tbuckley/cabot-search huggingface dataset:
A Potent, Metabolically Stable Tubulin Inhibitor Targets the Colchicine Binding Site and Overcomes Taxane Resistance
Authors: Kinsie E. Arnst, Yuxi Wang, Dong-Jin Hwang, Yi Xue, Terry Costello, David Hamilton, Qiang Chen, Jinliang Yang, Frank Park, James T. Dalton, Duane D. Miller, Wei Li
Journal: Cancer Research (2017)

Abstract Antimitotics that target tubulin are among the most useful chemotherapeutic drugs, but their clinical activity is often limited by the development of multidrug resistance. We recently discovered the novel small-molecule DJ101 as a potent and metabolically stable tubulin inhibitor that can circumvent the drug efflux pumps responsible for multidrug resistance of existing tubulin inhibitors. In this study, we determined the mechanism of action of this drug. The basis for its activity was illuminated by solving the crystal structure of DJ101 in complex with tubulin at a resolution of 2.8Å. Investigations of the potency of DJ101 in a panel of human metastatic melanoma cell lines harboring major clinically relevant mutations defined IC50 values of 7–10 nmol/L. In cells, DJ101 disrupted microtubule networks, suppressed anchorage-dependent melanoma colony formation, and impaired cancer cell migration. In melanoma-bearing mice, DJ101 administration inhibited tumor growth and reduced lung metastasis in the absence of observable toxicity. DJ101 also completely inhibited tumor growth in a paclitaxel-resistant xenograft mouse model of human prostate cancer (PC-3/TxR), where paclitaxel was minimally effective. Our findings offer preclinical proof of concept for the continued development of DJ101 as a next-generation tubulin inhibitor for cancer therapy. Significance: These findings offer preclinical proof of concept for the continued development of DJ101 as a next-generation antitubulin drug for cancer therapy. Cancer Res; 78(1); 265–77. ©2017 AACR.
Association Between Decline in Slow Vital Capacity and Respiratory Insufficiency, Use of Assisted Ventilation, Tracheostomy, or Death in Patients With Amyotrophic Lateral Sclerosis
Authors: Jinsy A. Andrews, Lisa Meng, Sarah F. Kulke, Stacy A. Rudnicki, Andrew A. Wolff, Michael E. Bozik, Fady I. Malik, Jeremy M. Shefner
Journal: JAMA Neurology (2017)

The prognostic value of slow vital capacity (SVC) in relation to respiratory function decline and disease progression in patients with amyotrophic lateral sclerosis (ALS) is not well understood.
Utility of PET/CT in the diagnosis of inflammatory rheumatic diseases: a systematic review and meta-analysis
Authors: Lucie Descamps, Louis Olagne, Charles Merlin, Florent Cachin, Martin Soubrier, Sylvain Mathieu
Journal: Annals of the Rheumatic Diseases (2017)

In an article published in the Annals of the Rheumatic Diseases , Schonau et al suggested that positron emitted tomography (PET)/CT is useful in determining the cause of unexplained fever/inflammation.1 In this letter, we wish to add further data to support the conclusions of this article. More and more, PET/CT is used to determine the cause of fever, systemic inflammation or atypical or resistant rheumatic disease. However, the utility of PET/CT in these diagnoses is not clear. Thus, we performed a meta-analysis to investigate the utility of PET/CT in the diagnosis of inflammatory rheumatic diseases.

We searched MEDLINE to identify all reports of interest published prior to June 2016 using the search terms: ‘(PET scan OR …
Nanoparticle formulation improves doxorubicin efficacy by enhancing host antitumor immunity
Authors: Eric M. Mastria, Leon Y. Cai, Matthew J. Kan, Xinghai Li, Jeffrey L. Schaal, Steven Fiering, Michael D. Gunn, Mark W. Dewhirst, Smita K. Nair, Ashutosh Chilkoti
Journal: Journal of Controlled Release (2017)
Acute acalculous cholecystitis during zika virus infection in an immunocompromised patient
Authors: Suzane Kioko Ono, Leda Bassit, Victor Van Vaisberg, Venâncio Avancini Ferreira Alves, Elia G. Caldini, Brian D. Herman, Reed Shabman, Nadia B. Fedorova, Denise Paranaguá‐Vezozzo, Caroline Torres Sampaio, Rafael Bandeira Lages, Débora Terrabuio, Wellington Andraus, Raymond F. Schinazi, Flair José Carrilho
Journal: Hepatology (2017)

