International workshop: what is needed to ensure outcome measures for Rett syndrome are fit-for-purpose for clinical trials? June 7, 2023, Nashville, USA.

Introduction: The clinical, research and advocacy communities for Rett syndrome are striving to achieve clinical trial readiness, including having fit-for-purpose clinical outcome assessments. This study aimed to (1) describe psychometric properties of clinical outcome assessment for Rett syndrome and (2) identify what is needed to ensure that fit-for-purpose clinical outcome assessments are available for clinical trials.

Methods: Clinical outcome assessments for the top 10 priority domains identified in the Voice of the Patient Report for Rett syndrome were compiled and available psychometric data were extracted.

Religion, spirituality, and DNA methylation in HPA-axis genes among Hispanic/Latino adults.

Aim: Investigate associations between religion and spirituality (R&S) and DNA methylation of four HPA-axis genes (i.e. 14 CpG sites) among 992 adults from the Hispanic Community Health Study/Study of Latinos cohorts.

L-Arginine supplementation as mitochondrial therapy in diabetic cardiomyopathy.

In patients with type II diabetes, the development of diabetic cardiomyopathy (DC) is associated with a high risk of mortality. Left ventricular hypertrophy, diastolic dysfunction, and exercise intolerance are the first signs of DC. The underlying mechanisms are not fully elucidated, and there is an urgent need for specific biomarkers and molecular targets for early diagnosis and treatment.

Partial-linear single-index Cox regression models with multiple time-dependent covariates.

Background: In cohort studies with time-to-event outcomes, covariates of interest often have values that change over time. The classical Cox regression model can handle time-dependent covariates but assumes linear effects on the log hazard function, which can be limiting in practice. Furthermore, when multiple correlated covariates are studied, it is of great interest to model their joint effects by allowing a flexible functional form and to delineate their relative contributions to survival risk.

Oral Microbiome Signatures as Potential Biomarkers for Gastric Cancer Risk Assessment.

Background: Gastric cancer (GC) is the fifth leading cause of cancer-related death worldwide. The oral microbiota was investigated for distinguishable characteristics between GC, premalignant gastric conditions (Pre-GC), and control participants.

Methods: Mouthwash samples from GC, Pre-GC, and control participants at a tertiary care center were prospectively collected.

Recent advances in the treatment of chronic pain and substance use disorders.

Among people with substance use disorders (SUDs), chronic pain is among the most common comorbid chronic health conditions. Chronic pain increases risk for poor SUD treatment outcomes, including risk for overdose. Given rising overdose rates across North America, a renewed research focus has emerged to better understand the contribution and treatment of chronic pain in the context of an SUD.

Understanding human papillomavirus vaccine response and efficacy in people living with HIV: A systematic mixed studies review and meta-analysis.

Coinfection with human papillomavirus (HPV) and HIV compounds the risks of developing cervical, anal, and HPV-associated oral neoplasia. Safe prophylactic vaccines are available to prevent HPV infections in people with HIV(PWH). Yet, vaccine efficacy and duration of protection remain questionable.

Smoking carcinogen induced inflammation promotes lung carcinogenesis via IRAK4 activation.

Purpose: Even though smoking is associated with lung cancer, the exact molecular pathways that link carcinogens with inflammation and oncogenic transformation are not well elucidated. Two major carcinogens in cigarette smoke, Nicotine-derived nitrosamine ketone, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo(α)pyrene (BaP) have not been tested in models that mimic inhaled exposure for prolonged periods of time.

Experimental Design: ICR mice were treated with intratracheal delivery of NNK and BaP (NB) for 18 months.

The Fifth Annual Symposium of the Midwest Aging Consortium.

As the healthcare burden caused by an increasingly aging population rapidly rises, a pressing need exists for innovative geroscience research that can elucidate aging mechanisms and precipitate the development of therapeutic interventions to support healthy aging. The Fifth Annual Midwest Aging Consortium Aging Research symposium, held from April 28-30, 2024, was hosted by The Ohio State University in Columbus, Ohio and featured presentations from investigators across the Midwestern United States. This report summarizes the research presented at the symposium, whose topics included cellular senescence and the aging brain, metabolism and metabolic interventions, nutrition, redox mechanisms and biomarkers, and stress mechanisms.

