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Background: A high proportion of sexual minorities like Hijras/Eunuch engage in sex work and thus become a high-risk population for HIV and sexually transmitted infections (STIs). Hence, we conducted a study with objective to assess prevalence of high-risk behavior among self-identified Hijras/Eunuch and associated factors. Material and Methods: A cross-sectional study was conducted in a field practice area of Tertiary Care Hospital from December 2019 to December 2020. All participants in the age group of 18 to 45 years were interviewed. Univariate and bivariate analysis was done to determine the correlates. Results: Out of 163, 85% of participants were involved in high-risk sexual behavior and 46.63% did only sex work, 51.5% of participants had comprehensive knowledge about HIV/STI. On applying logistic regression, the factors associated with high-risk sexual behavior include 18–24 years of age group, history of addiction, practicing paid sex, using psychotropic substances, comprehensive knowledge regarding HIV/STI, and comprehensive exposure to preventive measures. Conclusion: Our study findings suggest the urgent need for appropriate preventive measures to understand and address sexual health and risk behavior vulnerabilities faced by Hijras to make significant progress against the HIV epidemic in the country.

This paper introduces a novel quadruple-mode excited low-profile metasurface (MTS)-based broadband circularly polarized (CP) patch antenna. For a quadruple-mode excitation, the antenna uses a unique pac-man-shaped patch (PSP) as the primary CP radiator and above it a $4\times 4$ sized rectangular MTS, which acts as the secondary radiator. Characteristic mode analysis (CMA)-based mode manipulation approach facilitates effortless separation of two orthogonal modes (OMs) of PSP, creating a 90° phase difference for circular polarization. Further, to increase the design’s axial ratio bandwidth (ARBW), two additional OMs of the MTS layer are cascaded with the PSP modes. Consequently, the four OMs exhibit quadruple-mode excitation, and the design achieves broadband CP radiation. A prototype of the proposed antenna is fabricated using an FR-4 substrate, and the overall dimension of the antenna is $0.55\lambda \times 0.7\lambda \times 0.06\lambda $ at 6.46 GHz center operating frequency. The 10 dB impedance bandwidth of the antenna is 55.22% (4.68–8.25 GHz), and the 3 dB ARBW is 35.48% (5.1–7.3 GHz). It exhibits a peak gain of 6.2 dBi. The measurement results agree well with the simulation results.

Abstract In South Asia, declining water tables due to increased irrigation and labor shortages for manual weeding pose significant challenges for wheat production. Additionally, herbicide resistance, often resulting from poor management practices, further complicates weed problems. The objective of this study was to assess the impacts of traditional irrigation regimens (IRs) and herbicide application on wheat crops. The findings showed that when irrigation was applied at 100 mm CPE (IR4), and at 40 mm CPE (IR1), different combinations of herbicide to weed managment were tested. In comparison to the other treatments, application of irrigation at 40 mm cumulative pan evaporation (IR1) along with the Pendimethalin1000 g ha−1 (pre-em) in combination with clodinafop-propargyl 10% + metribuzin 22% + sulfosulfuron 4.2% at a rate of 1125 g ha−1 at 30 DAS (WM1) produced the best results in terms of crop yields, economic returns, relative water content, consumptive use, rate of water use, water use efficiency, water productivity, energy input–output, energy returns, energy productivity, energy intensity, specific energy, energy efficiency, maximum field capacity, available soil water, and soil profile moisture extraction pattern. The only exceptions were Pendimethalin1000g ha−1 (pre-em) combined with carfentrazone ethyl 20% + sulfosulfuron 25%WG), at the rate of 100 g ha−1 at 30 DAS (WM2) and the weed-free treatment (WM5), where the differences were not statistically significant. The yield of wheat grain (14.26 kg ha−1) and straw (14.41 kg ha−1) decreased as the unit dry matter production of weeds increased. The study recommends exploring additional weed control strategies and irrigation management options in future improve wheat yields in conventionally-tilled systems.

Neuroendocrine breast cancers (NEBCs) are a rare and distinct subtype of breast tumors, characterized by their neuroendocrine differentiation. Despite accounting for less than 1% of all breast cancers, NEBCs present unique diagnostic and therapeutic challenges due to their heterogeneous nature and variable prognosis. Accurate imaging plays a crucial role in the diagnosis, treatment planning, and follow-up of NEBCs, yet remains a complex area due to the rarity of these tumors and overlapping features with more common breast cancers. We present a series of 4 cases of primary NEBC, emphasizing the imaging features and their histopathological correlations. All patients presented with breast lump. Diagnostic Mammography followed by Ultrasound was performed in each case. All 4 cases were categorized as Breast Imaging- Reporting and Data System (BI-RADS)-4. Trucut biopsy was performed and histopathological analysis revealed the diagnosis of NEBC. Patients underwent Surgery followed by Chemotherapy, Hormonal Therapy or Radiation therapy alone or in combination with each other depending upon the histopathological characteristics.

Abstract Background Therapeutic targets supported by genetic evidence from genome-wide association studies (GWAS) show higher probability of success in clinical trials. GWAS is a powerful approach to identify links between genetic variants and phenotypic variation; however, identifying the genes driving associations identified in GWAS remains challenging. Integration of molecular quantitative trait loci (molQTL) such as expression QTL (eQTL) using mendelian randomization (MR) and colocalization analyses can help with the identification of causal genes. Careful interpretation remains warranted because eQTL can affect the expression of multiple genes within the same locus. Methods We used a combination of genomic features that include variant annotation, activity-by-contact maps, MR, and colocalization with molQTL to prioritize causal genes across 4,611 disease GWAS and meta-analyses from biobank studies, namely FinnGen, Estonian Biobank and UK Biobank. Results Genes identified using this approach are enriched for gold standard causal genes and capture known biological links between disease genetics and biology. In addition, we find that eQTL colocalizing with GWAS are statistically enriched for corresponding disease-relevant tissues. We show that predicted directionality from MR is generally consistent with matched drug mechanism of actions (> 85% for approved drugs). Compared to the nearest gene mapping method, genes supported by multi-omics evidences displayed higher enrichment in approved therapeutic targets (risk ratio 1.75 vs. 2.58 for genes with the highest level of support). Finally, using this approach, we detected anassociation between the IL6 receptor signal transduction gene IL6ST and polymyalgia rheumatica, an indication for which sarilumab, a monoclonal antibody against IL-6, has been recently approved. Conclusions Combining variant annotation, activity-by-contact maps, and molQTL increases performance to identify causal genes, while informing on directionality which can be translated to successful target identification and drug development.

