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Background: Streptococcus mutans, a bacterium commonly found in the oral cavity, displays remarkable adaptive capabilities that enable its survival in this unique environment. Maintaining good oral hygiene practices, adhering to hygienic behaviors, and adopting healthy dietary habits have been identified as potential factors for restraining the growth of cariogenic bacteria. While numerous strategies have been developed for managing dental caries, the ultimate goal is to identify preventive agents that can effectively halt the progression of caries and impede the development of new lesions. This review aims to explore the competent behavior of Streptococcus mutans, specifically its role in causing oral infections that can have prolonged effects on systemic health. The establishment, persistence, and strengthening of the interaction between species response and the human system contribute to this phenomenon. The implications of Streptococcus mutans in human health are significant, and as such, this review focuses extensively on its putative virulence factors, the mechanisms by which it exerts its virulence, and the clinical complications associated with its presence. By providing a comprehensive understanding of the molecular mechanisms employed by Streptococcus mutans and the consequences of its colonization in the oral cavity, this review expands our knowledge of the potential systemic implications associated with this bacterium. Ultimately, it calls for the development of targeted preventive strategies to mitigate the negative impact of Streptococcus mutans on both oral and systemic health.

Abstract Internet of Medical Things (IoMT) is a group of medical devices that connect the healthcare information technology to minimize the redundant hospital visit and healthcare system troubles. IoMT connect the patients to the doctor and transmit the medical data over the network. The spread of corona virus has put the people at high risk. Due to increasing number of cases and its stress on health professionals, IoMT technology is used in many healthcare centers. But, the security level and data classification accuracy was not improved by existing methods during the data communication. In order to solve these issues, Cayley–Purser Cryptographic Secured Communication based Jackknife Correlative Data Classification (CPCSC-JCDC) method is designed. The key objective of CPCSC-JCDC method is to collect the patient information through IoMT devices and send to the doctor in more secured manner. Initially in CPCSC-JCDC method, the patient data is collected. After the data collection process, the data gets encrypted with help of public key of the patient by using cayley–purser cryptosystem. After the encryption process, the data is sent to the doctor. The doctor receives and decrypts the patient data by using their private key. After decryption process, the doctor analyses the patient data and classifies the data as emergency case or normal case by using jackknife correlation function. This helps to minimize the patient readmission rate and increase the patient satisfaction level. Experimental evaluation is carried out by Novel Corona Virus 2019 dataset using different metrics like data classification accuracy, data classification time and security level. The evaluation result shows that CPCSC-JCDC method improves the security level as well as accuracy and minimizes the time consumption during data communication than existing works.

Abstract Cardiovascular diseases (CVD) are a predominant health concern globally, emphasizing the need for advanced diagnostic techniques. In our research, we present an avant-garde methodology that synergistically integrates ECG readings and retinal fundus images to facilitate the early disease tagging as well as triaging of the CVDs in the order of disease priority. Recognizing the intricate vascular network of the retina as a reflection of the cardiovascular system, alongwith the dynamic cardiac insights from ECG, we sought to provide a holistic diagnostic perspective. Initially, a Fast Fourier Transform (FFT) was applied to both the ECG and fundus images, transforming the data into the frequency domain. Subsequently, the Earth Mover’s Distance (EMD) was computed for the frequency-domain features of both modalities. These EMD values were then concatenated, forming a comprehensive feature set that was fed into a Neural Network classifier. This approach, leveraging the FFT’s spectral insights and EMD’s capability to capture nuanced data differences, offers a robust representation for CVD classification. Preliminary tests yielded a commendable accuracy of 84%, underscoring the potential of this combined diagnostic strategy. As we continue our research, we anticipate refining and validating the model further to enhance its clinical applicability in resource limited healthcare ecosystems prevalent across the Indian sub-continent and also the world at large.

Abstract Background Early childhood obesity prevention interventions that aim to change parent/caregiver practices related to infant (milk) feeding, food provision and parent feeding, movement (including activity, sedentary behaviour) and/or sleep health (i.e. target parental behaviour domains) are diverse and heterogeneously reported. We aimed to 1) systematically characterise the target behaviours, delivery features, and Behaviour Change Techniques (BCTs) used in interventions in the international Transforming Obesity Prevention for CHILDren (TOPCHILD) Collaboration, and 2) explore similarities and differences in BCTs used in interventions by target behaviour domains. Methods Annual systematic searches were performed in MEDLINE, Embase, Cochrane (CENTRAL), CINAHL, PsycINFO, and two clinical trial registries, from inception to February 2023. Trialists from eligible randomised controlled trials of parent-focused, behavioural early obesity prevention interventions shared unpublished intervention materials. Standardised approaches were used to code target behaviours, delivery features and BCTs in both published and unpublished intervention materials. Validation meetings confirmed coding with trialists. Narrative syntheses were performed. Results Thirty-two trials reporting 37 active intervention arms were included. Interventions targeted a range of behaviours. The most frequent combination was targeting all parental behaviour domains (infant [milk] feeding, food provision and parent feeding, movement, sleep health; n[intervention arms] = 15/37). Delivery features varied considerably. Most interventions were delivered by a health professional (n = 26/36), included facilitator training (n = 31/36), and were interactive (n = 28/36). Overall, 49 of 93 unique BCTs were coded to at least one target behaviour domain. The most frequently coded BCTs were: Instruction on how to perform a behaviour (n[intervention arms, separated by domain] = 102), Behavioural practice and rehearsal (n = 85), Information about health consequences (n = 85), Social support (unspecified) (n = 84), and Credible source (n = 77). Similar BCTs were often used for each target behaviour domain. Conclusions Our study provides the most comprehensive description of the behaviour change content of complex interventions targeting early childhood obesity prevention available to date. Our analysis revealed that interventions targeted multiple behaviour domains, with significant variation in delivery features. Despite the diverse range of BCTs coded, five BCTs were consistently identified across domains, though certain BCTs were more prevalent in specific domains. These findings can be used to examine effectiveness of components and inform intervention development and evaluation in future trials. Trial registration PROSPERO registration no. CRD42020177408.

As the global challenge for sustainable transportation rises, electric vehicles (EVs) have emerged as a promising solution to combat the adverse effects of conventional Internal Combustion (IC) engine vehicles on the environment. In India, the acceptance of EVs has been expanding momentum, driven by government plans, technological advancements, and raising environmental awareness. However, misconceptions persist regarding the complete ecological footprint of EVs. This paper aims to explore the prevalent misconceptions related to electric vehicles in India, focusing on two primary aspects: emissions and challenges. The study examines the lifecycle emissions, encompassing battery production, electricity generation, and disposal, to assess their environmental benefits comprehensively. Additionally, the research identifies challenges hindering EV adoption in India, including charging infrastructure, upfront costs, and range anxiety. The research draws on a combination of literature review, data analysis, and case studies to fully understand the current electric vehicle misconceptions and challenges in India. The study finds that with only 23% of India’s electricity from renewables, the rapid growth of EVs could increase emissions and up to 90% improper battery recycling and disposal further exacerbating environmental harm. By shedding light on misconceptions and challenges, this study aims to inform policymakers and stakeholders, facilitating a faster transition to cleaner and more sustainable transportation in India.

Abstract Macrophage plasticity is critical for maintaining immune function and developing solid tumors; however, the macrophage polarization mechanism remains incompletely understood. Our findings reveal that Mg2+ entry through distinct plasma membrane channels is critical to macrophage plasticity. Naïve macrophages displayed a previously unidentified Mg2+ dependent current, and TRPM7-like activity, which modulates its survival. Significantly, in M1 macrophages, Mg2+ entry is facilitated by a novel Mg²-dependent current that relies on extracellular Mg2+, which was crucial for activating iNOS/NFκB pathways and cellular bioenergetics, which drives pro-inflammatory cytokines. Conversely, in M2 macrophages, Mg2+ entry occurs primarily through TRPM7 channels, pivotal for IL-4 and IL-10-mediated anti-inflammatory cytokine secretion. Notably, the Mg2+ deficient diet or addition of TRPM7 agonist Naltriben suppresses the M1 phenotype while promoting angiogenic factors and fostering tumor growth. These findings suggest that Mg2+ flux via specific channels is indispensable for macrophage polarization, with its dysregulation playing a pivotal role in tumor progression.

