In Silico Evaluation of Algorithm-Based Clinical Decision Support Systems: Protocol for a Scoping Review.

Background: Integrating algorithm-based clinical decision support (CDS) systems poses significant challenges in evaluating their actual clinical value. Such CDS systems are traditionally assessed via controlled but resource-intensive clinical trials.

Objective: This paper presents a review protocol for preimplementation in silico evaluation methods to enable broadened impact analysis under simulated environments before clinical trials.

Investigating male factors and their relationships with reproductive health outcomes: a case-control study protocol for Towards Optimal Fertility, Fathering, and Fatherhood studY (TOFFFY) in Singapore.

Introduction: Despite the global prevalence of low fertility rates, male contributions to fertility and reproductive health outcomes have been understudied. This study aims to investigate the male contribution to fertility and explore the underlying biological mechanisms. Specifically, we aim to (1) identify male factors associated with successful pregnancy, (2) develop a fertility index incorporating modifiable factors for both males and females to predict pregnancy rate and (3) explore the relationship of male modifiable factors with semen parameters and molecular characteristics.

Age-specific prognosis of acute and steady minor elevations in cardiac troponin among non-acute myocardial infarction inpatients: a large real-world cohort study.

Background: The upper reference limit of normal (ULN) of cardiac troponin (cTn) for older adults can be higher than for young adults, while the same ULN is used for both older and young adults in the current clinical practice.

Methods: In this multicentre longitudinal cohort study, non-acute myocardial infarction (non-AMI) inpatients with at least two cTn concentrations hospitalised between 2013 and 2022 in the Tianjin Health and Medical Data Platform were included. Multivariable Cox proportional hazards and landmark regression models were used to estimate the risk of in-hospital, 30-day and 1-year mortality in different cTn groups (normal, stable minor elevation (1-2×ULN with variation ≤20%), acute minor elevation (1-2×ULN with variation >20%) and apparent elevation (>2×ULN)).

Development and Validation of a Clinical, CT, Genomic Classifier and BAL Scoring System for Diagnosing IPF.

The utility of incorporating a usual interstitial pneumonia (UIP) genomic classifier (GC) and bronchoalveolar lavage (BAL) cell count analysis alongside traditional clinical-imaging assessment in aiding in the multidisciplinary diagnosis of IPF in patients with a non-definite HRCT UIP pattern is uncertain.We reviewed consecutive adult patients presenting with fibrotic interstitial lung disease (fILD) and non-definite HRCT UIP pattern who underwent BAL and GC. The initial fILD diagnoses were re-evaluated after bronchoscopy and a final multidisciplinary consensus diagnosis was provided.

Zim4rv: an R package to modeling zero-inflated count phenotype on regional-based rare variants.

Background: With the advance of next-generation sequencing, various gene-based rare variant association tests have been developed, particularly for binary and continuous phenotypes. In contrast, fewer methods are available for traits not following binomial or normal distributions. To address this, we previously proposed a set of burden- and kernel-based rare variant tests for count data following zero-inflated Poisson (ZIP) distributions, referred to as ZIP-b and ZIP-k tests.

Cost-effectiveness analysis of trastuzumab emtansine for second-line treatment of HER2+ advanced breast cancer in Singapore.

Objective: To evaluate the cost-effectiveness of trastuzumab emtansine (T-DM1) compared to both lapatinib plus capecitabine (lapcap) and trastuzumab plus capecitabine (trascap) for treating human epidermal growth factor 2-positive advanced breast cancer patients, who have received prior treatment with trastuzumab and a taxane, in Singapore.

Research Design And Methods: A three-state partitioned survival model was used to evaluate the cost-effectiveness from the local healthcare system perspective. Key effectiveness data, including progression-free survival and overall survival from the pivotal EMILIA trial, were used alongside local clinician inputs.

A power dependence model of the impact of leader impostorism on supervisor support and undermining: The moderating role of power distance.

Leaders, often perceived as possessing exceptional confidence and competence, are not immune to feelings of self-doubt. Leader impostorism describes the experience that one's attributes, experiences, skills, and abilities fall short of the standards expected in the leadership role, resulting in a sense of deception in fulfilling leadership responsibilities. While existing research has examined the antecedents and individual outcomes of leader impostorism, its implications for leaders' treatment of subordinates remain largely unexplored.

Global increase in the occurrence and impact of multiyear droughts.

