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Abstract This study addresses the critical need for effective groundwater (GW) management in Muzaffarabad, Pakistan, amidst challenges posed by rapid urbanization and population growth. By integrating Support Vector Machine (SVM) and Weight of Evidence (WOE) techniques, this study aimed to delineate GW potential zones and assess water quality. This study fills the gap in applying advanced machine learning and geostatistical methods for accurate GW potential mapping. Eight thematic layers based on topography, hydrology, geology, and ecology were utilized to compute the GW potential model. Additionally, water quality analysis was performed on collected samples. The findings indicate that flat and gently sloping terrains, areas with an elevation range of 611 –687 m, and concave slope geometries are associated with higher GW potential. Additionally, proximity to drainage and high-density lineament zones contribute to increased GW potential. The results showed that 31.1% of the area had excellent GW potential according to the WOE model, whereas the SVM model indicated that only 20.3% fell in the excellent potential zone. Results showed that both models performed well in the delineating GW potential zones. Nevertheless, the application of the SVM method is highly recommended which will be benefited in GW resources management related to urban planning. The study also evaluates the spatial distribution of GW quality, with a focus on physical and chemical parameters, including electrical conductivity, pH, turbidity, total dissolved solids, calcium, magnesium, chloride, nitrate, and sulphate. Bacterial contamination assessment reveals that 76% of spring water samples (30 out of 39 samples) are contaminated with E.coli, raising public health concerns. Based on the chemical analysis of GW samples the study identified exceedances of WHO guidelines for calcium in two samples, magnesium in seven samples, sulphate in ten samples, and nitrate levels were below the WHO guideline across all samples. These results highlight localized chemical contamination issues that require targeted remediation efforts to safeguard water quality for public health.

Background: Depression, affecting 350 million globally, poses significant morbidity and mortality. The correlation between major depressive disorder (MDD) and obesity is noted, with studies indicating poorer treatment outcomes among obese individuals. Measuring weight and body mass index (BMI) could aid in predicting depression treatment outcomes, influencing drug efficacy due to their ease of measurement, amid the shared public health burden of MDD and obesity. Aims and Objectives: The aims and objectives of the study are to evaluate baseline BMI’s impact on antidepressant response in newly diagnosed outpatient department (OPD) patients at a tertiary care center. Materials and Methods: This longitudinal observational study was conducted with OPD patients at a tertiary care center, aged 18–65 years with newly diagnosed MDD. Assessment tools included the Diagnostic Criteria for Research accompanying the ICD-10, the Hamilton Rating Scale for Depression, and physical measurement devices. Sample size determination considered BMI groups: Normal to underweight (N1=120), overweight (N2=120), and obese (N3=70). The methodology involved patient history, examination, and follow-up assessments after 6 weeks, analyzing antidepressant response statistically. Results: Obese patients exhibited reduced treatment response rates compared to normal and overweight counterparts. Responders had lower mean BMI. Gender disparities in obesity prevalence were noted. Limitations: The study’s limitations include a small sample size of 310 cases, single-center design, and potential selection bias in a tertiary care setting. Conclusion: The findings underscore the complex relationship between BMI, depression severity, and treatment response. Obese individuals demonstrated higher initial depression scores and poorer treatment response, echoing previous research. The study highlights the need for personalized treatment approaches that consider individual BMI levels to optimize depression management strategies effectively.

Abstract In India, the spatial coverage of air pollution data is not homogeneous due to the regionally restricted number of monitoring stations. In a such situation, utilising satellite data might greatly influence choices aimed at enhancing the environment. It is essential to estimate significant air contaminants, comprehend their health impacts, and anticipate air quality to safeguard public health from dangerous pollutants. The current study intends to investigate the spatial and temporal heterogeneity of important air pollutants, such as sulphur dioxide, nitrogen dioxide, carbon monoxide, and ozone, utilising Sentinel-5P TROPOMI satellite images. A comprehensive spatiotemporal analysis of air quality was conducted for the entire country with a special focus on five metro cities from 2019 to 2022, encompassing the pre-COVID-19, during-COVID-19, and current scenarios. Seasonal research revealed that air pollutant concentrations are highest in the winter, followed by the summer and monsoon, with the exception of ozone. Ozone had the greatest concentrations throughout the summer season. The analysis has revealed that NO2 hotspots are predominantly located in megacities, while SO2 hotspots are associated with industrial clusters. Delhi exhibits high levels of NO2 pollution, while Kolkata is highly affected by SO2 pollution compared to other major cities. Notably, there was an 11% increase in SO2 concentrations in Kolkata and a 20% increase in NO2 concentrations in Delhi from 2019 to 2022. The COVID-19 lockdown saw significant drops in NO2 concentrations in 2020; specifically, − 20% in Mumbai, − 18% in Delhi, − 14% in Kolkata, − 12% in Chennai, and − 15% in Hyderabad. This study provides valuable insights into the seasonal, monthly, and yearly behaviour of pollutants and offers a novel approach for hotspot analysis, aiding in the identification of major air pollution sources. The results offer valuable insights for developing effective strategies to tackle air pollution, safeguard public health, and improve the overall environmental quality in India. The study underscores the importance of satellite data analysis and presents a comprehensive assessment of the impact of the shutdown on air quality, laying the groundwork for evidence-based decision-making and long-term pollution mitigation efforts.

Abstract Rose (Rosa sp.) is one of the most important ornamentals which is commercialize for its aesthetic values, essential oils, cosmetic, perfume, pharmaceuticals and food industries in the world. It has wide range of variations that is mostly distinguished by petal color differences which is interlinked with the phytochemicals, secondary metabolites and antinutrient properties. Here, we explored the color, bioactive compounds and antinutritional profiling and their association to sort out the most promising rose genotypes. For this purpose, we employed both quantitative and qualitative evaluation by colorimetric, spectrophotometric and visual analyses following standard protocols. The experiment was laid out in randomized complete block design (RCBD) with three replications where ten rose genotypes labelled R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 were used as plant materials. Results revealed in quantitative assessment, the maximum value of lightness, and the luminosity indicating a brightening of rose petals close to a yellow color from rose accessions R4, and R10, respectively which is further confirmed with the visually observed color of the respective rose petals. Proximate composition analyses showed that the highest amount of carotenoid and β-carotene was found in R10 rose genotype, anthocyanin and betacyanin in R7. Among the bioactive compounds, maximum tocopherol, phenolic and flavonoid content was recorded in R8, R6 and R3 while R1 showed the highest free radical scavenging potentiality with the lowest IC50 (82.60 µg/mL FW) compared to the others. Meanwhile, the enormous variation was observed among the studied rose genotypes regarding the antinutrient contents of tannin, alkaloid, saponin and phytate whereas some other antinutrient like steroids, coumarines, quinones, anthraquinone and phlobatanin were also figured out with their presence or absence following qualitative visualization strategies. Furthermore, according to the Principal Component Analysis (PCA), correlation matrix and cluster analysis, the ten rose genotypes were grouped into three clusters where, cluster-I composed of R3, R4, R5, R8, cluster-II: R9, R10 and cluster-III: R1, R2, R6, R7 where the rose genotypes under cluster III and cluster II were mostly contributed in the total variations by the studied variables. Therefore, the rose genotypes R9, R10 and R1, R2, R6, R7 might be potential valuable resources of bioactive compounds for utilization in cosmetics, food coloration, and drugs synthesis which have considerable health impact.

INTRODUCTION: India faces a burgeoning burden of type 2 diabetes mellitus, projected to reach 87 million by 2030, with alarmingly high undiagnosed cases. Early identification remains crucial for targeted health interventions. This study employed a validated risk assessment tool to identify high-risk individuals and explore associations with diabetes risk factors. Material and Methods: This cross-sectional study was conducted for 3 months among nondiabetic consenting adults (above 18 years) attending a limited-resource urban primary health center in the field practice area of a teaching hospital in Uttar Dinajpur, West Bengal. A predesigned, pretested schedule containing domains on sociodemographics, dietary, medical history, and validated risk assessment tool - the Indian Diabetes Risk Score (IDRS) was used to collect data from an estimated sample of 112 adults. RESULTS: Of all the participants who underwent diabetes risk assessment, the majority (67.9%) were females and residents (71.4%) of adjacent rural areas. Findings showed that the majority of participants were in the moderate-high risk category of developing diabetes, of which 16.07% had high, 57.14% had moderate, and 26.78% had low risk with an overall mean (standard deviation) risk score of 39.11 (18.63). Bivariate analysis showed a statistically significant relationship (P < 0.05) between diabetes risk score with age, education, hypertension, physical activity, dietary salt intake, and family history of diabetes. CONCLUSION: Simple, noninvasive diabetes risk assessment tools like IDRS provide cost-effective solutions in identifying at-risk individuals in primary care settings; therefore, it should be implemented in limited resource settings for early risk identification and management of diabetes, consequently decreasing the disease burden.

