tbuckley/cabot-search huggingface dataset:
Abstract P032: Initiating Hypertension Treatment To Prevent Incident Cardiovascular Disease: A Population Estimate Using The Cardiovascular Disease Policy Model
Authors: Susan Hennessy, Joanne Penko, Pamela Coxson, Pengxiao Wei, Ross Boylan, Azuka Atum, Brandon K Bellows, Yiyi Zhang, Dhruv S Kazi, Andrew E Moran, Kirsten Bibbins-Domingo
Journal: Circulation (2022)

Background: Hypertension is a leading preventable cause of CHD, stroke, and heart failure (HF). WHO hypertension guidelines recommend initiating first dose medication in hypertensive adults with access to healthcare, yet many US adults with a usual source of care are not receiving treatment. We estimate the population impact of initiating hypertensive therapy in untreated US adults with uncontrolled blood pressure (BP) and access to usual healthcare on incident CVD. Methods: We used the CVD Policy Model, a dynamic state-transition model of CVD risk factors, events, and outcomes to simulate the impact over 10 years of treating uncontrolled BP in our target population of US adults 35-94 years of age with no prior CVD, baseline systolic BP ≥140mmHg, and no current hypertensive medication use, estimated from National Health and Nutrition Examination Survey years 2015-2018. We initiated first dose medication in the target population reporting access to a usual source of healthcare and at least two visits per year. We used the Law, Morris and Wald equation to estimate the systolic BP effect size for a standard first dose of medication. Results: Initiating hypertension medications in those with currently untreated but with regular healthcare access would prevent 214,000 incident CVD events in the US, a quarter of which (52,000) are incident heart failure (Table 1). First dose treatment (and maintenance) would be expected to reduce incident CHD by 9.1%, HF by 6.1%, ischemic stroke by 8.1%, and hemorrhagic stroke by 11.3% over the decade, compared to no treatment. Treatment of hypertension would have the greatest relative benefit in the prevention on incident CVD events in those younger than 65, compared with those over 65 years of age. Conclusion: In the US population with regular access to healthcare, initiating first dose medications for hypertension in those with elevated blood pressure but currently untreated would reduce incident CVD in both sexes and all age groups, with particular benefit for prevention in those less than 65 years of age.
Association Between Socioeconomic Disadvantage and Decline in Function, Cognition, and Mental Health After Critical Illness Among Older Adults
Authors: Snigdha Jain, Terrence E. Murphy, John R. O’Leary, Linda Leo-Summers, Lauren E. Ferrante
Journal: Annals of Internal Medicine (2022)

Background: Older adults admitted to an intensive care unit (ICU) are at risk for developing impairments in function, cognition, and mental health. It is not known whether socioeconomically disadvantaged older persons are at greater risk for these impairments than their less vulnerable counterparts. Objective: To evaluate the association between socioeconomic disadvantage and decline in function, cognition, and mental health among older survivors of an ICU hospitalization. Design: Retrospective analysis of a longitudinal cohort study. Setting: Community-dwelling older adults in the National Health and Aging Trends Study (NHATS). Participants: Participants with ICU hospitalizations between 2011 and 2017. Measurements: Socioeconomic disadvantage was assessed as dual-eligible Medicare–Medicaid status. The outcome of function was defined as the count of disabilities in 7 activities of daily living and mobility tasks, the cognitive outcome as the transition from no or possible to probable dementia, and the mental health outcome as the Patient Health Questionnaire-4 score in the NHATS interview after ICU hospitalization. The analytic sample included 641 ICU hospitalizations for function, 458 for cognition, and 519 for mental health. Results: After accounting for sociodemographic and clinical characteristics, dual eligibility was associated with a 28% increase in disability after ICU hospitalization (incidence rate ratio, 1.28; 95% CI, 1.00 to 1.64); and nearly 10-fold greater odds of transitioning to probable dementia (odds ratio, 9.79; 95% CI, 3.46 to 27.65). Dual eligibility was not associated with symptoms of depression and anxiety after ICU hospitalization (incidence rate ratio, 1.33; 95% CI, 0.99 to 1.79). Limitation: Administrative data, variability in timing of baseline and outcome assessments, proxy selection. Conclusion: Dual-eligible older persons are at greater risk for decline in function and cognition after an ICU hospitalization than their more advantaged counterparts. This finding highlights the need to prioritize low-income seniors in rehabilitation and recovery efforts after critical illness and warrants investigation into factors leading to this disparity. Primary Funding Source: National Institute on Aging.
Retention of the NLRP3 Inflammasome–Primed Neutrophils in the Bone Marrow Is Essential for Myocardial Infarction–Induced Granulopoiesis
Authors: Gopalkrishna Sreejit, Sunil K. Nooti, Robert M. Jaggers, Baskaran Athmanathan, Ki Ho Park, Annas Al-Sharea, Jillian Johnson, Albert Dahdah, Man K.S. Lee, Jianjie Ma, Andrew J. Murphy, Prabhakara R. Nagareddy
Journal: Circulation (2021)

