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Design research on a smart infusion device to reduce medical workload and enhance patient safety
Letter by Tamirisa et al Regarding Article, “Race and Sex Differences in the Association of Bystander CPR for Cardiac Arrest”
Characterization of rice starch changes in saline and alkaline area under different fertilization conditions based on Raman spectral recognition technology
Low Penetrance Sarcomere Variants Contribute to Additive Risk in Hypertrophic Cardiomyopathy
BACKGROUND: Classically, hypertrophic cardiomyopathy (HCM) has been viewed as a single-gene (monogenic) disease caused by pathogenic variants in sarcomere genes. Pathogenic sarcomere variants are individually rare and convey high risk for developing HCM (highly penetrant). Recently, important polygenic contributions have also been characterized. Low penetrance sarcomere variants (LowSVs) at intermediate frequencies and effect sizes have not been systematically investigated. We hypothesize that LowSVs may be common in HCM with substantial influence on disease risk and severity. METHODS: Among all sarcomere variants observed in the Sarcomeric Human Cardiomyopathy Registry (SHaRe), we identified putative LowSVs defined by (1) population frequency greater than expected for highly penetrant (monogenic) HCM (allele frequency >5×10 -5 in the Genome Aggregation Database, gnomAD) and (2) moderate enrichment (>2×) in patients with HCM compared with gnomAD. LowSVs were examined for their association with disease severity and clinical outcomes. Functional effects of selected LowSVs were assessed using induced pluripotent stem cell–derived cardiomyocytes. Association of LowSVs with HCM-adjacent traits in the general population was tested using UK Biobank cardiac magnetic resonance imaging data. RESULTS: Among 6045 patients and 1159 unique variants in sarcomere genes, 12 LowSVs were identified. LowSVs were collectively common in the general population (1:350) and moderately enriched in HCM (aggregate odds ratio, 14.9 [95% CI, 12.5–17.9]). Isolated LowSVs were associated with an older age of HCM diagnosis and fewer adverse events. However, LowSVs in combination with a pathogenic sarcomere variant conferred higher morbidity (eg, composite adverse event hazard ratio, 5.4 [95% CI, 3.0–9.8] versus single pathogenic sarcomere variant, 2.0 [95% CI, 1.8–2.2]; P <0.001). An intermediate functional impact was validated for 2 specific LowSVs— MYBPC3 c.442G>A (partial splice gain) and TNNT2 c.832C>T (intermediate effect on contractile mechanics). Cardiac magnetic resonance imaging analysis of the general population revealed 5 of 12 LowSVs were significantly associated with HCM-adjacent traits without overt HCM. CONCLUSIONS: This study establishes a new class of low penetrance sarcomere variants that are relatively common in the population. When penetrant, isolated LowSVs cause mild HCM. In combination with pathogenic sarcomere variants, LowSVs markedly increase disease severity, supporting a clinically significant additive effect. Last, LowSVs also contribute to age-related remodeling even in the absence of overt HCM.
Micro-elimination initiative for hepatitis C screening: insight into gender gaps and undiagnosed individuals
Letter by Shang et al Regarding Article, “Race and Sex Differences in the Association of Bystander CPR for Cardiac Arrest”
Developing a more accurate population frequency of Marfan syndrome from predicted pathogenic FBN1 variants in the gnomAD cohorts
Bleeding and New Malignancy Diagnoses After Anticoagulation for Atrial Fibrillation: A Population-Based Cohort Study
BACKGROUND: Bleeding after starting anticoagulation for atrial fibrillation (AF) may be the first sign of malignancy, especially in elderly individuals. There are no recommendations to guide investigations for malignancy after new-onset bleeding after anticoagulation for AF. Our objective was to determine the association of bleeding after starting oral anticoagulation for AF with new diagnoses of malignancy in a population-wide sample. METHODS: We conducted a population-based cohort study using linked administrative data sets of people ≥66 years of age who newly initiated warfarin or direct oral anticoagulants after diagnosis with AF between 2008 and 2022. Follow-up was 2 years after starting anticoagulation. We excluded patients with valvular disease, chronic dialysis, venous thromboembolism, previous cancer, or previously documented bleeding. Bleeding was identified from hospital/emergency department discharge records and physician billings, then handled as a time-varying covariate in cause-specific regression models while adjusting for baseline characteristics. The primary outcome was incident malignancy. We also determined the site of origin of the malignancy and the stage at diagnosis if indicated in the Ontario Cancer Registry. Analyses were repeated while limiting the exposure to specific bleeding sites. RESULTS: Among 119 480 people (mean age, 77.4 years; 52% men) who started anticoagulants, 26 037 (21.8%) had documented bleeding, and 5800 (4.9%) were diagnosed with malignancy within the next 2 years. Bleeding was associated with a higher hazard of cancer diagnosis with a hazard ratio (HR) of 4.0 (95% CI, 3.8–4.3). The