tbuckley/cabot-search huggingface dataset:
Abstract MP017: Association of Change in Plasminogen Activator Inhibitor-1 Through Young Adulthood With Metabolic Disease in Middle Age: the Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Sadiya S Khan, Douglas E Vaughan, Laura A Colangelo, Kiang Liu, James M Shikany, Donald M Lloyd-Jones
Journal: Circulation (2017)

Introduction: Circulating plasminogen activator inhibitor-1 (PAI-1) levels are elevated in obesity and diabetes mellitus (DM) in cross-sectional studies. Preclinical studies support a role for PAI-1 in obesity development and insulin signaling. To date, no studies have investigated the prospective association of PAI-1 in young adults with incident obesity and DM. Hypothesis: Higher PAI-1 concentrations and greater increases in PAI-1 during young adulthood are associated with higher incidence of obesity and diabetes. Methods: We performed an ancillary study in CARDIA measuring PAI-1 in plasma at exam year (Y) 7 and Y20 in a subset of 1200 participants (ppts) free of obesity and DM at Y7. Multivariable logistic regression was used to examine the association between PAI-1 at Y7 and change from Y7 to Y20 with incident obesity and diabetes by Y30. Covariates for adjustment included demographics (age, race, sex, center, education), lifestyle risk factors (physical activity, energy intake, smoking), metabolic traits (BMI, fasting glucose [for DM]), and Y7 PAI-1 level. Results: At Y7, ppts (32±4 years, 54% female, 37% black) had mean BMI 24.5±3 kg/m 2 , fasting glucose 89±8 mg/dL, and median PAI-1 14 (IQR: 8-24) ng/mL. Median change in PAI-1 from Y7 to Y20 was +10.0 ng/mL (IQR: +1.0-28.0 ng/dL). Each 1 standard deviation higher ln(PAI-1) at Y7 was associated with an adjusted hazards ratio for incident DM of 1.35 (95% CI: 1.09-1.67). Each 1 standard deviation greater increase in PAI-1 from Y7 to Y20 was associated with an adjusted odds ratio (OR) for incident obesity and DM of 1.21 (1.02-1.43) and 1.36 (1.10-1.68), respectively. When examined by quartiles, the highest (vs. lowest) quartile of Y7 to Y20 PAI-1 change was associated with an adjusted OR of 2.37 (1.33-4.21) for incident obesity and 3.11 (1.45-6.68) for incident DM by Y30, independent of Y7 BMI and PAI-1 (FIGURE) . Conclusions: Higher plasma PAI-1 levels and greater increases in PAI-1 during young adulthood are positively associated with incident obesity and DM by middle age.
Birth weight and cardiovascular disease: The NHLBI Family Heart Study
Authors: Luc Djousse, Yuling Hong, Donna K Arnett, University of Minnesota, Steven C Hunt, Gerardo Heiss, R. Curtis Ellison
Journal: Circulation (2001)

P66 Epidemiologic studies have been inconsistent on the association between low birth weight and increased risk of cardiovascular disease (CVD). Little is known about potential mechanisms by which determinants of low birth weight affect CVD. We used data collected on 2,540 participants of the NHLBI Family Heart Study to assess the relation of birth weight to CVD, hypertension, and diabetes mellitus. Birth weight was obtained by self report. CVD was defined as positive history of myocardial infarction, coronary angioplasty, coronary bypass surgery, congestive heart failure, or stroke. Hypertension was defined as systolic blood pressure of at least 140 mm Hg, or diastolic pressure of at least 90 mm Hg, or use of antihypertensive medication. Diabetes mellitus was ascertained by medical history and pathologic blood sugar levels. We used generalized estimating equations to assess the prevalence odds ratios, adjusting for age, risk group, anthropometric, metabolic, and lifestyle factors. Prevalence odds ratios (95% CI) are presented below. Low birth weight was associated with increased prevalence odds of CVD compared with normal and large babies (p=0.0012). The trend was suggestive of increased prevalence odds of hypertension (p=0.05) and diabetes mellitus (p=0.0012) from the highest to the lowest category of birth weight. In conclusion, low birth weight was associated with increased prevalence odds ratio of CVD, diabetes mellitus, and hypertension. Low birth weight may add to other traditional risk factors in identifying subjects at low and high risk of CVD. Table 1.
Apolipoprotein E and Alzheimer's disease
Authors: Benjamin R. Troutwine, Laylan Hamid, Colton R. Lysaker, Taylor A. Strope, Heather M. Wilkins
Journal: Acta Pharmaceutica Sinica B (2021)