Patients with limited English proficiency (LEP) experience reduced pain assessment and treatment, less comprehensive physical exams, and fewer explanations of the next steps in care. These disparities persist in hospitals with staffed professional interpreters, raising questions about interpreter access and the impact on outcomes. A retrospective review of 1133 trauma activations at a single center Level 1 Trauma Center in 2021–2022 was conducted. Demographic, injury, and outcome data were drawn from the institutional trauma registry, and patient-preferred language was pulled from EMR data. Early interpreter use was defined as documentation of professional interpreter use within 24 h of arrival. LOS and ICU LOS were compared between language groups using Cox regression, and mortality was compared using Fischer's exact test. 1114 patients had data available on initial injury severity and preferred language. Of the 70 LEP patients, 62 (88.6 %) required an interpreter, and 41 of those (66.1 %) had evidence of professional interpreter use within 24 h of arrival. LEP patients who lacked early interpreter use had longer hospital stays than both English proficient (EP) patients (HR 0.59, p

Over the past four decades, obesity rates in the United States have consistently increased, with current estimates indicating that over 42% of adults are affected [1]. In contrast, burn injuries have decreased significantly during the same period, largely due to effective public awareness campaigns and improvements of safety regulations [2]. Despite these opposing trends, the percentage of burn patients at the author’s hospital with a concurrent diagnosis of obesity has risen, posing unique challenges for clinical providers. Patients with elevated body weight and extensive burns require special considerations for proper positioning, wound exposure, and minimizing ergonomic risks to healthcare workers [3]. Currently, there is a notable lack of comprehensive guidelines on operative strategies specifically tailored for this patient population. In response to this knowledge gap, the authors’ institution implemented novel surgical techniques designed to manage circumferential burn wounds in patients with higher body weight.

Abstract Current convolutional neural networks (CNNs) are not designed for large scientific images with rich multi-scale features, such as in satellite and microscopy domain. A new phase of development of CNNs especially designed for large images is awaited. However, application-independent high-quality and challenging datasets needed for such development are still missing. We present the ‘UltraMNIST dataset’ and associated benchmarks for this new research problem of ‘training CNNs for large images’. The dataset is simple, representative of wide-ranging challenges in scientific data, and easily customizable for different levels of complexity, smallest and largest features, and sizes of images. Two variants of the problem are discussed: standard version that facilitates the development of novel CNN methods for effective use of the best available GPU resources and the budget-aware version to promote the development of methods that work under constrained GPU memory. Several baselines are presented and the effect of reduced resolution is studied. The presented benchmark dataset and baselines will hopefully trigger the development of new CNN methods for large scientific images.

Abstract Background Residing in a disadvantaged neighborhood has been linked to increased mortality. However, the impact of residential segregation and social vulnerability on cause-specific mortality is understudied. Additionally, the circulating metabolic correlates of neighborhood sociodemographic environment remain unexplored. Therefore, we examined multiple neighborhood sociodemographic metrics, i.e., neighborhood deprivation index (NDI), residential segregation index (RSI), and social vulnerability index (SVI), with all-cause and cardiovascular disease (CVD) and cancer-specific mortality and circulating metabolites in the Southern Community Cohort Study (SCCS). Methods The SCCS is a prospective cohort of primarily low-income adults aged 40–79, enrolled from the southeastern United States during 2002–2009. This analysis included self-reported Black/African American or non-Hispanic White participants and excluded those who died or were lost to follow-up ≤ 1 year. Untargeted metabolite profiling was performed using baseline plasma samples in a subset of SCCS participants. Results Among 79,631 participants, 23,356 deaths (7214 from CVD and 5394 from cancer) were documented over a median 15-year follow-up. Higher NDI, RSI, and SVI were associated with increased all-cause, CVD, and cancer mortality, independent of standard clinical and sociodemographic risk factors and consistent between racial groups (standardized HRs among all participants were 1.07 to 1.20 in age/sex/race-adjusted model and 1.04 to 1.08 after comprehensive adjustment; all P

The triple planetary crisis of climate change, pollution, and biodiversity loss necessitates more holistic, comprehensive, and integrated public policy approaches. Within the United Nations Framework Convention on Climate Change, this crisis highlights significant conflicts over forms of knowledge and conceptualization, affecting how international policies are formed. Indigenous knowledge systems have become increasingly acknowledged for their vital role in addressing the challenges of the Anthropocene. Conferences of the Parties institutions like the International Indigenous Peoples Forum on Climate Change emphasize the critical, although not always recognized, importance of Indigenous territories, which contain eighty percent of the world’s biodiversity. Here, we show that research in paleoecology, archaeology and history demonstrates the long-term significance of traditional knowledge and Indigenous land management practices for contemporary ecosystem dynamics. Drawing from these varied studies and perspectives also reveal the socio-economic inequalities resulting from centuries of European colonialism. We showcase three case studies on; (i) pastoralism in eastern Africa, (ii) natural resource management in southeast Asia and (iii) adaptation to sea level rise in the Caribbean, which touch upon highly diverse human resilience strategies across space and time. Despite efforts at the COP28 to accelerate climate action and incorporate diverse knowledge systems, significant challenges remain. The need for a pluralistic knowledge, rather than a one-size-fits-all approach, blending scientific language with artistic and narrative forms, is proposed as critical for fostering effective communication and developing more effective and equitable solutions for global environmental governance.

BackgroundUnstable gait leading to falls negatively impacts the quality of life in many people with Parkinson’s disease (PD). Systematic review evidence provides moderate to strong evidence of efficacy for a wide range of physiotherapy-based interventions to reduce gait impairment. However, outcomes have often focused on gait assessments conducted in controlled laboratory or clinical environments.ObjectiveThis perspective investigates the complexities and challenges of conducting real-world gait assessments in people with PD and the factors that may influence the translation from improved lab-assessed gait to improved real-world gait.MethodsThrough a thorough review of current literature, we present an in-depth analysis of current methodological approaches to real-world gait assessments and the challenges that may influence the translation of an intervention’s success from lab-based outcomes to improved walking during daily life.ResultsWe identified six key factors that may influence the translation of intervention success into real-world environments at different stages of the process. These factors comprise the gait intervention, parameters analyzed, sensor setup, assessment protocols, characteristics of walking bouts, and medication status. We provide recommendations for each factor based on our synthesis of current literature.ConclusionThis perspective emphasizes the importance of measuring intervention success outside of the laboratory environment using real-world gait assessments. Our findings support the need for future studies to bridge the gap between proven efficacy for gait as assessed in controlled laboratory environments and real-world impact for people with PD.

