SLCO1B1 Functional Variants, Bilirubin, Statin-Induced Myotoxicity, and Recent Sub-Saharan African Ancestry: A Precision Medicine Health Equity Study.

Statin pharmacogenetic implementation guidelines are derived from evidence of primarily Eurocentrically biased study populations. Functional SLCO1B1 variants that are rare in these study populations have not been equitably investigated and are thus missing from guidelines. The objective of this precision medicine health equity study was to determine the clinical validity of understudied candidate functional SLCO1B1 variants common in people with 1,000 Genomes sub-Saharan African superpopulation (1KG-AFR-like) genetic similarity.

How positive and negative feedback following real interactions changes subsequent sender ratings.

Social evaluative feedback informs us about how others perceive us, constantly updates our expectations of what to receive, and simultaneously changes our view of the sender. However, little is known about the neuronal and behavioral responses when receiving incongruent positive or negative social evaluative feedback. This study (N = 40) investigated how receiving feedback from peers after a real-life interaction modulates behavioral responses and Event-Related Potentials (ERPs).

The Risk of Herpes Zoster in Patients with Depressive Disorders: A German Claims Database Analysis.

Introduction: Patients with depression were shown to be at increased risk of herpes zoster (HZ). However, an in-depth description of depression as a risk factor for HZ, postherpetic neuralgia (PHN), and HZ recurrence is lacking. The goal of this study was to quantify the risk of HZ, PHN, and HZ recurrence in people with depression and among depression-related subgroups in Germany.

Tumor Necrosis Factor-Alpha Inhibitor Use and Malignancy Risk: A Systematic Review and Patient Level Meta-Analysis.

Over the last two decades, tumor necrosis factor-alpha inhibitors (TNF-Is) have become standard therapies for chronic inflammatory disorders, with an ongoing expansion of indications and off-label applications [...

Genome-wide association study of prostate-specific antigen levels in 392,522 men identifies new loci and improves prediction across ancestry groups.

We conducted a multiancestry genome-wide association study of prostate-specific antigen (PSA) levels in 296,754 men (211,342 European ancestry, 58,236 African ancestry, 23,546 Hispanic/Latino and 3,630 Asian ancestry; 96.5% of participants were from the Million Veteran Program). We identified 318 independent genome-wide significant (P ≤ 5 × 10) variants, 184 of which were novel.

The antifungal peptide AnAFP from promotes nutrient mobilization through autophagic recycling during asexual development.

Antifungal peptides are promising drug candidates to fight fungal infections in the clinics and agriculture. However, recent data suggest that antifungal peptides might also play a role within their own producing organism to survive nutrient limiting conditions. We have therefore studied the function of the antifungal AnAFP in in more detail.

Unraveling the genetic landscape of susceptibility to multiple primary cancers.

With advances in cancer screening and treatment, there is a growing population of cancer survivors who may develop subsequent primary cancers. While hereditary cancer syndromes account for only a portion of multiple cancer cases, we sought to explore the role of common genetic variation in susceptibility to multiple primary tumors. We conducted a cross-ancestry genome-wide association study (GWAS) and transcriptome-wide association study (TWAS) of 10,983 individuals with multiple primary cancers, 84,475 individuals with single cancer, and 420,944 cancer-free controls from two large-scale studies.

Spatial Proteomics by Parallel Accumulation-Serial Fragmentation Supported MALDI MS/MS Imaging: A First Glance Into Multiplexed and Spatial Peptide Identification.

Rationale: In spatial proteomics, matrix-assisted laser desorption/ionization (MALDI) imaging enables rapid and cost-effective peptide measurements. Yet, in situ peptide identification remains challenging. Therefore, this study aims to integrate the trapped ion mobility spectrometry (TIMS)-based parallel accumulation-serial fragmentation (PASEF) into MALDI imaging of tryptic peptides to enable multiplexed MS/MS imaging.

Genome-Wide Association Analyses of HPV16 and HPV18 Seropositivity Identify Susceptibility Loci for Cervical Cancer.

Infection by high-risk human papillomavirus is known to exacerbate cervical cancer development. The host immune response is crucial in disease regression. Large-scale genetic association studies for cervical cancer have identified few susceptibility variants, mainly at the human leukocyte antigen locus on chromosome 6.

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.

Papilledema in Children With Cystic Fibrosis Receiving Elexacaftor/Tezacaftor/Ivacaftor: A Multicenter Case Series.

Following the approval of elexacaftor/tezacaftor/ivacaftor (ETI), there have been post-marketing reports and published cases of papilledema and intracranial hypertension in children with cystic fibrosis (CF) taking ETI. In those reports, the patients often presented with marked symptoms and concomitant hypervitaminosis A. In this multicenter case series, we report eight cases of papilledema in children with CF taking ETI that were diagnosed via routine eye exam, the majority of whom presented with minimal to no symptoms and all had normal serum Vitamin A levels.

Polygenic Risk Score and Upgrading in Patients With Prostate Cancer Receiving Active Surveillance.

Importance: Active surveillance is the preferred management strategy for patients with low- or favorable intermediate-risk prostate cancer (PCa); however, frequent health care visits can be costly and burdensome to patients. Identifying patients who may benefit from intensive vs passive surveillance could reduce these burdens.

