bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Genetic Architecture of Biological Age in Nine Human Organ Systems
Authors: Wen Junhao , Tian Ye Ella , Skampardoni Ioanna , Yang Zhijian , Cui Yuhan , Anagnostakis Filippos , Mamourian Elizabeth , Zhao Bingxin , Toga Arthur W. , Zaleskey Andrew , Davatzikos Christos 
Published: June 2023

AbstractUnderstanding the genetic basis of biological aging in multi-organ systems is vital for elucidating age-related disease mechanisms and identifying therapeutic interventions. This study characterized the genetic architecture of the biological age gap (BAG) across nine human organ systems in 377,028 individuals of European ancestry from the UK Biobank. We discovered 393 genomic loci-BAG pairs (P-value<5×10-8) linked to the brain, eye, cardiovascular, hepatic, immune, metabolic, musculoskeletal, pulmonary, and renal systems. We observed BAG-organ specificity and inter-organ connections. Genetic variants associated with the nine BAGs are predominantly specific to the respective organ system while exerting pleiotropic effects on traits linked to multiple organ systems. A gene-drug-disease network confirmed the involvement of the metabolic BAG-associated genes in drugs targeting various metabolic disorders. Genetic correlation analyses supported Cheverud’s Conjecture1– the genetic correlation between BAGs mirrors their phenotypic correlation. A causal network revealed potential causal effects linking chronic diseases (e.g., Alzheimer’s disease), body weight, and sleep duration to the BAG of multiple organ systems. Our findings shed light on promising therapeutic interventions to enhance human organ health within a complex multi-organ network, including lifestyle modifications and potential drug repositioning strategies for treating chronic diseases. All results are publicly available athttps://labs-laboratory.com/medicine.
Kinematic signature of high-risk labored breathing revealed by novel signal analysis
Authors: Ashe William B. , McNamara Brendan D. , Patel Swet M. , Shanno Julia N. , Innis Sarah E. , Hochheimer Camille J. , Barros Andrew J. , Williams Ronald D. , Ratcliffe Sarah J. , Moorman J. Randall , Gadrey Shrirang M. 
Published: June 2023

AbstractBreathing patterns (respiratory kinematics) contain vital prognostic information. They report on a dimension of physiology that is not captured by conventional vital signs. But for an informative physiomarker to become clinically valuable, it must be measureable with ease, accuracy, and reproducibility. We sought to enable the quantitative characterization of respiratory kinematics at the bedside. Using inertial sensors, we analyzed upper rib, lower rib, and abdominal motion of 108 patients with respiratory symptoms during a hospital encounter (582 two-minute recordings). We measured the average respiratory rate and 33 other signal characteristics that had an explainable correspondence with clinically significant breathing patterns. K-means clustering revealed that the respiratory kinematic information was optimally represented by adding 3 novel measures to the average respiratory rate. We selected measures representing respiratory rate variability, respiratory alternans (rib-predominant breaths alternating with abdomen-predominant ones), and recruitment of accessory muscles (increased upper rib excursion). Latent profile analysis of these measures revealed a phenotype consistent with labored breathing. Poisson regression showed that the rate at which a patient’s recordings exhibited the labored breathing phenotype was significantly associated (p<0.01) with the severity of illness (discharge home v/s acute-care hospitalization v/s critical-care hospitalization). Notably, labored breathing was frequently detectable (21%) when the respiratory rate was normal, and it improved discrimination for critical illness. These findings validate the feasibility of respiratory kinematic phenotyping in routine healthcare settings, and demonstrate its clinical value. Further research into respiratory kinematic characteristics may reveal novel pathophysiologic mechanisms, advance the efficacy of predictive analytics, and enhance patient safety.
Long-term Air Pollution Exposure are Associated with Higher Incidence of ST-elevation Myocardial Infarction and In-hospital Cardiogenic Shock
Authors: Cha Jinah , Choi Se Yeon , Rha Seung-Woon , Choi Byoung Geol , Byun Jae Kyeong , Hyun Sujin , Lee Min Woo , Kang Jaeho , Chu Wonsang , Park Soohyung , Park Eun Jin , Kang Dong Oh , Choi Cheol Ung , Kim Suhng Wook , Jeong Myung ho ,   the other Korea Acute Myocardial Infarction Registry (KAMIR) investigators
Published: June 2023