Persistent multiyear drought (MYD) events pose a growing threat to nature and humans in a changing climate. We identified and inventoried global MYDs by detecting spatiotemporally contiguous climatic anomalies, showing that MYDs have become drier, hotter, and led to increasingly diminished vegetation greenness. The global terrestrial land affected by MYDs has increased at a rate of 49,279 ± 14,771 square kilometers per year from 1980 to 2018.

Taming Highly Enolizable Aldehydes via Enzyme Catalysis for Enantiocomplementary Construction of β-Hydroxyphosphonates.

Taming highly enolizable aldehydes for catalytic asymmetric C-C coupling with nucleophiles remains an elusive challenge compared to widely explored simple alkyl or aryl aldehydes. Herein, we use ThDP-dependent enzymes to realize the direct C-C coupling of highly enolizable 2-phosphonate aldehydes with in situ-generated dynamically reversible nucleophiles (acyl anions). Unlike NHC-mediated reactions that yield complex mixtures of multiple adducts, our enzymatic process selectively produces biologically active β-hydroxy phosphonates with high yields (up to 95%) and excellent enantioselectivities (up to 99% ee).

Cross-Sectional Association Between Left Ventricular Geometric Patterns, Cortical Cerebral Microinfarcts, and Cognition.

Background: Left ventricular (LV) geometric patterns are associated with cognitive impairment and cerebral small vessel disease. As a novel magnetic resonance imaging marker of cerebral small vessel disease and a risk factor for cognitive dysfunction, cortical cerebral microinfarcts (CMIs) have been associated with heart disease through mechanisms including cardioembolism and cerebral hypoperfusion. Further investigation is required to determine whether cortical CMIs could arise from hemodynamic changes related to LV geometry, thus elucidating the connection between LV geometry and cognitive function.

Cost-Effectiveness Analysis of Inclisiran for the Treatment of Primary Hypercholesterolemia or Mixed Dyslipidemia in Singapore.

Objectives: This analysis evaluated the cost-effectiveness of inclisiran plus standard of care (SoC; comprising statins, ezetimibe, and fenofibrate) in primary hypercholesterolemia or mixed dyslipidemia from a Singapore healthcare system perspective. Inclisiran + SoC was separately compared with SoC, alirocumab + SoC, and evolocumab + SoC.

Methods: A lifetime Markov model in the United Kingdom (UK) was adapted to the Singapore setting.

Dynamic event-triggered tolerant containment control protocol for discrete multiagent systems based on finite index policy iteration algorithm.

For tolerant containment control of multi-agent systems, considering the challenges in modeling and the impact of actuator faults on system security and reliability, a finite index dynamic event-triggered policy iteration algorithm is proposed. This algorithm only requires input and output data, without relying on system models, and simultaneously considers the faults and energy consumption issues to improve the system reliability and save energy consumption. The conditions are provided to demonstrate the convergence and optimality of the algorithm, including a convergence speed, that is, the number of iterations required for convergence is finite.

A critical view of silk fibroin for non-viral gene therapy.

Exogenous genes are inserted into target cells during gene therapy in order to compensate or rectify disorders brought on by faulty or aberrant genes. However, gene therapy is still in its early stages because of its unsatisfactory therapeutic effects which are mainly due to low transfection efficiency of vectors, high toxicity, and poor target specificity. A natural polymer with numerous bioactive sites, good mechanical qualities, biodegradability, biocompatibility, and processability called silk fibroin has gained attention as a possible gene therapy vector.

Metabolomics signatures of serotonin reuptake inhibitor (escitalopram), serotonin norepinephrine reuptake inhibitor (duloxetine) and cognitive-behavioral therapy on key neurotransmitter pathways in major depressive disorder.

Metabolomics provides powerful tools that can inform about heterogeneity in disease and response to treatments. In this exploratory study, we employed an electrochemistry-based targeted metabolomics platform to assess the metabolic effects of three randomly-assigned treatments: escitalopram, duloxetine, and Cognitive-Behavioral Therapy (CBT) in 163 treatment-naïve outpatients with major depressive disorder. Serum samples from baseline and 12 weeks post-treatment were analyzed using targeted liquid chromatography-electrochemistry for metabolites related to tryptophan, tyrosine metabolism and related pathways.

Hepatic adverse events associated with ketamine and esketamine: A population-based disproportionality analysis.

