tbuckley/cabot-search huggingface dataset:
Abstract P079: Examining Associations Of Sexual Identity And Cardiovascular Disease Risk In A Nationally Representative Sample: The Mediating Role Of Sleep Duration
Authors: Billy A Caceres, Danny Vo, Yashika Sharma, Ipek Ensari, Kasey Jackman, Joseph Belloire
Journal: Circulation (2021)

Introduction: There is growing evidence that sexual minority (e.g., gay/lesbian and bisexual) adults have higher cardiovascular disease (CVD) risk and report shorter sleep duration than heterosexual adults. Previous research suggests that sleep duration is inversely associated with CVD risk in adults. To date, no study has examined the associations of sleep duration and objectively measured CVD risk in sexual minority adults. Hypothesis: We investigated the hypothesis that sexual minority adults have higher systolic and diastolic blood pressure (BP) and waist-to-height ratio (WHtr) than heterosexual adults and that sleep duration mediates these associations. Methods: Cross-sectional data from the National Health and Nutrition Examination Survey (2005-2016) were used. Sexual identity and sleep duration were assessed based on self-report. We used the average of systolic and diastolic BP across two readings to assess BP. We calculated the ratio between waist and height (in cm). We used sex-stratified linear regression models to compare CVD risk factors between sexual minority (i.e., gay/lesbian and bisexual) and heterosexual adults. Next, we used path analysis to determine whether the associations of sexual identity with systolic and diastolic BP and WHtr were mediated by sleep duration. Models were adjusted for demographic characteristics and tobacco use. Results: The sample included 17,858 adults. Participants had a mean age of 38.0 (SD = 12.1), 48.4% were female, and 65.6% were Non-Hispanic White. Gay men reported higher sleep duration ( B 0.27 [0.07]) relative to heterosexual men. However, WHtr and diastolic BP did not differ between gay and heterosexual men. No differences in sleep duration or diastolic BP were found between sexual minority and heterosexual women. Bisexual women had a higher systolic BP ( B 1.64 [0.70]) and WHtr ( B 0.02 [0.01]) than heterosexual women, but these associations were not mediated by sleep duration. Compared to heterosexual men, sleep duration partially mediated the associations of sexual identity with diastolic BP ( B - 0.12 [0.05]) and WHtr ( B - 0.01 [0.01]) in gay men. Conclusion: This is the first study to assess the associations of sexual identity, sleep duration, and an objectively measured marker of CVD risk in a nationally representative sample of US adults. We found that bisexual women had higher systolic BP and WHtr than heterosexual women and that higher sleep duration was associated with lower diastolic BP and WHtr in gay men. Findings can inform future studies investigating the interplay between sexual identity, sleep duration, and CVD risk in adults.
Comprehensive mapping of binding hot spots of SARS-CoV-2 RBD-specific neutralizing antibodies for tracking immune escape variants
Authors: Chunyan Yi, Xiaoyu Sun, Yixiao Lin, Chenjian Gu, Longfei Ding, Xiao Lu, Zhuo Yang, Yaguang Zhang, Liyan Ma, Wangpeng Gu, Aidong Qu, Xu Zhou, Xiuling Li, Jianqing Xu, Zhiyang Ling, Youhua Xie, Hongzhou Lu, Bing Sun
Journal: Genome Medicine (2021)