For the treatment of NSCLC one of the promising strategies is targeted inhibition of EGFR and its mutants. In this research work, we tend to epitomize design, synthesis, in-vitro anticancer evaluation of novel indole-thiazole derivatives as novel reversible EGFR inhibitor which have trifling toxicity. The structure of the novel indole-thiazole derivatives was designed considering the standard drug EAI045. The detailed study of first generation, second generation, third generation and fourth generation EGFR inhibitors was carried out before the designing of novel indole-thiazole derivatives. The results point toward the novel indole-thiazole derivatives 7(a-n) potential as moderate to excellent anticancer compounds. The SAR studies indicated that compounds 7e, 7f, 7 h, 7 k and 7 l reveals marvellous selective inhibition of EGFRL858R/ T790M over wild type EGFR. Especially, the synthesized compounds 7e (HCC827 IC 50 = 0.23 µM, H1975 IC 50 = 0.38 µM) and 7f (HCC827 IC 50 = 0.34 µM, H1975 IC 50 = 0.42 µM) revealed excellent in vitro anticancer activity and selectivity ratio. The compounds have also shown more selectivity towards cancer cells when compared with normal cell BEAS-2B. This shows that compounds will show minimal toxicity towards normal cells. The enzyme assay results revealed that the compound 7e has an ability to inhibit reversibly EGFR L858R/T790M. The compound 7e possibly appreciably inhibit colony formation and wound healing. The compound 7e was also able to induce apoptosis in cancer cells. The docking study also proofed the aptness to inhibit EGFR L858R/T790M of the synthesized compounds. Our findings suggest that the novel indole-thiazole derivatives 7(a-n), can specifically in vitro and at cellular level, target the mutant EGFRL858R/T790M and will open the new doors for the cancer therapy against EGFR L858R/T790M mutated cancer cells.

Objective To look for the prevalence of vitamin D deficiency (VDD) and its association with anti-TPO antibody and thyroid hormones (FT3, FT4, and TSH) levels in newly diagnosed patients with autoimmune thyroid disease (AITD). Methods In this case-control study, new-onset AITD hypothyroidism/hyperthyroidism patients (anti-TPO-Ab levels >60 IU/ml) were recruited (n = 50). Fifty age, sex, and BMI-matched euthyroid healthy individuals were taken as controls. Detailed clinical examination and necessary investigations such as serum FT3, FT4, TSH, anti-TPO-Ab, 25 OHD (25 hydroxy vitamin D), and iPTH were measured. Results The prevalence of VDD (25 OHD

Ethyl carbamate (EC) is a process contaminant found in fermented foods and alcoholic beverages. Metabolic conversion of ethyl carbamate generates vinyl carbamate (VC), a carcinogenic metabolite. EC, as a Group 2A probable human carcinogen, and the more potent VC, are known to cause tumors in rodents. However, their effects on the kidney are unknown and were explored here. Female A/J inbred mice received an intraperitoneal injection of vehicle or VC. Beginning 5 weeks after VC injection, mice showed signs of moribund state. Mouse necropsies revealed renal glomerular injury that histopathologically recapitulated human membranoproliferative glomerulonephritis (MPGN), as evidenced by light microscopy, immunostaining for immunoglobulins and complements, and electron microscopy. To determine the molecular pathomechanisms, a post-hoc analysis was performed on a publicly available RNA-Seq transcriptome of kidneys from control rats and rats treated with fermented wine containing high concentrations of EC. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the differentially expressed genes revealed that the complement and coagulation cascades were a top predicted biological process involved. Furthermore, pathway-based data integration and visualization revealed that key regulators of complement activation were altered by high EC treatment. Among these, complement factors (CF) D and H, critical positive and negative regulators of the alternative pathway, respectively, were most affected, with CFD induced by 3.49-fold and CFH repressed by 5.9-fold, underscoring a hyperactive alternative pathway. Consistently, exposure of primary glomerular endothelial cells to EC or VC resulted in induction of CFD and repression of CFH, accompanied by increased fixation of C3 and C5b9. This effect seems to be mediated by Ras, one of the top genes that interact with both EC and VC, as identified by analyzing the chemical-gene/protein interactions database. Indeed, EC or VC-elicited complement activation was associated with activation of Ras signaling, but was abolished by the Ras inhibitor farnesyl thiosalicylic acid. Collectively, our findings suggest that VC, a metabolite of EC, induces glomerular injury in mice akin to human MPGN, possibly via perturbing the expression of complement regulators, resulting in an effect that favors activation of the alternative complement pathway.

One of the most important concerns around the world nowadays is the drinking water quality. Silver ions (Ag+) are one of the heavy metal ions that can seriously degrade the water quality and therefore, the human health. Hence, the World Health Organization (WHO) fixed the maximum acceptable concentration of these ions in drinking water at approximately 0.93 µM. Thus, the development of cost-effective and efficient techniques and tools that can help to quantify Ag+ ions in drinking water is of great importance. Herein, we used a new, simple, eco-friendly and low-cost synthesis route to synthesize a sustainable hybrid carbon material, namely sulfonated reduced graphene oxide@graphene oxide (S-rGO@GO) that was utilized as electrode material for Ag+ ions electroanalysis in drinking water. The successful synthesis of S-rGO@GO was evidenced by XRD, Raman spectroscopy, XPS, FE-SEM and EDX. The electrochemical characterization of S-rGO@GO revealed its good affinities towards Ag+ and its good electron transport abilities. The sensor prepared from S-rGO@GO (S-rGO@GO/GCE) showed good repeatability and reproducibility. S-rGO@GO/GCE optimization revealed that its best performance is achieved when 5 µL of 1 mg/mL of S-rGO@GO suspension in ultrapure water is used for its fabrication and when the electrodeposition (Ag+ to Ag0) is carried out at -0.1 V vs. SCE for 200 s. The calibration of S-rGO@GO/GCE exhibited a linear relationship in the concentration range of 0.2 to 1.4 µM, with a sensitivity of (0.605 ± 0.015) µA/µM; the statistic LOD was found to be 0.0007 µM. Furthermore, S-rGO@GO/GCE has shown a great potential for real samples analysis.

Introduction Glioblastoma multiforme (GBM) is a devastating form of cancer with a poor prognosis despite available treatments. Managing recurrent GBM remains challenging and lacks guidelines. This study aims to provide practice patterns for managing recurrent GBMs in India.