Genetic variation in apolipoprotein E (APOE) influences Alzheimer's disease (AD) risk. APOE ε4 alleles are the strongest genetic risk factor for late onset sporadic AD. The AD risk is dose dependent, as those carrying one APOE ε4 allele have a 2-3-fold increased risk, while those carrying two ε4 alleles have a 10-15-fold increased risk. Individuals carrying APOE ε2 alleles have lower AD risk and those carrying APOE ε3 alleles have neutral risk. APOE is a lipoprotein which functions in lipid transport, metabolism, and inflammatory modulation. Isoform specific effects of APOE within the brain include alterations to Aβ, tau, neuroinflammation, and metabolism. Here we review the association of APOE with AD, the APOE isoform specific effects within brain and periphery, and potential therapeutics.
A Spheroid Model of Early and Late‐Stage Osteosarcoma Mimicking the Divergent Relationship between Tumor Elimination and Bone Regeneration
Authors: Fiona E. Freeman, Ross Burdis, Olwyn R. Mahon, Daniel J. Kelly, Natalie Artzi
Journal: Advanced Healthcare Materials (2021)

Osteosarcoma is the most diagnosed bone tumor in children. The use of tissue engineering strategies after malignant tumor resection remains a subject of scientific controversy. As a result, there is limited research that focuses on bone regeneration postresection, which is further compromised following chemotherapy. This study aims to develop the first co-culture spheroid model for osteosarcoma, to understand the divergent relationship between tumor elimination and bone regeneration. By manipulating the ratio of stromal to osteosarcoma cells the modelled cancer state (early/late) is modified, as is evident by the increased tumor growth rates and an upregulation of a panel of well-established osteosarcoma prognostic genes. Validation of the authors' model is conducted by analyzing its ability to mimic the cytotoxic effects of the FDA-approved chemotherapeutic Doxorubicin. Next, the model is used to investigate what effect osteogenic supplements have, if any, on tumor growth. When their model is treated with osteogenic supplements, there is a stimulatory effect on the surrounding stromal cells. However, when treated with chemotherapeutics this stimulatory effect is significantly diminished. Together, the results of this study present a novel multicellular model of osteosarcoma and provide a unique platform for screening potential therapeutic options for osteosarcoma before conducting in vivo experiments.
Health and economic benefits of achieving hepatitis C virus elimination in Pakistan: A modelling study and economic analysis
Authors: Aaron G. Lim, Nick Scott, Josephine G. Walker, Saeed Hamid, Margaret Hellard, Peter Vickerman
Journal: PLoS Medicine (2021)

