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PubMed2026

Technical note: reconstructing dose distributions from manually planned electron boosts in breast radiotherapy.

PURPOSE: In breast radiotherapy, delivery of manually-calculated electron boosts limits retrospective dose-response analyses as dose distribution is unavailable. This work evaluates the feasibility of reconstructing dose distributions from manually planned electron boosts in breast-conserving radiotherapy. METHODS: Only 72 out of 198 breast cancer patients had complete stored dose distributions from sequential electron boosts in the REQUITE study. Arbitrary data from 70/72 patients were used to develop and validate dose reconstruction method. Twenty patients were used to determine optimal parameters for Monte-Carlo-based (MC) electron dose reconstruction on RayStation (v.11B-R), considering CT-calibration curve, MC-history number, andcalculation grid resolution. Remaining 50 patients were used to quantify dose reconstruction accuracy. The similarity between reconstructed and stored dose was evaluated using 3D-gamma index and dosimetric parameters extracted from breast and tumour bed contours. Dose difference location was evaluated using dose-location histogram. RESULTS: Calculation grid resolution significantly impacted electron dose distribution (p < 0.01), where the finest grid (0.15 cm) showed highest similarity to stored doses. CT-calibration curve and MC-history number had a negligible influence on dose reconstruction. Dosimetric difference between reconstructed and stored doses was < 1 Gy for breast and tumour bed. Reconstructed dose was achieved > 90% gamma passing rate in the validation set. However, around 2.5 Gy dose differences were observed at the skin and tissue interface regions. CONCLUSIONS: Retrospective electron boost dose reconstruction is feasible with acceptable accuracy, and could increase data completeness in large cohort studies. Caution is advised when assessing dose near tissue interface and further validation is needed outside the REQUITE dataset.

Electrons↗

PubMed2026

Evaluating pregnancy and neonatal outcomes in mothers with genetic disease using electronic health care records.

PURPOSE: The effect of Mendelian disorders on pregnancy and neonatal outcomes is poorly understood because of their rarity and the challenge of compiling complete prenatal and postnatal records. METHODS: Using electronic health records from a single academic center, we developed a retrospective cohort of maternal-infant dyads. Cases were mothers with molecularly confirmed Mendelian disorders paired with live-born infants; controls had no documented genetic disease. Outcomes were evaluated overall, by organ system, and by individual disorder. RESULTS: The cohort included 58,912 dyads, 241 with genetic diagnoses and 58,671 controls. Although overall outcomes were generally favorable, mothers with genetic disorders had higher rates of cesarean delivery and neonatal intensive care unit admission, earlier gestational age, and lower Apgar scores. Neonatal risks were greatest among neurological and cardiovascular disorders. Known associations were replicated, including increased neonatal intensive care unit admission in 22q11.2 deletion syndrome, cesarean delivery in Turner syndrome, and gestational diabetes in cystic fibrosis. We also provided descriptive electronic-health-record-based case reports and case series for 35 disorders previously lacking published pregnancy outcome data. CONCLUSION: This study identifies elevated perinatal risks in specific Mendelian disease groups and demonstrates how electronic-health-record-linked data can support prenatal counseling, risk stratification, and individualized care for individuals with genetic disorders.

Humans↗

PubMed2026

Long-term petroleum pollution alters soil microbial communities via electron transfer capacity: Evidence from a 35-year chronosequence.

Petroleum pollution poses a serious threat to soil ecosystems, especially in areas surrounding oil wells, where contamination should not be overlooked. Through a 35-year longitudinal study of soils surrounding oil wells, we demonstrate that petroleum hydrocarbons accumulate predominantly in the top 10 cm of soil, reducing the electron acceptor capacity (EAC) by 61.59 % (from 12.68 to 4.87 μmole-/gC) and decreasing the electron transfer capacity (ETC) by 43 %. Structural equation modeling identified ETC as the critical mediator of microbial community shifts, with EAC playing a pivotal role in sustaining redox processes. Notably, hydrocarbon accumulation triggered a microbial succession: The abundance of Actinomycetota (including genera Rhodococcus, Arthrobacter, and Rubrobacter) showed the most significant fluctuations within 2 years, while Pseudomonadota (genera Methylobacter, Thiobacillus, and Pseudomonas), which were dominant in uncontaminated soils, decreased markedly during this period. This transition coincided with peak microbial dysbiosis (microbial dysbiosis index in 2022 reached 31.41 times that of controls). Within two to four years following mild petroleum stress, the bacterial community established a new structural configuration, revealing a crucial window for ecological recovery. The coupling between ETC reduction and microbial succession highlights the pivotal role of electron flux in soil recovery. Our findings establish a mechanistic framework for ETC-targeted restoration strategies to enhance bioremediation in petroleum-contaminated soils.