Introduction: Laparoscopic transperitoneal adrenalectomy was first described by Gagner M et al. Here, we present our experience of more than two decades of laparoscopic adrenalectomy performed in a single surgical unit at a tertiary care centre. Patients and Methods: A prospectively collected database of patients undergoing laparoscopic adrenalectomy from December 1994 to May 2020 was analysed retrospectively. The demographic profile, details of clinical workup and laboratory parameters were recorded in a pre-structured pro forma. Functional workup and anatomical imaging were performed for all the patients. Patients were taken up for surgery after adequate pre-operative optimisation using a multidisciplinary approach. All the patients were operated by a single surgical team of experienced laparoscopic surgeons. Results: A total of 158 patients underwent laparoscopic transperitoneal adrenalectomy. The majority patients were females (64.5%). The median tumour size was 5 cm (range, 1–18 cm). The diagnosis in the majority of the patients was pheochromocytoma (56.3%). The mean operative time was 80 min (range: 45–210 min). The most common complication was bleeding in 6 (3.7%) patients, which required laparotomy. The median duration of post-operative hospital stay was 3 days (range: 1–13). There was no 30-day mortality. The mean follow-up period was 15 months (range: 6–72 months), during which two patients developed local recurrence. Conclusion: The advantages of laparoscopic surgery are well established and have been extensively explored for the management of adrenal lesions. A multidisciplinary approach to management, consisting of endocrinologists, surgeons and anaesthesiologists is preferred. Pre-operative evaluation, optimisation and accurate selection of patients are crucial for successful laparoscopic adrenalectomy.

Abstract Background PSEN1, PSEN2, and APP mutations cause Alzheimer’s disease (AD) with an early age at onset (AAO) and progressive cognitive decline. PSEN1 mutations are more common and generally have an earlier AAO; however, certain PSEN1 mutations cause a later AAO, similar to those observed in PSEN2 and APP. Methods We examined whether common disease endotypes exist across these mutations with a later AAO (~ 55 years) using hiPSC-derived neurons from familial Alzheimer’s disease (FAD) patients harboring mutations in PSEN1 A79V , PSEN2 N141I , and APP V717I and mechanistically characterized by integrating RNA-seq and ATAC-seq. Results We identified common disease endotypes, such as dedifferentiation, dysregulation of synaptic signaling, repression of mitochondrial function and metabolism, and inflammation. We ascertained the master transcriptional regulators associated with these endotypes, including REST, ASCL1, and ZIC family members (activation), and NRF1 (repression). Conclusions FAD mutations share common regulatory changes within endotypes with varying severity, resulting in reversion to a less-differentiated state. The regulatory mechanisms described offer potential targets for therapeutic interventions.

Recently, efforts have been done to capitalize on the potential of multidisciplinary research in order to produce unique features in polymer technology. To improve its physical and chemical properties for any intended use, the most promising Polylactic acid (PLA) has recently been copolymerized using other polymeric or non-polymeric components. This investigation aims to employ the material extrusion (MEX) process to develop a new functionally grade structural material (FGSM) by alternate layer deposition of wood flour reinforced PLA (WPLA) and ceramic reinforced PLA (CPLA). The mechanical properties of the printed laminates are examined using tensile, compression and three point bend tests. The microscopic investigation is used to assess fracture morphologies. A numerical simulation is also performed using ABAQUS under standardized parametric settings to investigate the mechanical behaviour of the laminates. The experimental and numerical results are consistent, with a deviation about ∼1 %. The tensile, compressive, and flexural strength of the newly developed FGSM are 61.39, 95.4, and 107.8 % higher than those of WPLA printed laminates. Furthermore, the acquired mechanical behaviour results are merely comparable to those of CPLA printed laminates. DSC thermograms demonstrate that FGSM has a better glass transition temperature (66°C) and a cold crystalline temperature (87.63°C), which contributes to its thermal stability. Overall, the newly developed FGSM might be considered a viable alternative, mechanically strong, and less expensive polymer composite material for structural built applications in any engineering and related fields.

Abstract Chronic stress disrupts gut microbiota homeostasis, contributing to anxiety and depression. This study explored the effects of Limosilactobacillus reuteri fermented brown rice (FBR) on anxiety using an ICR mouse chronic mild stress (CMS) model. Anxiety was assessed through body weight, corticosterone levels, neurotransmitter profiles, and behavioral tests. A four-week FBR regimen reduced corticosterone, restored neurotransmitters like gamma-aminobutyric acid (GABA) and serotonin, and improved anxiety-related behaviors. Metagenomic (16S rRNA) and metabolomic analyses revealed enhanced amino acid metabolism, energy metabolism, and short-chain fatty acid (SCFA) production in FBR-treated mice. FBR-enriched beneficial gut bacteria, aligning the microbiota profile with that of non-stressed mice. FBR also modulated GABA receptor-related gene expression, promoting relaxation. Network pharmacology identified quercetin, GABA, glutamic acid, phenylalanine, and ferulic acid as bioactive compounds with neuroprotective potential. These findings highlight FBR’s potential as a gut-brain axis-targeted therapeutic for anxiety and stress-related disorders.

Abstract Background Widespread digital transformation necessitates developing digital competencies for public health practice. Given work in 2024 to update Canada’s public health core competencies, there are opportunities to consider digital competencies. In our previous research, we identified digital competency and training recommendations within the literature. In this study, we explored public health practitioners' experiences and perspectives on adapting identified digital competencies and training recommendations for Canada. Methods Between November and December 2023, we conducted an interpretive description using four focus groups with 19 public health practitioners working in regional and federal health authorities across Canada, with at least 3 years’ experience in current roles and experience using digital technologies in practice. We explored practitioners’ experiences using digital technologies and sought their opinions on how digital competency recommendations previously identified could be adapted to Canada’s context. To generate deep insights of practitioners’ subjective experiences and perspectives, we analyzed verbatim transcripts using Braun and Clarke’s reflexive thematic analysis. Results We identified three main themes: a) public health systems must evolve to support new digital competencies; b) strengthen the basics before extending towards digital competencies; and c) focus on building general digital competencies with options for specialization where necessary. Findings emphasized matching workforce digital competencies to public health system capabilities and meaningfully integrating digital competencies within existing curricula. Such integration can consider how digital technologies change current public health practice to ensure practitioners are better able to address contemporary public health problems. Findings demonstrated roles for specialized digital programs as resources for learning within health systems and emphasized hands-on real-world training approaches. Conclusion We need integrated, systems-focused approaches to digital competencies cutting across the current public health curriculum, while creating space for specialized digital public health competencies and roles. Further research is needed to understand requirements for enacting these recommendations in practice.

Exercise training in pulmonary arterial hypertension (PAH) has been gaining popularity with guidelines now recommending it as an important adjunct to medical therapy. Despite improvements in function and quality of life, an understanding of metabolic changes and their mechanisms remain unexplored. The objective of this study was therefore to understand the metabolic basis of exercise in a monocrotaline model of PAH.24 male Wistar rats (age: 8–12 weeks and mean body weight: [262.16 ​± ​24.49] gms) were assigned to one of the four groups (i.e., Control, PAH, Exercise and PAH ​+ ​Exercise). The exercise groups participated in treadmill running at 13.3 ​m/min, five days a week for five weeks. Demographic and clinical characteristics were monitored regularly. Following the intervention, LC-MS based metabolomics were performed on blood samples from all groups at the end of five weeks. Metabolite profiling, peak identification, alignment and isotope annotation were also performed. Statistical inference was carried out using dimensionality reducing techniques and analysis of variance.Partial-least-squares discrimination analysis and variable importance in the projection scores showed that the model was reliable, and not over lifting. The analysis demonstrated significant perturbations to lipid and amino acid metabolism, arginine and homocysteine pathways, sphingolipid (p ​

