tbuckley/cabot-search huggingface dataset:
Enzalutamide in combination with docetaxel in men with prostate cancer (PC): Preliminary results from a phase I study.
Authors: Mark T. Fleming, Dana E. Rathkopf, Jackie Gibbons, Amy C. Peterson, Alison Hannah, David Forer, Howard I. Scher, Michael J. Morris
Journal: Journal of Clinical Oncology (2013)

63 Background: Enzalutamide (ENZA), a novel oral androgen receptor (AR) inhibitor, inhibits AR signaling via inhibition of androgen binding to the AR, AR nuclear translocation, and nuclear AR-DNA binding. ENZA demonstrated a survival benefit in men with metastatic castration-resistant prostate cancer (mCRPC) who had received prior docetaxel (Scher et al, NEJM 2012; 367:1187). A Phase III study in men with progressive chemotherapy-naïve disease (PREVAIL), is ongoing. Docetaxel (DOC) is the current standard first-line chemotherapy for mCRPC. CYP3A4, which plays a role in DOC clearance, is induced by ENZA. Patients (pts) eligible to receive DOC may benefit from continued AR inhibition with ENZA, provided the combination is well tolerated with no unacceptable drug-drug interactions. Methods: This study evaluated the safety and pharmacokinetics (PK) of DOC co-administered with ENZA in men with mCRPC on androgen deprivation therapy. Pts received DOC (75 mg/m2) by 1-h infusion every 3 weeks, with corticosteroids. ENZA (160 mg/d) was started 24 h after the first DOC infusion. Plasma PK samples were collected for 24 h after Cycle (C) 1 and C2 DOC infusions to enable within-subject comparisons of DOC PK ± ENZA. A sample size of 18 pts able to receive ≥ 2 full doses of DOC was specified for PK analyses. Results: As of 21 Sept. 2012, 22 pts have been enrolled, 3 did not complete both C1 and C2; PK and C1 and C2 safety data are currently available from 15 pts reported here. The median age was 65 (range 46-80 yrs); 11 had ECOG performance status 1 (vs 0). Prior primary therapy included surgery (n=2), radiation (n=4) or both (n=5); median PSA was 44.7ng/mL (1.9-585). ANC&lt;1000mm3 was reported in 14 pts (1 febrile neutropenia), other adverse events in ≥4 pts included fatigue (11), dyspnea (6), alopecia (5), peripheral neuropathy (5), anemia (4) and dysgueusia (4). No seizures were reported. Preliminary PK data (n=15) show similar DOC exposure (within 20%) for DOC in combination with ENZA vs. DOC alone. Conclusions: This is the first evaluation of ENZA given in combination with DOC.In mCRPC pts ENZA does not appear to affect tolerability of DOC or have a clinically meaningful impact on DOC PK. Clinical trial information: NCT01565928.
Time Trends in the Incidence of Parkinson Disease
Authors: Rodolfo Savica, Brandon R. Grossardt, James H. Bower, J. Eric Ahlskog, Walter A. Rocca
Journal: JAMA Neurology (2016)

