tbuckley/cabot-search huggingface dataset:
Randomised controlled trials (RCTs) in sports injury research: authors—please report the compliance with the intervention
Authors: Rasmus Oestergaard Nielsen, Michael Lejbach Bertelsen, Daniel Ramskov, Camma Damsted, Evert Verhagen, Steef W Bredeweg, Daniel Theisen, Laurent Malisoux
Journal: British Journal of Sports Medicine (2019)

Background In randomised controlled trials (RCTs) of interventions that aim to prevent sports injuries, the intention-to-treat principle is a recommended analysis method and one emphasised in the Consolidated Standards of Reporting Trials (CONSORT) statement that guides quality reporting of such trials. However, an important element of injury prevention trials—compliance with the intervention—is not always well-reported. The purpose of the present educational review was to describe the compliance during follow-up in eight large-scale sports injury trials and address compliance issues that surfaced. Then, we discuss how readers and researchers might consider interpreting results from intention-to-treat analyses depending on the observed compliance with the intervention. Methods Data from seven different randomised trials and one experimental study were included in the present educational review. In the trials that used training programme as an intervention, we defined full compliance as having completed the programme within ±10% of the prescribed running distance (ProjectRun21 (PR21), RUNCLEVER, Start 2 Run) or time-spent-running in minutes (Groningen Novice Running (GRONORUN)) for each planned training session. In the trials using running shoes as the intervention, full compliance was defined as wearing the prescribed running shoe in all running sessions the participants completed during follow-up. Results In the trials that used a running programme intervention, the number of participants who had been fully compliant was 0 of 839 (0%) at 24-week follow-up in RUNCLEVER, 0 of 612 (0%) at 14-week follow-up in PR21, 12 of 56 (21%) at 4-week follow-up in Start 2 Run and 8 of 532 (1%) at 8-week follow-up in GRONORUN. In the trials using a shoe-related intervention, the numbers of participants who had been fully compliant at the end of follow-up were 207 of 304 (68%) in the 21 week trial, and 322 of 423 (76%), 521 of 577 (90%), 753 of 874 (86%) after 24-week follow-up in the other three trials, respectively. Conclusion The proportion of runners compliant at the end of follow-up ranged from 0% to 21% in the trials using running programme as intervention and from 68% to 90% in the trials using running shoes as intervention. We encourage sports injury researchers to carefully assess and report the compliance with intervention in their articles, use appropriate analytical approaches and take compliance into account when drawing study conclusions. In studies with low compliance, G-estimation may be a useful analytical tool provided certain assumptions are met.
Partha Kar: The NHS really isn’t a bad place to work
Authors: Partha Kar
Journal: BMJ (2019)

The NHS always polarises opinion, and many who work there are constantly divided over whether we should highlight its faults or champion it as a great place to work. If we dwell on its faults we can seem like dour shroud wavers, set on deterring the next generation from following in our footsteps. But, if we champion it unreservedly, we risk coming across as blindly optimistic evangelists.

I interact with enough junior doctors to know that they’re as dedicated to working hard and helping people as the doctors I trained with. It’s not their fault if today’s working hours …
Genomic copy number alterations in non-small cell lung cancers identified using CBS and MSA
Authors: M. S. Park, C. Ma, M. U. Aziz, S. Rao, K. Gold, M. Samanta, M. Guttman, G. R. Grant, A. Vachani, M. S. Brose
Journal: Journal of Clinical Oncology (2007)

