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In this work, the role of non-covalent n → σ* intramolecular interactions in bestowing stabilization to exceptionally low-lying LUMO molecules of Naphthalenediimides (NDI) and their radical ions have been investigated utilizing different electronic structure calculation methods at the DFT level of theory and X-ray crystallography. We compared the effect of electron donating groups (EDGs) and electron-withdrawing groups (EWGs), e.g. , OMe and F, respectively, at the para -positon of the phenylphosphonium groups integrated at the 2,6-positions of the NDI scaffold on the intramolecular P-O interactions and the evolving electronic effects. The natural bond orbital (NBO) analysis exhibited strong charge transfer from the imide O atoms of the NDI to the phosphorus atom of the phosphonium groups validating a donor-acceptor type of orbital interaction. Atoms in molecule (AIM) analysis also illustrated the strong P-O interaction, as the charge density, ρ ( r ), and the Laplacian of the density ∇ 2 ρ ( r b ) at BCP is within the range of well-known non-covalent interactions. These calculations also revealed long-range electronic communication between the EDGs/EWGs at the phenyl groups and the NDI scaffold.

Rickets, one of the leading causes of bony deformities and short stature, can be calciopenic (inciting event is defective intestinal calcium absorption) or phosphopenic (inciting event is phosphaturia). Early diagnosis and timely treatment of rickets are crucial for correction of the limb deformities. Guidelines exist for nutritional rickets, but the diagnosis and management of the relatively uncommon forms of rickets are complex. This consensus aims to formulate a simplified diagnostic approach for rickets, especially in resource-limited settings. The consensus statement has been formulated by a 29-member committee from the Endocrine Society of Bengal. The process included forming a working group, conducting a literature review, identifying controversies, drafting, and discussion at a consensus meeting. Participants rated their agreement with the clinical practice points, and a 70% consensus was required. Input integration and further review led to the final consensus statements. Children with suspected rickets should initially be examined for distinctive skeletal deformities. The diagnosis of rickets should be confirmed with characteristic radiographic abnormalities. It is advisable to order tests for serum calcium, inorganic phosphorus (Pi), liver function, 25-hydroxyvitamin D (25OHD), parathyroid hormone, creatinine, and potassium in all patients with rickets. In cases of refractory rickets, it is also recommended that assessments be conducted for spot urine calcium, Pi, creatinine, and, blood gas analysis. In children with rickets and metabolic acidosis, tests for glycosuria, uricosuria, aminoaciduria, low molecular weight proteinuria, and albuminuria should be conducted. In children with resistant calciopenic rickets and sufficient serum 25OHD levels, serum 1,25(OH)2D concentration should be tested. 1,25(OH)2 D and fibroblast growth factor 23 estimation is useful for certain forms of phosphopenic rickets.

Competing Interests: There are no conflicts of interest.

Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Organic π-scaffolds are being envisaged for new-age electron- and ion-responsive materials that can accumulate electrons as well as transport proton. However, such systems are extremely rare as electron-deficient scaffolds are unstable in aqueous solution. Here we detail the synthesis of a water-stable core-naphthalenediimide-nitrobenzyl-viologen based tetra-cation, which accumulates up to eight-electrons within an exceptionally narrow potential window of +0.05 V and -1.12 V. The supramolecular interactions and the ensuing ionic framework are tunable based on the three anions, e. g., Cl - , Br - and PF 6 - , that are investigated in this work. The ionic framework is formed and supported by a range of H-bonds, in which, the nitro benzyl groups act as pillars connecting the 1D water-tapes and the halide anions. The water molecules are hydrogen-bonded with the halide anions and bestow a facile pathway for the proton conduction, with proton conductivity up to 3.19×10 -3  S cm -1 . In contrast, the ionic assembly formed by the lipophilic PF 6 - anions do not host the water tapes and consequently the proton conductivity is found to be four orders of magnitude lower. This is a unique example, whereby proton conductivity is realized and is tunable within a highly electron-deficient, eight-electron acceptor, water-stable ionic supramolecular system., (© 2024 Wiley-VCH GmbH.)

In this work, we report the synthesis and photocatalytic properties of N,N -bis( n -hexyl)-2-bromo-6-( n -hexylamino)-1,4,5,8-naphthalenetetracarboxylic diimide photocatalyst, NDI-PC , in visible light. In the presence of air or oxidant, NDI-PC efficiently enables multiple photooxygenations of isoquinolines, thiocyanation of phenylimidazopyridines, functionalization of quinolinones by allowing regioselective installation of an SCN, SeCN, SPh, SePh, Cl, Br, or I group at the C-3 position, and isomerization of alkenes. Mechanistic investigations suggest an oxidative photoredox process for oxygenation and C-H functionalization, while isomerization is believed to proceed through a photosensitization pathway.

Torsemide is a loop diuretic used to manage edema associated with chronic kidney disease (CKD) and acute kidney injury (AKI). It acts by inhibiting sodium and chloride ions reabsorption in the ascending limb of the loop of Henle, thereby increasing urine output and reducing fluid accumulation. Compared to other diuretics, torsemide has an extended duration of action, higher bioavailability, and its elimination route is primarily through the hepatic route, making it effective in patients with CKD and AKI. Clinical studies indicate that torsemide can improve symptoms of fluid overload and potentially enhance renal function., (© Journal of the Association of Physicians of India 2024.)

Background Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit associated with an increase in sebum secretion. Topical treatment with adapalene and benzoyl peroxide (BPO) is considered effective when used either as monotherapy or in fixed-dose combinations. However, the combination gel of 0.3% adapalene with 2.5% benzoyl peroxide (A0.3%+BPO2.5%) has not been evaluated in Indian patients with acne. This study aimed to evaluate the safety and efficacy of A0.3%+BPO2.5% gel in Indian patients with moderate-to-severe acne vulgaris. Methodology This was a 12-week prospective, multicenter, open-label, phase IV study conducted at six centers in India. Safety was assessed based on local tolerability (stinging or burning, erythema, dryness, and scaling) and any reported adverse events. Efficacy was evaluated based on reductions in the number of inflammatory and noninflammatory lesions, the Investigator's Global Assessment (IGA) scale, and the Global Assessment of Improvement (GAI) score. The patient-reported outcome was measured using the Subject Satisfaction Questionnaire. Results Of the 135 patients, 132 completed the study between December 24, 2021, and July 18, 2022 (93.9% had moderate acne; 6.1% had severe acne at baseline). The A0.3%+BPO2.5% gel was well tolerated. The reductions in the severity scores of erythema, scaling, and dryness from baseline to week 12 were 38.9%, 47.4%, and 76.5%, respectively. A targeted reduction of ≥50% in the number of inflammatory and noninflammatory lesions was achieved in 115 (87.1%) and 109 (82.6%) patients, respectively. Based on the investigator's responses to the IGA questionnaire at week 12, 28% and 40.9% of patients had clear and almost clear skin, respectively. Using the GAI scale, investigators reported that at 12 weeks from baseline, most patients presented with improvements in symptoms, such as erythema, scaling, and dryness, and none reported any worsening. Treatment satisfaction was rated as 91% by the patients. Conclusions The A0.3%+BPO2.5% gel effectively reduced the inflammatory and noninflammatory lesions and was found to be safe and well tolerated in Indians with moderate‑to‑severe acne vulgaris., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Clinical Trials Registry - India issued approval CTRI/2021/06/034069. All patients provided written informed consent. Below are the names and approval numbers of centers where the trial was carried out: Basaveshwara Medical College & Hospital (Karnataka), Banaras Hindu University (Uttar Pradesh), College of Medicine & JNM Hospital (West Bengal), Om Sai Onco-Surgery Multispecialty Centre (Maharashtra), Post Graduate Institute of Medical Science (Chandigarh), and Derma World Skin & Hair Clinic (New Delhi) with IRB numbers ECR/1218/Inst/KA/2019, ECR/526/Inst/UP/2014/RR-17, ECR/674/Inst/WB/2014/RR-17, ECR/1112/Inst/MH/2018, ECR/25/Inst/CH/2013/RR-16, and ECR/310/Indt/DL/2018, respectively. The study was conducted with the approval of CDSCO (following the provisions outlined in the Drugs and Cosmetics Acts and Rules). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: The funding for manuscript development was supported by Galderma. Financial relationships: Dyotona Sen declare(s) employment from Galderma. Sameer Jadhwar declare(s) employment from Galderma. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Batra et al.)

