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The rapid advancement of Artificial Intelligence (AI) models such as Generative Adversarial Networks (GANs) has been a great success in the field of image synthesis and creation. Artificially generated GAN-based images are widely spread over the Internet along with the development in generation of natural and photorealistic images. While this could lead to better digital media and content, it also poses a risk to security, legitimacy, and authenticity. The advancement of AI-generated images, particularly those that are produced by Generative Adversarial Networks (GANs), has created a rising concern about the potential misuse of these images in spreading misinformation and creating deepfakes. Detecting such fake or AI-generated images has become an important challenge in maintaining the integrity of digital media. In this research, we have explored the application of the Vision Transformer (ViTs) model for detecting AI-generated images, leveraging the Kaggle dataset - a balanced collection of real and AI-generated images. The Vision Transformer is recognized for its innovative method of treating images as sequences of patches and excels at identifying long-range dependencies and complex patterns within images. That makes it exceptionally well-suited for this task of detecting fake images. We have fine-tuned the ViT model on the dataset, performing data augmentation techniques on it and leveraging pretrained weights to boost the model’s performance. The findings thus obtained demonstrate that the ViT model attains a high level of accuracy in differentiating between real and AI-generated images, outperforming traditional CNN-based approaches. Beyond performance evaluation, we also conducted an ablation study to examine the impact of various components of the ViT model, including the number of attention heads, patch size, the impact of data augmentation, and the depth of layers. The results obtained in this study indicate that the ViT model not only excels in accuracy but also provides a robust framework for detecting AI-generated images across diverse scenarios. Our study shows the strength of transformer based models in addressing the increasing challenge of AI-generated image detection, laying a foundation for future research in this critical area. This experiment highlights that when the ViT model is fine tuned with optimal data augmentation techniques, it gains state of the art performance in AI-generated image detection, emphasizing its potential for real-world applications.

Background: Maternal mortality remains a significant public health challenge, particularly in developing countries like India. Birth Preparedness and Complication Readiness (BPACR) is a critical component of antenatal care recommended by the World Health Organization (WHO) to reduce maternal mortality. The maternal mortality ratio (MMR) of Karnataka is 92 per 100,000 live births in SRS 2016-18. Since Karnataka had the highest MMR ratio among the southern states of India the present study was thus conducted to determine the BPACR among antenatal and postnatal women and assess the factors related to it. Methods: A community-based cross-sectional study was conducted at a government hospital in Bengaluru. A sample of 105 antenatal mothers in their third trimester and postnatal women (age ≥ 18 years) attending the hospital was included. Data were collected using a pretested questionnaire that assessed various indicators related to BPACR, including knowledge of danger signs, health service utilization, and preparation for childbirth. Results: The study found a high BPACR index of 78%, with 17% of women exhibiting good BPACR. Knowledge of danger signs during pregnancy was high (95.2%), but lower for labor (51.4%) and postpartum (44.7%) periods. Fewer women knew about danger signs in neonates (46.6%). Regarding preparedness, 97.1% of women had identified transport arrangements, while only 25.7% knew about the need for blood transfusion during delivery. Awareness regarding the Karnataka Mathrushree Scheme was low at 25.7%. Conclusion: The study highlights a relatively high level of BPACR among antenatal and postnatal mothers in urban Bengaluru. Strengthening education and counseling during antenatal care, involving family members, and community awareness campaigns can improve BPACR and ultimately contribute to safer motherhood.

The aim of this study is to describe genotype and phenotype of patients with bestrophinopathy. The case records were reviewed retrospectively, findings of multimodal imaging such as color fundus photograph, optical coherence tomography (OCT), fundus autofluorescence, electrophysiological, and genetic tests were noted. Twelve eyes of six patients from distinct Indian families with molecular diagnosis were enrolled. Exon 4 of BEST1 was mutated in 3 cases, while exons 2, 3, and 7 in others. Deletion is seen in Exon 7 and missense mutation in other exons. Sporadic autosomal dominant and recessive inheritance was observed in these families. Two patients had primary angle closure glaucoma with a history of consanguineous marriage and glaucoma in the family. Based on our findings, multifocal vitelliform subretinal deposits were the most common fundus finding in patients with autosomal recessive mutation while macular vitelliform lesion was seen with sporadic or autosomal dominant mutation; however, cosegregation analysis was not done. Baseline OCT showed macular and extramacular subretinal exudates, subretinal fluid, intraretinal cystic and schitic spaces, and thickened photoreceptors outer segment tips. Two patients developed abnormal vasculature and focal choroidal excavation in OCT. A severe reduction in the electro-oculogram Ardens ratio was noted while electroretinography was normal. Bestrophinopathy has a varied presentation with complex genotype-phenotype relationships. OCT is a noninvasive tool for monitoring and prognostication. Genetic testing of other family members should be facilitated.

The global health crisis triggered by the SARS-CoV-2 in 2019, known as the COVID-19 pandemic, prompted vaccination drives worldwide, including in India, to address the crisis. However, vaccine hesitancy remains a significant challenge to achieving vaccination goals. Hence, we conducted a systematic review and meta-analysis during 2021–2023 to estimate the prevalence of COVID-19 vaccine hesitancy among adults in India and identify associated factors. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Quality assessment was performed using the Joanna Briggs Institute checklist. Pooled prevalence estimates were calculated using a random-effects model. A total of 265 articles were identified, of which 21 full-text articles were included in the review. The pooled estimated prevalence of COVID-19 vaccine hesitancy among adults in India was found to be 28% (95% confidence interval: 27–29). Subgroup analysis revealed variations in hesitancy rates across different states, with higher rates observed in Jammu and Kashmir (44%), West Bengal (49%), and Maharashtra (39%). Gender-based analysis indicated higher hesitancy among males (36%) compared to females (26%). Among different study populations, medical students showed the lowest hesitancy rate (13%), whereas the general population exhibited the highest (34%). The findings suggest that vaccine hesitancy remains a significant concern in India, with one in four adults expressing hesitancy toward COVID-19 vaccination. Hesitancy rates vary across states, genders, and study populations. Addressing the factors contributing to hesitancy, such as safety concerns, lack of evidence, and misinformation, is crucial to enhance vaccine acceptance.

Abstract Background Cross-sectoral collaborations as exemplified by the One Health approach, are widely endorsed as pragmatic avenues for addressing zoonotic diseases, but operationalisation remain limited in low-and-middle income countries (LMICs). Complexities and competing interests and agendas of key stakeholders and the underlying politico-administrative context can all shape outcomes of collaborative arrangements. Evidence is building that organised collaborations are complex political initiatives where different objectives; individual and institutional agendas need to be reconciled to incentivise collaborations. Methods Drawing on a qualitative network analysis of published sources on ‘One Health’ stakeholders supplemented with 26 multi-scale (national-state-district level) key-informant interviews (including policymakers, disease managers and public health experts), this paper characterises the fragmented and complex characteristics of institutional networks involved in zoonoses prevention and control in India. Results Our results highlight how the local socio-political and institutional contexts interact to modulate how and when collaborations occur (or not), the associated contingencies and stakeholder innovations in circumventing existing barriers (e.g. competing interests, distrust between actors, departmental bureaucracy) to cross-sector collaborations and zoonoses management. Aside from principal actors negotiating common ground in some instance, they also capitalised on political/institutional pressure to subtly ‘manipulate’ their subordinates as a way of fostering collaboration, especially in instances when the institutional and political stakes are high. Conclusion Altogether our findings suggest that cross-sectoral collaborations are by-product of political and institutional tinkering as long as individual actors and institutional interests converge and these dynamics must be embraced to embed meaningful and sustainable collaborations in local socio-political and administrative contexts.

Abstract The traditional methods used in big data, like cluster creation and query-based data extraction, fail to yield accurate results on massive networks. To address such issues, the proposed approach involves using the Hadoop Distributed File System (HDFS) for data processing, the map-reduce programming paradigm for data processing, and query optimization techniques to quickly and effectively extract accurate outcomes from a variety of options with a high processing capacity. The methodology proposed in this work makes use of Gaussian Mixture Model (GMM) for data clustering and the Salp Swarm Algorithm (SSA) for optimization. The security of preprocessed data stored on networked clusters with interconnections has been ensured by SHA algorithms. Finally, incorporating into consideration the important parameters, evaluation findings for the experimental performance of the model in the indicated methodology are produced. For this work, the estimated range of input file sizes is 60–100 MB. The processing of 100 MB of input files yielded an accuracy of 96% and results for specificity and sensitivity of 90% and 93%, respectively. The outcomes have been compared with well-known methods like fuzzy C-means and K-means approaches, and the results show that the proposed method effectively distributes accurate data processing to cluster nodes with low latency. Moreover, it uses the least amount of memory resources possible when operating on functional CPUs. As a result, the proposed approach outperforms existing techniques.

