tbuckley/cabot-search huggingface dataset:
Should industry sponsor research?
Authors: T. Waterston, A. Nathwani, D. Morley, N. Shabde, N. Spencer, G. de Wildt, P. Zinkin, D. C A Candy, A Porter, J. Coussins
Journal: BMJ (1999)

Editor—The issue that Lucas fails to tackle in his article on collaborative research with infant formula companies is conflict of interest in relation to research.1 Much of his article justifies the need for bottle feeding (with which no one would argue), plays up the educational role of formula manufacturers (highly questionable, as their material has been shown to have biased content), and casts doubt on the long term benefits of breast feeding (not relevant to the key issue). He strays into the area of educational sponsorship, where there is far less justification for industry support than in research, which is notoriously difficult to fund.

Lucas makes virtually no mention of what the opponents of sponsorship are worried about: the aggressive sales tactics of formula manufacturers in poor developing countries (now confirmed in a global study that has been endorsed by Unicef2) and the inevitability of a bias towards formula feeding in those who take money from the industry. It is a blot on the reputation of paediatricians world wide that they have been seen to side with milk companies in what is a highly unbalanced marketing struggle; the example of the Indian Paediatric Association is a shining exception.

For most babies who need artificial milk, the present formulas serve them well and no further modification seems necessary. Perhaps a compromise approach is possible for the small number of research centres working on new preterm formulas. Could a formula company’s funds be channelled through an independent organisation and the company remain anonymous? It is essential not only that there is no conflict of interest but that researchers are seen to recognise the damage that can be done internationally by overt association between paediatricians and formula manufacturers.

We hope that the new sponsorship policy being worked on by the Royal College of Paediatrics and Child Health will clarify these issues and take a strong stand for breast feeding.
QTc dispersion also occurs in diabetes
Authors: G. Jermendy
Journal: BMJ (1996)

ment when they surely must have their own vari- ability data?The claim that the differences seen in this study were greater than the variability published earlier gives the impression that readers are asked to accept apples and oranges as identical.The third is relevance.The study reports values of QTc dispersion without QT duration, QT dispersion, and heart rate.Despite some probably appropriate criticism, Bazett's formula indicates that the duration of the QT interval depends on the heart rate.However, we fail to see why QT dispersion should depend not only on heart rate but also on the duration of QT interval in the same mathematical way.Heart rate itself is an important prognostic indicator in coronary artery disease.
Is postoperative distant metastasis equivalent to stage IV disease in non-small cell lung cancer (NSCLC)
Authors: I. Yoshino, Y. Ichinose, M. Yamaguchi, Y. Maehara
Journal: Journal of Clinical Oncology (2004)

7178 Background: In clinical trials for metastatic NSCLC, postoperative recurrence at distant organs was often treated as stage IV disease although its prognosis is unclear. The prognosis of patients with distant recurrence after operation was investigated. Methods: In 468 patients with NSCLC who underwent a curative resection, 118 suffered from recurrence at distant organs during a more than 5-year observation, and their disease-free interval (DFI) and postrecurrent survival (PRS) were analyzed. A follow-up examination that included a physical examination, complete blood count, blood chemistry, and chest X-ray, was done every 2 months for the first 2 years and thereafter every 3 months. Both CT and a radionuclide bone scan were routinely investigated once or twice a year. The recurrent lesion was confirmed by biopsy if clinically feasible. Results: The mean DFI and PRS were 448 days (22–3013) and 418 days (3–4235), respectively. The first recurrent site was detected in the lung in 42, bone in 30, brain in 29, lymph node in 16, liver in 12, adrenal gland in 5, and others in 4. Adjuvant therapies were performed in 45 patients, however, the treatment was not a significant factor for postrecurrent survival. The postrecurrent 2-year survival rate was 15.7 %. Based on the pathologic stage at the initial operation, DFIs were 752 days in I, 500 in II, 315 in IIIA and 101 in IIIB (p<0.05, I vs. IIIA or IIIB), and PRSs were 590 days in I, 381 in II, 257 in IIIA and 180 in IIIB (p<0.05, I vs. IIIA). The stage was the strongest and independent factor in the postrecurrent survival, and the hazard ratio of stage I/II-IIIB was 0.53 (p = 0.0063). Conclusions: Patients with stage I NSCLC exhibited a better prognosis even after recurrence at distant organs, therefore such a population should be omitted or stratified in clinical trials for metastatic NSCLC. Stage classification might indicate not only the status of progression but also the biological malignant potential in NSCLC. No significant financial relationships to disclose.
PWE-201 Magnetic resonance cholangiopancreatography should be the gold standard versus routine ultrasonography for gallstone pancreatitis
Authors: A Ghosh, R Brainerd, F Rughooputh, K Hamdan
Journal: Gut (2015)

