Evaluation of synaptotagmin-1 action models by all-atom molecular dynamics simulations.

Neurotransmitter release is triggered in microseconds by the two C domains of the Ca sensor synaptotagmin-1 and by SNARE complexes, which form four-helix bundles that bridge the vesicle and plasma membranes. The synaptotagmin-1 CB domain binds to the SNARE complex via a 'primary interface', but the mechanism that couples Ca-sensing to membrane fusion is unknown. Widespread models postulate that the synaptotagmin-1 Ca-binding loops accelerate membrane fusion by inducing membrane curvature, perturbing lipid bilayers or helping bridge the membranes, but these models do not seem compatible with SNARE binding through the primary interface, which orients the Ca-binding loops away from the fusion site.

Increase of nitrous oxide-induced neurological disorders - a German multicenter experience.

Background: Nitrous oxide (N₂O), commonly known as laughing gas, is widely recognized for its anesthetic and analgesic effects, and is frequently used in medical contexts. However, its misuse can lead to significant neurological complications, which are often under-recognized in clinical practice. Recent data on such cases in Germany are rare.

Discontiguous recurrences of IDH-wildtype glioblastoma share a common origin with the initial tumor and are frequently hypermutated.

Glioblastoma is the deadliest primary brain tumor, largely due to inevitable recurrence of the disease after treatment. While most recurrences are local, patients rarely present with a new discontiguous focus of glioblastoma. Little is currently known about the genetic profile of discontiguous recurrences.

Scale-up of CHO cell cultures: from 96-well-microtiter plates to stirred tank reactors across three orders of magnitude.

Background: For process development in mammalian cell cultivations, scale-up approaches are essential. A lot of studies concern the scale transfer between different-sized stirred tank reactors. However, process development usually starts in even smaller cultivation vessels like microtiter plates or shake flasks.

Effectiveness of workplace health promotion programs for industrial workers: a systematic review.

Background: Workplace health promotion is essential for individual and organisational well-being and disease prevention, also in industrial workers. As the transfer of the evidence on the effectiveness of such programs into practice is limited due to scattered effects, the need for a consolidation of the available studies is given. The purpose of this systematic review was to synthesise the evidence on the effectiveness of workplace health promotion programs for industrial workers.

Patient perspectives on stress after ICU and a short primary care based psychological intervention - results from a qualitative sub‑study of the PICTURE trial.

Background: Approximately 20-25% of patients who survive medical treatment at an intensive care unit (ICU) develop post-traumatic stress symptoms. There is currently a gap in follow-up care for them. As part of the PICTURE study, general practitioners (GPs) carried out a brief interview-based intervention.

Incidence of seroma and postoperative complications after breast surgery before and during the Covid-19 pandemic: results from a retrospective multicenter analysis.

Background: In recent years, there has been a growing number of case reports documenting delayed seroma in patients with a history of breast surgery and reconstruction. The occurrence of these seromas has been associated with prior SARS-CoV-2 infection or SARS-CoV-2 vaccination. So far, there are few systematic analyses on postoperative complications in breast surgery since the emergence of the SARS-CoV-2 pandemic.

Resolving tissue complexity by multimodal spatial omics modeling with MISO.

Spatial molecular profiling has provided biomedical researchers valuable opportunities to better understand the relationship between cellular localization and tissue function. Effectively modeling multimodal spatial omics data is crucial for understanding tissue complexity and underlying biology. Furthermore, improvements in spatial resolution have led to the advent of technologies that can generate spatial molecular data with subcellular resolution, requiring the development of computationally efficient methods that can handle the resulting large-scale datasets.

Biomechanical simulation of bed turning post-acetabular fracture fixation.

Before patients begin out-of-bed exercises following internal fixation surgery for acetabular fractures, turning over in bed serves as a crucial intervention to mitigate complications associated with prolonged bed rest. However, data on the safety of this maneuver post-surgery are limited, and the biomechanical evidence remains unclear. This study aims to introduce a novel loading protocol designed to preliminarily simulate the action of turning over in bed and to compare the biomechanical properties of two fixation methods for acetabular fractures under this new protocol.

