Dataset of single nucleotide polymorphisms of immune-associated genes in patients with SARS-CoV-2 infection.

The SARS-CoV-2 pandemic has affected nations globally leading to illness, death, and economic downturn. Why disease severity, ranging from no symptoms to the requirement for extracorporeal membrane oxygenation, varies between patients is still incompletely understood. Consequently, we aimed at understanding the impact of genetic factors on disease severity in infection with SARS-CoV-2. Here, we provide data on demographics, ABO blood group, human leukocyte antigen (HLA) type, as well as next-generation sequencing data of genes in the natural killer cell receptor family, the renin-angiotensin-aldosterone and kallikrein-kinin systems and others in 159 patients with SARS-CoV-2 infection, stratified into seven categories of disease severity. We provide single-nucleotide polymorphism (SNP) data on the patients and a protein structural analysis as a case study on a SNP in the SIGLEC7 gene, which was significantly associated with the clinical score. Our data represent a resource for correlation analyses involving genetic factors and disease severity and may help predict outcomes in infections with future SARS-CoV-2 variants and aid vaccine adaptation.

Genetic analysis of sudden unexpected death cases: Evaluation of library preparation methods to handle heterogeneous sample material.

Over the past years, next-generation sequencing (NGS) technologies revolutionized the possibilities in a broad range of application areas. Also in the field of forensic genetics, NGS continuously gained in importance and attentiveness. A significant number of sudden cardiac deaths (SCD) in the young is due to heritable arrhythmia syndromes emphasizing the need of examining the genetic basis in these cases also with regard to the identification of relatives and/or patients being at risk. As a result, high-throughput methods became of increasing value in molecular autopsy investigations enabling the analysis of a broad spectrum of genes. Most standard protocols are optimized for high-quality samples and frequently not directly applicable to challenging forensic sample material. In the present study, we intended to examine a comprehensive gene panel associated with SCD and inherited arrhythmogenic disorders. We compared three different hybridization-based library preparation technologies in order to implement a suitable NGS workflow for heterogeneous, forensic as well as diagnostic sample material. The results obtained indicated, that the Illumina technologies Nextera DNA Flex and TruSeq were compatible with samples exhibiting varying levels of degradation. In comparison, the TruSight method also resulted in good sequencing data, but seemed to be more dependent on DNA integrity. The preparation protocols evaluated in our study are not restricted to molecular autopsy investigations and might be helpful for and transferrable to further forensic research applications.

Prediction of the pathogenicity of antithrombin sequence variations by in silico methods.

Computational prediction tools have been developed to aid in the interpretation of novel sequence variations, but their utility within the diagnostic setting of antithrombin (AT) deficiency has not been evaluated to date. The aim of our study was to test the performance of different bioinformatic tools (Meta-SNP, MutPred, nsSNPAnalyzer, PANTHER, PhD-SNP, PMut, SIFT, SNAP, SNPs&Go, PolyPhen-2, PON-P2, and PredictSNP) in predicting the pathogenicity of AT sequence variations. We analysed all naturally occurring SERPINC1 missense mutations that have been previously characterised to be damaging with regard to the secretion or function of the AT molecule. Additionally, we analysed all reported non-synonymous exonic polymorphisms within SERPINC1 with a population allele frequency >1.0%. The in silico tools had accuracies of 62-96%, sensitivities of 59-98%, and specificities of 33-100% for the prediction of the pathogenicity of AT sequence variations; receiver operating characteristic analysis had area under the curves between 0.54-0.97. When mutations were grouped according to their effect on the phenotype of AT deficiency [type I or type II with a thrombin (IIRS) or heparin (IIHBS) binding defect or pleiotropic effects (IIPE)], we observed the lowest performance characteristics of the tools for mutations causing AT deficiency type IIHBS. Only three tools (MutPred, PhD-SNP, PolyPhen-2) detected mutants causing type IIHBS AT deficiency with high sensitivity (93%), the sensitivities of the other tools ranged between 36% and 79%. This study demonstrates that bioinformatic tools are useful for pathogenicity prediction for AT sequence variations, but they have substantially different performance characteristics, particularly for type IIHBS AT deficiency.

Cognitive-perceptual factors in noncardiac chest pain and cardiac chest pain.

