tbuckley/cabot-search huggingface dataset:
Fundamental Identifiability Limits in Molecular Epidemiology
Authors: Stilianos Louca, Angela McLaughlin, Ailene MacPherson, Jeffrey B Joy, Matthew W Pennell
Journal: Molecular Biology and Evolution (2021)

Viral phylogenies provide crucial information on the spread of infectious diseases, and many studies fit mathematical models to phylogenetic data to estimate epidemiological parameters such as the effective reproduction ratio (Re) over time. Such phylodynamic inferences often complement or even substitute for conventional surveillance data, particularly when sampling is poor or delayed. It remains generally unknown, however, how robust phylodynamic epidemiological inferences are, especially when there is uncertainty regarding pathogen prevalence and sampling intensity. Here, we use recently developed mathematical techniques to fully characterize the information that can possibly be extracted from serially collected viral phylogenetic data, in the context of the commonly used birth-death-sampling model. We show that for any candidate epidemiological scenario, there exists a myriad of alternative, markedly different, and yet plausible "congruent" scenarios that cannot be distinguished using phylogenetic data alone, no matter how large the data set. In the absence of strong constraints or rate priors across the entire study period, neither maximum-likelihood fitting nor Bayesian inference can reliably reconstruct the true epidemiological dynamics from phylogenetic data alone; rather, estimators can only converge to the "congruence class" of the true dynamics. We propose concrete and feasible strategies for making more robust epidemiological inferences from viral phylogenetic data.
Preferences for pre-exposure prophylaxis among U.S. military men who have sex with men: results of an adaptive choice based conjoint analysis study
Authors: José I. Gutierrez, Alex Dubov, Frederick L. Altice, David Vlahov
Journal: Military Medical Research (2021)

Abstract Background Pre-exposure prophylaxis (PrEP) prevents human immunodeficiency virus (HIV) infection, but its use remains low among U.S. military men who have sex with men (MSM), likely due to mis-matching with personal preferences. We conducted a study to characterize preferences to PrEP measures within this population. Methods HIV-negative military MSM were recruited through a closed, Lesbian, Gay, Bisexual, and Transgendered (LGBT) military social media group. The survey was anonymous, and consisted of five experimentally varied attributes in service delivery: dosing method, provider type, visit location, lab work evaluation location, and dispensing venue. Relative importance and part-worth utility scores were generated using hierarchical bayes (HB) estimation, and the randomized first choice model was used to examine participation interest across eight possible PrEP program scenarios. Results A total of 429 participants completed the survey. Among the eight scenarios with varying attributes, the most preferred scenario featured a daily tablet, PrEP injection or implant, along with a military provider, smartphone/telehealth visit, and on-base locations for lab evaluation and medication pick-up. The results also emphasized the importance for providers to be familiar with PrEP prescription knowledge, and to provide interactions sensitive to sexual identity and mental health. Conclusion A PrEP program consisting of daily tablet is preferred in military healthcare settings is preferred. Long-acting implants and injections are also desired.
