Altered Neural Responses to Punishment Learning in Conduct Disorder.

Objective: Conduct disorder (CD) is associated with deficits in the use of punishment for reinforcement learning (RL) and subsequent decision-making, contributing to reckless, antisocial, and aggressive behaviors. Here, we used functional magnetic resonance imaging (fMRI) to examine whether differences in behavioral learning rates derived from computational modeling, particularly for punishment, are reflected in aberrant neural responses in youths with CD compared to typically-developing controls (TDCs).

Methods: 75 youths with CD and 99 TDCs (9-18 years, 47% girls) performed a probabilistic RL task with punishment, reward, and neutral contingencies.

Focusing on microvascular function in heart failure with preserved ejection fraction.

Heart failure is a prevalent global health issue. Heart failure with preserved ejection fraction (HFpEF), which already represents half of all heart cases worldwide, is projected to further increase, driven by aging populations and rising cardiovascular risk factors. Effective therapies for HFpEF remain limited, particularly due to its pathophysiological heterogeneity and incomplete understanding of underlying pathomechanisms and implications.

A multimodal neural signature of face processing in autism within the fusiform gyrus.

Atypical face processing is commonly reported in autism. Its neural correlates have been explored extensively across single neuroimaging modalities within key regions of the face processing network, such as the fusiform gyrus (FFG). Nonetheless, it is poorly understood how variation in brain anatomy and function jointly impacts face processing and social functioning.

DARPin-induced reactivation of p53 in HPV-positive cells.

Infection of cells with high-risk strains of the human papillomavirus (HPV) causes cancer in various types of epithelial tissue. HPV infections are responsible for ~4.5% of all cancers worldwide.

A new hypothesis to explain disease dominance.

The onset and progression of dominant diseases are thought to result from haploinsufficiency or dominant negative effects. Here, we propose transcriptional adaptation (TA), a newly identified response to mRNA decay, as an additional cause of some dominant diseases. TA modulates the expression of so-called adapting genes, likely via mRNA decay products, resulting in genetic compensation or a worsening of the phenotype.

Detection of Hepatitis C Virus Infection from Patient Sera in Cell Culture Using Semi-Automated Image Analysis.

The study of hepatitis C virus (HCV) replication in cell culture is mainly based on cloned viral isolates requiring adaptation for efficient replication in Huh7 hepatoma cells. The analysis of wild-type (WT) isolates was enabled by the expression of SEC14L2 and by inhibitors targeting deleterious host factors. Here, we aimed to optimize cell culture models to allow infection with HCV from patient sera.

The endocannabinoid anandamide prevents TH17 programming of activated T lymphocytes while preserving TH1 responses.

Introduction: Anandamide (AEA) is an endocannabinoid that has recently been recognized as a regulator of various inflammatory diseases as well as cancer. While AEA was thought to predominantly engage cannabinoid (CB) receptors, recent findings suggest that, given its protective anti-inflammatory role in pathological conditions, anandamide may engage not only CB receptors.

Methods: In this study, we studied the role of exogenous AEA in a mouse AirPouch model of acute inflammation by examining immune cell infiltrates by flow cytometry.

The sarcoma ring trial: a case-based analysis of inter-center agreement across 21 German-speaking sarcoma centers.

Purpose: The management of soft tissue sarcoma (STS) at reference centers with specialized multidisciplinary tumor boards (MTB) improves patient survival. The German Cancer Society (DKG) certifies sarcoma centers in German-speaking countries, promoting high standards of care. This study investigated the variability in treatment recommendations for localized STS across different German-speaking tertiary sarcoma centers.

Long non-coding RNAs direct the SWI/SNF complex to cell type-specific enhancers.

The coordination of chromatin remodeling is essential for DNA accessibility and gene expression control. The highly conserved and ubiquitously expressed SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex plays a central role in cell type- and context-dependent gene expression. Despite the absence of a defined DNA recognition motif, SWI/SNF binds lineage specific enhancers genome-wide where it actively maintains open chromatin state.

Linear ubiquitination at damaged lysosomes induces local NFKB activation and controls cell survival.

Lysosomes are the major cellular organelles responsible for nutrient recycling and degradation of cellular material. Maintenance of lysosomal integrity is essential for cellular homeostasis and lysosomal membrane permeabilization (LMP) sensitizes toward cell death. Damaged lysosomes are repaired or degraded via lysophagy, during which glycans, exposed on ruptured lysosomal membranes, are recognized by galectins leading to K48- and K63-linked poly-ubiquitination (poly-Ub) of lysosomal proteins followed by recruitment of the macroautophagic/autophagic machinery and degradation.

Impact of inhibitory KIR ligand mismatch and other variables on outcomes following myeloablative posttransplant cyclophosphamide-based T-cell-replete haploidentical bone marrow transplantation.

Introduction: Posttransplant cyclophosphamide (PTCy) has revolutionized the landscape of human leukocyte antigen (HLA)-haploidentical hematopoietic cell transplantation (haplo-HCT), providing a pivotal therapeutic option for patients with hematological malignancies who lack an HLA-matched donor.

