3,395 results match your criteria: "Ludwig-Maximilians--University of Munich[Affiliation]"

Correcting PCR amplification errors in unique molecular identifiers to generate accurate numbers of sequencing molecules.

Nat Methods

March 2024

Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, National Institute of Health Research Oxford Biomedical Research Unit (BRU), University of Oxford, Oxford, UK.

Unique molecular identifiers are random oligonucleotide sequences that remove PCR amplification biases. However, the impact that PCR associated sequencing errors have on the accuracy of generating absolute counts of RNA molecules is underappreciated. We show that PCR errors are a source of inaccuracy in both bulk and single-cell sequencing data, and synthesizing unique molecular identifiers using homotrimeric nucleotide blocks provides an error-correcting solution that allows absolute counting of sequenced molecules.

View Article and Find Full Text PDF

Introduction: Hypercholesterolemia is a risk factor for premature arteriosclerosis. Inflammation and oxidative stress are thought to contribute to endothelial dysfunction preceding vasculopathy. We investigated the association between inflammation, glycocalyx biomarkers, endothelial function, and vascular parameters in children with hypercholesterolemia.

View Article and Find Full Text PDF

Introduction: Based on two diagnostic accuracy studies in high-prevalence settings, two distinctly different combinations of cut-off values have been recommended to identify persons at risk for somatic symptom disorder (SSD) with the combination of the Patient-Health Questionnaire-15 (PHQ-15) and the Somatic Symptom Disorder-B Criteria Scale (SSD-12). We investigated whether the reported sensitivity and specificity of both recommended cut-off combinations are transferable to primary care.

Methods: In a cross-sectional study, 420 unselected adult primary care patients completed PHQ-15 and SSD-12.

View Article and Find Full Text PDF

Newborn screening for aromatic l-amino acid decarboxylase deficiency - Strategies, results, and implication for prevalence calculations.

Mol Genet Metab

March 2024

Heidelberg University, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Department I, Division of Pediatric Neurology and Metabolic Medicine, Germany. Electronic address:

Background: Aromatic l-amino acid decarboxylase deficiency (AADCD) is a rare, autosomal-recessive neurometabolic disorder caused by variants in dopa decarboxylase (DDC) gene, resulting in a severe combined deficiency of serotonin, dopamine, norepinephrine, and epinephrine. Birth prevalence of AADCD varies by population. In pilot studies, 3-O-methyldopa (3-OMD) was shown to be a reliable biomarker for AADCD in high-throughput newborn screening (NBS) allowing an early diagnosis and access to gene therapy.

View Article and Find Full Text PDF

Introduction: Environmental pollutants injure the mucociliary elevator, thereby provoking disease progression in chronic obstructive pulmonary disease (COPD). Epithelial resilience mechanisms to environmental nanoparticles in health and disease are poorly characterised.

Methods: We delineated the impact of prevalent pollutants such as carbon and zinc oxide nanoparticles, on cellular function and progeny in primary human bronchial epithelial cells (pHBECs) from end-stage COPD (COPD-IV, n=4), early disease (COPD-II, n=3) and pulmonary healthy individuals (n=4).

View Article and Find Full Text PDF

ChatGPT fails challenging the recent ESCMID brain abscess guideline.

J Neurol

April 2024

Department of Neurology with Friedrich-Baur-Institute, LMU University Hospital, LMU Munich (en.), Klinikum Grosshadern of the Ludwig Maximilians University of Munich, Marchioninistr. 15, 81377, Munich, Germany.

Background: With artificial intelligence (AI) on the rise, it remains unclear if AI is able to professionally evaluate medical research and give scientifically valid recommendations.

Aim: This study aimed to assess the accuracy of ChatGPT's responses to ten key questions on brain abscess diagnostics and treatment in comparison to the guideline recently published by the European Society for Clinical Microbiology and Infectious Diseases (ESCMID).

Methods: All ten PECO (Population, Exposure, Comparator, Outcome) questions which had been developed during the guideline process were presented directly to ChatGPT.

View Article and Find Full Text PDF

MHC-I upregulation safeguards neoplastic T cells in the skin against NK cell-mediated eradication in mycosis fungoides.

Nat Commun

January 2024

Department of Dermatology, Lausanne University Hospital (CHUV) and Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.

Cancer-associated immune dysfunction is a major challenge for effective therapies. The emergence of antibodies targeting tumor cell-surface antigens led to advancements in the treatment of hematopoietic malignancies, particularly blood cancers. Yet their impact is constrained against tumors of hematopoietic origin manifesting in the skin.

View Article and Find Full Text PDF

Background: T cell immunoglobulin and mucin-domain containing-3 (TIM-3) is a cell surface molecule that was first discovered on T cells. However, recent studies revealed that it is also highly expressed in acute myeloid leukemia (AML) cells and it is related to AML progression. As, Glutamine appears to play a prominent role in malignant tumor progression, especially in their myeloid group, therefore, in this study we aimed to evaluate the relation between TIM-3/Galectin-9 axis and glutamine metabolism in two types of AML cell lines, HL-60 and THP-1.

