Impaired hydrogen sulfide biosynthesis underlies eccentric contraction-induced force loss in dystrophin-deficient skeletal muscle.

Eccentric contraction- (ECC) induced force loss is a hallmark of murine dystrophin-deficient (mdx) skeletal muscle that is used to assess efficacy of potential therapies for Duchenne muscular dystrophy. While virtually all key proteins involved in muscle contraction have been implicated in ECC force loss, a unifying mechanism that orchestrates force loss across such diverse molecular targets has not been identified. We showed that correcting defective hydrogen sulfide (H2S) signaling in mdx muscle prevented ECC force loss.

The burden of illness of the organ manifestations of systemic sclerosis: a pragmatic, targeted review.

Objectives: This structured, targeted literature review aimed to assess the mortality, humanistic and economic burden of eight organ manifestations which are commonly experienced by systemic sclerosis patients.

Methods: Identification of relevant literature was carried out by searching in Ovid MEDLINE and EMBASE, PubMed, and NHS Economic Evaluation Database in August 2023. Studies reporting original data on patients with systemic sclerosis with at least one of eight organ manifestations (interstitial lung disease and/or pulmonary hypertension, skin, peripheral vascular, musculoskeletal, gastrointestinal, cardiac or renal involvement) published within the last 15 years were included.

MALDI-MSI: A potential game changer in forensic sciences.

Matrix-assisted laser Desorption/Ionization Mass Spectrometry Imaging (MALDI MSI) is an analytical technique used for the spatial mapping of drugs, explosives, and organic samples, making it a game-changer in Forensic examination. It detects a wide range of biomolecules in their native state without specific tags, antibodies, labels, and dyes. This review aims to highlight the advancement of MALDI-MSI over time and its impact on Forensic Science due to high-resolution molecular imaging.

Epigenetics in the modern era of crop improvements.

Epigenetic mechanisms are integral to plant growth, development, and adaptation to environmental stimuli. Over the past two decades, our comprehension of these complex regulatory processes has expanded remarkably, producing a substantial body of knowledge on both locus-specific mechanisms and genome-wide regulatory patterns. Studies initially grounded in the model plant Arabidopsis have been broadened to encompass a diverse array of crop species, revealing the multifaceted roles of epigenetics in physiological and agronomic traits.

Fracture liaison service (FLS) is associated with lower subsequent fragility fracture risk and mortality: NoFRACT (the Norwegian capture the fracture initiative).

Unlabelled: Subsequent fracture rates and associated mortality were compared before and after the introduction of fracture liaison service (FLS). In 100,198 women and men, FLS was associated with 13% and 10% lower risk of subsequent fragility fractures and 18% and 15% lower mortality. The study suggests that FLS may prevent fractures.

Benchmarking the Efficacy of Salvage Systemic Therapies for Recurrent Meningioma: A RANO Group Systematic Review and Meta-analysis to Guide Clinical Trial Design.

Background: Despite advances in our understanding of the molecular underpinnings of meningioma progression and innovations in systemic and local treatments, recurrent meningiomas remain a substantial therapeutic challenge. The objective of this systematic review and meta-analysis is to provide a historical baseline, contemporary analysis, and propose a "rate of probable interest" to inform future clinical trial design and development on behalf of the RANO meningioma group.

Methods: PubMed, ClinicalTrials.

HIF1α Plays a Crucial Role in the Development of TFE3-Rearranged Renal Cell Carcinoma by Orchestrating a Metabolic Shift Toward Fatty Acid Synthesis.

Tumor development often requires cellular adaptation to a unique, high metabolic state; however, the molecular mechanisms that drive such metabolic changes in TFE3-rearranged renal cell carcinoma (TFE3-RCC) remain poorly understood. TFE3-RCC, a rare subtype of RCC, is defined by the formation of chimeric proteins involving the transcription factor TFE3. In this study, we analyzed cell lines and genetically engineered mice, demonstrating that the expression of the chimeric protein PRCC-TFE3 induced a hypoxia-related signature by transcriptionally upregulating HIF1α and HIF2α.