Ono, Suzane Kioko; Bassit, Leda; Van Vaisberg, Victor; Avancini Ferreira Alves, Venâncio; Caldini, Elia G.; Herman, Brian D.; Shabman, Reed; Fedorova, Nadia B.; Paranaguá‐Vezozzo, Denise; Sampaio, Caroline Torres; Lages, Rafael Bandeira; Terrabuio, Débora; Andraus, Wellington; Schinazi, Raymond F.; Carrilho, Flair José Author Information
Association of Blood Pressure Lowering With Mortality and Cardiovascular Disease Across Blood Pressure Levels
Authors: Mattias Brunström, Bo Carlberg
Journal: JAMA Internal Medicine (2017)

<h3>Importance</h3> High blood pressure (BP) is the most important risk factor for death and cardiovascular disease (CVD) worldwide. The optimal cutoff for treatment of high BP is debated. <h3>Objective</h3> To assess the association between BP lowering treatment and death and CVD at different BP levels. <h3>Data Sources</h3> Previous systematic reviews were identified from PubMed, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effect. Reference lists of these reviews were searched for randomized clinical trials. Randomized clinical trials published after November 1, 2015, were also searched for in PubMed and the Cochrane Central Register for Controlled Trials during February 2017. <h3>Study Selection</h3> Randomized clinical trials with at least 1000 patient-years of follow-up, comparing BP-lowering drugs vs placebo or different BP goals were included. <h3>Data Extraction and Synthesis</h3> Data were extracted from original publications. Risk of bias was assessed using the Cochrane Collaborations assessment tool. Relative risks (RRs) were pooled in random-effects meta-analyses with Knapp-Hartung modification. Results are reported according to PRISMA guidelines. <h3>Main Outcomes and Measures</h3> Prespecified outcomes of interest were all-cause mortality, cardiovascular mortality, major cardiovascular events, coronary heart disease (CHD), stroke, heart failure, and end-stage renal disease. <h3>Results</h3> Seventy-four unique trials, representing 306 273 unique participants (39.9% women and 60.1% men; mean age, 63.6 years) and 1.2 million person-years, were included in the meta-analyses. In primary prevention, the association of BP-lowering treatment with major cardiovascular events was dependent on baseline systolic BP (SBP). In trials with baseline SBP 160 mm Hg or above, treatment was associated with reduced risk for death (RR, 0.93; 95% CI, 0.87-1.00) and a substantial reduction of major cardiovascular events (RR, 0.78; 95% CI, 0.70-0.87). If baseline SBP ranged from 140 to 159 mm Hg, the association of treatment with mortality was similar (RR, 0.87; 95% CI, 0.75-1.00), but the association with major cardiovascular events was less pronounced (RR, 0.88; 95% CI, 0.80-0.96). In trials with baseline SBP below 140 mm Hg, treatment was not associated with mortality (RR, 0.98; 95% CI, 0.90-1.06) and major cardiovascular events (RR, 0.97; 95% CI, 0.90-1.04). In trials including people with previous CHD and mean baseline SBP of 138 mm Hg, treatment was associated with reduced risk for major cardiovascular events (RR, 0.90; 95% CI, 0.84-0.97), but was not associated with survival (RR, 0.98; 95% CI, 0.89-1.07). <h3>Conclusions and Relevance</h3> Primary preventive BP lowering is associated with reduced risk for death and CVD if baseline SBP is 140 mm Hg or higher. At lower BP levels, treatment is not associated with any benefit in primary prevention but might offer additional protection in patients with CHD.
Junior doctor who supplied benzodiazepines is suspended for 12 months
Authors: Clare Dyer
Journal: BMJ (2017)

A junior doctor who was cleared of culpable homicide in the overdose death of her friend but was convicted on other drug charges has been suspended for 12 months by a medical practitioners tribunal.

