bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of the pharmacological statin-associated muscle symptoms risk stratification (PSAMS-RS) score using real-world electronic health record data
Authors: Sun Boguang , Yew Pui Ying , Chi Chih-Lin , Song Meijia , Loth Matt , Liang Yue , Zhang Rui , Straka Robert J. 
Published: August 2023

AbstractIntroductionStatin-associated muscle symptoms (SAMS) contribute to the nonadherence to statin therapy. In a previous study, we successfully developed a pharmacological SAMS (PSAMS) phenotyping algorithm that distinguishes objective versus nocebo SAMS using structured and unstructured electronic health records (EHRs) data. Our aim in this paper was to develop a pharmacological SAMS risk stratification (PSAMS-RS) score using these same EHR data.MethodUsing our PSAMS phenotyping algorithm, SAMS cases and controls were identified using University of Minnesota (UMN) Fairview EHR data. The statin user cohort was temporally divided into derivation (1/1/2010 to 12/31/2018) and validation (1/1/2019 to 12/31/2020) cohorts. First, from a feature set of 38 variables, a Least Absolute Shrinkage and Selection Operator (LASSO) regression model was fitted to identify important features for PSAMS cases and their coefficients. A PSAMS-RS score was calculated by multiplying these coefficients by 100 and then adding together for individual integer scores. The clinical utility of PSAMS-RS in stratifying PSAMS risk was assessed by comparing the hazard ratio (HR) between 4th vs 1st score quartile.ResultsPSAMS cases were identified in 1.9% (310/16128) of the derivation and 1.5% (64/4182) of the validation cohort. After fitting LASSO regression, 16 out of 38 clinical features were determined to be significant predictors for PSAMS risk. These factors are male gender, chronic pulmonary disease, neurological disease, tobacco use, renal disease, alcohol use, ACE inhibitors, polypharmacy, cerebrovascular disease, hypothyroidism, lymphoma, peripheral vascular disease, coronary artery disease and concurrent uses of fibrates, beta blockers or ezetimibe. After adjusting for statin intensity, patients in the PSAMS score 4th quartile had an over seven-fold (derivation) (HR, 7.1; 95% CI, 4.03-12.45) and six-fold (validation) (HR, 6.1; 95% CI, 2.15-17.45) higher hazard of developing PSAMS versus those in 1st score quartile.ConclusionThe PSAMS-RS score can be a simple tool to stratify patients’ risk of developing PSAMS after statin initiation which can facilitate clinician-guided preemptive measures that may prevent potential PSAMS-related statin non-adherence.
Dynamic modes of Notch transcription hubs conferring memory and stochastic activation revealed by live imaging the co-activator Mastermind
Authors: deHaro-Arbona F Javier , Roussos Charalambos , Baloul Sarah , Townson Jonathan , Gomez-Lamarca Maria J. , Bray Sarah 
Published: August 2023

SummaryDevelopmental programming involves the accurate conversion of signaling levels and dynamics to transcriptional outputs. The transcriptional relay in the Notch pathway relies on nuclear complexes containing the coactivator Mastermind (Mam). By tracking these complexes in real time, we reveal that they promote formation of a dynamic transcription hub in Notch ON nuclei which concentrates key factors including the Mediator CDK module. The composition of the hub is labile and persists after Notch withdrawal conferring a memory that enables rapid reformation. Surprisingly, only a third of Notch ON hubs progress to a state with nascent transcription, that correlates with Polymerase II and core Mediator recruitment. This probability is increased by a second signal. The discovery that target-gene transcription is probabilistic has far-reaching implications because it implies that stochastic differences in Notch pathway output can arise downstream of receptor activation.
Performance of a large language model (ChatGPT-3.5) for Pooled Cohort Equation estimation of atherosclerotic cardiovascular disease risk
Authors: Marafino Ben J. , Liu Vincent X. 
Published: August 2023

