition as a significant vegetable and raw material in the nutraceutical, food, and pharmaceutical industries. The cultivation of carrot fields is susceptible to a wide range of biotic and abiotic hazards, which can significantly damage the plants health and decrease yield and quality. Scientific research mostly focuses on important biotic stressors, including pests like nematodes and carrot flies, as well as diseases such as cavity spots, crown or cottony rot, black rot, and leaf blight. The emerging challenges in the field include gaining a comprehensive understanding of the interaction between hosts and pathogens in the carrot-pathogen system, identifying the elements that contribute to disease development, expanding knowledge of systemic treatments, exploring host resistance mechanisms, developing integrated control programs, and enhancing resistance through breeding approaches. In fact, the primary carrot-growing regions in tropical and subtropical climates are experiencing abiotic pressures such as drought, salinity, and heat stress, which limit carrot production. This review provides an extensive, up-to-date overview of the literature on abiotic factors for enhanced and sustainable production, considering the use of intelligent technologies for farm management and production. Moreover, it addresses the current issues in the carrot production chain, opening new perspectives for the exploitation of carrots both as a food commodity and as a source of natural compounds.

Epilepsy is one of the most prevalent and serious brain disorders, affecting 70 million people worldwide. Antiseizure medications (ASMs) though relieve symptoms and prevent the occurrence of future seizures in epileptic patients have limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms for development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made and challenges facing in the development of NLRP3 inhibitors for the treatment of epilepsy.

Smart electronic devices and telemedicine are widely used in humans' daily lives. This provides remote treatment of patients using information and communications technology. New telemedicine technologies, such as the Internet of Medical Things (IoMT), make it easier for medical and computing devices to communicate regularly and effectively. Critical motivations for adapting the IoMT are reduced cost, increased quality of life, and timely medical intervention. IoMT is significant because it enables continuous, real-time patient monitoring during routine everyday activities using a variety of wearables and sensors. With big data, the IoMT technology makes excellent use of Artificial Intelligence (AI) to support disease detection and health condition prediction, alerting patients and healthcare providers. Many research studies have been conducted to explore various aspects of IoMT and its applications in the real world. However, it is challenging to comprehend all the techniques and solutions proposed by the research community. Therefore, this survey sheds light on some crucial aspects of IoMT technologies and explores the potential research gaps and directions the research community could tackle. The survey examines and discusses the characteristics of IoMT standards, protocols, and types. It then delves into the layers of IoMT and distinguishes them into Fog and edge. The studies published under each type were explored, and the limitations of these works were highlighted. The research gaps and directions on IoMT approaches and technologies were also highlighted. With such findings and research directions, further research endeavors could be carried out to address the issues and existing limitations in the IoMT.

Minirhizotron tubes were installed to monitor root growth dynamics of mature Shiraz grapevines in a rootstock trial established in the hot climate Riverina region of New South Wales, Australia. The vertical root distribution and seasonal root growth dynamics of Shiraz on own-roots and Shiraz grafted on the rootstocks Ramsey, 140 Ruggeri and Schwarzmann was studied for five seasons across a seven-year period to a depth of 60 cm. New root production was significantly influenced by genotype, soil depth, season, growth stage and year. Soil moisture and soil tem-perature were monitored at 10, 30 and 60 cm in the last two seasons. Soil moisture at 30 cm and soil temperature at all three depths were significant predictors of root growth. New root numbers were significantly higher in 140 Ruggeri than the other rootstocks. To the depth studied, 140 Ruggeri roots were evenly distributed from the topsoil down, whereas the majority of roots of Schwarzmann and Shiraz were located at intermediate depths in the 10-40 cm ad 20-40 cm zones respectively, while Ramsey roots were found at 20 cm or below. Depending on genotype, root growth occurred across several phenological stages but tended to peak at flowering. In some years we observed root growth in early and late winter at rates exceeding that of autumn, and this was associated with warmer temperatures during this period. Overall, seasonal rooting dynamics were responsive to abiotic factors but dominated by genotype.

