Search

Abstract We present the result of a search for the charged-lepton-flavor violating decay τ − → μ − μ + μ − using a 424 fb −1 sample of data recorded by the Belle II experiment at the SuperKEKB e + e − collider. The selection of e + e − → τ + τ − events is based on an inclusive reconstruction of the non-signal tau decay, and on a boosted decision tree to suppress background. We observe one signal candidate, which is compatible with the expectation from background processes. We set a 90% confidence level upper limit of 1.9 × 10 −8 on the branching fraction of the τ − → μ − μ + μ − decay, which is the most stringent bound to date.

Abstract Groundwater is a primary source of drinking water for billions worldwide. It plays a crucial role in irrigation, domestic, and industrial uses, and significantly contributes to drought resilience in various regions. However, excessive groundwater discharge has left many areas vulnerable to potable water shortages. Therefore, assessing groundwater potential zones (GWPZ) is essential for implementing sustainable management practices to ensure the availability of groundwater for present and future generations. This study aims to delineate areas with high groundwater potential in the Bankura district of West Bengal using four machine learning methods: Random Forest (RF), Adaptive Boosting (AdaBoost), Extreme Gradient Boosting (XGBoost), and Voting Ensemble (VE). The models used 161 data points, comprising 70% of the training dataset, to identify significant correlations between the presence and absence of groundwater in the region. Among the methods, Random Forest (RF) and Extreme Gradient Boosting (XGBoost) proved to be the most effective in mapping groundwater potential, suggesting their applicability in other regions with similar hydrogeological conditions. The performance metrics for RF are very good with a precision of 0.919, recall of 0.971, F1-score of 0.944, and accuracy of 0.943. This indicates a strong capability to accurately predict groundwater zones with minimal false positives and negatives. Adaptive Boosting (AdaBoost) demonstrated comparable performance across all metrics (precision: 0.919, recall: 0.971, F1-score: 0.944, accuracy: 0.943), highlighting its effectiveness in predicting groundwater potential areas accurately; whereas, Extreme Gradient Boosting (XGBoost) outperformed the other models slightly, with higher values in all metrics: precision (0.944), recall (0.971), F1-score (0.958), and accuracy (0.957), suggesting a more refined model performance. The Voting Ensemble (VE) approach also showed enhanced performance, mirroring XGBoost's metrics (precision: 0.944, recall: 0.971, F1-score: 0.958, accuracy: 0.957). This indicates that combining the strengths of individual models leads to better predictions. The groundwater potentiality zoning across the Bankura district varied significantly, with areas of very low potentiality accounting for 41.81% and very high potentiality at 24.35%. The uncertainty in predictions ranged from 0.0 to 0.75 across the study area, reflecting the variability in groundwater availability and the need for targeted management strategies. In summary, this study highlights the critical need for assessing and managing groundwater resources effectively using advanced machine learning techniques. The findings provide a foundation for better groundwater management practices, ensuring sustainable use and conservation in Bankura district and beyond.

Introduction: Obsessive-compulsive disorder (OCD) is characterized by underlying obsessions and yielding/nonyielding compulsions, which often leads to significant levels of distress for the individual. Recently, obsessive-compulsive symptoms have been grouped into various symptom dimensions. The Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS) gives a comprehensive picture regarding symptom severity in each individual dimension of OCD, while also providing a global severity score. Aims and Objectives: The psychometric properties of the Bengali adaptation of DY-BOCS have been assessed in this study. Material and Methods: A cross-sectional study was performed on 80 individuals suffering from OCD as per the ICD-10 DCR criteria. The Bengali version of the DY-BOCS and other scales for OCD, anxiety, and depression were administered to all of them. Inter-rater reliability was assessed for 34 individuals, and agreement between self and clinician-rated version of DY-BOCS was studied for 60 individuals. Internal consistency for items in a particular dimension of DY-BOCS, convergent validity, and divergent validity were also assessed. Results: Internal consistency was found to be excellent (Cronbach’s α > 0.90 in all domains), and inter-rater reliability was found to be good to excellent for all the six dimensions of the DY-BOCS (intraclass correlation values >0.80 for aggressive and miscellaneous domains and >0.90 in all other domains). High correlation was found between self and clinician-rated versions of DY-BOCS for the age group 18–35 years, the highest correlations being found for the Contamination (r = 0.82) and Aggressive domains (r = 0.75), while it was found to decrease in the older age group. Convergent validity and divergent validity were found to be satisfactory. Conclusion: The psychometric attributes of the Bengali version of DY-BOCS appear to be satisfactory and thus can be reasonably administered to the population having Bengali as their mother tongue.

Abstract We present measurements of the branching fractions of eight B ¯ 0 $$ {\overline{B}}^0 $$ → D (*)+ K − K S ∗ 0 $$ {K}_{(S)}^{\left(\ast \right)0} $$ , B − → D (*)0 K − K S ∗ 0 $$ {K}_{(S)}^{\left(\ast \right)0} $$ decay channels. The results are based on data from SuperKEKB electron-positron collisions at the Υ(4S) resonance collected with the Belle II detector, corresponding to an integrated luminosity of 362 fb −1. The event yields are extracted from fits to the distributions of the difference between expected and observed B meson energy, and are efficiency-corrected as a function of m(K − K S ∗ 0 $$ {K}_{(S)}^{\left(\ast \right)0} $$ ) and m(D (*) K S ∗ 0 $$ {K}_{(S)}^{\left(\ast \right)0} $$ ) in order to avoid dependence on the decay model. These results include the first observation of B ¯ 0 $$ {\overline{B}}^0 $$ → D + K − K S 0 $$ {K}_S^0 $$ , B − → D* 0 K − K S 0 $$ {K}_S^0 $$ , and B ¯ 0 $$ {\overline{B}}^0 $$ → D* + K − K S 0 $$ {K}_S^0 $$ decays and a significant improvement in the precision of the other channels compared to previous measurements. The helicity-angle distributions and the invariant mass distributions of the K − K S ∗ 0 $$ {K}_{(S)}^{\left(\ast \right)0} $$ systems are compatible with quasi-two-body decays via a resonant transition with spin-parity J P = 1− for the K − K S 0 $$ {K}_S^0 $$ systems and J P = 1+ for the K − K* 0 systems. We also present measurements of the branching fractions of four B ¯ 0 $$ {\overline{B}}^0 $$ → D (*)+ D s − $$ {D}_s^{-} $$ , B − → D (*)0 D s − $$ {D}_s^{-} $$ decay channels with a precision compatible to the current world averages.

Abstract Synthetic textile dye malachite green (MG) and heavy metals present in industrial wastewater are hazardous to the ecosystem. Bioremediation of dyes and heavy metals using dry-biomasses has advantages over chemical methods. This study screened an acclimatized, heavy metal-resistant, and dye-degrading Gram positive Bacillus licheniformis AG3 strain from the textile wastewater near Kolkata, West Bengal. The EDXRF analysis of this colored wastewater effluent showed 36.33 mg/L lead, significantly higher than the WHO recommendation. Previously, Bag et al. showed bioremediation of synthetic dyes using dry-biomass of Bacillus cereus M1 16 from an aqueous solution (Bag et al. Arch Microbiol 203(7):3811–3823, 2021). Here, a consortium of dry-biomasses of B. licheniformis AG3 and B. cereus M1 16 strains (1:1 w/w ratio) was prepared for the simultaneous removal of lead and MG from wastewater. Statistical optimization determines that the pH, initial concentration of contaminants, and dry-biomass concentrations are critical for bioremediation under batch procedures. Further, optimization using the response surface methodology showed that 0.01% consortium dry-biomasses eliminated a maximum of 99.35% MG and 96.01% lead (II) within 6 h. SEM–EDS and FTIR confirmed a strong surface biosorption. Furthermore, a fixed-bed biofilter column of the consortium dry-biomasses was prepared, which was able to remove 98.1% MG and 98.5% lead at the 0.5–1 mL/min flow rate. Together, this study developed a biofilter with a consortium dry biomasses of B. licheniformis AG3 and B. cereus M1 16 for the simultaneous removal of MG and lead from wastewater.

