tbuckley/cabot-search huggingface dataset:
Is unintentional doping real, or just an excuse?
Authors: Derwin King Chung Chan, Tracy Chor Wai Tang, Patrick Shu-Hang Yung, Daniel F Gucciardi, Martin S Hagger
Journal: British Journal of Sports Medicine (2017)

There has been increased attention on athletes' intentions and motives for doping.However, the majority of studies on doping intentions to date have assumed that doping is a consciously-controlled, goal-directed behaviour, and neglected the possibility that athletes could be unwittingly and unintentionally exposed to doping.Unintentional doping is often regarded as an excuse given by athletes caught doping, but it could happen in circumstances where athletes are unaware that the food, drinks, supplements, or medications they consume contain banned performanceenhancing drugs.Research into unintentional doping is in its infancy, but debates persist about the importance of this controversal topic.In this article we discuss the importance of unintentional doping as an issue in sport.We discuss the relevance of this research area based on statistics, reports, and recommendations (e.g., antidoping codes) offered by WADA, together with the evidence from recent empirical research.We also outline the importance of formative research on effective interventions to manage unintentional doping.
A FUNCTIONAL STUDY OF THE EFFECT OF THE 14 BP INSERTION DELETION POLYMORPHISM OF THE HLA-G GENE ON RESPONSE TO IMMUNOMODULATORY THERAPY IN INFLAMMATORY BOWEL DISEASE
Authors: B. Baburajan, N. Prescott, B. Hudspith, A. Ansari, M. Smith, M. Arenas-Hernandes, C. Mathew, L. Fairbanks, C. Lewis, A. Marinaki, J. Sanderson
Journal: Gut (2009)
Microbiomarkers in inflammatory bowel diseases: caveats come with caviar
Authors: Felix Sommer, Malte Christoph Rühlemann, Corinna Bang, Marc Höppner, Ateequr Rehman, Christoph Kaleta, Phillippe Schmitt-Kopplin, Astrid Dempfle, Stephan Weidinger, Eva Ellinghaus, Susanne Krauss-Etschmann, Dirk Schmidt-Arras, Konrad Aden, Dominik Schulte, David Ellinghaus, Stefan Schreiber, Andreas Tholey, Jan Rupp, Matthias Laudes, John F Baines, Philip Rosenstiel, Andre Franke
Journal: Gut (2017)

The largest numbers of commensal bacteria reside within our intestinal tract, with an increasing density from mouth to anus. Recently, a new estimate for the total number of bacteria (3.8×1013) in the 70 kg ‘reference man’ was reported.1 For human cells, the same authors revised past estimates to 3.0×1013 cells, out of which approximately 90% belong to the haematopoietic lineage. Hence, the widely cited 10:1 ratio of bacteria versus human cells received an update, showing that the number of bacteria in the body is actually of the same order as the number of human cells, and that the cumulative bacterial mass is about 200 g. Still, this large number of bacteria highlights their importance in maintaining health and metabolism. Different parts of the intestinal tract have different functions, tissue structure varies accordingly and gradients exist for several physicochemical parameters such as nutrients, pH or oxygen levels.2 Consequently, microbiota composition varies along the gut, but also between luminal and mucosa-attached communities of the same intestinal segment, and even along the crypt-villus axis in the epithelium. Thus, host–microbiota interactions are likely regionally specific and the local crosstalk determines intestinal function and physiology. Probably each human individual carries its own ‘microbial fingerprint’ (especially when considering genomic variation within the bacterial species’ populations), which is why forensic scientists started to exploit the use of this non-human organ.3

Recent large-scale analyses of population-based cohorts with >1000 samples validated that body mass index, age at sampling and gender are important covariates that need to be included in microbiome association analyses.4 In sum, Falony et al identified 18 covariates, including stool consistency, dietary factors and blood traits, cumulatively explaining 7.7% of the total variation in the gut microbiota, leaving 92.3% of the interindividual microbial variation unexplained. In a …
Somatostain receptor (SSTR)-targeted therapy in pulmonary large-cell neuroendocrine carcinoma (LCNEC) patients with intermediate proliferation rate (PR).
Authors: Haim Biran, Marina Perelman, Jair Bar, Tzila S. Zwas
Journal: Journal of Clinical Oncology (2012)