<h3>Introduction</h3> Acute gallstone pancreatitis may be caused by distal obstruction of the common bile duct, abnormal liver function tests (LFTs) and biliary ultrasonography (US) have been used to select those patients who should undergo magnetic resonance cholangiopancreatography (MRCP) and or subsequent endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was to compare the accuracy of predicting choledocholithiasis using abnormal LFTs and biliary US compared to routine MRCP. <h3>Method</h3> All patients admitted between January 2012 to March 2014 identified with gallstone pancreatitis (amylase &gt;300μL) were included in the study. Retrospective admission LFTs, US and MRCP reports were collated. <h3>Results</h3> Overall, 122 patients were admitted with gallstone pancreatitis and 47 patients underwent subsequent MRCP. Choledocholithiasis was seen in 55% (26/47). The mean bilirubin was higher in those with choledocholithiasis (18μmol/l (3–74) versus 44μmol/l (8–232) and ALP (134iμ/l (32–690) versus 196iμ/l (48–697). Abnormal bilirubin (&gt;21μmol) was associated with choledocholithiasis demonstrated at MRCP with a sensitivity of 65.38% (95% CI 44.33–87.79%) and specificity 57.14% (95% CI 43.22–70.29%) with a positive predictive value (PPV)of 68.4% (p = 0.007); ALP (&gt;140iμ/l) sensitivity 73.08% (95% CI 80.36–99.9%) and specificity 57.14% (95% CI 43.22–70.29%) with a PPV of 63% (p = 0.04) and ALT (&gt;53iμ/l) sensitivity 96.15 (95% CI 80.46–99.9%) and specificity 41.07% (95% CI 28.10–55.02%) with a PPV of 72.7% (p = 0.0009). Combined abnormal bilirubin, ALP and ALT for choledocholithiasis had a positive predictive value of 63% (p = 0.04). US demonstrated biliary duct dilation was not significantly associated with abnormal bilirubin, ALP or ALT. Furthermore, biliary duct dilatation on US had a sensitivity of 19.23% (95% CI 6.55–39.35%) and specificity 86.21% (95% CI 74.62–93.85) with a PPV 52% (P = 0.69) and was not significantly associated with choledocholithiasis demonstrated at MRCP. <h3>Conclusion</h3> MRCP should be the gold standard to investigate all patients with gallstone pancreatitis with abnormal LFTs as US biliary dilation alone or associated with abnormal LFTs is a poor predictor of common bile duct stones. <h3>Disclosure of interest</h3> None Declared.
Progesterone and Preterm Birth
Authors: John M O'Brien
Journal: New England Journal of Medicine (2007)

Progestogens (vaginal progesterone and intramuscular 17-hydroxyprogesterone acetate) are widely recommended for women at high risk of preterm birth.Typical regimens include 17-hydroxyprogesterone caproate (250 mg intramuscularly weekly), starting at 16-20 gestational weeks until 36 weeks or delivery for women with a singleton gestation and a history of spontaneous preterm birth, or vaginal progesterone (90-mg vaginal gel or 200-mg micronized vaginal soft capsules) for women with a short cervix (typically ≤25 mm).Although some randomized trials support this approach, neither of the largest trials (PROLONG for 17-hydroxyprogesterone acetate or OPPTIMUM for vaginal progesterone) demonstrated efficacy.There are almost no data on long-term effects, and none that shows benefit beyond the neonatal period.Although some analyses suggest the cost-effectiveness of the approach, a cervical length screening program followed by progesterone for those with a short cervix will reduce preterm birth rates by less than 0.5%.The present review assesses evidence on the efficacy, likely impact, and longterm effects of implementing the recommendations for progestogens in full.Clinicians and pregnant women can look forward to resolution of the conflicting views on efficacy once the Patient-Centered Outcomes Research Initiative (PCORI)-funded individual patient data meta-analysis is published.
Videotape recording of dynamic psychotherapy: supervisory tool or hindrance?
Authors: C T Friedman, J Yamamoto, G H Wolkon, L David
Journal: American Journal of Psychiatry (1978)

