Large-scale Studies Research Articles

Exploring the causal relationship between plasma lipids and varicose veins of lower extremity: A comprehensive two-sample Mendelian randomization study.

Varicose veins of the lower extremities (VVs) is a common chronic vascular disease, with high prevalence rates in some countries; however, their pathogenesis remains unclear. Some studies have identified associations between changes in specific plasma lipid molecules, such as phosphatidylethanolamine (PE), phosphatidylcholine (PC), and sphingomyelin (SM), and the onset of VVs, but due to confounders and reverse causality, the causal relationship remains unclear. Meanwhile, studies on the potential link between other plasma lipids beyond PE, PC, and SM and the risk of VVs in the lower extremities are lacking. This study aimed to explore the potential causal relationship between VVs and plasma lipid levels to provide theoretical insights into the interrelation of plasma lipids and VVs in their occurrence and progression. We conducted a two-sample Mendelian randomization (MR) analysis to assess the potential connection between genetically predicted levels of individual plasma lipids and the risk of developing VVs. We utilized data from a large-scale genome-wide association study involving 7174 Finnish individuals for 179 plasma lipidomes along with VVs genome-wide association study data from 408,455 UK individuals. MR analysis employed methods, such as inverse-variance weighting, weighted median, Bayesian Weighted Mendelian Randomization, and MR-Egger regression. The inverse-variance weighting method was primarily used to assess causality. The validity of the results was demonstrated through sensitivity analysis. In total, 12 lipids were found to have their plasma levels associated with an increased risk of VVs. This includes 3 types of PE, 7 types of PC, and 2 types of phosphatidylinositol. However, no significant causal relationship was found between the plasma levels of 11 types of SM and VVs. These results support the existence of a potential causal relationship between specific types of lipid levels and the risk of VVs, which can provide clues for further studies on biological mechanisms and the exploration of potential therapeutic targets.

Integrating the Energy Performance Gap into Life Cycle Assessments of Building Renovations

The environmental impact of building energy renovation is commonly evaluated through life cycle assessment (LCA). However, existing LCA studies often overlook the energy performance gap—a substantial disparity between calculated and actual energy use—when estimating operational energy use before and after renovation. This paper examines the influence of the energy performance gap on the comparative LCA between unrenovated and renovated buildings. First, a statistical correction model, based on a recent large-scale Flemish study, is developed to correct regulatory calculated energy use for space heating and domestic hot water in a pragmatic way. Subsequently, the model is applied to four single-family dwellings with different energy characteristics that underwent renovation in accordance with Flemish energy regulations. The results show that the anticipated environmental savings over a 60-year study period decrease significantly when the correction model is applied, reducing the estimated savings of 49–80% to 21–49%. Moreover, environmental payback times increase from 2.9–9.1 years to 10.4–22.5 years. Notably, neglecting the energy performance gap in LCAs leads to systematic underestimations of the material use significance. This research underscores the importance of integrating the energy performance gap into LCAs to obtain more accurate estimations of the environmental benefits of energy renovations.

A Novel Interaction between a 23-SNP Genetic Risk Score and Monounsaturated Fatty Acid Intake on HbA1c Levels in Southeast Asian Women.

Metabolic diseases result from interactions between genetic and lifestyle factors. Understanding the combined influences of single-nucleotide polymorphisms (SNPs) and lifestyle is crucial. This study employs genetic risk scores (GRS) to assess SNPs, providing insight beyond single gene/SNP studies by revealing synergistic effects. Here, we aim to investigate the association of a 23-SNP GRS with metabolic disease-related traits (obesity and type 2 diabetes) to understand if these associations are altered by lifestyle/dietary factors. For this study, 106 Minangkabau women were included and underwent physical, anthropometric, biochemical, dietary and genetic evaluations. The interaction of GRS with lifestyle factors was analyzed using linear regression models, adjusting for potential confounders. No statistically significant associations were observed between GRS and metabolic traits; however, this study demonstrates a novel interaction observed between 13-SNP GRS and monounsaturated fatty acid (MUFA) intake, and that it had an effect on HbA1c levels (p = 0.026). Minangkabau women with low MUFA intake (≤7.0 g/day) and >13 risk alleles had significantly higher HbA1c levels (p = 0.010). This finding has implications for public health, suggesting the need for large-scale studies to confirm our results before implementing dietary interventions in the Indonesian population. Identifying genetic influences on dietary response can inform personalized nutrition strategies to reduce the risk of metabolic disease.