AbstractDespite demonstrated facility for arithmetic and other quantitative tasks, the performance of ChatGPT and other large language models for clinical risk calculation have yet to be assessed. Using synthetic patient data, this preliminary study aimed to assess the calibration, reproducibility, and potential for sociodemographic bias of ChatGPT-derived Pooled Cohort Equation (PCE) scores of atherosclerotic cardiovascular disease risk as compared to true scores. We found that ChatGPT-derived PCE scores, despite being moderately associated with the true PCE scores, displayed poor calibration with respect to true PCE scores, and exhibited instability between repeated rounds of prompting, suggesting lack of reproducibility. Moreover, ChatGPT-derived PCE scores also appeared inappropriately sensitive to contextual indicators of the sociodemographic status of the synthetic patients in this study. Further work is needed to confirm these results, and to assess performance on a wider variety of prompts as well as in other settings beyond cardiovascular disease prevention where accurate risk calculation is also vital to appropriate clinical decision-making.Abstract FigureFigure. Underestimation of true PCE risk estimates (x-axis) by ChatGPT (y-axis) on synthetic patient data.
Individual level analysis of digital proximity tracing for COVID-19 in Belgium highlights major bottlenecks
Authors: Geenen Caspar , Raymenants Joren , Gorissen Sarah , Thibaut Jonathan , McVernon Jodie , Lorent Natalie , André Emmanuel 
Published: August 2023

AbstractTo complement labour-intensive conventional contact tracing, digital proximity tracing was implemented widely during the COVID-19 pandemic. However, the privacy-centred design of the dominant Google-Apple exposure notification framework has hindered assessment of its effectiveness. Between October 2021 and January 2022, we systematically collected app use and notification receipt data within a test and trace programme for university students in Leuven, Belgium. Due to low success rates in each studied step of the digital notification cascade, only 4.3% of exposed contacts (CI: 2.8-6.1%) received such notifications, resulting in 10 times more cases detected through conventional contact tracing. Moreover, the infection risk of digitally traced contacts (5.0%; CI: 3.0-7.7%) was lower than that of conventionally traced non-app users (9.8%; CI: 8.8-10.7%; p=0.002). Contrary to common perception as near instantaneous, there was a 1.2-day delay (CI: 0.6-2.2) between case PCR result and digital contact notifications. These results highlight major limitations of the dominant digital proximity tracing framework.
The whole day matters after stroke: Study protocol for a randomized controlled trial investigating the effect of a ‘sit less, move more, sleep better’ program early after stroke
Authors: Okusanya Deborah , Ezeugwa Joy , Khan Aiza , Buck Brian , Jickling Glen , Ezeugwu Victor 
Published: August 2023

AbstractBackgroundMovement-related behaviours, including prolonged sedentary behaviour, physical inactivity, and sleep disorders, are associated with worse functional outcomes poststroke. Addressing these co-dependent behaviours early after stroke may help to optimize recovery and improve overall quality of life for individuals with stroke.ObjectiveThis study aims to determine the feasibility and effect of a ‘sit less, move more, sleep better’ program early after stroke on functional mobility and global disability outcomes, while also exploring imaging and behavioral markers that may influence walking recovery.MethodsThe study is a single-blind (outcome assessor), single-center, parallel-group, randomized controlled trial. We will enroll 50 patients with acute ischemic stroke within 7 days from symptom onset, aged 18 years or older, and with ongoing walking goals. Demographic and stroke characteristics, including stroke risk factors, neuroimaging, and acute stroke treatments, will be determined and documented. All participants will wear an accelerometer for one week at three different time-points (baseline, 6, and 12 weeks) to assess movement-related behaviours.Following randomization, participants in the intervention arm will receive a ‘sit less, move more, sleep better’ program for up to 1 hour/day, 5 days/week, for 6 weeks to enhance self-efficacy for change. Participants in the control arm will receive usual inpatient and early supported stroke discharge care. The feasibility outcomes will include reach (enrolled/eligible), retention (completed/enrolled), adverse events, and program adherence. Other outcomes at 6 and 12 weeks include the modified Rankin Scale, Timed-Up and Go, movement-related behaviours, walking endurance, gait speed, cognition, stroke severity and quality of life.DiscussionAdopting a whole-day approach to poststroke rehabilitation will provide valuable insights into the relationship between optimizing movement-related behaviours early after stroke and their impact on functional outcomes. Through exploring person-specific behavioural and imaging markers, this study may inform precision rehabilitation strategies, and guide clinical decision making for more tailored interventions.
Preventable Deaths involving Sepsis in England and Wales, 2013-2022: A Systematic Case Series of Coroners’ Reports
Authors: Jindal Jessy , Launer David , France Harrison S , Hey Molly , Song Kaiyang , Portwood Clara , Richards Georgia , Dernie Francesco 
Published: August 2023

