tbuckley/cabot-search huggingface dataset:
Antibodies to Epstein-Barr Viral Capsid and Early Antigens Associated with Burkitt's Lymphoma and Lymphoblastic Lymphosarcoma in Israel2
Authors: T. Gotlieb-Stematsky, B. Ramot, A. Vonsover, E. Aghai, G. Kende, M. Ninio, M. Modan
Journal: JNCI Journal of the National Cancer Institute (1976)

Before and/or after chemotherapy was administered to patients with Burkitt's lymphoma (BL) or lymphoblastic lymphosarcoma (LLS), their sera and those of matched controls were tested for antibodies to Epstein-Barr virus (EBV) capsid antigen (VCA) and early antigen by the indirect immunofluorescence method. Ten of the 16 BL patients were Arab children and 8 of the 11 LLS patients were Jews of Asian-African origin. Although half the BL patients did not have elevated antibody titers when their disease was diagnosed, significantly higher ones were detected in the BL group as compared with the LLS patients and their matched controls; Arab patients had the highest titers. IgM antibodies specific for VCA were found in 2 patients concurrently with elevated titers. We found no correlation between the clinical course of BL and the patients' antibody titers to EBV.
Effect of 9–11 on U.S. national cancer clinical trials accrual and lack of effect of National Cancer Institute budget increases
Authors: A. Bleyer
Journal: Journal of Clinical Oncology (2007)

6551 Background: During the past decade, a variety of initiatives have been implemented to improve the accrual of cancer patients on clinical trials. In the U.S., these have included comprehensive reviews and recommendations by the two most recent National Cancer Institute (NCI) administrations, reorganization of the clinical trials infrastructure at the NCI, and campaigns by the NCI Cooperative Groups and their Coalition. During the past six years, additional funds were allocated to this effort as part of the doubling of the NCI budget. The impact of these efforts on national cancer treatment clinical trials was evaluated, with emphasis on age groups. Methods: Accrual data from NCI-sponsored treatment trials conducted between 1997 and 2006 were obtained from the NCI Cancer Therapy Evaluation Program. Entries were analyzed by patient age, gender, race, type of cancer treated, and calendar year of trial entry. Results: Overall, national cancer treatment trial entries declined after 9–11–2001 and in 2003 reached the lowest levels since 1997. As of 2005 accrual recovered to pre 9–11 levels only in 15–29 and &gt;60 year-olds, with the former demonstrating the greatest gain ( Table ). Entries among &lt;15 and 30–49 year- olds declined steadily since 1997 with no evidence for recovery as of 2005 ( Table ). Overall, the estimated proportion of the nation's cancer patients entered onto national treatment trials remains below 3%. Conclusions: Despite continued national and local efforts to increase the participation of cancer patients on clinical trials, accompanied by significant increases in the NIH and NCI budgets, there is little evidence of a beneficial impact. The effect of 9–11 has yet to be overcome, except in young and elderly adults, in whom specific, targeted initiatives appear to have been successful. The latter approaches may be useful to apply to other age groups, particularly in view of the recent cuts in the cooperative group budgets and current mandated decreases in study accruals. No significant financial relationships to disclose. [Table: see text]
Abstract 3989: MicroRNA-16 and microRNA-193b as serological predictors for chemoradiation response in esophageal squamous cell carcinoma patients
Authors: Nikki P. Lee, Kenneth K. Lai, Kin Tak Chan, Daniel K. Tong, Simon Law
Journal: Cancer Research (2015)