This paper presents a scalable solution for zero-sum, one-sided, partially observable stochastic games (Z-POSGs) in the realm of cybersecurity. Existing heuristic search value iteration (HSVI) methods often face significant challenges with scalability in large and complex networks. To overcome this limitation, we introduce an innovative approach that leverages core attack graphs summarized abstractions that streamline incremental strategy generation. This technique reduces the belief and action spaces, making it possible to manage large-scale networks more efficiently. By focusing the analysis on the core attack graph, our approach minimizes the necessity to process the entire network, leading to substantial reductions in time and memory requirements while maintaining solution accuracy. Our method achieves an average solution accuracy within an epsilon value of 0.68%. Additionally, experimental results show that the execution time on the core attack graph is reduced by around 45% compared to that on the original graph, showcasing its significant performance advantage. Furthermore, we successfully solved the largest instances, comprising up to 300 nodes, underscoring the scalability and efficiency of our approach in handling complex, large-scale networks. Comparative evaluations demonstrate that integrating core attack graphs with existing HSVI techniques not only enhances scalability but also preserves solution quality. These findings highlight the proposed method’s potential for effective and efficient application in large-scale cybersecurity networks, outperforming state-of-the-art solutions.

Global contexts in images are quite valuable in image-to-image translation problems. Conventional attention-based and graph-based models capture the global context to a large extent; however, these are computationally expensive. Moreover, existing approaches are limited to only learning the pairwise semantic relation between any two points in the image. In this paper, we present Latent Graph Attention (LGA), a computationally inexpensive (linear to the number of nodes) and stable modular framework for incorporating the global context in existing architectures. This framework particularly empowers small-scale architectures to achieve performance closer to that of large architectures, making the light-weight architectures more useful for edge devices with lower compute power and lower energy needs. LGA propagates information spatially using a network of locally connected graphs, thereby facilitating the construction of a semantically coherent relation between any two spatially distant points that also takes into account the influence of the intermediate pixels. Moreover, the depth of the graph network can be used to adapt the extent of contextual spread to the target dataset, thereby able to explicitly control the added computational cost. To enhance the learning mechanism of LGA, we also introduce a novel contrastive loss term that helps our LGA module to couple well with the original architecture at the expense of minimal additional computational load. We show that incorporating LGA improves performance in three challenging applications, namely transparent object segmentation, image restoration for dehazing and optical flow estimation.

Abstract We study here the response of photonic hydrogels (PHs), made of photonic crystals of homogeneous silica particles in polyacrylamide hydrogels (SPHs), to the uranyl ions UO 2 2+ in aqueous solutions. It is found that the reflection spectra of the SPH show a peak due to the Bragg diffraction, which exhibits a blue shift in the presence of UO 2 2+ . Upon exposure to the SPH, UO 2 2+ gets adsorbed on the SPH and forms complex coordinate bonds with multiple ligands on the SPH, which causes shrinking of hydrogel and leads to the blue shift in the diffraction peak. The amount of the blue shift in the diffraction peak increases monotonically up to UO 2 2+ concentrations as high as 2300µM. The equilibration time for the shift in the Bragg peak upon exposure to UO 2 2+ is found to be ~30 min. These results are in contrast to the earlier reports on photonic hydrogels of inhomogeneous microgel particles hydrogel (MPH), which shows the threshold UO 2 2+ concentration of ~600 µM, below which the diffraction peak exhibits a blue shift and a change to a red shift above it. The equilibration time for MPH is ~300min. The observed monotonic blue shift and the faster time response of the SPH to UO 2 2+ as compared to the MPH are explained in terms of homogeneous nature of silica particles in the SPH, against the porous and polymeric nature of microgels in the MPH. We also study the extraction of UO 2 2+ from aqueous solutions using the SPH. The extraction capacity estimated by the arsenazo-III analysis is found to be 112 mM/kg.

Background Comprehensive blood lipoprotein profiles and their association with incident coronary heart disease (CHD) among racially and geographically diverse populations remain understudied. Methods and Results We conducted nested case–control studies of CHD among 3438 individuals (1719 pairs), including 1084 White Americans (542 pairs), 1244 Black Americans (622 pairs), and 1110 Chinese adults (555 pairs). We examined 36 plasma lipids, lipoproteins, and apolipoproteins, measured by nuclear magnetic resonance spectroscopy, with incident CHD among all participants and subgroups by demographics, lifestyle, and metabolic health status using conditional or unconditional logistic regression adjusted for potential confounders. Conventionally measured blood lipids, that is, total cholesterol, triglycerides, low‐density lipoprotein‐cholesterol, and high‐density lipoprotein‐cholesterol, were each associated with incident CHD, with odds ratios (ORs) being 1.33, 1.32, 1.24, and 0.79 per 1‐SD increase among all participants. Seventeen lipoprotein biomarkers showed numerically stronger associations than conventional lipids, with ORs per 1‐SD among all participants ranging from 1.35 to 1.57 and a negative OR of 0.78 (all false discovery rate

This study investigates the influence of heavy ion irradiation on thin film transistors (TFTs) based on an a-Si:H/PolySi active layer and Schottky barrier-based source and drain. Through the use of Technology Computer-Aided Design (TCAD) simulations, we analyze the impact on device performance. We examine the ambipolar device characteristics by varying the thickness of the active layer (Poly-Si) and studying the corresponding physics. Our results reveal that reducing the active layer thickness from 140 to 80 nm decreases the magnitude of the threshold voltage (|VT|) for both nMOS and pMOS operating voltages. Additionally, the subthreshold slope is reduced for both nMOS and pMOS as the active layer thickness is decreased from 140 to 80 nm.Further, we investigated the transient response of the drain current to heavy ion irradiation in the sensitive regions across the Schottky barrier-based source and drain. We specifically analyze the phenomenon of bipolar amplification for various Linear Energy Transfer (LET) values, ranging from 0.1 MeV cm2/mg to 100 MeV cm2/mg. Our findings indicate that increasing the LET values from 0.1 MeV cm2/mg to 100 MeV cm2/mg results in amplified bipolar behavior and a drain current overshoot of over 10 % for both pMOS and nMOS operating voltages. To summarize, this work highlights the effects of heavy ion irradiation on TFTs with an a-Si:H/PolySi active layer and Schottky barrier-based source and drain. The study explores the influence of active layer thickness on device characteristics and demonstrates the transient response of drain current under different LET values. These findings contribute to a better understanding of the behavior and performance of TFTs subjected to heavy ion irradiation.