7695 Background: Lung cancer is the leading cause of cancer death in both men and women with a 5-yr survival rate of 15.5%. Previous studies have begun to characterized genomic copy number alterations of non-small-cell lung CA using array CGH and SNP arrays. We have used aCGH using our 1MB BAC arrays and two algorthims for making copy number alteration (CNA) determinations. We have also pursued the exact copy number gains and losses of several genes using Q-PCR. Methods: Genomic DNA from fresh frozen tumors of 27 patients with NSCLC. We performed aCGH using 1MB Arrays. We used CBS, and MSA to identify regions of CNA. We further pursued several genes of interest (including HRAS, CRK, and CDC42) identified using Q-PCR. Unsupervised hierarchical clustering was performed to look for distinct subgroups. Significant Analysis of Microarrays (SAM) was applied to identify the association between CNAs clinical parameters including tumor subtype, gender, lymph node involvement, tumor stage, and overall survival. Results: 240 regions of amplification and 181 regions of deletions were found, and included all previously published regions implicated in lung cancer. CNAs in &gt; 70% of tumors included amplifications in 1q, 3q, 5p, 6p, 11p, 16q, 20q, and Xq, and deletions in 1p, 8p and 13q. We verified CNAs of HRAS, CRK and CDC42 using Q-PCR. Hierarchical clustering revealed 2 subgroups: one with amplifications in 2q, 4p, 4q, 8q, 21q, 15q, and 16p, and the other with amplifications in 3q, and 5q. These were confirmed by supervised SAM analysis. Using SAM we found that gain of 2q, 4p and 10q, and loss of 16p and 19q were significantly present in adenocarcinomas. (q = 0, FDR = 0%). Gain of 10q, and loss of 6p and 14q were associated with female gender. (q = 0, FDR = 0%). Conclusions: We used aCGH to identify CNAs that characterize non-small cell lung CA tumors with the aim of finding key regions which may harbor important oncogenes and tumor suppressors. Several regions of CNA have been identified, several of which have been associated with clinical parameters. Because much heterogeneity exists in non-small-cell lung tumors, we have demonstrated that clustering analysis is useful in identifying subtypes which may possess prognostic and therapeutic significance. No significant financial relationships to disclose.
Artificial Intelligence-assisted System Improves Endoscopic Identification of Colorectal Neoplasms
Authors: Shin-ei Kudo, Masashi Misawa, Yuichi Mori, Kinichi Hotta, Kazuo Ohtsuka, Hiroaki Ikematsu, Yutaka Saito, Kenichi Takeda, Hiroki Nakamura, Katsuro Ichimasa, Tomoyuki Ishigaki, Naoya Toyoshima, Toyoki Kudo, Takemasa Hayashi, Kunihiko Wakamura, Toshiyuki Baba, Fumio Ishida, Haruhiro Inoue, Hayato Itoh, Masahiro Oda, Kensaku Mori
Journal: Clinical Gastroenterology and Hepatology (2019)
Doxycycline-Dependent Self-Inactivation of CRISPR-Cas9 to Temporally Regulate On- and Off-Target Editing
Authors: Anju Kelkar, Yuqi Zhu, Theodore Groth, Gino Stolfa, Aimee B. Stablewski, Naina Singhi, Michael Nemeth, Sriram Neelamegham
Journal: Molecular Therapy (2019)

Exome and deep sequencing of cells treated with a panel of lentiviral guide RNA demonstrate that both on- and off-target editing proceed in a time-dependent manner. Thus, methods to temporally control Cas9 activity would be beneficial. To address this need, we describe a "self-inactivating CRISPR (SiC)" system consisting of a single guide RNA that deactivates the Streptococcus pyogenes Cas9 nuclease in a doxycycline-dependent manner. This enables defined, temporal control of Cas9 activity in any cell type and also in vivo. Results show that SiC may enable a reduction in off-target editing, with less effect on on-target editing rates. This tool facilitates diverse applications including (1) the timed regulation of genetic knockouts in hard-to-transfect cells using lentivirus, including human leukocytes for the identification of glycogenes regulating leukocyte-endothelial cell adhesion; (2) genome-wide lentiviral sgRNA (single guide RNA) library applications where Cas9 activity is ablated after allowing pre-determined editing times. Thus, stable knockout cell pools are created for functional screens; and (3) temporal control of Cas9-mediated editing of myeloid and lymphoid cells in vivo, both in mouse peripheral blood and bone marrow. Overall, SiC enables temporal control of gene editing and may be applied in diverse application including studies that aim to reduce off-target genome editing. Exome and deep sequencing of cells treated with a panel of lentiviral guide RNA demonstrate that both on- and off-target editing proceed in a time-dependent manner. Thus, methods to temporally control Cas9 activity would be beneficial. To address this need, we describe a "self-inactivating CRISPR (SiC)" system consisting of a single guide RNA that deactivates the Streptococcus pyogenes Cas9 nuclease in a doxycycline-dependent manner. This enables defined, temporal control of Cas9 activity in any cell type and also in vivo. Results show that SiC may enable a reduction in off-target editing, with less effect on on-target editing rates. This tool facilitates diverse applications including (1) the timed regulation of genetic knockouts in hard-to-transfect cells using lentivirus, including human leukocytes for the identification of glycogenes regulating leukocyte-endothelial cell adhesion; (2) genome-wide lentiviral sgRNA (single guide RNA) library applications where Cas9 activity is ablated after allowing pre-determined editing times. Thus, stable knockout cell pools are created for functional screens; and (3) temporal control of Cas9-mediated editing of myeloid and lymphoid cells in vivo, both in mouse peripheral blood and bone marrow. Overall, SiC enables temporal control of gene editing and may be applied in diverse application including studies that aim to reduce off-target genome editing.
Life’s Simple 7 likely to be associated with dementia risk reduction in both midlife and older age groups
Authors: Janice L Atkins, João Delgado, David Melzer
Journal: BMJ (2019)

