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Background Arsenic is a natural drinking water contaminant affecting 26 million people in West Bengal, India. Chronic arsenic exposure causes cancer, cardiovascular disease, liver disease, neuropathies and ocular diseases. The aims of the present study were to assess bioindicators of hepatocellular injury as indicated by the levels of liver enzymes, to determine the auto immune status, as indicated by the amounts of anti-nuclear antibodies (ANA) and anti-dsDNA antibodies in their serum, and to predict cardiovascular risk in the arsenic exposed population. Methods Effect of chronic arsenic exposure on liver was determined by liver function tests. Autoimmune status was measured by measuring ANA and anti-dsDNA in serum. Inflammatory cytokines associated with increased cardiovascular disease risk, IL6, IL8 and MCP-1 were determined. Results Our results indicated that serum levels of bilirubin, alanine transaminase, aspartate transaminase, alkaline phosphatase and ANA were increased in the arsenic exposed population. Serum levels of IL6 and IL8 also increased in the arsenic exposed group. Conclusions Chronic arsenic exposure causes liver injury, increases the serum levels of autoimmune markers and imparts increased cardiovascular risk.

Background In the west, survival following treatment of childhood acute lymphoblastic leukaemia (ALL) approaches 90%. Outcomes in India do not exceed 70%. To address this disparity, the Indian Collaborative Childhood Leukaemia group (ICiCLe) developed in 2013 a contemporary treatment protocol for uniform risk-stratified management of first presentation ALL based on cytogenetics and minimal residual disease levels (MRD). A multicentre randomised clinical trial opened in 2016 (ICiCLe-ALL-14) and examines the benefit of randomised interventions to decrease toxicity and improve outcomes. Methods Patients 1–18 years with newly diagnosed ALL are categorised into four risk groups based on presentation features, tumour genetics and treatment response. Standard risk includes young (< 10 years) B cell precursor ALL (BCP-ALL) patients with low presentation leucocyte count (< 50 × 10 9 /L) and no high-risk features. Intermediate risk includes BCP-ALL patients with no high-risk features but are older and have high presentation leucocyte counts and/or bulky disease. High risk includes BCP-ALL patients with any high-risk feature, including high-risk genetics, central nervous system leukaemia, poor prednisolone response at treatment day 8 and high MRD (≥ 0·01%) at the end of induction. Patients with T-lineage ALL constitute the fourth risk group. All patients receive four intensive treatment blocks (induction, consolidation, interim maintenance, delayed intensification) followed by 96 weeks of maintenance. Treatment intensity varies by risk group. Clinical data management is based on a web-based remote data capture system. The first randomisation examines the toxicity impact of a shorter induction schedule of prednisolone (3 vs 5 weeks) in young non-high-risk BCP-ALL. The second randomisation examines the survival benefit of substituting doxorubicin with mitoxantrone in delayed intensification for all patients. Primary outcome measures include event-free survival (overall, by risk groups), sepsis rates in induction (first randomisation) and event-free survival rates following second randomisation. Discussion ICiCLe-ALL-14 is the first multicentre randomised childhood cancer clinical trial in India. The pre-trial phase allowed standardisation of risk-stratification diagnostics and established the feasibility of collaborative practice, uniform treatment, patient enrolment and data capture. Pre-trial observations confirm the impact of risk-stratified therapy in reducing treatment-related deaths and costs. Uniform practice across centres allows patients to access care locally, potentially decreasing financial hardship and dislocation. Trial registration Clinical Trials Registry-India (CTRI) CTRI/2015/12/006434 . Registered on 11 December 2015

Arsenic is one of the most toxic environmental toxicants. More than 150 million people worldwide are exposed to arsenic through ground water contamination. It is an exclusive human carcinogen. Although the hallmarks of arsenic toxicity are skin lesions and skin cancers, arsenic can also induce cancers in the lung, liver, kidney, urinary bladder, and other internal organs. Arsenic is a non-mutagenic compound but can induce significant cytogenetic damage as measured by chromosomal aberrations, sister chromatid exchanges, and micronuclei formation in human systems. These genotoxic end points are extensively used to predict genotoxic potentials of different environmental chemicals, drugs, pesticides, and insecticides. These cytogenetic end points are also used for evaluating cancer risk. Here, by critically reviewing and analyzing the existing literature, we conclude that inorganic arsenic is a genotoxic carcinogen.

