Optogenetic Clustering and Stimulation of the T Cell Receptor in Nongenetically Modified Human T Cells.

Methods for the precise temporal control of cell surface receptor activation are indispensable for the investigation of signaling processes in mammalian cells. Optogenetics enables such precise control, but its application in primary cells is limited by the imperative for genetic manipulation of target cells. We here describe a method that overcomes this obstacle and enables the precise activation of the T cell receptor in nongenetically engineered human T cells by light.

Claudins in vulvar cancer - from epithelial barrier to potential tumor-agnostic cancer therapy.

The immunohistochemical expression of various members of the claudin family has already been studied in pathological affections of the vulva whether to differentiate precancerous lesions from vulvar squamous cell carcinoma or in inflammatory conditions such as lichen sclerosus. From an oncological perspective, however, immunohistochemical analysis of claudin 18.2 protein expression has become increasingly clinically relevant nowadays since the impressive therapeutic benefits of the claudin 18.

Novel type 2 diabetes prediction score based on traditional risk factors and circulating metabolites: model derivation and validation in two large cohort studies.

Background: We aimed to evaluate the incremental predictive value of metabolomic biomarkers for assessing the 10-year risk of type 2 diabetes when added to the clinical Cambridge Diabetes Risk Score (CDRS).

Methods: We utilized 86,232 UK Biobank (UKB) participants (recruited between 13 March 2006 and 1 October 2010) for model derivation and internal validation. Additionally, we included 4383 participants from the German ESTHER cohort (recruited between 1 July 2000 and 30 June 2002 for external validation).

Injury prevention in youth football (soccer): a comprehensive description of the development process of the 'FUNBALL' programme.

Many football injury prevention programmes (IPPs) have been developed to target various injuries and populations. There was no specific IPP for youth players in place before. However, several existing IPPs designed for adults were also assessed in the youth population.

Client satisfaction, safety, and insights from a three-season survey on influenza vaccinations delivered at community pharmacies in Germany.

To address the challenges posed by influenza, its associated complications, and economic burden, the World Health Organization recommends a vaccination rate exceeding 75 % for populations at elevated risk of severe diseases. Presently, vaccination rates in Germany severely lag behind. To augment these rates, pilot projects have been initiated, allowing community pharmacists to administer vaccines.

Management of dyslipidaemia in patients with comorbidities - facing the challenge Value and limitations of lipid lowering drugs in liver disease Effects/Interactions of lipid-lowering agents on/with the liver.

Objectives: This review aims to examine the evidence on the benefits and risks of lipid lowering drugs in patients with liver disease. Elevated liver enzyme levels often lead to cautious discontinuation of these drugs, potentially withholding from patients their benefit in reducing cardiovascular disease morbidity and mortality.

Methods And Results: Using a literature search of PubMed, we examine the efficacy and safety profiles of various lipid lowering agents, including statins, ezetimibe, bempedoic acid, PCSK9 inhibitors, fibrates, and icosapent ethyl, focusing particularly on their potential side effects related to liver health.

Systematic assessment of COVID-19 host genetics using whole genome sequencing data.

Courses of SARS-CoV-2 infections are highly variable, ranging from asymptomatic to lethal COVID-19. Though research has shown that host genetic factors contribute to this variability, cohort-based joint analyses of variants from the entire allelic spectrum in individuals with confirmed SARS-CoV-2 infections are still lacking. Here, we present the results of whole genome sequencing in 1,220 mainly vaccine-naïve individuals with confirmed SARS-CoV-2 infection, including 827 hospitalized COVID-19 cases.

Synthesis and Properties of Symmetrical and Asymmetrical Polyferrocenylmethylenes.

The synthesis of differently substituted polyferrocenylmethylenes (PFM) via ring-opening transmetalation polymerization (ROTP) is reported. A number of novel, symmetrically and asymmetrically substituted carba[1]magnesocenophanes have been prepared, which were used as precursors and allowed investigations of the influence of different substitution patterns on the PFM polymer properties. The novel carba[1]magnesocenophanes have been fully characterized by 1H and 13C NMR spectroscopy, and structurally authenticated by single-crystal X-ray diffraction (SC-XRD).

