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.

Initial Multicenter Experience With a Novel Self-Expanding TAVR System in Patients With Aortic Valve Stenosis.

Background: As transcatheter aortic valve replacement is performed increasingly in younger, low-risk patients, the need for commissural alignment and coronary access has increased. Design elements of the JenaValve Trilogy (JVT) transcatheter heart valve (THV) ensure both.

Objectives: This study sought to evaluate the outcome of patients with aortic stenosis (AS) treated with this novel transfemoral, self-expanding THV.

Pharmacologically induced proteolysis of histone deacetylase-6 attenuates influenza virus replication despite limited anti-tumor effects.

The protein deacetylase HDAC6 has been controversially linked to cancer cell proliferation and viral propagation. We analyzed whether a pharmacological depletion of HDAC6 with a recent proteolysis-targeting chimera (PROTAC) kills tumor cells. We show that low micromolar doses of the cereblon-based PROTAC TH170, but not its inactive analog TH170E, induce proteasomal degradation of HDAC6.

Middle-throughput LC-MS-based platelet proteomics with minute sample amounts using semi-automated positive pressure FASP in 384-well format (PF384).

Comprehensive characterization of platelets requires various functional assays and analysis techniques, including omics-disciplines, each requiring an individual aliquot of a given sample. Consequently, the sample material per assay is often highly limited rendering downscaling a prerequisite for effective sample exploitation. Here we present a transfer of our recently introduced 96-well-based proteomics workflow (PF96) into the 384-well format (PF384) allowing for a significant increase in sensitivity when processing minute platelet protein amounts.

Discovery of Laacher See eruption in speleothem record synchronizes Greenland and central European Late Glacial climate change.

To assess the impact of ongoing, historically unprecedented Arctic ice melting, precisely synchronized chronologies are indispensable for past analogs of abrupt climate change. Around 12,900 years before present (B.P.

Impact of developmental temperature on neural growth, connectivity, and function.

Environmental temperature dictates the developmental pace of poikilothermic animals. In , slower development at lower temperatures results in higher brain connectivity, but the generality of such scaling across temperatures and brain regions and its impact on function are unclear. Here, we show that brain connectivity scales continuously across temperatures, in agreement with a first-principle model that postulates different metabolic constraints for the growth of the brain and the organism.

Clinical consequence of the 4-week X-ray control after ESIN osteosynthesis of forearm fractures in children.

Purpose: The absence of evidence based general guidelines for radiographic follow-ups of pediatric diaphyseal forearm fractures treated with ESIN results in an arbitrary array of X-ray examinations. In most pediatric traumatology departments, an X-ray check is carried out 4 weeks after ESIN osteosynthesis of forearm shaft fractures to detect incipient consolidation of the fracture. However, the elevated sensitivity to ionizing radiation requires special precautions in the pediatric populations.

BDNF levels in serum and CSF are associated with clinicoradiological characteristics of aggressive disease in MS patients.

Background: BDNF has increasingly gained attention as a key molecule controlling remyelination with a prominent role in neuroplasticity and neuroprotection. Still, it remains unclear how BDNF relates to clinicoradiological characteristics particularly at the early stage of the disease where precise prognosis for the further MS course is crucial.

Methods: BDNF, NfL and GFAP concentrations in serum and CSF were assessed in 106 treatment naïve patients with MS (pwMS) as well as 73 patients with other inflammatory/non-inflammatory neurological or somatoform disorders using a single molecule array HD-1 analyser.

Cost-effectiveness of follow-up algorithms for chronic thromboembolic pulmonary hypertension in pulmonary embolism survivors.

Introduction: Achieving an early diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) in pulmonary embolism (PE) survivors results in better quality of life and survival. Importantly, dedicated follow-up strategies to achieve an earlier CTEPH diagnosis involve costs that were not explicitly incorporated in the models assessing their cost-effectiveness. We performed an economic evaluation of 11 distinct PE follow-up algorithms to determine which should be preferred.

Effectiveness of a stepped-care programme of WHO psychological interventions in a population of migrants: results from the RESPOND randomized controlled trial.

Migrant populations - including labour migrants, undocumented migrants, asylum seekers, refugees, internationally displaced persons, and other populations on the move - are exposed to a variety of stressors that affect their mental health. We designed and tested the effectiveness of a stepped-care programme consisting of two scalable psychological interventions developed by the World Health Organization (WHO) and locally adapted for migrant populations. A parallel-group randomized controlled trial was conducted in Italy.

Tumor-infiltrating plasma cells are a prognostic factor in penile squamous cell carcinoma.

Penile cancer (PeCa) is a rare disease with poor prognosis in the metastatic stage. Neither effective adjuvant nor palliative therapeutic options are available. Research efforts in this field have so far failed to establish robust predictors of survival.