Background Modelling suggests that achieving the WHO incidence target for hepatitis C virus (HCV) elimination in Pakistan could cost US$3.87 billion over 2018 to 2030. However, the economic benefits from integrating services or improving productivity were not included. Methods and findings We adapt a HCV transmission model for Pakistan to estimate the impact, costs, and cost-effectiveness of achieving HCV elimination (reducing annual HCV incidence by 80% by 2030) with stand-alone service delivery, or partially integrating one-third of initial HCV testing into existing healthcare services. We estimate the net economic benefits by comparing the required investment in screening, treatment, and healthcare management to the economic productivity gains from reduced HCV-attributable absenteeism, presenteeism, and premature deaths. We also calculate the incremental cost-effectiveness ratio (ICER) per disability-adjusted life year (DALY) averted for HCV elimination versus maintaining current levels of HCV treatment. This is compared to an opportunity cost-based willingness-to-pay threshold for Pakistan (US$148 to US$198/DALY). Compared to existing levels of treatment, scaling up screening and treatment to achieve HCV elimination in Pakistan averts 5.57 (95% uncertainty interval (UI) 3.80 to 8.22) million DALYs and 333,000 (219,000 to 509,000) HCV-related deaths over 2018 to 2030. If HCV testing is partially integrated, this scale-up requires an investment of US$1.45 (1.32 to 1.60) billion but will result in US$1.30 (0.94 to 1.72) billion in improved economic productivity over 2018 to 2030. This elimination strategy is highly cost-effective (ICER = US$29 per DALY averted) by 2030, with it becoming cost-saving by 2031 and having a net economic benefit of US$9.10 (95% UI 6.54 to 11.99) billion by 2050. Limitations include uncertainty around what level of integration is possible within existing primary healthcare services as well as a lack of Pakistan-specific data on disease-related healthcare management costs or productivity losses due to HCV. Conclusions Investment in HCV elimination can bring about substantial societal health and economic benefits for Pakistan.
Pre-existing infant antibody-dependent cellular cytotoxicity associates with reduced HIV-1 acquisition and lower morbidity
Authors: Allison S Thomas, Yvetane Moreau, Wenqing Jiang, John E Isaac, Alexander Ewing, Laura F White, Athena P Kourtis, Manish Sagar
Journal: Cell Reports Medicine (2021)

In humans, pre-existing anti-HIV-1 neutralizing antibodies (nAbs) have not been associated with decreased HIV-1 acquisition. Here, we evaluate antibody-dependent cellular cytotoxicity (ADCC) present in pre-transmission infant and maternal plasma and breast milk (BM) against the contemporaneous maternal HIV-1 variants. HIV-1-exposed uninfected compared with HIV-1-exposed infected infants have higher ADCC and a combination of ADCC and nAb responses against their corresponding mother's strains. ADCC does not correlate with nAbs, suggesting they are independent activities. The infected infants with high ADCC compared with low ADCC, but not those with higher ADCC plus nAbs, have lower morbidity up to 1 year after birth. A higher IgA to IgG ratio, observed in BM supernatants and in a higher proportion of the infected compared with the uninfected infants, associates with lower ADCC. Against the exposure strains, ADCC, more than nAbs, associates with both lower mother-to-child transmission and decreased post-infection infant morbidity.
Genetic Variants Affecting Dopamine Signaling and Cognitive Impairment After Mechanical Ventilation
Authors: Laura Amado Rodríguez, Inés López Alonso, Jorge Blázquez Prieto, Adrián González López, Covadonga Huidobro Fernández, F. Ding, G. Tang, P. Pandharipande, E. Ely, Guillermo Muñiz Albaiceta, T. D. Girard
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
Genomic analysis of maternal carriage of group B Streptococcus and transmission routes of neonatal sepsis
Authors: Chien-Chung Lee, Ye Feng, Chyi-Liang Chen, Yuan-Ming Yeh, Mei-Hua Hsu, Wan-Ting Liao, Ying-Li Zhou, Petrus Tang, Cheng-Hsun Chiu
Journal: Journal of Infection (2021)
Association Between Baseline Diastolic Blood Pressure and the Efficacy of Intensive vs Standard Blood Pressure–Lowering Therapy
Authors: Andrew J. Foy, Edward J. Filippone, Eric Schaefer, Matt Nudy, Mohammed Ruzieh, Anne-Marie Dyer, Vernon M. Chinchilli, Gerald V. Naccarelli
Journal: JAMA Network Open (2021)

