DISCOntinuation of disease-modifying therapies in MS: The DISCOMS extension trial.

Background: In the DISCOMS (DISCOntinuation of disease-modifying therapies (DMTs) in multiple sclerosis (MS)) randomized clinical trial, we could not demonstrate that discontinuing MS DMTs in older, stable adults was not inferior to continuing DMTs. Relapses were rare in both groups, and most new disease activity was one to two new brain magnetic resonance imaging (MRI) lesions unassociated with clinical changes.

Objective/aims: Describe results of the DISCOMS extension study.

Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington's disease decades before clinical motor diagnosis.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with the age at which characteristic symptoms manifest strongly influenced by inherited HTT CAG length. Somatic CAG expansion occurs throughout life and understanding the impact of somatic expansion on neurodegeneration is key to developing therapeutic targets. In 57 HD gene expanded (HDGE) individuals, ~23 years before their predicted clinical motor diagnosis, no significant decline in clinical, cognitive or neuropsychiatric function was observed over 4.

Food groups, macronutrient intake and objective measures of total carotenoids and fatty acids in 16-to-24-year-olds following different plant-based diets compared to an omnivorous diet.

Background: Knowledge about the diet quality among youth who follow different types of plant-based diets is essential to understand whether support is required to ensure a well-planned diet that meets their nutritional needs. This study aimed to investigate how food groups, macronutrient intake, and objective blood measures varied between Norwegian youth following different plant-based diets compared to omnivorous diet.

Methods: Cross-sectional design, with healthy 16-to-24-year-olds (n = 165) recruited from the Agder area in Norway, following a vegan, lacto-ovo-vegetarian, pescatarian, flexitarian or omnivore diet.

Opposing roles of p38α-mediated phosphorylation and PRMT1-mediated arginine methylation in driving TDP-43 proteinopathy.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder typically characterized by insoluble inclusions of hyperphosphorylated TDP-43. The mechanisms underlying toxic TDP-43 accumulation are not understood. Persistent activation of p38 mitogen-activated protein kinase (MAPK) is implicated in ALS.

"They knew the same struggles": perceptions of a group coping skills intervention in patients with chronic graft-versus-host disease.

Purpose: Chronic graft-versus-host-disease (cGVHD), an inflammatory condition affecting allogeneic hematopoietic cell transplantation (HCT) survivors, is associated with a range of debilitating physical and psychological sequela. Yet HCT recipients with cGVHD are virtually absent from survivorship intervention research. We conducted a randomized clinical trial to evaluate the feasibility and preliminary efficacy of a multidisciplinary group coping skills intervention (Horizons) tailored to meet these patients' unique needs.

Rational selection of TbpB variants yields a bivalent vaccine with broad coverage against Neisseria gonorrhoeae.

Neisseria gonorrhoeae is an on-going public health problem due in part to the lack of success with efforts to develop an efficacious vaccine to prevent this sexually transmitted infection. The gonococcal transferrin binding protein B (TbpB) is an attractive candidate vaccine antigen. However, it exhibits high levels of antigenic variability, posing a significant obstacle in evoking a broadly protective immune response.

Longer term follow-up of abdominal symptoms (CFAbd-Score) after initiation of Elexacaftor / Tezacaftor / Ivacaftor in adults with cystic fibrosis.

Background: Whether improvements in gastrointestinal (GI) symptoms observed with Elexacaftor/Tezacaftor/Ivacaftor (ETI) treatment are sustained in the longer-term requires exploration. This study investigated how GI-symptoms change with longer-term ETI use in pancreatic insufficient adults with cystic fibrosis (awCF).

Methods: Participants completed up to three abdominal symptom questionnaires, employing the validated CFAbd-Score.

Impact of Endorectal Coil Use on Extraprostatic Extension Detection in Prostate MRI: A Retrospective Monocentric Study.

Rationale And Objectives: Accurate preoperative mpMRI-based detection of extraprostatic extension (EPE) in prostate cancer (PCa) is critical for surgical planning and patient outcomes. This study aims to evaluate the impact of endorectal coil (ERC) use on the diagnostic performance of mpMRI in detecting EPE.