The purpose of this study was to examine the problem of violent extremism among young people. Additionally, a youth violent extremism scale (YVES) was developed that takes into account the differences between and within Arab cultures. The goal was to produce a scale that could be used and tested within an Arab country or between Arab countries. The scale was developed in three stages: generation, refinement, and validation. A literature review and nomological network were utilized to show the scale's dimensions, correlations to those dimensions, and other relevant variables (such as the LSC, LSE, and criminality scale). A sample of 6726 young students from fifteen Arab countries and the authorities involved were selected. Findings showed that six factors were obtained through principal component factor analysis using Varimax and Kaiser normalization (29 items). A significant positive association was found (r=.651, p = 0.000), supporting the scale's validity. Using Cronbach's alpha, the scale reliability was strong and assessed at 0.98. The scale's construct validity was estimated by assessing the correlation between the Youth Violent Extremism scale and low self-control. A significant positive correlation (r=.651, p = 0.000) indicates the scale's validity. Findings showed significant differences between males and females in youth violent extremism (F = 13.678, α ≤0.000). Descriptive results showed, however, that females have a slightly higher mean of violent extremism than males (M =85.2 vs. 87.6), with a close variation (26 vs. 27) for males and females, respectively. In this study, a measurement tool was provided that can be used as a knowledge base for security strategies. The scale can be applied to identify legal, social, and educational policies and applications of violent extremism. Future research is needed to test the scale on different professions like teachers, police officers, and parents. Also, a need to test the scale on different age groups, settings, and cultures. A need for atheoretical and empirical framework for understanding and preventing youth violent extremism through promoting a more cohesive and resilient youth society.

Therapeutic phages are primarily chosen based on their in vitro bacteriolytic activity. Although anti-phage antibodies are known to inhibit phage infection, the influence of other immune system components is less well known. An important anti-bacterial and anti-viral innate immune system that may interact with phages is the complement system, a cascade of proteases that recognizes and targets invading microorganisms. In this study, we aimed to study the effects of serum components such as complement on the infectivity of different phages targeting Pseudomonas aeruginosa. We used a fluorescence-based assay to monitor the killing of P. aeruginosa by phages of different morphotypes in presence of human serum. Our results reveal that several myophages are inhibited by serum in a concentration-dependent way, while the activity of four podophages and one siphophage tested in this study is not affected by serum. By using specific nanobodies blocking different components of the complement cascade, we show that activation of the classical complement pathway is a driver of phage inhibition. To determine the mechanism of inhibition, we produced bioorthogonally labeled fluorescent phages to study their binding by means of microscopy and flow cytometry. We show that phage adsorption is hampered in presence of active complement. Our results indicate that interactions with complement may affect in vivo activity of therapeutically administered phages. A better understanding of this phenomenon is essential to optimize the design and application of therapeutic phage cocktails.

Background: Inflammatory demyelination and impaired recovery processes result in permanent neurodegeneration and neurological disability in patients with multiple sclerosis (MS). In terms of smoldering MS, chronic neuroinflammation develops in the early period of the disease and leads to confirmed disability accumulation. There is a great need to identify biomarkers of neuro-degeneration and disease progression. Methods: We evaluated the concentrations of the param-eters of brain injury (NF-H, GPAF, S100B, UCHL1) in the cerebrospinal fluid (CSF) and the se-lected interleukins (ILs) in serum of 123 relapsing-remitting MS (RRMS) and 88 progressive MS (PMS) patients. Results: The levels of GFAP, S100B and UCHL were higher in the PMS group compared to RRMS as opposed to the levels of NF-H. We observed a positive correlation be-tween the selected pro-inflammatory cytokines and the parameters of brain injury. The Ex-panded Disability Status Scale score (EDSS) increased with GFA and NF-H levels and correlated with the selected ILs. The concentrations of S100B, UCHL1 and NF-H reflected the duration of MS symptoms. Conclusions: The levels of brain injury parameters in the CSF and the selected serum ILs in MS patients seem to be promising biomarkers to determine neurodegeneration and neuroinflammation in smoldering MS. Further studies are warranted in this respect.

Cameroon introduced the malaria vaccine in its routine immunization programme on 22 January 2024, in the 42 districts out of 200, among the most at risk of malaria. A cross-sectional analysis of data on vaccine key events in the introduction roadmap and vaccine uptake during the first 30 days was conducted. In addition to available gray literature related to the introduction of the malaria vaccine, data on malaria vaccine uptake by vaccination session, collected through a digital platform, were analyzed. A total of 1,893 reports were received from 22 January 2024 to 21 February 2024 from 766 health facilities (85% of overall completeness). Two regions out of 10 recorded less than 80% of completeness. As of 21 February 2024, 13,811 children have received the first dose of the malaria vaccine, including 7,124 girls (51.6%) and 6,687 boys (48.4%). Thirty six percent of children were vaccinated through outreach sessions versus 61.5% through sessions in fixed posts. The overall monthly immunization coverage with the first dose was 37%. Early results have shown positive attitudes towards and acceptance of malaria vaccines. Suboptimal completeness of data reporting and low coverage highlight persistent gaps and challenges in vaccine rollout.