Low diastolic blood pressure (DBP) has been found to be associated with increased adverse cardiovascular events; however, it is unknown whether intensifying blood pressure therapy in patients with an already low DBP to achieve a lower systolic blood pressure (SBP) target is safe or effective.To evaluate whether there is an association of baseline DBP and intensification of blood pressure-lowering therapy with the outcomes of all-cause death and cardiovascular events.This cohort study analyzed patients who were randomized to intensive or standard BP control in the Action to Control Cardiovascular Risk in Diabetes-Blood Pressure (ACCORD-BP) trial and Systolic Blood Pressure Intervention Trial (SPRINT). Data were collected from September 1999 to June 2009 (ACCORD-BP) and from October 2010 to August 2015 (SPRINT). Data were analyzed from December 2020 to June 2021.Baseline DBP as a continuous variable.All-cause death and a composite cardiovascular end point (CVE) that included cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.A total of 14 094 patients (mean [SD] age, 66.2 [8.9] years; 8504 [60.4%] men) were included in this analysis. There were significant nonlinear associations between baseline DBP and all-cause death (eg, baseline DBP 50 vs 80 mm Hg: hazard ratio [HR], 1.48; 95% CI, 1.06-2.08; P = .02) and the composite CVE (eg, baseline DBP 50 vs 80 mm Hg: HR, 1.45; 95% CI, 1.27-3.04; P = .003) observed among all participants. Findings for the interaction between baseline DBP and treatment group assignment for all cause death did not reach statistical significance. For intensive vs standard therapy, the HR of death for a baseline DBP of 50 mm Hg was 1.80 (95% CI, 0.95-3.39; P = .07) and that for a baseline DBP of 80 mm Hg was 0.77 (95% CI, 0.59-1.01; P = .05). Overall, there was no interaction found between baseline DBP and treatment group assignment for the composite CVE. Over the range of baseline DBP values, significant reductions in the composite CVE for patients assigned to intensive vs standard therapy were found for baseline DBP values of 80 mm Hg (HR, 0.78; 95% CI, 0.62-0.98; P = .03) and 90 mm Hg (HR, 0.74; 95% CI, 0.55-0.98; P = .04).This pooled cohort study found no evidence of a significant interaction between baseline DBP and treatment intensity for all-cause death or for a composite CVE. These results are hypothesis generating and merit further study.
Covid-19: Prevalence rises among schoolchildren in England
Authors: Elisabeth Mahase
Journal: BMJ (2021)

An estimated one in 120 people in England were infected with SARS-CoV-2 in September, shows a study of more than100 000 volunteers. 1 The latest report from the React-1 study, published on 14 October by Imperial College London and the pollster Ipsos MORI, said that between 9 and 27 September 2021 a total of 764 positive results came from 100 527 swabs, giving a weighted prevalence of 0.83%.The authors said that prevalence seems to be remaining fairly stable overall, with the infection rate growing among under 18s (R number of 1.18) and falling among those aged 18-54 (R=0.81).Other notable findings from the report included that:• Prevalence was higher in people of black ethnicity (1.41%) than white (0.78%) • Prevalence was higher in larger households, ranging from 0.33% in single person households to 1.75% in households with six or more people• Prevalence was also higher in households with children (1.37%) than in those without children (0.4%) • Prevalence was 0.56% in people reporting two doses of vaccine and 1.73% in unvaccinated people, and • Overall effectiveness of vaccines against infection was estimated at 63% to 66%.Ipsos MORI's managing director for public affairs, Kelly Beaver, said, "While the rise since our last React-1 round in prevalence is concerning, it is encouraging that there has not been a commensurate rise in hospitalisations and deaths from covid-19."The React study programme director at Imperial, Paul Elliott, said, "Our latest data show that infections are high and rising in school aged children.Households with children also had a higher prevalence of infection, suggesting that children may be passing on the virus to those that they live with.These trends reinforce how important it is for children aged 12 and above to get vaccinated and help curb the spread of infection and minimise disruption to education." 1 UK Health Security Agency.REACT-1 study of coronavirus transmission: September 2021 final results.
P60.11 Trends in Molecular Testing for Metastatic Non-Small Cell Lung Cancer in The US Oncology Network Community Practices
Authors: N. Robert, L. Chen, J. Espirito, M. Karhade, E. Nwokeji, M. Evangelist, A. Spira, M. Neubauer, S. Bullock, R. Coleman
Journal: Journal of Thoracic Oncology (2021)
Non-18F-FDG-Avid Intrahepatic Metastasis of Breast Cancer Revealed by 68Ga-FAPI PET/CT
Authors: Qixin Wang, Wenxin Tang, Liang Cai, Yue Chen
Journal: Clinical Nuclear Medicine (2021)

