tbuckley/cabot-search huggingface dataset:
Meta-analysis of genome-wide association studies and functional assays decipher susceptibility genes for gastric cancer in Chinese populations
Authors: Caiwang Yan, Meng Zhu, Yanbing Ding, Ming Yang, Mengyun Wang, Gang Li, Chuanli Ren, Tongtong Huang, Wenjun Yang, Bangshun He, Meilin Wang, Fei Yu, Jinchen Wang, Ruoxin Zhang, Tianpei Wang, Jing Ni, Jiaping Chen, Yue Jiang, Juncheng Dai, Erbao Zhang, Hongxia Ma, Yanong Wang, Dazhi Xu, Shukui Wang, Yun Chen, Zekuan Xu, Jianwei Zhou, Guozhong Ji, Zhaoming Wang, Zhengdong Zhang, Zhibin Hu, Qingyi Wei, Hongbing Shen, Guangfu Jin
Journal: Gut (2019)

Objective Although a subset of genetic loci have been associated with gastric cancer (GC) risk, the underlying mechanisms are largely unknown. We aimed to identify new susceptibility genes and elucidate their mechanisms in GC development. Design We conducted a meta-analysis of four genome-wide association studies (GWASs) encompassing 3771 cases and 5426 controls. After targeted sequencing and functional annotation, we performed in vitro and in vivo experiments to confirm the functions of genetic variants and candidate genes. Moreover, we selected 33 promising variants for two-stage replication in 7035 cases and 8323 controls from other five studies. Results The meta-analysis of GWASs identified three loci at 1q22, 5p13.1 and 10q23.33 associated with GC risk at p&lt;5×10 − 8 and replicated seven known loci at p&lt;0.05. At 5p13.1, the risk rs59133000[C] allele enhanced the binding affinity of NF-κB1 (nuclear factor kappa B subunit 1) to the promoter of PRKAA1 , resulting in a reduced promoter activity and lower expression. The knockout of PRKAA1 promoted both GC cell proliferation and xenograft tumour growth in nude mice. At 10q23.33, the rs3781266[C] and rs3740365[T] risk alleles in complete linkage disequilibrium disrupted and created, respectively, the binding motifs of POU2F1 and PAX3, resulting in an increased enhancer activity and expression of NOC3L , while the NOC3L knockdown suppressed GC cell growth. Moreover, two new loci at 3q11.2 (OR=1.21, p=4.56×10 − 9 ) and 4q28.1 (OR=1.14, p=3.33×10 − 11 ) were associated with GC risk. Conclusion We identified 12 loci to be associated with GC risk in Chinese populations and deciphered the mechanisms of PRKAA1 at 5p13.1 and NOC3L at 10q23.33 in gastric tumourigenesis.
Correction to: Circular RNA profiling and its potential for esophageal squamous cell cancer diagnosis and prognosis
Authors: Liyuan Fan, Qiang Cao, Jia Liu, Junpeng Zhang, Baosheng Li
Journal: Molecular Cancer (2019)

After publication of the article [1], the author reported that this article contained error. In Funding section, the funding number provided 2016YFC0105100 should have been 2016YFC0105106.
Integration of patient-reported adverse events into a phase II chemotherapy treatment trial.
Authors: Ethan M. Basch, Maria Catherine Pietanza, Mark G. Kris, Mary Shaw, Camelia S. Sima, Lauren J. Rogak, Deborah Schrag
Journal: Journal of Clinical Oncology (2013)