Abstract Esophageal cancer is one of the most deadly malignancies along the gastrointestinal tract. Esophageal squamous cell carcinoma (ESCC) is the most common cell type occurring at the upper and middle part of the esophagus. Surgery remains the mainstay treatment for this malignancy, however the long-term prognosis is modest with a 5-year overall survival of approximately 30%. To improve the treatment outcome of this cancer, multimodal treatment strategies including neoadjuvant chemoradiation have been implemented. Such pre-surgery treatment indeed leads to better clinical outcome and increases the chance for cure. Unfortunately patients who do not respond may have to undergo prolonged, unnecessary and potentially toxic treatments with no benefits. Currently, there is no reliable method for chemoradiation response prediction. To address this clinical limitation, we have established a non-invasive assay to stratify chemoradiation responders from non-responders. This study is systematically divided into three phases. In the discovery phase (phase I), we found 23 human microRNAs (out of 742 human microRNAs) with more than 2.5-fold elevation in serum from chemoradiation responders when compared to non-responders. In the selection and small-scale validation phase (phase II), small-scale validation in an independent cohort showed that microRNA-16 and microRNA-193b were two most powerful candidates for indicating chemoradiation responders. In the large-scale validation phase (phase III), we have further validated and confirmed the feasibility of microRNA-16 and miroRNA-193b as discriminators for chemoradiation response in a large cohort of more than a hundred patients. Standard curves were also constructed for these two microRNAs for copy number quantitation. In all, we have newly established a highly sensitive and specific blood-based assay with specific cut-offs for discriminating ESCC patients who are responsive to chemoradiation. This assay works by quantitating the serum level of microRNA-16 and microRNA-193b in ESCC patients, such that patients would be advised to receive pre-surgery chemoradiation if they have elevated levels of circulatory microRNA-16 and microRNA-193b. The development of this assay will benefit patient care by formulating individualized treatment plans. Note: This abstract was not presented at the meeting. Citation Format: Nikki P. Lee, Kenneth K. Lai, Kin Tak Chan, Daniel K. Tong, Simon Law. MicroRNA-16 and microRNA-193b as serological predictors for chemoradiation response in esophageal squamous cell carcinoma patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3989. doi:10.1158/1538-7445.AM2015-3989
Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study
Authors: Van-Mai Cao-Lormeau, Alexandre Blake, Sandrine Mons, Stéphane Lastère, Claudine Roche, Jessica Vanhomwegen, Timothée Dub, Laure Baudouin, Anita Teissier, Philippe Larre, Anne-Laure Vial, Christophe Decam, Valérie Choumet, Susan K Halstead, Hugh J Willison, Lucile Musset, Jean-Claude Manuguerra, Philippe Despres, Emmanuel Fournier, Henri-Pierre Mallet, Didier Musso, Arnaud Fontanet, Jean Neil, Frédéric Ghawché
Journal: The Lancet (2016)
Improved Survival in Patients with First Relapsed or Refractory Acute Myeloid Leukemia (AML) Treated with Vosaroxin Plus Cytarabine Versus Placebo Plus Cytarabine: Results of a Phase 3 Double-Blind Randomized Controlled Multinational Study (VALOR)
Authors: Farhad Ravandi, Ellen Ritchie, Hamid Sayar, Jeffrey Lancet, Michael D. Craig, Norbert Vey, Stephen A. Strickland, Gary Schiller, Elias Jabbour, Harry P. Erba, Arnaud Pigneux, Heinz-August Horst, Christian Recher, Virginia M. Klimek, Jorge Cortes, Eric J. Feldman, Adam R. Craig, Judith A. Fox, Renee Ward, Jennifer Smith, Gary Acton, Cyrus Mehta, Hagop M. Kantarjian, Robert K Stuart
Journal: Blood (2014)
Relation of CSF neurotensin concentrations to symptoms and drug response of psychotic patients
Authors: D L Garver, G Bissette, J K Yao, C B Nemeroff
Journal: American Journal of Psychiatry (1991)