Microplastics, an emerging contaminant, are widespread in oceans around the world, and rivers are the key conveyors of these pollutants into the oceans. There exists a dearth of available data pertaining to seasonal fluctuation, spatial distribution and risk assessment of microplastics in rivers extending from upper reaches to the lower reaches. The collection of such data is of utmost importance for the purpose of formulating beneficial management strategies for riverine microplastics. In order to bridge this research gap, an investigation was made in the Periyar River in Kerala, India, which is exposed to anthropogenic stress and is at risk of microplastic pollution. A total of eighteen sites (six sites each from downstream, midstream and upstream) along the 244 km of the river were investigated across three seasons in a year. The study revealed a discernible pattern in the spatial distribution of microplastic concentrations, wherein there was a rise in abundance from the upstream to midstream and then a sudden increase of abundance along the downstream regions towards the lower reaches. The highest mean microplastic abundance of 124.95 items/L was obtained during the monsoon season followed by post-monsoon season i.e. 123.21 items/L and pre-monsoon i.e. 120.50 items/L. The predominant forms of microplastics were found to be fibres, fragments and filaments. Most prevalent polymer types acquired were polyethylene (PE) and polypropylene (PP). Pollution hazard index (PHI) and pollution load index (PLI) were also evaluated to assess the water quality of this river. The findings of this study conclude that the Periyar River is polluted with microplastics throughout its course and offer significant insights into the detection of microplastic origins in river systems and lend support to the implementation of potential measures aimed at mitigating their impact., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Alcohol Use Disorder (AUD) is a persistent condition linked to neuroinflammation, neuronal oxidative stress, and neurodegenerative processes. While the inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has demonstrated effectiveness in reducing liver inflammation associated with alcohol, its impact on the brain remains largely unexplored. This study aimed to assess the effects of alirocumab, a monoclonal antibody targeting PCSK9 to lower systemic low-density lipoprotein cholesterol (LDL-C), on central nervous system (CNS) pathology in a rat model of chronic alcohol exposure. Alirocumab (50 mg/kg) or vehicle was administered weekly for six weeks in 32 male rats subjected to a 35 % ethanol liquid diet or a control liquid diet (n = 8 per group). The study evaluated PCSK9 expression, LDL receptor (LDLR) expression, oxidative stress, and neuroinflammatory markers in brain tissues. Chronic ethanol exposure increased PCSK9 expression in the brain, while alirocumab treatment significantly upregulated neuronal LDLR and reduced oxidative stress in neurons and brain vasculature (3-NT, p22phox). Alirocumab also mitigated ethanol-induced microglia recruitment in the cortex and hippocampus (Iba1). Additionally, alirocumab decreased the expression of pro-inflammatory cytokines and chemokines (TNF, CCL2, CXCL3) in whole brain tissue and attenuated the upregulation of adhesion molecules in brain vasculature (ICAM1, VCAM1, eSelectin). This study presents novel evidence that alirocumab diminishes oxidative stress and modifies neuroimmune interactions in the brain elicited by chronic ethanol exposure. Further investigation is needed to elucidate the mechanisms by which PCSK9 signaling influences the brain in the context of chronic ethanol exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Background: Primary hyperaldosteronism (PH) is considered to contribute to increased risk of developing type 2 diabetes mellitus (T2DM) and prediabetes. Both PH and DM are associated with increased risk for hypertension, cardiovascular diseases, and chronic kidney diseases. However, data on prevalence of T2DM and prediabetes in PH, and impact of T2DM and prediabetes on presentation and cardio renal complications in PH at presentation is sparse., Aim: To determine the prevalence of T2DM and prediabetes in PH at diagnosis and impact on presentation and complications of PH., Methods: A retrospective cohort study was conducted in tertiary care settings in individuals with confirmed diagnosis of PH at presentation. Demographic variables, clinical presentations, duration and degree of hypertension, complications, laboratory parameters including sodium, potassium levels, plasma aldosterone concentration (PAC), plasma renin activity (PRA), and aldosterone to renin ratio (ARR) and cardio-renal parameters were collected. Comparison was done between three groups: PH with no DM (Group A) or with pre-diabetes (Group B) or with T2DM (Group C). P < 0.05 was statistically significant., Results: Among 78 individuals with confirmed PH, 62% had pre-diabetes or diabetes; with 37% having DM. Mean duration of T2DM was 5.97 ± 4.7 years. The mean levels of glycaemic parameters among the group A vs B vs C individuals were fasting plasma glucose (mg/dL): 87.9 ± 6.5, 105.4 ± 9.02, 130.6 ± 21.1; post prandial plasma glucose (mg/dL): 122.7 ± 9.8, 154.9 ± 14, 196.7 ± 38.0; glycated haemoglobin (%) (5.3 ± 0.2, 5.9 ± 0.2, 7.5 ± 0.6, P < 0.05 ), respectively. There was no significant difference in the biochemical parameters (PAC, PRA, ARR, sodium, potassium levels), presentation and complications between the groups. Cardio renal parameters or degree and duration of hypertension were comparable between the groups., Conclusion: Significant prevalence of T2DM and prediabetes in PH at diagnosis does not impact its presentation or complications. Early screening for undetected PH in T2DM and prediabetes subjects with hypertension may prevent complications., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

In quantum computing there are quite a few universal gate sets, each having their own characteristics. In this paper we study the Clifford+CS universal fault-tolerant gate set. The CS gate is used is many applications and this gate set is an important alternative to Clifford+T. We introduce a generating set in order to represent any unitary implementable by this gate set and with this we derive a bound on the CS-count of arbitrary multi-qubit unitaries. Analysing the channel representation of the generating set elements, we infer J n CS ⊂ J n T , where J n CS and J n T are the set of unitaries exactly implementable by the Clifford+CS and Clifford+T gate sets, respectively. We develop CS-count optimal synthesis algorithms for both approximately and exactly implementable multi-qubit unitaries. With the help of these we derive a CS-count-optimal circuit for Toffoli, implying J n Tof = J n CS , where J n Tof is the set of unitaries exactly implementable by the Clifford+Toffoli gate set. Such conclusions can have an important impact on resource estimates of quantum algorithms., (© 2024. The Author(s).)

Acenes and Naphthalene Diimides (NDIs) stand as distinguished classes of organic compounds, each possessing unique and intriguing properties that have garnered significant attention across various scientific disciplines. Acenes, characterized by linearly fused aromatic rings, have captivated researchers due to their diverse electronic structures and promising applications in materials science. On the other hand, NDIs, known for their distinctive electron-accepting properties, exhibit remarkable versatility in fields ranging from organic electronics, supramolecular to spin chemistry. In this review, we navigate through the fascinating realms of both acenes and NDIs before converging our focus on the highly diverse and distinctive subgroup of NDI-annulated heterocyclic acenes. This potentially important subgroup, has emerged as a subject of intense investigation, encapsulating their fascinating synthesis, optical and electrochemical characteristics, and multifaceted applications that span the realms of chemistry, physics, and biology. Through the exploration of their synthetic strategies, unique properties, and diverse applications, this review aims to offer a comprehensive understanding of the pivotal role played by NDI-based heterocyclic acenes in contemporary multidisciplinary research and technological innovation., (© 2024 Wiley-VCH GmbH.)