View Article and Find Full Text PDF

Safety and efficacy of secukinumab in patients with giant cell arteritis (TitAIN): a randomised, double-blind, placebo-controlled, phase 2 trial.

Lancet Rheumatol

June 2023

Department of Rheumatology and Clinical Immunology, Medical Centre-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Division of Rheumatology and Immunology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. Electronic address:

Background: The treatment of giant cell arteritis with glucocorticoid-sparing agents is an unmet medical need. We evaluated the efficacy and safety of secukinumab, an anti-interleukin-17A monoclonal antibody, in patients with giant cell arteritis.

Methods: We conducted a Bayesian randomised, parallel-group, double-blind, placebo-controlled, multicentre, phase 2 study at 11 clinics or hospitals in Germany.

View Article and Find Full Text PDF

Background And Aims: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population.

Methods: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.

View Article and Find Full Text PDF
Article Synopsis
  • Dermatomyositis is an inflammatory muscle disease characterized by rashes and muscle weakness, with recent research (ProDERM study) focused on the effectiveness of intravenous immunoglobulin (IVIg) as treatment.
  • This study involved 95 adult patients, comparing the effects of IVIg to a placebo over 16 weeks, followed by an extension period where all patients received IVIg.
  • Findings indicated that while some patients experienced treatment-related adverse events (TEAEs), IVIg showed a generally favorable safety profile, with adjustments in dosage reducing certain risks without causing severe complications.
View Article and Find Full Text PDF

Biallelic variants in the calpain regulatory subunit cause pulmonary arterial hypertension.

Genet Med Open

January 2023

Department of Pediatrics, Dr. von Hauner Children's Hospital, LMU Klinikum, Ludwig Maximilians University of Munich, German Center for Lung Research (DZL), Munich, Germany.

Purpose: The aim of this study was to identify the monogenic cause of pulmonary arterial hypertension (PAH), a multifactorial and often fatal disease, in 2 unrelated consanguine families.

Methods: We performed exome sequencing and validated variant pathogenicity by whole-blood RNA and protein expression analysis in both families. Further RNA sequencing of preserved lung tissue was performed to investigate the consequences on selected genes that are involved in angiogenesis, proliferation, and apoptosis.

View Article and Find Full Text PDF

Inflammatory biomarkers in PTSD: A look at the fineprint.

Brain Behav Immun Health

February 2024

Centre of Psychiatry, Psychotherapy and Special Education, Bezirkskrankenhaus Kaufbeuren, Germany.

View Article and Find Full Text PDF

Background: Genetic and experimental studies support a causal involvement of IL-6 (interleukin-6) signaling in atheroprogression. Although trials targeting IL-6 signaling are underway, any benefits must be balanced against an impaired host immune response. Dissecting the mechanisms that mediate the effects of IL-6 signaling on atherosclerosis could offer insights about novel drug targets with more specific effects.

View Article and Find Full Text PDF

Purpose: The present three-dimensional (3D) finite element analysis (FEA) was aimed to assess the biomechanical effects and fracture risks of four different interforaminal implant-prosthodontic anchoring configurations exposed to frontal trauma.

Material And Methods: A symphyseal frontal trauma of 1 MPa was applied to four dental implant models with different configurations (two unsplinted interforaminal implants [2IF-U], two splinted interforaminal implants [2IF-S], four unsplinted interforaminal implants[ 4IF-U], four splinted interforaminal implants [4IF-S]. By using a 3D-FEA analysis the effective cortical bone stress values were evaluated in four defined regions of interest (ROI) (ROI 1: symphyseal area; ROI 2: preforaminal area; ROI 3: mental foraminal area; and ROI 4: condylar neck) followed by a subsequent intermodel comparison.

View Article and Find Full Text PDF

Life-Saving Treatments for Spinal Muscular Atrophy: Global Access and Availability.