e17509 Background: LCNEC is classified as a high-grade (HG) foregut-derived neuroendocrine tumor (NET), exceeded only by small-cell lung carcinoma (SCLC) in terms of aggressiveness. It is a recent disease entity, only two decades old, and uncommon: 2%-3% of all lung cancer cases. Therefore, therapy guidelines are still evolving. Methods: A single institution observational study, consecutive series. Histopathology diagnosis conformed to WHO criteria for thoracic tumors (Travis et al, IARC Press, 2004). Immunohistochemistry included proliferation Ki67 index evaluation. SSTRs' affinity was assessed either by 111 In octreotate SPECT, or by Ga68 DOTA-NOC octreotate PET CT total body scans. Results: We have treated nine metastatic LCNEC patients over the last four years. Seven were scanned for presence of somatostatin receptors; 4 were positive. Three of the four had Ki67 staining ranging 10-20% (intermediate PR, IPR), one had 80% (high PR). All four have received octreotide LAR as a therapy component. In two cases octreotide was given upfront and conferred PFS of 18 and 8 months and, in the former- regression of hepatic lesions. The other patient also received 177 Lutetium radionuclide therapy (PRRT) upon progression, resulting in uptake normalization at an hepatic mass and stabilization of other lesions. The 3rd patient had started with induction chemotherapy and then maintained imaging-confirmed stable disease and normal function, during octreotide treatment, for three years. The fourth, HG patient, survived only 8 months. Three of the 9 patients are alive with disease on treatment, surviving 25+, 57+ and one, with 50% proliferation index and a negative DOTANOC scan, has survived 16+ months, with no targeted therapy. Conclusions: This small series illustrates the diagnostic value and therapeutic implication of SSTR scans, combined with Ki67 assessment, aiming at therapy selection for IPR subgroup, receptor positive, pulmonary LCNEC patients who can benefit from octreotide targeted therapy.
PTSD Psychotherapy Outcome Predicted by Brain Activation During Emotional Reactivity and Regulation
Authors: Gregory A. Fonzo, Madeleine S. Goodkind, Desmond J. Oathes, Yevgeniya V. Zaiko, Meredith Harvey, Kathy K. Peng, M. Elizabeth Weiss, Allison L. Thompson, Sanno E. Zack, Steven E. Lindley, Bruce A. Arnow, Booil Jo, James J. Gross, Barbara O. Rothbaum, Amit Etkin
Journal: American Journal of Psychiatry (2017)

Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but many patients do not respond. Brain functions governing treatment outcome are not well characterized. The authors examined brain systems relevant to emotional reactivity and regulation, constructs that are thought to be central to PTSD and exposure therapy effects, to identify the functional traits of individuals most likely to benefit from treatment.Individuals with PTSD underwent functional MRI (fMRI) while completing three tasks assessing emotional reactivity and regulation. Participants were then randomly assigned to immediate prolonged exposure treatment (N=36) or a waiting list condition (N=30). A random subset of the prolonged exposure group (N=17) underwent single-pulse transcranial magnetic stimulation (TMS) concurrent with fMRI to examine whether predictive activation patterns reflect causal influence within circuits. Linear mixed-effects modeling in line with the intent-to-treat principle was used to examine how baseline brain function moderated the effect of treatment on PTSD symptoms.At baseline, individuals with larger treatment-related symptom reductions (compared with the waiting list condition) demonstrated 1) greater dorsal prefrontal activation and 2) less left amygdala activation, both during emotion reactivity; 3) better inhibition of the left amygdala induced by single TMS pulses to the right dorsolateral prefrontal cortex; and 4) greater ventromedial prefrontal/ventral striatal activation during emotional conflict regulation. Reappraisal-related activation was not a significant moderator of the treatment effect.Capacity to benefit from prolonged exposure in PTSD is gated by the degree to which prefrontal resources are spontaneously engaged when superficially processing threat and adaptively mitigating emotional interference, but not when deliberately reducing negative emotionality.
Evaluation of risk recurrence in early breast cancer assessed by Oncotype DX and tumor cell dissemination to blood and bone marrow.
Authors: Bahriye Aktas, Agnes Bankfalvi, Martin Leonhard Heubner, Rainer Kimmig, Sabine Kasimir-Bauer
Journal: Journal of Clinical Oncology (2013)

