bluuebunny/crossref_metadata_2025_split huggingface dataset:
Joint Association of Albuminuria and Left Ventricular Hypertrophy with Incident Heart Failure in High-Risk Adults with Hypertension: a SPRINT substudy
Authors: Ahmad Muhammad Imtiaz , Kazibwe Richard , Soliman Mai Z. , Singh Sanjay , Chen Lin Y. , Soliman Elsayed Z. 
Published: July 2023

AbstractBackgroundAlbuminuria and left ventricular hypertrophy (LVH) are independent predictors of heart failure (HF), however their combined effect on risk of HF has not been explored previously.ObjectivesTo examine the joint associations of albuminuria and electrocardiographic (ECG) LVH with incident acute decompensated HF (ADHF), and whether albuminuria/LVH combinations modified the effects of blood pressure control strategy in reducing the risk of ADHF.Methods8,511 participants from the SPRINT (Systolic Blood Pressure Intervention Trial) were included. ECG-LVH was present if any of the following criteria: Cornell voltage, Cornell voltage product, or Sokolow Lyon were present. Albuminuria was defined as urine albumin-creatinine ratio (UACR) ≥30 mg/g. ADHF was defined as hospitalization or emergency visit for ADHF. Cox proportional hazard models were used to examine the association of neither LVH, nor albuminuria (reference), either LVH or albuminuria, and both (LVH + albuminuria) with incident ADHF.ResultsOver a median follow-up of 3.2 years, 182 cases of ADHF occurred. In adjusted models, concomitant albuminuria and LVH were associated with higher risk of ADHF than either albuminuria or LVH in isolation (HR (95% CI): 4.95 (3.22-7.62), 2.04 (1.39-3.00), and 1.47 (0.93-2.32), respectively (additive interactionp=0.01). The effect of intensive blood pressure in decreasing ADHF attenuated among participants with co-existing albuminuria and LVH without any interaction between treatment group assignment and albuminuria/LVH categories (interaction p-value= 0.26).ConclusionsAlbuminuria and LVH are additive predictors of ADHF. The effect of intensive blood pressure control in decreasing ADHF risk did not vary significantly across albuminuria/LVH combinations.URL:https://www.clinicaltrials.gov; Unique identifier:NCT01206062
Coronary Assessment in Heart Failure within a Safety-Net Setting: Disparities and Outcomes
Authors: Durstenfeld Matthew S. , Thakkar Anjali , Ma Yifei , Zier Lucas S. , Davis Jonathan D. , Hsue Priscilla Y. 
Published: July 2023

AbstractBackgroundThough ischemic cardiomyopathy is the leading cause of heart failure (HF), most patients do not undergo coronary assessment after heart failure diagnosis. In a safety-net population, referral patterns have not been studied, and it is unknown whether coronary assessment is associated with improved HF outcomes.MethodsUsing an electronic health record cohort of all individuals with HF within San Francisco Health Network from 2001-2019, we identified factors associated with completion of coronary assessment (invasive coronary angiography, nuclear stress, or coronary computed tomographic angiography). Then we emulated a randomized clinical trial of elective coronary assessment with outcomes of all-cause mortality and a composite outcome of mortality and emergent angiography. We used propensity scores to account for differences between groups. We used national death records to improve ascertainment of mortality.ResultsAmong 14,829 individuals with HF (median 62 years old, 5,855 [40%] women), 3,987 (26.9%) ever completed coronary assessment, with 2,467 (18.5%) assessed out of 13,301 with unknown CAD status at HF diagnosis. Women and older individuals were less likely to complete coronary assessment, with differences by race/ethnicity, medical history, substance use, housing, and echocardiographic findings. Among 5,972 eligible for inclusion in the “target trial,” 627 underwent early elective coronary assessment and 5,345 did not. Coronary assessment was associated with lower mortality (HR 0.84; 95% CI 0.72-0.97; p=0.025), reduced risk of the composite outcome, higher rates of revascularization, and higher use of medical therapy.ConclusionsIn a safety-net population, disparities in coronary assessment after HF diagnosis are not fully explained by CAD risk factors. Our target trial emulation suggests coronary assessment is associated with improved HF outcomes possibly related to higher rates of revascularization and GDMT use, but with low certainty that this is finding is not attributable to unmeasured confounding.Abstract FigureGraphical Abstract:
REDUCING DOOR‐TO‐BALLOON TIME USING EMS INITIATED APP BASED COMMUNICATION
Authors: Abrahim Christian , Capatina Alina , Kalyan‐Sundaram Arvind , Lotfi Amir 
Published: July 2023