The authors questioned residents and supervisors at a large clinic about their attitudes and experiences regarding clinical supervision. Half of the residents then videotaped one of their psychotherapy sessions and presented the tape in their next supervisory session. The procedure had little effect on patients, was anxiety-provoking for the residents, and had some diagnostic benefit for the supervisors. After the taping, the residents' views about taping were less positive than before the taping, but the supervisors' views did not change significantly.
Null Effect of Concurrent Feeding of Sodium Nitrite and Amino Acids to MRC Rats2
Authors: Melvin Greenblatt, V. R. C. Kommineni, William Lijinsky
Journal: JNCI Journal of the National Cancer Institute (1973)

The secondary L-amino acids, proline, hydroxyproline, and arginine, were fed together with sodium nitrite (NaNO2) tc MRC rats of both sexes for their lifetime. Controls were rats given the amino acid or NaNO2 alene, nitrosopyrrolidine (positive control), or no treatment. No tumorigenic effect was observed in animals receiving the amino acids and NaNO2 combined treatment. The null effect is probably due to the noncarcinogenicity of the nitrosoamine acids formed in the stomach and the lack of decarboxylation of nitrosoproline and nitrosohydroxyproline to the corresponding nitrosamine.
Impact of prior therapy with ketoconazol or abiraterone and pattern of PSA response in a cohort of patients with metastatic castrate resistant prostate cancer (mCRPC) receiving enzalutamide for postdocetaxel.
Authors: José Pablo Maroto Rey, Emilio Esteban, Alfonso Gomez De Liano Lista, Ana Ruiz Echevarria, Ana Virgili, Estela Moreno
Journal: Journal of Clinical Oncology (2014)

e16082 Background: Enzalutamide has proved activity in second line setting after progression to docetaxel-based chemotherapy in patients with mCRPC in a phase III trial compared to placebo. Objective: To analyze PSA progression free survival, patterns of PSA response, the impact of prior ketoconazol or abiraterone therapy and its relationship with survival in 40 patients treated within an expanded access program in two University Hospitals in Spain. Methods: All patients received Enzalutamide 160 mg per day until clinical progression. All patients had castrate levels of Testosterone and had failed to docetaxel. PSA levels were performed basally and followed under therapy every 4 weeks. Definitions of PSA response and progression were according to PCWG2 criteria. Four patients had previously been treated with Abiraterone, 7 patients with Ketoconazol and 1 patient both. Median number of cycles of docetaxel was 8 (2-12). 5 patients had been treated with Cabazitaxel. Results: Median age was 72 (46-88). Median ECOG 1 (0-2). Median basal PSA levels were 67.5 (2.7-886) U/L. PSA response after 4 weeks of therapy: 9/40 patients (22%) did not response, 19/40 47.5%, showed a reduction >30% and 11/40, 27.5% >50%. All patients achieved maximum PSA response by week 8. No flare effect was observed. Median time to PSA progression was 5.25 months (0.47-12.5); 6/40, 15% of patients maintained PSA response for more than a year. Median survival was 8.83 months (0.63-12.53). Median survival for patients with a PSA response >30% at week 4 was 11.23 (4.27-14.8) vs. 7.3 (0.63-12.63) for other patients. No differences in PSA response were observed for patients previously treated with ketoconazol. Of the five patients previously treated with abiraterone, 2 had PSA response, one of them for less than 4 weeks Conclusions: No PSA flare effect was observed under Enzalutamide. PSA response to Enzalutamide was observed by week 4 in 90% of patients that responded. PSA response >30% at week 4 might be a predictor of survival. Prior ketoconazol did not affect PSA response to Enzalutamide.
Clinical Relevance of Cd133 Positive Cells in Locally Advanced Non-Small Cell Lung Cancer
Authors: E.R. Haspinger, M. Platania, G. Bertolini, R. Caserini, E. Landoni, E. Roz, M.C. Garassino, N. Zilembo, F. Agustoni, M. Vitali, D. Serpico, R. Giovannetti, F. Gelsomino, P. Scanagatta, L. Taveccio, R. Gallucci, U. Pastorino, F.G.M. De Braud, G. Sozzi, L. Roz
Journal: Annals of Oncology (2014)
High rates of psychiatric diagnoses are found in young transgender women
Authors: Jacqui Wise
Journal: BMJ (2016)

