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Abstract Background Social vulnerability is a multidimensional concept based on multivariate factors in domains of physical, social, economic, environmental, etc., and the subsets that constitute it. When addressed effectively, it paves the way for resolving and recorrecting certain facets that play a key role in determining the degree of susceptibility and potentiality of a population to address adverse situations. Aim The current study aims at synthesising research works and providing a comprehensive overview of social vulnerability assessment in the health and disease arena. Subject and methods It incorporates the concept of vulnerability, approaches, indices, indicators, and methodologies regarding social vulnerability in the health and disease arena from selected associated research articles accessed from digital database sources. Results There is an evident trend in associating new tools and techniques with the assessment of social vulnerability, along with conventional methods. Conclusion The results provide a theoretical background for subsequent research and an update on the recent trends in this topic of interest.

Abstract Pharmacotherapy guidelines for type 2 diabetes (T2D) emphasize patient-centered care, but applying this approach effectively in outpatient practice remains challenging. Data-driven treatment optimization approaches could enhance individualized T2D management, but current approaches cannot account for drug-specific and dose-dependent variations in safety and efficacy. We developed and evaluated an AI Drug mix and dose Advisor (AIDA) for glycemic management, using electronic medical records from 107,854 T2D patients in the SingHealth Diabetes Registry. Given a patient’s medical profile, AIDA leverages a predict-then-optimize approach to identify the minimal drug mix and dose changes required to optimize glycemic control, subject to clinical knowledge-based guidelines. On unseen data from large internal, external, and temporal validation sets, AIDA recommendations were estimated to improve post-visit glycated hemoglobin (HbA1c) by an average of 0.40–0.68% over standard of care (P

Allosteric regulation plays a crucial role in modulating protein functions and represents a promising strategy in drug development, offering enhanced specificity and reduced toxicity compared to traditional active site inhibition. Existing computational methods for predicting allosteric sites on proteins often rely on static protein surface pocket features, normal mode analysis or extensive molecular dynamics simulations encompassing both the protein function modulator and the protein itself. In this study, we introduce an innovative methodology that employs a per amino acid residue classifier to distinguish allosteric site-forming residues (AFRs) from non-allosteric, or free residues (FRs). Our model, STINGAllo, exhibits robust performance, achieving Distance Center Center (DCC) success rate when all AFRs were predicted within pockets identified by FPocket, overall DCC, F1 score and a Matthews correlation coefficient (MCC) of 78 %, 60 %, 64 % and 64 % respectively. Furthermore, we identified key descriptors that characterize the internal protein nanoenvironment of AFRs, setting them apart from FRs. These descriptors include the sponge effect, distance to the protein centre of geometry (cg), hydrophobic interactions, electrostatic potentials, eccentricity, and graph bottleneck features.

North American pawpaw (Asimina triloba) is an undeveloped tree fruit crop indigenous to the eastern United States. Recent breeding efforts have set the stage for successful cultivation of pawpaw, but cultivar evaluations among geographically distinct environments are needed to advance this unique specialty crop. A significant genotype by environment experiment incorporating 10 pawpaw cultivars, 350 trees, and four sites across Missouri and Oklahoma (USA) was established in 2002–03. Data across 19 years of cultivar performance, tree growth, and fruit production at the three Missouri sites were evaluated. The cultivar “PA Golden” produced the largest trees, whereas “Overleese” struggled with long-term survival, tree growth, and fruit production. “PA Golden” also tended to produce earlier crops, whereas “Sunflower” produced very high yields later into the growing seasons compared with other cultivars. “Susquehanna” consistently produced the largest fruits, averaging 184 g across the three sites and multiple years. Pawpaw trees were very productive in the Missouri environment over 19 years and show excellent promise as an economically viable specialty crop.

Abstract Incremental sheet metal forming is a highly versatile die-less forming process for manufacturing complex sheet metal components. Robot-assisted incremental sheet forming, or roboforming, allows a wider range of tool motion, providing the capability to shape intricate components. This makes roboforming the most flexible variant of the incremental forming method. However, the serial arrangement of links and joints in a robotic manipulator results in low positional accuracy under forming loads due to insufficient structural stiffness. The stiffness of the machine frame and tool directly impacts the accuracy of the final formed profile. The impact of machine compliance on component shape in incremental sheet forming is substantial in roboforming. This work presents a methodology for systematic analysis of the factors contributing to the errors in the geometric shape of robot-based forming. Experimental and numerical methods are used to estimate the material springback, tool/tool holder deflections, and errors due to machine compliance. The CNC machine frame is relatively stiffer than the industrial robots, such that material springback is estimated based on the experimental trials on CNC for cone and variable wall angle cone profiles. Tool and tool holder deflections are estimated using finite element simulations. The analytical method using the Virtual Joint Model is used to model the joint stiffness, and consequently, the robot Cartesian stiffness is estimated to predict path deviation contributing to geometric shape errors. The proportional contribution of each factor in the overall deviation in the Roboforming is also quantified.

Abstract Artificial intelligence (AI) algorithms hold the potential to revolutionize radiology. However, a significant portion of the published literature lacks transparency and reproducibility, which hampers sustained progress toward clinical translation. Although several reporting guidelines have been proposed, identifying practical means to address these issues remains challenging. Here, we show the potential of cloud-based infrastructure for implementing and sharing transparent and reproducible AI-based radiology pipelines. We demonstrate end-to-end reproducibility from retrieving cloud-hosted data, through data pre-processing, deep learning inference, and post-processing, to the analysis and reporting of the final results. We successfully implement two distinct use cases, starting from recent literature on AI-based biomarkers for cancer imaging. Using cloud-hosted data and computing, we confirm the findings of these studies and extend the validation to previously unseen data for one of the use cases. Furthermore, we provide the community with transparent and easy-to-extend examples of pipelines impactful for the broader oncology field. Our approach demonstrates the potential of cloud resources for implementing, sharing, and using reproducible and transparent AI pipelines, which can accelerate the translation into clinical solutions.

Abstract This study demonstrates the efficacy of employing Rhizopus oryzae fungus inoculum as a potential solution to improve soil erodibility in coastal environments. A set of unconfined compression tests is conducted on Miami Beach sand treated with a R. oryzae inoculum. Our findings suggest that the R. oryzae fungus inoculum effectively improves the stability of sand by acting as a natural binding agent. This finding aligns with previous studies that utilized different Rhizopus species, such as Rhizopus oligosporus, to improve sand properties. However, a notable difference is observed; the R. oryzae-treated sand exhibits remarkable durability, maintaining significant strength over an extended period without water or dietary supply. The durability is likely attributable to the morphological characteristics of R. oryzae that extensively branches its mycelial network. This paper shares the new discovery to the bio-geotechnics research community, potentially allowing for the customization of soil improvement process by choosing between the fast-acting R. oligosporus and the longer-lasting R. oryzae.

