tbuckley/cabot-search huggingface dataset:
Abstract MP20: Ethnic Differences in Coronary Heart Disease and Stroke Diagnosis Among Blacks in the United States
Authors: Nishit Patel, Cheryl Dennison Himmelfarb, Ruth-Alma Turkson-Ocran, Yvonne Commodore-Mensah
Journal: Circulation (2019)

Introduction: African-Americans bear a disproportionate burden of atherosclerotic cardiovascular disease than other racial/ethnic groups in the U.S. With current globalization trends, Black immigrants from Africa and Caribbean Islands contribute to the ethnic diversity of Blacks in the U.S. Despite the diversity in socioeconomic status, culture and genetic admixture, Black immigrants are traditionally combined with African Americans, therefore limiting opportunities to understand the health of Black immigrants. Hypothesis: Ethnic differences in coronary heart disease (CHD) and stroke prevalence exist among African-Americans (AAs), African-immigrants (AIs) and Afro-Caribbean (ACs). Methods: We conducted a cross-sectional study of the 2010-2016 National Health Interview Survey. CHD and stroke diagnoses were self-reported. We performed a descriptive and multivariable logistic regression analyses adjusting for demographic and health characteristics and stratified by sex. Results: We included 34,513 participants who were AAs (N=30,516), AIs (N=1,371) and ACs (N=2,626). Significant differences in sociodemographic characteristics were observed. AIs were the youngest (39 years) with the highest proportion of college graduates (51%). AAs (42%) were more likely to report hypertension diagnosis than AIs (19%) and ACs (36%) (p&lt;0.05)Also, AAs (44%) were more likely to be overweight/obese than AIs (24%) and ACs (31%) (p&lt;0.05). Diabetes prevalence was similar for AAs (13.7%) and ACs (12.8%), and lower for AIs (6.3%). Adjusted models showed that AAs were more likely to report CHD or stroke diagnoses than AIs and ACs (p&lt;0.05). Sex-stratified models showed AA (4.2%) and AI (3.2%) women reporting similar rates of CHD diagnosis. (Table) Conclusion: Ethnic differences were noted in the prevalence of CHD and stroke diagnosis and risk among Blacks. Future studies should examine the health advantage of AIs and ACs to inform interventions and policy to improve the health of AAs and maintain the health of foreign-born Blacks.
Distinct Clinicopathological and Prognostic Features of Thin Nodular Primary Melanomas: An International Study from 17 Centers
Authors: Clio Dessinioti, Niki Dimou, Alan C Geller, Aravella Stergiopoulou, Serigne Lo, Ulrike Keim, Jeffrey E Gershenwald, Lauren E Haydu, Simone Ribero, Pietro Quaglino, Susana Puig, Josep Malvehy, Lidija Kandolf-Sekulovic, Tatjana Radevic, Roland Kaufmann, Laura Meister, Eduardo Nagore, Victor Traves, Grigorios G Champsas, Mihaela Plaka, Brigitte Dreno, Emilie Varey, David Moreno Ramirez, Reinhard Dummer, Joanna Mangana, Axel Hauschild, Friederike Egberts, Ketty Peris, Laura del Regno, Ana-Maria Forsea, Sabina A Zurac, Ricardo Vieira, Ana Brinca, Iris Zalaudek, Teresa Deinlein, Eleni Linos, Evangelos Evangelou, John F Thompson, Richard A Scolyer, Claus Garbe, Alexander J Stratigos
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background Nodular melanoma (NM) is more likely to be fatal compared with other melanoma subtypes, an effect attributed to its greater Breslow thickness. Methods Clinicopathological features of NM and superficial spreading melanoma (SSM) diagnosed in 17 centers in Europe (n = 15), the United States, and Australia between 2006 and 2015, were analyzed by multivariable logistic regression analysis, with emphasis on thin (T1 ≤ 1.0 mm) melanomas. Cox analysis assessed melanoma-specific survival. All statistical tests were two sided. Results In all, 20 132 melanomas (NM: 5062, SSM: 15 070) were included. Compared with T1 SSM, T1 NM was less likely to have regression (odds ratio [OR] = 0.46, 95% confidence interval [CI] = 0.29 to 0.72) or nevus remnants histologically (OR = 0.60, 95% CI = 0.42 to 0.85), and more likely to have mitoses (OR = 1.97, 95% CI = 1.33 to 2.93) and regional metastasis (OR = 1.77, 95% CI = 1.02 to 3.05). T1 NM had a higher mitotic rate than T1 SSM (adjusted geometric mean = 2.2, 95% CI = 1.9 to 2.5 vs 1.6, 95% CI = 1.5 to 1.7 per mm2, P &amp;lt; .001). Cox multivariable analysis showed a higher risk for melanoma-specific death for NM compared with SSM for T1 (HR = 2.10, 95% CI = 1.24 to 3.56) and T2 melanomas (HR = 1.30, 95% CI = 1.01 to 1.68), and after accounting for center heterogeneity, the difference was statistically significant only for T1 (HR = 2.20, 95% CI = 1.28 to 3.78). The NM subtype did not confer increased risk within each stratum (among localized tumors or cases with regional metastasis). Conclusions T1 NM (compared with T1 SSM) was associated with a constellation of aggressive characteristics that may confer a worse prognosis. Our results indicate NM is a high-risk melanoma subtype that should be considered for inclusion in future prognostic classifications of melanoma.
Efficacy of Bone Marrow Derived MSC for Steroid Refractory Acute GVHD Associates with Age and a Defined Molecular Profile of MSC Donors
Authors: Lotte van der Wagen, Febilla Fernando, Nagesha Appukudige, Anke Janssen, Kasper Westinga, Rick Admiraal, Magdalena Lorenowicz, Paul J. Coffer, Sacha Zeerleder, Jeroen J. Janssen, Gerwin Huls, Annoek Broers, Walter Jfm Van Der Velden, Marinus van Marwijk Kooij, Jaap Jan Boelens, Ineke Slaper-Cortenbach, Jurgen Kuball
Journal: Blood (2017)
Prognostic subclassification of Intermediate Hepatocellular Carcinoma (I-HCC): a multicentre cohort study with propensity score analysis.
Authors: Ramya Ramaswami, David James Pinato, Keiichi Kubota, Mitsuru Ishizuka, Tadaaki Arizumi, Masatoshi Kudo, Jeong Won Jang, Young Woon Kim, Mario Pirisi, Elias Allara, Rohini Sharma
Journal: Journal of Clinical Oncology (2015)