This study presents the validation process of the Questionnaire on Academic Stress in Secondary Education –QASSE-, designed to assess the wide variety of school sources and situations related to academic stress in adolescence, and their relationship with students’ physical and psychological well-being. Participants were 860 Spanish high school students (52.9% girls) with an average age of 14.62 years (SD = 1.8). Through a cross-validation process, EFA and CFA supported QASSE multifactorial structure with four first-order factors -academic overload, interaction with classmates, family pressure, and future-oriented perspective- and a second-order factor of academic stress, showing a significant and intense relationship with adolescents’ psychological and physical well-being. Results also highlight the effects of the gender*educational level interaction on the students’ stress, with girls showing higher levels of stress in the transition courses between educational phases (sophomore and junior years). The QASSE demonstrates good validity and reliability, showing potential for both research and educational application. The results show the high impact of the QASSE dimensions on psychological and physical well-being in adolescence, highlighting its special usefulness for designing and adjusting educational prevention and intervention actions in this area to the students’ specific characteristics and needs

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Although prognosis continually improved along years, a significant proportion of patients still relapse from the disease due to leukemia resistance to therapy. Methotrexate (MTX), a folic acid antagonist, is a chemotherapy agent commonly used against ALL and a immune-system suppressant for rheumatoid arthritis, that presents multiple and complex mechanisms of action and resistance. Previous studies have shown that MTX modulates the nuclear factor kappa B (NF-κB) pathway, an important family of transcription factors involved in inflammation, immunity, cell survival, and proliferation, frequently hyperactivated in ALL. Using gene set enrichment analysis (GSEA) on publicly available gene expression data from 161 newly diagnosed pediatric ALL patients, we found “TNF-α signaling pathway” to be the most enriched Cancer Hallmark in MTX poor responder patients. Transcriptomic analysis in a panel of ALL cell lines (6 BCP-ALL and 7 T-ALL) also identified the same pathway as differentially enriched among MTX resistant cell lines, as well as in slowly dividing cells. To better understand the crosstalk between NF-κB activity and MTX resistance, we genetically modified the cell lines to express luciferase under a NF-κB biding site promoter. We observed that the fold change in NF-κB activity triggered by TNF-α (but not MTX) treatment correlated with MTX resistance and proliferation across the lines. At the individual gene level, NFKB1 expression was directly associated with a poorer clinical response to MTX, and with both an increased TNF-α-triggered NF-κB activation and MTX resistance in the cell lines. Despite these results, pharmacological inhibition (with BAY 11-7082 and parthenolide) or stimulation (with exogenous TNF-α supplementation) of the NF-κB pathway did not alter MTX resistance of the cell lines significantly, evidencing a complex interplay between MTX and NF-κB in ALL.

(1) Background: The monkeypox virus (MPV) is a double-stranded DNA virus belonging to the Poxviridae family, Chordopoxvirinae subfamily, and Or-thopoxvirus genu. It was called monkeypox because it was first discovered in monkeys, in a Danish laboratory, in 1958. However, the actual reservoir for MPV is still unknown. (2) Methods & Results: We have reviewed the existing literature on the options for Monkeypox virus. There are three available vaccines for orthopoxviruses: ACAM2000, JYNNEOS, and LC16, with the first being a replicating vaccine and the latter being non or minimally replicating. (3) Conclusions: Smallpox vaccinations previously provided coincidental im-munity to MPV. ACAM2000(a live‐attenuated replicating vaccine) and JYNNEOS (a live‐attenuated, non-replicating vaccine) are two US FDA‐approved vaccines that can prevent monkeypox. However, ACAM2000 may cause serious side effects, including cardiac problems, whereas JYNNEOS is associated with fewer com-plications. The recent outbreaks across the globe have once again highlighted the need for constant monitoring and the development of novel prophylactic and therapeutic modalities. Based on available data, there is still a need to develop an effective and safe new generation of vaccines specific for monkeypox that are killed or mRNA before monkeypox is declared a pandemic.