Abstract 13050: Acute Alcohol-Induced Enhanced Cardiac Depression in a Canine Model of Chronic Alcohol Consumption: Adverse Effects on Left Ventricle and Myocyte Contraction, [Ca <sup>2+</sup> ] <sub>i</sub> Transient and Ca <sup>2+</sup> Current
Authors: Zhi Zhang, Che Cheng, Satoshi Masutani, Tiankai Li, Xiaowei Zhang, Xiaoqiang Sun, Jing Cao, David M Herrington, Heng Jie Cheng
Journal: Circulation (2020)

Background: Acute alcohol ingestion produces transient RAS activation. Alcoholics have an enhanced RAS activation after acute ethanol ingestion. Thus, chronic alcohol users may have enhanced cardiac functional responses to acute alcohol intake. However, it is unclear whether and how chronic alcohol intake alters cardiac response to acute alcohol exposure. We tested the hypothesis that acute alcohol may exacerbate cardiac depression and [Ca 2- ] i dysregulation, thus play important role in development of irreversible cardiomyopathy in alcoholics. Methods: We compared LV and cardiomyocyte response to acute alcohol in 6 chronically-instrumented conscious dogs before and 6 months after the once daily ingestion of alcohol (400 ml, 22% providing 33% of total daily caloric intake). Results: In conscious dogs, 6 months of alcohol significantly decreased LV contractility by 48% measured by the slopes of pressure-volume relations (E ES , 48%, 4.4 vs 8.4 mmHg/ml and M SW , 50.8 vs 98.6 mmHg) and increased the time constant of relaxation (τ, 78%, 47.8 vs 26.9 ms). In the alcoholic animals, when compared with the same animals prior to alcohol, acute alcohol (0.2 g/kg, iv, plasma level 62.3 ± 8 mg/dL) caused a greater decrease in LV contractility (47% vs 23%) and increase in τ (27% vs11%). In isolated myocytes, abrupt exposure to alcohol (250 mM) produced significant decreases in cell contraction, [Ca 2+ ] i transient ([Ca 2+ ] i ) and Ca 2+ current (I Ca,L ) in both normal and alcoholic myocytes. However, compared with the isolated cells obtained from LV biopsied tissues of the same animals prior to alcohol, the acute alcohol-induced decrease in I Ca,L (alcoholic: 50%, 1.3 vs 2.6; normal: 29%, 4.0 vs 5.6 pA/pF) was much greater in the alcoholic myocytes, the resulting reductions in the cell contractility, dL/dtmax (alcoholic: 46%, 36vs67; normal: 24%, 82vs108 μm/s), the percent shortening (49% vs 24%) and relengthening, dR/dtmax were doubled. Conclusion: In chronically alcohol-fed dogs, acute alcohol produces increased direct inhibition in LV and myocyte contractility, relaxation and exacerbates [Ca 2+ ] i hemostasis. The chronic alcohol-induced increased cardiac sensitivity to acute alcohol may play an important role in the functional impairment in alcoholic cardiomyopathy.
Long-term adverse effects following developmental exposure to daidzein
Authors: Retha Newbold, Wendy Jefferson, Elizabeth Padilla-Banks, Bill Bullock
Journal: Cancer Research (2004)

9  Exposure to naturally occurring and synthetic estrogenic compounds results in permanent alterations in the developing organism especially if exposure occurs during the critical stages of differentiation. Our laboratory has shown that perinatal exposure of mice to diethylstilbestrol (DES) results in impaired fertility, structural malformations, and lesions of the reproductive tract. Long-term consequences of DES exposure (1 mg/kg/day) on neonatal days 1-5 include a high incidence (> 90%) of uterine carcinoma in aged mice. Further, when equal estrogenic doses of DES (0.001 mg/kg/day) or genistein (50 mg/kg/day), a phytoestrogen found in soy products, were compared for long-term effects, the incidence of uterine adenocarcinoma was 31% and 35% respectively. Thus, the developing reproductive tract appears to be exquisitely sensitive to perturbation by chemicals with estrogenic activity. Because the nutritional and pharmaceutical use of phytoestrogens is increasing due to their proposed beneficial effects, we investigated the potential risks posed by daidzein, another soy phytoestrogen. Since genistein has been shown to be genotoxic in in vitro models while daidzein is nongenotoxic, it was possible to study the contribution of genotoxicity in the induction of uterine tumors. Outbred CD-1 mice were treated with daidzein (250 mg/kg/day) by subcutaneous injection on days 1-5 of neonatal life. This dose of daidzein is equal in estrogenicity to that of DES at 0.001 mg/kg/day and genistein at 50 mg/kg/day. Mice were sacrificed on day 5 following the last injection or at 18 months. At 5 days, uterine wet weight was increased over controls similar to DES or genistein at equal estrogenic doses. The estrogen responsive protein, lactoferrin (LF) was also increased in response to daidzein. Uteri from mice at 18 months of age were examined to evaluate a potential increased risk for histological abnormalities including uterine tumors later in life. Many of the long-term effects observed after DES and genistein treatment, including uterine adenocarcinoma, were observed after developmental exposure of daidzein. In fact, the incidence of uterine adenocarcinoma was 30% (6/20 mice) compared to 31% for DES and 35% for genistein. Similarities between the effects of DES, genistein and daidzein point to the need for further mechanistic studies in phytoestrogens and their role in long-term effects that follow developmental exposure.