Abstract Background The receptor-binding domain (RBD) variants of SARS-CoV-2 could impair antibody-mediated neutralization of the virus by host immunity; thus, prospective surveillance of antibody escape mutants and understanding the evolution of RBD are urgently needed. Methods Using the single B cell cloning technology, we isolated and characterized 93 RBD-specific antibodies from the memory B cells of four COVID-19 convalescent individuals in the early stage of the pandemic. Then, global RBD alanine scanning with a panel of 19 selected neutralizing antibodies (NAbs), including several broadly reactive NAbs, was performed. Furthermore, we assessed the impact of single natural mutation or co-mutations of concern at key positions of RBD on the neutralization escape and ACE2 binding function by recombinant proteins and pseudoviruses. Results Thirty-three amino acid positions within four independent antigenic sites (1 to 4) of RBD were identified as valuable indicators of antigenic changes in the RBD. The comprehensive escape mutation map not only confirms the widely circulating strains carrying important immune escape RBD mutations such as K417N, E484K, and L452R, but also facilitates the discovery of new immune escape-enabling mutations such as F486L, N450K, F490S, and R346S. Of note, these escape mutations could not affect the ACE2 binding affinity of RBD, among which L452R even enhanced binding. Furthermore, we showed that RBD co-mutations K417N, E484K, and N501Y present in B.1.351 appear more resistant to NAbs and human convalescent plasma from the early stage of the pandemic, possibly due to an additive effect. Conversely, double mutations E484Q and L452R present in B.1.617.1 variant show partial antibody evasion with no evidence for an additive effect. Conclusions Our study provides a global view of the determinants for neutralizing antibody recognition, antigenic conservation, and RBD conformation. The in-depth escape maps may have value for prospective surveillance of SARS-CoV-2 immune escape variants. Special attention should be paid to the accumulation of co-mutations at distinct major antigenic sites. Finally, the new broadly reactive NAbs described here represent new potential opportunities for the prevention and treatment of COVID-19.
New prognostic factor of bioavailability of the oral S-1 patients with advanced gastric carcinoma
Authors: Yoshimi Akamo, Takehiro Wakasugi, Hitoshi Funahashi, Hiromitsu Takeyama, Tadao Manabe
Journal: Cancer Research (2005)

3989  Oral S-1 has been expected for first-line chemotherapy of advanced gastric carcinoma, which efficacy, however, may depend on bioavailability. This study investigated the correlation between prognosis and bioavailability of oral S-1 in the patients. We measured plasma 5-fluorourail (5-FU) levels by high performance liquid chromatography (HPLC) over 6 hours after oral S-1 test (40 or 50 mg). Twenty-five patients with advanced gastric carcinoma were enrolled in this study after giving informed consent. The clinical profile of 25 patients who underwent the oral S-1 test was as follows: Age, 65(42-86) years; Sex (male / female), 13/12; Body surface, 1.37 (1.18-1.70) m2; S-1 dose, 40 mg for two patients and 50 mg for 23 patients; Clinical indication for S-1, curability C for 14 patients, recurrence for eight patient and unresectably advanced for 3 patients; Operative procedures, total gastrectomy for 12 patients, Billroth II for 6 patients, Billroth I for 4 patients, no procedure added for 2 patients and bypass for one patient. Plasma 5-FU levels were as follows, 47.6±41.9 ng/ml at 30 min after oral S-1, 83.5±47.4 ng/ml at one hour, 126.8 ± 52.2 ng/ml at 2 hours, 127.1 ± 57.5 ng/ml at 4 hours, 82.8 ± 47.7 ng/ml at 6 hours. The median AUC over 6 hours were 810 (253 -1547) ng-hr/ml. The bioavailability varied between patients, and the AUC of plasma 5-FU corresponded to this variety. The bioavailability of oral S-1 can be a prognostic factor in the patients of oral S-1. Median survival of all 25 patients was 8 months after the start of oral S-1. In the good bioavailability group(n=13): the AUC≥810 ng-hr/ml, median survival was 15 months, but in the poor bioavailability group(n=12): the AUC
Stuart Craig Lennox
Authors: Iain Lennox
Journal: BMJ (2021)

Stuart Craig Lennox was born on 25 May 1932 in Aberdeen and died on 4 August 2018 at his home in Little Hadham, Hertfordshire.

He qualified from the London Hospital 1956 and was house officer at the London Hospital and Southend Hospital in 1956-57. His general surgical training was at the London Hospital in 1957-60 and his cardiothoracic training at the London Hospital, the National Heart Hospital, and the Brompton Hospital in 1960-68.

