tbuckley/cabot-search huggingface dataset:
A blueprint for the primary prevention of cancer: Targeting established, modifiable risk factors
Authors: Susan M. Gapstur, Jeffrey M. Drope, Eric J. Jacobs, Lauren R. Teras, Marjorie L. McCullough, Clifford E. Douglas, Alpa V. Patel, Richard C. Wender, Otis W. Brawley
Journal: CA A Cancer Journal for Clinicians (2018)

Abstract In the United States, it is estimated that more than 1.7 million people will be diagnosed with cancer, and more than 600,000 will die of the disease in 2018. The financial costs associated with cancer risk factors and cancer care are enormous. To substantially reduce both the number of individuals diagnosed with and dying from cancer and the costs associated with cancer each year in the United States, government and industry and the public health, medical, and scientific communities must work together to develop, invest in, and implement comprehensive cancer control goals and strategies at the national level and expand ongoing initiatives at the state and local levels. This report is the second in a series of articles in this journal that, together, describe trends in cancer rates and the scientific evidence on cancer prevention, early detection, treatment, and survivorship to inform the identification of priorities for a comprehensive cancer control plan. Herein, we focus on existing evidence about established, modifiable risk factors for cancer, including prevalence estimates and the cancer burden due to each risk factor in the United States, and established primary prevention recommendations and interventions to reduce exposure to each risk factor.
卡泊三醇辅助与常规 MAL-PDT 治疗光化性角化病的比较
Authors: L.R. Torezan, B. Grinblat, M. Haedersdal, N. Valente, C. Festa-Neto, R.M. Szeimies
Journal: British Journal of Dermatology (2018)

光化性角化病 (Actinic keratosis, AK) 是影响全世界许多人的一种常见的皮肤恶变前病变(受影响的斑块), 尤其是白皙皮肤类型的人。它在 40 岁以后和在身体暴露于阳光的部位更常见。其可能会发展为一种叫做鳞状细胞癌 (SCC) 的皮肤癌。因此, 建议对每个 AK 病变进行充分的治疗。本研究旨在通过光动力疗法 (PDT) 治疗这些病变, 这是一个公认的方案。通常,局部 PDT 是一种联合药物(应用于病变)和光照(蓝色或红色)的治疗。最终结果是大量杀死癌细胞, 这将为这些患者带来高治愈率。然而, 与面部病变相比, 头皮上的 AK 有时难以治疗并且疗效水平较低。因此,我们的目的是探索 PDT 与名为卡泊三醇的众所周知的药物的联合应用是否会给患者带来任何好处。因此, 我们比较了:头皮的一半使用 CAL 和 PDT 治疗, 另一半仅用 PDT 治疗。然后对患者进行 3 个月的随访(监测)。我们发现该联合用药对于 AK 治疗是安全且更有效的, 尤其是当病变较厚时。副作用更加常见, 但患者耐受良好。这是首例采用 CAL 和 PDT 治疗 AK 的研究。
GW29-e0856 Optimal Status Markers for Heart Failure with Preserved Ejection Fraction
Authors: Thach Nguyen, Thao Dang, Phan Le Ngoc Ngan, Tu NT Nguyen, Dao Thanh Uyen Nhu, Nguyen Tran Kien An, Tarneem Darwish, Gianluca Rigatelli
Journal: Journal of the American College of Cardiology (2018)
Maternal Antibiotic Use During Pregnancy and Type 1 Diabetes in Children—A National Prospective Cohort Study
Authors: Martin Haupt-Jørgensen, Camilla S. Morgen, Tine Jess, Karsten Buschard, Knud Josefsen, Kristine Højgaard Allin, Julie Christine Antvorskov
Journal: Diabetes Care (2018)

Prenatal prescription of antibiotics is common but may perturb the composition of the intestinal microbiota in the offspring. In childhood the latter may alter the developing immune system to affect the pathogenesis of type 1 diabetes (1). Previous epidemiological studies reported conflicting results regarding the association between early exposure to antibiotics and childhood type 1 diabetes (2,3). Here we investigated the association in a Danish register setting.