Background: The intricate interplay between periodontal polymicrobial flora and an altered immune response is the central cause of periodontal disease. Multiple cell death methods and their interactions, along with the associated signaling pathways, significantly impact the initiation and advancement of periodontitis. Our speculation revolves around the role of the miR-223/Ras-associated binding protein (RAB12) signaling axis in regulating autophagy-induced pyroptosis, contributing to the pathophysiology of periodontitis. Thus, this study aimed to investigate miR-223 and RAB12 expression patterns in Stage III/Grade B periodontal disease. Materials and Methods: The study included 50 healthy individuals and 50 patients diagnosed with Stage III/Grade B periodontal disease. Clinical parameters were cataloged for each participant. miRNA-223 underwent an in silico analysis to identify its potential target genes. Gingival crevicular fluid (GCF) samples were collected from the subjects for real-time polymerase chain reaction to evaluate the expression of both miR-223 and the RAB12 gene. Results: The miRTargetLink2.0 analysis highlighted the RAB12 gene as a prime target for miR-223. In periodontal disease patients, miR-223 and RAB12 gene expressions significantly increased (15.21 and 34.70-fold changes, respectively; P < 0.05). Receiver operating characteristic analysis suggested that miR-223 is a potential biomarker for periodontal disease, with 76% diagnostic accuracy and an area under the curve of 0.777 (P < 0.01). Conclusion: MicroRNA-223 and its target gene RAB12 exhibit high expression levels in GCF samples from individuals with periodontal disease. This suggests modulation of autophagy and the signaling mechanism for pyroptotic cell death in periodontal tissues during pathogenesis. Consequently, the miR-223/RAB12 axis might represent a plausible link for periodontal disease.

Objective Protocol to explore what is known about communication between critical care providers and patients and families from culturally and linguistically diverse backgrounds (defined as people who are either from minority ethnic groups, non-English-speaking backgrounds who may have diverse cultural, linguistic, spiritual and religious affiliations and opinions) about death, dying, end-of-life care and organ donation in the intensive care unit (ICU).Introduction Patients from culturally and linguistically diverse backgrounds experience barriers to optimised care when admitted to the ICU. These barriers appear to derive from differences in language, cultural, societal and ethical expectations between patients, their families and healthcare professionals. These barriers may significantly impact the delivery of end-of-life care to patients from culturally and linguistically diverse backgrounds. Therefore, this has the potential for inadequate management of medical, psychological and existential distress.Inclusion criteria Studies of all designs reporting for adult (age ≥18 years) patients and family members from culturally and linguistically diverse backgrounds at end-of-life in the ICU setting will be included. Studies that report results for patients aged

BackgroundTelehealth interventions where providers offer support and coaching to patients with chronic conditions such as heart failure (HF) and type 2 diabetes mellitus (T2DM) are effective in improving health outcomes. However, the understanding of the content and structure of these interactions and how they relate to health care utilization remains incomplete. ObjectiveThis study aimed to characterize the content and structure of telecare conversations on lifestyle management for patients with HF and investigate how these conversations relate to health care utilization. MethodsWe leveraged real-world data from 50 patients with HF enrolled in a postdischarge telehealth program, with the primary intervention comprising a series of telephone calls from nurse telecarers over a 12-month period. For the full cohort, we transcribed 729 English-language calls and annotated conversation topics. For a subcohort (25 patients with both HF and T2DM), we annotated lifestyle management content with fine-grained dialogue acts describing typical conversational structures. For each patient, we identified calls with unusually high ratios of utterances on lifestyle management as lifestyle-focused calls. We further extracted structured data for inpatient admissions from 6 months before to 6 months after the intervention period. First, to understand conversational structures and content of lifestyle-focused calls, we compared the number of utterances, dialogue acts, and symptom attributes in lifestyle-focused calls to those in calls containing but not focused on lifestyle management. Second, to understand the perspectives of nurse telecarers on these calls, we conducted an expert evaluation where 2 nurse telecarers judged levels of concern and follow-up actions for lifestyle-focused and other calls (not focused on lifestyle management content). Finally, we assessed how the number of lifestyle-focused calls relates to the number of admissions, and to the average length of stay per admission. ResultsIn comparative analyses, lifestyle-focused calls had significantly fewer utterances (P=.01) and more dialogue acts (Padj=.005) than calls containing but not focused on lifestyle management. Lifestyle-focused calls did not contain deeper discussions on clinical symptoms. These findings indicate that lifestyle-focused calls entail short, intense discussions with greater emphasis on understanding patient experience and coaching than on clinical content. In the expert evaluation, nurse telecarers identified 24.2% (29/120) of calls assessed as concerning enough for follow-up. For these 29 calls, nurse telecarers were more attuned to concerns about symptoms and vitals (19/29, 65.5%) than lifestyle management concerns (4/29, 13.8%). The number of lifestyle-focused calls a patient had was modestly (but not significantly) associated with a lower average length of stay for inpatient admissions (Spearman ρ=-0.30; Padj=.06), but not with the number of admissions (Spearman ρ=-0.03; Padj=.84). ConclusionsOur approach and findings offer novel perspectives on the content, structure, and clinical associations of telehealth conversations on lifestyle management for patients with HF. Hence, our study could inform ways to enhance telehealth programs for self-care management in chronic conditions.

IntroductionDiabesity, characterized by obesity-driven Type 2 diabetes mellitus (T2DM), arises from intricate genetic and environmental interplays that induce various metabolic disorders. The systemic lipid and glucose homeostasis is controlled by an intricate cross-talk of internal glucose/insulin and fatty acid molecules to maintain a steady state of internal environment.MethodsIn this study, Caenorhabditis elegans were maintained to achieve glucose concentrations resembling the hyperglycemic conditions in diabetic patients to delve into the mechanistic foundations of diabesity. Various assays were conducted to measure intracellular triglyceride levels, lifespan, pharyngeal pumping rate, oxidative stress indicators, locomotor behavior, and dopamine signaling. Proteomic analysis was also performed to identify differentially regulated proteins and dysregulated KEGG pathways, and microscopy and immunofluorescence staining were employed to assess collagen production and anatomical integrity.ResultsWorms raised on diets high in glucose and cholesterol exhibited notably increased intracellular triglyceride levels, a decrease in both mean and maximum lifespan, and reduced pharyngeal pumping. The diabesity condition induced oxidative stress, evident from heightened ROS levels and distinct FT-IR spectroscopy patterns revealing lipid and protein alterations. Furthermore, impaired dopamine signaling and diminished locomotors behavior in diabesity-afflicted worms correlated with reduced motility. Through proteomic analysis, differentially regulated proteins encompassing dysregulated KEGG pathways included insulin signaling, Alzheimer’s disease, and nicotinic acetylcholine receptor signaling pathways were observed. Moreover, diabesity led to decreased collagen production, resulting in anatomical disruptions validated through microscopy and immunofluorescence staining.DiscussionThis underscores the impact of diabesity on cellular components and structural integrity in C. elegans, providing insights into diabesity-associated mechanisms.