Exploring the role of calf circumference as a predisposing factor for intra-hospital delirium: investigating potential gender differences: revealing potential gender variances

BackgroundMalnutrition and sarcopenia significantly increase the risk of intra-hospital delirium, particularly among older adults. Given the potential correlation between calf circumference (CC) and these conditions, CC emerges as a promising predisposing factor for delirium. This study aims to investigate the independent association between delirium and anthropometric parameters, focusing on evaluating CC’s predictive capacity for intra-hospital delirium risk. Additionally, it aims to compare CC’s predictive performance with the widely used Mini Nutritional Assessment (MNA), while also considering potential gender disparities.MethodsThis is a retrospective study which enrolled patients aged ≥ 65 years from September 2021 to March 2022 at the Padova Hospital (Italy). Physical characteristics, intra-hospital delirium incidence, and body composition were assessed. Sarcopenia was diagnosed using the 2019 European Consensus criteria.ResultsAmong 207 subjects, delirium affected 19% of patients. CC showed a significant association with intra-hospital delirium among the analyzed anthropometric parameters. ROC curves indicated that CC’s predictive capacity for delirium onset was comparable to MNA (p = 0.98), particularly in women. In a multivariable logistic regression model, female gender and higher cognitive and CC scores emerged as protective factors against delirium onset, with each unit increase in CC associated with a 24% reduction in the odds of delirium. Conversely, sarcopenia did not significantly influence delirium onset.ConclusionsCC shows promise as a predisposing factor for intra-hospital delirium, similar to MNA, albeit with significant gender differences. CC could serve as a valuable tool for assessing delirium risk among female patients. Further validation of these findings is necessary through larger-scale studies.

Characterization of neural networks involved in transdiagnostic emotion dysregulation from a pilot randomized controlled trial of a neurostimulation-enhanced behavioral intervention

BackgroundEmotional dysregulation is a serious and impairing mental health problem. We examined functional activity and connectivity of neural networks involved in emotional dysregulation at baseline and following a pilot neurostimulation-enhanced cognitive restructuring intervention in a transdiagnostic clinical adult sample. MethodsNeuroimaging data were analyzed from adults who scored 89 or higher on the Difficulties with Emotion Regulation (DERS) scale and had at least one DSM-5 diagnosis. These participants were part of a pilot randomized, double-blind, placebo-controlled trial combining a single therapeutic session of cognitive restructuring with active or sham transcranial magnetic stimulation over the dorsolateral prefrontal cortex. During the study, participants engaged in an emotional regulation task using personalized autobiographical stressors while undergoing functional magnetic resonance imaging (fMRI) before and after the pilot intervention. The fMRI task required participants to either experience the emotions associated with the memories or apply cognitive restructuring strategies to reduce their distress. ResultsWhole-brain fMRI results during regulation at baseline revealed increased activation in the dorsal frontoparietal network but decreased activation in the supplementary motor area, cingulate cortex, insula, and ventrolateral prefrontal cortex (vlPFC). Emotion dysregulation was associated with greater vmPFC and amygdala activation and functional connectivity between these regions. The strength of functional connectivity between the dlPFC and other frontal regions was also a marker of emotional dysregulation. Preliminary findings from a subset of participants who completed the follow-up fMRI scan showed that active neurostimulation improved behavioral indices of emotion regulation more than sham stimulation. A whole-brain generalized psychophysiological interaction analysis indicated that active neurostimulation selectively increased occipital cortex connectivity with both the insula and the dlPFC. Region-of-interest functional connectivity analyses showed that active neurostimulation selectively increased dlPFC connectivity with the insula and orbitofrontal cortex (OFC). ConclusionInsufficient neural specificity during the emotion regulation process and over-involvement of frontal regions may be a marker of emotional dysregulation across disorders. OFC, vlPFC, insula activity, and connectivity are associated with improved emotion regulation in transdiagnostic adults. In this pilot study, active neurostimulation led to neural changes in the emotion regulation network after a single session; however, the intervention findings are preliminary, given the small sample size. These functional network properties can inform future neuroscience-driven interventions and larger-scale studies.

