tbuckley/cabot-search huggingface dataset:
Endoscopic mucosal resection for large serrated lesions in comparison with adenomas: a prospective multicentre study of 2000 lesions
Authors: Maria Pellise, Nicholas G Burgess, Nicholas Tutticci, Luke F Hourigan, Simon A Zanati, Gregor J Brown, Rajvinder Singh, Stephen J Williams, Spiro C Raftopoulos, Donald Ormonde, Alan Moss, Karen Byth, Heok P'Ng, Hema Mahajan, Duncan McLeod, Michael J Bourke
Journal: Gut (2016)

<h3>Objective</h3> Endoscopic mucosal resection (EMR) is effective for large laterally spreading flat and sessile lesions (LSLs). Sessile serrated adenomas/polyps (SSA/Ps) are linked to the relative failure of colonoscopy to prevent proximal colorectal cancer. We aimed to examine the technical success, adverse events and recurrence following EMR for large SSA/Ps in comparison with large conventional adenomas. <h3>Design</h3> Over 74 months till August 2014, prospective multicentre data of LSLs ≥20 mm were analysed. A standardised dye-based conventional EMR technique followed by scheduled surveillance colonoscopy was used. <h3>Results</h3> From a total of 2000 lesions, 323 SSA/Ps in 246 patients and 1527 adenomas in 1425 patients were included for analysis. Technical success for EMR was superior in SSA/Ps compared with adenomas (99.1% vs 94.5%, p&lt;0.001). Significant bleeding and perforation were similar in both cohorts. The cumulative recurrence rates for adenomas after 6, 12, 18 and 24 months were 16.1%, 20.4%, 23.4% and 28.4%, respectively. For SSA/Ps, they were 6.3% at 6 months and 7.0% from 12 months onwards (p&lt;0.001). Following multivariable adjustment, the HR of recurrence for adenomas versus SSA/Ps was 1.7 (95% CI 0.9 to 3.0, p=0.097). Subgroup analysis by lesion size revealed an eightfold increased risk of recurrence for 20–25 mm adenomas versus SSA/Ps, but no significantly different risk between lesion types in larger lesion groups. <h3>Conclusion</h3> Recurrence after EMR of 20–25 mm LSLs is significantly less frequent in SSA/Ps compared with adenomatous lesions. SSA/Ps can be more effectively removed than adenomatous LSLs with equivalent safety. Ensuring complete initial resection is imperative for avoiding recurrence. <h3>Trial registration number</h3> ClinicalTrials.gov NCT01368289.
A note on racial bias in the admission of children and adolescents to state mental health facilities versus correctional facilities in New York
Authors: S L Kaplan, J Busner
Journal: American Journal of Psychiatry (1992)

In response to several studies suggesting that there is racial bias in the admission of proportionately more white children and adolescents to the child and adolescent mental health system than to the juvenile justice system, the authors tested whether white children and adolescents would be overrepresented compared with black children and adolescents in mental health facilities and underrepresented compared with black children and adolescents in juvenile correctional facilities when ethnic distribution in the general population was controlled.Ethnicity, age, and sex of all white, black, and Hispanic 10-18-year-olds admitted in a 1-year period to facilities of the Office of Mental Health and facilities of the correctional system (the Division for Youth) of New York State were converted into rates per 100,000 population by using U.S. census data for the state. Admission rates per 100,000 population for ethnicity, age, sex, and source of referral were then compared in the two types of facilities.There were no meaningful differences in population-corrected admission rates among black, white, and Hispanic children and adolescents in the state mental health system. In contrast, there was a vast preponderance of black children and adolescents admitted to the state juvenile correctional system. The systems have different points of entry: 100% of the juvenile justice admissions versus 17% of the mental health admissions were referred by the courts.Analysis of demographic variables failed to support an allegation of racial bias in admission to the child and adolescent public mental health system in New York State.
Response to angiotensin blockade with irbesartan in a patient with metastatic colorectal cancer
Authors: M.R. Jones, K.A. Schrader, Y. Shen, E. Pleasance, C. Ch'ng, N. Dar, S. Yip, D.J. Renouf, J.E. Schein, A.J. Mungall, Y. Zhao, R. Moore, Y. Ma, B.S. Sheffield, T. Ng, S.J.M. Jones, M.A. Marra, J. Laskin, H.J. Lim
Journal: Annals of Oncology (2016)

