tbuckley/cabot-search huggingface dataset:
C8orf76 Promotes Gastric Tumorigenicity and Metastasis by Directly Inducing lncRNA DUSP5P1 and Associates with Patient Outcomes
Authors: Xiaohong Wang, Qiaoyi Liang, Lianhai Zhang, Hongyan Gou, Ziyu Li, Huarong Chen, Yujuan Dong, Jiafu Ji, Jun Yu
Journal: Clinical Cancer Research (2019)

We identified for the first time that C8orf76 (chromosome 8 open reading frame 76) is preferentially amplified in gastric cancer. We elucidated its role and clinical significance in gastric carcinogenesis.The clinical impact of C8orf76 was assessed in 592 patients with gastric cancer. The biological function of C8orf76 was studied in vitro, in vivo, and in gastric cancer patient-derived organoid models. C8orf76 downstream effector and pathways were identified by RNA sequencing, chromatin immunoprecipitation sequencing, luciferase reporter, and electrophoretic mobility shift assay.C8orf76 was upregulated in 69.74% and 65.71% of two independent cohorts of gastric cancers and was positively associated with C8orf76 amplification. Multivariate analysis showed that gastric cancer patients with C8orf76 amplification (cohort I, n = 129; cohort II, n = 107) or overexpression (n = 356) had a significantly shortened survival. C8orf76 significantly promoted gastric cancer cell proliferation, cell-cycle transformation, and migration/invasion, but suppressed cell apoptosis. Silencing C8orf76 expression exerted opposite effects in vitro and significantly inhibited xenograft tumor growth, lung metastasis, and liver metastasis in nude mice. Silencing C8orf76 also significantly suppressed the growth of patient-derived organoids. Mechanically, C8orf76 activated MAPK/ERK signaling cascade. C8orf76 directly bound to the promoter region of lncRNA dual specificity phosphatase 5 pseudogene 1 (DUSP5P1) with a binding motif of AGGCTG and activated DUSP5P1 transcription. DUSP5P1 induced MAPK/ERK signaling and promoted gastric tumorigenesis. Knockdown DUSP5P1 abrogated the effect of C8orf76 in activating MAPK/ERK cascade and the tumor-promoting function.C8orf76 directly binds to oncogenic lncRNA DUSP5P1 to induce its expression and activates MAPK signaling. C8orf76 plays a pivotal oncogenic role in gastric carcinogenesis and is an independent prognostic factor for gastric cancer patients.
Different maturation pattern between myeloid dendritic cells and monocyte-derived dendritic cells in patients with immediate allergy reactions to betalactams
Authors: Alba Rodriguez-Nogales, Ruben Fernandez-SantaMaria, Maria Francisca Palomares Jerez, Adriana Ariza, Maria Jose Rodriguez, Miguel Gonzalez, Angela Martin-Serrano Ortiz, Ana Molina Bueno, Cristobalina Mayorga, Maria J. Torres, Tahia D. Fernandez
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 20282: Lipid Phosphate Phosphatase 3 and Lysophosphatidic Acid Receptors Expression in Human Atherosclerotic Plaques: Co-Localization of Relevant Lipid
Authors: Silvia Aldi, Gregory Hamm, Ljubica Perisic, Danielle van Keulen, Valur Emilson, Dennie Tempel, Kim Holmstrøm, Boye S Nielsen, Per Eriksson, Alain J van Gool, Jonathan Stauber, Ulf Hedin, Eva Hurt-Camejo
Journal: Circulation (2017)

Introduction: Single nucleotide polymorphisms (SNP) in the gene encoding lipid phosphate phosphohydrolase 3 (PPAP2B/LPP3) are associated with susceptibility to atherosclerotic cardiovascular diseas...
Call to Action: Urgent Challenges in Cardiovascular Disease: A Presidential Advisory From the American Heart Association
Authors: Mark McClellan, Nancy Brown, Robert M. Califf, John J. Warner
Journal: Circulation (2019)

Although advances in care have spurred improvements in cardiovascular outcomes, cardiovascular disease remains the leading cause of death in the United States and around the world. Previous declines in cardiovascular disease mortality have slowed and even reversed for certain demographics. Further concerns exist with regard to cardiovascular drug innovation, quality of care, and healthcare costs. The Value in Healthcare Initiative-Transforming Cardiovascular Care, a collaboration of the American Heart Association and Duke University, Robert J. Margolis, MD, Center for Health Policy, aims to increase access to and affordability of cardiovascular treatment and to decrease barriers to care. The following Call to Action describes trends in cardiovascular care, identifies gaps in areas of cardiovascular disease prevention and treatment, highlights challenges with medical product innovation, and finally, outlines a series of learning collaboratives that will aid in the development of road maps for transforming cardiovascular care.
Abstract 4298: Adipose-Derived Stem Cell Sheet Transplantation Therapy on Swine Chronic Heart Failure Model
Authors: Osamu Ishida, Ikuo Hagino, Noritoshi Nagaya, Tatsuya Shimizu, Yoshiki Sawa, Hidezo Mori, Toshikatsu Yagihara
Journal: Circulation (2008)