e11516 Background: The OncotypeDX assay is a validated genomic test that predicts the likelihood of breast cancer (BC) recurrence, patients’ (pts) survival within 10 years of diagnosis and benefit of chemotherapy in early-stage, N0, ER-pos BC. In addition, disseminated tumor cells (DTC) in the bone marrow (BM) and circulating tumor cells (CTCs) in blood, especially stemness like tumor cells (slCTCs) including cells being able to perform epithelial-mesenchymal transition (EMT), have been associated with worse outcome in BC. Here we use OncotypeDX as well as the presence of DTCs, CTCs and slCTCs to evaluate the risk for recurrence in early BC pts. Methods: In total, 90 pts with newly diagnosed HER2-neg early stage BC received breast conserving surgery and sentinel lymphonodectomy. 17 pts were ER-/PR-, 12 pts ER+/PR-, 3 pts ER-/PR+ and 59 pts were ER+/PR+. Analysis of OncotypeDX and KI67 were performed. In case of G2 tumors, UPA and PAI1 were determined as further proliferation markers in tissue samples. Two BM aspirates from these patients were analyzed by immunocytochemistry for DTCs using the pan-cytokeratin antibody A45-B/B3. Furthermore, 2 x5 ml blood were analyzed for CTCs with the AdnaTest BreastCancer for the detection of EpCAM, MUC-1, HER-2, and beta-Actin transcripts. The recovered c-DNA was additionally multiplex tested for the presence of slCTCs using the AdnaTest EMT (multiplex RT-PCR for TWIST, AKT2, PI3K), and the AdnaTest TumorStemCell (ALDH1). Results: OncotypeDX was performed in 68/91 cases. 30/68 pts (44%) had a low RS, 29/68 pts (43%) an intermediate RS and 9/68 pts (13%) a high RS, respectively. BM aspiration could be performed in 70/91 pts with a positivity rate of 34% (24/70) for DTCs. CTCs were detected in 16/68 (25%) evaluable pts and slCTCs in 27/62 (44%) pts, respectively. In preliminary statistical analysis, KI67, PR and grading are showing association to RS as well as the presence of slCTCs. Tissue samples of patients with G2 tumors (N=65) underwent evaluation for UPA/PAI1analysis. Conclusions: Final statistical analysis for the complete data set including correlations to RS with all evaluable parameter will be available for presentation at the ASCO.
Incidence and risk of rash to mTOR inhibitors in cancer patients: A meta-analysis of randomized controlled trials.
Authors: Raji Shameem, Mario E. Lacouture, Shenhong Wu
Journal: Journal of Clinical Oncology (2014)

e17585 Background: Inhibitors of the mammalian target of rapamycin (mTOR) are currently approved for the treatment of several cancers, and their use is associated with skin rash, which may lead to undesirable dose reductions or interruptions. A meta-analysis of randomized controlled trials (RCTs) was performed to determine the overall risk of developing rash with mTOR inhibitors. Methods: We searched the PubMed database and abstracts presented at the American Society of Clinical Oncology (ASCO) meetings up to December 2013 for relevant studies. Eligible studies included RCTs in which everolimus or temsirolimus was compared to controls in cancer patients. The summary incidence, relative risk (RR), and 95% confidence intervals (CI) were calculated using a random- or fixed-effects model depending on the heterogeneity of the included trials. Results: A total of 11 RCTs with 4,752 patients (mTORs: 2,725, controls: 2,027) with a variety of solid tumors were included in the analysis. The incidences of all-grade (grade 1-4) and high-grade rash (grade 3-4) were 27.3% (95% CI: 21.0-34.7%) and 1.0% (95% CI: 0.6-1.4%) respectively. In comparison with controls, mTOR inhibitors significantly increased the risk for developing all-grade rash (RR=3.55, 95% CI: 3.0-4.20, P<0.001) and high-grade rash (RR=4.25, 95% CI: 1.63-11.10, P=0.003). The increased risk of high-grade rash did not vary significantly among different tumors (P=0.91). There was no significant difference between everolimus and temsirolimus (P=0.60). There was also no significant difference between mTOR inhibitors alone and in combination with other agents (P=0.57). Conclusions: Everolimus and temsirolimus significantly increased the risk of rash in cancer patients. Early recognition and appropriate treatment is recommended.
Pericardial Tamponade Caused by a Hypersensitivity Response to Tuberculosis Reactivation after Anti–PD-1 Treatment in a Patient with Advanced Pulmonary Adenocarcinoma
Authors: Yi-Chun Chu, Ke-Chin Fang, Hsing-Chun Chen, Yi-Chen Yeh, Chih-En Tseng, Teh-Ying Chou, Chun-Liang Lai
Journal: Journal of Thoracic Oncology (2017)
TCR Repertoire Intratumor Heterogeneity in Localized Lung Adenocarcinomas: An Association with Predicted Neoantigen Heterogeneity and Postsurgical Recurrence
Authors: Alexandre Reuben, Rachel Gittelman, Jianjun Gao, Jiexin Zhang, Erik C. Yusko, Chang-Jiun Wu, Ryan Emerson, Jianhua Zhang, Christopher Tipton, Jun Li, Kelly Quek, Vancheswaran Gopalakrishnan, Runzhe Chen, Luis M. Vence, Tina Cascone, Marissa Vignali, Junya Fujimoto, Jaime Rodriguez-Canales, Edwin R. Parra, Latasha D. Little, Curtis Gumbs, Marie-Andrée Forget, Lorenzo Federico, Cara Haymaker, Carmen Behrens, Sharon Benzeno, Chantale Bernatchez, Boris Sepesi, Don L. Gibbons, Jennifer A. Wargo, William N. William, Stephen Swisher, John V. Heymach, Harlan Robins, J. Jack Lee, Padmanee Sharma, James P. Allison, P. Andrew Futreal, Ignacio I. Wistuba, Jianjun Zhang
Journal: Cancer Discovery (2017)