Choroid plexus volume is enlarged in long COVID and associated with cognitive and brain changes.

Patients with post-COVID condition (PCC) present with diverse symptoms which persist at long-term after SARS-CoV-2 infection. Among these symptoms, cognitive impairment is one of the most prevalent and has been related to brain structural and functional changes. The underlying mechanisms of these cognitive and brain alterations remain elusive but neuroinflammation and immune mechanisms have been majorly considered.

Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study.

In the MAIA study (median follow-up, 56.2 months), daratumumab plus lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival (PFS) and overall survival versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). In this post hoc analysis of clinically important subgroups in MAIA (median follow-up, 64.

Prognostic impact of expression of CD2, CD25, and/or CD30 in/on mast cells in systemic mastocytosis: a registry study of the European Competence Network on Mastocytosis.

Expression of CD2, CD25 and/or CD30 in extracutaneous mast cells (MC) is a minor diagnostic criterion for systemic mastocytosis (SM) in the classification of the World Health Organization and International Consensus Classification. So far, it remains unknown whether expression of these antigens on MC is of prognostic significance in SM. We performed a retrospective multi-center study of patients with SM using the data set of the registry of the European Competence Network on Mastocytosis, including 5034 patients with various MC disorders.

Eco-friendly sensing of hexavalent chromium ions via copper-doped carbon quantum dots: a fluorescent probe for water safety.

The hydrothermal synthesis is presented of copper-doped carbon dots (Cu-CDs) from citric acid, urea, and copper chloride, resulting in blue-fluorescent particles with stable emission at 438 nm when excited at 340 nm. Through comprehensive spectroscopic and microscopic characterization (FTIR, XPS, UV, and HRTEM), the Cu-CDs demonstrated remarkable stability across varying pH levels, ionic strengths, temperatures, and UV exposure. Notably, Cu-CDs exhibit ultra-sensitive and selective detection of hexavalent chromium [Cr(VI)] ions in aqueous environments driven by fluorescence quenching.

GestaltGAN: synthetic photorealistic portraits of individuals with rare genetic disorders.

The facial gestalt (overall facial morphology) is a characteristic clinical feature in many genetic disorders that is often essential for suspecting and establishing a specific diagnosis. Therefore, publishing images of individuals affected by pathogenic variants in disease-associated genes has been an important part of scientific communication. Furthermore, medical imaging data is also crucial for teaching and training deep-learning models such as GestaltMatcher.

Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia.

X-linked hypophosphataemia (XLH) is a rare metabolic bone disorder caused by pathogenic variants in the PHEX gene, which is predominantly expressed in osteoblasts, osteocytes and odontoblasts. XLH is characterized by increased synthesis of the bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23), which results in renal phosphate wasting with consecutive hypophosphataemia, rickets, osteomalacia, disproportionate short stature, oral manifestations, pseudofractures, craniosynostosis, enthesopathies and osteoarthritis. Patients with XLH should be provided with multidisciplinary care organized by a metabolic bone expert.

Single and multitarget stereotactic radiosurgery (SRS) with single isocenter in the treatment of multiple brain metastases (BM): institutional experience.

Introduction: SRS for the treatment of limited brain metastases (BM) is widely accepted, but there are still limitations in the management of numerous BM. Frameless single-isocenter multitarget SRS is a novel technique that allows for rapid treatment delivery to multiple BM. We report our preliminary clinical, dosimetric, and patient´s shifts outcomes with this technique.

Continental influx and pervasive matrilocality in Iron Age Britain.

Roman writers found the relative empowerment of Celtic women remarkable. In southern Britain, the Late Iron Age Durotriges tribe often buried women with substantial grave goods. Here we analyse 57 ancient genomes from Durotrigian burial sites and find an extended kin group centred around a single maternal lineage, with unrelated (presumably inward migrating) burials being predominantly male.

All-solid-state Li-S batteries with fast solid-solid sulfur reaction.