Introduction: Initial surge of thyroid-stimulating hormone (TSH) in neonates increases free and total triiodothyronine (T3) and tetraiodothyronine (T4) in 24-36 hours following birth, and the effect then gradually wanes off. As somatic and intellectual development is dependent on normal thyroid function especially in infancy, normative data in these children may be of immense value to diagnose hypothyroidism in this subset of infants. Comprehensive normative values of thyroid function parameters in preterm neonates are scarcely available. The objective of this study was to determine the normative value of thyroid function parameters in preterm neonates., Methods: Preterm neonates (n = 102) born at 34 and 35 weeks of gestation of euthyroid mothers from an iodine-sufficient population were evaluated for T3, T4, free thyroxine (FT4) and TSH during 3-7 days after birth and again after 1 month. The expected date of delivery (EDD) and Ballard score were used to identify the duration of gestation., Results: The mean gestational age was 34.7 ± 0.41 weeks. The mean (± SD) for T3 (ng/dl), T4 (μg/dl), FT4 (ng/ml) and TSH (μIU/ml) on days 3-7 following birth was as follows: 156 ± 44.6, 12.8 ± 3.7, 1.50 ± 0.54 and 7.13 ± 6.04, respectively. Around 4 weeks of age, values changed to 104 ± 38.4, 12.1 ± 4.02, 1.46 ± 0.42 and 3.25 ± 2.85, respectively. All parameters changed significantly around 4 weeks, except FT4. None of the parameters were correlated with gestational age or body weight at birth. Normative values for each parameter in percentiles were generated., Conclusion: This study generated the normative values of the thyroid function test during the first week and after around 4 weeks of life for premature neonates (born at 34-35 weeks)., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Endocrinology and Metabolism.)

R-loops are nucleic acid structures composed of a DNA:RNA hybrid with a displaced non-template single-stranded DNA. Current approaches to identify and map R-loop formation across the genome employ either an antibody targeted against R-loops (S9.6) or a catalytically inactivated form of RNase H1 (dRNH1), a nuclease that can bind and resolve DNA:RNA hybrids via RNA exonuclease activity. This overview article outlines several ways to map R-loops using either methodology, explaining the differences and similarities among the approaches. Bioinformatic analysis of R-loops involves several layers of quality control and processing before visualizing the data. This article provides resources and tools that can be used to accurately process R-loop mapping data and explains the advantages and disadvantages of the resources as compared to one another. © 2024 Wiley Periodicals LLC., (© 2024 Wiley Periodicals LLC.)

Plants produce a large repertoire of secondary metabolites. The pathways that lead to the biosynthesis of these metabolites are majorly conserved in the plant kingdom. However, a significant portion of these metabolites are specific to certain groups or species due to variations in the downstream pathways and evolution of the enzymes. These metabolites show spatiotemporal variation in their accumulation and are of great importance to plants due to their role in development, stress response and survival. A large number of these metabolites are in huge industrial demand due to their potential use as therapeutics, aromatics and more. Ethylene, as a plant hormone is long known, and its biosynthetic process, signaling mechanism and effects on development and response pathways have been characterized in many plants. Through exogenous treatments, ethylene and its inhibitors have been used to manipulate the production of various secondary metabolites. However, the research done on a limited number of plants in the last few years has only started to uncover the mechanisms through which ethylene regulates the accumulation of these metabolites. Often in association with other hormones, ethylene participates in fine-tuning the biosynthesis of the secondary metabolites, and brings specificity in the regulation depending on the plant, organ, tissue type and the prevailing conditions. This review summarizes the related studies, interprets the outcomes, and identifies the gaps that will help to breed better varieties of the related crops and produce high-value secondary metabolites for human benefits., Competing Interests: Conflict of interestsThe authors have no conflict of interest to declare that are relevant to the content of this article. The authors declare they have no financial interest., (© Prof. H.S. Srivastava Foundation for Science and Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The issue of microplastic contamination in seafood is progressively recognised as a significant global issue. This study presents novel findings regarding the detection of microplastics within the eggs of commercially available fish intended for consumption by humans. Eggs of Ompok bimaculatus, Heteropneustes fossilis, Mystus vittatus and Anabas testudineus collected from the Periyar River, Kerala, India were subjected to analysis for the potential presence of microplastics. Out of the 91 fishes (containing eggs) examined, microplastics were observed in the eggs of 2 species, i.e., Ompok bimaculatus and Mystus vittatus. The polymers recorded were polyethylene and polypropylene. Fish eggs are commonly consumed by humans and are highly esteemed as a delectable food. Considering the widespread consumption of fish eggs as a delicacy among humans, there exists a potential route for human exposure to microplastics, which raises concerns regarding public health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Inadequate water, sanitation and hygiene (WASH) may lead to an increase in water-borne diseases like diarrhoea. The objective of the study was to assess water, sanitation and hygiene in the urban slums of Patpur, Bankura and to determine the implications of WASH on the occurrence of diarrhoea among under-five (U-5) children., Materials and Methods: A cross-sectional observational study was conducted during January-March 2020 by interviewing persons involved in water collection from each of the 182 slum households of Patpur, by two-stage sampling using a pre-designed structured schedule and the core questions on drinking WASH for household surveys: 2018 update by UNICEF and WHO. For testing the association between categorical variables, a Chi-square test was done. Binary logistic regression and the Hosmer Lemeshow test were done to know the predictors of diarrhoea in U-5 children. A P value of < 0.05 was considered statistically significant., Results: The proportion of diarrhoea among U-5 children was 0.34. Limited drinking WASH services were found in 3.30, 45.05 and 24.18% of households, respectively. Mobile objects users for handwashing were 14.05 times more prone to diarrhoea in U-5 children than those who had fixed handwashing facilities at their dwellings, yards or plots. Feeding children without handwashing had 5.70 times increased chances of diarrhoea among U-5 children than those who washed their hands before feeding., Conclusion: Handwashing facilities (fixed, mobile object or no facility) and handwashing with soap and water before feeding the child significantly affected the occurrence of diarrhoea among U-5 children., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

Engagement of the T cell receptor (TCR) triggers molecular reprogramming leading to the acquisition of specialized effector functions by CD4 helper and CD8 cytotoxic T cells. While transcription factors, chemokines, and cytokines are known drivers in this process, the temporal proteomic and transcriptomic changes that regulate different stages of human primary T cell activation remain to be elucidated. Here, we report an integrative temporal proteomic and transcriptomic analysis of primary human CD4 and CD8 T cells following ex vivo stimulation with anti-CD3/CD28 beads, which revealed major transcriptome-proteome uncoupling. The early activation phase in both CD4 and CD8 T cells was associated with transient downregulation of the mRNA transcripts and protein of the central glucose transport GLUT1. In the proliferation phase, CD4 and CD8 T cells became transcriptionally more divergent while their proteome became more similar. In addition to the kinetics of proteome-transcriptome correlation, this study unveils selective transcriptional and translational metabolic reprogramming governing CD4 and CD8 T cell responses to TCR stimulation. This temporal transcriptome/proteome map of human T cell activation provides a reference map exploitable for future discovery of biomarkers and candidates targeting T cell responses., (© 2024. The Author(s).)

