tbuckley/cabot-search huggingface dataset:
Phase II study evaluating the association of gemcitabine, trastuzumab, and erlotinib as first-line treatment in patients with metastatic pancreatic adenocarcinoma (GATE 1).
Authors: Eric Assenat, Laurent Mineur, Caroline Mollevi, Catherine Lombard-Bohas, Thibault Mazard, Emmanuelle Samalin, Fabienne Portales, Thomas Walter, Marc Ychou
Journal: Journal of Clinical Oncology (2015)

379 Background: This study aimed to assess the efficacy and tolerance of the combinationof chemotherapy and two targeted therapies as a first-line treatment in metastatic pancreatic cancer patients. Methods: We designed a phase 2 open-label, non-comparative, multicenter study (NCT01204372). Patients received weekly 1000 mg/m² gemcitabine (3 weeks out of 4), weekly trastuzumab (4 mg/kg the first week, 2 mg/kg afterwards) and erlotinib 100 mg/day per os. The primary endpoint was the disease control rate (DCR) according to RECIST. Using a Fleming’s single-stage procedure, the trial was considered positive if 29 patients had a controlled disease (out of 57 evaluable patients). Secondary endpoints included the safety, the progression-free survival (PFS) and the overall survival (OS). An ancillary study addressed the EGFR, HER2 and KRAS status of the patients. Results: Between June 2010 and July 2013, 62 patients were recruited (37 men). The median age was 62 years (range 35-77). Performance status was 0 (n=27) and 1 (n=35). 10 patients had had a surgery of the primary tumor (PT), of whom 6 had been treated with a gemcitabine-based adjuvant chemotherapy (&gt; 6-month delay). PT were localized in the head (n=25), corpus (n=22) and tail (n=15) of pancreas. The number of metastatic sites varied from 1 (n=25) to ≥ 3 (n=15). The baseline median left ventricular ejection fraction was 65% (range 51-86%). All patients were evaluable for safety and 59 patients for efficacy. Main first cycle treatment-related toxicities included: grade 3 anorexia (27%), asthenia (13%), diarrhea (10%), anemia (6%), and thrombocytopenia (3%); grade 3-4 neutropenia (24%), and mucositis (6%); grade 2-3 cutaneous events (35%). No complete responses were observed. 11 patients had a partial response, 33 a stable disease and 15 a disease progression. Therefore, the DCR was 74.6% (95%CI: 61.6-85.0%). Definitive results for the secondary endpoints will be presented at the meeting. Conclusions: Our results showed that combining gemcitabine, trastuzumab and erlotinib is efficient in terms of DCR. A further study is necessary to investigate this promising association. Funding (Roche SAS). Clinical trial information: NCT01204372.
EFFECT OF PREVIOUS CONCUSSION ON SPORT-SPECIFIC SKILLS IN YOUTH ICE HOCKEY PLAYERS
Authors: Paul Eliason, Carly McKay, Willem Meeuwisse, Brent Hagel, Luc Nadeau, Carolyn Emery
Journal: British Journal of Sports Medicine (2017)

Background Hockey Canada developed the Hockey Canada Skills Test (HCST), which measures skill acquisition and development. Objective To investigate the effect of previous concussion on sport-specific skill performance in youth ice hockey players. Design Cross-sectional. Setting Ice hockey arenas in Calgary, Alberta, Canada. Participants 596 participants [525 males and 71 females, ages 11–17, representing elite (upper 30% by division of play) and non-elite (lower 70%) levels] recruited from minor ice hockey teams over three seasons of play (2012–2015). Assessment of Risk Factors Players completed a baseline questionnaire including the number, date of occurrence, and length of recovery for any previous concussions. Main Outcome Measurements On-ice skill performance was based on the HCST battery (forward agility weave, forward/backward speed skate, forward-to-backward transition agility, 6-repeat endurance skate). Multiple linear regression (adjusted for relative age, level of play, position, elite/non-elite, and musculoskeletal injury in the previous year), accounting for clustering by team, was conducted to explore the effect of history of concussion, number of previous concussions, time since most recent concussion, and severity of most recent concussion on HCST performance. Results A history of concussion and time since most recent concussion were not associated with any HCST component. Players reporting two or more concussions were 7.32 seconds faster (95% CI:3.59–11.05) than those with no history performing forward agility weave with puck. For every additional day to return to play post-concussion, player times were faster by: 0.11 seconds (95% CI:0.05–0.16) on forward agility weave with puck and 0.08 seconds (95% CI:0.04–0.13) without puck, 0.01 seconds (95% CI:0.01–0.02) on transition agility without puck, and 0.06 seconds (95% CI:0.03–0.1) on backward speed with puck and 0.05 seconds (95% CI:0.03–0.07) without puck. Conclusions Players with and without a history of concussion have similar HCST scores. Greater time loss following concussion was associated with better performance. The mechanism for this finding requires further exploration.
Phase I Study of Lee011 (Cdk4/6 Inhibitor) in Patients with Malignant Rhabdoid Tumors, Neuroblastoma, and Cyclin D–Cdk4/6 Pathway-Activated Tumors
Authors: B. Geoerger, F. Bourdeaut, S.G. Dubois, M.D. Dewire, A. Marabelle, A.D. Pearson, S. Modak, R. Kan, A. Matano, S.G. Bhansali, S. Parasuraman, S.N. Chi
Journal: Annals of Oncology (2014)
The effect of androgen deprivation therapy (ADT) on cognition in men with prostate cancer
Authors: Z. Allibhai, S. M. Alibhai
Journal: Journal of Clinical Oncology (2006)