Background: Cardiogenic shock (CS) is a complex, life-threatening condition that requires timely care of patients. The purpose of this study is to evaluate the characteristics and outcomes of patients transferred to a cardiac intensive-care unit from outside hospitals, compared to those of patients admitted directly to a CS centre. Methods: Patients admitted with CS (January 1, 2014-December 31, 2019) were analyzed. Clinical characteristics and outcomes were recorded. Results: A total of 916 patients were admitted with CS; 440 (48.0%) were transferred from outside hospitals, and 476 (52.0%) were admitted directly to our institution. Transferred patients were younger (56.5 ± 14.7 vs 63.3 ± 16.3 years, P < 0.001), required vasopressor support more often (63.6% vs 14.9%, P < 0.001), and required mechanical ventilation more often (40.6% vs 10.7%, P < 0.001) upon transfer to the cardiac intensive-care unit. Transferred patients more frequently required extracorporeal life support (8.9% vs 3.0%, P < 0.001), had a lower rate of requiring orthotopic heart transplantation (6.4% vs 14.6%, P < 0.001), and had a lower incidence of all-cause mortality during follow-up (52.3% vs 62.8%, P = 0.001). With a multivariate analysis, patients transferred from outside were found to be less likely to reach the composite endpoint of durable ventricular assist device, orthotopic heart transplantation, or death (hazard ratio 0.75, 95% confidence interval 0.62-0.90, P = 0.003). Conclusions: Marked differences are present in the characteristics and outcomes of patients transferred from outside institutions vs of those transferred from within our quaternary-care centre. Further studies are required to evaluate decision-making for transfer of CS patients and assess CS outcomes in the setting of standardized CS protocols and interventions. Résumé: Contexte: Le choc cardiogénique (CC) est une condition complexe qui met en jeu le pronostic vital et qui nécessite une prise en charge rapide des patients. L'objectif de cette étude est d'évaluer les caractéristiques et les pronostics des patients transférés dans une unité de soins intensifs cardiaques à partir d'hôpitaux extérieurs, par rapport à ceux des patients admis directement dans un centre spécialisé en CC. Méthodes: Les données des patients admis pour un CC (entre le 1er janvier 2014 et le 31 décembre 2019) ont été analysées. Les caractéristiques cliniques et les pronostics ont été enregistrés. Résultats: Au total, 916 patients ont été admis pour un CC; 440 (48,0 %) ont été transférés d'hôpitaux extérieurs et 476 (52,0 %) ont été admis directement dans notre établissement. Les patients transférés étaient plus jeunes (56,5 ± 14,7 vs 63,3 ± 16,3 ans, p < 0,001), nécessitaient plus souvent un soutien vasopresseur (63,6 % vs 14,9 %, p < 0,001) et plus souvent une ventilation mécanique (40,6 % vs 10,7 %, p < 0,001) lors de leur transfert à l'unité de soins intensifs cardiaques. Ces patients avaient aussi plus souvent besoin d'une assistance cardiorespiratoire extracorporelle (8,9 % vs 3,0 %, p < 0,001), avaient moins souvent besoin d'une transplantation cardiaque orthotopique (6,4 % vs 14,6 %, p < 0,001) et présentaient une incidence plus faible de mortalité toutes causes confondues lors du suivi (52,3 % vs 62,8 %, p = 0,001). Une analyse multivariée a montré que les patients transférés de l'extérieur étaient moins susceptibles d'atteindre le critère d'évaluation composite (dispositif d'assistance ventriculaire durable, transplantation cardiaque orthotopique ou décès) (rapport de risque 0,75, intervalle de confiance à 95 % 0,62-0,90, p = 0,003). Conclusions: Des différences marquées sont présentes dans les caractéristiques et les pronostics des patients transférés depuis des institutions extérieures par rapport à ceux admis directement dans notre centre de soins quaternaires. Des études supplémentaires sont nécessaires pour évaluer la prise de décision concernant le transfert des patients atteints de CC et évaluer les pronostics de la CC dans le cadre de protocoles et d'interventions de CC standardisés.

Rationale: This case highlights the rare yet critical diagnosis of hypermagnesemia in a preterm infant, who presented with symptoms mimicking necrotizing enterocolitis. It underscores the importance of considering hypermagnesemia as a differential diagnosis in neonatal respiratory distress and gastrointestinal symptoms, even when the cause is not immediately apparent. Patient’s Concern: An extremely low birth infant with respiratory distress further had episodes of apnoea and cyanosis. The infant eventually exhibited abdominal distension and bilious vomiting, symptoms mimicking necrotizing enterocolitis. Diagnosis: The infant’s clinical features were attributed to hypermagnesemia, despite no magnesium being administered and no apparent cause identified. Screening the apparently asymptomatic mother confirmed a serum magnesium level of 4 mg/dL, suggesting transplacental transfer as the likely cause of the neonate’s condition. Interventions: The newborn was treated supportively with adequate hydration and maintenance calcium gluconate. Outcomes: Magnesium levels decreased, and the baby showed signs of improvement. Lessons: Hypermagnesemia, though uncommon, should be investigated and considered even when the symptoms are not apparent.

Pulmonary sequestration is an uncommon congenital anomaly. It is usually diagnosed at a young age but can present in adults with recurrent episodes of pneumonia and cough. Isolated shortness of breath is an uncommon presentation of pulmonary sequestration and is rarely reported. We describe an adult male who presented with exertional dyspnea at a high altitude and was eventually diagnosed as a case of pulmonary sequestration. It is an uncommon developmental anomaly that can go undetected at a young age. In adults, it can present as isolated dyspnea, and a thorough work-up can lead to an accurate diagnosis.

Abstract Background Cardiogenic shock (CS) is associated with high in‐hospital mortality. Objective assessment of its severity and prognosis is paramount for timely therapeutic interventions. This study aimed to evaluate the efficacy of the shock index (SI) and its variants as prognostic indicators for in‐hospital mortality. Methods A retrospective study involving 1282 CS patients were evaluated. Baseline patient characteristics, clinical trajectory, hospital outcomes, and shock indices were collected and analysed. Receiver operating characteristic (ROC) curves were employed to determine the predictive accuracy of shock indices in predicting in‐hospital mortality. Results Of those evaluated, 866 (67.6%) survived until discharge. Non‐survivors were older (66.0 ± 13.7 vs. 57.4 ± 16.2, P

Abstract Background Acute kidney injury (AKI) occurs frequently in ST-elevation myocardial infarction with cardiogenic shock (CS-STEMI) and is a strong independent prognostic marker for short and intermediate-term outcomes. Owing to the delayed presentation and limited facilities for primary percutaneous coronary intervention in low- and middle-income countries, the incidence, predictors, and outcome of AKI are likely to be different compared to the developed countries. We performed a post hoc analysis of patients presenting with CS-STEMI over 7 years (2016–2022) at a tertiary referral center in North India. The primary outcome assessed was AKI and the secondary outcome was in-hospital mortality. Results Of the 426 patients, 194 (45.5%) patients developed AKI, as defined by the Kidney Disease Improving Global Outcomes criteria. Left ventricular (LV) pump failure with pulmonary edema [Odds ratio (OR) 1.67; 95% confidence interval (CI) 1.04–2.67], LV ejection fraction (OR 1.35 per 10% decrease in ejection fraction; CI 1.04–1.73), complete heart block (OR 2.06; CI 1.2–3.53), right ventricular infarction (OR 2.76; CI 1.39–5.49), mechanical complications (OR 3.89; CI 1.85–8.21), ventricular tachycardia (OR 2.80; CI 1.57–4.99), and non-revascularization (OR 2.2; CI 1.33–3.67) were independent predictors of AKI in multivariate logistic regression analysis. Additionally, AKI was a strong predictor of in-hospital mortality (univariate OR 30.61, CI 17.37–53.95). Conclusions There is a higher incidence of AKI in CS-STEMI in resource-limited settings and is associated with adverse short-term outcomes. Additional studies are needed to address the optimal strategies for the prevention and management of AKI in such settings.