BackgroundA patient suffering from metastatic colorectal cancer, treatment-related toxicity and resistance to standard chemotherapy and radiation was assessed as part of a personalized oncogenomics initiative to derive potential alternative therapeutic strategies.Patients and methodsWhole-genome and transcriptome sequencing was used to interrogate a metastatic tumor refractory to standard treatments of a patient with mismatch repair-deficient metastatic colorectal cancer.ResultsIntegrative genomic analysis indicated overexpression of the AP-1 transcriptional complex suggesting experimental therapeutic rationales, including blockade of the renin–angiotensin system. This led to the repurposing of the angiotensin II receptor antagonist, irbesartan, as an anticancer therapy, resulting in the patient experiencing a dramatic and durable response.ConclusionsThis case highlights the utility of comprehensive integrative genomic profiling and bioinformatics analysis to provide hypothetical rationales for personalized treatment options.
Sifalimumab, an anti-interferon-α monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study
Authors: Munther Khamashta, Joan T Merrill, Victoria P Werth, Richard Furie, Kenneth Kalunian, Gabor G Illei, Jorn Drappa, Liangwei Wang, Warren Greth
Journal: Annals of the Rheumatic Diseases (2016)

Objectives The efficacy and safety of sifalimumab were assessed in a phase IIb, randomised, double-blind, placebo-controlled study ( NCT01283139 ) of adults with moderate to severe active systemic lupus erythematosus (SLE). Methods 431 patients were randomised and received monthly intravenous sifalimumab (200 mg, 600 mg or 1200 mg) or placebo in addition to standard-of-care medications. Patients were stratified by disease activity, interferon gene-signature test (high vs low based on the expression of four genes) and geographical region. The primary efficacy end point was the percentage of patients achieving an SLE responder index response at week 52. Results Compared with placebo, a greater percentage of patients who received sifalimumab (all dosages) met the primary end point (placebo: 45.4%; 200 mg: 58.3%; 600 mg: 56.5%; 1200 mg 59.8%). Other improvements were seen in Cutaneous Lupus Erythematosus Disease Area and Severity Index score (200 mg and 1200 mg monthly), Physician's Global Assessment (600 mg and 1200 mg monthly), British Isles Lupus Assessment Group-based Composite Lupus Assessment (1200 mg monthly), 4-point reductions in the SLE Disease Activity Index−2000 score and reductions in counts of swollen joints and tender joints. Serious adverse events occurred in 17.6% of patients on placebo and 18.3% of patients on sifalimumab. Herpes zoster infections were more frequent with sifalimumab treatment. Conclusions Sifalimumab is a promising treatment for adults with SLE. Improvement was consistent across various clinical end points, including global and organ-specific measures of disease activity. Trial registration number NCT01283139; Results.
Detection of Bovine Leukemia Virus in B-Lymphocytes by the Syncytia Induction Assay 2
Authors: Prem S. Paul, Kem A. Pomeroy, Anthony E. Castro, Donald W. Johnson, Charles C. Muscoplat, Dale K. Sorensen
Journal: JNCI Journal of the National Cancer Institute (1977)

Bovine peripheral blood lymphocytes (PBL's) from 3 cows and 1 steer infected with bovine leukemia virus (BLV) were separated by fractionation through nylon wool columns into nylon-adherent and nonadherent cell populations. Nylon-adherent cells were enriched in B-lymphocytes, as determined by the presence of surface membrane immunoglobulins (slg), whereas nylon-nonadherent cells or "non-B-lymphocytes" contained few slg-bearing cells. PBL's and separated B- and non-B-lymphocyte populations were assayed for the presence of BLV by the induction of syncytia in bovine embryonic spleen cells. PBL's and B-lymphocyte populations both produced many syncytia, whereas non-B-lymphocytes yielded few or no syncytia. The specificity of syncytia induction for BLV was demonstrated by neutralization of syncytia formation by anti-BLV serum. PBL's from 2 control animals were negative for syncytia induction. This study presents further evidence that B-lymphocytes are the target cells for BLV infection.
Molecular Subtypes of<i>KIT/PDGFRA</i>Wild-Type Gastrointestinal Stromal Tumors
Authors: Sosipatros A. Boikos, Alberto S. Pappo, J. Keith Killian, Michael P. LaQuaglia, Chris B. Weldon, Suzanne George, Jonathan C. Trent, Margaret von Mehren, Jennifer A. Wright, Josh D. Schiffman, Margarita Raygada, Karel Pacak, Paul S. Meltzer, Markku M. Miettinen, Constantine Stratakis, Katherine A. Janeway, Lee J. Helman
Journal: JAMA Oncology (2016)

