An engineered Palivizumab IgG2 subclass for synthetic gp130 and fas mediated signaling.

Recently, we phenocopied Interleukin (IL-)6 signaling using the dimerized single-chain variable fragment (scFv) derived from the respiratory syncytial virus (RSV) IgG1-antibody Palivizumab (PLHFc) to activate a Palivizumab anti-idiotypic nanobody (AIP)-gp130 receptor fusion protein. Palivizumab was unable to activate STAT3 signaling, so we aimed to create a similar ligand capable of triggering this pathway. Here, we created three variants of the ligand called PLH0Fc, PLH4Fc and PLH8Fc by shortening the spacer region connecting PLH and Fc from 23 amino acids in PLHFc to 0 amino acids or expanding it by rigid linkers of 4 or 8 alpha helical loops, respectively.

Clinical predictors in acute optic neuritis: Analysis based on clinical trial data.

Purpose: To identify baseline clinical predictors of visual outcomes six months after acute optic neuritis using data from our completed clinical neuroprotection trial (TONE study).

Design: Secondary analysis of data from the TONE study cohort (NCT01962571).

Subjects: Total of 103 patients presenting within 10 days of a first episode of acute unilateral optic neuritis as a clinically isolated syndrome with baseline high contrast visual acuity (HCVA) < 20/40 Snellen (logMAR 0.

Optimal timing of stabilization and operative technique for extremity fractures in polytrauma patients: a systematic review and meta-analysis.

Purpose: In polytrauma patients, injuries involving the extremities are frequently seen. Treatment concepts vary from early definitive care to temporary fixation and delayed definite stabilization. This analysis therefor aims to illuminate the impact of timing for operative stabilization of extremity fractures on outcome factors in adult polytrauma patients.

Living Lab Dementia: process evaluation of an academic-practice partnership in German long term care for people living with dementia - study protocol.

Background: Living Labs, as a type of academic-practice partnerships, possess the potential to transform care and research into a participatory partnership and narrow the research-practice gap to improve evidence-based and Person-centred care. Given the lack of systematic investigations of Living Labs in healthcare, we will establish a dementia-specific academic-practice partnership (Living Lab Dementia) in Germany and conduct a process evaluation. The aim of this study is to gain insights into the intervention itself (mechanisms of impact) and its implementation process (degree of implementation, barriers, and facilitators).

Longitudinal association between DNA methylation and type 2 diabetes: findings from the KORA F4/FF4 study.

Background: Type 2 diabetes (T2D) has been linked to changes in DNA methylation levels, which can, in turn, alter transcriptional activity. However, most studies for epigenome-wide associations between T2D and DNA methylation comes from cross-sectional design. Few large-scale investigations have explored these associations longitudinally over multiple time-points.

Emotion processing of facial affect expression in patients with somatic symptom disorder with predominant pain-An EEG-study.

Despite their high prevalence, somatoform pain disorders are often not recognized early enough, not diagnosed reliably enough and not treated appropriately. Patients often experience a high level of suffering and the feeling of not being understood. For the medical care system, the symptoms represent a diagnostic and therapeutic challenge.

Multi-center brain age prediction via dual-modality fusion convolutional network.

Accurate prediction of brain age is crucial for identifying deviations between typical individual brain development trajectories and neuropsychiatric disease progression. Although current research has made progress, the effective application of brain age prediction models to multi-center datasets, particularly those with small-sample sizes, remains a significant challenge that is yet to be addressed. To this end, we propose a multi-center data correction method, which employs a domain adaptation correction strategy with Wasserstein distance of optimal transport, along with maximum mean discrepancy to improve the generalizability of brain-age prediction models on small-sample datasets.

Multinational retrospective analysis of bridging therapy prior to chimeric antigen receptor t cells for relapsed/refractory acute lymphoblastic leukemia in children and young adults.

Anti-CD19 chimeric antigen receptor T cells (CAR) are a well-established treatment option for children and young adults suffering from relapsed/refractory B-lineage acute lymphoblastic leukemia. Bridging therapy is used to control disease prior to start of lymphodepletion before CAR infusion and thereby improve efficacy of CAR therapy. However, the effect of different bridging strategies on outcome, side effects and response to CAR therapy is still poorly understood.

Discordance, accuracy and reproducibility study of pathologists' diagnosis of melanoma and melanocytic tumors.

Accurate melanoma diagnosis is crucial for patient outcomes and reliability of AI diagnostic tools. We assess interrater variability among eight expert pathologists reviewing histopathological images and clinical metadata of 792 melanoma-suspicious lesions prospectively collected at eight German hospitals. Moreover, we provide access to the largest panel-validated dataset featuring dermoscopic and histopathological images with metadata.

Topographic Axes of Wiring Space Converge to Genetic Topography in Shaping Human Cortical Layout.

Genetic information is involved in the gradual emergence of cortical areas since the neural tube begins to form, shaping the heterogeneous functions of neural circuits in the human brain. Informed by invasive tract-tracing measurements, the cortex exhibits marked interareal variation in connectivity profiles, revealing the heterogeneity across cortical areas. However, it remains unclear about the organizing principles possibly shared by genetics and cortical wiring to manifest the spatial heterogeneity across cortex.

Idecabtagene vicleucel or ciltacabtagene autoleucel for relapsed or refractory multiple myeloma: An international multicenter study.

Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) have revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM), but direct comparisons are lacking. Leveraging an international multicenter RRMM cohort, we compared the outcome of ide-cel ( = 162) versus cilta-cel ( = 42). Co-primary efficacy endpoints of the study were overall response rate (ORR) and progression-free survival (PFS).

Effects of Webcam Access to Preterm Infants in NICUs on Parental Psychological Strain.

Aim: To investigate whether webcam access for parents of infants in neonatal intensive care units influences parental postpartum depression and stress experiences.

Methods: Parents whose infants had a birth weight below 1500 g and who were admitted to one of the four participating tertiary care hospitals were eligible to participate in the study. The study followed the structure of a multi-centre cross-over pragmatic randomised controlled trial.

Acceptance of Evidence Transfer Within German Early Benefit Assessment of New Drugs for Pediatric and Adolescents Target Populations.

Background And Objective: In Germany, all new drugs undergo an early benefit assessment (EBA) by the decision-making body (G-BA). Due to limited access to clinical data in pediatric healthcare since 2017, evidence transfer has allowed for data from adult studies to be used in the EBA of pediatric drugs. This study examines the acceptance of evidence transfer, aiming to understand its correlation with granted added benefit.

Neonatal central nervous system infection by Ureaplasma species is rare, but relevant: results from a multicenter nationwide surveillance study.

Purpose: Ureaplasma species (spp.) are relevant contributors to preterm birth but may also cause invasive infections particularly in very immature preterm infants. This study aimed to assess the incidence of neonatal Ureaplasma infections of the central nervous system (CNS).

Minimally invasive versus open surgery for colonic diverticular disease: a nationwide analysis of German hospital data.

Background: This study aims to evaluate the current rates and outcomes of minimally invasive versus open surgery for colonic diverticular disease in Germany, using a nationwide dataset.

Methods: We analyzed data from 36 hospitals, encompassing approximately 1.25 million hospitalizations from 1 January 2019 to 31 December 2023.

The continuing significance of chiral agrochemicals.

Chemical crop protection is one of the most cost-effective methods for agriculture, as crop failures can be prevented, and sustainable growth can be enabled regardless of the seasons. Agricultural production must be significantly increased in the future to meet the food needs of a growing world population. However, the continued loss of established active ingredients due to consumer perceptions, changing needs of farmers and ever-changing regulatory requirements is higher than annually new active ingredients introduced to the market.

Contribution of hypoxia-inducible factor 1alpha to pathogenesis of sarcomeric hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) caused by autosomal-dominant mutations in genes coding for structural sarcomeric proteins, is the most common inherited heart disease. HCM is associated with myocardial hypertrophy, fibrosis and ventricular dysfunction. Hypoxia-inducible transcription factor-1α (Hif-1α) is the central master regulators of cellular hypoxia response and associated with HCM.

Histamine H receptor blockade alleviates neuropathic pain through the regulation of glial cells activation.

Neuropathic pain is a disorder affecting the somatosensory nervous system. However, this condition is also characterized by significant neuroinflammation, primarily involving CNS-resident non-neuronal cells. A promising target for developing new analgesics is histamine H receptor (HR); thus, we aimed to determine the influence of a novel HR antagonist/inverse agonist, E-98 (1-(7-(4-chlorophenoxy)heptyl)-3-methylpiperidine), on pain symptoms and glia activation in model of neuropathic pain in male mice (chronic constriction injury to the sciatic nerve).

Guaranteed efficient energy estimation of quantum many-body Hamiltonians using ShadowGrouping.

Estimation of the energy of quantum many-body systems is a paradigmatic task in various research fields. In particular, efficient energy estimation may be crucial in achieving a quantum advantage for a practically relevant problem. For instance, the measurement effort poses a critical bottleneck for variational quantum algorithms.

The ER protein CANX (calnexin)-mediated autophagy protects against alzheimer disease.

Although the relationship between macroautophagy/autophagy and Alzheimer disease (AD) is widely studied, the underlying mechanisms are poorly understood, especially the regulatory role of the initiation signaling of autophagy on AD. Here, we find that the ER transmembrane protein CANX (calnexin) is a novel interaction partner of the autophagy-inducing kinase ULK1 and is required for ULK1 recruitment to the ER under basal or starved conditions. Loss of CANX results in the inactivity of ULK1 kinase and inhibits autophagy flux.

Cerebral vasculitis related to neurosarcoidosis: a case series and systematic literature review.

Cerebral vasculitis is a rare but severe manifestation of neurosarcoidosis (NS) that has received little attention. The aim of the present study was to characterize clinical and diagnostic features as well as potential treatment strategies of cerebral vasculitis related to NS. We assessed 29 patients with cerebral vasculitis related to NS (15 female, mean age at time of diagnosis 45 years, SD = 11.

Subacute thyroiditis - Is it really linked to viral infection? Retrospective hospital patient registry study.

Objective: Subacute thyroiditis (SAT) is a painful inflammatory disorder of the thyroid gland, which - after a phase of thyrotoxicosis - leads to transient, or less frequently permanent hypothyroidism. Apart from a strong association with specific HLA alleles, the causes are uncertain. Viral disease has been hypothesised as a trigger, with Enteroviruses, namely Echoviruses and Coxsackieviruses, showing a seasonal distribution that coincides with the incidence of SAT.