Background: Once-weekly basal insulin icodec has been tested in clinical trials for efficacy and safety over currently available glargine-100 and degludec in different clinical settings for type 2 diabetes. We performed this meta-analysis to evaluate its overall safety and efficacy as compared to glargine-100 and degludec (nonicodec), from all available randomized controlled trials., Methods: Seven trials comparing once-daily basal insulin analogs to once-weekly basal insulin icodec were included. Based on available information, outcomes in terms of HbA1c, fasting plasma glucose reduction, and increase in time in range (TIR) were compared. Side-effects were compared for overall hypoglycemia, severe hypoglycemia, and weight gain. The pooled effect size for continuously distributed data was measured as a reduction in "estimated differences in mean (with 95% CI)." For categorical data, the pooled effect size was measured as the Mantel-Haenszel risk ratio (with 95% CI)., Results: Analyzing against the nonicodec comparators together, the "estimated mean changes" in HbA1c and fasting plasma glucose favoring icodec were -0.22% (-0.35, -0.10) and -1.59 mg% (-9.26, 6.08) respectively. The "estimated mean increment" in weight for icodec was 0.64 kg (0.61, 0.67). The "estimated mean percentage" increment in TIR for icodec was 4.24% (2.99, 5.49). The Mantel-Haenszel risk ratios for all hypoglycemic events and severe hypoglycemia for icodec were 1.24 (1.02, 1.50) (P = .03) and 0.81 (0.31, 2.08) (P is not significant), respectively, suggesting a 24% increased incidence of all hypoglycemia with icodec., Conclusion: Once-weekly basal insulin icodec as compared to once-daily basal insulin analogs had a slight increase in the risk of overall hypoglycemia and weight gain, without any difference in severe hypoglycemia, with similar glycemic control (in terms of fasting plasma glucose, HbA1c, and TIR)., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2023 AACE. Published by Elsevier Inc. All rights reserved.)

The evaluation of Weather Research and Forecasting (WRF) model has been performed for simulating episodic Heat Wave (HW) events of 2015 and 2016 with varied horizontal resolutions of 27 km for the entire India (d01), 9 km for the North West (NW (d02)) and South East (SE (d03)) domain. Study compares the maximum temperature (T max ) simulated by WRF model, using six different combination of parameterization schemes, with observations from the India Meteorological Department (IMD) during the HW events. Among the six experiments, Exp2 (i.e., combination of WSM6 microphysics (MP) together with radiation parameterization CAM, Yonsei (PBL), NOAH land surface and Grell-3D convective schemes) is found closest to the observations in reproducing the temperature. The model exhibits an uncertainty of ± 2 °C in maximum temperature (T max ) for both the regions, suggesting regional temperature is influenced by the location and complex orography. Overall, statistical results reveal that the best performance is achieved with Exp2. Further, to understand the dynamics of rising HW intensity, two case studies of HW days along with influencing parameters like T max , RH and prevailing wind distribution have been simulated. Model simulated T max during 2015 reaches up to 44 °C in NW and SE part of India. In 2016, HW is more prevailing towards NW, while in SE region T max reaches upto 34-38 °C with high RH (60-85%). The comparative research made it abundantly evident that these episodic events are unique in terms of duration and geographical spread which can be used to assess the WRF performance for future projections of HW., (© 2024. The Author(s).)

Background: Adrenal insufficiency (AI) in hemoglobin E (HbE)/beta thalassemia, including evaluation of mineralocorticoid axis, had not been studied., Aims and Objectives: In this study, we attempted to evaluate the prevalence of AI in HbE/beta thalassemia and wanted to determine if the prevalence of AI varied according to severity of HbE/beta thalassemia and transfusion requirements., Methods: In this observational, cross-sectional study, 104 patients with HbE/beta thalassemia were evaluated. Among them, 57 and 47 were transfusion dependent and non-transfusion dependent. According to Mahidol criteria, patients were classified into mild (n = 39), moderate (n = 39), and severe (n = 26) disease. Early morning (8 Am) serum cortisol, plasma ACTH, and plasma aldosterone, renin were measured. Patients with baseline cortisol of 5 to 18 μg/dL underwent both 1 μg and 250 μg short Synacthen test. According to these results, patients were classified as having either normal, subclinical, or overt (primary/secondary) adrenal dysfunction., Results: Adrenal insufficiency was found in 41% (n = 43). Among them 83.7% (n = 34) had primary AI and 16.3% (n = 9) had secondary AI. Thirty-three patients (31%) with normal or elevated ACTH and with low or normal aldosterone with high renin were diagnosed as having subclinical AI. There was no difference in prevalence of AI between transfusion dependent and non-transfusion dependent (P = .56) nor was there was any difference in prevalence of AI according to disease severity (P = .52)., Conclusion: Adrenal insufficiency is common in HbE/beta thalassemia and is independent of transfusion dependency and disease severity., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Control of visceral leishmaniasis (VL) depends on proinflammatory Th1 cells that activate infected tissue macrophages to kill resident intracellular parasites. However, proinflammatory cytokines produced by Th1 cells can damage tissues and require tight regulation. Th1 cell IL-10 production is an important cell-autologous mechanism to prevent such damage. However, IL-10-producing Th1 (type 1 regulatory; Tr1) cells can also delay control of parasites and the generation of immunity following drug treatment or vaccination. To identify molecules to target in order to alter the balance between Th1 and Tr1 cells for improved antiparasitic immunity, we compared the molecular and phenotypic profiles of Th1 and Tr1 cells in experimental VL caused by Leishmania donovani infection of C57BL/6J mice. We also identified a shared Tr1 cell protozoan signature by comparing the transcriptional profiles of Tr1 cells from mice with experimental VL and malaria. We identified LAG3 as an important coinhibitory receptor in patients with VL and experimental VL, and we reveal tissue-specific heterogeneity of coinhibitory receptor expression by Tr1 cells. We also discovered a role for the transcription factor Pbx1 in suppressing CD4+ T cell cytokine production. This work provides insights into the development and function of CD4+ T cells during protozoan parasitic infections and identifies key immunoregulatory molecules.

BRCA1-deficient cells have increased IRE1 RNase, which degrades multiple microRNAs. Reconstituting expression of one of these, miR-4638-5p, resulted in synthetic lethality in BRCA1-deficient cancer cells. We found that miR-4638-5p represses expression of TATDN2, a poorly characterized member of the TATD nuclease family. We discovered that human TATDN2 has RNA 3' exonuclease and endonuclease activity on double-stranded hairpin RNA structures. Given the cleavage of hairpin RNA by TATDN2, and that BRCA1-deficient cells have difficulty resolving R-loops, we tested whether TATDN2 could resolve R-loops. Using in vitro biochemical reconstitution assays, we found TATDN2 bound to R-loops and degraded the RNA strand but not DNA of multiple forms of R-loops in vitro in a Mg2+-dependent manner. Mutations in amino acids E593 and E705 predicted by Alphafold-2 to chelate an essential Mg2+ cation completely abrogated this R-loop resolution activity. Depleting TATDN2 increased cellular R-loops, DNA damage and chromosomal instability. Loss of TATDN2 resulted in poor replication fork progression in the presence of increased R-loops. Significantly, we found that TATDN2 is essential for survival of BRCA1-deficient cancer cells, but much less so for cognate BRCA1-repleted cancer cells. Thus, we propose that TATDN2 is a novel target for therapy of BRCA1-deficient cancers., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Aquatic weeds have exceptionally high reproduction rates, are rich in cellulose and hemicellulose, and contain a negligible amount of lignin, making them an ideal crop for the next generation of biofuels. Previously reported studies proposed that water hyacinth, water lettuce, common duckweeds, and water spinach can be managed or utilized using different advanced techniques; from them, anaerobic digestion is one of the feasible and cost-effective techniques to manage these biowastes. The present study was carried out to investigate the potential of utilizing four common aquatic weed species (water hyacinth, water lettuce, common duckweeds, and water spinach) as substrates for anaerobic digestion in order to produce biogas for use in biofuels. The high reproduction rates and high cellulose and hemicellulose content, coupled with low lignin content, of these aquatic weeds make them ideal candidates for this purpose. The study evaluated the feasibility of using anaerobic digestion as a management technique for these aquatic weeds, which are often considered invasive and difficult to control. The results from various studies indicate that these aquatic weeds are productive feedstock options for anaerobic digestion, yielding a high biogas output. Among the aquatic weeds studied, water hyacinth, water lettuce, and common duckweeds exhibit higher methane production compared to water spinach. The study provides an overview of the characteristics and management strategies of these aquatic weeds in relation to biogas production, with possible future developments in the field., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: In India, the awareness about the psycho-social dimension of chronic pain is minimal among physicians and patients. The research with community-based group therapies (like mindfulness) to address the psycho-social aspects in chronic pain patients remains limited. The aim of this randomized controlled trial was to see the effects of mindfulness on pain intensity, pain catastrophizing, chronic pain acceptance, perceived stress, well-being, and mindfulness characteristics., Materials and Methods: In this two-site, parallel group, clinical trial, 170 patients attending pain outdoors of two government hospitals in West Bengal, India, were randomized to attend five weekly in-person mindfulness sessions (cases) or usual care sessions (controls) within the hospital premises. Pre-program and post-program data were collected and analyzed using statistical methods like repeated measures analysis of variance., Results: In participants of the mindfulness group, significant changes post session were noted in pain intensity [F(1,326) = 15.0122; P = 0.0001291], pain acceptance [F(1,326) = 4.5311; P = 0.03403], and perceived stress score [F(1,326) = 13.2788; P = 0.0003122] compared to pre-session. The changes in pain catastrophizing, World Health Organization well-being and Freiburg mindfulness inventory scores were non-specific., Conclusion: Mindfulness had a positive influence on pain intensity, pain acceptance, and perceived stress of Indian chronic pain patients. The effects on pain catastrophizing, mindfulness characteristics, and well-being (non-specific) were also encouraging. Further studies will be required to substantiate these results., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Psychiatry.)

