Large-scale Population Studies Research Articles

Deciphering the Complexity of FSHD: A Multimodal Approach as a Model for Rare Disorders

Rare diseases are heterogeneous diseases characterized by various symptoms and signs. Due to the low prevalence of such conditions (less than 1 in 2000 people), medical expertise is limited, knowledge is poor and patients’ care provided by medical centers is inadequate. An accurate diagnosis is frequently challenging and ongoing research is also insufficient, thus complicating the understanding of the natural progression of the rarest disorders. This review aims at presenting the multimodal approach supported by the integration of multiple analyses and disciplines as a valuable solution to clarify complex genotype–phenotype correlations and promote an in-depth examination of rare disorders. Taking into account the literature from large-scale population studies and ongoing technological advancement, this review described some examples to show how a multi-skilled team can improve the complex diagnosis of rare diseases. In this regard, Facio-Scapulo-Humeral muscular Dystrophy (FSHD) represents a valuable example where a multimodal approach is essential for a more accurate and precise diagnosis, as well as for enhancing the management of patients and their families. Given their heterogeneity and complexity, rare diseases call for a distinctive multidisciplinary approach to enable diagnosis and clinical follow-up.

External validation of a deep learning model for automatic segmentation of skeletal muscle and adipose tissue on abdominal computed tomography images.

Body composition assessment using computed tomography (CT) images at the L3-level is increasingly applied in cancer research. Robust high-throughput automated segmentation is key to assess large patient cohorts and to support implementation of body composition analysis into routine clinical practice. We trained and externally validated a deep learning neural network (DLNN) to automatically segment L3-CT images. Expert-drawn segmentations of visceral and subcutaneous adipose tissue (VAT/SAT) and skeletal muscle (SM) of L3-CT-images of 3,187 patients undergoing abdominal surgery were used to train a DLNN. The external validation cohort was comprised of 2,535 patients with abdominal cancer. DLNN performance was evaluated with (geometric) Dice Similarity (DS) and Lin's Concordance Correlation Coefficient. There was a strong concordance between automatic and manual segmentations with median DS for SM, VAT, and SAT of 0.97 (interquartile range, IQR: 0.95-0.98), 0.98 (IQR: 0.95-0.98), and 0.95 (IQR: 0.92-0.97), respectively. Concordance correlations were excellent: SM 0.964 (0.959-0.968), VAT 0.998 (0.998-0.998), and SAT 0.992 (0.991-0.993). Bland-Altman metrics indicated only small and clinically insignificant systematic offsets; SM radiodensity: 0.23 hounsfield units (0.5%), SM: 1.26 cm2.m-2 (2.8%), VAT: -1.02 cm2.m-2 (1.7%), and SAT: 3.24 cm2.m-2 (4.6%). A robustly-performing and independently externally validated DLNN for automated body composition analysis was developed. CT-based body composition analysis is highly prognostic for long-term overall survival in oncology. This DLNN was succesfully trained and externally validated on several large patient cohorts and will therefore enable large scale population studies and implementation of body composition analysis into clinical practice.

Subjective measurement of physical activity and sedentary behaviour in children and adolescents with cerebral palsy: a scoping review

Purpose Physical activity is essential for maintaining overall health. Cost-effective and easily administered outcome instruments are valuable for clinical practice and large-scale population studies. The scoping review aimed to identify and map subjective instruments developed or validated to measure habitual physical activity and/or sedentary behaviour in children and adolescents with cerebral palsy aged 0–18 years across all levels of the GMFCS-E&R. Materials and methods This scoping review was conducted in accordance with the JBI methodology for scoping reviews and searched the databases PubMed, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, JBI Database of Systematic Reviews and Implementation Reports, Embase and Pedro to identify articles. Results From 288 full-text references, 13 studies met the inclusion criteria. Nine instruments measured habitual physical activity and/or sedentary behaviour in children and adolescents with cerebral palsy aged 18 months to 18 years. Six subjective instruments were tested for ambulatory children, while three instruments were tested in children and adolescents at GMFCS-E&R level I–V. Conclusion and implications Reporting of the psychometric properties were found on reliability in three instruments, while data on validity were reported in all instruments. Further studies assessing the psychometric properties of subjective instruments in the target population are needed.

PoweREST: Statistical Power Estimation for Spatial Transcriptomics Experiments to Detect Differentially Expressed Genes Between Two Conditions.