Changes over time in the incidence of parkinsonism and Parkinson disease (PD) remain uncertain.To investigate secular trends (period effects) and birth cohort trends in the incidence of parkinsonism and PD over 30 years in a geographically defined American population.We used the medical records-linkage system of the Rochester Epidemiology Project to identify incidence cases of PD and other types of parkinsonism in Olmsted County, Minnesota, from 1976 to 2005. All cases were classified by a movement disorder specialist using defined criteria through the review of the complete medical records within the system. The analyses for this study were conducted between May 2015 and January 2016.Incidence rates of parkinsonism and PD over 30 years. We tested for secular trends (period effects) using negative binomial regression models and for birth cohort effects using age-period-cohort models.Of 906 patients with parkinsonism, 501 were men, and the median age at onset was 74 years (interquartile range, 66-81 years). Of the 464 patients with PD, 275 were men, and the median age at onset was 73 years (interquartile range, 64-80 years). The overall incidence rates increased significantly over 30 years in men for both parkinsonism (relative risk [RR], 1.17 per decade; 95% CI, 1.03-1.33) and PD (RR, 1.24 per decade; 95% CI, 1.08-1.43). These trends were driven primarily by the older age groups. In particular, for men 70 years or older, incidence rates increased for both parkinsonism (RR, 1.24 per decade; 95% CI, 1.07-1.44) and PD (RR, 1.35 per decade; 95% CI, 1.10-1.65). The secular trends were not significant for women overall or in age strata. We observed an increased risk for both men and women born in the 1920 cohort (1915-1924). However, this birth cohort effect was significant only for PD and only in men.Our study suggests that the incidence of parkinsonism and PD may have increased between 1976 and 2005, particularly in men 70 years and older. These trends may be associated with the dramatic changes in smoking behavior that took place in the second half of the 20th century or with other lifestyle or environmental changes. However, the trends could be spurious and need to be confirmed in other populations.
Variations in breast cancer awareness among urban Tanzanian women.
Authors: Emma Perry Morse, Bertha Maegga, Getrud Joseph, Susan Miesfeldt
Journal: Journal of Clinical Oncology (2013)

e12561 Background: Nearly 70% of the 7.6 million cancer deaths occur annually in developing countries like Tanzania, with breast cancer being among the most common causes of cancer mortality. Although data are incomplete, late-stage disease is believed to limit breast cancer control in Tanzania, with delayed diagnosis linked to low levels of breast cancer awareness among women. The goal of this study was to explore awareness of this disease among low-income women accessing routine medical care from three district hospitals in Dar es Salaam, Tanzania. Methods: This survey-based study examined participants' knowledge, attitudes, and beliefs regarding breast cancer causes, risk factors, symptoms, early detection measures, treatment, and preferred education sources. Sociodemographic variations in knowledge of breast cancer risk factors, symptoms, and treatments were assessed. Results: Two hundred and twenty-five women, ages 18-55 years, participated. Over half (52%) reported a primary school education or less; 69.9% were married; 26.2% were unemployed. The average monthly household income was just below the Dar es Salaam mean. Ninety-eight percent were aware of breast cancer; 22% knew someone with a history of breast cancer. Among the 126 women who heard of breast self exam, 25% and 34% practiced it regularly and occasionally, respectively; 41% never practiced it. Only 6.2% had regular clinical breast exams. A minority knew of mammography (32%); &lt;2% had undergone a mammogram. Of the items listed, respondents correctly identified symptoms (51%), risk factors (31%), and treatments (51%). Data reflecting sociodemographic variations in knowledge will be shown. Preferred sources of breast cancer educational materials included group sessions, television or radio programs, and meetings with breast cancer survivors. Conclusions: This work provides valuable insight into preferred sources of breast cancer education among Tanzanian women.
Compensatory RNA polymerase 2 loading determines the efficacy and transcriptional selectivity of JQ1 in Myc-driven tumors
Authors: E Donato, O Croci, A Sabò, H Muller, M J Morelli, M Pelizzola, S Campaner
Journal: Leukemia (2016)

Inhibition of bromodomain and extraterminal motif (BET) proteins such as BRD4 bears great promise for cancer treatment and its efficacy has been frequently attributed to Myc downregulation. Here, we use B-cell tumors as a model to address the mechanism of action of JQ1, a widely used BET inhibitor. Although JQ1 led to widespread eviction of BRD4 from chromatin, its effect on gene transcription was limited to a restricted set of genes. This was unlinked to Myc downregulation or its chromatin association. Yet, JQ1-sensitive genes were enriched for Myc and E2F targets, were expressed at high levels, and showed high promoter occupancy by RNAPol2, BRD4, Myc and E2F. Their marked decrease in transcriptional elongation upon JQ1 treatment, indicated that BRD4-dependent promoter clearance was rate limiting for transcription. At JQ1-insensitive genes the drop in transcriptional elongation still occurred, but was compensated by enhanced RNAPol2 recruitment. Similar results were obtained with other inhibitors of transcriptional elongation. Thus, the selective transcriptional effects following JQ1 treatment are linked to the inability of JQ1-sensitive genes to sustain compensatory RNAPol2 recruitment to promoters. These observations highlight the role of BET proteins in supporting transcriptional elongation and rationalize how a general suppression of elongation may selectively affects transcription.
Supported self-management for COPD: making progress, but there are still challenges
Authors: Hilary Pinnock, Liz Steed, Rachel Jordan
Journal: European Respiratory Journal (2016)