Soil Microbiology↗

PubMed2026

Carbon monoxide-driven proton respiration enables facultative anaerobes to survive electron acceptor limitation.

Diverse microorganisms couple the oxidation of carbon monoxide gas (CO) to the reduction of protons, producing hydrogen gas (H2) using nickel-containing CO dehydrogenase/energy-converting hydrogenase (Ni-CODH/ECH). Although this process yields one of the lowest free-energy gains in biology, its physiological role at environmentally relevant CO levels remains unresolved. Here, we show that Ni-CODH/ECH functions as a survival-oriented energy conservation system that enables heterotrophic facultative anaerobes to survive electron acceptor limitation, rather than primarily supporting growth or CO detoxification. Analysis of 387 genomes of Anoxybacillaceae species revealed that Ni-CODH/ECH had a patchy distribution and, with one exception, was mutually exclusive with the oxygen-tolerant molybdenum-containing CODH, suggesting ecological specialization. Culture experiments using three isolates (Parageobacillus sp. G301, P. thermoglucosidasius NBRC 107763, and Thermolongibacillus altinsuensis B1-1) demonstrated that CO-dependent proton respiration is activated during stationary phase when exogenous electron acceptors are limiting, maintaining cell density under 25% CO, whereas no effect was observed in a Ni-CODH knockout (ΔcooCSF) strain. RNA-seq analysis of Parageobacillus sp. G301 under twelve conditions revealed that Ni-CODH/ECH genes are highly expressed (top 0.2%-1.9% of all genes) under electron acceptor-free conditions, independent of CO presence, under the predicted control of the redox-dependent transcriptional repressor Rex. ΔcooCSF cultures accumulated more CO than the wild-type (WT), suggesting trace CO scavenging by the WT. Together, our results redefine Ni-CODH/ECH as a redox-regulated auxiliary energy-conservation strategy that supports survival and maintenance in anaerobic energy-limited environments using two ubiquitous substrates. This work extends the carboxydovore paradigm of trace gas-based survival from aerobic to spatiotemporally variable anaerobic environments.

Carbon Monoxide↗

PubMed2026

CeOx-Induced Spatial and Electronic Modulation for General Direct Oxo Coupling in Transition Metal Hydroxides.

Electrochemical water splitting has emerged as a sustainable paradigm for hydrogen generation, where sluggish kinetics of the oxygen evolution reaction (OER) catalyzed by transition metal-based materials remain the critical bottleneck. Herein, we present a strategy that anchors CeOx nanoparticles (∼2 nm) onto two-dimensional Ni(OH)2 nanosheets, enabling dual modulation of spatial configuration and electronic states to accelerate O-O coupling. Spatially, interfacial lattice distortion between CeOx and Ni(OH)2 optimizes Ni-Ni dual-metal sites with reduced interatomic spacing. Electronically, dynamic modulation through reversible Ce3+/Ce4+ redox cycling positions Ce as an electronic regulation hub, stabilizing Ni species at the catalytically favorable +3 oxidation state through Ce─O─Ni interactions. This synergistic effect shifts the pathway from adsorbate evolution mechanism (AEM) to oxide pathway mechanism (OPM). The prepared CeOx@Ni(OH)2 achieves an overpotential of 152 mV at 10 mA cm-2 and operates continuously over 2000 h with limited performance decay. When integrated into an alkaline anion exchange membrane water electrolyzer (AEMWE), it requires 1.91 V to attain 1 A cm-2 and maintains stable operation for 450 h. This OPM activation strategy shows potential applicability across CeOx-loaded transition metal hydroxides, including Ni(OH)2, Co(OH)2, NiCo, and NiFe layered double hydroxides, offering a promising approach for alkaline OER enhancement.

alkaline water oxidation↗

PubMed2026

Electronic Nudges to Increase Influenza Vaccination in Immunosuppressed Adults Across the Age Spectrum: A Pooled Analysis of 2 Nationwide Randomized Trials.

