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Abstract Background Tuberculosis (TB) poses a significant social and economic burden to households of persons with TB (PwTB). Despite free diagnosis and care under the National TB Elimination Programme (NTEP), individuals often experience significant out-of-pocket expenditure and lost productivity, causing financial catastrophe. We estimated the costs incurred by the PwTB during TB care and identified the factors associated with the costs. Methods In our cross-sectional study, we used multi-stage sampling to select PwTB notified under the NTEP, whose treatment outcome was declared between May 2022 and February 2023. Total patient costs were measured through direct medical, non-medical and indirect costs. Catastrophic costs were defined as expenditure on TB care > 20% of the annual household income. We determined the factors influencing the total cost of TB care using median regression. We plotted concentration curves to depict the equity in distribution of catastrophic costs across income quintiles. We used a cluster-adjusted, generalized model to determine the factors associated with catastrophic costs. Results The mean (SD) age of the 1407 PwTB interviewed was 40.8 (16.8) years. Among them, 865 (61.5%) were male, and 786 (55.9%) were economically active. Thirty-four (2.4%) had Drug Resistant TB (DRTB), and 258 (18.3%) had been hospitalized for TB. The median (Interquartile range [IQR] and 95% confidence interval [CI]) of total costs of TB care was US$386.1 (130.8, 876.9). Direct costs accounted for 34% of the total costs, with a median of US$78.4 (43.3, 153.6), while indirect costs had a median of US$279.8 (18.9,699.4). PwTB

Introduction: Gouty tophi represents an uncommon outcome of prolonged gout. The urate crystal deposition in soft tissues characterizes it. They can present as tender, soft tissue masses, mimicking benign growths. Elbow tophi are uncommon but can cause significant morbidity. Case Report: A 65-year-old man with a history of chronic gout came in with noticeable swelling on the outer side of his right elbow. The swelling was firm in consistency, nonfluctuant, and mildly tender. Radiological and Histopathological investigations confirmed the diagnosis of tophaceous gout. A successful surgical excision was performed with uneventful post-operative results. Conclusion: This case study emphasizes the significance of suspecting tophaceous gout in individuals presenting with significant, unexplained swellings, especially in patients with a known history of gout. Prompt recognition and proper treatment are essential to avert further complications.

Our primary goal is to report a detailed case outlining the clinical and radiological characteristics of an extremely rare condition: bilateral internal carotid artery (ICA) stenosis with ruptured basilar tip aneurysm, and bilateral posterior cerebral arteries (PCAs) arising from the sac, treatment options, as well as its outcome. We searched the PUBMED database from 1980 to 2023 for similar case reports. Among seven similar cases found, two were conservatively managed, focusing on reducing intracranial pressure (ICP). One out of two survived, while one ended in fatality. In the other five cases, interventions (endovascular in four/STA-MCA (superficial temporal artery–middle cerebral artery) bypass in one) were pursued, resulting in significant recovery and discharge. Dealing with such complex cases with uncommon pathoanatomy poses treatment challenges due to their hemodynamics and the risk of collateral flow cessation despite multiple available treatment options.

Abstract As SARS-CoV-2 evolves, increasing in potential for greater transmissibility and immune escape, updated vaccines are needed to boost adaptive immunity to protect against COVID-19 caused by circulating strains. Here, we report features of the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine, which contains XBB.1.5-specific sequence changes, relative to the original BNT162b2 backbone, in the encoded prefusion-stabilized SARS-CoV-2 spike protein (S(P2)). Biophysical characterization of Omicron XBB.1.5 S(P2) demonstrated that it maintains a prefusion conformation and adopts a flexible, predominantly open, state, with high affinity for the human ACE-2 receptor. When administered as a 4th dose in BNT162b2-experienced mice, the monovalent Omicron XBB.1.5 vaccine elicited substantially higher serum neutralizing titers against pseudotyped viruses of Omicron XBB.1.5, XBB.1.16, XBB.1.16.1, XBB.2.3, EG.5.1 and HV.1 sublineages and phylogenetically distant BA.2.86 lineage than the bivalent Wild Type + Omicron BA.4/5 vaccine. Similar trends were observed against Omicron XBB sublineage pseudoviruses when the vaccine was administered as a 2-dose series in naive mice. Strong S-specific Th1 CD4+ and IFNγ+ CD8+ T cell responses were also observed. These findings, together with real world performance of the XBB.1.5-adapted vaccine, suggest that preclinical data for the monovalent Omicron XBB.1.5-adapted BNT162b2 was predictive of protective immunity against dominant SARS-CoV-2 strains.

