tbuckley/cabot-search huggingface dataset:
A novel, noninvasive, mRNA gene expression colon cancer screening methodology.
Authors: L. A. Boardman, Y. S. Chiu, O. Petrauskene, L. Wieczorek, D. H. Moore, K. V. Ballman, S. N. Thibodeau, H. Nelson
Journal: Journal of Clinical Oncology (2010)

3631 Background: An mRNA gene expression methodology testing noninvasive rectal swab samples for a panel of 16 genes, representing 4 metabolic pathways, has shown promise for detecting colon and rectal cancers in pilot studies. To test the screening potential of this methodology, we conducted a case-controlled, single-center study using samples collected from patients with a negative screening colonoscopy (Controls; n = 71) and from patients with colorectal cancer (CRC; n = 38). Methods: Controls were defined as polyp- and cancer-free patients with no family history of CRC. Rectal swabs were collected, coded, preserved in RNAProtect Ò solution (Qiagen), and RNA was isolated using RNeasy mini kit (Qiagen). Real time RT-PCR using reverse transcriptase (Invitrogen) and random primers and Oligo (dT) was performed on samples pretreated with RNAase-free DNase. PCR amplification with specific oligonucleotide primers was performed using Applied Biosystems 7500 Fast Real-Time PCR Systems for 16 different markers including CXCR2, osteopontin, cyclo-oxygenase-1 and 2, proliferating peroxisome activating receptor alpha, delta and gamma, growth- related oncogene alpha and gamma, interleukin-8, mCSF, p21, c-myc, CD44, cyclin D and serum amyloid A1. Classification was based on using Mahalanobis distances with a threshold set to ensure at least 90% sensitivity. Results: For the 71 controls, the median age was 57 years (range 50-81) and 37 were women. For the 38 cancer patients, the median age was 67 years (range 50-89) and 19 were women. Adenocarcinomas were identified in the following colon locations: cecum (10), ascending (10), transverse (3), sigmoid (12), and rectosigmoid (3). AJCC tumor stage was I (9); II (15): III (13); and IV (1). The final analysis results in a test performance with 92% sensitivity and 68% specificity using mean M-Distance calculation. Sensitivity is 92% and specificity is 60% using maximum M-Distance calculation. Conclusions: This mRNA gene expression methodology would fulfill current guidelines for screening which require a minimum sensitivity and specificity of 50%. Future studies will aim to improve the specificity and validate the technology. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration IntelliGene Scan IntelliGene Scan IntelliGene Scan IntelliGene Scan IntelliGene Scan
Use of a proteomic approach to link pyruvate kinase M2 expression to oxaliplatin resistance in colorectal cancer patients and human cell lines
Authors: A. Ginés, E. Martinez-Balibrea, C. Plasencia, A. Martinez-Cardus, E. Musulén, N. Neamati, J. L. Manzano, A. Abad
Journal: Journal of Clinical Oncology (2008)