Katy McAllister, 31, of Dundee, lost a close friend to an overdose in May 2015. Police, suspecting that she might have provided the drug, searched McAllister’s home with her permission soon afterwards. They found a small quantity of magic mushrooms, as well as midazolam from McAllister’s work.

Later, the same investigation found that McAllister had supplied a fellow doctor with diazepam from July 2014 to …
Some Unusual Paraneoplastic Syndromes
Authors: Wendela G. Pronk, Jan P. Baars, Paul Chr. de Jong, Anneke M. Westermann
Journal: Journal of Clinical Oncology (2003)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.07.099 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12829684 Some Unusual Paraneoplastic Syndromes CASE 2. DIGITAL ULCERATION AS A PARANEOPLASTIC SYNDROME IN OVARIAN CANCER Wendela G. PronkxWendela G. PronkSearch for articles by this author , Jan P. BaarsxJan P. BaarsSearch for articles by this author , Paul Chr. de JongxPaul Chr. de JongSearch for articles by this author , Anneke M. WestermannxAnneke M. WestermannSearch for articles by this author Show More Academic Medical Center, Amsterdam; Flevo Hospital, Almere; and St Anthonius Hospital, Nieuwegein, the Netherlands https://doi.org/10.1200/JCO.2003.07.099 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Development and Validation of a Novel Integrated Clinical-Genomic Risk Group Classification for Localized Prostate Cancer
Authors: Daniel E. Spratt, Jingbin Zhang, María Santiago-Jiménez, Robert T. Dess, John W. Davis, Robert B. Den, Adam P. Dicker, Christopher J. Kane, Alan Pollack, Radka Stoyanova, Firas Abdollah, Ashley E. Ross, Adam Cole, Edward Uchio, Josh M. Randall, Hao Nguyen, Shuang G. Zhao, Rohit Mehra, Andrew G. Glass, Lucia L.C. Lam, Jijumon Chelliserry, Marguerite du Plessis, Voleak Choeurng, Maria Aranes, Tyler Kolisnik, Jennifer Margrave, Jason Alter, Jennifer Jordan, Christine Buerki, Kasra Yousefi, Zaid Haddad, Elai Davicioni, Edouard J. Trabulsi, Stacy Loeb, Ashutosh Tewari, Peter R. Carroll, Sheila Weinmann, Edward M. Schaeffer, Eric A. Klein, R. Jeffrey Karnes, Felix Y. Feng, Paul L. Nguyen
Journal: Journal of Clinical Oncology (2017)

Purpose It is clinically challenging to integrate genomic-classifier results that report a numeric risk of recurrence into treatment recommendations for localized prostate cancer, which are founded in the framework of risk groups. We aimed to develop a novel clinical-genomic risk grouping system that can readily be incorporated into treatment guidelines for localized prostate cancer. Materials and Methods Two multicenter cohorts (n = 991) were used for training and validation of the clinical-genomic risk groups, and two additional cohorts (n = 5,937) were used for reclassification analyses. Competing risks analysis was used to estimate the risk of distant metastasis. Time-dependent c-indices were constructed to compare clinicopathologic risk models with the clinical-genomic risk groups. Results With a median follow-up of 8 years for patients in the training cohort, 10-year distant metastasis rates for National Comprehensive Cancer Network (NCCN) low, favorable-intermediate, unfavorable-intermediate, and high-risk were 7.3%, 9.2%, 38.0%, and 39.5%, respectively. In contrast, the three-tier clinical-genomic risk groups had 10-year distant metastasis rates of 3.5%, 29.4%, and 54.6%, for low-, intermediate-, and high-risk, respectively, which were consistent in the validation cohort (0%, 25.9%, and 55.2%, respectively). C-indices for the clinical-genomic risk grouping system (0.84; 95% CI, 0.61 to 0.93) were improved over NCCN (0.73; 95% CI, 0.60 to 0.86) and Cancer of the Prostate Risk Assessment (0.74; 95% CI, 0.65 to 0.84), and 30% of patients using NCCN low/intermediate/high would be reclassified by the new three-tier system and 67% of patients would be reclassified from NCCN six-tier (very-low- to very-high-risk) by the new six-tier system. Conclusion A commercially available genomic classifier in combination with standard clinicopathologic variables can generate a simple-to-use clinical-genomic risk grouping that more accurately identifies patients at low, intermediate, and high risk for metastasis and can be easily incorporated into current guidelines to better risk-stratify patients.
Prognostic role of tumor budding in stage II colorectal cancer: A meta-analysis of published studies.
Authors: Sandro Barni, Fausto Petrelli, Ezio Pezzica, Mary Cabiddu, Andrea Coinu, Karen Borgonovo, Mara Ghilardi, Veronica Lonati, Daniela Corti
Journal: Journal of Clinical Oncology (2015)