Background Phosphodiesterases degrade cyclic GMP (cGMP), the second messenger that mediates the cardioprotective effects of natriuretic peptides. High natriuretic peptide/cGMP ratio may reflect, in part, phosphodiesterase activity. Correlates of natriuretic peptide/cGMP in patients with heart failure with preserved ejection fraction are not well understood. Among patients with heart failure with preserved ejection fraction in the RELAX (Phosphodiesterase‐5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure With Preserved Ejection Fraction) trial, we examined (1) cross‐sectional correlates of circulating NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide)/cGMP ratio, (2) whether selective phosphodiesterase‐5 inhibition by sildenafil changed the ratio, and (3) whether the effect of sildenafil on 24‐week outcomes varied by baseline ratio. Methods and Results In 212 subjects, NT‐proBNP/cGMP ratio was calculated at randomization and 24 weeks. Correlates of the ratio and its change were examined in multivariable proportional odds models. Whether baseline ratio modified the sildenafil effect on outcomes was examined by interaction terms. Higher NT‐proBNP/cGMP ratio was associated with greater left ventricular mass and troponin, the presence of atrial fibrillation, and lower estimated glomerular filtration rate and peak oxygen consumption. Compared with placebo, sildenafil did not alter the ratio from baseline to 24 weeks (P=0.17). The effect of sildenafil on 24‐week change in peak oxygen consumption, left ventricular mass, or clinical composite outcome was not modified by baseline NT‐proBNP/cGMP ratio (P‐interaction >0.30 for all). Conclusions Among patients with heart failure with preserved ejection fraction, higher NT‐proBNP/cGMP ratio associated with an adverse cardiorenal phenotype, which was not improved by selective phosphodiesterase‐5 inhibition. Other phosphodiesterases may be greater contributors than phosphodiesterase‐5 to the adverse phenotype associated with a high natriuretic peptide/cGMP ratio in HFpEF. Registration Information clinicaltrials.gov. Identifier: NCT00763867.

Abstract Urban land and its expansion have profoundly impacted the global environment, including the stress change in the earth’s subsurface, even though urban land is a small fraction of the global land surface. Divulging such effects has never been more important, given the role of stress in determining the safety of the urban population against earthquakes. However, knowledge of this time-dependent non-linear effect of urbanization on the subsurface remains in the gray area. This study focuses on the area surrounding Delhi, the capital city of India, to understand the relative contribution of the building load created by rapid urbanization in exacerbating the subsurface state-of-stress. The results highlight that, since 2010, the modulation in the seismicity rate and the stability of basement thrust faults is linked not only to urbanization but also to decadal groundwater storage. Mounting evidence suggests that the rapid urbanization, and the resulting non-tectonic horizontal compression, stabilize faults in the Aravalli Delhi belt, which are destabilized due to the extensive groundwater extraction. This affects the decadal seismicity trend around the Aravalli Delhi fold belt. Nonetheless, the magnitude of this time-dependent deformation influence on the seismicity modulation remains uncertain. The findings from this study quantify the geomechanical impacts of urbanization in the Delhi area for the first time.

Abstract Objective To evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI). Background Administration of adrenergic blockade after severe TBI is common. To date, no prospective trial has rigorously evaluated this common therapy for benefit. Methods This phase II, single-center, double-blinded, pilot randomized placebo-controlled trial included patients aged 16–64 years with severe TBI (intracranial hemorrhage and Glasgow Coma Scale score ≤ 8) within 24 h of ICU admission. Patients received propranolol and clonidine or double placebo for 7 days. The primary outcome was ventilator-free days (VFDs) at 28 days. Secondary outcomes included catecholamine levels, hospital length of stay, mortality, and long-term functional status. A planned futility assessment was performed mid-study. Results Dose compliance was 99%, blinding was intact, and no open-label agents were used. No treatment patient experienced dysrhythmia, myocardial infarction, or cardiac arrest. The study was stopped for futility after enrolling 47 patients (26 placebo, 21 treatment), per a priori stopping rules. There was no significant difference in VFDs between treatment and control groups [0.3 days, 95% CI (− 5.4, 5.8), p = 1.0]. Other than improvement of features related to sympathetic hyperactivity (mean difference in Clinical Features Scale (CFS) 1.7 points, CI (0.4, 2.9), p = 0.012), there were no between-group differences in the secondary outcomes. Conclusion Despite the safety and feasibility of adrenergic blockade with propranolol and clonidine after severe TBI, the intervention did not alter the VFD outcome. Given the widespread use of these agents in TBI care, a multi-center investigation is warranted to determine whether adrenergic blockade is of therapeutic benefit in patients with severe TBI. Trial Registration Number NCT01322048.

Background and Aims: Modified electroconvulsive therapy is routinely used to treat complicated psychiatric disorders. Its therapeutic effect is directly proportional to induced seizure duration but it is associated with hemodynamic disturbances. The aim of this study was to evaluate the effect of a ketamine + propofol combination (“ketofol”) for electroconvulsive therapy and to compare these with the effects of propofol alone. Methods: In this prospective study, 60 patients aged 18–60 years with American Society of Anesthesiologists (ASA) Ι and ΙΙ for psychiatric disorders were included. Patients were divided into two groups (30 each). Group P received propofol at 10 mg/ml and group K received ketofo at 10 mg/ml (ketamine 5 mg/ml and propofol 5 mg/ml in a 1:1 ratio). Motor/electroencephalography (EEG) seizure duration, induction time, hemodynamic variables, recovery time, agitation score, and complications were recorded. Standard qualitative and quantitative tests were used to compare the data (e.g., unpaired student t-test, Chi-squared test, etc). A P value of < 0.05 was considered to be significant. Results: The mean duration of (motor/EEG) seizure was statistically significantly high in the ketofol group compared to the propofol group (P = 0.0001/0.0001). The mean induction time was significantly less in the ketofol group compared to propofol group (P = 0.0001). The recovery time was significantly early in group K patients compared to group P (P = 0.004). The ketofol group was more hemodynamically stable with comparable agitation score and side effects than patients in the propofol group. Conclusion: In modified ECT, ketofol was associated with longer seizure duration, lesser induction time, better hemodynamic stability, early recovery with comparable post ECT agitation and adverse effects compared to propofol alone.

A cropping system practice is the sequential cultivation of crops in different crop seasons of a year. Cropping system practices determine the land productivity and sustainability of agriculture in regions and, therefore, information on cropping systems of different regions in the form of maps and statistics form critical inputs in crop planning for optimal use of resources. Although satellite-based crop mapping is widely practiced, deriving cropping systems maps using satellites is less reported. Here, we developed moderate-resolution maps of the major cropping systems of South Asia for the year 2014–2015 using multi-temporal satellite data together with a spectral matching technique (SMT) developed with an extensive set of field observation data supplemented with expert-identified crops in high-resolution satellite images. We identified and mapped 27 major cropping systems of South Asia at 250 m spatial resolution. The rice-wheat cropping system is the dominant system, followed by millet-wheat and soybean-wheat. The map showing the cropping system practices of regions opens up many use cases related to the agriculture performance of the regions. Comparison of such maps of different time periods offers insights on sensitive regions and analysis of such maps in conjunction with resources maps such as climate, soil, etc., enables optimization of resources vis-à-vis enhancing land productivity. Thus, the current study offers new opportunities to revisit the cropping system practices and redesign the same to meet the challenges of food security and climate resilient agriculture.