During 1961 he was tasked to build, in the department of experimental surgery at the London Hospital, a profound hypothermia unit for open heart surgery and to train a team to use it. When this was achieved a study was undertaken to determine the relation, between the temperatures at various sites in the brain and those in the oesophagus and nasopharynx, while altering the rate of cooling and rewarming and the level of CO2 of the dog. A similar study was made assessing brain function under varying conditions by monitoring single neurone activity. While a registrar at the National Heart Hospital, Mr Lennox was involved with work on heart and lung transplantation carried out at the Royal Veterinary College. Later at the London Hospital he studied the use of mitral valve homografts in dogs.

Mr Lennox was also involved in retrospective and prospective clinical studies. He undertook a study of the surgical results of surgery for oat cell carcinoma at the London Hospital …
Abstract 16499: Hybrid Cryoballoon Pulmonary Vein Isolation and Radiofrequency Posterior Wall Isolation for Persistent Atrial Fibrillation
Authors: Heajung L Nguyen, Carlos Macias, Houman Khakpour, Jason S Bradfield, Kalyanam Shivkumar, Eric F Buch
Journal: Circulation (2020)

Introduction: Catheter ablation of persistent atrial fibrillation (AF) is associated with less successful outcomes compared to paroxysmal AF. The optimal ablation strategy for persistent AF is not well established. We report our center’s experience utilizing a hybrid ablation approach of cryoballoon (CB) pulmonary vein isolation (PVI) followed by radiofrequency (RF) left atrial posterior wall isolation (LAPWI). Methods: 134 patients with persistent AF who underwent catheter ablation between 2016 and 2019 at our center were retrospectively reviewed. Patients with congenital heart disease or prior left atrial ablation or surgery were excluded. Hybrid ablation (n=62) consisted of CB PVI followed by RF roof and floor lines resulting in LAPWI. The control group (n=72) had PVI ±LAPWI with either CB (n=38) or RF (n=34). Outcomes were monitored with office visits and 7-day Holter monitors at 3, 6, 12, and 24 months post-ablation. The primary endpoint was freedom from any documented atrial tachyarrhythmia over 30 seconds. Results: Concomitant atrial flutter ablation was performed in 19/62 (31%) and 5/72 (7%) of hybrid and control cases, respectively. There was no significant difference in procedure time, however fluoroscopy time was shorter with hybrid ablation compared to control (p&lt;.01). 18-month freedom from atrial tachyarrhythmias was 70.4% with hybrid ablation and 51.6% with PVI±LAPWI with a single energy source (p=.048). Among those with recurrence, mean AF burden was significantly lower with hybrid ablation (7%) than with a single-energy approach (60%). Conclusion: In this single center experience with multiple operators, hybrid CB-RF PVI and LAPWI reduced AF recurrence (incidence and burden) compared to PVI±LAPWI with a single energy source.
Iroquois Homeodomain 5 (Irx5) is Upregulated via Increased ER Stress in Type 2 Diabetic Hearts
Authors: Sato Tatsuya, Kuno Atsushi, Kobayashi Takeshi, Miki Takayuki, Tanno Masaya, Ishikawa Satoko, Miura Tetsuji, Tohse Noritsugu
Journal: Circulation (2013)
Abstract 15299: Outpatient Intravenous Lasix Trial in Reducing Hospitalization for Acute Decompensated Heart Failure (OUTLAST)
Authors: Carine E Hamo, Sahar S Abdelmoneim, Seol Young Han, Elizabeth Chandy, Cornelia Muntean, Saadat A Khan, Prasanthi Sunkesula, Marcella Meykler, Ramachandran Vidhya, Rosenberg Emelie, Igor Klem, Terrence Sacchi, John F Heitner
Journal: Circulation (2020)

