Nociceptor sodium channels shape subthreshold phase, upstroke, and shoulder of action potentials.

Voltage-gated sodium channels (VGSCs) in the peripheral nervous system shape action potentials (APs) and thereby support the detection of sensory stimuli. Most of the nine mammalian VGSC subtypes are expressed in nociceptors, but predominantly, three are linked to several human pain syndromes: while Nav1.7 is suggested to be a (sub-)threshold channel, Nav1.

A post-assembly conformational change makes the SARS-CoV-2 polymerase elongation-competent.

Coronaviruses (CoV) encode sixteen non-structural proteins (nsps), most of which form the replication-transcription complex (RTC). The RTC contains a core composed of one nsp12 RNA-dependent RNA polymerase (RdRp), two nsp8s and one nsp7. The core RTC recruits other nsps to synthesize all viral RNAs within the infected cell.

Curative-Intended Management of Synchronous Esophageal and Rectal Cancer-A Systematic Literature Review.

Purpose: Synchronous esophageal (EC) and rectal carcinoma (RC) is a rare and challenging condition, particularly in curative-intended treatment. Especially locally advanced tumors may not be suitable for primary resection and require individual multimodal treatment. This review examines curative-intended management of synchronous EC and RC.

Exceptional Uptake, Limited Protein Expression: Liver Macrophages Lost in Translation of Synthetic mRNA.

Most gene therapies exert their actions via manipulation of hepatocytes (parenchymal cells) and the reasons behind the suboptimal performance of synthetic mRNA in non-parenchymal cells (NPC) such as Kupffer cells (KC), and liver macrophages, remain unclear. Here, the spatio-temporal distribution of mRNA encoding enhanced green fluorescent protein (Egfp), siRNA, or both co-encapsulated into lipid nanoparticles (LNP) in the liver in vivo using real-time intravital imaging is investigated. Although both KC and hepatocytes demonstrate comparable high and rapid uptake of mRNA-LNP and siRNA-LNP in vivo, the translation of Egfp mRNA occurs exclusively in hepatocytes during intravital imaging.

Proenkephalin A 119-159 (penKid) and mortality in stable patients at high cardiovascular risk.

Background: Proenkephalin A 119-159 (penKid) is a novel blood biomarker for real-time assessment of kidney function and was found to be independently associated with worsening kidney function and mortality. A novel penKid-based estimated glomerular filtration rate equation (eGFR), outperforms current creatinine-based eGFR equations in predicting iohexol or iothalamate plasma clearance-based measured GFR. In this study, we aimed to evaluate the predictive value of penKid and eGFR for all-cause mortality in stable patients at high cardiovascular risk.

Crosstalk between periodontitis and cardiovascular risk.

Recent demographic developments resulted in an aged society with a rising disease burden of systemic and non-communicable diseases (NCDs). In cardiovascular disease (CVD), a NCD with high morbidity and mortality, recent preventive strategies include the investigation of comorbidities to reduce its significant economic burden. Periodontal disease, an oral bacterial-induced inflammatory disease of tooth-supporting tissue, is regulated in its prevalence and severity by the individual host response to a dysbiotic oral microbiota.

A bioprinted and scalable model of human tubulo-interstitial kidney fibrosis.

Chronic kidney disease (CKD) affects more than 10% of the global population. As kidney function negatively correlates with the presence of interstitial fibrosis, the development of new anti-fibrotic therapies holds promise to stabilize functional decline in CKD patients. The goal of the study was to generate a scalable bioprinted 3-dimensional kidney tubulo-interstitial disease model of kidney fibrosis.

T cell margination: investigating the detour of T cells following forimtamig treatment in humanized mice.

T cell bispecific antibodies (TCBs) are a promising new class of therapeutics for relapsed/refractory multiple myeloma. A frequently observed, yet incompletely understood effect of this treatment is the transient reduction of circulating T cell counts, also known as T cell margination (TCM). After administration of the GPRC5D-targeting TCB forimtamig (RG6234), TCM occurred in patients and correlated with cytokine release and soluble B cell maturation antigen decrease.

Random forest algorithm identifies miRNA signatures for breast cancer detection and classification from patient urine samples.

Background And Objectives: Breast cancer is the most common cancer in women, with one in eight women suffering from this disease in her lifetime. The implementation of centrally organized mammography screening for women between 50 and 69 years of age was a major step in the direction of early detection. However, the participation rate reaches approximately 50% of the eligible women, one reason being the painful compression of the breast, cited as a major issue for not participating in this very important program.

When most fMRI connectivity cannot be detected: Insights from time course reliability.