The relationship between salivary cytokines and oral cancer and their diagnostic capability for oral cancer: a systematic review and network meta-analysis

BackgroundOral cancer (OC) is a common malignancy in clinical practice. Saliva testing is a convenient and noninvasive early diagnostic technique for OC. Several salivary cytokines have been identified as potential biomarkers for OC, including IL-8, IL-6, TNF-α, IL-1β, and IL-10. Nonetheless, the optimal cytokine for OC diagnosis remains inconclusive and highly contentious.MethodsPubMed, Embase, Web of Science, and Cochrane Library databases were comprehensively retrieved to collect all case–control studies on OC. A meta-analysis was performed to compare the levels of salivary IL-8, IL-6, IL-10, TNF-α, and IL-1β in OC patients and healthy controls. Network meta-analysis (NMA) was carried out to probe into the accuracy of these salivary cytokines in diagnosing OC.ResultsThis analysis included 40 studies, encompassing 1280 individuals with OC and 1254 healthy controls. Significantly higher levels of salivary IL-8, IL-6, TNF-α, IL-1β, and IL-10 were observed in patients with OC in comparison to healthy controls. The results of NMA showed that TNF-α had the highest diagnostic accuracy for OC, with a sensitivity of 79% and a specificity of 92%, followed by IL-6 (sensitivity: 75%, specificity: 86%) and IL-8 (sensitivity: 80%, specificity: 80%).ConclusionThis study suggests that IL-8, IL-6, IL-10, TNF-α, and IL-1β may be potential diagnostic biomarkers for OC. Among them, TNF-α, IL-6, and IL-8 are highly accurate in the diagnosis of OC. Nevertheless, further studies that eliminate other confounding factors are warranted, and more standardized procedures and large-scale studies are needed to support the clinical use of saliva testing.

Effectiveness of whey protein supplementation on muscle strength and physical performance of older adults: A systematic review and meta-analysis of randomized clinical trials

BackgroundThe efficacy of whey protein supplement (WPS) in improving muscle strength, physical performance, and body composition in older adults has been widely promoted. However, the results of randomized clinical trials in this regard have been inconsistent. We aimed to determine the impact of WPS, compared to a placebo, during or without training on muscle strength, physical function, and body composition in older adults. MethodsRandomized controlled trials were thoroughly searched using PubMed, EMBASE, the Cochrane Library Database, Scopus databases up to June 2024. The analysis focused on key parameters such as handgrip strength (HS), leg press, knee extension, gait speed (GS), 6-minute walking test (6MWT), Timed-up and go test (TUG), lean body mass (LBM), fat mass (FM), and appendicular skeletal muscle mass (ASM). A pooled effect size was calculated using a random-effects model based on standard mean differences (SMD). ResultsThirty studies involving 2105 participants aged 60 and older met the inclusion criteria. The meta-analysis of 26 RCTs showed no significant positive effect of WPS on HS (n= 11, SMD: 0.18; 95% CI: –0.13, 0.49; I2= 69%), 6MWT (n= 5, SMD: -0.08; 95%CI: -0.31, 0.16; I2= 0%), GS test (n=4, SMD: -0.08; 95%CI: -0.43, 0.28; I2= 36%), TUG test (n=9, SMD: 0.0, 95% CI -0.15, 0.14; I2= 0%), LBM (n=11, SMD: 0.02; 95%CI: -0.13, 0.17; I2= 0%), FM (n=15, SMD: -0.04; 95%CI: -0.18, 0.10; I2= 0%). However, ASM significantly improved after WPS consumption but with high heterogeneity (n= 2, SMD: 0.39; 95%CI: 0.28, 0.51; I2= 69%). In interventions incorporating RE, statistically significant positive effects of WPS on lower body strength were observed (n= 11, SMD: 0.25; 95%CI: 0.05, 0.45; I2= 0%). ConclusionThe present meta-analysis indicates that whey protein supplementation (WPS), when combined with resistance training (RT), can enhance lower body strength but does not seem to have a significant beneficial effect on handgrip strength, physical performance, or body composition. Further large-scale studies are necessary to confirm these findings and elucidate the potential benefits of WPS in this population.