We read with interest the recent study1 by Sabia et al showing that adherence to Life’s Simple 7 ideal cardiovascular health recommendations in midlife (age 50 years) was associated with a lower dementia risk in later life, with …
Combined Intrahospital Remote Ischemic Perconditioning and Postconditioning Improves Clinical Outcome in ST-Elevation Myocardial Infarction
Authors: Thomas Stiermaier, Jan-Oluf Jensen, Karl-Philipp Rommel, Suzanne de Waha-Thiele, Georg Fuernau, Steffen Desch, Holger Thiele, Ingo Eitel
Journal: Circulation Research (2019)

Remote ischemic conditioning (RIC) or ischemic postconditioning (PostC) may protect the myocardium from ischemia-reperfusion injury in patients with ST-segment-elevation myocardial infarction.To determine whether combined intrahospital RIC and PostC or PostC alone in addition to primary percutaneous coronary intervention (PCI) reduce long-term clinical events after ST-segment-elevation myocardial infarction.The present study is a post hoc analysis of a prospective trial which randomized 696 ST-segment-elevation myocardial infarction patients with symptoms <12 hours 1:1:1 to either combined RIC and PostC in addition to primary PCI, PostC alone in addition to primary PCI, or conventional PCI (control). Three cycles of RIC were performed by inflation of an upper arm blood pressure cuff for 5 minutes followed by deflation for 5 minutes. PostC was performed after primary PCI via 4 cycles of 30 seconds balloon occlusions followed by 30 seconds of reperfusion. Major adverse cardiac events consisting of cardiac death, reinfarction, and new congestive heart failure were assessed during long-term follow-up. Follow-up data were obtained in 97% of patients in median 3.6 years after the index event (interquartile range, 2.9-4.2 years). Major adverse cardiac events occurred in 10.2% of patients in the combined RIC and PostC group and in 16.9% in the control group (odds ratio, 0.56; 95% CI, 0.32-0.97; P=0.04). The difference was driven by a significantly reduced rate of new congestive heart failure in the RIC and PostC group (2.7% versus 7.8%; odds ratio, 0.32; 95% CI, 0.13-0.84; P=0.02). In contrast, PostC alone did not reduce major adverse cardiac events compared with controls (14.1% versus 16.9%; odds ratio, 0.81; 95% CI, 0.48-1.35; P=0.41), and the reduction of new congestive heart failure was not statistically significant (3.5% versus 7.8%; odds ratio, 0.43; 95% CI, 0.18-1.03; P=0.05).Cardioprotection by combined intrahospital RIC and PostC in addition to primary PCI significantly reduced the rate of major adverse cardiac events and new congestive heart failure after ST-segment-elevation myocardial infarction.URL: http://www.clinicaltrials.gov . Unique identifier: NCT02158468.
ALX148 Is a High Affinity Sirpα Fusion Protein That Blocks CD47, Enhances the Activity of Anti-Cancer Antibodies and Checkpoint Inhibitors, and Has a Favorable Safety Profile in Preclinical Models
Authors: Steven E Kauder, Tracy C Kuo, Amy Chen, Ons Harrabi, Sony S Rocha, Laura Doyle, Sangeetha Bollini, Bora Han, Emma Ruth B Sangalang, Janet Sim, Sophia Randolph, Jaume Pons, Hong I Wan
Journal: Blood (2017)
Effect of caffeine treatment on low-dose γ- irradiation-induced chromatid-type aberrations in human leukemia cells and human normal fibroblast cells in culture
Authors: M. N. Jha, J. S. Bedford, S. Jha, K. Prasad
Journal: Journal of Clinical Oncology (2009)