Genomic intratumor heterogeneity (ITH) may be associated with postsurgical relapse of localized lung adenocarcinomas. Recently, mutations, through generation of neoantigens, were shown to alter tumor immunogenicity through T-cell responses. Here, we performed sequencing of the T-cell receptor (TCR) in 45 tumor regions from 11 localized lung adenocarcinomas and observed substantial intratumor differences in T-cell density and clonality with the majority of T-cell clones restricted to individual tumor regions. TCR ITH positively correlated with predicted neoantigen ITH, suggesting that spatial differences in the T-cell repertoire may be driven by distinct neoantigens in different tumor regions. Finally, a higher degree of TCR ITH was associated with an increased risk of postsurgical relapse and shorter disease-free survival, suggesting a potential clinical significance of T-cell repertoire heterogeneity.Significance: The present study provides insights into the ITH of the T-cell repertoire in localized lung adenocarcinomas and its potential biological and clinical impact. The results suggest that T-cell repertoire ITH may be tightly associated to genomic ITH and disease relapse. Cancer Discov; 7(10); 1088-97. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 1047.
Nivolumab in combination with daratumumab, with or without pomalidomide and dexamethasone, for relapsed/refractory multiple myeloma: 2 cohorts of the phase 1 CheckMate 039 safety study.
Authors: Alexander M. Lesokhin, Shaji Kumar, Mihaela A. Popa McKiver, Lili Zhu, Benedetto Farsaci, Ivan Borrello
Journal: Journal of Clinical Oncology (2017)

TPS3102 Background: Multiple myeloma (MM) is largely incurable despite available therapies, including immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and monoclonal antibodies (mAbs). As most MM patients (pts) eventually have relapsed/refractory (RR) disease, there is an unmet need. Myeloma cells upregulate PD-L1 [Liu et al, 2007]. Nivolumab (nivo), an immuno-oncology mAb, binds PD-1 on T cells and natural killer cells and inhibits signaling by PD-L1–expressing tumor cells, thus augmenting antitumor immunity. Nivo monotherapy has shown acceptable safety and modest clinical activity in RRMM [Lesokhin et al 2016]. Daratumumab (dara) is a cytolytic mAb that targets CD38+ myeloma cells, inducing antibody‐dependent cellular cytotoxicity, complement-dependent cytotoxicity, antibody-dependent cellular phagocytosis, and apoptosis, and may have an immunomodulatory role via depletion of CD38+ immune-suppressor cells [Dimopoulos et al 2016]. Dara is approved as monotherapy (US: after ≥3 prior lines of therapy; EU: after a prior PI and IMiD and progression on last therapy), and with lenalidomide/dexamethasone (dex) or bortezomib/dex (US: after ≥1 prior line of therapy for both combinations). Combining PD-1 and CD38 mAbs, immunotherapies with different mechanisms of action, may overcome resistance and improve outcomes. This phase 1 safety study (NCT01592370) includes multiple cohorts of nivo as monotherapy or in combination regimens across RR hematologic malignancies; 2 MM cohorts will evaluate nivo plus dara, with or without pomalidomide and dex. Methods: Eligible pts are aged ≥18 y, with RRMM after ≥2 prior therapies. Pts are RR to their last regimen, RR to prior IMiD and PI therapy, and agreed to bone marrow aspiration. Primary outcome of safety/tolerability will be measured by incidence of drug-related adverse events (AEs), serious AEs, and laboratory test abnormalities. Secondary endpoints include minimal residual disease, overall response rates and duration of response, and progression-free survival. Study funding: BMS. Writing support: C Tomas, Caudex, funded by BMS. Clinical trial information: NCT01592370.
Protesters show support for assisted dying campaigner
Authors: Abi Rimmer
Journal: BMJ (2017)

