tbuckley/cabot-search huggingface dataset:
The association between sexual orientation and screening of prevalent gender-specific cancers.
Authors: Michael Joseph Herriges, Ruben Pinkhasov, Keren Lehavot, Oleg Shapiro, Joseph M Jacob, Thomas Sanford, Nick Liu, Gennady Bratslavsky, Hanan Goldberg
Journal: Journal of Clinical Oncology (2021)

198 Background: Data on heterogeneity in cancer screening and diagnosis rates among sexual minorities (SMs) is lacking. Recent studies have shown SMs are more likely to engage in risky health behavior and have decreased healthcare utilization. However, few studies have examined how sexual orientation impacts cancer screening and prevalence. We therefore investigated whether sexual orientation affects prevalent gender-specific cancer including prostate (PCa), breast (BC), and cervical cancer (CC). Methods: This was a cross-sectional survey-based US study, including men and women aged 18+ from the Health Information National Trends Survey (HINTS) database (part of the National Cancer Institute’s division of cancer control and population sciences) between 2017-2019. The primary endpoint was individual-reported PCa, BC, and CC screening and prevalence rates among heterosexuals and homosexuals/bisexuals. Multivariable logistic regression analyses assessed association of various covariates with undergoing screening and diagnosis of these cancers. Results: Overall, 4,441 and 6,333 heterosexual men and women, respectively, were compared to 225 and 213 homosexual/bisexual men and women, respectively. Homosexuals/bisexuals were younger and less likely to be screened for PCa (34.7% vs 41.3%, p=0.013), BC (54.5% vs 80.7%, p=&lt;0.001), and CC (88.3% vs 95.4%, p=&lt;0.001). While rates of PCa and BC diagnosis were similar, more than twice as many homosexual/bisexual women were diagnosed with CC (4.2% vs 1.9%, p=0.023). Multivariable logistic regression models (Table) showed homosexuals/bisexuals were less likely to be screened for cancer with ORs of 0.61 (95% CI 0.39-0.95) for PCa, 0.52 (95% CI 0.30-0.92) for BC, and 0.21 (95% CI 0.09-0.46) for CC. Homosexuals/bisexuals were more likely to be diagnosed with any cancer with ORs of 1.64 (95% CI 1.06-2.54) in women only and 1.50 (95% CI 1.11-2.03) in men and women combined. Conclusions: Homosexuals/bisexuals in the US may be less likely to undergo screening of gender-specific prevalent malignancies, including PCa, BC, and CC. The implementation of cancer screening among SMs should be improved. [Table: see text]
Phase I with expansion clinical trial of seleno-l-methionine (SLM) in combination with axitinib in patients with relapsed clear cell renal cell carcinoma (ccRCC): Bench to bedside.
Authors: Yousef Zakharia, Ryan Reis, Rohan Garje, Umang Swami, Janelle M Born, James A. Brown, Kenneth Gerard Nepple, Bashar Abuqayas, Maheen Rajput, Andrew Bellizzi, Jessica C Sieren, Youcef M. Rustum
Journal: Journal of Clinical Oncology (2021)

