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At least 19 recordsLinked to original sources

PubMed2026

Optimizing Control Definitions in Opioid Use Disorder Genetic Research Using Electronic Health Records.

Amidst the opioid crisis, understanding the genetic basis of opioid use disorder (OUD) is crucial for identifying biological mechanisms and intervention points. However, genome-wide association studies (GWASs) have been hampered by inadequate sample sizes and often the use of control populations not assessed for prior opioid exposure. Because opioid exposure is a prerequisite for the development of OUD, consideration of exposure history in controls is important. Electronic health record data (EHR) paired with genomic information allow a broader sampling of patients with OUD and exposed controls. We leveraged data across two healthcare systems to evaluate the impact of using controls not screened for opioid exposure ('generic') versus minimally opioid-exposed control ('exposed'). First, at the phenotypic level, we conducted phenome-wide association studies (PheWAS) to compare the medical comorbidity profiles of OUD cases when using generic versus exposed controls. While PheWAS results for OUD-related comorbidities were more pronounced when using the generic group, 83% of the disease associations were overlapping and of similar effect sizes. Second, at the genetic level, we conducted GWAS (cases vs. generic; cases vs. exposed) and assessed differences in genetic correlations and degrees of phenotypic misclassification. Genetic results were concordant across control groups based on heritability (generic: 0.16 ± 0.07 vs. 0.10 ± 0.07), associations with the coding OPRM1 variant rs1799971 (pgeneric = 8.83E-03 vs. pexposed = 1.83E-02) and genetic correlations with prior OUD GWAS (rg-generic = 0.83 ± 0.26 vs. rg-exposed = 0.78 ± 0.27). Although GWASs were limited by sample size (Ngeneric = 6269, Nexposed = 6365), compared to an independent OUD GWAS (N = 425 944), the dilution value for the two GWAS was not different from 1, suggesting no major impact of phenotypic misclassification. This study represents the first effort to enhance OUD genetic research through optimization of control definitions using EHR data. Generic controls ascertained within the US health systems, where exposure to prescription opioids is high, offer a practical alternative for genetic studies of OUD.

Humans↗

PubMed2025

Optimal Control of Directional False Discovery Rates in Large-Scale Testing.

The high-throughput biomedical technology enables measurement of thousands of gene expression levels contemporaneously. A major task in analyzing these gene expression data is to identify both over-expressed and under-expressed genes. The popular two-group models select the non-null genes without further classifying them as overexpression or underexpression. Consequently, two-group decision rules are unable to constrain the numbers of falsely discovered over-expressed or under-expressed genes respectively. We propose a general three-group model that allows dependence between the test statistics and develop a decision rule that separately controls the two types of false discoveries. We show that the optimal decision rule in our three-group model has a special monotonic structure. By making use of this monotonic structure, we can linearize the two-directional false discovery rate constraints. We prove that our decision rule optimizes the expected number of true discoveries while controlling the proportions of falsely discovered over-expressed and under-expressed genes at desired levels simultaneously. The data-driven versions of the proposed procedures are suggested, and their consistency is established. Comparisons with state-of-the-art approaches and applications to genomic studies show that our procedures work well.

Humans↗

PubMed2026

Engineering Bacillus Subtilis for Efficient Biosynthesis of Riboflavin: Current Knowledge and Future Perspectives.

Riboflavin is an essential water-soluble vitamin that serves as a precursor for the biosynthesis of the flavin cofactors FMN and FAD, which play pivotal roles in numerous redox and energy metabolism reactions. With the growing global demand for sustainable vitamin production, microbial fermentation has become an attractive alternative to chemical synthesis due to its environmental and economic advantages. Among microbial hosts, Bacillus subtilis has emerged as a leading cell factory for riboflavin production owing to its GRAS status, well-characterized genetics, and efficient protein secretion system. This review provides a comprehensive overview of recent advances in metabolic engineering strategies to enhance riboflavin biosynthesis in B. subtilis. Key topics include strengthening biosynthetic and precursor pathways, relieving feedback inhibition, balancing metabolic flux and cell growth, employing adaptive laboratory evolution, and utilizing omics-guided optimization and 13C metabolic flux analysis. Moreover, the integration of synthetic biology tools such as riboswitch engineering, regulatory element design, and high-throughput screening has significantly accelerated strain improvement. Despite remarkable progress, challenges remain in achieving precise regulatory control, optimizing multi-gene expression, and enhancing genome integration efficiency. Future research combining multi-omics data, synthetic regulatory design, and machine learning-driven predictive modeling is expected to further advance the development of intelligent B. subtilis cell factories. However, the practical implementation of these systems remains constrained by the metabolic burden of overproduction and the lack of universal regulatory models that can predict strain performance across varying industrial scales.