Abstract In general, defects are crucial in designing the different properties of two-dimensional materials. Therefore large variations in the electric and optical characteristics of two-dimensional layered molybdenum disulphide might be attributed to defects. This study presents the design of a temperature and nitrogen sensor based on few-layer molybdenum disulfide sheets (FLMS), which was developed from bulk MoS2 (BMS) through an exfoliation approach. The produced sulfur defect, molybdenum defect, line defect, and plane defect were characterized by scanning transmission electron microscopy (STEM), which substantially impacts the sensing characteristics of the resulting FLMS. Our theoretical analysis validates that the sulfur vacancies of the MoS2 lattice improve sensing performance by promoting effective charge transfer and surface interactions with target analytes. The FLMS-based sensor showed a high sensitivity for detecting nitrogen gas with a detection limit (LOD) of ~ 0.18 ppm. Additionally, temperature-detecting capabilities were assessed over various temperatures, showing outstanding stability and repeatability. To the best of our knowledge, this material is the first of its kind, demonstrating visible N2 gas sensing with chromic behaviour.

Abstract Water pollution is a major concern for a decaying river. Polluted water reduces ecosystem services and human use of rivers. Therefore, the present study aims to assess the irrigation suitability of the Jalangi River water. A total of 34 pre-selected water samples were gathered from the source to the sink of the Jalangi River with an interval of 10 km and one secondary station’s data from February 2012 to January 2022 were used for this purpose. The Piper diagram exhibits that the Jalangi River water is Na+–HCO3 − types, and the alkaline earth (Ca2+ + Mg2+) outperforms alkalises (Na+ + K+) and weak acids (HCO3 − + CO3 2−) outperform strong acids (Cl− + SO4 2−). SAR values ranging from 0.35 to 0.64 show that water is suitable for irrigation and poses no sodicity risks. The %Na results show that 91.18% of water samples are good and acceptable for irrigation. RSC levels indicate a significant alkalinity hazard, with 94.12% of samples considered inappropriate for irrigation. PI findings show that 91.18% of water samples are suitable for irrigation. Apart from the spatial water samples, seasonal water samples exhibit a wide variations as per the nature of irrigation hazards. Gibbs plot demonstrates that the weathering of rocks determined the hydro-chemical evolution of Jalangi River water. This study identifies very little evaporation dominance for pre- and post-monsoon water. The analysis of variance (ANOVA) test illustrates that there are no spatial variations in water quality while seasonal variations are widely noted (p

Abstract Human papillomavirus (HPV) drives cervical cancer (CaCx) pathogenesis and viral oncoproteins jeopardize global gene expression in such cancers. In this study, our aim was to identify differentially expressed coding (DEcGs) and long noncoding RNA genes (DElncGs) specifically sense intronic and Natural Antisense Transcripts as they are located in the genic regions and may have a direct influence on the expression pattern of their neighbouring coding genes. We compared HPV16-positive CaCx patients (N = 44) with HPV-negative normal individuals (N = 34) by employing strand-specific RNA-seq and determined the relationships between DEcGs and DElncGs and their clinical implications. By performing Gene set enrichment and protein–protein interaction (PPI) analyses of DEcGs, we identified enrichment of processes crucial for abortive virus life cycle and cancer progression. The DEcGs formed 16 gene clusters which we identified through Molecular Complex Detection (MCODE) plugin of Cytoscape. All the gene clusters portrayed cancer-related functions. We recorded significantly correlated expression levels of 79 DElncGs with DEcGs at proximal genomic loci based on Pearson’s Correlation coefficients. Of these gene pairs, 24 pairs portrayed significantly altered correlation coefficients among patients, compared to normal individuals. Of these, 6 DEcGs of 6 such gene pairs, belonged to 5 of the identified gene clusters, one of which was survival-associated. Out of the 24 correlated DEcG: DElncG pairs, we identified 3 pairs, where expression of both members was significantly associated with patient overall survival. The findings justify the cooperative roles of these gene pairs, in patient prognostication, thereby bearing immense potential for translation. Thus, elucidation of correlative strengths between paired DElncGs and DEcGs in patient and normal samples, could serve as a foundation for identification of therapeutic and prognostic targets of HPV16-positive CaCx. Graphical abstract

Abstract Hybrid development is one of the most promising strategies for boosting crop yields. Parental lines used to create hybrids must have good per se performance and disease resistance for developing superior hybrids. Indian wheat line HD3209 was developed by introducing the rust resistance genes Lr19/Sr25 into the background of popular wheat variety HD2932. The wheat line HD3209 carrying Lr19/Sr25 has been successfully and rapidly converted to the CMS line A-HD3209, with 96.01% background genome recovery, based on selection for agro-morphological traits, rust resistance, pollen sterility, and foreground and background analyses utilizing SSR markers. The converted CMS line A-HD3209 was completely sterile and nearly identical to the recurrent parent HD3209. Based on high per se performance and rust resistance, the study concludes that the derived CMS line A-HD3209 is promising and can be employed successfully in hybrid development.

Background: Sensory processing (SP) indicates the ability of the nervous system to receive, analyze, process, and respond to external sensory input and coordinates motor movements accordingly. Children with various neurodevelopmental disorders, like autism spectrum disorder, have SP issues. However, studies regarding SP issues in attention-deficit/hyperactivity disorder (ADHD) compared to typically developing children are relatively less. Aims and Objectives: To study the SP pattern of children with ADHD, to compare with the control group, and to study the correlation of symptom severity with SP deficit in children with ADHD. Materials and Methods: All children attending the child guidance clinic at R. G. Kar Medical College and Hospital were screened, and children with ADHD without any other comorbid disorder as diagnosed by Diagnostic and Statistical Manual 5 were selected. Their ADHD symptom severity was assessed using the ADHD test, and SP was assessed using the Short Sensory Profile (SSP). Results: The SSP mean score of the children with ADHD was significantly different than the mean score of the control group, and the percentage of children having a definite difference in SP was significantly different in the ADHD children group compared to the control group. The severity of the SP deficit also correlates with the severity of ADHD symptoms, as found by the correlation study. Conclusion: Children with ADHD have shown a definite difference in SP compared to controls, and the severity of the sensory problem is proportionate to the severity of the symptoms of ADHD.