Background: Osteoporosis is commonly seen affecting the bones in post-menopausal females, especially in India. Dual energy X-ray absorptiometry (DEXA) is the gold standard for identifying osteoporosis in female patients. Digital panoramic radiography (OPG) is a common imaging modality used frequently in routine dental practice. Mandibular cortical index (MCI) on OPG can be used to diagnose osteoporosis. Therefore, this study evaluated the efficacy of MCI on OPG to help detect osteoporosis in postmenopausal Indian females. Aim: To evaluate the accuracy of OPG versus DEXA in predicting bone mineral density (BMD). Materials and Methods: The research involved forty-two women with a postmenopausal history for a minimum of a year. The BMD was measured using DEXA. OPG was taken, and analysis of the mandible on OPG was done by two observers using the MCI given by Klemetti et al. Results: OPG had an overall sensitivity and specificity of 71% in the normal group, sensitivity of 50%, specificity of 68% in the osteopenia group, and sensitivity of 36%, specificity of 89% in the osteoporotic group in predicting the BMD using MCI. A positive correlation was seen in the efficacy of OPG in predicting BMD in the normal (P = 0.031*) and osteoporotic groups (P = 0.000*). Conclusion: MCI on OPG helped diagnose normal and osteoporotic patients efficiently, but osteopenia was misdiagnosed as normal or osteoporotic. Hence, MCI alone should not be used to predict BMD.

Accurate flood forecasting is a crucial process for predicting the timing, occurrence, duration, and magnitude of floods in specific zones. This prediction often involves analyzing various hydrological, meteorological, and environmental parameters. In recent years, several soft computing techniques have been widely used for flood forecasting. In this study, flood forecasting for the Narmada River at the Hoshangabad gauging site in Madhya Pradesh, India, was conducted using an Artificial Neural Network (ANN) model, a Fuzzy Logic (FL) model, and an Adaptive Neuro-Fuzzy Inference System (ANFIS) model. To assess their capacity to handle different levels of information, three separate input data sets were used. Our objective was to compare the performance and evaluate the suitability of soft computing data-driven models for flood forecasting. For the development of these models, monthly discharge data spanning 33 years from six gauging sites were selected. Various performance measures, such as regression, root mean square error (RMSE), and percentage deviation, were used to compare and evaluate the performances of the different models. The results indicated that the ANN and ANFIS models performed similarly in some cases. However, the ANFIS model generally predicted much better than the ANN model in most cases. The ANFIS model, developed using the hybrid method, delivered the best performance with an RMSE of 211.97 and a coefficient of regression of 0.96, demonstrating the potential of using these models for flood forecasting. This research highlighted the effectiveness of soft computing techniques in flood forecasting and established useful suitability criteria that can be employed by flood control departments in various countries, regions, and states for accurate flood prognosis.

Abstract Antibiotic resistance is a significant threat, leaving us vulnerable to bacterial infections. Novel strategies are needed to combat bacterial resistance beyond discovering new antibiotics. This research focuses on using maleimide conjugated PEGylated liposomes (Mal-PL-Ab) to individually encapsulate a variety of antibiotics (ceftriaxone, cephalexin, doxycycline, piperacillin, ampicillin, and ceftazidime) and enhance their delivery against multi-drug resistant (MDR) bacteria like Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae). Mal-PL-Ab, with an average size of 84.2 nm ± 4.32 nm, successfully encapsulated these antibiotics with an encapsulation efficiency of 37.73 ± 3.19%. Compared to non-PEGylated liposomes (L-Ab), Mal-PL-Ab exhibited reduced toxicity in human dermal cells, emphasizing the importance of PEGylation in minimizing adverse effects. Mal-PL-Ab significantly decreased the minimum inhibitory concentration (MIC) values against both E. coli and K. pneumoniae by 9.33-fold and eightfold reduction (compared to non-PEGylated liposomes with 2.33-fold and 2.33fold reduction), respectively, indicating enhanced efficacy against MDR strains. Furthermore, in vitro scratch assay and gene expression analysis of human dermal fibroblast revealed that Mal-PL-Ab promoted cell proliferation, migration, and wound healing through upregulation of cell cycle, DNA repair, and angiogenesis-related genes. Harnessing the power of encapsulation, Mal-PL-Ab presents a novel avenue for enhanced antibiotic delivery and wound healing, potentially transcending the limitations of traditional options.

Abstract Solvent-extracted fractions of six Indian coal samples of different ranks were investigated using multiple geochemical, petrological and spectroscopic proxies and an attempt was made to indicate possible fingerprint regions for different polycyclic aromatic hydrocarbons (PAH) with the help of excitation-emission matrix (EEM). In this study, for the very first time, the influence of rank and maturation of organic matter in the characterisation of coal solvent-extracts from Indian coals were perceived from the viewpoint of fluorescence EEM. Vitrinite reflectance (VRo) values were used to determine the general ranks of the original coal samples viz. lignite, subbituminous, bituminous and anthracite. Different fluorescence peak regions corresponding to different fused aromatic ring (FAR) systems were delineated using the EEM and their indicative depositional environments could be inferred. Our observations indicate that solvent-extracted fractions of low rank coals comprise of a larger number of shorter carbon chains compared to the other samples. For the low rank coal samples, the solvent-extracts show a strong humic influence and the presence of smaller PAH rings while for the medium rank coals, the extracted fractions tend to show a more bimodal distribution of PAHs, possibly comprising of different sized PAHs. Higher fluorescence sensitivity and quick response of smaller PAHs impart a singular centralised region in the EEM for the low rank coal samples while interference in the fluorescence of differently sized PAHs indicate a multimodal distribution of the fluorophores in the medium rank coals. The high rank coal used in this study shows a bimodal distribution with very low intensity of the peaks, indicating the low abundance of extractable macromolecules, possibly as a result of deformation.

Abstract Background Surgical excision with clear histopathological margins is the preferred treatment to prevent progression of lentigo maligna (LM) to invasive melanoma. However, the assessment of resection margins on sun-damaged skin is challenging. We developed a deep learning model for detection of melanocytes in resection margins of LM. Methods In total, 353 whole slide images (WSIs) were included. 295 WSIs were used for training and 58 for validation and testing. The algorithm was trained with 3,973 manual pixel-wise annotations. The AI analyses were compared to those of three blinded dermatopathologists and two pathology residents, who performed their evaluations without AI and AI-assisted. Immunohistochemistry (SOX10) served as the reference standard. We used a dichotomized cutoff for low and high risk of recurrence (≤ 25 melanocytes in an area of 0.5 mm for low risk and > 25 for high risk). Results The AI model achieved an area under the receiver operating characteristic curve (AUC) of 0.84 in discriminating margins with low and high recurrence risk. In comparison, the AUC for dermatopathologists ranged from 0.72 to 0.90 and for the residents in pathology, 0.68 to 0.80. Additionally, with aid of the AI model the performance of two pathologists significantly improved. Conclusions The deep learning showed notable accuracy in detecting resection margins of LM with a high versus low risk of recurrence. Furthermore, the use of AI improved the performance of 2/5 pathologists. This automated tool could aid pathologists in the assessment or pre-screening of LM margins.

The scope of the emerging field of Ayurvedic-biology visualized thus far is confined to studies on dimensions pertaining to clinical and experimental pharmacology, basic trans-disciplinary science and drug design. However, given the multiple facets of classical Ayurveda knowledge system, its application in the field of organic agriculture perhaps also needs to be urgently explored. The urgency is due to the growing public acceptance of Ayurveda as a preferred clinical choice for well-being and disease management. The turnover of the sector across manufacturing and health services is estimated to be around Rs.1,00,000 crores per annum. Medicinal plants today and in the coming decade will therefore be required in large volumes and given that their applications are solely for enhancing health of humans, livestock (Pashu Ayurveda) and crops (Vriksh Ayurveda), it is imperative that they be cultivated in an organic manner employing the fusion of best available inter-cultural knowledge.The Ayurvedic subjects relevant for organic agriculture are Desh vichar, Dravya guna Shastra and Vriksh Ayurveda. From the perspective of modern biology subjects like soil micro biome, genetics, plant physiology and the natural geographical distribution of species are relevant.It must be stated at the very outset that this article is largely theoretical. While experiments in Vriksh Ayurveda have been attempted on a small scale, the fusion of Ayurveda and biology for improving organic agriculture of medicinal plants has thus far not been systematically explored.

