tbuckley/cabot-search huggingface dataset:
Abstract P272: The Association Between Sleep Apnea and Left Ventricular Structure and Function: The ECHO-SOL Ancillary Study
Authors: Rachel P Ogilvie, Michael V Genuardi, Sanjay R Patel, Jared W Magnani, Susan Redline, Martha L Daviglus, Neomi Shah, Alberto R Ramos, Jianwen Cai, Barry E Hurwitz, Mayank Kansal, Carlos J Rodriguez
Journal: Circulation (2019)

Background: Obstructive sleep apnea (OSA) initiates a range of pathophysiologic mechanisms which may promote cardiac disease, but few studies have examined the association of OSA with global longitudinal strain (GLS) and diastolic function, especially among middle aged and older Hispanics/Latinos in the United States. Methods: We examined cross-sectional data from adults aged 18-64 in the Hispanic Community Health Study/Study of Latinos ECHO-SOL Ancillary Study (2011-2014), a representative subsample of the parent study. OSA was assessed using an ARES Unicorder sleep apnea monitor for one night; the apnea-hypopnea index (AHI) was obtained. Echocardiographic measures evaluated left ventricular (LV) structure (LV mass index [LVMI], left atrial volume index), systolic function (ejection fraction, GLS) and diastolic function (E’ and E/e’ ratio). Potential confounders included age, sex, ethnicity, and body mass index. Multivariable linear regression was used to model the association between AHI and the echocardiographic outcomes. All analyses accounted for the complex survey design. Results: Among 1,506 participants (median age 55.0, interquartile range 49.0, 62.0, 58.3% female) with both sleep and echo data, 17.9% had an AHI ≥15 and 3.2% had an ejection fraction &lt;50%. Each 10-unit higher AHI was associated with 1.4 (95% CI 0.3, 2.5) g/m2 greater LVMI, 0.1 (0.0, 0.3) worse GLS, 0.2 (0.1, 0.3) lower E’, and 0.3 (0.1, 0.5) greater E/E’ ratio. There were no associations between AHI and left atrial volume index or ejection fraction. Conclusion: OSA was associated with poorer LV GLS and diastolic function indices, but associations with structure and ejection fraction were less consistent. Subclinical LV dysfunction may precede the onset of symptomatic disease in this at-risk population. Further studies are needed to determine the longitudinal association of OSA and cardiac remodeling.
Gabriel Weston: A window on to a hopeful landscape
Authors: Gabriel Weston
Journal: BMJ (2019)

Window bars are set to be phased out in all UK prisons and replaced with toughened glass. This is a safer alternative in terms of preventing contraband, and giving prisoners a more homely environment has been shown to improve their prospects of rehabilitation.

There will always be those who believe that prison ought to be horrible, that the people who end up there deserve what they get. But the truth is that our detention centres are crammed with many people we should consider patients.

An article published in Lancet Psychiatry in 2018 estimates that 90% of our incarcerated population have at least one mental or …
Meta-Analysis of the Prognostic Role of Late Gadolinium Enhancement and Global Systolic Impairment in Left Ventricular Noncompaction
Authors: Chrysanthos Grigoratos, Andrea Barison, Alexander Ivanov, Daniele Andreini, Mihaela-Silvia Amzulescu, Lukasz Mazurkiewicz, Antonio De Luca, Jacek Grzybowski, Pier Giorgio Masci, Magdalena Marczak, John F. Heitner, Juerg Schwitter, Bernhard L. Gerber, Michele Emdin, Giovanni Donato Aquaro
Journal: JACC. Cardiovascular imaging (2019)
The effect of the timing of biochemical failure after external beam radiotherapy or low-dose-rate brachytherapy for definitive prostate cancer treatment.
Authors: Jay P. Ciezki, Chandana A. Reddy, Omar Y. Mian, Rahul D. Tendulkar, James Ulchaker, Kenneth Angermeier, Steven Campbell, Andrew J. Stephenson, Mark Stovsky, Eric A. Klein
Journal: Journal of Clinical Oncology (2019)