Concentration and preservation of lactic acid bacteria (LAB) starter cultures for food production guarantee the long-term delivery of stable cultures in terms of viability and functional activity. One method that has commonly been used to prepare dried starter cultures for food applications is freeze-drying. During freeze-drying, the bacterial cells are exposed to stresses such as freezing, drying, and long-term exposure to low-water activity. Additionally, another added stress is introduced during the rehydration process. The purpose of this study was to evaluate the survival rates and fermentation performance of three (3) freeze-dried lactic acid bacterial cultures previously isolated from Ghanaian traditional fermented milk. LAB cultures, i.e., Lactobacillus delbrueckii, Lactococcus lactis and Leuconostoc mesenteroides were frozen in the chamber of a Telstar (Lyoquest) laboratory freeze dryer for 10 hrs at -55 °C (as single and combined cultures) using skimmed milk and cassava flour as cryoprotectants held in plastic or glass cryovial. For viability during storage, freeze-dried LAB cultures were stored in a refrigerator (4 °C) and at room temperature (25 °C) for 4-weeks. The survival of freeze-dried cultures was determined by growth kinetics at 600nm (OD₆₀₀). The performance of freeze-dried LAB cultures after 4-weeks storage was determined by their growth and acidification of milk during yogurt fermentation and consumer sensory evaluation of fermented milk using a 9-point hedonic scale. The survival rates for LAB ranged between 60.11% and 70.91% following freeze-drying. For single cultures, the highest survival was recorded for Lactobacillus delbrueckii (L12), whereas for combined cultures, the highest survival was observed for Lactococcus lactis (L3) combined with Lactobacillus delbrueckii (L12). During the fermentation process all the freeze-dried LAB cultures were able to acidify yogurt to a pH below 4, while yogurt produce from the spontaneous fermentation was characterized by low acidification. Yogurt fermented with freeze-dried lactic acid bacteria cultures, either single or combined strains, showed improved acceptability as compared to the spontaneously fermented yogurt. The consumer acceptability results showed that yogurts produced with combined starter culture of Lactoccus lactis and Lactobacillus delbrueckii or single culture of Lactococcus lactis were the most preferred products with Lactococcus lactis and Lactobacillus delbrueckii possessing high survival rates and high consumer acceptability in yogurt production. These findings are crucial and can be adopted for large-scale production and commercialization of yogurt production, however, in-depth investigation on the effects of freeze-drying and long-term storage on survival and performance of selected LAB cultures are needed.

PDEF is expressed in luminal epithelial cells of the prostate gland and associates with luminal phenotype. Hippo pathway regulates cell growth/proliferation, cellular homeostasis, and organ development by modulating phosphorylation of its downstream effectors. In previous studies, we observed decreased levels of PDEF during prostate cancer progression. In the present studies, we evaluated the effects of PDEF on total and phospho (Ser-127)YAP1 protein(a downstream effector of the Hippo pathway) levels in PC3 cells, a line of castrate resistant prostate cancer. We observed that the expression of PDEF in PC3 cells resulted in increased increased phospho(Ser127) -YAP1 protein levels. Our immunofluorescence analysis for YAP1 revealed an increased cytoplasmic/nuclear ratio of YAP1 in PDEF-PC3 cells as compared to VC-PC3 cells, suggesting PDEF may play a critical role in modulating YAP1 phosphorylation, and by extension in the regulation of the Hippo pathway. We also observed a decrease in YAP1 protein levels in prostate cancer tissues as compared to normal prostate tissues. Our analysis of multiple publicly available clinical cohorts revealed a gradual decrease in YAP1 mRNA expression during prostate cancer progression and metastasis. This decrease was similar to the decrease in PDEF levels which we reported earlier. In addition we observed further decreased in PDEF and YAP1 expression in Neuro-Endocrine Prostate Cancer (NEPC), and a direct correlation between PDEF and YAP1 expression. To the best of our knowledge, these results provide the first demonstration of modulation of YAP1 by PDEF in any system and suggest a cross-talk between PDEF and the Hippo pathway.

Artificial Intelligence (AI) and Machine Learning (ML) approaches that could learn from large data sources have been identified as useful tools to support clinicians in their decisional process; AI and ML implementations have had a rapid acceleration during the recent COVID-19 pandemic. However, many ML classifiers are “black box” to the final user, since their underlying reasoning process is often obscure. Additionally, the performance of such models suffer from poor generalization ability in presence of dataset shift. Here, we present a comparison between an explainable-by-design (“white box”) model (Bayesian Network (BN)) versus a black-box model (Random Forest), both studied with the aim to support clinicians of Policlinico San Matteo University Hospital in Pavia (Italy) during the triage of COVID-19 patients. Our aim is to evaluate whether the BN predictive performances are comparable with those of a widely used but less explainable ML model such as Random Forest and to test the generalization ability of the ML models across different waves of the pandemic.