Introduction There are insufficient scalable, evidence-based treatments to meet increasing mental health needs of young people. Offering interim, brief interventions for young persons with psychological distress can improve access to care and mitigate adverse effects of long waiting times. This study tests the efficacy of solution-focused brief therapy (SFBT), a strength-based, goal-directed intervention, in adolescents and young adults at a community-based youth mental health service in Singapore.Methods and analysis This is a fully powered, randomised, single-centre, two-arm, parallel, superiority, controlled trial. From September 2023 to March 2025, the study will recruit 124 participants (aged 16–30) presenting at a national youth mental health service in Singapore (CHAT, Centre of Excellence for Youth Mental Health) with clinically assessed general psychological distress, subthreshold or prodromal symptoms, or a first episode of a mood disorder. Participants will be excluded if they have high risk of suicide, psychosis, cognitive impairments, or current psychological treatments. Participants will be randomised in a 1:1 ratio to receive six-session, case manager delivered SFBT or treatment as usual (TAU) case management, and be followed up for 3 months post-intervention. Participants receiving SFBT are hypothesised to have greater improvements in self-reported psychological distress, from baseline to 8 weeks, compared with the control group. Secondary outcomes are self-reported depression and anxiety symptoms, and functional impairment. The study will also explore whether SFBT is associated with increased self-efficacy and decreased hopelessness, decreased downstream referrals post-intervention, and sustained clinical gains 3 months post-intervention compared with TAU. Adverse events and clinical deterioration will be recorded and reported.Ethics and dissemination The Institute of Mental Health (IMH) Institutional Research Review Committee (reference 822–2022) and the Singapore National Health Group Domain Specific Review Board (DSRB) (reference 2023/00052) have approved the study protocol. Findings will be published in international, peer-reviewed scientific journals. Summaries will be disseminated to study funders, mental healthcare systems administrators, and clinicians.Trial registration number ISRCTN13671612 https://doi.org/10.1186/ISRCTN13671612

Introduction: Composite resin is commonly used in dental restorations, though it is prone to degradation over time. Repairing these restorations is often preferable for issues such as discoloration, small areas of decay near the restoration margin, or for preserving tooth health without the need for complete removal. Method: Sixty acrylic blocks with cavities were restored using FILTEK-Z-250 XT composite resin, which was then light-cured. After 300 thermal cycles, the blocks were divided into three groups: control, diamond bur-abraded, and aluminum oxide air-abraded. Each group was further subdivided into two subgroups, treated with either Ivoclar Tetric N-bond or 3M ESPE Single Bond Universal adhesive. Shear bond strengths (SBSs) were tested after applying additional composite, and the types of fractures were analyzed. Results: The air-abrasion group (Group III) exhibited the highest SBS values compared to the other groups. Specifically, Group IIIb (air-abrasion combined with 3M ESPE Single Bond Universal adhesive) recorded the highest SBS values overall and within its subgroup. Conclusion: Treating the composite material’s surface with mechanical methods, especially air-abrasion, improves its repairability.

Introduction: Type 1 Diabetes Mellitus (T1DM) is a prevalent endocrine disease in children, requiring consistent management of diet, physical activity, insulin delivery, and glucose monitoring. Telemedicine has shown benefits for adults with chronic diseases, but its effectiveness for pediatric T1DM in India is less explored. This study compares glycemic control in pediatric T1DM patients before and after telephonic reinforcement. Methodology: A prospective interventional study was conducted at a tertiary healthcare center in India. Thirty-five pediatric T1DM patients were included, with baseline characteristics recorded. Patients received telephonic support three times a month for nine months, focusing on blood sugar monitoring, insulin administration, and follow-ups. Data were analyzed using paired t-tests with a significance level of P < 0.05. Results: The mean HbA1c level decreased significantly from 11.85 ± 1.15 at baseline to 9.05 ± 1.55 at nine months (P < 0.001). Conclusion: Telephonic reinforcement improved glycemic control and compliance in pediatric T1DM patients. Further studies with larger sample sizes are needed to validate these findings.

Bidder selection is a complex procurement decision that often surfaces in most project-based industries. The widely preferred institutional logic of low-cost bidder causes quality-related issues and poor revenue generation in the operations and maintenance phase. Therefore, the present research aims to evaluate bidder selection using the cost of quality principles. The research framework based on the cost of quality is formulated, and the risk of bidder selection associated with the cost of quality and revenue generation is assessed using @risk simulation software. The revenue generation of the facility is simulated with bid price and cost quality and subsequently validated using a case of a public-private partnership water supply project of Latur City in India. The research contribution entails that bidder selection based on price can be undertaken, provided the bidder has demonstrated evidence of the investment in the cost of quality. The research has demonstrated that the bidders possessing the larger water augmentation capacity and lower cost of quality expenditure are more likely to generate higher revenue than the competing bidders. Therefore, the bidder selection based on price alone will not yield adequate revenue generation during water operations and maintenance phases of water supply projects.

Morbidity and mortality caused by respiratory syncytial virus (RSV) in older adults and those with underlying health conditions can be potentially alleviated through vaccination. To assist vaccine policy decision-makers and payers, we estimated the annual economic burden of RSV-associated cardiorespiratory hospitalizations among insured US adults aged ≥18 y in the Merative MarketScan claims database from September through August of 2017–2018 and 2018–2019. Negative binomial regression models were used to estimate the number of RSV-associated cardiorespiratory hospitalizations using MarketScan-identified cardiorespiratory diagnosis codes in the presence or absence of RSV circulation per weekly laboratory test positivity percentages from the Centers for Disease Control and Prevention. This number was multiplied by mean cardiorespiratory hospitalization costs to estimate total costs for RSV-associated cardiorespiratory hospitalizations. Number and cost for International Classification of Diseases (ICD)-coded RSV hospitalizations were quantified from MarketScan. In 2017–2018 and 2018–2019, respectively, 18,515,878 and 16,462,120 adults with commercial or Medicare supplemental benefits were assessed. In 2017–2018, 301,248 cardiorespiratory hospitalizations were observed; 0.32% had RSV-specific ICD codes, costing $44,916,324, and 5.52% were RSV-associated cardiorespiratory hospitalizations, costing $734,078,602 (95% CI: $460,826,580–$1,103,358,799). In 2018–2019, 215,525 cardiorespiratory hospitalizations were observed; 0.34% had RSV-specific ICD codes, costing $33,053,105, and 3.14% were RSV-associated cardiorespiratory hospitalizations, costing $287,549,472 (95% CI: $173,377,778–$421,884,259). RSV contributes to substantial economic burden of cardiorespiratory hospitalizations among US adults. Modeling excess risk using viral positivity data provides a comprehensive estimation of RSV hospitalization burden and associated costs, compared with relying on ICD diagnosis codes alone.

A surge of interest in using non-thermal, non-toxic, and chemical-free food preservation methods is seen in recent years. At the same time, there is a requirement for fresh, minimally processed, and nutritious food in the market. Dense phase carbon dioxide (DPCD) is a non-thermal method of inactivating enzymes and microorganisms at temperatures below standard pasteurization to avoid thermal effects. Diverse research has been conducted to understate the mechanism and its effect on microorganisms such as bacteria, yeast, molds, and enzymes throughout the last few decades. The effects of this technology have been promising in the case of many liquid foods. Furthermore, researchers are working on the effect of DPCD in combination with other non-thermal processes such as irradiation, PEF, ultrasound, and HPP. This review compiles a substantial quantity of research on DPCD and provides an overview of DPCD processing equipment, mechanism, applications in liquid and solid foods, the emerging interest of DPCD in hurdle technology, and highlights its efficiency against microorganisms and enzymes, as well as its application in the food processing industry. DPCD offers new opportunities for better microbe control, enzyme inactivation at softer process settings, and improved quality and nutrient retention.