In recent decades, most electrical/electronic products possess non – biodegradable components. The expanding consumption of these goods and their eventual disposal pose a serious environmental threat. To cope up with this issue, biodegradable electrical/electronic components using biobased fibres can be an alternative option. The novel exploration of this research work is the usage of underutilized biobased fibres, such as Acacia Nilotica, Acacia Leucophloea and Prosopis Juliflora, as sustainable alternatives to traditional synthetic fibres in natural fibre-reinforced epoxy composites. The novelty lies in the combination of these natural fibres with ceramic fillers like Silicon Carbide, Boron Nitride and Aluminium Oxide, aiming to enhance the composite properties. The objective of the study is to optimize the type of fibre, fibre content (2 wt%, 4 wt% and 6 wt%) and types of fillers (1 wt%) combinations using the Box-Behnken Design to improve the dielectric properties of these composites. Analysis of Variance (ANOVA) is used to evaluate the relevance of each parameter on dielectric constant of the biobased fibre reinforced epoxy composite. The significant outcome is identified that Prosopis Juliflora (6 wt%) combined with Boron Nitride (1 wt%) yields an optimal dielectric constant of 1.11, highlighting the potential of these biobased fibres to serve as effective substitutes for conventional glass and carbon fibres for electrical insulating materials used in switchboards and socket pins to prevent electrical conduction and ensure safety. This research not only contributes to the field of sustainable materials but also addresses critical environmental concerns associated with electric/electronic waste.

Abstract Late onset Alzheimer’s disease (AD) is a progressive neurodegenerative disease, with brain changes beginning years before symptoms surface. AD is characterized by neuronal loss, the classic feature of the disease that underlies brain atrophy. However, GWAS reports and recent single-nucleus RNA sequencing (snRNA-seq) efforts have highlighted that glial cells, particularly microglia, claim a central role in AD pathophysiology. Here, we tailor pattern-learning algorithms to explore distinct gene programs by integrating the entire transcriptome, yielding distributed AD-predictive modules within the brain’s major cell-types. We show that these learned modules are biologically meaningful through the identification of new and relevant enriched signaling cascades. The predictive nature of our modules, especially in microglia, allows us to infer each subject’s progression along a disease pseudo-trajectory, confirmed by post-mortem pathological brain tissue markers. Additionally, we quantify the interplay between pairs of cell-type modules in the AD brain, and localized known AD risk genes to enriched module gene programs. Our collective findings advocate for a transition from cell-type-specificity to gene modules specificity to unlock the potential of unique gene programs, recasting the roles of recently reported genome-wide AD risk loci.

Abstract Determining acute ischemic stroke (AIS) etiology is fundamental to secondary stroke prevention efforts but can be diagnostically challenging. We trained and validated an automated classification tool, StrokeClassifier, using electronic health record (EHR) text from 2039 non-cryptogenic AIS patients at 2 academic hospitals to predict the 4-level outcome of stroke etiology adjudicated by agreement of at least 2 board-certified vascular neurologists’ review of the EHR. StrokeClassifier is an ensemble consensus meta-model of 9 machine learning classifiers applied to features extracted from discharge summary texts by natural language processing. StrokeClassifier was externally validated in 406 discharge summaries from the MIMIC-III dataset reviewed by a vascular neurologist to ascertain stroke etiology. Compared with vascular neurologists’ diagnoses, StrokeClassifier achieved the mean cross-validated accuracy of 0.74 and weighted F1 of 0.74 for multi-class classification. In MIMIC-III, its accuracy and weighted F1 were 0.70 and 0.71, respectively. In binary classification, the two metrics ranged from 0.77 to 0.96. The top 5 features contributing to stroke etiology prediction were atrial fibrillation, age, middle cerebral artery occlusion, internal carotid artery occlusion, and frontal stroke location. We designed a certainty heuristic to grade the confidence of StrokeClassifier’s diagnosis as non-cryptogenic by the degree of consensus among the 9 classifiers and applied it to 788 cryptogenic patients, reducing cryptogenic diagnoses from 25.2% to 7.2%. StrokeClassifier is a validated artificial intelligence tool that rivals the performance of vascular neurologists in classifying ischemic stroke etiology. With further training, StrokeClassifier may have downstream applications including its use as a clinical decision support system.

Abstract Potent and selective inhibition of the structurally homologous proteases of coagulation poses challenges for drug development. Hematophagous organisms frequently accomplish this by fashioning peptide inhibitors combining exosite and active site binding motifs. Inspired by this biological strategy, we create several EXACT inhibitors targeting thrombin and factor Xa de novo by linking EXosite-binding aptamers with small molecule ACTive site inhibitors. The aptamer component within the EXACT inhibitor (1) synergizes with and enhances the potency of small-molecule active site inhibitors by many hundred-fold (2) can redirect an active site inhibitor’s selectivity towards a different protease, and (3) enable efficient reversal of inhibition by an antidote that disrupts bivalent binding. One EXACT inhibitor, HD22-7A-DAB, demonstrates extraordinary anticoagulation activity, exhibiting great potential as a potent, rapid onset anticoagulant to support cardiovascular surgeries. Using this generalizable molecular engineering strategy, selective, potent, and rapidly reversible EXACT inhibitors can be created against many enzymes through simple oligonucleotide conjugation for numerous research and therapeutic applications.

Abstract Real-time, low-cost, and wireless mechanical vibration monitoring is necessary for industrial applications to track the operation status of equipment, environmental applications to proactively predict natural disasters, as well as day-to-day applications such as vital sign monitoring. Despite this urgent need, existing solutions, such as laser vibrometers, commercial Wi-Fi devices, and cameras, lack wide practical deployment due to their limited sensitivity and functionality. Here we proposed a fully passive, metamaterial-based vibration processing device, fabricated prototypes working at different frequencies ranging from 5 Hz to 285 Hz, and verified that the device can improve the sensitivity of wireless vibration measurement methods by more than ten times when attached to vibrating surfaces. Additionally, the device realizes an analog real-time vibration filtering/labeling effect, and the device also provides a platform for surface editing, which adds more functionalities to the current non-contact sensing systems. Finally, the working frequency of the device is widely adjustable over orders of magnitudes, broadening its applicability to different applications, such as structural health diagnosis, disaster warning, and vital signal monitoring.