Background Many infancy-onset epilepsies have a poor prognosis for seizure control and neurodevelopmental outcome. Ketogenic diets can improve seizures in older children and adults unresponsive to antiseizure medicines. We aimed to determine the effectiveness of the ketogenic diet in reducing seizure frequency compared to further antiseizure medicine in infants with drug-resistant epilepsy. Methods In this randomised, open-label trial, 136 infants with epilepsy, aged 1–24 months, with > 4 seizures/week and a previous trial of ≥ 2 antiseizure medicines were recruited from 19 hospitals in the United Kingdom. Following a 1- or 2-week observation period, participants were randomised to receive the classical ketogenic diet or a further antiseizure medicine for 8 weeks, using a computer-generated schedule without stratification. Treatment allocation was concealed from research nurses involved in patient care, but not from participants. The primary outcome was the number of seizures/day recorded during weeks 6–8. All analyses were intention to treat. The trial is registered with the European Union Drug Regulating Authorities Clinical Trials Database (2013-002195-40). Findings Between 1 January 2015 and 30 September 2021, 136 eligible infants were randomised. Sixty-one (78%) of 78 assigned to a ketogenic diet and 47 (81%) of 58 assigned to antiseizure medicine had primary outcome data. At 8 weeks, the number of seizures per day, accounting for the baseline rate and randomised group, was not significantly different between groups [median (interquartile range) ketogenic diet 5 (1, 16); antiseizure medicine 3 (2, 11), incidence rate ratio 1.33, 95%, confidence internal 0.84 to 2.11; p = 0.22]. A similar number of infants reported at least one serious adverse event in both groups [antiseizure medicine: 24/56 (43%), ketogenic diet: 40/78 (51%)]. The most common serious adverse events were seizures in both groups. Three infants died during the course of the trial, all of whom were randomised to the ketogenic diet arm; deaths were considered to be unrelated to treatment. Interpretation There was no evidence that a ketogenic diet was better than further antiseizure medicine in achieving seizure control in infants with epilepsy. The two treatments were similarly tolerated and a ketogenic diet appears safe to use in infants with epilepsy. A ketogenic diet could be a treatment option in infants whose seizures continue despite trial of two standard antiseizure medicines. Study registration This study was registered as EudraCT 2013-002195-40. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/10/18) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 16. See the NIHR Funding and Awards website for further award information. Plain language summary Many babies with epilepsy continue to have seizures (‘fits’), despite taking medicines. These babies are unlikely to make the same developmental progress as babies without epilepsy. Ketogenic diets are high in fat and low in carbohydrate and have been shown to reduce seizures in older children and adults. Babies (age 1–24 months) with epilepsy, who still had seizures despite having tried medicines, either started a ketogenic diet or another medicine. They then stayed on this treatment for 8 weeks. We wanted to know whether there was a difference in the number of seizures in the last 2 weeks of treatments compared to before. Seventy-eight babies started a ketogenic diet and 58 started another medicine. Overall, the number of seizures babies had every day was similar in both groups. A similar number of babies in both groups either had to go to hospital for some reason or stay in hospital for longer. This was mostly because of seizures. Two babies suffered ‘sudden unexpected death in epilepsy’ and another died during a planned surgery. These deaths were not thought to be related to the ketogenic diet. Both the ketogenic diet and the medicines helped to reduce the number of seizures in the babies. Babies in both groups had similar side effects. Doctors could consider starting a ketogenic diet in babies who continue to have seizures even though they have tried medicines to stop their seizures. Scientific summary Background Many infancy-onset epilepsies are poorly responsive to antiseizure medicines (ASMs) with poor prognosis for neurodevelopmental outcome. Ketogenic diets (KDs), which are high-fat, low-carbohydrate diets, have been shown to reduce seizures in older children with drug-resistant epilepsy. No high-quality evidence is available for infants. Objectives In this open-label randomised controlled trial, we compared the efficacy of the classical KD to a further appropriate ASM in infants with drug-resistant epilepsy. The primary outcome was the number of seizures recorded during weeks 6–8, accounting for the baseline rate and randomised group. Secondary outcomes at 8 weeks were the number of infants seizure-free in weeks 6–8 of the intervention period, responder rate (defined as the number showing more than a 50% improvement in seizure frequency compared to baseline), tolerance to KD and relationship between medium-chain fatty acids and seizure control. Secondary outcomes at 12 months were retention on treatment, quality of life and neurodevelopmental outcome. Adverse events were recorded throughout the trial. Serious adverse events were reported to the study sponsor. Methods Infants (age 1–24 months) with epilepsy, with an average ≥ 4 seizures/week and previous trials of ≥ 2 ASMs were recruited from 19 hospitals in the UK. Following a 1- or 2-week observation period, during which there were no changes to regular ASMs (emergency seizure treatments continued as required), participants were randomised to receive a classical KD or a further ASM for 8 weeks, using a computer-generated schedule without stratification. An allocation ratio of 1 : 1.35 was used to account for the therapist effect in the KD group only. Treatment allocation was concealed from research nurses involved in patient care, but not from participants. The primary outcome was the number of seizures/day recorded during weeks 6–8. All analyses were intention to treat. The following assessments were performed in all infants prior to randomisation: medical history, physical examination, administration of the Infant Toddler Quality of Life Questionnaire™ (ITQOL-97; © HealthActCHQ Inc. 2013) and Vineland Adaptive Behaviour Scales (Vineland™-II), and clinical laboratory assessments. Food diaries required for diet calculation were returned from parents/guardians of all participants a maximum of 1 week into the observation period. Parents/carers were asked to keep daily seizure diaries throughout the 8-week treatment periods for participants in both arms. Thereafter, they were requested to reduce seizure recording to at least 1–2 days per week, as clinically indicated, until 28 days before the final 12-month visit, when daily seizure recording recommenced. Follow-up visits were arranged at 4 weeks, 8 weeks, and 6, 9 and 12 months. Assessments included clinical review, physical examination, documentation of seizure frequency from seizure diaries, review of adverse events and concomitant medication, clinical laboratory assessments (8 weeks, and 6 and 12 months) and completion of tolerability questionnaire by parents/carers together with research nurses, the ITQOL-97 (8 weeks and 12 months) and Vineland-II (12 months). After the 8-week assessment, according to the infant’s clinical response to treatment (seizure outcome and tolerability), KD or ASM was then continued or changed; those randomised to the ASM arm then had the opportunity to start KD. Results Of 136 eligible infants, 78 were randomised to KD and 58 to ASM. Of 78 infants who started KD, 67 (86%) continued to 8 weeks, of which 61 (78%) had primary outcome data available; 53 (91% of those randomised to ASM group) started a further ASM, 49 (84%) continued to 8 weeks and 47 (81%) had primary outcome data available. The median number of daily seizures was not significantly different in both groups at 8 weeks [KD 5 (1, 16); ASM 3 (2, 11), incidence rate ratio (IRR) 1.33, 95% confidence interval (CI) 0.84 to 2.11; p = 0.22]. The odds ratio (OR) of achieving ≥ 50% seizure reduction was 1.21 (95% CI 0.55 to 2.65) and 0.88 (0.27 to 2.80) for seizure freedom. A total of 7/63 infants (11%) in the KD group were seizure-free, compared with 6/48 (13%) in the ASM group (OR 0.88, 95% CI 0.27 to 2.80). A higher proportion of infants in the ASM group changed the number or dose of concurrent ASMs during the intervention period [24/48 (50%)] compared to KD [9/66 (14%)]. The side-effect score at 8 weeks was similar in both groups [KD median 40; interquartile range (IQR) 38–42; ASM median 41 IQR 39‒44) and there were no clinically significant differences other than those expected in clinical or laboratory parameters between groups. At 8 weeks, median scores within the ITQOL-97 were numerically higher (suggesting better health) in the KD group for 7 of the 12 concepts. The infant’s pain, its global behaviour, impact on parental time and family cohesion were equal between the two groups, although general perceptions of the infant’s health were numerically higher in the ASM arm. A numerically larger proportion of parents/guardians of infants in the KD group perceived their child’s health to be ‘much better than a year ago’ (10/40, 25%) compared to those in the ASM group (3/32, 9%); numerically more parents/guardians of infants in the ASM group perceived their child’s health to be ‘much worse than a year ago’ (8/32, 25%) compared to those in the KD group (2/40, 5%). Of 66 infants randomised to KD > 12 months before the study end date, 31 (47%) continued the diet to 12 months; of 47 randomised to further ASM > 12 months before the study end date, 21 (45%) continued the ASM to 12 months. For those who reported data, there were no differences between groups for any concept within the ITQOL-97 at 12 months, except for the infant’s temperament and mood (coefficient −6.09, 95% CI −11.63 to −0.54) and the infant getting along with others (coefficient −6.79, 95% CI −12.97 to −0.60), which favoured the ASM group. A similar proportion of parents/guardians of infants in both groups perceived their child’s health to be ‘much better than a year ago’ (12/24 50% ASM; 11/30 37% KD) or ‘much worse than a year ago’ (0/24, 0% ASM; 1/30, 3% KD). Within the Vineland-II there were neither significant differences between groups in the overall standardised score nor domain standard scores at 12 months. The Daily living domain sum of v-scale scores was nominally improved in the ASM group (coefficient 2.23, 95% CI −4.22 to −0.25). A total of 73 serious adverse events (SAEs) were reported in the ASM group and 161 in the KD group. A similar proportion of infants in both groups reported at least 1 SAE (43% ASM; 51% KD) – most commonly seizures. Three infants died in the KD arm, all considered unrelated to treatment. Conclusions There was no evidence that KD was better than further ASM in achieving seizure control in infants with epilepsy. The two treatments were similarly tolerated and KD appeared safe to use in infants with epilepsy. KD could be a treatment option in infants whose seizures continue despite trial of two standard ASMs. Further trials are needed with larger cohorts at 12-month follow-up and beyond, particularly to look at quality of life and neurodevelopment, perhaps with alternative study design. Study registration This study was registered as EudraCT 2013-002195-40. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/10/18) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 16. See the NIHR Funding and Awards website for further award information.

Key Clinical Message Cholecystocolonic fistula occurring as a complication of colonic diverticular disease is a rarely encountered clinical entity in which the patient may remain asymptomatic or present with vague abdominal or systemic symptoms. Imaging studies are usually not very reliable or effective in detecting direct communication between gallbladder and colon. However, indirect signs such as pneumobilia, gallstones, gallbladder adherent to colon and colonic diverticulosis may help reach the diagnosis. Treatment of cholecystocolonic fistula in symptomatic patients is usually surgical. However, in asymptomatic patients or patients with risk factors and comorbidities, non‐surgical options such as conservative management or biliary stenting can be considered.

Key Clinical Message Kawasaki disease (KD), a self‐limiting vasculitis, can present with a broader spectrum of vascular involvements, necessitating early recognition and prompt management. This case exemplifies the importance of involving multiple teams on board in managing complex presentations of KD. It also highlights the importance of close monitoring for the progression of the disease spectrum as well as family education to ensure favorable outcomes. The case also emphasizes the importance of long‐term follow‐up and further research to understand the prognosis, early screening tools, and possible complications due to multi‐organ involvement in KD along with their management strategies. Abstract Kawasaki disease (KD) is a multisystem vascular inflammatory syndrome, which predominantly affects the small and medium vessels in children within the age group of less than 5 years. The most threatened complication is the development of coronary artery aneurysms (CAAs). We present an extremely rare case of KD in a 2‐month, 21‐day‐old male infant with extensive vascular involvement, expanding the disease spectrum beyond the involvement of coronary arteries. These included aneurysmal dilatations of both internal carotid arteries, the descending aorta, bilateral multilevel intercostal arteries, coeliac artery, superior mesenteric artery, and both renal arteries. Implementing a multidisciplinary approach with early treatment via intravenous immunoglobulin (IVIG) and dexamethasone proved to be most effective in the patient's management. Despite unique challenges such as severe coronary dilation and pseudomonas sepsis during the special care, the patient was stabilized and discharged after 11 days of hospital stay, highlighting the importance of early prompt management and a centered approach to evaluate in a broader spectrum. This case emphasizes the importance of long‐term follow‐up and further research to understand the prognosis, early screening tools, and possible complications due to multi‐organ involvement in KD along with their management strategies.