14626 Background: ADT plays a central role in the management of prostate cancer. However, there is emerging evidence that ADT use may adversely affect cognition. Given the long natural history of prostate cancer and the elderly population it predominantly affects, this may be an important survivorship issue in this population. Methods: We performed a MEDLINE search of English-language literature from 1966 to December 2005 and identified eight prospective studies that evaluated the effect of ADT on cognition and one study that investigated the effect of therapy on the cognition of patients receiving ADT. Due to differences in study design and outcomes, studies could not be combined meta-analytically. Results: Studies were small, ranging from 19–82 patients. ADT was used in the neoadjuvant setting in 2 studies, a neoadjuvant or adjuvant setting in 1 study, and in a palliative setting for high-risk disease in 5 studies. Controls were featured in 4 studies. Follow-up ranged from 6 to 13 months. A variety of cognitive domains were assessed (using traditional and computer-based neuropsychological tasks). Whereas 4 studies found worsening in one or more domains in patients over time, 4 studies showed either no worsening or improvement in one or more cognitive domains after ADT was instituted. No cognitive domain was consistently affected by ADT. Three of the studies included follow-up 3 months after ADT was stopped and all 3 showed at least some improvement in cognitive function. Short-term supplementation with estradiol did not improve cognitive function in 1 study. There were fundamental differences across studies in terms of patient populations, cognitive domains tested and specific tests used, and type of ADT. Other important limitations included small sample sizes, limited follow-up, and practice effects. Conclusions: The impact of ADT on cognitive function and its potential reversibility are unclear, and further studies are needed. In the meantime, clinicians and patients should continue to carefully weigh the potential benefits and risks of ADT when making treatment decisions. No significant financial relationships to disclose.
Active Staphylococcus aureus infection: Is it a contra-indication to the repair of complex hernias with synthetic mesh? A prospective observational study on the outcomes of synthetic mesh replacement, in patients with chronic mesh infection caused by Staphylococcus aureus
Authors: Claudio Birolini, Jocielle Santos de Miranda, Edivaldo Massazo Utiyama, Samir Rasslan, Dario Birolini
Journal: International Journal of Surgery (2016)
The Predictive Role of Maladaptive Parental Behaviors, Early Sleep Problems, and Child/Mother Psychological Factors
Authors: Valérie Simard
Journal: JAMA Pediatrics (2008)

This study aimed to determine if maladaptive parental behaviors and mother/child psychological characteristics predict future sleep disturbances in 50-month-old to 6-year-old preschoolers. It found that maladaptive parental behaviors develop in reaction to preexisting sleep difficulties and that early sleep difficulties are more predictive than parental behaviors in explaining bad dreams and a reduction in total sleep time.
Parallels in the Epidemiology of Selected Anogenital Carcinomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R K Peters, T M Mack, L Bernstein
Journal: JNCI Journal of the National Cancer Institute (1984)

Characteristics of Los Angeles, Calif., residents in whom carcinomas of the cervix, vulva, vagina, anus, and penis were diagnosed during the period 1972–81 were compared with those of all residents and with those in whom any cancer was diagnosed during the same period. At all five sites, risks for squamous and transitional cell carcinomas generally increased with decreasing social class, were low among Jews (not explained by social class), and were elevated among persons who were separated or divorced at diagnosis compared to married persons. Single men had a striking excess of anal but not penile carcinomas. The five sites represent contiguous and histologically similar tissues, and the clinical literature suggests common risk factors, e.g., sexually transmitted infections and other forms of chronic irritation. These observations are all consistent with the hypothesis that tumors at these sites have common or similar etiologic elements.
Cannabis Use and Risk of Psychiatric Disorders
Authors: Carlos Blanco, Deborah S. Hasin, Melanie M. Wall, Ludwing Flórez-Salamanca, Nicolas Hoertel, Shuai Wang, Bradley T. Kerridge, Mark Olfson
Journal: JAMA Psychiatry (2016)