Introduction: Conventionally, the raw wound after gingival excision is protected with non eugenol periodontal pack, in order to alleviate pain and preserve healing tissue which includes some potential disadvantages such as patient intolerance, pack loosening, speech difficulties and plaque accumulation. Aim: To clinically evaluate wound healing following the use of a resorbable periodontal dressing following gingival excisional procedures and to compare the outcomes with the conventional COE-PAKTM periodontal dressing. Materials and Methods: A randomised controlled trial was conducted in the Department of Periodontology, SRM Dental College, Chennai, Tamil Nadu, India from June 2022 to March 2023. Patients requiring gingival excision for gingival pigmentation, gummy smile correction and crown lengthening were included in this study, 36 patients in control group were treated with Laser assisted surgery followed by conventional COE-PAKTM and 36 patients in test group were treated with Laser assisted surgery protected with resorbable pack (RESO-PAC®). Wound healing scores (Landry’s scale) and patient comfort assessment {Visual Analogue Score (VAS)} was recorded at 7, 14 days following therapy. Data were analysed with IBM Statistical Packages for Social Sciences (SPSS) software 17.0 version using Independent t-test with level of significance 5%. Results: A total of 72 patients (38 males and 34 females) with a mean age range of 32.6 years were randomised into two study groups. Following the intervention, two participants in the test group and one subject in the control group could not report for the seven day follow-up and hence, the data of 69 participants, control (n=35) and test (n= 34) was used for final analysis. Both test and control groups showed satisfactory healing. Results in the test group were significantly better with respect to both wound healing and VAS assessment. Statistically significant difference was noted in the Wound Healing Index (WHI), VAS and Pain Intensity (PI) scores at the 7th and 14th day follow-ups (p

Abstract About one-third of individuals with diabetes develop diabetic retinopathy (DR), with one-tenth experiencing vision-threatening conditions such as diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR). Current treatments only show recovery in 50% of cases, and the disease often remains asymptomatic. Therefore, novel early detection methods and new biomarkers are crucial. Our study aims to summarise evidence on the role of altered exosomal regulatory noncoding RNAs in DR, based on human studies. Observational studies delineating the different exosomal noncoding RNAs in DR were searched systematically from inception to June 2024 in PubMed-MEDLINE and SCOPUS databases. Preferred Reporting Items of Systematic Reviews and Meta-analysis (PRISMA) 2020 guidelines was used to conduct this systematic review (Prospero ID: CRD42023406724). We synthesised data from 13 human studies that assessed the expression of exosomal regulatory ncRNAs from individuals with DR. Among the 13 studies, nine focused on miRNA, while three examined lncRNA and one on circRNA. Although no common genes were identified across the studies, the review underscores the critical roles of exosomal noncoding RNAs in the pathogenesis of diabetic retinopathy, highlighting their potential as therapeutic targets. Future studies should aim for a unified approach in terms of sample selection, RNA analysis, and appropriate controls for a comprehension of exosomal expression patterns for early diagnosis of DR.

Abstract This paper demonstrates the merits of nested Compressive Sensing (CS) approach for Electrocardiogram (ECG) signals using discrete wavelet transform (DWT) and discrete cosine transform (DCT) as sensing matrix and sparsifying matrix. The implementation of CS framework is done using Gradient Projection for Sparse Reconstruction (GPSR). It is tested on 9 ECG signals of different arrhythmia categories obtained from MITBIH and BIDMC dataset. It is analysed for 3 different combinations, case (1) DCT sensing and DWT sparsification, case (2) DWT sensing and DCT sparsification and case (3) DWT sensing and DWT sparsification. A novel hybrid nested CS approach is proposed as case (4) which is a combination of case (2) in higher level and case (1) in lower level. This nested method yields the best PRD of 1.39 for CR = 0.2 and performs better than all proposed cases. This proposed approach involves a fair method of discarding the measurements in all frequency band and performs better than the state of the art work when the sampling rate is reduced by 4 times for ECG signal 100.dat from MIT-BIH (Massachusetts Institute of Technology-Beth Israel Hospital) database for CR = 0.2. It is shown that the reconstruction time of the proposed nested CS approach is lesser than non-nested CS approach.

Abstract In recent years, renewable energy attracts the researchers interest due to its environment free nature and abundant availability. Solar photovoltaic (PV) is widely used to generation power from the sun light. Major issue in solar PV power generation is tracking of the peak power from the available multiple power peaks in the operating points. A proper MPPT algorithm is required to capture the maximum power point (MPP) from the characteristic curves of a solar PV under partial shaded conditions (PSC). An optimized maximum power point tracking (MPPT) and fault classification in solar PV systems are presented in this research work. To select the best optimization model for MPPT under PSC, the nature-inspired dragonfly algorithm (DA), moth flame optimization algorithm (MFOA), grasshopper optimization algorithm (GOA), and salp swarm optimization algorithm (SSOA) are used in this work to evaluate the tracking efficiency (TE) of the solar PV systems. From the simulation results, SSOA exhibits a supreme TE of 98.38%, which is better than the other algorithms like DA, GOA, and MFOA. To further classify the faults in solar PV systems, random forest (RF), artificial neural network (ANN), support vector machine (SVM), and convolutional neural network (CNN) models are employed. Among all, CNN provides a maximum accuracy of 94.11% in fault classification. Simulation analysis demonstrates the proof-of-concept for maximum TE and classification accuracy for all the methods. Thus, the optimized MPPT and fault classification models can be combined to enhance the overall performance of solar PV systems.

Abstract Background Thyroid dysfunction in pregnancy can adversely impact maternal and fetal outcomes. However, the association between thyroid status and specific adverse outcomes needs clarity, especially in understudied regions. Objective This prospective cohort study aimed to illuminate the multifaceted associations between maternal thyroid dysfunction and feto-maternal outcomes in Gujarat, India. Methods This hospital-based cohort study recruited and monitored 500 euthyroid, 250 hypothyroid, and 150 hyperthyroid pregnant women until delivery. Maternal thyroid status was determined by serum thyroid stimulating hormone (TSH) and free thyroxine (fT4) levels. Adverse fetal outcomes included preterm birth, neonatal intensive care unit (NICU) admission, respiratory issues, and low APGAR scores. Maternal outcomes included preeclampsia, haemorrhage, hypertension, postpartum thyroiditis, and thromboembolism. Relative risks quantified associations between thyroid dysfunction and outcomes. Results Compared to euthyroid women, hypothyroid women had a higher RR for preterm birth (RR 1.8, 95% CI 1.1–3.0), low APGAR score (RR 2.5, 95% CI 1.5–4.1), preeclampsia (RR 3.0, 95% CI 1.9–4.8), postpartum haemorrhage (RR 1.6, 95% CI 1.2–2.1), and venous thromboembolism (RR 3.1, 95% CI 1.7–5.7). Hyperthyroid women had over twice the risk of low APGAR score (RR 1.8, 95% CI 0.9–3.5), neonatal hypoglycemia (RR 1.5, 95% CI 0.5–4.3), respiratory distress (RR 1.4, 95% CI 0.7–2.8), and postpartum thyroiditis (RR 2.3, 95% CI 1.1–4.8). Conclusion Maternal thyroid dysfunction escalates risks for adverse fetal and maternal outcomes. Thyroid monitoring and management during pregnancy are critical to mitigate complications.

Abstract The Internet of Things (IoT) detects context through sensors capturing data from dynamic physical environments, in order to inform automation decisions within cyber physical systems (CPS). Diverse types of uncertainty in the IoT pipeline can propagate within and across nodes, involving complex interactions with security, privacy, and trust that remain largely unexplored. This paper conducts an in-depth analysis of the types of uncertainties in IoT and how they propagate within IoT nodes and networks. We consider adversarial uncertainty in the context of distributed IoT networks to capture perturbations due to malicious actors in the network that can influence IoT security, privacy and trust. We examine the propagation of adversarial uncertainty and well-known uncertainty types, namely aleatoric and epistemic uncertainty, within the five distinct stages of sensing, communication, storage, processing and decision-making in an IoT pipeline, across network layer boundaries, and across nodes within an IoT network. Using this mapping, we analyse the interactions between the uncertainty types and their propagation, and security, privacy, and trust in IoT. Based on this analysis, we discuss guidelines and considerations for mitigating uncertainty in IoT through a smart grid use case study.