Recent advancements in Spatial Transcriptomics (ST) have significantly enhanced biological research in various domains. However, the high cost of current ST data generation techniques restricts its application in large-scale population studies. Consequently, there is a pressing need to maximize the use of available resources to achieve robust statistical power. One fundamental question in ST analysis is to detect differentially expressed genes (DEGs) among different conditions using ST data. Such DEG analysis is often performed but the associated power calculation is rarely discussed in the literature. To address this gap, we introduce, PoweREST (https://github.com/lanshui98/PoweREST), a power estimation tool designed to support power calculation of DEG detection with 10X Genomics Visium data. PoweREST enables power estimation both before any ST experiments or after preliminary data are collected, making it suitable for a wide variety of power analyses in ST studies. We also provide a user-friendly, program-free web application (https://lanshui.shinyapps.io/PoweREST/), allowing users to interactively calculate and visualize the study power along with relevant the parameters.

The Role of Furin and Its Therapeutic Potential in Cardiovascular Disease Risk.

Furin is an important proteolytic enzyme, converting several proteins from inactive precursors to their active forms. Recently, proteo-genomic analyses in European and East Asian populations suggested a causal association of furin with ischaemic heart disease, and there is growing interest in its role in cardiovascular disease (CVD) aetiology. In this narrative review, we present a critical appraisal of evidence from population studies to assess furin's role in CVD risk and potential as a drug target for CVD. Whilst most observational studies report positive associations between furin expression and CVD risk, some studies report opposing effects, which may reflect the complex biological roles of furin and its substrates. Genetic variation in FURIN is also associated with CVD and its risk factors. We found no evidence of current clinical development of furin as a drug target for CVD, although several phase 1 and 2 clinical trials of furin inhibitors as a type of cancer immunotherapy have been completed. The growing field of proteo-genomics in large-scale population studies may inform the future development of furin and other potential drug targets to improve the treatment and prevention of CVD.

Association between insulin resistance and vascular damage in an adult population in China: a cross-sectional study

There is a relative scarcity of large-scale population studies investigating the relationship between the insulin resistance index of homeostasis model assessment (HOMA-IR) and vascular damage. Therefore, we assessed the association between HOMA-IR and vascular damage in adults aged 18 years and older in China. A total of 17,985 research subjects were included. Vascular damage markers and relevant laboratory tests were measured. HOMA-IR was calculated as (fasting insulin * fasting blood glucose)/22.5. Vascular damage included arteriosclerosis (ba-PWV > 1800 cm/s), peripheral artery disease (ABI < 0.9), and microalbuminuria (UACR > 30 mg/g). The relationship between HOMA-IR and vascular damage was analyzed using the RCS. The restricted cubic spline (RCS) analysis suggested that HOMA-IR was nonlinearly associated with arteriosclerosis (P for no-liner < 0.01), peripheral artery disease (P for no-liner < 0.01), and microalbuminuria (P for no-liner < 0.01). Further segmented regression analyses revealed that in study subjects with HOMA-IR < 5, we found that HOMA-IR was associated with an increased OR for arteriosclerosis (OR: 1.36, 95% CI (1.28, 1.45), P < 0.01), peripheral artery disease (OR: 1.33, 95% CI (1.10, 1.60), P < 0.01) and microalbuminuria (OR: 1.59, 95% CI (1.49, 1.70), P < 0.01). HOMA-IR is an independent risk factor for vascular damage, both macrovascular and microvascular. The phenomenon of saturation of HOMA-IR with vascular damage needs further investigation.

The unique association between the level of plateletcrit and the prevalence of diabetic kidney disease: a cross-sectional study.