Respiratory specialists familiar with the success of supported self-management in asthma [1] may be excused for feeling disappointed by the evolution of evidence in chronic obstructive pulmonary disease (COPD). The promise of early studies [2–4] was seemingly dashed by a series of negative trials [5, 6] and a trial was even terminated early for fear of a detrimental effect [7]. The most recent Cochrane review, however, concludes that interventions to support self-management reduce respiratory-related and all-cause admissions, reduce dyspnoea and improve quality of life [8]. The interventions in the included studies were heterogeneous and complex; and it was not possible to identify the individual components of supported self-management responsible for effective outcomes. A wider review of trial-level data was also unable to identify the most important components [9]. The study by Jonkman et al. [10] in this issue of the European Respiratory Journal , which explores the characteristics of effective self-management interventions in an individual patient data meta-analysis, is therefore a useful contribution to the literature. Self-management is not a time-limited intervention but on-going support to help a person live with their condition(s) <http://ow.ly/10luZq>
Scottish outbreak of Escherichia coli O157, November-December 1996
Authors: J M Cowden
Journal: Eurosurveillance (1997)

On the afternoon of Friday 22 November 1996, Lanarkshire Health Board s Public Health Department became aware of 15 cases of possible Escherichia coli O157 infection (five of which had been confirmed microbiologically) in residents of the town of Wishaw i
Cardiac and respiratory activity in panic disorder: effects of sleep and sleep lactate infusions
Authors: H W Koenigsberg, C P Pollak, J Fine, T Kakuma
Journal: American Journal of Psychiatry (1994)

This study examined cardiac and respiratory activity in panic disorder patients and healthy comparison subjects during sleep, when the effects of anxious cognition and expectancy set are minimized.Heart rate, respiratory rate, end-tidal PCO2, and oxygen saturation were recorded for 11 panic disorder patients and 12 comparison subjects before and during sleep and before and after infusions of sodium lactate and a saline control.Panic disorder patients had higher oxygen saturations than comparison subjects before sleep onset and during sleep stages 0 and 2 before any infusions. The two groups did not differ on other respiratory variables and heart rate. Panic disorder patients responded to lactate infusions during stage 3-4 sleep with greater increases in heart rate and oxygen saturation, and possibly in respiratory rate and end-tidal PCO2, than comparison subjects. The saline control infusion had little effect.These findings suggest that panic disorder patients have greater cardiac and respiratory reactivity than healthy comparison subjects during sleep, when the influence of cognitive factors is minimal or absent.
Erratum to “Traditional and new composite endpoints in heart failure clinical trials: facilitating comprehensive efficacy assessments and improving trial efficiency” [Eur J Heart Fail 2016;18:482‐489]
Authors: Stefan D. Anker, Stefan Schroeder, Dan Atar, Jeroen J. Bax, Claudio Ceconi, Martin R. Cowie, Adam Crisp, Fabienne Dominjon, Ian Ford, Hossein‐Ardeschir Ghofrani, Savion Gropper, Gerhard Hindricks, Mark A. Hlatky, Richard Holcomb, Narimon Honarpour, J. Wouter Jukema, Albert M. Kim, Michael Kunz, Martin Lefkowitz, Chantal Le Floch, Ulf Landmesser, Theresa A. McDonagh, John J. McMurray, Bela Merkely, Milton Packer, Krishna Prasad, James Revkin, Giuseppe M.C. Rosano, Ransi Somaratne, Wendy Gattis Stough, Adriaan A. Voors, Frank Ruschitzka
Journal: European Journal of Heart Failure (2016)
Use of a Soehendra stent retriever in dilation of an anastomotic biliary stricture in a post-liver transplant patient
Authors: Esraa Mohamed, Paul Kröner, Ujjwal Kumar, Klaus Mönkemüller
Journal: Endoscopy (2016)