Double perovskite materials have emerged as key players in the realm of advanced materials due to their unique structural and functional properties. This research mainly focuses on the synthesis and comprehensive characterization of Ba2CoWO6 double perovskite nanopowders utilizing a high-temperature conventional solid-state reaction technique. The successful formation of Ba2CoWO6 powders was confirmed through detailed analysis employing advanced characterization techniques. Rietveld refinement of X-ray diffraction (XRD) and Raman data established that Ba2CoWO6 crystallizes in a cubic crystal structure with the space group Fm-3m, indicative of a highly ordered perovskite lattice. The typical crystallite size, approximately 65 nm, highlights the nanocrystalline nature of the material. Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) discovered a distinctive morphology characterized by spherical shaped particles, suggesting a complex particle formation process influenced by synthesis conditions. To probe the electronic structure, X-ray Photoelectron Spectroscopy (XPS) identified cobalt and tungsten valence states, critical for understanding dielectric properties associated with localized charge carriers. The semiconducting character of the synthesized Ba2CoWO6 nanocrystalline material was confirmed through UV-Visible analysis, which revealed an energy bandgap value of 3.3 eV, which aligns well with the theoretical predictions, indicating the accuracy and reliability of the experimental results. The photoluminescence spectrum exhibited two distinct emissions in the blue-green region. These emissions were attributed to the transitions 3P0→3H4, 3P0→3H5, and 3P0→3H6, primarily resulting from the contributions of Ba2+ ions. The dielectric characteristics of the compound were analyzed across a different range of frequencies, spanning from 1 kHz to 1 MHz. Magnetic characterization using Vibrating Sample Magnetometry (VSM) revealed antiferromagnetic behavior of Ba2CoWO6 ceramics at room temperature, attributed to super-exchange interactions between Co3+ and W5+ ions mediated by oxygen ions in the perovskite lattice. Additionally, first-principles calculations based on the Generalized Gradient Approximation (GGA+U) with a modified Becke–Johnson (mBJ) potential were employed to gain a deeper understanding of the structural and electronic properties of the materials. This approach involved systematically varying the Hubbard U parameter to optimize the description of electron correlation effects. These results deliver an extensive understanding of the structural, optical, morphological, electronic, and magnetic properties of Ba2CoWO6 ceramics, underscoring their potential for electronic and magnetic device applications.

Abstract Pre-harvest sprouting (PHS) in groundnut leads to substantial yield losses and reduced seed quality, resulting in reduced market value of groundnuts. Breeding cultivars with 14–21 days of fresh seed dormancy (FSD) holds promise for precisely mitigating the yield and quality deterioration. In view of this, six multi-locus genome-wide association study (ML-GWAS) models alongside a single-locus GWAS (SL-GWAS) model were employed on a groundnut mini-core collection using multi season phenotyping and 58 K “Axiom_Arachis” array genotyping data. A total of 9 significant SNP-trait associations (STAs) for FSD were detected on A01, A04, A08, A09, B02, B04, B05, B07 and B09 chromosomes using six ML-GWAS models. Additionally, the SL-GWAS model identified 38 STAs across 14 chromosomes of groundnut. A single STA on chromosome B02 (qFSD-B02-1) was consistently identified in both ML-GWAS and SL-GWAS models. Furthermore, candidate gene mining identified nine high confidence genes viz., Cytochrome P450 705 A, Dormancy/auxin associated family protein, WRKY family transcription factor, Protein kinase superfamily protein, serine/threonine protein phosphatase, myb transcription factor, transcriptional regulator STERILE APETALA-like, ethylene-responsive transcription factor 7-like and F-box protein interaction domain protein as prime regulators involved in Abscisic acid/Gibberellic acid signaling pathways regulating dormancy/germination. In addition, three of the allele-specific markers developed from the identified STAs were validated across a diverse panel. These markers hold potential for increasing dormancy in groundnut through marker-assisted selection (MAS). Thus, this research offers insights into genetic and molecular mechanisms underlying groundnut seed dormancy in addition to providing markers and donors for breeding future varieties with 2–3 weeks of FSD.

Abstract Background Tuberculosis (TB) remains a global health challenge, with 1.3 million deaths in 2022. Ten countries in the European Union (EU) and European Economic Area (EEA) accounted for 88.3% of TB cases, of which 23.8% were from Romania. Evidence shows that mental health issues, decreased quality of life and negative socio-economic impact are common among TB patients; however, there is limited evidence available in Romania. The main aim of this study is to longitudinally assess the quality of life, mental health, and socio-economic status of patients with drug-resistant TB (DR TB) in Romania. Methods A prospective cohort study was conducted at the Marius Nasta Institute of Pneumology in Bucharest, Romania, enrolling 50 participants with DR TB. Demographic data, clinical examinations, laboratory test and medical history were recorded at study start. At baseline (week two), month 10, and month 20 we also administered the Short-Form-36 and Kessler Psychological Distress Scale to assess health-related quality of life and mental health status, and socio-economic questionnaires to 46 participants. Results Of the 46 participants with median age of 48.9 years, 71.7% were males. Majority of the participants were employed at the baseline but due to the rigorous treatment and hospitalization had to take sick leave, thereby affecting the individual and household income. 26.1% and 39.3% of participants reported psychological distress at baseline and at the end of month 20, respectively. The quality-of-life scores improved during treatment: PCS with a mean of 67.0 (SD-33.9) at baseline, 63.3 (SD-31.9) at month 10 and 70.3 (SD-30.3) at month 20, and MCS with 62.8 (SD-30.6), 67.8 (SD-29) and 70.8 (SD-27.3), accordingly, but differences were not significant. Conclusions We examined the socio-economic impact, quality of life, and psychological distress among patients affected by DR TB in Romania. The results of this study suggest that social and psychological support will ensure a better standard of living during and following TB treatment.

Abstract Semliki Forest virus (SFV) is a neuropathogenic alphavirus which is of interest both as a model neurotropic alphavirus and as an oncolytic virus with proven potency in preclinical cancer models. In laboratory mice, peripherally administered SFV infiltrates the central nervous system (CNS) and causes encephalitis of varying severity. The route of SFV CNS entrance is poorly understood but has been considered to occur through the blood-brain barrier. Here we show that neuroinvasion of intravenously administered SFV is strictly dependent on very-low-density-lipoprotein receptor (VLDLR) which acts as an entry receptor for SFV. Moreover, SFV primarily enters the CNS through the blood-cerebrospinal fluid (B-CSF) barrier via infecting choroid plexus epithelial cells which show distinctly high expression of VLDLR. This is the first indication of neurotropic alphavirus utilizing choroid plexus for CNS entry, and VLDLR playing a specific and crucial role for mediating SFV entry through this pathway.

Background: Cognitive impairments in individuals with psychotic disorders impact day-to-day activities and social and occupational functioning (Bowie CR, 2006). Most of the cognitive interventions were developed in the west focusing mainly on clinical research and were not available in routine care. Adaptability and accessibility of these techniques in low-resource settings like India had major challenges. Keeping this in mind, Compensatory Cognitive Training (CCT), being an economical and noncomputerized intervention, was adapted to be used for an urban English-speaking population in India. Aim: The study aimed to determine the acceptability and feasibility of delivering CCT to persons with schizophrenia through virtual one-on-one sessions. Materials and Methods: Patients with a diagnosis of schizophrenia were assessed for their subjective and objective cognitive deficits. CCT was delivered for 13 participants as a virtual one – one session. Three participants dropped out midway. Semistructured interview was conducted with all ten participants who completed the intervention to understand their acceptability of Virtual CCT. Feasibility was assessed using a visual analog scale on their attendance, involvement, and comprehending ability. The mean percentile scores on cognitive domains at baseline and end of intervention were analyzed. Results: Significant change was observed in specific domains of cognition. Participant involvement, lesser dropout rates, and their feedback indicated that Virtual CCT is a feasible and acceptable intervention. Conclusion: Virtually delivered CCT appears to be an acceptable and feasible intervention to increase access to cognitive interventions for persons with schizophrenia in LAMI countries. This needs to be tested in larger populations.

Purpose: Organ motion can significantly affect the accurate delivery of radiation doses to the tumor, particularly for sites such as the breast, lung, abdomen, and pelvis. Managing this motion during treatment is crucial. One strategy employed to manage motion induced from respiration is breath-hold (BH), which enhances the geometric precision of dose delivery. Our institute is transitioning to using the ExacTrac Dynamic system to facilitate patient BH using surface-guided cameras. Only 20% of our linacs are equipped with surface guidance capabilities, and due to a high patient stereotactic throughput, the ability to perform in-bunker coaching for BH patients within the bunker is limited. To address this challenge, a time-of-flight camera (ToF) was developed to coach radiotherapy patients undergoing BH procedures, allowing them to gain confidence in the process outside of the bunker and before treatment. Methods: The camera underwent testing for absolute and relative accuracy, responsiveness under various environmental conditions, and comparison with the Elekta Active Breathing Coordinator (ABC) to establish correlation and testing on volunteers independently to assess usability. Results: The results showed that the absolute distance measured by the camera was nonlinear due to square light modulation, which was retrospectively corrected. Relative accuracy was tested with a QUASAR motion phantom, with results agreeing to within ± 2 mm. The camera response was found to be unaffected by changes in lighting or temperature, though it overresponded under extreme temperatures. The comparison with the Elekta ABC system yielded comparable results between lung volume and changes in surface distance during BH. All volunteers successfully followed instructions and maintained BH within ± 1 mm tolerance. Conclusions: This study demonstrates the feasibility of using a cost-effective ToF camera to coach patients before imaging/treatment, saving valuable LINAC linac and imaging system time.

