Cytogenetic analysis of 3488 patients with recurrent pregnancy loss: An experience of two decades from a tertiary care center in South India.

Background: Recurrent pregnancy loss (RPL) affects approximately 15-20% of couples. Constitutional chromosomal abnormalities (CA) are an important cause of RPL because the gametes of carriers may have chromosomal imbalance which is lethal to the fetus. Therefore, the identification of CA helps to provide information about likely outcome of pregnancy in carriers.

A microfluidic sucrose gap platform using trilaminar flow with on-chip switching and novel calibration: Challenges and limitations.

Gap junction connectivity is crucial to intercellular communication and plays a key role in many critical processes in developmental biology. However, direct analysis of gap junction connectivity in populations of developing cells has proven difficult due to the limitations of patch clamp and dye diffusion based technologies. We re-examine a microfluidic technique based on the principle of laminar flow, which aims to electrically measure gap junction connectivity.

A microfluidic sucrose gap device for electrical measurement of gap junction connectivity.

A microfluidic device has been designed to electrically measure average intercellular connectivity in a cell monolayer. This proof-of-concept design uses elastomeric microvalves to isolate cells across three microfluidic chambers, creating a direct microscale analog of benchtop sucrose gap physiology rigs. The device operation has been verified for normal rat kidney cells (NRK-49F) using a chemical gap junction blocker, 2-aminoethoxydiphenyl borate (2-APB).

Specialty-specific Evaluation of Virtual care Outcomes: A retrospective QUality and safety analysis (S-EVOQUe).

The objective was to compare specialty-specific 7- and 30-day outcomes between virtual care visits and in-person visits which occurred during the SARS-CoV-2 pandemic. Using administrative data from provincial databases in Ontario, ambulatory care visits occurring virtually and in-person during specific timeframes within the pandemic were analyzed. Virtual care visits were matched with corresponding in-person visits based on multiple baseline patient characteristics.

Real-World Experience with CDK4/6 Inhibitors in the First-Line Palliative Setting for HR+/HER2- Advanced Breast Cancer.

Introduction: CDK4/6 inhibitors in combination with aromatase inhibitors (AIs) are the standard first-line treatment for hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer. Landmark trials have demonstrated a comparable progression-free survival (PFS) across CDK4/6 inhibitors, but the overall survival (OS) outcomes have varied. This study aimed to evaluate the real-world PFS and OS for palbociclib and ribociclib when combined with AIs in patients with HR+/HER2- advanced breast cancer.

Robust collection and processing for label-free single voxel proteomics.

With advanced mass spectrometry (MS)-based proteomics, genome-scale proteome coverage can be achieved from bulk tissues. However, such bulk measurement lacks spatial resolution and obscures tissue heterogeneity, precluding proteome mapping of tissue microenvironment. Here we report an integrated wet collection of single microscale tissue voxels and Surfactant-assisted One-Pot voxel processing method termed wcSOP for robust label-free single voxel proteomics.

Heterozygous UBR5 variants result in a neurodevelopmental syndrome with developmental delay, autism, and intellectual disability.

E3 ubiquitin ligases have been linked to developmental diseases including autism, Angelman syndrome (UBE3A), and Johanson-Blizzard syndrome (JBS) (UBR1). Here, we report variants in the E3 ligase UBR5 in 29 individuals presenting with a neurodevelopmental syndrome that includes developmental delay, autism, intellectual disability, epilepsy, movement disorders, and/or genital anomalies. Their phenotype is distinct from JBS due to the absence of exocrine pancreatic insufficiency and the presence of autism, epilepsy, and, in some probands, a movement disorder.

Cell therapy with human IL-10-producing ILC2s limits xenogeneic graft-versus-host disease by inhibiting pathogenic T cell responses.

Interleukin-10 (IL-10)-producing group 2 innate lymphoid cells (ILC2) regulate inflammatory immune responses, yet their therapeutic potential remains largely unexplored. Here, we demonstrate that cell therapy with human ILC2 inhibits pathogenic T cell responses in humanized mouse models of graft-versus-host disease (GVHD), resulting in reduced GVHD severity and improved overall survival without limiting the graft-versus-leukemia effect. ILC2 conferred superior protection from GVHD than IL-10 ILC2s, and blocking IL-10 and IL-4 abrogated ILC2 protective effects, indicating that these cytokines are important for the protective effects of ILC2.

Single cell profiling of hematopoietic stem cell transplant recipients reveals TGF-β1 and IL-2 confer immunoregulatory functions to NK cells.

Natural killer (NK) cell activity is influenced by cytokines and microenvironment factors, resulting in remarkably diverse functions, by contributing to inflammatory responses or serving as rheostats of adaptive immunity. Using single cell RNA sequencing (scRNA-seq), we identified a CD56NK cell population associated with hematopoietic stem cell transplant recipients protected from acute graft-versus-host disease (GVHD). We further define a role for the combination of interleukin-2 (IL-2) and transforming growth factor β1 (TGF-β1) in promoting a regulatory phenotype in NK cells.

Blood biomarker discovery for autism spectrum disorder: A proteomic analysis.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and social interaction and restricted, repetitive patterns of behavior, interests, or activities. Given the lack of specific pharmacological therapy for ASD and the clinical heterogeneity of the disorder, current biomarker research efforts are geared mainly toward identifying markers for determining ASD risk or for assisting with a diagnosis. A wide range of putative biological markers for ASD are currently being investigated.