AbstractBackgroundReducing door-to-balloon (D2B) time for ST-Segment Elevation Myocardial Infarctions (STEMI) has been shown to be effective in improving outcomes. Delays still occur due to various factors such as time to lab activation and diagnostic clarification in equivocal cases. We propose that early communication through a mobile application between Emergency Medical Services (EMS) and in-hospital providers can reduce EMS-to-balloon time and D2B time.MethodsWe implemented the General Devices Company, Inc. e-BridgeTM mobile application for EMS providers. The app allowed real-time communication and data transmission between EMS providers and the cardiac catheterization lab and emergency department staff. A single-center, retrospective observational study was conducted on 795 STEMI activations undergoing emergent coronary angiography between January 2017 and July 2020. After exclusions, sample size was determined to be 428. The implementation of the app occurred on May 14th, 2019, and EMS transmissions were utilized in 132 patient cases during the study period.ResultsThe implementation of the application resulted in a significant reduction in D2B time by 7.2 minutes (61.2 minutes vs. 68.36 minutes, p=0.005, CI -12.2 to -2.14) and ED board time by 4.41 minutes (29.38 minutes vs. 24.98 minutes, p=0.01, CI -7.8 to -1). There was a trend towards a reduction in First Medical Contact to balloon time, although it was not statistically significant. Further analysis revealed that the application did not significantly reduce D2B time or First Medical Contact to balloon time during the day shift but had a significant improvement in these metrics during the night shift.ConclusionThe implementation of app-based communication between EMS providers and in-hospital providers using GPS tracking resulted in statistically significant reductions in First Medical Contact to balloon time and D2B time at our institution. This approach holds promise in improving the timely management of STEMI patients, particularly during the night shift.
Dexmedetomidine decreases cerebral hyperperfusion incidence following carotid stenting: A randomized, double-blind trial
Authors: Chang Enqiang , Wu Lingzhi , Li Xinyi , Zhou Jinpeng , Zhi Hui , Sun Min , Chen Guanyu , Li Li , Li Tianxiao , Ma Daqing , Zhang Jiaqiang 
Published: July 2023

AbstractBackgroundCerebral hyperperfusion syndrome (CHS) is not a common but severe complication after carotid artery stenting (CAS). We investigated whether prophylactic low-dose dexmedetomidine, a selective α2-adrenoceptor agonist, can decrease cerebral hyperperfusion induced brain injury after carotid artery stenting.MethodsThis randomised, double-blind, placebo-controlled trial was conducted in a tertiary-care hospital in Zhengzhou, China. Patients aged 18 to 80 years old who had undergone CAS and from whom written informed consent was obtained, were enrolled between Jul 20, 2019 and Oct 10, 2022. Patients were randomly assigned to receive either intravenous dexmedetomidine (0·1 μg/kg/h, from insertion of the laryngeal mask until 72hr on postoperative day 3) (n = 80) or placebo (intravenous normal saline) (n = 80). The primary endpoint was the incidence of cerebral hyperperfusion (CH) and cerebral hyperperfusion syndrome (CHS), which were assessed six times with Transcranial Doppler sonography (TCD) during the postoperative three days. This study was registered with the Chinese Clinical Trial Registry,www.chictr.org.cn, ChiCTR1900024416.ResultsCH occurred in 30 (37·5%) of 80 patients given a placebo and in 9 (11·2%) of 80 patients given dexmedetomidine (odds ratio [OR] 0·211, 95% CI 0·09-0·48; p<0·001). Further, CHS was significantly lower in the Dex group than in the placebo group (2.5% vs 13·75%; [OR] 0·16, 95% CI 0·03-0·71; p=0·017). Correspondingly, dexmedetomidine significantly upregulated serum brain-derived neurotrophic factor (BDNF) and downregulated neuronal injury biomarker neurofilament light chain (Nfl). The hierarchical clustering analysis revealed little difference in lipids metabolites between the two groups pre- and post-operatively, with Dex treatment uniquely increased lysphosphatidylethanolamine (LPE).ConclusionsA low prophylactic dose of dexmedetomidine significantly decreased the occurrence of cerebral hyperperfusion and cerebral hyperperfusion syndrome during the first three days after carotid artery stenting surgery.
Variegate expression of Cre recombinase in hematopoietic cells in CD11c-cre transgenic mice
Authors: Murat Claire , Guerder Sylvie 
Published: July 2023