Exploring the antibacterial efficacy of Satureja hortensis and Bacillus subtilis extracts in combating Xanthomonas citri

Biofilm plays a critical role in protecting the associated bacterial colonies. Citrus canker caused by Xanthomonas citri, resulted in remarkable yield reduction in citrus orchards. This study aims to evaluate the anti-biofilm properties of S. hortensis and B. subtilis extracts against X. citri. The antibacterial effects of both extracts were evaluated using the disk diffusion method and 96-well microdilution plates. Crystal violet and XTT procedures were employed to assess the inhibition of adhesion and antibiofilm effects of both extracts. The checkboard titration method was applied to determine the synergistic effects of the plant-bacterial extracts. The antibiofilm effects were confirmed by the light microscopy method. The results showed that the antibacterial and antibiofilm properties of both extracts varied. The MIC values of S. hortensis and B. subtilis extracts were 6.25 and 50 mg/ml, respectively. In these concentrations the inhibition of adhesion effects of S. hortensis and B. subtilis were 70% and 80%, whereas their antibiofilm effects were 60% and 72%. S. hortensis and B. subtilis extracts showed 63% and 76% antibiofilm activity, respectively, using the XTT test. The extracts showed synergistic effects, resulting in higher inhibition rates in combinatorial applications. Molecular docking results also confirmed that the secondary metabolites of S. hortensis could interact with different X. citri proteins differentially. Further large-scale studies on combinatorial antibiofilm effects of plant and bacterial extracts against citrus pathogens will provide new opportunities to develop safe and applicable reagents to control these destructive diseases.

Characterization of pre- and on-treatment soluble immune mediators and the tumor microenvironment in NSCLC patients receiving PD-1/L1 inhibitor monotherapy

BackgroundDespite the favorable therapeutic efficacy observed with ICI monotherapy, the majority of non-small cell lung cancer (NSCLC) patients do not respond. Therefore, identifying patients who could optimally benefit from ICI treatment remains a challenge.MethodsAmong 183 patients with advanced or recurrent NSCLC who received ICI monotherapy, we analyzed 110 patients whose pre- and post-treatment plasma samples were available. Seventy-three soluble immune mediators were measured at ICI initiation and 6 weeks later. To identify useful biomarkers, we analyzed the association of pre-treatment levels and on-treatment changes of soluble immune mediators with survival of patients. The associations of pre-treatment or on-treatment biomarkers with irAE development, PD-L1 expression, CD8+ TIL density, and neutrophil to lymphocyte ratio (NLR) were also analyzed.ResultsUnivariate analysis showed that pre-treatment biomarkers included 6 immune mediators, whereas on-treatment biomarkers included 8 immune mediators. Multivariate analysis showed that pre-treatment biomarkers included 4 immune mediators (CCL19, CCL21, CXCL5, CXCL10), whereas on-treatment biomarkers included 5 immune mediators (CCL7, CCL19, CCL23, CCL25, IL-32). IrAE development was associated with on-treatment change in CCL23. PD-L1 expression was associated with the pre-treatment levels of TNFSF13B and the on-treatment change in CCL25. CD8+ TIL density was associated with the pre-treatment CXCL10 level, whereas NLR was correlated with pre-treatment levels of CCL13 and CCL17.ConclusionWe identified several soluble immune mediators as pre-treatment and on-treatment biomarkers of survival in patients with NSCLC treated with ICI monotherapy. Some of these biomarkers were associated with other possible predictors, including irAE development, PD-L1 expression, CD8+ TIL density and NLR. Further large-scale studies are needed to establish biomarkers for patients with NSCLC who received ICI monotherapy.

