LONP1 Variants Are Associated With Clinically Diverse Phenotypes.

LONP1 encodes a mitochondrial protease essential for protein quality control and metabolism. Variants in LONP1 are associated with a diverse and expanding spectrum of disorders, including Cerebral, Ocular, Dental, Auricular, and Skeletal anomalies syndrome (CODAS), congenital diaphragmatic hernia (CDH), and neurodevelopmental disorders (NDD), with some individuals exhibiting features of mitochondrial encephalopathy. We report 16 novel LONP1 variants identified in 16 individuals (11 with NDD, 5 with CDH), further expanding the clinical spectrum.

Genetic and epigenetic analysis of plasma glial fibrillary acidic protein (GFAP) levels in PTSD.

Glial fibrillary acidic protein (GFAP) is an astrocytic marker that can be assessed in blood using single molecule array technology. Recent studies suggest that individuals with posttraumatic stress disorder (PTSD) have suppressed circulating levels of this CNS biomarker. This study examined the hypothesis that PTSD and plasma GFAP levels share common genetic and epigenetic pathways.

Health disparities in neurology.

Health disparities are preventable differences in health between different populations, and they are endemic throughout medicine owing to social, economic and environmental disadvantages. Neurology is no exception, and health disparities for systematically marginalized groups are present in the prevention, diagnosis, treatment and outcomes of all neurological disorders. The aetiology of these disparities is complex and multifactorial, reflecting the interplay of structural, institutional and individual-level factors.

Myeloid progenitor dysregulation fuels immunosuppressive macrophages in tumours.

Monocyte-derived macrophages (mo-macs) often drive immunosuppression in the tumour microenvironment (TME) and tumour-enhanced myelopoiesis in the bone marrow fuels these populations. Here we performed paired transcriptome and chromatin accessibility analysis over the continuum of myeloid progenitors, circulating monocytes and tumour-infiltrating mo-macs in mice and in patients with lung cancer to identify myeloid progenitor programs that fuel pro-tumorigenic mo-macs. We show that lung tumours prime accessibility for Nfe2l2 (NRF2) in bone marrow myeloid progenitors as a cytoprotective response to oxidative stress, enhancing myelopoiesis while dampening interferon response and promoting immunosuppression.

Neuronal activity-dependent mechanisms of small cell lung cancer pathogenesis.

Neural activity is increasingly recognized as a crucial regulator of cancer growth. In the brain, neuronal activity robustly influences glioma growth through paracrine mechanisms and by electrochemical integration of malignant cells into neural circuitry via neuron-to-glioma synapses. Outside of the central nervous system, innervation of tumours such as prostate, head and neck, breast, pancreatic, and gastrointestinal cancers by peripheral nerves similarly regulates cancer progression.

A Framework for Mandated Reporting for Substance-Related Parental Abuse and Neglect.

Clinicians face the prospect of mandated reporting when a patient reports, either during the intake appointment or during the course of addiction treatment, their risky substance use-related behavior around a child. Beyond legal considerations, many factors might influence a clinician's decision whether or not to report the case to child protective services (CPS). Although there is literature regarding mandated reporting in the setting of pre- or perinatal substance use, there is limited literature regarding the mandated reporting obligation in the setting of postnatal substance use around children.

Tandem CAR-T cells targeting mesothelin and MUC16 overcome tumor heterogeneity by targeting one antigen at a time.

Background: Tumor heterogeneity and antigen escape are mechanisms of resistance to chimeric antigen receptor (CAR)-T cell therapy, especially in solid tumors. Targeting multiple antigens with a unique CAR construct could be a strategy for a better tumor control than monospecific CAR-T cells on heterogeneous models. To overcome tumor heterogeneity, we targeted mesothelin (meso) and Mucin 16 (MUC16), two antigens commonly expressed in solid tumors, using a tandem CAR design.

Comparing radiologically evident injuries among cisgender and transgender women.

Background: Despite the high prevalence of violence among transgender and gender-diverse individuals, injury disparities remain understudied and are often attributed to underreporting. To address this limitation, we analysed radiology reports to objectively compare the prevalence and patterns of injuries between transgender women and cisgender women.

Methods: We used the Research Patient Data Registry at a level 1 trauma centre in the USA to identify 263 transgender women and 525 age-matched, race-matched and ethnicity-matched cisgender women.

Identifying Electronic Health Record Tasks and Activity Using Computer Vision.

Background: Time spent in the electronic health record (EHR) is an important measure of clinical activity. Vendor-derived EHR use metrics may not correspond to actual EHR experience. Raw EHR audit logs enable customized EHR use metrics, but translating discrete timestamps to time intervals is challenging.

Associations of body mass index, waist circumference, and weight-adjusted waist index with body composition and biomarkers: A multinational pooled analysis.

Background: The widely-used anthropometric indices, such as body mass index (BMI) and waist circumference (WC), have limitations in their use as indicators of body composition. Recent studies proposed weight-adjusted waist index (WWI=WC/√(body weight)) as an alternative index for body composition but it is unclear whether WWI reflects body composition in different racial/ethnic groups.