Acute myocardial infarction (MI) results in overzealous production and infiltration of neutrophils to the ischemic heart. This is mediated in part by granulopoiesis induced by the S100A8/A9-NLRP3-IL-1β signaling axis in injury-exposed neutrophils. Despite the transcriptional upregulation of the NLRP3 (Nod Like Receptor Family Pyrin Domain-Containing 3) inflammasome and associated signaling components in neutrophils, the serum levels of IL-1β (interleukin-1β), the effector molecule in granulopoiesis, were not affected by MI, suggesting that IL-1β is not released systemically. We hypothesize that IL-1β is released locally within the bone marrow (BM) by inflammasome-primed and reverse-migrating neutrophils.Using a combination of time-dependent parabiosis and flow cytometry techniques, we first characterized the migration patterns of different blood cell types across the parabiotic barrier. We next induced MI in parabiotic mice by permanent ligation of the left anterior descending artery and examined the ability of injury-exposed neutrophils to permeate the parabiotic barrier and induce granulopoiesis in noninfarcted parabionts. Last, using multiple neutrophil adoptive and BM transplant studies, we studied the molecular mechanisms that govern reverse migration and retention of the primed neutrophils, IL-1β secretion, and granulopoiesis. Cardiac function was assessed by echocardiography.MI promoted greater accumulation of the inflammasome-primed neutrophils in the BM. Introducing a time-dependent parabiotic barrier to the free movement of neutrophils inhibited their ability to stimulate granulopoiesis in the noninfarcted parabionts. Previous priming of the NLRP3 inflammasome is not a prerequisite, but the presence of a functional CXCR4 (C-X-C-motif chemokine receptor 4) on the primed-neutrophils and elevated serum S100A8/A9 levels are necessary for homing and retention of the reverse-migrating neutrophils. In the BM, the primed-neutrophils secrete IL-1β through formation of gasdermin D pores and promote granulopoiesis. Pharmacological and genetic strategies aimed at the inhibition of neutrophil homing or release of IL-1β in the BM markedly suppressed MI-induced granulopoiesis and improved cardiac function.Our data reveal a new paradigm of how circulatory cells establish a direct communication between organs by delivering signaling molecules (eg, IL-1β) directly at the sites of action rather through systemic release. We suggest that this pathway may exist to limit the off-target effects of systemic IL-1β release.
Piezo1 Is a Mechanosensor Channel in Central Nervous System Capillaries
Authors: Osama F. Harraz, Nicholas R. Klug, Amanda J. Senatore, David C. Hill-Eubanks, Mark T. Nelson
Journal: Circulation Research (2022)

