Pancreatic islet autoantibodies and their association with glycemic status in cystic fibrosis patients: A comprehensive meta-analysis.

Background: The role of autoimmune beta-cell damage in cystic fibrosis-related glucose abnormalities remains unclear. This study evaluates the prevalence of pancreatic islet autoantibodies (AABs) by glycemic status and age, and assesses the risk of developing cystic fibrosis-related diabetes (CFRD) in people with cystic fibrosis (pwCF).

Methods: A random-effects meta-analysis examined AABs against glutamic acid decarboxylase (GADA), insulin (IAA), islet cell (ICA), islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) in pwCF (CRD42023482663).

The paradoxical relationship of sensorimotor deficit and lesion volume in acute ischemic stroke.

Understanding the relationship between the degree of neurological deficit and lesion volume is key to predicting outcomes in patients with acute ischemic stroke (AIS). Over the past 40 years, AIS research has relied on a perceived linear relationship between lesion volumes and neurological deficit. Here, we found that these variables do not show a relationship in a mouse model of AIS.

Effect of Vaginal Laser and Topical Therapies on Vulvovaginal Atrophy Symptoms in Breast Cancer Patients: A Systematic Review and Meta-Analysis.

: Vulvovaginal atrophy (VVA) significantly impacts the quality of life in breast cancer patients leading to symptoms like vaginal dryness, dyspareunia, and genital discomfort. Quality of life in this context is measured using validated scales like the Vaginal Health Index, Visual Analog Scale (VAS), and the Female Sexual Function Index (FSFI). : We performed a systematic review and meta-analysis to identify effective treatment options for VVA, including topical estrogen, systemic hormone therapy, vaginal DHEA, ospemifene, and non-hormonal methods like intravaginal laser therapy, moisturizers, and lubricants.

Accuracy of conventional versus additive cast-fabrication in implant prosthodontics: A systematic review and meta-analysis of in vitro studies.

Purpose: Additive cast-fabrication has yet to be used as commonly in implant prosthodontics as conventional methods. This review aimed to investigate the accuracy of additive cast-fabrication in implant prosthodontics.

Study Selection: The study protocol was registered in the PROSPERO database (CRD42022374972).

Collateral is brain: Low perfusion triggers spreading depolarization and futile reperfusion after acute ischemic stroke.

Futile reperfusion is a phenomenon of inadequate perfusion despite successful recanalization after acute ischemic stroke (AIS). It is associated with poor patient outcomes and has received increasing interest due to its clinical diagnosis becoming more common. However, the underlying mechanisms remain elusive, and experimental studies are focused on the pathological background of futile reperfusion.

consICA: an R package for robust reference-free deconvolution of multi-omics data.

Motivation: Deciphering molecular signals from omics data helps understanding cellular processes and disease progression. Effective algorithms for extracting these signals are essential, with a strong emphasis on robustness and reproducibility.

Results: R/Bioconductor package implements consensus independent component analysis (ICA)-a data-driven deconvolution method to decompose heterogeneous omics data and extract features suitable for patient stratification and multimodal data integration.

Platelet-rich plasma (PRP) treatment of the ovaries significantly improves fertility parameters and reproductive outcomes in diminished ovarian reserve patients: a systematic review and meta-analysis.

Introduction: The incidence of infertility caused by diminished ovarian reserve has become a significant problem worldwide. The beneficial effect of PRP treatment of the ovaries has already been described, but the high-level evidence of its effectiveness has not yet been proven.

Materials And Methods: A systematic search was performed in five databases, until March 12th, 2024.

Discovery of active mouse, plant and fungal cytochrome P450s in endogenous proteomes and upon expression in planta.

Eukaryotes produce a large number of cytochrome P450s that mediate the synthesis and degradation of diverse endogenous and exogenous metabolites. Yet, most of these P450s are uncharacterized and global tools to study these challenging, membrane-resident enzymes remain to be exploited. Here, we applied activity profiling of plant, mouse and fungal P450s with chemical probes that become reactive when oxidized by P450 enzymes.