Abstract Quantum networks are designed to transmit quantum bits (qubits) among quantum devices to enable new network resources for the applications. Entanglement distribution and entanglement swapping are fundamental procedures that are required in several network operations. However, they are probabilistic operations, which can lead to severe network performance degradation. This article investigates the engineering problem of resource allocation in quantum networks, considering factors like entanglement distribution probability, quantum memory characteristics, and fidelity. We model this as an optimization model to obtain an optimal solution. In particular, we formulate an integer linear programming (ILP) and develop a heuristic algorithm, aiming to minimize the number of required entangled qubit pairs (Bell pairs or EPR pairs) in any adjacent pair in the quantum network. Extensive simulations are performed to compare the performance of proposed ILP and heuristic. In all the cases, the heuristic produces a comparable solution to the optimal one. Simulation results ensure that the value of maximum utilized Bell pairs in a quantum network highly depends on the value of the probability of entangled pairs established, considering the time in the quantum memory besides the number of incoming requests.

Abstract Malignant mesothelioma is a rare tumour caused by asbestos exposure that originates mainly from the pleural lining or the peritoneum. Treatment options are limited, and the prognosis is dismal. Although immune checkpoint blockade (ICB) can improve survival outcomes, the determinants of responsiveness remain elusive. Here, we report the outcomes of a multi-centre phase II clinical trial (MiST4, NCT03654833) evaluating atezolizumab and bevacizumab (AtzBev) in patients with relapsed mesothelioma. We also use tumour tissue and gut microbiome sequencing, as well as tumour spatial immunophenotyping to identify factors associated with treatment response. MIST4 met its primary endpoint with 50% 12-week disease control, and the treatment was tolerable. Aneuploidy, notably uniparental disomy (UPD), homologous recombination deficiency (HRD), epithelial-mesenchymal transition and inflammation with CD68+ monocytes were identified as tumour-intrinsic resistance factors. The log-ratio of gut-resident microbial genera positively correlated with radiological response to AtzBev and CD8+ T cell infiltration, but was inversely correlated with UPD, HRD and tumour infiltration by CD68+ monocytes. In summary, a model is proposed in which both intrinsic and extrinsic determinants in mesothelioma cooperate to modify the tumour microenvironment and confer clinical sensitivity to AtzBev. Gut microbiota represent a potentially modifiable factor with potential to improve immunotherapy outcomes for individuals with this cancer of unmet need.

Abstract The k-Nearest Neighbors (kNN) method, established in 1951, has since evolved into a pivotal tool in data mining, recommendation systems, and Internet of Things (IoT), among other areas. This paper presents a comprehensive review and performance analysis of modifications made to enhance the exact kNN techniques, particularly focusing on kNN Search and kNN Join for high-dimensional data. We delve deep into 31 kNN search methods and 12 kNN join methods, providing a methodological overview and analytical insight into each, emphasizing their strengths, limitations, and applicability. An important feature of our study is the provision of the source code for each of the kNN methods discussed, fostering ease of experimentation and comparative analysis for readers. Motivated by the rising significance of kNN in high-dimensional spaces and a recognized gap in comprehensive surveys on exact kNN techniques, our work seeks to bridge this gap. Additionally, we outline existing challenges and present potential directions for future research in the domain of kNN techniques, offering a holistic guide that amalgamates, compares, and dissects existing methodologies in a coherent manner. Graphical Abstract

Abstract Our objectives were to ascertain the following: (1) the prevalence and socioeconomic distribution of hypertension (HTN), undiagnosed for HTN, and untreated cases of HTN‐diagnosed individuals; (2) the relationship between SES and the prevalence of HTN, undiagnosed for HTN, and untreated for HTN; and (3) whether sex moderate this association. Data from the 2017–18 Bangladesh Demographic Health Survey were used. 11,776 participants who were 18 years of age or older responded to our analysis. The age‐adjusted prevalence of HTN, undiagnosed for HTN, and untreated cases was 25.1%, 57.2%, and 12.3%. Compared to females, males were less likely to have HTN but more likely to have undiagnosed HTN. People in the rich SES groups had a higher odd of (adjusted odds ratio [aoR] 1.25; 95% confidence interval [CI] 1.08–3.45) of having HTN compared to those in the poor SES group. When compared to individuals in the poor SES group, those in the rich SES group had lower odds of undiagnosed (aoR 0.57; 95% CI 0.44–0.74) and untreated (aoR 0.56; 95% CI 0.31–0.98) for HTN. Sex moderated the association between SES and HTN prevalence, which showed that men from rich SES were more likely to suffer from HTN than men from poor SES. According to this study, the government and other pertinent stakeholders should concentrate more on developing suitable policy measures to reduce the risk of HTN, particularly for men in rich socioeconomic groups. They should also concentrate on screening and diagnosing HTN in socioeconomically disadvantaged populations, regardless of sex.

Abstract We present an analysis of the process e + e − → π + π − Υ(nS) (where n = 1, 2, or 3) reconstructed in 19.6 fb −1 of Belle II data during a special run of the SuperKEKB collider at four energy points near the peak of the Υ(10753) resonance. By analyzing the mass distribution of the π + π − Υ(nS) system and the Born cross sections of the e + e − → π + π − Υ(nS) process, we report the first observation of Υ(10753) decays to the π + π − Υ(1S) and π + π − Υ(2S) final states, and find no evidence for decays to π + π − Υ(3S). Possible intermediate states in the π + π − Υ(1S, 2S) transitions are also investigated, and no evidence for decays proceeding via the π ∓ Z b ± $$ {\pi}^{\mp }{Z}_b^{\pm } $$ or f 0(980)Υ(nS) intermediate states is found. We measure Born cross sections for the e + e − → π + π − Υ(nS) process that, combined with results from Belle, obtain the mass and width of Υ(10753) to be (10756.6 ± 2.7 ± 0.9) MeV/c 2 and (29.0 ± 8.8 ± 1.2) MeV, respectively. The relative ratios of the Born cross sections at the Υ(10753) resonance peak are also reported for the first time.

Aims: Transfusion after primary total hip arthroplasty (THA) has become rare, and identification of causative factors allows preventive measures. The aim of this study was to determine patient-specific factors that increase the risk of needing a blood transfusion. Methods: All patients who underwent elective THA were analyzed retrospectively in this single-centre study from 2020 to 2021. A total of 2,892 patients were included. Transfusion-related parameters were evaluated. A multiple logistic regression was performed to determine whether age, BMI, American Society of Anesthesiologists (ASA) grade, sex, or preoperative haemoglobin (Hb) could predict the need for transfusion within the examined patient population. Results: The overall transfusion rate was 1.2%. Compared to the group of patients without blood transfusion, the transfused group was on average older (aged 73.8 years (SD 9.7) vs 68.6 years (SD 10.1); p = 0.020) and was mostly female (p = 0.003), but showed no significant differences in terms of BMI (28.3 kg/m2 (SD 5.9) vs 28.7 kg/m2 (SD 5.2); p = 0.720) or ASA grade (2.2 (SD 0.5) vs 2.1 (SD 0.4); p = 0.378). The regression model identified a cutoff Hb level of < 7.6 mmol/l (< 12.2 g/dl), aged > 73 years, and a BMI of 35.4 kg/m² or higher as the three most reliable predictors associated with postoperative transfusion in THA. Conclusion: The possibility of transfusion is predictable based on preoperatively available parameters. The proposed thresholds for preoperative Hb level, age, and BMI can help identify patients and take preventive measures if necessary. Cite this article: Bone Jt Open 2024;5(7):560–564.