Abstract Background Metabolic-associated fatty liver disease (MAFLD) is a major public health problem worldwide. This study aimed to determine the prevalence of MAFLD and evaluate the diagnostic accuracy of the Fatty Liver Index (FLI) compared to ultrasonography for detecting fatty liver in adults attending a tertiary care hospital in Gujarat, India. Methods This cross-sectional study included 500 adults visiting the outpatient department between January 2023 and December 2023. MAFLD was diagnosed on ultrasound. FLI was calculated using body mass index, waist circumference, triglycerides, and gamma-glutamyl transpeptidase levels. FLI ≥ 60 indicated fatty liver. Logistic regression analysis identified factors associated with fatty liver. Results MAFLD prevalence was 32.2% on ultrasound. High FLI (≥ 60) was present in 26.2%. Male sex, higher BMI, waist circumference, night shift work, diabetes, and triglycerides were independent predictors of fatty liver. FLI showed excellent diagnostic accuracy with a sensitivity of 96%, specificity of 92.5%, and AUC of 0.92 for detecting fatty liver on ultrasound. Conclusion MAFLD prevalence among adults was high in this hospital-based sample. FLI can serve as an accurate non-invasive tool for identifying individuals with a high probability of MAFLD. These findings emphasize the need for larger population-based studies and the implementation of regular MAFLD screening programs in high-risk groups.

Microvascular complications of diabetic retinopathy (DR) may require surgical intervention in the form of vitrectomy. Since its inception, diabetic vitrectomy has evolved with introduction of better instruments, newer techniques, and smaller port sizes. Common indications for diabetic vitrectomy include nonresolving vitreous hemorrhage, tractional retinal detachment, epiretinal membrane, progression of fibrovascular membranes despite laser therapy, recalcitrant diabetic macular edema, and neovascular glaucoma. Preoperative systemic stabilization is essential prior to planning surgery. Surgical techniques commonly used in diabetic vitrectomy are segmentation, delamination, and rarely en-bloc dissection. Modification in surgical techniques such as chandelier-assisted bimanual dissection and pharmacological adjuvants improve surgical outcomes in these patients. Prognosis in these patients could be improved with early intervention. Studies evaluating the outcome of vitrectomy in patients with early proliferative DR are required to understand the appropriate time of intervention in patients. Treatment aimed at arresting the progression of DR and gene therapy are avenues that need further evaluation. The following review will focus on covering the epidemiology of DR, indications of vitrectomy, preoperative considerations, surgical procedures of diabetic vitrectomy, methods of membrane dissection, pharmacological adjuvants to vitrectomy, outcomes of diabetic vitrectomy, and future directions of diabetic vitrectomy.

Abstract Adoptive T-cell immunotherapy holds great promise for the treatment of viral complications in immunocompromised patients resistant to standard anti-viral strategies. We present a retrospective analysis of 78 patients from 19 hospitals across Australia and New Zealand, treated over the last 15 years with “off-the-shelf” allogeneic T cells directed to a combination of Epstein–Barr virus (EBV), cytomegalovirus (CMV), BK polyomavirus (BKV), John Cunningham virus (JCV) and/or adenovirus (AdV) under the Australian Therapeutic Goods Administration’s Special Access Scheme. Most patients had severe post-transplant viral complications, including drug-resistant end-organ CMV disease, BKV-associated haemorrhagic cystitis and EBV-driven post-transplant lymphoproliferative disorder. Adoptive immunotherapy is well tolerated with few adverse effects. Importantly, 46/71 (65%) patients show definitive clinical improvement including reduction in viral load, clinical symptoms and complete resolution of end-organ disease. In addition, seven high-risk patients remain disease free. Based on this long-term encouraging clinical experience, we propose that a dedicated nationally funded centre for anti-viral cellular therapies should be considered to provide T cell therapies for critically ill patients for compassionate use.

Fabrication of haemostatic materials with excellent antimicrobial, biocompatible and biodegradable properties remains as a major challenge in the field of medicine. Haemostatic agents play vital role in protecting patients and military individuals during emergency situations. Natural polymers serve as promising materials for fabricating haemostatic compounds due to their efficacy in promoting hemostasis and wound healing. In the present work, sodium alginate/aloe vera/sericin (SA/AV/S) scaffold has been fabricated using a simple cost-effective casting method. The prepared SA/AV/S scaffolds were characterised for their physicochemical properties such as scanning electron microscope, UV–visible spectroscopy and Fourier transform infra-red spectroscopy. SA/AV/S scaffold showed good mechanical strength, swelling behaviour and antibacterial activity. In vitro experiments using erythrocytes proved the hemocompatible and biocompatible features of SA/AV/S scaffold. In vitro blood clotting assay performed using human blood demonstrated the haemostatic and blood absorption properties of SA/AV/S scaffold. Scratch wound assay was performed to study the wound healing efficacy of prepared scaffolds. Chick embryo chorioallantoic membrane assay carried out using fertilised embryos proved the angiogenic property of SA/AV/S scaffold. Thus, SA/AV/S scaffold could serve as a potential haemostatic healthcare product due to its outstanding haemostatic, antimicrobial, hemocompatible, biocompatible and angiogenic properties.

Systemic lupus erythematosus (SLE) is the prototype of an autoimmune disease with various manifestations in the skin and several other organs. Subacute cutaneous lupus erythematosus may present with annular and psoriasiform lesions. There have been case reports of pustular lesions in SLE. Herein, we describe a known case of SLE, who developed pustular and crusted lesions which complicated the course of the disease. We considered Acute Generalised Exanthematous Pustulosis, Subcorneal Pustular Dermatosis, Pustular Psoriasis, Pustular Vasculitis, and Pustular Folliculitis as our initial differential diagnosis. A potassium hydroxide mount from crusted lesions showed scabies mites. With these findings, a diagnosis of SLE complicated with crusted scabies was made. She was managed with multiple systemic immunosuppressant and antiscabetic measures following which clinical improvement was seen with remission of her lesions.

Introduction: Childhood obesity is associated with chronic low-grade systemic inflammation, which results in obesity-related comorbidities. This study compared the inflammatory markers between obese and normal children and assessed obesity-related comorbidities. Methods: In this cross-sectional analytical study, 40 obese children between 5-18 years of age were recruited as cases, and an equal number of age and gender-matched normal children as the control. The inflammatory markers-high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), and adiponectin were compared between the groups. Hypothyroidism, dyslipidemia, insulin resistance, hypertension, and nonalcoholic fatty liver disease (NAFLD) were screened among obese children. Results: We observed a male-female ratio of 1.5:1 in each group. The median hs-CRP between obese and normal children were 2.53 mg/L (0.94,6.85) and 0.77 mg/L (0.19,7.19), and the median IL-6 levels were 3.56 pg/ml (2.17,5.48) and 3.76 pg/ml (1.08,7.91) respectively. The median IL-10 levels between obese and control groups were 2.06 pg/ml (0.35,6.3) and 1.82 pg/ml (0.41,6.5), and the median adiponectin levels between the groups were 8.6 mcg/ml (6.65,16.04) and 9.79 mcg/ml (8.45,11.91) respectively. We didn’t observe significant differences in the markers between the groups. Dyslipidemia, insulin resistance, and metabolic syndrome were seen in 80%, 52.5%, and 45% of obese children, respectively. Other comorbidities-NAFLD, hypertension, and hypothyroidism, were observed in 27.5%, 25%, and 7.5% of obese children, respectively. IL-6 had a significant positive correlation with total cholesterol (r = 0.40), LDL levels (r = 0.50), and HDL (r = 0.32). Conclusion: There was no difference in inflammatory markers between obese and normal children. Dyslipidemia and insulin resistance were the most common comorbidities.