The Danish National Birth Cohort (DNBC) provided data from 100,418 pregnant women recruited between 1996 and 2002 and their children born between 1997 and 2003 ( n = 96,840). The women provided information on exposures during and after pregnancy. Antibiotic prescription during pregnancy was obtained from the Danish National Prescription Registry (anatomical therapeutic chemical code J01), and type 1 diabetes diagnoses (diagnostic codes DE10 and DE14) during childhood and adolescence were obtained from the Danish National Patient Register. The children were followed until 2014 (mean follow-up time 14.3 years [range 11.5–18.4 years, SD 1.4]). We excluded ( n = 4,828) twins and triplets, children born before gestational week 26, children weighing <500 g at birth, and stillbirths, leaving 92,012 children for unadjusted analyses. Socioeconomic status, parity, maternal diabetes, smoking …
Seamless environment of antineoplastic drugs preparation combining robotic system and isolators
Authors: Junko Kuroda, Yuusuke Tashiro, Noriko Kitou, Takuya Morikawa, Ayaka Okuzono, Yuki Aoki, Yumiko Iguchi, Masashi Takemoto, Kazunori Kimura
Journal: Annals of Oncology (2018)
Topical glyceryl trinitrate for the treatment of tendinopathies: a systematic review
Authors: Dimitris Challoumas, Paul D Kirwan, Dmytro Borysov, Christopher Clifford, Michael McLean, Neal L Millar
Journal: British Journal of Sports Medicine (2018)

To produce a best evidence synthesis of the clinical effects of topical glyceryl trinitrate (GTN) in the treatment of tendinopathies.A systematic review of published randomised controlled trials (RCTs) of the use of GTN in patients with tendinopathy.MEDLINE, Embase, Scopus and CINAHL from database inception to January 2018.We examined RCTs comparing the effects of topical GTN with either placebo or other treatments on tendinopathy. Overall quality of each eligible study was determined based on a combined assessment of internal validity, external validity and precision. The level of evidence for each assessed parameter was rated based on the system by van Tulder et al.A total of 10 eligible RCTs were identified including patients with tendinopathy of the rotator cuff (n=4), wrist extensors (n=3), Achilles (n=2) and patellar (n=1) tendons. For all tendinopathies, improvements in pain were significant when comparing GTN versus placebo in the short term (<8 weeks; poor evidence). Significant improvements in midterm outcomes for treatment with GTN versus placebo included the following: patient satisfaction (strong evidence); chances of being asymptomatic with activities of daily living (strong evidence); range of movement (moderate evidence); strength (moderate evidence); pain (at night and with activity; poor evidence) and local tenderness (poor evidence). Patients treated with topical GTN reported a higher incidence of headaches than those who received placebo (moderate evidence).Treatment of tendinopathies with topical GTN for up to 6 months appears to be superior to placebo and may therefore be a useful adjunct to the treating healthcare professions.
E2a-Pbx1 direct targets and secondary mutations in leukemogenesis
Authors: Christofer Diakos, Yuanyuan Xiao, Jerry Hofmann, Shichun Zheng, Michelle Kang, Mi Zhou, Sheng Zhong, John Wiencke, Ru-Fang Yeh, Joseph Wiemels
Journal: Cancer Research (2008)