6583 Background: It has been shown that patient reporting of symptomatic adverse events (AEs) is feasible during routine chemotherapy, and that patients report AEs that clinicians otherwise miss. It is not known if this approach is feasible in a treatment trial; whether clinicians will agree or disagree with patent-reported AE grades; or if clinicians will take actions based on patients' AE reports. Methods: Patients with advanced non-small cell lung cancer enrolling in a single-arm phase 2 trial of paclitaxel, pemetrexed, and bevacizumab at Memorial Sloan-Kettering Cancer Center (NCT00807573) reported 13 validated plain language questions adapted from the NCI's Common Terminology Criteria for Adverse Events (CTCAE), via iPads in waiting areas before each visit. Patients’ grades were transmitted to an investigator web page via which clinicians could agree or reassign each of the CTCAE grades, which were then transmitted to the institutional database as the official reported AEs for the trial. The proportion of patients and clinicians reporting AEs at each visit was tabulated with an a priori average compliance threshold set at 75% to conclude feasibility of the approach. The rate of clinician agreement with patient grades was computed. The frequency of clinical actions in response to patient-reported grade 3/4 AEs was calculated (ie, chemotherapy dose modification, ER referral, supportive medication). Results: 44 patients were enrolled between 1/09-9/11 (mean age 59; 50% female; 93% white), encompassing 721 total clinic visits (median 10; range 1-65). Patients reported AEs at visits 99.6% of the time and clinicians 98.7% of the time. Median time between patient self-reports and clinician reviews was 1 hour (range 0.2-18). Across symptoms, clinicians agreed with patients 93% of the time (weighted kappas .83 to .92), increasing the grade 5% of the time and decreasing it 2%. Clinical actions were taken in response to 67% of patient-reported grade 3/4 AEs. 71% of clinicians stated patient reporting informed their toxicity grading. Conclusions: Collection of patient-reported AEs at clinic visits via computer is feasible in a chemotherapy trial. Clinicians agree with patients’ self-reported AE grades and act on this information.
Development and external validation study of a melanoma risk prediction model incorporating clinically assessed naevi and solar lentigines
Authors: K. Vuong, B.K. Armstrong, M. Drummond, J.L. Hopper, J.H. Barrett, J.R. Davies, D.T. Bishop, J. Newton‐Bishop, J.F. Aitken, G.G. Giles, H. Schmid, M.A. Jenkins, G.J. Mann, K. McGeechan, A.E. Cust
Journal: British Journal of Dermatology (2019)

Background Melanoma risk prediction models could be useful for matching preventive interventions to patients' risk. Objectives To develop and validate a model for incident first-primary cutaneous melanoma using clinically assessed risk factors. Methods We used unconditional logistic regression with backward selection from the Australian Melanoma Family Study (461 cases and 329 controls) in which age, sex and city of recruitment were kept in each step, and we externally validated it using the Leeds Melanoma Case–Control Study (960 cases and 513 controls). Candidate predictors included clinically assessed whole-body naevi and solar lentigines, and self-assessed pigmentation phenotype, sun exposure, family history and history of keratinocyte cancer. We evaluated the predictive strength and discrimination of the model risk factors using odds per age- and sex-adjusted SD (OPERA) and the area under curve (AUC), and calibration using the Hosmer–Lemeshow test. Results The final model included the number of naevi ≥ 2 mm in diameter on the whole body, solar lentigines on the upper back (a six-level scale), hair colour at age 18 years and personal history of keratinocyte cancer. Naevi was the strongest risk factor; the OPERA was 3·51 [95% confidence interval (CI) 2·71–4·54] in the Australian study and 2·56 (95% CI 2·23–2·95) in the Leeds study. The AUC was 0·79 (95% CI 0·76–0·83) in the Australian study and 0·73 (95% CI 0·70–0·75) in the Leeds study. The Hosmer–Lemeshow test P-value was 0·30 in the Australian study and < 0·001 in the Leeds study. Conclusions This model had good discrimination and could be used by clinicians to stratify patients by melanoma risk for the targeting of preventive interventions. What's already known about this topic? Melanoma risk prediction models may be useful in prevention by tailoring interventions to personalized risk levels. For reasons of feasibility, time and cost many melanoma prediction models use self-assessed risk factors. However, individuals tend to underestimate their naevus numbers. What does this study add? We present a melanoma risk prediction model, which includes clinically-assessed whole-body naevi and solar lentigines, and self-assessed risk factors including pigmentation phenotype and history of keratinocyte cancer. This model performs well on discrimination, the model's ability to distinguish between individuals with and without melanoma, and may assist clinicians to stratify patients by melanoma risk for targeted preventive interventions.
The acute kidney injury to chronic kidney disease transition in a mouse model of acute cardiorenal syndrome emphasizes the role of inflammation
Authors: Katsuyuki Matsushita, Turgay Saritas, Mahaba B. Eiwaz, Nicholas McClellan, Ian Coe, Wenbin Zhu, Mohammed Z. Ferdaus, Lynn Y. Sakai, James A. McCormick, Michael P. Hutchens
Journal: Kidney International (2019)