Glioblastoma-instructed microglia transition to heterogeneous phenotypic states with phagocytic and dendritic cell-like features in patient tumors and patient-derived orthotopic xenografts.

Background: A major contributing factor to glioblastoma (GBM) development and progression is its ability to evade the immune system by creating an immune-suppressive environment, where GBM-associated myeloid cells, including resident microglia and peripheral monocyte-derived macrophages, play critical pro-tumoral roles. However, it is unclear whether recruited myeloid cells are phenotypically and functionally identical in GBM patients and whether this heterogeneity is recapitulated in patient-derived orthotopic xenografts (PDOXs). A thorough understanding of the GBM ecosystem and its recapitulation in preclinical models is currently missing, leading to inaccurate results and failures of clinical trials.

AllergoOncology: Biomarkers and refined classification for research in the allergy and glioma nexus-A joint EAACI-EANO position paper.

Epidemiological studies have explored the relationship between allergic diseases and cancer risk or prognosis in AllergoOncology. Some studies suggest an inverse association, but uncertainties remain, including in IgE-mediated diseases and glioma. Allergic disease stems from a Th2-biased immune response to allergens in predisposed atopic individuals.

Beyond the Gut: A Systematic Review and Meta-analysis of Advanced Therapies for Inflammatory Bowel Disease-associated Extraintestinal Manifestations.

Background And Aims: Extraintestinal manifestations are frequent in patients with inflammatory bowel disease and have a negative impact on quality of life. Currently, however, there is no evidence available to determine which drug should be recommended for these patients beyond anti-tumour necrosis factor [anti-TNF] treatment. We aimed to analyse the frequency of new extraintestinal manifestations and the behaviour of pre-existing extraintestinal manifestations during advanced therapy.

Effect of Chitosan on the Number of in Saliva: A Meta-Analysis and Systematic Review.

We conducted a meta-analysis and systematic review to investigate the efficacy of chitosan-containing chewing gums, and to test their inhibitory effects on . The systematic search was performed in three databases (Cochrane Library, EMBASE, and PubMed) and included English-language randomized-controlled trials to compare the efficacy of chitosan in reducing the number of . To assess the certainty of evidence, the GRADE tool was used.

Glioblastoma-instructed microglia transition to heterogeneous phenotypic states with phagocytic and dendritic cell-like features in patient tumors and patient-derived orthotopic xenografts.

Background: A major contributing factor to glioblastoma (GBM) development and progression is its ability to evade the immune system by creating an immune-suppressive environment, where GBM-associated myeloid cells, including resident microglia and peripheral monocyte-derived macrophages, play critical pro-tumoral roles. However, it is unclear whether recruited myeloid cells are phenotypically and functionally identical in GBM patients and whether this heterogeneity is recapitulated in patient-derived orthotopic xenografts (PDOXs). A thorough understanding of the GBM ecosystem and its recapitulation in preclinical models is currently missing, leading to inaccurate results and failures of clinical trials.

Club cells employ regeneration mechanisms during lung tumorigenesis.

The high plasticity of lung epithelial cells, has for many years, confounded the correct identification of the cell-of-origin of lung adenocarcinoma (LUAD), one of the deadliest malignancies worldwide. Here, we employ lineage-tracing mouse models to investigate the cell of origin of Eml4-Alk LUAD, and show that Club and Alveolar type 2 (AT2) cells give rise to tumours. We focus on Club cell originated tumours and find that Club cells experience an epigenetic switch by which they lose their lineage fidelity and gain an AT2-like phenotype after oncogenic transformation.

Systematic evaluation of cell-type deconvolution pipelines for sequencing-based bulk DNA methylomes.

DNA methylation analysis by sequencing is becoming increasingly popular, yielding methylomes at single-base pair and single-molecule resolution. It has tremendous potential for cell-type heterogeneity analysis using intrinsic read-level information. Although diverse deconvolution methods were developed to infer cell-type composition based on bulk sequencing-based methylomes, systematic evaluation has not been performed yet.