Wild-type (WT) gastrointestinal stromal tumors (GISTs), which lack KIT and PDGFRA gene mutations, are the primary form of GIST in children and occasionally occur in adults. They respond poorly to standard targeted therapy. Better molecular and clinical characterization could improve management.To evaluate the clinical and tumor genomic features of WT GIST.Patients enrolled in an observational study at the National Institutes of Health starting in 2008 and were evaluated in a GIST clinic held once or twice yearly. Patients provided access to existing medical records and tumor specimens. Self-referred or physician-referred patients younger than 19 years with GIST or 19 years or older with known WT GIST (no mutations in KIT or PDGFRA) were recruited; 116 patients with WT GIST were enrolled, and 95 had adequate tumor specimen available. Tumors were characterized by immunohistochemical analysis (IHC) for succinate dehydrogenase (SDH) subunit B, sequencing of SDH genes, and determination of SDHC promoter methylation. Testing of germline SDH genes was offered to consenting patients and families.For classification, tumors were characterized by SDHA, B, C, or D (SDHX) mutations and other genetic and epigenetic alterations, including presence of mutations in germline. Clinical characteristics were categorized.Wild-type GIST specimens from 95 patients (median age, 23 [range, 7-78] years; 70% female) were classified into 3 molecular subtypes: SDH-competent (n = 11), defined by detection of SDHB by IHC; and 2 types of SDH-deficient GIST (n = 84). Of SDH-deficient tumors, 63 (67%) had SDH mutations, and in 31 of 38 (82%), the SDHX mutation was also present in germline. Twenty-one (22%) SDH-deficient tumors had methylation of the SDHC promoter leading to silencing of expression. Mutations in known cancer-associated pathways were identified in 9 of 11 SDH-competent tumors. Among patients with SDH-mutant tumors, 62% were female (39 of 63), median (range) age was 23 (7-58) years, and approximately 30% presented with metastases (liver [12 of 58], peritoneal [6 of 58], lymph node [15 of 23]). SDHC-epimutant tumors mostly affected young females (20 of 21; median [range] age, 15 [8-50] years), and approximately 40% presented with metastases (liver [7 of 19], peritoneal [1 of 19], lymph node [3 of 8]). SDH-deficient tumors occurred only in the stomach and had an indolent course.An observational study of WT GIST permitted the evaluation of a large number of patients with this rare disease. Three molecular subtypes with implications for prognosis and clinical management were identified.
New Xenograft Model of Multiple Myeloma and Efficacy of a Humanized Antibody Against Human Interleukin-6 Receptor
Authors: Toshiaki Tsunenari, Yasuo Koishihara, Akito Nakamura, Miki Moriya, Hiroyuki Ohkawa, Hideo Goto, Chihiro Shimazaki, Masao Nakagawa, Yoshiyuki Ohsugi, Tadamitsu Kishimoto, Ken-ichi Akamatsu
Journal: Blood (1997)
Prevention of acute dystonic reactions in patients beginning high- potency neuroleptics [published erratum appears in Am J Psychiatry 1986 Sep;143(9):1204]
Authors: R S Winslow, V Stillner, D J Coons, M W Robison, M W Robinson
Journal: American Journal of Psychiatry (1986)

The authors performed a prospective double-blind study of 39 inpatients beginning high-potency neuroleptics. Patients were randomly assigned to a 7-day course of benztropine or placebo in addition to a neuroleptic. Of 17 patients receiving placebo, eight (47%) suffered an acute dystonic reaction; of 22 patients receiving benztropine, none suffered this reaction--a highly significant difference. The authors also found minimal anticholinergic toxicity attributable to the addition of benztropine to the neuroleptic regimen. These results suggest that an initial 7-day prophylaxis with benztropine is a high-benefit, low-risk adjunctive treatment to neuroleptic therapy.
Injury recurrence is lower at the highest professional football level than at national and amateur levels: does sports medicine and sports physiotherapy deliver?
Authors: Martin Hägglund, Markus Waldén, Jan Ekstrand
Journal: British Journal of Sports Medicine (2016)