Background: Excessive daytime sleepiness (EDS), a cardinal symptom of obstructive sleep apnea (OSA) is assessed using Epworth Sleepiness Scale (ESS). Some limitations of ESS include graded responses, inapplicable situations and equal scores for active and passive situations. To overcome these limitations, we developed a novel sleepiness scale and evaluated its performance in patients with OSA. Methods: The study was executed in multiple phases. After determining applicability of items in the ESS, a 6-item questionnaire was developed comprising OSA symptoms and self-reported ‘sleepy’ situations, dichotomized responses and weighted scoring. After content and face validation by experts, the scale was tested for applicability and its performance was compared with ESS in patients with suspected OSA. Results: In phase I, applicability of ESS was tested in 189 participants, of whom 98 (51.8 %) participants found multiple items inapplicable.In phase II, 34 self-reported sleepy situations from 200 participants were narrowed down to a 6-item questionnaire, based on expert validation. This scale was named the Indian Sleepiness Scale (ISS) and was tested for applicability in phase III in 226 participants from diverse literacy backgrounds, who found all situations applicable.In phase IV, ISS and ESS were administered to 335 patients with suspected OSA. OSA was confirmed on polysomnography in 294 (87.7 %) patients. A cut-off score of ≥6 was derived for ISS; at this cut-off score, the ISS which was more sensitive than ESS (71.1 % vs 43.2 %). Conclusions: The Indian Sleepiness Scale was found to be widely applicable and more sensitive than ESS for sleepiness evaluation in patients with OSA.

Summary: Reactive changes of glial cells during neuroinflammation impact brain disorders and disease progression. Elucidating the mechanisms that control reactive gliosis may help us to understand brain pathophysiology and improve outcomes. Here, we report that adult ablation of autism spectrum disorder (ASD)-associated CHD8 in astrocytes attenuates reactive gliosis via remodeling chromatin accessibility, changing gene expression. Conditional Chd8 deletion in astrocytes, but not microglia, suppresses reactive gliosis by impeding astrocyte proliferation and morphological elaboration. Astrocyte Chd8 ablation alleviates lipopolysaccharide-induced neuroinflammation and septic-associated hypothermia in mice. Astrocytic CHD8 plays an important role in neuroinflammation by altering the chromatin landscape, regulating metabolic and lipid-associated pathways, and astrocyte-microglia crosstalk. Moreover, we show that reactive gliosis can be directly mitigated in vivo using an adeno-associated virus (AAV)-mediated Chd8 gene editing strategy. These findings uncover a role of ASD-associated CHD8 in the adult brain, which may warrant future exploration of targeting chromatin remodelers in reactive gliosis and neuroinflammation in injury and neurological diseases.

Background Studies have shown inconclusive results on the effectiveness of cerebral protection devices (CPDs) with transcatheter aortic valve replacement. We aimed to analyze the national statistics on stroke and other outcomes with CPD use. Methods and Results The Nationwide Readmissions Database (2017–2020) was queried to obtain data on patients undergoing transcatheter aortic valve replacement. Outcomes were compared between patients with a CPD and patients without a CPD. Of 271 804 patients undergoing transcatheter aortic valve replacement, CPD was used in 7.3% of patients. In a multivariable logistic regression analysis, CPD use was not associated with lower overall stroke rates (1.6% versus 1.9% without CPD; odds ratio, 0.95 [95% CI, 0.84–1.07]; P=0.364), but it was significantly associated with lower major stroke rates (1.2% versus 1.5% without CPD; odds ratio, 0.85 [95% CI, 0.74–0.98]; P=0.02). Patients with a CPD also had a shorter length of stay, higher routine discharges to home/self‐care (74.9% versus 70.6%), and lower mortality rates (0.7% versus 1.3%). The 30‐day (9.6% versus 11.7%) and 180‐day (24.6% versus 28.2%) readmission rates were significantly lower in the CPD cohort. Among patients who developed stroke, patients with a CPD had more frequent routine discharges. Prior valve surgery was associated with the highest risk of overall and major stroke. Conclusions CPD use during transcatheter aortic valve replacement was not independently associated with a lower risk of overall stroke but was associated with a lower risk of major stroke in a multivariable model. Data from future randomized trials that may offset any potential confounders in our study are required to help identify patients who would benefit from the use of these devices.

Background: Hepatitis B infection has been associated with the development of gestational diabetes but the underlying mechanism is not known. Objective: To examine associations between viral activity, gestational diabetes mellitus (GDM), and insulin resistance in pregnant people with chronic hepatitis B infection (HBV). Design: Prospective cohort study across three tertiary maternity centres in Melbourne, Australia, between May 2021 and April 2023. Methods: Participants were followed prospectively through pregnancy to evaluate subsequent GDM diagnosis. Demographics, pregnancy outcomes, and markers of viral activity were compared between those with GDM versus those without. Logistic regression analysis was performed pre- and post-adjustment for known confounders. Sub-group analysis of participants from South East Asia (SEA) was performed. Outcome measures included GDM diagnosis, insulin resistance (Homeostatic Model Assessment Insulin Resistance score (HOMA-IR) score), HBV activity as measured by liver function tests, HBV viral load, hepatitis B e antigen, and quantitative hepatitis B surface antigen (quantHBsAg). Results: A total of 113 women were recruited. One third (38/112, 33.9%) developed GDM, mostly diagnosed on isolated postprandial hyperglycaemia (25/38, 65.8%). Over half were born in SEA (66/113, 58.4%). Mean quantHBsAg was significantly lower in those with GDM ( p = 0.044). No other associations were identified between GDM or HOMA-IR and markers of hepatic activity on multivariate logistic regression analysis and on sub-group analysis of those born in SEA. Conclusions: QuantHBsAg was significantly lower in those with GDM; otherwise, no association between GDM and measures of HBV viral activity was found. QuantHBsAg may be useful as an early pregnancy marker for GDM risk and warrants further research.

Objectives We sought to determine the relationship between the degree of left ventricular ejection fraction (LVEF) impairment and the frequency and type of bleeding events after percutaneous coronary intervention (PCI).Design This was an observational retrospective cohort analysis. Patients who underwent PCI from 2009 to 2017 were identified from our institutional National Cardiovascular Disease Registry (NCDR) CathPCI database. Patients were stratified by pre-PCI LVEF: preserved (≥50%), mildly reduced (41%–49%) and reduced (≤40%) LVEF.Primary outcome measures The outcome was major bleeding, defined by NCDR criteria. Events were classified based on bleeding aetiology and analysed by multivariable logistic regression.Results Among 13 537 PCIs, there were 817 bleeding events (6%). The rate of bleeding due to any cause, blood transfusion, gastrointestinal bleeding and coronary artery perforation or tamponade each increased in a stepwise fashion comparing preserved, mildly reduced and reduced LVEF reduction (p

Introduction: Road Traffic accidents (RTA) in India are the sixth among the leading cause of death. The cranial nerves serve several essential functions. Loss of these functions can adversely affect the quality of life. This study was conducted to assess the incidence of Cranial Nerve Injury (CNI), radiological and clinical patterns and to ascertain the significant and often debilitating effect of CNI in otherwise non-life threatening Traumatic Brain Injuries. Methodology: This prospective study was conducted in the Department of Neurosurgery, SRIHER between April 2019 and September 2021. A total of 62 patients among the 402 patients with TBI had CNI. Patients with GCS

Abstract Public imaging datasets are critical for the development and evaluation of automated tools in cancer imaging. Unfortunately, many do not include annotations or image-derived features, complicating downstream analysis. Artificial intelligence-based annotation tools have been shown to achieve acceptable performance and can be used to automatically annotate large datasets. As part of the effort to enrich public data available within NCI Imaging Data Commons (IDC), here we introduce AI-generated annotations for two collections containing computed tomography images of the chest, NSCLC-Radiomics, and a subset of the National Lung Screening Trial. Using publicly available AI algorithms, we derived volumetric annotations of thoracic organs-at-risk, their corresponding radiomics features, and slice-level annotations of anatomical landmarks and regions. The resulting annotations are publicly available within IDC, where the DICOM format is used to harmonize the data and achieve FAIR (Findable, Accessible, Interoperable, Reusable) data principles. The annotations are accompanied by cloud-enabled notebooks demonstrating their use. This study reinforces the need for large, publicly accessible curated datasets and demonstrates how AI can aid in cancer imaging.

