tbuckley/cabot-search huggingface dataset:
Abstract P118: Serious Financial Difficulties Impact Subclinical Cardiovascular Disease Among Mexican Women
Authors: Kaela Connors, Mario H Flores-Torres, Unnur Valdimarsdóttir, Ruy Lopez-Ridaura, Carlos Cantu-Brito, Andres Catzin-Kuhlmann, Beatriz Beatriz, Martin Lajous
Journal: Circulation (2019)

Introduction: Sudden loss of income has been previously associated to all-cause mortality. Diminished financial resources may result in reduced access to healthcare. On the other hand, the psychological stress associated with economic loss may also affect cardiovascular health through a combination of negative physiological changes and unhealthy lifestyle choices. Hypothesis: We hypothesize that serious financial difficulties will increase cardiovascular risk in Mexican women. Methods: We categorized 1,764 employed and insured disease-free women from the Mexican Teachers’ Cohort according to their response to ‘Have you ever had serious financial difficulties (for example, not enough money for food or place to live)?’ included in a self-reported instrument on life stressors conducted 2013 and 2016. On the same visit, carotid artery intima-media thickness (IMT) was measured by standardized neurologists on both carotid arteries through ultrasound following international guidelines and log transformed. We defined carotid atherosclerosis as an intima media thickness of ≥0.8mm in either of the carotid arteries or the presence of plaque. We collected data on cofounders (age, site, and socio-economic status calculated based on score of household assets), perceived stress (Perceived Stress Scale-10), and other potential intermediates (body mass index, smoking, hypercholesterolemia, hypertension, and diabetes). We used multivariable linear and logistic regression models to assess the association of serious financial difficulties, IMT, and carotid atherosclerosis. Results: The average age of the study population was 49.4 (SD±5.0) years and 312 (17.8%) women reported exposure to serious financial difficulties as adults. High levels of perceived stress (62.2% vs. 42.5%), obesity (42.0% vs. 36.2%), smoking (9.3% vs. 6.7%), hypercholesterolemia (33.3% vs. 31.7%), and diabetes (10.3% vs. 7.5%) were more common among women with serious financial difficulties relative to women without. Women with serious financial difficulties had 1.7% (95% CI 0.2, 3.3) higher mean IMT than women without after adjusting for potential confounders. The prevalence of carotid atherosclerosis was 26.6% in women who experienced serious financial difficulties and 20.9% in women without such exposure. The multivariable-adjusted odds ratio for carotid atherosclerosis among women with serious financial difficulties was 1.40 (95% CI 1.03, 1.90) relative to women without. Adjusting for potential intermediates did not alter the interpretation of our results. Conclusion: Serious financial difficulties were associated to subclinical cardiovascular disease among employed and insured Mexican women.
Myeloma Cells Have the Ability to Suppress Th1-Inducing Capacity but Enhance Th2-Mediated Response of Dendritic Cells By Producing Factors Other Than Soluble SLAMF7
Authors: Yoshiko Azuma, Tomoki Ito, Muneo Inaba, Kai Imai, Hideaki Yoshimura, Masaaki Hotta, Takahisa Nakanishi, Shinya Fujita, Aya Nakaya, Atsushi Satake, Kazuyoshi Ishii, Shosaku Nomura
Journal: Blood (2018)
Impaired expression of Type I and Type II interferon-receptors in HCV infected chronic liver disease and liver cirrhosis
Authors: Partha K. Chandra, Feyza Gunduz, Sidhartha Hazari, Ramazan Kurt, Rajesh Panigrahi, Bret Poat, David S. Bruce, Ari J. Cohen, Humberto E. Bohorquez, Ian C. Carmody, George E. Loss, Tong Wu, Luis A. Balart, Srikanta Dash
Journal: Hepatology (2014)
Early changes in renal function and late cardiovascular disease risk in testicular cancer survivors with 25 years follow-up.