Methods: In this retrospective analysis involving 54 adult patients undergoing PTCy-based haplo-HCT, we evaluated the impact of inhibitory killer immunoglobulin-like receptor (KIR)/HLA mismatch, alongside patient, donor, and transplant factors, on clinical outcomes within a homogeneous cohort characterized by a myeloablative conditioning regimen and bone marrow graft.

Results: With a median follow-up of 73.

Predicting cisplatin tolerability in older adults with head and neck cancer - Insights for improved chemoradiation outcomes.

Purpose: Cumulative cisplatin doses of ≥ 200 mg/m improve survival in adults with head-and-neck squamous cell carcinoma (HNSCC) undergoing chemoradiation, but many older adults with HNSCC cannot receive this prognostically relevant dose due to toxicities. This study aims to develop predictive models to assess the likelihood of older adults with HNSCC receiving ≥ 200 mg/m cisplatin during chemoradiation.

Methods: 366 patients from the SENIOR database, an international cohort of adults ≥ 65 years with HNSCC, received definitive chemoradiation with single-agent cisplatin and were analyzed.

Femoral or Radial Secondary Access in TAVR: A Subanalysis From the Multicenter PULSE Registry.

Background: Transradial secondary access (TR-SA) may serve as an alternative to the traditional femoral secondary access (TF-SA) for pigtail placement in transcatheter aortic valve replacement (TAVR).

Objectives: The aim of this study was to assess the incidence of secondary access-related vascular complications after TR-SA or TF-SA in TAVR.

Methods: The PULSE (Plug or sUture based vascuLar cloSurE after TAVR) registry retrospectively evaluated data of 10,120 patients who underwent transfemoral TAVR at 10 heart centers from 2016 to 2021.

SLP2 and MIC13 synergistically coordinate MICOS assembly and crista junction formation.

The MICOS complex, essential for cristae organization, comprises MIC10 and MIC60 subcomplexes, with MIC13 as a crucial subunit. mutations cause severe mitochondrial hepato-encephalopathy, cristae defects, and MIC10-subcomplex loss. We demonstrate that depletion of the mitochondrial protease YME1L in KO stabilizes MIC10-subcomplex, restoring MIC60-MIC10 interaction and crista junction (CJ) defects, indicating MIC13 is crucial for MIC10-subcomplex stabilization rather than MIC60-MIC10 bridging.

Systematic assessment of COVID-19 host genetics using whole genome sequencing data.

Courses of SARS-CoV-2 infections are highly variable, ranging from asymptomatic to lethal COVID-19. Though research has shown that host genetic factors contribute to this variability, cohort-based joint analyses of variants from the entire allelic spectrum in individuals with confirmed SARS-CoV-2 infections are still lacking. Here, we present the results of whole genome sequencing in 1,220 mainly vaccine-naïve individuals with confirmed SARS-CoV-2 infection, including 827 hospitalized COVID-19 cases.

A retrospective, multicentric, nationwide analysis of the impact of splenectomy on survival of pancreatic cancer patients.

Objective: Splenectomy is regularly performed in total and distal pancreatectomy due to technical reasons, lymph node dissection and radicality of the operation. However, the spleen serves as an important organ for competent immune function, and its removal is associated with an increased incidence of cancer and a worse outcome in some cancer entities (Haematologica 99:392-398, 2014; Dis Colon Rectum 51:213-217, 2008; Dis Esophagus 21:334-339, 2008). The impact of splenectomy in pancreatic cancer is not fully resolved (J Am Coll Surg 188:516-521, 1999; J Surg Oncol 119:784-793, 2019).

Diagnostic Accuracy of Lung and Abdominal Ultrasound for Tuberculosis in a German Multicenter Cohort of Patients With Presumed Tuberculosis Disease.

Background: There is limited evidence on point-of-care ultrasound for tuberculosis (TB), but studies suggest high sensitivity, especially for lung ultrasound (LUS). However, insufficient data are available on specificity of the examination and its generalizability to a broader patient population.

Aims: Our study aimed to establish accuracy for lung, chest, and abdominal ultrasound, individually and in combination, for TB diagnosis.

Design, Synthesis, and Biochemical Evaluation of Novel MLK3 Inhibitors: A Target Hopping Example.

The human kinome has tremendous medical potential. In the past decade, mixed-lineage protein kinase 3 (MLK3) has emerged as an interesting and druggable target in oncogenic signaling. The important role of MLK3 has been demonstrated in several types of cancer.

Regulation of the blood-brain barrier function by peripheral cues in health and disease.

The blood-brain barrier (BBB) is formed by microvascular endothelial cells which are ensembled with pericytes, astrocytes, microglia and neurons in the neurovascular unit (NVU) that is crucial for neuronal function. Given that the NVU and the BBB are highly dynamic and regulated structures, their integrity is continuously challenged by intrinsic and extrinsic factors. Herein, factors from peripheral organs such as gonadal and adrenal hormones may influence vascular function also in CNS endothelial cells in a sex- and age-dependent manner.