The ClinGen Syndromic Disorders Gene Curation Expert Panel: Assessing the Clinical Validity of 111 Gene-Disease Relationships.

Purpose: The Clinical Genome Resource (ClinGen) Gene Curation Expert Panels (GCEPs) have historically focused on specific organ systems or phenotypes; thus, the ClinGen Syndromic Disorders GCEP (SD-GCEP) was formed to address an unmet need.

Methods: The SD-GCEP applied ClinGen's framework to evaluate the clinical validity of genes associated with rare syndromic disorders. 111 Gene-Disease Relationships (GDRs) associated with 100 genes spanning the clinical spectrum of syndromic disorders were curated.

Effect of Cangrelor on Infarct Size in ST-Segment-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (The PITRI Trial).

Background: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention.

Methods: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore.

Umbilical Cord Plasma Lysophospholipids and Triacylglycerols Associated with Birthweight Percentiles.

Dysregulated transplacental lipid transfer and fetal-placental lipid metabolism affect birthweight, as does maternal hyperglycemia. As the mechanisms are unclear, we aimed to identify the lipids in umbilical cord plasma that were most associated with birthweight. Seventy-five Chinese women with singleton pregnancies recruited into the GUSTO mother-offspring cohort were selected from across the glycemic range based on a mid-gestation 75 g oral glucose tolerance test, excluding pre-existing diabetes.

Ocular Surface Evaluation in Immunoglobulin G4-Related Ophthalmic Disease.

Purpose: To evaluate the functional and structural changes of the meibomian glands and ocular surface in immunoglobulin G4-related ophthalmic disease (IgG4-ROD) patients.

Design: Cross-sectional, matched case-control comparison study.

Methods: This study included 64 patients with biopsy-proven IgG4-ROD (aged 63.

Stroke genetics informs drug discovery and risk prediction across ancestries.

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.

Rapid and Sensitive Direct Detection of Endotoxins by Pyrolysis-Gas Chromatography-Mass Spectrometry.

The capability of pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) for the direct analysis of endotoxins is demonstrated in this research article using the lipopolysaccharides of 10. Analytical methods based on evolved gas analysis-MS, single-shot (SS) Py-GC-MS, and multishot heart cut Py-GC-MS were investigated. Among the various methods developed, the SS Py-GC-MS method shows superior potential for identifying bacterial endotoxins effectively through their biomarkers.

The placental lipidome of maternal antenatal depression predicts socio-emotional problems in the offspring.

While maternal mental health strongly influences neurodevelopment and health in the offspring, little is known about the determinants of inter-individual variation in the mental health of mothers. Likewise, the in utero biological pathways by which variation in maternal mental health affects offspring development remain to be defined. Previous studies implicate lipids, consistent with a known influence on cognitive and emotional function, but the relevance for maternal mental health and offspring neurodevelopment is unclear.

Recommendations for pathologic practice using digital pathology: consensus report of the Korean Society of Pathologists.

Digital pathology (DP) using whole slide imaging (WSI) is becoming a fundamental issue in pathology with recent advances and the rapid development of associated technologies. However, the available evidence on its diagnostic uses and practical advice for pathologists on implementing DP remains insufficient, particularly in light of the exponential growth of this industry. To inform DP implementation in Korea, we developed relevant and timely recommendations.

Genome-Wide Association Study Meta-Analysis of Stroke in 22 000 Individuals of African Descent Identifies Novel Associations With Stroke.

Background And Purpose: Stroke is a complex disease with multiple genetic and environmental risk factors. Blacks endure a nearly 2-fold greater risk of stroke and are 2× to 3× more likely to die from stroke than European Americans.

Methods: The COMPASS (Consortium of Minority Population Genome-Wide Association Studies of Stroke) has conducted a genome-wide association meta-analysis of stroke in >22 000 individuals of African ancestry (3734 cases, 18 317 controls) from 13 cohorts.

Introduction to digital pathology and computer-aided pathology.

Digital pathology (DP) is no longer an unfamiliar term for pathologists, but it is still difficult for many pathologists to understand the engineering and mathematics concepts involved in DP. Computer-aided pathology (CAP) aids pathologists in diagnosis. However, some consider CAP a threat to the existence of pathologists and are skeptical of its clinical utility.

Updated international consensus report on the investigation and management of primary immune thrombocytopenia.

Over the last decade, there have been numerous developments and changes in treatment practices for the management of patients with immune thrombocytopenia (ITP). This article is an update of the International Consensus Report published in 2010. A critical review was performed to identify all relevant articles published between 2009 and 2018.