e22113 Background: It is estimated that low dose radiation can increase the risk of cancer as well as mutations. However, the interaction of low dose radiation with caffeine has not been adequately investigated. We investigated the effects of caffeine on low dose- gamma-radiation-induced chromosomal damage in human T leukemia cells (Jurket T-cells) and two normal human fibroblast cell lines (AG1522 and GM 2149). Method: Jurkat cells were maintained in RPMI 1640 medium and fibroblast in alpha-minimal essential medium (MEM) All cells were incubated at 37o C in a humidified atmosphere of 5% CO2 in air. Cells from the exponential phase were treated with 1 mg/ml caffeine ( control cells received same amount of solvent) and irradiated with low doses (3, 5, 10, 20 and 40 cGy,), using a 137 Cs-gamma radiation source. Colcemid at a concentration of 0.1 μg/ml was added to every flask. Cells were fixed in methanol: acetic acid solution and stained with Giemsa. 100 irradiated and un-irradiated metaphase- like cells were scored for chromatid-type aberrations. Results: Low dose gamma-radiation increased the levels of chromatid breaks(dose dependent) in both normal and cancer cells; however, cancer cells appeared to be more sensitive than the normal cells. Caffeine treatment markedly increased chromatid aberrations in Jurkat T-cells at all radiation doses but not in normal cells. Previously, we reported that caffeine eliminates gamma-ray-induced G2 delay in other human tumor cells but not normal cells (Jha, et.al., Radiat. Res. 157, 26–31, 2002). Conclusions: The mechanisms that may underlie this differential effect of caffeine in cancer and normal cells are unknown, but if one result of a G2 delay is to allow more time for chromosome breakage rejoining processes to occur, then elimination of this delay by caffeine in tumor cells but not normal cells might account for the difference. To the extent these observations are generally true for tumor vs normal cells, the differential sensitization could have an impact in improving the efficacy of radiation therapy. No significant financial relationships to disclose.
Moral reasoning performance determines epistemic peerdom
Authors: William H B McAuliffe, Michael E McCullough
Journal: Behavioral and Brain Sciences (2019)

Abstract We offer a friendly criticism of May's fantastic book on moral reasoning: It is overly charitable to the argument that moral disagreement undermines moral knowledge. To highlight the role that reasoning quality plays in moral judgments, we review literature that he did not mention showing that individual differences in intelligence and cognitive reflection explain much of moral disagreement. The burden is on skeptics of moral knowledge to show that moral disagreement arises from non-rational origins.
A phase II trial of definitive chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) in advanced esophageal cancer (KDOG 0501-P2).
Authors: Katsuhiko Higuchi, Shouko Komori, Satoshi Tanabe, Chikatoshi Katada, Mizutomo Azuma, Hiromichi Ishiyama, Tohru Sasaki, Kenji Ishido, Natsuya Katada, Kazushige Hayakawa, Wasaburo Koizumi
Journal: Journal of Clinical Oncology (2013)

4070 Background: Our previous phase I study (Radiother Oncol 2008,87:398) provided evidence that definitive chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) was tolerable and active in patients with advanced esophageal cancer (AEC). This phase II study was conducted to confirm the efficacy and toxicity of DCF-R in AEC. Methods: Patients with previously untreated carcinoma of the thoracic esophagus who had T4 tumors, M1 lymph-node metastasis, or both received an infusion of docetaxel (35 mg/m 2 ) and an infusion of cisplatin (40 mg/m 2 ) on day 1 and a continuous infusion of 5-fluorouracil (400mg/m 2 /day) on days 1-5, every 2 weeks, plus concurrent radiation (RT). The total RT dose was initially 61.2, but was lowered to multiple-field irradiation with 50.4 Gy to decrease esophagitis and late toxicity. Consequently, the number of cycles of DCF administered during RT was modified from 4 to 3. After DCF-R, patients received at least 2 cycles of DCF (docetaxel 40 mg/m 2 on day 1, cisplatin 60 mg/m 2 on day 1, and 5-fluorouracil 600 mg/m 2 on days 1-5, every 4 weeks). The primary endpoint was the clinical complete response rate (cCRR). Secondary endpoints were response rate (RR), progression free survival (PFS), overall survival, and safety. Results: 42 patients (36 men, 6 women) were enrolled. The median age was 62 years (range: 46-75). PS 0/1/2 was 14/25/3. TNM classification T4M0/non-T4M1LYM/T4M1LYM was 20/12/10. The total scheduled dose of RT 61.2Gy /50.4Gy was 12/30 patients. The RR was 90.5% and the cCRR was 52.4% (95% CI:37.3-67.5%). As of January 2013, the median PFS was 11.1 months and the median survival time was 23.1 months. Grade 3 or higher major toxicities comprised leukopenia (71.4%), neutropenia (57.2%), anemia (16.7%), febrile neutropenia (38.1%), anorexia (31.0%), and esophagitis (28.6%). There was one treatment-related death caused by aspiration pneumonia. Grade 3 or higher late toxicities comprised one pericardial effusion (Grade 4), one case of esophagitis (Grade 3), and one case of thoracic aortic aneurysm (Grade 3). Conclusions: DCF-R frequently caused myelosuppression, but was highly active and suggested be a promising regimen in AEC. Clinical trial information: 000002029.
Development of a Dynamic Model for Personalized Risk Assessment in Large B-Cell Lymphoma
Authors: David M. Kurtz, Florian Scherer, Michael Jin, Joanne Soo, Alexander Craig, Mohammad S Esfahani, Jacob J Chabon, Henning Stehr, Chih Long Liu, Robert Tibshirani, Lauren S. Maeda, Neel K. Gupta, Michael Khodadoust, Ranjana H. Advani, Ronald Levy, Aaron Newman, Jason R. Westin, Gianluca Gaidano, Davide Rossi, Maximilian Diehn, Ash A. Alizadeh
Journal: Blood (2017)
Ethnic minority patients need equity, not just equality
Authors: Selena R Yang, Anita Y Jiang
Journal: BMJ (2019)