Materials And Methods: This retrospective study with prospectively collected data included participants who underwent mpMRI and subsequent radical prostatectomy for PCa between 2007 and 2024.

Gastrointestinal cancer incidence after lung transplantation in sarcoidosis patients.

Background: The risk of gastrointestinal (GI) cancer after lung transplantation (LTx) in sarcoidosis patients is not well defined. Given the cancer risks linked to sarcoidosis and organ transplantation, this study investigated the incidence of GI malignancies (DNM), comparing LTx recipients with sarcoidosis or idiopathic pulmonary fibrosis (IPF).

Methods: We analyzed data from the United Network for Organ Sharing registry, including adults with sarcoidosis or IPF who underwent LTx between May 2005 and December 2018.

Common Questions and Misconceptions About Energy Drinks: What Does the Scientific Evidence Really Show?

Energy drinks are a commonly consumed beverage, and studies suggest a possible performance-enhancing effect. A Google Scholar search using the keywords "energy drinks" and "exercise" yields numerous results, underscoring the voluminous research on this topic. However, there are questions regarding the effectiveness and safety of energy drinks.

Clinicopathologic and genomic features associated with brain metastasis after resection of lung adenocarcinoma.

Objective: To identify clinicopathologic and genomic features associated with brain metastasis after resection of lung adenocarcinoma (LUAD) and to evaluate survival after brain metastasis.

Methods: Patients who underwent complete resection of stage I-IIIA LUAD between 2011 and 2020 were included. A subset of patients had broad-based panel next-generation sequencing performed on their tumors.

Real World Data from an Italian Outpatient Clinical Setting and from Home Care Assistance of Treatment-Experienced PWH Switching to CAB + RPV Regimen: A Prospective Observational Study.

The new Cabotegravir + Rilpivirine long acting (CAB + RPV) is the injectable regimen for treatment-experienced people with HIV (PWH). Little data from real-world settings are available, particularly in more complex PWH. We aimed to investigate the effectiveness of CAB + RPV in our real-life cohort of experienced PWH.

Cross-modal contrastive learning for unified placenta analysis using photographs.

The placenta is vital to maternal and child health but often overlooked in pregnancy studies. Addressing the need for a more accessible and cost-effective method of placental assessment, our study introduces a computational tool designed for the analysis of placental photographs. Leveraging images and pathology reports collected from sites in the United States and Uganda over a 12-year period, we developed a cross-modal contrastive learning algorithm consisting of pre-alignment, distillation, and retrieval modules.

NPA7: A Dual Receptor Activating Peptide That Inhibits Cardiac Oxidative Stress.

Background: Cardiomyocyte oxidative stress significantly contributes to the progression of hypertension-induced heart failure, highlighting the need for targeted therapies. We developed a novel peptide, NPA7, that coactivates the GC-A (guanylyl cyclase A)/cGMP and MasR (Mas receptor)/cAMP pathway. This study aimed to test NPA7's ability to inhibit oxidative stress by modulating the p62-KEAP1 (Kelch-like ECH-associated protein 1)-NRF2 (nuclear factor erythroid 2-related factor 2) pathway in human cardiomyocytes (HCMs) and a rat model of hypertension.

Respiratory Syncytial Virus and Other Respiratory Viruses in Hospitalized Infants During the 2023-2024 Winter Season in Mexico.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children. During the COVID-19 pandemic, a significant change in the epidemiology of RSV and other viruses occurred worldwide, leading to a reduction in the circulation of these infectious agents. After the pandemic, the resurgence of seasonal respiratory viruses occurred, but some features of these infections contrast to those registered prior to the pandemic.

Improved Genetic Characterization of Hypercholesterolemia in Latvian Patients with Familial Hypercholesterolemia: A Combined Monogenic and Polygenic Approach Using Whole-Genome Sequencing.

