Reconstructing the population history of the Nicobarese.

The Nicobarese are the major tribal groups in the Nicobar district, situated south of the Andaman group of Islands. Linguistic phylogeny suggests that the linguistic ancestors of the Nicobarese settled the Nicobar archipelago in the early Holocene. So far, genetic research on them is low-resolution and restricted to the haploid DNA markers.

Mapping the FF domain folding pathway via structures of transiently populated folding intermediates.

Despite the tremendous accomplishments of AlpaFold2/3 in predicting biomolecular structure, the protein folding problem remains unsolved in the sense that accurate atomistic models of how protein molecules fold into their native conformations from an unfolded ensemble are still elusive. Here, using chemical exchange saturation transfer (CEST) NMR experiments and a comprehensive four-state kinetic model of the folding trajectory of a 71 residue four-helix bundle FF domain from human HYPA/FBP11 we present an atomic resolution structure of a transiently formed intermediate, I2, that along with the structure of a second intermediate, I1, provides a description of the FF domain folding trajectory. By recording CEST profiles as a function of urea concentration the extent of compaction along the folding pathway is evaluated.

Indian Brachytherapy Society consensus recommendations for brachytherapy in breast cancer.

Purpose: This consensus statement of Indian Brachytherapy Society (IBS) aims to generate practical and reproducible guidelines allowing for direct implementation in the Indian scenario.

Material And Methods: IBS board of directors appointed a panel of physicians with expertise in breast cancer and, in particular, breast brachytherapy, to develop a consensus statement. First, a literature review on breast brachytherapy was conducted, focusing on randomized trials, prospective studies, and multi-institutional series.

Bulk Condensation by an Active Interface.

We present experiments, supported by mechanically detailed simulations, establishing bulk condensation of a hard-bead fluid by a tiny population of orientable motile grains that self-assembles into a moving polarized monolayer. In a quasi-1D geometry two such layers, oppositely aligned, immobilize the condensed nonmotile component. We account for our observations through a continuum theory with a naturally nonreciprocal Cahn-Hilliard structure, whose predicted trends as a function of packing fraction are consistent with our observations.

Searching for Asymmetric and Heavily Precessing Binary Black Holes in the Gravitational Wave Data from the LIGO Third Observing Run.

Leveraging the features of the GstLAL pipeline, we present the results of a matched filtering search for asymmetric binary black hole systems with heavily misaligned spins in LIGO and Virgo data taken during the third observing run. Our target systems show strong imprints of precession whereas current searches have nonoptimal sensitivity in detecting them. After measuring the sensitivity improvement brought by our search over standard spin-aligned searches, we report the detection of 30 gravitational wave events already discovered in the latest version of the Gravitational Wave Transient Catalog.

Systemic Cancer Hallmarks as Novel Markers Associated with Progression-Free Survival in Gastroenteropancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy.

Introduction: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of tumors often detected at the metastatic stage. The aim of this study was to profile the peripheral blood transcriptome through RNA-Seq and investigate the association of the systemic cancer hallmarks with progression-free survival, in peptide receptor radionuclide therapy (PRRT)-treated GEP-NET patients.

Methods: The cohorts were discovery cohort [PRRT-naïve well-differentiated GEP-NETs, n = 59; age- and sex-matched healthy individuals, n = 38], and independent evaluation cohort [GEP-NETs, n = 66].

Evaluating anticancer potentials of potentized preparations in an in-vivo xenograft model.

Background: Xenografts in immunodeficient mice play a pivotal role in testing novel anti-cancer treatments. Xenograft models expedite the drug discovery process, offering a cost-effective alternative to conventional animal models and providing essential data for clinical trials. We have followed the approach described by the Developmental Therapeutics Program of the National Cancer Institute (NCI), USA to investigate the therapeutic responses.

RAPID-CRISPR: highly sensitive diagnostic assay for detection of PML::RARA isoforms in acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL), distinguished by the presence of PML::RARA fusion transcript, is a medical emergency because of its high early death rate, which is preventable when diagnosed early. Current diagnostic methods are precise and reliable but are time intensive, require sophisticated instruments, and analytical expertise. This study has redefined APL identification by CRISPR system (RAPID-CRISPR) to rapidly (<3 hours) detect PML::RARA.

Mathematical basis and toolchain for hierarchical optimization of biochemical networks.