The liver, as a crucial metabolic organ, undergoes significant pathological changes during the aging process, which can have a profound impact on overall health. To gain a comprehensive understanding of these alterations, we employed data-driven approaches, along with biochemical methods, histology, and immunohistochemistry techniques, to systematically investigate the effects of aging on the liver. Our study utilized a well-established rat aging model provided by the National Institute of Aging. Systems biology approaches were used to analyze genome-wide transcriptomics data from liver samples obtained from young (4-5 months old) and aging (20-21 months old) Fischer 344 rats. Our findings revealed pathological changes occurring in various essential biological processes in aging livers. These included mitochondrial dysfunction, increased oxidative/nitrative stress, decreased NAD + content, impaired amino acid and protein synthesis, heightened inflammation, disrupted lipid metabolism, enhanced apoptosis, senescence, and fibrosis. These results were validated using independent datasets from both human and rat aging studies. Furthermore, by employing co-expression network analysis, we identified novel driver genes responsible for liver aging, confirmed our findings in human aging subjects, and pointed out the cellular localization of the driver genes using single-cell RNA-sequencing human data. Our study led to the discovery and validation of a liver-specific gene, proprotein convertase subtilisin/kexin type 9 (PCSK9), as a potential therapeutic target for mitigating the pathological processes associated with aging in the liver. This finding envisions new possibilities for developing interventions aimed to improve liver health during the aging process., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: The objective of this study was to investigate the effect of the size of pesticide pictograms on comprehensibility and their adherence to principles of familiarity, compatibility, and standardization. Pictograms usually involve complex details, and space limitation demands size reductions, which reduces overall comprehensibility, especially in agriculture and healthcare., Methods: Two experiments were conducted. In experiment 1, the effect of different sizes of pictograms on comprehension was tested. In experiment 2, the level of compliance for different ergonomic principles on different sizes of pictograms was investigated., Results: Results of experiment 1 indicated significant variation in comprehension level ( p  < .05), with maximum comprehension for the size 15 mm × 15 mm (87.6%) and minimum comprehension for the size 7 mm × 7 mm (69.4%). Results of experiment 2 indicated significant variation in compliance of ergonomic principles with different pictogram sizes ( p  < .05), with maximum compliance for the size 15 mm × 15 mm (7.7, 7.7, 7.6) and minimum compliance for the size 7 mm × 7 mm (6.3, 6.3, 6.3). A significant increase in the comprehensibility of pictograms and their adherence to familiarity, compatibility, and standardization was observed with the increase in the sizes of pictograms., Conclusion: The smallest size of pictograms with a mean comprehension level ≥ 65% and scores for familiarity, compatibility, and standardization ≥ 7 (on a scale of 1 to 10) was 10 mm × 10 mm. The potential application of this research is to identify the most comprehensible size of pictograms that adhere to the principles of familiarity, compatibility, and standardization.

Cardiovascular diseases (CVDs) are the leading cause of death among elderly people. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important regulator of cholesterol metabolism. Herein, we investigated the role of PCSK9 in age-related CVD. Both in humans and rats, blood PCSK9 level correlated positively with increasing age and the development of cardiovascular dysfunction. Age-related fatty degeneration of liver tissue positively correlated with serum PCSK9 levels in the rat model, while development of age-related nonalcoholic fatty liver disease correlated with cardiovascular functional impairment. Network analysis identified PCSK9 as an important factor in age-associated lipid alterations and it correlated positively with intima-media thickness, a clinical parameter of CVD risk. PCSK9 inhibition with alirocumab effectively reduced the CVD progression in aging rats, suggesting that PCSK9 plays an important role in cardiovascular aging., Competing Interests: The study was supported by the intramural program of National Institute on Alcohol Abuse and Alcoholism/National Institutes of Health Grant 1ZIAAA000375-17 (to Dr Pachar) and partly by the National Institute on Alcohol Abuse and Alcoholism/National Institutes of Health Grant R01 AG072895 (to WXD). The research was supported by project NKFIH-1277-2/2020 by the Thematic Excellence Programme (2020-4.1.1.-TKP2020) of the Ministry for Innovation and Technology in Hungary, within the framework of the Bioimaging Thematic Programme of Semmelweis University. Project no. RRF-2.3.1-21-2022-00003 has been implemented with the support provided by the European Union. Drs Fabian and Kovacs have received personal fees from Argus Cognitive, Inc, outside the submitted work. Dr Tokodi was formerly an employee of Argus Cognitive, Inc. Dr Merkely has received grants from Boston Scientific and Medtronic and personal fees from Biotronik, Abbott, AstraZeneca, Novartis, and Boehringer Ingelheim, outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Introduction: A structured dedicated health programme for Type 1 diabetes mellitus (T1DM) has been initiated in the state of West Bengal, India., Aim: The aim is to provide comprehensive healthcare to all children, adolescents and young adults living with T1DM, along with the provision of free supply of insulin, glucose measuring devices, blood glucose test strips, and other logistics. The strategic framework for programme implementation is to utilise the infrastructure and manpower of the already existing non-communicable disease (NCD) clinic under National Health Mission., Methodology: Establishing dedicated T1DM clinics in each district hospital by utilising existing healthcare delivery systems, intensive training and hand-holding of named human resources; providing comprehensive healthcare service and structured diabetes education to all T1DM patients; and building an electronic registry of patients are important components of the programme. T1DM clinics run once a week on the same day throughout the state. All T1DM patients are treated with the correct dose of insulin, both human regular insulin and glargine insulin. Patients are routinely monitored monthly to ensure good glycaemic control and prevent complications of the disease. Routine anthropometric examination and required laboratory investigations are conducted in the set-up of the already existing NCD clinic. Ongoing monitoring and evaluation of the T1DM programme are being conducted in terms of glycated haemoglobin (HbA1c) values, growth and development, complication rates, psychological well-being, quality of life, and direct and indirect expenditure incurred by families. Through this programme, any bottlenecks or gaps in service delivery will be identified and corrective measures will be adopted to ensure better health outcomes for those living with T1DM., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Endocrinology and Metabolism.)