322 Background: Hypoxia induced factor 1α/2α (HIFs) and vascular endothelial growth factor (VEGF) are overexpressed in ccRCC and associated with increased tumor angiogenesis, vascular instability and drug resistance. In xenografts, high dose SLM resulted in sustained down regulation of HIFs, normalization of tumor vasculature that resulted in increased drug delivery, and therapeutic synergy with anti-VEGF therapeutic. These effects were highly SLM dose, sequence, and schedule dependent. Methods: After completion of the escalating phase I (3+3) trial, the non-toxic SLM dose of 4000μg was administered orally twice daily (BID) for 14 days, followed by once daily in combination with axitinib 5 mg BID. The primary endpoint is safety and the secondary end point include overall response rate (ORR), progression free survival (PFS), and overall survival (OS). To assess the potential effects of SLM on tumor vascular function, dual energy computed tomography (DECT) was conducted at baseline, day 14 of SLM, and at 3 months of SLM + axitinib. Results: Thirty subjects are screened. Of whom 25 have efficacy data (3 subjects screen failure, 1 withdrew, 1 taken off study prior to first scan due to progression with brain lesions likely present prior to study entry). 13/25 (52%) have confirmed response (CR/PR). Two subjects had CR lasting for at least 35 and 44 months, 6 subjects achieved stable disease (SD) lasting at least 6 months accounting for disease control rate (DCR) of 76%, mPFS is 9.5 months. 5/30 patients have sarcomatoid features, all of which are evaluable for efficacy with 1 PR achieved (20%). In the 20 patients without sarcomatoid features, 12/20 achieved PR (60%). The most prevalent adverse events (AE) included fatigue, diarrhea, anorexia, nausea, hoarseness, weight loss, and hypertension. No deaths nor grade 4 toxicities observed. The blood selenium concentrations achieved in the 4000μg SLM dose cohorts are similar to those determined molecularly and therapeutically synergistic with axitinib in xenografts and are being achieved clinically without significant toxicity. DECT data demonstrated increased iodine uptake by tumor lesions, but not in normal tissues, on day 14 SLM treatment and decreased in these same lesions at 3 months of SLM/axitinib. Conclusions: Blood selenium concentrations and duration of treatment seem to be critical determinants of response. Pre and concurrent treatment with SLM enhance the ORR and PFS of axitinib, with no additional toxicity. Currently documented responses are similar across IMDC risk groups. Clinical trial information: NCT02535533 .
Abstract P268: High Large and Small Artery Elasticity Indexes Decrease the Risk to Develop Hypertension in Women: Skaraborg Hypertension Project
Authors: Bledar Daka, Margareta I Hellgren, Lennart Råstam, Ulf Lindblad
Journal: Circulation (2018)

Aims: The aim was to investigate whether non-invasive measurements of the diastolic pulse wave form predicts the incidence of hypertension in population-based cohort. Methods: Longitudinal observational study. Between 2002-2005 a sample of 2816 subjects (1400 men) was randomly invited in a cohort study with the goal to study early detection of risk factors for cardiovascular disease. The cohort was followed up between 2012-2014. The mean follow-up time was 9.9 years (±1.1) and in a representative sample of 1327 subjects the protocol was completed. Body mass index was calculated based on measurements at the study clinic. Blood pressure was measured with participants in supine position twice after five minutes rest and the mean was used in analyses. Hypertension was defined based on JNC 8, and diabetes on WHO criteria from 1999. C1 and C2 were assessed using HDI/Pulse wave CR-2000 (Eagan, MN) and were based on three repetitive measurements within 5 min with the patient in a rested supine position. The mean value of the three measurements was used for the statistical calculations. The association between C1 and C2 and systolic and diastolic blood pressure was investigated with linear regression and possible confounding was adjusted in the multivariable regression models. Results: The 99 women and 103 men with hypertension at baseline were excluded from analyses. During the follow-up 73 new cases with hypertension were found in women and 95 cases in men. Systolic and diastolic blood pressure was significantly higher at follow-up in both men and women (Men: Baseline SBP 120 (12) mmHg DBP 71 (9) mmHg; Follow-up SBP 125 (12) mmHg DBP 73 (9) mmHg- Women Baseline SBP 115 (13) mmHg DBP 67 (8) mmHg; Follow-up SBP 121 (14) mmHg DBP 70 (9) mmHg). At baseline a strong association was found between both elasticity indexes (C1 and C2) and systolic and diastolic blood pressure in both men and women. C1 was strongly and negatively associated with systolic blood pressure after adjustments for age, BMI, and baseline systolic blood pressure in both men and women (Men .β=-.15 p&lt;0.001, Women β=-.10 p=0.007). Similar results were found for diastolic blood pressure. In similar analyses for C2 was also significantly associated with systolic blood pressure at follow up (Men .β=-.11 p=0.007, Women β=-.10 p=0.013). When analyzing incident cases with hypertension we found that both C1 and C2 could predict hypertension in women but not in men in a model including age, BMI and systolic blood pressure at baseline (C1 Men OR=.97 CI .91, 1.04 Women OR=.87 CI=.79, .97 C2 Men OR=.97 CI .84, 1.03 Women OR=.85 CI=.73, .98) Conclusions: This study showed that elasticity indexes are strongly associated with systolic and diastolic blood pressure at follow-up regardless baseline blood pressure at baseline in both men and women. Moreover, high indecxes of artery elasticity C1 and C2 decrease the risk for future hypertension in women.
Estimating disease burden attributable to household air pollution: new methods within the Global Burden of Disease Study
Authors: F B Bennitt, S S Wozniak, K Causey, K Burkart, M Brauer
Journal: The Lancet Global Health (2021)