BACKGROUND: Immunosuppressed individuals face higher risk of severe influenza complications, yet vaccination coverage remains low. We aimed to assess the effect of electronic letter-based nudges on influenza vaccination uptake by immunosuppression status. METHODS: We performed a participant-level pooled analysis of 2 methodologically harmonized, nationwide, pragmatic randomized clinical trials during the 2023-2024 influenza season. Adults aged ≥65 years (NUDGE-FLU-2) and adults aged 18-64 years with chronic conditions (NUDGE-FLU-CHRONIC) were included, with immunosuppression defined by an immunosuppressive diagnosis or a filled prescription for immunosuppressive therapy. Participants were randomized in a 2.45:1:1:1:1:1:1 ratio to usual care or 1 of 6 electronic letter interventions. The primary outcome was receipt of influenza vaccination by 1 January 2024 ascertained from nationwide administrative health registries. Effect modification by immunosuppression status was assessed using binomial regression. RESULTS: Among 1 181 254 participants (mean age 67 years; 73 830 [6.3%] immunosuppressed), 66.1% were vaccinated. Any letter increased vaccine uptake compared with usual care (absolute difference, 2.79% points; 95% confidence interval [CI], 2.60-2.98; P < .001), with greater effect among immunosuppressed individuals (+4.12 vs +2.70% points; Pinteraction = .002). In younger adults with chronic conditions, letter-based nudges increased vaccination rates by 11.7% points overall and by 13.3% points among those with immunosuppression (Pinteraction = .007). Among immunosuppressed individuals, nudging effects appeared greater for those with immunosuppressive conditions than for those receiving immunosuppressive treatment. CONCLUSIONS: Electronic letter-based nudges increased influenza vaccination rates, with greater benefit among immunosuppressed individuals. These findings support implementation of low-cost, letter-based nudging strategies to improve vaccine uptake in this high-risk population. Clinical Trials Registration. NCT06030726 and NCT06030739.

Adolescent↗

PubMed2026

Educational Effects of Electronic Documents and Videos on Parents' Responses to Acute Illness in Young Children: A Randomized Controlled Trial.

AIM: This study compared changes associated with electronic document-based and video-based education for parents responding to acute illness in young children, focusing on self-reported knowledge, anxiety, and satisfaction. METHODS: A randomized controlled trial with pre- and post-intervention measurements was conducted among 140 adults in Japan who self-reported raising a child under 3 years of age and having experienced their child's acute illness. Participants were assigned to an electronic document group or a video group (n = 70 each). Self-reported knowledge was assessed using a researcher-developed questionnaire, and anxiety was measured using the State-Trait Anxiety Inventory. Pre-post changes and between-group differences in change scores were examined. RESULTS: Total self-reported knowledge scores increased significantly in both groups (p < 0.01), with no significant between-group difference. The video group showed significant improvements in items related to symptoms requiring attention at home and information sources, whereas the electronic document group improved in items related to symptoms requiring medical consultation and emergency calls. State and trait anxiety did not change significantly in either group. Satisfaction was high in both groups. CONCLUSIONS: Both educational formats may support parents' learning about responses to acute illness in young children, although appropriate formats may differ according to the educational content. Information provision alone may have limited effects on anxiety; therefore, future parent education should incorporate interactive and reassurance-focused approaches. TRIAL REGISTRATION: UMIN-CTR: UMIN000056457.

Humans↗

PubMed2026

Electron shuttles facilitate methane-dependent arsenate reduction in paddy soils.

Methane-dependent arsenate reduction (M-AsR) occurs widely in paddy soils and can substantially enhance arsenic mobilization, posing potential ecological risks. However, the role of electron shuttles in this process remains poorly understood. In this study, we investigated the influence of anthraquinone-2,6-disulfonate (AQDS) on M-AsR in paddy soils. Fourteen-day incubation showed that 1 mmol/L AQDS facilitated 50.88 % of arsenate reduction and 31.31 % of methane oxidation. Quantitative polymerase chain reaction analysis revealed that AQDS significantly increased the abundance of functional genes associated with arsenate reduction (arrA, arsC) and anaerobic methane oxidation (mcrA) (P < 0.05). Microbial community analysis revealed that AQDS addition enriched Cloacibacterium, Sphingorhabdus, and Methylocystis, while decreasing the relative abundance of Methylobacter and Methylomonas. These findings indicate that electron shuttles facilitate M-AsR by modulating functional microbial populations, providing valuable insights into arsenic biogeochemistry and the coupled cycling of methane and arsenic in paddy soils.