Objective: Utility of corneal confocal microscopy (CCM) in children and adolescents with type 1 diabetes mellitus (T1DM) without neuropathic symptoms or signs and minimal abnormality in large and small nerve fiber function tests remains largely undetermined. This study aimed to evaluate the performance of CCM in comparison to thermal detection thresholds (TDT) testing and nerve conduction studies (NCS) for detecting neuropathy in children with T1DM., Methods: A cohort of children and adolescents with T1DM (n = 51) and healthy controls (n = 50) underwent evaluation for symptoms and signs of neurological deficits, including warm detection threshold, cold detection threshold, vibration perception threshold, NCS, and CCM., Results: Children with T1DM had no or very minimal neuropathic symptoms and deficits based on the Toronto Clinical Neuropathy Score, yet NCS abnormalities were present in 18 (35%), small fiber dysfunction defined by an abnormal TDT was found in 13 (25.5%) and CCM abnormalities were present in 25 (49%). CCM was abnormal in a majority of T1DM children with abnormal TDT (12/13, 92%) and abnormal NCS (16/18, 88%). CCM additionally was able to detect small fiber abnormalities in 13/38 (34%) in T1DM with a normal TDT and in 9/33 (27%) with normal NCS., Conclusion: CCM was able to detect corneal nerve loss in children with and without abnormalities in TDT and NCS., Competing Interests: Disclosure The authors have no multiplicity of interest to disclose., (Copyright © 2023 AACE. Published by Elsevier Inc. All rights reserved.)

Aims: Psoriasis is an immune-mediated skin disease characterized by keratinocytes hyperproliferation, abnormal differentiation and inflammation. Therefore, this study aimed to investigate in-vitro and in-vivo anti-inflammatory and anti-proliferative activity to evaluate anti-psoriatic potential of apigenin., Main Methods: For in-vivo study, 5 % imiquimod cream was used to induce psoriasis-like skin inflammation in BALB/c mice to mimic human psoriatic conditions. PASI score, CosCam score, histopathology, immunohistochemistry, qRT-PCR, and ELISA were done to evaluate the anti-psoriatic potential of topically applied apigenin. For in-vitro studies, LPS-induced inflammation in RAW 264.7 was done, and qRT-PCR, ELISA, and immunofluorescence were conducted to evaluate the anti-inflammatory activity of apigenin. Migration and cell doubling assay in HaCaT cells were performed to assess the anti-proliferative effect of apigenin. Acute dermal toxicity profile of apigenin has also been done as per OECD guidelines., Key Findings: Results showed that apigenin significantly reduce the PASI and CosCam scores, ameliorate the deteriorating histopathology, and effectively downregulated the expression of CCR6, IL-17A, and NF-κB. Apigenin effectively downregulated the expression and secretion of pro-inflammatory cytokines through IL-23/IL-17/IL-22 axis. Apigenin suppressed nuclear translocation of NF-κB in LPS-induced RAW 264.7 cells. Cell migration and cell doubling assay in HaCaT cells showing the anti-proliferative potential of apigenin and it was found safe in acute dermal toxicity study., Significance: Apigenin was found effective against psoriasis in both in-vitro and in-vivo models suggesting apigenin as a potential candidate for the development of anti-psoriatic agent., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Lifestyle modifications and medication compliance are key strategies., Objectives: To evaluate the effect of community-based care delivered by trained primary healthcare providers in management of hypertension., Materials and Methods: A longitudinal study was conducted between two groups of newly diagnosed hypertensive patients to evaluate the impact of an educational intervention. Six blocks in a district were chosen with pairwise matching. All primary healthcare providers of one block in each pair were randomized to receive the intervention and the other was controlled. Next screening for risk factors, detection of hypertension, counseling, and follow-up care were provided. The patients within the control group received usual care as per clinician's discretion. A total of 227 patients in the "study" group and 230 patients in the "control" group were recruited from 12 subcenters selected randomly. Data analysis was done by χ 2 test, t test, and GLM analysis using SPSS 16., Results: Patients in the intervention blocks demonstrated a statistically significant mean reduction in SBP of 16.14 ± 0.82 and DBP by 11.65 ± 0.53 compared to 9.83 ± 1.02 and 7.68 ± 0.66, respectively, in the control blocks after adjusting for age, sex, and baseline blood pressure at one-year follow-up. Regarding lifestyle-related cardiovascular risk factors, statistically significant differences were found in favor of the intervention group., Conclusion: The study supports and reinforces the utilization of trained primary healthcare providers under the NPCDCS program in screening and promoting blood pressure control by preventive services to hypertensive patients in the community., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Family Medicine and Primary Care.)

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have recently been recommended as preferred agents for management of hyperglycemia in type 2 diabetes, primarily based on their ability to reduce a composite of major cardiovascular adverse events (3-point major adverse cardiovascular events [MACE]), predominantly by reducing cardiovascular death. However, reduction of the individual components, myocardial infarction (MI), or stroke (fatal and nonfatal) events have not been well explored., Methods: In this meta-analysis, we included data available from cardiovascular outcome trials only, which were event-driven, randomized, and placebo-controlled. Pooled efficacy outcomes included Mantel Haenszel (MH) risk ratio using fixed model (with 95% CI) for fatal and nonfatal MI, stroke, and total MI and stroke., Findings: Data from 4 eligible trials included 42,568 subjects. Total MACE, MI, and stroke were reported in 4176, 2157, and 1288 subjects, respectively. SGLT2is did not significantly reduce either MI or stroke individually or in totality. The MH risk ratio (95% CI) for fatal and nonfatal MI and stroke with different SGLT2is was found to be 0.93 (95% CI, 0.85-1.01) and 1.00 (95% CI, 0.89-1.11), respectively. For total atherosclerotic cardiovascular disease (ASCVD) events, MH risk ratio (95% CI) was 0.95 (95% CI, 0.89-1.02). For all nonfatal ASCVD (combined nonfatal MI and nonfatal stroke), MH risk ratio (95% CI) was 0.94 (95% CI, 0.88-1.02)., Interpretation: SGLT2is reduce MACE without any discernable significant reduction of the incidence of MI or stroke (fatal and nonfatal), probably implicating mechanisms unrelated to anti-atherogenic effects., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Social equity is a critical component of social justice and is measured in multiple ways. Conventionally, researchers use literacy levels, workforce participation, political participation and representation, corporate presence, and demographic parity as indicators of social and economic equity. We add law enforcement outcomes to this literature by examining the demographic profiles of convicts in prisons in India for each state and compare it with that of the population of the respective state. To test whether entrenched social inequities have permeated into the law enforcement system, we use three indicators of social identity-religion, caste, and domicile-to create a social equity index (SEI). This is a composite index combining caste, religion and domicile similar in method to the Human Development Index which combines income, education and health. Our indicators are not considered in other popular development indices and is a conceptual innovation. Our paper innovates by combining prison data and census data at the state level over the two latest census rounds (2001 and 2011). We use a spatial panel analysis as well as a distributional dynamics approach to test for bias and transitions over time at the state level. We find that entrenched social hierarchies are mirrored in conviction outcomes and that social identities influence law enforcement. In contrast to earlier studies, we find that states that are conventionally considered to perform poorly in terms of economic and human development have done better in terms of social equity than economically advanced states., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mukhopadhyay et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aim: The 5-year survival rate of pancreatic ductal adenocarcinoma (PDAC) is approximately 11% and has only improved marginally over the last three decades. For operable PDAC, resection and adjuvant FOLFIRINOX chemotherapy is standard of care. There is growing interest in perioperative regimens to improve outcomes. The non-randomized Phase II study "Gemcitabine and Abraxane for resectable Pancreatic cancer" (GAP) demonstrated the feasibility of perioperative gemcitabine/abraxane. Long-term survival in PDAC requires an effective immune response; hence, we undertook this translational study of the GAP trial cohort to identify immune-oncology biomarkers for clinical use., Methods: We combined Nanostring nCounter technology with immunohistochemistry to investigate the correlation between gene expression and overall patient survival. Findings were investigated in samples from the International Cancer Genome Consortium (ICGC, n = 88) and the Australian Pancreatic Genome Initiative (APGI, n = 227)., Results: We confirmed that human equilibrative nucleoside transporter 1 (hENT1) expression was not a prognostic marker in PDAC but patients with high levels of hENT1 were more likely to live longer than 24 months post-surgery. Additionally, CD274 (PD-L1) and two novel biomarkers of survival, cathepsin W (CTSW) and C-reactive protein (CRP), were identified in the GAP cohort (n = 19). CRP expression was confirmed in data from the ICGC. Although PD-L1 and CTSW proteins were not significant across all three cohorts, results show that low CRP mRNA and protein expression are associated with longer overall survival in all three patient groups., Conclusion: PDAC patients with long survival have higher hENT1 expression levels. Furthermore, CRP expression is a biomarker of poor prognosis following perioperative chemotherapy and resection in PDAC patients and thus may be useful for identifying patients who could benefit from more aggressive adjuvant strategies., (© 2023 The Authors. Asia-Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.)