BackgroundDespite a substantial reduction in the use of solid fuels worldwide, exposure to household air pollution (HAP) from use of these fuels for cooking remains a leading risk factor for global disease burden. Among environmental risk factors, the contribution of HAP to disease burden is second only to ambient particulate matter pollution. We present updates to our modeling methodology as well as our latest findings on attributable burden estimates.MethodsWe estimated HAP-attributable burden for cataract, chronic obstructive pulmonary disease, ischaemic heart disease, lower respiratory infections, lung cancer, neonatal disorders, stroke, and type 2 diabetes for 204 countries and territories from 1990 to 2019. We used spatio-temporal Gaussian Process Regression to model data from observational surveys and censuses reporting primary cooking fuel to estimate the proportion of individuals using a specific solid-fuel type (wood, coal/charcoal, agricultural residues, or dung) by location. We converted the fuel exposure estimates to year, location, and sex/age-specific PM2·5 exposures with a regression mapping function using household air pollution measurements. Using a Bayesian meta-regression tool, we estimated relative risk as a function of PM2·5 exposure for each disease based upon a systematic review of the epidemiological literature on indoor and ambient air pollution. We then combined our exposure estimates and relative risks to estimate population attributable fractions and attributable burden for each cause.FindingsIn 2019, 91·5 million global disability-adjusted life years (DALYs) (95% uncertainty interval 67·0–119) were attributable to HAP, a decline of more than 50% from 1990. We estimated 2·31 million (1·63–3·12) global deaths were attributable to HAP and accounted for over 4% of all deaths in 2019. HAP-attributable burden remains highest in sub-Saharan Africa and south Asia, with 3770·3 (2876·4–4720·2) and 2068·0 (1412·5–2799·7) age-standardised DALYs per 100 000 population, respectively.InterpretationAlthough the disease burden attributable to HAP decreased considerably between 1990 and 2019, it remains a significant risk factor. Our internally consistent methodology and comprehensive approach to estimation of HAP-attributable burden provides a robust resource for global health interventions. Efforts to transition to cleaner household energy sources should be accelerated.FundingBill & Melinda Gates Foundation.
Abstract IA-08: High parameter single cell analysis has driven deep understanding of immune processes
Authors: Garry P. Nolan
Journal: Clinical Cancer Research (2021)

Abstract High parameter single cell analysis has driven deep understanding of immune processes. Using a next-generation single-cell “mass cytometry” platform we quantify surface and cytokine or drug responsive indices of kinase target with 45 or more parameter analyses (e.g. 45 antibodies, viability, nucleic acid content, and relative cell size). Similarly, we have developed two advanced technologies termed MIBI and CODEX that enable deep phenotyping of solid tissue in both fresh frozen and FFPE formats (50 – 100 markers). Collectively, the systems allow for subcellular analysis from the 70nm resolution scale to whole tissue in 3D. I will present evidence of deep internal order in immune functionality demonstrating that differentiation and immune activities have evolved with a definable “shape”. Further, specific cellular neighborhoods of immune cells are now definable with unique abilities to affect cellular phenotypes—and these neighborhoods alter in various cancer disease states. In addition to cancer, these shapes and neighborhoods are altered during immune action and “imprinted” during, and after, pathogen attack, traumatic injury, or auto-immune disease. Hierarchies of functionally defined trans-cellular modules are observed that can be used for mechanistic and clinical insights in cancer and immune therapies. Citation Format: Garry P. Nolan. High parameter single cell analysis has driven deep understanding of immune processes [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr IA-08.
Abstract 11367: Is Low Flow State With Normal Left Ventricular Ejection Fraction a Clinical Disorder? Cardiac Magnetic Resonance Imaging Investigation in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Yifang Yuan, David Herrington, David Zhao, Joao Lima, Diego A Malaver, Brandon Stacey, Min Pu
Journal: Circulation (2018)