Despite the implementation of next-generation sequencing-based genetic testing on patients with clinical familial hypercholesterolemia (FH), most cases lack complete genetic characterization. We aim to investigate the utility of the polygenic risk score (PRS) in specifying the genetic background of patients from the Latvian Registry of FH (LRFH). We analyzed the whole-genome sequencing (WGS) data of the clinically diagnosed FH patients (n = 339) and controls selected from the Latvian reference population (n = 515).

Predicting the Impact of Polysulfone Dialyzers and Binder Dialysate Flow Rate on Bilirubin Removal.

Liver failure is the 12th leading cause of death worldwide. Protein-bound toxins such as bilirubin are responsible for many complications of the disease. Binder dialysis systems use albumin or another binding molecule in dialysate and detoxifying sorbent columns to remove these toxins.

Obinutuzumab in Combination with Alternative Chlorambucil Schedules in Front-Line Treatment of Chronic Lymphocytic Leukemia: A Study by KroHem, the Croatian Cooperative Group for Hematologic Diseases.

Obinutuzumab was approved for front-line treatment of chronic lymphocytic leukemia in combination with chlorambucil pulses administered every 2 wks. Alternative schedules of chlorambucil enable the administration of higher total chlorambucil doses, and have better antileukemia activity. So far, evidence on the feasibility of combining obinutuzumab with alternative chlorambucil schedules is lacking.

The blood metabolome of cognitive function and brain health in middle-aged adults - influences of genes, gut microbiome, and exposome.

Increasing evidence suggests the involvement of metabolic alterations in neurological disorders, including Alzheimer's disease (AD), and highlights the significance of the peripheral metabolome, influenced by genetic factors and modifiable environmental exposures, for brain health. In this study, we examined 1,387 metabolites in plasma samples from 1,082 dementia-free middle-aged participants of the population-based Rotterdam Study. We assessed the relation of metabolites with general cognition (G-factor) and magnetic resonance imaging (MRI) markers using linear regression and estimated the variance of these metabolites explained by genes, gut microbiome, lifestyle factors, common clinical comorbidities, and medication using gradient boosting decision tree analysis.

Acute Myeloid Leukemia Skews Therapeutic WT1-specific CD8 TCR-T Cells Towards an NK-like Phenotype that Compromises Function and Persistence.

Acute myeloid leukemia (AML) that is relapsed and/or refractory post-allogeneic hematopoietic cell transplantation (HCT) is usually fatal. In a prior study, we demonstrated that AML relapse in high-risk patients was prevented by post-HCT immunotherapy with Epstein-Barr virus (EBV)-specific donor CD8 T cells engineered to express a high-affinity Wilms Tumor Antigen 1 (WT1)-specific T-cell receptor (T). However, in the present study, infusion of EBV- or Cytomegalovirus (CMV)-specific T did not clearly improve outcomes in fifteen patients with active disease post-HCT.

Prediction of checkpoint inhibitor immunotherapy efficacy for cancer using routine blood tests and clinical data.

Predicting whether a patient with cancer will benefit from immune checkpoint inhibitors (ICIs) without resorting to advanced genomic or immunologic assays is an important clinical need. To address this, we developed and evaluated SCORPIO, a machine learning system that utilizes routine blood tests (complete blood count and comprehensive metabolic profile) alongside clinical characteristics from 9,745 ICI-treated patients across 21 cancer types. SCORPIO was trained on data from 1,628 patients across 17 cancer types from Memorial Sloan Kettering Cancer Center.

Pharmacological characterization of cannabidiol as a negative allosteric modulator of the 5-HT receptor.

Promising clinical evidence suggests that psychedelic compounds, like lysergic acid diethylamide (LSD), have therapeutic value for treatment of psychiatric disorders. However, they often produce hallucinations and dissociative states, likely mediated by the serotonin (5-HT) receptor 5-HT, raising challenges regarding therapeutic scalability. Given the reported antipsychotic effects of cannabidiol (CBD) and its promiscuous binding at many receptors, we assessed whether CBD could modulate 5-HT signalling.