tbuckley/cabot-search huggingface dataset:
Efficacy of Sequential Ipilimumab Monotherapy versus Best Supportive Care for Unresectable Locally Advanced/Metastatic Gastric or Gastroesophageal Junction Cancer
Authors: Yung-Jue Bang, Jae Yong Cho, Yeul Hong Kim, Jin Won Kim, Maria Di Bartolomeo, Jaffer A. Ajani, Kensei Yamaguchi, Agnes Balogh, Teresa Sanchez, Markus Moehler
Journal: Clinical Cancer Research (2017)

Purpose: Ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated protein-4 interactions, enhances T-cell activation and promotes tumor immunity. This phase II study evaluated the safety and efficacy of ipilimumab monotherapy versus best supportive care (BSC) among patients with advanced/metastatic gastric or gastroesophageal junction cancer who achieved at least stable disease with first-line chemotherapy.Experimental Design: Eligible patients were randomized to ipilimumab 10 mg/kg every 3 weeks for four doses, then 10 mg/kg every 12 weeks for up to 3 years, or BSC, which could include continuation of fluoropyrimidine until progression or toxicity. The primary endpoint was immune-related progression-free survival (irPFS); secondary endpoints included PFS by modified World Health Organization criteria and overall survival (OS).Results: Of 143 patients screened, 57 were randomized to each arm. irPFS with ipilimumab versus BSC was not improved [2.92 months, 95% confidence interval (CI), 1.61-5.16 vs. 4.90 months, 95% CI, 3.45-6.54, HR = 1.44; 80% CI, 1.09-1.91; P = 0.097], resulting in study cessation. At study closeout, which occurred 8 months after the interim analysis, the median OS durations were 12.7 months (95% CI, 10.5-18.9) and 12.1 months (95% CI, 9.3-not estimable), respectively. Grade 3/4 treatment-related adverse events occurred in 23% of ipilimumab-treated patients, in whom diarrhea (9%) and fatigue (5%) were most frequent, and in 9% of active BSC-treated patients.Conclusions: Although ipilimumab at 10 mg/kg was manageable, it did not improve irPFS versus BSC. However, comparable median OS of approximately 1 year and a favorable safety profile support the investigation of ipilimumab in combination with other therapies for advanced gastric cancer. Clin Cancer Res; 23(19); 5671-8. ©2017 AACR.
Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses
Authors: Timothy P. Sheahan, Amy C. Sims, Rachel L. Graham, Vineet D. Menachery, Lisa E. Gralinski, James B. Case, Sarah R. Leist, Krzysztof Pyrc, Joy Y. Feng, Iva Trantcheva, Roy Bannister, Yeojin Park, Darius Babusis, Michael O. Clarke, Richard L. Mackman, Jamie E. Spahn, Christopher A. Palmiotti, Dustin Siegel, Adrian S. Ray, Tomas Cihlar, Robert Jordan, Mark R. Denison, Ralph S. Baric
Journal: Science Translational Medicine (2017)

Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses in vitro and in vivo.
Unsustainable pressure on GPs has led to dip in patient satisfaction, says BMA
Authors: Abi Rimmer
Journal: BMJ (2017)

Unsustainable pressure on GP services and increasing GP workloads have led to a decrease in patient satisfaction with the service, the BMA has said.

The latest figures from NHS England’s GP patient survey showed a slight decline in the proportion of patients who rated their overall experience of their GP surgery as good, down from 85.7% in 2016 to 84.8% in 2017.1 The survey received responses from 808 332 patients after 2 157 769 questionnaires were sent out nationally, a response rate of 37.5%.