The study investigated the effects of FMD vaccination on acute phase response and milk composition in the HF crossbred cows (n = 12) using a cross-over experimental design. In trial 1, one group (n = 6) received inactivated trivalent oil-adjuvanted FMD vaccine [day post-vaccination, (dpv) 0], while the mock-vaccinated group received saline (n = 6). After a cooling period of 15 days, the trial was repeated by swapping groups. The body temperature, dry matter intake (DMI) and milk yield were recorded. Haemato-biochemical parameters, haptoglobin and cortisol concentrations were also assessed. A significant (p

Background The aims of this study were to understand the incidence and outcomes of patients with cardiogenic shock (CS) due to severe aortic stenosis (AS), and the impact of conventional treatment strategies in this population. Methods and Results All patients admitted to the Cleveland Clinic cardiac intensive care unit between January 1, 2010 and December 31, 2021 with CS were retrospectively identified and categorized into those with CS in the setting of severe AS versus CS without AS. The impact of various treatment strategies on mortality was further assessed. We identified 2754 patients with CS during the study period, of whom 216 patients (8%) had CS in the setting of severe AS. Medical management was associated with the highest 30‐day mortality when compared with either balloon aortic valve replacement or aortic valve replacement (surgical or transcatheter aortic valve replacement) (hazard ratio, 3.69 [95% CI, 2.04–6.66]; P

Este consenso de nomenclatura y clasificación para la válvula aórtica bicúspide congénita y su aortopatía está basado en la evidencia y destinado a ser utilizado universalmente por médicos (tanto pediatras como de adultos), médicos ecocardiografistas, especialistas en imágenes avanzadas cardiovasculares, cardiólogos intervencionistas, cirujanos cardiovasculares, patólogos, genetistas e investigadores que abarcan estas áreas de investigación clínica y básica. Siempre y cuando se disponga de nueva investigación clave y de referencia, este consenso internacional puede estar sujeto a cambios de acuerdo con datos basados en la evidencia1.

Anti-Mullerian hormone (AMH) is considered a biomarker of ovarian follicular reserve and fertility in humans and farm animals. A study was carried out to evaluate the peripheral AMH concentration in high and low fertile crossbred cows. Vrindavani crossbred cows (n=60) at the institutional dairy farm were used for the study. The age-specific decline in AMH concentration was evident, with the highest concentration at 4-6 years (134.8±17.74 pg/mL) corresponding to second to third parity. Retrospective assessment of fertility using 217 lactation records in crossbred cows revealed that circulatory AMH was higher by 69 pg/mL in the high fertile cows than those of low fertile cows. It was concluded that the serum AMH concentration was influenced by age and parity. Further, serum AMH concentrations were found to be higher in the group of cows that had superior fertility records in comparison to the group with low-performing animals.

Abstract Management strategies and the use of advanced technologies are equally important for determining the sample number and sampling frame for successful field sampling for animal disease prevalence studies. The quality of the biological samples collected in the field has a direct bearing on the integrity of the data generated, prevalence estimates and subsequent policy decisions on disease control. Hence, compromising the quality of biological samples collected in the field could potentially undermine the priority setting principles in disease control strategies. Biological samples collected from domestic animals in the field are precious materials and require meticulous planning for sample collection, sample storage in the field, transportation, and storage in the laboratory. Poorly managed field sampling has a significant detrimental impact on the sample quality and quantity and directly affects the accuracy of disease prevalence data. A bad choice of sampling tools, containers, storage and transport all have a negative impact on the integrity of the sample and consequently have an impact on the outcome. Over the last two years, as part of our one health animal sampling work in India, we have observed challenges and opportunities in the field sampling of animals for disease prevalence studies. This paper aims to provide information on management practices and technologies for efficient biological sample collection from the field and ensure that good quality samples are available for testing.

Understanding spatial and geometrical patterns of urbanization is crucial in tackling associated problems. As urbanization progresses through various stages of development, it reflects different forms, patterns, and interactions based on its physical and functional aspects. Spatial metrics is a well-acclaimed technique for quantifying urban morphological characteristics. The current study was conducted for Tiruchirappalli and six tier-urban centers located within a 40-kilometers radius to comprehend the comparative growth and spatial patterns. The urban centers are divided into eight zones based on direction for more precise quantification. The study employed Landsat 5 and 8 satellite images to classify land use/cover for the periods 1996, 2008, and 2020. FRAGSTAT is the software application used to analyze spatial metrics, at patch, class, and landscape levels. The study generated a significant amount of data about spatial and geometric patterns of growth. Area, edge, and aggregation metrics indicated that zones in Manachanallur, Manapparai, Musiri, Thiruverumbur, and Thuraiyur had protrusive urban growth during the study period. Transport networks have been the instrumental factor for such growth. Diversity metrics revealed Tiruchirappalli and Thiruverumbur have abundant patches of various classes in many of their zones since they retain patches like open, vegetation, and water bodies extensively. Shape metrics across all urban centers during the period 1996-2008 were more irregular in shape; it has become significantly smooth during 2008-2020 due to infill developments on the fringe areas. The period 1996-2008 recorded a huge transition of open areas into built-ups, attributing to infill development, especially inside the urban centers; similarly, during the period 2008-2020, edge expansion has been recorded widely across the urban centers. The current study is a significant contribution to urban research in understanding relative spatial and geometric patterns of urbanization.

ABSTRACTSoy meal, a substantial byproduct of soy-oil processing, is rich in crude protein (44–49%), crude ash (5.2–9.1%), minerals, and vitamins. Only 2% of the total soy meal is consumed by humans, while 97% is utilized for animal feed and other industrial purposes. In this study, we use soy meal from non-genetically modified high oleic (Non-GMO-HO) soybean oil processing to develop value-added food products. In this study, soy meal was spray-dried using 5–15% maltodextrin and gum Arabic as a drying aid because trial investigations revealed that the sticky behavior of soy meal powder, which impacts product yield. The physical properties, such as colour, flowability (m3/h), moisture content (%), water activity (Aw), hygroscopicity (%), reconstitution properties, viscosity (mPa-s), thermal degradation behavior, and particle size distribution, were investigated to analyze the impact of drying aid on the quality of soy meal powder. JMP 14.0.0 Pro software was used to conduct the statistical analysis. Spray-dried soy meal powder can be used in reconstituted beverages, infant formulas, soy-based cookies, meat analogs, carrier agents, and more.