Introduction: “Low flow state” (LFS) is defined as stroke volume index (SVi) <35 ml/m2. LFS has been used for classification and management of symptomatic low-flow low-gradient aortic stenosis with...
Short-term preoperative nutritional intervention for cleft lip and/or palate surgery eligibility: an effectiveness evaluation in six countries
Authors: Shady Said, Lily Chattopadhyay, Melissa DiBona, Charlotte Steppling, Dede Kwadjo, Mamy Ramamonjisoa, Wendy Gallardo, Fatima Almenfarez, Samanta Rosales, Ibrahim Nthalika, William Magee, Allyn Auslander
Journal: The Lancet Global Health (2021)

BackgroundChildren with cleft lip and/or palate (CL/P) are highly susceptible to malnutrition, which can restrict their ability to receive safe surgery. Ready-to-use therapeutic foods (RUTF) are an effective treatment for children with malnutrition; however, the effectiveness of short-term nutritional supplementation in preparing patients for cleft surgery has not been demonstrated. We studied the effectiveness of RUTF in transitioning malnourished patients with CL/P, who were initially ineligible for surgery, into surgical candidates.MethodsA cohort of patients with CL/P who were initially deemed ineligible for surgery due to malnutrition from Ghana, Honduras, Malawi, Madagascar, Nicaragua, and Venezuela was followed by Operation Smile. Patients were enrolled in a nutrition program that provided RUTF packets and tracked age, weight, and height at each visit. A WHO Z score was calculated for each patient to longitudinally track malnutrition status. Patients were considered eligible for surgery when their Z scores were in the normal range (Z>–1). The study was part of a collaborative programme between Operation Smile (NGO), Birdsong Peanuts (peanut shellers and distributors), and MANA Nutrition (RUTF producer).Findings556 patients were recruited between June, 2017, and January, 2020. Initially, 28·2% (n=157) were diagnosed with severe malnutrition, 21·0% (n=117) with moderate malnutrition, and 50·7% (n=282) with mild malnutrition. Most patients (325 [66·4%]) presented for at least one return visit. Of patients who returned, 207 (56·1%) became eligible for surgery; 32 (15·5%) initially with severe malnutrition, 30 (14·5%) with moderate malnutrition, and 145 (70·0%) with mild malnutrition. By the second visit, the mean Z score increased significantly from −2·5 (moderate malnutrition) to −1·7 (mild malnutrition) (p<0·001). Mean time to attain surgical eligibility from enrolment was 6 weeks (range 1–103 weeks). There was a significant difference in the proportion of patients who became eligible by country (p<0·001).InterpretationMalnutrition prevents many children with CL/P in low-income and middle-income countries from receiving surgical care, even when provided for free, creating a larger disparity in access to surgery. In an average of 6 weeks with an approximate cost of US $30 per patient, RUTF transitioned over half of these patients into safe surgical candidates, making it an effective short-term preoperative nutritional intervention. Through unique partnerships, the expansion of cost-effective, large-scale nutrition programmes can play a pivotal role in ensuring those at the highest risk of living with unrepaired CL/P receive timely and safe surgical care.FundingBirdsong Peanuts.
The AbC-19 Rapid Test had 85% sensitivity and 99% specificity for detecting previous SARS-CoV-2 infection
Authors: Barnet Eskin
Journal: Annals of Internal Medicine (2021)