Abstract Background The increase in global population has elevated the food demand which in turn escalated the food animal production systems, especially poultry industries. For a long time, antibiotics are used worldwide to safeguard animals from diseases and for high production performances. Over usage of antibiotics has led to severe side effects such as antibiotic resistance among pathogenic bacteria, harming the beneficial bacteria in the gut, and stacking up of residuals in animal food products. It is the need of the hour to find a competent alternative to antibiotics. Probiotics have gained major attention as safe, feasible, and efficient alternatives to commercial antibiotics. Main body Probiotics meaning “prolife” are live, non-pathogenic microorganisms that when given in sufficient amount confer an advantage to the host health and well-being. Probiotics are reported to improve growth, production performance, immunity, and digestibility, safeguard gut microflora, and enhance egg and meat quality traits in poultry. Proper selection of probiotics strains is crucial before their commercialization. This systematic review focuses on the mechanism of action of probiotics and summarizes the potential role of different probiotics supplementation for enhancing the production and shielding the health and immunity of poultry flocks. Conclusions Probiotics has got a beneficial impact on the health and immunity of poultry, showing their competence as an alternative to commercial antibiotics. Modern experimental techniques are required to shed more light on the capabilities of probiotics and their usage for animal health.

Introduction: Gestational Diabetes Mellitus (GDM) is a chronic and progressive disease characterised by changes in the metabolism of carbohydrates, lipids, and proteins, leading to glucose intolerance. The foetal heart in GDM is affected throughout the gestational period, which may result in hyperplasia and hypertrophy of myocardial cells. Aim: To determine the cardiac function and structural changes in infants of gestational diabetic mothers using Doppler-echocardiographic data. Materials and Methods: A cross-sectional analytical study was conducted on 30 infants of mothers with GDM and 30 infants of non diabetic mothers at the Department of Physiology, R.G. Kar Medical College and Hospital, in collaboration with the Departments of Paediatric Medicine and Cardiology from January 2023 to August 2023. Neonatal screening echocardiography was performed by a cardiologist using a Philips Echocardiograph machine, Model: EPIQ 7C, Software Version: 4.0.2, with a linear convex probe of S8-3 MHz frequency to assess cardiac structure and function using 2D, M mode, and Conventional Doppler. The parameters studied included aortic root diameter (mm), left atrial diameter (mm), Interventricular Septal (IVS) in diastole (mm), left ventricular posterior wall thickness in diastole (mm), left ventricular internal diameter in diastole (mm), left ventricular internal diameter in end systole (mm), left ventricular fractional shortening (%), and left ventricular ejection fraction (%). Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) version-20.0 with an Independent Student’s t-test. Results: The mean gestational age for the cases was 38.50±2.57 weeks and 39.30±1.97 weeks for controls. The mean maternal age for cases was 25±4.37 years and for controls was 27±5.03 years. The left atrial diameter in cases (12.83±2.14 mm) was significantly smaller than that of the control (14.20±0.55 mm). The left ventricular posterior wall diameter in diastole was significantly increased in cases (4.53±0.50 mm) compared to controls (3.87±0.35 mm). Significant differences were observed in the interventricular septum in diastole {cases: 4.73±0.45 mm, control: 3.97±0.32 mm} and in the left ventricular internal diameter in end systole {cases: 12.30±1.84 mm, control: 13.83±1.02 mm} between cases and controls. Aortic root diameter was increased in 13.3% of cases. The percentage of left ventricular fractional shortening (cases: 35.47±3.74 %, Control: 38.53±2.43 %), Left Ventricular Ejection fraction (cases: 67.63±4.52 %, control: 72.17±4.89 %) were significantly decreased in cases compared to control. Conclusion: The present study demonstrated the development of ventricular hypertrophy and compromised myocardial contractility in infants of diabetic mothers.

Abstract The outcome of CRISPR-Cas-mediated genome modifications is dependent on DNA double-strand break (DSB) processing and repair pathway choice. Homology-directed repair (HDR) of protein-blocked DSBs requires DNA end resection that is initiated by the endonuclease activity of the MRE11 complex. Using reconstituted reactions, we show that Cas9 breaks are unexpectedly not directly resectable by the MRE11 complex. In contrast, breaks catalyzed by Cas12a are readily processed. Cas9, unlike Cas12a, bridges the broken ends, preventing DSB detection and processing by MRE11. We demonstrate that Cas9 must be dislocated after DNA cleavage to allow DNA end resection and repair. Using single molecule and bulk biochemical assays, we next find that the HLTF translocase directly removes Cas9 from broken ends, which allows DSB processing by DNA end resection or non-homologous end-joining machineries. Mechanistically, the activity of HLTF requires its HIRAN domain and the release of the 3′-end generated by the cleavage of the non-target DNA strand by the Cas9 RuvC domain. Consequently, HLTF removes the H840A but not the D10A Cas9 nickase. The removal of Cas9 H840A by HLTF explains the different cellular impact of the two Cas9 nickase variants in human cells, with potential implications for gene editing.

Abstract Background Tandem running is a recruitment method found in some species of ants where one ant follows another ant to reach a destination having maintained a physical contact with its antennae, throughout the journey. It is considered that the exchange of information regarding the destination among the nestmates happened during the process of tandem running. We examined the impact of restricting antennal movement on tandem running by using Diacamma indicum, a tandem-running ponerine ant by following 480 tandem runs across 9 treatment colonies and comparing it with 10 control relocating colonies. Result Though all the 19 colonies relocated successfully, treatment colonies took significantly longer time to do so. Restricted antennal movement did not influence the ability to become tandem leaders, initiate tandem runs or the work organization significantly. However, antennae-restricted ants performed fewer tandem runs and took significantly longer time. Followers with single or both antennae-restriction performed significantly higher number of interruptions and the alignment between the leader and follower was impacted as antenna-restricted followers subtended a greater angle and walked more to the side of the leader as compared to the control followers. Conclusion This study showed unhindered movement of the followers’ antennae is important for tandem-running ants. In the next step, to gain a comprehensive understanding of this recruitment method, it is essential to individually delineate different sensory modalities.

Background: Changes in cognitive functioning with the progression of age have been suggested as indicator of potential degenerative disorders in older adults. With growing age, deterioration in executive functions happens and is noticeable from the difficulties in day-to-day planning, problem-solving, decision-making, and inhibition or fluency in the elderly. However, in the early stages, it might be tricky to clinically identify if the decline in the cognitive functions is clinically significant or not. Verbal fluency is a valuable executive function and posited as one of the indicators of cognitive impairment. Within this construct, categorical and semantic fluency are inclined to indicate the verbal stimulus recognition and association. It is suggested that the capability to distinguish and associate verbal stimulus could be at different levels of decline with aging with a possible pattern of decline from the early stage of old age and later and distinct among males and females. This progressive decline and changes in verbal fluency could indicate the probable occurrence of cognitive impairment in the aging population. The study aimed to explore the verbal and semantic fluency as an indicator of the progression of cognitive decline with aging and to explore the sex differences in verbal fluency of the studied sample if any. Methodology: Hundred individuals of both sexes in the age range of 50–70 years were selected for the study. The Controlled Oral Word Association Test (COWA) and animal naming test were administered to measure the semantic and categorical verbal fluency of the participants. Results: Results suggest significant changes in verbal fluency with aging in the participants. However, the sex difference in verbal fluency was marginal, as males performed slightly better on the naming task but not in the word association task. Conclusions: Changes in verbal fluency are evident and prominent among the aging population and could be a valuable tool for early identification and intervention, decreasing the risks of degeneration and improving the quality of life of the elderly.