This research reports the development of 3D carbon nanostructures that can provide unique capabilities for manufacturing carbon nanotube (CNT) electronic components, electrochemical probes, biosensors, and tissue scaffolds. The shaped CNT arrays were grown on patterned catalytic substrate by chemical vapor deposition (CVD) method. The new fabrication process for catalyst patterning based on combination of nanoimprint lithography (NIL), magnetron sputtering, and reactive etching techniques was studied. The optimal process parameters for each technique were evaluated. The catalyst was made by deposition of Fe and Co nanoparticles over an alumina support layer on a Si/SiO2 substrate. The metal particles were deposited using direct current (DC) magnetron sputtering technique, with a particle ranging from 6 nm to 12 nm and density from 70 to 1000 particles/micron. The Alumina layer was deposited by radio frequency (RF) and reactive pulsed DC sputtering, and the effect of sputtering parameters on surface roughness was studied. The pattern was developed by thermal NIL using Si master-molds with PMMA and NRX1025 polymers as thermal resists. Catalyst patterns of lines, dots, and holes ranging from 70 nm to 500 nm were produced and characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Vertically aligned CNTs were successfully grown on patterned catalyst and their quality was evaluated by SEM and micro-Raman. The results confirm that the new fabrication process has the ability to control the size and shape of CNT arrays with superior quality.

Abstract Quantifiable decline in the maternal body temperature during the pre-calving offers the possibilities for predicting the calving that can improve the calving management. As infrared thermography (IRT) is a simple non-contact tool for precise measurement of surface temperature, we investigated the use of IRT to establish thermal signatures around calving in the Murrah buffalo. The IRT of eye, right lateral, left lateral and rear side of udder skin surface temperature (USST) were recorded at 6 h interval from 96 h before the expected date of calving, at the time of calving and 24 h post-calving in Murrah buffaloes (n = 28). In parallel, blood samples were collected for progesterone (P4) assay. The results revealed that the IRT of the eye, right and left lateral and rear side of USST showed a significant decrease in the temperature from 48 h pre-calving till the onset of calving with a ΔT (°C) of 0.56, 0.91, 0.70, and 0.90, respectively. Mean USST significantly declined from 48 h pre-calving with a ΔT of 0.85 °C. The residual temperature of both eye and various ROI of the udder also followed a similar and significant declining trend from 48 to 0 h of calving indicating that circadian influence on the USST was minimum. Plasma P4 concentration significantly decreased from 72 h pre-calving till calving. It is concluded that a marked reduction in the IRT of the USST at 6–12 h pre-calving would be useful in predicting the onset of calving in the Murrah buffalo.

Introduction: Low Birth Weight (LBW) is a commonly encountered problem in developing countries. Growth is the single most important predictor of morbidity and mortality in a LBW infant. LBW babies show a pattern of growth, different from normal weighing babies. Aim: To assess the growth pattern of LBW infants in first six months of life. Materials and Methods: This prospective cohort study was done in Department of Paediatrics, of Kilpauk Medical College and Hospital, a tertiary care hospital in Southern India, from September 2019 to August 2020. Total 310 LBW infants, of which 200 were term and rest preterm were included and followed-up at the ages of three and six months. Clinical details including gender, gestational age, order of birth, length of stay in nursery, maternal and neonatal morbidities, type of feeding and intercurrent illness were noted. The weight, length and head circumference of the infants were measured by standard methods and interpreted using appropriate charts. The anthropometric measures were converted into z-score and compared. The outcome variables were statistically analysed using Chi-square test. Results: Out of 310 babies, 172 (55.5%) were girls and 200 (64.5%) were term babies. Six month follow-up rate was 92%. A total of 228 (79%) infants were on exclusive breastfeeding while the remaining 21% were partially breastfed. The prevalence (95% confidence interval) of undernutrition, short stature and microcephaly at six months were 54.9% (48.93-60.76), 62.2% (56.34-67.88) and 30.7% (25.47-36.47), respectively. Fall in standard deviation score of length, weight and head circumference was observed which was more pronounced in preterm than in term infants (p

Objective:To compare and analyze the precision, accuracy, and reliability of commonly used cone-beam computed tomography (CBCT) software in predicting the mesiodistal diameter of impacted canines.Methods:This study was conducted on 11 patients (six males and five females, mean age: 17.5±5.5 years) with either unilateral or bilateral impacted canines in the maxilla or mandible. DICOM data sets of the patients obtained from CBCT scans were then loaded and visualized with four selected CBCT software to measure the widest mesiodistal diameter of the impacted teeth. Physical measurements using a digital vernier caliper, kept as a control, were also made on the extracted teeth and orthodontically erupted teeth. The collected data underwent statistical analysis, and the statistical significance level was set at p

Objective Patients with moderate aortic stenosis (AS) exhibit high morbidity and mortality. Limited evidence exists on the role of aortic valve replacement (AVR) in this patient population. To investigate the benefit of AVR in moderate AS on survival and left ventricular function.Methods In a retrospective cohort study, patients with moderate AS between 2008 and 2016 were selected from the Cleveland Clinic echocardiography database and followed until 2018. Patients were classified as receiving AVR or managed medically (clinical surveillance). All-cause and cardiovascular mortality were assessed by survival analyses. Temporal haemodynamic and structural changes were assessed with longitudinal analyses using linear mixed effects models.Results We included 1421 patients (mean age, 75.3±5.4 years and 39.9% women) followed over a median duration of 6 years. Patients in the AVR group had lower risk of all-cause (adjusted HR (aHR)=0.51, 95% CI: 0.34 to 0.77; p=0.001) and cardiovascular mortality (aHR=0.50, 95% CI: 0.31 to 0.80; p=0.004) compared with those in the clinical surveillance group irrespective of sex, receipt of other open-heart surgeries and underlying malignancy. These findings were seen only in those with preserved left ventricular ejection fraction (LVEF) ≥50%. Further, patients in the AVR group had a significant trend towards an increase in LVEF and a decrease in right ventricular systolic pressure compared with those in the clinical surveillance group.Conclusions In patients with moderate AS, AVR was associated with favourable clinical outcomes and left ventricular remodelling.