HRs for any malignancy were 5.0 (95% CI, 4.6–5.5) for gastrointestinal, 5.0 (95% CI, 4.4–5.7) for genitourinary, 4.0 (95% CI, 3.5–4.6) for respiratory, 1.8 (95% CI, 1.4–2.2) for intracranial, and 1.5 (95% CI, 1.2–2.0) for nasopharyngeal bleeds. The HRs were substantially higher for cancers concordant with the bleeding site (gastrointestinal, 15.4; genitourinary, 11.8; respiratory, 10.1). Cancers were diagnosed at an earlier stage after bleeding (27.6% stage 4 after bleeding versus 31.3% without bleeding; P =0.029). CONCLUSIONS: In anticoagulated patients with AF, bleeding was strongly associated with new cancer diagnoses. Antecedent bleeding was associated with cancer diagnosis at an earlier stage. This highlights the importance of timely investigations in patients with bleeding after anticoagulation for AF, rather than attributing bleeding as an expected adverse effect.
Application of rapid evaporative ionization mass spectrometry in preclinical and clinical analyses of steatotic liver tissues and cells
Abstract Rapid evaporative ionization mass spectrometry (REIMS) shows promise as a preparation-free tissue analysis tool with the prospect for real-time diagnostics. Given that hepatic steatosis is characterized by shifts in lipid species and abundance, we selected it as basis for method development, as REIMS specifically measures lipidomic profiles. However, further validation and protocol refinement are necessary to establish its clinical utility. In this study, we applied REIMS to steatotic human liver tissues, focusing on its ability to differentiate varying degrees of steatosis. We established standardized protocols for tissue handling and lipid analysis, which were essential for reliable data interpretation. Notably, our findings revealed that tissue size impacts REIMS sensitivity, with smaller samples yielding lower total ion counts and altered lipid profiles. Through principal component analysis, we identified key lipid classes, namely triacylglycerides, fatty acids, and glycerophospholipids. Despite a missing link between triacylglyceride abundance and degree of steatosis, we successfully identified condition-specific lipid patterns, with ceramides emerging as markers of advanced steatosis. Our study provides a protocol for the measurements of lipid standards showing the detailed degradation of specific lipids using iKnife-coupled REIMS. It highlights the pitfalls and limitations and provides critical recommendations for REIMS use. It also emphasizes the need for standardized biobanking and tissue preparation to ensure accurate lipid profiling, laying the groundwork for future protocol adjustments required for clinical application.
Prognostic Relevance of Type 4a Myocardial Infarction and Periprocedural Myocardial Injury in Patients With Non–ST-Segment–Elevation Myocardial Infarction
BACKGROUND: Periprocedural myocardial injury (PMI) with or without type 4a myocardial infarction (MI) might occur in patients with non–ST-segment–elevation MI (NSTEMI) after percutaneous coronary intervention (PCI). This study investigated the incidence and prognostic relevance of these events, according to current definitions, in patients with NSTEMI undergoing PCI. The best cardiac troponin I (cTnI) threshold of PMI for prognostic stratification is also suggested. METHODS: Consecutive patients with NSTEMI from January 2017 to April 2022 undergoing PCI with stable or falling pre-PCI cTnI levels were enrolled. According to the Fourth Universal Definition of Myocardial Infarction, the study population was stratified into those experiencing (1) PMI with type 4a MI, (2) PMI without type 4a MI, or (3) no PMI. Post-PCI cTnI increase >20% with an absolute postprocedural value of ≥5 times the 99th percentile upper reference limit within 48 hours after PCI was used to define PMI. The primary end point was 1-year all-cause mortality, and the secondary end point consisted of major adverse cardiovascular events at 1 year, including all-cause mortality, nonfatal reinfarction, urgent revascularization, nonfatal ischemic stroke, and hospitalization for heart failure. Internal validation was performed in patients enrolled between May 2022 and April 2023. RESULTS: Among 1412 patients with NSTEMI undergoing PCI with stable or falling cTnI levels at baseline, 240 (17%) experienced PMI with type 4a MI, 288 (20.4%) experienced PMI without type 4a MI, and 884 (62.6%) experienced no PMI. PMI was associated with an increased risk of adverse clinical outcomes, with patients with type 4a MI demonstrating the highest rates of 1-year all-cause mortality and major adverse cardiovascular events. A post-PCI ΔcTnI >20% but ≤40% showed similar outcomes to patients without PMI, whereas >40% was identified as the optimal threshold for prognostically relevant PMI, confirmed in an internal validation cohort of 305 patients. CONCLUSIONS: Periprocedural ischemic events were frequent in patients with NSTEMI undergoing PCI with prognostic implications. A post-PCI ΔcTnI >40%, combined with an absolute postprocedural value of ≥5 times the 99th percentile upper reference limit, was identified as the optimal threshold for diagnosing prognostically relevant PMI. Recognizing these events may improve risk stratification and management of patients with NSTEMI.