Introduction. Adipose-derived stem cells (ASCs) are one of the promising cell sources of the cell transplantation therapy for the damaged heart. Grafted cell death early after the transplantation i...
Detectable IgG against a Cimex lectularius allergen after a report of bed bug bites among NYC children
Authors: Adnan Divjan, Hadler A. daSilva, Luis M. Acosta, Andrew G. Rundle, Andrzej Weichsel, William R. Montfort, Greg Freyer, Rachel L. Miller, Matthew S. Perzanowski
Journal: Journal of Allergy and Clinical Immunology (2019)
Contribution of clinical trials to improved clinical outcomes for patients with metastatic breast cancer (MBC).
Authors: Ji Yun Lee, Sung Hee Lim, Min-Young Lee, Haesu Kim, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
Journal: Journal of Clinical Oncology (2015)

e12596 Background: Metastatic breast cancer (MBC) remains a devastating and largely incurable disease. Over the past decade, clinical trials with new therapeutic agents with or without molecular targeted therapeutics have become a main issue for patients with MBC challenging daily clinical practice, especially in Korea. We aimed to evaluate whether incorporation of clinical trials into the treatments of MBC can affect clinical outcomes. Methods: A total of 863 patients with metastatic disease at either initial diagnosis or recurrence after receiving adjuvant systemic treatments following surgery between Jan 2000 to Dec 2013 were retrospectively reviewed from the breast cancer database of Samsung Medical Center. Results: Among the 806 patients selected for inclusion, 187 (23%) patients were participated in clinical trials and 223 clinical trials conducted from 2000 to 2014. When compared with earlier periods (N = 10 for 2000-2004), clinical trial enrollment were significantly increased over time: N = 103 for 2005-2009, P = 0.024 and N = 110 for 2010-2014, P = 0.046. Multivariate analysis for overall survival revealed that biologic subtype, DRFI (distant recurrence free interval), and clinical trial enrollment were identified as independent predictors. The patients who participated in clinical trial showed improved survival with a hazard ratio of 0.75 (95% CI, 0.59-0.95), which was associated with a 25% reduction in the risk of death. However, subgroup analysis showed that this improved survival benefit did not maintained in patients with TNBC (triple negative breast cancer). Conclusions: The present study suggests that incorporation of clinical trials into daily clinical practice may get more benefit for patients with MBC in terms of overall survival. Further research for economic evaluation of involvement of clinical trials is warranted.
Physician Burnout in the Electronic Health Record Era
Authors: Mukesh Kapoor
Journal: Annals of Internal Medicine (2019)

Letters5 February 2019Physician Burnout in the Electronic Health Record EraMukesh Kapoor, MDMukesh Kapoor, MDUnity Sleep Disorders Center, Rochester Regional Health, Rochester, New York (M.K.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L18-0601 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Downing and colleagues (1) note that changing the current unnecessary and burdensome clinical documentation requirements in the United States will go a long way in reducing physician burnout. At the same time, much can be done to modify EHRs and their associated infrastructure to reduce the strain on physicians. Years down the road, I would not be surprised to see an epidemic of musculoskeletal injuries in health care workers ranging from carpal tunnel syndrome to degenerative joint disease of the cervical spine due to spending hours at a desk, glaring into a monitor, clicking repeatedly on a ...Reference1. Downing NL, Bates DW, Longhurst CA. Physician burnout in the electronic health record era: are we ignoring the real cause? Ann Intern Med. 2018;169:50-1. [PMID: 29801050]. doi:10.7326/M18-0139 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Unity Sleep Disorders Center, Rochester Regional Health, Rochester, New York (M.K.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L18-0601. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoPhysician Burnout in the Electronic Health Record Era: Are We Ignoring the Real Cause? N. Lance Downing , David W. Bates , and Christopher A. Longhurst Physician Burnout in the Electronic Health Record Era Donald E. Girard Physician Burnout in the Electronic Health Record Era N. Lance Downing , David W. Bates , and Christopher A. Longhurst Metrics Cited byAssociation of Electronic Health Record Use With Physician Fatigue and Efficiency 5 February 2019Volume 170, Issue 3Page: 216KeywordsComputersConflicts of interestDegenerative joint diseaseDisclosureElectronic medical recordsHealth care providersMusculoskeletal injurySpine ePublished: 5 February 2019 Issue Published: 5 February 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Use of MLH1 methylation analysis versus BRAF V600E mutation testing to select patients for Lynch syndrome genetic testing in a Chinese population: A large consecutive cohort study.
Authors: Wenmiao Wang, Lin Dong, Shuangmei Zou, Ning Lu
Journal: Journal of Clinical Oncology (2019)

