tbuckley/cabot-search huggingface dataset:
Overexpression of lncRNA IGFBP4–1 reprograms energy metabolism to promote lung cancer progression
Authors: Binyao Yang, Lisha Zhang, Yi Cao, Shuai Chen, Jun Cao, Di Wu, Jiansong Chen, Huali Xiong, Zihua Pan, Fuman Qiu, Jinbin Chen, Xiaoxuan Ling, Maosheng Yan, Suli Huang, Shiyu Zhou, Tiegang Li, Lei Yang, Yunchao Huang, Jiachun Lu
Journal: Molecular Cancer (2017)

Reprogrammed energy metabolism as an emerging hallmark of cancer has recently drawn special attention since it facilitate cell growth and proliferation. Recently, long noncoding RNAs (lncRNAs) have been served as key regulators implicated in tumor development and progression by promoting proliferation, invasion and metastasis. However, the associations of lncRNAs with cellular energy metabolism in lung cancer (LC) need to be clarified. Here, we conducted bioinformatics analysis and found insulin-like growth factor binding protein 4–1 (IGFBP4–1) as a new candidate lncRNA located in the upstream region of IGFBP4 gene. The expression levels of lnc-IGFBP4–1, mRNA levels of IGFBP4 in 159 paired lung cancer samples and adjacent, histological normal tissues by qRT-PCR. Over-expression and RNA interference (RNAi) approaches were adopted to investigate the biological functions of lnc-IGFBP4–1. The intracellular ATP level was measured using the Cell Titer-Glo Luminescent Cell Viability Assay kit, and changes in metabolic enzymes were examined in cancer cells and normal pulmonary epithelial cells with qRT-PCR. Our results showed that lnc-IGFBP4–1 was significantly up-regulated in LC tissues compared with corresponding non-tumor tissues (P < 0.01), and its expression level was significantly correlated with TNM stage (P < 0.01) and lymph node metastasis (P < 0.05). Further investigation showed that overexpression of lnc-IGFBP4–1 significantly promoted LC cell proliferation in vitro and in vivo, while downregulation of endogenous lnc-IGFBP4–1 could inhibited cell proliferation and induce apoptosis. Moreover, we found lnc-IGFBP4–1 could influences ATP production levels and expression of enzymes including HK2, PDK1 and LDHA, in addition, decline in both ATP production and these enzymes in response to 2-DG and 2-DG-combined Rho123, respectively, was observed in lnc-IGFBP4–1-overespressing LC cells, indicative of an enhanced aerobic glycolysis rate. Finally, lnc-IGFBP4–1 was observed to negatively correlate with gene IGFBP4, and lower expression level of IGFPB4 was found after lnc-IGFBP4–1-overexpression was transfected into PC9 cells, higher expression level of IGFPB4 was also found after lnc-IGFBP4–1-downregulation was transfected into GLC-82 cells, which indicates that IGFBP4 may exert its targeting function regulated by lnc-IGFBP4–1. Taken together, these findings provide the first evidence that lnc-IGFBP4–1 is significantly up-regulated in LC tissues and plays a positive role in cell proliferation and metastasis through possible mechanism of reprogramming tumor cell energy metabolism, which suggests that lnc-IGFBP4–1 may be a promising biomarker in LC development and progression and as a potential therapeutic target for LC intervention.
Supplemental Nutrition Assistance Program (SNAP) Participation and Health Care Expenditures Among Low-Income Adults
Authors: Seth A. Berkowitz, Hilary K. Seligman, Joseph Rigdon, James B. Meigs, Sanjay Basu
Journal: JAMA Internal Medicine (2017)