e15139 Background: The clinical heterogeneity of I-HCC significantly impacts on management options. Transarterial chemoembolization (TACE) is standard of care, however selected patients may be offered liver resection (LR), whilst others qualify for best supportive care only. The I-HCC subclassification score developed by Bolondi et al. consists of 4 stages and includes the Child-Pugh class, tumour number, size and presence of portal vein thrombosis (Bscore). We evaluated the prognostic effect of the Bscore on overall survival (OS) in a large multicentre retrospective cohort study of patients with I-HCC stratifying by treatment modality (TACE or LR). Methods: Consecutive patients from centres in Japan, Korea, Italy and the UK who underwent TACE or LR between 2001 and 2014 were enrolled (n = 1423). Baseline characteristics were used to derive the Bscore score in I-HCC patients (n = 611). Propensity score matching (PSM) was applied between LR and TACE patients to match on baseline characteristics (age, gender, hepatitis status and INR). Cox regression models with PSM were used to determine the prognostic significance of the 4 stage Bscore in patients treated with TACE (n = 449) versus LR (n = 162), independent of treatment. Results: Among 611 I-HCC patients, 75% were men and 25% women, with a mean age of 69 years and median OS of 37 months. In all I-HCC patients irrespective of treatment Bscore was predictive of OS (p < 0.001). Median OS BScore 1 - 51 months, 2 – 38.3 months, 3 – 24.3 months, 4 -15.6 months. Proportional hazards assumption was met when PSM was applied and Bscore remained significant in predicting OS (n = 483, p < 0.001). When Bscore was stratified in accordance to treatment modality using PSM, Bscore was predictive in treatment with TACE but not LR (p < 0.001 vs. p = 0.047). Conclusions: The Bscore optimizes prognostic prediction in I-HCC, reducing clinical heterogeneity. However, preliminary results suggest its validity is limited to patients undergoing TACE.
The effects of message framing on cervical cancer screening: A randomized controlled trial.
Authors: Hiroyuki Fujiwara, Akihiro Shimoda, Yoshiki Ishikawa, Yuji Takei, Shizuo Machida, Akiyo Taneichi, Mai Ohashi, Yoshifumi Takahashi, Hiroyuki Morisawa, Takahiro Koyanagi, Yasushi Saga, Mitsuaki Suzuki
Journal: Journal of Clinical Oncology (2015)