Aim: The aim of the study was to develop a simple prediction model based on previous treatment plans for head-and-neck cancer (HNC)., Materials and Methods: This study was conducted on 95 patients who underwent volumetric-modulated arc therapy (VMAT) with curative intent for HNC at our institute between January 2016 and December 2022 with intact bilateral parotid glands. Two simple prediction models were used: one linear regression model and one exponential model. Both models use fractional overlapping parotid volume with planning target volume (PTV) as a predictor of mean parotid dose. The fractional overlapping volume was calculated as the difference between the volume of the parotid gland minus the volume of the parotid gland outside the PTV plus a 2 mm margin, divided by the volume of the parotid gland. Statistical calculations were done using data analysis tools and Solver in Microsoft Excel (Microsoft Office 2013, Redmond, WA, USA). To enhance the accuracy of the results, outliers were excluded with residuals >2 standard deviations below and above the residuals. R 2 and root-mean-square error were calculated for both models to evaluate the quality of the predictions. The normality of both models' residuals was validated using the Shapiro-Wilk test., Results: Both linear and exponential prediction models exhibited strong correlation statistics, with r 2 = 0.85 and 0.82, respectively. The authors found a fractional overlap of 16.4% and 18.9% in linear and exponential models that predict parotid mean dose 26 Gy. The implementation was carried out on a cohort of 12 prospective patients, demonstrating a remarkable improvement in minimizing the dose to the parotid glands., Conclusion: In this single-institutional study, the authors successfully developed a prediction model for mean parotid dose in HNC patients undergoing radiotherapy. The model showed promising accuracy and has the potential to assist planners in optimizing treatment plans and minimizing radiation-related toxicity. It is possible to avoid under sparing the organs at risks in some cases and wasting time or effort on physically impossible goals in others using this prediction model. As a result, planning resources can be used much more efficiently. Future studies should focus on validating the model's performance using external datasets and exploring its integration into clinical practice., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Medical Physics.)

Background and Aim: Primary glomerular disease accounts for one-sixth of all chronic kidney diseases (CKDs) in India. We remain limited in our ability to effectively treat these conditions because of lack of understanding of the disease mechanisms and lack of predictors to identify the clinical course and therapeutic responsiveness. We propose to develop a network of investigators in glomerular diseases, collect information in a systematic fashion to understand the clinical outcomes, answer translational research questions better, and identify and recruit patients for clinical trials., Materials and Methods: This is a prospective, observational study. The Indian TrANslational GlomerulonephrItis BioLogy nEtwork (I-TANGIBLE) cohort will enroll patients (>18 years) with biopsy-proven minimal change disease (MCD), focal segmental glomerulonephritis (FSGS), membranous nephropathy (MN), IgA nephropathy (IgAN), or membranoproliferative glomerulonephritis (MPGN) (immune complex- and complement-mediated), with first biopsy taken within 2 years of enrollment. Patients with estimated glomerular filtration (eGFR) rate <15 ml/min/1.73 m 2 for >3 months at the time of screening, kidney transplant or bone marrow transplant recipients, patients with active malignancy, and patients with active hepatitis B/C replication or human immunodeficiency virus (HIV)-I/II will be excluded. Clinical details including history, medication history and details, and family history will be obtained. Consenting patient's blood and urine samples will be collected and stored, aligned to their clinical follow-up., Expected Outcomes: The network will allow accurate ascertainment of disease burden of glomerular diseases across study sites, establishment of the treatment pattern of common glomerular diseases, investigation of medium- and long-term outcomes (remission, relapse, rate of eGFR decline), and building a suitable infrastructure to carry out clinical trials in primary glomerular disease., Competing Interests: Dr. Vivekanand Jha has received grant funding from GSK, Baxter, Astra Zeneca, Boerhringer Ingelheim, NephroPlus, and Zydus Cadilla, under the policy of all honoraria being paid to the organization. All the other authors do not have any conflict of interest to declare., (Copyright: © 2023 Indian Journal of Nephrology.)

Background: Spirituality is an important dimension of life. The medical practitioner's well-being is an under-appreciated priority in India. As research on spirituality is minimal, this study attempts to introduce an online 6-week Eastern spirituality-based educational program for physicians. The primary aim was to see the effects of the intervention on the well-being of the participants. The secondary aim was to form an opinion about an extension to medical practice., Materials and Methods: A total of 60 medical practitioners were randomized into two groups- one attended the spirituality sessions while the other placebo "self-care" sessions. Quantitative outcome measures were Warwick-Edinburg Mental Well-being Scale (WEMWBS) and World Health Organization (WHO) Well-being Index (WHO-5) noted pre and postprogram. Qualitative data was collected to support the quantitative outcomes. Statistical tests used were unpaired and paired t-tests for quantitative data. A 5-point Likert scale and Cochran's Q test were used for the qualitative data., Results: In the spirituality group, postsession WEMWBS and WHO-5 scores improved with p &lt; 0.0001 and p = 0.0033, respectively. Regarding qualitative data, 94.44% of physicians "agreed/strongly agreed" in favor of the benefits of sessions with p = 0.0242 and Q = 5.0793. A total of 86.67% of physicians felt the sessions have helped them to understand other's spirituality-related problems and made them more confident to discuss spirituality with others., Conclusion: The online Eastern spirituality program had a positive impact on the well-being of Indian medical practitioners. There appears to be a potential for extension to the medical care setting. The results need to be substantiated by further studies., (© Journal of the Association of Physicians of India 2011.)

Prime Editing is a CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) based genome editing technique having promising potential in terms of reducing off target activity. It introduces fragments of DNA sequences into the target site using a guide RNA (gRNA) molecule, composed of both the sequence that is to be inserted into the target site along with an inactive Cas9 nickase and a reverse transcriptase. Prime Editing can cause insertions, deletions, and various point mutations for reverting the phenetic characteristics of a disease specially tested in human adult stem cells and cancer cell lines. The main aim of our review is to explore how Prime Editing and its various forms are being utilized as an emerging tool to cure deleterious diseases like cancer, also as a delivery strategy of the tool into cells. There are almost five generations of Prime Editors (PE) with increasing levels of efficiency from one level to another that have huge clinical potential in correcting mutations; however, the necessity for a pegRNA design is extremely significant. But besides having such advantages, the limitations of this technology particularly include generation of double nicks while optimizing the efficiency of PE3. So, it is important to consider all such consequences and customize PE as per requirements., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The proliferation and differentiation of hepatic progenitor cells (HPCs) drive the homeostatic renewal of the liver under diverse conditions. Liver regeneration is associated with an increase in Axin2 + Cnr1 + HPCs, along with a marked increase in the levels of the endocannabinoid anandamide (AEA). But the molecular mechanism linking AEA signaling to HPC proliferation and/or differentiation has not been explored. Here, we show that in vitro exposure of HPCs to AEA triggers both cell cycling and differentiation along with increased expression of Cnr1, Krt19, and Axin2. Mechanistically, we found that AEA promotes the nuclear localization of the transcription factor β-catenin, with subsequent induction of its downstream targets. Systemic analyses of cells after CRISPR-mediated knockout of the β-catenin-regulated transcriptome revealed that AEA modulates β-catenin-dependent cell cycling and differentiation, as well as interleukin pathways. Further, we found that AEA promotes OXPHOS in HPCs when amino acids and glucose are readily available as substrates, but AEA inhibits it when the cells rely primarily on fatty acid oxidation. Thus, the endocannabinoid system promotes hepatocyte renewal and maturation by stimulating the proliferation of Axin2 + Cnr1 + HPCs via the β-catenin pathways while modulating the metabolic activity of their precursor cells., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Cannabinoid CB 2 receptor (CB 2 R) agonists are investigated as therapeutic agents in the clinic. However, their molecular mode-of-action is not fully understood. Here, we report the discovery of LEI-102, a CB 2 R agonist, used in conjunction with three other CBR ligands (APD371, HU308, and CP55,940) to investigate the selective CB 2 R activation by binding kinetics, site-directed mutagenesis, and cryo-EM studies. We identify key residues for CB 2 R activation. Highly lipophilic HU308 and the endocannabinoids, but not the more polar LEI-102, APD371, and CP55,940, reach the binding pocket through a membrane channel in TM1-TM7. Favorable physico-chemical properties of LEI-102 enable oral efficacy in a chemotherapy-induced nephropathy model. This study delineates the molecular mechanism of CB 2 R activation by selective agonists and highlights the role of lipophilicity in CB 2 R engagement. This may have implications for GPCR drug design and sheds light on their activation by endogenous ligands., (© 2023. The Author(s).)