The benefits of AI in pathology are demonstrated by the growing potential of diagnostic accuracy and efficiency in tissue segmentation, cancer detection and grading. In this scoping review, we studied how artificial intelligence (AI) technologies have been developed for usage in pathology. In the study, a literature search on databases and publisher portals PubMed, ScienceDirect, ProQuest, and CINAHL was conducted to collect peer-reviewed studies published between 2019 and 2023. Then after a thorough database search, 57 articles covering the topic were included out of 19 185 potential ones and were categorised into groups by their main purposes, such as pre-processing, segmentation, analysis, and prediction. The findings demonstrate that AI technologies like deep learning and convolutional neural networks (CNNs) enhance medical imaging for tissue segmentation and cancer detection by reducing human error and variability.

Introduction: Hemiarthroplasty is recognized as a prominent therapeutic option for neck of femur fracture without preexisting acetabular pathology; however, there are controversies in the scientific literature regarding this. The study aims to analyze epidemiology of patients sustaining neck of femur fracture and the functional outcomes following hemiarthroplasty. Methods: This is a observational cross-section study in a single tertiary care center of Nepal. Senior citizens, 60 years or above patients, with neck of femur fracture who underwent hemiarthroplasty from January 2017 to December 2022 were included in the study. Patient related data were retrieved from the medical record department of the hospital. A semi-structured proforma was designed which included patient demographic information, operative details and follow up evaluation using Modified Harris Hip Score. Ethical approval was obtained from the Institutional Review Committee (Reference number: 34/24). Results: The median Modified Harris Hip score for patients who received hemiarthroplasty for neck of femur fracture from January 2017 to December 2022 was 79 (IQR: 74-86), with 4 (9.30%) achieving excellent results, 19 (41.19%) good, 14 (32.56%) fair, and 6 (13.95%) poor outcomes. Conclusions: Hemiarthroplasty emerges as a valuable treatment for femoral neck fractures in senior citizens, aged 60 and above, providing good functional results.

The bromodomain and extraterminal (BET) family of proteins show altered expression across various cancers. The members of the bromodomain (BRD) family contain epigenetic reader domains that bind to acetylated lysine residues in both histone and non-histone proteins. Since BRD proteins are involved in cancer initiation and progression, therapeutic targeting of these proteins has recently been an area of interest. In experimental settings, JQ1, a commonly used BRD inhibitor, is the first known inhibitor to target BRD-containing protein 4 (BRD4), a ubiquitously expressed BRD and extraterminal family protein. BRD4 is necessary for a normal cell cycle, and its aberrant expression activates pro-inflammatory cytokines, leading to tumor initiation and progression. Various BRD4 inhibitors have been developed recently and tested in preclinical settings and are now in clinical trials. However, as with many targeted therapies, BRD inhibitor treatment can lead to resistance to treatment. Here, we investigated the kinases up-regulated on JQ1 treatment that may serve as target for combination therapy along with BRD inhibitors. To identify kinase targets, we performed a comparative analysis of gene expression data using RNA from BRD inhibitor-treated cells or BRD-modulated cells and identified overexpression of several kinases, including FYN, NEK9, and ADCK5. We further validated, by immunoblotting, the overexpression of FYN tyrosine kinase; NEK9 serine/threonine kinase and ADCK5, an atypical kinase, to confirm their overexpression after BRD inhibitor treatment. Importantly, our studies show that targeting FYN or NEK9 along with BRD inhibitor effectively reduces proliferation of cancer cells. Therefore, our research emphasizes a potential approach of utilizing inhibitors targeting some of the overexpressed kinases in conjunction with BRD inhibitors to enhance therapeutic effectiveness.

Abstract Background Treatment with regorafenib, a multiple-kinase inhibitor, to manage metastatic colorectal cancers (mCRCs) shows a modest improvement in overall survival but is associated with severe toxicities. Thus, to reduce regorafenib-induced toxicity, we used regorafenib at low concentration along with a dual JAK/HDAC small-molecule inhibitor (JAK/HDACi) to leverage the advantages of both JAK and HDAC inhibition to enhance antitumor activity. The therapeutic efficacy and safety of the combination treatment was evaluated with CRC models. Methods The cytotoxicity of JAK/HDACi, regorafenib, and their combination were tested with normal colonic and CRC cells exhibiting various genetic backgrounds. Kinomic, ATAC-seq, RNA-seq, cell cycle, and apoptosis analyses were performed to evaluate the cellular functions/molecular alterations affected by the combination. Efficacy of the combination was assessed using patient-derived xenograft (PDX) and experimental metastasis models of CRC. To evaluate the interplay between tumor, its microenvironment, and modulation of immune response, MC38 syngeneic mice were utilized. Results The combination therapy decreased cell viability; phosphorylation of JAKs, STAT3, EGFR, and other key kinases; and inhibited deacetylation of histone H3K9, H4K8, and alpha tubulin proteins. It induced cell cycle arrest at G0-G1 phase and apoptosis of CRC cells. Whole transcriptomic analysis showed that combination treatment modulated molecules involved in apoptosis, extracellular matrix-receptor interaction, and focal adhesion pathways. It synergistically reduces PDX tumor growth and experimental metastasis, and, in a syngeneic mouse model, the treatment enhances the antitumor immune response as evidenced by higher infiltration of CD45 and cytotoxic cells. Pharmacokinetic studies showed that combination increased the bioavailability of regorafenib. Conclusions The combination treatment was more effective than with regorafenib or JAK/HDACi alone, and had minimal toxicity. A clinical trial to evaluate this combination for treatment of mCRCs is warranted.

Abstract Background Tuberculosis remains a global health challenge, with central nervous system tuberculosis (CNSTB) affecting 5–10% of extrapulmonary tuberculosis cases, leading to severe complications in children aged 2 to 4 years. Despite timely diagnosis and intervention, management of CNSTB is a challenge. Thalidomide, a TNF-α inhibitor, is a potential therapeutic option in cases resistant to adjuvant corticosteroid therapy. This case report describes the management of complicated CNSTB utilising thalidomide, a less commonly used drug, with a favourable outcome. Clinical presentation A 3-year-old boy diagnosed with CNSTB and having a ventriculoperitoneal shunt presented with left-sided hemiparesis. He was previously diagnosed with tubercular meningitis at 2.5 years of age. On anti-tubercular treatment and corticosteroid, he had a complicated course with drug-induced liver injury (DILI) and paradoxical reaction. Despite a year of anti-tubercular therapy, there was a deterioration in neurological symptoms, accompanied by an increase in the number of tuberculomas observed on MRI. Adjuvant treatment with thalidomide proved effective in suppressing immunological activation, leading to a reduction in tuberculomas. Conclusion This case highlights the intricacies of CNSTB, including complications and refractory tuberculomas. Thalidomide was effective in managing these challenges, offering a potential therapeutic option in challenging CNSTB cases. Positive clinical and radiological responses underscore the need to further explore thalidomide as an adjunctive therapy in similar paediatric cases.

Aims: To compare the lung functions of TOPD phenotype patients and COPD patients other than TOPD phenotype. Settings and design: Retro-prospective cohort study. Introduction: Globally, tuberculosis (TB) has emerged as a risk factor for the development of chronic obstructive pulmonary disease (COPD) and is one of the leading causes of mortality and morbidity. This entity has been titled as TOPD phenotype (tuberculosis-associated obstructive pulmonary disease), and it has been mentioned in various literatures in the past by various authors. However, it is still a matter of debate whether pattern of chronic airflow obstruction in COPD and TOPD phenotype is different or same. Methodology: We enrolled a total of 100 patients, in that 50 of whom had obstructive airway symptoms with a history of (treated) pulmonary tuberculosis (with a microbiological or radiological evidence in the past) and 50 of whom were diagnosed with COPD without any history of tuberculosis. Both groups underwent spirometry and impulse oscillometry (IOS) tests. Results were recorded and compared. Results: The mean age of patients with TOPD was 49.51 ± 5.15, while COPD was 48.54 ± 5.94. The chance of exacerbation was higher in the TOPD group (94.0%) owing to poor lung function. The majority of TOPD patients were in GOLD II stage, while COPD patients were in GOLD I stage. Spirometry and IOS of TOPD patients revealed a significant difference as compared to COPD patients. Conclusion: We found that overall lung function was poorer in the TOPD group as compared to the COPD group.