Picrorhiza kurroa Royle ex Benth (P. kurroa) is an important medicinal plant in the ayurvedic system for treating various liver and inflammatory conditions. The present study aimed to extract the phytocompounds from various extracts (Acetone, Chloroform, Ethanol, Ethyl acetate, Hexane, and Methanol) of P. kurroa. Further, the major phytocompounds were nano-encapsulated by PLGA (Poly-lactic-co-glycolic acid) method and characterized to enhance activity towards the target. The highest polyphenolic value was found to be 323.2 ± 16.6 and 316.3 ± 12.1 μg GAEq./mg in ethanolic and methanolic extracts. The highest flavonoid value was found to be 280.3 ± 19.8 and 300.8 ± 15.2 in ethanolic and methanolic extracts μg QEq./mg. P. kurroa exhibited DPPH radical scavenging with IC50 of 38.2 ± 1.1 and 43.7 ± 1.8 μg/mL and also showed potent ferric reducing power and total antioxidant activities. The major phytocompounds, such as apocynin (AP) and vanillic acid (VA), were confirmed using HPLC. Further, the nano-encapsulation of apocynin and vanillic acid successfully achieved by PLGA methods. The average particle size of nano-encapsulated apocynin, vanillic acid is 350 nm, 204.4 nm, and zeta potential were −25.3 mv and −11.2 mv. Nanoformulations showed an apocynin and vanillic acid encapsulation efficiency of 93.6% and 93.3%, respectively. SEM and AFM confirmed the round and smooth morphology of the nanoparticles. The results of XRD confirmed the amorphous nature of nanoformulations. FTIR technique confirm the presence of biomolecules inside the polymer. The thermal stability of nanoformulations determined by DSC analysis showed endothermic peak. The prepared and characterization apocynin, vanillic acid nanoparticles revealed their good quality index, suggesting that potential use in pharmacy and phytotherapy as a source of natural antioxidant.

Introduction: Soil salinity poses a severe threat to rice production, resulting in stunted growth, leaf damage, and substantial yield losses. This study focuses on developing an early maturing seedling stage salinity tolerant rice variety by integrating conventional breeding methods with marker assisted breeding (MAB) approaches.Methods: Seedling-stage salinity tolerance Quantitative Trait Locus (QTL) “Saltol” from the salt-tolerant parent FL478 was introduced into the high-yielding but salt-sensitive rice variety ADT 45. This was achieved through a combination of conventional breeding and MAB. The breeding process involved rigorous selection, screening, and physiological parameter assessments.Results: KKL(R) 3 (KR 15066) identified as the top performing Recombinant Inbred Line (RIL), consistently demonstrating maximum mean grain yields under both salinity (3435.6 kg/ha) and normal (6421.8 kg/ha) conditions. In comparison to the early maturing, salt-tolerant national check variety CSR 10, KKL(R) 3 exhibited a substantial yield increase over 50%.Discussion: The notable improvement observed in KKL(R) 3 positions it as a promising variety for release, offering a reliable solution to maximize yields, ensure food security, and promote agricultural sustainability in both saline and non-saline environments. The study highlights the effectiveness of MAB in developing salt-tolerant rice varieties and emphasizes the significance of the Saltol QTL in enhancing seedling stage salinity tolerance. The potential release of KKL(R) 3 has the capacity to revolutionize rice production in salt affected regions, providing farmers with a reliable solution to maximize yields and contribute to food security while ensuring agricultural sustainability.

Background Patients who experience in-hospital ST-segment elevation myocardial infarction (iSTEMI) represent a uniquely high-risk cohort owing to delays in diagnosis, prolonged time to reperfusion and increased mortality. Quality initiatives aimed at improving the care of this vulnerable, yet understudied population are needed.Methods This study included consecutive patients with iSTEMI treated with percutaneous coronary intervention (PCI) between 1 January 2011 and 15 July 2019 at a single, tertiary referral centre. A comprehensive iSTEMI protocol (CSP) was implemented on 15 July 2014, incorporating: (1) cardiology fellow activation of the catheterisation lab using standardised criteria, (2) nursing chest pain protocol, (3) improved electronic access to electrocardiographic studies, (4) checklist for initial triage and management, (5) 24/7/365 catheterisation lab readiness and (6) radial-first PCI approach. Key metrics and clinical outcomes were compared before and after CSP implementation.Results Among 125 total subjects, the post-CSP cohort (n=81) was younger, had more males and were more likely to be hospitalised for cardiac-related reasons relative to the pre-CSP cohort (n=44) who were more likely hospitalised for operative-related aetiologies. After CSP adoption, median ECG-to-first-device-activation time decreased from 113 min to 64 min (p

Purpose: CDKL5 deficiency disorder (CDD) is a developmental and epileptic encephalopathy with multisystemic comorbidities. Cardiovascular involvement in CDD was shown in animal models but is yet poorly described in CDD cohorts. Methods: We identified 38 individuals with genetically confirmed CDD through the Cleveland Clinic CDD specialty clinic and matched 190 individuals with non-genetic epilepsy to them as a comparison group. Natural language processing was applied to yield Human Phenotype Ontology (HPO) terms from medical records. We conducted HPO association testing and manual chart review to explore cardiovascular comorbidities associated with CDD. Results: We extracted 243,541 HPO terms from 30,512 medical encounters. Phenome-wide analysis confirmed well-established CDD phenotypes and identified association of tachycardia with CDD (Odds ratio 4.2, 95% confidence interval (CI) 1.75-9.93, Padj < .001). We found a 99.6-fold enrichment of supraventricular tachycardia (SVT) in CDD encounter notes (Padj < .001), which led to identification of 2 cases of fetal/neonatal onset SVT previously undescribed in CDD. Tachycardia in CDD individuals was associated with the presence of other autonomic symptoms (Odds ratio 5.63, 95% CI 1.08-40.3, P = .038). Conclusion: CDD is associated with tachycardia, potentially including early-onset SVT. Alongside prospective validation studies, semiautomated genotype-phenotype analysis with matched controls is a scalable, rapid, and efficient approach for validating known and identifying novel phenotype associations.

Oropouche virus (OROV) is a member of the Peribunyaviridae family and the causative agent of a dengue-like febrile illness transmitted by mosquitoes. Although mild symptoms generally occur, complications such as encephalitis and meningitis may develop. A lack of proper diagnosis, makes it a potential candidate for new epidemics and outbreaks like other known arboviruses such as Dengue, Yellow Fever and Zika virus. The study of natural molecules as potential antiviral compounds is a promising alternative for antiviral therapies. Wedelolactone (WDL) has been demonstrated to inhibit some viral proteins and virus replication, making it useful to target a wide range of viruses. In this study, we report the in silico effects of WDL on the OROV N-terminal polymerase and its potential inhibitory effects on several steps of viral infection in mammalian cells in vitro, which revealed that WDL indeed acts as a potential inhibitor molecule against OROV infection.