With rising rates of marijuana use in the general population and an increasing number of states legalizing recreational marijuana use and authorizing medical marijuana programs, there are renewed clinical and policy concerns regarding the mental health effects of cannabis use.To examine prospective associations between cannabis use and risk of mental health and substance use disorders in the general adult population.A nationally representative sample of US adults aged 18 years or older was interviewed 3 years apart in the National Epidemiologic Survey on Alcohol and Related Conditions (wave 1, 2001-2002; wave 2, 2004-2005). The primary analyses were limited to 34 653 respondents who were interviewed in both waves. Data analysis was conducted from March 15 to November 30, 2015.We used multiple regression and propensity score matching to estimate the strength of independent associations between cannabis use at wave 1 and incident and prevalent psychiatric disorders at wave 2. Psychiatric disorders were measured with a structured interview (Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV). In both analyses, the same set of wave 1 confounders was used, including sociodemographic characteristics, family history of substance use disorder, disturbed family environment, childhood parental loss, low self-esteem, social deviance, education, recent trauma, past and present psychiatric disorders, and respondent's history of divorce.In the multiple regression analysis of 34 653 respondents (14 564 male [47.9% weighted]; mean [SD] age, 45.1 [17.3] years), cannabis use in wave 1 (2001-2002), which was reported by 1279 respondents, was significantly associated with substance use disorders in wave 2 (2004-2005) (any substance use disorder: odds ratio [OR], 6.2; 95% CI, 4.1-9.4; any alcohol use disorder: OR, 2.7; 95% CI, 1.9-3.8; any cannabis use disorder: OR, 9.5; 95% CI, 6.4-14.1; any other drug use disorder: OR, 2.6; 95% CI, 1.6-4.4; and nicotine dependence: OR, 1.7; 95% CI, 1.2-2.4), but not any mood disorder (OR, 1.1; 95% CI, 0.8-1.4) or anxiety disorder (OR, 0.9; 95% CI, 0.7-1.1). The same general pattern of results was observed in the multiple regression analyses of wave 2 prevalent psychiatric disorders and in the propensity score-matched analysis of incident and prevalent psychiatric disorders.Within the general population, cannabis use is associated with an increased risk for several substance use disorders. Physicians and policy makers should take these associations of cannabis use under careful consideration.
Abstract 18744: Peripheral Blood Gene Expression Reflects Differences Between Coronary Artery Calcification and Stenosis as Assessed by Coronary Artery Calcium Scanning and Ct Angiogaphy
Authors: Szilard Voros, Matthew J Budoff, William Kraus, Gregory Thomas, Michael Elashoff, James Wingrove, Steven Rosenberg
Journal: Circulation (2012)

Background. We previously validated a composite peripheral blood gene expression score (GES) based on age, sex and 23 genes to detect obstructive coronary artery disease (CAD), using invasive coronary angiography as gold standard (≥50% diameter stenosis). Plaque and stenosis can also be assessed by cardiovascular CT. Methods. 614 symptomatic patients with no known CAD or diabetes from the COMPASS and PREDICT studies underwent CAC and CTA by institutional protocols and GES was measured according to Corus® CAD protocols in the CardioDx CLIA laboratory (Palo Alto, CA). CAC was expressed as Agatston score. For qualitative analysis, each of the 17 segments was graded for stenosis as 0: none, 1: minimal, 2: mild, 3: moderate and 4: severe; segment involvement score (SIS) was calculated by adding all segments with any plaque and segment stenosis score (SSS) by summing individual segment scores. Patients from COMPASS (N=394) also underwent quantitative measurements of calcified, high-density and low-density non-calcified plaque, as previously described. Expression levels of the 23 genes were analyzed by age and sex-adjusted logistic regression. Results. In the 614 patients, mean age was 57±10; 50% were men. Overall GES was significantly correlated with CAC (r=0.35) and MPS (r=0.41), both p&lt;0.001. Individual gene expression level analysis showed that genes from the myeloid lineage, including S100A12/8, were significantly increased and T cell genes decreased with increasing MPS, whereas only innate immunity (myeloid and NK, S100A12/8, SLAMF7) genes were significantly increased with increasing calcification. In the quantitative analysis set (N=394, mean age: 55±12, 50% men) a similar pattern was observed with only neutrophil genes significantly upregulated with calcification, whereas both B and T cell genes were downregulated with increasing MPS. Conclusions. Gene expression and qualitative and quantitative cardiac CT data showed that peripheral blood gene expression changes for overall maximum percent stenosis and calcification differ. MPS was associated with increased expression of innate immune genes and decreased lymphocyte gene expression, while calcification was associated with increases in innate immune gene expression.
CCR9 in cancer: oncogenic role and therapeutic targeting
Authors: Zhenbo Tu, Ruijing Xiao, Jie Xiong, Kingsley M. Tembo, Xinzhou Deng, Meng Xiong, Pan Liu, Meng Wang, Qiuping Zhang
Journal: Journal of Hematology & Oncology (2016)