AbstractBackgroundPrevious studies have reported the association between myocardial infarction (MI) and air pollution (AP). However, limited information is available regarding the long-term effects of AP on the relative incidence rates of ST-elevation MI (STEMI) and Non-ST-elevation MI (NSTEMI).MethodsStudy subjects were enrolled from the Korea Acute MI registry (KAMIR) and KAMIR-National Institutes of Health (NIH). A total of 45,619 eligible patients with AMI were enrolled between January 2006 and December 2015. We investigated the association between long-term exposure to AP and compared the incidence of STEMI with those of NSTEMI. Mixed-effect regression models were used to examine the association between the annual average ambient AP before MI onset and the incidence of STEMI compared with that of NSTEMI, and to evaluate the association of AP with the incidence of in-hospital cardiogenic shock.ResultsAfter mixed-effect regression model analysis, each 1 μg/m3increase in particulate matter (PM) 10 µm or less in diameter (PM10) was associated with increased incidence of STEMI compared with NSTEMI (odds ratio [OR]:1.009, 95% Confidence Interval [CI]: 1.002–1.016; p = 0.012). For in-hospital cardiogenic shock complication, each 1 μg/m3increase in PM10and 1 part per billion increase in SO2were associated with increased risk, PM10(OR:1.033, 95% CI, 1.018–1.050; p < 0.001), SO2(OR:1.104, 95% CI, 1.006–1.212; p = 0.037), respectively.ConclusionA high concentration of air pollutants, particularly PM10,was an environmental risk factor for an increase incidence of development of STEMI. PM10and SO2were found to be risk factors for in-hospital cardiogenic shock complications. Policy-level strategies and clinical efforts to reduce AP exposure are necessary to prevent the incidence of STEMI and severe cardiovascular complications.
Late presenter thrombolysis for ischemic stroke between 4.5-24 hours after last known well: a retrospective cohort study
Authors: Leung Lester Y. , Zebelean Devin , Melkumova Emiliya , Skeels Katelyn , Madan Neel , Thaler David E. 
Published: June 2023

BackgroundTwo RCTs demonstrated efficacy and safety of IV alteplase for patients with acute ischemic stroke (AIS) who awaken with symptoms or with last known well (LKW) more than 4.5 hours prior to arrival. However, real world experience using CT perfusion (CTP) or DWI-MRI for patient selection in the U.S. is limited. We developed the Tufts Late Presenter Thrombolysis (LPT) protocol to offer alteplase to patients with wakeup stroke, known LKW more than 4.5 hours, or unknown LKW likely more than 4.5 hours and less than 24 hours, using CTP or DWI-MRI to aid patient selection.MethodsWe reviewed ED stroke codes from our Comprehensive Stroke Center between 1/1/20-12/31/22 to identify patients treated with alteplase. Data were collected on demographics, comorbidities, LKW-to-treatment time (LTT), imaging modality, imaging findings, NIHSS, vessel occlusions, endovascular therapy (EVT), symptomatic ICH, and 90 days mRS. Outcomes for comparative analyses included process times (door to needle, door to CT) and clinical outcomes (90 day mRS, symptomatic ICH).ResultsForty-three of 118 patients (36%) presenting with AIS and treated with thrombolysis were treated between 4.5-24 hours after LKW. Patients treated in the 4.5 hour window and the later window had similar demographics, comorbidities, NIHSS, and EVT rates. CTP was used in the majority of LPT cases. The median penumbra was 45.04 mL (11.55-83.21), and the median core infarct was 5.92 mL (1.89-16.7). Symptomatic intracranial hemorrhage occurred in one LPT case (2.3%). Favorable mRS (0-1) was achieved by 36% of LPT patients with documented 90 day mRS.ConclusionsA pragmatic protocol offering thrombolysis to late presenters may be safe and achieve favorable outcomes.
Echocardiographic Evaluation of Spironolactone on Myocardial Remodeling in Atrial Fibrillation with Preserved Ejection Fraction: the INSPIRE-AF randomized controlled trial
Authors: Rujic Dragana , Schou Morten , Madsen Per Lav , Egstrup Kenneth 
Published: June 2023