Food insecurity is associated with high health care expenditures, but the effectiveness of food insecurity interventions on health care costs is unknown.To determine whether the Supplemental Nutrition Assistance Program (SNAP), which addresses food insecurity, can reduce health care expenditures.This is a retrospective cohort study of 4447 noninstitutionalized adults with income below 200% of the federal poverty threshold who participated in the 2011 National Health Interview Survey (NHIS) and the 2012-2013 Medical Expenditure Panel Survey (MEPS).Self-reported SNAP participation in 2011.Total health care expenditures (all paid claims and out-of-pocket costs) in the 2012-2013 period. To test whether SNAP participation was associated with lower subsequent health care expenditures, we used generalized linear modeling (gamma distribution, log link, with survey design information), adjusting for demographics (age, gender, race/ethnicity), socioeconomic factors (income, education, Social Security Disability Insurance disability, urban/rural), census region, health insurance, and self-reported medical conditions. We also conducted sensitivity analyses as a robustness check for these modeling assumptions.A total of 4447 participants (2567 women and 1880 men) were enrolled in the study, mean (SE) age, 42.7 (0.5) years; 1889 were SNAP participants, and 2558 were not. Compared with other low-income adults, SNAP participants were younger (mean [SE] age, 40.3 [0.6] vs 44.1 [0.7] years), more likely to have public insurance or be uninsured (84.9% vs 67.7%), and more likely to be disabled (24.2% vs 10.6%) (P < .001 for all). In age- and gender-adjusted models, health care expenditures between those who did and did not participate in SNAP were similar (difference, $34; 95% CI, -$1097 to $1165). In fully adjusted models, SNAP was associated with lower estimated annual health care expenditures (-$1409; 95% CI, -$2694 to -$125). Sensitivity analyses were consistent with these results, also indicating that SNAP participation was associated with significantly lower estimated expenditures.SNAP enrollment is associated with reduced health care spending among low-income American adults, a finding consistent across several analytic approaches. Encouraging SNAP enrollment among eligible adults may help reduce health care costs in the United States.
Barcelona Bio‐HF Calculator Version 2.0: incorporation of angiotensin II receptor blocker neprilysin inhibitor (ARNI) and risk for heart failure hospitalization
Authors: Josep Lupón, Joanne Simpson, John J.V. McMurray, Marta de Antonio, Joan Vila, Isaac Subirana, Jaume Barallat, Pedro Moliner, Mar Domingo, Elisabet Zamora, Antoni Bayes‐Genis
Journal: European Journal of Heart Failure (2017)
Injury surveillance during a national female youth football tournament in kenya
Authors: M Lislevand, K Steffen, A Junge, J Dvorak, T E Andersen
Journal: British Journal of Sports Medicine (2011)

Background Football in Kenya is not only a leisure activity, but also a tool for community and individual development. Studies on injury risk in female youth football players in Africa are limited. Objective To analyze the incidence, characteristics and circumstances of injuries. Design Prospective cohort study. Setting A two-day female youth football tournament in Nairobi, Kenya. Participants A total of 938 players from 69 teams participated in the tournament. All players were included in the study. Main outcome measurements Any physical complaints incurred by a player during a match were registered by trained Kenyan injury reporters. The injury reporters were supported by four physiotherapists and two doctors. All complaints were registered regardless of their consequence. Results A total of 123 injuries were reported from 106 matches. The incidence of all injuries was 93.3 injuries/1000 h (95% CI 76.8 to 109.8). Most injuries allowed the players to continue to play (n=98; 81%). Players under the age of 13 (RR=2.16; 95% CI 1.34 to 3.47; p=0.002) and 16 (RR=2.17; 95% CI 1.35 to 3.50; p=0.002) had an increased risk of injury compared to those over 16. Eight injuries (7%; 6.1 injuries/1000 h; 95% CI 1.9 to 10.3) were expected to result in absence from play of 1–7 days. The injuries most commonly involved the lower limb (n=100; 82%). A contusion to the ankle (n=15; 12%) and foot/toe (n=15; 12%) were the most common specific injury types. Most acute injuries (89 of 113, 79%) were caused by player contact. Conclusion The incidence of injuries among female youth football players in a national tournament in Kenya was high, with players under the age of 13 and 16 at greatest risk. However, most injuries were minor and did not prevent continued participation in the tournament. This can be seen as positive, as football plays a vital role in individual and community development in Kenya.
Biofabricating atherosclerotic plaques: In vitro engineering of a three-dimensional human fibroatheroma model
Authors: Anna Mallone, Chantal Stenger, Arnold Von Eckardstein, Simon P. Hoerstrup, Benedikt Weber
Journal: Biomaterials (2017)