AbstractPurposeCoroners’ Prevention of Future Death (PFDs) reports are an under-utilised resource to learn about preventable deaths in England and Wales. We aimed to identify sepsis-related PFDs and explore the causes and concerns in this subset of preventable sepsis deaths.Methods4305 reports were acquired from the Courts and Tribunals Judiciary website between July 2013 and November 2022, which were screened for sepsis. Demographic information, coroners concerns and responses to these reports were extracted and analysed, including a detailed paediatric subgroup analysis.Results265 reports (6% of total PFDs) involved sepsis-related deaths. The most common cause of death in these reports was “sepsis without septic shock” (42%) and the most common site of infection was the respiratory system (18%) followed by gastrointestinal (16%) and skin (13%) infections. Specific pathogens were named in few reports (27%). Many deaths involved multimorbid patients (49%) or those with recent surgery (26%). Coroners named 773 individual concerns, the most frequent were: a failure to keep accurate records or notes (28%), failure in communication or handover (27%) or failure to recognise risk factors or comorbidities (20%). Paediatric cases frequently reported issues with sepsis screening tools (26%). Sepsis PFDs resulted in 421 individual reports being sent, of which 45% received no response. Most organisations who did respond acknowledged concerns and initiated a new change (74%).ConclusionSepsis-related PFDs provide valuable insights into preventable causes of sepsis and identify important sources of improvement in sepsis care. Wider dissemination of findings is vital to learn from these reports.
Projecting Omicron scenarios in the US while tracking population-level immunity
Authors: Bouchnita Anass , Bi Kaiming , Fox Spencer , Meyers Lauren Ancel 
Published: August 2023

AbstractThroughout the COVID-19 pandemic, changes in policy, shifts in behavior, and the emergence of new SARS-CoV-2 variants spurred multiple waves of transmission. Accurate assessments of the changing risks were vital for ensuring adequate healthcare capacity, designing mitigation strategies, and communicating effectively with the public. Here, we introduce a model of COVID-19 transmission and vaccination that provided rapid and reliable projections as the BA.1, BA.4 and BA.5 variants emerged and spread across the US. For example, our three-week ahead national projection of the early 2021 peak in COVID-19 hospitalizations was only one day later and 11.6-13.3% higher than the actual peak, while our projected peak in mortality was two days earlier and 0.22-4.7% higher than reported. We track population-level immunity from prior infections and vaccination in terms of the percent reduction in overall susceptibility relative to a completely naive population. As of October 1, 2022, we estimate that the US population had a 36.52% reduction in overall susceptibility to the BA.4/BA.5 variants, with 61.8%, 15.06%, and 23.54% of immunity attributable to infections, primary series vaccination, and booster vaccination, respectively. We retrospectively projected the potential impact of expanding booster coverage starting on July 15, 2022, and found that a five-fold increase in weekly boosting rates would have resulted in 70% of people over 65 vaccinated by Oct 10, 2022 and averted 25,000 (95% CI: 14,400-35,700) deaths during the BA.4/BA.5 surge. Our model provides coherent variables for tracking population-level immunity in the increasingly complex landscape of variants and vaccines and enables robust simulations of plausible scenarios for the emergence and mitigation of novel COVID variants.
High amino-acid intake in early life is associated with systolic but not diastolic arterial hypertension at 5-years of age in children born very preterm
Authors: Rozé Jean-Christophe , Bacchetta Justine , Lapillonne Alexandre , Boudred Farid , Picaud Jean-Charles , Marchand-Martin Laetitia , Bruel-Tessoulin Alexandra , Haramba Jérome , Biran Valérie , Darmaun Dominique , Ancel Pierre-Yves 
Published: August 2023