[Resilience as an integral component of action competence in internal medicine].

Physicians in internal medicine are exposed to high levels of stress. Conditions of chronic emotional fatigue and burnout are widespread. Resilience, the ability to cope with difficult situations and to adapt to adverse circumstances, is essential.

Molecular dynamics-guided reaction discovery reveals endoperoxide-to-alkoxy radical isomerization as key branching point in α-pinene ozonolysis.

Secondary organic aerosols (SOAs) significantly impact Earth's climate and human health. Although the oxidation of volatile organic compounds (VOCs) has been recognized as the major contributor to the atmospheric SOA budget, the mechanisms by which this process produces SOA-forming highly oxygenated organic molecules (HOMs) remain unclear. A major challenge is navigating the complex chemical landscape of these transformations, which traditional hypothesis-driven methods fail to thoroughly investigate.

[Arthropathy as the first manifestation of undiagnosed hemochromatosis: a case report on an unusual course].

A 54-year-old man presented with increasing arthralgia and swelling of the metacarpophalangeal (MCP) joints II and III for approximately 2 years. He also reported morning stiffness and joint pain in both knees and feet.Both MCP joints II and III and the proximal interphalangeal joints II and III were tender without visible swelling.

Diketopiperazine/piperidine alkaloid as a potential broad-spectrum coronaviral entry inhibitor identified by supercomputer-based virtual screening from a large natural product-based library.

The COVID-19 pandemic has underscored the urgent need for antiviral agents capable of targeting a broad range of coronaviruses, including emerging variants of SARS-CoV-2. While vaccines have been pivotal, the search for drugs that can prevent viral entry into host cells remains crucial, especially against evolving viral forms and other coronaviruses. In this study, we investigated natural products as a source of antiviral agents, focusing on their potential to block the spike protein's receptor-binding domain (RBD).

The role of intolerance of uncertainty in health anxiety in cancer patients: Exploring demographic and cancer-related variations.

Purpose: Health anxiety (HA) is a critical issue for cancer patients. This study investigates the role of intolerance of uncertainty (IU) in HA among a heterogeneous sample of cancer patients, comparing those with hematological malignancies and solid tumor cancers. It also explores the impact of demographic and cancer-related factors on HA.

Evolutionary Pressures Shape Undifferentiated Pleomorphic Sarcoma Development and Radiotherapy Response.

Radiotherapy is an integral component in the treatment of many types of cancer, with approximately half of cancer patients receiving radiotherapy. Systemic therapy applies pressure that can select for resistant tumor subpopulations, underscoring the importance of understanding how radiation impacts tumor evolution to improve treatment outcomes. We integrated temporal genomic profiling of 120 spatially distinct tumor regions from 20 patients with undifferentiated pleomorphic sarcomas (UPS), longitudinal circulating tumor DNA (ctDNA) analysis, and evolutionary biology computational pipelines to study UPS evolution during tumorigenesis and in response to radiotherapy.

HSPG-binding peptide Pep19-2.5 is a potent inhibitor of HPV16 infection.

Peptide-based therapeutics are gaining attention for their potential to target various viral and host cell factors. One notable example is Pep19-2.5 (Aspidasept), a synthetic anti-lipopolysaccharide peptide that binds to heparan sulfate proteoglycans (HSPGs) and has demonstrated inhibitory effects against certain bacteria and enveloped viruses.

Protonation effects in protein-ligand complexes - a case study of endothiapepsin and pepstatin A with computational and experimental methods.

Protonation states serve as an essential molecular recognition motif for biological processes. Their correct consideration is key to successful drug design campaigns, since chemoinformatic tools usually deal with default protonation states of ligands and proteins and miss atypical protonation states. The protonation pattern for the Endothiapepsin/PepstatinA (EP/pepA) complex is investigated using different dry lab and wet lab techniques.

Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis.

Obesity poses a global health challenge, demanding a deeper understanding of adipose tissue (AT) and its mitochondria. This study describes the role of the mitochondrial protein Methylation-controlled J protein (MCJ/DnaJC15) in orchestrating brown adipose tissue (BAT) thermogenesis. Here we show how MCJ expression decreases during obesity, as evident in human and mouse adipose tissue samples.

Type 1 diabetes incidence curves differ by age for girls and boys between 1996 and 2022: Results from the North Rhine-Westphalia Diabetes Registry, Germany.

The type 1 diabetes incidence was analyzed in 0- to 14-year-old children in North Rhine-Westphalia, Germany, from 1996 to 2022. The data revealed an overall increasing trend, with variations by age and sex. The incidence increased in boys across age groups but peaked in girls in the 5-9-year age group.