Bacillus subtilis↗

PubMed2025

Human papillomavirus (HPV) genotypes extended prevalence in the female population from a city in Northern Chile.

BACKGROUND: Cervical cancer is primarily associated with the presence of human papillomavirus (HPV), with high-risk genotypes HPV-16 and HPV-18 being the focus of vaccination programs in developing countries such as Chile. Preventive screening for cervical cancer in women aged 25 to 64 years remains centered on cytological techniques and is primarily performed based on clinical suspicion of cervical lesions. However, extended screening for HPV genotypes using DNA amplification methods is not routinely applied to the Chilean female population yet. This study aimed to determine the prevalence of high- and low-risk HPV genotypes in women without known risk factors in a city in northern Chile. METHODS: Cervicovaginal brushing samples were obtained from 390 women from Antofagasta city, Northern Chile, aged between 25 and 64 years; genomic DNA was extracted, and multiplex real-time PCR analysis was used to identify a larger group of high- and low-risk HPV genotypes. RESULTS: Among 390 samples, HPV prevalence was 36.9%, of which 54.9% were high-risk genotypes, 18.7% were low-risk genotypes, and 26.4% showed mixed infection with both high- and low-risk genotypes. High-risk genotypes 16, 58, 39, and 31 were the most frequently identified among HPV-positive samples. Furthermore, a significant association was observed between HPV presence and both age and suspicion of cervical alteration, and women testing positive for other sexually transmitted infections (STIs) were more likely to acquire HPV. CONCLUSIONS: Implementing a screening program that incorporates extended HPV genotyping in Chile, including testing for high-risk genotypes 16, 18, 31, 39, and 58, is crucial to optimize control, early detection, and vaccination efforts for Chilean circulating HPV genotypes that are not covered by the actual vaccine, thus contributing to a more effective reduction in the burden of disease associated with the virus.

Humans↗

PubMed2026

Technology choice, glycemic control and patient-reported outcome measures in adults with type 1 diabetes: A randomized crossover trial comparing a smart insulin pen with an automated insulin delivery system (EBIACE-1).

AIMS: To compare glycemic outcomes and patient-reported outcome measures (PROMs) between smart insulin pens (SIP) and an automated insulin delivery (AID) system in adults with type 1 diabetes (T1D), and to identify individuals able to maintain near-optimal glycemic control using SIP. METHODS: EBIACE-1 was a randomized, open-label, crossover trial including 31 adults with T1D. Participants received SIP (InPen™) and AID (MiniMed™ 780G) for 6 months each. Co-primary outcomes were time in range (TIR 70-180 mg/dL) and HbA1c. Treatment effects were assessed using longitudinal models in intention-to-treat (ITT) and per-protocol (PP) analyses. Predictors of near-optimal glycemic control with SIP were evaluated using multivariable logistic regression. RESULTS: AID improved glycemic control versus SIP, with higher TIR (81 % vs 66 %; +15 %, 95 % CI 10-19; P < 0.001) and lower HbA1c (6.9 % [52 mmol/mol] vs 7.3 % [56 mmol/mol]; -0.4 %, 95 % CI - 0.6 to - 0.3; P < 0.001). Near-optimal glycemic control with SIP was achieved by 12 of 26 participants (46 %). In exploratory analyses, higher baseline diabetes-related life interference was associated with a lower probability of achieving this outcome. CONCLUSIONS: AID provides superior glycemic control, although nearly half of participants achieved near-optimal control with SIP, supporting a personalized approach to technology selection.

Adult↗

PubMed2026

Design and optimization of a kinase-controlled allosteric switch.