Capillaries are equipped to sense neurovascular coupling agents released onto the outer wall of a capillary, translating these external signals into electrical/Ca 2+ changes that play a crucial role in blood flow regulation and ensuring that neuronal demands are met. However, control mechanisms attributable to forces imposed onto the lumen are less clear. Here, we show that Piezo1 channels act as mechanosensors in central nervous system capillaries. Electrophysiological analyses confirmed expression and function of Piezo1 channels in brain cortical and retinal capillaries. Activation of Piezo1 channels evoked currents that were sensitive to endothelial cell–specific Piezo1 deletion. Using genetically encoded Ca 2+ indicator mice and an ex vivo pressurized retina preparation, we found that activation of Piezo1 channels by mechanical forces triggered Ca 2+ signals in capillary endothelial cells. Collectively, these findings indicate that Piezo1 channels are capillary mechanosensors that initiate crucial Ca 2+ signals and could, therefore, have a profound impact on central nervous system blood flow control.
A multilevel, multidimensional scale for measuring housing insecurity in urban slums and informal settlements: a psychometric study
Authors: Godfred O Boateng, Ellis Adjei Adams
Journal: The Lancet Global Health (2022)

Housing insecurity is a pervasive challenge in the cities and urban areas of low-income and middle-income countries (LMICs), particularly in the informal settlements where disproportionately high number of urban residents live. Despite this persistent challenge and its impact on health and well-being, there are currently no comprehensive, standardised, and validated instruments for measuring housing insecurity in these regions. We aimed to develop and validate a housing insecurity scale that can be used in urban slums and informal settlements in LMICs.Using a complementary set of qualitative and quantitative techniques, we used data collected from three urban slums in Ghana (n=1036) on housing deprivations and characteristics, slum severity, resource insecurity, health outcomes, and socio-demography in the development of the scale. Following item generation, domain identification, and content validation, we identified 28 items that were tested for tetrachoric and Biserial correlations. We extracted an optimal number of factors and tested for dimensionality using confirmatory factor analysis and second-order confirmatory factor analysis. We also tested for reliability and validity of the scale. Tests of concurrent and predictive validity were assessed against slum severity scores, and indoor air quality and health status, respectively.The resultant scale is a multilevel multidimensional scale consisting of 17 items that subdivide into three subscales: lack of essential utility (α=0·63), built environment deficiency (α=0·80), and tenancy challenges (α=0·82). The composite scale was reliable, with a coefficient alpha of 0·83. Concurrent validity showed a significant association between the composite housing insecurity scores and slum severity scores (β=0·29, 95% CI 0·26-0·32). For predictive validity, housing insecurity increased the likelihood of poor indoor air quality (OR 1·35, 1·29-1·42) and poor health (β=0·03, 0·01-0·04). Convergent and discriminant validity and known group comparisons also supported the validity of the scale. Using the mean scores for housing insecurity, about 53·3% of our study population would be classified as experiencing severe housing insecurity in the past year.To our knowledge, this is the first reliable and validated scale developed to measure housing insecurity in urban slums and informal settlements in LMICs. It can be used to test a range of hypotheses about the role of housing insecurity in several environmental and health outcomes; to assess and plan clinical, programmatic, and policy interventions; and to aid in tracking progress made on Sustainable Development Goal 11.Center for Research and Scholarship Pilot Project Grant (313420) at the University of Texas at Arlington and the Keough School of Global Affairs at the University of Notre Dame.
Abstract P235: Association Between Food Insecurity And Blood Pressure In A Multiethnic Population
Authors: Claire T Ing, Jane Lim, Joseph K Kaholokula, Todd B Seto, Peter Hovmand, Rachel Novotny
Journal: Circulation (2022)