e12568 Background: The burden of cervical cancer has been immense. Organized screening programs have helped reduce mortality from this disease, and the cervical cancer rate in Japan is extremely low. Although previous studies revealed that client reminders are an effective means of enhancing cervical cancer screening attendance, it remains unclear what information will be most effective when included in these reminders. Methods: In October 2013, 2,538 women aged 20–39 years who had not participated in screening in the fiscal year were selected from a Japanese urban community setting. Participants were randomly divided into 4 groups (intervention groups; A, B and C, control group; D): group A received a printed reminder with information on the possible benefit of participating in screening (gain-framed message; n = 622), group B receiving a printed reminder with information on the possible risk of not participating in screening (loss-framed message; n = 625), group C received a printed reminder with information on their duty to participate in screening (social norm message; n = 637), and group D received a printed reminder with only basic information about the appointment (usual information; n = 650). Results: Out of 2,534 participants, a total of 227 (9.0%) participated in cervical cancer screening, of whom 193 (10.2%) were in an intervention group and 34 (5.2%) were in the control group (p < 0.001). Logistic regression analysis revealed that there was a significant difference in the screening rate between group A (gain) and D (usual) (p < 0.001), and between group C (norm) and D (usual) (p < 0.001). However, there was no significant difference in the screening rate between group B (loss) and D (usual) (p = 0.120). Conclusions: Intervention with a printed reminder describing the possible benefits of participating in cervical cancer screening was significantly more effective than a reminder containing only the usual information, while intervention with a printed reminder describing the possible risk of not participating in cervical cancer screening was not significantly more effective compared to those with only the usual information.
Whole genome and transcriptome analysis (WGTA) of metastatic adrenocortical carcinoma (mACC).
Authors: Jean-Michel Lavoie, Veronika Csizmok, Gang Wang, Laura Williamson, Marco A. Marra, Janessa J. Laskin, Steven J. M. Jones, Daniel John Renouf, Christian K. Kollmannsberger
Journal: Journal of Clinical Oncology (2019)

e16123 Background: mACC is a rare disease, and no standard treatments exist beyond cytotoxic chemotherapy and mitotane. Recurrent molecular changes have been described, but their clinical significance is still poorly understood, and whether they can guide treatment is unknown. Methods: The genomic and transcriptomic profiles of 6 pts with mACC were analyzed as part of a prospective molecular profiling clinical trial (NCT02155621). Findings were correlated with histopathological and clinical data. Results: Whole genome sequencing of six ACC tumors and matched normal tissues was performed; whole-transcriptome sequencing was performed on five of the six tumors. All cases met Weiss criteria for ACC (including 1 pt with oncocytic ACC). Profiling revealed gain of function variations in CTNBB1 gene in 3 cases (p.S45A, p.S45P and homozygous deletion of exons 2 and 3). A stop-gained mutation (Q167*) and a homozygous copy loss of TP53 gene was observed in 2 cases; mutations of CTNBB1 and TP53 co-occurred in one case. Variations in other DNA repair genes included germline FANCA Q1362* and somatic BRCA2 E790* stop-gained mutations, and a structural variation in RAD52. Copy number amplification was observed for KDM5A (2/6) and RAD52 (2/6), while NF1 (1/6), CDKN2A (1/6), CDKN2B (1/6) and RB1 (2/6) were subjected to homozygous copy losses. Average ploidy models: one diploid, 4 triploid and one tetraploid case; whole chromosome copy losses and gains were seen in all samples. Three cases showed high homologous repair deficiency scores; associated with respectively, an in-frame deletion of V613 in ATM, a TP53 homozygous loss, and a structural variant of RAD52. All six cases exhibit signature 3 or signature 8. At last follow-up, 2 pts remained alive. Treatments included cytotoxic chemotherapy, mitotane, streptozotocin, sunitinib, avelumab with a SMAC mimetic (NCT02022098), a TTK inhibitor (NCT02792465) on the basis of a CTNNB1 mutation and temozolomide with olaparib on the basis of ATM loss. Conclusions: Our findings recapitulate published data on the molecular profile of mACC and support previous findings of large scale chromosomal variation. We identify new potential drivers in chromatin remodelling, cell cycle, and DNA damage repair genes.
The SGLT2 Inhibitor Dapagliflozin Reduces Liver Fat but Does Not Affect Tissue Insulin Sensitivity: A Randomized, Double-Blind, Placebo-Controlled Study With 8-Week Treatment in Type 2 Diabetes Patients
Authors: Aino Latva-Rasku, Miikka-Juhani Honka, Joel Kullberg, Nina Mononen, Terho Lehtimäki, Juha Saltevo, Anna K. Kirjavainen, Virva Saunavaara, Patricia Iozzo, Lars Johansson, Jan Oscarsson, Jarna C. Hannukainen, Pirjo Nuutila
Journal: Diabetes Care (2019)