Methane↗

PubMed2024

Cryo-electron tomography reveals coupled flavivirus replication, budding and maturation.

Flaviviruses replicate their genomes in replication organelles (ROs) formed as bud-like invaginations on the endoplasmic reticulum (ER) membrane, which also functions as the site for virion assembly. While this localization is well established, it is not known to what extent viral membrane remodeling, genome replication, virion assembly, and maturation are coordinated. Here, we imaged tick-borne flavivirus replication in human cells using cryo-electron tomography. We find that the RO membrane bud is shaped by a combination of a curvature-establishing coat and the pressure from intraluminal template RNA. A protein complex at the RO base extends to an adjacent membrane, where immature virions bud. Naturally occurring furin site variants determine whether virions mature in the immediate vicinity of ROs. We further visualize replication in mouse brain tissue by cryo-electron tomography. Taken together, these findings reveal a close spatial coupling of flavivirus genome replication, budding, and maturation.

Journal Article↗

PubMed2026

Program to Avoid Cerebrovascular Events Through Systematic Electronic Tracking and Tailoring of an Eminent Risk Factor: A Randomized Trial.

BACKGROUND: Individuals residing in the southeastern United States experience disproportionately worse stroke outcomes. Although blood pressure (BP) reduction is among the most effective strategies for improving stroke outcomes, fewer than one third of survivors of stroke achieve BP control within 1 year of the index event. METHODS: The PACESETTER (Program to Avoid Cerebrovascular Events Through Systematic Electronic Tracking and Tailoring of an Eminent Risk Factor) trial enrolled patients with stroke and uncontrolled BP from 3 safety-net health care systems in South Carolina. Patients were randomized 1:1 to the PACESETTER intervention, which included a Bluetooth-enabled electronic pill tray, a BP monitor, and a smartphone application for automated data transmission of medication adherence and BP data to a central server or to usual care. The primary outcome was systolic BP <130 mm Hg at 12 months, analyzed according to the intention-to-treat principle. RESULTS: The trial was stopped early due to low recruitment during the COVID-19 and funding constraints. Between September 2019 and February 2023, 120 participants were randomized to PACESETTER (n=60) or the usual care arm (n=60). At 4 months, systolic BP <130 mm Hg favored the PACESETTER arm (48.8% versus 29.3%, P=0.07), but no significant difference was observed at 12 months (50% versus 47.2%, P=0.82). CONCLUSIONS: Because the trial was terminated prematurely, the effect of the PACESETTER intervention on 12-month BP control after stroke remains uncertain. A trial completed to its full term and sufficiently powered to also evaluate key short-term end points is needed. REGISTRATION: URL: https://www.clinicalstrial.org; Unique Identifier: NCT03401489.

Aged↗

PubMed2026

Genome-wide association study of asthma with high treatment burden and/or worse outcomes defined using electronic healthcare data in UK Biobank.

BACKGROUND: In ∼10% of asthma patients, symptoms remain uncontrolled despite maximal treatment, representing an unmet clinical need. The causal variants, genes and pathways underlying genetic risk factors have not been fully elucidated, and it is unclear whether there are unique genetic risk factors for this asthma subtype. METHODS: We used electronic healthcare records linked to UK Biobank to identify asthma patients with high treatment burden and/or worse outcomes. We performed a genome-wide association study (GWAS) with this case population and healthy controls. We sought replication for associated (p≤5×10-6) signals in four independent studies (12 152 cases and 32 316 controls). Replicated signals were fine-mapped and linked to genes and pathways. RESULTS: In total, 7681 participants met our case definition and showed enrichment for adult-onset asthma, female gender and higher body mass index compared to asthma individuals not meeting case criteria. GWAS with 7681 cases and 38 405 controls revealed 21 reproducible association signals that had previously been associated with asthma, but had a larger effect size in our study. Variant-to-gene mapping highlighted 85 candidate genes, five of which were considered high confidence (BACH2, D2HGDH, IL1RL1, RPS26, SMAD3). CONCLUSION: We present the first use of electronic healthcare records in UK Biobank to identify a subtype of asthma enriched for patients with high treatment burden and/or worse outcomes. Our findings support the role of known asthma genes, highlighting genetic risk variants with stronger effect in these groups of patients. The prioritised genes provide potential therapeutic opportunities for this difficult-to-treat patient population.