Abstract The recent article by Harit et al. in Human Genomics reported a novel association of the C allele of rs479200 in the human EGLN1 gene with severe COVID-19 in Indian patients. The gene in context is an oxygen-sensor gene whose T allele has been reported to contribute to the inability to cope with hypoxia due to increased expression of the EGLN1 gene and therefore persons with TT genotype of EGLN1 rs479200 are more susceptible to severe manifestations of hypoxia. In contrast to this dogma, Harit et al. showed that the C allele is associated with the worsening of COVID-19 hypoxia without suggesting or even discussing the scientific plausibility of the association. The article also suffers from certain epidemiological, statistical, and mathematical issues that need to be critically elaborated and discussed. In this context, the findings of Harit et al. may be re-evaluated.

Abstract Background Small extracellular vesicle (sEV) analysis can potentially improve cancer detection and diagnostics. However, this potential has been constrained by insufficient sensitivity, dynamic range, and the need for complex labeling. Methods In this study, we demonstrate the combination of PANORAMA and fluorescence imaging for single sEV analysis. The co-acquisition of PANORAMA and fluorescence images enables label-free visualization, enumeration, size determination, and enables detection of cargo microRNAs (miRs). Results An increased sEV count is observed in human plasma samples from patients with cancer, regardless of cancer type. The cargo miR-21 provides molecular specificity within the same sEV population at the single unit level, which pinpoints the sEVs subset of cancer origin. Using cancer cells-implanted animals, cancer-specific sEVs from 20 µl of plasma can be detected before tumors were palpable. The level plateaus between 5–15 absolute sEV count (ASC) per µl with tumors ≥8 mm3. In healthy human individuals (N = 106), the levels are on average 1.5 ASC/µl (+/− 0.95) without miR-21 expression. However, for stage I–III cancer patients (N = 205), nearly all (204 out of 205) have levels exceeding 3.5 ASC/µl with an average of 12.2 ASC/µl (±9.6), and a variable proportion of miR-21 labeling among different tumor types with 100% cancer specificity. Using a threshold of 3.5 ASC/µl to test a separate sample set in a blinded fashion yields accurate classification of healthy individuals from cancer patients. Conclusions Our techniques and findings can impact the understanding of cancer biology and the development of new cancer detection and diagnostic technologies.

Abstract Illegal file sharing of copyrighted contents through popular file sharing networks poses an enormous threat to providers of digital contents, such as, games, softwares, music and movies. Though empirical studies of network effects on piracy is a well-studied domain, the dynamics of peer effect in the context of evolving social contagion has not been enough explored using dynamical models. In this research, we methodically study the trends of online piracy with a continuous ODE approach and differential equations on graphs to have a clear comparative view. We first formulate a compartmental model to study bifurcations and thresholds mathematically. We later move on with a network-based analysis to illustrate the proliferation of online piracy dynamics with an epidemiological approach over a social network. We figure out a solution for this online piracy problem by developing awareness among individuals and introducing media campaigns, which could be a valuable factor in eradicating and controlling online piracy. Next, using degree-block approximation, network analysis has been performed to investigate the phenomena from a heterogeneous approach and to derive the threshold condition for the persistence of piracy in the population in a steady state. Considering the dual control of positive peer influence and media-driven awareness, we examine the system through realistic parameter selection to better understand the complexity of the dynamics and suggest policy implications.

Abstract Background System contributors to resident burnout and well-being have been under-studied. We sought to determine factors associated with resident burnout and identify at risk groups. Methods We performed a US national survey between July 15 2022 and April 21, 2023 of residents in 36 specialties in 14 institutions, using the validated Mini ReZ survey with three 5 item subscales: 1) supportive workplace, 2) work pace/electronic medical record (EMR) stress, and 3) residency-specific factors (sleep, peer support, recognition by program, interruptions and staff relationships). Multilevel regressions and thematic analysis of 497 comments determined factors related to burnout. Results Of 1118 respondents (approximate median response rate 32%), 48% were female, 57% White, 21% Asian, 6% LatinX and 4% Black, with 25% PGY 1 s, 25% PGY 2 s, and 22% PGY 3 s. Programs included internal medicine (15.1%) and family medicine (11.3%) among 36 specialties. Burnout (found in 42%) was higher in females (51% vs 30% in males, p = 0.001) and PGY 2’s (48% vs 35% in PGY-1 s, p = 0.029). Challenges included chaotic environments (41%) and sleep impairment (32%); favorable aspects included teamwork (94%), peer support (93%), staff support (87%) and program recognition (68%). Worklife subscales were consistently lower in females while PGY-2’s reported the least supportive work environments. Worklife challenges relating to burnout included sleep impairment (adjusted Odds Ratio (aOR) 2.82 (95% CIs 1.94, 4.19), absolute risk difference (ARD) in burnout 15.9%), poor work control (aOR 2.25 (1.42, 3.58), ARD 12.2%) and chaos (aOR 1.73 (1.22, 2.47), ARD 7.9%); program recognition was related to lower burnout (aOR 0.520 (0.356, 0.760), ARD 9.3%). These variables explained 55% of burnout variance. Qualitative data confirmed sleep impairment, lack of schedule control, excess EMR and patient volume as stressors. Conclusions These data provide a nomenclature and systematic method for addressing well-being during residency. Work conditions for females and PGY 2’s may merit attention first.

Abstract Triticum militinae (2n = 4X = 28, AtAtGG), belonging to the secondary gene pool of wheat, is known to carry resistance to many diseases. Though some disease resistance genes were reported from T. timopheevii, the closest wild relative of T. militinae, there are no reports from T. militinae. Twenty-one T. militinae Derivatives (TMD lines) developed at the Division of Genetics, IARI, New Delhi, were evaluated for leaf and stripe rusts at seedling and adult plant stages. Eight TMD lines (6–4, 6–5, 11–6, 12–4, 12–8, 12–12, 13–7 and 13–9) showed seedling resistance to both leaf and stripe rusts while six TMD lines (7–5, 7–6, 11–5, 13–1, 13–3 and 13–4) showed seedling resistance to leaf rust but adult plant resistance to stripe rust and three TMD lines (9–1, 9–2 and 15) showed seedling resistance to leaf rust but susceptibility to stripe rust. Three TMD lines (2–7, 2–8 and 6–1) with adult plant resistance to leaf and stripe rusts were found to carry the known gene Lr34/Yr18. Ten TMD lines (7–5, 7–6, 9–1, 9–2, 11–5, 11–6, 12–12, 12–4, 12–8, and 15) with seedling resistance to leaf rust, showing absence of known genes Lr18 and Lr50 with linked markers requires further confirmation by the test of allelism studies. As not a single stripe rust resistance gene has been reported from T. militinae or its close relative T. timpopheevii, all the 8 TMD lines (6–4, 6–5, 11–6,12–4, 12–8, 12–12, 13–7 and 13–9) identified of carrying seedling resistance to stripe rust and 3 TMD lines (13–1, 13–3 and 13–4) identified of carrying adult plant resistance to stripe rust are expected to carry unknown genes. Also, all the TMD lines were found to be cytologically stable and thus can be used in inheritance and mapping studies.

Abstract Recent technologies such as spatial transcriptomics, enable the measurement of gene expressions at the single-cell level along with the spatial locations of these cells in the tissue. Spatial clustering of the cells provides valuable insights into the understanding of the functional organization of the tissue. However, most such clustering methods involve some dimension reduction that leads to a loss of the inherent dependency structure among genes at any spatial location in the tissue. This destroys valuable insights of gene co-expression patterns apart from possibly impacting spatial clustering performance. In spatial transcriptomics, the matrix-variate gene expression data, along with spatial coordinates of the single cells, provides information on both gene expression dependencies and cell spatial dependencies through its row and column covariances. In this work, we propose a joint Bayesian approach to simultaneously estimate these gene and spatial cell correlations. These estimates provide data summaries for downstream analyses. We illustrate our method with simulations and analysis of several real spatial transcriptomic datasets. Our work elucidates gene co-expression networks as well as clear spatial clustering patterns of the cells. Furthermore, our analysis reveals that downstream spatial-differential analysis may aid in the discovery of unknown cell types from known marker genes.