The authors investigated the putative endogenous antipsychotic neurotensin in relation to both psychotic symptoms and patterns of response during treatment with an antipsychotic drug.Twenty recently admitted patients with mood-incongruent psychoses underwent 1) interviews with the Schedule for Affective Disorders and Schizophrenia for diagnostic evaluation and symptom profiles, 2) drug-free baseline measurements of CSF neurotensin and homovanillic acid, and 3) close monitoring of a therapeutic trial of haloperidol to determine latency of antipsychotic response.A relative deficiency in CSF neurotensin was found in a subgroup of psychotic women whose clinical response to haloperidol was delayed for 11 to 35 days after initiation of the neuroleptic. These patients had greater thought disorder, delusions-hallucinations, behavioral disorganization, and impaired functioning than did psychotic patients with higher CSF concentrations of neurotensin. Neurotensin concentrations increased during treatment with haloperidol.The study provides further evidence that there is diminished availability of neurotensin in some psychotic patients, with increases in neurotensin early in neuroleptic treatment. Exploration of neurotensin receptor agonists as a potentially novel class of antipsychotic compounds is suggested.
Genetic Profiling By Targeted, Deep Resequencing Confirms That a Murine Xenograft Model Of Acute Myeloid Leukemia (AML) Recapitulates The Mutational Landscape Of The Human Disease and Provides Evidence For Clonal Heterogeneity and Clonal Evolution
Authors: Maja Rothenberg-Thurley, Binje Vick, Stephanie Schneider, Bianka Ksienzyk, Philipp A Greif, Michael Fiegl, Marion Subklewe, Wolfgang Hiddemann, Karsten Spiekermann, Irmela Jeremias, Klaus H. Metzeler
Journal: Blood (2013)
Phase II study of panitumumab (P) in combination with FOLFOXIRI as first-line treatment of metastatic colorectal cancer (mCRC): Activity in molecularly selected patients (pts).
Authors: Sara Lonardi, Lorenzo Fornaro, Francesca Bergamo, Marta Schirripa, Giuseppe Aprile, Manfredi Morvillo, Gianluca Masi, Fotios Loupakis, Lorenzo Calvetti, Chiara Cremolini, Lisa Salvatore, Alberto Zaniboni, Vittorina Zagonel, Alfredo Falcone
Journal: Journal of Clinical Oncology (2012)

3555 Background: GONO-FOLFOXIRI demonstrated higher activity and efficacy compared to FOLFIRI. P with oxaliplatin- or irinotecan-based doublets is feasible and associated with improved activity in KRAS codon 12-13 wild-type pts. BRAF and other RAS rare mutations have been suggested as additional potential biomarkers for anti-EGFR agents. Methods: Pts with untreated unresectable mCRC and wild-type BRAF-RAS genes were enrolled in this GONO multicenter phase II trial of biweekly P 6 mg/kg d1 with a modified FOLFOXIRI regimen (IRI 150 mg/m 2 d1, OXA 85 mg/m 2 d1, l-LV 200 mg/m 2 d1 and 5FU 3000 mg/m 2 48-h continuous infusion d1, reduced to 2400 mg/m 2 due to grade 3-4 toxicity in 2 of first 3 pts enrolled). Primary end-point was response rate (RR, RECIST Criteria). Based on a two stage Simon’s Minimax design (p0=60%, p1=80%; a=0.05, β =0.2) at least 26 responses on 36 evaluable pts should be observed to satisfy the primary end-point. Results: 37 out of 87 screened pts were enrolled (M/F, 57/43%; median age 63 years, range 33-72; ECOG PS 0/1-2, 76/24%; primary colon/rectum, 70/30%; primary on site, 42%; sites of disease single/multiple, 54/46%; liver only mts, 35%). Among the first 3 pts treated with 5FU 3000 mg/m 2 , 2 experienced SAEs (1 grade 4 diarrhea and neutropenia; 1 grade 3 diarrhea). Grade 3-4 toxicities observed among the 34 pts treated at the amended dose were: neutropenia 53% (2 febrile neutropenia); diarrhea 32%; stomatitis 15%; neurotoxicity (grade 2-3) 30%; cutaneous rash 24%. Delays or dose reductions were needed only in 9% and 10% of the total 310 cycles, respectively. One SAE (febrile neutropenia and sepsis) resulting in pt death occurred after amendment. 32 partial responses, 4 disease stabilizations and 1 progression were observed, with a RR of 86% (95% CI: 75-97%). 9 pts underwent local procedures on metastases, achieving an R0 resection in 8 and a pathologic complete response in 3 of them. At a median follow-up of 7.4 months mPFS has not been reached. Conclusions: In molecularly selected unresectable pts adding P to FOLFOXIRI resulted in high activity and interesting resection rate. The regimen appears feasible. Further follow-up is needed to assess long-term outcome.
Abstract 15883: Insomnia and Risk of Cardiovascular Disease
Authors: Chien-Yi Hsu, Chin-Chou Huang, Po-Hsun Huang, Chia-Hung Chiang, Hsin-Bang Leu
Journal: Circulation (2012)