e14544 Background: tumor budding, defined as the presence of tumor cells at the invasive front of carcinomas, is known as a poor prognostic factor in colorectal cancer (CRC). In this meta-analysis we have evaluated its significance in stage II CRC through a systematic review of the literature. Methods: were have searched PubMed, EMBASE, Web of Science, and SCOPUS for studies that extimated the correlation between tumor budding and 5-year overall survival (OS) in stage II CRC patients. Published data were extracted and used to calculate odds ratios (ORs) for 5-year death, and hazard ratios (HRs) for overall survival (OS) amongst patients with high grade tumor budding, using multivariate analysis. Data were pooled using the Mantel–Haenszel random-effect model. Results: 12 studies were analysed for a total of 1652 patients. High grade budding was associated with inferior 5-year OS (OR for death, 6.25; 95% confidence interval [CI], 4.04–9.67; P < 0.00001). The absolute difference in 5-year OS was -25% (95% CI, -18–-33%, P < 0.00001). In particular the presence of high grade budding was associated with an increased risk of death (HR for death, 3.68; 95% CI, 2.16–6.28, P < 0.00001). The sensitivity analysis by stage (II vs mixed stages), site (colon only vs colon and rectal/rectosigmoid cancer), duration of follow-up ( > 5 vs < 5 years) and method of analysis (Ueno vs Wang vs Hase vs others) revealed no differences in the HR for death (P for subgroup difference, 0.87, 0.83, 0.54 and 0.7, respectively). Conclusions: presence of tumor budding must be considered a poor prognostic factor in early stages CRC, in particular in stage II, where it is associated with a poor outcome. This histologic variable could therefore help to stratify patients with node negative CRC and guide decision making with respect to adjuvant chemotherapy administration.
CD38-bispecific antibody pretargeted radioimmunotherapy for multiple myeloma and other B-cell malignancies
Authors: Damian J. Green, Shyril O’Steen, Yukang Lin, Melissa L. Comstock, Aimee L. Kenoyer, Donald K. Hamlin, D. Scott Wilbur, Darrell R. Fisher, Margaret Nartea, Mark D. Hylarides, Ajay K. Gopal, Theodore A. Gooley, Johnnie J. Orozco, Brian G. Till, Kelly D. Orcutt, K. Dane Wittrup, Oliver W. Press
Journal: Blood (2017)
Abstract 20920: Does Provider Gender Matter? Guideline Concordance in Post-Cardiac Arrest Care
Authors: Kyle T McDaniel, Jessica L Nelson, Stacie L Daugherty, Edward P Havranek, Sarah M Perman
Journal: Circulation (2017)