Background: The rising global incidence of Caesarean section (CS) potentially reflects healthcare disparities between Particularly Vulnerable Tribal Groups (PVTG) and non-PVTG populations. This study analyzed CS patterns, indications, and outcomes between these groups at a district hospital in Gajapati, India. Methods: This prospective observational study examined 1,374 CS cases (177 PVTG and 1,197 non-PVTG) from October 2023 to October 2024. The analysis incorporated CS indications, APGAR scores, Robson classification, maternal age, and delivery timing using descriptive statistics and chi-square tests. Results: Previous CS emerged as the primary indication in both groups (PVTG, 29.9%; non-PVTG, 39.3%). PVTG women demonstrated higher rates of malpresentation (4.0% vs. 1.0%) and younger maternal age (23.2% vs. 19.3% for ages 18-20). Robson Group 5 predominated in non-PVTG cases (41.0% vs. 28.4%), while nocturnal CS rates were elevated among PVTG women (4.1% vs. 1.4%). Conclusions: The identified disparities necessitate targeted interventions, including enhanced antenatal care for young PVTG mothers, VBAC promotion among non-PVTG women, and improved round-the-clock obstetric services in the tribal regions.

Exceptional reduced graphene oxide-based nanocomposites (NCs) were synthesized using Al2O3-CuO-ZnO (ACZ) nanoparticles (NPs) through a controlled hydrothermal method. Nanomaterials with improved optical, magnetic, antibacterial, adsorption, anticorrosive, and photocatalytic characteristics were synthesized, showing synergistic behavior. To understand key structural features, the NCs were thoroughly examined using energy-dispersive X-ray analysis, SEM, X-ray diffraction, FTIR, and UV-Vis. spectroscopy. Adding ACZ NPs in the rGO matrix, increased magnetic, anticorrosive, improved antibacterial efficacy against Gram-positive bacteria, and photocatalytic activities. The NCs were exposed to sunlight and UVA and UVB light to degrade methylene blue (MB) dye i.e., 89.21 % in 75 min. The anti-corrosive characteristics (95.9 %) were examined against mild steel using a 1.0 N H2SO4 at room temperature at a very low concentration i.e., 10 ppm. The magnetic behavior of the NCs was examined with the help of Gouy’s balance. The induced current showed a clear relationship to the applied magnetic field strength, indicating that the NCs are paramagnetic. The antibacterial effects of the NCs were evaluated against S. aureus and E. coli at different concentrations. The ACZ@rGO NCs exhibited exceptional versatility, showing great promise for water purification, adsorption, corrosion protection, photocatalytic processes, biomedical technologies, and environmental restoration.