Chromoblastomycosis (CBM) and phaeohyphomycosis (FEO) are infections caused by melanized filamentous fungal agents, primarily found in tropical and subtropical regions. Both infections pose significant challenges for the correct identification of the causative agent due to their morphological similarity, making conventional methods of morphological analysis highly subjective. Therefore, molecular techniques are necessary for the precise determination of these species. In this regard, this study aimed to contribute to a new methodology based on PCR-RFLP for the identification of agents causing CBM and FEO. Sequences from the ITS region were used to identify potential restriction enzyme sites in silico, followed by in vitro validation using the selected restriction enzymes. The obtained results were compared with species identification through morphological analyses and sequencing. The results demonstrated that the PCR-RFLP applied in this study accurately identified two major agents of chromoblastomycosis, Fonsecaea pedrosoi and Fonsecaea monophora, as well as Cladophialophora bantiana and Exophiala dermatitidis, both causative agents of phaeohyphomycosis. In this context, the proposed assay can complement current methods for identifying these species, aiding in diagnosis, and contributing to the proper management of these infections.

This study delves into the dynamics of 'Variations' and 'Claims' within construction projects, specifically under the FIDIC-Red Book 1999 framework. The study aims to identify, categorize, and devise mitigation strategies for key types of variations and claims aligning with the FIDIC conditions of contract. The research is drawing on inputs from construction industry professionals including contract administrators and project managers, focusing on the MENA region. This choice is driven by the region's extensive adoption of FIDIC standards and its rapidly growing construction sector. Data collection encompassed a questionnaire distributed to 80 industry experts predominantly through interviews that focused on countries like Saudi Arabia, UAE, Kuwait, and Egypt. These locations were chosen to reflect diverse construction practices and the involvement of international firms. Utilizing SPSS-V.25 for statistical analysis, the study uncovers the most prevalent and impactful causes of variations and claims, highlighting the critical need for managerial intervention. A key feature is the integration of scientometric analysis for a quantitative finding. A significant addition to the methodology is the implementation of a k-means clustering analysis. The survey had high internal consistency with a Cronbach's alpha of 0.97, and respondents reported frequent and significant claims like delayed drawings, ambiguous documents, and client changes. The results showed that effective claims management requires clear communication and balanced contracts, while poor design and contract documentation cause variations and claims. Spearman's correlation showed strong positive relationships between certain claim types and causes, emphasizing the importance of dealing with these factors to reduce claims. Most respondents said the survey could predict and reduce claims.

This article investigates the features of heat and mass transfer for the steady two-dimensional Williamson nanofluid flow across an exponentially stretched surface depending on suction/injection. The boundary conditions incorporate the impacts of the Brownian motion and thermophoresis boundary. The analysis of heat transfer is carried out for the two cases of prescribed exponential order surface temperature (PEST) and prescribed exponential order heat flux (PEHF). The ongoing flow problem is mathematically modeled under the basic laws of motion and heat transfer. The similarity variables are allowed to transmute the governing equations of the problem into a similarity ordinary differential equation (ODEs). The solution of this reduced non-linear system of ODEs is supported by the Homotopy analysis method (HAM). The combination of HAM arrangements is acquired by plotting the h-curve. In order to evaluate the influence of several emergent parameters, the outcomes are presented numerically and are plotted diagrammatically as a consequence of velocity, temperature and concentration proles.

Crown gall (Agrobacterium tumefaciens), crown/root rot (Phytophthora spp.), root lesion disease (Pratylenchus vulnus), and tree vigor are key traits affecting productivity and quality of walnuts in California. Non-inoculated hybrid rootstocks were analyzed by RNA-seq to examine pre-formed factors affecting these traits. Enrichment analysis of the differentially expressed genes revealed that increased expression of cell wall biogenesis-related genes plays a key role in susceptibility to A. tumefaciens, Phytophthora spp., increased vigor, but not P. vulnus. Analysis of the predicted subcellular loci of the encoded proteins revealed that many gene products associated with vigor and susceptibility were targeted to the plasma membrane and extracellular space, connecting these traits to sustaining barrier function. We observed that RNA processing and splicing, along with predicted nuclear targeting, were associated with resistance to A. tumefaciens, Phytophthora spp., low vigor, but not P. vulnus. Four genes within the J. microcarpa QTL region for resistance to A. tumefaciens and Phytophthora spp. were represented among our transcripts, with two of the genes being differentially expressed in association with resistance to A. tumefaciens and decreased vigor. No differential expression related to Phytophthora spp. or P. vulnus traits was observed in this region. Additionally, the J. microcarpa haplotype expressed more transcripts associated with resistance to A. tumefaciens, Phytophthora spp., and low vigor, but not P. vulnus than the J. regia haplotype. We also report unique and shared hormone and defense responses associated with each trait. This research suggests a link between cell wall biogenesis, vigor, and critical root diseases of walnut.