Background: Iodine deficiency disorder results in avoidable brain damage, cognitive impairment, and inhibited growth and development among children. The aim of this study was to ascertain pervasiveness of IDD in the Bhuj City of Kutch district of Gujarat by measuring urinary iodine excretion levels(UIE) and iodine intake from salt among school-going children. Material and methods: A cross-sectional investigation was conducted to evaluate iodine deficiency levels in 350 schoolchildren of both genders, 6-12 years of ages, from Bhuj Taluka, a subdivision of the Kachchh district. The evaluation involved estimating urinary iodine levels through the Sandell–Kolthoff reaction and determining the iodine levels in samples of cooking salt using Spot testing kit (STK). Results: With a median iodine levels in urine of 166.93 μg/L, there appears to be no biochemical evidence of iodine deficiency in the region. Approximately 98.57% of salt samples found iodine levels exceeding 15 ppm, while only about 1.42% had iodine levels below 15 ppm, indicating that household salt samples contain adequate iodine levels. Conclusions: The region's median concentration of Iodine content found in urine 166.93μg/L, suggesting the absence of biochemical iodine deficiency. Analysis of salt samples revealed that approximately 98.57% contained iodine levels exceeding 15 ppm, while only about 1.42% had iodine content below this threshold. This indicates that household salt samples possess adequate iodine levels, aligning with criteria for monitoring progress in eradicating iodine deficiency disorders as a public health concern.

Abstract African American (AA) women are twice as likely to develop triple-negative breast cancer (TNBC) as women of European descent. Additionally, AA women with TNBC present a much more aggressive disease course than their European American (EA) counterparts. Thus, there is an unmet clinical need to identify race-specific biomarkers and improve survival outcomes in AA patients with TNBC. The minus-end directed microtubule motor protein kinesin family member C1 (KIFC1) promotes centrosome clustering and chromosomal instability and is often overexpressed in TNBC. Previous findings suggest that KIFC1 plays a role in cell proliferation and migration in TNBC cells from AAs and that the levels of nuclear KIFC1 (nKIFC1) are particularly high in AA patients with TNBC. The nuclear localization of KIFC1 in interphase may underlie its previously unrecognized race-specific association. In this study, we found that in TNBC cells derived from AAs, nKIFC1 interacted with the tumor suppressor myosin heavy chain 9 (MYH9) over EA cells. Treatment of AA TNBC cells with commercial inhibitors of KIFC1 and MYH9 disrupted the interaction between KIFC1 and MYH9. To characterize the racial differences in the KIFC1-MYH9-MYC axis in TNBC, we established homozygous KIFC1 knockout (KO) TNBC cell lines. KIFC1 KO significantly inhibited proliferation, migration, and invasion in AA TNBC cells but not in EA TNBC cells. RNA sequencing analysis showed significant downregulation of genes involved in cell migration, invasion, and metastasis upon KIFC1 KO in TNBC cell lines from AAs compared to those from EAs. These data indicate that mechanistically, the role of nKIFC1 in driving TNBC progression and metastasis is stronger in AA patients than in EA patients, and that KIFC1 may be a critical therapeutic target for AA patients with TNBC. Graphical abstract

The skin microbiome consists of bacteria, fungi, viruses, and mites, which play a crucial role in maintaining skin health and immune function. Imbalances in this microbial community, known as dysbiosis, are implicated in various dermatological conditions. While skincare products are known to influence the skin microbiome, the effects of dermatological procedures have not been extensively studied. Here, we perform a scoping review to outline the studies investigating the impacts of dermatological interventions on the skin microbiome. Phototherapy emerged as the most studied intervention, encompassing UV phototherapy, light therapy, laser therapy, and photodynamic therapy. Chemical interventions, such as chemical peels, micropigmentation, and debridement, have comparatively limited studies describing their impacts on the skin microbiome. To date, no studies have been done on a wide variety of common dermatological procedures such as cryotherapy, skin grafts, and dermabrasion, which may have stronger likelihoods of affecting the skin microbiome. This underscores the need for further research on the influences of dermatological procedures, especially chemical and physical interventions, on the skin microbiome. More comprehensive pre-clinical and clinical studies are essential not only for understanding the long-term consequences of these procedures, but also for optimizing patient outcomes in dermatological care.

Background: Our study highlights the assessment of inter-radicular septum (IRS) on cone beam CT (CBCT) as an important pretreatment tool for immediate maxillary molar implant (IMI) placement. The aim of our study was to evaluate the suitability of the IRS of the maxillary first and second molars on CBCT to receive IMI. Objectives: The objectives of our study were to measure and compare IRS dimensions of the first and second molars and to assess the suitability of maxillary first and second molars to house an immediate implant. Method: In total, 200 CBCT scans (100 each for first and second molars) that display IRS completely were selected for the study. The IRS was analyzed in all three dimensions. Then, the percentage of first and second maxillary molars that were suitable to receive an IMI based on Smith and Tarnow’s classification was calculated. Results: It was found that 89% first and 71% of second molars were eligible sites for IMI. Conclusion: Careful evaluation of IRS will lead to a better prognosis for IMI.

Telemedicine is crucial in supporting the healthcare sector in developing countries as it can assist in various scenarios, such as low physician-to-population ratios, lack of access to specialty physicians, and patient and physician needs in remote areas. The study aimed to assess the knowledge, perception, and practice of telemedicine among undergraduate medical students, recognizing the importance of equipping future healthcare professionals with the necessary skills and understanding of this technology. A cross-sectional study was conducted among 307 undergraduate medical students at a tertiary care teaching hospital. A structured questionnaire was used to collect data on demographic information, computer literacy, knowledge, perception, and practice of telemedicine. Data entry and analysis were done using Microsoft Office Excel 2010. The mean, percentage, and standard deviation were calculated to describe the characteristics of respondents. This study found that 75.8% of participants were aware of telemedicine; however, only 18.8% recognized its use for prescribing drugs. Additionally, 59.9% had a low level of perception towards telemedicine. Although 45% agreed to incorporate telemedicine into medical education, 61% preferred traditional hospital visits due to concerns about information, expertise, and technical challenges. The study emphasizes the imperative for telemedicine training to address the existing knowledge gap. It underscores the critical importance of integrating telemedicine education into medical curricula at an early stage.

The current work aims to screen the phytoconstitutes of the Lactuca virosa leaves ethanolic extract by using GC-MS analysis and investigate its antibacterial activity. GC-MS analysis was conducted to identify the various phytochemical constituents within the ethanolic extracts of Lactuca virosa. Subsequently, protein-ligand docking was performed using proteins PDBID: 6AHT and 5C5H, revealing a strong affinity between the bioactive compounds and the proteins, indicating potent inhibitory action. Furthermore, each concentration of Lactuca virosa was assessed for antibacterial activity using Minimum Inhibitory Concentration (MIC) against bacterial strains including Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa and Streptococcus mutans. Preliminary phytochemical testing revealed the presence of alkaloids, coumarins, flavonoids, glycosides, phenols, terpenoids, oils, and resins. GC-MS showed the presence of many bioactive compounds in extract. Docking results highlighted that two compounds exhibited the most favourable binding energies of approximately -8.1 kcal/mol and -8.5 kcal/mol with 6AHT, and -8.8 kcal/mol with 5C5H. The ethanolic extract of 0.4mg concentration has shown good antibacterial activity against gram positive bacteria. The study identifies a new source of antibacterial compounds, which could lead to the development of new drugs, particularly effective against gram positive strains like Bacillus cereus and Streptococcus mutans. Keywords: Lactuca virosa, GC-MS, Docking, ADMET, Antibacterial Activity

Gossypiboma, a retained surgical sponge, is a rare complication following any surgical procedure and is primarily a result of human error. Such patients often have vague clinical presentations and the diagnosis often comes as a surprise and has serious medicolegal implications. We present a case of a 28-year-old female with a long-standing duration of 9 months with purulent discharge from the operated scar site of Lower segment caesarean section done 2 years back and then diagnosed to have a gossypiboma in the ureterovesical space causing structuring of the ipsilateral ureter which was successfully managed by Exploratory laparotomy with removal of the retained gossypiboma and right sided ureteric reimplantation.