This study focuses on the probable use of carbonized char prepared from PET plastic bottles for heavy metals (HMs) adsorption (Cd2+, Pb2+, Cu2+, and Zn2+). The prepared adsorbent is characterized by field-emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX), and Fourier-transform infrared spectroscopy (FTIR). Batch adsorption experiments were conducted with the influencing of different operational conditions: contact time (1–180 min), adsorbate concentration (25–300 mg/L), adsorbent dose (0.5–6 g/L), pH (3–7), and temperature (25–60 ºC). High coefficient value [Cd2+ (R2 = 0.99), Pb2+ (R2 = 0.97), Cu2+ (R2 = 0.94), and Zn2+ (R2 = 0.98)] of process optimization model suggest that this model was significant, where pH and adsorbent dose expressively stimulus removal efficiency including 86.68, 73.66, 67.10, and 57.04% for Cd2+, Pb2+, Cu2+, and Zn2+ at pH (7), respectively. Furthermore, ANN and BB-RSM revealed a good association between the tested and projected values. The maximum monolayer adsorption capacity of Cd2+, Pb2+, Cu2+, and Zn2+ was 263.157, 78.740, 196.078, and 84.745 mg/g, respectively. Pseudo-second-order was the well-suited kinetics, where Langmuir and Freundlich isotherm could explain better for equilibrium adsorption data. Thermodynamic study shows HMs adsorption is favorable, exothermic, and spontaneous. HIGHLIGHTS Carbonized adsorbent was prepared from PET bottle waste by a simple thermal dissociation method.; Response surface methodology and artificial neural network express a strong correlation between the experimental and projected heavy metal removal efficiency.; Carbonized adsorbents reveal satisfactory results for experimental (Cd = 86.68%, Pb = 73.66%, Cu = 67.10%, and Zn = 57.04%) and real wastewater applications (Cd = 99.2%, Pb = 62.20%, Cu = 97.63%, and Zn = 64.47%).;

Abstract Introduction Anaemia is a disease of public health importance with multi-causal pathways. Previous literature suggests the role of indoor air pollution (IAP) on haemoglobin levels, but this has been studied less due to logistic constraints. A high proportion of the population in developing countries, including India, still depends on unclean fuel, which exacerbates IAP. The objective was to study the association between anaemia and IAP among the older Indian adult population (≥ 45 years) as per gender. Methods Our study analysed the nationally representative dataset of the Longitudinal Ageing Study in India (LASI 2017–18, Wave-1). We have documented the association of anaemia (outcome variable) with IAP (explanatory variable). To reduce the confounding effects of demographic and socioeconomic; health related and behavioural covariates; propensity score matching (PSM) was conducted. Nested multilevel regression modelling was conducted. States and union territories were categorised cross tabulated as low, middle and high as per anaemia and IAP exposure. P value female (51.63%)). The odds of having anaemia was significantly 1.19 times higher (AOR 1.19 (1.09–1.31)) among participants using unclean/ solid fuel. The adjusted odds were significantly higher among participants exposed to pollution-generating sources (AOR 1.30; 1.18–1.43), and household indoor smoking (AOR 1.17 (1.07–1.29). The odds of having anaemia were significantly higher (AOR 1.26; 1.15–1.38) among participants exposed to IAP, which was higher in males (AOR 1.36; 1.15–1.61) than females (AOR 1.21; 1.08–1.35). Empowered Action Group (EAG) states like Uttar Pradesh, Chhattisgarh, Madhya Pradesh, Bihar had both high anaemia and IAP exposure. Conclusion This study established the positive association of anaemia with indoor air pollution among older Indian adults through a nationally representative large dataset. The association was higher among men. Further research is recommended to understand detailed causation and to establish temporality. It is a high time to implement positive intervention nationally to decrease solid/ unclean fuel usage, vulnerable ventilation, indoor smoking, IAP and health hazards associated with these with more focused actions towards EAG states.

Context: Reported literatures revealed the problems of access and misconceptions, low contraceptive usage and high unmet need for family planning among the tribes. Aims: Our aim was to find out the prevalence of contraceptive usage, unmet need and their determinants among tribal married reproductive women. Settings and Design: A community-based, observational, analytical research using cross-sectional design was conducted among 290 tribal women of the Nadia district of West Bengal. Subjects and Methods: After obtaining ethical clearance, an interviewer-administered pre-designed, structured proforma was used to collect information on socio-demographic attributes, marital history, contraceptives and fertility status, unmet needs and the reasons for not using contraceptives. Statistical Analysis Used: Bi-variate analysis was used to know the differences and a two-tailed significance test with a P value of 0.05 or less was considered statistically significant. Results: The present study revealed a high prevalence of teenage marriage (60.7%) and pregnancy (27.6%). Every one in six tribal women was illiterate. The contraceptive prevalence rate was 43.8%. Tubectomy (38.6%) was the most common method (38.6%) and unfelt need (19.6%) was the most common reason for non-use. Age, occupation of women, social class, living status, marital duration, number of living children and desire to have a future child were found to be associated with the current contraceptive use. Social class, number of living children, contraceptive awareness, source and place of availability, abortion history, opposition from family and husband, and husband participation all were significantly associated with the unmet need for family planning. Conclusion: In-depth counselling focusing on achieving a satisfactory level of awareness and acceptance of family planning methods may help to achieve reproductive health by reducing unmet needs.

Abstract In recent years, the growth spurt of medical imaging data has led to the development of various machine learning algorithms for various healthcare applications. The MedMNISTv2 dataset, a comprehensive benchmark for 2D biomedical image classification, encompasses diverse medical imaging modalities such as Fundus Camera, Breast Ultrasound, Colon Pathology, Blood Cell Microscope etc. Highly accurate classifications performed on these datasets is crucial for identification of various diseases and determining the course of treatment. This research paper presents a comprehensive analysis of four subsets within the MedMNISTv2 dataset: BloodMNIST, BreastMNIST, PathMNIST and RetinaMNIST. Each of these selected datasets is of diverse data modalities and comes with various sample sizes, and have been selected to analyze the efficiency of the model against diverse data modalities. The study explores the idea of assessing the Vision Transformer Model’s ability to capture intricate patterns and features crucial for these medical image classification and thereby transcend the benchmark metrics substantially. The methodology includes pre-processing the input images which is followed by training the ViT-base-patch16-224 model on the mentioned datasets. The performance of the model is assessed using key metrices and by comparing the classification accuracies achieved with the benchmark accuracies. With the assistance of ViT, the new benchmarks achieved for BloodMNIST, BreastMNIST, PathMNIST and RetinaMNIST are 97.90%, 90.38%, 94.62% and 57%, respectively. The study highlights the promise of Vision transformer models in medical image analysis, preparing the way for their adoption and further exploration in healthcare applications, aiming to enhance diagnostic accuracy and assist medical professionals in clinical decision-making.