Occasionally, bile duct strictures in patients who have undergone liver transplantation are impossible to traverse, dilate, and stent. Herein we present a novel technique for the dilation of a recalcitrant stricture using the Soehendra stent retriever device.
Safety and Efficacy of Allogeneic Hematopoetic Stem Cell Transplant (HSCT) after Treatment with Programmed Cell Death 1 (PD-1) Inhibitors
Authors: Reid W. Merryman, Haesook T. Kim, Pier Luigi Zinzani, Carmelo Carlo-Stella, Stephen M Ansell, Ahmad S. Halwani, Miguel-Angel Perales, Vincent T. Ho, Joseph H. Antin, Jerome Ritz, Robert J. Soiffer, Philippe Armand
Journal: Blood (2015)
A Prospective Study of Sudden Cardiac Death among Children and Young Adults
Authors: Richard D. Bagnall, Robert G. Weintraub, Jodie Ingles, Johan Duflou, Laura Yeates, Lien Lam, Andrew M. Davis, Tina Thompson, Vanessa Connell, Jennie Wallace, Charles Naylor, Jackie Crawford, Donald R. Love, Lavinia Hallam, Jodi White, Christopher Lawrence, Matthew Lynch, Natalie Morgan, Paul James, Desirée du Sart, Rajesh Puranik, Neil Langlois, Jitendra Vohra, Ingrid Winship, John Atherton, Julie McGaughran, Jonathan R. Skinner, Christopher Semsarian
Journal: New England Journal of Medicine (2016)

Sudden cardiac death among children and young adults is a devastating event. We performed a prospective, population-based, clinical and genetic study of sudden cardiac death among children and young adults.
BL-8040, a Peptidic CXCR4 Antagonist, Induces Leukemia Cell Death and Specific Leukemia Cell Mobilization in Relapsed/Refractory Acute Myeloid Leukemia Patients in an Ongoing Phase IIa Clinical Trial
Authors: Gautam Borthakur, Arnon Nagler, Yishai Ofran, Jacob M. Rowe, Jessica K. Altman, Olga Frankfurt, Martin S. Tallman, Irit Avivi, Amnon Peled, Yaron Pereg, Adam Foley-Comer, Lena Russovsky, Arnon Aharon, Teresa McQueen, Naveen Pemmaraju, Carlos E. Bueso-Ramos, Jorge E. Cortes, Michael Andreeff
Journal: Blood (2014)
Acute Rheumatic Fever with Carditis in Pregnancy
Authors: Thomas J. Roess
Journal: New England Journal of Medicine (1958)

THE occurrence of acute rheumatic fever during pregnancy has seldom been reported, and various authors are in agreement that it is a rare entity.1 2 3 4 I recently had the opportunity to care for a patient with acute rheumatic fever, rheumatic carditis and marked congestive heart failure complicating pregnancy. The literature reveals only 2 similar cases with a favorable outcome.5 , 6 It was believed, therefore, that this case should be reported.Case ReportA 25-year-old woman was admitted to the 2500th USAF Hospital on February 25, 1957, with chief complaints of shortness of breath and swelling of the ankles of approximately 4 weeks' . . .
MLN2480, an investigational oral pan-RAF kinase inhibitor, in patients (pts) with relapsed or refractory solid tumors: Phase I study.
Authors: Drew Warren Rasco, Anthony J. Olszanski, Amita Patnaik, Guillermo Espino, Rachel Neuwirth, Stephanie Faucette, Michael Bargfrede, Esha A. Gangolli, Russell M Walker, Michelle Kneissl, Viviana Bozon
Journal: Journal of Clinical Oncology (2013)

