Simultaneous Bioanalytical Method Development and Validation of Navitoclax and Doxorubicin in Rat Plasma Using UHPLC-HESI-LTQ-MS.

A simple, sensitive, and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was successfully developed and validated to determine navitoclax and doxorubicin in rat plasma. Ketoconazole and daunorubicin were employed as internal standards to ensure accurate quantification and method consistency. The sample preparation involved a straightforward protein precipitation technique, which facilitated efficient extraction of the analytes from the plasma matrix.

Improving the histologic detection of DSA-negative antibody-mediated rejection in kidney transplants.

Emerging treatments for antibody-mediated rejection (ABMR, NEJM391(2):122-132) have increased the importance of ABMR detection when donor-specific antibody (DSA) is negative. We addressed this issue in the Trifecta-Kidney study (ClinicalTrials.gov #NCT04239703) using three centralized tests in 690 kidney transplant biopsies: DSA (One Lambda Inc.

Leveraging RAS-mSIN1 interaction to selectively inhibit mTORC2 employing competitive RAS binding peptide: implications in breast cancer metastasis.

The pivotal role of mTORC2 in cancer progression and metastasis underscores its potential as drug target. Despite this, selective inhibition of mTORC2 without affecting mTORC1 represents an unmet need in cancer therapy. We aimed to exploit RAS-mSIN1 interaction for selective mTORC2 targeting.

Causes of Prolonged Cold Ischemia Time After Arrival of Deceased Donor Kidney at Implanting Center: Results From a Prospective Audit.

Background: Deceased donor kidney transplants often face delays, leading to prolonged cold ischemia time (CIT), yet data on post-allograft arrival delays are scarce.

Objectives: This audit aims to identify and characterize the delays contributing to CIT prolongation after allograft arrival at the implanting center.

Design: Data was collected prospectively from 14 UK centers between February and September 2022.

Evaluation of a national digital pre-implantation biopsy service for deceased-donor kidney transplantation in the UK (Pithia trial); a stepped-wedge cluster randomised registry trial.

Background: Pre-implantation biopsy may help select kidneys retrieved from elderly deceased donors for transplantation, but concerns persist that it may cause unnecessary discard of kidneys that would have provided acceptable transplant function. The PITHIA trial tested the hypothesis that introduction of a National Digital Pathology Service (NDPS) would increase the proportion of kidneys transplanted from elderly donors and/or improve their function.

Methods: A stepped-wedge cluster randomised controlled registry trial delivered the NDPS to 22 UK kidney transplant centres (clusters) in 5 sequences at four-monthly intervals, using a restricted randomisation technique to ensure similar cluster sizes in the intervention and control status.

Glucosinolate and Sugar Profiles in Space-Grown Radish.

The quest to establish permanent outposts in space, the Moon, and Mars requires growing plants for nutrition, water purification, and carbon/nutrient recycling, as well as the psychological well-being of crews and personnel on extra-terrestrial platforms/outposts. To achieve these essential goals, the safety, quality, and sustainability of plant material grown in space should be comparable to Earth-grown crops. In this study, radish plants were grown at 2500 ppm CO in two successive grow-outs on the International Space Station and at similar CO partial pressure at the Kennedy Space Center.

The effects of acute exposure to prolonged sitting, with and without interruption, on central and peripheral pulse wave velocity: A systematic review and meta-analysis.

Introduction: Sedentary behavior, specifically an acute bout of prolonged uninterrupted sitting, is associated with heightened cardiovascular disease (CVD) risk, with increased arterial stiffness (AS) being implicated as a principal pathophysiological mechanism. The current systematic review, with meta-analysis, aimed to consolidate the AS response to (1) prolonged uninterrupted sitting and (2) interrupted sitting, as assessed by central and peripheral pulse wave velocity (PWV).

Methods: In total, 326 articles were identified, of which 11 and seven met the inclusion criteria for objectives (1) and (2), respectively.

Functional and structural characterization of treatment-emergent nirmatrelvir resistance mutations at low frequencies in the main protease (Mpro) reveals a unique evolutionary route for SARS-CoV-2 to gain resistance.

Background: The main protease (Mpro) is one of the most attractive targets for antiviral drug discovery against SARS-CoV-2. Mutations in Mpro have been linked to resistance against nirmatrelvir-ritonavir (NIR-RIT), an important therapy for SARS-CoV-2 infection. This study aimed to identify low-frequency antiviral resistance mutations in Mpro from NIR-RIT-treated patients and to analyze the enzymatic properties, inhibitor susceptibility, and structural features of new Mpro clinical variants.

Evaluating purified exosome product and its role in neurologic and functional recovery following spinal cord injury in female rats.

Introduction: Exosomes represent extracellular vesicles that mediate intercellular interactions and have been extensively studied for their therapeutic potential. Purified exosomes product (PEP) from human plasma is reported to aid in tissue repair but has never been evaluated as a potential therapy for spinal cord injury (SCI).

Objective: We aim to investigate the effects of PEP on axon myelination, reduction in cavity size, and functional improvements in rats following SCI.

Corrigendum to "Exploring the factors contributing to increase in facility child births in Bangladesh between 2004 and 2017-2018" [Heliyon Volume 9, Issue 5, MAY 2023, Article e15875].

[This corrects the article DOI: 10.1016/j.heliyon.

SOX Genes in Spinal Cord Injury: Redefining Neural Stem Cell Regeneration Strategies.

The study design is literature review. The sex-determining region Y gene (SRY)-related high mobility group box (HMG)-box (SOX) gene family has primarily been associated with neural development and sex determination and is a key component of human embryonic development. Recent studies on zebrafish models have demonstrated that the unique ability of the latter for central nervous tissue (CNS) repair following injury is largely mediated by SOX genes.