Post-translational control enables rapid and precise regulation of cell behavior. Despite these advantages, general strategies to build phosphorylation-based synthetic circuits are limited. Here we reasoned that engineered allostery, a technique that has been applied to design light- and chemically gated protein switches, could also be used to engineer phosphorylation-controlled protein switches (phospho-switches). Using an allosterically controllable Gal4 transcription factor as a scaffold, we show that a classic kinase Förster resonance energy transfer biosensor architecture can be used as a starting point for phospho-switch design. We optimize all features of the phospho-switch to develop an ERK-controlled transcription factor with a 20-fold phosphorylation-dependent change in transcriptional output. The resulting synthetic ERK-responsive transcription factor responds with comparable sensitivity to the c-fos promoter and reveals spatial ERK signaling patterns in mammalian developmental organoids. We further show that our switch architecture can be generalized to other input kinases and allosterically controlled targets. This work provides a general platform for a new generation of kinase-responsive tools for biosensing and synthetic biology applications.

Allosteric Regulation↗

PubMed2026

Comparative Efficacy of Non-opioid Analgesic Drugs for Chronic Cancer Pain: A Bayesian Network Meta-analysis.

PURPOSE: While opioids remain the primary pharmacological intervention for cancer pain management, their clinical utility is frequently compromised by dose-limiting toxicities. This study aimed to determine the comparative efficacy, opioid-sparing potential, and clinical hierarchy of non-opioid adjuvant drug classes. The study was structured around the PICO framework to evaluate the pharmacological strategies currently utilized in multimodal clinical oncology. METHODS: A systematic search of electronic databases (PubMed, Embase, Cochrane) was conducted for randomized controlled trials (RCTs) published between 2000 and 2025. The primary outcome was global analgesic efficacy (standardized mean difference [SMD]), while secondary outcomes included the opioid-sparing effect, defined as the percentage reduction in morphine equivalent daily dose (MEDD) and the incidence of treatment-emergent adverse events (Harms). A Bayesian network meta-analysis (NMA) was performed to rank treatments using SUCRA values. The methodological quality was assessed using the Cochrane Risk of Bias (RoB 2.0) tool. RESULTS: Twenty-three RCTs (n = 1845) met the inclusion criteria. Nonsteroidal anti-inflammatory drugs (NSAIDs) (-1.10) and anticonvulsants (-1.06) demonstrated the most robust analgesic effects. The SUCRA ranking confirmed a clear hierarchy, with the combination of anticonvulsants and antidepressants showing the highest probability of efficacy. A significant opioid-sparing effect was observed for gabapentinoids and ketamine, facilitating MEDD reduction. While serious adverse events were rare, minor harms (somnolence, dizziness) were more frequent in the most effective classes. CONCLUSION: Our NMA provides a robust evidence base for a "Clinical Tier" system, ranking adjuvants by their balance of efficacy and safety. These findings support the early integration of Tier I agents (anticonvulsants and NSAIDs) to optimize pain control and reduce opioid-related toxicities in chronic cancer pain management.

Humans↗

PubMed2026

Integrating genomics, multi-omics, CRISPR and speed breeding for stress-resilient vegetable legume improvement.

Vegetable legumes are nutritionally and ecologically important crops. However, their genetic improvement has not kept pace with the increasing challenges posed by climate change due to the polygenic nature of stress tolerance, narrow genetic diversity, and the persistent gap between molecular discoveries and field-level cultivar development. Although recent reviews have examined individual genomic tools or specific stress responses, a comprehensive synthesis integrating genomics-assisted breeding, multi-omics technologies, genome editing, and speed breeding within a unified crop improvement framework has been lacking. This review addresses that gap by critically evaluating how these complementary approaches can accelerate the development of stress-resilient vegetable legumes, including pea, common bean, cowpea, faba bean, cluster bean, yard-long bean, and hyacinth bean. This review synthesizes advances in QTL mapping, genome-wide association studies, transcriptomics, metabolomics, and CRISPR-based functional genomics that have identified key regulators and pathways underlying resistance to major biotic and abiotic stresses. Rather than considering these technologies independently, the review emphasizes their convergence into a systems-level breeding framework integrating genomic discovery, functional validation, predictive breeding, and accelerated generation advancement to improve breeding efficiency. Speed breeding, enabling up to seven to eight generations annually under optimized controlled-environment experimental conditions in cowpea, is discussed as a complementary strategy with genomic selection and genome editing. The review further identifies major translational bottlenecks, including transformation recalcitrance, limited genomic resources for underutilized vegetable legumes, inadequate multi-environment validation, and fragmented omics integration, and presents an integrated systems-breeding framework to bridge the gap between gene discovery and cultivar development.

