Integration of 168,000 samples reveals global patterns of the human gut microbiome.

The factors shaping human microbiome variation are a major focus of biomedical research. While other fields have used large sequencing compendia to extract insights requiring otherwise impractical sample sizes, the microbiome field has lacked a comparably sized resource for the 16S rRNA gene amplicon sequencing commonly used to quantify microbiome composition. To address this gap, we processed 168,464 publicly available human gut microbiome samples with a uniform pipeline.

Does exercise demonstrate a dose-dependent benefit with cognition in Parkinson's disease?

Background: Exercise confers motor benefits in Parkinson's disease (PD) and may even have disease modifying effects. While the impact of exercise on motor symptoms and quality of life is well-studied in PD, its relationship with cognitive performance warrants further attention.

Methods: In people with PD, self-reported exercise information was quantified using the Rapid Assessment of Physical Activity (RAPA).

Pembrolizumab in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) and non-MSI-H/non-dMMR advanced endometrial cancer: Phase 2 KEYNOTE-158 study results.

Objective: We report updated results with longer follow-up in patients with MSI-H/dMMR endometrial cancer (EC) in cohort D (advanced EC of any MSI/dMMR status) and cohort K (any MSI-H/dMMR advanced solid tumor, except colorectal) of the phase 2 KEYNOTE-158 study (NCT02628067) and the first results from patients with non-MSI-H/non-dMMR advanced EC (cohort D).

Methods: Patients received pembrolizumab 200 mg Q3W for ≥35 cycles. The primary endpoint was objective response rate (ORR) per RECIST v1.

Elevating performance and interpretability of in silico classifiers for drug proarrhythmia risk evaluations using multi-biomarker approach with ranking algorithm.

Background And Objective: Using electrophysiological simulations and machine learning to predict drug proarrhythmia risk has gained popularity due to its effectiveness. The leading in silico drug assessment system mainly uses a single biomarker (qNet) to predict proarrhythmia risk, offering good performance and straightforward interpretation. Other advanced classifiers incorporating additional physiological biomarkers provide better predictive capabilities but are less intuitive.

Opportunities for microphysiological systems from the view of Japanese industries.

Regulatory authorities and pharmaceutical companies in Europe and the United States have paid attention to microphysiological systems (MPS), and various consortia and academic societies have been established. They are actively working toward their implementation under individual company or regulatory acceptance. In Japan, some AMED projects, academic societies, and consortia have also been established and activities have begun.

Micro-physiological system of human lung: The current status and application to drug discovery.

Various attempts have been made to elucidate the mechanisms of human lung development, its physiological functions, and diseases, in the hope of new drug discovery. Recent technological advancements in experimental animals, cell culture, gene editing, and analytical methods have provided new insights and therapeutic strategies. However, the results obtained from animal experiments are often inconsistent with those obtained from human data because of reproducibility issues caused by structural and physiological differences between mice and humans.

Claudins as diagnostic tools and therapeutic targets-Glimpse of the horizon.

Claudins (CLDNs) play a crucial and indispensable role as fundamental components within the structure of tight junctions. Due to the distinct and unique distribution pattern exhibited by CLDNs in both normal and malignant tissues, these proteins have garnered significant attention as pivotal targets for systemic anti-cancer therapy and as noteworthy diagnostic markers. This review provides a comprehensive and detailed elucidation of the fundamental understanding surrounding CLDNs, their intricate expression patterns, the potential role they play in cancer diagnosis and therapeutic potentials; all encapsulated within a succinct summary of the cutting-edge advancements and the information derived from various clinical trials.

Evaluation and Management of Congenital Cytomegalovirus Infection.

The purpose of this review is to serve as an update on congenital cytomegalovirus (CMV) evaluation and management for obstetrician-gynecologists and to provide a framework for counseling birthing people at risk for or diagnosed with a primary CMV infection or reactivation or reinfection during pregnancy. A DNA virus, CMV is the most common congenital viral infection and the most common cause of nongenetic childhood hearing loss in the United States. The risk of congenital CMV infection from transplacental viral transfer depends on the gestational age at the time of maternal infection and whether the infection is primary or nonprimary.