Abstract Background Internship is a phase of training wherein medical graduates acquire the skills and competencies required to function independently. It has been reported that interns lack confidence in performing common procedures, as these skills are often learnt through self-learning or performing without supervision. This type of learning endangers patient safety and fails to instil the required confidence in the student. Training in skills laboratories provide opportunity to learn clinical skills in a safe environment. However, skills laboratories are resource-intensive, and there is limited information on different training approaches, such as blended learning, and how the trainees perceive their usefulness. Hence, we conducted this pilot study to assess the perceived usefulness of a blended learning approach for skills training among medical interns. Methods This mixed methods study was conducted in the skills laboratory of an apex medical institute in India, among 42 interns posted for the Interns Skill-based Clinical Induction Program (ISCIP). In this training, a blended learning approach was adopted, which comprised of two components - an online e-learning module, followed by a hands-on training session. The trainees were asked to complete a feedback form and grade different components of the online session, and hands-on session on a five-item Likert-based scale. The scores were expressed as the mean (SD) of a maximum possible score of 5 for each of the components. In order to gain insight of the perceived usefulness of skills training among learners, focused group discussions (FGDs) were conducted. Results The mean (SD) score for perceived importance ranged from 5 (0) to 4.9 (0.2) for various skills. The proportion of interns who felt confident in performing the skill after the training was 88.1% for IV cannulation to 97.6% handwashing, and gloving and gowning. The findings of the qualitative component revealed that interns found the training to be useful and interesting. It was perceived to be more ethical, uniform, well-structured, and provided an opportunity to practice a skill repeatedly. Conclusions The blended learning approach was perceived to be useful among the medical interns. Further research may be conducted in other medical institutes to assess the effectiveness of skills training. Clinical trial registration number Not applicable, as the study is not a trial.

Although the gene MEN1 has a long-standing association with cancer, its mechanisms of action remain incompletely understood, acting both as a tumour suppressor in neuroendocrine tumours and as an oncogene in leukaemia. The best-characterised isoform of the encoded protein, MENIN, is the 610-amino acid MENIN isoform 2. We hypothesise that some of the complexity of MEN1 biology can be attributed to a currently unappreciated contribution of different MENIN isoforms. Through in silico data mining, we show alternative splicing along the entire length of MEN1. Splice junction data suggest that the transcript encoding MENIN isoform 2 is the most abundant in all tissues examined, making a strong argument for this to be the reference transcript/protein isoform of MEN1. We also report novel splicing events, including a novel exon from within intron 7 that is relatively highly expressed in many tissues. These splicing events are predicted to contribute to MENIN diversity by generating isoforms with in-frame insertions, deletions or unique amino termini that, in turn, could have altered interactions with partner proteins. Finally, we have compiled 2574 unique genomic variants reported in MEN1 within somatic and germline databases and have identified several variants that could impact individual MENIN isoforms. We have also collated studies pertinent to MENIN function in the literature and summarised the impact of MEN1 variants on 74 biological variables. We propose a set of four MEN1 variants, MENINL22R, MENINH139D, MENINA242V and MENINW436R, that represent a cohort with different biological properties, which should be investigated concurrently to better dissect MENIN function.

Abstract The study explored rural livelihood sustainability in South Asia and Africa through a bibliometric analysis and systematic review approach. The purpose of the study was to identify the trend of scholarly discourse, the dominant themes that have attracted scholarly interest over the past decade, and to shed light on the emerging opportunities for enhancing rural livelihood sustainability. The study carefully selected 139 articles sourced from Scopus, Web of Science, Google Scholar, and other institutional websites. Our findings revealed noticeable growth in scholarly output over the past decade and identified some scholars with noteworthy contributions. Notably, it was found that the impact of climate change, drought, poverty, and food security on rural livelihoods has largely dominated the scholarly investigations over the period. However, the potentials of pyrolis, biochar, and dryland forestry for rural livelihood sustainability were found to be underexplored. In light of these insights, we recommend the scholarly community develop much interest in less explored areas that equally hold great potential for enhancing rural livelihoods. We also recommend that rural livelihood programming by policymakers must seek the integration of indigenous knowledge and be tailored to strengthen the resilience of rural households against the perils of climate change and weather variability.

Background: Coronary artery disease (CAD) prevalence in young individuals is rising, particularly in South Asian populations. Carotid artery hemodynamic parameters and their relation with CAD have not been studied much in young patients. Aims and Objectives: The aim of the study was to study the relationship between Carotid artery hemodynamic parameters, and CAD severity in young patients. Materials and Methods: A cross-sectional and single-center study was conducted involving consecutive patients undergoing coronary angiography due to acute coronary syndrome and aged under 40. Carotid ultrasonography and Doppler were performed to assess Carotid artery hemodynamic parameters. Gensini and SYNTAX scores were used to evaluate the severity and complexity of CAD. A total of 136 patients were included in the study. Results: The mean age was 36.24±4.030 years, with 92 males. CAD patients demonstrated significantly increased carotid intima-media thickness (CIMT) (0.730±0.157 vs. 0.488±0.09; P

Abstract Amphibians represent a diverse group of tetrapods, marked by deep divergence times between their three systematic orders and families. Studying amphibian biology through the genomics lens increases our understanding of the features of this animal class and that of other terrestrial vertebrates. The need for amphibian genomic resources is more urgent than ever due to the increasing threats to this group. Amphibians are one of the most imperiled taxonomic groups, with approximately 41% of species threatened with extinction due to habitat loss, changes in land use patterns, disease, climate change, and their synergistic effects. Amphibian genomic resources have provided a better understanding of ontogenetic diversity, tissue regeneration, diverse life history and reproductive modes, anti-predator strategies, and resilience and adaptive responses. They also serve as essential models for studying broad genomic traits, such as evolutionary genome expansions and contractions, as they exhibit the widest range of genome sizes among all animal taxa and possess multiple mechanisms of genetic sex determination. Despite these features, genome sequencing of amphibians has significantly lagged behind that of other vertebrates, primarily due to the challenges of assembling their large, repeat-rich genomes and the relative lack of societal support. The emergence of long-read sequencing technologies, combined with advanced molecular and computational techniques that improve scaffolding and reduce computational workloads, is now making it possible to address some of these challenges. To promote and accelerate the production and use of amphibian genomics research through international coordination and collaboration, we launched the Amphibian Genomics Consortium (AGC, https://mvs.unimelb.edu.au/amphibian-genomics-consortium ) in early 2023. This burgeoning community already has more than 282 members from 41 countries. The AGC aims to leverage the diverse capabilities of its members to advance genomic resources for amphibians and bridge the implementation gap between biologists, bioinformaticians, and conservation practitioners. Here we evaluate the state of the field of amphibian genomics, highlight previous studies, present challenges to overcome, and call on the research and conservation communities to unite as part of the AGC to enable amphibian genomics research to “leap” to the next level.

Abstract Background Cognitive deficits are the core component in persons with schizophrenia which impacts their socio-occupational functioning. Also, cognitive deficits cause significant impairment with the person’s quality of life [3]. Hence, targeting such a pivotal aspect in persons with schizophrenia through suitable interventions is very important. Developed countries have designed various cognitive remediation programs using computers involving high-end software which cannot be generalized to low-resource settings, like India, due to various factors including sociocultural factors, educational standards, and living standards of the patient population. Compensatory cognitive training (CCT) was developed to be “brief, practical, low-tech” and found to be effective in the west [9]. As there are no structured cognitive intervention modules in India, we have adapted the English CCT manual to be used for an urban population in Chennai, India. CCT was found to be feasible in face-to-face group sessions in our setting [12] and is found to be feasible and acceptable as virtual one–one intervention (unpublished data). Therefore, this study aims to evaluate the effectiveness of V-CCT in enhancing cognition and socio-occupational functioning. Methods The proposed study will be a multicenter assessor-blinded randomized controlled trial at two clinical sites in Chennai, India. The preparatory phase of the study would include translation of the manual to the local language, recruitment and training of research assistants, and pilot testing using the translated manual. The second phase will be the main randomized controlled trial (RCT), during which a total of 160 persons diagnosed with schizophrenia will be recruited from both sites. After obtaining informed consent, baseline assessments will be conducted on cognition, functioning, self-esteem, and quality of life. Participants will be randomly assigned to either the virtual CCT group or the control group using a computer-generated randomization table. End-line assessments will be conducted 6 weeks after the baseline by research assistants who are blinded to the randomization post-intervention. Discussion If V-CCT is found to be effective, it will be available for use in Tamil for persons with schizophrenia, and it will have an effect on their functioning, quality of life, and self-esteem. Trial registration The study is registered under Clinical trial registry-India (CTRI), and the registration number is CTRI/2024/04/065267. Registered on April 2024.