AbstractIn this study, we performed an in-depth analysis of Cre expression in the widely used CD11c-Cre transgenic mice generated by the group of Boris Reizis. In contrast to previous observation, using the highly sensitive Rosa-26-floxed-tdTomato reporter mouse line, we show variegated expression of Cre in multiple hematopoietic linage cells starting in hematopoietic stem cells. We found that in the CD11c-Cre driver mice: (1) Cre is expressed in cDC linage cells and pDC starting from the myeloid dendritic cell precursor, as expected ; (2) Cre is expressed in a substantial fraction of hematopoietic stem cells and common lymphoid progenitors ; (3) Cre is expressed in more than 50% of all leukocytes. Hence, this study indicates that the reporter mice used to characterize Cre expression in Cre-driver mice should be selected with caution and considering the sensitivity of the reporter system. This study also suggests that the interpretation of some reports may need to be re-considered based on a careful evaluation of the cell type-specificity of Cre-mediated in their model.
Naturally segregating genetic variants contribute to thermal tolerance in aD. melanogaster model system
Authors: Williams-Simon Patricka A. , Oster Camille , Moaton Jordyn A. , Ghidey Ronel , Ng’oma Enoch , Middleton Kevin M. , Zars Troy , King Elizabeth G. 
Published: July 2023

AbstractThermal tolerance is a fundamental physiological complex trait for survival in many species. For example, everyday tasks such as foraging, finding a mate, and avoiding predation, are highly dependent on how well an organism can tolerate extreme temperatures. Understanding the general architecture of the natural variants of the genes that control this trait is of high importance if we want to better comprehend how this trait evolves in natural populations. Here, we take a multipronged approach to further dissect the genetic architecture that controls thermal tolerance in natural populations using the Drosophila Synthetic Population Resource (DSPR) as a model system. First, we used quantitative genetics and Quantitative Trait Loci (QTL) mapping to identify major effect regions within the genome that influences thermal tolerance, then integrated RNA-sequencing to identify differences in gene expression, and lastly, we used the RNAi system to 1) alter tissue-specific gene expression and 2) functionally validate our findings. This powerful integration of approaches not only allows for the identification of the genetic basis of thermal tolerance but also the physiology of thermal tolerance in a natural population, which ultimately elucidates thermal tolerance through a fitness-associated lens.
Assessment of population dynamics of endangeredT. putitora(Ham, 1822) in the breeding and nursery grounds of Western Himalaya
Authors: Rana Priyanka , Nautiyal Prakash 
Published: July 2023

AbstractThe present study analyzed the population characteristics ofTor putitorain their breeding and nursery grounds located in Western Himalayan region. From a sample size of 400 individuals, growth parameters such as asymptotic length, growth rate and growth performance index were estimated as 80.01 cm, 0.810 per year and 3.71 per year while the potential longevity was estimated as 4.6 years. The mortality parameters such as total, natural and fishing mortality were estimated as 2.88 /year, 1.05/ year and 1.83 / year respectively. The length at 25 %, 50% and 75% susceptibility to capture was estimated as 40.87 cm, 38.11 cm and 35.34 cm respectively. The fishing mortality and exploitation beyond optimum level and maximum sustainable exploitation ratio (Emax) indicate the overly exploitation of Mahseer resources in their breeding and nursery grounds. This indicates that the examined breeding and nursery grounds in Western Himalaya are facing intense “growth and recruitment overfishing” which may result in stock collapse in the forthcoming years.
In vitrobroad-spectrum antiviral activity of MIT-001, a mitochondria-targeted reactive oxygen species scavenger, against severe acute respiratory syndrome coronavirus 2 and multiple zoonotic viruses
Authors: Lim Taehun , Rajoriya Shivani , Kim Bohyeon , Natasha Augustine , Im Hyeonjoo , Shim Hyun Soo , Yoo Junsang , Kim Jong Woo , Lee Eun-Woo , Shin Hye Jin , Kim Soon Ha , Kim Won-Keun 
Published: July 2023

AbstractThe COVID-19 pandemic caused by SARS-CoV-2 becomes a serious threat to global health and requires the development of effective antiviral therapies. Current therapies that target viral proteins have limited efficacy with side effects. In this study, we investigated the antiviral activity of MIT-001, a small molecule reactive oxygen species (ROS) scavenger targeting mitochondria, against SARS-CoV-2 and other zoonotic virusesin vitro. The antiviral activity of MIT-001 was quantified by RT-qPCR and plaque assay. We also evaluated the functional analysis of MIT-001 by JC-1 staining to measure mitochondrial depolarization, total RNA sequencing to investigate gene expression changes, and immunoblot to quantify protein expression levels. The results showed that MIT-001 effectively inhibited the replication of B.1.617.2 and BA.1 strains, Zika virus, Seoul virus, and Vaccinia virus. Treatment with MIT-001 restored the expression of heme oxygenase-1 (HMOX1) and NAD(P)H: quinone oxidoreductase 1 (NqO1) genes, anti-oxidant enzymes reduced by SARS-CoV-2, to normal levels. The presence of MIT-001 also alleviated mitochondrial depolarization caused by SARS-CoV-2 infection. These findings highlight the potential of MIT-001 as a broad-spectrum antiviral compound that targets for zoonotic RNA and DNA viruses, providing a promising therapeutic approach to combat viral infection.
Nuclear envelope assembly relies on CHMP-7 in the absence of BAF-LEM-mediated hole closure
Authors: Barger Sarah R. , Penfield Lauren , Bahmanyar Shirin 
Published: July 2023