Abstract Disabled 2 (Dab2), an adaptor protein, is up regulated in the hair follicle stem cells (HFSCs); however, its role in any tissue stem cells has not been studied. In the present study, we have reported that Dab2 conditional knockout (Dab2-cKO) mice exhibited a delay in the HF cycle due to perturbed activation of HFSCs. Further, Dab2-cKO mice showed a reduction in the number of HFSCs and reduced colony forming ability of HFSCs. Dab2-cKO mice showed extended quiescence of HFSCs concomitant with an increased expression of Nfatc1. Dab2-cKO mice showed a decreased expression of anti-aging genes such as Col17a1, decorin, Sirt2 and Sirt7. Dab2-cKO mice did not show full hair coat recovery in aged mice thereby suggesting an accelerated aging process. Overall, we unveil for the first time, the role of Dab2 that regulate activation and self-renewal of HFSCs.

Abstract Human immunodeficiency virus type-1 (HIV-1) is responsible for significant mortality and morbidity worldwide. Despite complete control of viral replication with antiretrovirals, cells with integrated HIV-1 provirus can produce viral transcripts. In a cross-sectional study of 84 HIV+ individuals of whom 43 were followed longitudinally, we found that HIV-1 RNAs are present in extracellular vesicles (EVs) derived from cerebrospinal fluid and serum of all individuals. We used seven digital droplet polymerase chain reaction assays to evaluate the transcriptional status of the latent reservoir. EV-associated viral RNA was more abundant in the CSF and correlated with neurocognitive dysfunction in both, the cross-sectional and longitudinal studies. Sequencing studies suggested compartmentalization of defective viral transcripts in the serum and CSF. These findings suggest previous studies have underestimated the viral burden and there is a significant relationship between latent viral transcription and CNS complications of long-term disease despite the adequate use of antiretrovirals.

Rainfall is the major component of the hydrologic cycle and it is the primary source of runoff. The main purpose of this study was to estimate daily discharge by employing an Adaptive Neuro-Fuzzy Inference System (ANFIS) model using rainfall and soil moisture data at three different depths (5 cm, 100 cm and bedrock) for the Damanganga basin. The length of the data for the study period 1983–2022 is 39 years. The model employed nine membership functions for each variable of soil moisture, rainfall, discharge and 30 rules were optimized. The results were compared considering a range of model performance indicators as correlation coefficient (R2) and Nash–Sutcliffe efficiency (NSE) coefficient. The model application results shows that soil moisture at bedrock gives more precise value of daily discharge with (R2) and NSE value as 0.9936 and 0.9981, respectively, as compared to the soil moisture at depths of 5 and 100 cm. The better results obtained for the measurement of soil moisture in the deeper soil layer are consistent with the hydrological behavior anticipated for the analyzed catchment, where the root-zone soil layer is the driver of the runoff response rather than the surface observations. This study can be helpful to hydrologists in selecting appropriate rainfall–runoff models. HIGHLIGHTS To estimate the daily discharge by employing an Adaptive Neuro-Fuzzy Inference System (ANFIS) model using rainfall and soil moisture data.; The model employed nine membership functions for each variable of soil moisture, rainfall, discharge and 30 rules were optimized.; The results were compared considering a range of model performance indicators such as correlation coefficient (R2) and Nash-Sutcliffe efficiency (NSE) coefficient.;

The urban population of the world houses almost 13% in low-elevation coastal zones (LECZ). Major cities with a population of more than five million, which account for almost two-thirds of the world's large cities, reside in low-elevation coastal zones. These areas house some of the most important socioeconomic activities, and they are also environmentally delicate. According to the IPCC 2007 report, there will be an 8–88 cm rise in sea level between 2000 and 2100 AD, which will have an unpredictable and massive impact on land up to 9 m elevation above MSL. This study discusses the rise in sea level, climate vulnerability, and future problems using elevation-based GIS analysis, accomplishing socioeconomic vulnerability and exposure. The statistics suggest that more than 26% of the population lies within a 9 m contour interval, whereas a 20 m contour accommodated 81% of the total population. In figures, it is estimated that over 1,632,200 people by 2011, which is expected to rise to 4,048,894 people by 2050, are exposed to 100-year flood events. Thus, the study clinched that a significant number of people in Surat confront flooding due to the extreme rise in water level during this period. HIGHLIGHTS Approximately 81.10% district population lived within 20 m of MSL in 2011.; The major population is accumulated within 9–20 m range approximately 54.41%.; By 2080, in worst-case SSPs585 (80 cm rise), approximately 9,536,712 individuals with US $3,004.35 billion value of assets will be subjected to 1 in 100-YRP.; For SSPs245, 3.617 m SLR would put around 4,168,260 individuals and assets worth over US$710.73 billion at risk of flooding by 2050.;

Background: Dengue fever and scrub typhus are endemic diseases in India. The aim was to study and compare clinical, biochemical, and hematological parameters between the dengue and dengue-scrub study groups. Materials and Methods: A retrospective hospital-based, cross-sectional study conducted at a tertiary care rural center. Various clinical, biochemical, and hematological parameters of dengue patients with random selection as the control group were compared with the dengue-scrub coinfection group (46 cases) as cases. The statistical significance was determined using an independent t-test. P < 0.05 was considered statistically significant. The t-test and the Mann–Whitney U-test were used. Results: Among the 86 cases (2.05%), scrub and dengue contributed 46 cases, followed by 27 cases of COVID-19 and dengue, four cases of malaria and scrub, three cases of malaria and dengue, and a single case of dengue with typhoid and leptospirosis with dengue. Serum albumin (P = 0.003, moderate effect size), serum globulin (P = 0.001, large effect size), alkaline phosphatase (P = 0.001, moderate effect size), and serum urea (P = 0.012, moderate effect size) levels were significantly different between only dengue and dengue-scrub group. In addition, the difference in hemoglobin levels, red blood cell count, white blood cell count, platelet count, cell variables, and ratios of those with dengue and scrub versus those with only dengue was significant (P < 0.05) with moderate-to-large effect size. Conclusion: Certain biochemical and hematological parameters such as albumin, globulin, alkaline phosphatase, platelet count, neutrophil-to-lymphocyte ratio, and platelet lymphocyte ratio can be used to support the diagnosis of coinfection (dengue-scrub).

Background: Diabetes is the leading cause of death and disability among cardiovascular disease patients. By 2025, India will have people with diabetes to one in every five diabetics worldwide. Aim: The study examines the relationship between glycosylated hemoglobin (HbA1c) levels and left ventricular diastolic dysfunction (LVDD) in type 2 diabetes patients. Settings and Design: This was a cross-sectional observational study. Materials and Methods: Over 2 years, 345 subjects with type 2 diabetes mellitus who gave informed consent and met the inclusion criteria were studied. The HbA1c test was performed using ion-exchange high-performance liquid chromatography. Electrocardiogram and two-dimensional echocardiography were used to evaluate cardiac dysfunctions. The relationship between potential variables and outcomes was determined using logistic regression. Statistical Analysis: All statistical analyses were carried out using STATA version 13 (College Station, TX: Stata Corp LP). Results: Mean HbA1c levels were found to be higher in patients with LVDD (10.40% ± 4.25%) compared to normal LVDD (7.51% ±3.18%) (P = 0.004) in the current study. The predicted left ventricular (LV) function with an area under the receiver operating characteristic curve of 0.883. Conclusions: LVDD is a common finding in people with type 2 diabetes. LVDD causes various cardiac complications, including LV hypertrophy, which is concerning. The current findings suggest that HbA1c is a reliable predictor of LVDD that can be used for screening in resource-limited areas where echocardiography is unavailable. In addition, regular HbA1c screening and blood sugar control can help prevent cardiovascular complications caused by LVDD in type 2 diabetic patients.

Background: There is no surrogate biological marker for detecting stroke. Because of this, mean platelet volume (MPV) and RDW may be used to predict the occurrence of stroke. Aim: This study aims to see if there is a link between platelet volume and acute ischemic stroke, as well as between red cell distribution width and acute ischemic stroke. Setting and Design: This was a cross-sectional study from February 2021 to January 2023. Materials and Methods: The present cross-sectional study was conducted to assess the role of mean platelet volume and red cell distribution width in acute ischemic stroke. Statistical Analysis: For the analysis, SPSS version 20 was utilized. Results: A total of 300 patients were included in this study. The small vessel infarct (9.05 ± 1.24 fL) had less MPV than the large vessel infarct (9.10 ± 1.10 fL), but there was no statistically significant difference between the two (P = 0.74). The average red blood cell width was lower in minor stroke infarcts (15.06% ±2.01%) than in large stroke infarcts (15.5% ±7.26%), but no statistically significant difference was found in the study. Fifty-three (17.67%) patients had a deadly outcome, and 247 (82.33%) had been cured when a final diagnosis was made. Conclusions: Stroke is the world’s leading cause of mortality, caused by cerebral vascular blockage or hemorrhage. However, there is no biological substitute marker for stroke diagnosis. RDW and MPV are potential biomarkers for this function and can forecast the incidence of stroke.