Associations of Circadian Eating Pattern and Diet Quality with Substantial Postpartum Weight Retention.

Besides food quantity and quality, food timing and frequency may contribute to weight regulation. It is unclear if these factors during pregnancy can influence maternal weight retention after childbirth. We thus aimed to examine the associations of maternal circadian eating pattern and diet quality in pregnancy with substantial postpartum weight retention (PPWR) at 18 months in an Asian cohort.

A Multicenter Pilot Study on the Clinical Utility of Computational Modeling for Flow-Diverter Treatment Planning.

Background And Purpose: Selection of the correct flow-diverter size is critical for cerebral aneurysm treatment success, but it remains challenging due to the interplay of device size, anatomy, and deployment. Current convention does not address these challenges well. The goals of this pilot study were to determine whether computational modeling improves flow-diverter sizing over current convention and to validate simulated deployments.

Fournier Gangrene Associated With Sodium-Glucose Cotransporter-2 Inhibitors: A Review of Spontaneous Postmarketing Cases.

Background: Use of sodium-glucose cotransporter-2 (SGLT2) inhibitors has been associated with Fournier gangrene (FG), a rare urologic emergency characterized by necrotizing infection of the external genitalia, perineum, and perianal region.

Objective: To describe and compare reported cases of FG in diabetic adults receiving treatment with SGLT2 inhibitors or other antiglycemic agents.

Design: Descriptive case series.

Female adiposity and time-to-pregnancy: a multiethnic prospective cohort.

Study Question: Are higher overall and central adiposity associated with reduced fecundability, measured by time-to-pregnancy (TTP), in Asian women?

Summary Answer: Higher overall adiposity, but not central adiposity, was associated with longer TTP in Asian women.

What Is Known Already: High body mass index (BMI) has been associated with a longer TTP, although the associations of body composition and distribution with TTP are less clear. There are no previous studies of TTP in Asian women, who have a relatively higher percentage of body fat and abdominal fat at relatively lower BMI.

Seven-Year Treatment Outcome of Entecavir in a Real-World Cohort: Effects on Clinical Parameters, HBsAg and HBcrAg Levels.

Objectives: We aimed to determine the levels of alanine aminotransferase (ALT), hepatitis B virus DNA (HBV DNA), HBsAg, and a novel viral marker (hepatitis B core-related antigen (HBcrAg)); hepatitis B e antigen (HBeAg) seroconversion and drug resistance rates after 7 years of entecavir treatment in chronic hepatitis B (CHB) patients.

Methods: Two hundred and twenty-two Chinese CHB patients on continuous entecavir treatment were recruited. Serologic, virologic, biochemical outcomes, and the occurrence of entecavir signature mutations were determined.

Combined treatment of Nimotuzumab and rapamycin is effective against temozolomide-resistant human gliomas regardless of the EGFR mutation status.

Background: The treatment of glioblastoma multiforme (GBM) is an unmet clinical need. The 5-year survival rate of patients with GBM is less than 3%. Temozolomide (TMZ) remains the standard first-line treatment regimen for gliomas despite the fact that more than 90% of recurrent gliomas do not respond to TMZ after repeated exposure.

Disturbed flow promotes endothelial senescence via a p53-dependent pathway.

Objective: Although atherosclerosis is associated with systemic risk factors such as age, high cholesterol, and obesity, plaque formation occurs predominately at branches and bends that are exposed to disturbed patterns of blood flow. The molecular mechanisms that link disturbed flow-generated mechanical forces with arterial injury are uncertain. To illuminate them, we investigated the effects of flow on endothelial cell (EC) senescence.

The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study protocol.

Background And Purpose: Epidemiological studies of intracerebral hemorrhage (ICH) have consistently demonstrated variation in incidence, location, age at presentation, and outcomes among non-Hispanic white, black, and Hispanic populations. We report here the design and methods for this large, prospective, multi-center case-control study of ICH.

Methods: The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study is a multi-center, prospective case-control study of ICH.

Combined temozolomide and radiation as an initial treatment for anaplastic glioma.

Aim: Combined temozolomide (TMZ) and radiation therapy (RT) is often used as initial treatment for anaplastic glioma. However, there is no prospective randomized data available that proves the efficacy of the combination for anaplastic glioma. In this retrospective study we aimed to compare the outcome of patients who had combined TMZ and RT with those who had RT alone for the initial treatment of anaplastic glioma in our centers.