Atherosclerotic plaques are cholesterol-induced inflammatory niches accumulating in the vascular sub-endothelial space. Cellular and extracellular composition of human plaques is maneuvered by local inflammation that leads to alterations in the original vascular microenvironment and to the recruitment of an invading fibrous layer (fibroatharoma). In the present study we introduce a bioengineered three-dimensional model of human fibroatheroma (ps-plaque) assembled with a tailored hanging-drop protocol. Using vi-SNE based multidimensional flow cytometry data analysis we compared the myeloid cell-populations in ps-plaques to those in plaques isolated from human carotid arteries. We observed that plasmacytoid and activated dendritic cells are the main myeloid components of human carotid plaques and that both cell types are present in the biofabricated model. We found that low-density lipoproteins affect cell viability and contribute to population polarization in ps-plaques. The current work describes the first human bioengineered in vitro model of late atherosclerotic lesion for the investigation of atherosclerosis aetiopathogenesis.
Hepatectomy followed by adjuvant chemotherapy with capecitabine plus oxaliplatin for three months for colorectal cancer liver metastases: A multicenter phase 2 study.
Authors: Hiroki Hashida, Hironaga Satake, Hiroaki Tanioka, Yasuhiro Miyake, Shinichi Yoshioka, Takanori Watanabe, Masato Matsuura, Takahisa Kyogoku, Michio Inukai, Takeshi Kotake, Yoshihiro Okita, Yukimasa Hatachi, Hisateru Yasui, Masahito Kotaka, Takeshi Kato, Satoshi Kaihara, Akihito Tsuji
Journal: Journal of Clinical Oncology (2017)

e15015 Background: Hepatic resection is one of the treatment strategies for resectable colorectal cancer liver metastases (CLM). The role of neoadjuvant and adjuvant chemotherapy in the management of initially resectable CLM is still unclear. Adjuvant chemotherapy consisting of capecitabine plus oxaliplatin (CapeOx) appears to be equivalent to FOLFOX in patients with stage III colon cancer. Furthermore, some studies suggest that adjuvant chemotherapy for three months after curative resection for stage II/III colorectal cancer has equivalent efficacy to adjuvant chemotherapy for 6 months. We initiated a multi-institutional, single-arm, open label, phase II trial to confirm the feasibility of adjuvant CapeOx for three months for post curative resection of CLM. Methods: Patients received one course of capecitabine followed by four courses of CapeOx for a total five courses (15 weeks) as adjuvant chemotherapy after curative resection of CLM. CapeOx consisted of a 2-hour intravenous infusion of oxaliplatin 130 mg/m 2 on day 1 plus oral capecitabine 1,000 mg/m 2 twice daily for 2 weeks in a 3-week cycle. The primary endpoint was completion rate of adjuvant chemotherapy. We set a threshold completion rate of protocol treatment of 45% and an expected completion rate of 70%. Given a one-sided α of 0.1 and statistical power of 80%, a minimum of 25 patients was required. Results: From May 2013 to November 2015, Twenty-eight patients were enrolled from six institutions: median age 69.5y, 54% male, 78.5% left-sided primary. Of the patients, 15 were synchronous metastases and 13 were metachronous. The locations of the metastases were unilobar in 20 patients and bilobar in 8. The mean number of lesions resected was two (range, 1 to 4). The mean size of largest tumor was 31 mm (range, 2 to 112 mm). Among the 28 patients, 20 (71.4 %: 95% CI, 53.6 to 89.3%) completed the protocol treatment. The most common grade 3 or 4 toxicities were neutropenia (29%). No treatment related death was observed. Conclusions: Adjuvant CapeOx for three months for post curative resection of CLM was feasible. Clinical trial information: UMIN000011164.
Pharmacogenomic Testing and Warfarin
Authors: Jon D. Emery
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 16880: Identifying Non-invasive Tools to Distinguish Acute Myocarditis From Dilated Cardiomyopathy in Children
Authors: Divya Suthar, Debra Dodd, Justin Godown
Journal: Circulation (2016)

Introduction: Children with dilated cardiomyopathy (DCM) often require orthotopic heart transplantation. In contrast, children with acute myocarditis may present with similar clinical features to D...
Genomic Landscape of Atypical Adenomatous Hyperplasia Reveals Divergent Modes to Lung Adenocarcinoma
Authors: Smruthy Sivakumar, F. Anthony San Lucas, Tina L. McDowell, Wenhua Lang, Li Xu, Junya Fujimoto, Jianjun Zhang, P. Andrew Futreal, Junya Fukuoka, Yasushi Yatabe, Steven M. Dubinett, Avrum E. Spira, Jerry Fowler, Ernest T. Hawk, Ignacio I. Wistuba, Paul Scheet, Humam Kadara
Journal: Cancer Research (2017)

