8,110 results match your criteria: "Germany T.P.; and AOK Research Institute WIdO[Affiliation]"

One in ten adults in Europe have chronic insomnia, which is characterised by frequent and persistent difficulties initiating and/or maintaining sleep and daily functioning impairments. Regional differences in practices and access to healthcare services lead to variable clinical care across Europe. Typically, a patient with chronic insomnia (a) will usually present to a primary care physician; (b) will not be offered cognitive behavioural therapy for insomnia-the recommended first-line treatment; (c) will instead receive sleep hygiene recommendations and eventually pharmacotherapy to manage their long-term condition; and (d) will use medications such as GABA receptor agonists for longer than the approved duration.

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Clinical testing panels for ALS: global distribution, consistency, and challenges.

Amyotroph Lateral Scler Frontotemporal Degener

August 2023

Department of Genetics, Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.

: In 2021, the Clinical Genome Resource (ClinGen) amyotrophic lateral sclerosis (ALS) spectrum disorders Gene Curation Expert Panel (GCEP) was established to evaluate the strength of evidence for genes previously reported to be associated with ALS. Through this endeavor, we will provide standardized guidance to laboratories on which genes should be included in clinical genetic testing panels for ALS. In this manuscript, we aimed to assess the heterogeneity in the current global landscape of clinical genetic testing for ALS.

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Article Synopsis
  • Computationally designed protein nanoparticles are gaining attention as a new platform for creating vaccines and biologics, but they often have trouble being secreted from eukaryotic cells.
  • The research reveals that the design of these nanoparticles can unintentionally create hidden sections that mimic transmembrane domains, hindering their secretion.
  • A new computational tool, called the Degreaser, helps redesign these nanoparticles to eliminate the problematic regions, significantly improving their secretion efficiency while maintaining stability, making them more applicable in biotechnology.
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Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors.

N Engl J Med

March 2023

From Sarcoma Medical Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical College, New York (M.G.), and Northwell Health Cancer Institute, New Hyde Park (T.P.) - all in New York; the Department of Sarcoma Medical Oncology, Division of Cancer Medicine, University of Texas M.D. Anderson Cancer Center, Houston (R.R.); the Department of Oncology, McGill University, Montreal (T.A.); the Department of General Medical Oncology, University Hospitals Leuven, KU Leuven, Leuven (P.S.), the Department of Medical Oncology, Ghent University Hospital, Ghent University, Ghent (L.L.), and King Albert II Cancer Institute, Cliniques Universitaires Saint-Luc, Catholic University of Louvain, Brussels (F.M.) - all in Belgium; the Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam (W.T.G.), and the Department of Medical Oncology, Leiden University Medical Center, Leiden (H.G.) - both in the Netherlands; the Department of Medicine, University of Colorado Cancer Center, Aurora (B.A.W.); Duke Cancer Institute, Duke University Medical Center (R.F.R.), and PharPoint Research (S.M.) - both in Durham, NC; SpringWorks Therapeutics, Stamford (A.L., L.M.S.), and Smilow Cancer Hospital, Yale Cancer Center, Yale School of Medicine, Yale University, New Haven (H.D.) - both in Connecticut; the Department of Hematology and Oncology, Mayo Clinic, Jacksonville (S.A.), and Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami (G.D.) - both in Florida; the Sarcoma Oncology Center, Santa Monica (S.C.), the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (N.F.), and the Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford (N.Q.B.) - all in California; the Sarcoma and Bone Cancer Treatment Center, Dana-Farber Cancer Institute and Harvard Medical School (P.M.), and the Henri and Belinda Termeer Center for Targeted Therapies, Massachusetts General Hospital Cancer Center (G.M.C.) - both in Boston; Washington University in St. Louis, St. Louis (B.A.V.T.); the Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, and Fondazione Policlinico Universitario Campus Bio-Medico - both in Rome (B.V.), the Osteoncology, Bone and Soft Tissue Sarcoma, and Innovative Therapy Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna (E.P.), the Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (S.S.), and Medical Oncology, Candiolo Cancer Institute FPO-IRCCS, Candiolo (G.G.) - all in Italy; the Royal Marsden NHS Foundation Trust (C.B.) and the Department of Medical Oncology, University College London Hospital Foundation Trust (P.D.) - both in London; the University of Michigan Rogel Cancer Center, Ann Arbor (R.C.); the Ohio State University Comprehensive Cancer Center, Columbus (G.T.), and the Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati (J.G.P.); the Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee (J.C.), and the University of Wisconsin Carbone Cancer Center, Madison (H.H.B.); the Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania, Philadelphia (L.H.), and the University of Pittsburgh Medical Center, Pittsburgh (M.A.B.); the Sarcoma Center Berlin-Brandenburg, Helios Klinikum Berlin-Buch, Berlin (P.R.), and the University of Heidelberg, Mannheim University Medical Center, Mannheim Cancer Center, Sarcoma Unit, Mannheim (B.K.) - both in Germany; the Knight Cancer Institute, Oregon Health and Science University, Portland (L.E.D., S.K.); and the Division of Medical Oncology, University of Washington, the Clinical Research Division, Fred Hutchinson Cancer Research Center, and Seattle Cancer Care Alliance, Seattle (E.L.).