Acute cardiorenal syndrome is a common complication of acute cardiovascular disease. Studies of acute kidney injury (AKI) to chronic kidney disease (CKD) transition, including patients suffering acute cardiovascular disease, report high rates of CKD development. Therefore, acute cardiorenal syndrome associates with CKD, but no study has established causation. To define this we used a murine cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) model or sham procedure on male mice. CA was induced with potassium chloride while CPR consisted of chest compressions and epinephrine eight minutes later. Two weeks after AKI was induced by CA/CPR, the measured glomerular filtration rate (GFR) was not different from sham. However, after seven weeks the mice developed CKD, recapitulating clinical observations. One day, and one, two, and seven weeks after CA/CPR, the GFR was measured, and renal tissue sections were evaluated for various indices of injury and inflammation. One day after CA/CPR, acute cardiorenal syndrome was indicated by a significant reduction of the mean GFR (649 in sham, vs. 25 μL/min/100g in CA/CPR animals), KIM-1 positive tubules, and acute tubular necrosis. Renal inflammation developed, with F4/80 positive and CD3-positive cells infiltrating the kidney one day and one week after CA/CPR, respectively. Although there was functional recovery with normalization of GFR two weeks after CA/CPR, deposition of tubulointerstitial matrix proteins α-smooth muscle actin and fibrillin-1 progressed, along with a significantly reduced mean GFR (623 in sham vs. 409 μL/min/100g in CA/CPR animals), proteinuria, increased tissue transforming growth factor-β, and fibrosis establishing the development of CKD seven weeks after CA/CPR. Thus, murine CA/CPR, a model of acute cardiorenal syndrome, causes an AKI-CKD transition likely due to prolonged renal inflammation.Graphical abstract
연구논문 : 간세포암종 환자에서 간동맥화학색전술 후 급성 신부전의 빈도 및 위험인자
Authors: 장병국 ( Byoung Kuk Jang ), 이승현 ( Seung Hyun Lee ), 정우진 ( Woo Jin Chung ), 박경식 ( Kyung Sik Park ), 조광범 ( Kwang Bum Cho ), 황재석 ( Jae Seok Hwang ), 김영환 ( Young Hwan Kim ), 최진수 ( Jin Soo Choi ), 권중혁 ( Jung Hyeok Kwon )
Journal: Clinical and Molecular Hepatology (2008)
Eradicating cervical cancer is unlikely
Authors: Peter M B English
Journal: BMJ (2019)

Researchers say that high coverage of human papillomavirus vaccination could eradicate cervical cancer. There are at least 100 serotypes of HPV.1 The two vaccines currently used in the UK, Gardasil and Cervarix, cover the two strains of HPV that are most likely to cause cancer. Gardasil 9 covers the same two strains as the original Gardasil vaccine plus an additional five oncogenic strains—in total, …
Programming of Distinct Chemokine-Dependent and -Independent Search Strategies for Th1 and Th2 Cells Optimizes Function at Inflamed Sites
Authors: Alison Gaylo-Moynihan, Hen Prizant, Milan Popović, Ninoshka R.J. Fernandes, Christopher S. Anderson, Kevin K. Chiou, Hannah Bell, Dillon C. Schrock, Justin Schumacher, Tara Capece, Brandon L. Walling, David J. Topham, Jim Miller, Alan V. Smrcka, Minsoo Kim, Angela Hughson, Deborah J. Fowell
Journal: Immunity (2019)
Oblimersen (O) in combination with docetaxel (T), adriamycin (A), and cyclophosphamide (C) as neoadjuvant systemic therapy (NST) in primary breast cancer (PBC): Final results of a multicentric phase I study
Authors: J. Rom, B. Schlehe, F. Marmé, F. Schuetz, M. Eichbaum, H. Sinn, T. Buechele, C. Sohn, G. von Minckwitz, A. Schneeweiss
Journal: Journal of Clinical Oncology (2007)