Journal Article↗

PubMed2026

Comparison of summative assessments between simulated electronic health records versus traditional paper-based patient cases: A non-inferiority randomized controlled trial.

INTRODUCTION: Electronic health records are fundamental to contemporary pharmacy practice, yet evidence supporting their use in pharmacy education is lacking. This single-center, non-inferiority randomized controlled trial with blinded outcome assessment evaluated whether delivering patient cases via a simulated academic EHR (aEHR) was non-inferior to a traditional paper-based format in student exam performance. METHODS: 53 third-year PharmD students at the University of British Columbia were randomized 1:1 to complete a mock summative examination using either the aEHR or paper-based case delivery, stratified by self-reported EHR comfort level. The primary outcome was mean written exam score (%). Non-inferiority was pre-specified at a margin of 14%. Adjusted linear regression was used for the primary analysis, with a multiple imputation sensitivity analysis. Student perceptions were explored through post-exam focus groups analyzed using inductive thematic analysis. RESULTS: 42 students (21 per group) completed the exam and were included in the primary analysis. Mean scores were 66% (SD 11) in the aEHR group and 68% (SD 10) in the paper group. The adjusted mean difference (paper minus aEHR) was -2.2% (95% CI -9.2% to +4.8%), satisfying non-inferiority but not superiority. Sensitivity analysis (n = 53) yielded consistent results (-2.3%; 95% CI -7.1% to +4.1%). Focus groups revealed initial student anxiety with the aEHR but recognized its alignment with clinical practice. DISCUSSION: These findings support the feasibility of integrating simulated EHRs into summative pharmacy assessments without compromising performance. CONCLUSION: Simulated EHRs are a non-inferior assessment medium compared with paper-based formats and represent a viable step toward technology-driven pharmacy practice environments.

Humans↗

PubMed2026

Associations between smart infusion pump-electronic health record interoperability and healthcare outcomes: A systematic review.

OBJECTIVE: This study synthesized available evidence on the associations between smart infusion pump-electronic health record (EHR) interoperability and healthcare outcomes. METHODS: A systematic review of PubMed, CINAHL, Embase, and Scopus databases identified 901 records, which were imported into Rayyan® for duplicate removal, independent screening by three reviewers, and resolution of discrepancies. Eligible studies were peer-reviewed, data-driven, and reported associations between smart infusion pump-EHR interoperability and healthcare outcomes. Studies focused solely on technical validation or interoperability prototypes were excluded. A backward citation search identified additional studies. Two reviewers independently extracted and cross-validated study characteristics using standardized templates. Methodological quality was assessed with the Joanna Briggs Institute Critical Appraisal Tools. RESULTS: Twenty records of 14 full-text studies and 6 conference proceedings were included. Most records reported positive associations between smart infusion pump-EHR interoperability and outcomes related to safety (e.g., medication administration errors, safety-reported events, pump alerts, and compliance with interoperability and drug library), operational efficiency (e.g., programming and documentation time and technical issues), financial performance (e.g., charges captured, and cost avoided), and user experience domains. Most studies used observational designs, reflecting real-world interoperability implementations, where controlling confounding factors is challenging. Limited reporting of baseline characteristics, pump type, and sample sizes limited comparability across studies. CONCLUSIONS: Smart infusion pump-EHR interoperability was associated with improvements in patient safety, efficiency, charge capture, and user experience, with variable findings across studies. Future research should use rigorous methodologies and standardized measures, examine relationships across outcome domains, assess limitations of pump-EHR interoperability, and evaluate underexplored outcomes, including team communication, cognitive workload, and AI-enabled pumps. IMPLICATIONS FOR CLINICAL PRACTICE: Interoperability should be viewed as a component of a broader sociotechnical system, in which technology, user, workflow, clinical content, and organizational practices collectively determine overall effectiveness.