Abstract 16181: Impact of Magnetic Resonance Imaging on Functional Integrity of Non-conditional Cardiovascular Implantable Electronic Devices
Authors: Garima Dahiya, Adam Wetzel, Andreas Kyvernitakis, Loretta Gevenosky, RONALD WILLIAMS, Moneal Shah, Victor Farah, Mark Doyle, Robert Biederman
Journal: Circulation (2020)

Introduction: Magnetic Resonance Imaging (MRI) non-conditional cardiovascular implantable electronic devices (CIEDs) have historically restricted the use of MRI. We investigated the impact of MRI on the functional integrity of CIEDs. Methods: In this prospective, observational single-center study, we enrolled patients undergoing MRI over a 5-year period. Prior to assessing the impact of MRI on CIED integrity, we performed interrogations in sequential duplication to assess the intrinsic variability of the device. Subsequently, we performed interrogations immediately after MRI and monitored changes in device parameters and clinical events. Results: We completed 492 MRI studies, 283 (58%) in patients with permanent pacemakers (PPMs), and 209 (42%) with implantable cardioverter defibrillators (ICDs). Subsequent MRI exposures occurred in 73 of 492 (15%) encounters. Accounting for intrinsic variability in CIED lead parameters, there were no significant changes in RA, RV, or LV lead parameters after MRI, regardless of the region of scan (thoracic vs non-thoracic), type of CIED (PPMs vs ICDs) and among those with serial MRIs. When ranked for % change pre- to post-MRI, the majority of RA, RV, and LV metrics for thresholds, sensing, and impedance conformed to ≤20% change. No significant clinical adverse cardiac events or effect on device microcircuitry occurred during the study. Conclusion: Incorporating a novel reproducibility tactic, there were no clinically meaningful device parameter changes nor were there adverse clinical events during or following MRIs, suggesting the effects of MRI on non-conditional CIED integrity are far less than previously perceived.
Neonatal Withdrawal Syndrome following Late in utero Exposure to Selective Serotonin Reuptake Inhibitors: A Systematic Review and Meta-Analysis of Observational Studies
Authors: Jianjun Wang, Fiammetta Cosci
Journal: Psychotherapy and Psychosomatics (2021)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; A clear picture of neonatal withdrawal signs due to in utero selective serotonin reuptake inhibitor (SSRI) exposure and its consequences is still missing. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; A systematic review and a meta-analysis were performed to provide an overview of neonatal withdrawal signs following late in utero exposure to SSRIs and to quantify the corresponding risks. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; MEDLINE, Web of Science, and Embase were searched from inception to January 2021. The Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed. English-language observational studies reporting on acute postpartum outcomes following late in utero exposure to SSRIs or SSRIs/venlafaxine were evaluated. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Of 2,269 citations reviewed, 79 studies were assessed for eligibility; 13 were included in the qualitative analysis of the literature, which allowed us to identify 26 signs. A meta-analysis was run separately for studies on SSRI exposure (&lt;i&gt;n&lt;/i&gt; = 3) and those on SSRI/venlafaxine exposure (&lt;i&gt;n&lt;/i&gt; = 6). Hypoglycemia was identified as a withdrawal sign based on the SSRI studies. Tremors, hypotonia, tachycardia, rapid breathing, respiratory distress, and hypertonia were identified as withdrawal signs based on the SSRI/venlafaxine studies. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; The present work provides a framework for the identification of neonatal SSRI withdrawal syndrome. Tapering and discontinuation of antidepressant drugs before and during the early phase of pregnancy are worth attempting to prevent the occurrence of this syndrome.