Abstract There is a dearth of knowledge about the pathogenesis of premalignant lung lesions, especially for atypical adenomatous hyperplasia (AAH), the only known precursor for the major lung cancer subtype adenocarcinoma (LUAD). In this study, we performed deep DNA and RNA sequencing analyses of a set of AAH, LUAD, and normal tissues. Somatic BRAF variants were found in AAHs from 5 of 22 (23%) patients, 4 of 5 of whom had matched LUAD with driver EGFR mutations. KRAS mutations were present in AAHs from 4 of 22 (18%) of patients. KRAS mutations in AAH were only found in ever-smokers and were exclusive to BRAF-mutant cases. Integrative analysis revealed profiles expressed in KRAS-mutant cases (UBE2C, REL) and BRAF-mutant cases (MAX) of AAH, or common to both sets of cases (suppressed AXL). Gene sets associated with suppressed antitumor (Th1; IL12A, GZMB) and elevated protumor (CCR2, CTLA-4) immune signaling were enriched in AAH development and progression. Our results reveal potentially divergent BRAF or KRAS pathways in AAH as well as immune dysregulation in the pathogenesis of this premalignant lung lesion. Cancer Res; 77(22); 6119–30. ©2017 AACR.
Abstract 391: The Pathophysiological Role of MYBPHL in Dilated Cardiomyopathy
Authors: David Y Barefield, Megan J Puckelwartz, Lisa Dellefave-Castillo, Elizabeth M McNally
Journal: Circulation Research (2016)

Background: Cardiomyopathy is a leading cause of heart failure and is highly heritable. One common form of cardiomyopathy is dilated cardiomyopathy (DCM), which currently has over 70 identified genes that have been described as causative for the disease. Genetic testing for DCM employs gene panels and has a sensitivity of mutation detection less than 50%, indicating that additional genes contribute to DCM. Here, we employed whole genome sequencing (WGS) in a family with DCM and heart block who had previously undergone unrevealing genetic testing. We identified a premature stop codon in the MYBPHL gene, a gene that has not previously been linked to DCM as a likely cause of DCM in this family. Myosin binding protein H Like (MyBP-HL) is a muscle-expressed protein bearing structural similarity to myosin binding protein C (MyBP-C), which is commonly mutated gene in cardiomyopathies. Objective: Determine the physiological and pathophysiological role of Mybphl . Results: RNA-seq and qPCR from mouse hearts revealed that Mybphl is highly expressed in the right and left atria with lower expression in the ventricle and virtually no expression in skeletal muscle. As MyBP-HL shares a high homology with the myofilament proteins cardiac myosin binding protein-C and H, we investigated if MyBP-HL is also myofilament-associated. We determined that MyBP-HL protein is myofilament-associated in the atria although not clearly so in ventricle. To assess the requirement of MyBP-HL in cardiac function, we used a mouse model with an insertional disruption of the Mybphl gene. These mice have deficits in in vivo cardiac function, with reduced fractional shortening. In addition, ECG recordings from the Mybphl null mice show conduction system abnormalities affecting atrioventricular conduction. Conclusions: WGS identified a premature stop codon in MYBPHL in human DCM. A mouse model with a disrupted Mybphl gene showed similar pathophysiological features as the humans with reduced ventricular function and cardiac conduction system abnormalities. MyBP-HL is an important protein for normal cardiac function.
HLAProfiler utilizes k-mer profiles to improve HLA calling accuracy for rare and common alleles in RNA-seq data
Authors: Martin L. Buchkovich, Chad C. Brown, Kimberly Robasky, Shengjie Chai, Sharon Westfall, Benjamin G. Vincent, Eric T. Weimer, Jason G. Powers
Journal: Genome Medicine (2017)