With promises for high specific energy, high safety and low cost, the all-solid-state lithium-sulfur battery (ASSLSB) is ideal for next-generation energy storage. However, the poor rate performance and short cycle life caused by the sluggish solid-solid sulfur redox reaction (SSSRR) at the three-phase boundaries remain to be solved. Here we demonstrate a fast SSSRR enabled by lithium thioborophosphate iodide (LBPSI) glass-phase solid electrolytes (GSEs).

Massively parallel characterization of transcriptional regulatory elements.

The human genome contains millions of candidate cis-regulatory elements (cCREs) with cell-type-specific activities that shape both health and many disease states. However, we lack a functional understanding of the sequence features that control the activity and cell-type-specific features of these cCREs. Here we used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test the regulatory activity of more than 680,000 sequences, representing an extensive set of annotated cCREs among three cell types (HepG2, K562 and WTC11), and found that 41.

Ancient DNA reveals reproductive barrier despite shared Avar-period culture.

After a long-distance migration, Avars with Eastern Asian ancestry arrived in Eastern Central Europe in 567 to 568 CE and encountered groups with very different European ancestry. We used ancient genome-wide data of 722 individuals and fine-grained interdisciplinary analysis of large seventh- to eighth-century CE neighbouring cemeteries south of Vienna (Austria) to address the centuries-long impact of this encounter. We found that even 200 years after immigration, the ancestry at one site (Leobersdorf) remained dominantly East Asian-like, whereas the other site (Mödling) shows local, European-like ancestry.

Specification of claustro-amygdalar and palaeocortical neurons and circuits.

The ventrolateral pallial (VLp) excitatory neurons in the claustro-amygdalar complex and piriform cortex (PIR; which forms part of the palaeocortex) form reciprocal connections with the prefrontal cortex (PFC), integrating cognitive and sensory information that results in adaptive behaviours. Early-life disruptions in these circuits are linked to neuropsychiatric disorders, highlighting the importance of understanding their development. Here we reveal that the transcription factors SOX4, SOX11 and TFAP2D have a pivotal role in the development, identity and PFC connectivity of these excitatory neurons.

Feasibility and potential effect of a pilot blended digital behavior change intervention promoting sustainable diets over a year.

Well-designed effective interventions promoting sustainable diets are urgently needed to benefit both human and planetary health. This study evaluated the feasibility, acceptability, and potential impact of a pilot blended digital intervention aimed at promoting sustainable diets. We conducted a series of ABA n-of-1 trials with baseline, intervention, and follow-up phases over the course of a year, involving twelve participants.

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT.

Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsing forms of multiple sclerosis (MS) that are refractory to disease-modifying therapy (DMT). AHSCT after failure of high-efficacy DMT in aggressive forms of relapsing-remitting MS is a generally accepted indication, yet the optimal placement of this approach in the treatment sequence is not universally agreed upon. Uncertainties also remain with respect to other indications, such as in rapidly evolving, severe, treatment-naive MS, progressive MS, and neuromyelitis optica spectrum disorder (NMOSD).

Implications for the diagnosis of aspiration and aspergillosis in critically ill patients with detection of galactomannan in broncho-alveolar lavage fluids.

Invasive infections with Aspergillus fumigatus in ICU patients are linked to high morbidity and mortality. Diagnosing invasive pulmonary aspergillosis (IPA) in non-immunosuppressed patients is difficult, as Aspergillus antigen (galactomannan [GM]) may have other causes. This retrospective study analyzed 160 ICU surgical patients with positive GM in broncho-alveolar lavage fluid (BALF), classifying them based on AspICU criteria for suspected IPA (pIPA) or aspiration.

Treatment of patients with tumor/treatment-related hypothalamic obesity in the first two years following surgical treatment or radiotherapy.

Survivors of sellar/suprasellar tumors involving hypothalamic structures face a risk of impaired quality of life, including tumor- and/or treatment-related hypothalamic obesity (TTR-HO) defined as abnormal weight gain resulting in severe persistent obesity due to physical, tumor- and/or treatment related damage of the hypothalamus. We analyze German claims data to better understand treatment pathways for patients living TTR-HO during the two years following the index surgical treatment. A database algorithm identified patients with TTR-HO in a representative German payer claims database between 2010 and 2021 (n = 5.