Authors: Sjoukje Lubberts, Joost A.B. Kampman, Hink Boer, Coby Meijer, Gerjan J. Navis, Jourik A. Gietema
Journal: Journal of Clinical Oncology (2015)

4541 Background: Cisplatin-based chemotherapy (CT) for testicular cancer (TC) leads to an increased cardiovascular disease (CVD) risk, related to endothelial damage by circulating platinum levels of which renal function is the main determinant (J Clin Oncol 30, 2012 (suppl- abstr 4528)). Aim was to investigate the role of pre-CT renal function and early treatment-related decrease of renal function in relation to late CVD development. Methods: We performed a retrospective study in TC patients (pts) treated with cisplatin-based CT from 1980-1989. Renal function was determined before and after completion of at least 1 course CT with 125I-iothalamate clearance which is the gold standard for glomerular filtration rate (GFR). Follow-up regarding CVD was collected in 5-yr survivors from hospital records and via general practitioners. Results: 50 pts, median age of 28 yrs (17-53) at start of CT, were eligible. All pts started with a normal renal function (GFR ≥ 90 ml/min/1.73m2), median GFR was 129 ml/min/1.73m2 (93-185). After start of CT median GFR decrease was 43 ml/min/1.73m2 (-90-+11). 52% ended up with GFR impairment classified as chronic kidney disease (GFR < 90 ml/min/1.73 m2). There were 38 5-yr survivors with a median follow-up of 20 yrs (6-32). 8 (21%) developed CVD median 14 yrs (8-26) after CT (3 strokes, 2 myocardial infarctions, 1 coronary artery disease, 2 peripheral artery disease). Pts with late CVD had lower pre-CT GFR. Pts who ended up with a GFR <90 ml/min/1.73m2 developed more frequently CVD (7/19 (37%) vs 1/19 (5%); p=.042). Conclusions: A GFR < 90 ml/min/1.73 m2 after CT is associated with an increased risk of late CVD after median 14 yrs. Patients with impaired renal function after treatment should be monitored closely regarding (risk factors for) CVD. Characteristics of 5-year survivors, n=38. CVD (n=8) No CVD (n=30) P* Age pre-CT (yrs) median (range) 30 (24-53) 26 (17-52) .037 Cum cisplatinum dose (mg/m2) 400 (375-800) 400 (350-800) .688 GFR pre-CT (ml/min/1.73m2) 104 (93-154) 132 (100-185) .013 Change in GFR (ml/min/1.73m2) -38 (-76-+11) -49 (-77- -6) .299 After CT GFR < 90 ml/min (n,%) 7/8 (88%) 12/30 (40%) .042 * Mann-Whitney U / Fisher exact test.
Invasive urothelial cancer (iUC) with FGFR3 hotspot mutation/fusion (FGFR3+): A molecularly and clinically distinctive entity?
Authors: Jose Mauricio S. C. Mota, Min Yuen Teo, Han Li, Arjun Vasant Balar, Matthew I. Milowsky, Samuel Aaron Funt, Chung-Han Lee, Ashley Marie Regazzi, Michael F. Berger, David B. Solit, Dean F. Bajorin, Jonathan E. Rosenberg, Gopa Iyer
Journal: Journal of Clinical Oncology (2019)