Abstract We report results from a study of B ± → DK ± decays followed by D decaying to the CP-even final state K + K − and CP-odd final state K S 0 π 0 $$ {K}_S^0{\pi}^0 $$ , where D is an admixture of D 0 and D ¯ 0 $$ {\overline{D}}^0 $$ states. These decays are sensitive to the Cabibbo-Kobayashi-Maskawa unitarity-triangle angle ϕ 3. The results are based on a combined analysis of the final data set of 772 × 106 B B ¯ $$ B\overline{B} $$ pairs collected by the Belle experiment and a data set of 198 × 106 B B ¯ $$ B\overline{B} $$ pairs collected by the Belle II experiment, both in electron-positron collisions at the Υ(4S) resonance. We measure the CP asymmetries to be A $$ \mathcal{A} $$ CP+ = (+12.5 ± 5.8 ± 1.4)% and A $$ \mathcal{A} $$ CP− = (−16.7 ± 5.7 ± 0.6)%, and the ratios of branching fractions to be R $$ \mathcal{R} $$ CP+ = 1.164 ± 0.081 ± 0.036 and R $$ \mathcal{R} $$ CP− = 1.151 ± 0.074 ± 0.019. The first contribution to the uncertainties is statistical, and the second is systematic. The asymmetries A $$ \mathcal{A} $$ CP+ and A $$ \mathcal{A} $$ CP− have similar magnitudes and opposite signs; their difference corresponds to 3.5 standard deviations. From these values we calculate 68.3% confidence intervals of (8.5 ° < ϕ 3 < 16.5 ° ) or (84.5 ° < ϕ 3 < 95.5 ° ) or (163.3 ° < ϕ 3 < 171.5 ° ) and 0.321 < r B < 0.465.

Abstract We define and compute the leading sphere diagram contribution to the entropy of the BTZ black hole supported by Kalb-Ramond flux in bosonic string theory. In a winding condensate description, integrating exactly over the constant mode for the radial direction of AdS3 reduces the problem to one of the correlation functions of winding operators in the free theory. The volume of the residual PSL(2,ℂ) gauge group of the sphere is canceled by the action of conformal transformations on the winding interaction insertions. We formulate a precise version of the replica trick in terms of (infinitesimally) non-integer winding condensates to produce the entropy of the BTZ black hole. The resulting entropy can be calculated from the one-point function of a non-local operator on the worldsheet.

Abstract We conjecture a two-dimensional conformal field theory built out of a linear dilaton and a compact βγ system deformed by winding condensates on each of the compact cycles. In particular, explicit expressions of the residues of the correlation functions are provided. As a worldsheet theory, it describes a stringy black hole in AdS3 (supported by the Kalb-Ramond flux) at the Hawking-Page temperature. It is expected to be connected to the Horowitz-Polchinski-like solution near the Hagedorn temperature of thermal AdS3 and Euclidean BTZ blackhole as we vary the temperature.

Abstract The traditional Haber-Bosch process for ammonia production is energy-intensive and relies on harsh conditions. Plasmonic materials are considered a sustainable alternative to this process. In plasmonics, the ability to localize and enhance light fields beyond the diffraction limit offers a promising avenue for harnessing visible light for photocatalysis. Moreover, the integration of plasmonic metals with various catalysts presents a promising avenue to improve efficiency and selectivity. However, cost and stability challenges hinder large-scale applications. Researchers are actively exploring new materials, optimizing catalyst design, and improving stability to overcome these hurdles. This Review delves into the intricacies of plasmonic catalysis, including material design, co-catalyst selection, and the use of nanotechnologies for precise control of metal properties in plasmonic catalysis. It emphasizes understanding energy flow at material interfaces. Ultimately, the Review aims to establish a foundation for efficient nitrogen fixation through plasmonic photocatalysis, paving the way for a more sustainable future.

Objectives: Schizophrenia is a persistent and incapacitating psychiatric condition characterized by symptoms with positive, negative, affective, and cognitive domains. Sleep disturbances represent an important facet of this disorder, impacting both the quality of life and influencing its overall outcome. In the cross-sectional study, we intended to investigate the polysomnographic findings of patients with schizophrenia showing predominantly positive symptoms as opposed to those presenting with predominantly negative symptoms and also as compared to normal population. Methods: This study had a cross-sectional design, involving the recruitment of 60 medication-naive patients diagnosed with schizophrenia according to the ICD-10 criteria and 30 study participants representing normal population. The cases were subdivided into two groups: one characterized by predominantly positive symptoms and the other characterized by predominantly negative symptoms. Both the groups received overnight polysomnography, and study variables were recorded. Results: All the sleep parameters were deranged in patients with schizophrenia as compared to normal controls in the general population, with significantly more pronounced differences found in those with predominant positive symptoms for most variables (p < 0.001). The only exception was the duration of N3 (slow-wave sleep) which was significantly decreased in patients with negative symptoms compared to those with positive symptoms (p < 0.001). But no significant differences were found between the negative and positive symptom domain groups in mean rapid eye movement (REM) latency, duration of N1 and N2 sleep, and total percentage of REM sleep. Conclusion: This study highlights substantial variations in sleep patterns between the negative and positive symptom domains of schizophrenia and also as compared to the general population. Further study is imperative to explore the link between circadian integrity and symptoms of the various domains of schizophrenia.

Background: The Comet assay is a technique used to detect DNA damage at the single-cell level. This study aimed to investigate the potential relationship between the histopathological grading of oral squamous cell carcinoma (OSCC) and genotoxicity (DNA damage). Methods: Blood samples were collected from both normal subjects and patients diagnosed with OSCC. Slides prepared for the Comet assay were analyzed using an electrofluorescent microscope with a calibrated eyepiece to measure the total image length and head diameter. DNA tail length was calculated by subtracting the head diameter from the total length. Results: In the evaluation of DNA damage in 26 OSCC patients compared to 10 controls, a significantly higher level of DNA damage was observed in OSCC patients (P < 0.001). When considering different histological grades, the mean DNA damage was found to be highest in poorly differentiated (29.9 μm), followed by moderately differentiated (25.60 μm), and lowest in well-differentiated (23.28 μm) cases. Although differences in the average DNA damage did not reach statistical significance among the histological grades (P > 0.05), all “t” values fell below the critical values at the 5% level, indicating no significant differences between the stages. Conclusions: The extent of DNA damage in OSCC was highest in poorly differentiated cases, followed by moderately differentiated and well-differentiated cases. These findings suggest a potential link between histopathological grading and DNA damage in OSCC.

Abstract Background This systematic review and meta-analysis aimed to compare the efficacy and safety of cangrelor as compared to ticagrelor in patients with ST-elevated myocardial infarction (STEMI) who underwent percutaneous intervention. Methods PubMed, Embase, Scopus, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov databases were searched for relevant head-on-comparison or swapping studies. The primary outcome was the rate of high platelet reactivity (HPR) at specific time intervals after stopping cangrelor infusion during the first 24 h. Secondary outcomes were the risks of thrombosis, all-cause mortality and bleeding. Pooled odds ratios (ORs) were calculated using random-effects models. Results A total of 1018 studies were screened and eight were included in the analysis. There were four head-on-comparison studies and four swapping studies. There was no significant difference in the proportion of patients achieving a high platelet reactivity in swapping studies [OR, 0.71 (95% CI 0.04, 13.87), p = 0.82, i 2 = 88%]. In head-on-comparison studies, PRU from Fig. 2B shows there was no significant reduction in high platelet reactivity [mean difference – 77.83 (95% CI − 238.84, 83.18), p

ABSTRACTThe Shillong Plateau is the only elevated topography in the Himalayan foreland bounded and crisscrossed by several prominent faults and shear zones. The plateau is situated in a complex tectonic compressional set up, owing to which the fault systems both at the periphery and within tend to be neotectonically active. Due to the elevation difference of the plateau with the Brahmaputra and Meghna River valleys flanking it, coupled with the impervious lithologies present, an intricate network of drainage system has developed in the plateau. In this paper, morphometric and structural analyses of four selected drainage basins from the east-central part of Shillong Plateau have been carried out to comprehend the effects of neotectonic reactivation of fault systems and associated basin tilting which in turn controls the development of drainage pattern. This has led to the understanding of the effects of the ever-evolving fluvial landforms on the anthroposphere in this part of Indian sub-continent, where the agrarian-economy is completely dependent on the intricate fluvial systems.

