Protocol for genome-wide analysis of somatic variants at single-cell resolution using primary template-directed DNA amplification.

The study of somatic mutations in single cells provides insights into aging and carcinogenesis, which is complicated by the dependency on whole-genome amplification (WGA). Here, we describe a detailed workflow starting from single-cell isolation to WGA by primary template-directed amplification (PTA), sequencing, quality control, and downstream analyses. A machine learning approach, the PTA Analysis Toolkit (PTATO), is used to filter the hundreds to thousands of artificial variants induced by WGA from true mutations at high sensitivity and accuracy.

Associations between momentary mental states and concurrent social functioning after remission from first episode psychosis: A HAMLETT ecological momentary assessment study.

Background: Symptom severity and social functioning are important outcomes after first episode psychosis (FEP), yet current evidence about associations between them is inconsistent and lacks (subclinical) momentary insights.

Methods: The current Ecological Momentary Assessment (EMA) study was conducted in 58 people in remission from FEP, as part of the HAMLETT (Handling Antipsychotic Medication: Long-term Evaluation of Targeted Treatment) trial. At baseline, participants were prompted to report momentary mental states and social context 10x/day for eight consecutive days, including psychotic experiences (PEs), motivation/drive and negative affect, that may indicate proxies of (subclinical) psychotic, negative and general affective symptoms, respectively.

Does the treatment modality affect nosocomial pneumonia and other in-hospital outcomes in patients with combined injuries to the ribs and clavicle? A propensity score weighted analysis of a retrospective cohort.

Objective: What is the effect of surgical or conservative treatment on the in-hospital outcomes of patients with combined fractures of the clavicle and ribs?

Design: Retrospective cohort study.

Setting: Two level-1 trauma centers and academic teaching hospitals in Boston, Massachusetts.

Patients: All adult patients with a clavicle fracture and ≥3 rib fractures admitted from 2016 to 2021.

Development and validation of a gonadotropin dose selection model for optimized ovarian stimulation in IVF/ICSI: an individual participant data meta-analysis.

Background: The ovarian response to gonadotropin stimulation varies widely among women, and could impact the probability of live birth as well as treatment risks. Many studies have evaluated the impact of different gonadotropin starting doses, mainly based on predictive variables like ovarian reserve tests (ORT) including anti-Müllerian hormone (AMH), antral follicle count (AFC), and basal follicle-stimulating hormone (bFSH). A Cochrane systematic review revealed that individualizing the gonadotropin starting dose does not affect efficacy in terms of ongoing pregnancy/live birth rates, but may reduce treatment risks such as the development of ovarian hyperstimulation syndrome (OHSS).

A novel 3D image registration technique for augmented reality vision in minimally invasive thoracoscopic pulmonary segmentectomy.

Purpose: In this feasibility study, we aimed to create a dedicated pulmonary augmented reality (AR) workflow to enable a semi-automated intraoperative overlay of the pulmonary anatomy during video-assisted thoracoscopic surgery (VATS) or robot-assisted thoracoscopic surgery (RATS).

Methods: Initially, the stereoscopic cameras were calibrated to obtain the intrinsic camera parameters. Intraoperatively, stereoscopic images were recorded and a 3D point cloud was generated from these images.

A Systematic Review of Challenges and Opportunities in the Implementation of Managed Entry Agreements for Advanced Therapy Medicinal Products.

Purpose: Managed Entry Agreements (MEAs) are agreements between firms and competent authorities for pricing and reimbursement, designed to enable coverage of new medicines while managing uncertainties around their financial impact or performance. Although these agreements can facilitate patient access, their complexity and costs seem to dampen enthusiasm for implementation. Nevertheless, MEAs remain a potential route, particularly for high-cost drugs with uncertain value claims.

Uncomplicated Type B Aortic Dissection - A European Multicentre Cross-Sectional Evaluation.

Objectives: A multicentre European randomized control trial - European Uncomplicated Type B Aortic Repair (EU-TBAR) is being developed to compare pre-emptive TEVAR with custom-made devices vs conventional OMT. The pre-trial set-up is confluent on different pillars, including evaluation of 1) European activity, trends, and governance, 2) outcome reporting, and 3) cost evaluation. This article aimed to demonstrate the observational cross-sectional survey results from participating centres and highlight the risk assessment, activity, practices, and governance of uncomplicated type B aortic dissection (uTBAD).

The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression.

Objective: To determine the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcome in treatment-resistant depression.

