DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.

The roles of vision and proprioception in spatial tuning of sensory attenuation.

When we touch ourselves, the pressure appears weaker compared to when someone else touches us, an effect known as sensory attenuation. Sensory attenuation is spatially tuned and does only occur if the positions of the touching and the touched body-party spatially coincide. Here, we ask about the contribution of visual or proprioceptive signals to determine self-touch.

The US4ABL Strategy: A Systematic Ultrasound-Guided Approach for Left Atrial and Ventricular Ablation Procedures.

: The safety and efficacy of electrophysiological (EP) procedures using ultrasound (US) guidance are being increasingly studied. We investigated if a systematic workflow with ultrasound guidance (the US4ABL), comprising four steps (transesophageal echocardiography (TEE) for left atrial thrombus exclusion, US of the groin vessels to guide femoral access, TEE-aided transseptal puncture, and transthoracic echocardiography (TTE) for exclusion of pericardial tamponade after the procedure), reduces the number of complications and fluoroscopy duration and dose. : A total of 212 consecutive patients underwent left-sided ablations using the US4ABL workflow and were compared to a group of 299 patients who underwent the same type of ablations using post-procedural TTE to exclude tamponade (standard group: venous and/or arterial access by palpation and fluoroscopy, and pressure guided transseptal puncture).

Discharge Against Medical Advice in Cancer Patients: Insights from a Multicenter Study in Germany.

Background: Discharge against medical advice (DAMA) disrupts continuity of care and is associated with increased readmission rates, morbidity, and mortality. While extensively studied in general hospital populations, its prevalence and associated factors in cancer patients, where treatment adherence is critical for outcomes, remain underexplored.

Methods: This multicenter, cross-sectional study analyzed anonymized data from the IQVIA hospital database, including cancer patients hospitalized in 36 German hospitals between January 2019 and December 2023.

Dead or Alive: Exploratory Analysis of Selected Apoptosis- and Autophagy-Related Proteins in Human Endometrial Stromal Cells of Fertile Females and Their Potential Role During Embryo Implantation.

To date, very little is known about how apoptosis and autophagy affect human endometrial stromal cells (ESCs), particularly how these processes might determine the depth of implantation in humans. Before investigating how apoptosis and autophagy might modulate the implantation process in an infertile population, it is necessary to clarify how these processes are regulated in healthy individuals. This study examined the protein expression related to apoptosis and autophagy in primary ESCs from fertile women, particularly in the context of decidualization and embryo contact, using Western blot analysis.

Distribution and Maturity of Medial Collagen Fibers in Thoracoabdominal Post-Dissection Aortic Aneurysms: A Comparative Study of Marfan and Non-Marfan Patients.

Thoracoabdominal aortic aneurysms (TAAAs) are rare but serious conditions characterized by dilation of the aorta characterized by remodeling of the vessel wall, with changes in the elastin and collagen content. Individuals with Marfan syndrome have a genetic predisposition for elastic fiber fragmentation and elastin degradation and are prone to early aneurysm formation and progression. Our objective was to analyze the medial collagen characteristics through histological, polarized light microscopy, and electron microscopy methods across the thoracic and abdominal aorta in twenty-five patients undergoing open surgical repair, including nine with Marfan syndrome.

The Diverse Binding Modes Explain the Nanomolar Levels of Inhibitory Activities Against 1-Deoxy-d-Xylulose 5-Phosphate Reductoisomerase from Exhibited by Reverse Hydroxamate Analogs of Fosmidomycin with Varying -Substituents.

It is established that reverse hydroxamate analogs of fosmidomycin inhibit the growth of by inhibiting 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), the second enzyme of the non-mevalonate pathway, which is absent in humans. Recent biochemical studies have demonstrated that novel reverse fosmidomycin analogs with phenylalkyl substituents at the hydroxamate nitrogen exhibit inhibitory activities against DXR at the nanomolar level. Moreover, crystallographic analyses have revealed that the phenyl moiety of the -phenylpropyl substituent is accommodated in a previously unidentified subpocket within the active site of DXR.

Novel CAD/CAM-splint-based navigation protocol enhances intraoperative maxillary position control in orthognathic surgery: a case control study.

Background: Virtual surgical planning for orthognathic surgery typically relies on two methods for intraoperative plan transfer: CAD/CAM occlusal splints and patient-specific implants (PSI). While CAD/CAM splints may offer limited accuracy, particularly in the vertical dimension, PSIs are constrained by higher costs and extended preparation times. Surgical navigation has emerged as a potential alternative, but existing protocols often involve invasive registration or lack transparent evaluation.

Outcomes in patients with acute myeloid leukemia older than 70 years within the last 30 years, a single center experience.

As median age of patients with acute myeloid leukemia is 72 years, older patients continue to be a vulnerable cohort representing significant challenges in clinical practice. Patient-specific comorbidities as well as leukemia-specific unfavorable molecular- and cytogenetics confer even poorer outcomes. Treatment of AML therefore needs to be less toxic to prevent harm while lowering or eradicating leukemic burden to prolong survival.

Longitudinal Psychological Distress After Malignant Brain Tumor Diagnosis: A Multilevel Analysis of Patients and Their Caregivers.

Objective: Malignant brain tumors are associated with debilitating symptoms and a poor prognosis, resulting in high psychological distress for patients and caregivers. There is a lack of longitudinal studies investigating psychological distress in this group. This study evaluated fear of progression (FoP), anxiety and depression in patients and their caregivers in the 6 months following malignant brain tumor diagnosis.

DNTT-mediated DNA Damage Response Drives Inotuzumab Ozogamicin Resistance in B-cell Acute Lymphoblastic Leukemia.