Aim: This study aims to assess whether endodontic cryotherapy can effectively lower discomfort after a single root canal visit. Material and Method: Thirty-six patients aged 18–32 years requiring single-visit root canal treatment (RCT) were divided into three groups at random, with twelve people in each: group 1 (control group), group 2 (normal saline), and group 3 (cold saline). After root canal therapy was finished, group 1 got no further treatment, group 2 got standard saline irrigation at room temperature, and group 3 got cold saline irrigation at 35.6–41°F. A visual analog scale (VAS) was used to measure pain after 6, 12, 24, and 48 hours after therapy. Result: Preliminary results indicated a marked reduction in pain in group 3 relative to groups 1 and 2 at 6, 12, and 24 hours post-treatment (P < 0.05). At 48 hours, pain levels had significantly diminished across all groups, with group 3 consistently exhibiting the lowest VAS scores. Conclusion: Endodontic cryotherapy using cold saline irrigation shows significant efficacy in reducing post-treatment pain after single-visit RCT when compared to normal saline and no additional intervention. These findings suggest that integrating cryotherapy could be a valuable adjunct in endodontic pain management.

Background Ni-kshay Poshan Yojana (NPY), a direct benefit transfer scheme under the National Tuberculosis Elimination Program (NTEP) in India, provides a monthly benefit of INR500 for nutritional support of persons with TB (PwTB). Objectives To determine the proportion of PwTB receiving at least one NPY instalment and pattern of utilisation; to ascertain factors associated with NPY non-receipt and association of NPY receipt with TB treatment outcome. Methods In our cross-sectional study, we used multi-stage sampling to select PwTB whose treatment outcome was declared between May 2022 and February 2023. A cluster-adjusted, generalized linear model was used to identify factors associated with the non-receipt of NPY and determine association between NPY receipt and TB treatment outcome. Results Among 3201 PwTB, 2888 (92.7%; 95% CI 89.8%, 94.8%) had received at least one NPY instalment, and 1903 (64.2%; 95% CI 58.9%, 69.2%) self-reported receipt of benefit. The median (IQR) time to receipt of first instalment was 105 (60,174) days. Non-receipt was significantly higher among PwTB from states with low TB score (aPR = 2.34; 95%CI 1.51, 3.62), who do not have bank account (aPR = 2.48; 95%CI 1.93, 3.19) and with unknown/missing diabetic status (aPR = 1.69; 95%CI 1.11, 2.55). Unfavorable treatment outcomes were associated with non-receipt of NPY (aPR 4.93; 95%CI 3.61,6.75) after adjusting for potential confounders. Conclusion Majority of the PwTB received at least one NPY instalment, but they experience significant delays. Most of the recipients utilised NPY for nutrition. Longitudinal follow-up studies are required to study the impact of NPY on treatment outcomes.

Macrophages are integral part of the body's defense against pathogens and serve as vital regulators of inflammation. Adaptor molecules, featuring diverse domains, intricately orchestrate the recruitment and transmission of inflammatory responses through signaling cascades. Key domains involved in macrophage polarization include Toll-like receptors (TLRs), Src Homology2 (SH2) and other small domains, alongside receptor tyrosine kinases, crucial for pathway activation. This review aims to elucidate the enigmatic role of macrophage adaptor molecules in modulating macrophage activation, emphasizing their diverse roles and potential therapeutic and investigative avenues for further exploration.

This study presents a comprehensive dataset comparing three diagnostic methodologies—microbial culture, polymerase chain reaction (PCR), and precision metagenomics (precision metagenomics)—for the detection and classification of uropathogens in urine samples from patients with suspected urinary tract infections (UTIs). While microbial culture remains the gold standard for UTI diagnosis, it has limitations in sensitivity, particularly for fastidious or non-culturable microorganisms. PCR offers higher sensitivity but is restricted to pre-targeted organisms, limiting its diagnostic range. Precision Metagenomics, a target-agnostic sequencing method, provides a more inclusive approach by enabling the identification of a broad spectrum of pathogens, including bacteria, viruses, fungi, and parasites, without prior knowledge of the organisms. The dataset includes 47 urine samples, each analyzed by microbial culture, PCR, and precision metagenomics, followed by bioinformatic classification using the Explify® platform. precision metagenomics identified significantly more uropathogens (62 distinct organisms) compared to PCR (19 organisms) and microbial culture (13 organisms), with 98 % of samples testing positive for polymicrobial infections via precision metagenomics. The precision metagenomics method demonstrated superior diagnostic yield by detecting pathogens that were missed by both microbial culture and PCR, particularly in culture-negative and PCR-negative cases. This dataset holds substantial reuse potential for further research into the microbiome of urinary tract infections, pathogen discovery, antimicrobial resistance studies, and the development of more accurate diagnostic models for UTI management. By offering insights into both polymicrobial infections and rare pathogens, this dataset supports the advancement of diagnostic strategies for complex and chronic UTIs.

