Feasibility of newborn screening for pyridoxine-dependent epilepsy.

Background: Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is a developmental epileptic encephalopathy historically characterized by seizures that are resistant to antiseizure medications. Treatment with pyridoxine and lysine reduction therapies are associated with seizure control and improved developmental outcomes. In rare circumstances, patients have died prior to diagnosis and treatment with pyridoxine, and many patients are diagnosed after six months of age when lysine reduction therapies have limited efficacy.

Metabolic Aging as an Increased Risk for Chronic Obstructive Pulmonary Disease.

Background/objectives: Both aging and chronic obstructive pulmonary disease (COPD) are strongly associated with changes in the metabolome; however, it is unknown whether there are common aging/COPD metabolomic signatures and if accelerated aging is associated with COPD.

Methods: Plasma from 5704 subjects from the Genetic Epidemiology of COPD study (COPDGene) and 2449 subjects from Subpopulations and intermediate outcome measures in COPD study (SPIROMICS) were profiled using the Metabolon global metabolomics platform (1013 annotated metabolites). Post-bronchodilator spirometry measures of airflow obstruction (forced expiratory volume at one second (FEV)/forced vital capacity (FVC) < 0.

A Pharmacokinetic/Toxicodynamic Model of Cisplatin Nephrotoxicity Using the Kidney Injury Molecule-1 Biomarker.

Cisplatin is a platinum-based chemotherapeutic that causes acute kidney injury in over 30% of patients. The aim of this study was to develop a population pharmacokinetic/toxicodynamic (PKTD) model of cisplatin-induced kidney injury that incorporated plasma total platinum and urinary kidney injury molecule-1 (KIM-1) concentrations. Cancer patients receiving their first or second round of cisplatin-containing chemotherapy (n=39) were prospectively randomized to a 5-HT antagonist (5-HTA) antiemetic (ondansetron, granisetron, or palonosetron) and had blood and urine collected over 10 days.

SHAPE: A visual computing pipeline for interactive landmarking of 3D photograms and patient reporting for assessing craniosynostosis.

3D photogrammetry is a cost-effective, non-invasive imaging modality that does not require the use of ionizing radiation or sedation. Therefore, it is specifically valuable in pediatrics and is used to support the diagnosis and longitudinal study of craniofacial developmental pathologies such as craniosynostosis - the premature fusion of one or more cranial sutures resulting in local cranial growth restrictions and cranial malformations. Analysis of 3D photogrammetry requires the identification of craniofacial landmarks to segment the head surface and compute metrics to quantify anomalies.

Impact of an Online Group-Coaching Program on Ambulatory Faculty Physician Well-Being: A Randomized Trial.

Background: Physician burnout contributes to distress, turnover, and poor patient outcomes. Evidence suggests individual professional coaching may mitigate burnout but is costly and time intensive. Group coaching evidence is lacking.

Time to Therapy May Not Impact Diagnosis Upstaging in Patients Referred for Management of Luminal Gastrointestinal Neoplasia.

Background: The COVID-19 pandemic dramatically impacted endoscopy practice. Recommendations were to postpone elective cases, including procedures for removal of luminal neoplasia. This provided a natural experiment to evaluate outcomes related to these decisions and the impact of time to procedure on change in histology.

MIRO2 promotes cancer invasion and metastasis via MYO9B suppression of RhoA activity.

Metastasis to vital organs remains the leading cause of cancer-related deaths, emphasizing an urgent need for actionable targets in advanced-stage cancer. The role of mitochondrial Rho GTPase 2 (MIRO2) in prostate cancer growth was recently reported; however, whether MIRO2 is important for additional steps in the metastatic cascade is unknown. Here, we show that knockdown of MIRO2 ubiquitously reduces tumor cell invasion in vitro and suppresses metastatic burden in prostate and breast cancer mouse models.

Defining Midwifery-Led Care in the United States Using Concept Analysis.

National health policy initiatives recommend increased integration of midwifery care in the United States to improve care quality and reduce maternal health disparities. However, the service models through which midwives provide midwifery care and produce quality outcomes are poorly understood. Midwifery-led care is a service model frequently associated with improved outcomes compared with other models.

Trends in Demographic Characteristics and Risk Factors among Individuals with Syphilis in Colorado from 2011-2020.

Background: Identify opportunities to improve syphilis screening by describing changes in patient characteristics and risk factors among individuals with syphilis and by comparing cases with and without an indication for syphilis screening.

Methods: This retrospective cohort study used Colorado public health surveillance data to identify 8,326 syphilis diagnoses from 2011-2020. Demographics, clinical characteristics, and risk factors were compared across 2-year groups and between individuals with and without an indication for screening.

What Motivates Older Sedentary People Living With HIV in the United States to Participate in an Exercise Trial? A Qualitative Study.

Although exercise supports the physical function and health of older people living with HIV (PLWH), less than half of PLWH globally achieve recommended levels of activity. A qualitative descriptive design was used to determine what motivates sedentary PLWH, 50 years and older, to participate in an exercise trial. Interviews were conducted with PLWH who participated in an exercise trial (n = 30) and PLWH who declined enrollment in the same exercise trial (n = 4).

Flexibility and resilience in equity-centered research: lessons learned conducting a randomized controlled trial of a family-based substance use prevention program for American Indian families.