It found that the proportion …
Vital Signs: Changes in Opioid Prescribing in the United States, 2006–2015
Authors: Gery P. Guy, Kun Zhang, Michele K. Bohm, Jan Losby, Brian Lewis, Randall Young, Louise B. Murphy, Deborah Dowell
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Prescription opioid-related overdose deaths increased sharply during 1999-2010 in the United States in parallel with increased opioid prescribing. CDC assessed changes in national-level and county-level opioid prescribing during 2006-2015.CDC analyzed retail prescription data from QuintilesIMS to assess opioid prescribing in the United States from 2006 to 2015, including rates, amounts, dosages, and durations prescribed. CDC examined county-level prescribing patterns in 2010 and 2015.The amount of opioids prescribed in the United States peaked at 782 morphine milligram equivalents (MME) per capita in 2010 and then decreased to 640 MME per capita in 2015. Despite significant decreases, the amount of opioids prescribed in 2015 remained approximately three times as high as in 1999 and varied substantially across the country. County-level factors associated with higher amounts of prescribed opioids include a larger percentage of non-Hispanic whites; a higher prevalence of diabetes and arthritis; micropolitan status (i.e., town/city; nonmetro); and higher unemployment and Medicaid enrollment.Despite reductions in opioid prescribing in some parts of the country, the amount of opioids prescribed remains high relative to 1999 levels and varies substantially at the county-level. Given associations between opioid prescribing, opioid use disorder, and overdose rates, health care providers should carefully weigh the benefits and risks when prescribing opioids outside of end-of-life care, follow evidence-based guidelines, such as CDC's Guideline for Prescribing Opioids for Chronic Pain, and consider nonopioid therapy for chronic pain treatment. State and local jurisdictions can use these findings combined with Prescription Drug Monitoring Program data to identify areas with prescribing patterns that place patients at risk for opioid use disorder and overdose and to target interventions with prescribers based on opioid prescribing guidelines.
Can we still improve long term oncologic outcome of patients with anal carcinoma after multimodality treatment?
Authors: Rodica Anghel, Laurentia Gales, Luiza Serbanescu, Mihai Georgescu, Vanessa Moldoveanu, Fabiana Curea, Inga Botnariuc, Oana Trifanescu
Journal: Annals of Oncology (2017)
Over half of anaesthetic trainees have had car crash or near miss after night shift, survey finds
Authors: Abi Rimmer
Journal: BMJ (2017)

Over half (57%) of anaesthetic trainees have experienced a crash or near miss when driving home after a night shift, a survey conducted by the Association of Anaesthetists of Great Britain and Ireland has found.

The study, published in Anaesthesia , outlined the findings of the survey, which received 2170 responses from UK anaesthetic trainees.1

Most (84%) of the respondents said that they had felt too tired to drive home after a night shift, and 57% said that they had experienced a crash or near miss in doing so.

Respondents talked about falling asleep at the wheel and about being woken by rumble strips on the road, the paper said. …
Inhibition of IKKɛ and TBK1 Improves Glucose Control in a Subset of Patients with Type 2 Diabetes
Authors: Elif A. Oral, Shannon M. Reilly, Andrew V. Gomez, Rasimcan Meral, Laura Butz, Nevin Ajluni, Thomas L. Chenevert, Evgenia Korytnaya, Adam H. Neidert, Rita Hench, Diana Rus, Jeffrey F. Horowitz, BreAnne Poirier, Peng Zhao, Kim Lehmann, Mohit Jain, Ruth Yu, Christopher Liddle, Maryam Ahmadian, Michael Downes, Ronald M. Evans, Alan R. Saltiel
Journal: Cell Metabolism (2017)
Whole genome sequencing (WGS) for food-borne pathogen surveillance and control – taking the pulse
Authors: Jacob Moran-Gilad
Journal: Eurosurveillance (2017)

Preview this article: Whole genome sequencing (WGS) for food-borne pathogen surveillance and control – taking the pulse, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/22/23/eurosurv-22-23-1-1.gif
High Illicit Drug Abuse and Suicide in Organ Donors With Type 1 Diabetes
Authors: Laura M. Jacobsen, Michael J. Haller, Alice Parish, Matthew J. Gurka, S. Robert Levine, Clive Wasserfall, Martha Campbell-Thompson, John Kaddis, Alberto Pugliese, Mark A. Atkinson, Desmond A. Schatz
Journal: Diabetes Care (2017)

Organ donors with type 1 diabetes represent a unique population for research. Through a combination of immunological, metabolic, and physiological analyses, researchers utilizing such tissues seek to understand the etiopathogenic events that result in this disorder. The Network for Pancreatic Organ Donors with Diabetes (nPOD) program collects, processes, and distributes pancreata and disease-relevant tissues to investigators throughout the world for this purpose (1). Information is also available, through medical records of organ donors, related to causes of death and psychological factors, including drug use and suicide, that impact life with type 1 diabetes.

We reviewed the terminal hospitalization records for the first 100 organ donors with type 1 diabetes in the nPOD database, noting cause, circumstance, and mechanism of death; laboratory results; and history of illicit drug use. Donors were 45% female and 79% Caucasian. Mean age at time of death was 28 years (range 4–61) with mean disease duration of 16 years (range 0.25–52). Causes of death, based on death certificate, are presented …
Enterococci in orthopaedic infections: Who is at risk getting infected?
Authors: Ilker Uçkay, Daniela Pires, Americo Agostinho, Nastassia Guanziroli, Mehmet Öztürk, Placido Bartolone, Philippe Tscholl, Michael Betz, Didier Pittet
Journal: Journal of Infection (2017)
Analysis of Temporal Variability in the Short-term Effects of Ambient Air Pollutants on Nonaccidental Mortality in Rome, Italy (1998–2014)
Authors: Matteo Renzi, Massimo Stafoggia, Annunziata Faustini, Giulia Cesaroni, Giorgio Cattani, Francesco Forastiere
Journal: Environmental Health Perspectives (2017)