11047 Background: The Bcl-2 downregulator O in combination with standard cytotoxic chemotherapy leads to synergistic antitumor effects in preclinical trials. To evaluate maximum tolerated dose (MTD), safety and preliminary efficacy of O in combination with TAC as NST in PBC we performed a multicentric phase I study. Methods: Previously untreated patients with PBC T2–4a-c N0–3 M0 received escalating doses of O as a 24 hour continuous infusion on day (d) 1–7 in combination with T 75mg/m 2 , A 50mg/m 2 and C 500 mg/m 2 on day 5 followed by five three weekly cycles of TAC without O. Results: A total of twenty-eight patients with a median age of 50 years were enrolled. 61% of tumors were T2, 43% grade 3, 68% ductal-invasive, and 64% hormone receptor positive. Patients received O in a dose of 3 mg/kg/d (cohort I, 9 patients), 5 mg/kg/d (II, 9 patients), and 7 mg/kg/d (III, 10 patients), respectively. No dose-limiting toxicity occurred. Most common adverse events [all National Cancer Institute-Common Toxicity Criteria (NCI-CTC) grade = 2] were fatigue, nausea, alopecia, headache and flue-like symptoms observed in 78% (I), 89% (II), and 90% (III) of patients, respectively. Following OTAC the most severe hematological toxicity was neutropenia (NCI-CTC grade 1–2/3/4) which developed in 0/0/56% of patients (I), 11/0/56% of patients (II), and 20/20/50% of patients (III), respectively. At least 50% reduction in tumor volume was oberved in 14 patients. Five patients (18%) achieved a pathologic complete response (3 patients in cohort I, 2 patients in cohort II). Conclusions: O up to a dose of 7 mg/kg/d given as a 24 hour infusion on day 1–7 can be safely administered in combination with standard TAC on day 5 as NST in patients with PBC. The preliminary efficacy warrants further evaluation of this combination in a randomised trial. No significant financial relationships to disclose.
Acute palliative care unit in a comprehensive cancer center (CCC): Financial and clinical outcomes
Authors: A. F. Elsayem, D. Hui, Z. Li, M. Flores, W. A. Atkinson, E. Bruera
Journal: Journal of Clinical Oncology (2009)

e20518 Background: Acute palliative care units (APCU) in CCCs improves symptom control for advanced cancer patients and supports their families. However, these services are not available in the majority of cancer centers. Concerns regarding financial reimbursements represent a major barrier for establishing APCUs. The purpose of this study is to report the clinical outcomes and compare the financial outcomes of our APCU as compared to other services at our CCC. Methods: We reviewed all admissions to the APCU over the last 5 fiscal years for demographic information, length of stay, discharges, survival, hospital billings and collection of charges, and compared these to the rest of the institution. Results: 2,510 unique patients were admitted to the APCU. Median age was 59 years (19–101) and 51% were female. The median length of stay in APCU was 8 days (Q1-Q3 6–10). Median survival of patients discharged home, to health care facilities and hospice were 53, 22, and 13 days, respectively (p&lt;0.001, log rank test), with 6 month survival of 20%, 4%, and 2%, respectively. Professional collections ranged from 42–47% of charges for APCU, vs. 32–38% for rest of the CCC and were stable over the 5 year period. Hospital collections were 47–51% of charges for APCU, vs. 55–57% for the rest of the CCC. The payer mix included commercial 1155 (46%), Medicare 755 (30%), Medicaid 126 (5%), mixed 127 (5%), indigent 198 (8%), and others 149 (6%). Conclusions: The ACPU has reimbursement outcomes consistent with the American acute care model and comparable to the rest of the CCC for last 5 years. The APCU is as viable as any other clinical programs in our institution. Further research is needed to investigate possible reasons for lack of APCU in cancer centers. No significant financial relationships to disclose.
Walking on Eggshells With Trainees in the Clinical Learning Environment—Avoiding the Eggshells Is Not the Answer
Authors: Melanie A. Gold, Susan L. Rosenthal, Milton L. Wainberg
Journal: JAMA Pediatrics (2019)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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 Pediatrics journal
Abstract 5134: Effects of Vitamins C and E and Beta Carotene on the Occurrence of Venous Thromboembolism: A Randomized Trial in Women at High Cardiovascular Risk
Authors: Robert J Glynn, JoAnn E Manson
Journal: Circulation (2008)

Background: Limited observational and randomized evidence suggests that antioxidant intake or supplement use may lower the risk of venous thromboembolism (VTE). Methods: The Women’s Antioxidant Car...
Evaluation of predictive factors for response to darbepoetin alfa (DA): A prospective study
Authors: H. T. Steinmetz, F. Fandel, M. Hellmich, M. Neise, A. Aldaud, C. Lerchenmüller, A. Tsamaloukas, C. Weiligmann, S. Schmitz
Journal: Journal of Clinical Oncology (2006)