Aberrant expression of xenobiotic metabolism and DNA repair genes is critical to lung cancer pathogenesis. This study aims to identify the cis-regulatory variants of the genes modulating lung cancer risk among tobacco smokers and altering their chemotherapy responses. From a list of 2984 SNVs, prioritization and functional annotation revealed 22 cis-eQTLs of 14 genes within the gene expression-correlated DNase I hypersensitive sites using lung tissue-specific ENCODE, GTEx, Roadmap Epigenomics, and TCGA datasets. The 22 cis-regulatory variants predictably alter the binding of 44 transcription factors (TFs) expressed in lung tissue. Interestingly, 6 reported lung cancer-associated variants were found in linkage disequilibrium (LD) with 5 prioritized cis-eQTLs from our study. A case-control study with 3 promoter cis-eQTLs (p < 0.01) on 101 lung cancer patients and 401 healthy controls from eastern India with confirmed smoking history revealed an association of rs3764821 (ALDH3B1) (OR = 2.53, 95% CI = 1.57-4.07, p = 0.00014) and rs3748523 (RAD52) (OR = 1.69, 95% CI = 1.17-2.47, p = 0.006) with lung cancer risk. The effect of different chemotherapy regimens on the overall survival of lung cancer patients to the associated variants showed that the risk alleles of both variants significantly decreased (p < 0.05) patient survival., (© 2023. The Author(s).)

The necessity to record and store biological data is increasing in due course of time. However, it is quite difficult to understand biological mechanisms and keep a track of these events in some storage mediums. DNA (deoxyribonucleic acid) is the best candidate for the storage of cellular events in the biological system. It is energy efficient as well as stable at the same time. DNA-based writers and memory devices are continually evolving and finding new avenues in terms of their wide range of applications. Among all the DNA-based storage devices that employ enzymes like recombinases, nucleases, integrases, and polymerases, one of the most popular tools used for these devices is the emerging and versatile CRISPR Cas technology. CRISPR Cas is a prokaryotic immune system that keeps a memory of viral attacks and protects prokaryotes from potential future infections. The main aim of this short review is to study such molecular recorders and writers that employ CRISPR Cas technologies and obtain an in-depth overview of the mechanisms involved and the applications of these molecular devices., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Real-time streamflow forecasting is essential to manage water resources effectively in a reservoir-regulated basin. However, forecasting becomes challenging without weather and upstream reservoir outflows forecasts in real-time. In this context, a novel hybrid approach is proposed in this study to forecast the streamflows and reservoir outflows in real-time. In this approach, the Explainable Machine Learning model is embedded with a conceptual reservoir module for forecasting streamflows using short-term weather forecasts. Long Short Term Memory (LSTM), a Machine Learning model, is used in this study to predict the streamflow, and the model's explainability is examined by Shapley additive explanations method (SHAP). Panchet reservoir catchment, which contains Tenughat and Konar reservoirs, is selected as a study area. The LSTM model performance is excellent in predicting the streamflows of Tenughat, Konar and Panchet catchments with NSE values of 0.93, 0.87, and 0.96, respectively. The SHAP method identified the high-impact variables as streamflows and precipitation of 1-day lag. In forecasting, bias-corrected Global Forecast System data is used with the LSTM model to forecast the streamflows in three catchments. The inflows are forecasted well up to a 3-day lead in Tenughat and Konar reservoirs with NSE values above 0.88 and 0.87, respectively. The reservoir module performance in forecasting Tenughat and Konar reservoirs' outflows with the inflow forecasts is also promising up to a 3-day lead with NSE values above 0.88 for both reservoirs. The inflows forecasting to Panchet reservoir with reservoirs' outflows as additional inputs is excellent up to 5-day lead (NSE = 0.96-0.88). However, the forecasting error increased from 77 m 3 /s to 134 m 3 /s with the lead time. This approach could provide an efficient way to reduce flood risks in the reservoir-regulated basin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Inhibiting individual histone deacetylase (HDAC) is emerging as well-tolerated anticancer strategy compared with pan-HDAC inhibitors. Through preclinical studies, we demonstrated that the sensitivity to the leading HDAC6 inhibitor (HDAC6i) ricolinstat can be predicted by a computational network-based algorithm (HDAC6 score). Analysis of ~3,000 human breast cancers (BCs) showed that ~30% of them could benefice from HDAC6i therapy. Thus, we designed a phase 1b dose-escalation clinical trial to evaluate the activity of ricolinostat plus nab-paclitaxel in patients with metastatic BC (MBC) (NCT02632071). Study results showed that the two agents can be safely combined, that clinical activity is identified in patients with HR + /HER2 - disease and that the HDAC6 score has potential as predictive biomarker. Analysis of other tumor types also identified multiple cohorts with predicted sensitivity to HDAC6i's. Mechanistically, we have linked the anticancer activity of HDAC6i's to their ability to induce c-Myc hyperacetylation (ac-K148) promoting its proteasome-mediated degradation in sensitive cancer cells., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Non-communicable diseases including metabolic health disorders are becoming area of concern for low/middle income countries with poor health-care resources. Present study was planned to assess the prevalence of metabolically unhealthy (MU) subjects in the community and proportion of the MU subjects having the risk of significant Non-alcoholic Fatty Liver Disease (NAFLD) using a step-wise evaluation strategy in a resource-poor setting., Methods: Study was performed in 19 community development blocks of Birbhum district, West Bengal, India. Every fifth member in the electoral list was included for the first step evaluation (n = 79,957/1,019,365, 7.8%) to detect any metabolic risk. Subjects with any metabolic risk in the first step (n = 9819/41,095, 24%) were taken for second step evaluation with Fasting blood glucose (FBG) and ALT. Subjects with elevated FBG and/or ALT in the second step (n = 1403/5283, 27%) were taken into third step evaluation., Finding: At least one risk factor was found in 51.4% (n = 41,095/79,957). 63% (n = 885/1403) of the subjects with metabolic abnormality (third step) had MU state making its overall prevalence of 1.1% (n = 885/79,957). 53% of MU subjects (n = 470/885) had 'persistently elevated ALT' suggesting the risk of having significant NAFLD., Interpretation: Step-wise evaluation strategy could detect the subjects at risk, actually having MU state and proportion of MU subjects at risk of having 'persistently elevated ALT' (surrogate of significant NAFLD) in the community with minimum utilization of scarce resources., Funding: This study was funded by Bristol Myers Squibb Foundation, USA, under the program 'Together on Diabetes Asia' (Project Number: 1205 - LFWB)., Competing Interests: We were not paid by any pharmaceutical company or any other agency to write this article. Authors were not precluded from accessing data in the study and all of them accept the responsibility to submit for publication. All the authors declare no conflict of interest., (© 2023 The Author(s).)