Methods: For treatment-resistant depression, 233 participants received a single dose of 25, 10, or 1 mg of COMP360 psilocybin (a proprietary, pharmaceutical-grade synthesized psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.) with psychological support.

Generation and characterization of novel induced pluripotent stem cell (iPSC) lines derived from three symptomatic carriers of a pathogenic MYH11 variant and two non-carrier relatives.

A novel pathogenic variant in the MYH11 gene (c.4559+1G>A) leading to exon 32 skipping, is a rare cause of familial aortic aneurysms and dissections (fTAAD). The phenotype has proven highly variable with reduced penetrance.

Trends in the Incidence, Organization of Care, and Surgical Treatment of Medullary Thyroid Cancer: A Population-Based Study.

Medullary thyroid cancer (MTC) is a rare cancer with variable disease course. To enable optimal care, centralization and consensus guidelines are essential. This study describes trends in the incidence, organization of care, surgical treatment, and outcomes of MTC over 30 years in the Netherlands.

State of the art of CT myocardial perfusion.

Coronary computed tomography angiography (CCTA) is a powerful tool to rule out coronary artery disease (CAD). In the last decade, myocardial perfusion CT (CTP) technique has been developed for the evaluation of myocardial ischemia, thereby increasing positive predictive value for diagnosis of obstructive CAD. A diagnostic strategy combining CCTA and perfusion acquisitions provides both anatomical coronary evaluation and functional evaluation of the stenosis, increasing the specificity and the positive predictive value of cardiac CT.

C21ORF2 mutations point towards primary cilia dysfunction in amyotrophic lateral sclerosis.

Progressive loss of motor neurons is the hallmark of the neurodegenerative disease amyotrophic lateral sclerosis (ALS), but the underlying disease mechanisms remain incompletely understood. In this study, we investigate the effects of C21ORF2 mutations, a gene recently linked to ALS, and find that primary cilia are dysfunctional. Human patient-derived mutant C21ORF2 motor neurons have a reduced ciliary frequency and length.

Quantitative F-FDG PET-CT can assess presence and extent of interstitial lung disease in early severe diffuse cutaneous systemic sclerosis.

Background: This study aimed to assess the quantitative uptake of F-FDG PET-CT in the lungs of patients with early severe diffuse cutaneous systemic sclerosis (SSc) with and without interstitial lung disease (ILD), compared to controls. In patients with SSc-ILD, F-FDG uptake was correlated to high-resolution computed tomography (HRCT) and pulmonary function test (PFT) parameters.

Methods: A prospective, cross-sectional study was conducted, involving 15 patients with SSc-ILD, 5 patients with SSc without ILD, and 7 controls without SSc.

European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics - Update 2024.

This guideline was developed in close collaboration with multidisciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF) and the European Organization for Research and Treatment of Cancer (EORTC). Recommendations for the diagnosis and treatment of melanoma were developed on the basis of systematic literature research and consensus conferences. Cutaneous melanoma (CM) is the most dangerous form of skin tumor and accounts for 90 % of skin cancer mortality.

Uneven Distribution of Purkinje Cell Injury in the Cerebellar Vermis of Term Neonates with Hypoxic-Ischemic Encephalopathy.

In term neonates with hypoxic-ischemic encephalopathy (HIE), cerebellar injury is becoming more and more acknowledged. Animal studies demonstrated that Purkinje cells (PCs) are especially vulnerable for hypoxic-ischemic injury. In neonates, however, the extent and pattern of PC injury has not been investigated.

An evolutionary perspective on the relationship between kinetochore size and CENP-E dependence for chromosome alignment.

Chromosome alignment during mitosis can occur as a consequence of bi-orientation or is assisted by the CENP-E (kinesin-7) motor at kinetochores. We previously found that Indian muntjac chromosomes with larger kinetochores bi-orient more efficiently and are biased to align in a CENP-E-independent manner, suggesting that CENP-E dependence for chromosome alignment negatively correlates with kinetochore size. Here, we used targeted phylogenetic profiling of CENP-E in monocentric (localized centromeres) and holocentric (centromeres spanning the entire chromosome length) clades to test this hypothesis at an evolutionary scale.

Clinical Characterization of a National Cohort of Patients With Germline Variants Including Late-Onset Phenotypes.

Introduction: disorder is a recently introduced term for phenotypes associated with germline Wilms Tumor 1 () variants, including glomerulopathy, urogenital anomalies, and Wilms tumor. Previous studies showed a bias toward missense variants in the DNA-binding/Zinc-finger domain of (exon 8 and 9) and patients with early-onset glomerulopathy. Thorough genotype-phenotype correlations including follow-up data on late-onset glomerulopathy risk are lacking.