Introduction: Hospitalization for acute decompensated heart failure (ADHF) remains a major source of morbidity and mortality. While previous studies have shown outpatient intravenous (IV) diuretic therapy to be safe and cost-effective, there have been no randomized controlled trials to evaluate the utilization of continued outpatient IV furosemide diuretic maintenance treatment in patients with HF following hospitalization for ADHF. Hypothesis: We hypothesized that 30-day hospital readmission from ADHF would be lower with routine, standardized outpatient IV diuretic treatment along with a comprehensive HF care approach vs standard treatment. Methods: In a single center, prospective, randomized, double-blind study, 100 patients were randomized to receive standard of care (Group 1), IV placebo infusion (Group 2), or IV furosemide infusion (Group 3) over 3 hours, biweekly for a one-month period following hospitalization for ADHF. Patients in Groups 2 and 3 also received a comprehensive HF care protocol including bi-weekly clinic visits for dose-adjusted IV-diuretics, medication adjustment, laboratory, weight, and blood pressure-monitoring, and education during infusion visits. Echocardiography, Kansas City Cardiomyopathy Questionnaire (KCCQ) and depression questionnaires were performed at baseline and 30-day follow-up. The primary outcome was 30-day re-hospitalization for ADHF. Results: Overall, a total of 94 patients were included in the study (mean age 64 years, 56% males, 69% African American, 70% HF reduced ejection fraction). There were a total of 14 (15%) readmissions for ADHF at 30 days, 6 (17.1%) in Group 1, 7 (22.6%) in Group 2, and 1 (3.7%) in Group 3 (overall p=0.11; p=0.037 comparing Group 2 and Group 3). Patients receiving IV furosemide infusion experienced significantly greater urine output and weight loss compared to those receiving placebo without any significant increase creatinine and no significant between group differences in echocardiography parameters, KCCQ or depression scores. Conclusions: The use of a standardized protocol of outpatient IV furosemide infusion for a one-month period following hospitalization for ADHF was found to be safe and efficacious in reducing 30-day re-hospitalization.
An oral antisense oligonucleotide for PCSK9 inhibition
Authors: Peter Gennemark, Katrin Walter, Niclas Clemmensen, Dinko Rekić, Catarina A.M. Nilsson, Jane Knöchel, Mikko Hölttä, Linda Wernevik, Birgitta Rosengren, Dorota Kakol-Palm, Yanfeng Wang, Rosie Z. Yu, Richard S. Geary, Stan J. Riney, Brett P. Monia, Rikard Isaksson, Rasmus Jansson-Löfmark, Cristina S. J. Rocha, Daniel Lindén, Eva Hurt-Camejo, Rosanne Crooke, Lloyd Tillman, Tina Rydén-Bergsten, Björn Carlsson, Ulf Andersson, Marie Elebring, Anna Tivesten, Nigel Davies
Journal: Science Translational Medicine (2021)

Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce low-density lipoprotein (LDL) cholesterol and are used for treatment of dyslipidemia. Current PCSK9 inhibitors are administered via subcutaneous injection. We present a highly potent, chemically modified PCSK9 antisense oligonucleotide (ASO) with potential for oral delivery. Past attempts at oral delivery using earlier-generation ASO chemistries and transient permeation enhancers provided encouraging data, suggesting that improving potency of the ASO could make oral delivery a reality. The constrained ethyl chemistry and liver targeting enabled by N-acetylgalactosamine conjugation make this ASO highly potent. A single subcutaneous dose of 90 mg reduced PCSK9 by >90% in humans with elevated LDL cholesterol and a monthly subcutaneous dose of around 25 mg is predicted to reduce PCSK9 by 80% at steady state. To investigate the feasibility of oral administration, the ASO was coformulated in a tablet with sodium caprate as permeation enhancer. Repeated oral daily dosing in dogs resulted in a bioavailability of 7% in the liver (target organ), about fivefold greater than the plasma bioavailability. Target engagement after oral administration was confirmed by intrajejunal administration of a rat-specific surrogate ASO in solution with the enhancer to rats and by plasma PCSK9 and LDL cholesterol lowering in cynomolgus monkey after tablet administration. On the basis of an assumption of 5% liver bioavailability after oral administration in humans, a daily dose of 15 mg is predicted to reduce circulating PCSK9 by 80% at steady state, supporting the development of the compound for oral administration to treat dyslipidemia.
Novel point-of-care biomarker combination tests to differentiate acute bacterial from viral respiratory tract infections to guide antibiotic prescribing: a systematic review
Authors: Henry C. Carlton, Jelena Savović, Sarah Dawson, Philip J. Mitchelmore, Martha M.C. Elwenspoek
Journal: Clinical Microbiology and Infection (2021)