The human leukocyte antigen (HLA) system is a genomic region involved in regulating the human immune system by encoding cell membrane major histocompatibility complex (MHC) proteins that are responsible for self-recognition. Understanding the variation in this region provides important insights into autoimmune disorders, disease susceptibility, oncological immunotherapy, regenerative medicine, transplant rejection, and toxicogenomics. Traditional approaches to HLA typing are low throughput, target only a few genes, are labor intensive and costly, or require specialized protocols. RNA sequencing promises a relatively inexpensive, high-throughput solution for HLA calling across all genes, with the bonus of complete transcriptome information and widespread availability of historical data. Existing tools have been limited in their ability to accurately and comprehensively call HLA genes from RNA-seq data. We created HLAProfiler ( https://github.com/ExpressionAnalysis/HLAProfiler ), a k-mer profile-based method for HLA calling in RNA-seq data which can identify rare and common HLA alleles with > 99% accuracy at two-field precision in both biological and simulated data. For 68% of novel alleles not present in the reference database, HLAProfiler can correctly identify the two-field precision or exact coding sequence, a significant advance over existing algorithms. HLAProfiler allows for accurate HLA calls in RNA-seq data, reliably expanding the utility of these data in HLA-related research and enabling advances across a broad range of disciplines. Additionally, by using the observed data to identify potential novel alleles and update partial alleles, HLAProfiler will facilitate further improvements to the existing database of reference HLA alleles. HLAProfiler is available at https://expressionanalysis.github.io/HLAProfiler/ .
Antisynthetase syndrome or what else? Different perspectives indicate the need for new classification criteria
Authors: Lorenzo Cavagna, Santos Castañeda, Carlo Sciré, Miguel A Gonzalez-Gay
Journal: Annals of the Rheumatic Diseases (2017)

We read with great interest the extended report by Lilleker et al 1 on the EuroMyositis registry. Our attention was particularly addressed to antisynthetase syndrome (ASSD) because in the last years we and all members of the AENEAS (American and European Network of Antisynthetase Syndrome) collaborative group strongly contributed2–7 to increase the knowledge on this peculiar disease.

We think that a comparison between our cohorts could be of interest and useful for clinicians, even if the lack of some data in the EuroMyositis paper does not allow us to perform statistical analysis. Both groups collected a very large number of patients (AENEAS collaborative group 813 cases, EuroMyositis 512 cases). The comparison of available …
Evaluation of local and distant recurrences pattern in patients with triple negative breast cancer according to age.
Authors: Julia Caroline Radosa, Anne Eaton, Michelle Stempel, Amrin Khander, Cornelia Liedtke, Erich-Franz Solomayer, Maria Gunthner-Biller, Monica Morrow, Tari A. King
Journal: Journal of Clinical Oncology (2015)

1095 Background: Triple negative breast cancer (TNBC) and young patient age are both associated with an increased risk of local (LR) and distant recurrence (DR). In young women with TNBC it is unclear whether age or subtype is driving prognosis. Here we examine outcomes in a large population of patients with TNBC according to age. Methods: Our prospectively maintained database was reviewed to identify all patients treated for primary TNBC from 1998 to 2011. Clinical data and outcomes were abstracted from medical records. Comparisons were made between patients < 40 and ≥ 40 years of age at diagnosis and multivariate models adjusted for disease stage, grade and treatment were used to identify factors independently associated with LR and DR. Cumulative incidence of LR and DR and disease free survival (DFS) were compared using competing risks methodology and log-rank tests. Results: Among 1930 patients with TNBC, 289 (15%) were < 40 and 1641 (85 %) were ≥ 40 years of age at diagnosis. Younger patients were more likely to have larger tumors (median 2.0 cm vs 1.7 cm, p = 0.001), positive nodes (47% vs 36%, p = 0.022), to receive mastectomy (61 % vs 42 %, p < 0.0001) and adjuvant chemotherapy (91 % vs 81 %, p < 0.0001). On univariate analysis there was no difference in LR by age (5 yr LR = 6% in both groups), although in the subset (n = 1066) treated with breast conserving therapy (BCT), patients < 40 had higher rates of LR (5 yr LR = 10% vs 6%, p = 0.03). Cumulative incidence of DR was higher for younger patients (5 yr DR = 20% vs 14%, p = 0.04). At a median followup of 74 months (0-201) there was no difference in DFS by age (6-yr DFS = 74% under 40 vs 75% ≥ 40). On multivariate analysis, BCT, nodal positivity, larger tumor size and no chemotherapy were associated with increased risk of LR. Larger tumor size, LVI and nodal positivity were associated with increased risk of DR. Age was not associated with either LR or DR. Conclusions: In this large population of women with TNBC treated at a single institution, younger patients were more likely to present with higher stage disease and experienced higher rates of LR when treated with BCT. However, after adjusting for stage, grade and treatment young age was not associated with an increased risk of local or distant recurrence.