459 Background: FGFR3+ is ubiquitous in non-invasive UC but found in ~16% of iUC. We sought to characterize the genomic landscape and response to platinum-based chemotherapy (ctx) of FGFR3+ iUC in the neoadjuvant (NAC) and metastatic (mUC) setting. Methods: Two molecularly-characterized cohorts were used for the study objective: (1) NAC-treated muscle invasive UC, incorporating consecutively sequenced standard of care UC and patients (pts) from a phase II trial (Iyer et al, JCO 2018); (2) mUC treated with platinum ctx, with FGFR3- mUC from a published work (Teo et al, CCR 2017) serving as comparator. iUC with hotspot mutations / fusions were considered FGFR3+. Clinical outcomes and frequency of altered genes were compared. Results: In the NAC cohort, 87 pts were identified (NAC response: pT0 [n = 20, 23%], &lt;pT2 [n = 22, 25%], ≥pT2 [n = 45, 52%]). FGFR3+ (n = 11, 13%) was associated with a trend towards poor NAC response and was found in 0/20 pT0 (0%), 3/22 &lt;pT2 (14%) and 8/45 ≥pT2 (18%) (Cochran-Armitage, p=0.06). Among ≥pT2 tumors, FGFR3+ was associated with shorter recurrence-free survival (3.7 vs 17.6 months; HR 4.8 95% CI 1.9–12.1). 49 FGFR3+ mUC pts were identified and compared to FGFR3- mUC (n = 82). FGFR3+ had a numerically higher rate of lung metastasis (42% vs 29%, p = 0.25). 1 st line therapies included: platinum-based ctx (n = 27), non-platinum ctx (n = 4), immunotherapy (IO, n = 13), ctx + IO (n = 4), and FGFR inhibitor (n = 1). Platinum ctx response rate for 21/27 evaluable FGFR3+ pts was 40%. FGFR3+ mUC had similar overall survival (OS, median 25.7 vs 15.8 months, HR 0.7, 95%CI 0.4-1.2; 1-year OS: 70% vs 59%) and progression-free survival (median: 7.2 vs 7.1 months, HR 1.3, 95% CI 0.8-2.1). Frequencies of altered genes are tabulated. No differences in mutational load were seen. Conclusions: FGFR3+ iUC is a genomically distinct subset of iUC. Despite low responses to NAC ctx, FGFR3+ had similar responses, PFS, and OS in the mUC setting. [Table: see text]
Precision medicine for the discovery of treatable mechanisms in severe asthma
Authors: Kian Fan Chung, Ian M. Adcock
Journal: Allergy (2019)

Abstract Although the complex disease of asthma has been defined as being heterogeneous, the extent of its endophenotypes remains unclear. The pharmacological approach to initiating treatment has, until recently, been based on disease control and severity. The introduction of antibody therapies targeting the Type 2 inflammation pathway for patients with severe asthma has resulted in the recognition of an allergic and an eosinophilic phenotype, which are not mutually exclusive. Concomitantly, molecular phenotyping based on a transcriptomic analysis of bronchial epithelial and sputum cells has identified a Type 2 high inflammation cluster characterized by eosinophilia and recurrent exacerbations, as well as Type 2 low clusters linked with IL ‐6 trans‐signalling, interferon pathways, inflammasome activation and mitochondrial oxidative phosphorylation pathways. Systems biology approaches are establishing the links between these pathways or mechanisms, and clinical and physiologic features. Validation of these pathways contributes to defining endotypes and treatable mechanisms. Precision medicine approaches are necessary to link treatable mechanisms with treatable traits and biomarkers derived from clinical, physiologic and inflammatory features of clinical phenotypes. The deep molecular phenotyping of airway samples along with noninvasive biomarkers linked to bioinformatic and machine learning techniques will enable the rapid detection of molecular mechanisms that transgresses beyond the concept of treatable traits.