A prospective blinded diagnostic accuracy study to assess the accuracy of fetal weight estimation at term by clinical method using Leopold's maneuvers and ultrasonography in predicting the actual birth weight.

Context: Over-medicalization of normal pregnancy is associated with unnecessary inductions of labor leading to operative deliveries. In a busy outpatient department (OPD) or low-resource setup where ultrasound availability, experience, and cost will be a concern, routine ultrasound at term can be avoided if the clinical estimation of fetal weight is more or less equal to the actual birth weight.

Aims: To assess the reliability and validity of fetal weight estimation at term by ultrasound and clinical estimation.

Point-of-care ultrasound in palliative medicine residency programs: report of a national survey and local workshop.

Purpose: Point-of-care ultrasound (POCUS) is used in various clinical specialties to improve diagnostic and procedural accuracy and has many potential applications in palliative care. However, it is unclear what is the current state of training and use of POCUS in palliative care in Canada. Our objectives were to understand the current state of training and use of POCUS in Canadian Palliative Medicine subspecialty residency programs and to develop and implement a local training workshop for POCUS in palliative care.

ENA-001 Reverses Xylazine/Fentanyl Combination-Induced Respiratory Depression in Rats: A Qualitative Pilot Study.

Xylazine exacerbates the respiratory depression induced by fentanyl. Because xylazine is a non-opioid, it is resistant to reversal by opioid receptor antagonists such as naloxone (e.g.

A Case of Malignant Pleural Mesothelioma With Unknown Asbestos Exposure.

Malignant pleural mesothelioma (MPM) is a rare, locally invasive tumor that develops from mesothelial cells lining the lung's pleura. It is mostly associated with prolonged asbestos exposure. The long latency period between asbestos exposure and clinical symptoms makes diagnosing MPM challenging.

Access barriers to anti-CD19+ CART therapy for NHL across a community transplant and cellular therapy network.

We analyzed access barriers to anti-CD19+ chimeric antigen receptor T cells (CARTs) for non-Hodgkin lymphoma (NHL) within a community-based transplant and cell therapy network registry. A total of 357 intended recipients for approved anti-CD19+ CARTs were identified between 2018 to 2022. The median age at referral was 61 years; referral years were 2018 (4%), 2019 (14%), 2020 (18%), 2021 (26%), and 2022 (38%).

Effectiveness of peer support interventions in improving mothers' psychosocial well-being during the perinatal period: A systematic review and meta-analysis.

Background: Many mothers experience poor psychological outcomes during their perinatal period. The presence of depression and anxiety has a significant adverse impact on the mother's health and the infant's development.

Aim: This review aimed to examine the effectiveness of peer support interventions in improving depression, anxiety, and perceived social support among mothers during the perinatal period.

Leptin bioavailability and markers of brain atrophy and vascular injury in the middle age.

Introduction: We investigated the associations of leptin markers with cognitive function and magnetic resonance imaging (MRI) measures of brain atrophy and vascular injury in healthy middle-aged adults.

Methods: We included 2262 cognitively healthy participants from the Framingham Heart Study with neuropsychological evaluation; of these, 2028 also had available brain MRI. Concentrations of leptin, soluble leptin receptor (sOB-R), and their ratio (free leptin index [FLI]), indicating leptin bioavailability, were measured using enzyme-linked immunosorbent assays.

Impact of prior inotuzumab ozogamicin treatment on brexucabtagene autoleucel outcomes in adults with B-cell ALL.

The effect of prior inotuzumab ozogamicin (InO) treatment on brexucabtagene autoleucel (brexu-cel) outcomes remains unclear in adults with acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter analysis of 189 patients with relapsed/refractory ALL treated with brexu-cel. Over half of the patients received InO before brexu-cel (InO exposed).

The burden of diabetes-associated multiple long-term conditions on years of life spent and lost.

Diabetes mellitus is a central driver of multiple long-term conditions (MLTCs), but population-based studies have not clearly characterized the burden across the life course. We estimated the age of onset, years of life spent and loss associated with diabetes-related MLTCs among 46 million English adults. We found that morbidity patterns extend beyond classic diabetes complications and accelerate the onset of severe MLTCs by 20 years earlier in life in women and 15 years earlier in men.

Recommendations for Development and Validation of a Fit-For-Purpose Biomarker Assays Using Western Blotting; An-AAPS Sponsored Initiative to Harmonize Industry Practices.

Western blot (WB) assays are routinely used for detection and quantification of biomarkers. Although assay validation to measure biomarkers in complex matrices has become a mainstay process for ligand binding assays (LBA) and mass spectrometry (MS), no guidelines exist yet validate biomarker methods using WB techniques. In this cross-industry white paper, we outlined in detail the key steps for development and for validation of WB assays for protein biomarkers under different contexts of use (COU).

2023 White Paper on Recent Issues in Bioanalysis: EU IVDR 2017/746 Implementation/Impact, IVD/CDx/CLIA Approved Assays, High Dimensional Cytometry, Multiplexing Technologies, LBA Tissue Analysis, Vaccine Study Endpoints, Cell-Based Assays for Biomarkers, Cell Therapy and Vaccines ( - Recommendations on Development & Validation of Biomarkers, IVD, CDx, Cell-Based, Flow Cytometry, Ligand-Binding and Enzyme Assays; Advanced Critical Reagents Strategies).

The 17 Workshop on Recent Issues in Bioanalysis (17 WRIB) took place in Orlando, FL, USA on 19-23 June 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 17 WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.