Meaningful and effective community engagement lies at the core of equity-centered research, which is a powerful tool for addressing health disparities in American Indian (AI) communities. It is essential for centering Indigenous wisdom as a source of solutions and disrupting Western-centric perspectives and inequitable and exclusionary research practices. This paper reports on lessons learned implementing an effectiveness trial of the Thiwáhe Glúwaš'akapi program (TG) program (translated as "sacred home in which families are made strong")-a family-based substance use prevention program-in a post-pandemic era with an American Indian reservation community that has confronted extreme challenges.

Anticancer Effect of C19-Position Substituted Geldanamycin Derivatives Targeting NRF2-NQO1-activated Esophageal Squamous Cell Carcinoma.

In esophageal squamous cell carcinoma, genetic activation of NRF2 increases resistance to chemotherapy and radiotherapy, which results in a significantly worse prognosis for patients. Therefore NRF2-activated cancers create an urgent clinical need to identify new therapeutic options. In this context, we previously identified the geldanamycin family of HSP90 inhibitors, which includes 17DMAG, to be synthetic lethal with NRF2 activity.

Hyperglycemia Inhibits AAA Expansion: Examining the Role of Lysyl Oxidase.

Abdominal aortic aneurysm (AAA) is a common, progressive and potentially fatal dilation of the most distal aortic segment. Multiple studies with longitudinal follow-up of AAA have identified markedly slower progression among patients affected with diabetes. Understanding the molecular pathway responsible for the growth inhibition could have implications for therapy in nondiabetic AAA patients.

BRD4 inhibition rewires cardiac macrophages toward a protective phenotype marked by low MHC class II expression.

Bromodomain and extra-terminal domain (BET) proteins, including BRD4, bind acetylated chromatin and co-activate gene transcription. A BET inhibitor, JQ1, prevents and reverses pathological cardiac remodeling in preclinical models of heart failure. However, the underlying cellular mechanisms by which JQ1 improves cardiac structure and function remain poorly defined.

Does Orthopaedic Resident Pelvis Fluoroscopy Knowledge improve with testing with a Novel Pelvis Model and Educational website?

Purpose: We tested whether residents would improve in fluoroscopy knowledge and ability after using an inexpensive novel pelvis model and educational website.

Methods: Twenty-four orthopaedic residents were recruited from three United States residency programs and randomised into two groups with equal numbers of juniors and seniors. The OrthoAcademy group received educational materials from a website ( www.

Hearing in Two Closely Related Species ( and ).

The genus has been extensively used as a model for ecological, behavioral, and evolutionary investigations. We used auditory brainstem responses (ABRs), craniofacial morphology, and pinna measurements to compare characteristics that impact hearing in two wild-caught species, . We observed significant statistical differences in craniofacial and pinna attributes between species with overall exhibiting larger features than .

Outcomes and management of invasive procedures in participants with hemophilia A post gene therapy: a post hoc analysis of the GENEr8-1 phase III trial.

Background: Hemophilia A is caused by coagulation factor VIII (FVIII) deficiency and increases bleeding risk during invasive procedures.

Objectives: To investigate FVIII concentrate use and bleeding outcomes for invasive procedures after valoctocogene roxaparvovec gene transfer.

Design: This manuscript presents post hoc analysis of the phase III GENEr8-1 trial.

Navigating the complex care landscape: Addressing challenges and advancing adult care frameworks for individuals with cerebral palsy.

Despite cerebral palsy (CP) being the most common motor disability in childhood, there are more adults living with CP than children. The necessitates a systematic approach to the care of adults with CP. This perspective piece presents the complex nature of a lifespan approach to the care of a childhood-onset disability.

Feasibility of using an artificially intelligent chatbot to increase access to information and sexual and reproductive health services.

Background: Following the US Supreme Court decision overturning Roe v. Wade, there is evidence of limitations in access to safe abortion care. Artificially intelligent (AI)-enabled conversational chatbots are becoming an appealing option to support access to care, but generative AI systems can misinform and hallucinate and risk reinforcing problematic bias and stigma related to sexual and reproductive healthcare.

Single-cell multi-omics analysis identifies metabolism-linked epigenetic reprogramming as a driver of therapy-resistant medulloblastoma.

Medulloblastoma (MB) is the most prevalent malignant brain tumor in children, exhibiting clinical and genomic heterogeneity. Of the four major subgroups, Group 3 tumors (MYC-MB), display high levels of MYC and metastasis rates. Despite treatment with surgery, radiation, and chemotherapy, patients with Group 3 MB are more likely to develop aggressive recurrent tumors with poor survival.

A specific gene expression program underlies antigen archiving by lymphatic endothelial cells in mammalian lymph nodes.

Lymph node (LN) lymphatic endothelial cells (LEC) actively acquire and archive foreign antigens. Here, we address questions of how LECs achieve durable antigen archiving and whether LECs with high levels of antigen express unique transcriptional programs. We used single cell sequencing in dissociated LN tissue and spatial transcriptomics to quantify antigen levels in LEC subsets and dendritic cell populations at multiple time points after immunization and determined that ceiling and floor LECs archive antigen for the longest duration.

Population Pharmacokinetic Model of Platinum Disposition in Cancer Patients Receiving Cisplatin and Randomized to 5-HT Antagonist Antiemetic Drugs.

Cisplatin is a platinum-based chemotherapeutic drug used to treat many types of cancer. The aim of this study was to develop a population pharmacokinetic model that incorporates plasma unbound and bound platinum levels. Cancer patients undergoing their first or second cycle of cisplatin-containing chemotherapy (n = 33) were prospectively randomized to receive a 5-hydroxytryptamine (5-HT) antagonist (5-HTA) antiemetic (ondansetron, granisetron, or palonosetron) followed by blood collection over 10 days.