Age-dependent effects of Delaire facemask therapy for class III malocclusion : Impact on maxillary sutures and palatal morphology.

Background And Aim: Treatment effects of a combined rapid maxillary expansion (RME) and Delaire facemask (DFM) therapy have so far only been scientifically investigated through cephalometric analyses. The combination of cephalometric, dental cast and cone-beam computed tomography (CBCT) scan analysis was not yet used for investigating morphologic changes of the tooth-bearing palate. The aim of the present study was to determine whether patient age at treatment begin has an influence upon palatal length changes after RME/DFM therapy, and to what extent transverse palatal sutures contribute to these.

π-Lewis Base Activation of Carbonyls and Hexafluorobenzene.

We report hitherto elusive side-on η2-bonded palladium(0) carbonyl (anthraquinone, benzaldehyde) and arene (benzene, hexa-fluorobenzene) palladium(0) complexes and present the catalytic hydrodefluorination of hexafluorobenzene by cyclohexene. The comparison with respective cyclohexene, pyridine and tetrahydrofuran complexes reveals that the experimental ligand binding strengths follow the order THF < C6H6 < C6F6 < cyclohexene < pyridine < benzaldehyde < anthraquinone. To understand this surprising order, the complexes' electronic structures were elucidated by nuclear magnetic resonance (NMR), single crystal X-Ray diffraction (sc-XRD), ultraviolet/visible (UV/Vis) electronic absorption, infrared (IR) vibrational, Pd L3-edge X-ray absorption (XAS), and X-ray photoelectron (XP) spectroscopic techniques, complemented by Density Functional Theory (DFT) calculations including energy decomposition (EDA-NOCV) and effective oxidation state (EOS) analyses.

Collagen scaffold-seeded iTenocytes accelerate the healing and functional recovery of Achilles tendon defects in a rat model.

Introduction: Tendon injuries represent an ongoing challenge in clinical practice due to poor regenerative capacity, structure, and biomechanical function recovery of ruptured tendons. This study is focused on the assessment of a novel strategy to repair ruptured Achilles tendons in a Nude rat model using stem cell-seeded biomaterial.

Methods: Specifically, we have used induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) overexpressing the early tendon marker Scleraxis (SCX, iMSC, iTenocytes) in combination with an elastic collagen scaffold.

Distribution of spine classes shows intra-neuronal dendritic heterogeneity in mouse cortex.

Significance: Neuronal dendritic spines are central elements for memory and learning. Their morphology correlates with synaptic strength and is a proxy for function. Classic light microscopy cannot resolve spine morphology well, and techniques with higher resolution (electron microscopy and super-resolution light microscopy) typically do not provide spine data in large fields of view, e.

Single-trial neurodynamics reveal N400 and P600 coupling in language comprehension.

Theories of the electrophysiology of language comprehension are mostly informed by event-related potential effects observed between condition averages. We here argue that a dissociation between competing effect-level explanations of event-related potentials can be achieved by turning to predictions and analyses at the single-trial level. Specifically, we examine the single-trial dynamics in event-related potential data that exhibited a biphasic N400-P600 effect pattern.

Is Stopping of Testosterone-Lowering Medication in Men Convicted of Sexual Offenses Associated With an Increase in Recidivism Risk?

There is some evidence that testosterone-lowering medications (TLM) may be an effective treatment for men convicted of sexual offenses by attenuating paraphilic sexual fantasies and behaviors and reducing the recidivism risk. To date, however, only little is known about the effects of TLM stopping on risk-relevant aspects. Therefore, the current study aimed at examining the recidivism risk as measured by Stable-2007 as well as official records of reoffenses in 29 men having stopped TLM treatment as compared to 37 men with ongoing TLM treatment.

Endosonography in head and neck imaging and surgery.