Hepcidin-25 was identified as the main iron regulator in the human body by binding to the sole iron-exporter ferroportin. Studies showed that the N-terminus of hepcidin is responsible for this interaction, the same N-terminus that encompasses a small copper(II)-binding site known as ATCUN (amino terminal Cu(II)- and Ni(II)- binding) motif. Interestingly, this copper-binding property is largely ignored in most papers dealing with hepcidin-25. In this context, detailed investigations of the formed complex of hepcidin-25 with copper could reveal insights into its biological role. The present work is mainly focused on the study of the metal-bound form of hepcidin-25, which could be considered the biologically active form. The first part is devoted to the reversed-phase chromatographic separation of copper-bound and copper-free hepcidin-25, which was achieved by applying basic mobile phases containing 0.1% ammonia. Further, mass spectrometry (tandem mass spectrometry MS/MS, high resolution mass spectrometry HRMS) and nuclear magnetic resonance (NMR) spectroscopy were employed to characterize the copper-peptide. Lastly, a 3D model of hepcidin-25 with bound copper(II) is presented. The identification of metal complexes and potential isoforms and isomers, from which the latter usually are left undetected by mass spectrometry, led to the conclusion that complementary analytical methods are needed to characterize a peptide calibrant or reference material comprehensively. Quantitative nuclear magnetic resonance (qNMR), inductively-coupled plasma mass spectrometry (ICP-MS), ion-mobility spectrometry (IMS) and chiral amino acid analysis (AAA) should be considered among others.

This paper presents a comprehensive cost-benefit analysis of producing alternative phosphorus (P) fertilizers from recycled water treatment residuals (Fe-WTR) and cowshed effluents, under the umbrella of circular economy approach. Fe-WTR is compared to a synthetic adsorbent, layered double hydroxide (LDH). Dairy wastewater is used as a P source for both adsorbents. The cost of 1 ton P-Fe-WTR sums up to 329 Euro. In contrast, the use of synthetic adsorbents (P-LDH) incurs significantly higher costs, amounting to 3329 Euros per ton, underscoring the economic advantage of utilizing waste-derived materials. Adopting Fe-WTR fertilizer not only offers substantial cost savings by avoiding landfill fees (40-150 Euros per ton) and wastewater discharge fines (500 Euros per ton) but also reduces environmental impacts. This sustainable method mitigates eutrophication and pollution, presenting a dual benefit of cost-effectiveness and environmental protection. Although our results are based on a specific case study, they reflect the potential value of extending the circular economic approach to P production worldwide: Recycling P from waste streams can be economically viable and environmentally preferable at large, aligning with global sustainability goals and demonstrating the practicality of circular economy principles in environmental management.

Abstract: Effectiveness of a Single Fixed Dose 3 mg Rasburicase for Prevention and Management of Hyperuricemia of Tumor Lysis Syndrome in adult Cancer Patients Background: Tumor lysis syndrome (TLS) is a potentially life-threatening complication associated with certain types of cancer. Rasburicase is an essential medicine required to prevent and treat the hyperuricemia associated with TLS. Due to a shortage of rasburicase during the COVID-19 pandemic, a fixed dose strategy of 3 mg rasburicase had been used in many adult cancer patients in our center. Objective: The objective of this study was to assess the effectiveness of a 3 mg fixed dose of rasburicase in preventing and managing hyperuricemia associated with TLS in adult cancer patients. Methods: We conducted a retrospective, observational cohort study between March 2020 and November 2022. The study included adult patients who received a fixed dose of 3 mg rasburicase. The primary outcome measure was the reduction in serum UA levels of

Laser in situ keratomileusis (LASIK) is the gold standard in the surgical correction of refractive errors on the cornea. It entails the creation of a superficial hinged corneal flap by a femtosecond laser, ablation of the underlying stromal bed by an excimer laser, and reposition of the flap. The corneal flap can be build in a 2-dimension (2D) fashion with tapered edges, or in a 3-dimension (3D) fashion, with angled sidecut. The latter reduces the risk of flap dislocation and infiltration of epithelial cells. This retrospective study compares with optical coherence tomography 3D and 2D flaps, and respective intra- and early post-operative complications. Four hundred consecutive eyes were included, 200 for each group. In the 3D group, the mean edge angle was 92°. The procedure was in average 5.2 seconds slower in the 3D group (p=0). Non visually significant flap folds were found in 13 eyes of the 2D group and in 7 eyes of the 3D group (p= 0.17). An intracorneal opaque bubble layer induced by laser photodisruption was more commonly observed in the 3D group (9 eyes vs. 2; p=0.03). In conclusion, the creation of a LASIK flap by a 3D-femtosecond laser cut was safe and effective.