28 Background: To assess the effect of the timing of biochemical failure (bF) after definitive radiotherapy with external beam (EBRT) or low dose-rate brachytherapy (LDR) on clinical failure (cF) and prostate cancer-specific mortality (PCSM). Methods: From 1996 to 2009, 4478 patients were treated and by 2010, 456 patients were noted to have a bF. They were categorized as early (&lt; 5 years post-therapy) or late (≥ 5 years post-therapy) failures. Factors thought to influence cF and PCSM were scored. Cox regression was used to assess the timing of bF on cF and Fine and Gray regression was used to assess the timing of bF on PCSM. Results: There were 330 (72.4 %) patients categorized as early and 126 (27.6 %) as late failures. The median PSA follow-up post-radiotherapy for the early bF group is 82 months vs. 155 months for the late bF group, and the median PSA follow-up post-bF is 54 months for the early bF group vs. 69 months for the late bF group. The early failures were more likely to be high-risk (p = 0.0080), have a higher Gleason score (p = 0.0008), and use ADT (p = 0.0325). The five-year rate of cF post early bF is 61% vs 43% post late bF (p &lt;0.0001). The five-year rate of PCSM post early bF is 27% vs 9% post late bF (p &lt;0.0001). The multivariable analyses assessing the cF and PCSM are shown in Table. Conclusions: Early bF is associated with higher rates of cF and PCSM. Patients treated with LDR have a lower risk of PCSM. [Table: see text]
Abstract MP03: Aortic Stiffening and Intracranial Atherosclerosis: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)
Authors: Priya Palta, Ye Qiao, Jingkai Wei, Michelle Meyer, Hiro Tanaka, David Knopman, Gerardo Heiss, Bruce Wasserman
Journal: Circulation (2019)

Introduction: Stiffening of the aorta is associated with increased pulse pressure and transmission of pulsatile energy into the cerebral circulation. An association between increased aortic stiffening with intracranial atherosclerotic disease (ICAD) has not been widely studied. We tested the hypothesis that loss of aortic elasticity (i.e. higher aortic stiffness) is associated with a higher presence of ICAD. Methods: ARIC-NCS participants (n=1412; mean age: 76 years; 42% male; 30% Black) with measures of aortic stiffness and vascular brain magnetic resonance imaging (MRI) at the visit 5 (2011-2013) examination were included. Aortic stiffness was measured by carotid-femoral pulse wave velocity (cfPWV) using the VP-1000 Plus device (Omron Co., Japan). cfPWV was discretized into high vs. low aortic stiffness based on the upper 25 th percentile, 13.4 m/s. Brain MRI was performed on 3.0 Tesla scanners using a standardized protocol that included an MR angiography (MRA) and high isotropic resolution vessel MRI. Presence of ICAD was defined as eccentric wall thickening with or without luminal stenosis on MRA. We first examined the functional form relationship between continuous measures of cfPWV and ICAD. Comparing those with high vs. low aortic stiffening, we estimated the prevalence odds of ICAD using logistic regression. Models were adjusted for age, sex, race-center, education, smoking, heart rate, blood-pressure lowering medication, diabetes, LDL-cholesterol, and minutes/week of physical activity. Sampling weights were used for generalizability to the full ARIC cohort at visit 5. We tested for effect modification by race, sex, diabetes, central systolic blood pressure, and use of blood pressure-lowering medication. Results: The mean cfPWV was higher among participants with ICAD (12.6 ± 3.2 m/s) compared to those without ICAD (11.2 ± 2.9 m/s). cfPWV was associated with ICAD in a monotonic, linear fashion (p&lt;0.05). The presence of ICAD was 50.6% among participants with high aortic stiffness (cfPWV above the upper 25th percentile; n=354) compared to 30.2% among participants with low aortic stiffness (n=1058). Compared to participants with low aortic stiffness, those with high aortic stiffness had two-fold higher odds of ICAD (odds ratio (OR): 1.97, 95% confidence interval (CI): 1.68, 2.33). No statistically significant modification of this association was observed. Results were robust to exclusions for prevalent stroke (n=43) and prevalent cardiovascular disease (n=153). Conclusions: Aortic stiffness, a highly prevalent trait among older men and women, is associated with ICAD presence quantified by magnetic resonance angiography. Aortic stiffness, its risk factors and the factors associated with the preservation of aortic elasticity, may play a role in modifying the risk of intracranial atherosclerosis.
Abstract P304: Underuse of Cardiovascular Medications in Individuals With Lower Extremity Peripheral Artery Disease: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Simin Hua, Carmen R Isasi, Jorge R Kizer, Kunihiro Matsushita, Matthew A Allison, Qibin Qi, Sonia G Ponce, Wassim Tarraf, Martha Daviglus, Robert Kaplan
Journal: Circulation (2019)