The activation of platelets in individuals with type 2 diabetes mellitus (T2DM) triggers inflammation and hemodynamic abnormalities, contributing to the development of diabetic kidney disease (DKD). Despite this, research into the relationship between plateletcrit (PCT) levels and DKD is sparse, with inconsistent conclusions drawn regarding the connection between various platelet parameters and DKD. This highlights the necessity for comprehensive, large-scale population studies. Therefore, our objective is to explore the association between PCT levels and various platelet parameters in relation to DKD. In this cross-sectional study, hematological parameter data were collected from a cohort of 4,302 hospitalized Chinese patients. We analyzed the relationships between PCT, platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), platelet large cell ratio (P-LCR), and DKD, along with the urinary albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR). Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic potential of these parameters. DKD patients exhibited significantly higher PCT levels compared to those without DKD. Multivariate regression analysis identified elevated PCT and PLT levels as potential independent risk factors for both DKD and UACR, while lower MPV levels might serve as independent protective factors for eGFR. The areas under the ROC curve for PCT in relation to DKD and UACR (≥30 mg/g) were 0.523 and 0.526, respectively. The area under the ROC curve for PLT in relation to UACR (≥30 mg/g) was 0.523. PCT demonstrates a weak diagnostic value for T2DM patients at risk of developing DKD and experiencing proteinuria, and PLT shows a similarly modest diagnostic utility for detecting proteinuria. These insights contribute to a deeper understanding of the complex dynamics involved in DKD. Additionally, incorporating these markers into routine clinical assessments could enhance risk stratification, facilitating early interventions and personalized management strategies.

Malaria resistance-related biological adaptation and complex evolutionary footprints inferred from one integrative Tai-Kadai-related genomic resource

Pathogen‒host adaptative interactions and complex population demographical processes, including admixture, drift, and Darwen selection, have considerably shaped the Neolithic-to-Modern Western Eurasian population structure and genetic susceptibility to modern human diseases. However, the genetic footprints of evolutionary events in East Asia remain unknown due to the underrepresentation of genomic diversity and the design of large-scale population studies. We reported one aggregated database of genome-wide SNP variations from 796 Tai-Kadai (TK) genomes, including that of Bouyei first reported here, to explore the genetic history, population structure, and biological adaptative features of TK people from southern China and Southeast Asia. We found geography-related population substructure among TK people using the state-of-the-art population genetic structure reconstruction techniques based on the allele frequency spectrum and haplotype-resolved phased fragments. We found that the northern TK people from Guizhou harbored one TK-dominant ancestry maximized in the Bouyei people, and the southern TK people from Thailand were more influenced by Southeast Asians and indigenous people. We reconstructed fitted admixture models and demographic graphs, which showed that TK people received gene flow from ancient southern rice farmer-related lineages related to the Hmong-Mien and Austroasiatic people and from northern millet farmers associated with the Sino-Tibetan people. Biological adaptation focused on our identified unique TK lineages related to Bouyei, which showed many adaptive signatures conferring Malaria resistance and low-rate lipid metabolism. Further gene enrichment, the allele frequency distribution of derived alleles, and their correlation with the incidence of Malaria further confirmed that CR1 played an essential role in the resistance of Malaria in the ancient "Baiyue" tribes.

Gene polymorphism as a cause of hemorrhagic complications in patients with non-valvular atrial fibrillation treated with oral vitamin K-independent anticoagulants.

Atrial fibrillation (AF) accounts for 40% of all cardiac arrhythmias and is associated with a high risk of stroke and systemic thromboembolic complications. Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that have been proven to prevent stroke in patients with non-valvular AF. This review summarizes the pharmacokinetics, pharmacodynamics, and drug interactions of DOACs, as well as new data from pharmacogenetic studies of these drugs. This review is aimed at analyzing the scientific literature on the gene polymorphisms involved in the metabolism of DOACs. We searched PubMed, Cochrane, Google Scholar, and CyberLeninka (Russian version) databases with keywords: 'dabigatran', 'apixaban', 'rivaroxaban', 'edoxaban', 'gene polymorphism', 'pharmacogenetics', 'ABCB1', 'CES1', 'SULT1A', 'ABCG2', and 'CYP3A4'. The articles referred for this review include (1) full-text articles; (2) study design with meta-analysis, an observational study in patients taking DOAC; and (3) data on the single-nucleotide polymorphisms and kinetic parameters of DOACs (plasma concentration), or a particular clinical outcome, published in English and Russian languages during the last 10 years. The ages of the patients ranged from 18 to 75 years. Out of 114 reviewed works, 24 were found eligible. As per the available pharmacogenomic data, polymorphisms affecting DOACs are different. This may aid in developing individual approaches to optimize DOAC pharmacotherapy to reduce the risk of hemorrhagic complications. However, large-scale population studies are required to determine the dosage of the new oral anticoagulants based on genotyping. Information on the genetic effects is limited owing to the lack of large-scale studies. Uncovering the mechanisms of the genetic basis of sensitivity to DOACs helps in developing personalized therapy based on patient-specific genetic variants and improves the efficacy and safety of DOACs in the general population.