Abstract Rheumatoid arthritis (RA) is an autoimmune disorder with a varying range of organs involved leading to adverse outcomes. However, very little is known, with conflicting results about the association between RA and atrial fibrillation (AF). We aim to evaluate the association between RA and AF, and other clinical outcomes. We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until September 10, 2023. Primary clinical outcomes were AF. Secondary outcomes were acute coronary syndrome (ACS), stroke, and all‐cause mortality (ACM). A total of 4 679 930 patients were included in the analysis, with 81 677 patients in the RA group and 4 493 993 patients in the nonrheumatoid arthritis (NRA) group. The mean age of the patients was 57.2 years. Pooled analysis of primary outcomes shows that RA groups of patients had a significantly higher risk of AF (odds ratios [OR], 1.53; 95% confidence interval [CI]: [1.16–2.03], p

Abstract We present the Urban Nature Indexes (UNI), a comprehensive tool that measures urban ecological performance under one standard framework linked to global commitments. The UNI was developed by interdisciplinary experts and evaluated by practitioners from diverse cities to capture each city’s ecological footprint from local to global scale. The UNI comprises six themes (consumption drivers, human pressures, habitat status, species status, nature’s contributions to people, and governance responses) that encompass measurable impacts on climate change, biodiversity loss, ecosystem services, pollution, consumption, water management, and equity within one comprehensive system. Cities then adapt the UNI to their context and capacity by selecting among indicator topics within each theme. This adaptability and holistic approach position the UNI as an essential instrument for nature-positive transformations. With the institutional support of IUCN, the UNI offers an opportunity for cities to assess and enhance their contributions towards a more sustainable and biodiverse future.

Agricultural soil contamination is increasing day-by-day and becoming a major problem over the globe. Trace elements accumulation in the bulk soil is frequently documented, however, there is no precise mechanism of their distribution in the different soil aggregates level. We collected twelve composite soil samples from banana fields, fallow land, rice cultivated with pond water (rice field-I), and rice cultivated with rain water (rice field-II). We separated soil samples into four different size of aggregates (4-2, 2–0.25, 0.25–0.053, 0.05). Moreover, macroaggregate acted as an accumulator for Fe, Mn, and As, while all the aggregate fractions acted as accumulators for Cu and Zn. Our study indicated that MWD, SOC, aggregate size and composition, and metal species were the controlling factors of trace elements accumulation and distribution in the various sizes of soil aggregates.

Routinely collected health data (RCD) including electronic health records, disease registries, health administrative data and wearables data are not specifically collected for research purposes. Analysis of these data poses unique methodological challenges that must be addressed when conducting research, particularly as availability and use increase. This scoping review aimed to identify methodological challenges in research using RCD from existing literature (registered protocol: https://doi.org/10.17605/OSF.IO/EBM4D). We searched 6 electronic databases, including medical, health economics, nursing and psychology research databases, between Jan 2015 and Jan 2023, combining multiple “RCD” and “research” search terms (e.g., epidemiologic, informatics, pharmaceutical research). After screening abstracts and full-texts, we doubly extracted methodological themes, categorizing them into different study stages. We screened more than 23,000 records and included 430 papers. Bias and confounding were the most common methodological issues identified, discussed in relation to both study design and data analysis. Data quality, including data accuracy, validation, completeness, timeliness and cleaning, also posed substantial challenges, particularly during data processing stage. Record linkage and conducting analyses using distributed health networks also pose unique methodological challenges. Heterogeneity, incorporating social determinants of health and statistical models that address methodological challenges are also described in the literature. External validity and reporting are important considerations for RCD research. Our review identified several methodological challenges facing researchers using RCD. These issues should be addressed to ensure methodologically sound research. These findings will inform the development of a standardized protocol template and accompanying educational platform aimed at enhancing methodological quality and transparency when conducting research using RCD.

IntroductionKnowledge of the risk of developing cardiovascular diseases (CVD) in the population is an important risk management strategy for the prevention of this disease. This is especially true for India, which has resource-restrained settings with an increased risk in a younger population for the development of the disease. An important modifiable risk factor for CVD is hypertension, with its influence on the development of CVD.MethodsThe data from the first wave of the Longitudinal Ageing Study in India (LASI) was used to calculate the 10-year CVD Risk Score among older adults ≥45 years using a WHO (2019) non-laboratory- based chart for South Asia. Univariate analysis was done using Pearson’s chi-square test, and multivariable analysis using ordinal logistic regression. Categories of CVD risk score were considered as dependent variable. Socio-demographic variables, regular exercise, history of diabetes and hyperlipidaemia were considered as the independent variables. Relationship between CVD Risk score and hypertensives and self-reported hypertensives were presented using restricted cubic splines.ResultTwo-thirds (68.8%) of the population had a 10-year CVD risk of

In p-MFCs living plants photosynthesize within a bio-electrochemical circuit. The plant exudes organic waste material from the roots. In the rhizosphere, bacteria consume these wastes by oxidizing them in contrast to the atmosphere that reduces it. This redox reaction along with photosynthesis can be harnessed as bioelectricity. In this work, the plant Withania somnifera (L.) Dunal was used for generating bioelectricity from the root exudates and organic matter available in the soil. An open circuit voltage of 930±21 mV was achieved between multiple cycles of operation. The cell voltage further increased to 1260±140 mV with enrichment in the form of discards from vegetable matter. The peak recorded voltage was 1400 mV. Graphite fibre felt electrodes ensured uniform microbial growth with power densities that were achieved at 57 mW/m2 and 84 mW/m2 with and without enrichment respectively. ATR-FTIR demonstrated complete degradation of specific compounds attached to the carbon matrix in the soil along with the polysaccharide content from the enrichments. Additionally, this work also monitored the changes in soil pH and its homogeneity, the impact of photosynthetically active radiation, humidity, and the presence of CO2 in the air, and how it affects plant growth and ultimately the microbes at the rhizosphere which accounted for the bioremediation and the resultant bioelectricity production. SEM imaging provided additional evidence that the presence of electrochemically active soil bacteria, an anaerobic environment, and electrode characteristics are crucial for the development of conductive biofilms.

In response to Mazaheri et al.'s critique, we revisited our study (Valentini et al., 2022) on the relationship between peak alpha frequency (PAF) and pain. Their commentary prompted us to reassess our data to address the independence between slow and slowing alpha brain oscillations, as well as the predictivity of slow alpha oscillations in pain perception. Bayesian correlation analyses revealed mixed support for independence. Investigating predictivity, we found inconsistent associations between pre-PAF and unpleasantness ratings. We critically reflected on methodological and theoretical issues on the path to PAF validation as a pain biomarker. We emphasized the need for diversified methodology and analytical approaches as well as robust findings across research groups.