18514 Background: Therapy with erythropoiesis-stimulating factors (ESF) can ameliorate the anaemia associated with cancer and chemotherapy, reduce the need for transfusions and improve quality of life. However, as many as 30–50% of pts. do not respond, even to very high doses of ESF. Methods: In January 2003, we commenced a prospective phase-2 study to evaluate the value of predictive factors for response to DA. The following 5 factors, which had been previously determined as predictive factors in several retrospective studies, were investigated: serum erythropoietin &lt; 100 mU/ml before therapy (Epo-d0); increase in reticulocytes &gt; 40,000/μl (Reti-d14) and in soluble transferrin receptor ≥ 25% (sTfR-d14), both after 2 weeks; increase in reticulocytes &gt; 40,000/μl (Reti-d28) and in Hb &gt; 1 g/dl (Hb-d28), both after 4 weeks. Response was defined as Δ Hb &gt; 2 g/dl or Hb ≥ 12 g/dl within 8–12 weeks. Pts. with solid tumours receiving chemotherapy, ECOG &lt; 2 and Hb &lt; 11g/dl or significant decrease in Hb &gt; 1.5 g/dl within 4 weeks received DA 150 μg/QW or 300 μg/Q2W sc. and 300 μg/QW if Hb &lt; 1 g/dl at d28. Results: Between 01/03 and 09/05 196 pts., 112 female and 84 male, median age 66 years, were treated and evaluated for response. 119 pts. (60.7%) had a response as defined (PP analysis: 68.3%). The predictive value of the 5 factors are given in the Table . In a multiple logistic regression analysis of all 5 factors the ROC has an AUC of 0.78 (95% CI 0.71–0.84). The reduced logistic classification rule (with cutoff 0.5) based on an increase in sTfR &gt; 25% on day14, reticulocytes &gt; 40,000/μl and Hb &gt; 1 g/dl, both on day 28, had the same AUC and its positive / negative predictive value was 88.1% (=74/84) and 59.8% (=67/112) respectively. Conclusions: In contrast to observations made in pts. with lymphoproliferative malignancies, the pretherapeutic serum erythropoietin level has no or very little predictive value for response to DA in anaemic pts. with solid tumours. Supported by AMGEN, Germany with an unrestricted grant. [Table: see text] [Table: see text]
Inflammatory Cytokines Associated With Failure of Lower-Extremity Endovascular Revascularization (LER): A Prospective Study of a Population With Diabetes
Authors: Federico Biscetti, Pietro Manuel Ferraro, William R. Hiatt, Flavia Angelini, Elisabetta Nardella, Andrea Leonardo Cecchini, Angelo Santoliquido, Dario Pitocco, Raffaele Landolfi, Andrea Flex
Journal: Diabetes Care (2019)

OBJECTIVE Peripheral artery disease (PAD) is one of the most relevant complications of diabetes. Although several pharmacological and revascularization approaches are available for treating patients with diabetes and PAD, an endovascular approach is often associated with postprocedural complications that can increase the risk for acute limb ischemia or amputation. However, no definitive molecular associations have been described that could explain the difference in outcomes after endovascular treatment in patients with diabetes, PAD, and chronic limb-threatening ischemia (CLTI). RESEARCH DESIGN AND METHODS We evaluated the relationship between the levels of the main cytokines associated with diabetic atherosclerosis and the outcomes after endovascular procedures in patients with diabetes, PAD, and CLTI. RESULTS A total of 299 patients with below-the-knee occlusive disease who were undergoing an angioplasty procedure were enrolled. The levels of key cytokines—osteoprotegerin (OPG), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP)—were measured, and major adverse limb events (MALE) and major adverse cardiovascular events (MACE) were assessed 1, 3, 6, and 12 months after the procedure. There was a linear trend from the lowest to the highest quartile for each cytokine at baseline and incident MALE. A linear association was also observed between increasing levels of each cytokine and incident MACE. Receiver operating characteristics models were constructed using clinical and laboratory risk factors, and the inclusion of cytokines significantly improved the prediction of incident events. CONCLUSIONS We demonstrated that elevated OPG, TNF-α, IL-6, and CRP levels at baseline correlate with worse vascular outcomes in patients with diabetes, PAD, and CLTI undergoing an endovascular procedure.