Objective: To investigate associations between a polygenic risk score (PRS) and risk of upgrading and other prostate tumor features in patients receiving active surveillance.

Unraveling the genetic landscape of susceptibility to multiple primary cancers.

With advances in cancer screening and treatment, there is a growing population of cancer survivors who may develop subsequent primary cancers. While hereditary cancer syndromes account for only a portion of multiple cancer cases, we sought to explore the role of common genetic variation in susceptibility to multiple primary tumors. We conducted a cross-ancestry genome-wide association study (GWAS) and transcriptome-wide association study (TWAS) of 10,983 individuals with multiple primary cancers, 84,475 individuals with single cancer, and 420,944 cancer-free controls from two large-scale studies.

Health care costs of incident ADHD in children and adolescents in Germany - A claims data analysis within the framework of the consortium project INTEGRATE-ADHD.

Background: Attention-deficit/hyperactivity disorder (ADHD) is associated with increased costs for the family, the health care system and the society. Previous cost-of-illness studies in Germany usually focused on prevalent ADHD. This study addressed the research gap on health care resource utilisation and costs of children and adolescents with incident ADHD diagnosis using nationwide claims data from the statutory health insurance DAK-Gesundheit.

Psychometric evaluation of the Clinical Interview for Externalizing Disorders (ILF-EXTERNAL) in an online setting - Results from the consortium project INTEGRATE-ADHD.

Background: The study examines the psychometric properties of the ADHD section of the semi-structured diagnostic interview ILF-EXTERNAL, which was conducted online via video chat.

Methods: As part of the INTEGRATE-ADHD research project, 202 children and adolescents (age = 12.87 years, = 3.

ADHD in children and adolescents: Guideline-based online assessment in the consortium project INTEGRATE-ADHD.

Background: The consortium project INTEGRATE-ADHD compared administrative data on the presence of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents with the results of a parent survey and a comprehensive clinical assessment based on the S3 guideline of the Association of the Scientific Medical Societies in Germany (AWMF). Due to the COVID-19 pandemic, the clinical assessment was carried out online.

Methods: The article describes how a guideline-based clinical assessment of ADHD can be implemented in an online setting.

When do parents report their child's administrative ADHD diagnosis? A utilisation-based analysis from the consortium project INTEGRATE-ADHD.

Background: This article examines discrepancies in the frequency of diagnoses of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents in Germany using information on health care utilisation from both administrative and parent-reported survey data linked at person level.

Methods: 5,461 parents of 0- to 17-year-olds insured with DAK-Gesundheit in 2020 and being registered with a confirmed administrative ADHD diagnosis (ICD-10 F90.0-9) in at least one quarter in 2020 (M1Q criterion) were surveyed online on their child's ADHD diagnosis, utilisation of specialist care and therapeutic service providers.

Risk and protective factors associated with health-related quality of life in children and adolescents with ADHD in Germany - Findings from the consortium project INTEGRATE-ADHD.

Background: The health-related quality of life (HRQoL) of individuals living with Attention-deficit/hyperactivity disorder (ADHD) is known to be impaired. Identifying factors that influence HRQoL can provide important information for the development of prevention and intervention programmes for affected children and adolescents. The aim of the present study was to investigate health care-related and psychosocial risk and protective factors for HRQoL in children and adolescents with an administrative ADHD diagnosis.

Out of focus but still relevant? Influenza-related resource utilization and vaccination coverage gaps in adults below 60 years of age with underlying conditions: an analysis of 2016-2024 real-world data in Germany.

Background: In 2003, the WHO aimed for a 75% or higher influenza vaccination rate among at-risk populations. However, this target was achieved in a few groups during selected seasons in some European countries, and never in Germany. Adults with underlying conditions (UCs) are a critical negleted group for influenza vaccination.

Switchable protection and exposure of a sensitive squaraine dye within a redox active rotaxane.

In nature, molecular environments in proteins can sterically protect and stabilize reactive species such as organic radicals through non-covalent interactions. Here, we report a near-infrared fluorescent rotaxane in which the stabilization of a chemically labile squaraine fluorophore by the coordination of a tetralactam macrocycle can be controlled chemically and electrochemically. The rotaxane can be switched between two co-conformations in which the wheel either stabilizes or exposes the fluorophore.

Enhancing Colorimetric Detection of Nucleic Acids on Nitrocellulose Membranes: Cutting-Edge Applications in Diagnostics and Forensics.

This study re-introduces a protein-free rapid test method for nucleic acids on paper based lateral flow assays utilizing special multichannel nitrocellulose membranes and DNA-Gold conjugates, achieving significantly enhanced sensitivity, easier protocols, reduced time of detection, reduced costs of production and advanced multiplexing possibilities. A protein-free nucleic acid-based lateral flow assay (NALFA) with a limit of detection of 1 pmol of DNA is shown for the first time. The total production duration of such an assay was successfully reduced from the currently known several days to just a few hours.

Correction Factor Evaluation and Between-System Comparison of Behavioral Threshold Predictions From Auditory Brainstem Response Measures in Infants.

Purpose: Auditory brainstem response (ABR) thresholds are corrected to estimate behavioral thresholds in infants. Corrections were validated, and a comparison of behavioral threshold estimates between systems was conducted to inform equipment transition and protocols in Ontario, Canada.

Method: In Study 1, a retrospective file review was conducted.