A patient with intrahepatic breast cancer metastasis underwent both 18F-FDG and 68Ga-FAPI PET/CT. However, the lesions are only 68Ga-FAPI avid. Our case illustrates that 68Ga-FAPI PET/CT can be more sensitive in detecting intrahepatic metastasis of breast cancer in some cases.
Role of club doctors in the mental health management of Australian rules football players: a Delphi study
Authors: Ben Weber, Jason Bos, Elizabeth Mary Clancy, Ranjit Menon, Tom Cross, Kate Hall
Journal: British Journal of Sports Medicine (2021)

Professional team athletes experience a range of mental health problems, both sports and non-sports related. However, there is limited information available for those charged with responsibility for managing these mental health conditions, particularly within the context of professional sporting clubs. This paper reports on consensus findings from a study of club doctors, who are primary care providers for professional team athletes within a specific code, the Australian Football League (AFL). Drawing on findings from a systematic literature search, a two-round Delphi procedure was used to develop a consensus on best practice for managing mental health conditions for club doctors as primary care providers for professional team athletes. Participants in this study were current and former club doctors employed in professional AFL clubs across Australia, with 28 doctors participating across two survey rounds. Overall, 77 statements were presented, with 50 endorsed as essential or important by ≥ 80% of the participants across the two rounds. Primary themes across nine domains include: (1) Prevention and Mental Health Promotion Activities; (2) Screening; (3) Engaging External Specialists; (4) Duty of Care; (5) Treatment: Assessment, Treatment and Case Coordination; (6) Communication; (7) Confidentiality; (8) Sleep Management and (9) Substance Use Management. This study is the first to offer club doctors working in professional team settings consensus guidelines for the management of mental health conditions, and the opportunity for greater clarification and consistency in role delivery.
<i>Helicobacter pylori</i>infection disturbs the tumor immune microenvironment and is associated with a discrepant prognosis in gastric de novo diffuse large B-cell lymphoma
Authors: Yuwei Deng, Wenjia Su, Junwen Zhu, Hongfei Ji, Xiaoping Zhou, Jingshu Geng, Jiayu Zhu, Qingyuan Zhang
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Gastric diffuse large B-cell lymphoma (gDLBCL) related to Helicobacter pylori infection exhibits a wide spectrum of prognosis, and the tumor immune microenvironment (TIME) affects tumor progression. However, there are few studies on the correlation between prognosis and changes of TIME induced by H. pylori infection in de novo gDLBCL. Methods A retrospective study was performed to determine the prognostic value of TIME related to H. pylori infection in de novo gDLBCL. A total of 252 patients were included and have been treated with standard rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy or other similar regimens in addition to H. pylori eradication (HPE). All patients were stratified by H. pylori infection, HPE efficacy, and preliminary TIME evaluation using conventional criteria. Statistical analyses were conducted. To assess the mechanism, 30 subjects were assessed for H. pylori infection. The components and spatial distributions of TIME were analyzed. Results The median follow-up of the 252 patients was 66.6 months (range 0.7–119.2), and the 5-year overall survival (OS) was 78.0%. A total of 109 H . pylori- positive cases with pathological complete remission and high tumor-infiltrating T lymphocytes (cohort 1) had significantly higher 5-year progression-free survival (88.1% vs 70.5%, p&lt;0.001) and OS (89.2% vs 76.6%, p&lt;0.001) than the other 143 patients (cohort 2). Among 30 patients, 19 were cytotoxin-associated gene A-marked as the cohort 1 subset. Compared with cohort 2, cohort 1 exhibited increased inflammatory factors (tumor necrosis factor-α, interferon γ, etc) and decreased immunosuppressive components (PD-L1, PD-1, IL-10, etc). There was reduced NF-kB activation. Cancer-promoting immune cells (PD-1hiTim-3+ CTL, Tregs, M2-like macrophages, etc) occupied a minor spatial distribution, while the antitumor subtypes increased, corresponding to favorable survival. Conclusion H. pylori- evoked inflammatory responses disturb the TIME, causing a differential prognosis in de novo gDLBCL, which can be used to identify patients who could benefit from HPE and immunochemotherapy.
OA09.02 Atezo-Brain: Single Arm Phase II Study of Atezolizumab Plus Chemotherapy in Stage IV NSCLC With Untreated Brain Metastases
Authors: E. Nadal, B. Massuti, G. Huidobro, R. Lopez Castro, A. Estival, J. Mosquera, I. Sullivan, E. Felip, A. Blasco, M. Guirado, M. Simó, E. Pereira, V. Navarro, J. Bruna
Journal: Journal of Thoracic Oncology (2021)
Abstract 22: When Laws Save Lives: Impact of Legislation Requiring Cardiopulmonary Resuscitation Education in High Schools on Survival After Sudden Cardiac Arrest
Authors: Victoria L Vetter, Katherine F Dalldorf, Joseph Rossano, Maryam Y Naim, Andrew C Glatz, Kimberly Vellano, Bryan McNally, Heather Griffis
Journal: Circulation (2018)