Transgender women have a high prevalence of major depressive disorder, generalised anxiety disorder, suicidality, post-traumatic stress disorder, and substance dependence, research published in JAMA Paediatrics has found.1

The study of 298 sexually active transgender women aged 16 to 29 years found that 41% had one or more mental health or substance dependence diagnoses, and nearly one in five had two or more psychiatric …
MTR-16MISMATCH REPAIR DEFECTS PREDICT CLINICAL OUTCOME OF PRIMARY AND RECURRENT MALIGNANT GLIOMAS
Authors: Kuniaki Saito, Saki Shimizu, Kaori Suzuki, Keiichi Kobayashi, Nobuyoshi Sasaki, Satoshi Kume, Yoshiaki Shiokawa, Motoo Nagane
Journal: Neuro-Oncology (2015)

INTRODUCTION: Temozolomide (TMZ), a standard drug for glioblastoma (GBM), induces inactivation of the DNA mismatch repair (MMR) system and hence causes hypermutator phenotype in the glioma especially with methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter. MMR defects are also found in primary gliomas and are associated with resistance to TMZ and malignant progression to secondary GBM. However, the association between alteration of MMR system and clinical outcome of both primary and recurrent GBMs was yet to be elucidated. METHODS: We analyzed protein expression of MLH1, MSH2, MSH6, and PMS2 as well as MGMT methylation in a set of 117 primary GBMs and 34 paired sample of initial and recurrent gliomas. Protein expression was analyzed by Western blotting and/or immunohistochemistry. MGMT methylation was determined by methylation-specific PCR. Progression-free and overall survival times according to each molecular status were reviewed. RESULTS: Loss of MMR protein expression (MLH1, MSH2, MSH6, and PMS2) was observed in 12%, 10%, 50%, and 16% of the primary samples, respectively. Inactivation of MSH6 during the recurrence was associated with MGMT methylation at recurrence (p = 0.02), while MGMT methylation of the initial samples did not predict the changes of any MMR protein. Malignant progression from lower grade glioma was associated with inactivation of MSH6 (p = 0.035). Loss of MMR protein expression, as well as unmethylated MGMT promoter, was associated with shorter overall survival in patients with primary GBMs. In contrast, MMR inactivation was associated with longer survival in patients with recurrent GBMs, while MGMT methylation was not. CONCLUSION: Inactivation of MMR protein was associated with resistance to TMZ for primary GBMs, malignant progression of lower grade gliomas, and was predictive factor for survival of the patients with recurrent GBMs. Further investigation to define optimal treatment for glioma according to MGMT and MMR status is warranted.
Phase Ii Study of Individualized Sunitinib As First-Line Therapy for Metastatic Clear Cell Renal Cell Cancer (Mrcc)
Authors: G.A. Bjarnason, B. Naveen, E. Winquist, C.K. Kollmannsberger, C. Canil, S. North, D.S. Ernst, R.J. Macfarlane, D. Heng, P. Zalewski, S.J. Hotte, D. Soulières, P. Venner, I.F. Tannock, M.N. Reaume, A. Kapoor, B.J. Eigl, D.J. Ruether, B. Boyd, J. Knox
Journal: Annals of Oncology (2014)
Widespread Implementation of Appropriate Use Criteria for Cardiac Imaging—Which Are “Appropriate”?
Authors: Robert C. Hendel
Journal: JAMA Cardiology (2016)