Epigenetic reprogramming of airway macrophages promotes polarization and inflammation in muco-obstructive lung disease.

Lung diseases, such as cystic fibrosis and COPD, are characterized by mucus obstruction and chronic airway inflammation, but their mechanistic link remains poorly understood. Here, we focus on the function of the mucostatic airway microenvironment on epigenetic reprogramming of airway macrophages (AM) and resulting transcriptomic and phenotypical changes. Using a mouse model of muco-obstructive lung disease (Scnn1b-transgenic), we identify epigenetically controlled, differentially regulated pathways and transcription factors involved in inflammatory responses and macrophage polarization.

Malignant astrocyte swelling and impaired glutamate clearance drive the expansion of injurious spreading depolarization foci.

Spreading depolarizations (SDs) indicate injury progression and predict worse clinical outcome in acute brain injury. We demonstrate in rodents that acute brain swelling upon cerebral ischemia impairs astroglial glutamate clearance and increases the tissue area invaded by SD. The cytotoxic extracellular glutamate accumulation (>15 µM) predisposes an extensive bulk of tissue (4-5 mm) for a yet undescribed simultaneous depolarization (SiD).

Epigenetic Modulation of Radiation-Induced Diacylglycerol Kinase Alpha Expression Prevents Pro-Fibrotic Fibroblast Response.

Radiotherapy, a common component in cancer treatment, can induce adverse effects including fibrosis in co-irradiated tissues. We previously showed that differential DNA methylation at an enhancer of diacylglycerol kinase alpha () in normal dermal fibroblasts is associated with radiation-induced fibrosis. After irradiation, the transcription factor EGR1 is induced and binds to the hypomethylated enhancer, leading to increased and pro-fibrotic marker expression.

Epigenetic analysis of patients with T-ALL identifies poor outcomes and a hypomethylating agent-responsive subgroup.

Adult "T cell" acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that is associated with poor outcomes, requiring additional therapeutic options. The DNA methylation landscapes of adult T-ALL remain undercharacterized. Here, we systematically analyzed the DNA methylation profiles of normal thymic-sorted T cell subpopulations and 143 primary adult T-ALLs as part of the French GRAALL 2003-2005 trial.

Astrocyte Ca Waves and Subsequent Non-Synchronized Ca Oscillations Coincide with Arteriole Diameter Changes in Response to Spreading Depolarization.

Spreading depolarization (SD) is a wave of mass depolarization that causes profound perfusion changes in acute cerebrovascular diseases. Although the astrocyte response is secondary to the neuronal depolarization with SD, it remains to be explored how glial activity is altered after the passage of SD. Here, we describe post-SD high frequency astrocyte Ca oscillations in the mouse somatosensory cortex.

Integrative analysis reveals early and distinct genetic and epigenetic changes in intraductal papillary and tubulopapillary cholangiocarcinogenesis.

Objective: A detailed understanding of the molecular alterations in different forms of cholangiocarcinogenesis is crucial for a better understanding of cholangiocarcinoma (CCA) and may pave the way to early diagnosis and better treatment options.

Design: We analysed a clinicopathologically well-characterised patient cohort (n=54) with high-grade intraductal papillary (IPNB) or tubulopapillary (ITPN) neoplastic precursor lesions of the biliary tract and correlated the results with an independent non-IPNB/ITPN associated CCA cohort (n=294). The triplet sample set of non-neoplastic biliary epithelium, precursor and invasive CCA was analysed by next generation sequencing, DNA copy number and genome-wide methylation profiling.

Methrix: an R/Bioconductor package for systematic aggregation and analysis of bisulfite sequencing data.

Motivation: Whole-genome bisulfite sequencing (WGBS) measures DNA methylation at base pair resolution resulting in large bedGraph like coverage files. Current options for processing such files are hindered by discrepancies in file format specification, speed, and memory requirements.

Results: We developed methrix, an R package, which provides a toolset for systematic analysis of large datasets.