Can Galanin Be Used as a Marker of Microvascular Dysfunction in Prehypertensives?

Coronary microvascular dysfunction is present in large percentage of the population, and it has been shown to have a pathological and prognostic role in many conditions. Therefore, early detection of microvascular dysfunction is important, especially in selected populations. The aim of this study was to investigate the association of galanin with coronary flow reserve (CFR) in prehypertensive individuals to determine whether it can be used as a marker to detect microvascular dysfunction. A total of 100 participants, 50 prehypertensive and 50 normotensive were included in this prospective study. Serum galanin levels were measured and CFR was calculated by detailed transthoracic echocardiography. CFR was significantly lower in the prehypertensive group (p<0.001). Also, galanin values were numerically lower in the prehypertensive group, but the difference between the groups did not reach statistical significance (p=0.062). There was no significant correlation between CFR and galanin (r=-0.161, p=0.11). Lower CFR values in prehypertensives suggest that microvascular dysfunction starts above normotensive values even if hypertension does not develop. The reason why low galanin levels were not statistically significant in prehypertensives and no correlation was found between galanin and CFR may be due to the small study population. Relationship between galanin, prehypertension and microvascular dysfunction will become clearer if large-scale population studies are carried out.

A history of cardiovascular magnetic resonance imaging in clinical practice and population science.

Cardiovascular magnetic resonance (CMR) imaging has become an invaluable clinical and research tool. Starting from the discovery of nuclear magnetic resonance, this article provides a brief overview of the key developments that have led to CMR as it is today, and how it became the modality of choice for large-scale population studies.

Pupil involving oculomotor palsy- Examination, Cause and Outcome Outcome

BACKGROUND: A patient with a third cranial nerve (CN III) palsy can be a stress inducing event for an optometrist due to the potentially life-threatening etiologies and infrequency of their presentation. The pathogenesis of a CN III palsy can vary from innocuous to life threatening. Palsy of the third cranial nerve results in an impairment of eye movement and / or pupillary response to light depending on the extent of the palsy. CASE REPORT: This case reviews a recent onset of a complete right oculomotor palsy. Literature of similar cases detail the likelihood of variable causes, and while a diagnostic work-up is indicated based on the risk, the etiology of the palsy in this case was determined to be more benign in nature. CONCLUSION: Large scale population studies in the literature reveal the etiology of a CN III palsy from life-threatening conditions is lower than indicated based on published case reports. However, a complete evaluation of a patient including neuro-imagining is still warranted due to the potential life-threatening complications. Further population studies with increased diversity need to be performed to advance knowledge in this area.

Genetic Control of Alternative Splicing and its Distinct Role in Colorectal Cancer Mechanisms

Dysregulation of alternative splicing is implicated in many human diseases and understanding the genetic variation underlying transcript splicing is essential to dissect the molecular mechanisms of cancers. We aimed to provide a comprehensive functional dissection of splicing quantitative trait loci (sQTLs) in cancer and focus on elucidating its distinct role in colorectal cancer (CRC) mechanisms. Firstly, we performed a comprehensive sQTL analysis to identify genetic variants that control mRNA splicing across 33 cancer types from TCGA and independently validated in our 154 CRC tissues. Then, large-scale, multicenter, multiethnic case-control studies (34,585 cases and 76,023 controls) were conducted to examine the association of these sQTLs with CRC risk. A series of biological experiments in vitro and in vivo were performed to investigate the potential mechanisms of the candidate sQTLs and target genes. The molecular characterization of sQTL revealed its distinct role in cancer susceptibility. Tumor-specific sQTL further showed better response to cancer development. Besides, functionally informed polygenetic risk score highlighted the potentiality of sQTLs in the CRC prediction. Complemented by large-scale population studies, we identified that the risk allele (T) of a multi-ancestry-associated sQTL rs61746794 significantly increased the risk of CRC in Chinese populations (OR=1.20, 95% CI=1.12-1.29, P=8.82×10-7) and European populations (OR=1.11, 95% CI=1.07-1.16, P=1.13×10-7). rs61746794-T facilitated PRMT7 exon 16 splicing mediated by the RBP PRPF8, thus increasing the level of canonical PRMT7 isoform (PRMT7-V2). Overexpression of PRMT7-V2 significantly enhanced the growth of CRC cells and xenograft tumors, compared with PRMT7-V1. Mechanistically, PRMT7-V2 functions as an epigenetic writer that catalyzes the arginine methylation of H4R3 and H3R2, subsequently regulating diverse biological processes, including YAP, AKT, and KRAS pathway. A selective PRMT7 inhibitor, SGC3027, exhibited antitumor effects on human CRC cells. Our study provide an informative sQTLs resource and insights into the regulatory mechanisms linking splicing variants to cancer risk, serving as biomarkers and therapeutic targets.