This CME article explores the evolving role of endosonography in otorhinolaryngology and head and neck surgery. Endosonography offers significant potential to improve imaging inside the upper respiratory tract, particularly with advancements in probe technology and imaging resolution. The article will describe the sonoanatomy of the oral cavity, pharynx, and larynx and the selection of probes and scanning techniques used for the various anatomical sites.

A multi-scale circuit model bridges molecular modeling and experimental measurements of conductive metal-organic framework supercapacitors.

A multi-scale model is crucial for combining experiments and simulations to reveal the energy storage mechanism. As novel electrode materials, conductive metal-organic frameworks (c-MOFs) provide an ideal platform for understanding the energy storage process in supercapacitors. However, the prevailing circuit models lack consideration of the distinctive transmission path of c-MOFs, which hinders accurate descriptions of c-MOF supercapacitors.

A family of NADPH/NADP biosensors reveals in vivo dynamics of central redox metabolism across eukaryotes.

The NADPH/NADP redox couple is central to metabolism and redox signalling. NADP redox state is differentially regulated by distinct enzymatic machineries at the subcellular compartment level. Nonetheless, a detailed understanding of subcellular NADP redox dynamics is limited by the availability of appropriate tools.

Odor prediction of whiskies based on their molecular composition.

Aroma compositions are usually complex mixtures of odor-active compounds exhibiting diverse molecular structures. Due to chemical interactions of these compounds in the olfactory system, assessing or even predicting the olfactory quality of such mixtures is a difficult task, not only for statistical models, but even for trained assessors. Here, we combine fast automated analytical assessment tools with human sensory data of 11 experienced panelists and machine learning algorithms.

Identifying optimal substrate classes of membrane transporters.

Membrane transporters are responsible for moving a wide variety of molecules across biological membranes, making them integral to key biological pathways in all organisms. Identifying all membrane transporters within a (meta-)proteome, along with their specific substrates, provides important information for various research fields, including biotechnology, pharmacology, and metabolomics. Protein datasets are frequently annotated with thousands of molecular functions that form complex networks, often with partial or full redundancy and hierarchical relationships.

Subsequent Thyroid Carcinomas in Children and Adolescents Registered in the German MET Consortium (1997-2023).

Among childhood cancer survivors, the cumulative incidence rate of differentiated thyroid carcinomas (DTCs) is estimated to be 8-11%. Although the association of DTC with prior radiotherapy is well-studied, the association with chemotherapy remains less understood. Most studies focused on young adults, leaving a knowledge gap on subsequent DTC occurring in childhood and adolescence.

Temporal trends in gender, etiology, severity and outcomes of acute pancreatitis in a third-tier Chinese city from 2013 to 2021.

Background: To evaluate temporal trends in gender, etiology, severity, outcomes, cost and median length of stay (MLS) in patients with acute pancreatitis (AP) in a third-tier Chinese city.

Methods: Patients with AP admitted to a university hospital between January 2013 and December 2021. Relationships between etiology, prevalence of severe acute pancreatitis (SAP) and survey years were investigated by joinpoint regression analysis.

Discovery of 7,9-Dibromo-dihydrodibenzofuran as a Potent Casein Kinase 2 (CK2) Inhibitor: Synthesis, Biological Evaluation, and Structural Studies on /-Isomers.

The human protein kinase CK2 is a promising target for cancer treatment. Only two CK2 inhibitors have reached clinical trials until today. Among others, a dibenzofuran scaffold has emerged as highly prospective for the development of new CK2 inhibitors.

Challenging granulomatous differential diagnosis of CNS lesions in a 75-year-old patient with indolent lymphoma.

We report here on a patient with concomitant indolent lymphoma who showed a rapid progressive deterioration of his general condition and emerging neurological symptoms. The combination of severe B symptoms with hypermetabolic involvement of the adrenal glands and multiple central nervous system (CNS) lesions initially suggested a malignant disease. However, when the patient presented to us with biopsy results from one of the CNS lesions, the biopsy revealed granulomatous inflammation but no evidence of malignancy.