Autism spectrum disorder related phenotypes in a mouse model lacking the neuronal actin binding protein profilin 2.

Introduction: Profilin 2 (PFN2) is an actin binding protein highly expressed in the brain that participates in actin dynamics. It has been shown in vitro and in vivo that in neurons it functions both post-synaptically to shape and maintain dendritic arborizations and spine density and plasticity, as well as pre-synaptically to regulate vesicle exocytosis. PFN2 was also found in protein complexes with proteins that have been implicated in or are causative of autism spectrum disorder.

Body Temperature Differences Between Green And Brown Grasshoppers Do Not Result From Thermal Physiology or Thermal Preferences.

Colour polymorphisms correspond to the co-occurrence of several distinct colour morphs that vary in hue and/or brightness, independently of sex, age or any other state-dependent modifiers. Colour morphs could represent different life-history strategies, maximising their fitness locally in the trait space through trade-offs between all their biological functions. This mechanism could play a role in the maintenance of the green-brown polymorphism in Orthoptera.

Bioactivated scaffolds promote angiogenesis and lymphangiogenesis for dermal regeneration in vivo.

Chronic wounds represent an unresolved medical challenge with significant impact for patients' quality of life and global healthcare. Diverse in origin, ischemic-hypoxic and inflammatory conditions play central roles as pathological features that impede proper tissue regeneration. In this study, we propose an innovative approach to address this challenge.

Villain Action in Lattice Gauge Theory.

We prove that Villain interaction applied to lattice gauge theory can be obtained as the limit of both Wilson and Manton interactions on a larger graph which we call the . This is the lattice gauge theory analog of a well-known property for spin () models where Villain type interactions are the limit of spin systems defined on a . Perhaps surprisingly in the setting of lattice gauge theory, our proof also applies to non-Abelian lattice theory such as (3)-lattice gauge theory and its limiting Villain interaction.

Evolutionary and epidemic dynamics of COVID-19 in Germany exemplified by three Bayesian phylodynamic case studies.

The importance of genomic surveillance strategies for pathogens has been particularly evident during the coronavirus disease 2019 (COVID-19) pandemic, as genomic data from the causative agent, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), have guided public health decisions worldwide. Bayesian phylodynamic inference, integrating epidemiology and evolutionary biology, has become an essential tool in genomic epidemiological surveillance. It enables the estimation of epidemiological parameters, such as the reproductive number, from pathogen sequence data alone.

Feasibility study of 4D-online monitoring of density gradients induced by lung cancer treatment using carbon ions.

Tumor motion is a major challenge for scanned ion-beam therapy. In the case of lung tumors, strong under- and overdosage can be induced due to the high density gradients between the tumor- and bone tissues compared to lung tissues. This work proposes a non-invasive concept for 4D monitoring of high density gradients in carbon ion beam therapy, by detecting charged fragments.

Control of medical digital twins with artificial neural networks.

The objective of precision medicine is to tailor interventions to an individual patient's unique characteristics. A key technology for this purpose involves medical digital twins, computational models of human biology that can be personalized and dynamically updated to incorporate patient-specific data. Certain aspects of human biology, such as the immune system, are not easily captured with physics-based models, such as differential equations.

Bayesian Windkessel calibration using optimized zero-dimensional surrogate models.

Bayesian boundary condition (BC) calibration approaches from clinical measurements have successfully quantified inherent uncertainties in cardiovascular fluid dynamics simulations. However, estimating the posterior distribution for all BC parameters in three-dimensional (3D) simulations has been unattainable due to infeasible computational demand. We propose an efficient method to identify Windkessel parameter posteriors: We only evaluate the 3D model once for an initial choice of BCs and use the result to create a highly accurate zero-dimensional (0D) surrogate.

Care for the Dying: A Scoping Review of Measures for Clinical Practice With Qualitative Synthesis.