2547 Background: MLN2480 is an investigational pan-RAF kinase inhibitor. In vivo, MLN2480 showed antitumor activity in melanoma, colon, lung, and pancreatic cancer xenograft models. This first-in-human study aimed to evaluate the safety of MLN2480, determine the MTD/recommended phase 2 dose (RP2D), and evaluate pharmacokinetics (PK) and preliminary efficacy. Methods: Pts aged ≥18 yrs with advanced solid tumors who had failed/were not candidates for standard therapy received oral MLN2480 every other day (Q2D) in 22-d cycles, with dose escalation (3+3 design) based on DLTs in cycle 1. AEs were graded per NCI-CTCAE v4.03. Blood samples for plasma PK assessment were taken pre-dose and at multiple times post-dose, d 1 and 21, cycle 1. Results: 24 pts (10 male, median age 64.5 yrs [range 37–83]) have been treated at 20, 40, 80, 135, 200, and 280 mg (n=4, 3, 3, 3, 4, and 7), respectively. The most common tumors included colorectal cancer in 11 pts and non-small-cell lung cancer in 2 pts. Pts received a median of 2 (range 1–6) cycles. 2 pts treated at 280 mg had DLTs: grade 3 macular rash and grade 3 periorbital edema. 20 pts had drug-related AEs, including fatigue 46%, arthralgia 25%, maculopapular rash 21%, and myalgia 17%. 4 pts had drug-related grade ≥3 AEs, which included the 2 DLTs listed above, anemia, dyspnea, and fatigue. No keratocanthomas/ squamous cutaneous carcinomas have been seen to date. 4 pts discontinued due to AEs. There were 3 on-study deaths (1 treatment-related per investigator; dyspnea and respiratory failure). At 20–200 mg MLN2480 PK data (13 pts) exhibited rapid absorption (median T max 2 hr), low fluctuation at steady state (mean peak to trough ratio 2.1), and mean accumulation half-life of 67 hr. Overall mean accumulation was 2.6-fold following repeated Q2D dosing for 21 d. Steady-state (d 21) exposures increased in an approximately dose-proportional manner over 20–200 mg range. No pts had an objective response to date; no pts with BRAF mutation enrolled to date. Conclusions: In this first-in-human study (n=24), the safety profile of MLN2480 up to 200 mg Q2D was acceptable. Accrual continues at 200 mg to confirm the MTD. Melanoma expansion cohorts are planned at the RP2D using a Q2D 28-d cycle. Clinical trial information: NCT01425008.
Analysis of neuroendocrine marker synaptophysin and stem-cell related marker CD133 on circulating tumor cells (CTC) in patients with metastatic non-small cellular lung cancer (NSCLC).
Authors: Verena Kuemmerlen, Anna Puggina, Alberto Fusi, Ulrich Keilholz
Journal: Journal of Clinical Oncology (2012)