The financial impact of MD-PhD training compared with MD training for academic physicians.

To reduce debt burden and encourage the pursuit of research-focused careers, most MD-PhD programs provide medical school tuition remission and an annual stipend. However, prolonged training compared with MD physicians postpones the time until MD-PhD physicians earn a full salary. We compared lifetime earning potential for MD-PhD physicians in academia with their MD colleagues in the same clinical specialty.

Mitochondrial pathways of copper neurotoxicity: focus on mitochondrial dynamics and mitophagy.

Copper (Cu) is essential for brain development and function, yet its overload induces neuronal damage and contributes to neurodegeneration and other neurological disorders. Multiple studies demonstrated that Cu neurotoxicity is associated with mitochondrial dysfunction, routinely assessed by reduction of mitochondrial membrane potential. Nonetheless, the role of alterations of mitochondrial dynamics in brain mitochondrial dysfunction induced by Cu exposure is still debatable.

Dematiaceous Molds.

Dematiaceous molds are darkly pigmented environmental molds found worldwide, especially prevalent in tropical and subtropical regions. Common genera include Bipolaris, Cladophialophora, Exophiala, and Alternaria. They cause disease in both immunocompetent and immunocompromised individuals, presenting as cutaneous infections, allergic sinusitis, pneumonia, and, rarely, disseminated infections.

Performance of Clinical Scoring Systems in the Diagnosis of Transthyretin Amyloid Cardiomyopathy in a Diverse Patient Cohort.

Background: Two diagnostic clinical scoring systems, the ATTR-CM Score and the T-AMYLO Score, have been proposed but not validated in diverse populations, despite Black race being an important risk factor for transthyretin amyloid cardiomyopathy (ATTR-CM). The aim of this study was to evaluate their performance in diagnosing ATTR-CM in a diverse patient cohort.

Methods: This retrospective single-center study analyzed patients who underwent a 99mTc-pyrophosphate single photon emission computed tomography scan (Tc-PYP) for workup of suspected ATTR-CM.

Engineering and structures of Crimean-Congo hemorrhagic fever virus glycoprotein complexes.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tickborne virus that can cause severe disease in humans with case fatality rates of 10%-40%. Although structures of CCHFV glycoproteins GP38 and Gc have provided insights into viral entry and defined epitopes of neutralizing and protective antibodies, the structure of glycoprotein Gn and its interactions with GP38 and Gc have remained elusive. Here, we use structure-guided protein engineering to produce a stabilized GP38-Gn-Gc heterotrimeric glycoprotein complex (GP38-Gn-Gc).

Botulinum Toxin Treatment in Thyroid Eye Disease: A Systematic Review and Meta-analysis.

Purpose: Thyroid eye disease-related retraction and strabismus treatment is complicated by the activity level of the disease. Botulinum toxin injection can provide relief of symptoms in lieu of, or while waiting for surgery, radiation, or alternative medications. This study reviews techniques, outcomes, and effectiveness of botulinum toxin usage in thyroid eye disease.

"Bringing greater research fluency into our educational vision": A qualitative research study on improving Traditional Chinese Medicine research education.

The main objective of this qualitative analysis is to increase the quality of Traditional Chinese Medicine (TCM) research education. Subject matter experts and stakeholders were sent a list of possible topics to include in a research course and were asked to comment on it, add or subtract topics, and suggest appropriate research papers to use, lessons learned in their topic areas and possible stand-alone topics for inclusion in other courses. Their feedback was used to revise the topic list, create a list of foundational research papers to include in a research course and devise a list of stand-alone topics that could be included in the general TCM research curriculum.

Treatment-induced ripple effect: a systematic review exploring the abscopal phenomenon in Glioblastoma multiforme.