The literature describes a plethora of different measures to support healthcare professionals in the care for the dying. The aim is the identification and assessment of measures for the care in the dying phase to give healthcare professionals of all disciplines an overview on such measures in form of a self-developed toolkit. Two databases were searched systematically and all measures found ( = 7368 publications, = 308 measures) were categorized into six categories and integrated into a toolkit.

Importance of the mustelids from the Early Pleistocene site Schernfeld (Bavaria, Germany) on the Eurasian context.

The Early Pleistocene fossil site of Schernfeld, a karst fissure filled with an ossiferous breccia, is well known due to the abundant fossil remains, mainly of micromammals and carnivores. Since the discovery, the taxonomic status of the Schernfeld mustelids has caused controversy and, consequently, various authors have listed different species. Until recently, none of these species has been the subject of adequate studies.

Three-Dimensional Polyglycerol-PEG-Based Hydrogels as a Universal High-Sensitivity Platform for SPR Analysis.

We developed a three-dimensional (3D) polyglycerol-poly(ethylene glycol)-based hydrogel as a new biosensing matrix for affinity analysis by surface plasmon resonance to enable a high loading of ligands for small molecule analysis while lacking a carbohydrate structure to reduce nonspecific binding. The hydrogel was synthesized by cross-linking a polyglycerol functionalized with carboxylate and maleimide groups with a dithiolated poly(ethylene glycol) by thiol-click chemistry. We demonstrated that the hydrogel coating enabled a high immobilization capacity of biomolecules and led to less nonspecific binding.

Highly efficient isolation and multistep analysis of tumor cells from whole blood.

We present a microfluidic solution for improved tumor cell analysis based on selection-free isolation of nucleated cells from whole blood. It consists of a high-density silicon microcavity array combined with the novel fluidic strategy of microfluidic decanting. This enables multistep on-chip staining protocols comprising sample loading-blocking-extracellular staining-fixation-permeabilization and intracellular staining to quantify tumor cells.

The major phytocannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), affect the function of CatSper calcium channels in human sperm.

Study Question: Do the main psychoactive phytocannabinoid delta-9-tetrahydrocannabinol (THC) and its non-psychoactive analog cannabidiol (CBD) affect human sperm function?

Summary Answer: THC and CBD affect the sperm-specific Ca2+ channel CatSper, suppress activation of the channel by progesterone (P4) and prostaglandin E1 (PGE1), and THC also alters human sperm function in vitro.

What Is Known Already: Marijuana (Cannabis sativa) is one of the most commonly used recreational drugs worldwide. Although the effects of phytocannabinoids on semen parameters have been studied, there is no evidence of a direct impact of THC and CBD on human sperm.

Diagnostics, reconstructive approaches, and outcomes in female urethroplasty patients.

Objectives: To gain further understanding of current outcomes regarding urethroplasty for female urethral stricture disease.

Methods: The European Association of Urology Section of Genitourinary Reconstructive Surgeons formed the Female Reconstruction Group to enhance multicentric collaboration, and to generate more evidence on the most effective treatment options for female patients with recurrent urethral stricture. Patients were eligible for inclusion if they had a urethral stricture and had undergone one of three reconstructive procedures, namely ventral onlay flap (VOFU), ventral onlay graft (VOGU) or dorsal onlay graft (DOGU) urethroplasty.

Experimental Approaches to Visualize Effector Protein Translocation During Host-Pathogen Interactions.

Bacterial pathogens deliver effector proteins into host cells by deploying sophisticated secretion systems. This effector translocation during host-pathogen interactions is a prerequisite for the manipulation of host cells and organisms and is important for pathogenesis. Analyses of dynamics and kinetics of translocation, subcellular localization, and cellular targets of effector proteins lead to understanding the mode of action and function of effector proteins in host-pathogen interplay.

Outcomes of biosynthetic collagen prostheses with comparison to cryopreserved arterial homografts for bypass reconstruction in infrainguinal vascular graft infections.