4396   E2a-Pbx1 is expressed as a result of the t(1;19) chromosomal translocation in nearly 5% of acute lymphoblastic leukemia cases. The E2a-Pbx1 chimeric transcription factor contains the N-terminal transactivation domain of E2A fused to the C-terminal DNA-binding homeodomain of Pbx1. Previews studies indicate that additional genetic events may be required for E2A-Pbx1-leukemic transformation, based on long incubation times and the monoclonal nature of tumors observed in mouse models. While there is no doubt of its oncogenic potential, the mechanisms of E2a-Pbx1-mediated pre-B cell transformation and the nature of direct E2a-Pbx1 target genes and additional events that complement the fusion oncogene to create full-blown leukemia are still unclear. Herein we used chromatin immunoprecipitation (ChIP-chip) assays to identify direct targets of E2a-Pbx1, and we used gene and miRNA expression arrays of siRNA E2a-Pbx1-silenced cells to evaluate changes in expression induced by the fusion protein. To identify complementary genetic rearrangements, analyses of primary E2a-Pbx1 leukemias were performed to detect copy number changes and loss of heterozygosity which might identify mutations that synergize with the direct/functional E2a-Pbx1 targets to produce the leukemic phenotype. Our data identified members of the WNT pathway as direct targets of E2a-Pbx1. Expression data from E2a-Pbx1 silenced cells support this finding as they demonstrate a functional regulation of this pathway. We further show a differential impact of E2a-Pbx1 silencing on the miRNA profile and identify E2a-Pbx1 dependent miRNAs. Using CGH arrays on primary E2a-Pbx1 samples we were able to pinpoint candidate secondary mutations as well as broad genetic categories: cases with 1q+, 1q+ combined with 9p-, and, separately, cases with +8. In summary we present direct and functional E2a-Pbx1 targets as well as candidate secondary mutations. We propose a model where direct and functional E2a-Pbx1 driven pathways, which might include both genes and miRNAs, might collaborate with functional complementary events to produce E2a-Pbx1-positive leukemia.
Empagliflozin directly improves diastolic function in human heart failure
Authors: Steffen Pabel, Stefan Wagner, Hannah Bollenberg, Philipp Bengel, Árpád Kovács, Christian Schach, Petros Tirilomis, Julian Mustroph, André Renner, Jan Gummert, Thomas Fischer, Sophie Van Linthout, Carsten Tschöpe, Katrin Streckfuss‐Bömeke, Gerd Hasenfuss, Lars S. Maier, Nazha Hamdani, Samuel Sossalla
Journal: European Journal of Heart Failure (2018)
GW29-e0437 STAT3 Regulation of Cystathionine γ-Lyase Confers Promising Therapy of Anthracycline Cardiomyopathy to an Endogenous Hydrogen Sulfide Donor S-Propargyl-Cysteine
Authors: Jian Wu, Zhijun Wang, Wei Guo, Yizhun Zhu
Journal: Journal of the American College of Cardiology (2018)
Real world incidence, severity and timing of adverse events (AEs) among patients with metastatic non-small cell lung cancer (NSCLC) receiving second-line (2L) immuno-oncology (IO) therapy vs chemotherapy (C)
Authors: M.E. Gutierrez, A.D. Norden, D.C. Lane, B.F. Canavan, E.D. Nwokeji, Y. Xu, S. Kaur, S.L. Goldberg, L. Noh, L. Siegartel, J. Whittington, K. Tuell, B. Korytowsky
Journal: Annals of Oncology (2018)
The Lancet Commission on global mental health and sustainable development
Authors: Vikram Patel, Shekhar Saxena, Crick Lund, Graham Thornicroft, Florence Baingana, Paul Bolton, Dan Chisholm, Pamela Y Collins, Janice L Cooper, Julian Eaton, Helen Herrman, Mohammad M Herzallah, Yueqin Huang, Mark J D Jordans, Arthur Kleinman, Maria Elena Medina-Mora, Ellen Morgan, Unaiza Niaz, Olayinka Omigbodun, Martin Prince, Atif Rahman, Benedetto Saraceno, Bidyut K Sarkar, Mary De Silva, Ilina Singh, Dan J Stein, Charlene Sunkel, JÜrgen UnÜtzer
Journal: The Lancet (2018)
GDP- <scp>l</scp> -fucose synthase is a CD4 <sup>+</sup> T cell–specific autoantigen in DRB3*02:02 patients with multiple sclerosis
Authors: Raquel Planas, Radleigh Santos, Paula Tomas-Ojer, Carolina Cruciani, Andreas Lutterotti, Wolfgang Faigle, Nicole Schaeren-Wiemers, Carmen Espejo, Herena Eixarch, Clemencia Pinilla, Roland Martin, Mireia Sospedra
Journal: Science Translational Medicine (2018)