The association between short-term air pollution exposure and daily mortality has been widely investigated, but little is known about the temporal variability of the effect estimates. We examined the temporal relationship between exposure to particulate matter (PM) (PM10, PM2.5) and gases (NO2, SO2, and CO) with mortality in a large metropolitan area over the last 17 y.Our analysis included 359,447 nonaccidental deaths among ≥35-y-old individuals in Rome, Italy, over the study period 1998–2014. We related daily concentrations to mortality counts with a time-series Poisson regression analysis adjusted for long-term trends, meteorology, and population dynamics.Annual average concentrations decreased over the study period for all pollutants (e.g., from 42.9 to 26.6 μg/m3 for PM10). Each pollutant was positively associated with mortality, with estimated percentage increases over the entire study period ranging from 0.19% (95% CI: 0.13, 0.26) for a 1-Mg/m3 increase in CO (0–1 d lag) to 3.03% (95% CI: 2.44, 3.63) for a 10-μg/m3 increase in NO2 (0–5 d lag). We did not observe clear temporal patterns in year- or period-specific effect estimates for any pollutant. For example, we estimated that a 10-μg/m3 increase in PM10 was associated with 1.16% (95% CI: 0.53, 1.79), 0.99% (95% CI: 0.23, 1.77), and 1.87% (95% CI: 1.00, 2.74) increases in mortality for the periods 2001–2005, 2006–2010, and 2011–2014, respectively, and corresponding estimates for a 10-μg/m3 increase in NO2 were 4.20% (95% CI: 3.15, 5.25), 1.78% (95% CI: 0.73, 2.85), and 3.32% (95% CI: 2.03, 4.63).Mean concentrations of air pollutants have decreased over the last two decades in Rome, but effect estimates for a fixed increment in each exposure were generally consistent. These findings suggest that there has been little or no change in the overall toxicity of the air pollution mixture over time. https://doi.org/10.1289/EHP19.
HLA Haplotypes Are Associated with Multiple Myeloma Risk in the African American Multiple Myeloma Study (AAMMS)
Authors: Loren Gragert, Amie Hwang, Leon Bernal-Mizrachi, Sikander Ailawadhi, Seema Singhal, David J. Vandenberg, Xin Sheng, Alexander Stram, David V. Conti, Kristin A. Rand, Chi Song, John J. Graff, Nalini Janakiraman, Jayesh Mehta, Daniel O. Stram, Cathryn Bock, Laurence Kolonel, Graham A. Colditz, Ann Mohrbacher, Edward S. Peters, Howard Terebelo, Ajay K Nooka, Ravi Vij, African Ancestry Breast and Prostate Consortium, P N Hari, Meral Beksac, Brian C.-H. Chiu, Michael H. Tomasson, Jeffrey Zonder, Carol Ann Huff, Robert Z. Orlowski, Sagar Lonial, Christopher A. Haiman, Wendy Cozen
Journal: Blood (2016)
Informed Consent for Gastrointestinal Endoscopy: A View of Endoscopists in Croatia
Authors: M Banić, D Kardum, Ž Babić, M Urek, I Grgurević, Ž Čabrijan, M Tadić, I Lešnjaković, M Kujundžić, I Rotkvić
Journal: Endoscopy (2006)

Background/Aim: Practice of obtaining informed consent before undertaking any endoscopic examination indicate there are many differences and deficiencies in this process. The aim of this study was to get insight to the view of gastrointestinal endoscopists' in Croatia, in regard to obtaining a patient's consent, formally or informally, as a key aspect of their medical practice in gastroenterology.
Neoadjuvant chemoradiotherapy or chemotherapy preoperative on outcomes of patients with locally advanced or irresecable gastric cancer(LAGC)
Authors: Consuelo Diaz, German Calderillo, Erika Ruiz-Garcia, Marytere Herrera, López Horacio, Padilla Alejandro, Flores Manuel, Viridiana Calderillo, Alberto Takahashi, Javier Ruan, Vela Itzel, Lino Saul, Luis Aguilar J, Roberto Herrera-Goepfert, Hinojosa Jose, Angel Gomez, Abelardo Meneses
Journal: Annals of Oncology (2017)
Pregnancy outcome in women undergoing liver biopsy during pregnancy: A nationwide population‐based cohort study
Authors: Jonas F. Ludvigsson, Hanns‐Ulrich Marschall, Hannes Hagström, Jonas Höijer, Olof Stephansson
Journal: Hepatology (2017)