4121 Background: Resistance to anticancer drugs is a major obstacle preventing effective treatment of disseminated cancers. Understanding the molecular basis to chemoresistance is likely to provide better treatment. The aim of this work was to gain further understanding of the molecular mechanisms involved in oxaliplatin resistance in colorectal cancer (CRC) cells by using a proteomic approach and translate it to the clinical setting. Methods: An oxaliplatin resistant cell line (HTOXAR3) was established from human HT29 CRC cells. Proteins were extracted and analyzed through comparative proteomics. Results were confirmed by western blotting (WB) and Real Time Quantitative PCR. A tissue microarray constructed with 41 metastatic paraffin-embedded colorectal adenocarcinomas from patients treated with oxaliplatin + 5FU was used to determine p53, Ki-67 and bcl-2 expression. RNA from these tumors was subjected to RTQPCR to assess PKM2 mRNA expression. Differences in response were analyzed by contingency tables and chi-square test. Results: HTOXAR3 were 6 fold-resistant as compared to HT29 cells. Of the 47 spots >4 fold over-expressed or down-regulated in HTOXAR3 vs. HT29 cells, Mass Spectrometry, WB and RTQPCR confirmed down-regulation of PKM2 in HTOXAR3. In a panel of 8 CRC cell lines, we found a negative correlation between OXA resistance and PKM2 mRNA levels (spearman r = -0.846, p = 0.008). Oxaliplatin exposure in both HT29 and HTOXAR3 led to PKM2 mRNA up-regulation. Patients with the lowest PKM2 levels had lower response rates to oxaliplatin-based treatment (20% vs. 64.5% p =0.026) and overexpressed p53 (90% vs. 50%, p = 0.032). High PKM2 levels were associated with high ki-67 levels (p = 0.048). Conclusions: By using proteomics we have identified PKM2 as a putative predictive marker of response in CRC patients treated with oxaliplatin plus 5FU as first line chemotherapy. No significant financial relationships to disclose.
Targeted Suppression of Interleukin-1 Signaling Attenuates Leukemic Cellular Growth and Disease Progression in Primary Human Cells and Murine Models of Acute Myeloid leukemia­­
Authors: Alyssa Carey, David Edwards, Christopher A. Eide, Elie Traer, Jeffrey W. Tyner, Grover C. Bagby, Brian J. Druker, Anupriya Agarwal
Journal: Blood (2014)
Bendamustine + Rituximab-Combinations and R-CHOP Achieve a Major Survival Improvement Of Patients With Follicular Lymphoma In Routine Care
Authors: Rudolf Weide, Stefan Feiten, Vera Friesenhahn, Jochen Heymanns, Kristina Kleboth, Jörg Thomalla, Christoph van Roye, Hubert Köppler
Journal: Blood (2013)
Abstract 17623: A Case of Biopsy-proven Immunoglobulin G4-Related Disease Associated With Multiple Giant Coronary Artery Aneurysms, Peripheral Arterial Aneurysms, End Stage Renal Disease, and Heart Failure
Authors: Mark D Benson, Cathryn Byrne-Dugan, Dale Adler, Mark Feinberg, Deepak Bhatt
Journal: Circulation (2015)

A 54-year-old man with remote large cell non-Hodgkin’s lymphoma in remission following R-CHOP and severe atopic dermatitis was transferred from another hospital with a non-ST elevation myocardial infarction. Over the preceding year, the patient had suffered recurrent admissions for acutely decompensated heart failure with a newly depressed left ventricular ejection fraction (LVEF) of 20% by echocardiography and rapidly progressive end-stage renal disease of unclear etiology requiring the initiation of hemodialysis. Prior workup had demonstrated an infrarenal abdominal aortic aneurysm and bilateral common iliac artery aneurysms with subsequent computed tomography (CT) additionally demonstrating a superior mesenteric artery aneurysm. The patient was taken for immediate coronary arteriography, which demonstrated giant aneurysms in the left main and right coronary arteries, as well as multivessel severe stenoses. CT coronary angiogram demonstrated significant circumferential wall thickening throughout the coronary vasculature. Given concern for IgG4-related disease (IgG4-RD), a renal biopsy was pursued that confirmed the diagnosis. 18F-fluorodeoxyglucose positron emission tomography-CT identified only mild aortic inflammation. The patient was treated with high-dose steroids and rituximab. The serological inflammatory markers improved, and he underwent coronary artery bypass grafting. Pericardial, aortic adventitial, left internal mammary artery, and saphenous vein biopsies showed cardiovascular involvement of IgG4-RD. The patient has been maintained on rituximab with normalization of his LVEF and no recurrence of chest pain over the past eighteen months. IgG4-RD is a fibroinflammatory systemic disease newly described in 2003 and only recently found to involve the cardiovascular system with several reports of peripheral aneurysmal disease. To our knowledge, the current case represents the first report of a patient successfully treated for biopsy-proven IgG4-RD associated with coronary artery disease and left ventricular systolic dysfunction. IgG4-RD may represent a novel mechanism underlying some forms of peripheral and coronary arterial disease and may offer new insights into vascular biology.
NHS must do more to tackle white male dominance of leadership roles, Labour Party says
Authors: Abi Rimmer
Journal: BMJ (2016)