GDP- l -fucose synthase is an autoantigen recognized by cerebrospinal fluid–infiltrating CD4 + T cells from HLA-DRB3* patients with multiple sclerosis.
VX-445–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles
Authors: Dominic Keating, Gautham Marigowda, Lucy Burr, Cori Daines, Marcus A. Mall, Edward F. McKone, Bonnie W. Ramsey, Steven M. Rowe, Laura A. Sass, Elizabeth Tullis, Charlotte M. McKee, Samuel M. Moskowitz, Sarah Robertson, Jessica Savage, Christopher Simard, Fredrick Van Goor, David Waltz, Fengjuan Xuan, Tim Young, Jennifer L. Taylor-Cousar
Journal: New England Journal of Medicine (2018)

VX-445 is a next-generation cystic fibrosis transmembrane conductance regulator (CFTR) corrector designed to restore Phe508del CFTR protein function in patients with cystic fibrosis when administered with tezacaftor and ivacaftor (VX-445–tezacaftor–ivacaftor).
Abstract 212: Acute Myocardial Infarction in the Acute Phase in Kawasaki Disease in Mexican Children.
Authors: William Sarmiento-Robles, Luis M Garrido-Garcia
Journal: Circulation (2015)

Background: Kawasaki disease (KD) is an acute febrile vasculitis of unknown origin. Despite treatment with intravenous immunoglobulin during the acute phase of the disease, up to 5% of those affected will develop coronary aneurysms predisposing them to thrombotic complications that could result in myocardial infarction (AMI). In Mexico there are few reports of ischemic complications secondary to KD. Objective: To describe the clinical features, the laboratory parameters, treatment used and the outcome of children who presented with myocardial infarction during the acute phase of KD in a third level facility in Mexico City Methods: From our Institutional Database of KD we search for children who presented AMI in the acute phase of the disease from August 1995 to August 2014. We analyzed gender, age, clinical manifestations, time from the onset of the symptoms to diagnosis, laboratory parameters, treatment used, and outcome in the acute phase of the disease. Results: Eight infants were diagnosed with AMI during the study period. The median age at diagnosis was 8 months (range 2 to 53 months). Seven patients were male (87.5%). The median from the onset of the clinical manifestations to diagnosis of KD was 22 days (range 4 to 26 days). All patients developed giant coronary aneurysms (median Z-score 18.98, with a range of Z-score from 11.58 - 27.70). An abnormal EKG and abnormal perfusion tests demonstrated the myocardial infarction in all cases. Two patients died in the acute phase of cardiogenic shock, one more patient died of dilated cardiomyopathy 12 months after coronary bypass surgery with an overall mortality of 62.5% of this group. Conclusions: AMI is a fatal complication of KD. In our small series it was associated with a delayed diagnosis of the disease and therefore the development of giant coronary aneurysms. Treatment of AMI in children after KD is a medical challenge with a poor prognosis in children.
Prohibited Stimulants in Dietary Supplements After Enforcement Action by the US Food and Drug Administration
Authors: Pieter A. Cohen, Anita Wen, Roy Gerona
Journal: JAMA Internal Medicine (2018)

This analysis of dietary supplements purchased in 2014 and purchased again in 2017 examines whether stimulants that were initially present were still present after issuance of public notices by the US Food and Drug Administration to remove potentially hazardous ingredients.
PNU-74654 enhances the antiproliferative effects of 5-FU in breast cancer and antagonizes thrombin induced cell growth via the Wnt pathway
Authors: S. Shahid Sales, A. Avan, F. Rahmani, S.M. Hassanian, M. Hashemzehi, F. Amerizadeh, G.A. Ferns, M. Khazaei
Journal: Annals of Oncology (2018)
The Ewing Family of Tumors Relies on BCL-2 and BCL-XL to Escape PARP Inhibitor Toxicity
Authors: Daniel A.R. Heisey, Timothy L. Lochmann, Konstantinos V. Floros, Colin M. Coon, Krista M. Powell, Sheeba Jacob, Marissa L. Calbert, Maninderjit S. Ghotra, Giovanna T. Stein, Yuki Kato Maves, Steven C. Smith, Cyril H. Benes, Joel D. Leverson, Andrew J. Souers, Sosipatros A. Boikos, Anthony C. Faber
Journal: Clinical Cancer Research (2018)