A case of resected anaplastic carcinoma of the pancreas producing granulocyte-colony stimulating factor with literature review

BackgroundGranulocyte colony-stimulating factor (G-CSF)-producing tumors have been reported in various organs, and the prognosis of patients with G-CSF-producing pancreatic cancers is particularly dismal. In this report, we present a case of G-CSF-producing anaplastic carcinoma of the pancreas (ACP), characterized by early postoperative recurrence and rapid, uncontrolled growth.Case presentationA 74-year-old man presented to our hospital with complaints of abdominal fullness and pain after eating. On admission, it was observed that the peripheral leukocyte counts and serum G-CSF levels were significantly elevated (23,770/µL and 251 pg/mL, respectively). Computed tomography of the abdomen revealed a pancreatic head tumor involving the superior mesenteric vein. Pathologically, ultrasound-guided fine-needle aspiration confirmed ACP. Subsequently, we performed a subtotal stomach-preserving pancreaticoduodenectomy with portal vein reconstruction and partial transverse colon resection. On postoperative day (POD) 7, the leukocyte count decreased from 21,180/μL to 8490/μL; moreover, computed tomography revealed liver metastasis. Therefore, mFOLFILINOX chemotherapy was initiated on POD 30. However, the tumor exhibited rapid progression, and the patient died on POD 45.ConclusionsG-CSF-producing ACP is rare, and the prognosis of patients is extremely poor. Basic research is required to develop effective drugs against G-CSF-producing tumors, and large-scale studies using national databases are needed to develop multidisciplinary treatment methods.

Feasibility Study on the Use of NO2 and PM2.5 Sensors for Exposure Assessment and Indoor Source Apportionment at Fixed Locations.

Recent advances in sensor technology for air pollution monitoring open new possibilities in the field of environmental epidemiology. The low spatial resolution of fixed outdoor measurement stations and modelling uncertainties currently limit the understanding of personal exposure. In this context, air quality sensor systems (AQSSs) offer significant potential to enhance personal exposure assessment. A pilot study was conducted to investigate the feasibility of the NO2 sensor model B43F and the particulate matter (PM) sensor model OPC-R1, both from Alphasense (UK), for use in epidemiological studies. Seven patients with chronic obstructive pulmonary disease (COPD) or asthma had built-for-purpose sensor systems placed inside and outside of their homes at fixed locations for one month. Participants documented their indoor activities, presence in the house, window status, and symptom severity and performed a peak expiratory flow test. The potential inhaled doses of PM2.5 and NO2 were calculated using different data sources such as outdoor data from air quality monitoring stations, indoor data from AQSSs, and generic inhalation rates (IR) or activity-specific IR. Moreover, the relation between indoor and outdoor air quality obtained with AQSSs, an indoor source apportionment study, and an evaluation of the suitability of the AQSS data for studying the relationship between air quality and health were investigated. The results highlight the value of the sensor data and the importance of monitoring indoor air quality and activity patterns to avoid exposure misclassification. The use of AQSSs at fixed locations shows promise for larger-scale and/or long-term epidemiological studies.

A genome-wide association study of occupational creativity and its relations with well-being and career success

Creativity is one defining characteristic of human species. There have been mixed findings on how creativity relates to well-being, and little is known about its relationship with career success. We conduct a large-scale genome-wide association study to examine the genetic architecture of occupational creativity, and its genetic correlations with well-being and career success. The SNP-h2 estimates range from 0.08 (for managerial creativity) to 0.22 (for artistic creativity). We record positive genetic correlations between occupational creativity with autism, and positive traits and well-being variables (e.g., physical height, and low levels of neuroticism, BMI, and non-cancer illness). While creativity share positive genetic overlaps with indicators of high career success (i.e., income, occupational status, and job satisfaction), it also has a positive genetic correlation with age at first birth and a negative genetic correlation with number of children, indicating creativity-related genes may reduce reproductive success.