BackgroundAcute respiratory tract infections (RTIs) are the most common reason to seek medical care, with many patients receiving inappropriate antibiotics. Novel testing approaches to identify aetiology at the point-of-care are required to accurately guide antibiotic treatment.ObjectiveTo assess the diagnostic accuracy of biomarker combinations to rapidly differentiate between acute bacterial or viral RTI aetiology.Data sourcesMEDLINE, Embase and Web of Science databases were searched to February 2021.Study eligibility criteriaDiagnostic accuracy studies comparing accuracy of point-of-care and rapid diagnostic tests in primary or secondary care, consisting of biomarker combinations, to identify bacterial or viral aetiology of RTI.MethodsRisk of bias was assessed using the QUADAS-2 tool. Sensitivity and specificity of tests reported by more than one study were meta-analysed using a random effects model.ResultsTwenty observational studies (3514 patients) were identified. Eighteen were judged at high risk of bias. For bacterial aetiologies, sensitivity ranged from 61% to 100% and specificity from 18% to 96%. For viral aetiologies, sensitivity ranged from 59% to 97% and specificity from 74% to 100%. Studies evaluating two commercial tests were meta-analysed. For ImmunoXpert, the summary sensitivity and specificity were 85% (95% CI 75%–91%, k = 4) and 86% (95% CI 73%–93%, k = 4) for bacterial infections, and 90% (95% CI 79%–96%, k = 3) and 92% (95% CI 83%–96%, k = 3) for viral infections, respectively. FebriDx had pooled sensitivity and specificity of 84% (95% CI 75%–90%, k = 4) and 93% (95% CI 90%–95%, k = 4) for bacterial infections, and 87% (95% CI 72%–95%; k = 4) and 82% (95% CI 66%–86%, k = 4) for viral infections, respectively.ConclusionCombinations of biomarkers show potential clinical utility in discriminating the aetiology of RTIs. However, the limitations in the evidence base, due to a high proportion of studies with high risk of bias, preclude firm conclusions. Future research should be in primary care and evaluate patient outcomes and cost-effectiveness with experimental study designs.Clinical trialPROSPERO registration number: CRD42020178973.
Standardized Uptake Value Illuminates Tumor Inflammation and Treatment Response
Authors: Casey W. Williamson, Dmitriy Zamarin, Jyoti Mayadev
Journal: Clinical Cancer Research (2021)

Maximum standardized uptake value (SUVmax) on PET imaging is prognostic in cervical cancer. It was recently demonstrated that low pretreatment SUVmax is associated with superior prognosis and is correlated with decreased inflammatory signaling and myeloid-derived cell infiltration into the tumor microenvironment, potentially identifying susceptibility to targeted therapies.See related article by Floberg et al., p. 4245.
Brief Report: Diagnosing the Tight Building Syndrome
Authors: Sherry A. Rogers
Journal: Environmental Health Perspectives (1987)