Abstract Background Loss of AZGP1 expression is a biomarker associated with progression to castration resistance, development of metastasis, and poor disease-specific survival in prostate cancer. However, high expression of AZGP1 cells in prostate cancer has been reported to increase proliferation and invasion. The exact role of AZGP1 in prostate cancer progression remains elusive. Method AZGP1 knockout and overexpressing prostate cancer cells were generated using a lentiviral system. The effects of AZGP1 under- or over-expression in prostate cancer cells were evaluated by in vitro cell proliferation, migration, and invasion assays. Heterozygous AZGP1± mice were obtained from European Mouse Mutant Archive (EMMA), and prostate tissues from homozygous knockout male mice were collected at 2, 6 and 10 months for histological analysis. In vivo xenografts generated from AZGP1 under- or over-expressing prostate cancer cells were used to determine the role of AZGP1 in prostate cancer tumor growth, and subsequent proteomics analysis was conducted to elucidate the mechanisms of AZGP1 action in prostate cancer progression. AZGP1 expression and microvessel density were measured in human prostate cancer samples on a tissue microarray of 215 independent patient samples. Result Neither the knockout nor overexpression of AZGP1 exhibited significant effects on prostate cancer cell proliferation, clonal growth, migration, or invasion in vitro. The prostates of AZGP1−/− mice initially appeared to have grossly normal morphology; however, we observed fibrosis in the periglandular stroma and higher blood vessel density in the mouse prostate by 6 months. In PC3 and DU145 mouse xenografts, over-expression of AZGP1 did not affect tumor growth. Instead, these tumors displayed decreased microvessel density compared to xenografts derived from PC3 and DU145 control cells, suggesting that AZGP1 functions to inhibit angiogenesis in prostate cancer. Proteomics profiling further indicated that, compared to control xenografts, AZGP1 overexpressing PC3 xenografts are enriched with angiogenesis pathway proteins, including YWHAZ, EPHA2, SERPINE1, and PDCD6, MMP9, GPX1, HSPB1, COL18A1, RNH1, and ANXA1. In vitro functional studies show that AZGP1 inhibits human umbilical vein endothelial cell proliferation, migration, tubular formation and branching. Additionally, tumor microarray analysis shows that AZGP1 expression is negatively correlated with blood vessel density in human prostate cancer tissues. Conclusion AZGP1 is a negative regulator of angiogenesis, such that loss of AZGP1 promotes angiogenesis in prostate cancer. AZGP1 likely exerts heterotypical effects on cells in the tumor microenvironment, such as stromal and endothelial cells. This study sheds light on the anti-angiogenic characteristics of AZGP1 in the prostate and provides a rationale to target AZGP1 to inhibit prostate cancer progression.

Introduction: Urinary bladder cancer is the 10th most common cancer worldwide. Cystoscopy and biopsy/Transurethral Resection of Bladder Tumour (TURBT) are the best techniques for diagnosing and staging urinary bladder cancers. Urothelial Carcinomas (UC), particularly in transurethral resection biopsies, can pose diagnostic difficulties due to limited material. Immunohistochemistry (IHC) plays a valuable role in these settings, and many immunostains are being utilised for diagnostic evaluation. However, the relationship of these immunomarkers with histological grade and their prognostic utility has not been adequately explored. Aim: To analyse expression of Her2Neu, E-cadherin, p63, and GATA3 in UC and its relation with histological grading and prognosis. Materials and Methods: This was an observational cross-sectional study conducted in the Pathology Department of IPGMER and SSKM Hospital, Kolkata, West Bengal, India over two years (November 2020-October 2022). Samples of 100 bladder carcinoma patients with predominant TURBT specimens were included in the study. The histopathological reports and tumour grading were done according to the World Health Organisation (WHO) classification of urinary bladder tumours. The Formalin Fixed Paraffin-embedded (FFPE) sections of the tumour blocks were subjected to IHC staining, and the results were interpreted accordingly. Statistical analysis was performed with the help of the Statistical Package for Social Sciences (SPSS), IBM (version 25.0). Unpaired t-test and Z-test (Standard Normal Deviate) were used to test the significant difference between two proportions. Results: The mean age of the study population was 59.69±14.53 years, and there was a male preponderance (male: female=3.54:1). Histopathological examination revealed 55% to be of low-grade morphology. Overall, 53% of cases were in T1 stage, and the rest were in T2 stage. On IHC analysis, E-cadherin showed a statistically significant decrease in intensity with increasing grade (p-value

Abstract The COVID-19 pandemic has profoundly reshaped human life. The development of COVID-19 vaccines has offered a semblance of normalcy. However, obstacles to vaccination have led to substantial loss of life and economic burdens. In this study, we analyze data from a prominent health insurance provider in the United States to uncover the underlying reasons behind the inability, refusal, or hesitancy to receive vaccinations. Our research proposes a methodology for pinpointing affected population groups and suggests strategies to mitigate vaccination barriers and hesitations. Furthermore, we estimate potential cost savings resulting from the implementation of these strategies. To achieve our objectives, we employed Bayesian data mining methods to streamline data dimensions and identify significant variables (features) influencing vaccination decisions. Comparative analysis reveals that the Bayesian method outperforms cutting-edge alternatives, demonstrating superior performance.

Background: Awareness during anesthesia is a major anesthetic concern. Depth of anesthesia is commonly assessed in clinical practice by the patient’s clinical signs and symptoms such as blood pressure, heart rate variability, and body movement. At present, many studies have focused on qCON monitoring for sedative depth, but only a few studies have focused on qNOX monitoring for analgesic depth. Aims and Objectives: The aim of the present study was to evaluate the relative efficacy of qCON and qNOX versus commonly used vital signs such as blood pressure and heart rate in monitoring the anesthetic depth and analgesia. Materials and Methods: A total of 100 patients of either sex and of ASA Physical status I & II, scheduled for urogenital surgeries, were selected and randomly placed into two groups. Group A was monitored by conventional clinical technique and Group B was monitored by qCON and qNOX indices. The primary outcome was the total dose of propofol and fentanyl required to maintain the depth of anesthesia and analgesia. The secondary outcomes were propofol and fentanyl adjustment frequency, infusion duration, and quality of recovery from anesthesia. Results: Results showed statistically significant differences between the two groups in mean dose of both propofol (P=0.000) and fentanyl (P=0.006), adjustment frequency of both propofol (P=0.000) and fentanyl (P=0.010), time required to voluntary eye-opening (P=0.000) and extubation time (P=0.000) and visual analog scale score (P=0.000). There was no statistically significant difference found in infusion duration (P=0.317) and Ramsay Sedation Score (P=0.709) between the groups. Conclusion: Using the qCON and qNOX indices, an anesthesiologist can monitor the depth of anesthesia and analgesia more effectively and can adjust the anesthetic or analgesic drug dosing in a better possible way with lesser requirement of drugs than with conventional clinical monitoring.

Abstract Objectives Intraoperative frozen-section evaluation is a valuable technique for detecting positive margins intraoperatively for oral squamous cell carcinoma. We conducted this study to determine the diagnostic accuracy of frozen section in detecting margin status and the effect of tumor grade and stage on diagnostic accuracy. Results A total of 251 biopsy-proven cases of oral squamous cell carcinoma were included in this study. The tissue specimen resected during surgery was sent to the laboratory for frozen section evaluation. The frozen section results were then compared with the permanent section results to determine the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy. The mean age of the patients included in the study was 51.65 ± 10.03 years, with male predominance (55.4%). The overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of frozen section were 88.81%, 94.84%, 95.20%, 88.10%, and 91.63%, respectively. We conclude that frozen section is a useful technique in determining the margin status intraoperatively in oral cancers, with high diagnostic accuracy. Moreover, certain clinical parameters such as age, gender, disease duration, and tumor stage and grade appear to affect the diagnostic accuracy of frozen section.

Background: A small number of studies are available to assess the role of stressful life events (SLEs) in obsessive-compulsive disorder (OCD). The previous studies have reported contradictory results and they have methodological limitations. Aims and Objectives: The objectives of our study are (i) to find out the frequency of life events in patients with OCD in comparison to their matched healthy controls and (ii) to find out the impact of life events on the severity of the disorder. Materials and Methods: Sixty patients fulfilling Diagnostic and Statistical Manual of Mental Disorder, 5th edition (DSM-V) criteria of OCD were rated with Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Rating Scale for Anxiety (HAM-A), Hamilton Rating Scale for Depression (HAM-D), and Presumptive Stressful Life Events Scale (PSLES). A group of 60 normal controls were also rated on PSLES. Finally, both groups were compared in terms of life events. Results: The frequency of life events, past 1 year (t=5.307, P=0.006) and lifetime (t=11.527, P

Background: Supraglottic airway devices are frequently used instead of endotracheal intubation in laparoscopic surgeries. Two such devices, I-gel (IG) and Baska mask (BM), have been compared with respect to their sealing properties and leak fraction (LF) in comparison to the endotracheal tube. Aims and Objectives: The aim of the present study is to compare the performance of IG and BM with endotracheal tube in patients undergoing laparoscopic cholecystectomy under general anesthesia. Materials and Methods: In this randomized trial, 84 patients scheduled for laparoscopic cholecystectomy under general anesthesia were randomized to group (endotracheal tube [ETT], n=28), group BM (BM, n=28), or group IG (IG, n=28). All the patients received standard general anesthesia and the airway was maintained with either of three devices. The primary outcomes were the difference in the LF and airway sealing pressure (ASP) at different time points before and after pneumoperitoneum. Secondary outcomes were insertion-time, number of insertion attempts, and gastric insufflations. Heart rate and blood pressure were recorded. Complications such as sore throat, coughing, laryngospasm, blood staining of the device, and aspiration were noted. Results: P-values of LF of the three groups at time points T- after insertion (Ti), T-after pneumoperitoneum (Tp), and T- after peritoneal deflation (Tr) were 0.000 each and P-values of ASP at those time points were 0.000 each, respectively. Insertion time was significantly less for IG than ET (P

Abstract Macrophages are associated with innate immune response and M1-polarized macrophages exhibit pro-inflammatory functions. Nanoparticles of natural or synthetic compounds are potential triggers of innate immunity. As2O3 is the major component of the homeopathic drug, Arsenic album 30C.This has been claimed to have immune-boosting activities, however, has not been validated experimentally. Here we elucidated the underlying mechanism of Ars. alb 30C-mediated immune priming in murine macrophage cell line. Transmission Electron Microscopy (TEM) and X-ray diffraction (XRD) used for the structural analysis of the drug reveals the presence of crystalline As2O3 nanoparticles of cubic structure. Similarly, signatures of M1-macrophage polarization were observed by surface enhanced Raman scattering (SERS) in RAW 264.7 cells with concomitant over expression of M1 cell surface marker, CD80 and transcription factor, NF-κB, respectively. We also observed a significant increase in pro-inflammatory cytokines like iNOS, TNF-α, IL-6, and COX-2 expression with unaltered ROS and apoptosis in drug-treated cells. Enhanced expression of Toll-like receptors 3 and 7 were observed both in transcriptional and translational levels after the drug treatment. In sum, our findings for the first time indicated the presence of crystalline As2O3 cubic nanostructure in Ars. alb 30C which facilitates modulation of innate immunity by activating macrophage polarization.