Tobacco use and khat chewing among adolescents in Yemen: a large-scale school-based cross-sectional study

ObjectiveThe present study sought to assess the prevalence and determinants of tobacco use (cigarette smoking and shisha use) and khat chewing among Yemeni adolescents, and to evaluate their knowledge and attitudes toward these habits.MethodsThis school-based cross-sectional study was conducted among 13 to 19-year-old students attending middle/high schools (both private and public) across five main cities in Yemen. Data were collected using self-administered questionnaires comprising questions/items related to sociodemographic data, cigarette smoking, shisha use, khat chewing, and knowledge on and attitudes toward these habits. Bivariate and multivariate analyses were used to explore the most determinant factors.ResultsA total of 7505 students were recruited from 42 schools across five major cities in Yemen. The prevalence rates of khat chewing, cigarette smoking, and shisha use were 42.4%, 6.8%, and 19.3%, respectively. Compared to females, male subjects reported significantly higher prevalence of khat chewing (51.4% vs. 23.5%, p < 0.001), shisha use (20.3% vs. 17.2%, p < 0.01), and cigarette smoking (8.8% vs. 2.6%, p < 0.001). Male gender, older age, poor knowledge, khat chewing, parents’ low education level, and parents’ and peers’ smoking habits were significant determinants of adolescents’ cigarette smoking status. Private education, male gender, older age, poor knowledge, parents’ low education level, and parents’ and peers’ khat chewing habits were significant determinants of adolescents’ khat chewing status. The participant’s knowledge of and attitudes toward tobacco use and khat chewing were inadequate.ConclusionThe prevalence of khat chewing, shisha use, and to lesser extent cigarette smoking among Yemeni adolescents is high that needs immediate intervention. The results highlight the urgent need to implement prevention strategies to tackle these habits among the youth in Yemen.

The Ubiquitin Tale: Current Strategies and Future Challenges.

Ubiquitin (Ub) is often considered a structurally conserved protein. Ubiquitination plays a prominent role in the regulation of physiological pathways. Since the first mention of Ub in protein degradation pathways, a plethora of nonproteolytic functions of this post-translational modification have been identified and investigated in detail. In addition, several other structurally and functionally related proteins have been identified and investigated for their Ub-like structures and functions. Ubiquitination and Ub-like modifications play vital roles in modulating the pathways involved in crucial biological processes and thus affect the global proteome. In this Review, we provide a snapshot of pathways, substrates, diseases, and novel therapeutic targets that are associated with ubiquitination or Ub-like modifications. In the past few years, a large number of proteomic studies have identified pools of ubiquitinated proteins (ubiquitylomes) involved or induced in healthy or stressed conditions. These comprehensive studies involving identification of new ubiquitination substrates and sites contribute enormously to our understanding of ubiquitination in more depth. However, with the current tools, there are certain limitations that need to be addressed. We review recent technological advancements in ubiquitylomic studies and their limitations and challenges. Overall, large-scale ubiquitylomic studies contribute toward understanding global ubiquitination in the contexts of normal and disease conditions.

Musical training does not enhance neural sound encoding at early stages of the auditory system: A large-scale multisite investigation.

Musical training has been associated with enhanced neural processing of sounds, as measured via the frequency following response (FFR), implying the potential for human subcortical neural plasticity. We conducted a large-scale multi-site preregistered study (n > 260) to replicate and extend the findings underpinning this important relationship. We failed to replicate any of the major findings published previously in smaller studies. Musical training was related neither to enhanced spectral encoding strength of a speech stimulus (/da/) in babble nor to a stronger neural-stimulus correlation. Similarly, the strength of neural tracking of a speech sound with a time-varying pitch was not related to either years of musical training or age of onset of musical training. Our findings provide no evidence for plasticity of early auditory responses based on musical training and exposure.

Predictors of sleepiness in a large-scale epidemiology study ESSE-RF.

To identify predictors of excessive daytime sleepiness we analyzed data from the 'Epidemiology of cardiovascular diseases in regions of Russia (ESSE-RF)' study. Data from participants of the cohort study ESSE-RF (2012-2013), aged 25-64 years, from 13 regions of Russia were analyzed (2012-2013). The participants were interviewed regarding their sleep complaints, including difficulties with initiating and maintaining sleep, sleepiness, and use of sleeping pills. Sleepiness was considered significant if it occurred at least three times a week. The examination encompassed social, demographic, and anthropometric measures, lifestyle factors, self-reported diseases, and laboratory parameters. The final analysis included 13,255 respondents. Frequent (≥3 times/week) sleepiness was reported by 5,8%, and occasional sleepiness (1-2 times/week) by 10.8% of respondents. Multivariate regression analysis identified significant predictors of frequent sleepiness. Sleep complaints (insomnia, sleep apnea, snoring) and frequent use of sleep medication were prominent factors. Additionally, age, female gender, higher education, and retirement status were associated with sleepiness. Beyond demographics and sleep, the analysis revealed predictors: abnormal anxiety levels, low high-density lipoprotein, high salt intake and following medical conditions: arrhythmia, hypertension, myocardial infarction, other heart diseases, and renal disease. This study identified a significant prevalence of EDS in Russians, aligning with global trends. However, findings suggest potential regional variations. Analysis revealed a complex interplay of factors contributing to EDS, highlighting the importance of individualized treatment approaches for improved sleep health.

