Compromised anti-osteoclastogenic and immunomodulatory functions of regulatory B cells (Bregs) aggravate inflammatory bone loss in post-menopausal osteoporosis.

Regulatory-B-cells (Bregs) modulate immune-homeostasis. Variations in the number and function of Bregs have been associated with various immune-related ailments, highlighting the importance of Bregs under inflammatory-conditions. Previously, we discovered the anti-osteoclastogenic-potential of Bregs.

Nr4a1 and Nr4a3 redundantly control clonal deletion and contribute to an anergy-like transcriptome in auto-reactive thymocytes to impose tolerance in mice.

The Nr4a nuclear hormone receptors are transcriptionally upregulated in response to antigen recognition by the T cell receptor (TCR) in the thymus and are implicated in clonal deletion, but the mechanisms by which they operate are not clear. Moreover, their role in central tolerance is obscured by redundancy among the Nr4a family members and by their reported functions in Treg generation and maintenance. Here we take advantage of competitive bone marrow chimeras and the OT-II/RIPmOVA model to show that Nr4a1 and Nr4a3 are essential for the upregulation of Bcl2l11/BIM and thymic clonal deletion by self-antigen.

Multipronged strategy for protection and motivation of healthcare workers during the COVID-19 pandemic: a real-life study.

Objective: We aimed to assess risk of COVID-19 infection & seroprotection status in healthcare workers (HCWs) in both hospital and community settings following an intensive vaccination drive in India.

Setting: Tertiary Care Hospital.

Methods: We surveyed COVID-19 exposure risk, personal protective equipment (PPE) compliance, vaccination status, mental health & COVID-19 infection rate across different HCW cadres.

Machine Learning Approaches for Neuroblastoma Risk Prediction and Stratification.

Machine learning (ML) holds great promise in advancing risk prediction and stratification for neuroblastoma, a highly heterogeneous pediatric cancer. By utilizing large-scale biological and clinical data, ML models can detect complex patterns that traditional approaches often overlook, enabling more personalized treatments and better patient outcomes. Various ML techniques, such as support vector machines, random forests, and deep learning, have shown superior performance in predicting survival, relapse, and treatment responses in neuroblastoma patients compared to conventional methods.

Selection Criteria for Oils, Surfactants, and Co-Surfactants in Ocular Nanoemulsion Formulation: A Mini Review.

The ocular nanoemulsions (NE) are biphasic systems mainly composed of oil and water emulsified by surfactants/cosurfactants. The extensive surface area of ocular NE enhances corneal contact, leading to improved drug penetration and making it a preferable delivery system. They can also increase the solubility of drugs across the ocular barrier with improved residence time.

A triad of somatic mutagenesis converges in self-reactive B cells to cause a virus-induced autoimmune disease.

The unexplained association between infection and autoimmune disease is strongest for hepatitis C virus-induced cryoglobulinemic vasculitis (HCV-cryovas). To analyze its origins, we traced the evolution of pathogenic rheumatoid factor (RF) autoantibodies in four HCV-cryovas patients by deep single-cell multi-omic analysis, revealing three sources of B cell somatic mutation converged to drive the accumulation of a large disease-causing clone. A method for quantifying low-affinity binding revealed recurring antibody variable domain combinations created by V(D)J recombination that bound self-immunoglobulin G (IgG) but not viral E2 antigen.

Towards the photodeposition of SiGe-type materials oligomers of cyclogermapentenes and cyclosilapentenes.

This article provides an alternative pathway towards cyclosilapentenes (, SiH2-iPr and SpiroSi) involving the use of Rieke magnesium to activate the requisite dienes for synthesis. Subsequent metal-mediated dehydrocoupling of cyclosilapentene and mixtures with another cyclogermapentene gives oligomers with backbone Si-Si (number average molecular weight, = 1.0 kDa) and Si-Ge ( = 1.

Characterization and molecular targeting of CFIm25 (NUDT21/CPSF5) mRNA using miRNAs.