The aim of this study was to investigate tissue-specific effects of dapagliflozin on insulin sensitivity and liver and body fat in patients with type 2 diabetes.This randomized, double-blind, parallel group, placebo-controlled study recruited 32 patients with type 2 diabetes. Enrolled patients were to have HbA1c 6.5-10.5% (48-91 mmol/mol) and ≥3 months of stable treatment with metformin, dipeptidyl peptidase 4 inhibitor, or their combination. Patients were randomized 1:1 to receive 10 mg dapagliflozin or placebo daily for 8 weeks. Before and after the intervention, tissue insulin sensitivity was measured using [18F]-fluorodeoxyglucose and positron emission tomography during hyperinsulinemic-euglycemic clamp. Liver proton density fat fraction (PDFF) and adipose tissue volumes were assessed using MRI, and blood biomarkers were analyzed.After 8 weeks, glycemic control was improved by dapagliflozin (placebo-corrected change in HbA1c -0.39%, P < 0.01), but whole-body glucose uptake was not increased (P = 0.90). Tissue-specific insulin-stimulated glucose uptake did not change in skeletal muscle, liver, myocardium, or white and brown adipose tissue, and endogenous glucose production remained unaffected. However, there were significant placebo-corrected decreases in liver PDFF (-3.74%, P < 0.01), liver volume (-0.10 L, P < 0.05), visceral adipose tissue volume (-0.35 L, P < 0.01), interleukin-6 (-1.87 pg/mL, P < 0.05), and N-terminal prohormone of brain natriuretic peptide (-96 ng/L, P = 0.03).In this study, 8 weeks of treatment with dapagliflozin reduced liver PDFF and the volume of visceral adipose tissue in obese patients with type 2 diabetes. Although glycemic control was improved, no effect on tissue-level insulin sensitivity was observed.
Effects of exercise and airway clearance (positive expiratory pressure) on mucus clearance in cystic fibrosis: a randomised crossover trial
Authors: Tiffany J. Dwyer, Evangelia Daviskas, Rahizan Zainuldin, Jordan Verschuer, Stefan Eberl, Peter T.P. Bye, Jennifer A. Alison
Journal: European Respiratory Journal (2019)

Exercise improves mucus clearance in people without lung disease and those with chronic bronchitis. No study has investigated exercise alone for mucus clearance in cystic fibrosis (CF). The aim of this study was to compare the effects of treadmill exercise to resting breathing and airway clearance with positive expiratory pressure (PEP) therapy on mucus clearance in adults with CF. This 3-day randomised, controlled, crossover trial included 14 adults with mild to severe CF lung disease (forced expiratory volume in 1 s % predicted 31–113%). Interventions were 20 min of resting breathing (control), treadmill exercise at 60% of the participant's peak oxygen consumption or PEP therapy (including huffing and coughing). Mucus clearance was measured using the radioaerosol technique and gamma camera imaging. Treadmill exercise improved whole lung mucus clearance compared to resting breathing (mean difference 3%, 95% CI 2–4); however, exercise alone was less effective than PEP therapy (mean difference −7%, 95% CI −6– −8). When comparing treadmill exercise to PEP therapy, there were no significant differences in mucus clearance from the intermediate and peripheral lung regions, but significantly less clearance from the central lung region (likely reflecting the huffing and coughing that was only in PEP therapy). It is recommended that huffing and coughing are included to maximise mucus clearance with exercise.
Testicular Adrenal Rest Tumors: Current Insights on Prevalence, Characteristics, Origin, and Treatment
Authors: Manon Engels, Paul N Span, Antonius E van Herwaarden, Fred C G J Sweep, Nike M M L Stikkelbroeck, Hedi L Claahsen-van der Grinten
Journal: Endocrine Reviews (2019)

This review provides the reader with current insights on testicular adrenal rest tumors (TARTs), a complication in male patients with congenital adrenal hyperplasia (CAH). In recent studies, an overall TART prevalence of 40% (range, 14% to 89%) in classic patients with CAH is found. Reported differences are mainly caused by the method of detection and the selected patient population. Biochemically, histologically, and molecularly, TARTs exhibit particular adrenal characteristics and were therefore thought to originate from aberrant adrenal cells. More recently, TARTs have been found to also exhibit testicular characteristics. This has led to the hypothesis of pluripotent cells as the origin of TARTs. High concentrations of ACTH could cause hyperplasia of these pluripotent cells, as TARTs appear to be associated with poor hormonal control with concomitant elevated ACTH. Unfortunately, as yet there are no methods to prevent the development of TARTs, nor are there guidelines to treat patients with TARTs. Intensified glucocorticoid treatment could improve fertility status in some cases, although studies report contradicting results. TARTs can also lead to irreversible testicular damage, and therefore semen cryopreservation could be offered to patients with TARTs. Further research should focus on the etiology and pharmacological treatment to prevent TART development or to treat TARTs and improve the fertility status of patients with TARTs.
Percent genome alteration and outcomes after radical prostatectomy in African American men.
Authors: Farzana A Faisal, Scott A. Tomlins, Edward M. Schaeffer, Tamara L. Lotan
Journal: Journal of Clinical Oncology (2019)