Advancing age and mortality due to pollution exposure: a comprehensive review.

The global aging population has been increasingly vulnerable to environmental stressors, particularly air pollution. Advancing age is associated with physiological declines and a higher prevalence of chronic diseases, heightening susceptibility to pollution-related health effects. This review explores the relationship between advancing age and mortality/morbidity due to pollution exposure, consolidating evidence on how pollution exacerbates health risks in elderly populations.

Costimulation blockade: the next generation.

Purpose Of Review: Calcineurin inhibitors (CNIs) are central to immunosuppression in kidney transplantation (KT), improving short-term outcomes but falling short in enhancing long-term outcomes due to cardiovascular, metabolic, and renal complications. Belatacept, an FDA-approved costimulation blocker, offers a less toxic alternative to CNIs but is limited by its intravenous administration and reduced efficacy in high-immunological-risk patients.

Recent Findings: Emerging therapies target more specific pathways to improve efficacy and accessibility.

The impact of pancreas transplantation on diabetic complications: A systematic review.

Background: Pancreas Transplantation (PT) provides optimal treatment for patients with severe complicated Type 1 Diabetes Mellitus (T1DM). Restoration of beta-cell mass allows return to euglycaemia and insulin independence. We aimed to examine its impact on the secondary complications associated with severe T1DM including diabetic eye disease, neuropathy and cardiovascular disease.

Preventive effects of thymoquinone on glyco-nitro-oxidized human fibrinogen: A comprehensive biophysical study projecting possible therapeutic role in diabetes and associated complications.

Persistence of long-term hyperglycemia results in the glyco-oxidation of plasma proteins, which is considered to be a significant factor in metabolic dysfunction, linking hyperglycemia to the emergence of vascular complications. Methylglyoxal (MGO), a dicarbonyl species formed excessively under diabetes, elevates the oxidative stress, enhancing the generation of superoxide anion, which ultimately reacts with nitric oxide (NO•) to form peroxynitrite (PON). PON, being a powerful nitro-oxidizing agent distorts protein structure, hampering its function.

A Promising Druggable Target for Translational Therapy of Ovarian Cancer: A Molecular Profiling of Therapeutic Innovations, Extracellular Vesicle Acquired Resistance, and Signaling Pathways.

Ovarian cancer (OC) ranks as the fifth leading cause of cancer-related deaths in the United States, posing a significant threat to female health. Late-stage diagnoses, driven by elusive symptoms often masquerading as gastrointestinal issues, contribute to a concerning 70% of cases being identified in advanced stages. While early-stage OC brags a 90% cure rate, progression involving pelvic organs or extending beyond the peritoneal cavity drastically diminishes it.

Tissue-based Gene Expression Diagnosis of Mild and Moderate T-cell-mediated Rejection to Guide Therapy in Kidney Transplants.

Background: Mild histologic lesions of tubulo-interstitial inflammation could represent a "response-to-wounding" rather than allorecognition. Tissue gene expression may complement histopathology for T-cell-mediated rejection (TCMR) diagnostics.

Methods: We report on the incorporation of tissue gene expression testing using a Molecular Microscope Diagnostic System into the management of kidney transplant biopsies with suspected TCMR.

Auto-Rad: End-to-End Report Generation from Lumber Spine MRI Using Vision-Language Model.

Lumbar spinal stenosis (LSS) is a major cause of chronic lower back and leg pain, and is traditionally diagnosed through labor-intensive analysis of magnetic resonance imaging (MRI) scans by radiologists. This study aims to streamline the diagnostic process by developing an automated radiology report generation (ARRG) system using a vision-language (VL) model. We utilized a Generative Image-to-Text (GIT) model, originally designed for visual question answering (VQA) and image captioning.

Apoptosis: A Comprehensive Overview of Signaling Pathways, Morphological Changes, and Physiological Significance and Therapeutic Implications.

Cell survival and death are intricately governed by apoptosis, a meticulously controlled programmed cell death. Apoptosis is vital in facilitating embryonic development and maintaining tissue homeostasis and immunological functioning. It is a complex interplay of intrinsic and extrinsic signaling pathways that ultimately converges on executing the apoptotic program.

Development of age-specific population-based paediatric computational phantoms for image-based data mining and other radiotherapy applications.

Computational anatomical models have many applications in paediatric radiotherapy. Age-specific computational anatomical models were historically developed to represent average and/or healthy individuals, where cancer patients may present with anatomical variations caused by the disease and/or treatment effects. We developed RT-PAL, a library of computational age-specific voxelized anatomical models tailored to represent the paediatric radiotherapy population.

Hepatocellular carcinoma antibodies preferably identify nitro-oxidative-DNA lesions induced by 4-Chloro-orthophenylenediamine and DEANO.

The widespread use of oxidative hair colouring cosmetics threatens public health. Phenylenediamine derivatives serve as the main pigment in permanent hair colours. They interact with biological macromolecules, altering their functional and structural physiology.

A pituitary gland squeezed upward by intrasellar kissing carotid arteries: Mimicking a pituitary microadenoma.

Background: Intrasellar kissing carotid arteries are a rare variant in which bilateral internal carotid arteries run very near each other at their cavernous sinus portion. We encountered a woman with the pituitary gland mimicking a pituitary microadenoma because the pituitary gland was compressed bilaterally by intrasellar kissing carotid arteries.

Case Description: A 61-year-old woman with a chronic headache underwent magnetic resonance imaging, which revealed a sellar mass measuring 10.