Background Previous injury is a well-documented risk factor for football injury. The time trends and patterns of recurrent injuries at different playing levels are not clear. Aim To compare recurrent injury proportions, incidences and patterns between different football playing levels, and to study time trends in recurrent injury incidence. Methods Time-loss injuries were collected from injury surveillance of 43 top-level European professional teams (240 team-seasons), 19 Swedish premier division teams (82 team-seasons) and 10 Swedish amateur teams (10 team-seasons). Recurrent injury was defined as an injury of the same type and at the same site as an index injury within the preceding year, with injury &lt;2 months defined as an early recurrence, and &gt;2 months as a delayed recurrence. Seasonal trend for recurrent injury incidence, expressed as the average annual percentage of change, was analysed using linear regression. Results 13 050 injuries were included, 2449 (18.8%) being recurrent injuries, with 1944 early (14.9%) and 505 delayed recurrences (3.9%). Recurrence proportions were highest in the second half of the competitive season for all cohorts. Recurrence proportions differed between playing levels, with 35.1% in the amateur cohort, 25.0% in the Swedish elite cohort and 16.6% in the European cohort (χ 2 overall effect, p&lt;0.001). A decreasing trend was observed in recurrent injury incidence in the European cohort, a −2.9% average annual change over the 14-year study period (95% CI −5.4% to −0.4%, p=0.026). Similarly, a decreasing tendency was also seen in the Swedish premier division. Conclusions Recurrence proportions showed an inverse relationship with playing level, and recurrent injury incidence has decreased over the past decade.
Filamentous Protein of Basal Cell Epithelioma: Characteristics In Vivo and In Vitro&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Joseph Kubilus, Ph.D., Howard P. Baden, M.D.
 5, Norah McGilvray
Journal: JNCI Journal of the National Cancer Institute (1980)

The sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) pattern of the citrate-soluble fibrous protein isolated from human basal cell epitheliomas showed polypeptides with molecular weights of 43,000, 45,000, and 59,000. These polypeptides, found in the protein of normal epidermis, were present in a different proportion in this tumor tissue. Basal cell epitheliomas were cultured by the use of killed murine 3T3 feeder layers but only when 10(-9) M cholera toxin was present. The SDS-PAGE pattern of fibrous protein from cultured tumor cells was identical to the pattern of cultured normal human epidermal cells, and cornified cell envelopes were found in both types of cultures. Electron microscopy showed stratified cells that contained desmosomes, tonofilaments, and keratohyalin granules.
The group psychotherapy dropout phenomenon revisited
Authors: L M Lothstein
Journal: American Journal of Psychiatry (1978)

In this two-year study, patients referred for group therapy were extensively screened and carefully prepared for the therapy. In spite of this effort there was a 29% dorpout rate after group therapy began. All of the therapists reported that they disliked the patients who dropped out, and many of these patients were seen as hostile toward the therapists. The author suggests that for many groups the dropout phenomenom may be basic to the establishment of group cohesiveness and that instead of trying to prevent or reduce the dropout phenomenon, efforts should be directed toward reconceptualizing the more positive aspects of it.
Phase I study of Debio1143 (AT406) in combination with daunorubicin (D) and cytarabine (C) in patients with poor-risk acute myeloid leukemia (AML).
Authors: John F. DiPersio, Harry Paul Erba, Richard A. Larson, Selina M. Luger, Kenneth Francis Mangan, Martin S. Tallman, Jeffrey Mark Brill, Gregoire Vuagniaux, Elisabeth Rouits, Claudio Zanna, J. Mel Sorensen
Journal: Journal of Clinical Oncology (2014)