Abstract 036: Contemporary Estimates of Obesity Incidence of Among Children in the United States
Authors: Shakia T Hardy, Carmen Ng, Solveig Cunningham, Michael Kramer
Journal: Circulation (2019)

Introduction: Childhood obesity is a growing epidemic in the United States with approximately 1 in 5 children being obese. Although prevalence estimates for childhood obesity are regularly updated, little is known about the current incidence of childhood obesity among a nationally representative population, since initial estimates were provided by the Early Childhood Longitudinal Study Kindergarten (ECLS-K) Class of 1998. Methods: We estimated the annual incidence of obesity and the cumulative incidence of obesity over 5 years using the contemporary ECLS-K Class of 2011 (analytic sample = 7019). Height and weight were measured at eight time points between kindergarten (2010) and fourth grade (2015). We defined normal weight (&lt;85 th percentile), overweight (85 th -95 th percentile), and obesity (&gt;95 th percentile) using Centers for Disease Control and Prevention sex-and age-specific growth curves. Results: At kindergarten entry (mean age 5.6 years), 15.5% of children were overweight and 14.7% of children were obese; in fourth grade (mean age 10.1 years) overweight prevalence had increased to 17.3% and obesity prevalence had increased to 20.1%. Kindergarteners who were overweight were 6 times as likely as normal-weight kindergarteners to become obese by fourth grade (5-year cumulative incidence, 30.5% vs. 5.2%). In early elementary school, annualized obesity incidence proportions were higher over summer breaks (5.6% and 5.4% during summer breaks from Kindergarten to first grade and first grade to second grade, respectively) than during the school year (3.8% and 3.8% during Kindergarten and first grade school years, respectively). Incident obesity was higher among boys compared girls, non-Hispanic black and Hispanic children compared to non-Hispanic white children, and among those from the poorest socioeconomic quintiles compared to the highest socioeconomic quintile. Conclusions: Incident obesity between the ages of 5 and 10 years was more likely to have occurred during summer breaks and primarily among children who had entered kindergarten overweight. Childhood obesity prevention efforts should focus on the prevention of overweight prior to kindergarten and investigate causes of summer weight gain during elementary school.
Abstract P232: Better Dietary Quality is Associated with Lower Circulating Ceramide Concentrations in the Framingham Offspring Cohort
Authors: Maura E Walker, Vanessa Xanthakis, Lynn L Moore, Vasan Ramachandran, Paul F Jacques
Journal: Circulation (2019)

Introduction: Diet quality may alter cardiometabolic risk by the modification of circulating lipid species. Ceramides are a class of sphingolipid implicated in cardiometabolic risk. We hypothesized that a higher diet quality may be associated with lower plasma concentrations of three ceramide species. Methods: Diet quality was reflective of adherence to the 2010 Dietary Guidelines for Americans and was determined using the 2010 dietary guideline adherence index (DGAI-2010) score. The DGAI-2010 score is composed of 14 energy specific components and 11 healthy choice components. A higher score represents higher adherence with a maximum score of 100. We determined the average cumulative DGAI-2010, reflective of usual diet quality over 14 years. Plasma ceramide concentrations were assayed using a validated LC-MS/MS protocol. Participants of Framingham Offspring cohort (N = 2174; mean age, 66 years; 55% women) according to quartile of DGAI-2010 score. Multivariable linear regression was used to relate diet quality to plasma ceramide concentrations (C16:0, C22:0, and C24:0), and to ceramide ratios (C22:0/C16:0 and C24:0/C16:0). An initial model was adjusted for age, sex, smoking status, use of lipid-lowering medication, total energy intake, and physical activity, and then additionally for body mass index (BMI). Results: The median (IQR) DGAI-2010 score within each quartile was Q1: 49 (7), Q2: 58 (4), Q3: 65 (3), and Q4: 73 (6). On average participants in the highest quartile (Q4) of DGAI-2010 score were older, more likely to be a woman, less likely to smoke, were slightly more physically active, and had a lower BMI (P trend &lt;0.05). The DGAI-2010 score was inversely associated with concentrations of the C16:0, C22:0, and C24:0 ceramides and the C22:0/C16:0 ratio (all P trend &lt;0.05) but not the C24:0/C16:0 ratio ( Table 1 ). Conclusion: Inverse relations of dietary quality and select circulating ceramide species may help elucidate how diet may influence cardiometabolic risk.