Article Synopsis
  • * ! The trial showed that nirogacestat significantly improved progression-free survival (76% event-free at 2 years) compared to placebo (44%), with a higher rate of objective responses (41% vs. 8%).
  • * ! While nirogacestat had notable benefits, it also caused common side effects like diarrhea (84%) and nausea (54%), and 75% of women of childbearing potential experienced issues related to ovarian function.
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  • The study examines the impact of treating paravalvular regurgitation (PVR) after transcatheter aortic valve implantation (TAVI) and its association with morbidity and mortality.
  • A total of 201 patients were treated for moderate PVR using various interventions, including redo-TAVI, plug closure, and balloon valvuloplasty, with outcomes measured at 30 days and 1 year.
  • Findings indicate that successful reduction of aortic regurgitation (AR) to mild levels significantly improved 1-year mortality rates, suggesting that treatment decisions and patient selection for PVR interventions need further research.
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Background: Randomized controlled trials (RCTs) from low- and middle-income settings suggested that early initiation of antiretroviral therapy (ART) leads to higher mortality rates among people with HIV (PWH) who present with cryptococcal meningitis (CM). There is limited information about the impact of ART timing on mortality rates in similar people in high-income settings.

Methods: Data on ART-naive PWH with CM diagnosed from 1994 to 2012 from Europe/North America were pooled from the COHERE, NA-ACCORD, and CNICS HIV cohort collaborations.

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Article Synopsis
  • * A virtual 3-day hackathon brought together 49 early-career scientists from 12 countries, focusing on building tools and pipelines specifically for PD research, with each team working on one of nine distinct projects.
  • * The hackathon not only generated resources to enhance research but also provided training and networking opportunities, ultimately fostering creative problem-solving and collaboration essential for emerging researchers in data science.
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Objective: To estimate the risk of progression to stage 3 type 1 diabetes based on varying definitions of multiple islet autoantibody positivity (mIA).

Research Design And Methods: Type 1 Diabetes Intelligence (T1DI) is a combined prospective data set of children from Finland, Germany, Sweden, and the U.S.

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A New CSRML Structure-Based Fingerprint Method for Profiling and Categorizing Per- and Polyfluoroalkyl Substances (PFAS).

Chem Res Toxicol

March 2023

Center for Computational Toxicology & Exposure, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, Durham, North Carolina 27711, United States.

The term PFAS encompasses diverse per- and polyfluorinated alkyl (and increasingly aromatic) chemicals spanning industrial processes, commercial uses, environmental occurrence, and potential concerns. With increased chemical curation, currently exceeding 14,000 structures in the PFASSTRUCTV5 inventory on EPA's CompTox Chemicals Dashboard, has come increased motivation to profile, categorize, and analyze the PFAS structure space using modern cheminformatics approaches. Making use of the publicly available ToxPrint chemotypes and ChemoTyper application, we have developed a new PFAS-specific fingerprint set consisting of 129 TxP_PFAS chemotypes coded in CSRML, a chemical-based XML-query language.