Pharmacy professionals are part of the solution to reduce GPs’ workload
Authors: Steven Williams, Lawrence Brad, Darren Jones, Jamie Hayes
Journal: BMJ (2021)

We are sure that many general practitioners share Salisbury’s pain about the current workload in general practice,1 but we are also confident that many general practices have discovered that having a pharmacy team (clinical pharmacists and pharmacy technicians) as part of their practice, primary care network, or local health board can substantially reduce administrative workload (one post saving …
COVID-19 outbreaks following full reopening of primary and secondary schools in England: Cross-sectional national surveillance, November 2020
Authors: Felicity Aiano, Anna A Mensah, Kelsey McOwat, Chinelo Obi, Amoolya Vusirikala, Annabel A Powell, Jessica Flood, Johanna Bosowski, Louise Letley, Samuel Jones, Zahin Amin-Chowdhury, Joanne Lacy, Iain Hayden, Sharif A Ismail, Mary E Ramsay, Shamez N Ladhani, Vanessa Saliba
Journal: The Lancet Regional Health - Europe (2021)

The full reopening of schools in September 2020 was associated with an increase in COVID-19 cases and outbreaks in educational settings across England.Primary and secondary schools reporting an outbreak (≥2 laboratory-confirmed cases within 14 days) to Public Health England (PHE) between 31 August and 18 October 2020 were contacted in November 2020 to complete an online questionnaire.There were 969 school outbreaks reported to PHE, comprising 2% (n = 450) of primary schools and 10% (n = 519) of secondary schools in England. Of the 369 geographically-representative schools contacted, 179 completed the questionnaire (100 primary schools, 79 secondary schools) and 2,314 cases were reported. Outbreaks were larger and across more year groups in secondary schools than in primary schools. Teaching staff were more likely to be the index case in primary (48/100, 48%) than secondary (25/79, 32%) school outbreaks (P = 0.027). When an outbreak occurred, attack rates were higher in staff (881/17,362; 5.07; 95%CI, 4.75-5.41) than students, especially primary school teaching staff (378/3852; 9.81%; 95%CI, 8.90-10.82%) compared to secondary school teaching staff (284/7146; 3.97%; 95%CI, 3.79-5.69%). Secondary school students (1105/91,919; 1.20%; 95%CI, 1.13-1.28%) had higher attack rates than primary school students (328/39,027; 0.84%; 95%CI, 0.75-0.94%).A higher proportion of secondary schools than primary schools reported a COVID-19 outbreak and experienced larger outbreaks across multiple school year groups. The higher attack rate among teaching staff during an outbreak, especially in primary schools, suggests that additional protective measures may be needed.PHE.