Source CitationMulchandani R, Jones HE, Taylor-Phillips S, et al. Accuracy of UK Rapid Test Consortium (UK-RTC) "AbC-19 Rapid Test" for detection of previous SARS-CoV-2 infection in key workers: test accuracy study. BMJ. 2020;371:m4262. https://pubmed.ncbi.nlm.nih.gov/33177070/AbstractClinical Impact RatingsGIM/FP/GP: Emergency Med: Hospitalists: Critical Care:
Second COVID-19 infection in a patient with granulomatosis with polyangiitis on rituximab
Authors: Marcia A Friedman, Kevin L Winthrop
Journal: Annals of the Rheumatic Diseases (2021)

Observational data suggest there may be an association between rituximab and severe COVID-19 outcomes.1–3 Anti-CD20 therapies impair humoral response, theoretically increasing the risk of prolonged SARS-CoV-2 infection and shedding, as well as subsequent reinfection. Here, we report a patient with granulomatosis with polyangiitis (GPA) being treated with rituximab who appears to have developed recurrent SARS-CoV-2 infections in the setting of high-risk employment and on recovery ultimately had no detectable SARS-CoV-2 IgG antibodies. This case highlights a potential risk of rituximab in patients with rheumatic disease, which will become especially relevant as rituximab may impair the immunogenicity of SARS-CoV-2 vaccines.

A woman in her 30s with a history of limited GPA on rituximab developed COVID-19 twice (figure 1). GPA manifestations have included erosive sinusitis, otitis, saddle nose deformity and orbital pseudotumour. She started rituximab in February 2019. The most recent dose of rituximab 1000 mg was given on 28 September 2020. On 14 August, a disease flare was treated with a 3-week prednisone taper, which completed approximately 4 weeks before COVID-19 infection. She works in an assisted living facility with ongoing staff and resident COVID-19 …
Prevalence and Prognosis of Lynch Syndrome and Sporadic Mismatch Repair Deficiency in Endometrial Cancer
Authors: Cathalijne C B Post, Ellen Stelloo, Vincent T H B M Smit, Dina Ruano, Carli M Tops, Lisa Vermij, Tessa A Rutten, Ina M Jürgenliemk-Schulz, Ludy C H W Lutgens, Jan J Jobsen, Remi A Nout, Emma J Crosbie, Melanie E Powell, Linda Mileshkin, Alexandra Leary, Paul Bessette, Hein Putter, Stephanie M de Boer, Nanda Horeweg, Maartje Nielsen, Tom van Wezel, Tjalling Bosse, Carien L Creutzberg
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background Standard screening of endometrial cancer (EC) for Lynch syndrome (LS) is gaining traction; however, the prognostic impact of an underlying hereditary etiology is unknown. We established the prevalence, prognosis, and subsequent primary cancer incidence of patients with LS-associated EC in relation to sporadic mismatch repair deficient (MMRd)-EC in the large combined Post Operative Radiation Therapy in Endometrial Carcinoma-1, -2, and -3 trial cohort. Methods After MMR-immunohistochemistry, MLH1-promoter methylation testing, and next-generation sequencing, tumors were classified into 3 groups according to the molecular cause of their MMRd-EC. Kaplan-Meier method, log-rank test, and Cox model were used for survival analysis. Competing risk analysis was used to estimate the subsequent cancer probability. All statistical tests were 2-sided. Results Among the 1336 ECs, 410 (30.7%) were MMRd. A total of 380 (92.7%) were fully triaged: 275 (72.4%) were MLH1-hypermethylated MMRd-ECs; 36 (9.5%) LS MMRd-ECs, and 69 (18.2%) MMRd-ECs due to other causes. Limiting screening of EC patients to 60 years or younger or to 70 years or younger would have resulted in missing 18 (50.0%) and 6 (16.7%) LS diagnoses, respectively. Five-year recurrence-free survival was 91.7% (95% confidence interval [CI] = 83.1% to 100%; hazard ratio = 0.45, 95% CI = 0.16 to 1.24, P = .12) for LS, 95.5% (95% CI = 90.7% to 100%; hazard ratio = 0.17, 95% CI = 0.05 to 0.55, P = .003) for “other” vs 78.6% (95% CI = 73.8% to 83.7%) for MLH1-hypermethylated MMRd-EC. The probability of subsequent LS-associated cancer at 10 years was 11.6% (95% CI = 0.0% to 24.7%), 1.5% (95% CI = 0.0% to 4.3%), and 7.0% (95% CI = 3.0% to 10.9%) within the LS, “other,” and MLH1-hypermethylated MMRd-EC groups, respectively. Conclusions The LS prevalence in the Post Operative Radiation Therapy in Endometrial Carcinoma trial population was 2.8% and among MMRd-ECs was 9.5%. Patients with LS-associated ECs showed a trend towards better recurrence-free survival and higher risk for second cancers compared with patients with MLH1-hypermethylated MMRd-EC.
Free fatty acid receptor 4 responds to endogenous fatty acids to protect the heart from pressure overload
Authors: Katherine A Murphy, Brian A Harsch, Chastity L Healy, Sonal S Joshi, Shue Huang, Rachel E Walker, Brandon M Wagner, Katherine M Ernste, Wei Huang, Robert C Block, Casey D Wright, Nathan Tintle, Brian C Jensen, Quinn S Wells, Gregory C Shearer, Timothy D O’Connell
Journal: Cardiovascular Research (2021)