Combining unequal variance signal detection theory with the health belief model to optimize shared decision making in tinnitus patients: part 1-model development.

Introduction: The results from different Cochrane studies justify considerable professional equipoise concerning different treatment options for tinnitus. In case of professional equipoise, Shared Decision Making (SDM) is an indispensable tool for guiding patients to the intervention that best fits their needs. To improve SDM we developed a method to assess the accuracy and utility of decisions made by tinnitus patients when freely choosing between different treatment options during their patient journey.

Validation of prognostic models predicting mortality or ICU admission in patients with COVID-19 in low- and middle-income countries: a global individual participant data meta-analysis.

Background: We evaluated the performance of prognostic models for predicting mortality or ICU admission in hospitalized patients with COVID-19 in the World Health Organization (WHO) Global Clinical Platform, a repository of individual-level clinical data of patients hospitalized with COVID-19, including in low- and middle-income countries (LMICs).

Methods: We identified eligible multivariable prognostic models for predicting overall mortality and ICU admission during hospital stay in patients with confirmed or suspected COVID-19 from a living review of COVID-19 prediction models. These models were evaluated using data contributed to the WHO Global Clinical Platform for COVID-19 from nine LMICs (Burkina Faso, Cameroon, Democratic Republic of Congo, Guinea, India, Niger, Nigeria, Zambia, and Zimbabwe).

Epigenome-wide association studies identify novel DNA methylation sites associated with PTSD: a meta-analysis of 23 military and civilian cohorts.

Background: The occurrence of post-traumatic stress disorder (PTSD) following a traumatic event is associated with biological differences that can represent the susceptibility to PTSD, the impact of trauma, or the sequelae of PTSD itself. These effects include differences in DNA methylation (DNAm), an important form of epigenetic gene regulation, at multiple CpG loci across the genome. Moreover, these effects can be shared or specific to both central and peripheral tissues.

The plasma lipidome varies with the severity of metabolic dysfunction-associated steatotic liver disease.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with many aspects of disturbed metabolic health. MASLD encompasses a wide spectrum of liver diseases, ranging from isolated steatosis to metabolic dysfunction-associated steatohepatitis (MASH), up to fibrosis, cirrhosis, and ultimately hepatocellular carcinoma. Limited noninvasive diagnostic tools are currently available to distinguish the various stages of MASLD and as such liver biopsy remains the gold standard for MASLD diagnostics.

Impaired liver function: effect on paclitaxel toxicity, dose modifications and overall survival.

Background: The anticancer drug paclitaxel is primarily metabolized in the liver. Previous studies have indicated a correlation between impaired liver function and paclitaxel toxicity, which may indicate dose reduction. Since the evidence is limited, the aim of this study was to investigate the effect of impaired liver function on the hematological toxicity of paclitaxel, dose modifications and overall survival (OS).

An hiPSC-CM approach for electrophysiological phenotyping of a patient-specific case of short-coupled TdP.

Introduction: A healthy young woman, age 26 without prior cardiac complications, experienced an out-of-hospital cardiac arrest caused by ventricular fibrillation (VF), which coincided with a fever. Comprehensive diagnostics including echo, CMR, exercise testing, and genetic sequencing, did not identify any potential cause. This led to the diagnosis of idiopathic VF and installment of an implantable cardioverter defibrillator, which six months later appropriately intervened another VF episode under conditions comparable to the first event.

A mixed method study investigating the key translational competencies acquired during a challenge-based course.

Background: The translational domain is a complex subfield of the biomedical life sciences focused on bridging the gap between scientific research and clinical application, with the ultimate goal of improving patient care through healthcare innovations. Professionals in this field, ranging from researchers to clinicians and industry experts, require specific core competencies. These include communication, collaboration, boundary crossing, innovation, and the ability to integrate diverse scientific domains.

Exploring the association of metabolic factors and chronic musculoskeletal pain over a period of 10 years - the Doetinchem Cohort Study.

Objective: To examine (a) the association between metabolic factors and chronic musculoskeletal pain (CMP), (b) metabolic predictors of CMP 10 years later, and (c) the association and evolution of metabolic factors across different CMP trajectory groups.

Design: Data from the longitudinal Doetinchem Cohort Study were used. We used round 4 (2003-2007), with 4519 participants aged 36-75 years, as the baseline for the present study, with follow-up measurements in round 5 (2008-2012), and 6 (2013-2017), including self-reported pain and metabolic factors, which were measured either via self-report or physical assessment.