Serum cytokeratin-19 fragments (CYFRA 21–1) for the prediction of overall survival in patients with hepatocellular carcinoma
Authors: Gian Paolo Caviglia, Antonella Olivero, Michela Ciruolo, Patrizia Carucci, Emanuela Rolle, Chiara Rosso, Maria Lorena Abate, Alessandra Risso, Ramy Younes, Antonina Smedile, Giorgio Maria Saracco, Elisabetta Bugianesi, Silvia Gaia
Journal: Journal of Hepatology (2020)
구연 : 제한효소분절질량다형성(RFMP)을 이용한 라미부딘 내성 B형 간염바이러스의 검출
Authors: 황성규, 김남근, 한진희, 김형태, 고광현, 홍성표, 박필원, 임규성, 정현재, 지미선, 김은옥, 문명순, 이환석, 김석준, 유왕돈, 김수옥, 홍선표
Journal: Clinical and Molecular Hepatology (2003)

배경/목적: 만성B형간염의 치료에 사용되는 뉴클레오사이드 유도체인 라미부딘은 지속 사용시 B형간염바이러스(HBV)의 중합효소인 P 유전자에 돌연변이를 유발하게 되는데, 중합효소의 활성 부위인 tyrosine, methionine, aspartate, aspartate (YMDD) motif의 M552I (YIDD)와 M552V (YVDD)가 내성을 유발하는 주요 돌연변이로 보고되고 있다. 현재 제한효소분절길이다형성(RFLP), 염기서열분석 및 hybridization (LiPA) 방법이 내성 바이러스의 분석에 활용되고 있으나, 1) 야생형과 변이형 혼합감염의 진단이 어려운 점 (RFLP, 염기서열분석, LiPA), 2) 임상적 응용 범위가 협소한 점(RFLP), 3) 분석 기술의 사용이 불편한 점 (RFLP, 염기서열분석), 4) 새로운 변이의 동정이 어려운 점(RFLP, LiPA), 5) 고비용(염기서열분석, LiPA)의 문제점으로 인해 임상적 사용이 크게 제한을 받고 있는 실정이다. 본 연구는 자동화 말디토프 (MALDI-T) 질량 분석 기술을 응용한 제한효소분절질량다형성(Restriction Fragment Mass Polymorphism, RFMP) 방법을 이용하여 내성 바이러스의 검출과 새로운 변이형의 동정을 대용량으로 정확하게 수행할 수 있는 지의 여부를 알아보고자 하였다. 대상과 방법: Type IIS 제한효소의 인지 부위를 포함하며 HBV P 유전자의 YMDD motif의 upstream에 결합하도록 제작된 특수 시발체(primer)를 이용하여 중합연쇄반응(PCR) 반응을 하고, 해당 제한효소로 절단하게 되면, YMDD motif를 포함하는 7mer와 13mer의 올리고머가 형성된다. 이 두 가지의 올리고머 (allele-diagnostic fragments)는 YMDD motif에 출현하는 돌연변이의 종류에 따라 특정 질량을 가지게 되는데, 이 두 분자의 질량을 말디토프 질량분석기에서 측정함으로써 바이러스의 변이를 파악하게 된다. 결과: RFMP 방법의 검출한계와 야생형과 변이형 바이러스가 공존할 때의 식별능력을 분석하였을 때, 야생형 중에 변이형의 비율이 0.1% 미만일 때, 그리고 혈청 1mL 당 HBV 게놈이 100 copies까지도 유의하게 변이 바이러스를 검출하였다. 기존 방법인 RFLP와 sequencing으로 HBV 변이형이 동정되었던 환자 20명의 혈청을 RFMP 방법으로 분석한 결과, 정확성 외에도 바이러스 breakthrough 6개월 전에 변이 바이러스의 출현을 조기 검출할 수 있었다. 또한 RFLP 방법에 의해 검출하지 못한 새로운 바이러스 변이들을 검출하였고 중복 감염시 혼합 바이러스 간의 상대적 양을 파악할 수 있었다. 결론: RFMP 방법은 높은 정확도, 민감도, 변이 바이러스 특이도 및 중복 감염 바이러스의 상대량 분석능력을 갖는 새로운 내성바이러스 검출 방법으로 대량의 임상 샘플을 신속한 처리가 가능하므로 라미부딘 및 항바이러스제 치료 예후 및 질환 경과의 임상적 이해에 활용되길 기대한다.