e18010 Background: In NSCLC heterogeneity or switch to neuroendocrine phenotype and the expression of stem-cell related markers have been associated with higher tumor aggressiveness. We evaluated the presence of CTC bearing stem cell-related marker CD133+ and the neuroendocrine marker synaptophysin (SYP) in patients with metastatic non small cellular lung cancer (NSCLC). Methods: Forty-four blood samples (20 mL) were collected after informed consent from 16 consecutive patients (pts) with metastatic NSCLC before and during chemotherapy at our Institution. Blood was enriched for tumor cells by CD45 depletion using a magnetic bead separation technique and potential CTC were identified by flow cytometry. CTC were defined as EpCAM+ CK7/8 + CD45-CD53-. Multiparameter cytometry assessed surface expression of the combinations of CD133 and SYP. Results: CTC phenotype: Twenty-five of all 44 samples (57%) were found positive for presence of at least 1 CTC. The median number of CTC was 4 (range: 1-9) / 10mL blood. Twelve samples (27%) showed to be positive for the cancer putative stem cell marker CD133. The median number of CD133+ CTC was 2 (range: 1-7) / 10mL. Seventeen samples (38%) were positive for SYP with a median number of 2 SYN+ CTC (range: 1-6 ) /10ml. Eleven samples (25%) resulted double positive for CD133 and SYP. Tumor heterogeneity: Twelve of the 16 patients (75%) had at least one sample positive for CTC. In 3 pts (25%) CTC expressed only SYP, in 5 pts (42%) both the markers and in 4 pts (33%) neither CD133 nor SYP were expressed. Conclusions: A higher rate of CD133-SYP-double positive CTC compared to the single positive CTC was observed. This suggests that the switch to the neuroendocrine phenotype might occur concomitantly with a stem-cell like more resistant and aggressive phenotype. It needs to be clarified, whether the presence of stem-cell like and neuroendocrine CTC may be a predictive factor for treatment response and outcome in patients with metastatic NSCLC.
10. Biophysics of cell membrane and nanoparticle interface
Authors: Nicholas A. Peppas, Ruth Duncan, Gary E. Wnek, Allan S. Hoffman, Guang Hui Gao, Sung Wan Kim, Doo Sung Lee, Michael Hadjiargyrou, Elka Touitou, Denize Ainbinder, Russell Mumper, Alain Rolland, Takuro Niidome, Vinod Labhasetwar, Shi Liu, Guangyuan Zhou, Yubin Huang, Zhigang Xie, Xiabin Jing, Noemi Csaba
Journal: Journal of Controlled Release (2014)
Deletion Size Influences Clinical Outcome In Patients with Chronic Lymphocytic Leukemia; 13q Deletion Anatomy, Cooperating Lesions and Cancer Pathogenesis
Authors: Helen Parker, Matthew JJ Rose-Zerilli, Anton Parker, Tracy Chaplin, Anne Catherine Gardiner, Mike Griffiths, Andrew Collins, Bryan D Young, David Graham Oscier, Jonathan C. Strefford
Journal: Blood (2010)
D7-01: 4-dimensional respiration-gated radiotherapy for concurrent chemo-radiotherapy in lung cancer
Authors: Suresh Senan, Femke O. Spoelstra, Erik C. Phernambucq, John R. van Sörnsen de Koste, Johan C. Cuijpers, Egbert F. Smit, Ben J. Slotman, Frank J. Lagerwaard
Journal: Journal of Thoracic Oncology (2007)
Deciphering clinical phenotypes in acute viral lower respiratory tract infection: Bronchiolitis is not an island
Authors: Steve Cunningham, Harish Nair, Harry Campbell
Journal: Thorax (2016)

Bronchiolitis is an internationally recognised diagnosis that is commonly applied to children across healthcare systems. In the UK, 2% of all infants are admitted to paediatric hospitals each year with a diagnosis of bronchiolitis, typically over 6–8 weeks winter peak period. Globally, bronchiolitis is just as common though seasons are more diffuse and variable in tropical climates. For such a common disease, there remain significant gaps in our understanding of its pathophysiology and also its inter-relationship with other common lower respiratory tract disease in young children. This lack of data is now restraining progress in the development of management and therapeutics for the preschool age group who are most affected by lower respiratory tract disease (both for infections, ie, respiratory syncytial virus (RSV) and for the response to infection, ie, wheeze phenotypes). So the study by Dumas et al in Thorax is welcome, as they attempt to stratify subgroups of patients with a clinical diagnosis of bronchiolitis.1

Yet, despite being a common condition in young children, it has proven challenging to develop an international consensus on what precisely defines bronchiolitis from a clinical perspective and how this differs from other common lower respiratory conditions. Most paediatricians consider that they would instantly recognise a case, but agreement may be less consistent when clinicians are less experienced, children are older, have clinical risk factors or present outside the peak RSV season. In many ways this reflects gaps in our current knowledge about lower respiratory tract disease in young children, as the diagnosis of bronchiolitis is intended to be the clinical representation of typical histological features within the bronchioles of those affected: oedematous bronchioles filled with necrotic epithelium and neutrophils, bound together by mucous.2 As a histological review of only the most severe cases of bronchiolitis (resulting in death) have informed this …
Acute pancreatitis after endoscopic biopsy of the minor duodenal papilla in an individual with pancreas divisum
Authors: Woo Jeong
Journal: Endoscopy (2016)

A healthy 47-year-old man underwent esophagogastroduodenoscopy (EGD) for general examination. A small polyp 4 mm in size was seen in the second portion of the duodenum; its location was proximal to the major duodenal papilla ([Fig. 1 a]). An endoscopic biopsy was taken ([Fig. 1 b]). The biopsy findings showed normal duodenal mucosa.