Liver biopsy is an important procedure in the investigation of liver disease. We examined pregnancy outcomes in women who underwent liver biopsy during pregnancy. In a nationwide population‐based cohort study we linked data from the Swedish Medical Birth Registry (for births between 1992 and 2011) with those from the Swedish Patient Registry. We identified 23 pregnancies exposed to liver biopsy. We calculated relative risks (RRs) for adverse pregnancy outcomes according to liver biopsy status using 1,953,887 unexposed pregnancies with and without a record of liver disease as reference. Our main outcome measures were stillbirth and preterm birth. There were no stillbirths in pregnancies exposed to liver biopsies compared with 0.3% stillbirths in unexposed pregnancies, and 3/23 (13%) exposed pregnancies were preterm (RR, 2.6; 95% confidence interval, 0.9‐7.5). Compared to women with a record of liver disease, preterm birth was not increased in those exposed to liver biopsy (RR, 0.9; 95% confidence interval, 0.1‐6.0). Except for an increased risk of small for gestational age birth in pregnancies exposed to liver biopsy (RR, 5.2; 95% confidence interval, 1.8‐14.8), other adverse pregnancy outcomes were independent of liver biopsy status when the analysis was restricted to women with a diagnosis of liver disease. Compared with unexposed sibling pregnancies, pregnancies with a liver biopsy were 7 days shorter, but birth weights did not differ between the siblings (–67 g; P &gt; 0.05). Conclusion : Apart from a moderately increased risk of preterm birth and small for gestational age, there was no association between liver biopsy during pregnancy and adverse pregnancy outcome; potential excess risks should be weighed against the advantages of having a liver biopsy that may influence clinical management of the patient and indirectly fetal health. (H epatology 2017).
PRMT1-Mediated Translation Regulation Is a Crucial Vulnerability of Cancer
Authors: Jessie Hao-Ru Hsu, Benjamin Hubbell-Engler, Guillaume Adelmant, Jialiang Huang, Cailin E. Joyce, Francisca Vazquez, Barbara A. Weir, Philip Montgomery, Aviad Tsherniak, Andrew O. Giacomelli, Jennifer A. Perry, Jennifer Trowbridge, Yuko Fujiwara, Glenn S. Cowley, Huafeng Xie, Woojin Kim, Carl D. Novina, William C. Hahn, Jarrod A. Marto, Stuart H. Orkin
Journal: Cancer Research (2017)

Through an shRNA screen, we identified the protein arginine methyltransferase Prmt1 as a vulnerable intervention point in murine p53/Rb-null osteosarcomas, the human counterpart of which lacks effective therapeutic options. Depletion of Prmt1 in p53-deficient cells impaired tumor initiation and maintenance in vitro and in vivo Mechanistic studies reveal that translation-associated pathways were enriched for Prmt1 downstream targets, implicating Prmt1 in translation control. In particular, loss of Prmt1 led to a decrease in arginine methylation of the translation initiation complex, thereby disrupting its assembly and inhibiting translation. p53/Rb-null cells were sensitive to p53-induced translation stress, and analysis of human cancer cell line data from Project Achilles further revealed that Prmt1 and translation-associated pathways converged on the same functional networks. We propose that targeted therapy against Prmt1 and its associated translation-related pathways offer a mechanistic rationale for treatment of osteosarcomas and other cancers that exhibit dependencies on translation stress response. Cancer Res; 77(17); 4613-25. ©2017 AACR.
Evaluation of Chest Pain in the Emergency Department
Authors: Martin F. Sturman
Journal: Annals of Internal Medicine (1995)

Letters15 August 1995Evaluation of Chest Pain in the Emergency DepartmentMartin F. SturmanMartin F. SturmanSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-4-199508150-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Drs. Kaul and Abbott [1] provide an excellent overview in their editorial. Unfortunately, although they advocate common-sense clinical approaches to identifying anginal pain, they overlook the importance of identifying causes of nonanginal chest pain, which are by far the most common cause of thoracic pain, even in the elderly. Moreover, the authors reject probability-based computer models (based on clinical findings) because they imply that diagnostic certainty is achievable in the real world. Further, they are confused by the difference between pre- and post-test probability when they state that “average experiences” are unreliable in predicting an event for ...References1. Kaul S, Abbott RD. Evaluation of chest pain in the emergency department (Editorial). Ann Intern Med. 1994; 121:976-8. Google Scholar2. Sturman MF, Perez M. The probability of cardiac disease: Framingham revisited. Rev Port Cardiol. 1990; 9:455-61. Google Scholar3. Sturman MF. Effective Medical Imaging: A Signs and Symptoms Approach. Baltimore: Williams and Wilkins; 1993:5-8. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 August 1995Volume 123, Issue 4Page: 314-318KeywordsComputed axial tomographyElderlyEmergency departmentHospitalizationsInternational classification of diseases ninth revisionIschemiaMyocardial infarctionRadionuclide imagingSimulation and modelingThorax ePublished: 15 August 2000 Issue Published: 15 August 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The Value of Leucocyte Count in Diagnosis of Appendicitis
Authors: A Ghallab, Y Abddaim, A Muhammad, S Mahmood, D Mcavinchey
Journal: Endoscopy (2006)

