Prioritizing protein targets for dyslipidaemia and cardiovascular diseases using Mendelian randomization in South Asians.

South Asians are at higher risk of dyslipidaemia-a modifiable risk factor for cardiovascular diseases (CVDs). We aimed to identify protein targets for dyslipidaemia and CVDs in this population. We used a two-sample Mendelian randomization (MR) approach, supplemented with MR-Egger, weighted median, colocalization, and generalized MR (GMR), to evaluate the effect of 2,800 plasma proteins on high/low/non-high-density lipoprotein cholesterol (HDL-C/LDL-C/nonHDL-C), total cholesterol, and triglycerides.

High-throughput identification of calcium-regulated proteins across diverse proteomes.

Calcium ions play important roles in nearly every biological process, yet whole-proteome analysis of calcium effectors has been hindered by a lack of high-throughput, unbiased, and quantitative methods to identify protein-calcium engagement. To address this, we adapted protein thermostability assays in budding yeast, human cells, and mouse mitochondria. Based on calcium-dependent thermostability, we identified 2,884 putative calcium-regulated proteins across human, mouse, and yeast proteomes.

Management of cytomegalovirus infections - Swedish recommendations 2023.

Cytomegalovirus (CMV) infection, which mostly causes a subclinical infection early in life, has important clinical consequences in certain patient groups. CMV is the most common congenital infection and can cause permanent disabilities such as hearing loss and motor- and cognitive deficits in affected infants. In allogeneic haematopoietic stem cell and solid organ transplant recipients, CMV still is an important infectious complication with a risk for life-threatening disease.

Recurrent adamantinomatous craniopharyngiomas show MAPK pathway activation, clonal evolution and rare TP53-loss-mediated malignant progression.

The two types of craniopharyngioma, adamantinomatous (ACP) and papillary (PCP), are clinically relevant tumours in children and adults. Although the biology of primary craniopharyngioma is starting to be unravelled, little is known about the biology of recurrence. To fill this gap in knowledge, we have analysed through methylation array, RNA sequencing and pERK1/2 immunohistochemistry a cohort of paired primary and recurrent samples (32 samples from 14 cases of ACP and 4 cases of PCP).

[Shortfalls of new data 2017-2020 in the German transplant registry].

Introduction: Recently, considerable deficiencies of legacy data (2006–2016) of the newly established German Transplant Registry were described. Current data (2017–2020) of the registry are subject to the present assessment.

Material And Methods: The registry is divided in 80 elements containing different topics.

Integrative genomic analyses of European intrahepatic cholangiocarcinoma: Novel ROS1 fusion gene and PBX1 as prognostic marker.

Background: Cholangiocarcinoma (CCA) is a fatal cancer of the bile duct with a poor prognosis owing to limited therapeutic options. The incidence of intrahepatic CCA (iCCA) is increasing worldwide, and its molecular basis is emerging. Environmental factors may contribute to regional differences in the mutation spectrum of European patients with iCCA, which are underrepresented in systematic genomic and transcriptomic studies of the disease.

Allee effects introduced by density dependent phenology.

We consider a hybrid model of an annual species with the timing of a stage transition governed by density dependent phenology. We show that the model can produce a strong Allee effect as well as overcompensation. The density dependent probability distribution that describes how population emergence is spread over time plays an important role in determining population dynamics.

Unravelling genetic architecture of circulatory amino acid levels, and their effect on risk of complex disorders.

Variations in serum amino acid levels are linked to a multitude of complex disorders. We report the largest genome-wide association study (GWAS) on nine serum amino acids in the UK Biobank participants (117 944, European descent). We identified 34 genomic loci for circulatory levels of alanine, 48 loci for glutamine, 44 loci for glycine, 16 loci for histidine, 11 loci for isoleucine, 19 loci for leucine, 9 loci for phenylalanine, 32 loci for tyrosine and 20 loci for valine.

[The German Transplant Registry - An Analysis of Legacy Data 2006-2016].

Introduction: In 2018, medical transplant data from three institutions were merged to create a German transplant registry. Since June 2021, access to data of the registry has been available. It was planned to analyze the registry data in order to compare special allocation rules with regular allocation for heart, liver, lung, and kidney transplantation.

Spread and persistence for integro-difference equations with shifting habitat and strong Allee effect.

We study an integro-difference equation model that describes the spatial dynamics of a species with a strong Allee effect in a shifting habitat. We examine the case of a shifting semi-infinite bad habitat connected to a semi-infinite good habitat. In this case we rigorously establish species persistence (non-persistence) if the habitat shift speed is less (greater) than the asymptotic spreading speed of the species in the good habitat.

High-Throughput Identification of Calcium Regulated Proteins Across Diverse Proteomes.