Introduction: Recent studies have suggested that female physicians are more likely to adhere to clinical practice guidelines in medical care. When clinical guidelines for post-cardiac arrest care are adhered to patients have better outcomes. Hypothesis: We hypothesize that gender of the attending provider may affect guideline concordance in post-cardiac arrest care. Methods: We identified 139 out-of-hospital cardiac arrest patients treated at an academic tertiary care facility between 12/2013 and12/2016. Patients were over 18 years of age, suffered a medical cardiac arrest and were comatose at hospital admission. Demographic data and arrest characteristics were collected. The gender of the admitting provider and the provider who lead the first documented family meeting were abstracted. To assess for evidence based practice, we utilized 4 previously cited guidelines that are associated with improved survival; a.) was coronary angiography completed within 24 hours of admission, b.) was targeted temperature management initiated, c.) was target temperature achieved, and d.) did withdrawal of life sustaining therapy occur before 72 hours from return of spontaneous circulation? Results: Of the total cohort, 61.9% were male, mean age was 57.5 ±16.2 years, 36.6% had an initial shockable rhythm and 41.7% received bystander CPR. Fifty-six (40.3%) individuals survived to hospital discharge. Approximately 28.8% of the cohort was admitted to the hospital by a female attending physician. Guideline adherence by provider gender is described in the Table. No statistically significant differences were appreciated when examining the frequency of guideline concordant care and attending physician gender. Conclusions: In this small cohort of post-cardiac arrest patients, provider gender does not appear to affect post-arrest care guideline adherence. Further study in a large, multi-center cohort may yield different findings.
Surto de tricofitose cutánea, uma infecção fúngica devida a Trichophyton tonsurans, numa equipa de judô de alto nível
Authors: D. M. Poisson, Didier Rousseau, D Defo, E Estève
Journal: Eurosurveillance (2005)

Entre Outubro 2004 e Abril 2005 ocurreu um surto de 49 casos de tricofitose cutanea produzida por Trichophyton tonsurans, numa equipa de judo de alto nivel de 131 membros em Orleans, no centro da Franca. A equipa estava dividida em cinco grupos : cadetes-juniors masculinos (n=44), cadetes-juniors femininos (n=33), estudantes universitarios masculinos (n=15), estudantes universitarias femininas (n=21) e um grupo chamado “grupo technico” composto de judokas de alto nivel que tinham terminado os estudos academicos (n=18). O surto afectou 86% dos cadetes-juniors masculinos, mas so seis membros do grupo technico (33%) e cinco dos 69 outros membros da equipa (7%) (cadetes-juniors femininos e estudantes). No artigo seguinte, vem descrito o surto e os resultados duma investigacao que revelou um factor de risco conhecido para o grupo technico : compartir uma maquina electrica de cortar o cabelo. As praticas de higiene pessoal eram otimas no grupo de cadetes-juniors masculinos; a alta taxa de ataque neste grupo poderia estar ligada com a deficiencia nas instalacoes de chuveiro no ginasio, o que os levou a tomar a ducha so varias horas depois do final do treino diario.
Abstract 17687: Glycemic Variability is Associated With Left Ventricular Global Systolic Function in Patients With ST-Segment Elevation Myocardial Infarction: UCG Strain Analysis
Authors: Jin Kirigaya, Noriaki Iwahashi, Yasushi Matsuzawa, Masaaki Konishi, Nobuhiko Maejima, Masami Kosuge, Kiyoshi Hibi, Kazuo Kimura, Kouichi Tamura
Journal: Circulation (2017)

Background:  Previous studies have shown that Glycemic Variability (GV) is associated with cardiovascular events in patients with ST-segment elevation myocardial infarction (STEMI). However, the association between GV and left ventricular function in patients with STEMI remains unclear. In this study, we explored the relationship between GV and global left ventricular systolic longitudinal strain (GLS) in patients with a first STEMI in chronic phase.   Methods:  Consecutive 120 patients with a first STEMI (64±12 years, 83% male, max CPK=2883 IU/L, LAD 63/LCX 8/RCA 49), who had undergone reperfusion therapy within 12 hours after onset were enrolled. We analyzed GV by a continuous glucose monitoring system (CGM: iPRO2, Medtronics) at 2 weeks and mean amplitude of glycemic excursions (MAGE) as the parameter of GV. We assessed global longitudinal left ventricular systolic strain (GLS) measured by echocardiography at 7 months from discharge.   Results:  MAGE was negatively correlated with GLS (r=0.27; p   Conclusions:  In patients with a first STEMI, MAGE was the independent predictor of global systolic longitudinal strain (GLS) in chronic phase. It may be beneficial to blunt GV for improved LV function and clinical outcomes in patients with repurfused STEMI.
P3.02b-006 Role of TP53 Mutations in Determining Primary Resistance to First-Line Tyrosine Kinase Inhibitors in EGFR-Mutated NSCLC Patients
Authors: Paola Ulivi, Matteo Canale, Angelo Delmonte, Elisabetta Petracci, Elisa Chiadini, Claudio Dazzi, Maximilian Papi, Laura Capelli, Claudia Casanova, Nicoletta De Luigi, Marita Mariotti, Alessandro Gamboni, Rita Chiari, Chiara Bennati, Daniele Calistri, Vienna Ludovini, Lucio Crinò, Dino Amadori
Journal: Journal of Thoracic Oncology (2017)
CGRP — The Next Frontier for Migraine
Authors: Andrew D. Hershey
Journal: New England Journal of Medicine (2017)