Liver-resident NK cells suppress autoimmune cholangitis and limit the proliferation of CD4+ T cells
Authors: Zhi-Bin Zhao, Fang-Ting Lu, Hong-Di Ma, Yin-Hu Wang, Wei Yang, Jie Long, Qi Miao, Weici Zhang, Zhigang Tian, William M. Ridgway, Jie Cao, M. Eric Gershwin, Zhe-Xiong Lian
Journal: Cellular and Molecular Immunology (2019)
Experiences of gender-based violence in women asylum seekers from El Salvador, Honduras, and Guatemala: a retrospective, qualitative study
Authors: Eileen Wang, Megan D'Andrea, Kimberly Baranowski, Elizabeth Singer
Journal: The Lancet Global Health (2019)

BackgroundIn 2016, around 65 000 women fled gender-based violence in the Northern Triangle (NTCA) countries of El Salvador, Honduras, and Guatemala, and attempted to seek asylum in the USA. Some women participate in medical evaluations by clinicians to document the effect of these human rights violations as part of the asylum process. The aim of this study is to elucidate the forms of persecution experienced by women in this region, and the physical and psychological sequelae of this violence.MethodsWe undertook a retrospective, qualitative study of asylum-seeking adult women fleeing gender-based violence from the NTCA who were seen by evaluators in the Mount Sinai Human Rights Program from February, 2014, to August, 2018. We included any case in which the client self-identified as female, came from an NTCA country, and received a psychological evaluation. This study was approved by the Mount Sinai Institutional Review Board. We used a modified consensual qualitative research (CQR-M) approach to identify themes found across the archived and de-identified affidavits written as part of the medical evaluation.FindingsWe included data from 70 women; mean age was 29·4 years (SD 6·5; range 18–55 years]. 24 women identified as Salvadoran, 15 as Guatemalan, and 31 as Honduran. All women reported violence perpetrated by their communities, families, intimate partners, and/or powerful gangs, and faced justice systems in their countries that they felt would not protect them. They had been subject to: verbal (50 women [71%]), physical (57 [81%]), and sexual (59 [84%]) assaults; death threats (58 [83%]); control (40 [57%]); extortion (24 [34%]); and harm, or threats of harm, to their children (50 [43%] and 22 [31%], respectively). Evaluators identified psychological symptoms associated with anxiety (56 women [80%]), depression (64 [91%]), and post-traumatic stress disorder (56 [80%]), as well as suicidality (33 [47%]). Women also reported physical injury including bruising, head injury and loss of consciousness, and gynaecological harm including miscarriage and forced sterilisation. Many women had been displaced within their own countries before fleeing and stated that they travelled with their children, experienced hazardous conditions and violence during their journey, and were detained on arrival in the USA. Finally, the women reported resilience associated with their religious beliefs, family, temperament, and ability to make meaning from their experiences.InterpretationThis study highlights the systemic nature of gender-based violence in the NTCA. The results also describe the perils that women from the NTCA encountered during their migration and demonstrate the continued structural violence that awaits them if they are denied asylum and returned to their countries of origin.FundingNone.
Is Nitric Oxide Nephro- or Cardioprotective?
Authors: Maxime Coutrot, François Dépret, Matthieu Legrand
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

artery pressure during exercise in ePAH have been unclear.Dynamic pulmonary vasoconstriction has been previously implicated (9, 10); however, in comparison with control subjects and subjects with PAH, our findings show the presence of a distinct vascular pathology at rest in subjects with ePAH, represented by increased perfusion heterogeneity across image resolutions (length scale spectrum 10-110 mm).Whether this pattern heralds permanent vascular remodeling cannot be determined by our data, and a longitudinal study will be required to definitively evaluate whether this pathology relates to an intermediate PAH phenotype (10) or whether this unique perfusion pattern represents a distinct disease process.