The study details the synthesis of pure ZnO and gCN/ZnO nanocomposite using thermal poly-condensation and hydrothermal methods for the purpose of photocatalytic degradation of Rhodamine B (RhB) dye. Characterization of the synthesized material was conducted using FTIR, XRD, HRTEM, and EDS techniques, confirming the successful synthesis of the gCN/ZnO nanocomposite. The results of the study demonstrate the superiority of the gCN/ZnO nanocomposite as a material for sunlight-driven photocatalysis of Rhodamine B dye, exhibiting a degradation efficiency of 78 % in 120 min, surpassing the 53 % efficiency of pristine gCN within the same timeframe.

Summary: In mammalian cells, the Golgi exists in ribbon architecture—individual stacks laterally linked to each other by tubular structures. Golgi architecture changes dynamically to cater to cellular needs. Loss of architecture is linked with pathological conditions like cancer and neurodegeneration. Not much is known about the regulators of Golgi dynamics. Here, we demonstrate that CARP2 (caspase-8- and caspase-10-associated RING-containing protein 2), an endosomal ubiquitin ligase and a known regulator of cell migration, modulates Golgi dynamics. Epidermal growth factor (EGF) treatment modestly increases CARP2 protein and disperses Golgi. An exogenous supply of CARP2 also leads to Golgi dispersal. Conversely, Golgi remains intact in CARP2 knockout (KO) cells upon EGF treatment. CARP2 variants defective in either endosomal association or ligase activity are unable to affect Golgi dispersal. Importantly, CARP2 targets Golgin45 for ubiquitination and degradation in EGF-stimulated cells. Collectively, our findings unravel the existence of crosstalk between endosomal ubiquitin signaling and Golgi dynamics.

The present study illustrates the mechanical and wear behaviour of Al-MWCNT composites by varying MWCNTs concentration (0 %,0.25 %, 0.50 % & 1 %) by weight in composites. These composites were synthesized through sintering in the muffle furnace after mechanical alloying which involved flattening and welding particles to form flake-shaped lamellar particles. The presence of MWCNT lamellas restricted grain growth, creating a 2D aluminium layer between the MWCNTs during sintering. Increasing the MWCNT content in aluminum refined the interlayer thickness of the composites. The compressive strength of Al is increased exponentially with the addition of CNTs. By adding CNTs to aluminium, the maximum strength was reached at 460 MPa in 1% samples, and the compression strength of the aluminium increased by 84 % as well. The sintered composites exhibited higher hardness and its value increased significantly when CNTs were added to the Al composite. The wear resistance of aluminium is substantially increased when CNTs are added, and the maximum wear resistance is achieved when CNTs are added at 0.5 wt%. The addition of CNTs reduced wear resistance, which could be attributed to the decrease in interface adhesion and agglomeration effects of CNTs.

Diabetes is a chronic disease that affects millions of humans worldwide. This review article provides an analysis of the recent advancements in non-invasive blood glucose monitoring, detailing methods and techniques, with a special focus on Electromagnetic wave microwave glucose sensors. While optical, thermal, and electromagnetic techniques have been discussed, the primary emphasis is focussed on microwave frequency sensors due to their distinct advantages. Microwave sensors exhibit rapid response times, require minimal user intervention, and hold potential for continuous monitoring, renders them extremely potential for real-world applications. Additionally, their reduced susceptibility to physiological interferences further enhances their appeal. This review critically assesses the performance of microwave glucose sensors by considering factors such as accuracy, sensitivity, specificity, and user comfort. Moreover, it sheds light on the challenges and upcoming directions in the growth of microwave sensors, including the need for reduction and integration with wearable platforms. By concentrating on microwave sensors within the broader context of non-invasive glucose monitoring, this article aims to offer significant enlightenment that may drive further innovation in diabetes care.