White men still dominate senior leadership positions in the NHS in England, an investigation by the Labour Party’s health team has found.1

Through a freedom of information request Labour found that only 2% of chairs of NHS trusts came from a black, Asian, or other ethnic minority background and that less than a third (28%) were women. Labour said that its findings showed that the NHS “has a long way to go before the boards of acute and ambulance trusts are anywhere …
Особливості перебігу патології верхнього відділу шлунково-кишкового тракту у хворих з орофарингеальним кандидозом
Authors: I.V. Kushnirenko
Journal: GASTROENTEROLOGY (2016)

У статті подано результати вивчення шостої шкали коморбідності The Cumulative Illness Rating Scale, у якій наведені захворювання верхнього відділу травного тракту у хворих з орофарингеальним кандидозом порівняно з пацієнтами, у яких гриби не виявлено, та з особами iз незначним/помірним ростом грибів роду Candida на слизовій оболонці ротової порожнини. Визначено, що при однаковій частоті хронічного гастродуоденіту та хронічного гастриту для пацієнтiв з орофарингеальним кандидозом характерним є зменшення частоти як гастроезофагеальної рефлюксної хвороби — в 1,6 і 1,5 раза порівняно з тими, у яких гриби не знайдено, та з тими, у кого рiст незначний/помірний (р &lt; 0,05 і р &lt; 0,05 відповідно), так і виразкової хвороби із рубцевою деформацією в луковиці дванадцятипалої кишки — у 2,1 раза порівняно із особами, у яких гриби не виявлено (р &lt; 0,05). За наявності гастроезофагеальної рефлюксної хвороби ризик орофарингеального кандидозу у хворих вірогiдно менший (відношення шансів (ВШ) = 0,49, 95% довiрчий iнтервал (ДI) = 0,29–0,83) порівняно із пацiєнтами, у яких гриби не виявлено. Кандидоз стравоходу зареєстрований майже у третини хворих з орофарингеальним кандидозом, що вірогiдно вище порівняно з тими, у кого гриби не знайдено (n = 1) (р &lt; 0,001), та у чотири рази вище, нiж у хворих iз незначним/помірним ростом (р &lt; 0,001). Висока оцінка шансів виявлення кандидозу стравоходу при орофарингеальному кандидозі (ВШ = 55,00, 95% ДI = 7,43–407,07) свідчить про здатність грибів Candida при надмірному рості на слизовій оболонці ротової порожнини адгезуватися та проростати в слизову оболонку в дистальних відділах верхнього відділу травного тракту. Висока прогностична оцінка виявлення орофарингеального кандидозу за наявності інфекції Нelicobacter pylori у хворих на гастроентерологічну патологію свідчить про єдність патогенетичних процесів (ВШ = 5,76, 95 % ДI = 2,95–11,26).Подальше вивчення стану імунного захисту в умовах надмірного росту грибів роду Candida у хворих гастроентерологічного профілю дозволить пояснити особливості коморбідного стану при цій патології.
Myelodysplastic Syndromes (MDS) With 20q Deletion Show a High Frequency Of Associated Cytogenetic and Molecular Lesions With An Association To U2AF1, SRSF2, and Prognostically Adverse ASXL1 Mutations
Authors: Ulrike Bacher, Torsten Haferlach, Susanne Schnittger, Melanie Zenger, Manja Meggendorfer, Andreas Roller, Vera Grossmann, Maria Theresa Krauth, Sabine Jeromin, Tamara Alpermann, Alexander Kohlmann, Wolfgang Kern, Claudia Haferlach
Journal: Blood (2013)
Results of the Safety Run-in Phase of CLL14 (BO25323): A Prospective, Open-Label, Multicenter Randomized Phase III Trial to Compare the Efficacy and Safety of Obinutuzumab and Venetoclax (GDC-0199/ABT-199) with Obinutuzumab and Chlorambucil in Patients with Previously Untreated CLL and Coexisting Medical Conditions
Authors: Kirsten Fischer, Anna-Maria Fink, Helen Bishop, Mark Dixon, Jasmin Bahlo, Michael Y. Choi, Robert Weinkove, K. Sue Robinson, Martin Dreyling, Till Seiler, Stephen Opat, Carolyn Owen, Javier Lopez, Nadine Kutsch, Eugen Tausch, Matthias Ritgen, Rod A. Humerickhouse, Kathryn Humphrey, Michael K. Wenger, Valentin Goede, Barbara Eichhorst, Clemens-Martin Wendtner, Stephan Stilgenbauer, Thomas J. Kipps, Michael Hallek
Journal: Blood (2015)
Normal-Weight Central Obesity and Mortality Risk
Authors: Rickey E. Carter, David O. Hodge, Francisco Lopez-Jimenez
Journal: Annals of Internal Medicine (2016)