Fabaceae↗

PubMed2026

From Variability to Consensus: Rescoring Harmonizes Peptide Identification across Diverse Search Engines and Data Sets.

Peptide-spectrum match (PSM) rescoring has become standard in proteomics workflows, improving peptide identification accuracy across diverse search engines. Despite the availability of multiple rescoring strategies, systematic comparisons spanning several search engines, data sets, and database configurations remain limited. Here, we benchmarked seven publicly available search engines, evaluating standard target-decoy-based false discovery rate (FDR) estimation alongside Percolator, MS2Rescore, and Oktoberfest across four data sets acquired on different mass spectrometry platforms in data-dependent mode and searched against protein databases of varying size and composition. Rescoring substantially increased identification consensus and reduced variability between search engines, with prediction-based approaches yielding the largest gains. While database size had limited impact for human data sets, it significantly affected identification rates on a metaproteomic data set. Entrapment-based evaluation indicated generally adequate FDR control across methods, although prediction-based rescoring exhibited a higher tendency toward FDR underestimation in specific configurations. Overall, advanced rescoring strategies harmonize peptide identification outcomes across search engines, thereby enhancing robustness and comparability in proteomics analyses. However, careful feature selection and appropriate database choice remain essential to ensure reliable FDR control and optimal performance across diverse experimental settings.

Search Engine↗

PubMed2017

Addressing current challenges in cancer immunotherapy with mathematical and computational modelling.

The goal of cancer immunotherapy is to boost a patient's immune response to a tumour. Yet, the design of an effective immunotherapy is complicated by various factors, including a potentially immunosuppressive tumour microenvironment, immune-modulating effects of conventional treatments and therapy-related toxicities. These complexities can be incorporated into mathematical and computational models of cancer immunotherapy that can then be used to aid in rational therapy design. In this review, we survey modelling approaches under the umbrella of the major challenges facing immunotherapy development, which encompass tumour classification, optimal treatment scheduling and combination therapy design. Although overlapping, each challenge has presented unique opportunities for modellers to make contributions using analytical and numerical analysis of model outcomes, as well as optimization algorithms. We discuss several examples of models that have grown in complexity as more biological information has become available, showcasing how model development is a dynamic process interlinked with the rapid advances in tumour-immune biology. We conclude the review with recommendations for modellers both with respect to methodology and biological direction that might help keep modellers at the forefront of cancer immunotherapy development.

Computer Simulation↗

PubMed2026

Swab Testing to Optimize Pneumonia Treatment With Empiric Vancomycin: A Randomized Controlled Trial.

BACKGROUND: Fear of methicillin-resistant Staphylococcus aureus (MRSA) as a cause of community-acquired pneumonia (CAP) frequently leads to empiric vancomycin coverage. Data evaluating the use of MRSA polymerase chain reaction (PCR) nasal swab testing to guide vancomycin de-escalation is limited for patients in the intensive care unit (ICU). METHODS: Swab Testing to Optimize Pneumonia Treatment With Empiric Vancomycin (STOP-Vanc) is a pragmatic, prospective, single-center, non-blinded randomized trial in which adult ICU patients with suspicion of CAP were randomized 1:1 to receive usual care either with (intervention) or without (control) the addition of MRSA nares PCR testing following ICU admission. The primary outcome was vancomycin-free hours alive, defined as the expected number of hours alive and free of vancomycin use within the first 7 days of trial enrollment as estimated using a longitudinal proportional odds state transition model adjusted for baseline covariates. RESULTS: A total of 277 adult ICU patients were randomized. Methicillin-resistant Staphylococcus aureus PCR nasal swab testing had a negative predictive value (NPV) of 98.9% in the intervention arm. The primary endpoint, vancomycin-free hours alive, was 105.7 in the control arm and 109.7 in the intervention arm (adjusted difference, 4 hours; 95% CI, -9.5-18.2; P = .458). CONCLUSIONS: Despite MRSA PCR nasal swab testing demonstrating a high NPV in this critically ill population, MRSA PCR nasal swab testing did not decrease the duration of vancomycin use or 30-day mortality among ICU patients with suspected CAP. Additional clinician education and antimicrobial stewardship interventions might be needed to reduce vancomycin use in this patient population. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT06272994 (STOP-Vanc).