Background: Anemia is a clinical sign of the most prevalent nutritional deficiency in pregnant women worldwide. Histopathological study of the placenta provides valuable information on changes due to anemia in pregnancy. Aim: The present study was undertaken to evaluate the significance of macroscopic and histopathological changes in the placenta due to deficiency anemia in pregnancy consequently affecting the delivery outcome. Material and methods: An observational, prospective, cross-sectional study was conducted for one year. All the obstetric patients having hemoglobin (Hb) less than 11gm/dl were included in the study. After applying the exclusion criteria, 57 cases were included in the study. After delivery, the placenta was collected, fixed in formalin, weight measured, dimensions noted and volume was calculated. Gross features were noted and representative tissue was taken for histopathological study. Results: Term pregnancy was found commonly in mild anaemia (17 cases, 30%), preterm delivery in moderate anemia (14 cases, 25%), and Intrauterine fetal death (IUFD) /abortion in severe anemia (2 cases, 3%). The frequency of the presence of increased placental weight, decreased vascularity, increased fibrosis, and endarteritis are obliterans was found significantly higher in higher grades of anemia than in mild anemia. The same gross and histopathological features were significantly associated with poor obstetric outcomes (IUFD/abortion, preterm delivery) than good obstetric outcomes (term pregnancy). Conclusion: Studies of the placenta have a significant role in understanding the pathophysiology of anemia in pregnancy.

Abstract Accurate and in-time prediction of crop yield plays a crucial role in the planning, management, and decision-making processes within the agricultural sector. In this investigation, utilizing area under irrigation (%) as an exogenous variable, we have made an exertion to assess the suitability of different hybrid models such as ARIMAX (Autoregressive Integrated Moving Average with eXogenous Regressor)–TDNN (Time-Delay Neural Network), ARIMAX–NLSVR (Non-Linear Support Vector Regression), ARIMAX–WNN (Wavelet Neural Network), ARIMAX–CNN (Convolutional Neural Network), ARIMAX–RNN (Recurrent Neural Network) and ARIMAX–LSTM (Long Short Term Memory) as compared to their individual counterparts for yield forecasting of major Rabi crops in India. The accuracy of the ARIMA model has also been considered as a benchmark. Empirical outcomes reveal that the ARIMAX–LSTM hybrid modeling combination outperforms all other time series models in terms of root mean square error (RMSE) and mean absolute percentage error (MAPE) values. For these models, an average improvement of RMSE and MAPE values has been observed to be 10.41% and 12.28%, respectively over all other competing models and 15.83% and 18.42%, respectively over the benchmark ARIMA model. The incorporation of the area under irrigation (%) as an exogenous variable in the ARIMAX framework and the inbuilt capability of the LSTM model to process complex non-linear patterns have been observed to significantly enhance the accuracy of forecasting. The performance supremacy of other hybrid models over their individual counterparts has also been evident. The results also suggest avoiding any performance generalization of individual models for their hybrid structures.

Introduction- A schwannoma is a benign tumor that develops from Schwann cells. It’s known to occur more frequently in women than men, and about one third occur in the head & neck area. However, it is rarely associated with the trigeminal nerve, and especially, schwannomas related to the infraorbital nerve are rare. Case report- A 24-year-old male jute mill worker presented with painless swelling over left side of face for the last 12 years. On examination, localized, nontender, firm 3cm x 3cm swelling was found over left maxilla. Computed Tomography scan showed a well-defined heterogenous oval mass over the left maxilla extending over infraorbital foramen. Aspiration cytology of lesion showed good numbers of spindle cells in groups and dispersedly with fibrous strands. Diagnosis of schwannoma probably arising from terminal branch/trunk of infraorbital nerve was made. Surgical excision of lesion was done under general anesthesia. Histopathological examination of the excised lesion showed grossly firm and gray mass. Microscopically the lesion showed admixture of dense and loose areas referred to as Antoni A and Antoni B areas respectively. Discussion- Infraorbital nerve schwannoma is a possible diagnosis in case of a swelling over the maxilla.

Parents are an essential element of family intervention for all children, including those with autism spectrum disorders (ASDs). We can better understand and address parents’ knowledge gaps about ASD through in-depth research and inquiry into parents’ current level of understanding, attitude, and perception. We aimed to assess the knowledge, attitude, and perception of ASD and influencing factors towards ASD among a group of parents with and without a child diagnosed with ASD in Sakaka, Al-Jouf Region, Saudi Arabia. Using the cross-sectional study design, information from the parents was gathered using a pretested questionnaire that included validated scales for measuring knowledge, attitudes, and perceptions related to ASD. The required number of participants was selected using the convenience sampling method. We used Spearman’s correlation test to determine the strength and direction of correlation between each domain. As a last step, we analyzed the influencing factors using binomial logistic regression. Among the 400 participants, 41.2% had high knowledge, 69.1% had a positive attitude, and 60.3% had a high perception of ASD. We found that knowledge was significantly higher among the parents with autistic individuals in the family (p = 038). The high and positive attitude was significantly greater among females (p = 0.010) and parents with high income (p = 0.007), and the perception was significantly associated with females (p = 0.037) and highly educated participants (p = 0.046). Furthermore, we found a positive correlation between knowledge, attitude, and perception. Overall, only less than half of the participants had a high knowledge of ASD. Hence, we recommend awareness-raising programs for the parents in this region. Furthermore, a prospective study involving parents from all provinces of Saudi Arabia is recommended.

The primary goal is to examine the association between women's decision-making autonomy and utilization of antenatal care services among ever-married women in India. The entire study has been accomplished with the help of secondary data composed from the latest round of the National Family Health Survey (NFHS-5) conducted during 2019-21. A total of 34,618 ever-married women aged 15-49 with at least one live birth preceding five years of the survey have been taken into consideration in this study. Bivariate and multivariate analyses were conducted for proper illustration of the outcome. A sizable proportion of women did not fulfill the WHO-recommended criterion of obtaining ANC services. Utilization of full ANC services is found in some regions of southern, eastern, northern, and northeastern states, and in some districts of Gujarat. After adjusting the other explanatory variables, the result of multivariate analysis indicates that women's autonomy is significantly and positively associated with the utilization of full antenatal care services. Women who participate actively in decision-making are more likely to use full ANC services (AOR: 1.316, 95% CI: 1.197-1.446, p

IntroductionLiterature regarding the impact of esophagectomy approach on hospitalizations costs and short-term outcomes is limited. Moreover, few have examined how institutional MIS experience affects costs. We thus examined utilization trends, costs, and short-term outcomes of open and minimally invasive (MIS) esophagectomy as well as assessing the relationship between institutional MIS volume and hospitalization costs.MethodsAll adults undergoing elective esophagectomy were identified from the 2016-2020 Nationwide Readmissions Database. Multiple regression models were used to assess approach with costs, in-hospital mortality, and major complications. Additionally, annual hospital MIS esophagectomy volume was modeled as a restricted cubic spline against costs. Institutions performing > 16 cases/year corresponding with the inflection point were categorized as high-volume hospitals (HVH). We subsequently examined the association of HVH status with costs, in-hospital mortality, and major complications in patients undergoing minimally invasive esophagectomy.ResultsOf an estimated 29,116 patients meeting inclusion, 10,876 (37.4%) underwent MIS esophagectomy. MIS approaches were associated with $10,600 in increased incremental costs (95% CI 8,800-12,500), but lower odds of in-hospital mortality (AOR 0.76; 95% CI 0.61-0.96) or major complications (AOR 0.68; 95% CI 0.60, 0.77). Moreover, HVH status was associated with decreased adjusted costs, as well as lower odds of postoperative complications for patients undergoing MIS operations.ConclusionIn this nationwide study, MIS esophagectomy was associated with increased hospitalization costs, but improved short-term outcomes. In MIS operations, cost differences were mitigated by volume, as HVH status was linked with decreased costs in the setting of decreased odds of complications. Centralization of care to HVH centers should be considered as MIS approaches are increasingly utilized.