Objective: We examined the associations of WWI, BMI, and WC with dual-energy x-ray absorptiometry (DEXA)-measured body composition, biomarkers (fasting blood glucose, HDL-cholestrol, LDL-cholestrol, triglyceride), and handgrip strength.

Excitatory cortical neurons from CDKL5 deficiency disorder patient-derived organoids show early hyperexcitability not identified in neurogenin2 induced neurons.

CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy resulting from variants in cyclin-dependent kinase-like 5 (CDKL5) that lead to impaired kinase activity or loss of function. CDD is one of the most common genetic etiologies identified in epilepsy cohorts. To study how CDKL5 variants impact human neuronal activity, gene expression and morphology, CDD patient-derived induced pluripotent stem cells and their isogenic controls were differentiated into excitatory neurons using either an NGN2 induction protocol or a guided cortical organoid differentiation.

Designing Patient-Centered Communication Aids in Pediatric Surgery Using Large Language Models.

Introduction: Large language models (LLMs) have been shown to translate information from highly specific domains into lay-digestible terms. Pediatric surgery remains an area in which it is difficult to communicate clinical information in an age-appropriate manner, given the vast diversity in language comprehension levels across patient populations and the complexity of procedures performed. This study evaluates LLMs as tools for generating explanations of common pediatric surgeries to increase efficiency and quality of communication.

Liver disease in people with latent autoimmune diabetes in adults (LADA): A cross-sectional study using magnetic resonance elastography.

Aims: To investigate liver disease and its risk factors in LADA compared to type 1 (T1D) and type 2 (T2D) diabetes.

Methods: Liver magnetic resonance (MR) and MR elastography were used to measure proton density fat fraction (PDFF) and stiffness in 31 people with LADA matched for gender, body mass index (BMI) and disease duration with 31 people with T2D, and for gender, BMI and age with 31 people with T1D. Visceral adipose tissue (VAT) was quantified by DXA.

Detection of heterogeneous resistance mechanisms to tyrosine kinase inhibitors from cell-free DNA.

Though there has been substantial progress in the development of anti-human epidermal growth factor receptor 2 (HER2) therapies to treat HER2-positive metastatic breast cancer (MBC) within the past two decades, most patients still experience disease progression and cancer-related death. HER2-directed tyrosine kinase inhibitors can be highly effective therapies for patients with HER2-positive MBC; however, an understanding of resistance mechanisms is needed to better inform treatment approaches. We performed whole-exome sequencing on 111 patients with 73 tumor biopsies and 120 cell-free DNA samples to assess mechanisms of resistance.

Intra-arterial thrombolytics after successful recanalization in endovascular thrombectomy for large-vessel occlusion acute ischemic stroke: A comprehensive meta-analysis of randomized controlled trials.

Background: Intra-arterial thrombolytics (IAT) as adjunctive therapy for large vessel occlusion acute ischemic stroke (LVO-AIS) after successful endovascular thrombectomy (EVT) may improve outcomes. This meta-analysis evaluates the efficacy and safety of IAT in this context.

Methods: We identified randomized controlled trials (RCTs) comparing IAT versus placebo or no IAT in LVO-AIS patients with successful recanalization post-EVT, including published studies and recent conference data.

Implementing Social Media Strategies in Community-Partnered HIV Research: Practical Considerations From 3 Ongoing Studies.

Background: In recent years, social media has emerged as a pivotal tool in implementation science efforts to address the HIV epidemic. Engaging community partners is essential to ensure the successful and equitable implementation of social media strategies. There is a notable lack of scholarship addressing the operational considerations for studies using social media strategies in community-partnered HIV research.

Visual analysis of subarachnoid hemorrhage research hotspots based on CiteSpace and VOSviewer: A retrospective study.

Objective: To analyze the hotspots and frontiers in the field of subarachnoid hemorrhage using the bibliometrics method and providing references for academic research.

Methods: All published studies related to subarachnoid hemorrhage published in the Web of Science core database from 1 January 2016 to 25 September 2021 were retrospectively identified using VOSviewer and CiteSpace software. Visualization VOSviewer and CiteSpace software were used to perform statistical and cluster analyses on authors, countries, institutions, keywords, and co-cited documents.

Nocturnal Oxygen Therapy for Central Sleep Apnea in Patients with Heart Failure: A Multi-site, Double-blind, Sham-controlled Randomized Clinical Trial (LOFT-HF).

Rationale: There are insufficient data to inform the management of central sleep apnea (CSA) in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Nocturnal oxygen therapy (NOT) has been postulated to benefit CSA patients with HFrEF, but has not been rigorously studied. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.

PASS-01: Randomized Phase II Trial of Modified FOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel and Molecular Correlatives for Previously Untreated Metastatic Pancreatic Cancer.

Purpose: To assess modified folinic acid/leucovorin, fluorouracil, irinotecan, oxaliplatin (FOLFIRINOX; mFFX) versus gemcitabine/nab-paclitaxel (GnP) in de novo metastatic pancreatic ductal adenocarcinoma (PDAC) and explore predictive biomarkers.

Patients And Methods: Patients were randomly assigned 1:1 to mFFX or GnP with exclusion of germline pathogenic variants in or . The primary end point was progression-free survival (PFS) between arms with 0.