Abstract Background Ni-kshay Poshan Yojana (NPY) is a direct benefit transfer scheme of the Government of India introduced in 2018 to support the additional nutritional requirements of persons with TB (PwTB). Our recent nationwide evaluation of implementation and utilization of NPY using programmatic data of PwTB from nine randomly selected Indian states, reported a 70% coverage and high median delay in benefit credit. We undertook a qualitative study between January and July 2023, to understand the detailed implementation process of NPY and explore the enablers and barriers to effective implementation and utilization of the NPY scheme. Methods We followed a grounded theory approach to inductively develop theoretical explanations for social phenomena through data generated from multiple sources. We conducted 36 in-depth interviews of national, district and field-level staff of the National Tuberculosis Elimination Programme (NTEP) and NPY beneficiaries from 30 districts across nine states of India, selected using theoretical sampling. An analytical framework developed through inductive coding of a set of six interviews, guided the coding of the subsequent interviews. Categories and themes emerged through constant comparison and the data collection continued until theoretical saturation. Results Stakeholders perceived NPY as a beneficial initiative. Strong political commitment from the state administration, mainstreaming of NTEP work with the district public healthcare delivery system, availability of good geographic and internet connectivity and state-specific grievance redressal mechanisms and innovations were identified as enablers of implementation. However, the complex, multi-level benefit approval process, difficulties in accessing banking services, perceived inadequacy of benefits and overworked human resources in the NTEP were identified as barriers to implementation and utilization. Conclusion The optimal utilization of NPY is enabled by strong political commitment and challenged by its lengthy implementation process and delayed disbursal of benefits. We recommend greater operational simplicity in NPY implementation, integrating NTEP activities with the public health system to reduce the burden on the program staff, and revising the benefit amount more equitably.

Background: Cerebral venous sinus thrombosis (CVST) is a rare cerebrovascular condition characterized by the formation of blood clots in the cerebral venous sinuses, which are responsible for draining blood and cerebrospinal fluid from the brain. CVST represents a significant cause of stroke in young individuals, with a mortality rate ranging from 6% to 15%. Methods: Common clinical presentations include symptoms like headaches, seizures, altered mental state, and focal neurological deficits. In India, a noteworthy occurrence of CVST is observed among postpartum women, while alcoholism poses a significant risk factor for males. Results: This study identifies headaches as the most prevalent initial symptom of CVST, followed by seizures and focal neurological deficits. The superior sagittal sinus is the most frequently affected in these patients. Notably, 83.3% of patients in this study achieved a favorable outcome. However, a midline shift exceeding 10mm was identified as a predictive factor for an unfavorable outcome in this series. Conclusions: Contrary to previous perceptions, CVST is not uncommon in males. The early diagnosis and prompt intervention have a positive impact on overall patient outcomes. This research sheds light on the importance of recognizing CVST in a broader demographic, its common symptoms, and the critical role of timely intervention for improved patient prognosis.