Background And Aims: Managing infrainguinal vascular graft infections (VGI) in bypass reconstruction is complex. Although an autologous vein is the preferred graft material, alternative conduits are required when autologous veins are unavailable. This study aimed to compare the efficacy of cryopreserved arterial homografts and biosynthetic glutaraldehydemodifiedovine collagen grafts (Omniflow II) for the treatment of infrainguinal VGI.

Patient Needs and Treatment Goals in Chronic Atopic Pruritus: Does Eczema Make a Difference?

Chronic pruritus (≥ 6 weeks) is a frequent symptom in atopic diseases, with phenotypes ranging from non-lesional skin to inflammatory diseases like atopic dermatitis. Data on patients' needs and treatment goals depending on the skin phenotype and disease burden are limited. This study aimed to analyse the impact of distinct phenotypes of chronic atopic pruritus on disease burden and treatment goals.

Progress in skin gene therapy: from the inside and out.

The skin is the largest organ of the body and forms and serves as the barrier for preventing external material from accessing and damaging internal organs. As the outward interface to the environment, it is accessible for the application of therapeutic agents and cellular and gene therapy represent attractive and promising options to treat severe genetic conditions for which palliation has long been the main stay. However, because of its barrier function, transit across and to the sub-dermal compartment can be challenging.

Pair cross-correlation analysis for assessing protein co-localization.

Measuring co-localization of different types of molecules is essential to understand molecular organization in biological systems. The pair cross-correlation (PCC) function computed from two-color microscopy images provides a measure of co-localization between differently labeled molecules. Here, we compute a theoretical expression for the PCC function between two molecules using two-dimensional Gaussian distributions as the effective point spread functions for single molecules.

Complication and Revision Rate in Complex Intraarticular Calcaneal Fractures: Extended Lateral vs Sinus Tarsi Approach.

Background: Adequate surgical treatment of intra-articular calcaneal fractures is challenging. Current clinical evidence on the superiority of either the extended lateral approach (ELA) or the sinus tarsi approach (STA) and their impact on radiologic and functional outcome remains inconclusive, and studies are characterized by low case numbers and short follow-up periods. We hypothesized that using STA would lead to fewer complications and revisions, without impairing fracture reduction or short- to midterm outcome.

Access and pricing of medicines for patients with rare diseases in the European Union: an industry perspective. A 2025 update.

Introduction: In a previous publication, we provided an overview of the current situation of patient access to orphan drugs in the European Union (EU), of the evolving rare disease policy landscape and recommendations for areas of improvement throughout the lifecycle of orphan drugs. This article aims to provide an update on evolving new policies impacting access to orphan drugs in the European Union from a health technology developers perspective.

Areas Covered: We provide an update of the emerging competitiveness gap in the pharmaceutical sector between the EU and the United States.

Validation of RBDtector: An Open-Source Automated Software for Scoring REM Sleep Without Atonia.

Accurate quantification of REM sleep without atonia (RSWA) is essential in the diagnosis of idiopathic/isolated REM sleep behaviour disorder (iRBD). This study aims to validate RBDtector, a free and open-source tool for automated RSWA quantification using the Sleep Innsbruck Barcelona (SINBAR) scoring method, by comparing its performance against human visual scoring in a large independent cohort of subjects with iRBD and healthy controls. Muscle activity from 118 iRBD participants and 37 healthy controls that underwent polysomnography was analysed by RBDtector and compared with human visual scoring.

Post COVID symptom burden in patients supported with extracorporeal membrane oxygenation: A prospective 2-year follow-up analysis.

Objectives: A systematic characterization of the long-term sequelae after the severest form of COVID-19 requiring ECMO-therapy is lacking. Here, we present 2-year follow-up data of COVID-19 ECMO survivors, and analyze the cardiopulmonary, neurocognitive, psychological, and functional status, plus health-related quality of life (HRQL).

Methods: From 04/2020 to 09/2021, 60 COVID patients were supported with ECMO.