BackgroundTranscatheter mitral valve replacement (TMVR) has garnered interest as a viable alternative to the traditional surgical mitral valve replacement (SMVR) for high-risk patients requiring redo operations. This study aims to evaluate the association of TMVR with selected clinical and financial outcomes.MethodsAdults undergoing isolated redo mitral valve replacement were identified in the 2016-2020 Nationwide Readmissions Database and categorized into TMVR or SMVR cohorts. Various regression models were developed to assess the association between TMVR and in-hospital mortality, as well as additional secondary outcomes. Transseptal and transapical catheter-based approaches were also compared in relation to study endpoints.ResultsOf an estimated 7,725 patients, 2,941 (38.1%) underwent TMVR. During the study period, the proportion of TMVR for redo operations increased from 17.8% to 46.7% (nptrendConclusionsIn this retrospective cohort study, we noted TMVR to yield similar odds of in-hospital mortality as SMVR, but fewer complications and reduced healthcare expenditures. Moreover, transseptal approaches were associated with lower adjusted mortality, shorter pLOS, but higher cost, relative to the transapical. Our findings suggest that TMVR represent a cost-effective and safe treatment modality for patients requiring redo mitral valve procedures. Nevertheless, future studies examining long-term outcomes associated with SMVR and TMVR in redo mitral valve operations, are needed.

BackgroundReversible cerebral vasoconstriction syndrome (RCVS) is a syndrome of recurrent thunderclap headaches and reversible vasoconstriction of the cerebral arteries on neuroimaging within 3 months of onset. Initial non-contrast computed tomography (CT) can reveal abnormalities such as ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage (SAH) can be present in patients with RCVS and may delay diagnosis.AimsWe conducted a systematic review and meta-analysis in accordance with the PRISMA guidelines. We aimed to estimate the prevalence of imaging abnormalities on initial non-contrast CT head in adult patients with RCVS.Data sources & eligibility criteriaWe searched electronic databases including MEDLINE, EMBASE, and the Cochrane Register of Clinical Trials from inception to August 2, 2022. Eligible studies included articles reporting the prevalence of non-contrast CT abnormalities on initial neuroimaging in patients with RCVS, aged 18 and older. Case series, observational studies and clinical trials were included. Data was extracted directly from included papers using a standardized data charting form.ResultsThe search yielded 722 titles with duplicates removed. Twenty studies that included 379 patients with RCVS met inclusion criteria. We classified non-contrast CT abnormalities as either ischemic stroke, ICH, or SAH. We pooled prevalence data using a random effects model with the inverse-variance weighted method. The most common imaging finding was SAH with a pooled prevalence of 24% (95% CI:17%-33%), followed by ICH at 14% (95% CI:8%-22%), and ischemic stroke at 10% (95% CI:7%-14%). The pooled prevalence of any of these imaging abnormalities on initial non-contrast CT was 31% (95% CI:23%-40%). Risk of bias was moderate to very-high-risk for case-series and low-risk for observational studies.ConclusionOur review demonstrates that one-third of patients with RCVS will have an abnormality on initial non-contrast CT head, including either an ischemic stroke, ICH, or SAH. These findings highlight the diagnostic challenges of RCVS imaging and contribute to our understanding of this disease.

BackgroundWhile insurance reimbursements allay a portion of costs associated with cardiac operations, uncovered and additional fees are absorbed by patients. An examination of financial toxicity (FT), defined as the burden of patient medical expenses on quality of life, is warranted. Therefore, the present study used a nationally representative database to demonstrate the association between insurance status and risk of financial toxicity (FT) among patients undergoing major cardiac operations.MethodsAdults admitted for elective coronary artery bypass grafting (CABG) and isolated or concomitant valve operations were assessed using the 2016-2019 National Inpatient Sample. FT risk was defined as out-of-pocket expenditure >40% of post-subsistence income. Regression models were developed to determine factors associated with FT risk in insured and uninsured populations. To demonstrate the association between insurance status and risk of FT among patients undergoing major cardiac operations.ResultsOf an estimated 567,865 patients, 15.6% were at risk of FT. A greater proportion of uninsured patients were at risk of FT (81.3 vs. 14.8%, pConclusionUninsured patients demonstrated higher FT risk after undergoing major cardiac operation. Hispanic race, longer lengths of stay, and combined CABG-valve operations were independently associated with increased risk of FT amongst the uninsured. Conversely, non-income factors did not impact FT risk in the insured cohort. Culturally-informed reimbursement strategies are necessary to reduce disparities in already financially disadvantaged populations.

Introduction Fifty per cent of patients with cancer require radiotherapy during their disease course, however, only 10%–40% of patients in low-income and middle-income countries (LMICs) have access to it. A shortfall in specialised workforce has been identified as the most significant barrier to expanding radiotherapy capacity. Artificial intelligence (AI)-based software has been developed to automate both the delineation of anatomical target structures and the definition of the position, size and shape of the radiation beams. Proposed advantages include improved treatment accuracy, as well as a reduction in the time (from weeks to minutes) and human resources needed to deliver radiotherapy.Methods ARCHERY is a non-randomised prospective study to evaluate the quality and economic impact of AI-based automated radiotherapy treatment planning for cervical, head and neck, and prostate cancers, which are endemic in LMICs, and for which radiotherapy is the primary curative treatment modality. The sample size of 990 patients (330 for each cancer type) has been calculated based on an estimated 95% treatment plan acceptability rate. Time and cost savings will be analysed as secondary outcome measures using the time-driven activity-based costing model. The 48-month study will take place in six public sector cancer hospitals in India (n=2), Jordan (n=1), Malaysia (n=1) and South Africa (n=2) to support implementation of the software in LMICs.Ethics and dissemination The study has received ethical approval from University College London (UCL) and each of the six study sites. If the study objectives are met, the AI-based software will be offered as a not-for-profit web service to public sector state hospitals in LMICs to support expansion of high quality radiotherapy capacity, improving access to and affordability of this key modality of cancer cure and control. Public and policy engagement plans will involve patients as key partners.

Introduction Transfusions in surgery can be life-saving interventions, but inappropriate transfusions may lack clinical benefit and cause harm. Transfusion decision-making in surgery is complex and frequently informed by haemoglobin (Hgb) measurement in the operating room. Point-of-care testing for haemoglobin (POCT-Hgb) is increasingly relied on given its simplicity and rapid provision of results. POCT-Hgb devices lack adequate validation in the operative setting, particularly for Hgb values within the transfusion zone (60–100 g/L). This study aims to examine the accuracy of intraoperative POCT-Hgb instruments in non-cardiac surgery, and the association between POCT-Hgb measurements and transfusion decision-making.Methods and analysis PREMISE is an observational prospective method comparison study. Enrolment will occur when adult patients undergoing major non-cardiac surgery require POCT-Hgb, as determined by the treating team. Three concurrent POCT-Hgb results, considered as index tests, will be compared with a laboratory analysis of Hgb (lab-Hgb), considered the gold standard. Participants may have multiple POCT-Hgb measurements during surgery. The primary outcome is the difference in individual Hgb measurements between POCT-Hgb and lab-Hgb, primarily among measurements that are within the transfusion zone. Secondary outcomes include POCT-Hgb accuracy within the entire cohort, postoperative morbidity, mortality and transfusion rates. The sample size is 1750 POCT-Hgb measurements to obtain a minimum of 652 Hgb measurements

BackgroundOutpatient chemotherapy often leaves patients to grapple with a range of complex side effects at home. Leveraging tailored evidence-based content to monitor and manage these symptoms remains an untapped potential among patients with gastrointestinal (GI) cancer. ObjectiveThis study aims to bridge the gap in outpatient chemotherapy care by integrating a cutting-edge text messaging system with a chatbot interface. This approach seeks to enable real-time monitoring and proactive management of side effects in patients with GI cancer undergoing intravenous chemotherapy. MethodsReal-Time Chemotherapy-Associated Side Effects Monitoring Supportive System (RT-CAMSS) was developed iteratively, incorporating patient-centered inputs and evidence-based information. It synthesizes chemotherapy knowledge, self-care symptom management skills, emotional support, and healthy lifestyle recommendations. In a single-arm 2-month pilot study, patients with GI cancer undergoing chemotherapy received tailored intervention messages thrice a week and a weekly Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events–based symptom assessment via a chatbot interface. Baseline and postintervention patient surveys and interviews were conducted. ResultsOut of 45 eligible patients, 34 were enrolled (76% consent rate). The mean age was 61 (SD 12) years, with 19 (56%) being females and 21 (62%) non-Hispanic White. The most common cancer type was pancreatic (n=18, 53%), followed by colon (n=12, 35%) and stomach (n=4, 12%). In total, 27 (79% retention rate) participants completed the postintervention follow-up. In total, 20 patients texted back at least once to seek additional information, with the keyword “chemo” or “support” texted the most. Among those who used the chatbot system checker, fatigue emerged as the most frequently reported symptom (n=15), followed by neuropathy (n=7). Adjusted for multiple comparisons, patients engaging with the platform exhibited significantly improved Patient Activation Measure (3.70, 95% CI –6.919 to –0.499; P=.02). Postintervention interviews and satisfaction surveys revealed that participants found the intervention was user-friendly and were provided with valuable information. ConclusionsCapitalizing on mobile technology communication holds tremendous scalability for enhancing health care services. This study presents initial evidence of the engagement and acceptability of RT-CAMSS, warranting further evaluation in a controlled clinical trial setting.