A significant clinical challenge in patients with colorectal cancer (CRC), which adversely impacts patient survival, is the development of therapy resistance leading to a relapse. Therapy resistance and relapse in CRC is associated with the formation of lipid droplets (LD) by stimulating de novo lipogenesis (DNL). However, the molecular mechanisms underlying the increase in DNL and the susceptibility to DNL-targeted therapies remain unclear. Our study demonstrates that colorectal drug-tolerant persister cells (DTPs) over-express Lipin1 (LPIN1), which facilitates the sequestration of free fatty acids into LDs. The increased expression is mediated by the ETS1-PTPN1-c-Src-CEBPβ pathway. Blocking the conversion of free fatty acids into LDs by treatment with statins or inhibiting lipin1 expression disrupts lipid homeostasis, leading to lipotoxicity and ferroptotic cell death in both DTPs and patient-derived organoids (PDOs) in vitro. Ferroptosis inhibitors or N-acetylcysteine (NAC) can alleviate lipid ROS and cell death resulting from lipin1 inhibition. This strategy also significantly reduces tumor growth in CRC DTP mouse xenograft and patient-derived xenograft (PDX) models. Our findings highlight a new metabolic vulnerability in CRC DTPs, PDO, and PDX models and provide a framework for the rational repurposing of statins. Targeting the phosphatidic acid (PA) to diacylglycerol (DAG) conversion to prevent lipid droplet formation could be an effective therapeutic approach for therapy-resistant CRC.

ABSTRACT Nitric oxide (·NO) is one of the toxic metabolites that bacteria can be exposed to within phagosomes. Gre factors, which are also known as transcript cleavage factors or transcription elongation factors, relieve back-tracked transcription elongation complexes by cleaving nascent RNAs, which allows transcription to resume after stalling. Here we discovered that loss of both Gre factors in Escherichia coli, GreA and GreB, significantly compromised ·NO detoxification due to ·NO-induced phenotypic heterogeneity in ΔgreAΔgreB populations, which did not occur in wild-type cultures. Under normal culturing conditions, both wild-type and ΔgreAΔgreB synthesized transcripts uniformly, whereas treatment with ·NO led to bimodal transcript levels in ΔgreAΔgreB that were unimodal in wild-type. Interestingly, exposure to another toxic metabolite of phagosomes, hydrogen peroxide (H2O2), produced analogous results. Furthermore, we showed that loss of Gre factors led to cheating under ·NO stress where transcriptionally deficient cells benefited from the detoxification activities of the transcriptionally proficient subpopulation. Collectively, these results show that loss of Gre factor activities produces phenotypic heterogeneity under ·NO and H2O2 stress that can yield cheating between subpopulations.IMPORTANCEToxic metabolite stress occurs in a broad range of contexts that are important to human health, microbial ecology, and biotechnology, whereas Gre factors are highly conserved throughout the bacterial kingdom. Here we discovered that loss of Gre factors in E. coli leads to phenotypic heterogeneity under ·NO and H2O2 stress, which we further show with ·NO results in cheating between subpopulations. Collectively, these data suggest that Gre factors play a role in coping with toxic metabolite stress, and that loss of Gre factors can produce cheating between neighbors.

Genotyping is the process of determining the genetic makeup of an organism by examining its DNA sequences using various genetic markers. It has been widely used in various fields, such as agriculture, biomedical and conservation research, to study genetic diversity, inheritance, the genetic basis of disease-associated traits, evolution, adaptation, etc., Genotyping markers have evolved immensely and are broadly classified as random markers (RFLP, RAPD, AFLP, etc.) and functional markers (SCoT, CDDP, SRAP, etc.). However, functional markers are very limited in genotype studies, especially in animal science, despite their advantages in overcoming the limitations of random markers, which are directly linked with phenotypic traits, high specificity, and similar logistic requirements. The current review surveyed the available random and functional markers for genotyping applications, focusing on livestock including plant and microbe domains. This review article summarises the application, advantages, and limitations of developed markers and methods for genotyping applications. This review aims to make the reader aware of all available markers, their design principles, and methods, and we discuss the marker inheritance patterns of RLFP and AFLP. The review further outlines the marker selection for particular applications and endorses the application of functional markers in genotyping research.

ABSTRACT Background Immune stressors, such as lipopolysaccharides (LPS), profoundly affect microbiota balance, leading to gut dysbiosis. This imbalance disrupts the metabolic phenotype and structural integrity of the gut, increasing intestinal permeability. During puberty, a critical surge in estrogen levels is crucial for mammary gland development. However, inflammation originating from the gut in this period may interfere with this development, potentially heightening breast cancer risk later. The long‐term effects of pubertal inflammation on mammary development and breast cancer risk are underexplored. Such episodes can dysregulate cytokine levels and microRNA expression, altering mammary cell gene expression, and predisposing them to tumorigenesis. Methods This study hypothesizes that prebiotics, specifically Lentinula edodes Cultured Extract (AHCC), can counteract LPS's adverse effects. Using BALB/c mice, an acute LPS dose was administered at puberty, and breast cancer predisposition was assessed at 13 weeks. Cytokine and tumor‐related microRNA levels, tumor development, and cancer stem cells were explored through immunoassays and qRT‐PCR. Results Results show that LPS induces lasting effects on cytokine and microRNA expression in mammary glands and tumors. AHCC modulates cytokine expression, including IL‐1β, IL‐17A/F, and IL‐23, and mitigates LPS‐induced IL‐6 in mammary glands. It also regulates microRNA expression linked to tumor progression and suppression, particularly counteracting the upregulation of oncogenic miR‐21, miR‐92, and miR‐155. Although AHCC slightly alters some tumor‐suppressive microRNAs, these changes are modest, highlighting a complex regulatory role that warrants further study. Conclusion These findings underscore the potential of dietary interventions like AHCC to mitigate pubertal LPS‐induced inflammation on mammary gland development and tumor formation, suggesting a preventive strategy against breast cancer.

ObjectiveKyasanur Forest Disease (KFD) is a viral zoonosis reported from Karnataka, India. We investigated cases in the Shivamogga district, Karnataka, to describe the epidemiology and identify risk factors in the affected block in 2022.MethodsA case was defined as a laboratory-confirmed KFD-positive resident of Shivamogga from 1 January-31 May 2022. We extracted the records of KFD cases from district surveillance. We conducted a 1:3 case-control study in the Thirthahalli block. We enrolled laboratory-confirmed KFD-positive Thirthahalli residents from January to May 2022 as cases, and residents without “fever with myalgia” as controls. We reported adjusted odds ratios (aOR) with 95% confidence intervals (CI).ResultsShivamogga reported 35 cases, with a median age of 46 (4–75) years, of which 51% were men, and one death. Among 25 cases and 90 controls, knowledge of avoiding recent monkey death sites was low (cases = 0%, controls = 11%). Monkey death sites within 500 m [aOR = 8.6 (1.8–41.9)] and household tick exposure [aOR = 3.7 (1.3–10.7)] were independent risk factors.ConclusionThis was a laboratory-confirmed cluster of KFD cases in Thirthahalli, with residence near a monkey death site and household tick exposure considered significant risk factors. We recommend evaluating monkey carcass disposal procedures and increasing awareness of tick protective measures.

Over the past three decades, there has been an increase in the severity of fungal infections, affecting several individuals and claiming the lives of more than 1.6 million people every year. Species of Candida are one of the causatives of invasive fungal infections, and the extensive use of antifungals for their treatment has led to the emergence of drug resistance in these species, highlighting the need for the exploration of effective and cost-effective therapeutics. Drug repurposing is an important solution for alternative therapeutics. There are many studies where antifungal indications of any existing drug have been analyzed with an aim to establish new antimycotic therapeutics in a short time and with a lower budget. In this review, efforts are made to compile the literature on repurposed drugs against clinical isolates of Candida and fungal pathogens to better illustrate drug repurposing's role in the treatment of candidiasis.