Humans↗

PubMed2026

Development and validation of a plasma miRNA-CEA biomarker panel for early detection of lung cancer.

Lung cancer remains a leading cause of cancer-related mortality worldwide, underscoring the critical need for early detection to improve patient outcomes. This study aimed to develop and validate a plasma microRNA biomarker panel for the early detection of non-small cell lung cancer in a Japanese cohort. We enrolled 525 participants, comprising 261 LC cases and 264 non-LC controls, divided into optimization and validation cohorts. A 12-miRNA panel was optimized and further combined with CEA to enhance diagnostic performance. The miRNA-alone model demonstrated robust performance in both the optimization (AUC = 77.0%) and validation cohorts (AUC = 77.9%). Integration with CEA significantly improved accuracy, achieving AUCs of 86.2% in optimization and 84.9% in validation, with particularly high performance in late-stage cancers (AUC = 94.4%) and squamous cell carcinoma (AUC = 90.7%). Sensitivity and specificity thresholds were evaluated, enabling model customization for diverse clinical scenarios. These findings highlight the potential of the miRNA-CEA panel as a minimally invasive tool for early LC detection, especially in non-smoking populations.

Humans↗

PubMed2026

Hypervirulent Klebsiella pneumoniae ST23 causing pyogenic liver abscess and metastatic endogenous endophthalmitis in Europe: a case report.

INTRODUCTION AND IMPORTANCE: Pyogenic liver abscess (PLA) has traditionally been considered prevalent in Asia. However, its incidence is increasing in Europe. Klebsiella pneumoniae (Kp) has emerged as the leading causative pathogen, and hypervirulent strains pose a higher risk of invasive disease and metastatic complications, such as endogenous endophthalmitis (EE). CASE PRESENTATION: The case describes a 77-year-old woman who presented with fever and right upper quadrant abdominal pain. She was diagnosed with a second episode of PLA within 3 months, caused by Kp. Despite prompt antimicrobial therapy and percutaneous transhepatic drainage, the patient developed acute vision loss in the left eye during hospitalization. Ophthalmologic assessment confirmed EE secondary to bacteremia. Whole-genome sequencing identified the isolate as hypervirulent Kp (hvKp) sequence type 23 (ST23). While the liver abscess resolved following treatment, the patient sustained permanent loss of vision in the affected eye despite aggressive medical and surgical management. CLINICAL DISCUSSION: This case illustrates the invasive nature of hvKp and its potential for recurrence and metastatic complications. Improved recognition through targeted virulence testing is essential to avoid underdiagnosis. CONCLUSION: This case highlights the aggressive nature of hvKp. Early recognition of systemic and ocular symptoms, prompt ophthalmologic evaluation, and timely source control are essential. Optimal management requires multidisciplinary collaboration and the use of molecular diagnostics, including whole-genome sequencing, to identify hypervirulent lineages and support surveillance.

Klebsiella pneumoniae↗

PubMed2026

Dispositional optimism and open-label placebo responses in hair cortisol concentrations and psychological distress-A randomized controlled trial.

Open-label placebo (OLP) treatments show beneficial effects on various health-related outcomes, but studies investigating OLP effects on physiological measures remain scarce. This randomized controlled trial examined the effect of a 4-week OLP intervention on psychological distress and hair cortisol concentrations (HCC) in 202 healthy university students preparing for mandatory oral exams and whether dispositional optimism moderates the OLP effects. Participants were randomly assigned to an OLP or control group. Psychological distress was repeatedly assessed via negative affect, test anxiety, and subjective stress. HCC was measured before and within the intervention. Treatment expectations were additionally examined in interaction with optimism. Results show that OLPs significantly reduced psychological distress and HCC compared to the controls. Optimism moderated the OLP effect on HCC, with less optimistic individuals demonstrating the strongest reduction, independent of expectation. Optimism did not moderate OLP effects in psychological distress. However, the OLP effect on psychological distress depended on the three-way interaction of group, optimism, and expectation. The results suggest that OLPs alleviate the psychophysiological impact of a real-life stressor and indicate that optimism and expectation differently shape psychological and physiological OLP responses. These findings are discussed within the framework of the interactionist perspective.

Humans↗

PubMed2026

Using the OPTIMAL Theory to Optimize Aerodynamics in Respiratory Training for Healthy Adults and Individuals With Parkinson's Disease.