Engineering transition metal dichalcogenides-based semiconducting two-dimensional (2D) layered materials for photo(electro)chemical (PEC) hydrogen evolution reaction (HER) by water splitting is an enduring challenge. Here, alloy-assisted photoconductivity and photoresponse from CVD-grown MoS2(1-x)Se2x (MSSE) 2D ternary atomic layered alloy-based photodetector device is presented for the realization of PEC HER. The explicit role of ‘S–Se’ and ‘Se2’ atomic alloy sites including chalcogen-induced vacancy defects on the photoconductivity/photoresponse and PEC HER performance of MSSE 2D alloy is investigated. Alloy formation, atomic site-by-site ‘Se’ composition and atomic structure are characterized using Raman/Photoluminescence (PL) spectroscopy, high-angle annular dark field (HAADF)- scanning transmission electron microscopy (STEM) extensively and supported with Auger Electron Spectroscopy (AES) mapping. Further, the local density and concentration of S–Se, Se2 atomic sites and defects were quantitatively estimated using HAADF-STEM image analysis in correlation with AES and it is found between the range of ∼15–20 % in MSSE alloy. A 10-fold high photoresponsivity in the case of MSSE concerning as-grown MS having fast photocurrent growth time and the prolonged decay time originates from the ‘Se’ and this alloy assisted states to enhance the PEC performance of MSSE alloy. The enhanced PEC HER activity of MSSE alloy was identified in terms of overpotential and current density. In addition, increased density of states as a function of ‘Se’ alloying, shifts in a p-band centre and lowers ΔGH* according to density functional theory calculations, which makes MSSE alloy an efficient HER activity. Further, the PEC stability and presence of the ‘S–Se’ and ‘Se2’ alloying and their role towards HER have been correlated by the spectral line shape analysis of PL and Raman spectra from post-PEC HER catalysts. These experimental and theoretical findings establish the role of chalcogen, and transition metal-based 2D alloy, leading to the design of new PECs of engineered 2D atomic layer interfaces.

Abstract This article reports the development of a microscopy imaging system that gives feasibility for studying spatio-temporal dynamics of physiological activities of alive biological specimens (over entire volume not only for a particular section, i.e., in 4D). The imaging technology facilitates to obtain two image frames of a section of the larger specimen ( $$\sim \text {mm}$$ ∼ mm ) with different FOVs at different resolutions or magnifications simultaneously in real-time (in addition to recovery of 3D (volume) information). Again, this imaging system addresses the longstanding challenges of housing multiple light sources (6 at the maximum till date) in microscopy (in general) and light sheet fluorescence microscopy (LSFM) (in particular), by using a tuneable pulsed laser source (with an operating wavelength in the range $$\sim 420$$ ∼ 420 –670 nm) in contrast to the conventional CW laser source being adopted for inducing photo-excitation of tagged fluorophores. In the present study, we employ four wavelengths ( $$\sim$$ ∼ 488 nm, 585 nm, 590 nm, and 594 nm). Our study also demonstrates quantitative characterization of spatio-temporal dynamics (velocity—both amplitude and direction) of organelles (mitochondria) and their mutual correlationships. Mitochondria close to the nucleus (or in clustered cells) are observed to possess a lower degree of freedom in comparison to that at the cellular periphery (or isolated cells). In addition, the study demonstrates real-time observation and recording of the development and growth of all tracheal branches during the entire period ( $$\sim 95$$ ∼ 95 min) of embryonic development (Drosophila). The experimental results—with experiments being conducted in various and diversified biological specimens (Drosophila melanogaster, mouse embryo, and HeLa cells)—demonstrate that the study is of great scientific impact both from the aspects of technology and biological sciences.