The nucleus is highly organized to facilitate coordinated gene transcription. Measuring the rheological properties of the nucleus and its sub-compartments will be crucial to understand the principles underlying nuclear organization. Here, we show that strongly localized temperature gradients (approaching 1°C/µm) can lead to substantial intra-nuclear chromatin displacements (>1 µm), while nuclear area and lamina shape remain unaffected. Using particle image velocimetry (PIV), intra-nuclear displacement fields can be calculated and converted into spatio-temporally resolved maps of various strain components. Using this approach, we show that chromatin displacements are highly reversible, indicating that elastic contributions are dominant in maintaining nuclear organization on the time scale of seconds. In genetically inverted nuclei, centrally compacted heterochromatin displays high resistance to deformation, giving a rigid, solid-like appearance. Correlating spatially resolved strain maps with fluorescent reporters in conventional interphase nuclei reveals that various nuclear compartments possess distinct mechanical identities. Surprisingly, both densely and loosely packed chromatin showed high resistance to deformation, compared to medium dense chromatin. Equally, nucleoli display particularly high resistance and strong local anchoring to heterochromatin. Our results establish how localized temperature gradients can be used to drive nuclear compartments out of mechanical equilibrium to obtain spatial maps of their material responses.

Apocynin (AP) and vanillic acid (VA) are rich antioxidant has a broad spectrum of pharmacological activities. However, its practical administration has been limited due to poor aqueous solubility and bioavailability. Hence Cyclodextrins are used to improve the solubility and oral bioavailability of AP and VA via Hydroxypropyl beta-cyclodextrin (HPBCD) formulation. HPBCD inclusion complex with AP-VA was synthesized and characterized for its physicochemical properties. The average particle size of HPBCD-AP-VA was 164.1 ± 1.3nm, 146.7 ± 2.0nm, and zeta potential was -30.0 mv and -17.3 mv. The encapsulation `efficiency was found to be 97% and 95%, respectively. AFM, SEM, and TEM confirmed the size, spherical nature, and smooth surface of the inclusion complex. The results of XRD, DSC and FTIR, indicated that AP-VA successfully entered the cavity of HPBCD. In vitro bioaccessibility result revealed that HPBCD inclusions were more accessible when compared to Native form. Further, in vivo bioavailability study showed high concentration of HPBCD-AP-VA complex in plasma (25mg/kg bwt) and compared to Native. The Tmax and AUC of HPBCD complex in plasma was 2h and 253.46 ± 3.42, 249.28 ± 2.31 respectively. The results of the study revealed that using HPBCD to encapsulate AP-VA can be beneficial for the pharmacological uses.

IntroductionMycobacterium orygis, a member of MTBC has been identified in higher numbers in the recent years from animals of South Asia. Comparative genomics of this important zoonotic pathogen is not available which can provide data on the molecular difference between other MTBC members. Hence, the present study was carried out to isolate, whole genome sequence M. orygis from different animal species (cattle, buffalo and deer) and to identify molecular marker for the differentiation of M. orygis from other MTBC members.MethodsIsolation and whole genome sequencing of M. orygis was carried out for 9 samples (4 cattle, 4 deer and 1 buffalo) died due to tuberculosis. Comparative genomics employing 53 genomes (44 from database and 9 newly sequenced) was performed to identify SNPs, spoligotype, pangenome structure, and region of difference.ResultsM. orygis was isolated from water buffalo and sambar deer which is the first of its kind report worldwide. Comparative pangenomics of all M. orygis strains worldwide (n= 53) showed a closed pangenome structure which is also reported for the first time. Pairwise SNP between TANUVAS_2, TANUVAS_4, TANUVAS_5, TANUVAS_7 and NIRTAH144 was less than 15 indicating that the same M. orygis strain may be the cause for infection. Region of difference prediction showed absence of RD7, RD8, RD9, RD10, RD12, RD301, RD315 in all the M. orygis analyzed. SNPs in virulence gene, PE35 was found to be unique to M. orygis which can be used as marker for identification.ConclusionThe present study is yet another supportive evidence that M. orygis is more prevalent among animals in South Asia and the zoonotic potential of this organism needs to be evaluated.

Maternal immunisation, a low cost and high efficacy intervention is recommended for its pathogen specific protection. Evidence suggests that maternal immunisation has another significant impact: reduction of preterm birth (PTB), the single greatest cause of childhood morbidity and mortality globally. Our overarching question is: how does maternal immunisation modify the immune system in pregnant women and/or their newborn to reduce adverse pregnancy outcomes and enhance the newborn infant’s capacity to protect itself from infectious diseases during early childhood? To answer this question we are conducting a multi-site, prospective observational cohort study collecting maternal and infant biological samples at defined time points during pregnancy and post-partum from nulliparous women. We aim to enrol 400 women and determine the immune trajectory in pregnancy and the impact of maternal immunisation (including influenza, pertussis and/or COVID-19 vaccines) on this trajectory. The results are expected to identify areas that can be targeted for future intervention studies.

As emerging evidence indicates that FMD vaccination causes variable degrees of pregnancy loss in the beef cow, the study was conducted at NDRI SRS in sub-tropical conditions in the year 2021 to investigate its effects on the pregnancy rate in the dairy cow when they were bred within 14 days of FMD vaccination. Retrospective data on AI done within 14 days post FMD vaccination (dpv -14 to +14) and the corresponding pregnancy outcome were collected for 6 years (January 2016 to January 2021) and each record was categorized into AI pre-vaccination (dpv -14 to -1) or AI post-vaccination (dpv 0 to 14). After excluding repeat breeding cows and pregnant heifers, the final dataset consisted of 47 records derived from crossbred and Deoni cows. The binary outcome variable pregnancy was regressed on the categorical predictor variables such as day of AI with respect to dpv 0, stage of lactation and parity. The results indicated that the odds of pregnancy in the AI post-vaccinated group was 0.47 (95% confidence interval: 0.10-1.88) value) as compared with AI pre-vaccinated group. It can be concluded that FMD vaccination has no significant effect on pregnancy outcome if the animals are bred 14 days before and 14 days after FMD vaccination (irrespective of breed, age, parity, days in milk).

Abstract Due to commonalities in pathophysiology, age-related macular degeneration (AMD) represents a uniquely accessible model to investigate therapies for neurodegenerative diseases, leading us to examine whether pathways of disease progression are shared across neurodegenerative conditions. Here we use single-nucleus RNA sequencing to profile lesions from 11 postmortem human retinas with age-related macular degeneration and 6 control retinas with no history of retinal disease. We create a machine-learning pipeline based on recent advances in data geometry and topology and identify activated glial populations enriched in the early phase of disease. Examining single-cell data from Alzheimer’s disease and progressive multiple sclerosis with our pipeline, we find a similar glial activation profile enriched in the early phase of these neurodegenerative diseases. In late-stage age-related macular degeneration, we identify a microglia-to-astrocyte signaling axis mediated by interleukin-1β which drives angiogenesis characteristic of disease pathogenesis. We validated this mechanism using in vitro and in vivo assays in mouse, identifying a possible new therapeutic target for AMD and possibly other neurodegenerative conditions. Thus, due to shared glial states, the retina provides a potential system for investigating therapeutic approaches in neurodegenerative diseases.