OBJECTIVE: Noncardiac chest pain (NCCP) is a common condition associated with considerable patient distress and substantial healthcare costs. Our aim was to investigate associations between illness perceptions, anxiety sensitivity, somatic amplification, and experience of chest pain, and to assess whether a multifactorial model including these factors can distinguish patients with NCCP from patients with cardiac chest pain (CCP). METHODS: A total of 240 patients with chest pain answered questionnaires concerning anxiety sensitivity (Anxiety Sensitivity Index-3), somatic amplification (Somatosensory Amplification Scale), illness perceptions (Illness Perception Questionnaire-Brief, health concerns, and heart disease conviction), and pain characteristics (intensity, disability, and frequency) before the evaluation of chest pain causation. They were classified as having NCCP or CCP by cardiac angiography. Partial correlation analyses and binary logistic regression analyses were performed. RESULTS: Seventy percent of patients with chest pain were classified as having NCCP. A range of cognitive-perceptual factors were associated with the experience of chest pain. On multivariate analyses, the only psychological factor found to differentiate NCCP from CCP was elevated somatic amplification (relative risk = 1.06, 95% confidence interval = 1.00-1.13). CONCLUSIONS: The current DSM-5 proposal with regard to somatic symptom disorder recommends using psychological factors as diagnostic criteria for medically unexplained symptoms while placing less emphasis on the criterion of lack of somatic causation. In this study, an association between pain characteristics and cognitive-perceptual factors was found both for patients with NCCP and for patients with CCP. We found no evidence for a specific profile of psychological characteristics distinguishing patients with NCCP from patients with CCP, except for somatic amplification.

Impulse control disorders in obese patients.

The aim of this study was to determine the prevalence of impulse control disorders (ICDs) in morbidly obese individuals. One hundred bariatric surgery candidates were examined using a module of the Structured Clinical Interview for DSM-IV that has been developed for ICDs. Nineteen per cent suffered from at least one current ICD and 27% met the criteria for any lifetime ICD, most frequently skin picking (current, 8%; lifetime, 9%), compulsive buying (current 6%, lifetime 8%), and intermittent explosive disorder (current, 5%; lifetime, 10%). Patients with regular binge eating (N = 25) reported significantly more often a history of at least one ICD compared with those without binge eating. The results indicate a high prevalence of ICDs among morbidly obese prebariatric surgery patients that are related to regular binge eating.

Classification characteristics of the Patient Health Questionnaire-15 for screening somatoform disorders in a primary care setting.

BACKGROUND: This study examines how effectively the Patient Health Questionnaire-15 (PHQ-15), a self-administered screening instrument, recognizes somatoform symptoms and somatoform disorders in a German primary care setting. METHODS: A selected sample of 308 patients (mean age 47.2 years, 71.4% women) from two regular primary care practices was screened with the PHQ-15 and additionally examined with structured interviews. Their primary care physicians rated symptoms reported in the interview as either "medically explained" or "medically unexplained." RESULTS: Seventy-six percent of the symptoms were judged as medically unexplained. The PHQ-15 correlated significantly with the total number of symptoms as well as the number of somatoform symptoms (both r=0.63; P≤.001). A comparison between the most frequently reported symptoms in the interview and the 15 items of the PHQ-15 revealed that even though the PHQ-15 does not differentiate between medically explained and medically unexplained symptoms, it does catch many somatoform symptoms. When used to predict the diagnosis of a somatoform disorder, a cutoff of 10 points in the PHQ-15 was identified as optimal, resulting in a sensitivity of 80.2% and specificity of 58.5%. However, the cutoff has to be adjusted according to specific research or clinical purposes. CONCLUSION: Several previous results could be confirmed, and under consideration of some limitations, the PHQ-15 seems to be a valuable tool for identifying somatoform symptoms and disorders in primary care.

Structure of the RNA-binding domain of Nodamura virus protein B2, a suppressor of RNA interference.

Protein B2 from Nodamura virus (NMV B2), a member of the Nodavirus family, acts as a suppressor of RNA interference (RNAi). The N-terminal domain of NMV B2, consisting of residues 1-79, recognizes double-stranded RNA (dsRNA). The 2.5 A crystal structure of the RNA-binding domain of NMV B2 shows a dimeric, helical bundle structure. The structure shows a conserved set of RNA-binding residues compared with flock house virus B2, despite limited sequence identity. The crystal packing places the RNA-binding residues along one face of symmetry-related molecules, suggesting a potential platform for recognition of dsRNA.