BACKGROUND: The OPTIMAL (Optimizing Performance Through Intrinsic Motivation and Attention for Learning) theory is a motor learning framework proposing that optimizing intrinsic motivation enhances motor performance and learning. The theory identifies three key components-Enhanced Expectancies (EE), Autonomy Support (AS) and External Focus of Attention (EF)-which facilitate more efficient, goal-directed movement. These components have been shown to improve motor outcomes in limb-based tasks; however, their application to respiratory training, particularly in clinical contexts such as voice and swallowing therapy in patients with Parkinson's disease (pwPD), has not yet been systematically explored. AIMS: This study aimed to investigate whether implementing OPTIMAL theory strategies during a respiratory muscle strength training (RMST) task improves immediate respiratory motor performance in healthy adults and pwPD. Additionally, we aimed to examine the effects of these strategies on motivation and cognitive engagement. METHODS: This quasi-randomized, single-session trial included 47 participants: Healthy CONTROL (n = 17), Healthy OPTIMAL (n = 16) and PD OPTIMAL (n = 14). Healthy participants were quasi-randomly assigned to either intervention or control conditions, whereas pwPD completed the intervention only. All participants completed a single respiratory session that included baseline, practice and retention phases. Outcome measures included peak expiratory flow, cough peak expiratory flow, cognitive engagement (EEG-based Cognitive Engagement Index) and self-administered motivation questionnaire. OUTCOMES AND RESULTS: Exhalation force improved from baseline to retention in the Healthy OPTIMAL group (baseline: M = 296 L/min; retention: M = 338 L/min; p < 0.001) and the PD OPTIMAL group (baseline: M = 315 L/min; retention: M = 370 L/min; p < 0.0001), but not in the Healthy CONTROL group (p > 0.05). No significant changes in cough strength were observed in any group. No correlations were found between cognitive engagement and exhalation force or motivation scores. However, motivation increased more in the Healthy OPTIMAL group (Questionnaire 1: M = 57.2; Questionnaire 2: M = 60.7) and the PD OPTIMAL group (Questionnaire 1: M = 60.1; Questionnaire 2: M = 62.8) than in the Healthy CONTROL group (Questionnaire 1: M = 61.1; Questionnaire 2: M = 62.5). CONCLUSIONS AND IMPLICATIONS: Implementing the OPTIMAL theory enhances immediate respiratory motor performance in both healthy participants and pwPD. OPTIMAL theory has clinical value in voice and swallowing therapy, although further research is needed to establish long-term efficacy and clinical impact. WHAT THIS PAPER ADDS: What is already known on the subject Motivation is a critical factor in rehabilitation. The OPTIMAL theory has been shown to improve both motivation and motor performance in limb-based tasks. Its impact on respiratory training, however, has not been previously examined. What this paper adds to the existing knowledge This study shows that applying OPTIMAL strategies during a respiratory muscle strength training task significantly improved peak expiratory flow in both healthy adults and people with Parkinson's disease. What are the potential or clinical implications of this work? Integrating the OPTIMAL theory principles into respiratory therapy may enhance motor outcomes, supporting voice, swallowing and cough rehabilitation.

Humans↗

PubMed2025

A Digital Tool for Clinical Evidence-Driven Guideline Development by Studying Properties of Trial Eligible and Ineligible Populations: Development and Usability Study.