Neurol Clin Pract

February 2024

Department of Neurology (VDA, BR), Yale University School of Medicine, New Haven, CT; Department of Neurology (BTD), Boston Children's Hospital, MA; Department of Medicine (AAA), King Saud Bin Abdulaziz University for Health Sciences; Neuromuscular Integrated Practice Unit (AA), Neuroscience Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; Department of Pediatrics (NB), University of Zagreb Medical School, Croatia; Genetics and Genomic Medicine Division (TB-O), Sidra Medicine and Hamad Medical Corporation, Doha, Qatar; Department of Pediatrics (GB), Klinik Favoriten, Vienna, Austria; Department of Pediatrics (CC), Clínica Meds, Santiago, Chile; Department of Medical Genetics and Pediatrics (Y-HC), National Taiwan University Hospital, Taipei; Department of Neurology (MAF), Sydney Children's Hospital Network, New South Wales, Australia; Department of Paediatrics and Child Health (GK), College of Health Sciences, University of Zimbabwe, Harare; Department of Neurology (SK), Bombay Hospital, India; Department of Pediatrics (JM), University of Calgary Cumming School of Medicine, Alberta, Canada; John Walton Muscular Dystrophy Research Centre (CM-B), Newcastle University, Newcastle Upon Tyne, United Kingdom; Department of Child (DO), Adolescent, and Developmental Neurology, Children's Hospital, University Medical Centre Ljubljana, Slovenia; Department of Medical Genetics (GP), University of Calgary Cumming School of Medicine, Alberta, Canada; Neurometabolic Unit (FBP), University of Sao Paulo, Brazil; Department of Pediatrics (IPC), Hospital Universitari i Politècnic La Fe, Valencia, Spain; Child Neurology and ICU Department (SQ-R), Raymond Poincaré University Hospital (UVSQ), Garche, France; Institute of Medical Genetics (KS), Tokyo Women's Medical University, Japan; Department of Neurology (J-HS), Pusan National University Yangsan Hospital, South Korea; Neuromuscular Unit (JFV-C), Hospital Universitario y Politécnico la Fe, Valencia, Spain; Friedrich-Baur-Institute (MCW), Department of Neurology, Ludwig-Maximilians-University of Munich, Germany; Department of Paediatrics (JW), University of Colombo, Sri Lanka; Department of Pediatrics (HX), Peking University First Hospital, China; and Department of Neurology (RCG), University of Rochester Medical Center, NY.

Article Synopsis
  • Spinal muscular atrophy (SMA) is a serious neurodegenerative disorder that has seen significant treatment advancements, allowing many patients to lead normal lives, particularly with therapies like Nusinersen, risdiplam, and onasemnogene abeparvovec-xioi now approved.
  • A qualitative study surveyed healthcare providers in 21 countries to explore the availability and implementation of SMA treatments, revealing inconsistencies in drug access, newborn screening, and significant economic barriers to care.
  • The findings emphasize the global inequalities in SMA management and highlight the need for expanded newborn screening to ensure better treatment access and address future challenges in genetic disease therapies.
View Article and Find Full Text PDF

Background: The role of cytoreductive surgery combined with hyperthermic intrathoracic chemotherapy (CRS+HITOC) for patients with secondary pleural metastases has scarcely been investigated.

Patients And Methods: We conducted a retrospective, multicentre study investigating the outcome of CRS+HITOC for 31 patients with pleural metastases from different primary tumours in four high-volume departments of thoracic surgery in Germany. The primary endpoint was overall survival (OS).

View Article and Find Full Text PDF

Draft genome sequences of two thermophilic, spore-forming strains isolated from dairy products.

Microbiol Resour Announc

January 2024

Department of Veterinary Sciences, Faculty of Veterinary Medicine, Ludwig-Maximilians University of Munich, Oberschleiβheim, Germany.

The presence of thermophilic spore-forming bacteria is challenging in industrial food processing. The presented genome sequences of , isolated from raw milk and cocoa powder, provide insights into how to prevent damage to minimally processed foods and products with extended shelf life, such as milk products.

View Article and Find Full Text PDF

How organisms obtain energy to survive and reproduce is fundamental to ecology, yet researchers use theoretical concepts represented by simplified models to estimate diet and predict community interactions. Such simplistic models can sometimes limit our understanding of ecological principles. We used a polyphagous species with a wide distribution, the brown bear (Ursus arctos), to illustrate how disparate theoretical frameworks in ecology can affect conclusions regarding ecological communities.

View Article and Find Full Text PDF

Ex vivo tissue perturbations coupled to single-cell RNA-seq reveal multilineage cell circuit dynamics in human lung fibrogenesis.

Sci Transl Med

December 2023

Comprehensive Pneumology Center (CPC) with the CPC-M bioArchive/Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Member of the German Center for Lung Research (DZL), 81377 Munich, Germany.

Pulmonary fibrosis develops as a consequence of failed regeneration after injury. Analyzing mechanisms of regeneration and fibrogenesis directly in human tissue has been hampered by the lack of organotypic models and analytical techniques. In this work, we coupled ex vivo cytokine and drug perturbations of human precision-cut lung slices (hPCLS) with single-cell RNA sequencing and induced a multilineage circuit of fibrogenic cell states in hPCLS.

View Article and Find Full Text PDF

Background: The parametric go/no-go (PGNG) task is a computerized task that is designed to measure cognitive flexibility, response inhibition, and working memory. The PGNG task has been shown to measure core executive functions (EFs) in a psychometrically sound, brief, and ecologically valid manner.

Objective: To analyze the psychometric properties of the Dutch version of the PGNG task in a convenience sample of nonclinical adults.

View Article and Find Full Text PDF