It was recently demonstrated that the EWSR1-FLI1 t(11;22)(q24;12) translocation contributes to the hypersensitivity of Ewing sarcoma to PARP inhibitors, prompting clinical evaluation of olaparib in a cohort of heavily pretreated Ewing sarcoma tumors. Unfortunately, olaparib activity was disappointing, suggesting an underappreciated resistance mechanism to PARP inhibition in patients with Ewing sarcoma. We sought to elucidate the resistance factors to PARP inhibitor therapy in Ewing sarcoma and identify a rational drug combination capable of rescuing PARP inhibitor activity.We employed a pair of cell lines derived from the same patient with Ewing sarcoma prior to and following chemotherapy, a panel of Ewing sarcoma cell lines, and several patient-derived xenograft (PDX) and cell line xenograft models.We found olaparib sensitivity was diminished following chemotherapy. The matched cell line pair revealed increased expression of the antiapoptotic protein BCL-2 in the chemotherapy-resistant cells, conferring apoptotic resistance to olaparib. Resistance to olaparib was maintained in this chemotherapy-resistant model in vivo, whereas the addition of the BCL-2/XL inhibitor navitoclax led to tumor growth inhibition. In 2 PDXs, olaparib and navitoclax were minimally effective as monotherapy, yet induced dramatic tumor growth inhibition when dosed in combination. We found that EWS-FLI1 increases BCL-2 expression; however, inhibition of BCL-2 alone by venetoclax is insufficient to sensitize Ewing sarcoma cells to olaparib, revealing a dual necessity for BCL-2 and BCL-XL in Ewing sarcoma survival.These data reveal BCL-2 and BCL-XL act together to drive olaparib resistance in Ewing sarcoma and reveal a novel, rational combination therapy that may be put forward for clinical trial testing.
Area Deprivation and Regional Disparities in Treatment and Outcome Quality of 29,284 Pediatric Patients With Type 1 Diabetes in Germany: A Cross-sectional Multicenter DPV Analysis
Authors: Marie Auzanneau, Stefanie Lanzinger, Barbara Bohn, Peter Kroschwald, Ursula Kuhnle-Krahl, Paul Martin Holterhus, Kerstin Placzek, Johannes Hamann, Rainer Bachran, Joachim Rosenbauer, Werner Maier
Journal: Diabetes Care (2018)

This study analyzed whether area deprivation is associated with disparities in health care of pediatric type 1 diabetes in Germany.We selected patients <20 years of age with type 1 diabetes and German residence documented in the "diabetes patient follow-up" (Diabetes-Patienten-Verlaufsdokumentation [DPV]) registry for 2015/2016. Area deprivation was assessed by quintiles of the German Index of Multiple Deprivation (GIMD 2010) at the district level and was assigned to patients. To investigate associations between GIMD 2010 and indicators of diabetes care, we used multivariable regression models (linear, logistic, and Poisson) adjusting for sex, age, migration background, diabetes duration, and German federal state.We analyzed data from 29,284 patients. From the least to the most deprived quintile, use of continuous glucose monitoring systems (CGMS) decreased from 6.3 to 3.4% and use of long-acting insulin analogs from 80.8 to 64.3%, whereas use of rapid-acting insulin analogs increased from 74.7 to 79.0%; average HbA1c increased from 7.84 to 8.07% (62 to 65 mmol/mol), and the prevalence of overweight from 11.8 to 15.5%, but the rate of severe hypoglycemia decreased from 12.1 to 6.9 events/100 patient-years. Associations with other parameters showed a more complex pattern (use of continuous subcutaneous insulin infusion [CSII]) or were not significant.Area deprivation was associated not only with key outcomes in pediatric type 1 diabetes but also with treatment modalities. Our results show, in particular, that the access to CGMS and CSII could be improved in the most deprived regions in Germany.
Serum Metabolites as Diagnostic Biomarkers for Cholangiocarcinoma, Hepatocellular Carcinoma, and Primary Sclerosing Cholangitis
Authors: Jesus M. Banales, Mercedes Iñarrairaegui, Ander Arbelaiz, Piotr Milkiewicz, Jordi Muntané, Luis Muñoz‐Bellvis, Adelaida La Casta, Luis M. Gonzalez, Enara Arretxe, Cristina Alonso, Ibon Martínez‐Arranz, Ainhoa Lapitz, Alvaro Santos‐Laso, Matias A. Avila, Maria L. Martínez‐Chantar, Luis Bujanda, Jose J.G. Marin, Bruno Sangro, Rocio I.R. Macias
Journal: Hepatology (2018)