Hypertension (HTN) is the strongest modifiable risk factor for CVD that is disproportionately higher in racial/ethnic groups, e.g., Native Hawaiians. Native Hawaiians have over a 50% prevalence of HTN (i.e., systolic blood pressure (SBP) of ≥130mmHg or diastolic blood pressure (DBP) of ≥80mmHg), placing them at higher risk for CVD. Behavioral/biological risk factors (e.g., BMI, diet, physical activity) are often the focus of epidemiological and intervention research; yet, socioeconomic factors, such as food insecurity, also affect blood pressure. The purpose of this study is to examine the association between food insecurity and SBP and DBP in Native Hawaiians communities, controlling for demographics and behavioral/biological risk factors. Participants in this 2020, cross-sectional study (N = 125) were from six, predominantly Native Hawaiian communities across Hawai‘i. Demographic variables included age, sex, education, and race/ethnicity. Potential confounding variables were leisure-time physical activity, daily servings of processed meat, daily servings of red meat, daily servings of fruit and vegetables, resilience, BMI, use of HTN medication, and COVID-19 related mental health. To assess food insecurity participants were asked to indicate how often money for food runs out by the end of the month on a 5-point Likert scale, with higher scores indicating greater frequency. SBP and DBP were measured according to a standardized protocol. All confounding variables with a significant bivariate correlation with SBP or DBP were entered into the respective multiple regression model. Participants were predominantly female (73, 58.4%), had some college or were college graduates (73, 58.4%), a mean age of 39.2yrs ( SD =9.9) and mean BMI of 31.6 ( SD =8.7). Mean SBP and DBP were in the normotensive range, 122.9±17.5 and 79.5±11.9, respectively. Female sex ( β =-9.9, SE =2.6, p &lt;0.001), daily servings of fruit and vegetables ( β =-2.35, SE =1.04, p =0.026), BMI ( β =0.76, SE =0.16, p &lt;0.001), use of HTN medication ( β =14.01, SE =4.90, p =0.005), and food insecurity ( β =2.09, SE =0.95, p=0.030) were associated with SBP ( R 2 =0.40, SE =14.05, p &lt;0.001). Male sex, fewer daily servings of fruit and vegetables, greater BMI, use of HTN medication, and more food insecurity were significantly associated with higher DBP. Female sex ( β =-5.03, SE =1.90, p =0.009), BMI ( β =0.51, SE =0.12, p &lt;0.001), and food insecurity ( β =1.36, SE =0.69, p =0.05) were associated with DBP ( R 2 =0.31, SE =10.18, p &lt;0.001). Male sex, greater BMI, and more food insecurity were significantly associated with higher DBP. After controlling for potential confounders, food insecurity retains a significant, independent association with both SBP and DBP such that a greater frequency of food insecurity was related to higher SBP and DBP. This provides additional evidence for the idea that food insecurity may directly impact CVD risk.
Brain 18F-FDG PET in Cowden Syndrome
Authors: Justine Grangeret, Solene Frismand, Marie Muller, Mathilde Renaud, Antoine Verger
Journal: Clinical Nuclear Medicine (2022)

Abstract Cowden disease is associated with neurodevelopmental abnormalities such as macrocephaly, autism spectrum disorder, and developmental delay. Our understanding of neuroimaging anomalies in patients with PTEN mutations is limited to anatomical MRI abnormalities including white matter abnormalities, meningiomas, arteriovenous malformations, and cortical dysplasia. Our current communication extends the neurological Cowden syndrome phenotype by using brain 18 F-FDG PET/CT imaging as a useful complementary approach to MRI to explore movement disorders and neuropsychiatric syndromes in a patient with Cowden disease. Brain 18 F-FDG PET/CT showed diffuse hypometabolism of the prefrontal mesial and dorsolateral areas including supplementary motor areas, the pons extended to the cerebellum.
An Evolving Role for AXL in Metastatic Renal Cell Carcinoma
Authors: Andrew W. Hahn, Daniel J. George, Neeraj Agarwal
Journal: Clinical Cancer Research (2021)