Identify characteristics of Vietnamese oral squamous cell carcinoma patients by machine learning on transcriptome and clinical-histopathological analysis.

Background/purpose: Oral squamous cell carcinoma (OSCC) is notorious for its low survival rates, due to the advanced stage at which it is commonly diagnosed. To enhance early detection and improve prognostic assessments, our study harnesses the power of machine learning (ML) to dissect and interpret complex patterns within mRNA-sequencing (RNA-seq) data and clinical-histopathological features.

Materials And Methods: 206 retrospective Vietnamese OSCC formalin-fixed paraffin-embedded (FFPE) tumor samples, of which 101 were subjected to RNA-seq for classification based on gene expression.

Prognostic significance of immune reconstitution following CD19 CAR T-cell therapy for relapsed/refractory B-cell lymphoma.

Immune deficits after CD19 chimeric antigen receptor (CAR) T-cell therapy can be long-lasting, predisposing patients to infections and non-relapse mortality. In B-cell non-Hodgkin lymphoma (B-NHL), the prognostic impact of immune reconstitution (IR) remains ill-defined, and detailed cross-product comparisons have not been performed to date. In this retrospective observational study, we longitudinally characterized lymphocyte subsets and immunoglobulin levels in 105 B-NHL patients to assess patterns of immune recovery arising after CD19 CAR-T.

Global Perspectives on Returning Genetic Research Results in Parkinson Disease.

Background And Objectives: In the era of precision medicine, genetic test results have become increasingly relevant in the care of patients with Parkinson disease (PD). While large research consortia are performing widespread research genetic testing to accelerate discoveries, debate continues about whether, and to what extent, the results should be returned to patients. Ethically, it is imperative to keep participants informed, especially when findings are potentially actionable.

Increased neutrophil elastase in affected lobes of bronchiectasis and correlation of its levels between sputum and bronchial lavage fluid.

Background: Neutrophil elastase (NE) has been proposed as a potential biomarker for evaluating the severity and prognosis of bronchiectasis. This study aimed to compare bronchial lavage quantification of NE levels and activities with those of sputum.

Methods: A cross-sectional study was conducted in which 24 Vietnamese adults with bronchiectasis were enrolled from June 2023 to August 2023.

Overlapping and differential neuropharmacological mechanisms of stimulants and nonstimulants for attention-deficit/hyperactivity disorder: a comparative neuroimaging analysis.

Background: Psychostimulants and nonstimulants have partially overlapping pharmacological targets on attention-deficit/hyperactivity disorder (ADHD), but whether their neuroimaging underpinnings differ is elusive. We aimed to identify overlapping and medication-specific brain functional mechanisms of psychostimulants and nonstimulants on ADHD.

Methods: After a systematic literature search and database construction, the imputed maps of separate and pooled neuropharmacological mechanisms were meta-analyzed by Seed-based Mapping toolbox, followed by large-scale network analysis to uncover potential coactivation patterns and meta-regression analysis to examine the modulatory effects of age and sex.

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges.

Engineered T cells secreting αB7-H3-αCD3 bispecific engagers for enhanced anti-tumor activity against B7-H3 positive multiple myeloma: a novel therapeutic approach.

Background: Multiple myeloma (MM) is an incurable plasma cell malignancy with increasing global incidence. Chimeric antigen receptor (CAR) T-cell therapy targeting BCMA has shown efficacy in relapsed or refractory MM, but it faces resistance due to antigen loss and the tumor microenvironment. Bispecific T-cell engaging (BITE) antibodies also encounter clinical challenges, including short half-lives requiring continuous infusion and potential toxicities.

Early initiation of ceftaroline-based combination therapy for methicillin-resistant Staphylococcus aureus bacteremia.

Purpose: Monotherapy with vancomycin or daptomycin remains guideline-based care for methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B) despite concerns regarding efficacy. Limited data support potential benefit of combination therapy with ceftaroline as initial therapy. We present an assessment of outcomes of patients initiated on early combination therapy for MRSA-B.

An exploratory analysis of differences in serum protein expression by sex in patients with systemic sclerosis associated interstitial lung disease.