Cancer is currently one of the leading causes of death worldwide and is one of the most challenging major public health problems. The main challenges faced by clinicians in the management and treatment of cancer mainly arise from difficulties in early diagnosis and the emergence of tumor chemoresistance and metastasis. The structures of chemokine receptor 9 (CCR9) and its specific ligand chemokine ligand 25 (CCL25) have been elucidated, and, interestingly, a number of studies have demonstrated that CCR9 is a potential tumor biomarker in diagnosis and therapy, as it has been found to be highly expressed in a wide range of cancers. This expression pattern suggests that CCR9 may participate in many important biological activities involved in cancer progression. Researchers have shown that CCR9 that has been activated by its specific ligand CCL25 can interact with many signaling pathways, especially those involved in tumor chemoresistance and metastasis. This review, therefore, focuses on CCR9 induction activity and summarizes what is currently known regarding its role in cancers and its potential application in tumor-targeted therapy.
Abstract A1-10: The iCOGS breast cancer GWAS reveals 4 unique signals in the PTHLH region in patients of European origin
Authors: Adam N. Freeman, T John Martin, Michael A. Henderson, Enes Makalic, Miroslaw K. Kapuscinski, Daniel F. Schmidt, John Hopper
Journal: Cancer Research (2015)

Abstract Parathyroid hormone-related protein (PTHrP), the product of the PTHLH gene, has long been implicated in breast cancer. Its expression is thought to favor and, potentially, facilitate metastasis to bone. Paradoxically, a prospective clinical study clinical suggests that its production in primary breast cancers is actually protective, affording a better prognosis than its absence. Multiple recent Genome-Wide Association Studies (GWAS) have confirmed a single susceptibility locus immediately upstream of the PTHLH gene to be associated with breast cancer. This was again reproduced in the recent iCOGS GWAS, which involved over 90,000 European subjects. In spite of a single SNP, rs10771399, being uniquely reported and reproduced by prior studies, we demonstrate 4 discrete overlapping signals by utilizing forward selection logistic regression and LASSO techniques. Two of these signals are centered and superimposed around rs10771399, ~40kbp upstream of PTHLH, a third lies a further 100kbp upstream, and the fourth lies a further 250kbp upstream over the next gene, CCDC91. While the causation of this signal remains elusive, multiple putatively contributory variations are captured by these signals. Citation Format: Adam N. Freeman, T John Martin, Michael A. Henderson, Enes Makalic, Miroslaw K. Kapuscinski, Daniel F. Schmidt, John Hopper. The iCOGS breast cancer GWAS reveals 4 unique signals in the PTHLH region in patients of European origin. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A1-10.
Murine T Lymphocytes Incapable of Producing Macrophage Inhibitory Protein-1 Are Impaired in Causing Graft-Versus-Host Disease Across a Class I But Not Class II Major Histocompatibility Complex Barrier
Authors: Jonathan S. Serody, Donald N. Cook, Suzanne L. Kirby, Elizabeth Reap, Thomas C. Shea, Jeffrey A. Frelinger
Journal: Blood (1999)
pH gradient difference around ischemic brain tissue can serve as a trigger for delivering polyethylene glycol-conjugated urokinase nanogels
Authors: Wei Cui, Ran Liu, Haiqiang Jin, Pu Lv, Yuyao Sun, Xi Men, Saina Yang, Xiaozhong Qu, Zhenzhong Yang, Yining Huang
Journal: Journal of Controlled Release (2016)
Increased Risk of Chronic Graft-Versus-Host Disease, Obstructive Bronchiolitis, and Alopecia With Busulfan Versus Total Body Irradiation: Long-Term Results of a Randomized Trial in Allogeneic Marrow Recipients With Leukemia
Authors: O. Ringdén, M. Remberger, T. Ruutu, J. Nikoskelainen, L. Volin, L. Vindeløv, T. Parkkali, S. Lenhoff, B. Sallerfors, L. Mellander, P. Ljungman, N. Jacobsen
Journal: Blood (1999)
Phase II trial of gemcitabine plus trastuzumab in minimally pretreated HER2 overexpressing metastatic breast cancer
Authors: N. W. Peacock, J. Bearden, F. Schnell, M. White, F. A. Greco, H. A. Burris, J. H. Barton, J. D. Hainsworth, D. R. Spigel, D. A. Yardley
Journal: Journal of Clinical Oncology (2005)