Abstract MP36: The Development Of A Centralized Recruitment Process For Covid-19 Research: Hopkins Opportunity For Participant Engagement Registry
Authors: Oluwabunmi Ogungbe, Hailey Miller, Anna Peeler, Lewis-Land Cassie, Scott Carey, Cyd Lacanienta, Elizabeth Martinez, Megan Singleton, Kelly T Gleason, Jeanne Keruly, Daniel Ford, Cheryl R Dennison Himmelfarb
Journal: Circulation (2021)

Introduction: The COVID-19 pandemic has required urgent scientific response to investigate the disease, its prevention and treatment and interactions with cardiovascular conditions. Consequently, a centralized workflow was needed to effectively recruit, screen and connect volunteers to COVID-19 research opportunities. Objective: To create a centralized registry to match eligible and interested volunteers ≥18 years with COVID-19 outpatient research studies at an academic health system. Methods: Key stakeholders, including researchers and participant advocates, collaborated to build the Hopkins Opportunity for Participant Engagement (HOPE) Registry in English and Spanish. REDCap, a secure web-based application, served as the Registry platform. Study teams recruiting for outpatient studies were invited to present their studies through the Registry. Study volunteers were recruited using multiple methods, including patient portal messages, email, social media, and online advertisement. The Registry included COVID testing results and participant survey of demographic and COVID-19 related questions. Branching logic was used to pre-screen and present participating studies for which the person was eligible. The individual then selected which studies, if any, they were interested in. Study teams received an automatic notification and reached out directly to individuals expressing interest in their study ( Figure ). Results: The HOPE Registry includes 7 studies and has enrolled 4186 people. Over half (55%) were &gt;55 years and the majority were female (64%). Racial/ethnic groups represented were Whites (80%), Black s (9%), Asians (4.7%), Hispanics (5%), and American Indian (0.3%). Participants were interested in: 29%, treatment study; 37%, vaccine study; and 66%, donating plasma. Within 10 weeks, 585 persons were matched with an actively recruiting study. Conclusions: The ongoing HOPE registry has shown promise in engaging individuals with COVID-19 research and improving research recruitment workflow.
Abstract P109: Plasma Metabolomic Signature Of Healthy Dietary Patterns In The Chronic Renal Insufficiency Cohort (CRIC) Study
Authors: Hyunju Kim, Cheryl A Anderson, Emily A Hu, Zihe Zheng, Lawrence J Appel, Jiang He, Harold I Feldman, Amanda Anderson, Ana Ricardo, Zeenat Y Bhat, Tanika N Kelly, Jing Chen, Morgan Grams, Joe Coresh, Eugene P Rhee, Casey M Rebholz
Journal: Circulation (2021)

Introduction: In individuals with chronic kidney disease (CKD), healthy dietary patterns are inversely associated with CKD progression. Metabolomics, an approach which measures many small molecules in biofluids, can identify biomarkers of healthy dietary patterns and elucidate metabolic pathways underlying diet-disease associations. Hypothesis: We hypothesized that adherence to 4 healthy dietary patterns would be associated with a set of known metabolites in CKD patients. Methods: We examined associations between 634 plasma metabolites assessed using the Broad platform at year 1 and Healthy Eating Index (HEI)-2015, Alternative Healthy Eating Index (AHEI)-2010, the Dietary Approaches to Stop Hypertension (DASH) diet, and alternate Mediterranean diet (aMED), and their food components in 1,117 participants in the CRIC Study. Usual dietary intakes were assessed using a food frequency questionnaire at baseline and year 2. We conducted multivariable linear regression models to study associations between diet scores and individual plasma metabolites, adjusting for sociodemographic characteristics, health behaviors, and clinical factors. Results: After Bonferroni correction, we identified a total of 362 diet-metabolite associations (HEI=78; AHEI=127; DASH=97; aMED=60), and 101 metabolites were associated with more than 1 dietary pattern. The most common metabolite categories were triacylglycerols and diacylglycerols. Most lipids were negatively associated with healthy dietary patterns, except for cholesterols esters and triacylglycerols with ≥7 double bonds. Triacylglycerols with high number of double bonds were positively associated with healthy fat intake (e.g., higher monounsaturated and polyunsaturated fatty acid, omega-3 fatty acid, fish) within HEI, AHEI, and aMED ( Table ). Conclusions: We identified many metabolites associated with healthy dietary patterns, indicative of food consumption. If replicated, they may be considered biomarkers of healthy dietary patterns in CKD patients.