High tumoral expression of AXL was associated with inferior response to anti-PD-1 therapy and increased tumoral programmed death ligand 1 (PD-L1) expression in patients with metastatic renal cell carcinoma, with particularly poor outcomes in those with high AXL and PD-L1. AXL expression has potential as a biomarker and therapeutic target.See related article by Terry et al., p. 6749.
Ultrasensitive profiling of UV-induced mutations identifies thousands of subclinical facial tumors in tuberous sclerosis complex
Authors: Katarzyna Klonowska, Joannes M. Grevelink, Krinio Giannikou, Barbara A. Ogorek, Zachary T. Herbert, Aaron R. Thorner, Thomas N. Darling, Joel Moss, David J. Kwiatkowski
Journal: Journal of Clinical Investigation (2022)

BackgroundTuberous sclerosis complex (TSC) is a neurogenetic syndrome due to loss-of-function mutations in TSC2 or TSC1, characterized by tumors at multiple body sites, including facial angiofibroma (FAF). Here, an ultrasensitive assessment of the extent and range of UV-induced mutations in TSC facial skin was performed.MethodsA multiplex high-sensitivity PCR assay (MHPA) was developed, enabling mutation detection at extremely low (<0.1%) variant allele frequencies (VAFs).ResultsMHPA assays were developed for both TSC2 and TP53, and applied to 81 samples, including 66 skin biopsies. UV-induced second-hit mutation causing inactivation of TSC2 was pervasive in TSC facial skin with an average of 4.8 mutations per 2-mm biopsy at median VAF 0.08%, generating more than 150,000 incipient facial tumors (subclinical "micro-FAFs") in the average TSC subject. The MHPA analysis also led to the identification of a refined UV-related indel signature and a recurrent complex mutation pattern, consisting of both a single-nucleotide or dinucleotide variant and a 1- to 9-nucleotide deletion, in cis.ConclusionTSC facial skin can be viewed as harboring a patchwork of clonal fibroblast proliferations (micro-FAFs) with indolent growth, a small proportion of which develop into clinically observable FAF. Our observations also expand the spectrum of UV-related mutation signatures.FundingThis work was supported by the TSC Alliance; the Engles Family Fund for Research in TSC and LAM; and the NIH, National Heart, Lung, and Blood Institute (U01HL131022-04 and Intramural Research Program).
Performance of the European Society of Cardiology 0/1-Hour, 0/2-Hour, and 0/3-Hour Algorithms for Rapid Triage of Acute Myocardial Infarction
Authors: Cho-Han Chiang, Cho-Hung Chiang, John W. Pickering, Kiril M. Stoyanov, Derek P. Chew, Johannes T. Neumann, Francisco Ojeda, Nils A. Sörensen, Ke-Ying Su, Peter Kavsak, Andrew Worster, Kenji Inoue, Tonje R. Johannessen, Dan Atar, Michael Amann, Willibald Hochholzer, Arash Mokhtari, Ulf Ekelund, Raphael Twerenbold, Christian Mueller, Philipp Bahrmann, Nicolas Buttinger, Maureen Dooley, Onlak Ruangsomboon, Richard M. Nowak, Christopher R. DeFilippi, William F. Peacock, Tomas G. Neilan, Michael A. Liu, Wan-Ting Hsu, Gin Hoong Lee, Pui-Un Tang, Kevin Sheng-Kai Ma, Dirk Westermann, Stefan Blankenberg, Evangelos Giannitsis, Martin P. Than, Chien-Chang Lee
Journal: Annals of Internal Medicine (2021)

