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.

Gene expression dynamics in fibroblasts during early-stage murine pancreatic carcinogenesis.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive growth and metastasis, partly driven by fibroblast-mediated stromal interactions. Using RNA sequencing of fibroblasts from early-stage KPC mouse models, we identified significant upregulation of genes involved in adipogenesis, fatty acid metabolism, and the ROS pathway. ANGPTL4, a key adipogenesis regulator, was highly expressed in fibroblasts and promoted pancreatic cancer cell proliferation and migration through paracrine signaling.

Expanding the Chemical Space of Reverse Fosmidomycin Analogs.

Multidrug-resistant pathogens pose a major threat to human health, necessitating the identification of new drug targets and lead compounds that are not susceptible to cross-resistance. This study demonstrates that novel reverse thia analogs of the phosphonohydroxamic acid antibiotic fosmidomycin inhibit 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), an essential enzyme for , , and that is absent in humans. Some novel analogs with large α-phenyl substituents exhibited strong inhibition across these three DXR orthologues, surpassing the inhibitory activity of fosmidomycin.

Effects on impulsivity and delay discounting of intermittent theta burst stimulation add-on to dialectical behavioral therapy in borderline personality disorder: a randomized, sham-controlled pilot trial.

Background: Dialectical behavioral therapy (DBT) and repetitive transcranial magnetic stimulation (rTMS) are both effective in treating borderline personality disorder (BPD). Impulsivity and impaired decision-making are prominent features of BPD, and therapeutic interventions targeting these symptoms could lead to significant improvements.

Objective/hypothesis: We hypothesized that intermittent theta burst stimulation (iTBS), a modified rTMS protocol that targets the left dorsolateral prefrontal cortex, would enhance the therapeutic effects of DBT, leading to greater improvements in impulsivity and decision-making compared with sham stimulation.

Deep-Learning-based Automated Identification of Ventriculoperitoneal-Shunt Valve Models from Skull X-rays.

Introduction: Ventriculoperitoneal shunts (VPS) are an essential part of the treatment of hydrocephalus, with numerous valve models available with different ways of indicating pressure levels. The model types often need to be identified on X‑rays to assess pressure levels using a matching template. Artificial intelligence (AI), in particular deep learning, is ideally suited to automate repetitive tasks such as identifying different VPS valve models.

Engineering organoids as cerebral disease models.

Cerebral organoids pioneered in replicating complex brain tissue architectures in vitro, offering a vast potential for human disease modeling. They enable the in vitro study of human physiological and pathophysiological mechanisms of various neurological diseases and disorders. The trajectory of technological advancements in brain organoid generation and engineering over the past decade indicates that the technology might, in the future, mature into indispensable solutions at the horizon of personalized and regenerative medicine.