Background: Systemic sclerosis (SSc) is a rare connective tissue disease, frequently affecting the skin, lungs, and pulmonary vasculature. Approximately 30-50% of SSc patients develop interstitial lung disease (SSc-ILD), with 30-35% of related deaths attributed to it. Even though men are less likely to develop systemic sclerosis, they have a higher incidence of SSc-ILD than women, and they tend to develop it at a younger age with a higher mortality rate.

Predictive equation derived from 6,497 doubly labelled water measurements enables the detection of erroneous self-reported energy intake.

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years.

Glycogen synthase GYS1 overactivation contributes to glycogen insolubility and malto-oligoglucan-associated neurodegenerative disease.

Polyglucosans are glycogen molecules with overlong chains, which are hyperphosphorylated in the neurodegenerative Lafora disease (LD). Brain polyglucosan bodies (PBs) cause fatal neurodegenerative diseases including Lafora disease and adult polyglucosan body disease (ABPD), for which treatments, biomarkers, and good understanding of their pathogenesis are currently missing. Mutations in the genes for the phosphatase laforin or the E3 ubiquitin ligase malin can cause LD.

Prognostic, biological, and structural implications of FLT3-JMD point mutations in acute myeloid leukemia: an analysis of Alliance studies.

The FLT3 gene frequently undergoes mutations in acute myeloid leukemia (AML), with internal tandem duplications (ITD) and tyrosine kinase domain (TKD) point mutations (PMs) being most common. Recently, PMs and deletions in the FLT3 juxtamembrane domain (JMD) have been identified, but their biological and clinical significance remains poorly understood. We analyzed 1660 patients with de novo AML and found FLT3-JMD mutations, mostly PMs, in 2% of the patients.

Involvement of p38 MAPK and MAPKAPK2 in promoting cell death and the inflammatory response to ischemic stress associated with necrotic glioblastoma.

The association of necrosis in tumors with poor prognosis implies a potential tumor-promoting role. However, the mechanisms underlying cell death in this context and how damaged tissue contributes to tumor progression remain unclear. Here, we identified p38 mitogen-activated protein kinases (p38 MAPK, a.

Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms.

Coronavirus disease 2019 (COVID-19) presents a wide spectrum of symptoms, the causes of which remain poorly understood. This study explored the associations between autoantibodies (AABs), particularly those targeting G protein-coupled receptors (GPCRs) and renin‒angiotensin system (RAS) molecules, and the clinical manifestations of COVID-19. Using a cross-sectional analysis of 244 individuals, we applied multivariate analysis of variance, principal component analysis, and multinomial regression to examine the relationships between AAB levels and key symptoms.

Pre-T cell receptor-α immunodeficiency detected exclusively using whole genome sequencing.

Maturation of αβ lineage T cells in the thymus relies on the formation and cell surface expression of a pre-T cell receptor (TCR) complex, composed of TCRβ chain and pre-TCRα (pTCRα) chain heterodimers, giving rise to a diverse T cell repertoire. Genetic aberrations in key molecules involved in T cell development lead to profound T cell immunodeficiency. Definitive genetic diagnosis guides treatment choices and counseling.

Neutrophil adhesion to vessel walls impairs pulmonary circulation in COVID-19 pathology.

Microthrombus formation is associated with COVID-19 severity; however, the detailed mechanism remains unclear. In this study, we investigated mouse models with severe pneumonia caused by SARS-CoV-2 infection by using our in vivo two-photon imaging system. In the lungs of SARS-CoV-2-infected mice, increased expression of adhesion molecules in intravascular neutrophils prolonged adhesion time to the vessel wall, resulting in platelet aggregation and impaired lung perfusion.

Robust collection and processing for label-free single voxel proteomics.

With advanced mass spectrometry (MS)-based proteomics, genome-scale proteome coverage can be achieved from bulk tissues. However, such bulk measurement lacks spatial resolution and obscures tissue heterogeneity, precluding proteome mapping of tissue microenvironment. Here we report an integrated wet collection of single microscale tissue voxels and Surfactant-assisted One-Pot voxel processing method termed wcSOP for robust label-free single voxel proteomics.