Purpose: This systematic review aimed to collate and synthesize the available literature on the abscopal effect in Glioblastoma multiforme (GBM) neoplasms, focusing on the reported biochemical mechanisms driving the abscopal effect.

Methods: A systematic search was conducted in PubMed, Cochrane Database of Systematic Reviews, and Epistemonikos from inception to May 1, 2023. Studies exploring the abscopal effect in GBM were included.

The alphavirus determinants of intercellular long extension formation.

The alphavirus chikungunya virus (CHIKV) is a serious human pathogen that can cause large-scale epidemics characterized by fever and joint pain and often resulting in chronic arthritis. Infection by alphaviruses including CHIKV and the closely related Semliki Forest virus (SFV) can induce the formation of filopodia-like intercellular long extensions (ILEs). ILEs emanate from an infected cell, stably attach to a neighboring cell, and mediate cell-to-cell viral transmission that is resistant to neutralizing antibodies.

Cardiovascular mortality trends and disparities in U.S. breast cancer patients, 1999-2020: a population-based retrospective study.

Background: Breast cancer survivors face a higher risk of cardiovascular disease (CVD) compared to non-breast cancer patients, yet contemporary data on CVD-related mortality within this group remains scarce.

Objective: To investigate trends and disparities in CVD mortality among breast cancer patients.

Methods: We queried the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC Wonder) and conducted serial cross-sectional analyses on national death certificate data for CVD mortality in breast cancer patients aged 25 and above from 1999 to 2020.

Interictal burden in migraine patients at the outset of CGRP monoclonal antibody prevention.

Background: The total burden of migraine includes not only the episodes with headache pain but extends throughout the interictal periods. Interictal symptoms and associated psychological responses may profoundly impact well-being and drive treatment-seeking behavior.

Methods: A cross-sectional online survey was conducted with participants aged ≥ 18 years, 250 with episodic migraine (EM) and 250 with chronic migraine (CM), having ≥ 4 monthly migraine headache days.

Nucleosome fibre topology guides transcription factor binding to enhancers.

Cellular identity requires the concerted action of multiple transcription factors (TFs) bound together to enhancers of cell-type-specific genes. Despite TFs recognizing specific DNA motifs within accessible chromatin, this information is insufficient to explain how TFs select enhancers. Here we compared four different TF combinations that induce different cell states, analysing TF genome occupancy, chromatin accessibility, nucleosome positioning and 3D genome organization at the nucleosome resolution.

Neuroanatomical and pharmaco-physiological effects of hypoxia and esketamine on breathing, the sympathetic nerve system, and cortical function.

Acute hypoxic ventilatory response is an important reflex that helps maintain breathing during low oxygen levels, but it is attenuated by most general anaesthetics. Analgesic doses of ketamine and esketamine are known to have respiratory stimulant effects. In their recent study in the British Journal of Anaesthesia, Jansen and colleagues show that low-dose esketamine preserved the acute hypoxic ventilatory response, while increasing breathing rate, systolic blood pressure, and heart rate.

Transophthalmic Artery Embolization of Anterior Skull Base Meningiomas: Technical Case Series.

Background And Purpose: Preoperative embolization of anterior skull base meningiomas can facilitate surgical resection by reducing tumor vascularity. However, transophthalmic artery embolization carries risks of visual complications. This study aimed to evaluate the safety and efficacy of this technique using modern endovascular tools.

Untargeted metabolome atlas for sleep-related phenotypes in the Hispanic community health study/study of Latinos.

Background: Sleep is essential to maintaining health and wellbeing of individuals, influencing a variety of outcomes from mental health to cardiometabolic disease. This study aims to assess the relationships between various sleep-related phenotypes and blood metabolites.

Methods: Utilising data from the Hispanic Community Health Study/Study of Latinos, we performed association analyses between 40 sleep-related phenotypes, grouped in several domains (sleep disordered breathing (SDB), sleep duration, sleep timing, self-reported insomnia symptoms, excessive daytime sleepiness (EDS), and heart rate during sleep), and 768 metabolites measured via untargeted metabolomics profiling.