For more than a decade, organizations such as the American College of Radiology (ACR) and the American College of Cardiology Foundation (ACCF) have published criteria delineating the appropriate use of cardiac imaging.These specialty society guidance documents are designed to provide clinicians with recommendations regarding the use of imaging and are focused on reducing unnecessary and inappropriate testing.In general, both the ACR and ACCF use similar methods in the construction of appropriate use criteria (AUC), by performing careful evidence reviews and providing a standardized rating of multiple clinical indications by the use of the UCLA/RAND methodology with a modified Delphi approach. 1However, substantial methodological differences exist between each organization's approach to AUC, including the ACCF's greater reliance of risk stratification based on clinical factors, which results in a far greater specificity of clinical indications with the ACCF version.Furthermore, the hierarchical nature of the ACCF AUC readily lend these criteria to be adopted into clinical decision support tools. 1 In this issue of JAMA Cardiology, Winchester et al 2 compare 2 sets of appropriate use criteria, one derived from the ACR and the other led by the ACCF.Substantial discordance in appropriateness categorization was noted (22.3%), and more complete "coverage" of all clinical situations was demonstrated with the ACCF AUC.A significant limitation of this article relates to the use of an older version of the ACCF AUC.This singlemodality set of AUC was published 7 years ago 3 and has largely been superseded by the 2013 multimodality AUC, 4 which should serve as the current standard for the evaluation of appropriate use.While many indications were rated similarly with regard to radionuclide imaging, several important differences in appropriateness classification were noted, including the appropriateness of radionuclide imaging after CABG, the value in high-risk asymptomatic individuals, and its use in the preoperative assessment of patients before intermediate-risk surgery. 5 A concern raised by Winchester et al 2 is the finding that there were far more abnormal imaging studies or individuals with ischemia with an inappropriate designation from the ACR (35.4% and 17.5%, respectively) than with the ACCF AUC (7.3% and 2.6%, respectively).Although it is well described that studies designated as inappropriate may still have abnormal test results, as reported in 6 trials, 5 the fact that the frequency may be higher using the ACR criteria is worrisome.Another important consideration related to the use of AUC is how often testing for inappropriate indications provides useful prognostic information, thus potentially supporting the recommendation not to perform a test for an inappropriate indi-
Abstract 19091: Platelet mTOR is an Important Mediator of Arterial Thrombosis
Authors: Yong-Joo Ahn, Maya Hwewon Kim, Hyung-Hwan Kim
Journal: Circulation (2013)

Background: Arterial thrombosis is responsible for peripheral vascular disease, ischemic stroke, and myocardial infarction. Mammalian target of rapamycin (mTOR) inhibition promotes arterial thrombosis. To determine the contributions of platelet specific mTOR deficiency to arterial thrombosis, we generated platelet specific mTOR deficient mice. To determine the rescue effect of platelet mTOR deficiency, we also generated platelet specific TSC1 deficient (PF4Cre-TSC1 flox/flox ) mice. Because the effect of mTOR activation on thrombus formation in vivo has not yet been studied, we hypothesize that mTOR signaling pathway in platelets may play an important role in arterial thrombosis. Methods and Results: To determine the role of platelet mTOR in arterial thrombosis, we generated a mouse strain with platelet-specific mTOR deficiency (PF4Cre-mTOR flox/flox ) using conditional mTOR flox/flox mice and platelet-specific PF4Cre mice. PF4Cre-mTOR flox/flox mice did not show any obvious phenotypic abnormalities. Arterial thrombus formation was investigated using in vivo ferric chloride induced thrombosis model. Ferric Chloride (5% FeCl 3 ) induced thrombotic occlusion. Rapamycin treatment and mTOR conditional knockout induced arterial thrombosis significantly. Compared to PF4Cre mice, PF4Cre-TSC1 flox/flox mice exhibited elongated thrombotic occlusion time by 51.7%. Platelet specific mTOR deficiency induced arterial thrombosis quickly compare to the WT via activation of p-S6, a downstream target of mTORC1 and inhibition of p-Rictor of mTORC2. Conclusion: These finding indicate that platelet specific mTOR deficiency resulted in significantly induced arterial thrombosis but delayed at the platelet specific TSC1 deficient mice. These results suggest that activation of mTORC1 may have therapeutic benefits in arterial thrombosis.
CBIO-40THREE-DIMENSIONAL ASSESSMENT OF BYSTANDER EFFECTS OF MESENCHYMAL STEM CELLS CARRYING A CYTOSINE DEAMINASE GENE ON GLIOMA CELLS
Authors: Jin Hwa Jung, Andrew Kim, Da-Young Chang, Sung-Soo Kim, Haeyoung Suh-Kim
Journal: Neuro-Oncology (2015)

Stem cells carrying a suicide gene have emerged as therapeutic candidates for their cytotoxic bystander effects on neighboring cancers, while being non-
Digital Dermal Patterns in Large-Bowel Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A M Nomura, M P Mi, G N Stemmermann
Journal: JNCI Journal of the National Cancer Institute (1981)

The digital dermal patterns of 149 patients with large-bowel cancer and 298 population-based controls were studied. The patterns were very similar between the 2 groups. Also, no significant differences were found in total ridge counts, which suggests that antenatal factors, related to the formation of digital patterns, are not associated with the risk of large-bowel cancer.