Humans↗

PubMed2025

Integrating explainable artificial intelligence with multiomics systems biology and electronic health record data mining for personalized drug repurposing in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by region- and patient-specific molecular heterogeneity, which hinders therapeutic design. In this study, we introduce PRISM-ML (PRecision-medicine using Interpretable Systems and Multiomics with Machine Learning), an open-source integrated analysis pipeline that combines interpretable machine learning with systems biology and electronic health records data mining to elucidate the molecular diversity of AD and predict promising drug repurposing opportunities. First, we integrated and harmonized transcriptomic (bulk RNA-seq) and genomic (genome-wide association study) data from 2105 brain samples, each with matched data from the same individual (1363 AD patients, 742 controls; 9 tissues), sourced from three independent studies. Random forest classifiers with SHapley Additive exPlanations identified patient-specific biomarkers; unsupervised clustering resolved 36 molecularly distinct subtissues (defined as clusters of samples within a brain tissue that share a specific expression pattern); and gene-gene coexpression networks prioritized 262 high-centrality bottleneck genes as putative regulators of dysregulated pathways. Next, knowledge graph-based drug repurposing predicted six Food and Drug Administration (FDA)-approved drugs that simultaneously target multiple bottleneck genes and multiple AD-relevant pathways. Notably, in a large US de-identified insurance-claims database (n = 364 733), exposure to promethazine, one of the candidate drugs, was associated with a 57%-62% lower incidence of AD versus an active antihistamine comparator (adjusted hazard ratio 0.38; inverse-probability weighted 0.43; both P < .001), providing real-world support for its repurposing potential. In summary, PRISM-ML, as an explainable multiomics analysis pipeline, is readily transferable to other complex diseases, advancing precision medicine.

Alzheimer Disease↗

PubMed2026

Toward a Better Paradigm for Head and Neck Cancer Treatment Applying AI (HNC-TACTIC): Protocol for an International Cohort Study of Electronic Health Records.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) cause considerable morbidity and mortality. Multimodal treatment strategies can cause significant toxicity, and therapy options are limited for recurrent disease. Immunotherapy has emerged as a promising approach. However, patient response variability underscores the need for better predictive markers. OBJECTIVE: This study aims to use artificial intelligence to develop two predictive models in patients with HNSCC to assess (1) progression or recurrence following primary curative treatment and (2) long-term survival after immunotherapy schemes in recurrent and metastatic disease. This study will also describe the characteristics of patients with early, locally advanced, and recurrent or metastatic cancers. METHODS: This is a retrospective, observational study of data captured in electronic health records (EHRs) from participating hospitals between January 1, 2014, and December 31, 2021. This study's population comprises adults diagnosed with HNSCC at any stage. Study variables, including demographics, comorbidities, clinical variables, treatments, and outcomes, will be extracted using EHRead, a technology that applies natural language processing and machine learning to extract and analyze structured and unstructured clinical information in deidentified EHRs. Predictive models based on dynamic risk stratification for treatment response and progression or recurrence will be developed using multivariable logistic regressions, decision tree classifiers, and random forest approaches. Descriptive and outcome analyses will be shown for different anatomic subsites and stratified by stage and treatment. RESULTS: This study began enrolling sites in July 2021 and is currently ongoing. By December 2025, data from 10 centers has been collected, comprising a total of 151,934,990 EHRs from 2,159,719 patients. CONCLUSIONS: Development of predictive models using artificial intelligence will advance clinical understanding of HNSCC to improve patient outcomes.

Humans↗

PubMed2026

Integrated electronic nose, GC-MS, and metagenomic analyses reveal volatile flavor and microbial community differences in heap-fermented grains of Jiangxiangxing Baijiu across different fermentation degrees.