Association of medicinal plant consumption with all-cause mortality and cognitive impairment in older adult: A large prospective cohort study

BackgroundPanax ginseng and other medicinal plants have long been believed to have beneficial effects on health, and there is substantial evidence supporting their mechanisms of action. However, the extent of the health benefits derived from consuming these medicinal plants lacks substantial evidence from large-scale longitudinal population studies. The purpose of this study was to analyze the effect of consuming these medicinal plants on all-cause mortality and cognitive impairment. MethodsA population-based cohort study was conducted using the Chinese Longitudinal Healthy Longevity Survey (CLHLS), which was established in 1998 and has been followed up till now. The main exposure was the frequency of eating medicinal plants, including Panax ginseng, Astragalus membranaceus, Lycium barbarum, Angelica sinensis, etc. According to the consumption patterns of medicinal plants, the participants were divided into three groups: frequent use, occasional use, and rarely or never use group. The participants were individually tracked to determine their mortality and cognitive impairment status during the period from 2008 to 2018. Cox proportional hazards regression and competing risk model were used to calculate the hazard ratio (HR) for the association between the use of medicinal plants and the all-cause mortality and cognitive impairment. ResultsAmong 13,918 participants, the average age was 87.2 ± 11.3 years old, and 70.1% (9,754/13,918) of the participants died during follow-up. The proportion of those frequently using, occasionally using, and rarely using medicinal plants was 8.4%, 20.7%, and 70.8%, respectively. Compared with the rarely or never use group, the occasional and frequent use groups demonstrated significantly lower risks for all-cause mortality, with HR of 0.75 (95% CI: 0.71 – 0.79) and 0.53 (95% CI: 0.49 – 0.58), respectively. The protective effect of medicinal plants against all-cause mortality decreased with increasing age in the subgroup analysis. Additionally, frequent use of medicinal plants reduced the risk of cognitive impairment in the competing risk model (HR = 0.73, 95% CI: 0.60 – 0.87). However, there was no protective effect on cognitive function for those who occasional use medicinal plants. ConclusionIn elderly individuals, occasional and frequent use of medicinal plants was associated with reductions in risk of all-cause mortality, and frequent use of medicinal plants could reduce the risk of cognitive impairment.

Characterization of global research trends and prospects on sudden coronary death: A literature visualization analysis

BackgroundSudden coronary death is a major global public health issue that has a significant impact on both individuals and society. Nowadays, scholars are active in sudden coronary death all over the world. However, no relevant bibliometric studies have been published. Here, we aim to gain a better understanding the current state of research and to explore potential new research directions through bibliometric analysis. MethodsArticles and reviews on sudden coronary death from 2012 to 2023 were retrieved from the Web of Science Core Collection (WoSCC). The topic search was conducted using the following keywords: (((“sudden cardiac death” OR “sudden death”) AND (coronary OR “myocardial infarction”)) OR “sudden coronary death”). Knowledge maps of authors, countries, institutions, journals, keywords, and citations were conducted by CiteSpace. Publication dynamics, hotspots, and frontiers were analyzed independently by authors. ResultsA total of 2914 articles were identified from January 1, 2012 to June 20, 2023. The USA (n = 972) contributed the greatest absolute productivity and UK (centrality = 0.13) built a robust global collaboration. Harvard University was the institution with the highest number of publications (n = 143). Huikuri HV and Junttila MJ were the most published authors who devoted to searching for biomarkers of sudden coronary death. American Journal of Cardiology was the journal with the most publications, and Circulation was the most cited journal. Left ventricular ejection fraction, society, inflammation, and fractional flow reserve became novel burst words that lasted until 2023. Research on etiology and pathology, role of early risk factors in risk stratification, potential predictive biomarkers and novel measurement methods for the prevention and management of sudden coronary death were identified as the research hotspots and frontiers. ConclusionOur knowledge and understanding of sudden coronary death have significantly improved. Ongoing efforts should focus on the various etiologies and pathologies of sudden coronary death. Furthermore, a novel sudden coronary death risk model, large-scale population studies, and the rational use of multiple indicators to individualize the assessment of sudden coronary death and other risk factors are other emerging research trends.