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The complement system plays a crucial role in host defense, homeostasis, and tissue regeneration and bridges the innate and the adaptive immune systems. Although the genetic variants in complement C2 (c.839_849+17del; p.

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Continuous symmetry breaking in a two-dimensional Rydberg array.

Nature

April 2023

Institute of Optics Graduate School, CNRS, Charles Fabry Laboratory, University of Paris-Saclay, Palaiseau Cedex, France.

Spontaneous symmetry breaking underlies much of our classification of phases of matter and their associated transitions. The nature of the underlying symmetry being broken determines many of the qualitative properties of the phase; this is illustrated by the case of discrete versus continuous symmetry breaking. Indeed, in contrast to the discrete case, the breaking of a continuous symmetry leads to the emergence of gapless Goldstone modes controlling, for instance, the thermodynamic stability of the ordered phase.

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Article Synopsis
  • Atrial fibrillation (AF) is a major contributor to ischemic stroke, which greatly impacts health and mortality rates, especially as the aging population grows.
  • There are various stroke prevention methods available, yet significant questions persist regarding the best strategies for both broader populations and individual patients in managing AF.
  • The National Heart, Lung, and Blood Institute workshop highlighted research areas for improvement, including risk assessment tools, challenges related to oral anticoagulants, and the effectiveness of different left atrial appendage closure techniques in stroke prevention for AF patients.
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Novel Variants of in Patients with Intellectual Disability.

Int J Mol Sci

February 2023

Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, 47057 Duisburg, Germany.

SOX4 is a transcription factor with pleiotropic functions required for different developmental processes, such as corticogenesis. As with all SOX proteins, it contains a conserved high mobility group (HMG) and exerts its function via interaction with other transcription factors, such as POU3F2. Recently, pathogenic variants have been identified in several patients who had clinical features overlapping with Coffin-Siris syndrome.

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Charcot-Marie-Tooth disease (CMT) and autosomal recessive spastic ataxia of Charlevoix-Saguenay type (ARSACS) are large heterogeneous groups of sensory, neurological genetic disorders characterized by sensory neuropathies, muscular atrophies, abnormal sensory conduction velocities, and ataxia. CMT2EE (OMIM: 618400) is caused by mutations in (OMIM: 137960), CMT4F (OMIM: 614895) is caused by (OMIM: 605725), CMTX1 (OMIM: 302800) is caused by mutations in (OMIM: 304040), and ARSACS (OMIM: 270550) is caused by mutations in (OMIM: 604490). In this study, we enrolled four families: DG-01, BD-06, MR-01, and ICP-RD11, with 16 affected individuals, for clinical and molecular diagnoses.

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Gait Analysis to Monitor Fracture Healing of the Lower Leg.

Bioengineering (Basel)

February 2023

Werner Siemens-Endowed Chair for Innovative Implant Development (Fracture Healing), Clinics and Institutes of Surgery, Saarland University, 66421 Homburg, Germany.

Fracture healing is typically monitored by infrequent radiographs. Radiographs come at the cost of radiation exposure and reflect fracture healing with a time lag due to delayed fracture mineralization following increases in stiffness. Since union problems frequently occur after fractures, better and timelier methods to monitor the healing process are required.

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Article Synopsis
  • The global scientific community has sequenced over 11 million SARS-CoV-2 genomes by May 2022, allowing real-time tracking of virus evolution.
  • Outbreak.info is a platform that monitors over 40 million variants and mutations across 7,000 locations, providing valuable insights for researchers and public health officials.
  • The platform features user-friendly visualizations and robust infrastructure for data ingestion and dissemination, supporting genomic surveillance and hypothesis generation regarding the pandemic.
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Deep learning approaches are playing an ever-increasing role throughout diagnostic medicine, especially in neuroradiology, to solve a wide range of problems such as segmentation, synthesis of missing sequences, and image quality improvement. Of particular interest is their application in the reduction of gadolinium-based contrast agents, the administration of which has been under cautious reevaluation in recent years because of concerns about gadolinium deposition and its unclear long-term consequences. A growing number of studies are investigating the reduction (low-dose approach) or even complete substitution (zero-dose approach) of gadolinium-based contrast agents in diverse patient populations using a variety of deep learning methods.