704 Background: Gemcitabine is an exciting novel deoxcytidine analog demonstrating synergism, when combined with trastuzumab, in human breast cancer cell lines. Trastuzumab plus chemotherapy, has yielded superior ORR, TTP, as well as survival as compared to chemotherapy alone in HER2+ tumors. This study evaluates the clinical activity of gemcitabine administered with trastuzumab in minimally pretreated HER2 amplified MBC. Methods: Eligibility: Pts with HER2 3+ or FISH + tumors, 0–1 prior MBC regimens, bidimensional disease, doxorubicin < 360 mg/m2, and LVEF ≥ 50%. Treatment consisted of gemcitabine 1000 mg/m2 days 1, 8, 15, q28 days in conjunction with 4 mg/kg trastuzumab D1 and then 2 mg/kg for 8 consecutive weeks followed by D1, 8, 15 administration of a q28d schedule with gemcitabine, both continuing until disease progression or toxicity. Results: 40 pts were enrolled between 7–5–01 & 11–19–04 with 33 evaluable for response. Median age is 57. 28 pts were HER2 3+ and 6 FISH+. Sites of metastatic disease included 13 lung, 19 liver, 16 bone, 17 soft tissue; the majority of pts had ≥ 2 metastatic sites of disease. 21 pts had prior adjuvant therapy, 21 pts prior doxorubicin & 26 pts prior taxanes. 19 pts had no prior MBC therapy, 17 pts-1 line, 3 pts ≥ 2 lines of MBC therapy. Clinical benefit rate of 66% was noted with 3 CRs, 8 PRs and 11 with SD. 11 pts progressed and 4 are unevaluable. A median of 3.5 cycles were delivered (range 1 - 14). G 3/4 heme toxicity was notable for neutropenia in 21 pts- accompanied by fever in only 1 pt, thrombocytopenia-5, and anemia-1pt. G 3/4 non-heme toxicity consisted of fatigue-5, pulmonary-4, nausea-4, vomiting-3, and edema-2 pts. Cardiac dysfunction was noted in 1 pt. Median survival was 18.8 mo with a median PFS of 3.9 mo. Conclusion: Gemcitabine plus trastuzumab is safe and well tolerated in minimally pretreated HER2+ MBC pts, the majority of whom were anthracycline and taxane pretreated. This preliminary analysis supports the suggestion of enhanced anti-tumor activity between gemcitabine and trastuzumab, with the preliminary median survival surpassing that expected for either agent alone at this juncture of treatment. Final data to be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Lilly Oncology Genentech, Lilly Oncology Genentech, Lilly Oncology
Long Term Outcome of Paclitaxel- and Sirolimus-Eluting Stents Versus Bare Metal Stents. From Western Denmark Heart Registry
Authors: Per Thayssen, Anne Kaltoft, Hans-Henrik Tilsted Hansen, Jens Flensted Lassen, L.O. Jensen, Michael Mæng, K.N. Hansen, Klaus Rasmussen, Morten Madsen, Søren Paaske Johnsen, Lars Pedersen, Henrik Toft Sørensen, Leif Thuesen
Journal: Journal of the American College of Cardiology (2009)
Abstract 11038: Echocardiography After Resect-Plicate-Release for Obstructive Hypertrophic Cardiomyopathy
Authors: Dan G Halpern, Jose Ricardo Po, Rajiv Joshi, Glenda Winson, Bette Kim, Sandhya K Balaram, Dan G Swistel, Mark V Sherrid
Journal: Circulation (2013)

Background: Anatomic features in hypertrophic cardiomyopathy (HCM) causing LV outflow obstruction are septal hypertrophy, elongated mitral leaflets and anteriorly displaced papillary muscles. The n...
Ex vivo expanded peripheral blood progenitor cells provide rapid neutrophil recovery after high-dose chemotherapy in patients with breast cancer
Authors: Ian McNiece, Roy Jones, Scott I. Bearman, Pablo Cagnoni, Yago Nieto, Wilbur Franklin, John Ryder, Andrea Steele, Judy Stoltz, Peggy Russell, Janet McDermitt, Christopher Hogan, James Murphy, Elizabeth J. Shpall
Journal: Blood (2000)