AbstractBackgroundBy means of echocardiographic assessment and deformation analysis we sought to evaluate the effect of spironolactone versus placebo in addition to standard treatment in patients with paroxysmal or persistent atrial fibrillation (AF) and preserved ejection fraction regarding the performance of the left atrium (LA) and the left ventricle (LV), and quality of life (QOL).MethodsPresent double-blind, placebo-controlled study enrolled 125 patients with a history of paroxysmal (n=58) and persistent (n=67) non-valvular AF and LVEF ≥45% that were randomized to spironolactone 25 mg (n=63) or placebo (n=62) once daily in addition to optimal standard treatment. Comprehensive echocardiography and QOL were obtained at inclusion and after 12 months. The primary outcome was 12-month change in LA reservoir function as assessed by peak atrial longitudinal strain (PALS) and peak strain rate (SR-s). Secondary outcomes included LA phasic volumes, global longitudinal strain of left ventricle (GLS), E/e’ ratio, QOL, and recurrent documented episodes of AF.ResultsSpironolactone improved the LA reservoir function documented by PALS and SR-s (P =0.03 and P =0.02 for adjusted treatment effect, respectively) but only when adjusting for the parallel changes in blood pressure. Blood pressure significantly reduced in the spironolactone-treated subjects and affected primary outcomes, but not diastolic indices of LV. Transmitral E velocity and E/e’ ratio reduced significantly by spironolactone (P=0.009 for adjusted treatment effect). No differences in secondary outcome parameters were found across treatment groups including volumes, LA geometry, GLS, total number AF recurrences, time-to-first AF recurrence or QOL.ConclusionSpironolactone improved left atrial reservoir function by lowering blood pressure and decrease E/e’ ratio but did not affect left atrial volumes or geometry, quality of life or recurrent episodes of atrial fibrillation.Trial registration:ClinicalTrials.org identifierNCT02764619and EudraCT identifier 2013-000797-30.
Exploring patient-, provider-, and health facility-level determinants of blood pressure among patients with hypertension: A multicenter study in Ghana
Authors: Byiringiro Samuel , Hinneh Thomas , Commodore-Mensah Yvonne , Masteller Jill , Sarfo Fred Stephen , Perrin Nancy , Assibey Shadrack , Himmelfarb Cheryl R. 
Published: June 2023

AbstractOptimal blood pressure (BP) control is essential in averting cardiovascular disease and associated complications. Multi-level factors influence the achievement of BP targets in hypertension management. We explored patient-, provider-, and health facility-level factors of systolic and diastolic BP and controlled BP status among patients with hypertension in Ghana, where the burden of hypertension and cardiovascular disease is rising. Using a cross-sectional design, we recruited 15 health facilities, and from each facility, four healthcare professionals who managed patients with hypertension and 15 patients diagnosed with hypertension. The primary outcome of interest was systolic and diastolic BP; the secondary outcome was BP control (<140/90 mmHg) in compliance with Ghana’s national standard treatment guidelines. We used mixed-effects regression models to explore the patient- and facility-level predictors of the outcomes. From the 15 health facilities, we recruited 67 healthcare providers with a mean (SD) age of 32 (7) and 224 patients with a mean (SD) age of 60.5 (12.7). Most (182 [81%]) of the patient participants were female, and almost half (109 [49%]) had controlled BP. At the patient level, secondary school education (Coeff.:-7.69, 95% CI: -15.13, -0.26) was associated with lower systolic BP than a lower level of education; and traveling for 30 minutes to 1 hour to the health facility was associated with higher diastolic BP (Coeff.:3.75, 95% CI: 0.12, 7.38) and lower odds of BP control (OR: 0.51, 95% CI: 0.28, 0.92) than traveling less than 30 minutes. Receiving care at government health facilities was associated with less systolic BP (Coeff.: - 19.4; 95% CI: -33.58, -5.22) than private health facilities. A higher patient-to-physician or physician assistant ratio was associated with more elevated systolic BP (Coeff.: 23.06, 95% CI: 10.06, 36.05) and lower odds of controlled BP (OR: 0.18, 95% CI: 0.05, 0.74). Further research is warranted to identify effective strategies to address the multi-level factors influencing hypertension control and to mitigate the rising burden of hypertension in Ghana.
Assessment of relationship between Google Trend search data on clinical symptoms and cases reported during the first wave of COVID-19 outbreak in India
Authors: Vavilala Hariprasad , Mopuri Rajasekhar , Mutheneni Srinivasa Rao 
Published: June 2023