An Epidemiologic Study of the Incidence and Mortality of Abdominal Aortic Aneurysms in Koreans Aged ≥50 Years from 2009 to 2018 Based on a National Database.

Large-scale population studies of the incidence of and mortality from abdominal aortic aneurysm (AAA) are needed to develop healthcare policies and priorities. The aim of this study was to estimate the incidence of AAA and the all-cause mortality from it among Koreans aged ≥50 years from 2009 to 2018 using data from the Korean National Health Insurance System Database. The crude and standardized incidence and all-cause mortality of the disease among patients with unruptured AAA were calculated. A total of 73,933 AAA patients were identified. The overall incidence of AAA in adults ≥50 years during the study period was 37.5 per 100,000 population (49.7 per 100,000 in men and 26.8 per 100,000 in women), with an increase from 32.33 per 100,000 persons in 2009 to 46.85 per 100,000 in 2018. The crude all-cause mortality rate of patients with untreated AAA was 21.26/100 person-years in 2009 and 8.87/100 person-years in 2018, with decreasing trends observed both in men and women. This nationwide study showed that the incidence of AAA in Koreans aged ≥50 years in 2018 was 63.40 per 100,000 in men and 32.07 per 100,000 in women. The overall rates were 0.06% and 0.03%, respectively, with an increasing trend. Mortality has decreased in both treated and untreated patients. The observed increase in incidence suggests a rising burden of AAA in the Korean population, particularly among men. The decreasing mortality rates may indicate improvements in the management and treatment of AAA over the study period.

Genetic control of N-glycosylation of human blood plasma proteins.

Glycosylation is an important protein modification, which influences the physical and chemical properties as well as biological function of these proteins. Large-scale population studies have shown that the levels of various plasma protein N-glycans are associated with many multifactorial human diseases. Observed associations between protein glycosylation levels and human diseases have led to the conclusion that N-glycans can be considered a potential source of biomarkers and therapeutic targets. Although biochemical pathways of glycosylation are well studied, the understanding of the mechanisms underlying general and tissue-specific regulation of these biochemical reactions in vivo is limited. This complicates both the interpretation of the observed associations between protein glycosylation levels and human diseases, and the development of glycan-based biomarkers and therapeutics. By the beginning of the 2010s, high-throughput methods of N-glycome profiling had become available, allowing research into the genetic control of N-glycosylation using quantitative genetics methods, including genome-wide association studies (GWAS). Application of these methods has made it possible to find previously unknown regulators of N-glycosylation and expanded the understanding of the role of N-glycans in the control of multifactorial diseases and human complex traits. The present review considers the current knowledge of the genetic control of variability in the levels of N-glycosylation of plasma proteins in human populations. It briefly describes the most popular physical-chemical methods of N-glycome profiling and the databases that contain genes involved in the biosynthesis of N-glycans. It also reviews the results of studies of environmental and genetic factors contributing to the variability of N-glycans as well as the mapping results of the genomic loci of N-glycans by GWAS. The results of functional in vitro and in silico studies are described. The review summarizes the current progress in human glycogenomics and suggests possible directions for further research.

The effects of coagulation factors on the risk of endometriosis: a Mendelian randomization study