Letters16 August 2016Normal-Weight Central Obesity and Mortality RiskRickey E. Carter, PhD, David O. Hodge, MS, and Francisco Lopez-Jimenez, MD, MSRickey E. Carter, PhDFrom Mayo Clinic, Rochester, Minnesota.Search for more papers by this author, David O. Hodge, MSFrom Mayo Clinic, Rochester, Minnesota.Search for more papers by this author, and Francisco Lopez-Jimenez, MD, MSFrom Mayo Clinic, Rochester, Minnesota.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L16-0073 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dr. Yu raises important points about the interpretation of our models. Her critique of the statement that BMI was not associated with mortality in men is appropriate given the statistically significant interaction. However, this statement was not based on the interpretation of a single parameter estimate in the model. Figures 1 and 2 were specifically developed to present the combined effects of these variables (that is, the combined interaction and main effects), which Dr. Yu suggests is the appropriate course. From a pragmatic perspective, the higher-order interaction was estimated with a coefficient of 0.002 (a natural logarithm of ... Author, Article, and Disclosure InformationAffiliations: From Mayo Clinic, Rochester, Minnesota.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-2525. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoNormal-Weight Central Obesity: Implications for Total and Cardiovascular Mortality Karine R. Sahakyan , Virend K. Somers , Juan P. Rodriguez-Escudero , David O. Hodge , Rickey E. Carter , Ondrej Sochor , Thais Coutinho , Michael D. Jensen , Véronique L. Roger , Prachi Singh , and Francisco Lopez-Jimenez Normal-Weight Central Obesity and Mortality Risk Yan Yu Correction: A Cost Analysis of the American Board of Internal Medicine's Maintenance-of-Certification Program Metrics 16 August 2016Volume 165, Issue 4Page: 298-299KeywordsBody mass indexDisclosureHazard ratioMortalityObesityOverweight ePublished: 16 August 2016 Issue Published: 16 August 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Obama turns his hand to health policy analysis
Authors: Douglas Kamerow
Journal: BMJ (2016)

But the US president’s JAMA article was not externally peer reviewed



As someone who writes about health policy, I was interested to see Barack Obama’s recent article in JAMA assessing the Affordable Care Act.1 It is not uncommon to see a US president commenting in a newspaper op-ed column, and a few previous presidents have also written commentaries for medical journals. But Obama’s six page JAMA “special communication,” with six graphs—several with new data—and 68 references, seemed more like a research article than an op-ed piece.