Introduction: The underuse of cardiovascular therapies among individuals with lower extremity peripheral artery disease (PAD) has been reported. However, little is known about this in the Hispanic/Latinos, who may have limited access to health care and worse clinical outcomes than non-Hispanics. Methods: We studied the cross-sectional use of cardiovascular therapies including antiplatelet, lipid-lowering and antihypertensive medications among 826 HCHS/SOL participants who reported a PAD diagnosis by a physician. We studied the factors that may be associated with use of cardiovascular medications, including demographic, socioeconomic factors, acculturation, access to health care and comorbidities. Survey Poisson regression was used to generate the prevalence ratios. Factors in age-adjusted models with P≤0.10 were included in multivariate regression. Results: A total of 723 participants with medical history of PAD were free of coronary heart disease (CHD, mean age=53) while 103 patients had concurrent CHD (mean age=56). The overall age-adjusted prevalence of antiplatelet, lipid-lowering and antihypertensive medications were 31%, 26% and 34%, respectively. Individuals of Mexican background had low health insurance coverage (42%) and low use of antiplatelet (20%), statin (17%) and antihypertensive (47% among hypertensive individuals) medications. More advanced age, number of doctor visits (2+ vs 0-1) in the past year and number of cardiovascular risk factors (2+ vs 0-1) were significantly associated with using cardiovascular medications in adjusted models. Compared with those with PAD alone, individuals with PAD and concurrent CHD were more likely to use antiplatelet (PR=1.44, 95% CI 1.13-1.82) and statin (PR=1.56 [1.17-2.07]) treatment in the multivariate analysis. Conclusions: We found underuse of cardiovascular medications among Hispanic/Latino individuals with medical history of PAD. More efforts should be directed in eliminating treatment disparities in this important race-ethnic group.
Effect of long-term corticosteroid treatment on microRNA and gene-expression profiles in COPD
Authors: Alen Faiz, Katrina Steiling, Mirjam P. Roffel, Dirkje S. Postma, Avrum Spira, Marc E. Lenburg, Malte Borggrewe, Tim R. Eijgenraam, Marnix R. Jonker, Gerard H. Koppelman, Simon D. Pouwels, Gang Liu, Yuriy O. Alekseyev, Stephen Lam, Pieter S. Hiemstra, Peter J. Sterk, Wim Timens, Corry-Anke Brandsma, Irene H. Heijink, Maarten van den Berge
Journal: European Respiratory Journal (2019)

The aim was to investigate whether microRNA (miRNA) expression is modulated by inhaled corticosteroid (ICS) treatmentWe performed genome-wide miRNA analysis on bronchial biopsies of 69 moderate/severe chronic obstructive pulmonary disease (COPD) patients at baseline and after 6- and 30-month treatment with the ICS fluticasone propionate or placebo. The effect of ICS on miRNA expression was validated in differentiated primary bronchial epithelial cultures, and functional studies were conducted in BEAS-2B cells. MiRNAs affected by ICS and their predicted targets were compared to an independent miRNA dataset of bronchial brushings from COPD patients and healthy controls.Treatment with ICS for both 6 and 30 months significantly altered the expression of four miRNAs, including miR-320d, which was increased during ICS treatment compared with placebo. The ICS-induced increase of miR-320d was confirmed in primary airway epithelial cells. MiR-320d negatively correlated targets were enriched for pro-inflammatory genes and were increased in the bronchial brushes of patients with lower lung function in the independent dataset. Overexpression of miR-320d in BEAS-2B cells dampened cigarette smoke extract-induced pro-inflammatory activity via inhibition of nuclear factor-κB.Collectively, we identified miR-320d as a novel mediator of ICS, regulating the pro-inflammatory response of the airway epithelium.
Abstract B77: Perillyl alcohol derivatives as anticancer agents
Authors: Thomas C. Chen, Axel H. Schonthal, Florence H. Hofman
Journal: Clinical Cancer Research (2018)

