A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Recognising ethnocultural diversity in chronic pain assessment: validation of the Pictorial Representation of Illness and Self Measure (PRISM) for use with culturally diverse communities

Abstract Background A comprehensive and accurate assessment of pain is critical for successful pain management. However, there is a lack of reliable and valid assessment tools for exploring multidimensional aspects of the chronic pain experience in culturally and linguistically diverse communities. This study investigates the reliability and validity of the Pictorial Representation of Illness and Self Measure + (PRISM+) for evaluating pain-related suffering and the sociocultural context of chronic pain within culturally and linguistically diverse patient cohorts. Method Three prospective validation studies are reported for three culturally and linguistically diverse communities. Two hundred and fifty-one patients with chronic pain who self-identified as Assyrian (n = 85), Arabic (n = 83) or Vietnamese (n = 83) completed a PRISM+ assessment, alongside a battery of standardised pain assessments. To evaluate construct validity, the position of the ‘pain’ disk placement was correlated with the Brief Pain Inventory (BPI), Depression Anxiety and Stress Scale (DASS), and the Short-Form 36 Health Survey (SF-36). For content validity, thematic analysis of patient narratives accompanying each disk placement was conducted. Test-retest reliability of repeated ‘pain’ and five additional disks (PRISM+) values was analysed using intra-class correlation coefficients. Results The PRISM pain assessment demonstrated moderate to good test-retest reliability for Arabic (ICC 0.76; 95% CI 0.65–0.84), Assyrian (ICC 0.65; 95% CI 0.50–0.76) and Vietnamese (ICC 0.82; 95% CI 0.73–0.88) patients. Moderate correlations between the PRISM ‘pain’ disk and sub-scores for the BPI, DASS and SF-36 were found (p < 0.001). Patient interpretations of the ‘pain’ disk aligned with accepted definitions of suffering, supporting content validity for PRISM. For the additional disks (PRISM+), moderate to good test-retest reliability (ICC 0.67–0.88) was observed and qualitative analysis highlighted each disk reflected social and cultural values. Conclusion The PRISM demonstrates acceptable psychometric properties for measuring pain-related suffering for participants with chronic pain across three culturally and linguistically diverse communities. The use of additional disks (PRISM+) presents a reliable and valid option for exploring social and cultural dimensions of chronic pain in clinical encounters

RNA-seq data of Oryza sativa cultivar Kuku Belang under PEG treatment

Drought stress is the main abiotic factor affecting rice production. Rain-fed upland rice which is grown on unbounded fields and totally dependent on rainfall for moisture is more prone to drought stress compared to rice from other ecosystems. However, upland rice has adapted to this limited water condition, thus are more drought tolerant than rice from other ecosystems. We performed the first transcriptome sequencing of drought tolerant indica upland rice cultivar Kuku Belang to identify differentially expressed genes related to drought tolerance mechanism. Raw reads for non-treated and PEG-treated Oryza sativa subspecies indica cv. Kuku Belang were deposited in the NCBI SRA database with accession number SRP074520 (https://www.ncbi.nlm.nih.gov/sra?term=SRP074520)

A study on the relationship between the Bangko Sentral regulations and banks\u27 merger decisions

There has been little research done in the Philippines that has examined the relationship of banking regulations with the decision of the banks to merge. Bangko Sentral has been consistent in encouraging banks to merge since the Asian financial crisis in 1997. The odds of a bank being involved in a merger may be affected by the banks\u27 capital adequacy, asset quality, management competence, earnings and liquidity and as well as other factors such as economic health of a state, interest rate and banking competition. The group used logistic regression in examining these factors in relation to the banks\u27 decision to merge. However, the encouragement of Bangko Sentral through its regulations still has affected the banking industry\u27s merger activities

Salmonella enterica isolated from infections in Australian livestock remain susceptible to critical antimicrobials

Salmonella enterica is a zoonotic pathogen causing a variety of diseases in humans and animals. Many countries are reporting an increase in the prevalence of multidrug-resistant (MDR) S. enterica in food animals. The aim of this study was to determine whether S. enterica isolated from livestock in New South Wales, Australia, have similar resistance traits to those reported internationally. Salmonella enterica (n = 165) from clinical infections in food animals between 2007 and 2011 were serotyped and tested for susceptibility to 18 antimicrobials. Also, 22 antimicrobial resistance genes (ARGs), 3 integrons and 18 plasmid replicon types were screened for using PCR. Most isolates (66.1%) remained susceptible to all antimicrobials; 8.5% of the isolates were resistant to four or more antimicrobials. Antimicrobials with the highest prevalence of resistance were sulfafurazole (28.5%), ampicillin (17.0%), tetracycline (15.8%) and trimethoprim (8.5%). There was no resistance to fluoroquinolones or third-generation cephalosporins. The most common ARGs were bla (15.2%), sul2 (10.3%), tetB (9.1%), tetA (5.5%), aphA1 (4.8%) and dhfrV (4.8%). Class 1 integrons (7.9%) and IncFIIA (69.7%) were the most commonly detected integron and plasmid replicon types, respectively. Class 1 integrons were positively associated with MDR phenotypes and ARG carriage (P ≤ 0.001). Internationally prominent MDR serovars associated with severe disease in humans (e.g. AmpC-positive Salmonella Newport) were not detected. Overall, the comparatively favourable resistance status of S. enterica in Australian livestock represents minimal public health risk associated with MDR strains and supports a conservative approach to the registration of antimicrobial drug classes in food-producing animals. Crown Copyrigh