Introduction: Matrix Metalloproteinase 3 (MMP3) is a vital member of the MMP family, known for its wide range of substrate specificity and proteolytic activity against Extracellular Matrix (ECM) components. The role of functional polymorphisms in the MMP genes has been previously investigated in relation to cancer susceptibility, particularly breast cancer. Several Single-Nucleotide Polymorphisms (SNPs) in the MMP3 gene have been linked to a number of clinical illnesses, such as Coronary Artery Disease (CAD); however, the results were not entirely conclusive. Aim: To identify pathogenic missense SNPs in the human MMP3 gene and analyse their effects on structure and function. Materials and Methods: This was a record-based cross-sectional study performed using data retrieved from online resources. The analysis was conducted using a series of different bioinformatic tools, for which ethical clearance was obtained from the institution. The online tools used included Sorting Intolerant from Tolerant (SIFT), PolyPhen-2, PhD-SNP, PANTHER, PROVEAN, and SNPs and GO to predict harmful non synonymous SNPs (nsSNPs). Further analysis was performed using I-Mutant 2.0, MutPred2, Consurf, and HOPE software. These tools were able to filter out damaging SNPs and predict the impact of deleterious SNPs on the structure and function of the MMP3 protein. Results: This study predicted two potentially pathogenic SNPs (D175Y and Y116C) out of 443 missense SNPs from dbSNP, which is a database of SNPs available on the National Centre for Biotechnology Information website. Further analysis revealed that these SNPs were located in highly conserved regions and were predicted to decrease protein stability. Conclusion: In this study, two potentially pathogenic SNPs (D175Y and Y116C) were identified. Characterisation of these SNPs can help us gain a better understanding of the molecular basis of clinical conditions. The results of this study can be further validated by designing population-based studies and wet lab experiments. This will help in augmenting research and personalised medicine.

Introduction: Eating disorders (EDs) are debilitating mental illnesses that can lead to significant medical complications from malnutrition. Eating disorders are on the rise in Asia and the prevalence is expected to increase. The aim of this study was to understand the characteristics of local patients and evaluate our current inpatient nutritional rehabilitation protocol for anorexia nervosa (AN). Methods: Retrospective descriptive data were gathered from 47 patients diagnosed with AN. Patients with admissions were further stratified according to their nutritional management based on whether they were on the AN protocol or standard hospital care. Data on their rate of weight gain, length of stay and calorie prescription were collected. Results: Similar to previous studies, the majority of AN patients were female (96.7%). However, the age at presentation of AN in this study, as compared with previous local studies, had decreased (14 vs. 16 years). We also found that patients on the AN protocol were prescribed a higher amount of calories than those given standard care (2,700 vs. 2,317 calories). Patients on the AN protocol achieved a higher rate of weight gain per week (1.15 vs. 0.29 kg) and had a shorter length of hospital stay (23 vs. 36 days). Conclusion: Patients with AN appear to be presenting at a younger age. Medical stabilisation of AN patients can be achieved more quickly through a higher calorie inpatient AN treatment protocol. Future local studies examining actual calorie consumption, its effect on weight gain trajectory, severity of refeeding syndrome and time to remission will be beneficial.

Abstract Aims New tools are needed to identify heart failure (HF) risk earlier in its course. We evaluated the association of multidimensional cardiopulmonary exercise testing (CPET) phenotypes with subclinical risk markers and predicted long‐term HF risk in a large community‐based cohort. Methods and results We studied 2532 Framingham Heart Study participants [age 53 ± 9 years, 52% women, body mass index (BMI) 28.0 ± 5.3 kg/m2, peak oxygen uptake (VO2) 21.1 ± 5.9 kg/m2 in women, 26.4 ± 6.7 kg/m2 in men] who underwent maximum effort CPET and were not taking atrioventricular nodal blocking agents. Higher peak VO2 was associated with a lower estimated HF risk score (Spearman correlation r: −0.60 in men and −0.55 in women, P

Purpose: While testosterone therapy can improve the various pathologies associated with adult-onset testosterone deficiency (TD), Summary of Product Characteristics (SPC) of five testosterone preparations caution that treatment may be associated with hypertension. This paper evaluates the impact of testosterone undecanoate (TU) on blood pressure (BP) in men with adult-onset TD. Materials and Methods: Of 737 men with adult-onset TD in an on-going, observational, prospective, cumulative registry, we studied changes in BP using non-parametric sign-rank tests at final assessment and fixed time points. We used multiple regression analysis to establish factors (baseline BP, age, change/baseline waist circumference [WC] and hematocrit [HCT] and follow-up) potentially associated with BP change in men on TU. Results: TU was associated with significant reductions in systolic, diastolic BP and pulse pressure, regardless of antihypertensive therapy (at baseline or during follow-up), larger reductions were seen with concurrent antihypertensive therapy. In men never on antihypertensive agents, median changes (interquartile range [IQR]) in systolic BP, diastolic BP and pulse pressure were -12.5 (-19.0, -8.0), -8.0 (-14.0, -3.0), and -6.0 (-10.0, -1.0) mmHg, respectively at final assessment, with only baseline BP values inversely associated with these changes (HCT and WC were not significantly associated). In men not on TU, systolic BP, diastolic BP, and pulse pressure significantly increased. In the TU treated men only 1 of the 152 men (not on antihypertensive agents at baseline) were started on antihypertensives during follow-up. In contrast 33 of the 202 men on antihypertensives (at baseline or follow-up) had the antihypertensive agent discontinued by the end of the follow-up. Conclusions: TU was associated with lowering of BP during follow-up irrespective of antihypertensive therapy, with greater reductions in men with higher baseline BP. In the context of SPC warnings, our long-term data provide reassurance on the effect of TU on BP.

The adverse effects of traditional pharmaceutical immunosuppressive regimens have been a major obstacle to successful allograft survival in vascularized composite tissue allotransplantation (VCA) cases. Consequently, there is a pressing need to explore alternative approaches to reduce reliance on conventional immunotherapy. Cell therapy, encompassing immune-cell-based and stem-cell-based regimens, has emerged as a promising avenue of research. Immune cells can be categorized into two main systems: innate immunity and adaptive immunity. Innate immunity comprises tolerogenic dendritic cells, regulatory macrophages, and invariant natural killer T cells, while adaptive immunity includes T regulatory cells and B regulatory cells. Investigations are currently underway to assess the potential of these immune cell populations in inducing immune tolerance. Furthermore, mixed chimerism therapy, involving the transplantation of hematopoietic stem and progenitor cells and mesenchymal stem cells (MSC), shows promise in promoting allograft tolerance. Additionally, extracellular vesicles (EVs) derived from MSCs offer a novel avenue for extending allograft survival. This review provides a comprehensive summary of cutting-edge research on immune cell therapies, mixed chimerism therapies, and MSCs-derived EVs in the context of VCAs. Findings from preclinical and clinical studies demonstrate the tremendous potential of these alternative therapies in optimizing allograft survival in VCAs.

Abstract Whole genome sequences (WGS) enable discovery of rare variants which may contribute to missing heritability of coronary artery disease (CAD). To measure their contribution, we apply the GREML-LDMS-I approach to WGS of 4949 cases and 17,494 controls of European ancestry from the NHLBI TOPMed program. We estimate CAD heritability at 34.3% assuming a prevalence of 8.2%. Ultra-rare (minor allele frequency ≤ 0.1%) variants with low linkage disequilibrium (LD) score contribute ~50% of the heritability. We also investigate CAD heritability enrichment using a diverse set of functional annotations: i) constraint; ii) predicted protein-altering impact; iii) cis-regulatory elements from a cell-specific chromatin atlas of the human coronary; and iv) annotation principal components representing a wide range of functional processes. We observe marked enrichment of CAD heritability for most functional annotations. These results reveal the predominant role of ultra-rare variants in low LD on the heritability of CAD. Moreover, they highlight several functional processes including cell type-specific regulatory mechanisms as key drivers of CAD genetic risk.