ABSTRACTBACKGROUNDThe life course of individuals born very premature is a topic of increasing concern as their neonatal survival has dramatically increased. In a national, prospective, population-based birth cohort, EPIPAGE-2, we observed that amino-acid intakes greater than 3.5 g/kg/day at day 7 after birth were independently associated with higher intelligence quotient at 5 years. As the association between high early amino-acid intake and later HBP in this population is debated, we assessed blood pressure (BP) at 5 years.METHODSThis cohort was initiated in 2011, and approved by ethics committees. Eligible infants were those born between 24 and 29 weeks of gestation and alive on day7 after birth. Infants were distributed in two groups of 717 infants matched on propensity score on whether or not they were exposed to high amino-acid intake (>3.5 g/kg/d at Day7); 455 control term infants were also enrolled. Assessment at 5-year occurred from September 2016 to December 2017. A value>95thpercentile of reference values for age and height defined systolic and/or diastolic HBP.RESULTSBP at five years of age was assessed for 389 and 385 children in exposed and non-exposed groups. Rates (%) of systolic HBP were 18.0% (95%CI, 14.5 to 22.2), 13.3% (95%CI, 10.3 to 17.0), and 8.5% (95%CI, 6.5 to 11.1) in exposed, non-exposed preterm infants, and term infants, respectively; and 9.0% (95%CI, 6.6 to 12.3), 10.2% (95%CI, 7.5 to 13.6), 5.4% (95%CI, 3.8 to 7.6) % for diastolic HBP, in exposed, non-exposed and term-born groups, respectively. Perinatal characteristics of exposed and non-exposed infants were similar, except for nutrition intake at day3 and day7 after birth. Exposure to high early amino-acid intake, and maximal serum creatinine between day3 and day7 were two independent risk factors for systolic HBP (aOR, 1.60 [95% CI, 1.05 to 2.43] and aOR, 1.59 [95% CI, 1.12 to 2.26] by 50 µmol/L, respectively) but not for diastolic HBP (aOR, 0.84 [95% CI, 0.50 to 1.39] and aOR, 1.09 [95% CI, 0.71 to 1.67] by 50 µmol/L, respectively).CONCLUSIONSThese observations confirm the risk for HBP in young children born very preterm. Higher amino-acid intake and creatinine values in the first week of life were associated with childhood systolic HBP. These results suggest that mechanisms to childhood systolic HBP involves neonatal renal challenge by high amino-acid intake or dysfunction.
Genetic variants associated with the risk of stroke in sickle cell disease: a systematic review and meta-analysis
Authors: Kumari Aradhana , Chauhan Ganesh , Chaudhuri Partha Kumar , Prasad Anupa 
Published: August 2023

AbstractBackgroundSickle cell disease (SCD) is the commonest cause of stroke in children. As it is a rare disease, studies investigating the association with complications like stroke in SCD have small sample sizes. Here, we performed a systematic review and meta-analysis of the studies exploring an association of genetic variants with stroke to get a better indication of their association with stroke.MethodsPubMed and Google Scholar were searched to identify studies that had performed an association analysis of genetic variants for the risk of stroke in SCD patients. After screening of eligible studies, summary statistics of association analysis with stroke and other general information were extracted. Meta-analysis was performed using the fixed effect method on the tool METAL and forest plots were plotted using the R program. The random effect model was performed as a sensitivity analysis for loci where significant heterogeneity was observed.Results408 studies were identified using the search term and after screening 39 studies that cumulatively analysed 11,780 SCD patients were included. These 39 studies included a total of 2,401 SCD patients with stroke, predominantly included individuals of African ancestry (N=16). Three of these studies performed whole exome sequencing while 36 performed single nucleotide-based genotyping. Though the studies reported association with 109 loci, meta-analyses could be performed only for 12 loci that had data from two or more studies. After meta-analysis we observed that four loci were significantly associated with risk for stroke: -α3.7kbAlpha-thalassemia deletion(P= 0.00000027), rs489347-TEK(P= 0.00081), rs2238432-ADCY9 (P= 0.00085) and rs11853426-ANXA2(P= 0.0034).ConclusionEthnic representation of regions with a high prevalence of SCD like the Mediterranean basin and India needs to be improved for genetic studies on associated complications like stroke. Larger genome-wide collaborative studies on SCD and associated complications including stroke needs to be performed.
Scanning electron microscopy observations on the surface morphology of placenta villi from HIV-positive women having preterm birth while receiving antiretroviral therapy
Authors: Obimbo Moses M. , Ochieng’ Shem , Gesaka Samwel R. , Ogeng’o Julius 
Published: August 2023