AbstractInfodemiology and infoveillance approaches have been extensively used in recent years to support traditional epidemiology and disease surveillance. Hence, the present study aimed to explore the association between Google Trends (GTs) search of clinical symptoms and cases reported during the first wave of COVID-19. The GT data from January 30, 2020, to September 30, 2020, and daily COVID-19 cases in India and a few selected states were collected from the Ministry of Health and Family Welfare, Government of India. Correlation analysis was performed between the GT index values and the number of confirmed cases. Followed by, the COVID-19 cases were predicted using Bayesian regression and classical linear regression models. A strong association was observed between the search index of clinical symptoms and reported COVID-19 cases (cold: R=0.41, headache: R=0.46, fever: R=0.66, loss of taste: R=0.78, loss of smell R=0.86) across India. Similarly, lagged correlations were also observed (loss of smell, loss of taste, loss of taste and loss of smell, fever and headache show 3, 9, 1, 9, and 13 days lag periods respectively). Besides this, the Bayesian regression model was outperformed (MAE: 0.331164, RMSE: 0.411087) for predicting the COVID-19 cases in India and regionally than the frequentist linear regression (MAE: 0.33134, RMSE: 0.411316). The study helps health authorities better prepare and planning of health care facility timely to avoid adverse impacts.
Naked-Eye Detection of LAMP-Produced Nucleic Acids in Saliva using Chitosan-capped AuNPs in a Single-Tube Assay
Authors: Grammatikos Stylianos , Svoliantopoulos Ioannis , Gizeli Electra 
Published: June 2023

AbstractLoop-mediated isothermal amplification (LAMP) is a low-technology molecular assay highly adaptable to point-of-care (POC) applications. However, achieving sensitive naked-eye detection of the amplified target in a crude sample is challenging. Herein, we report a simple, yet highly efficient and sensitive methodology for the colorimetric visualization of a single target copy in saliva, using chitosan-capped gold nanoparticles (Chit-AuNPs) synthesized via a green chemistry approach. The presence or absence of free Chit in the Chit-AuNPs solution was shown to affect LAMP colorimetric detection oppositely: the observed stabilization in the negative samples and aggregation in the positive samples in the presence of free Chit was reversed in the case of neat Chit-AuNPs. The mechanism of the two assays was investigated and attributed to electrostatic and depletion effects exerted between the Chit-AuNPs, free Chit and the solution components. The developed contamination-free, one-tube assay successfully amplified and detected down to 1-5 cfu ofSalmonellaand 10 copies of SARS-CoV-2 per reaction (25 μL) in the presence of 20% saliva, making the method suitable for POC applications. Compared to the commonly used pH sensitive dyes, Chit-AuNPs are shown to have an enhanced sensitivity toward the naked-eye colorimetric observation owing to the direct detection of DNA amplicons. Thus, this is a simple, highly sensitive, fast and versatile naked-eye detection methodology that could be coupled to any LAMP or RT-LAMP assay, avoiding the need of using complicated sample pretreatments and/or AuNPs long and laborious functionalization processes.Abstract Figure
SARS-CoV-2 seroprevalence in pregnant women during the first three COVID-19 waves in The Gambia
Authors: Janha Ramatoulie E. , Bah Alasana , Jah Hawanatu , Touray Fatima , Idris Yahaya , Keita Saikou , Gaye Yassin , Jallow Samba , Faye-Joof Tisbeh , Njie Baboucarr , Craik Rachel , Mohammed Nuredin I. , von Dadelszen Peter , D’Alessandro Umberto , Roca Anna ,   the PRECISE Network
Published: June 2023

AbstractObjectivesSARS-CoV-2 transmission in Sub-Saharan Africa has probably been underestimated. Population-based seroprevalence studies are needed to determine the extent of transmission in the continent.MethodsBlood samples from a cohort of Gambian pregnant women were tested for SARS-CoV-2 total IgM/IgG before (Pre-pandemic1:October-December 2019 andPre-pandemic2:February-June 2020) and during the pandemic (Post-wave1: October-December 2020,Post-wave2:May-June 2021; andPost-wave3: October-December 2021). Samples positive for total SARS-CoV-2 IgM/IgG were tested for protein-specific antibodies.ResultsSARS-CoV-2 total IgM/IgG seroprevalence was 0.9% 95%CI (0.2, 4.9) inPre-pandemic1; 4.1% (1.4, 11.4) inPre-pandemic2; 31.1% (25.2, 37.7) inPost-wave1; 62.5% (55.8, 68.8) inPost-wave2and 90.0% (85.1, 93.5) inPost-wave3.S-protein IgG and NCP-protein IgG seroprevalence also increased at eachPost-waveperiod. Although S-protein IgG and NCP-protein IgG seroprevalence was similar atPost-wave1, S-protein IgG seroprevalence was higher atPost-wave2andPost-wave3, [prevalence difference (PD) 13.5 (0.1, 26.8) and prevalence ratio (PR) 1.5 (1.0, 2.3) inPost-wave2; and 22.9 (9.2, 36.6) and 1.4 (1.1, 1.8) inPost-wave3respectively, p<0.001].ConclusionSARS-CoV-2 transmission in The Gambia during the first three COVID-19 waves was high, differing significantly from official numbers of COVID-19 cases reported. Our findings are important for policy makers in managing the near-endemic COVID-19.HighlightsHigh specificity of the IgM/IgG SARS-CoV-2 test using samples collected prepandemicVery high (>90%) SARS-CoV-2 seroprevalence after third COVID-19 wave in The GambiaHigh SARS-CoV-2 transmission contrasts with low number of COVID-19 reported cases
Trends in medication use after the onset of the COVID-19 pandemic in the Republic of Ireland: an interrupted time series study
Authors: Mattsson Molly , Hong Jung Ah , Frazer John Scott , Frazer Glenn Ross , Moriarty Frank 
Published: June 2023

