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Background In June 2019, Nipah virus (NiV) infection was detected in a 21-year-old male (index case) of Ernakulum, Kerala, India. This study was undertaken to determine if NiV was in circulation in Pteropus species ( spp) in those areas where the index case had visit history in 1 month. Methods Specialized techniques were used to trap the Pteropus medius bats (random sampling) in the vicinity of the index case area. Throat and rectal swabs samples of 141 bats along with visceral organs of 92 bats were collected to detect the presence of NiV by real-time reverse transcriptase-polymerase chain reaction (qRTPCR). Serum samples of 52 bats were tested for anti-NiV Immunoglobulin (Ig) G antibodies by Enzyme-Linked Immunosorbent Assay (ELISA). The complete genome of NiV was sequenced by next-generation sequencing (NGS) from the tissues and swab samples of bats. Results One rectal swab sample and three bats visceral organs were found positive for the NiV. Interestingly, 20.68% (12/58) of Pteropus were positive for anti-NiV IgG antibodies. NiV sequences of 18,172; 17,200 and 15,100 nucleotide bps could be retrieved from three Pteropus bats. Conclusion A distinct cluster of NiV sequences, with significant net-evolutionary nucleotide divergence, was obtained, suggesting the circulation of new genotype (I-India) in South India. NiV Positivity in Pteropus spp. of bats revealed that NiV is circulating in many districts of Kerala state, and active surveillance of NiV should be immediately set up to know the hotspot area for NiV infection.

Background: This first-in-human, phase I clinical trial of p28 (NSC745104), a 28-amino-acid fragment of the cupredoxin azurin, investigated the safety, tolerability, pharmacokinetics and preliminary activity of p28 in patients with p53 + metastatic solid tumours. Methods: A total of 15 patients were administered p28 i.v. as a short infusion three times per week for 4 weeks followed by a 2-week rest under an accelerated titration 3+3 dose escalation design until either a grade 3-related adverse event occurred or the maximum tolerated dose (MTD) was reached. Single-dose and steady-state serum pharmacokinetics were characterised. Assessments included toxicity, best objective response by RECIST 1.1 Criteria, and overall survival. Results: No patients exhibited any dose-limiting toxicities (DLTs), significant adverse events or exhibited an immune response (IgG) to the peptide. The No Observed Adverse Effect Level (NOAEL) and MTD were not reached. Seven patients demonstrated stable disease for 7–61 weeks, three a partial response for 44–125 weeks, and one a complete response for 139 weeks. Three patients are still alive at 158, 140, and 110 weeks post therapy completion. Conclusion: p28 was tolerated with no significant adverse events. An MTD was not reached. Evidence of anti-tumour activity indicates a highly favourable therapeutic index and demonstrates proof of concept for this new class of non-HDM2-mediated peptide inhibitors of p53 ubiquitination.

A bstract Neutrino oscillation experiments provide a unique window in exploring several new physics scenarios beyond the standard three flavour. One such scenario is quantum decoherence in neutrino oscillation which tends to destroy the interference pattern of neutrinos reaching the far detector from the source. In this work, we study the decoherence in neutrino oscillation in the context of the ESSnuSB experiment. We consider the energy-independent decoherence parameter and derive the analytical expressions for P μe and P μμ probabilities in vacuum. We have computed the capability of ESSnuSB to put bounds on the decoherence parameters namely, Γ 21 and Γ 32 and found that the constraints on Γ 21 are competitive compared to the DUNE bounds and better than the most stringent LBL ones from MINOS/MINOS+. We have also investigated the impact of decoherence on the ESSnuSB measurement of the Dirac CP phase δ CP and concluded that it remains robust in the presence of new physics.