Abstract The use of the monoterpene perillyl alcohol (POH) for intranasal delivery to brain tumors was first popularized in Brazil. As monotherapy, POH has been found to be nontoxic, and to have anticancer activity in a subset of patients with malignant gliomas. The presumed route of delivery is presumed to be a cranial nerve (olfactory, trigeminal) to brain delivery, bypassing the blood-brain barrier. POH, itself, as a monoterpene is a clear liquid that we have found to be lipophilic in its consistency. We have explored the possibility of taking drugs that are out of patent, but with antibrain tumor activity, chemically conjugating them to POH, and creating a new drug. The process of drug discovery consisted of preclinical determination of: 1) feasibility of chemical conjugation, 2) determination of increased BBB penetrance using a BBB permeability program, 3) determination of functional activity via MTT and colony formation assays, 4) determination of mechanism of action, 5) determination of pharmacokinetic and pharmacodynamics action, and 6) functional activity against intracranial tumors (gliomas, metastatic breast carcinoma, medulloblastomas) demonstrated using established in vivo syngeneic and immune-deficient rodent models. Once these six preclinical steps are validated, formal application for IND status can be prepared by: 1) GMP production of drug, 2) formal toxicity testing using large and small animal models under acute and chronic administration, and 3) clinical trial indication for Phase I/IIa. This method has been successfully employed using temozolomide (TMZ) to create TMZ-POH linked via a carbamate bond (TMZ-POH; NEO212). The same method has been performed for the phosphodiesterase type IV inhibitor rolipram (RP-POH, NEO214), valproic acid (VA-POH; NEO216), 3 bromopyruvate (3BP-POH; NEO218). In each case, we were surprised by the mechanistic differences observed from the native compound to the new drug after POH conjugation. For instance, NEO212 is a DNA-alkylating agent, but with 3x the BBB penetration, 10x the cytotoxic potency, and 3x the stability. This presentation will demonstrate our discovery process using our POH conjugates, and our current IND process for NEO212, which we hope to bring to the clinic in the next 6 months. Citation Format: Thomas C. Chen, Axel H. Schonthal, Florence H. Hofman. Perillyl alcohol derivatives as anticancer agents [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B77.
Sox8 is essential for M cell maturation to accelerate IgA response at the early stage after weaning in mice
Authors: Shunsuke Kimura, Nobuhide Kobayashi, Yutaka Nakamura, Takashi Kanaya, Daisuke Takahashi, Ryoji Fujiki, Mami Mutoh, Yuuki Obata, Toshihiko Iwanaga, Tomoo Nakagawa, Naoya Kato, Shintaro Sato, Tsuneyasu Kaisho, Hiroshi Ohno, Koji Hase
Journal: The Journal of Experimental Medicine (2019)

Microfold (M) cells residing in the follicle-associated epithelium (FAE) of the gut-associated lymphoid tissue are specialized for antigen uptake to initiate mucosal immune responses. The molecular machinery and biological significance of M cell differentiation, however, remain to be fully elucidated. Here, we demonstrate that Sox8, a member of the SRY-related HMG box transcription factor family, is specifically expressed by M cells in the intestinal epithelium. The expression of Sox8 requires activation of RANKL-RelB signaling. Chromatin immunoprecipitation and luciferase assays revealed that Sox8 directly binds the promoter region of Gp2 to increase Gp2 expression, which is the hallmark of functionally mature M cells. Furthermore, genetic deletion of Sox8 causes a marked decrease in the number of mature M cells, resulting in reduced antigen uptake in Peyer’s patches. Consequently, juvenile Sox8-deficient mice showed attenuated germinal center reactions and antigen-specific IgA responses. These findings indicate that Sox8 plays an essential role in the development of M cells to establish mucosal immune responses.
Warfarin versus aspirin prevents portal vein thrombosis after laparoscopic splenectomy and azygoportal disconnection: A randomized clinical trial
Authors: Dou-Sheng Bai, Bing-Lan Xia, Chi Zhang, Jing Ye, Jian-Jun Qian, Sheng-Jie Jin, Guo-Qing Jiang
Journal: International Journal of Surgery (2019)
Plasmacytoid variant urothelial carcinoma: Clinicopathologic outcomes and experience with neoadjuvant chemotherapy.
Authors: Kyle J Ericson, Lewis Thomas, Byron H Lee
Journal: Journal of Clinical Oncology (2019)