A Common Longitudinal Intensive Care Unit data Format (CLIF) to enable multi-institutional federated critical illness research.

Critical illness, or acute organ failure requiring life support, threatens over five million American lives annually. Electronic health record (EHR) data are a source of granular information that could generate crucial insights into the nature and optimal treatment of critical illness. However, data management, security, and standardization are barriers to large-scale critical illness EHR studies. A consortium of critical care physicians and data scientists from eight US healthcare systems developed the Common Longitudinal Intensive Care Unit (ICU) data Format (CLIF), an open-source database format that harmonizes a minimum set of ICU Data Elements for use in critical illness research. We created a pipeline to process adult ICU EHR data at each site. After development and iteration, we conducted two proof-of-concept studies with a federated research architecture: 1) an external validation of an in-hospital mortality prediction model for critically ill patients and 2) an assessment of 72-hour temperature trajectories and their association with mechanical ventilation and in-hospital mortality using group-based trajectory models. We converted longitudinal data from 94,356 critically ill patients treated in 2020-2021 (mean age 60.6 years [standard deviation 17.2], 30% Black, 7% Hispanic, 45% female) across 8 health systems and 33 hospitals into the CLIF format, The in-hospital mortality prediction model performed well in the health system where it was derived (0.81 AUC, 0.06 Brier score). Performance across CLIF consortium sites varied (AUCs: 0.74-0.83, Brier scores: 0.06-0.01), and demonstrated some degradation in predictive capability. Temperature trajectories were similar across health systems. Hypothermic and hyperthermic-slow-resolver patients consistently had the highest mortality. CLIF facilitates efficient, rigorous, and reproducible critical care research. Our federated case studies showcase CLIF's potential for disease sub-phenotyping and clinical decision-support evaluation. Future applications include pragmatic EHR-based trials, target trial emulations, foundational multi-modal AI models of critical illness, and real-time critical care quality dashboards.

The association between initial post-resuscitation diastolic blood pressure and survival after pediatric cardiac arrest: a retrospective study

BackgroundLimited research has analyzed the association between diastolic blood pressure (DBP) and survival after pediatric cardiopulmonary resuscitation (CPR). This study aimed to explore the association between post-resuscitation diastolic blood pressure and survival in pediatric patients who underwent CPR.MethodThis retrospective single-center study included pediatric patients admitted to the pediatric intensive care unit of Asan Medical Center between January 2016 to November 2022. Patients undergoing extracorporeal CPR and those with unavailable data were excluded. The primary endpoint was survival to ICU discharge.ResultsA total of 106 patients were included, with 67 (63.2%) achieving survival to ICU discharge. Multivariate logistic regression analysis identified DBP within 1 h after ROSC as the sole significant variable (p = 0.002, aOR, 1.043; 95% CI, 1.016–1.070). Additionally, DBP within 1 h demonstrated an area under the ROC curve of 0.7 (0.592–0.809) for survival to ICU discharge, along with mean blood pressure within the same timeframe.ConclusionOur study highlights the importance of DBP within 1-hour post-ROSC as a significant prognostic factor for survival to ICU discharge. However, further validation through further prospective large-scale studies is warranted to confirm the appropriate post-resuscitation DBP of pediatric patients.

Evaluation of Germicidal UV-C Light for Suppression of Grape Powdery Mildew and Botrytis Bunch Rot in Western Oregon.