DECODE enables high-throughput mapping of antibody epitopes at single amino acid resolution.

Antibodies are extensively used in biomedical research, clinical fields, and disease treatment. However, to enhance the reproducibility and reliability of antibody-based experiments, it is crucial to have a detailed understanding of the antibody's target specificity and epitope. In this study, we developed a high-throughput and precise epitope analysis method, DECODE (Decoding Epitope Composition by Optimized-mRNA-display, Data analysis, and Expression sequencing).

Regulation and Compliance in Telemedicine: Viewpoint.

The US COVID-19 Public Health Emergency ended on May 11, 2023. Lawmakers and regulators extended some flexibilities while they deliberate effective long-term telemedicine policy. Here, we discuss critical challenges in telemedicine compliance and regulation grounded in scholarly literature and current events.

Comparative- and Cost-Effectiveness Research Determining the Optimal Intervention for Advancing Transgender Women With HIV to Full Viral Suppression (Text Me, Alexis!): Protocol for a Randomized Controlled Trial.

Background: Many transgender women with HIV achieve suboptimal advancement through the HIV Care Continuum, including poor HIV health care usage, retention in HIV medical care, and rates of viral suppression. These issues are exacerbated by comorbid conditions, such as substance use disorder, which is also associated with reduced quality of life, increased overdose deaths, usage of high-cost health care services, engagement in a street economy, and cycles of incarceration. Thus, it is critical that efforts to End the HIV Epidemic include effective interventions to link and retain transgender women in HIV care through full viral suppression.

Health State Utility Values in Fabry Disease: Insights from the Pegunigalsidase Alfa Clinical Trials.

Introduction: Fabry disease (FD) is a rare lysosomal storage disorder that is associated with pain and progressive damage to the renal, cardiac, and cerebrovascular systems. Enzyme replacement therapy (ERT) is one of the treatment options for FD and the most recently approved ERT agent, pegunigalsidase alfa, has shown clinical efficacy in three phase 3 clinical trials of adults with FD: BALANCE, BRIDGE, and BRIGHT. Recent published guidelines support the mapping of health utility state data to the EuroQol-5 Dimension-3 Level (EQ-5D-3L) index to align with the preferred methodology used by the National Institute for Health and Care Excellence (NICE).

A Canadian real-world, multi-center, prospective, observational study assessing the treatment duration, the treatment sequence, and the overall survival for patients treated with endocrine therapy ± targeted therapy in HR + HER2-negative advanced breast cancer.

Purpose: Understanding real-world treatment patterns and their effectiveness in HR + HER2- advanced breast cancer (aBC) in Canadian patients.

Patient And Methods: This was a multi-center, observational, prospective cohort study including men and pre-/peri-/postmenopausal women with HR + HER2- aBC receiving endocrine therapy (ET) or ET + targeted therapy (ET + TT). The primary objective was duration of treatment (DOT) with ET and ET + TT.

Efficacy of ramucirumab combined with erlotinib or osimertinib in untreated EGFR-mutated NSCLC patients with asymptomatic brain metastases: insights from molecular biomarkers in the RELAY-brain trial.

Background: The RELAY-Brain trial examined the clinical utility and survival impacts of ramucirumab (RAM) combined with epidermal growth factor receptor (EGFR)-TKI in patients with EGFR-mutated non-small-cell lung cancer (NSCLC) with brain metastases. Although RAM combined with erlotinib (ERL) is known to have clinical benefits, the benefits in patients with baseline brain metastases remain unclear. This report examined the long-term follow-up data (Japan Registry of Clinical Trials: jRCTs2051190027) of the same patients, analyzing relevant biomarkers from tumor and plasma samples.

Improving postsurgical paresis in brain tumor patients by transcranial magnetic stimulation.