Changes in protein levels of the mammalian cleavage factor, CFIm25, play a role in regulating pathological processes including neural dysfunction, fibrosis, and tumorigenesis. However, despite these effects, little is known about how CFIm25 (NUDT21) expression is regulated at the RNA level. A potential regulator of NUDT21 mRNA are small non-coding microRNAs (miRNAs).

Effect of strain on the electronic structure and polaronic conductivity of LiFePO.

Improving the electronic properties of active cathode materials can significantly impact the design of rechargeable batteries. In this study, we investigated the influence of micro-strain on the structural and electronic properties of LiFePO (LFP) by performing combined core-level spectroscopy analysis and electrical conductivity measurements. High-resolution X-ray diffraction measurements, followed by Rietveld refinement analysis, revealed an increase in unit cell parameters due to the enhanced micro-strain in the lattice structure.

Predictors of severity factors associated with severe scrub typhus among children in a Tertiary Care Hospital.

Background Objectives: Scrub typhus is an acute febrile zoonotic disease caused by the obligate intracellular gram-negative bacteria Orientia tsutsugamushi. Growing data over the last few years on the Indian subcontinent suggest that it is one of the most widespread but under-reported diseases. The study aimed to document the clinical and paraclinical profile and evaluate complications of scrub typhus in severe and nonsevere pediatric age groups.

Meta-QTL analysis for mining of candidate genes and constitutive gene network development for viral disease resistance in maize ( L.).

Viral diseases severely impact maize yields, with occurrences of maize viruses reported worldwide. Deployment of genetic resistance in a plant breeding program is a sustainable solution to minimize yield loss to viral diseases. The meta-QTL (MQTL) has demonstrated to be a promising approach to pinpoint the most robust QTL(s)/candidate gene(s) in the form of an overlapping or common genomic region identified through leveraging on different research studies that independently report genomic regions significantly associated with the target traits.

Modeling tumor dynamics and predicting response to chemo-, targeted-, and immune-therapies in a murine model of pancreatic cancer.

We seek to establish a parsimonious mathematical framework for understanding the interaction and dynamics of the response of pancreatic cancer to the NGC triple chemotherapy regimen (mNab-paclitaxel, gemcitabine, and cisplatin), stromal-targeting drugs (calcipotriol and losartan), and an immune checkpoint inhibitor (anti-PD-L1). We developed a set of ordinary differential equations describing changes in tumor size (growth and regression) under the influence of five cocktails of treatments. Model calibration relies on three tumor volume measurements obtained over a 14-day period in a genetically engineered pancreatic cancer model (KrasLSLG12D-Trp53LSLR172H-Pdx1-Cre).

A Rare Case Report: Managing PCL Avulsion Fracture with a Fracture of the Proximal Tibial Shaft.

Introduction: Posterior cruciate ligament (PCL) avulsion fractures of the tibia with ipsilateral tibial shaft represent a rare but challenging orthopedic injury, necessitating careful consideration of surgical interventions for optimal outcomes. This case report presents the successful management of tibial shaft fracture (proximal 1/3rd junction) along with ipsilateral PCL avulsion fracture of tibia using a novel approach using open reduction internal fixation (ORIF) of tibial shaft with Locking compression plate (LCP) with cannulated cancellous screw and spiked washer fixation of PCL avulsion. There are no case reports or research articles available for the management of PCL avulsion fracture of tibia associated with ipsilateral tibial shaft fracture.

Comparison of Clinical and Radiological Outcomes of Three-Column Lumbar Osteotomies with and without Interbody Cages for Adult Spinal Deformity.

Background Context: Correcting sagittal malalignment in adult spinal deformity (ASD) is a challenging task, often requiring complex surgical interventions like pedicle subtraction osteotomies (PSOs). Different types of three-column osteotomies (3COs), including Schwab 3, Schwab 4, Schwab 4 with interbody cages, and the "sandwich" technique, aim to optimize alignment and fusion outcomes. The role of interbody cages in enhancing fusion and segmental correction remains unclear.