BackgroundEndometriosis is recognized as a complex gynecological disorder that can cause severe pain and infertility, affecting 6–10% of all reproductive-aged women. Endometriosis is a condition in which endometrial tissue, which normally lines the inside of the uterus, deposits in other tissues. The etiology and pathogenesis of endometriosis remain ambiguous. Despite debates, it is generally agreed that endometriosis is a chronic inflammatory disease, and patients with endometriosis appear to be in a hypercoagulable state. The coagulation system plays important roles in hemostasis and inflammatory responses. Therefore, the purpose of this study is to use publicly available GWAS summary statistics to examine the causal relationship between coagulation factors and the risk of endometriosis.MethodsTo investigate the causal relationship between coagulation factors and the risk of endometriosis, a two-sample Mendelian randomization (MR) analytic framework was used. A series of quality control procedures were followed in order to select eligible instrumental variables that were strongly associated with the exposures (vWF, ADAMTS13, aPTT, FVIII, FXI, FVII, FX, ETP, PAI-1, protein C, and plasmin). Two independent cohorts of European ancestry with endometriosis GWAS summary statistics were used: UK Biobank (4354 cases and 217,500 controls) and FinnGen (8288 cases and 68,969 controls). We conducted MR analyses separately in the UK Biobank and FinnGen, followed by a meta-analysis. The Cochran’s Q test, MR-Egger intercept test, and leave-one-out sensitivity analyses were used to assess the heterogeneities, horizontal pleiotropy, and stabilities of SNPs in endometriosis.ResultsOur two-sample MR analysis of 11 coagulation factors in the UK Biobank suggested a reliable causal effect of genetically predicted plasma ADAMTS13 level on decreased endometriosis risk. A negative causal effect of ADAMTS13 and a positive causal effect of vWF on endometriosis were observed in the FinnGen. In the meta-analysis, the causal associations remained significant with a strong effect size. The MR analyses also identified potential causal effects of ADAMTS13 and vWF on different sub-phenotypes of endometrioses.ConclusionsOur MR analysis based on GWAS data from large-scale population studies demonstrated the causal associations between ADAMTS13/vWF and the risk of endometriosis. These findings suggest that these coagulation factors are involved in the development of endometriosis and may represent potential therapeutic targets for the management of this complex disease.

Short- and Long-Term Stability of Aromatic Amines in Human Urine.

Several aromatic amines (AAs) are established by the International Agency for Research on Cancer as carcinogenic (group 1) or probable/possible carcinogens to humans (group 2A/2B). AAs can be found in mainstream and sidestream smoke from combustible tobacco products, as well as in certain environmental pollution and occupational exposure from several chemical industry sectors. Exposure to AAs can be estimated by measuring their concentrations in urine; however, information about the short-term and long-term stabilities of AAs in urine need to be characterized before conducting large-scale population studies on AA exposure and the potentially harmful effects of AA exposure. In this report, the storage stability of o-toluidine, 2,6-dimethylaniline, o-anisidine, 1-aminonaphthalene, 2-aminonaphthalene, and 4-aminobiphenyl fortified in pooled, filtered, non-smokers' urine is analyzed by isotope dilution gas chromatography-triple quadrupole mass spectrometry (ID GC-MS/MS). The six AAs were measured in urine samples stored at ~20 °C (collection temperature), 4 °C and 10 °C (short-term transit temperatures), and -20 °C and -70 °C (long-term storage temperatures) over a 10-day period. All six analytes were stable for 10 days at transit and long-term storage temperatures but showed reduced recovery at 20 °C. The instability of the target AAs at 20 °C suggests that immediate storage of freshly voided urine at low temperatures is needed to attenuate degradation. A subset of the urine samples was analyzed following a longer storage duration at -70 °C: all AAs were stable for up to 14 months at this temperature. The stability of the six AAs in urine samples can be maintained at the various temperature levels and storage times expected in a typical study set.

Recruitment discrimination of lifetime classic psychedelic users is unjustified: Evidence from employees' motivation-based workplace absenteeism

AbstractBackground and aimsAlthough large-scale population studies have linked the use of classic psychedelics (lysergic acid diethylamide, psilocybin, or mescaline) to reduced odds of physical health problems, mental health problems, and criminal behavior, the roughly 35 million adults in the United States who have used classic psychedelics are nonetheless stigmatized in the American job market. Various federal organizations in the United States automatically reject applicants on the sole basis of prior psychedelic use, thereby practicing an open form of legal discrimination against these applicants. The present study investigates whether this discrimination can be justified based on associations between lifetime classic psychedelic use and motivationally-based workplace absenteeism.MethodsUsing pooled cross-sectional data from the National Survey on Drug Use and Health (2013–2019) on 193,320 employed adults in the United States, this study tests whether lifetime classic psychedelic use predicts the number of workdays employees skipped in the last month (i.e., motivationally-based workplace absenteeism).ResultsAfter adjusting for sociodemographics, physical health indicators, and other substance use, no significant association between lifetime classic psychedelic use and motivationally-based workplace absenteeism is found.ConclusionThis study builds on classic psychedelic research that is just beginning to take work-specific outcomes into account and offers empirical justification for the elimination of arbitrary drug-based recruitment policies in the workplace.