This research investigates the potential of flint glass as a foundational material for photonic crystal configurations designed to achieve high nonlinear coefficients across various communication wavelengths. We explore dispersion management within telecom bands using flint glass-based micro-structured optical fibers, employing numerical analysis via the finite element method to assess optical properties. In this study, three different basic MOF structures (hexagonal, square, and octagonal) were created using flint glass background material rather of the commonly utilized fused silica material, and the numerically was assessed in contrast to prior studies and designs. Among the configurations studied, the octagonal arrangement (FGO-MOF) excels in dispersion compensation, achieving −136.6 ps/(nm.km) at 1.55 µm. Conversely, the hexagonal air hole ring cladding design (FGH-MOF) displays higher nonlinearity (770.5 W−1.km−1), a smaller effective area (1.115 µm2), and a high numerical aperture (0.6378). In contrast, the square air hole ring cladding optical fiber (FGS-MOF) exhibits low confinement loss (6.309 × 10−7 dB/cm) at 1.55 µm but with comparatively less favorable optical properties. Our study demonstrates that the hexagonal microstructured optical fiber with flint glass (FGH-MOF) offers superior performance in dispersion compensation, nonlinearity, and low loss within telecom bands. This finding suggests promising applications in high-bit-rate communication systems, biomedical sensing, and supercontinuum generation, presenting exciting avenues for further research and practical implementation.

Background: Sodium glucose cotransporter 2 inhibitors are recommended for the treatment of heart failure due to their cardioprotective effects, despite primarily being used as antidiabetic medications. However, the comparative profile of two antidiabetic drugs, sodium glucose cotransporter 2 inhibitors with dipeptidyl peptidase 4 inhibitor remains unclear. Study hypothesis: This study aims to compare the safety and efficacy profiles of sodium glucose cotransporter 2 inhibitors versus dipeptidyl peptidase 4 inhibitor drugs. Methods: A comprehensive search was conducted in PubMed, Scopus, Web of Science, Google Scholar, and ClinicalTrials.gov using appropriate Medical Subject Headings terms from inception until February 23, 2023. The outcomes were pooled using a random-effects model for hazard ratio with a 95% confidence interval. A p -value of

Staphylococcus aureus, a prevalent component of the human microbiota, is associated with skin infections to life-threatening diseases, presenting challenges in treatment options and necessitating the development of effective treatments. This study integrated computational and in vitro approaches to identify promising phytocompounds with therapeutic potential. Staphopain B emerged as a target protein for its role in immune evasion, exhibiting stability during molecular dynamic simulation (MDS) with a root mean square deviation value of 2.376 Å. Screening 115 phytocompounds with antibacterial properties from the PubChem database identified 12 with drug-like properties, nine of which showed superior binding affinity to Staphopain B compared to a commercial antibiotic, doxycycline (−7.8 kcal mol−1). Notably, epoxyazadiradione and nimbolide displayed higher estimated free energy of binding scores (−7.91 and −7.93 kcal mol−1, respectively), indicating strong protein–ligand interactions. The root mean square fluctuation values for epoxyazadiradione and nimbolide were 1.097 and 1.034 Å, respectively, which was confirmed through MDS. Crude ethanolic extracts (100% and 70%) of neem (Azadirachta indica) leaves demonstrated narrow inhibition against the bacteria in comparison to doxycycline in the disc-diffusion assay. This study underscores the potential of phytocompounds as therapeutic agents against S. aureus; however, further in vitro experiments and testing of the phytocompounds in vivo are required.

Key Clinical Message Lateral medullary syndrome, resulting from cerebellar/brainstem infarction, can occur due to cardioembolic stroke from atrial fibrillation caused by rheumatic heart disease. This rare association highlights the importance of strict arrhythmia management, prophylactic anticoagulation, and timely diagnosis to prevent debilitating neurological outcomes.

We report a case of symptomatic supraventricular tachycardia who had absent VA conduction during electrophysiology study. The interesting finding was appearance of VA conduction only at a specific cycle length of ventricular pacing which reproducibly induced a sustained orthodromic re-entrant tachycardia (ORT). We review the literature and conclude that supernormal AP conduction can explain such phenomenon.

Internet applications rely on Secure Socket Layer (SSL)/Transport Security Layer (TSL) certifications to establish secure communication. However, the centralized nature of certificate authorities (CAs) poses a risk, as malicious third parties could exploit the CA to issue fake certificates to malicious web servers, potentially compromising the privacy and integrity of user data. In this paper, we demonstrate how the utilization of decentralized certificate verification with blockchain technology can effectively address and mitigate such attacks. We present a decentralized public key infrastructure (PKI) based on a distributed trust model, e.g., Web of Trust (WoT) and blockchain technologies, to overcome vulnerabilities like single points of failure and to prevent tampering with existing certificates. In addition, our infrastructure establishes a trusted key-ring network that decouples the authentication process from CAs in order to enhance secure certificate issuance and accelerate the revocation process. Furthermore, as a proof of concept, we present the implementation of our proposed system in the Ethereum blockchain, confirming that the proposed framework meets the five identified requirements. Our experimental results demonstrate the effectiveness of our proposed system in practice, albeit with additional overhead compared to conventional PKIs.

Abstract Hyperactivation of YAP/TAZ, the Hippo pathway downstream effectors, is common in human cancer. The requirement of YAP/TAZ for cancer cell survival in preclinical models, prompted the development of pharmacological inhibitors that suppress their transcriptional activity. However, systemic YAP/TAZ inhibition may sometimes have unpredictable patient outcomes, with limited or even adverse effects because YAP/TAZ action is not simply tumor promoting but also tumor suppressive in some cell types. Here, we review the role of the Hippo pathway in distinct tumor cell populations, discuss the impact of inhibiting Hippo output on tumor growth, and examine current developments in YAP/TAZ inhibitors.

Abstract Congenital Prosopagnosia (CP) is an innate impairment in face perception with heterogeneous characteristics. It is still unclear if and to what degree holistic processing of faces is disrupted in CP. Such disruption would be expected to lead to a focus on local features of the face. In this study, we used binocular rivalry (BR) to implicitly measure face perception in conditions that favour holistic or local processing. The underlying assumption is that if stimulus saliency affects the perceptual dominance of a given stimulus in BR, one can deduce how salient a stimulus is for a given group (here: participants with and without CP) based on the measured perceptual dominance. A further open question is whether the deficit in face processing in CP extends to the processing of the facial display of emotions. In experiment 1, we compared predominance of upright and inverted faces displaying different emotions (fearful, happy, neutral) vs. houses between participants with CP (N = 21) and with normal face perception (N = 21). The results suggest that CP observers process emotions in faces automatically but rely more on local features than controls. The inversion of faces, which is supposed to disturb holistic processing, affected controls in a more pronounced way than participants with CP. In experiment 2, we introduced the Thatcher effect in BR by inverting the eye and mouth regions of the presented faces in the hope of further increasing the effect of face inversion. However, our expectations were not borne out by the results. Critically, both experiments showed that inversion effects were more pronounced in controls than in CP, suggesting that holistic face processing is less relevant in CP. We find BR to be a useful implicit test for assessing visual processing specificities in neurological participants.

Abstract Interactions between extracellular matrix (ECM) proteins and β1 integrins play an essential role maintaining vascular integrity in the brain, particularly under vascular remodeling conditions. As blood vessels in the spinal cord are reported to have distinct properties from those in the brain, here we examined the impact of β1 integrin inhibition on spinal cord vascular integrity, both under normoxic conditions, when blood vessels are stable, and during exposure to chronic mild hypoxia (CMH), when extensive vascular remodeling occurs. We found that a function-blocking β1 integrin antibody triggered a small degree of vascular disruption in the spinal cord under normoxic conditions, but under hypoxic conditions, it greatly enhanced (20-fold) vascular disruption, preferentially in spinal cord white matter (WM). This resulted in elevated microglial activation as well as marked loss of myelin integrity and reduced density of oligodendroglial cells. To understand why vascular breakdown is localized to WM, we compared expression levels of major BBB components of WM and grey matter (GM) blood vessels, but this revealed no obvious differences. Interestingly however, hypoxyprobe staining demonstrated that the most severe levels of spinal cord hypoxia induced by CMH occurred in the WM. Analysis of brain tissue revealed a similar preferential vulnerability of WM tracts to show vascular disruption under these conditions. Taken together, these findings demonstrate an essential role for β1 integrins in maintaining vascular integrity in the spinal cord, and unexpectedly, reveal a novel and fundamental difference between WM and GM blood vessels in their dependence on β1 integrin function during hypoxic exposure. Our data support the concept that the preferential WM vulnerability described may be less a result of intrinsic differences in vascular barrier properties between WM and GM, and more a consequence of differences in vascular density and architecture.