Germicidal UV light (UV-C) has been shown to effectively suppress several plant pathogens as well as some arthropod pests. Recent reports describe the efficacy of nighttime applications of UV-C at doses from 100 to 200 J/m2 in vineyards to reduce grape powdery mildew (Erysiphe necator). Our in vitro studies confirmed the efficacy of UV-C to inhibit germination of E. necator and Botrytis cinerea conidia, demonstrated a range of tolerances to UV-C within a collection of E. necator isolates, and showed growth stage-specific effects of UV-C on B. cinerea. Nighttime use of UV-C was evaluated at 48 to 96 J/m2 in small plot trials (<1,000 vines) from 2020 to 2023. Once- or twice-weekly UV-C applications significantly reduced the incidence of foliar powdery mildew compared with non-UV-C-treated controls (P < 0.02). Suppression of powdery mildew on fruit was less consistent, where once or twice weekly UV-C exposure reduced powdery mildew disease severity in 2020 (P = 0.04), 2021 (P = 0.02), and 2023 (P = 0.003) but less so in 2022 (P = 0.07). Bunch rot severity was not significantly reduced with UV-C treatment in any year of the study. Application of UV-C until the onset of fruit color change (veraison) also had a minimal effect on the fruit-soluble solids, pH, anthocyanins, or phenolics in harvested fruit at any UV-C dose or frequency (P > 0.10). Suppression of powdery mildew by nighttime application of UV-C at lower doses in small plots suggests that such treatments merit further evaluation in larger-scale studies in Western Oregon.

Clinical characteristics and outcomes of band keratopathy: a 10-year retrospective analysis

Background: Band keratopathy is a chronic, degenerative corneal disease resulting from gradual calcium deposition in the superficial cornea. Herein, we report the spectrum of causes, treatment outcomes, and recurrence rates of band keratopathy at a tertiary referral center throughout one decade. Methods: This retrospective study included patients with clinical diagnoses of band keratopathy who were treated with combined ethylenediaminetetraacetic acid (EDTA) and superficial keratectomy with or without amniotic membrane transplantation (AMT). Patient medical records were reviewed, and detailed demographic and ophthalmological data, such as baseline and last follow-up best-corrected distance visual acuity (BCDVA), ocular or medical comorbidities, type of intervention, postoperative follow-up duration, relevant complications, and recurrence were recorded. Results: A total of 32 eyes of 29 patients with 3 (10.3%) bilateral and 26 (89.7%) unilateral cases of treatment-requiring bank keratopathy were included. The mean (standard deviation [SD]) (range) age was 39.4 (22.4) (2–74) years, and most patients were female. The most common secondary cause was previous vitreoretinal surgery with silicone oil tamponade (15.6%); however, idiopathic cases were the most common (18.8%). Systemic comorbidities were present in 27.6% of patients, consisting of hypertension, diabetes mellitus, epilepsy, coronary artery disease, Behcet’s disease, and juvenile idiopathic arthritis; however, none of the patients had systemic diseases associated with hypercalcemia. Two of the 3 patients with bilateral involvement had chronic uveitis secondary to systemic rheumatological disease. The mean (SD) follow-up duration was 5.6 (4.0) years, and no serious postoperative complications occurred. The mean (SD) baseline and final BCDVA in logarithm of the minimum angle of resolution (logMAR) were 1.98 (1.0) and 1.7 (1.0), respectively (P &gt; 0.05). Combined EDTA chelation and superficial keratectomy with and without AMT were performed in 12.5% and 87.5% of eyes, respectively. Recurrence was observed in 37.5% of eyes within the mean (SD) (range) follow-up of 9.4 (9.1) (1–32) months. Seven of the 12 eyes with recurrence underwent re-EDTA chelation combined with superficial keratectomy and AMT; however, 5 patients managed conservatively. Conclusions: In this study, band keratopathy requiring intervention more commonly affected female individuals and was unilateral. Most cases were idiopathic. Systemic comorbidities were present in approximately one-third of cases. Managing band keratopathy using a combination of EDTA chelation and superficial keratectomy with or without AMT could be a potential treatment modality. Further large-scale studies are required to provide robust conclusions regarding the efficacy and safety of this management approach.