Migraine is a common problem for adults and children. In its global burden as a disease, it is consistently in the top 10, and among neurologic disorders, it is second only to stroke in its number of associated disability-adjusted life-years.1,2 Currently, treatment for migraine involves a multipronged approach of abortive, preventive, and biobehavioral therapies, as well as treatments that have been developed for other diseases, such as antiepileptic medications. The complexity of migraine, which is considered to be a polygenetic disease with environmental modifiers, is the main reason for the paucity of migraine-specific treatments. In the 1980s, the first acute . . .
Living goals: Prepare to die.
Authors: Zankhana Mehta, Susan Smith, Jane Henrichs, Andrea Berger, Loreen Comstock, Mellar Davis
Journal: Journal of Clinical Oncology (2017)

157 Background: Living Goals (LGs), a home-based program, is a collaboration between Geisinger Health Plan, Geisinger Home care and Hospice and Palliative Medicine. Program investigated an early intervention in those with serious illness and transition to hospice in a timely manner during FY 2015- 2017. Methods: LGs visits were led by a registered nurse after referral from physicians based on the surprise question (it would not be a surprise if this patient died within one year). Nurse facilitated end-of-life discussions and provided resources available for supportive care. LGs visits were free up to 10 visits to each patient. Results: 94 patients were enrolled in LGs from 128 referrals.59 (63%) patients transitioned to hospice and 41 (69%) were transitioned within first month of LGs visit averaging 1.4 visits. 59 patients enrolled in hospice. The median length of time between LG Start of care (SOC) and Hospice SOC is 9 days (IQR: 3-73).57 LGs patients discharged from hospice had a median length of stay (LOS) of 39 days (IQR: 10-85). For the subset of patients in FY 2015 (n = 13) median LOS was 26 days (IQR: 10-57)), in FY 2016 (n = 26) the median LOS was 27 days (IQR: 7-73), in FY 2017 (n = 18) the median LOS is 66 days (IQR: 28-144). In FY 2014, 513 hospice patients were discharged before initiation of LGs and the median LOS was 19 days (IQR: 6-61). As of now, there is a significantly longer stay for LG patients than FY 2014 hospice patients (p = 0.0130). Conclusions: This innovative home based program, appears to have a great potential in the future for delivering ongoing hospice and palliative needs to seriously ill patients.
Recurrence of primary biliary cholangitis after liver transplantation affects graft survival : a multi-center study from the Global PBC study group
Authors: Aldo J Montano-Loza, Bettina E Hansen, Davide Roccarina, Douglas Thorburn, Palak J Trivedi, Gideon Hirschfield, Christophe Corpechot, Raoul Poupon, Jerome Dumortier, Alexie Bosch, Emiliano G Giostra, Yvon Calmus, Albert Pares, Anna Reig, Irene Franceschet, Annarosa Floreani, Jorn C Goet, Maren H Harms, Henk R van Buuren, Natalie Van den Ende, Frederik Nevens, Xavier Verhelst, Maria F Donato, Federica Malinverno, Andrew Mason
Journal: Hepatology (2017)
Sustained miRNA delivery from an injectable hydrogel promotes cardiomyocyte proliferation and functional regeneration after ischaemic injury
Authors: Leo L. Wang, Ying Liu, Jennifer J. Chung, Tao Wang, Ann C. Gaffey, Minmin Lu, Christina A. Cavanaugh, Su Zhou, Rahul Kanade, Pavan Atluri, Edward E. Morrisey, Jason A. Burdick
Journal: Nature Biomedical Engineering (2017)