The fermentation degree of heap-fermented grains in Jiangxiangxing Baijiu production is a critical factor influencing base Baijiu quality. However, conventional assessment methods largely rely on empirical experience and therefore suffer from limited objectivity and accuracy. In this study, integrated volatile profiling and metagenomic approaches were employed to investigate volatile characteristics and microbial functional potential differentiation in fermented grains with different fermentation degrees (under-fermented, normally fermented, and over-fermented). Significant differences in physicochemical properties were observed among fermentation degrees, particularly in acidity and reducing sugar content. Electronic nose analysis revealed distinct sensor response patterns among different fermentation degrees, indicating differences in overall volatile odor fingerprint patterns. A total of 81 volatile compounds were identified by HS-SPME-GC-MS, with aldehydes, ketones, and pyrazines showing pronounced variations among fermentation degrees, and acetaldehyde exhibiting strong discriminatory potential. LEfSe analysis identified 18 microbial taxa as potential biomarkers associated with different fermentation degrees, including Pichia kudriavzevii, Lentibacillus daiqui, and Acetobacter pasteurianus. Correlation analysis revealed significant positive associations between acetaldehyde levels and Acetobacter abundance. Furthermore, KEGG, CAZy, and eggNOG analyses revealed differentiated functional potentials among fermentation degrees, providing insights into the potential metabolic basis associated with flavor differentiation. Overall, these findings highlight that fermentation degree differentiation is closely associated with coordinated changes in physicochemical conditions, microbial communities, and functional potentials, providing ecological insights into flavor differentiation and theoretical support for objective fermentation degree evaluation and quality control of Jiangxiangxing Baijiu production.

Fermentation↗

PubMed2023

Phenotypic presentation of Mendelian disease across the diagnostic trajectory in electronic health records.

PURPOSE: To investigate the phenotypic presentation of Mendelian disease across the diagnostic trajectory in the electronic health record (EHR). METHODS: We applied a conceptual model to delineate the diagnostic trajectory of Mendelian disease to the EHRs of patients affected by 1 of 9 Mendelian diseases. We assessed data availability and phenotype ascertainment across the diagnostic trajectory using phenotype risk scores and validated our findings via chart review of patients with hereditary connective tissue disorders. RESULTS: We identified 896 individuals with genetically confirmed diagnoses, 216 (24%) of whom had fully ascertained diagnostic trajectories. Phenotype risk scores increased following clinical suspicion and diagnosis (P < 1 × 10-4, Wilcoxon rank sum test). We found that of all International Classification of Disease-based phenotypes in the EHR, 66% were recorded after clinical suspicion, and manual chart review yielded consistent results. CONCLUSION: Using a novel conceptual model to study the diagnostic trajectory of genetic disease in the EHR, we demonstrated that phenotype ascertainment is, in large part, driven by the clinical examinations and studies prompted by clinical suspicion of a genetic disease, a process we term diagnostic convergence. Algorithms designed to detect undiagnosed genetic disease should consider censoring EHR data at the first date of clinical suspicion to avoid data leakage.

Humans↗

PubMed2024

Evolving knowledge of red flag clinical features associated with TTR p.(Val142Ile) in a diverse electronic health-record-linked biobank.

PURPOSE: Previous studies have established red flags that raise clinical suspicion for the hereditary form of transthyretin amyloidosis (ATTRv). However, these have not been specifically evaluated for the most common associated variant, TTR p.(Val142Ile). METHODS: Using an ancestrally diverse electronic health-record-linked biobank with exome sequence data from 27,630 unrelated adults, we evaluated 9 ATTRv-related clinical features among TTR p.(Val142Ile)-positive and -negative individuals. RESULTS: Among 337 variant-positive individuals (median age 63, 60% female), 10 (3.0%) were diagnosed with amyloidosis. TTR p.(Val142Ile) was associated with increased odds of cardiomyopathy/heart failure (CM/HF), atrial fibrillation, polyneuropathy, carpal tunnel syndrome, and proteinuria, but only in individuals ≥60 years. These features were evident 1.7 to 7.7 years earlier in variant-positive vs -negative individuals (hazard ratio [HR] 1.37, P = 3.99 × 10-2; HR 1.78, P = 2.52 × 10-3; HR 1.78, P = 1.70 × 10-3; HR 1.81, P = 5.14 × 10-3; HR 1.60, P = 1.94 × 10-2, respectively). By age 50, the cumulative incidence of CM/HF was 3.5-fold higher, and by age 60, the incidences of CM/HF, polyneuropathy, and proteinuria were 2-fold higher in variant-positive individuals. CONCLUSION: This study clarifies red flags that are associated with TTR p.(Val142Ile) in an age-dependent manner. With modifying therapies being available, early diagnosis of ATTRv in variant-positive individuals through the recognition of key clinical features is paramount.

Humans↗