Differentiating Cystic Lesions in the Sellar Region of the Brain Using Artificial Intelligence and Machine Learning for Early Diagnosis: A Prospective Review of the Novel Diagnostic Modalities.

This paper investigates the potential of artificial intelligence (AI) and machine learning (ML) to enhance the differentiation of cystic lesions in the sellar region, such as pituitary adenomas, Rathke cleft cysts (RCCs) and craniopharyngiomas (CP), through the use of advanced neuroimaging techniques, particularly magnetic resonance imaging (MRI). The goal is to explore how AI-driven models, including convolutional neural networks (CNNs), deep learning, and ensemble methods, can overcome the limitations of traditional diagnostic approaches, providing more accurate and early differentiation of these lesions. The review incorporates findings from critical studies, such as using the Open Access Series of Imaging Studies (OASIS) dataset (Kaggle, San Francisco, USA) for MRI-based brain research, highlighting the significance of statistical rigor and automated segmentation in developing reliable AI models.

mHealth-based intervention by community workers to support family caregivers of persons with dementia living at home: study protocol for a cluster randomised controlled trial.

Background: India is undergoing a significant demographic shift with a growing older population, leading to an anticipated increase in people with dementia. Family caregivers, who are predominantly informal, carry the burden of care within households, facing numerous challenges that impact their well-being. Despite the cultural emphasis on family support, there is a lack of targeted interventions for caregivers in India.

Comparative Analysis of Outcomes in Adult Spinal Deformity Patients with Proximal Junctional Kyphosis or Failure Initially Fused to Upper Versus Lower Thoracic Spine.

Patients with proximal junctional kyphosis (PJK) or failure (PJF) may demonstrate disparate outcomes and recovery when fused to the upper (UT) versus lower (LT) thoracic spine. Few studies have distinguished the reoperation and recovery abilities of patients with PJK or PJF when fused to the upper (UT) versus lower (LT) thoracic spine. Adult spine deformity patients ≥ 18 yrs with preoperative and 5-year (5Y) data fused to the sacrum/pelvis were included.

Structure-Based Design of Small-Molecule Inhibitors of Human Interleukin-6.

Human Interleukin-6 (hIL-6) is a pro inflammatory cytokine that binds to its receptor, IL-6Rα followed by binding to gp130 and subsequent dimerization to form a hexamer signaling complex. A critical inflammation mediator, hIL-6 is associated with a diverse range of diseases and monoclonal antibodies are in clinical use that either target IL-6Rα or hIL-6 to inhibit signaling. Here, we perform high throughput structure-based computational screening using ensemble docking for small molecule antagonists for which the target conformations were taken from 600 ns long molecular dynamics simulations of the apo protein.

Subclinical pancreatic exocrine insufficiency is associated with osteopathy in patients with chronic pancreatitis: Implications for management.

Background And Aims: Patients with chronic pancreatitis (CP) may develop pancreatic exocrine insufficiency (PEI) but data regarding subclinical PEI are scarce. Our objective was to detect subclinical PEI in patients with CP and its functional consequences.

Methods: We prospectively included patients with CP from April 2018-December 2021.

The gap between surgeon goal and achieved sagittal alignment in adult cervical spine deformity surgery.

Objective: Malalignment following cervical spine deformity (CSD) surgery can negatively impact outcomes and increase complications. Despite the growing ability to plan alignment, it remains unclear whether preoperative goals are achieved with surgery. The objective of this study was to assess how good surgeons are at achieving their preoperative goal alignment following CSD surgery.

Pituitary adenylate cyclase-activating polypeptide (PACAP)overexpression in the paraventricular nucleus of the thalamus alters motivated and affective behavior in female rats.

Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) has been found to be involved in a wide range of motivated and affective behaviors. While the PACAP-38 isoform is more densely expressed than PACAP-27 in most of the brain, PACAP-27 is more highly expressed in the rodent paraventricular nucleus of the thalamus (PVT), where females also have greater expression than males. Notably, the role of PACAP-27 expression in cells of the PVT has not been explored.