BACKGROUND: Clinical guideline development preferentially relies on evidence from randomized controlled trials (RCTs). RCTs are gold-standard methods to evaluate the efficacy of treatments with the highest internal validity but limited external validity, in the sense that their findings may not always be applicable to or generalizable to clinical populations or population characteristics. The external validity of RCTs for the clinical population is constrained by the lack of tailored epidemiological data analysis designed for this purpose due to data governance, consistency of disease or condition definitions, and reduplicated effort in analysis code. OBJECTIVE: This study aims to develop a digital tool that characterizes the overall population and differences between clinical trial eligible and ineligible populations from the clinical populations of a disease or condition regarding demography (eg, age, gender, ethnicity), comorbidity, coprescription, hospitalization, and mortality. Currently, the process is complex, onerous, and time-consuming, whereas a real-time tool may be used to rapidly inform a guideline developer's judgment about the applicability of evidence. METHODS: The National Institute for Health and Care Excellence-particularly the gout guideline development group-and the Scottish Intercollegiate Guidelines Network guideline developers were consulted to gather their requirements and evidential data needs when developing guidelines. An R Shiny (R Foundation for Statistical Computing) tool was designed and developed using electronic primary health care data linked with hospitalization and mortality data built upon an optimized data architecture. Disclosure control mechanisms were built into the tool to ensure data confidentiality. The tool was deployed within a Trusted Research Environment, allowing only trusted preapproved researchers to conduct analysis. RESULTS: The tool supports 128 chronic health conditions as index conditions and 161 conditions as comorbidities (33 in addition to the 128 index conditions). It enables 2 types of analyses via the graphic interface: overall population and stratified by user-defined eligibility criteria. The analyses produce an overview of statistical tables (eg, age, gender) of the index condition population and, within the overview groupings, produce details on, for example, electronic frailty index, comorbidities, and coprescriptions. The disclosure control mechanism is integral to the tool, limiting tabular counts to meet local governance needs. An exemplary result for gout as an index condition is presented to demonstrate the tool's functionality. Guideline developers from the National Institute for Health and Care Excellence and the Scottish Intercollegiate Guidelines Network provided positive feedback on the tool. CONCLUSIONS: The tool is a proof-of-concept, and the user feedback has demonstrated that this is a step toward computer-interpretable guideline development. Using the digital tool can potentially improve evidence-driven guideline development through the availability of real-world data in real time.

Humans↗

PubMed2025

qcCHIP: an R package to identify clonal hematopoiesis variants using cohort-specific data characteristics.

SUMMARY: Clonal hematopoiesis (CH) is a molecular biomarker associated with various adverse outcomes in both healthy individuals and those with underlying conditions, including cancer. Detecting CH usually involves genomic sequencing of individual blood samples followed by robust bioinformatics data filtering. We report an R package, qcCHIP, a bioinformatics pipeline that implements permutation-based parameter optimization to guide quality control filtering and cohort-specific CH identification. We benchmark qcCHIP under various data settings, including different sequencing depths, ranges of cohort sizes, with and without normal-tumor paired samples, and across different cancer types. We show that qcCHIP allows users to customize analysis needs to generate CH calls based on cohort-specific data characteristics. AVAILABILITY AND IMPLEMENTATION: qcCHIP R package is freely accessible at GitHub https://github.com/tenglab/qcCHIP and DOI: 10.5281/zenodo.16421861.

Humans↗

PubMed2026

Optimizing smoking cessation pharmacotherapy and counseling for adult primary care patients: a factorial randomized controlled trial.

BACKGROUND: Even with the most effective smoking cessation pharmacotherapies (i.e., varenicline or combination nicotine replacement [C-NRT]), the majority of people ultimately return to smoking. This research explored how to optimize the use of varenicline and C-NRT to promote smoking cessation. METHODS: Primary care patients participated in a 2x2x2x2 factorial experiment that evaluated 4 factors: 1) Medication Type (Varenicline vs. C-NRT [patch + mini-lozenge]), 2) Preparation (pre-quit) Medication (4 Weeks vs. Standard); 3) Medication Duration (Extended [24 weeks] vs. Standard [12 weeks]); and 4) Counseling Type (Cessation Counseling [4 sessions] vs. Referral Support [2 sessions focused on use of referral resources]). This study was discontinued prior to reaching the proposed sample size (N = 608) due to pandemic-related budgetary constraints. RESULTS: Participants (N = 496) were 55% women and 45.6% Black individuals. There were no statistically significant main effects of the 4 factors on abstinence at 12, 26 or 52 weeks. There was a 3-way interaction between Medication Type, Preparation Medication, and Counseling Type (p = 0.04) predicting the primary outcome of biochemically confirmed abstinence at 52 weeks; cessation counseling vs. referral support improved varenicline quit rates when 4 weeks versus 1 week of pre-quit medication was offered. For C-NRT, counseling type did not significantly improve quit rates regardless of the use of preparation medication. CONCLUSIONS: There was no robust evidence that enhanced pre-quit or extended duration of varenicline or C-NRT increased abstinence rates. More intensive counseling may support cessation for different pharmacotherapy regimens. Given the lack of consistent findings, this research should be viewed as exploratory to guide future research.

Humans↗