Mayank Gupta,1,&ast; Anand S Patil,2,&ast; Ahish Chitneni,3 Michael E Schatman,4 Hemant Kalia,5 Timothy R Deer,6 Dawood Sayed,7 Amol Soin,8 Ganesan Baranidharan,9 Peter Staats,10 Leonardo Kapural,11 Phani Ashok Attaluri,12 Paul Verrills,13 Sudhir Diwan,14 Danielle Levin,4 Nimisha Halder,15 Alaa A Abd-Elsayed16 1Kansas Pain Management & Neuroscience Research Center, LLC, Overland Park, KS, USA; 2St. Luke’s Rehabilitation Medical Center, Spokane, WA, USA; 3Newyork-Presbyterian, New York, NY, USA; 4Department of Anesthesiology, Perioperative Care & Pain Medicine, NYU Grossman School of Medicine, New York, NY, USA; 5Rochester Regional Health System, Rochester, NY, USA; 6The Spine and Nerve Center of the Virginias, Charleston, WV, USA; 7The University of Kansas Health System, Kansas City, KS, USA; 8The Ohio Pain Clinic, Dayton, OH, USA; 9Leeds Teaching Hospitals NHS Trust, Leeds, UK; 10National Spine & Pain Centers, Frederick, MD, USA; 11Carolinas Pain Institute, Winston-Salem, NC, USA; 12Olathe Health, Olathe, KS, USA; 13Metro Pain Group, Clayton, VIC, Australia; 14Manhattan Spine & Pain, New York, NY, USA; 15Kansas City University, Kansas City, MO, USA; 16UW Health Pain Services, University of Wisconsin-Madison, Madison, WI, USA&ast;These authors contributed equally to this workCorrespondence: Mayank Gupta, Kansas Pain Management & Neuroscience Research Center, LLC, Overland Park, KS, USA, Email mayank.g@kansaspainmanagement.comAbstract: In this article, we propose a new diagnostic paradigm known as Chronic Abdominal Discomfort Syndrome (CADS). Patient’s presentation centers around chronic abdominal pain not explained by acute pathology with or without accompanying dyspepsia, bloating, nausea and vomiting among other symptoms. The pathophysiology is noted to be neurogenic, possibly stemming from visceral sympathetic nerves or abdominal wall afferent nerves. Diagnosis is supported by signs or symptoms traversing clinical, diagnostic and functional criteria. Included is a tool which can assist clinicians in diagnosing patients with CADS per those domains. We hope to facilitate primary care physicians’ and gastroenterologists’ utilization of our criteria to provide guidance for selecting which patients may benefit from further interventions or evaluation by a pain physician. The pain physician may then offer interventions to provide the patient with relief.Keywords: CADS, chronic abdominal pain, neurogenic abdominal pain, chronic abdominal discomfort

Abstract Alzheimer’s disease (AD) progression and pathology show pronounced sex differences, but the factors driving these remain poorly understood. To gain insights into early AD-associated molecular changes and their sex dependency for tau pathology in the cortex, we performed single-cell RNA-seq in the THY-Tau22 AD mouse model. By examining cell type-specific and cell type-agnostic AD-related gene activity changes and their sex-dimorphism for individual genes, pathways and cellular sub-networks, we identified both statistically significant alterations and interpreted the upstream mechanisms controlling them. Our results confirm several significant sex-dependent alterations in gene activity in the THY-Tau22 model mice compared to controls, with more pronounced alterations in females. Both changes shared across multiple cell types and cell type-specific changes were observed. The differential genes showed significant over-representation of known AD-relevant processes, such as pathways associated with neuronal differentiation, programmed cell death and inflammatory responses. Regulatory network analysis of these genes revealed upstream regulators that modulate many of the downstream targets with sex-dependent changes. Most key regulators have been previously implicated in AD, such as Egr1, Klf4, Chchd2, complement system genes, and myelin-associated glycoproteins. Comparing with similar data from the Tg2576 AD mouse model and human AD patients, we identified multiple genes with consistent, cell type-specific and sex-dependent alterations across all three datasets. These shared changes were particularly evident in the expression of myelin-associated genes such as Mbp and Plp1 in oligodendrocytes. In summary, we observed significant cell type-specific transcriptomic changes in the THY-Tau22 mouse model, with a strong over-representation of known AD-associated genes and processes. These include both sex-neutral and sex-specific patterns, characterized by consistent shifts in upstream master regulators and downstream target genes. Collectively, these findings provide insights into mechanisms influencing sex-specific susceptibility to AD and reveal key regulatory proteins that could be targeted for developing treatments addressing sex-dependent AD pathology.

Abstract Development of safe, highly effective and affordable enteric fever vaccines is a global health priority. Live, oral typhoid vaccines induce strong mucosal immunity and long-term protection, but safety remains a concern. In contrast, efficacy wears off rapidly for injectable, polysaccharide-based vaccines, which elicit poor mucosal response. We previously reported Salmonella Typhi outer membrane protein, T2544 as a potential candidate for bivalent (S. Typhi and S. Paratyphi A) vaccine development. Here, we show that intranasal immunization with a subunit vaccine (chimera of T2544 and cholera toxin B subunit) induced strong systemic and intestinal mucosal immunity and protection from S. Typhi challenge in a mouse model. CTB-T2544 augmented gut-homing receptor expression on lymphocytes that produced Th1 and Th17 cytokines, secretory IgA in stool that inhibited bacterial motility and epithelial attachment, antibody recall response and affinity maturation with increased number of follicular helper T cells and CD4+ central and effector memory cells.

Abstract Background Plasmodium vivax remains a major challenge for malaria control and elimination due to its ability to cause relapsing illness. To prevent relapses the Indian National Center for Vector Borne Diseases Control (NCVBDC) recommends treatment with primaquine at a dose of 0.25 mg/kg/day provided over 14 days. Shorter treatment courses may improve adherence and treatment effectiveness. Methods This is a hospital-based, randomised, controlled, open-label trial in two centres in India. Patients above the age of 16 years, with uncomplicated vivax malaria, G6PD activity of ≥ 30% of the adjusted male median (AMM) and haemoglobin levels ≥ 8 g/dL will be recruited into the study and randomised in a 1:1 ratio to receive standard schizonticidal treatment plus 7-day primaquine at 0.50 mg/kg/day or standard care with schizonticidal treatment plus 14-day primaquine at 0.25 mg/kg/day. Patients will be followed up for 6 months. The primary endpoint is the incidence risk of any P. vivax parasitaemia at 6 months. Safety outcomes include the incidence risk of severe anaemia (haemoglobin < 8 g/dL), the risk of blood transfusion, a > 25% fall in haemoglobin and an acute drop in haemoglobin of > 5 g/dL during primaquine treatment. Discussion This study will evaluate the efficacy and safety of a 7-day primaquine regimen compared to the standard 14-day regimen in India. Results from this trial are likely to directly inform national treatment guidelines. Trial registration Trial is registered on CTRI portal, Registration No: CTRI/2022/12/048283.