Free fatty acid receptor 4 (Ffar4) is a G-protein-coupled receptor for endogenous medium-/long-chain fatty acids that attenuates metabolic disease and inflammation. However, the function of Ffar4 in the heart is unclear. Given its putative beneficial role, we hypothesized that Ffar4 would protect the heart from pathologic stress.
Steatotic Hepatocytes Release Mature VLDL Through Methionine and Tyrosine Metabolism in a Keap1‐Nrf2–Dependent Manner
Authors: Akitoshi Sano, Eiji Kakazu, Shin Hamada, Jun Inoue, Masashi Ninomiya, Tomoaki Iwata, Mio Tsuruoka, Kosuke Sato, Atsushi Masamune
Journal: Hepatology (2021)

NAFLD is a lipotoxic disease wherein hepatic steatosis and oxidative stress are key pathogenic features. However, whether free amino acids (FAAs) are associated with the oxidative stress response against lipotoxicity has yet to be determined. We hypothesized that an imbalance of FAAs aggravates hepatic steatosis by interfering with the oxidative stress sensor.C57BL/6 mouse immortalized hepatocytes, primary hepatocytes, and organoids were employed. Steatotic hepatocytes treated with oleic acid (OA) were cultured under FAA-modifying media based on the concentrations of FAAs in the hepatic portal blood of wild-type (WT) mice. As in vivo experiments, WT hepatocyte-specific Kelch-like ECH-associated protein 1 (Keap1) knockout mice (Keap1∆hepa ) and Cre- control mice (Keap1fx/fx ) were fed high-fat (HF) diets with modified amino acid content. The correlations were analyzed between the areas of lipid droplets (LDs) around central vein and plasma OA/FAA ratio in 61 patients with NAFLD. Mice fed an HF, Met-restricted, and tyrosine (Tyr)-deficient diet showed the NAFLD-like phenotype in which the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), triglyceride-rich VLDL, and fumarate were decreased in liver, but Keap1∆hepa ameliorated these phenomena. Reactive oxygen species and LDs induced by the deprivation of Met and Tyr were prevented in hepatic organoids generated from Keap1∆hepa . Dimethyl fumarate, an Nrf2 inducer, ameliorated the steatosis and increased the hepatic fumarate reduced by the deprivation of Met and Tyr in vitro. OA/Met or Tyr ratio in peripheral blood was associated with the hepatic steatosis in patients with NAFLD.An imbalance between free fatty acids and Met and Tyr induces hepatic steatosis by disturbing the VLDL assembling through the Keap1-Nrf2 system.