– In this study, we focused on isolating fungi capable of producing extracellular chitin, a critical component of fungal cell walls. Aspergillus niger was chosen as the candidate, and we aimed to optimise chitin production. Initially, one variable at a time (OVAT) method was used to enhance chitin yield under the best fermentation conditions. Subsequently, the Plackett-Burman design was employed to identify the key medium components influencing chitin production. These factors were then fine-tuned using the Central Composite Design, resulting in the optimal concentrations of dipotassium hydrogen phosphate (0.7 mg/l), calcium chloride (0.5 mg/l), thymine hydrochloride (0.5 mg/l), and pH (4), as confirmed by ANOVA. The application of response surface methodology (RSM) led to a remarkable improvement in chitin yield, increasing it from 1.14 g/l to an impressive 4.42 g/l, a substantial 3.34-fold enhancement compared to unoptimized conditions. Additionally, we explored the antioxidant activity of the produced chitin, revealing its promising properties with a scavenging activity ranging from 32% to 55% at concentrations of 1–2 mg/ml, surpassing the control. In conclusion, our study successfully optimized chitin production from Aspergillus niger and demonstrated the remarkable antioxidant potential of the produced chitin, highlighting its significance in various applications.

Introduction: The incidence of trauma is on an increasing trend worldwide. It has drastically increased due to urbanization, vehicular congestion, alcoholism, and poor infrastructure facilities, especially in developing countries. In the Armed Forces, the additional burden of trauma is also seen due to various unit activities, organized sports, and other adventure sports. Head injury cases are often associated with various ocular injuries. These ocular injuries, if subtle in nature, can be missed initially and progress into ophthalmological complications and rarely into permanent visual impairment. The aim of this study was to critically analyze the association of various ocular injuries in patients with head injury. Materials and Methods: A cross-sectional study was conducted in a tertiary-level Armed Forces Hospital from July 2016 to December 2018. A total of 40 patients were evaluated who had head injury along with ocular injuries. The Glasgow Coma Scale (GCS) was used to assess the severity of the head injury. Ocular manifestations such as subconjunctival hemorrhage, ecchymosis, soft tissue injuries such as lid tear, corneal injuries, and bony and associated nerve injuries were evaluated. Results: A total of 40 patients with head injury with ocular manifestations were studied. Road traffic accident (RTA) was the most common cause, followed by accidental fall from height and sports injuries. There was a male preponderance (n = 32 (80%)) over females (n = 8 (20%)). Unilateral ocular manifestation (n = 32 (80%)) was more common than bilateral involvement (n = 8 (20%)). The most frequent ocular manifestations were subconjunctival hemorrhage and ecchymosis (35 (87.5%)), followed by lid laceration (6 (15%)), corneal tear (04 (10%)), vitreous hemorrhage (01 (2.5%)), evisceration (2 (05%)), and cranial nerve injury (06 (12.5%)). Orbital wall fracture was seen in 15 (37.5%) patients, including lateral wall fracture (n = 08 (20%)), medial wall fracture (n = 04 (10%)), orbital floor fracture (n = 02 (05%)), and orbital roof fracture (n = 01 (2.5%)). Conclusion: Ocular injuries can occur in patients with head injury irrespective of the mode and kinematics involved (severe head injury may present with minimal ocular manifestations or vice versa). These patients require hospitalization, observation, thorough ophthalmic evaluation, and periodic assessment to minimize morbidity and complications.

Determining an accurate state of lubrication is of utmost importance for the precise functionality of machine elements and to achieve elongated life and durability. In this work, a homogenized mixed-lubrication model is developed to study the effect of surface topographies on the coefficient of friction. Various measured real surface topographies are integrated in the model using the roughness homogenization method. The shear-thinning behavior of the lubricant is incorporated by employing the Eyring constitutive relation. Several Stribeck curves are generated to analyze the effect of roughness lays and root mean square (RMS) roughness on the coefficient of friction. The homogenized mixed lubrication model is validated against experimental rolling/sliding ball-on-disc results, and a good agreement between simulated and experimental coefficient of friction is found.

BackgroundFreezing of Gait (FOG) is a motor symptom frequently observed in advanced Parkinson’s disease. However, due to its paroxysmal nature and diverse presentation, assessing FOG in a clinical setting can be challenging. Before FOG can be fully investigated, it is critical that a reliable experimental setting is established in which FOG can be evoked in a standardized manner, but the efficacy of various gait tasks and triggers for eliciting FOG remains unclear.ObjectivesThis study aimed to conduct a systematic review of the existing literature and evaluate the available evidence for the relationship between specific motor tasks, triggers, and FOG episodes in individuals with Parkinson’s disease (PwPD).MethodsWe conducted a literature search on four online databases (PubMed, Web of Science, EMBASE, and Cochrane Library) using the keywords “Parkinson’s disease,” “Freezing of Gait”, “triggers” and “tasks”. A total of 128 articles met the inclusion criteria and were included in our analysis.ResultsThe review found that a wide range of gait tasks were employed in studies assessing FOG among PD patients. However, three tasks (turning, dual tasking, and straight walking) emerged as the most frequently used. Turning (28%) appears to be the most effective trigger for eliciting FOG in PwPD, followed by walking through a doorway (14%) and dual tasking (10%).ConclusionThis review thereby supports the utilisation of turning, especially a 360-degree turn, as a reliable trigger for FOG in PwPD. This finding could be beneficial to clinicians conducting clinical evaluations and researchers aiming to assess FOG in a laboratory environment.

Abstract Although extreme weather events recur periodically everywhere, the impacts of their simultaneous occurrence on crop yields are globally unknown. In this study, we estimate the impacts of combined hot and dry extremes as well as cold and wet extremes on maize, rice, soybean, and wheat yields using gridded weather data and reported crop yield data at the global scale for 1980–2009. Our results show that co-occurring extremely hot and dry events have globally consistent negative effects on the yields of all inspected crop types. Extremely cold and wet conditions were observed to reduce crop yields globally too, although to a lesser extent and the impacts being more uncertain and inconsistent. Critically, we found that over the study period, the probability of co-occurring extreme hot and dry events during the growing season increased across all inspected crop types; wheat showing the largest, up to a six-fold, increase. Hence, our study highlights the potentially detrimental impacts that increasing climate variability can have on global food production.