Abstract Background Women’s health is usually looked upon in terms of their reproductive health. However, cardio-vascular diseases are one of the leading causes of death and disability among women, globally as well as in India. Risk factors of today can be disease of tomorrow. Gradience in level of epidemiological transition is observed across different states. The study aims to estimate the national and regional prevalence, and sociodemographic determinants of biological and behavioural risk factors for cardiovascular diseases. Materials and methods The present study was conducted among women in the age group of 15 to 49 years using nationally representative sample from fifth round National Family Health Survey in India. The data analysis in the current study included 7,24,115 women in the age group of 15 to 49 years. SPSS version 20 was used for the purpose of analysis. Weighted prevalence was computed for the studied behavioral and biological (dependent variable) risk factors using women specific weights as provided in the dataset. Binary logistic regression model was employed to calculate the adjusted odds ratio (OR) with the corresponding 95% confidence interval (CI) to study the sociodemographic determinants (independent variables) of these risk factors. Results Highest prevalent risk factor for cardiovascular diseases was reported to be central obesity (78.2%), followed by overweight/obesity (23.9%), oral contraceptive use (13.4%), raised blood pressure (11.8%), raised blood sugar (8.6%), tobacco use (4.0%), and alcohol use (0.7%). Higher odds of all the studied risk factors were reported with increasing age. All of the studied risk factors, except for alcohol consumption [OR (95%CI): 0.9 (0.8–0.96)], had higher odds in rural areas compared to urban areas. Compared to other castes, the odds of tobacco [OR (95% CI): 2.01 (1.91–2.08)] and alcohol consumption [OR (95% CI): 5.76 (5.12–6.28)], and raised blood pressure [OR (95% CI): 1.07(1.04–1.11)] was significantly higher among the people belonging to schedule tribe. Conclusion and recommendation The present study highlights the state-wise disparities in the burden and predictors of risk factors for cardio-vascular diseases among women of reproductive age. The study provides insights to these disparities, and focuses on the need of tailoring the disease prevention and control measures suiting to the local needs.

Abstract Background Patients with TB have additional nutritional requirements and thus additional costs to the household. Ni-kshay Poshan Yojana(NPY) is a Direct Benefit Transfer (DBT) scheme under the National Tuberculosis Elimination Programme(NTEP) in India which offers INR 500 monthly to all notified patients with TB for nutritional support during the period of anti-TB treatment. Five years after its implementation, we conducted the first nationwide evaluation of NPY. Methods In our retrospective cohort study using programmatic data of patients notified with TB in nine randomly selected Indian states between 2018 and 2022, we estimated the proportion of patients who received at least one NPY instalment and the median time to receive the first instalment. We determined the factors associated (i) with non-receipt of NPY using a generalised linear model with Poisson family and log link and (ii) with time taken to receive first NPY benefit in 2022 using quantile regression at 50th percentile. Results Overall, 3,712,551 patients were notified between 2018 and 2022. During this period, the proportion who received at least one NPY instalment had increased from 56.9% to 76.1%. Non-receipt was significantly higher among patients notified by private sector (aRR 2.10;2.08,2.12), reactive for HIV (aRR 1.69;1.64,1.74) and with missing/undetermined diabetic status (aRR 2.02;1.98,2.05). The median(IQR) time to receive the first instalment had reduced from 200(109,331) days in 2018 to 91(51,149) days in 2022. Patients from private sector(106.9;106.3,107.4days), those with HIV-reactive (103.7;101.8,105.7days), DRTB(104.6;102.6,106.7days) and missing/undetermined diabetic status (115.3;114,116.6days) experienced longer delays. Conclusions The coverage of NPY among patients with TB had increased and the time to receipt of benefit had halved in the past five years. Three-fourths of the patients received at least one NPY instalment, more than half of whom had waited over three months to receive the first instalment. NTEP has to focus on timely transfer of benefits to enable patients to meet their additional nutritional demands, experience treatment success and avoid catastrophic expenditure.