Background And Objectives: Recently, reduction of transcallosal inhibition by contralateral navigated repetitive transcranial magnetic stimulation (nrTMS) improved neurorehabilitation of glioma patients with new postoperative paresis. This multicentric study examines the effect of postoperative nrTMS in brain tumor patients to treat surgery-related upper extremity paresis.

Methods: This is a secondary analysis of two randomized and three one-arm studies in brain tumor patients with new/progressive postoperative paresis.

Patient-centered outcomes for clinical trials in chronic rhinosinusitis with or without nasal polyps and allergic fungal rhinosinusitis.

Background: Chronic rhinosinusitis (inclusive of subtypes with nasal polyps [CRSwNP], without nasal polyps [CRSsNP], and allergic fungal rhinosinusitis [AFRS]) causes inflammation of the nose mucosa and paranasal sinuses. Unfortunately, evidence supporting use of clinical outcome assessments (COAs) in regulated clinical trials to assess key measurement concepts of these conditions is limited.

Objective: To identify key disease-related symptoms and impacts, potential outcomes of interest for new treatments, and COAs available to measure those outcomes among adult and adolescent individuals living with CRSwNP, CRSsNP, and AFRS.

Evolution of sleep disordered breathing in infants with achondroplasia.

Purpose: Children with achondroplasia (ACH) are at risk for sudden death in infancy due to sleep disordered breathing (SDB) and foramen magnum stenosis (FMS). Sleep studies and neuroimaging are performed in infants with ACH, but interpretation of infant studies is challenging. We sought to describe baseline data on polysomnography (PSG) indices in infants with achondroplasia as well as effects of age and surgery on these parameters.

A physiologically based pharmacokinetic (PBPK) model describing the kinetics of a commercial mixture α-, β-, and γ-hexabromocyclododecane exposure in mice.

Hexabromocyclododecane (HBCD) is a brominated flame retardant, that is added, but not chemically bonded, to consumer products. HBCD is sold as a commercial-grade HBCD mixture containing three major stereoisomers: alpha (α), beta (β), and gamma (γ), with relative amounts of 12% for α-HBCD, 6% for β-HBCD, and 82% for γ-HBCD. HBCDs are widely measured in the environment and in biological matrices.

Skeletal muscle elastic modulus in marathon distance runners.

Skeletal muscle shear elastic modulus is a non-invasive surrogate for early detection of muscle damage and soreness consequent to unaccustomed eccentric muscle work. We investigated the influence of marathon distance running on skeletal muscle shear elastic modulus. Shear modulus of the rectus femoris was measured via ultrasound shear wave elastography in 80 participants (30 female, 50 male) before and after running a World Marathon Major.

Relationship quality, parenting practices, and adolescent mental health across diverse U.S. populations.

Various parenting practices and behaviors have been consistently linked to children and youth's mental health outcomes (Pinquart, 2016, 2017) through identified psychological and biological mechanisms (Hoeve et al., 2009). The quality of the dyadic parent-child relationship is less commonly studied but may be important in mediating the efficacy of parenting practices and understanding cultural differences in how parenting practices affect development outcomes (Ho et al.

Pembrolizumab ± paricalcitol in metastatic pancreatic cancer postmaximal cytoreduction.

Lessons Learned: Intravenous paricalcitol did not improve the efficacy of pembrolizumab, likely related to the short half-life.

Background: Immunotherapy has limited benefit in the treatment of advanced pancreatic cancer with the tumor microenvironment playing a key role in immune resistance. In preclinical studies, vitamin D receptor (VDR) agonists have been shown to sensitize pancreatic tumors to PD-1 blockade.

Is it time to retire preoperative radiation for localized esophageal and gastro-esophageal adenocarcinoma?

Whether preoperative chemoradiotherapy (CRT) or perioperative chemotherapy is superior for localized esophageal or gastro-esophageal junction (GEJ) cancers has been a topic of long-standing debate. For years, standard of care in the United States for localized esophageal or GEJ adenocarcinoma (EAC) has been physician's choice between the 2 strategies. More recently, adjuvant immunotherapy has also been introduced into the treatment approach for those who received neoadjuvant CRT.