Despite being extremely potent against malignancies, cisplatin (CIS) has limited practical applicability due to its adverse effects such as testicular damage. Consequently, it becomes necessary to reduce its toxicity. In this study, cilostazol, a selective phosphodiesterase-3 inhibitor that is frequently used in the treatment of intermittent claudication, was examined for its ability to abrogate CIS-induces testicular toxicity and its ameliorative effect was compared with two phosphodiesterase inhibitors, tadalafil and pentoxifylline. The study also focused on the possible mechanisms involved in the proposed protective effect. Ten groups of rats were included; Group (1): control, Groups (2-4): 5 mg/kg tadalafil or 75 mg/kg pentoxifylline or 20 mg/kg cilostazol respectively), Group (5):7 mg/kg CIS, Group (6&7): CIS + 5 mg/kg tadalafil or 75 mg/kg pentoxifylline, Group (8-10) CIS+ 5, 10 or 20 mg/kg cilostazol respectively. CIS treated rats showed a significant decrease in testicular function, serum testosterone and reduced glutathione levels, and significant elevation in malondialdehyde, total nitrite levels, tumor necrosis factor-alpha and nuclear factor-kappa β alongside caspase-3. These outcomes were confirmed by marked testicular architecture deterioration. Contrary, Cilostazol in a dose-dependent manner showed potential protection against testicular toxicity, reversion of the disrupted testicular function and improvement of the histological alterations through rebalancing of oxidative stress, inflammatory and apoptotic biomarkers. In addition, cilostazol exerted more pronounced protective effect in comparison to tadalafil and pentoxifylline. In conclusion, administrations of cilostazol might ameliorate cisplatin-induced testicular impairment through alteration of oxidative stress, inflammation, and apoptotic pathway, offering a promising treatment for cisplatin -intoxication in the testes.

A shrimp oil rich in omega-3 lipids and carotenoids is obtained in remarkably high 5 wt% yield extending to pink shrimp processing waste (head and carapace) the circular economy approach to extract fish oil from fish processing by-products using d-limonene. Biobased limonene, a powerful antimicrobial and antioxidant agent, is an excellent solvent for both lipids and astaxanthin-based carotenoids preventing oxidative degradation during the extraction cycle including solvent and oil separation at 85°C. A new low cost route is established to extract valued marine oil from biowaste annually made available in over 2.2 million tonnes.

Kinetic parameters of SO2 adsorption on unburned carbons from lignite fly ash and activated carbons based on hard coal dust were determined. The model studies were performed using the linear and non-linear regression method for the following models: pseudo first and second-order, intraparticle diffusion, and chemisorption on a heterogeneous surface. The quality of the fitting of a given model to empirical data was assessed based on: R2, R, Δq, SSE, ARE, χ2, HYBRID, MPSD, EABS, and SNE. It was clearly shown that it is the linear regression that more accurately reflects the behaviour of the adsorption system, which is consistent with the first-order kinetic reaction – for activated carbons (SO2+Ar) or chemisorption on a heterogeneous surface – for unburned carbons (SO2+Ar and SO2+Ar+H2O(g)+O2) and activated carbons (SO2+Ar+H2O(g)+O2). Importantly, usually, each of the approaches (linear/non-linear) indicated a different mechanism of the studied phenomenon. A certain universality of the χ2 and HYBRID functions has been proved, the minimization of which repeatedly led to the lowest SNE values for the indicated models. Fitting data by any of the non-linear equations based on the R or R2 functions only, cannot be treated as evidence/prerequisite of the existence of a given adsorption mechanism.

Social connectedness connection is a core dimension of health and wellness among all populations, yet the experience of moving to, and living in, a new country makes social and community-level influences particularly salient for immigrants. We interviewed 38 Latino immigrants living in a nontraditional migration area to explore the social and community foundations of health and wellness. Illustrated in a model of socioecological connectednesssocial connection, Using hybrid (inductive/deductive) qualitative analysis, we identified seven themesdomains of social connection from the perspective of the interviewed participants: 1) Lens of the individual is a filter for the social world; 2) Immigrant experience colors everything; 3) Interpersonal support enhances quality of life; 4) Community belonging fosters a sense of connectedness; 5) Community capital boosts security; 6) Community navigation promotes integration; and 7) Social acceptance strengthens inclusion. In the healthcare field, we lack conceptual clarity of the distinct connectedness domains that drive positive health outcomes in immigrant populations. Social connection domains generated by participants are consistent with the scientific literature, but this study identifies the specific social factors that immigrants describe as most salient to their own health and wellness. Our community-generated understanding of socioecological connectednesssocial connection can be used by healthcare providers to reduce risks and build on assets that will improve the health of immigrants living in nontraditional migration areas. health. Additionally, our model of socioecological connectednessthese results might serve as a foundation for a quantitative measure that can be used by providers to more accurately and comprehensively assess connectedness social connection of their patients and by researchers to evaluate the effectiveness of community-level interventions for immigrants.