Single-nucleotide mutations in human SIX1 result in amino acid substitutions in either the protein-protein interaction domain or the homeodomain, and cause ∼4% of branchio-otic (BOS) and branchio-oto-renal (BOR) cases. The phenotypic variation between patients with the same mutation, even within affected members of the same family, make it difficult to functionally distinguish between the different SIX1 mutations. We made four of the BOS/BOR substitutions in the Xenopus Six1 protein (V17E, R110W, W122R, Y129C), which is 100% identical to human in both the protein-protein interaction domain and the homeodomain, and expressed them in embryos to determine whether they cause differential changes in early craniofacial gene expression, otic gene expression or otic morphology. We confirmed that, similar to the human mutants, all four mutant Xenopus Six1 proteins access the nucleus but are transcriptionally deficient. Analysis of craniofacial gene expression showed that each mutant causes specific, often different and highly variable disruptions in the size of the domains of neural border zone, neural crest and pre-placodal ectoderm genes. Each mutant also had differential effects on genes that pattern the otic vesicle. Assessment of the tadpole inner ear demonstrated that while the auditory and vestibular structures formed, the volume of the otic cartilaginous capsule, otoliths, lumen and a subset of the hair cell-containing sensory patches were reduced. This detailed description of the effects of BOS/BOR-associated SIX1 mutations in the embryo indicates that each causes subtle changes in gene expression in the embryonic ectoderm and otocyst, leading to inner ear morphological anomalies.

Globalization has led to massive rise in cross border trade. Increase in E-commerce business has contributed to this too. As a result, a continuous and complex logistics network of supply chains operate across the globe round the clock. Transportation of goods is the most essential activity of this network. Statistics reveals that approximately 90 percent of world’s goods are transported via sea route. This intense network of shipment poses a huge threat to marine ecosystem in numerous ways. One of the most dangerous events for marine ecosystem is oil spill. Oil spill from vessels and pipelines are a major reason behind mortality of marine wildlife. The present work focuses on developing a cost-effective sustainable solution for mitigation of marine oil spill. It was found from existing literature that peels of some fruits have substantial oil absorbing capacity. This fact was experimentally validated and a reduced scale prototype was designed aiming for the task of deployment in case of oil spill in marine waters. The experimental results show that the proposed model floats on water after absorbing oil up to its saturation value. It was also found that through appropriate mechanical setup, absorbed oil can be extracted for reuse or processing.

A bstract Neutrino oscillations constitute an excellent tool to probe physics beyond the Standard Model. In this paper, we investigate the potential of the ESSnuSB experiment to constrain the effects of flavour-dependent long-range forces (LRFs) in neutrino oscillations, which may arise due to the extension of the Standard Model gauge group by introducing new U(1) symmetries. Focusing on three specific U(1) symmetries — L e − L μ , L e − L τ , and L μ − L τ , we demonstrate that ESSnuSB offers a favourable environment to search for LRF effects. Our analyses reveal that ESSnuSB can set 90% confidence level bounds of V eμ < 2.99 × 10 − 14 eV, V eτ < 2.05 × 10 − 14 eV, and V μτ < 1.81 × 10 − 14 eV, which are competitive to the upcoming Deep Underground Neutrino Experiment (DUNE). It is also observed that reducing the systematic uncertainties from 5% to 2% improves the ESSnuSB limits on V αβ . Interestingly, we find limited correlations between LRF parameters and the less constrained lepton mixing parameters θ 23 and δ CP , preserving the robustness of ESSnuSB’s sensitivity to CP violation. Even under extreme LRF potentials ( V αβ ≫ 10 − 13 eV), the CP-violation sensitivity and δ CP precision remain largely unaffected. These results establish ESSnuSB as a competitive experimental setup for probing LRF effects, complementing constraints from other neutrino sources and offering critical insights into the physics of long-range forces.

Heart failure (HF) and diabetes mellitus (DM) are major public health issues that place significant burden on patients and health care systems. Patients with both HF and DM are at higher risk of adverse cardiovascular and HF outcomes than those with either disease in isolation. Different antihyperglycemic medications (even within the same medication class) have conflicting results of benefit or harm in patients with established and incident HF. Recent data highlight the importance of a renewed focus on optimal pharmacotherapy for this population with DM and HF (or at risk for HF). Both HF and DM require major lifestyle modification for optimal management, in terms of both optimizing health behaviors (eg, physical activity, diet) and adherence to complex medical and self-care regimens. Mobile health (mHealth) technologies (eg, apps, wearables) are widely available in the community and may play a role in optimizing the health status of patients; however, there is limited and conflicting information on whether such technologies are actually beneficial in at-risk populations. In this article, we summarize current strategies, including mobile health interventions, to improve physical activity levels, drug adherence, and outcomes in patients with DM, HF, or both and describe the design and rationale for the Technologies to improve drug Adherence and Reinforce Guideline based Exercise Targets in patients with heart Failure and Diabetes Mellitus trial, which is designed to test the efficacy of using mHealth technology to improve health behaviors and outcomes in this high-risk population.