Abstract A study was undertaken to determine the contents of trace metals in 60 topsoils and 80 brinjal fruits samples from a famous brinjal-producing area of Bangladesh using atomic absorption spectrophotometer. The study also looked at soil pollution levels, dietary intake of nutritionally important trace elements, and human health risks from toxic metals induced by dermal soil exposure and consumption of brinjal. The content of Pb, Ni, Cd, Cu, Fe, Mn, and Zn in brinjal fruits harvested from farmer′s fields ranged from 0.204–0.729, 0.031–0.212, 5.00 for Cd, indicating moderate to significant enrichment of these metals in the soil. The study also revealed that brinjal consumption provides a tiny amount of nutritionally important trace elements required for an adult human. Regarding the computed incremental lifetime cancer risks (ILCR), the study revealed that the values for Pb and Ni in all samples and Cd in 40% of samples were several hundred times higher for males and females than the USEPA threshold level due to oral ingestion of brinjal fruits. In contrast, dermal exposures to soil trace elements were within an acceptable range. The PCA results revealed that the contents of Cd, Pb, Ni, and Cu in soils showed strong positive correlations with those elements present in brinjal. The current study suggests future traceability research, focusing on pinpointing potential entry routes for toxic elements into the vegetable food chain.

Abstract The Axin family of scaffolding proteins control diverse processes, such as facilitating the interactions between cellular components and providing specificity to signaling pathways. While several Axin family members have been discovered in metazoans and shown to play crucial roles, their mechanism of action are not well understood. The Caenorhabditis elegans Axin homolog, pry-1, is a powerful tool for identifying interacting genes and downstream effectors that function in a conserved manner to regulate Axin-mediated signaling. Our lab and others have established pry-1’s essential role in developmental processes that affect the reproductive system, seam cells, and a posterior P lineage cell, P11.p. Additionally, pry-1 is crucial for lipid metabolism, stress responses, and aging. In this study, we expanded on our previous work on pry-1 by reporting a novel interacting gene named picd-1 (p ry-1-interacting and Cabin1 domain-containing). PICD-1 protein shares sequence conservation with CABIN1, a component of the HUCA complex. Our findings have revealed that PICD-1 is involved in several pry-1-mediated processes, including stress response and lifespan maintenance. picd-1’s expression overlapped with that of pry-1 in multiple tissues throughout the lifespan. Furthermore, PRY-1 and PICD-1 inhibited CREB-regulated transcriptional coactivator homolog CRTC-1, which promotes longevity in a calcineurin-dependent manner. Overall, our study has demonstrated that picd-1 is necessary for mediating pry-1 function and provides the basis to investigate whether Cabin-1 domain-containing protein plays a similar role in Axin signaling in other systems.

Abstract The current research work was an innovative approach providing dual advantages of waste bioremediation and an effective biorefinery. The study attempted to exploit wastewater like aqua discharge and solid wastes like poultry litter/cow dung for cyanobacterial cultivation. Aqua discharge appended with 7.5 g L−1 poultry litter turned out as the best combination generating 46% higher carbohydrate yield than BG-11 control. A. variabilis cultivation in this waste-utilized medium also revealed its excellent bioremediation ability. While 100% removal was observed for nitrite, nitrate, and orthophosphate, a respective 74% and 81% reduction was noted for ammonium and total organic carbon. Chemical and biological oxygen demands were also reduced by 90%. This work was also novel in developing a sequential design for the production of bioethanol and co-products like exopolysaccharides, sodium copper chlorophyllin, C-phycocyanin, and poly-β-hydroxybutyrate from the same cyanobacterial biomass. The developed biorefinery implementing the waste-utilized medium was one of its kind, enabling biomass valorization of 61%. Therefore, the present study would provide a leading-edge for tackling the high production costs that limit the practical viability of biorefinery projects. The recyclability of the bioremediated wastewater would not only curtail freshwater usage, the waste disposal concerns would also be mitigated to a great extent.

Hydatid cyst of brain in an extremely rare entity. A case of primary hydatidosis of brain without any involvement of other areas is even rarer. Most commonly involved areas are liver and lung because of rich vascularity and vicinity to portal circulation. Central Nervous System (CNS) or most importantly cases of hydatid cysts of brain are very rare. This case report is about a 7-yearold girl, from eastern India, who presented with multiple hydatid cysts in cranial cavity. She presented with headache, sudden loss of balance, short time memory loss. On Magnetic Resonanace Imaging (MRI), multiple cystic lesions were noted in cranial cavity. Magnetic Resonance (MR) Spectroscopy findings were suggestive of hydatid disease. These cysts were removed through neurosurgical intervention. The diagnosis was confirmed by gross and microscopic examination. Importance of keeping hydatidosis as a differential diagnosis while working up cases of cystic Space-occupying Lesion (SOL) of the brain in children is evident here.

Abstract Land surface temperature (LST) is a preeminent state variable that controls the energy and water exchange between the Earth’s surface and the atmosphere. At the landscape-scale, LST is derived from thermal infrared radiance measured using space-borne radiometers. In contrast, plot-scale LST estimation at flux tower sites is commonly based on the inversion of upwelling longwave radiation captured by tower-mounted radiometers, whereas the role of the downwelling longwave radiation component is often ignored. We found that neglecting the reflected downwelling longwave radiation leads not only to substantial bias in plot-scale LST estimation, but also have important implications for the estimation of surface emissivity on which LST is co-dependent. The present study proposes a novel method for simultaneous estimation of LST and emissivity at the plot-scale and addresses in detail the consequences of omitting down-welling longwave radiation as frequently done in the literature. Our analysis uses ten eddy covariance sites with different land cover types and found that the LST values obtained using both upwelling and downwelling longwave radiation components are 0.5–1.5 K lower than estimates using only upwelling longwave radiation. Furthermore, the proposed method helps identify inconsistencies between plot-scale radiometric and aerodynamic measurements, likely due to footprint mismatch between measurement approaches. We also found that such inconsistencies can be removed by slight corrections to the upwelling longwave component and subsequent energy balance closure, resulting in realistic estimates of surface emissivity and consistent relationships between energy fluxes and surface-air temperature differences. The correspondence between plot-scale LST and landscape-scale LST depends on site-specific characteristics, such as canopy density, sensor locations and viewing angles. Here we also quantify the uncertainty in plot-scale LST estimates due to uncertainty in tower-based measurements using the different methods. The results of this work have significant implications for the combined use of aerodynamic and radiometric measurements to understand the interactions and feedbacks between LST and surface-atmosphere exchange processes.

Abstract Particle production and event topology are very strongly correlated in high-energy hadronic and nuclear collisions. Event topology is decided by the underlying particle production dynamics and medium effects. Transverse spherocity is an event shape observable, which has been used in pp and heavy-ion collisions to separate the events based on their geometrical shapes. It has the unique capability to distinguish between jetty and isotropic events. In this work, we have implemented transverse spherocity in Pb–Pb collisions at $$\sqrt{s_\text{NN}}$$ s NN = 5.02 TeV using A Multi-Phase Transport Model (AMPT). While awaiting for experimental explorations, we perform a feasibility study of transverse spherocity dependence of some of the global observables in heavy-ion collisions at the Large Hadron Collider energies. These global observables include the Bjorken energy density ( $$\varepsilon _\text{Bj}$$ ε Bj ), squared speed of sound ( $$c_\text{s}^2$$ c s 2 ) in the medium and the kinetic freeze-out properties for different collision centralities. The present study reveals about the usefulness of event topology dependent measurements in heavy-ion collisions.

Abstract Nitric oxide (NO) modulates plant response to biotic and abiotic stresses by S-nitrosylation-mediated protein post-translational modification. Nitrate reductase (NR) and S-nitrosoglutathione reductase (GSNOR) enzymes are essential for NO synthesis and the maintenance of Nitric oxide/S-nitroso glutathione (NO/GSNO) homeostasis, respectively. S-nitrosoglutathione, formed by the S-nitrosylation reaction of NO with glutathione, plays a significant physiological role as the mobile reservoir of NO. The genome-wide analysis identified nine NR (NIA) and three GSNOR genes in the wheat genome. Phylogenic analysis revealed that the nine NIA genes +were clustered into four groups and the 3 GSNORs into two groups. qRT-PCR expression profiling of NIAs and GSNORs was done in Chinese spring (CS), a leaf rust susceptible wheat line showing compatible interaction, and Transfer (TR), leaf rust-resistant wheat line showing incompatible interaction, post-inoculation with leaf rust pathotype 77–5 (121-R-63). All the NIA genes showed upregulation during incompatible interaction in comparison with the compatible reaction. The GSNOR genes showed a variable pattern of expression: the TaGSNOR1 showed little change, whereas TaGSNOR2 showed higher expression during the incompatible response. TaGSNOR3 showed a rise of expression both in compatible and incompatible reactions. Before inoculation and after 72 h of pathogen inoculation, NO localization was studied in both compatible and incompatible reactions. The S-nitrosothiol accumulation, NR, and glutathione reductase activity showed a consistent increase in the incompatible interactions. The results demonstrate that both NR and GSNOR plays significant role in defence against the leaf rust pathogen in wheat by modulating NO homeostasis or signalling.