This paper presents the results of quantitative research regarding the examination of the levels of efficiency of the fire protection system and the training of employees in Electrical power distribution of Serbia for fire protection, ie the analysis of the manner of implementation of fire protection measures, and determining whether these measures are adequately applied. Following the subject set in this way, the aim of the research was set, and that is the scientific analysis of the manner of application of fire protection measures. The results of this research showed that the employees of Electro distribution Belgrade perceive the preparedness of their company highly positively and certain socio-demographic characteristics also affect certain attitudes, especially those related to the experience with fire, the knowledge of employees to react in case of fire, and the choice of the appropriate response, assessment of the readiness of the company and the employees themselves. It was found that knowledge of how to react in case of fire is influenced by gender and level of education; the choice of one of the methods of action in case of fire is influenced by gender; the assessment of the readiness of the employees themselves is influenced by the marital status; the desire of employees to participate in training to increase their preparedness for fires is influenced by gender. The results of the research can be used to improve the preparedness of employees in various organizations to respond to disasters caused by fires.

The involvement of the prefrontal cortical dopaminergic system in psychopathology of epilepsies and comorbid conditions such as autism spectrum disorder (ASD) still needs to be explored. We used autoradiography to study the D1-like (D1DR) and D2-like (D2DR) receptor binding density in the prefrontal cortex of normal Wistar rats and Wistar-derived strains with generalized convulsive and/or nonconvulsive epilepsies. WAG/Rij rats served as a model for non-convulsive absence epilepsy, WAG/Rij-AGS as a model of mixed convulsive/non-convulsive forms, and KM strain was a model for convulsive epilepsy comorbiding with ASD-like behavioral phenotype. Prefrontal cortex of rats with any of epileptic pathology studied, demonstrated profound decreases in binding densities to both D1DR, D2DR; the effects were localized in the primary and secondary anterior cingulate cortexi, and adjacent regions. The local decreased D1DR and D2DR binding densities were independent (not correlated) from each other. The particular group of epileptic rats with ASD-like phenotype (KM strain), displayed changes in the lateral prefrontal cortex and adjacent regions: D1DR were lowered, but those to D2DR elevated, in anterior dysgranular insular cortex and adjacent regions. Thus, epilepsy-related changes in the dopaminergic system of rat archeocortex were localized in the medial regions, whereas ASD-related candidates were seen in the lateral aspects. The findings point to putative local dopaminergic dysfunctions, associated with generalized epilepsies and/or ASD.

The aim of this review was to provide an update on the potential of cell therapies to restore or replace damaged and/or lost cells in retinal degenerative and optic nerve diseases, describing the available cell sources and the challenges involved in such treatments when these techniques are applied in real clinical practice. Sources include human fetal retinal stem cells, allogenic cadaveric human cells, adult hippocampal neural stem cells, human CNS stem cells, ciliary pigmented epithelial cells, limbal stem cells, retinal progenitor cells (RPCs), human pluripotent stem cells (PSCs) (including both human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs)) and mesenchymal stem cells (MSCs). Of these, RPCs, PSCs and MSCs have already entered early-stage clinical trials since they can all differentiate into RPE, photoreceptors or ganglion cells, and have demonstrated safety, while showing some indicators of efficacy. Stem/progenitor cell therapies for retinal diseases still have some drawbacks, such as the inhibition of proliferation and/or differentiation in vitro (with the exception of RPE) and the limited long-term survival and functioning of grafts in vivo. Some other issues remain to be solved concerning the clinical translation of cell-based therapy, including (1) the ability to enrich for specific retinal subtypes; (2) cell survival; (3) cell delivery, which may need to incorporate a scaffold to induce correct cell polarization, which increases the size of the retinotomy in surgery and, therefore, the chance of severe complications; (4) the need to induce retinal detachment to perform the subretinal placement of the transplanted cell; and (5) the evaluation of the risk of tumor formation caused by the undifferentiated stem cells and prolific progenitor cells. Despite these challenges, stem/progenitor cells represent the most promising strategy for retinal and optic nerve disease treatment in the near future, and therapeutics assisted by gene techniques, neuroprotective compounds and artificial devices can be applied to fulfil clinical needs.