Inotuzumab Ozogamicin (InO) is an antibody-calicheamicin conjugate with striking efficacy in B-cell acute lymphoblastic leukemia (B-ALL). However, there is wide inter-patient variability in treatment response, and the genetic basis of this variation remains largely unknown. Using a genome-wide CRISPR screen, we discovered the loss of DNTT as a primary driver of InO resistance.

How I do it - focused Sylvian approach for clipping of middle cerebral artery aneurysms.

Background: The Focused Sylvian Approach (FSA) is a refined, minimally invasive technique for clipping small to medium-sized middle cerebral artery (MCA) aneurysms, prioritizing safety and aesthetics.

Method: The craniotomy remains confined to the superior temporal line, with the incision concealed within the temporal muscle. The Sylvian fissure is carefully dissected to preserve venous structures.

Coverage bias in small molecule machine learning.

Small molecule machine learning aims to predict chemical, biochemical, or biological properties from molecular structures, with applications such as toxicity prediction, ligand binding, and pharmacokinetics. A recent trend is developing end-to-end models that avoid explicit domain knowledge. These models assume no coverage bias in training and evaluation data, meaning the data are representative of the true distribution.

Effect of applying a diabetes risk score on lifestyle counselling and shared decision-making in primary care: A pragmatic cluster randomised trial.

Aims: There is a lack of studies on the impact of diabetes risk scores on diabetes prevention. The aim of this study was to investigate the effect of applying a non-invasive diabetes risk score as component of routine health checks on counselling intensity and shared decision-making (SDM) in primary care.

Methods: Cluster randomised trial, in which primary care physicians (n = 30) enrolled participants (n = 315) with statutory health insurance without known diabetes, ≥ 35 years of age with a body mass index (BMI) ≥ 27.

Subthalamic nucleus deep brain stimulation in the beta frequency range boosts cortical beta oscillations and slows down movement.

Recordings from Parkinson's disease (PD) patients typically show strong beta-band oscillations (13-35Hz), which can be modulated by deep brain stimulation (DBS). While high-frequency DBS (>100Hz) ameliorates motor symptoms and reduces beta activity in basal ganglia and motor cortex, the effects of low-frequency DBS (<30Hz) are less clear. Clarifying these effects is relevant for the debate about the role of beta oscillations in motor slowing, which might be causal or epiphenomenal.

LFA-1: A potential key player in microglia-mediated neuroprotection against oxygen-glucose deprivation in vitro.

For the last 38 years, all neuroprotective agents for patients with ischemic stroke have failed in clinical trials. The innate immune system, particularly microglia, is a much-discussed target for neuroprotective agents. Promising results for neuroprotection by inhibition of integrins with drugs such as natalizumab in animal stroke models have not been translated into clinical practice.

The influence of sintering of osteoporotic vertebral fractures on the sagittal lumbar profile and degenerative changes.

Background: Osteoporosis, a skeletal disorder affecting nearly 20% of the global population, poses a significant health concern, with osteoporotic vertebral body fractures (VBF) representing a common clinical manifestation. The impact of osteoporotic sintering fractures in the thoracolumbar spine on the sagittal lumbar profile is incompletely understood and may lead to the onset of clinical symptoms in previously asymptomatic patients.

Methods: This retrospective single-center study analyzed data from patients presenting with osteoporotic spine fractures between 2017 and 2022.

Altered cortical network dynamics during observing and preparing action in patients with corticobasal syndrome.

Corticobasal syndrome (CBS) is characterized not only by parkinsonism but also by higher-order cortical dysfunctions, such as apraxia. However, the electrophysiological mechanisms underlying these symptoms remain poorly understood. To explore the pathophysiology of CBS, we recorded magnetoencephalographic (MEG) data from 17 CBS patients and 20 age-matched controls during an observe-to-imitate task.

Insulin amyloid morphology is encoded in H-bonds and electrostatics interactions ruling protein phase separation.

Ion-protein interactions regulate biological processes and are the basis of key strategies of modulating protein phase diagrams and stability in drug development. Here, we report the mechanisms by which H-bonds and electrostatic interactions in ion-protein systems determine phase separation and amyloid formation. Using microscopy, small-angle X-ray scattering, circular dichroism and atomistic molecular dynamics (MD) simulations, we found that anions specifically interacting with insulin induced phase separation by neutralising the protein charge and forming H-bond bridges between insulin molecules.

Real-World Prevalence, Incidence and Management of Systemic Lupus Erythematosus in Germany: A Retrospective Claims Data Analysis.

Introduction: This study evaluated the prevalence and incidence of systemic lupus erythematosus (SLE) in Germany and explored real-world data on sequence of therapy (SOT; sequence of drugs as prescribed in clinical practice).

Methods: This retrospective, observational, longitudinal cohort study using German claims data from the WIG2 GmbH Scientific Institute for Health Economics and Health System Research database (January 2011-December 2019), extrapolated to the statutory health insurance (SHI)-insured population, evaluated prevalence and incidence in an epidemiological analysis group and SLE treatment patterns in an incident cohort (subgroup ≥ 18 years of age with incident disease and ≥ 24-month follow-up post index date). Analyses were descriptive.

Comparative analysis of adenosine 1 receptor expression and function in hippocampal and hypothalamic neurons.

Background: Adenosine, an ATP degradation product, is a sleep pressure factor. The adenosine 1 receptor (A1R) reports sleep need. Histaminergic neurons (HN) of the tuberomamillary nucleus (TMN) fire exclusively during wakefulness and promote arousal.