Unsurprisingly the article received a lot of attention from the journal and from readers. Not many medical journal articles have three accompanying commentaries (one by the editor) when they are published. Fewer still stimulate a near full page editorial in the New York Times .2 Obama’s article invites questions about its …
Myeloid Derived Suppressor Cells (MDSCs) Are Increased and Exert Immunosuppressive Activity In CML Patients At Diagnosis
Authors: Cesarina Giallongo, Nunziatina Parrinello, Daniele Tibullo, Piera La Cava, Alessandra Romano, Annalisa Chiarenza, Fabio Stagno, Paolo G. Vigneri, Giuseppe A. Palumbo, Francesco Di Raimondo
Journal: Blood (2013)
Retroviral Vector-Producing Mesenchymal Stem Cells for Tumor Tracking and Therapeutic Gene Amplification in Suicide Cancer Gene Therapy.
Authors: Ryosuke Uchibori, Takashi Okada, Takayuki Ito, Masashi Urabe, Hiroaki Mizukami, Akihiro Kume, Keiya Ozawa
Journal: Blood (2007)
Integrated Delivery of Antiretroviral Treatment and Pre-exposure Prophylaxis to HIV-1–Serodiscordant Couples: A Prospective Implementation Study in Kenya and Uganda
Authors: Jared M. Baeten, Renee Heffron, Lara Kidoguchi, Nelly R. Mugo, Elly Katabira, Elizabeth A. Bukusi, Stephen Asiimwe, Jessica E. Haberer, Jennifer Morton, Kenneth Ngure, Nulu Bulya, Josephine Odoyo, Edna Tindimwebwa, Craig Hendrix, Mark A. Marzinke, Norma C. Ware, Monique A. Wyatt, Susan Morrison, Harald Haugen, Andrew Mujugira, Deborah Donnell, Connie Celum
Journal: PLoS Medicine (2016)

Background Antiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings. Methods and Findings Between November 5, 2012, and January 5, 2015, we enrolled and followed 1,013 heterosexual HIV-1-serodiscordant couples in Kenya and Uganda in a prospective implementation study. ART and PrEP were offered through a pragmatic strategy, with ART promoted for all couples and PrEP offered until 6 mo after ART initiation by the HIV-1 infected partner, permitting time to achieve virologic suppression. One thousand thirteen couples were enrolled, 78% of partnerships initiated ART, and 97% used PrEP, during a median follow-up of 0.9 years. Objective measures of adherence to both prevention strategies demonstrated high use (≥85%). Given the low HIV-1 incidence observed in the study, an additional analysis was added to compare observed incidence to incidence estimated under a simulated counterfactual model constructed using data from a prior prospective study of HIV-1-serodiscordant couples. Counterfactual simulations predicted 39.7 HIV-1 infections would be expected in the population at an incidence of 5.2 per 100 person-years (95% CI 3.7–6.9). However, only two incident HIV-1 infections were observed, at an incidence of 0.2 per 100 person-years (95% CI 0.0–0.9, p < 0.0001 versus predicted). The use of a non-concurrent comparison of HIV-1 incidence is a potential limitation of this approach; however, it would not have been ethical to enroll a contemporaneous population not provided access to ART and PrEP. Conclusions Integrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of <0.5% per year compared to an expected incidence of >5% per year.
Longer-Lived Parents and Cardiovascular Outcomes
Authors: Janice L. Atkins, Luke C. Pilling, Alessandro Ble, Ambarish Dutta, Lorna W. Harries, Anna Murray, Carol Brayne, Jean-Marie Robine, George A. Kuchel, Luigi Ferrucci, David Melzer
Journal: Journal of the American College of Cardiology (2016)
Interseason variability of a functional movement test, the 9+ screening battery, in professional male football players
Authors: A Bakken, S Targett, T Bere, C Eirale, A Farooq, J L Tol, R Whiteley, E Witvrouw, K M Khan, R Bahr
Journal: British Journal of Sports Medicine (2016)