Precambrian shield areas are often metal-enriched. Unlike many other contemporary shields, the Mikir Hills, however, does not have any history of metal production in the past. Ultrabasic–basic–intermediate to acid and alkaline magmatics of Precambrian to Cretaceous age depict evidences of mineralization in the shield. Poor understanding of the geological and geo-chronological events is responsible for branding barren signature to the shield. Recently generated geo-chronological data on mineralized Palaeoproterozoic granitoids of the shield provide cognizance to its geological evolution. The merit of metallogenic appraisal brightens as the geochronological data produced recently indicate the existence of granitoids of Palaeoproterozoic age in this craton. Moreover, recent studies have revealed that a majority of felsic to intermediate magmatics with distinct mineralization signatures are mantle-derived I-type granitoids and their metal contents are derived from similar source region. Features of hypogene alteration found prominence in a studied mineralized porphyry granitoid of Kuthori–Bagori locality of Kaziranga magmatic suite having calc-alkaline affinity. Local and regional-scale shearing has been observed and the structural elements are oriented in NNE–SSW to NE–SW directions. They are sporadically mineralized throughout the craton.

Background & objectives: Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has globally affected 195 countries. In India, suspected cases were screened for SARS-CoV-2 as per the advisory of the Ministry of Health and Family Welfare. The objective of this study was to characterize SARS-CoV-2 sequences from three identified positive cases as on February 29, 2020. Methods: Throat swab/nasal swab specimens for a total of 881 suspected cases were screened by E gene and confirmed by RdRp (1), RdRp (2) and N gene real-time reverse transcription-polymerase chain reactions and next-generation sequencing. Phylogenetic analysis, molecular characterization and prediction of B- and T-cell epitopes for Indian SARS-CoV-2 sequences were undertaken. Results: Three cases with a travel history from Wuhan, China, were confirmed positive for SARS-CoV-2. Almost complete (29,851 nucleotides) genomes of case 1, case 3 and a fragmented genome for case 2 were obtained. The sequences of Indian SARS-CoV-2 though not identical showed high (~99.98%) identity with Wuhan seafood market pneumonia virus (accession number: NC 045512). Phylogenetic analysis showed that the Indian sequences belonged to different clusters. Predicted linear B-cell epitopes were found to be concentrated in the S1 domain of spike protein, and a conformational epitope was identified in the receptor-binding domain. The predicted T-cell epitopes showed broad human leucocyte antigen allele coverage of A and B supertypes predominant in the Indian population. Interpretation & conclusions: The two SARS-CoV-2 sequences obtained from India represent two different introductions into the country. The genetic heterogeneity is as noted globally. The identified B- and T-cell epitopes may be considered suitable for future experiments towards the design of vaccines and diagnostics. Continuous monitoring and analysis of the sequences of new cases from India and the other affected countries would be vital to understand the genetic evolution and rates of substitution of the SARS-CoV-2.

Several single-nucleotide mutations in SIX1 underlie branchio-otic/branchio-oto-renal (BOR) syndrome, but the clinical literature has not been able to correlate different variants with specific phenotypes. We previously assessed whether variants in either the cofactor binding domain (V17E, R110W) or the DNA binding domain (W122R, Y129C) might differentially affect early embryonic gene expression, and found that each variant had a different combination of effects on neural crest and placode gene expression. Since the otic vesicle gives rise to the inner ear, which is consistently affected in BOR, herein we focused on whether the variants differentially affected the otic expression of genes previously found to be likely Six1 targets. We found that V17E, which does not bind Eya cofactors, was as effective as wild-type Six1 in reducing most otic target genes, whereas R110W, W122R and Y129C, which bind Eya, were significantly less effective. Notably, V17E reduced the otic expression of prdm1, whereas R110W, W122R and Y129C expanded it. Since each mutant has defective transcriptional activity but differs in their ability to interact with Eya cofactors, we propose that altered cofactor interactions at the mutated sites differentially interfere with their ability to drive otic gene expression, and these differences may contribute to patient phenotype variability.