Objective: Although accumulating evidence shows sleep disorders may increase the risk of cardiovascular disease, the association is not consistent. We investigated the association between insomnia and the risk of development of acute myocardial infarction (AMI) and/or ischemic stroke by using a nationwide, population-based cohort database in Taiwan. Methods: Our analyses were conducted using information from a random sample of 2 million people enrolled in the nationally representative Taiwan National Health Insurance Research Database. Cases with depression, anxiety disorder, sleep apnea, seizure disorder, and substance abuse were excluded. Totally 43,180 subjects who were aged 45 years or more, including 10,871 subjects who had diagnosis of insomnia during the study period (exposure group) and an age, sex, comorbidity-matched 32,309 subjects without insomnia (non-exposure group) were identified. Study end points were defined for the occurrence of cardiovascular events including AMI or stroke during follo...
Identification, Characterization, and Control of Potential Human Carcinogens: A Framework for Federal Decision-Making
Authors: D R Calkins, R L Dixon, C R Gerber, D Zarin, G S Omenn
Journal: JNCI Journal of the National Cancer Institute (1980)

A two-stage process is proposed for a uniform framework for Federal agency decisions regarding the identification, characterization, and control of potential human carcinogens. Stage I would include the identification, through epidemiologic and/or laboratory studies, of chemicals that represent a potential carcinogenic risk and the characterization of that risk. Stage II would encompass the actual regulatory decision-making process regarding control of potential carcinogens. Stage I relies predominantly on scientific activity and judgment. Centralized management could enhance the efficiency and effectiveness of this process. The new National Toxicology Program may be able to perform this function. Stage II judgments are social and political. Centralization of stage II decision-making is not possible under current law.
Effects of exercise training in patients with chronic obstructive pulmonary disease—a narrative review for FYSS (Swedish Physical Activity Exercise Prescription Book): Table 1
Authors: M Emtner, K Wadell
Journal: British Journal of Sports Medicine (2016)

The aims of this review were to determine the level of evidence for exercise training in the management of patients with chronic obstructive pulmonary disease (COPD) and provide evidence-based recommendations on exercise training. This review was performed in PubMed and Cochrane Library. Included studies investigated patients with COPD who had been randomised to exercise training or no training. Six systematic reviews were included. The methodological quality was scored using a grading system (GRADE). The analysis showed that aerobic and resistance training in patients in a stable state of COPD results in improved health-related quality of life and decreased dyspnoea, anxiety and depression (moderately strong scientific evidence, grade +++), and increased physical capacity and decreased dyspnoea in daily activities (limited scientific evidence, grade ++). In patients with an acute exacerbation, aerobic and resistance training, performed directly after the exacerbation, results in improved health-related quality of life (moderately strong scientific evidence, grade +++), improved exercise capacity and decreased mortality and hospitalisation (limited scientific evidence, grade ++). Thus, patients with COPD should be recommended to take part in exercise training.
Abstract 314: Loss of Sarcospan has a Deleterious Effect on Cardiac Function in Aged Mice
Authors: Michelle S Parvatiyar, Jamie L Marshall, Maria C Jordan, Reginald T Nguyen, Kenneth P Roos, Rachelle H Crosbie-Watson
Journal: Circulation Research (2014)

Sarcospan (SSPN) has been shown to have an important role in stabilizing sarcolemmal dystrophin- and utrophin-glycoprotein adhesion complexes. Loss of sarcolemmal integrity leads to immune cell infiltration and inappropriate exchange of cellular contents with the extracellular milieu. Our laboratory has shown SSPN loss destabilizes skeletal muscle adhesion and reduces sarcolemmal dystrophin localization, whereas its complete loss due to mutation underlies development of Duchenne muscular dystrophy (DMD). Loss of dystrophin leads to cardiac dysfunction and early mortality in DMD patients. The role of SSPN in the heart is unknown. We present immunofluorescence data revealing reduction of dystrophin and the sarcoglycans with a coordinate increase of β1D integrin levels at the SSPN-null cardiac sarcolemma relative to WT. Also, SSPN loss decreases cardiac P-Akt levels, disrupting signaling promoting compensatory physiological hypertrophy. These studies suggest a fundamental role for SSPN in cardiac maintenance and function, since left ventricular mass increases with age and upon isoproterenol administration (0.8 mg/day for two wks). Aged SSPN-null mice developed hypertrophy, evidenced as increased heart/body weight ratio and left ventricular wall dimension. The SSPN-null mice lacked the characteristic initial rise in cardiac output, left ventricular ejection fraction (LvEF %), induced by chronic β-adrenergic stimulation. Functionally, aged SSPN-null hearts had an increased E/A ratio indicating restrictive ventricular filling and decreased fractional shortening F/S (%) upon isoproterenol administration. Aged untreated SSPN-null hearts had increased fibrosis compared to aged WT controls, however isoproterenol treated SSPN-null hearts displayed exacerbated fibrotic response compared to WT. To assess whether SSPN-null hearts have altered gene expression profiles during progression of pathogenesis, qRT-PCR will be utilized to measure differences in expression of fetal gene and calcium-handling proteins. In summary, we have found that SSPN has an important role in maintaining cardiac function, its loss exacerbates the hypertrophic response and localization of stabilizing adhesion complexes at the cardiac muscle sarcolemma.
Endogenous transmembrane protein UT2 inhibits pSTAT3 and suppresses hematological malignancy
Authors: Dongjun Lee, Ying-Hua Wang, Demetrios Kalaitzidis, Janani Ramachandran, Homare Eda, David B. Sykes, Noopur Raje, David T. Scadden
Journal: Journal of Clinical Investigation (2016)