Background and Aims: The bilateral superficial cervical plexus block (BSCPB) is efficacious for post-operative analgesia in thyroid surgeries. We assessed the analgesic efficacy of dexmedetomidine and dexamethasone administered as adjuvants with 0.25 percent ropivacaine in BSCPB for thyroidectomy under general anaesthesia with regard to the duration of analgesia, total amount of rescue analgesic requirement, changes in intra- and post-operative haemodynamic parameters, VAS scores, and adverse events, if any. Methods: A prospective double-blind trial was planned with 80 adults undergoing thyroidectomy, randomized into two equal groups and given BSCPB with 20 ml 0.25% ropivacaine with adjuvants as either dexmedetomidine 50μg (group A) or dexamethasone 4mg (group B), 10 ml on each side, after the induction of general anaesthesia. Post-operative pain was monitored using the visual analog scale and the duration of analgesia was measured by time to first rescue analgesia. Post-operative haemodynamics and any adverse events were recorded. Results: The mean duration of analgesia was slightly prolonged in group A but statistically non-significant as compared to group B (1037 ± 97 vs. 1004 ± 122 minutes; P0.18). The post-operative median VAS scores and vital parameters were relatively comparable for both groups (P > 0.05) for the first 24h. There was a significant reduction in the incidence of PONV (P < 0.05) in group B. Conclusion: Although dexamethasone offers a slight advantage of decreased incidence of PONV, BSCPB using ropivacaine with either dexmedetomidine or dexamethasone as an adjuvant imparted adequate analgesia with stable haemodynamics and may be used as a pre-emptive analgesic technique in thyroid surgeries.

Hypertensive crisis is rare in children. Among the rarest causes leading to this acute crisis, is bilateral adrenal tumour as a part of a syndrome, Von Hippel Lindau syndrome. The treatment is based on the excision of the adrenal tumour followed by long term surviellence. The authors present a case where conventional imaging with ultrasound and contrast enhanced CT scan demonstrated a right side adrenal tumour with raised catecholamines.The small left side tumour got missed on conventional imaging and got picked up on DOTA scan. The persistence of hypertension in post operative period can be related to such hidden functioning tumours. In view of the size of tumour & raised dopamine associated with high incidence of malignancy, robotic surgery was used for bilateral adrenal tumour excision which confirmed the diagnosis of Pheochromocytoma (PCC).

In routine monitoring of radiation workers to detect internal contamination due to Pu/Am, it is assumed that intake has occurred at the midpoint of the monitoring interval. Radiation worker is normally monitored at the end of the annual monitoring interval, within a span of ±1 month under a routine in vivo monitoring program. An uncertainty is introduced in intake estimation as the time of intake can vary over the entire monitoring interval. In this work, uncertainties introduced in the intake estimation of Type M and S compounds of Pu/Am are evaluated due to unknown time of intake for annual and biennial monitoring frequency.

Objectives: In this study the authors have tried to examine the role of magnesium alone or in combination with diltiazem and / or amiodarone in prevention of atrial fibrillation (AF) following off-pump coronary artery bypass grafting (CABG). Background: AF after CABG is common and contributes to morbidity and mortality. Various pharmacological preventive measures including magnesium, amiodarone, diltiazem, and combination therapy among others have been tried to lower the incidence of AF. Most of the studies have been performed in patients undergoing conventional on-pump CABG. In this uncontrolled trial, efficacy of magnesium alone or in combination with amiodarone and / or diltiazem has been studied in patients undergoing off-pump CABG. Methods: One hundred and fifty patients undergoing off-pump CABG were divided into 3 groups, Group M (n=21) received intraoperative magnesium infusion at 30mg/ kg over 1 hour after midline sternotomy; Group MD (n=78) received magnesium infusion in similar manner with diltiazem infusion at 0.05 μg/kg/hr throughout the intraoperative period; Group AMD (n=51) received preoperative oral amiodarone at a dose of 200 mg three times a day for 3 days followed by 200 mg twice daily for another 3 days followed by 200 mg once daily till the day of surgery along with magnesium and diltiazem infusion as in other groups. AF lasting more than 10 min or requiring medical intervention was considered as AF. Results: The overall incidence of postoperative AF was 12.6% with 11.7% in group AMD, 19% in group M, and 11.5% in group MD, which was not statistically significant. Conclusions: It is concluded that the use of amiodarone and/or diltiazem in addition to magnesium did not result in additional benefit of lowering the incidence of AF.

Estimation of good velocity models under complex near-surface conditions remains a topic of ongoing research. We propose to predict near-surface velocity profiles from surface-waves transformed to phase velocity-frequency panels in a data-driven manner using deep neural networks. This is a different approach from many recent works that attempt to estimate velocity from directly reflected body waves or guided waves. A secondary objective is to analyze the influence on the prediction accuracy of various commonly employed deep learning practices, such as transfer learning and data augmentations. Through numerical experiments on synthetic data as well as a real geophysical example, we demonstrate that transfer learning as well as data augmentations are helpful when using deep learning for velocity estimation. A third and final objective is to study lack of generalization of deep learning models for out-of-distribution (OOD) data in the context of our problem, and present a novel approach to tackle it. We propose a domain adaptation network for training deep learning models that uses a priori knowledge on the range of velocity values in order to constrain mapping of the output. The final comparison on field data, which was not part of the training data, show the deep neural network predictions compare favorably with a conventional velocity model estimation obtained with a dispersion curve inversion workflow.

In this study, the status of T cell-dependent cytokine gene expressions in the acute phase (3-day post-infection and 5-day post-infection) of infection with vaccine virus strains of New castle disease virus (NDV) (R2B and Lasota), Avian infectious bronchitis virus (AIBV) (Massachusetts H120), and Infectious Bursal Disease virus (IBDV) in SPF chicken of seven day age was evaluated. The birds were divided into four groups, each having six birds. Each group of birds was inoculated with the prescribed dose of different vaccines at 7 days of age. Blood was collected before inoculation (uninfected), at the 3rd and 5th day post-inoculation. Presence of virus in peripheral blood confirmed by real-time reverse-transcription PCR assay and quantitation of cytokine was performed in peripheral blood by real time PCR assay. It was observed that the infection with different vaccine strains of viruses in poultry modulates cytokine expression in order to elicit antiviral immune responses. AIBV and NDV viruses markedly up-regulate IL- 2, IL-12, p40, IL-4, IL-5, and IL-13 whereas, IBDV induces prolonged up-regulation of IFN-γ, IL-10 genes.