Prospective Multicenter Validation of Androgen Receptor Splice Variant 7 and Hormone Therapy Resistance in High-Risk Castration-Resistant Prostate Cancer: The PROPHECY Study
Authors: Andrew J. Armstrong, Susan Halabi, Jun Luo, David M. Nanus, Paraskevi Giannakakou, Russell Z. Szmulewitz, Daniel C. Danila, Patrick Healy, Monika Anand, Colin J. Rothwell, Julia Rasmussen, Blair Thornburg, William R. Berry, Rhonda S. Wilder, Changxue Lu, Yan Chen, John L. Silberstein, Gabor Kemeny, Giuseppe Galletti, Jason A. Somarelli, Santosh Gupta, Simon G. Gregory, Howard I. Scher, Ryan Dittamore, Scott T. Tagawa, Emmanuel S. Antonarakis, Daniel J. George
Journal: Journal of Clinical Oncology (2019)

Androgen receptor splice variant 7 (AR-V7) results in a truncated receptor, which leads to ligand-independent constitutive activation that is not inhibited by anti-androgen therapies, including abiraterone or enzalutamide. Given that previous reports suggested that circulating tumor cell (CTC) AR-V7 detection is a poor prognostic indicator for the clinical efficacy of secondary hormone therapies, we conducted a prospective multicenter validation study.PROPHECY ( ClinicalTrials.gov identifier: NCT02269982) is a multicenter, prospective-blinded study of men with high-risk mCRPC starting abiraterone acetate or enzalutamide treatment. The primary objective was to validate the prognostic significance of baseline CTC AR-V7 on the basis of radiographic or clinical progression free-survival (PFS) by using the Johns Hopkins University modified-AdnaTest CTC AR-V7 mRNA assay and the Epic Sciences CTC nuclear-specific AR-V7 protein assay. Overall survival (OS) and prostate-specific antigen responses were secondary end points.We enrolled 118 men with mCRPC who were starting abiraterone or enzalutamide treatment. AR-V7 detection by both the Johns Hopkins and Epic AR-V7 assays was independently associated with shorter PFS (hazard ratio, 1.9 [95% CI, 1.1 to 3.3; P = .032] and 2.4 [95% CI, 1.1 to 5.1; P = .020], respectively) and OS (hazard ratio, 4.2 [95% CI, 2.1 to 8.5] and 3.5 [95% CI, 1.6 to 8.1], respectively) after adjusting for CTC number and clinical prognostic factors. Men with AR-V7-positive mCRPC had fewer confirmed prostate-specific antigen responses (0% to 11%) or soft tissue responses (0% to 6%). The observed percentage agreement between the two AR-V7 assays was 82%.Detection of AR-V7 in CTCs by two blood-based assays is independently associated with shorter PFS and OS with abiraterone or enzalutamide, and such men with mCRPC should be offered alternative treatments.
Value of renal gene panel diagnostics in adults waiting for kidney transplantation due to undetermined end-stage renal disease
Authors: Isabel Ottlewski, Johannes Münch, Timo Wagner, Ria Schönauer, Anette Bachmann, Antje Weimann, Julia Hentschel, Tom H. Lindner, Daniel Seehofer, Carsten Bergmann, Rami Abou Jamra, Jan Halbritter
Journal: Kidney International (2019)

End-stage renal disease (ESRD) of undetermined etiology is highly prevalent and constitutes a significant clinical challenge, particularly in the context of kidney transplantation (KT). Despite the identification of numerous rare hereditary nephropathies over the last few decades, patients with undetermined ESRD are not being systematically investigated for rare genetic causes in clinical practice. To address this, we utilized mutation analysis in patients on the kidney transplant waitlist and scrutinized underlying renal diagnoses of 142 patients in a single center KT-waitlist. This cohort was stratified into 85 cases of determined and 57 cases of undetermined ESRD. The latter patients were analyzed by a renal gene panel for mutations in 209 genes associated with ESRD. The most likely genetic diagnoses in 12% of the tested individuals with undetermined ESRD were established. All of these patients showed mutations in genes encoding components of the glomerular filtration barrier. Taken together, hereditary nephropathies, including autosomal dominant polycystic kidney disease, were identified in 35 of the 142 patients of the waitlist cohort. By significantly increasing the proportion of hereditary diagnoses from 29 to 35 patients, the rate of undetermined ESRD significantly decreased from 57 to 51 patients. This study demonstrates the beneficial use of genetic diagnostics in significantly unraveling undetermined ESRD cases prior to KT. Thus, in the absence of renal histology or the presence of unspecific histological conditions, such as hypertensive nephrosclerosis, focal segmental glomerulosclerosis or thrombotic microangiopathy, genetic analysis may provide a robust and specific renal diagnosis and allow for optimizing pre- and post-KT management.Graphical abstract