The level of correlation between two phenomena is limited by the accuracy at which these phenomena are measured. Despite numerous group reliability studies, the strength of the fMRI connectivity that can be detected given the within-subject time course reliability remains elusive. Moreover, it is unclear how within-subject time course reliability limits the robust detection of connectivity on the group level.

Alpha-1 Antitrypsin Inclusions Sequester GRP78 in a Bile Acid-Inducible Manner.

Background And Aims: The homozygous PiZ mutation (PIZZ genotype) constitutes the predominant cause of severe alpha-1 antitrypsin (AAT) deficiency and leads to liver disease via hepatocellular AAT aggregation. We systematically analysed the composition of AAT aggregates and studied the impact of bile acids.

Methods: AAT inclusions were isolated from livers of PiZ overexpressing mice and PIZZ humans via fluorescence-activated and immunomagnetic sorting (FACS/MACS), while insoluble proteins were obtained via Triton-X extraction.

Polyol pathway-generated fructose is indispensable for growth and survival of non-small cell lung cancer.

Despite recent treatment advances, non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer-related deaths worldwide, and therefore it necessitates the exploration of new therapy options. One commonly shared feature of malignant cells is their ability to hijack metabolic pathways to confer survival or proliferation. In this study, we highlight the importance of the polyol pathway (PP) in NSCLC metabolism.

Sleeve-gastrectomy results in improved metabolism and a massive stress response of the liver proteome in a mouse model of metabolic dysfunction-associated steatohepatitis.

Background: Bariatric surgery has been shown to improve the histopathological findings in patients with obesity and metabolic dysfunction-associated steatohepatitis, but there are also reports about non-responders or progressive disease after bariatric interventions. Therefore, it is of utmost importance to understand the pathophysiological processes in the liver after bariatric surgery.

Materials And Methods: In the present study, 4 weeks old male C57/Bl6 mice were fed a Western Diet to induce metabolic dysfunction-associated steatohepatitis and sleeve-gastrectomy (SG), or sham operation in the pair-fed and ad libitum control group were performed.

plaque formation model to unravel biofilm formation dynamics on implant abutment surfaces.

Background: Biofilm formation on implant-abutment surfaces can cause inflammatory reactions. Ethical concerns often limit intraoral testing, necessitating preliminary in vitro or animal studies. Here, we propose an in vitro model using human saliva and hypothesize that this model has the potential to closely mimic the dynamics of biofilm formation on implant-abutment material surfaces in vivo.

Gpr55 deficiency crucially alters cardiomyocyte homeostasis and counteracts angiotensin II induced maladaption in female mice.

Background And Purpose: Cannabis stimulates several G-protein-coupled-receptors and causes bradycardia and hypotension upon sustained consumption. Moreover, in vitro studies suggest an interference of cannabinoid-signalling with cardiomyocyte contractility and hypertrophy. We aimed at revealing a functional contribution of the cannabinoid-sensitive receptor GPR55 to cardiomyocyte homeostasis and neurohumorally induced hypertrophy in vivo.

Zero-Shot LLMs for Named Entity Recognition: Targeting Cardiac Function Indicators in German Clinical Texts.

Introduction: Large Language Models (LLMs) like ChatGPT have become increasingly prevalent. In medicine, many potential areas arise where LLMs may offer added value. Our research focuses on the use of open-source LLM alternatives like Llama 3, Gemma, Mistral, and Mixtral to extract medical parameters from German clinical texts.

Molecular Hydrogen and Extracorporeal Gas Exchange: A Match Made in Heaven? An In Vitro Pilot Study.

Extracorporeal circulation (ECC) is frequently implemented in a vast array of modalities such as hemodialysis, cardiopulmonary bypass, extracorporeal membrane oxygenation (ECMO), and others. Patients receiving any such therapy are frequently encumbered with chronic inflammation, which is inherently accompanied by oxidative stress. However, ECC treatments themselves are also responsible for sustaining or promoting inflammation.

Assessing the Reliability of Machine Learning Explanations in ECG Analysis Through Feature Attribution.

Feature attribution methods stand as a popular approach for explaining the decisions made by convolutional neural networks. Given their nature as local explainability tools, these methods fall short in providing a systematic evaluation of their global meaningfulness. This limitation often gives rise to confirmation bias, where explanations are crafted after the fact.

The calcium-sensing-receptor (CaSR) in adipocytes contributes to sex-differences in the susceptibility to high fat diet induced obesity and atherosclerosis.

Background: Female mice are more resistant to obesogenic effects of a high-fat diet (HFD), compared to male mice. Although the underlying mechanisms are poorly understood, sex hormones seem to play an important role. Interestingly, the activity of the oestrogen receptor-α (ERα) is affected by the calcium-sensing-receptor (CaSR).