Background Studies in mice and small patient subsets implicate metabolic dysfunction in cardiac remodeling in aortic stenosis, but no large comprehensive studies of human metabolism in aortic stenosis with long‐term follow‐up and characterization currently exist. Methods and Results Within a multicenter prospective cohort study, we used principal components analysis to summarize 12 echocardiographic measures of left ventricular structure and function pre–transcatheter aortic valve implantation in 519 subjects (derivation). We used least absolute shrinkage and selection operator regression across 221 metabolites to define metabolic signatures for each structural pattern and measured their relation to death and multimorbidity in the original cohort and up to 2 validation cohorts (N=543 for overall validation). In the derivation cohort (519 individuals; median age, 84 years, 45% women, 95% White individuals), we identified 3 axes of left ventricular remodeling, broadly specifying systolic function, diastolic function, and chamber volumes. Metabolite signatures of each axis specified both known and novel pathways in hypertrophy and cardiac dysfunction. Over a median of 3.1 years (205 deaths), a metabolite score for diastolic function was independently associated with post–transcatheter aortic valve implantation death (adjusted hazard ratio per 1 SD increase in score, 1.54 [95% CI, 1.25–1.90]; P

The observation of magnetic diode behavior with ultra-low forward voltage renders new venue for energetically efficient spintronic device research in the unconventional system of two-dimensional permalloy honeycomb lattice. However, detailed understanding of temperature and magnetic field tuning of diode behaviors are imperative to any practical application. In this report, our study unveils many important properties of magnetic diode that not only pave the way for practical applications, but also underlines the role of emergent phenomena of magnetic charge correlation on honeycomb vertices. We find that magnetic diode behavior persists across a broad temperature range. In a surprising observation, magnetic field application tends to induce a peculiar reentrant characteristic where diode behavior is suppressed in remnant field but reappears after warming to room temperature. Analysis of $I-V$ data suggests a modest energy gap, $∖sim$ 0.03 - 0.1 eV, which is comparable to magnetic Coulomb’s interaction energy between emergent magnetic charges on honeycomb vertices in the reverse biased state. It affirms the role of magnetic charge correlation in unidirectional conduction in 2D honeycomb lattice. The experimental results are expected to spur the utilization of magnetic diode in next generation spintronic device applications.

Abstract Background The Open Targets (OT) Platform integrates a wide range of data sources on target-disease associations to facilitate identification of potential therapeutic drug targets to treat human diseases. However, due to the complexity that targets are usually functionally pleiotropic and efficacious for multiple indications, challenges in identifying novel target to indication associations remain. Specifically, persistent need exists for new methods for integration of novel target-disease association evidence and biological knowledge bases via advanced computational methods. These offer promise for increasing power for identification of the most promising target-disease pairs for therapeutic development. Here we introduce a novel approach by integrating additional target-disease features with machine learning models to further uncover druggable disease to target indications. Results We derived novel target-disease associations as supplemental features to OT platform-based associations using three data sources: (1) target tissue specificity from GTEx expression profiles; (2) target semantic similarities based on gene ontology; and (3) functional interactions among targets by embedding them from protein–protein interaction (PPI) networks. Machine learning models were applied to evaluate feature importance and performance benchmarks for predicting targets with known drug indications. The evaluation results show the newly integrated features demonstrate higher importance than current features in OT. In addition, these also show superior performance over association benchmarks and may support discovery of novel therapeutic indications for highly pursued targets. Conclusion Our newly generated features can be used to represent additional underlying biological relatedness among targets and diseases to further empower improved performance for predicting novel indications for drug targets through advanced machine learning models. The proposed methodology enables a powerful new approach for systematic evaluation of drug targets with novel indications.

The impact of non-Gaussian height distribution and spectral properties on the lubrication performance of counterformal (point) contacts is quantitatively studied (film parameter, Λ, and asperity load ratio, La) by developing a mixed lubrication model. The Weibull height distribution function and power spectral density (PSD) are used to generate artificial surface topographies (non-Gaussian and Gaussian, isotropic), as these surface topographies are found in many tribological components. The set of variables needed to parametrize and their effect on mixed lubrication is discussed, including the shape parameter, the autocorrelation length, the wavelength ratio, and the Hurst coefficient. It is revealed that a rough surface with a lower shape parameter exhibits higher hydrodynamic lift. The spectral properties (the autocorrelation length and the wavelength ratio) of rough surfaces significantly affect the film parameter and the hydrodynamic and asperity pressures. The film parameter is slightly influenced by the Hurst coefficient.

The primary cause of atherosclerotic cardiovascular disease (ASCVD) is elevated levels of low-density lipoprotein cholesterol (LDL-C). Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in this process by binding to the LDL receptor (LDL-R) domain, leading to reduced influx of LDL-C and decreased LDL-R cell surface presentation on hepatocytes, resulting higher circulating levels of LDL-C. As a consequence, PCSK9 has been identified as a crucial target for drug development against dyslipidemia and hypercholesterolemia, aiming to lower plasma LDL-C levels. This research endeavors to identify promising inhibitory candidates that target the allosteric site of PCSK9 through an in silico approach. To start with, the FDA-approved Drug Library from Selleckchem was selected and virtually screened by docking studies using Glide extra-precision (XP) docking mode and Smina software (Version 1.1.2). Subsequently, rescoring of 100 drug compounds showing good average docking scores were performed using Gnina software (Version 1.0) to generate CNN Score and CNN binding affinity. Among the drug compounds, amikacin, bestatin, and natamycin were found to exhibit higher docking scores and CNN affinities against the PCSK9 enzyme. Molecular dynamics simulations further confirmed that these drug molecules established the stable protein–ligand complexes when compared to the apo structure of PCSK9 and the complex with the co-crystallized ligand structure. Moreover, the MM-GBSA calculations revealed binding free energy values ranging from −84.22 to −76.39 kcal/mol, which were found comparable to those obtained for the co-crystallized ligand structure. In conclusion, these identified drug molecules have the potential to serve as inhibitors PCSK9 enzyme and these finding could pave the way for the development of new PCSK9 inhibitory drugs in future in vitro research.

Ghorbani and colleagues describe versican-V1 as an inhibitor of remyelination using transgenic mice that illuminate new GFP + oligodendrocytes. Mechanisms of versican-V1 include the direct inhibition of oligodendrocytes, and elevating Th17 cells.

This experiment was carried out to investigate the plant performance of tomato var. Manisha under foliar spray of zinc and boron in Randomized Complete Blocked Design with five treatments and four replications. The treatments were control (T0), two levels of chelated zinc (T1:30 ppm and T2:60 ppm), and the two levels of borax (T3:30 ppm and T4:60 ppm) applied in two installments (15 and 35 DAT by foliar spray). The results showed significance increase in parameters such as plant height (86 cm), plant leaves number (52.47), branches number (8.21), clusters number (19.32), fruits number (22.73), fruit diameter (5.58 cm), fruit weight (59.71 gm) and yield (56.56 t/ha) with the foliar application of chelated zinc at the dose of 30 ppm. Furthermore, early flowering (23.70 days) was observed at borax 30 ppm concentration. The results can recommend the tomato growers to apply chelated zinc and borax at the dosages of 30 ppm which denotes use of 30 mg per liter. The results clearly depict the potential increase in yield and other parameters of tomato cv. Manisha, using easily available source of zinc and boron, i.e. chelated zinc and borax.