7029 Background: Treatment of AML remains difficult due to the development of treatment resistance. Inhibitors of apoptosis proteins (IAPs) are key negative modulators of apoptosis which represent attractive targets to overcome resistance to chemotherapy. The small molecule Debio 1143 (formerly AT-406) is an orally-active IAP antagonist able to promote apoptosis by restoring caspase activity and modulating the nuclear factor kappa-B signalling in multiple preclinical models, alone and/or in combination with chemotherapy. Methods: This multi-center, dose escalation study aimed to evaluate tolerability, pharmacokinetics (PK), pharmacodynamics, and efficacy of Debio 1143 when given along with D and C to poor-risk patients with AML during the induction cycle. Sequential patient cohorts received 100, 200, 300, or 400 mg of oral Debio 1143 on treatment days 1-5. Results: Twenty-nine patients were enrolled of whom 23 completed the study. Most common adverse events of any grade deemed related to the treatment were nausea (31% of patients), diarrhoea (14%), and febrile neutropenia (14%). 3 patients had dose-limiting toxicities: a G3/4 reversible ALT/AST elevation at 100mg, a G3 mucositis resulted in electrolyte abnormalities and cardiac arrhythmia at 200 mg, and a neutropenic fever and G4 heart failure at 400 mg. The maximum tolerated dose was not reached. Exposure was highly variable and increase exceeded dose-proportionality but no accumulation over 5 days was observed. Tmax was reached in about 2h and T1/2 was about 6h at day 1. PK of D and C were rather homogeneous among Debio 1143 dose groups. Debio 1143-induced degradation of cIAP-1 was detectable in CD34/CD117+ cells already at the lower dose. A total of 13 (47%) patients achieved complete remission, the majority in the 100 mg dose cohort. Of these, 8 (62%) relapsed still within the study period. Responders more frequently showed plasma increases of tumor necrosis factor alpha and IL-8 after the first dose of Debio 1143. Conclusions: Debio 1143 at doses up to 400 mg/day showed good tolerability and can be safely combined with D and C. The efficacy data are inconclusive but warrant further studies in subsets of patients with AML. Clinical trial information: NCT01265199.
Lymphoproliferative Diseases of Fowl: Chromosome Breaks Caused in Lymphocytes by JM-V Herpesvirus2
Authors: J. W. Yoon, S. N. Kim, E. C. Hahn, A. J. Kenyon
Journal: JNCI Journal of the National Cancer Institute (1976)

Chromosome preparations were made of bone marrow cells and peripheral lymphocytes isolated from chicks that developed leukemia following infection with JM-V herpes-virus. Karyotypic analysis revealed a high frequency of chromosome breaks and aneuploidy, as well as some pulverization of chromosomes. The number of chromosome breaks began to increase at 2-3 days post infection, and by 5 days post infection it reached 12.7% of bone marrow cells and 17.2% of peripheral lymphocytes. Similarly, the number of aneuploid metaphase figures increased rapidly and reached 12% of bone marrow cells and 19% of peripheral lymphocytes at 5 days post infection. Some specificity was observed in the chromosomes that were affected.
PTU-086 Results of the initial pilot of the new JAG approved web-based e-Portfolio for trainees in endoscopy
Authors: T Mehta, J Wood, L Pettitt, H Youssef, B Disney, L Merricks, S Harnden, B McKaig, K Dowler, R Valori, P Dunckley
Journal: Gut (2010)

<h3>Introduction</h3> To date there has been no uniform way for trainees to log endoscopic experience. There is an increased requirement for trainees to provide evidence of endoscopic experience and performance. A new JETS e-Portfolio for trainee endoscopists has been designed and sponsored by JAG and the National Endoscopy Team. This web-based system will form part of the JAG Endoscopy Training System (JETS). The JETS E-Portfolio has been designed to provide a user-friendly, web-based, easily accessible portal for logging procedures. It creates detailed outputs that provide all of the summary and performance data required for annual trainee assessments and JAG accreditation. Data input takes a minimal amount of time and the e-Portfolio supports the JAG-approved directly observed procedures (DOPS) forms; the learning objectives from which auto-populate a personal development plan. <h3>Methods</h3> The JETS e-Portfolio was piloted during a 3 month period between April and July 2009 across Gloucestershire NHS Trust and New Cross Hospital, Wolverhampton. All trainees were invited by e-mail to start using the system. All trainees and trainers were asked to feedback on the applicability, acceptability and functionality of e-Portfolio. Here we present the uptake data. <h3>Results</h3> 23 (88%) trainees have chosen to log on to use the system. During the pilot, these trainees added 1529 procedures from 301 lists. 53.2% of trainees added &gt;20 procedures. This is an average of 13 lists and 66.5 procedures per trainee. 97 DOPS were recorded, an average of 4.2 per trainee. Nurse endoscopists were more likely to use the system (141 procedures added per endoscopist) compared with medical trainees (95 procedures per trainee or surgical trainees (20 procedures per trainee). Of those trainees that fed back, all felt that the system was well designed and easy to use and all wanted to continue to use the system. <h3>Conclusion</h3> Results from this pilot show an excellent voluntary uptake of the JETS e-Portfolio by trainees. Feedback was good. A final version of the JETS e-Portfolio had now been released and can be used by any trainee in any trust. Further information can be found on the JAG website.