Calcium ions play important roles in nearly every biological process, yet whole-proteome analysis of calcium effectors has been hindered by lack of high-throughput, unbiased, and quantitative methods to identify proteins-calcium engagement. To address this, we adapted protein thermostability assays in the budding yeast, human cells, and mouse mitochondria. Based on calcium-dependent thermostability, we identified 2884 putative calcium-regulated proteins across human, mouse, and yeast proteomes.

Tepotinib in patients with non-small cell lung cancer with high-level MET amplification detected by liquid biopsy: VISION Cohort B.

High-level MET amplification (METamp) is a primary driver in ∼1%-2% of non-small cell lung cancers (NSCLCs). Cohort B of the phase 2 VISION trial evaluates tepotinib, an oral MET inhibitor, in patients with advanced NSCLC with high-level METamp who were enrolled by liquid biopsy. While the study was halted before the enrollment of the planned 60 patients, the results of 24 enrolled patients are presented here.

Forced Traveling Waves in a Reaction-Diffusion Equation with Strong Allee Effect and Shifting Habitat.

We study a reaction-diffusion equation that describes the growth of a population with a strong Allee effect in a bounded habitat which shifts at a speed [Formula: see text]. We demonstrate that the existence of forced positive traveling waves depends on habitat size L, and [Formula: see text], the speed of traveling wave for the corresponding reaction-diffusion equation with the same growth function all over the entire unbounded spatial domain. It is shown that for [Formula: see text] there exists a positive number [Formula: see text] such that for [Formula: see text] there are two positive traveling waves and for [Formula: see text] there is no positive traveling wave.

Tepotinib Treatment in Patients With MET Exon 14-Skipping Non-Small Cell Lung Cancer: Long-term Follow-up of the VISION Phase 2 Nonrandomized Clinical Trial.

Importance: MET inhibitors have recently demonstrated clinical activity in patients with MET exon 14 (METex14)-skipping non-small cell lung cancer (NSCLC); however, data with longer follow-up and in larger populations are needed to further optimize therapeutic approaches.

Objective: To assess the long-term efficacy and safety of tepotinib, a potent and highly selective MET inhibitor, in patients with METex14-skipping NSCLC in the VISION study.

Design, Setting, And Participants: The VISION phase 2 nonrandomized clinical trial was a multicohort, open-label, multicenter study that enrolled patients with METex14-skipping advanced/metastatic NSCLC (cohorts A and C) from September 2016 to May 2021.

Microvascular invasion of hepatocellular carcinoma predicts microvascular invasion of its recurrence: potential implications for salvage liver transplantation?

Background: Microvascular invasion (MVI) can only be assessed on a full surgical specimen. We aimed at evaluating, whether the histology of the primary tumor is predictive of MVI in a hepatocellular carcinoma (HCC) recurrence.

Methods: Patients, who underwent liver resection or orthotopic liver transplantation (OLT) for recurrent HCC from January 2001 until June 2018 were eligible for this retrospective analysis.

Minimal requirements for ISO15189 validation and accreditation of three next generation sequencing procedures for SARS-CoV-2 surveillance in clinical setting.

Rapid and recurrent breakthroughs of new SARS-CoV-2 strains (variants) have prompted public health authorities worldwide to set up surveillance networks to monitor the circulation of variants of concern. The use of next-generation sequencing technologies has raised the need for quality control assessment as required in clinical laboratories. The present study is the first to propose a validation guide for SARS-CoV-2 typing using three different NGS methods fulfilling ISO15189 standards.

House design and risk of malaria, acute respiratory infection and gastrointestinal illness in Uganda: A cohort study.

House construction is rapidly modernizing across Africa but the potential benefits for human health are poorly understood. We hypothesised that improvements to housing would be associated with reductions in malaria, acute respiratory infection (ARI) and gastrointestinal illness in an area of low malaria endemicity in Uganda. Data were analysed from a cohort study of male and female child and adult residents (n = 531) of 80 randomly-selected households in Nagongera sub-county, followed for 24 months (October 4, 2017 to October 31, 2019).

Unravelling morphoea aetiopathogenesis by next-generation sequencing of paired skin biopsies.

Background: Morphoea can have a significant disease burden. Aetiopathogenesis remains poorly understood, with very limited existing genetic studies. Linear morphoea (LM) may follow Blascho's lines of epidermal development, providing potential pathogenic clues.

Characterization of trial duration in traditional and emerging postural control measures.

Researchers may select from varied technological and practical options when evaluating balance. Methodological choices inform the quantitative outcomes observed and allow practitioners to diagnose balance abnormalities. Past investigations have differed widely on sampling duration, and these discrepancies hinder comparisons among studies and confidence in outcomes where trials were excessively short.