ABSTRACT: Objectives: Drug resistance in leprosy is an emerging concern, leading to treatment failures, recurrences, and potential spread of resistant Mycobacterium leprae in the community. In this study, we aimed to assess drug resistance prevalence and patterns amongst leprosy patients at a tertiary care referral hospital in India. Methods: Mutations in drug resistance determining regions for dapsone, rifampicin, and ofloxacin of the M. leprae genome in DNA extracted from skin biopsies of 136 leprosy patients (treatment-naive = 67, with persistent skin lesions = 35, with recurrence = 34) were analysed by polymerase chain reaction followed by Sanger sequencing. Wild-type strain (Thai-53) was used as a reference strain. Results: Resistance mutations were identified in a total of 23 patients, constituting 16.9% of the cohort. Within this subset of 23 cases, resistance to ofloxacin was observed in 17 individuals (12.5%), while resistance to both dapsone and rifampicin was detected in three patients each (2.2% for both). The occurrence of ofloxacin resistance showed minimal disparity between recurrent and treatment-naive cases, at 17.6% and 16.4%, respectively. Dapsone resistance emerged in two treatment-naive cases and one case with persistent skin lesions. Notably, none of the treatment-naive cases or those with recurrence/relapse exhibited rifampicin resistance. Subsequently, no statistically significant correlation was identified between other clinical variables and the presence of antimicrobial resistance. Conclusions: The occurrence of resistance to the current multidrug therapy regimen (specifically dapsone and rifampicin) and to ofloxacin, a secondary antileprosy medication in M. leprae, represents a concerning scenario. This calls for an expansion towards bactericidal drug options and the establishment of robust surveillance for drug resistance in countries burdened with high leprosy rates. Moreover, the introduction of stringent antimicrobial stewardship initiatives is imperative. As a single centre study, it represents a limited, cross-sectional view of the real situation in the field.

Abstract Legionella pneumophila (LP) secretes more than 300 effectors into the host cytosol to facilitate intracellular replication. One of these effectors, SidH, 253 kDa in size with no sequence similarity to proteins of known function is toxic when overexpressed in host cells. SidH is regulated by the LP metaeffector LubX which targets SidH for degradation in a temporal manner during LP infection. The mechanism underlying the toxicity of SidH and its role in LP infection are unknown. Here, we determined the cryo-EM structure of SidH at 2.7 Å revealing a unique alpha helical arrangement with no overall similarity to known protein structures. Surprisingly, purified SidH came bound to a E. coli EF-Tu/t-RNA/GTP ternary complex which could be modeled into the cryo-EM density. Mutation of residues disrupting the SidH-tRNA interface and SidH-EF-Tu interface abolish the toxicity of overexpressed SidH in human cells, a phenotype confirmed in infection of Acanthamoeba castellani. We also present the cryo-EM structure of SidH in complex with a U-box domain containing ubiquitin ligase LubX delineating the mechanism of regulation of SidH. Our data provide the basis for the toxicity of SidH and into its regulation by the metaeffector LubX.

Summary: Transcription factors (TFs) are important mediators of aberrant transcriptional programs in cancer cells. In this study, we focus on TF activity (TFa) as a biomarker for cell-line-selective anti-proliferative effects, in that high TFa predicts sensitivity to loss of function of a given gene (i.e., genetic dependencies [GDs]). Our linear-regression-based framework identifies 3,047 pan-cancer and 3,952 cancer-type-specific candidate TFa-GD associations from cell line data, which are then cross-examined for impact on survival in patient cohorts. One of the most prominent biomarkers is TEAD1 activity, whose associations with its predicted GDs are validated through experimental evidence as proof of concept. Overall, these TFa-GD associations represent an attractive resource for identifying innovative, biomarker-driven hypotheses for drug discovery programs in oncology.

Summary: NLP is a well-established field in ML for developing language models that capture the sequence of words in a sentence. Similarly, drug molecule structures can also be represented as sequences using the SMILES notation. However, unlike natural language texts, special characters in drug SMILES have specific meanings and cannot be ignored. We introduce a novel NLP-based method that extracts interpretable sequences and essential features from drug SMILES notation using N-grams. Our method compares these features to Morgan fingerprint bit-vectors using UMAP-based embedding, and we validate its effectiveness through two personalized drug screening (PSD) case studies. Our NLP-based features are sparse and, when combined with gene expressions and disease phenotype features, produce better ML models for PSD. This approach provides a new way to analyze drug molecule structures represented as SMILES notation, which can help accelerate drug discovery efforts. We have also made our method accessible through a Python library.