Introduction: Thirty eight states have laws requiring education of high school students on cardiopulmonary resuscitation (CPR) and the use of automated external defibrillators (AED). No study has measured the association of these laws and outcomes. Hypothesis: Out of hospital cardiac arrests (OHCAs) occurring in states with CPR high school education laws will have higher bystander CPR, survival, and favorable neurological survival than states without such laws. Methods: We conducted an analysis of the Cardiac Arrest Registry to Enhance Survival database and included all nontraumatic OHCAs with at least 50% population catchment from 1/2013-12/2017 in all ages. We excluded OHCAs witnessed by 911 responders, in healthcare facilities, or nursing homes. Outcomes were bystander CPR, survival to hospital discharge and neurologically favorable survival (Cerebral Performance Category score of 1 or 2 at hospital discharge). Chi-square tests were used to assess associations. Results: The 110,902 subjects with OHCA included Male, 64.0%; &lt;18 yrs., 3.2%; &lt;35 yrs., 10.7%; &lt;50 yrs., 23.9%; White, 49.3%; Black, 19.1%; Hispanic, 2.3%; Other, 2.9%; Unknown, 26.5%. Most OHCAs occurred at home, 81.4%. 44.4% were witnessed by bystanders. 75.5% occurred in states with CPR high school education laws. A higher percent of OHCAs received bystander CPR prior to emergency medical services (EMS) arrival in states with CPR high school education laws (40.1%) compared to states without laws (37.0%) (p&lt;0.001). Bystander CPR was less common in males (40.3% vs. 37.7% for females), those &gt;50 yrs. (38.9% vs. 40.7% for ≤50 yrs.), Black and Hispanic subjects (25.7% and 34.9%, respectively, vs. 42.4% for Whites) (p&lt;0.001 for all). Overall survival to hospital discharge was 10.4%; 8.8% had a favorable neurological outcome. A higher percent survived to hospital discharge in states with CPR high school education laws (11.0%) compared to states without laws (8.7%) (p&lt;0.001). Neurologically favorable survival was more likely in states with CPR high school education laws, (9.3%) compared to states without laws (7.5%) (p&lt;0.001). Conclusions: Bystander CPR, survival to hospital discharge, and neurologically favorable survival was higher in states that had CPR high school education laws.