493 Background: Within MLH1-deficient colorectal cancer (CRC), BRAF mutation and MLH1 promotor hypermethylation strongly suggest a sporadic origin, providing exclusion criteria for Lynch syndrome (LS). However, the prevalence of BRAF mutation in Chinese CRCs are lower than that reported in Western countries, leading to concerns on the specificity of BRAF mutation for LS screening. The aim of this study was to assess the clinical usefulness of BRAF V600E mutation tesing and MLH1 promoter hypermethylation analyses to improve the yield of the diagnostic algorithm for discriminating LS in Chinese population. Methods: 4104 consecutive patients who had undergone surgery for CRCs between December 2011 and December 2014 in Chinese National Cancer Center were reviewed. 169 patients with MLH1 deficiency were analyzed. The MLH1 methylation status was evaluated by methylation-specific PCR; the BRAF mutation status was assessed by real-time PCR. Germline mutation testing was performed on 28 patients with BRAF-negative staining/MLH1 hypermethylation and family cancer history. Results: 52.9% (89/169) of patients displayed MLH1 hypermethylation. However, the BRAF mutation was found in 17.2% (29/169) of patients, and only 29.2% (26/89) of CRCs displaying MLH1 promoter hypermethylation harbored BRAF mutation, much lower from that reported by the western countries. Somatic methylation was identified in five LS patients. A CRC history in at least one first-degree relative had an outstanding ability to select patients with MLH1 hypermethylation for germline mutation testing, with 100% sensitivity and 82.6% specificity. Conclusions: The prevalence of BRAF mutation in Chinese CRCs are lower than that reported in Western countries leading to a decreased efficacy on triage patients for germline mutation. On the countary, MLH1 methylation analysis can improve the diagostic yield of LS, therefore play an indispensable role in LS screening among Chinese population.
Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial
Authors: Benjamin H. Mullish, Julie A. K. McDonald, Mark R. Thursz, Julian R. Marchesi
Journal: Hepatology (2017)

Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. TO THE EDITOR: The study by Bajaj et al. evaluating the safety and efficacy of fecal microbiota transplant (FMT) as treatment for hepatic encephalopathy (HE)1 raises several questions. The first issue concerns the omission of specific detail regarding the medical therapy being used to treat HE in participants at recruitment, and the implication that lactulose/rifaximin was restarted after FMT in the treatment arm. If there was greater use of medical therapy for HE in the FMT arm compared with standard‐of‐care, this difference may be an alternative explanation for the apparent reduced HE burden in these patients. Furthermore, recommencement of rifaximin shortly after FMT would surely be inappropriate, as the broad‐spectrum nature of this nonabsorbable antibiotic2 would intuitively minimize the chance of successful colonization of recipients with bacterial communities present within the FMT. There is another issue with regard to appropriate donor selection. The authors describe using machine learning to select a donor with high relative abundance of Lachnospiraceae and Ruminococcaceae in the stool, given that these microbial families are found at reduced relative abundance in the stool of patients with HE.4 However, the data presented demonstrate that the relative abundance of these two families in FMT‐treated patients appears to be no different than baseline levels by day 15 post‐FMT (remaining throughout at levels much lower than that of the donor), and the Shannon diversity index was also statistically unchanged from baseline at this time point. Given the time scale of these microbial changes, it seems unfeasible that the apparent improvement in PHES testing/EncephalApp‐Stroop and reduced HE events (all outcomes measured at day 15 post‐FMT or later) was attributable to Lachnospiraceae and Ruminococcaceae members derived from the FMT. Recent data demonstrate that sterile stool filtrates may have similar efficacy in treating recurrent Clostridium difficile infection as conventional FMT,5 consistent with bacterially‐derived proteins, gut metabolites, bacteriophages, or other filtrate components being the mediators of FMT's efficacy in treating this condition, as opposed to intact microorganisms. By extrapolation, for future studies in this area, a more rational means of donor selection may be based around not purely matching the structure of the gut microbiota, but to select donors with the gut microbiota functionality missing in HE.
Detection of Adrenal Insufficiency (AI) in severe and moderate asthma employing standard ACTH response curve of non-asthmatic healthy controls and with comparison with non-asthmatics with past history of high dose systemic steroid use.
Authors: Michiko Haida, Katsutoshi Ogawa, Takahiro Inoue, Akihiko Hashiguchi
Journal: Journal of Allergy and Clinical Immunology (2019)
Updated developments on molecular imaging and therapeutic strategies directed against necrosis
Authors: Dongjian Zhang, Meng Gao, Qiaomei Jin, Yicheng Ni, Jian Zhang
Journal: Acta Pharmaceutica Sinica B (2019)