Background And Objective: To determine whether there is disproportionate reporting of hepatobiliary disorders in the United States (US) FDA Adverse Event Reporting System (FAERS) for individuals prescribed ketamine or esketamine.

Design: We identified Medical Dictionary for Regulatory Activities (MedDRA) terms in the FAERS related to hepatobiliary disorders.

Main Measures: Formulations of ketamine and esketamine were evaluated for the proportionality of reporting for each hepatobiliary disorder parameter using the reporting odds ratio (ROR).

Finerenone and new-onset diabetes in heart failure: a prespecified analysis of the FINEARTS-HF trial.

Background: Data on the effect of mineralocorticoid receptor antagonist therapy on HbA levels and new-onset diabetes are conflicting. We aimed to examine the effect of oral finerenone, compared with placebo, on incident diabetes in the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure (FINEARTS-HF) trial.

Methods: In this randomised, double-blind, placebo-controlled trial, 6001 participants with heart failure with New York Heart Association functional class II-IV, left ventricular ejection fraction 40% or higher, evidence of structural heart disease, and elevated N-terminal pro-B-type natriuretic peptide levels were randomly assigned to finerenone or placebo, administered orally.

Mangrove-based carbon market projects: What stakeholders need to address during pre-feasibility assessment.

Mangrove-based carbon market projects (MbCMP) aim to conserve, protect and restore mangrove habitats in order to generate high quality blue carbon credits via a crediting program, as a contribution to climate change mitigation/adaptation, biodiversity conservation, ecosystem services provision and local socio-economic development. The blue carbon credits generated are transferable, verifiable and sold through carbon markets to earn additional income for governments and local communities. The main aim of the paper is to provide important considerations for pre-field planning, that is, how challenges associated with fieldwork, project implementation, and monitoring reporting and verification (MRV) can be addressed with proper pre-field planning.

Rapid on-site determination of heavy metals and metalloids in contaminated biochar samples by accelerated leaching process coupled with voltammetric sensors.

Heavy metals and metalloids are the most common environmental pollutants. Toxicity characteristic leaching procedure (TCLP) is a standard operating procedure that is used to assess heavy metal and metalloid compositions, and evaluate the hazardous nature of waste and waste-derived materials for reuse or disposal, such as determining landfill suitability. However, TCLP and the following detections are time-consuming and require bulky laboratory-based instruments and trained personnel.

Change surface regression for nonlinear subgroup identification with application to warfarin pharmacogenomics data.

Pharmacogenomics stands as a pivotal driver toward personalized medicine, aiming to optimize drug efficacy while minimizing adverse effects by uncovering the impact of genetic variations on inter-individual outcome variability. Despite its promise, the intricate landscape of drug metabolism introduces complexity, where the correlation between drug response and genes can be shaped by numerous nongenetic factors, often exhibiting heterogeneity across diverse subpopulations. This challenge is particularly pronounced in datasets such as the International Warfarin Pharmacogenetic Consortium (IWPC), which encompasses diverse patient information from multiple nations.

Draft genomes of fluoroquinolone-resistant subspecies strains isolated from Cambodian poultry marketplaces.

High-quality draft genomes of six subspecies strains from Cambodian poultry marketplaces were sequenced. The strains were identified as Corvallis-, Monschaui-, and Kentucky-serovars. The fluoroquinolone resistance gene, was found in three strains in different Cambodian provinces.

Enhancing Small-for-Gestational-Age Prediction: Multi-Country Validation of Nuchal Thickness, Estimated Fetal Weight, and Machine Learning Models.

Objective: The first objective is to develop a nuchal thickness reference chart. The second objective is to compare rule-based algorithms and machine learning models in predicting small-for-gestational-age infants.

Method: This retrospective study involved singleton pregnancies at University Malaya Medical Centre, Malaysia, developed a nuchal thickness chart and evaluated its predictive value for small-for-gestational-age using Malaysian and Singapore cohorts.

Two Head and Neck Cancers in an Adult With Intellectual Disability and Rett Syndrome: A Case Report.

The cases of head and neck cancer among persons with intellectual disability (PWID) are infrequently reported and therefore poorly understood. PWID often face increased barriers of access to healthcare, which can be further compounded when faced with a cancer diagnosis. This report presents the case of a 34-year-old Chinese female patient with Rett syndrome and intellectual disability, presenting with two primary cancers of the tongue and the trachea.