Abstract Background This observational study aims to establish the feasibility of using x-ray images of radio-opaque chemoembolisation deposits in patients as a method for real-time image-guided radiation therapy of hepatocellular carcinoma. Methods This study will recruit 50 hepatocellular carcinoma patients who have had or will have stereotactic ablative radiation therapy and have had transarterial chemoembolisation with a radio-opaque agent. X-ray and computed tomography images of the patients will be analysed retrospectively. Additionally, a deep learning method for real-time motion tracking will be developed. We hypothesise that: (i) deep learning software can be developed that will successfully track the contrast agent mass on two thirds of cone beam computed tomography (CBCT) projection and intra-treatment images (ii), the mean and standard deviation (mm) difference in the location of the mass between ground truth and deep learning detection are ≤ 2 mm and ≤ 3 mm respectively and (iii) statistical modelling of study data will predict tracking success in 85% of trial participants. Discussion Developing a real-time tracking method will enable increased targeting accuracy, without the need for additional invasive procedures to implant fiducial markers. Trial registration Registered to ClinicalTrials.gov (NCT05169177) 12th October 2021.

Abstract The CUT and homeodomain are ubiquitous DNA binding elements often tandemly arranged in multiple transcription factor families. However, how the CUT and homeodomain work concertedly to bind DNA remains unknown. Using ONECUT2, a driver and therapeutic target of advanced prostate cancer, we show that while the CUT initiates DNA binding, the homeodomain thermodynamically stabilizes the ONECUT2-DNA complex through allosteric modulation of CUT. We identify an arginine pair in the ONECUT family homeodomain that can adapt to DNA sequence variations. Base interactions by this ONECUT family-specific arginine pair as well as the evolutionarily conserved residues are critical for optimal DNA binding and ONECUT2 transcriptional activity in a prostate cancer model. The evolutionarily conserved base interactions additionally determine the ONECUT2-DNA binding energetics. These findings provide insights into the cooperative DNA binding by CUT-homeodomain proteins.

Abstract The ubiquitin E3 ligase cereblon (CRBN) is the target of therapeutic drugs thalidomide and lenalidomide and is recruited by most targeted protein degraders (PROTACs and molecular glues) in clinical development. Biophysical and structural investigation of CRBN has been limited by current constructs that either require co-expression with the adaptor DDB1 or inadequately represent full-length protein, with high-resolution structures of degrader ternary complexes remaining rare. We present the design of CRBNmidi, a construct that readily expresses from E. coli with high yields as soluble, stable protein without DDB1. We benchmark CRBNmidi for wild-type functionality through a suite of biophysical techniques and solve high-resolution co-crystal structures of its binary and ternary complexes with degraders. We qualify CRBNmidi as an enabling tool to accelerate structure-based discovery of the next generation of CRBN based therapeutics.

Hasan Rawashdeh,1,2 Aparna Ramachandran,1 Jenny M Yang,1 Gemma Blain,1 Jon Hyett1,3 1Department of Women and Babies, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; 2Department of Obstetrics and Gynaecology, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Obstetrics and Gynaecology, Western Sydney University, Sydney, NSW, AustraliaCorrespondence: Hasan Rawashdeh, Department of Obstetrics and Gynaecology, Jordan University of Science and Technology, Irbid, Jordan, Tel +00 962 7 9828 4038, Email hmrawashdeh@just.edu.joBackground: Preterm birth (PTB) is associated with significant neonatal mortality and morbidity. Universal measurement of cervical length has been proposed as a screening tool to direct intervention to prevent PTB.Aim: To assess the impact of the introduction of sonographic mid-trimester cervical length screening on the use of cervical cerclage and PTB.Material and Methods: A retrospective cohort study reviewed two groups of women who underwent cervical cerclage before and after the introduction of universal sonographic cervical length screening. Demographics and outcomes were compared using Student’s t test, Fisher’s Exact test and Kaplan–Meier analysis.Results: Following introduction of universal cervical length screening, the overall rate of cerclage increased from 2.5/1000 births to 6.0/1000 births (p < 0.01). There was a reduction in the proportion of sutures placed purely based on maternal history (50.0% to 30.4%; p < 0.001), while the proportion of sutures placed following ultrasound assessment increased in both high- (21.7 to 36.6%) and low-risk (11.7% to 30.4%) women (p < 0.001). The overall rate of PTB < 37 weeks in women has a cerclage was 25.7% and was highest in women undergoing rescue cerclage (64.3%; p < 0.01). There was no difference in the rate of PTB between high- and low-risk women undergoing history- or ultrasound-indicated cerclage. Mean pregnancy length was most prolonged in low-risk women undergoing ultrasound-indicated cerclage, extending gestation from 33.9 to 38.3 weeks (p < 0.01).Conclusion: Universal cervical length screening results in an increase in the use of cerclage, specifically on the basis of the ultrasound findings. Women who were at low risk but then underwent ultrasound-indicated cerclage experienced most prolongation of pregnancy. Women who were at high risk but had a suture on the basis of ultrasound findings-indicated cerclage represent an alternative method of management with no significant difference in the gestational age of delivery.Keywords: cerclage, premature birth, cervical length measurement, progesterone, ultrasonography

Introduction: Retrograde intrarenal surgery (RIRS) is the standard treatment for renal calculi. Direct visualization and fragmentation are its major advantages. The variable stone clearance rates and the ergonomic challenges faced by urologists are a few limitations. Table tilt enhances stone clearance and improves surgical ergonomics by facilitating better access to stones and reducing procedural strain. Subjects and Methods: In this prospective study, patients with intrarenal calculi were randomized into standard lithotomy RIRS (S-RIRS) and table-tilted RIRS (T-RIRS) groups. Specified table tilts were suggested for each of the stone locations. The outcomes with regard to stone clearance, operative and lasing time, and ergonomics were studied. Results: About 100 patients were studied, with 50 in each group. The overall operating time and lasing time in the T-RIRS group were less than that in the S-RIRS group (P < 0.001). The complication rates were the same in both groups. Most surgeons felt that the surgical ergonomics was better in the T-RIRS group (P < 0.001). When stone-free status was analyzed, seven patients in the S-RIRS group and one in the T-RIRS group had residual stones. The mean Borg category-ratio 10 (CR-10) scores in the S-RIRS and T-RIRS groups were 4.18 and 2.20, respectively (P < 0.001). Conclusions: This is the first study to document the distinct advantages of T-RIRS and its benefits on surgical ergonomics. T-RIRS resulted in significantly shorter operative and lasing times, particularly for stones in lower calyces. Surgical ergonomics, assessed by the Borg CR-10 scale, were significantly better in the T-RIRS group. T-RIRS should become a standard of care for patients undergoing RIRS.

Objective: This study functional endoscopic sinus surgery (FESS) is a surgical procedure requiring minimal bleeding to optimize the surgical field. This study aimed to evaluate the effectiveness of magnesium sulfate, lignocaine, and propofol in attenuating hemodynamic response. The primary objective of this study was to compare the efficacy of these agents in reducing hemodynamic response. The secondary objectives included assessing the quality of the surgical field, recovery time, and total neuromuscular dose. Methods: We randomly allocated 105 patients scheduled for FESS into three groups: lignocaine, propofol, and magnesium sulfate. Heart rate and mean arterial pressure were recorded every 5 min for the first 30 min, followed by measurements every 10 min at the end of the procedure. Moreover, recovery time, total neuromuscular blocking dose, and surgical field score were noted upon completion of the procedure. Statistical analysis was conducted using the number cruncher statistical systems version 9.0.8 software. Results: All three groups showed comparable hemodynamic response and surgical field scores. The recovery time was notably longer in the magnesium sulfate group [10.94 min (2.45)] than in the lignocaine [4.37 min (1.03)] [95% confidence interval (CI) -7.32, -5.83; P=0.000] and propofol groups [4.60 min (0.60)] (95% CI 5.60, 7.095; P=0.000). Moreover, the total neuromuscular blocking agent used was significantly lower in the magnesium sulfate group [5.89 mg (0.47)] than in the lignocaine [6.26 mg (0.56)] (95% CI 0.66, 0.03; P=0.035). Conclusion: Propofol, magnesium sulfate, and lignocaine exerted equal efficacy in attenuating hemodynamic responses during surgery and ensuring a satisfactory surgical field. However, magnesium sulfate led to significantly longer recovery timescompared withpropofol and lignocaine. In addition, magnesium sulfate required a significantly lower total dose of neuromuscular blocking agentsthan lignocaine.