AbstractBarrier-to-autointegration factor (BAF) is a DNA binding protein that crosslinks chromatin to assemble the nuclear envelope (NE) after mitosis. BAF also binds the Lap2b-Emerin-Man1 (LEM) domain family of NE proteins to repair interphase ruptures. The NE adaptors to ESCRTs, LEMD2-CHMP7, seal NE holes surrounding mitotic spindle microtubules (MTs), but whether NE hole closure in mitosis involves BAF-LEM binding is not known. Here, we analyze NE sealing after meiosis II inC. elegansoocytes to show that BAF-LEM binding and LEM-2LEMD2-CHMP-7 have distinct roles in hole closure around spindle MTs. LEM-2/EMR-1emerinfunction redundantly with BAF-1 to seal the NE. Compromising BAF-LEM binding revealed an additional role for EMR-1 in maintenance of the NE permeability barrier and an essential role for LEM-2-CHMP-7 in preventing NE assembly failure. The WH domain of LEM-2 recruits the majority of CHMP-7 to the NE inC. elegansand a LEM-2 -independent pool of CHMP-7, which is mostly enriched in the nucleoplasm, also contributes to NE stability. Thus, NE hole closure surrounding spindle MTs requires redundant mechanisms that safeguard against failure in NE assembly to support embryogenesis.
Selective endocytic uptake of targeted liposomes occurs within a narrow range of liposome diameter
Authors: Ashby Grant , Keng Kayla E. , Hayden Carl C. , Gollapudi Sadhana , Houser Justin R. , Jamal Sabah , Stachowiak Jeanne C. 
Published: July 2023

AbstractCell surface receptors facilitate signaling and nutrient uptake. These processes are dynamic, requiring receptors to be actively recycled by endocytosis. Due to their differential expression in disease states, receptors are often the target of drug-carrier particles, which are adorned with ligands that bind specifically to receptors. These targeted particles are taken into the cell by multiple routes of internalization, where the best-characterized pathway is clathrin-mediated endocytosis. Most studies of particle uptake have utilized bulk assays, rather than observing individual endocytic events. As a result, the detailed mechanisms of particle uptake remain obscure. To address this gap, we have employed a live-cell imaging approach to study the uptake of individual liposomes as they interact with clathrin-coated structures. By tracking individual internalization events, we find that the size of liposomes, rather than the density of the ligands on their surfaces, primarily determines their probability of uptake. Interestingly, targeting has the greatest impact on endocytosis of liposomes of intermediate diameters, with the smallest and largest liposomes being internalized or excluded, respectively, regardless of whether they are targeted. These findings, which highlight a previously unexplored limitation of targeted delivery, can be used to design more effective drug carriers.
Establishing thresholds for cytokine storm and defining their relationship to disease severity in respiratory viral infections
Authors: Souquette Aisha , Crawford Jeremy Chase , Wolf Joshua , Blair Ashley , Agrawal Mona , Boywid Laura , McNair Kristin , Hysmith Nicholas D. , Hundman Chloe , Bahadoran Azadeh , Arnold Sandra R. ,   SJTRC Study Team, Smallwood Heather S. , Green Amanda , Thomas Paul G. 
Published: July 2023