AbstractBackgroundPreterm birth is a significant global issue. Antiretroviral therapy (ART) use and human immunodeficiency virus (HIV) infection have both been linked in recent research as independent risk factors for preterm birth. Although there has been evidence linking preterm delivery to significant pathological alterations in the placenta, it is still unclear how exactly HIV and ART harm the placenta and raise the risk of prematurity. To explain the increased risk of preterm birth (PTB), we set out to describe the surface morphological alterations in placenta villi associated with HIV and ART.Methods and materialsWe collected and processed 160 placentas from 40 HIV-positive women on ART and 40 HIV-negative women who had preterm deliveries, 40 HIV-positive women and 40 HIV - negative women with term delivery in Nairobi, Kenya. The placenta biopsies were harvested, washed in phosphate buffer solution, and processed for scanning electron microscopy. The dried tissue was mounted onto specimen stubs, sputter coated with gold and visualized using Zeiss Merlin FESEM in-lens. Forty representative samples, 10 from each group, were randomly selected and examined by investigators who were blinded to maternal HIV serostatus.ResultsThe average gestational age for preterm and term births was 34 and 39 weeks, respectively. The average age of the mothers of preterm and term babies was 26.8 + 4.6 years and 24.3 + 4.3 years, respectively. The villous core of the placenta from HIV-negative patients was covered with microvilli that varied in size and appearance, and there were hardly any residual red blood cells. Placenta from HIV-positive women with preterm birth had widespread damage with shrunken and wrinkled villi, predominant blunting of the microvilli, with attendant syncytiotrophoblast disruption, and significant erythrocyte adhesion within extensive fibrillar meshwork and on surface of the syncytium.ConclusionOur results show distinctive alterations in the placenta of HIV-positive mothers who gave birth prematurely, which may impair the syncytium’s ability to function normally. Microvilli blunting, syncytial disruptions, and syncytial erythrocyte adhesion might be the symptoms of a deeper biological process. Further work to understand the effect of HIV/ART on the syncytiotrophoblast in relation to prematurity is recommended.
Longitudinal genomic surveillance of multidrug-resistantEscherichia colicarriage in critical care patients
Authors: Chaar Mira El , Khoury Yaralynn , Douglas Gavin M. , Kazzi Samir El , Jisr Tamima , Soussi Shatha , Merhi Georgi , Moghnieh Rima A. , Shapiro B. Jesse 
Published: August 2023

AbstractBackgroundColonization with multidrug resistantE. colistrains causes a substantial health burden in hospitalized patients. We performed a longitudinal genomics study to investigate the colonization of resistantE. colistrains in critically ill patients, and to identify evolutionary changes and strain replacement events within patients.MethodsPatients were admitted to the intensive care unit and haematology wards at a major hospital in Lebanon. Perianal swabs were collected from participants on admission and during hospitalization, which were screened for extended-spectrum beta-lactamases and carbapenem-resistant Enterobacterales. We performed whole-genome sequencing and analysis onE. colistrains isolated from patients at multiple time points.ResultsTheE. coliisolates were genetically diverse, with 13 sequence types (STs) identified among 21 isolates sequenced. Five patients were colonized by ST131 encoding CTX-M-27, a type of beta-lactamase gene not previously been observed in Lebanon. Among the eight patients whose residentE. colistrains were tracked over time, five harbored the sameE. colistrain with relatively few mutations over the 5 to 10 days of hospitalization. The other three patients were colonized by differentE. colistrains over time.ConclusionOur study provides evidence of strain diversity within patients during their hospitalization. While strains varied in their antimicrobial resistance profiles, the number of resistance genes did not increase over time. We also show that ST131 encoding CTX-M-27, which appears to be emerging as a globally important multidrug resistantE. colistrain, is also prevalent among critical care patients and deserves further monitoring.