Campaign for Dignity in Dying

More than 200 people took to a boat on the Thames outside the Houses of Parliament in London last week to show their support for Noel Conway, who is attempting to overturn the ban on assisted dying in the UK.

Conway, a retired college lecturer from Shropshire, was given a diagnosis of amyotrophic lateral sclerosis, a form of motor neurone disease, in November 2014, and is not expected to live more than 12 months.

He was too ill to attend the High Court in London …
Correlation between vitamin D deficiency and metastatic breast carcinoma in a predominantly Hispanic population: A retrospective study.
Authors: Saurabh Deepak Chitnis, Andrea M. Popescu-Martinez
Journal: Journal of Clinical Oncology (2017)

e12553 Background: There have been numerous studies conducted linking Vitamin D deficiency to various cancers, including cancers of the breast. Studies associating Vitamin D deficiency and Breast cancer have shown mixed results in patients with no clear consensus. Recently published in vitro studies have shown that the active form of Vitamin D can inhibit the metastatic capability of breast cancer cell lines to bone. Based on this we aimed to elucidate whether there exists any correlation between Vitamin D deficiency at diagnosis and Metastatic breast cancer. Methods: Retrospective analysis of the EMR for women diagnosed with breast cancer and enrolled in Oncology database seen at NYMC-Metropolitan Hospital Center from 2010-2016 was done. Patients were grouped into either breast cancer with metastases or without metastases and their Vitamin D levels at diagnosis were reviewed. Patients with 25- Hydroxy Vitamin D levels measured within one year of diagnosis of breast cancer were included for the study. Study was planned from 2010-2016 specifically as Vitamin D levels for patients were not monitored as frequently prior to 2010. Results: From total of 102 patients who started follow up with Oncology clinic during the study time period, 2 were referred to our center for further management with diagnosis made prior to 2010 and were not included in the study. Out of the 100 patients considered, 58 patients had Vitamin D levels measured within a year of diagnosis of breast cancer and were included in the study. 70% of the population was Latino/Hispanic. The table represents the results of the study. Odds ratio for a patient with Vit D deficiency to develop metastatic breast cancer was 0.92 and relative risk was calculated to be 0.93. Conclusions: Based on above results, the outcome was similar in both groups. The odd’s ratio and the relative risk imply that there was no difference evidenced between both groups. These findings signify that there was no direct correlation between Metastatic breast cancer and Vitamin D deficiency at time of diagnosis in the population seen at our center. [Table: see text]
General practitioners' awareness of colorectal cancer.
Authors: S Nichols
Journal: BMJ (1990)

A survey was carried out in Portsmouth to find out what general practitioners knew about colorectal cancer and what their views were on screening. A random sample of general practitioners was interviewed by questionnaire and the remainder asked to complete the questionnaire themselves. The overall response rate was 62%. There was a higher response rate from women doctors and from the group that was interviewed. For some questions there was a difference in the pattern of responses given by the interview group and the group who completed the questionnaire themselves.The level of knowledge of colorectal cancer varied according to which aspect was questioned. The general practitioners knew the symptoms well but were less aware of the vital statistics and risk factors. Most doctors were not in favour of screening by testing for faecal occult blood.