Aims: The accurate diagnosis of appendicitis is considered as a real difficult diagnostic dilemma. WBCs was considered by most surgeons as a significant diagnostic parameter for appendicitis. The aim of our study is to evaluate real value of WBCs reading in identifying or excluding appendicitis.
Abstract 9772: Antagonism of Rosuvastatin-induced Elevation of Circulating PCSK9 in Hamsters by Liver-specific Knockdown of HNF1α or HNF1β
Authors: Bin Dong, Amar B Singh, Vikram R Shende, Jingwen Liu
Journal: Circulation (2015)

Proprotein convertase subtilisin/kexin type 9 (PCSK9) induces hepatic LDL receptor (LDLR) degradation and lowers the removal of LDL-cholesterol from circulation. Thus, PCSK9 has become an important therapeutic target for the treatment of hypercholesterolemia. The transcription of PCSK9 is prominently controlled by the HNF1 binding motif embedded in its proximal promoter region that binds to HNF1α or HNF1β as homodimers or heterodimers. Our previous in vivo studies showed that only HNF1α but not HNF1β regulates PCSK9 transcription in mouse liver. Statin has been shown to elevate circulating PCSK9 levels through stimulating PCSK9 gene transcription, which reduces the clinical efficacy of statin in LDL-cholesterol reduction. In this study, we utilized adenoviral shRNA expression vectors (Ad-shHNF1α and Ad-shHNF1β) to generate liver specific knockdown of HNF1α or HNF1β in hamsters to examine the impact of reduced expression of HNF1 transcription factors on statin-induced elevation of PCSK9. Administration of rosuvastatin (RSV) at a daily dose of 15 mg/kg to hamsters infected with a control adenovirus significantly increased liver PCSK9 mRNA levels by 94% and serum PCSK9 levels by 37%. However, injection of Ad-shHNF1α into hamsters largely abolished the RSV-induced elevation of PCSK9 serum levels and hepatic mRNA levels, which was accompanied by a significant increase in liver LDLR protein abundance by 64% as compared to hamsters injected with control virus. Surprisingly, injection of Ad-shHNF1β produced similar inhibitory effects on the RSV-induced PCSK9 expression as that of Ad-shHNF1α. This was different from the negative results of HNF1β knockdown conducted in mice. In addition to changes in PCSK9 levels, we observed a modest but significant reduction in serum non-HDL cholesterol level after knockdown of HNF1α (27%) or HNF1β (32%) in hamsters treated with RSV. Altogether, our study demonstrates that unlike mice, both HNF1α and HNF1β are positive regulators of hepatic PCSK9 transcription in hamster species and that transient, liver specific knockdown of either HNF1α or HNF1β could antagonize the RSV-induced elevation of serum PCSK9 and non-HDL cholesterol levels.
Haploidentical Stem Cell Transplantation after Myeloabaltive Conditioning Is a Valid and Safe Option for Young Patients with Refractory or Relapsed Aggressive Non-Hodgkin Lymphoma: A Study Compared with HLA-Matched Transplant
Authors: Haiwen Huang, Xiaofang Xiao, Jia Chen, Zhengming Jin, Xiaowen Tang, Huiying Qiu, Chengcheng Fu, Yue Han, Miao Miao, Huirong Chang, Aining Sun, Depei Wu
Journal: Blood (2016)
Items dispensed in England rise sharply in 10 years
Authors: Anne Gulland
Journal: BMJ (2017)

The number of drugs dispensed in the community has risen sharply in the past 10 years, annual figures of prescribing rates have shown.1

Data from NHS Digital show that 1.1 billion items were dispensed in the community in England in 2016, up 46.8% from 2006, when 752 million items were dispensed. However, the cost of prescriptions increased by a smaller rate over the period, rising by 12.3% from £8.2bn in 2006 to £9.2bn in 2016.

The figures show a 1.9% increase in the number of items dispensed from 2015 to 2016, but the total cost decreased by …