Cell death plays important roles in living organisms and is a hallmark of numerous disorders such as cardiovascular diseases, sepsis and acute pancreatitis. Moreover, cell death also plays a pivotal role in the treatment of certain diseases, for example, cancer. Noninvasive visualization of cell death contributes to gained insight into diseases, development of individualized treatment plans, evaluation of treatment responses, and prediction of patient prognosis. On the other hand, cell death can also be targeted for the treatment of diseases. Although there are many ways for a cell to die, only apoptosis and necrosis have been extensively studied in terms of cell death related theranostics. This review mainly focuses on molecular imaging and therapeutic strategies directed against necrosis. Necrosis shares common morphological characteristics including the rupture of cell membrane integrity and release of cellular contents, which provide potential biomarkers for visualization of necrosis and necrosis targeted therapy. In the present review, we summarize the updated joint efforts to develop molecular imaging probes and therapeutic strategies targeting the biomarkers exposed by necrotic cells. Moreover, we also discuss the challenges in developing necrosis imaging probes and propose several biomarkers of necrosis that deserve to be explored in future imaging and therapy research.
Targeting IDH1-Mutated Malignancies with NRF2 Blockade
Authors: Yang Liu, Yanxin Lu, Orieta Celiku, Aiguo Li, Qixin Wu, Yiqiang Zhou, Chunzhang Yang
Journal: JNCI Journal of the National Cancer Institute (2018)

Neomorphic IDH1 mutations disrupt the redox balance by promoting reactive oxygen species (ROS) production. However, the mechanism by which IDH1-mutant cells maintain ROS homeostasis remains elusive. It is also not known whether reprogrammed ROS homeostasis establishes targetable vulnerability in IDH1-mutated cancers.We investigated ROS homeostasis in wild-type (GSC827, GSC923, GSC627, and GSC711) and IDH1-mutated cells (IDH1R132C- and IDH1R132H-transduced U87, U251; MGG152, and TS603 cells). We analyzed the stability and transcriptional activity of NRF2 in IDH1-mutated cells. The oxidative DNA damage was analyzed using NRF2-targeting small interfering RNA. Moreover, we evaluated the effect of the NRF2 inhibitor brusatol in an IDH1-mutated subcutaneous xenograft nude mouse model (control group, n = 5; brusatol-treated group, n = 6). All statistical tests were two-sided.We showed that IDH1-mutated cells develop a dependency on the NRF2 antioxidative pathway. Genetic or pharmacologic blockade of NRF2 not only disrupted ROS homeostasis (mean [SD] ROS levels increased by 317 [42.1]%, P = .001, in IDH1R132C and by 286. 5 [48.7]%, P = .003, in IDH1R132H cells) but also enhanced oxidative DNA damage and decreased proliferation of IDH1-mutated cells. Brusatol selectively suppressed IDH1-mutated cancer progression in vivo (mean [SD] final tumor volume was 761.6 [391.6] mm3 in the control and 246.2 [215] mm3 in the brusatol-treated group, P = .02).IDH1 mutation reprograms ROS homeostasis in cancer cells, which leads to dependency on the NRF2 antioxidant pathway for ROS scavenging. NRF2 blockade might be a novel therapeutic approach to treat malignancies with IDH1 mutation.
Prediction of peritoneal recurrences of gastric cancer by qPCR analysis of peritoneal lavage fluids.
Authors: Koki Nakanishi, Mitsuro Kanda, Shinichi Umeda, Chie Tanaka, Daisuke Kobayashi, Masamichi Hayashi, Suguru Yamada, Goro Nakayama, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera
Journal: Journal of Clinical Oncology (2019)