Chemical characteristics of groundwater and surface water affected by human activities in the upper Jinzi River Basin, China
Abstract Water resources, as critical ecological and environmental assets, are essential to the social and economic development of countries and regions worldwide. The Jinzi River valley functions as a discharge area for industrial and domestic sewage from mining operations and residential communities along both banks. However, due to human activities, both groundwater and surface water in the region have been contaminated to varying extents. Multiple gold mines are located in the research area. Due to years of unregulated mining, this has had a serious impact on the local ecological environment and water quality. However, research on groundwater and surface water in this region, which are crucial components of the ecological environment, remains limited. This study integrates local socio-economic and hydrogeological conditions, employing methods such as multivariate statistical analysis, the Piper trilinear diagram, the Gibbs model, and ionic ratio relationships to analyze the characteristics and origins of major ions in the region. (1) The primary hydrochemical type of surface water was HCO3-Ca·Na, while groundwater was predominantly of the HCO3-Ca·Mg type. This hydrochemical pattern was consistent across the region, with ion concentrations significantly higher in areas dominated by carbonate rock compared to those with silicate rock. (2) Using principal component analysis, water–rock interaction modeling, and ion source analysis, it was determined that groundwater chemistry was primarily influenced by the weathering of diorite and carbonate rock, along with inputs from domestic and agricultural wastewater. In contrast, surface water chemistry was largely controlled by the weathering of carbonate rocks and the discharge of industrial wastewater. (3) Components such as SO4 2−, NO3 −, Cl−, and total dissolved solids in surface water exhibited a pronounced sensitivity to human activities, with their concentrations significantly exceeding those in groundwater. This indicates that surface water is more heavily impacted by human activities, particularly from industrial, agricultural, and domestic wastewater sources.
Risk of Cancer in Newborns With Congenital Heart Disease and Their Mothers: A Nationwide Cohort Study
Untethered wavelength-selective multi-shape programmable hybrid soft robot
Troponin is associated with mortality and significant coronary artery disease in patients treated for atrial fibrillation in the emergency department
Development of a nomogram model to predict 30-day mortality in ICU cancer patients with acute pulmonary embolism
Deep transfer learning for seismic characterization of strike-slip faults in karstified carbonates from the northern Tarim basin
Molecular, biophysical, and biochemical studies on irradiated Zea mays seeds using various sources of gamma rays for dosimetrical applications
Hyperspectral remote sensing image destriping via spectral-spatial factorization
Integrative spatiotemporal modeling of biomolecular processes: Application to the assembly of the nuclear pore complex
Dynamic processes involving biomolecules are essential for the function of the cell. Here, we introduce an integrative method for computing models of these processes based on multiple heterogeneous sources of information, including time-resolved experimental data and physical models of dynamic processes. First, for each time point, a set of coarse models of compositional and structural heterogeneity is computed (heterogeneity models). Second, for each heterogeneity model, a set of static integrative structure models is computed (a snapshot model). Finally, these snapshot models are selected and connected into a series of trajectories that optimize the likelihood of both the snapshot models and transitions between them (a trajectory model). The method is demonstrated by application to the assembly process of the human nuclear pore complex in the context of the reforming nuclear envelope during mitotic cell division, based on live-cell correlated electron tomography, bulk fluorescence correlation spectroscopy–calibrated quantitative live imaging, and a structural model of the fully assembled nuclear pore complex. Modeling of the assembly process improves the model precision over static integrative structure modeling alone. The method is applicable to a wide range of time-dependent systems in cell biology and is available to the broader scientific community through an implementation in the open source Integrative Modeling Platform (IMP) software.