483 Background: Plasmacytoid variant histology is a rare variant that is often locally advanced at diagnosis. Data is limited to small series and the ideal treatment remains unknown. Here we report the clinicopathologic features and outcomes of 29 patients with plasmacytoid variant histology, including 12 patients treated with neoadjuvant chemotherapy (NAC) and 4 with adjuvant or salvage immunotherapy. Methods: All cystectomies performed from 2011-2018 at our institution were reviewed. Patients with plasmacytoid features on transurethral resection or cystectomy were included. Categorical variables were compared using chi-squared tests and survival outcomes were analyzed with log-rank analysis. Results: A total of 993 patients underwent cystectomy for malignancy. Of these, 29 patients (2.9%) had plasmacytoid variant features. At cystectomy, 65.5% were ≥ pT3, 48.2% were node positive, and 13.8% had positive soft-tissue margins. Twelve patients died during the observed period (41.4%), with a median time to death of 7.2 months. Among surviving patients, median follow-up was 21.9 months. Of the 4 patients with positive margins, survival was significantly worse than those with negative margins (p&lt;0.005); all 4 died with a median survival of 1.8 months. Cisplatin based NAC was given to 12 patients (41.4%). NAC was not associated with a survival benefit over cystectomy alone (median survival 27.7 and 51.9 months, respectively; p=0.07), complete response (pT0), or organ confined disease (&lt; pT3). Four patients (13.8%) received adjuvant or salvage checkpoint inhibitors; all surviving with a median follow-up of 28.7 months. Conclusions: Consistent with prior reports, plasmacytoid variants were uncommon and locally advanced. While our rate of positive margins was lower than in previous series, patients with positive margins universally did poorly. NAC was not associated with improved survival or pathologic outcomes. Our findings suggest plasmacytoid variants may not respond well to NAC, though no definitive conclusions can be drawn due to the small number of patients and retrospective design.
Free facilities or false promises? The effects of Accredited Social Health Activists' home visits on maternal and newborn health equity in Uttar Pradesh, India: a mixed methods study
Authors: Andrea Blanchard, Shahnaz Ansari, Rajni Rajput, Arup Kumar Das, Tanja Houweling, Timothy Colbourn, Audrey Prost
Journal: The Lancet Global Health (2019)

BackgroundThe state of Uttar Pradesh has one of the highest neonatal mortality rates in India (45 per 1000 livebirths), with substantially more deaths among the poorest people. To address this, India's National Health Mission has trained community-based incentivised volunteers called Accredited Social Health Activists (ASHAs) to visit all pregnant women at home and support them to deliver their babies in public hospitals or clinics. Contextual processes greatly shape community-based efforts to reduce health inequities, yet few studies have examined these dynamics. We undertook a mixed methods study to understand the extent to which, how, and in what circumstances ASHAs' home visits reduce gaps between socioeconomic groups in institutional delivery rates in Uttar Pradesh, India.MethodsWe conducted generalised linear modelling using a cross-sectional survey in a representative random sample of women who had given birth within the last 2 months in 25 districts in 2014–15. We conducted qualitative social mapping and focus group discussions in four villages that were more and less remote in two districts, with purposively selected ASHAs, and mothers from higher and lower socioeconomic groups (n=134). We used thematic framework analysis. Sigma Institutional Review Board and University College London Research Ethics Committee provided ethics approval.FindingsWe included data from 57 778 women. Institutional delivery rates were 7 and 12 percentage points more equal between the highest and lowest caste (RR 1·09 [95% CI 1·04–1·14] vs 1·25 [1·17–1·33]) and education groups (1·29 [1·26 −1·31] vs 1·66 [1·61–1·70]), respectively, in women who received any third trimester home visits from ASHAs compared with no visit. The qualitative data showed that ASHAs' promotion of incentives and free care influenced families of lower socioeconomic position to deliver their babies in public community health centres. However, many of these families lost faith in the facilities when they experienced indirect costs, lack of medicines or transport, and poor treatment, particularly in the remote villages. These issues also led complicated deliveries to be referred to higher-level, often private, hospitals that poor families can ill afford, and wealthier families to opt directly for private care.InterpretationThis study provides guidance for adapting implementation strategies within socioeconomic and health system contexts by strategically supporting ASHAs to build relationships with all families, eliminating indirect costs and other accessibility barriers, and strengthening the quality of care at public health facilities where most needed. This would help alleviate families' widespread reliance on emergency and expensive delivery care, and reinforce ASHAs' role in improving maternal and newborn health equity.FundingNone.
Beyond trait reductionism: Implications of network structures for dimensional models of psychopathology
Authors: Robert F. Bornstein
Journal: Behavioral and Brain Sciences (2019)

Abstract Borsboom et al. discuss the implications of network structures for neurobiology-based reductionism, but inherent in the network approach is that dimensional models of psychopathology are untenable as well. Insofar as mental disorders are complex dynamic constellations of symptoms, the “trait reductionism” of dimensional psychopathology frameworks suffers from the same limitations as neurobiological reductionism.