Background To evaluate the treatment cost and cost effectiveness of a risk‐stratified therapy to treat pediatric acute lymphoblastic leukemia (ALL) in India. Methods The cost of total treatment duration was calculated for a retrospective cohort of ALL children treated at a tertiary care facility. Children were risk stratified into standard (SR), intermediate (IR) and high (HR) for B‐cell precursor ALL, and T‐ALL. Cost of therapy was obtained from the hospital electronic billing systems and details of outpatient (OP) and inpatient (IP) from electronic medical records. Cost effectiveness was calculated in disability‐adjusted life years. Results One hundred and forty five patients, SR (50), IR (36), HR (39), and T‐ALL (20) were analyzed. Median cost of the entire treatment for SR, IR, HR, and T‐ALL was found to be$3900, $ 5500,$7400, and $ 8700, respectively, with chemotherapy contributing to 25%–35% of total cost. Out‐patient costs were significantly lower for SR (p < 0.0001). OP costs were higher than in‐patient costs for SR and IR, while in‐patient costs were higher in T‐ALL. Costs for non‐therapy admissions were significantly higher in HR and T‐ALL (p < 0.0001), representing over 50% of costs of in‐patient therapy. HR and T‐ALL also had longer durations of non‐therapy admissions. Based on WHO‐CHOICE guidelines, the risk‐stratified approach was very cost effective for all categories of patients. Conclusions Risk‐stratified approach to treat childhood ALL is very cost‐effective for all categories in our setting. The cost for SR and IR patients is significantly reduced through decreased IP admissions for both, chemotherapy and non‐chemotherapy reasons. With the ICiCLe‐ALL‐14 risk stratified approach, ALL treatment cost for low‐risk patients is significantly lower as compared to intermediate and high‐risk groups. Additionally, it is a cost‐effective intervention in a low‐middle income country.

In the state of West Bengal in India, over 26 million individuals are exposed to arsenic via drinking water. Dermatological, non-dermatological disorders and cancers are associated with arsenic toxicity. Of late, there has been a decrease in the arsenic concentration in drinking water owing to governmental efforts, raising the possibility of remediation. A cross-sectional study was conducted, where 189 arsenicosis and 171 unexposed individuals were recruited at two time points, (2005–06 and 2010–11) with concomitant decrease in the level of arsenic exposure via drinking water in the arsenicosis group in 2010–11. Parameters studied included dermatological, non-dermatological health status and cytogenetic damage. Decrease of arsenic exposure (190.1  μ g/l to 37.94  μ g/l) resulted in significant decline in the number of individuals having dermatological disorders ( P <0.01) and in the severity of each dermatological outcome ( P <0.0001). Micronucleus formation in urothelial cells and lymphocytes decreased significantly ( P <0.001). However, there was a significant ( P <0.001) rise in the incidence of each of the non-dermatological diseases, that is, peripheral neuropathy, conjunctivitis and respiratory distress over the period. Thirteen (6.87%) of the initially recruited arsenicosis individuals died of cancer, in this period. Remediation by arsenic-safe drinking water can reduce dermatological manifestations and cytogenetic insult; but is unable to counter the non-dermatological symptoms.

For our fifth anniversary, we reconnected with authors of recent Comments and Perspectives in Nature Machine Intelligence and asked them how the topic they wrote about developed. We also wanted to know what other topics in AI they found exciting, surprising or worrying, and what their hopes and expectations are for AI in 2024—and the next five years. A recurring theme is the ongoing developments in large language models and generative AI, their transformative effect on the scientific process and concerns about ethical implications.

This study examines the practical applications and methodological implications of Machine Translation in Indian Languages, specifically Bangla, Malayalam, and Telugu, within emerging translation workflows and in relation to existing evaluation frameworks. The choice of languages prioritized in this study is motivated by a triangulation of linguistic diversity, which illustrates the significance of multilingual accommodation of educational technology under NEP 2020. This is further supported by the largest MOOC portal, i.e., NPTEL, which has served as a corpus to facilitate the arguments presented in this paper. The curation of a spontaneous speech corpora that accounts for lucid delivery of technical concepts, considering the retention of suitable register and lexical choices are crucial in a diverse country like India. The findings of this study highlight metric-specific sensitivity and the challenges of morphologically rich and semantically compact features when tested against surface overlapping metrics.

Tumor Necrosis Factor Receptor 1 (TNFR1) signaling regulates cell fate in inflammation, immune responses, and tumorigenesis. While TNF-α–mediated TNFR1 pathways are well known, the role of receptor clustering remains unclear. Utilizing homo-FRET using fluorescence anisotropy, we show that intra-cluster receptor density (IRD) governs TNFR1 signaling outcomes. Soluble TNF-α (sTNF-α) increases IRD at cluster cores but decreases it at rims via receptor reorganization. Reducing IRD through membrane tension, zafirlukast, actin depolymerization, or cholesterol depletion suppresses sTNF-α signaling, whereas increasing IRD by lowering membrane tension or exposing cells in a 3D gel-like microenvironment triggers ligand-independent activation. These findings reveal IRD as a key regulator of receptor signaling, with potential relevance across related receptor families and innovative strategies in modulating TNFR1 signaling. Intra-cluster receptor density (IRD) is critical for TNFR1 signal modulation, with higher IRD activating and lower IRD impairing the TNFR1 signaling.

Knowledge bases (KBs) are often incomplete and constantly changing in practice. Yet, in many question answering applications coupled with knowledge bases, the sparse nature of KBs is often overlooked. To this end, we propose a case-based reasoning approach, CBR-iKB, for knowledge base question answering (KBQA) with incomplete-KB as our main focus. Our method ensembles decisions from multiple reasoning chains with a novel nonparametric reasoning algorithm. By design, CBR-iKB can seamlessly adapt to changes in KBs without any task-specific training or fine-tuning. Our method achieves 100% accuracy on MetaQA and establishes new state-of-the-art on multiple benchmarks. For instance, CBR-iKB achieves an accuracy of 70% on WebQSP under the incomplete-KB setting, outperforming the existing state-of-the-art method by 22.3%.