The Nine Plus screening battery test (9+) is a functional movement test intended to identify limitations in fundamental movement patterns predisposing athletes to injury. However, the interseason variability is unknown.To examine the variability of the 9+ test between 2 consecutive seasons in professional male football players.Asymptomatic Qatar Star League players (n=220) completed the 9+ at the beginning of the 2013 and 2014 seasons. Time-loss injuries in training and matches were obtained from the Aspetar Injury and Illness Surveillance Program. No intervention was initiated between test occasions.A significant increase in the mean total score of 1.6 points (95% CI 1.0 to 2.2, p<0.001) was found from season 1 (22.2±4.1 (SD)) to season 2 (23.8±3.3). The variability was large, as shown by an intraclass correlation coefficient (ICC) of 0.24 (95% CI 0.11 to 0.36) and a minimal detectable change (MDC) of 8.7 points. Of the 220 players, 136 (61.8%) suffered a time-loss injury between the 2 tests. There was an improvement in mean total scores in the injured (+2.0±0.4 (SE), p<0.001) group but not in the uninjured group (+0.9±0.5, p=0.089). The variability from season 1 to season 2 was large both in the injured (ICC 0.25, 0.09 to 0.40, MDC 8.3) and uninjured (ICC 0.24, 0.02 to 0.43, MDC 9.1) groups.The 9+ demonstrated substantial intraindividual variability in the total score between 2 consecutive seasons, irrespective of injury. A change above 8 points is necessary to represent a real change in the 9+ test between seasons.
Comprehensive Geriatric Assessment-Guided Therapy Does Improve Outcomes of Older Patients With Advanced Lung Cancer
Authors: Ajeet Gajra, Kah Poh Loh, Arti Hurria, Hyman Muss, Ron Maggiore, William Dale, Heidi D. Klepin, Allison Magnuson, Stuart M. Lichtman, Grant R. Williams, Armin Shahrokhni, Supriya G. Mohile
Journal: Journal of Clinical Oncology (2016)
Guillain-Barré Syndrome During Ongoing Zika Virus Transmission — Puerto Rico, January 1–July 31, 2016
Authors: Emilio Dirlikov, Chelsea G. Major, Marrielle Mayshack, Nicole Medina, Desiree Matos, Kyle R. Ryff, Jomil Torres-Aponte, Rebecca Alkis, Jorge Munoz-Jordan, Candimar Colon-Sanchez, Jorge L. Salinas, Daniel M. Pastula, Myriam Garcia, Marangely Olivero Segarra, Graciela Malave, Dana L. Thomas, Gloria M. Rodríguez-Vega, Carlos A. Luciano, James Sejvar, Tyler M. Sharp, Brenda Rivera-Garcia
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Guillain-Barré syndrome (GBS) is a postinfectious autoimmune disorder characterized by bilateral flaccid limb weakness attributable to peripheral nerve damage (1). Increased GBS incidence has been reported in countries with local transmission of Zika virus, a flavivirus transmitted primarily by certain Aedes species mosquitoes (2). In Puerto Rico, three arthropod-borne viruses (arboviruses) are currently circulating: Zika, dengue, and chikungunya. The first locally acquired Zika virus infection in Puerto Rico was reported in December 2015 (3). In February 2016, the Puerto Rico Department of Health (PRDH), with assistance from CDC, implemented the GBS Passive Surveillance System (GBPSS) to identify new cases of suspected GBS (4). Fifty-six suspected cases of GBS with onset of neurologic signs during January 1-July 31, 2016, were identified. Thirty-four (61%) patients had evidence of Zika virus or flavivirus infection; the median age of these patients was 55 years (range = 21-88 years), and 20 (59%) patients were female. These 34 patients were residents of seven of eight PRDH public health regions. All 34 patients were hospitalized and treated with intravenous immunoglobulin G (IVIg), the standard treatment for GBS; 21 (62%) required intensive care unit admission, including 12 (35%) who required endotracheal intubation and mechanical ventilation. One patient died of septic shock after treatment for GBS. Additionally, 26 cases of neurologic conditions other than GBS were reported through GBPSS, including seven (27%) in patients with evidence of Zika virus or flavivirus infection. Residents of and travelers to Puerto Rico and countries with active Zika virus transmission should follow recommendations for prevention of Zika virus infections.* Persons with signs or symptoms consistent with GBS should promptly seek medical attention. Health care providers in areas with ongoing local transmission seeing patients with neurologic illnesses should consider GBS and report suspected cases to public health authorities.