Early and differential diagnosis of intrahepatic cholangiocarcinoma (iCCA) and hepatocellular carcinoma (HCC) by noninvasive methods represents a current clinical challenge. The analysis of low‐molecular‐weight metabolites by new high‐throughput techniques is a strategy for identifying biomarkers. Here, we have investigated whether serum metabolome can provide useful biomarkers in the diagnosis of iCCA and HCC and could discriminate iCCA from HCC. Because primary sclerosing cholangitis (PSC) is a risk factor for CCA, serum metabolic profiles of PSC and CCA have also been compared. The analysis of the levels of lipids and amino acids in the serum of patients with iCCA, HCC, and PSC and healthy individuals (n = 20/group) showed differential profiles. Several metabolites presented high diagnostic value for iCCA versus control, HCC versus control, and PSC versus control, with areas under the receiver operating characteristic curve (AUC) greater than those found in serum for the nonspecific tumor markers carbohydrate antigen 19‐9 (CA 19‐9) and alpha‐fetoprotein (AFP), commonly used to help in the diagnosis of iCCA and HCC, respectively. The development of an algorithm combining glycine, aspartic acid, SM(42:3), and SM(43:2) permitted to accurately differentiate in the diagnosis of both types of tumors (biopsy‐proven). The proposed model yielded 0.890 AUC, 75% sensitivity, and 90% specificity. Another algorithm by combination of PC(34:3) and histidine accurately permitted to differentiate PSC from iCCA, with an AUC of 0.990, 100% sensitivity, and 70% specificity. These results were validated in independent cohorts of 14‐15 patients per group and compared with profiles found in patients with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Conclusion: Specific changes in serum concentrations of certain metabolites are useful to differentiate iCCA from HCC or PSC, and could help in the early diagnosis of these diseases.
What we must learn from mesh
Authors: Fiona Godlee
Journal: BMJ (2018)

What can we learn from the shameful story of vaginal mesh? That thousands of women have been irreversibly harmed; that implants were approved on the flimsiest of evidence; that surgeons weren’t adequately trained and patients weren’t properly informed; that the dash for mesh, fuelled by its manufacturers, stopped the development of alternatives; that surgeons failed to set up mesh registries that would have identified complications sooner; and that the National Institute for Health and Clinical Excellence and the UK regulators let them off the hook (doi:10.1136/bmj.k4137, doi:10.1136/bmj.k4164). As our …
A phase I trial of BI 754091, a programmed death receptor 1 (PD-1) inhibitor, in patients with advanced solid tumors
Authors: Melissa Johnson, Manish Patel, Lillian Siu, Raid Aljumaily, Mark Kozloff, Ulka Vaishampayan, Mabrouk Elgadi, Miaomiao Ge, Christine Duffy, Ralph Graeser, Susanne Buschke, Sheetal Khedkar, Suzanne F. Jones, Howard A. Burris
Journal: Annals of Oncology (2018)