Biological signalling systems are complex, and efforts to build mechanistic models must confront a huge parameter space, indirect and sparse data, and frequently encounter multiscale and multiphysics phenomena. We present HOSS, a framework for Hierarchical Optimization of Systems Simulations, to address such problems. HOSS operates by breaking down extensive systems models into individual pathway blocks organized in a nested hierarchy.

Groundwater hydrogeochemistry and potential health risk assessment through exposure to elevated arsenic in Darrang district of north bank plain of the Brahmaputra.

The current study investigates groundwater contamination in Darrang district, situated in the flood-prone Brahmaputra Valley. This research evaluates the concentrations and geospatial distributions of iron, fluoride, and arsenic in groundwater samples (n = 347) and assesses their potential ecotoxicological risks to human health. Multivariate statistical techniques were used to investigate the sources and the mobilization mechanism of the contaminants in the aquifer system.

Apoptosis-Inducing Activity of a 2-Hydroxyphenyl Benzamide-Based Self-Assembled Anion Channel.

Despite the significant interest in designing artificial ion channels, there is limited availability of channel-forming molecules to tackle complex issues, especially in biological systems. Moreover, a major challenge is the scarcity of chloride transporters that can selectively induce toxicity in cancer cells while minimizing harm to normal healthy cells. This work reports a series of 2-hydroxyphenyl benzamide-based small molecules 1 a-1 c, which self-assemble to form barrel rosette-type artificial ion channels that adequately transport chloride ions across membranes.

International cross-sectional survey on current and updated definitions of intra-abdominal hypertension and abdominal compartment syndrome.

Background: The Abdominal Compartment Society (WSACS) established consensus definitions and recommendations for the management of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) in 2006, and they were last updated in 2013. The WSACS conducted an international survey between 2022 and 2023 to seek the agreement of healthcare practitioners (HCPs) worldwide on current and new candidate statements that may be used for future guidelines.

Methods: A self-administered, online cross-sectional survey was conducted under the auspices of the WSACS to assess the level of agreement among HCPs over current and new candidate statements.

A universal niche geometry governs the response of ecosystems to environmental perturbations.

How ecosystems respond to environmental perturbations is a fundamental question in ecology, made especially challenging due to the strong coupling between species and their environment. Here, we introduce a theoretical framework for calculating the steady-state response of ecosystems to environmental perturbations in generalized consumer-resource. Our construction is applicable to a wide class of systems, including models with non-reciprocal interactions, cross-feeding, and non-linear growth/consumption rates.

Evolution of Robotics in Neurosurgery.

Technology and neurosurgery have gone hand in hand since a long time. Technological development of robotics in neurosurgery over the last couple of decades has been rapid, yet it still has a long way to go before it becomes a "routine" element of the standard neurosurgical procedure. Apart from the obvious advantages they have over humans, that is, precision, consistency, endurance, and reproducibility, robots also provide additional freedom of movement beyond what is anatomically feasible for humans.

High Diagnostic Accuracy of Arterial Phase CT in Differentiating Pheochromocytoma in Good/Poor Washout Adrenal Masses.

Introduction: Differentiating pheochromocytomas from other adrenal masses based on computed tomography (CT) characteristics remains challenging, particularly in lipid-poor lesions with variable washout patterns. This study evaluated CT features for distinguishing pheochromocytomas in good and poor washout subcohorts.

Methods: We prospectively analyzed 72 patients with unilateral lipid-poor adrenal masses.

Updated cancer burden in oldest old: A population-based study using 2022 Globocan estimates.

Background: The global population aged 80 years or older is expected to triple by 2050, leading to an increased cancer burden in the oldest population. This study describes the estimated cancer incidence and mortality in 2022 and projections for 2050 in the oldest old, analyzed globally and by world regions and World Bank income levels, for all sexes combined, as well as separately for males and females.

Methods: Using GLOBOCAN 2022 estimates, we reported the estimated number of new cancer cases (excluding non-melanoma skin cancers), deaths, and truncated age-standardized incidence (ASIR) and mortality rates (ASMR) (per 100,000 individuals aged 80 years or older).

In silico screening of phytochemicals against chromatin modifier, SETD7 for remodeling of the immunosuppressive tumor microenvironment in renal cancer.

The tumor microenvironment and immune evasion function in a complex cellular network profoundly challenge the clinical outcome of promising therapies. Our recently published study reported that the subset of genes upregulated in ccRCC due to H3K4me1 and DNA demethylation potentially leads to an immunosuppressive environment. Thus, modulating H3K4me1 chromatin modifier SETD7 with a natural inhibitor in combination with immunotherapy might improve the immune landscape for a better therapeutic outcome.