52 Background: Peritoneal lavage cytology has been regarded as the only reliable method detect free cancer cells in the abdominal cavity. However, there certainly are patients who experience peritoneal recurrences despite negative cytology. Methods: Using qRT-PCR analysis, mRNA levels of 9 candidate molecular markers were quantified in peritoneal lavage fluids of from 187 patients with gastric cancer and 30 benign disease controls. ROC curve analysis was conducted to compare accuracies of the candidate markers. The cut-off points were set at the highest values of the benign disease controls. We evaluated predictive values of molecular markers in peritoneal lavage fluids for peritoneal recurrence. Results: From the result of ROC curve analysis, synaptotagmin XIII ( SYT13) and carcinoembryonic antigen ( CEA) mRNA levels were identified as predictive markers for peritoneal recurrences (The AUC value, 0.771, 0.775, respectively). 162 patients who had no concomitant peritoneal metastasis and were negative for lavage cytology (P0CY0), 13 patients (8.2%) had peritoneal recurrences. Those with either positive SYT13 or CEA mRNA level in peritoneal lavage fluids had significantly shorter peritoneal recurrence-free survival times compared to those with negative (3-years peritoneal recurrence-free survival rates, 69.5% vs 95.6%; P = 0.0069 and 79.3% vs. 93.4%; P = 0.0211, respectively). By combination of SYT13 and CEA, patients with both markers-positive had the greatest prevalence of peritoneal recurrences. Moreover, the peritoneal recurrence free survival curves of the both markers-positive group approached to that of the positive for lavage cytology group. Univariate analysis revealed that both SYT13-positive and CEA-positive were prognostic factors for peritoneal recurrence (hazard ratio: 4.21 and 3.53, respectively). In the multivariable analysis, SYT13-positive was found to be statistically significant independent prognostic factors (hazard ratio: 3.84, 95% confidence interval 1.24-13.2, P = 0.0202). Conclusions: SYT13 and CEA levels in peritoneal lavage fluids accurately predict peritoneal recurrences in patients with P0CY0.
Efficacy and safety of oral basal insulin versus subcutaneous insulin glargine in type 2 diabetes: a randomised, double-blind, phase 2 trial
Authors: Inge B Halberg, Karsten Lyby, Karsten Wassermann, Tim Heise, Eric Zijlstra, Leona Plum-Mörschel
Journal: The Lancet Diabetes & Endocrinology (2019)
Association of <i>MUC5B</i> promoter polymorphism with interstitial lung disease in myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis
Authors: Natsumi Namba, Aya Kawasaki, Ken-ei Sada, Fumio Hirano, Shigeto Kobayashi, Hidehiro Yamada, Hiroshi Furukawa, Kota Shimada, Atsushi Hashimoto, Toshihiro Matsui, Kenji Nagasaka, Takahiko Sugihara, Aika Suzuki, Kunihiro Yamagata, Takayuki Sumida, Shigeto Tohma, Sakae Homma, Shoichi Ozaki, Hiroshi Hashimoto, Hirofumi Makino, Yoshihiro Arimura, Masayoshi Harigai, Naoyuki Tsuchiya
Journal: Annals of the Rheumatic Diseases (2019)

Interstitial lung disease (ILD) is a major complication and a prognostic factor of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).1 The prevalence of ILD is higher in Japanese AAV as compared with European populations.1 In a Japanese inception cohort study, 45.0% of patients with microscopic polyangiitis (MPA) were complicated by ILD.2 Such ethnic difference suggests a role for genetic background in the development of AAV-associated ILD (AAV-ILD).

Single nucleotide polymorphism (SNP) rs35705950(G/T) in the promotor region of MUC5B, encoding mucin 5B, is a strong genetic factor for idiopathic pulmonary fibrosis (IPF). The risk allele T was associated with overexpression of mucin 5B in the lung.3 Recently, rs35705950 has been associated with rheumatoid arthritis-associated ILD (RA-ILD).4 

Here, we examined whether rs35705950 is associated with AAV-ILD in case-control and case–case association studies. About 474 Japanese patients with AAV and 842 healthy Japanese controls were recruited at rheumatology or nephrology centres based on the clinical diagnosis of AAV, and classified according to the European Medicines Agency algorithm.5 The patients were examined for the presence or absence of ILD using CT or high-resolution CT (HRCT) by site investigators. 163 patients were reported positive and 264 negative for ILD (see online supplementary table S1,S2). This study was conducted in accordance with the Declaration of Helsinki.### Supplementary data

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Genotyping was performed using TaqMan SNP Genotyping Assays (Assay ID: C\__\_|1582254\_20) (Thermo Fisher Scientific, Waltham, Massachusetts, USA). Odds ratios (ORs), 95% confidence intervals …