AbstractThe COVID-19 pandemic had a substantial impact on healthcare delivery, particularly in general practice. This study aimed to evaluate how dispensing of medications in primary care in Ireland changed following the COVID-19 pandemic’s onset compared to expected trends. This interrupted time series study used data on medications prescribed in general practice 2016-2022 to patient eligible for state health cover, approximately one third of the population. Dispensing volumes for all therapeutic subgroups (ATC2 codes) and commonly dispensed medications were summarised. Pre-pandemic data was used to forecast expected trends (with 99% prediction intervals) using the Holt-Winters method, and these were compared to observed dispensing from March 2020 onwards. Most (31/77) therapeutic subgroups had dispensing significantly different from forecast in March 2020. Drugs for obstructive airway disease had the largest difference, with dispensing 26.2% (99%CI 19.5%-33.6%) higher than forecasted. Only two subgroups were significantly lower than forecasted, other gynaecologicals (17.7% lower, 99%CI 6.3%-26.6%) and dressings (11.6%, 99%CI 9.4%-41.6%). Dispensing of amoxicillin products and oral prednisolone were lower than forecasted in the months following the pandemic’s onset, particularly during winter 2020/2021. There was a spike in dispensing for many long-term medications in March 2020, while pandemic restrictions likely contributed to reductions for other medications.
Establishing Fully-Automated Fundus-Controlled Dark Adaptometry: A Validation and Retest-Reliability Study
Authors: Oertli Jeannine , Pfau Kristina , Scholl Hendrik P.N. , Jeffrey Brett G. , Pfau Maximilian 
Published: June 2023

ABSTRACTPurposeTo establish and validate a novel fundus-controlled dark-adaptometry method.MethodsWe developed a custom dark-adaptometry software for the S-MAIA device using the open perimetry interface. In the validation-substudy, participants underwent dark-adaptometry testing with a comparator device (MonCvONE, 59% rhodopsin bleach, cyan and red stimuli centered at 2°, 4°, and 6° eccentricity). Following a brief break (approx. 5 min), the participants were bleached again and underwent dark-adaptometry testing with the S-MAIA device (same loci). In the retest reliability-substudy, participants were tested twice with the S-MAIA device (same loci as above).Nonlinear curve fitting was applied to extract dark-adaptation curve parameters. Validity and repeatability were summarized in terms of the mean bias and 95% limits of agreement (LoAs).ResultsIn the validation-substudy (N=20 participants, median age [IQR] 31.5 years [25.8, 62.0]), measures of rod-mediated dark-adaptation showed little to no between method differences for the cone-rod-break-time (bias [95% CI] of +0.09 min [-0.5, 0.67]), rod-intercept-time (+0.42 min [-0.51, 1.35]), and S2 slope (-0.03 LogUnits/min [-0.04, -0.02]).In the retest reliability-substudy (N=10 participants, 32.0 years [27.0, 57.5]), the corresponding LoAs were (cone-rod-break-time) -3.01 to 2.02 min, (rod-intercept-time) -3.95 to 2.94min, and (S2 slope) -0.09 to 0.07 LogUnits/min. The LoAs for the steady-state cone and rod thresholds were -0.27 to 0.31 LogUnits and -0.32 to 0.27 LogUnits.ConclusionsThe devised fundus-controlled dark-adaptometry method yields valid and reliable results. Fundus-controlled dark-adaptometry solves the critical need for localized testing of the visual cycle in eyes with unstable fixation (e.g., in the setting of subretinal gene therapy).