24 Background: African American (AA) men have a higher incidence of and mortality from prostate cancer (PCa) than European American (EA) men. The potential biological determinants of these racial disparities are unknown. Cancer genome evaluations with available clinical outcome data have been limited to EA cohorts. Here we characterize PCa genomes from a large cohort of AA men and identify the associations between genomic alterations and clinical outcomes. Methods: Cancer genomes from 205 AA men treated with radical prostatectomy (RP) were profiled for known somatic mutations and percent genome alteration (PGA; defined as percentage of tumor genome with copy number variation). Logistic regression and Cox proportional hazard analyses assessed the association of genomic alterations with clinical outcomes in multivariate models. PGA was dichotomized by quartiles in analytical models (≤75th percentile vs. &gt;75th percentile). Results: The median PGA was 3.7% and increased with pathologic grade (p&lt;0.001) and stage (p=0.02). Median follow-up was 5 years. AA men with the highest quartile of PGA had significantly worse biochemical recurrence (BCR)-free survival (10 year: 33.5% vs. 50.2%; p=0.006) and metastasis-free survival (10 year: 47.9% vs. 89.0%; p&lt;0.001) than men with lower quartiles of PGA. PGAwas associated with increased risks of higher grade (OR 2.0, 95% CI 1.1-3.7, p=0.03), higher stage (OR 2.0, 95% CI 1.1-3.8, p=0.03), BCR (univariate: HR 1.9, 95% CI 1.2-3.2, p=0.01), and metastasis (HR 9.6, 95% CI 2.9-31.3, p&lt;0.001). The most common somatic mutations were SPOP (12.5%, 123/184), FOXA1 (9.2%, 17/184), and TP53 (4.4%, 8/184). Only TP53 was associated with increased risks of adverse outcomes: higher stage (OR 5.3, 95% CI 1.5-19.4, p=0.01), BCR (univariate: HR 2.4, 95% CI 1.0-5.9, p=0.06), and metastasis (HR 9.5, 95% CI 2.2-40.6, p=0.002). Conclusions: In AA men, PCa genome profiles reveal unique genomic alterations. Notably, PGA in AA men predicts adverse pathologic and oncologic outcomes after RP and can potentially be considered a prognostic biomarker in this racial group. This research highlights the importance of racial ancestry in cancer genomics studies and precision medicine strategies.
Osseointegration: Long‐Term Prevention of Bacterial Infection and Enhanced Osteoinductivity of a Hybrid Coating with Selective Silver Toxicity (Adv. Healthcare Mater. 5/2019)
Authors: Kai Xie, Ziao Zhou, Yu Guo, Lei Wang, Guoyuan Li, Shuang Zhao, Xiangmei Liu, Jun Li, Wenbo Jiang, Shuilin Wu, Yongqiang Hao
Journal: Advanced Healthcare Materials (2019)

In article number 1801465 by Wenbo Jiang, Shuilin Wu, Yongqiang Hao, and co-workers, HA/Ag/CS coatings are designed to prevent biofilm formation and enhance osteoinductivity of Ti implants. Organic chelators CS and PDA are used to reduce the rapid silver ion release from AgNPs. Due to the double chelating effect of PDA and CS, the coating exhibits excellent antibacterial effects with good osteogenic performance and longitudinal biocompatibility.
“To rout or snort in the sleepe” a detailed medical description of sleep-disordered breathing and its consequences by Georg Grau in 1688
Authors: Sven Rupprecht, Doris Schönefeld, Nasim Kroegel, Otto W. Witte, Matthias Schwab, Ekkehart Paditz
Journal: European Respiratory Journal (2019)

<b>Description of sleep disordered breathing and its consequences was made as early as the 17th century, including upper airway pathology during sleep, risk factors for SDB and medical consequences, simply based on detailed medical observation and examination</b>http://ow.ly/SVRq30o98KV
Abstract 16399: Cardiac Rehabilitation Increases Plasma Brain-Derived Neurotrophic Factor Levels in Patients With Heart Failure
Authors: Seiji Takashio, Yoichi Goto, Toshihisa Anzai, Kenichi Tsujita
Journal: Circulation (2017)

Introduction: Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, which regulates neuronal differentiation and functions. Low levels of BDNF potentially play a role in ...