AbstractPrevious studies have identified cytokines associated with respiratory virus infection illness outcome. However, few studies have included comprehensive cytokine panels, longitudinal analyses, and/or simultaneous assessment across the severity spectrum. This, coupled with subjective definitions of cytokine storm syndrome (CSS), have contributed to inconsistent findings of cytokine signatures, particularly with COVID severity. Here, we measured 38 plasma cytokines and compared profiles in healthy, SARS-CoV-2 infected, and multisystem inflammatory syndrome in children (MIS-C) patients (n = 169). Infected patients spanned the severity spectrum and were classified as Asymptomatic, Mild, Moderate or Severe. Our results showed acute cytokine profiles and longitudinal dynamics of IL1Ra, IL10, MIP1b, and IP10 can differentiate COVID severity groups. Only 4% of acutely infected patients exhibited hypercytokinemia. Of these subjects, 3 were Mild, 3 Moderate, and 1 Severe, highlighting the lack of association between CSS and COVID severity. Additionally, we identified IL1Ra and TNFa as potential biomarkers for patients at high risk for long COVID. Lastly, we compare hypercytokinemia profiles across COVID and influenza patients and show distinct elevated cytokine signatures, wherein influenza induces the most elevated cytokine profile. Together, these results identify key analytes that, if obtained at early time points, can predict COVID illness outcome and/or risk of complications, and provide novel insight for improving the conceptual framework of hypercytokinemia, wherein CSS is a subgroup that requires concomitant severe clinical manifestations, and including a list of cytokines that can distinguish between subtypes of hypercytokinemia.
Comparative Reconstruction of SARS-CoV-2 transmission in three African countries using a mathematical model integrating immunity data
Authors: Naffeti Bechir , BenAribi Walid , Kebir Amira , Diara Maryam , Schoenhals Matthieu , Vigan-Womas Inès , Dellagi Koussay , BenMiled Slimane 
Published: July 2023

ABSTRACTObjectivesAfrica has experienced fewer coronavirus disease 2019 (COVID-19) cases and deaths than other regions, with a contrasting epidemiological situation between countries, raising questions regarding the determinants of disease spread in Africa.MethodWe built a susceptible–exposed–infected–recovered model including COVID-19 mortality data where recovery class is structured by specific immunization and modeled by a partial differential equation considering the opposed effects of immunity decline and immunization. This model was applied to Tunisia, Senegal, and Madagascar.FindingSenegal and Tunisia experienced two epidemic phases. Initially, infections emerged in naive individuals and were limited by social distancing. Variants of concern (VOCs) were also introduced. The second phase was characterized by successive epidemic waves driven by new VOCs that escaped host immunity. Meanwhile, Madagascar demonstrated a different profile, characterized by longer intervals between epidemic waves, increasing the pool of susceptible individuals who had lost their protective immunity. The impact of vaccination in Tunisia and Senegal on model parameters was evaluated.InterpretationLoss of immunity and vaccination-induced immunity have played crucial role in controlling the African pandemic. Severe acute respiratory syndrome coronavirus 2 has become endemic now and will continue to circulate in African populations. However, previous infections provide significant protection against severe diseases, thus providing a basis for future vaccination strategies.
Risk Stratification of Advanced Fibrosis in HIV Patients With Hepatic Steatosis Using the NAFLD Fibrosis and BARD Scores
Authors: Yendewa George A. , Khazan Ana , Jacobson Jeffrey M. 
Published: July 2023

ABSTRACTBackgroundNonalcoholic fatty liver disease (NAFLD) is increasingly prevalent in people with HIV (PWH), yet the risk factors for disease progression are poorly understood, due to inadequate surveillance. We employed non-invasive methods to estimate the prevalence and associated factors of advanced NAFLD in PWH.MethodsWe conducted a retrospective study of PWH enrolled in our clinic from 2005 to 2022. We employed imaging (ultrasound, computer tomography, magnetic resonance imaging, and transient elastography) or biopsy reports to identify cases of hepatic steatosis. We excluded patients with harmful alcohol use, hepatitis B or C infection, and other specified etiologies. We used the NAFLD Fibrosis Score (NFS), BARD Score, AST to Platelet Index (APRI), and Fibrosis-4 (FIB-4) Score to stratify fibrosis. We used logistic regression to identify predictors of advanced fibrosis.ResultsAmong 3959 PWH in care, 1201 had available imaging or liver biopsies. After exclusions, 114 of the remaining 783 had evidence of hepatic steatosis (prevalence 14.6%). The majority were male (71.1%), with mean age 46.1 years, and mean body mass index (BMI) 31.4 ± 8.1 kg/m2. About 24% had lean NAFLD (BMI < 25 kg/m2). Based on the NFS, 27.2% had advanced fibrosis, which was corroborated by estimates from the other scores. In adjusted regression analysis, advanced fibrosis was associated with BMI > 35 kg/m2(4.43, 1.27-15.48), thrombocytopenia (4.85, 1.27-18.62) and hypoalbuminemia (9.01, 2.39-33.91).ConclusionWe found a NAFLD prevalence of 14.6%, with 27.2% of cases having advanced fibrosis. Our study provides practical insights into the surveillance of NAFLD in PWH.