The 2020 European Society of Cardiology (ESC) guidelines recommend using the 0/1-hour and 0/2-hour algorithms over the 0/3-hour algorithm as the first and second choices of high-sensitivity cardiac troponin (hs-cTn)-based strategies for triage of patients with suspected acute myocardial infarction (AMI). To evaluate the diagnostic accuracies of the ESC 0/1-hour, 0/2-hour, and 0/3-hour algorithms. PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from 1 January 2011 to 31 December 2020. (PROSPERO: CRD42020216479). Prospective studies that evaluated the ESC 0/1-hour, 0/2-hour, or 0/3-hour algorithms in adult patients presenting with suspected AMI. The primary outcome was index AMI. Twenty unique cohorts were identified. Primary data were obtained from investigators of 16 cohorts and aggregate data were extracted from 4 cohorts. Two independent authors assessed each study for methodological quality. A total of 32 studies (20 cohorts) with 30 066 patients were analyzed. The 0/1-hour algorithm had a pooled sensitivity of 99.1% (95% CI, 98.5% to 99.5%) and negative predictive value (NPV) of 99.8% (CI, 99.6% to 99.9%) for ruling out AMI. The 0/2-hour algorithm had a pooled sensitivity of 98.6% (CI, 97.2% to 99.3%) and NPV of 99.6% (CI, 99.4% to 99.8%). The 0/3-hour algorithm had a pooled sensitivity of 93.7% (CI, 87.4% to 97.0%) and NPV of 98.7% (CI, 97.7% to 99.3%). Sensitivity of the 0/3-hour algorithm was attenuated in studies that did not use clinical criteria (GRACE score <140 and pain-free) compared with studies that used clinical criteria (90.2% [CI, 82.9 to 94.6] vs. 98.4% [CI, 88.6 to 99.8]). All 3 algorithms had similar specificities and positive predictive values for ruling in AMI, but heterogeneity across studies was substantial. Diagnostic performance was similar across the hs-cTnT (Elecsys; Roche), hs-cTnI (Architect; Abbott), and hs-cTnI (Centaur/Atellica; Siemens) assays. Diagnostic accuracy, inclusion and exclusion criteria, and cardiac troponin sampling time varied among studies. The ESC 0/1-hour and 0/2-hour algorithms have higher sensitivities and NPVs than the 0/3-hour algorithm for index AMI. National Taiwan University Hospital.
Increased 68Ga-FAPI Activity in Chondrosarcoma of Nasal Cavity
Authors: Xiao Yang, Lei Ou, Duo Xu, Yue Chen, Huipan Liu
Journal: Clinical Nuclear Medicine (2022)

Abstract Chondrosarcoma is a rare entity tumor, which mainly appears in long bones and pelvic bones, but rarely in nasal cavity. Herein, we report the 68 Ga-FAPI PET/CT findings in a 54-year-old man with chondrosarcoma of nasal cavity.
Immunotherapies to optimize pregnancy outcomes in subfertile women
Authors: Marcelo Borges Cavalcante, Manoel Sarno, Ricardo Barini
Journal: Human Reproduction Update (2022)

Journal Article Immunotherapies to optimize pregnancy outcomes in subfertile women Get access Marcelo Borges Cavalcante, Marcelo Borges Cavalcante Postgraduate Program in Medical Sciences, University of Fortaleza (UNIFOR), Fortaleza-CE, BrazilCONCEPTUS—Reproductive Medicine, Fortaleza-CE, Brazil Correspondence address. Postgraduate Program in Medical Sciences, University of Fortaleza (UNIFOR), Fortaleza-CE 60.192-215, Brazil. E-mail: marcelocavalcante.med@gmail.com https://orcid.org/0000-0001-9943-9731 Search for other works by this author on: Oxford Academic PubMed Google Scholar Manoel Sarno, Manoel Sarno Department of Gynecology and Obstetrics, Federal University of Bahia (UFBA), Salvador-BA, Brazil https://orcid.org/0000-0002-2312-0932 Search for other works by this author on: Oxford Academic PubMed Google Scholar Ricardo Barini Ricardo Barini Department of Obstetrics and Gynecology, State University of Campinas (UNICAMP), Campinas, Brazil https://orcid.org/0000-0002-4138-6945 Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Reproduction Update, Volume 28, Issue 4, July-August 2022, Pages 601–602, https://doi.org/10.1093/humupd/dmac017 Published: 06 May 2022