Regulation of STAT3 activation is critical for normal and malignant hematopoietic cell proliferation. Here, we have reported that the endogenous transmembrane protein upstream-of-mTORC2 (UT2) negatively regulates activation of STAT3. Specifically, we determined that UT2 interacts directly with GP130 and inhibits phosphorylation of STAT3 on tyrosine 705 (STAT3Y705). This reduces cytokine signaling including IL6 that is implicated in multiple myeloma and other hematopoietic malignancies. Modulation of UT2 resulted in inverse effects on animal survival in myeloma models. Samples from multiple myeloma patients also revealed a decreased copy number of UT2 and decreased expression of UT2 in genomic and transcriptomic analyses, respectively. Together, these studies identify a transmembrane protein that functions to negatively regulate cytokine signaling through GP130 and pSTAT3Y705 and is molecularly and mechanistically distinct from the suppressors of cytokine signaling (SOCS) family of genes. Moreover, this work provides evidence that perturbations of this activation-dampening molecule participate in hematologic malignancies and may serve as a key determinant of multiple myeloma pathophysiology. UT2 is a negative regulator shared across STAT3 and mTORC2 signaling cascades, functioning as a tumor suppressor in hematologic malignancies driven by those pathways.
Clinical Genomics
Authors: Arjun K. Manrai, John P. A. Ioannidis, Isaac S. Kohane
Journal: JAMA (2016)

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Reflections on “Emil Kraepelin: Icon and Reality”
Authors: Rael D. Strous, Annette A. Opler, Lewis A. Opler
Journal: American Journal of Psychiatry (2016)

for gender compared with individuals with the LL genotypefrom 3.4% to 1.6% for women, and from 2.2% to 1.0% for men (B520.78,SE50.36,Z522.17, odds ratio50.46,p50.03).In addition, considering the dominant model for the three maltreatment exposure strata, Figure 1 presents a graphical representation of a disordinal or crossover interaction, which is in accordance with the literature regarding the differential susceptibility hypothesis (3).Our results suggest that reactivity differed along the maltreatment spectrum.The probability of depression increases as a function of the number of copies of the S allele and exposure to maltreatment, but it decreases in the group of S allele carriers reporting no experience of maltreatment.These findings concur with the concept of differential susceptibility (4), according to which the direction of responsiveness depends on the nature of the environmental experience.Following this model, it could be argued that individuals with an increased biological sensitivity to context (in this case, S allele carriers) can benefit from a protective environment (here defined by proxy as the absence of maltreatment).Unfortunately, up to now, most of our psychiatric research is still focused on the "dark side" of environmental influences.Future studies should also address the "bright side," investigating the association between positive environments and better mental health outcomes.In this way, we would have more data to confirm or refute the role of the differential susceptibility hypothesis in mental health disorders.
Pharmaceutical Policy Reform — Balancing Affordability with Incentives for Innovation
Authors: Rena M. Conti, Meredith B. Rosenthal
Journal: New England Journal of Medicine (2016)

Interview with Dr. Rena Conti on policy proposals that could help rein in the cost of prescription drugs. (09:14)Download In response to concern about high prices of prescription drugs, presidential candidates and lawmakers have proposed a number of policy changes, including enhancing market forces that put pressure on companies to set lower prescription-drug prices out of self-interest.