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Human cleavage and polyadenylation specificity factor (CPSF)73 (also known as CPSF3) is the endoribonuclease that catalyzes the cleavage reaction for the 3'-end processing of pre-mRNAs. The active site of CPSF73 is located at the interface between a metallo-β-lactamase domain and a β-CASP domain. Two metal ions are coordinated by conserved residues, five His and two Asp, in the active site, and they are critical for the nuclease reaction.

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We report a detailed study on the magnetic behaviors and magnetocaloric (MC) effect of a single crystal of lithium samarium tetraphosphate, LiSm(PO). The analyses of temperature-dependent magnetization data have revealed magnetic ordering established with decreasing temperature below , where is the minimum of a d/d curve and varies as a linear function of the applied field . The Curie temperature has been extrapolated from () data, as → 0, to be about 0.

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Bat pluripotent stem cells reveal unusual entanglement between host and viruses.

Cell

March 2023

Huffington Center for Cell-Based Research in Parkinson's disease, Icahn School of Medicine at Mount Sinai, New York, NY 10502, USA; Department of Cell, Developmental, and Regenerative Biology, and Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10502, USA; Paratus Sciences, 430 East 29th Street, Suite 600, New York, NY 10016, USA. Electronic address:

Article Synopsis
  • * Researchers developed induced pluripotent stem cells (iPSCs) from two bat species, the greater horseshoe bat and the greater mouse-eared bat, which display similar characteristics and a gene expression profile linked to viral infection.
  • * The findings indicate that bats host many viral sequences and have adapted mechanisms for virus tolerance, paving the way for further investigations into bat biology, their relationship with viruses, and the genetic basis of their unique traits.
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Purpose: To investigate the effect of Rose Bengal photodynamic therapy (RB-PDT) on viability and proliferation of human limbal epithelial stem cells (T-LSCs), human corneal epithelial cells (HCE-T), human limbal fibroblasts (LFCs), and human normal and keratoconus fibroblasts (HCFs and KC-HCFs) .

Methods: T-LSCs and HCE-T cell lines were used in this research. LFCs were isolated from healthy donor corneal limbi (n = 5), HCFs from healthy human donor corneas (n = 5), and KC-HCFs from penetrating keratoplasties of keratoconus patients (n = 5).

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Congenital Synostosis of the Knee: Long-term Outcomes of Limb Reconstruction Surgery.

J Pediatr Orthop

April 2023

International Center for Limb Lengthening, Rubin Institute for Advanced Orthopedics, Sinai Hospital of Baltimore, Baltimore, MD.

Background: Congenital synostosis of the knee is a rare condition with limited data on treatment options and outcomes. This study reports clinical findings, treatment approach, and surgical/clinical outcomes for congenital synostosis of the knee.

Methods: An institutional review board-approved retrospective review of patients with congenital synostosis of the knee presenting to 2 institutions between 1997 and 2021 was performed.

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Background: Incidence is one of the most important epidemiologic indices in surveillance. However, determining incidence is complex and requires time-consuming cohort studies or registries with date of diagnosis. Estimating incidence from prevalence using mathematical relationships may facilitate surveillance efforts.

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Early computational detection of potential high-risk SARS-CoV-2 variants.

Comput Biol Med

March 2023

BioNTech SE, An der Goldgrube 12, 55131, Mainz, Germany. Electronic address:

The ongoing COVID-19 pandemic is leading to the discovery of hundreds of novel SARS-CoV-2 variants daily. While most variants do not impact the course of the pandemic, some variants pose an increased risk when the acquired mutations allow better evasion of antibody neutralisation or increased transmissibility. Early detection of such high-risk variants (HRVs) is paramount for the proper management of the pandemic.

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Rationale And Objectives: In breast MRI with diffusion-weighted imaging (DWI), fat suppression is essential for eliminating the dominant lipid signal. This investigation evaluates a combined water-excitation-spectral-fatsat method (WEXfs) versus standard spectral attenuated inversion recovery (SPAIR) in high-resolution 3-Tesla breast MRI.

Materials And Methods: Multiparametric breast MRI with 2 echo-planar DWI sequences was performed in 83 patients (50.

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