Over the last 6 years, increasing numbers of patients have presented with symptoms reminiscent of these UFFI victims (5), but they had no history of UFFI exposure (6, 7). Measurements of ambient levels of formaldehyde have shown that new mobile homes, newly constructed homes with particleboard subflooring, offices recently renovated with paneling or prefabricated walls, new clothing, or even new carpeting or new furnishings, and homes with new beds and cabinetry can accumulate as much formaldehyde, as a result of offgassing, as a UFFI home (8-11). A variety of other commonly encountered volatile substances are capable of inducing the same symptoms (12->5). For example, the mean reported levels for formaldehyde in indoor air in residences was 0.03 ppm for houses without UFFI and 0.12 ppm for houses with UFFI (with and without complaints) (h1). Some mobile homes had levels of 0.4 ppm, and the mean level for several hospitals was 0.55 ppm. Guidelines are needed to facilitate diagnosis and identification of the triggering agents. Attacks of headache, nausea, inability to concentrate, mental obtundation, dizziness, lethargy, arrhythmia, flushing, laryngitis, dopiness, irritability, dysphonia, unwarranted depression, arthralgia, and extreme weakness, although nonspecific, are some of the most common symptoms of EI and frequently lead to a sequence of diagnostic evaluations which are ineffective; psychiatric evaluation is often suggested. With proper questioning, the victim will often be able to associate the onset of disease with the purchase of new carpeting, furniture, beds, cabinets, renovation of Diagnosing the Tight Building Syndrome
Abstract 16930: Despite Prior Results, Heart Transplant Recipients Over 70 Have Worse Survival Outcomes Based on the 2019 United Network for Organ Sharing Database
Authors: Jay Kanaparthi, Mohammed Kashem, Manish Suryapalam, Yoshiya Toyoda
Journal: Circulation (2020)

Introduction: As the prevalence of heart failure increases by age, it is critical we understand the role of heart transplantation (HTx) in older patients. Recent long term studies have indicated no difference in HTx outcomes between recipients 70 years or older and those ages 60-69. But these studies included data from the 1980-90s, introducing significant variance due poorer outcomes across age groups in that era. We analyzed the most recent United Network for Organ Sharing (UNOS) database, stratified by time frames before and after 2000, to demonstrate this statistical discrepancy and derive a more representative comparison of modern survival by age group. Hypothesis: HTx recipients 70+ years old may not actually have comparable survival to those 60-69 years of age, when assessing more recent HTx data. Methods: All UNOS HTx recipients over 60 years of age (n=20,446) were divided into 2 cohorts: those 60-69 and those ≥70 years old, which were analyzed over two time frames: transplant date 1987-1999 and 2000-2019. Demographic data (gender, ethnicity, BMI) as well as peri-operative factors (ICU stay, ischemic time, and length of stay) were evaluated for significance using Chi-Squared and H-Tests as appropriate. Kaplan-Meier Curve with log-rank tests were used to assess 10 year survival outcomes. Results: 19,129 patients were 60-69 years old, and 1,317 were ≥70 years old, with mean ages of 64.0±2.7 and 71.3±1.6 years respectively. The distribution of demographic and peri-operative factors was significantly different between the cohorts, with p&lt;0.05 for values. Survival analysis indicated no significance in the earlier timeframe (1987-1999) with p=0.341, but indicated significance in the later timeframe (2000-2019), with p=0.004. Conclusion: The results indicate that since 2000, recipients 60-69 years of age have better 10- year post transplant survival than older recipients, a relationship previously obscured by worse outcomes in early data.
XCR1+ type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis
Authors: Aleksandra Deczkowska, Eyal David, Pierluigi Ramadori, Dominik Pfister, Michal Safran, Baoguo Li, Amir Giladi, Diego Adhemar Jaitin, Oren Barboy, Merav Cohen, Ido Yofe, Chamutal Gur, Shir Shlomi-Loubaton, Sandrine Henri, Yousuf Suhail, Mengjie Qiu, Shing Kam, Hila Hermon, Eylon Lahat, Gil Ben Yakov, Oranit Cohen-Ezra, Yana Davidov, Mariya Likhter, David Goitein, Susanne Roth, Achim Weber, Bernard Malissen, Assaf Weiner, Ziv Ben-Ari, Mathias Heikenwälder, Eran Elinav, Ido Amit
Journal: Nature Medicine (2021)