Kmietowicz and colleagues refer to disparities affecting ethnic minorities across the health service.1

Race is widely accepted to be a social rather than biological construct used to explain cultural differences, so ethnicity is rarely used to guide clinical practice. Some studies have shown that there is more genetic variation within a race than between races.2 New clinical trials, however, …
A Text-Book of Sanitary and Applied Chemistry, or The Chemistry of Water, Air and Food.
Journal: JAMA (1906)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Intraoperative radiotherapy in early breast cancer: 400 consecutive patients in one institution.
Authors: Mariana Steiner, Michele Leviov, Arie Biterman, Eitan Shiloni, Jehudit Goldman
Journal: Journal of Clinical Oncology (2013)

1108 Background: From 2006 we offer intraoperative radiotherapy as the only post lumpectomy breast irradiation as an alternative to the standard post-operative WBRT in low risk early breast cancer patients (age &gt; 60, invasive ductal carcinoma &lt; 2 cm and clinically negative axilla). Younger patients (&gt;50) or patients with tumors up to 3.5 cm or other histologies are treated too if they are not candidate for standard local therapy. In patients found to have high risk tumor characteristics at final pathology, additional local breast therapy is considered. Methods: Intrabeam System is used administering 20 Gy at the surface of surgical cavity. Results: 400 patients were treated. Their median age was 70 years (55-90). Median clinical tumor size was 12 mm (5-30). 14.5% had mild to moderate local complications: 6.5% wound infection, 5.8% complicated seromas, 1.7% bleeding or hematoma and 0.5% small skin necrosis. 6.2% experienced major complications: 2.5% required surgical intervention, 2% had late healing (&gt; 90 days), 1% required IV antibiotics and 0.7% had grade III RTOG fibrosis. Median pathologic size was 14 mm (1-40). Pathologic free margins &gt; 1mm were obtained in 98.8% of patients. 15.5 % were found to have axillary l-nodes involved (11% one node only), 12% of patients had adverse unexpected breast pathologic findings (7.5% EDCIS or LVI) and 11% had additional local therapy, most of them WBRT. Median follow up is 30 months (1-76) in the whole group and 43 months (3-76) in the first 200 patients treated. Seven ipsilateral breast failures (1.7%) and one axillary recurrence were observed, all had radical local therapy. Four patients developed systemic disease (1%), one of them with simultaneous breast recurrence and one had contralateral breast cancer. Conclusions: We conclude that intraoperative radiotherapy using the Intrabeam system is feasible and may offer an alternative to whole breast RT in low risk breast cancer patients. Clinically significant local morbidity rate is low and self limiting. Longer follow up is needed to evaluate final results and late toxicity.
Transcatheter aortic valve replacements alter circulating serum factors to mediate myofibroblast deactivation
Authors: Brian A. Aguado, Katherine B. Schuetze, Joseph C. Grim, Cierra J. Walker, Anne C. Cox, Tova L. Ceccato, Aik-Choon Tan, Carmen C. Sucharov, Leslie A. Leinwand, Matthew R. G. Taylor, Timothy A. McKinsey, Kristi S. Anseth
Journal: Science Translational Medicine (2019)

Transcatheter aortic valve replacement alters a patient’s serum proteome, reversing valvular interstitial cell and cardiac myofibroblast activation.