tbuckley/cabot-search huggingface dataset:
Declaration of transparency for each research article
Authors: D. G. Altman, D. Moher
Journal: BMJ (2013)

An antidote to inadequate reporting of research 

> “It is the responsibility of everyone involved to ensure that the published record is an unbiased, accurate representation of research.”1

The research record is often manipulated for short term gain but at the risk of harm to patients. The medical research community needs to implement changes to ensure that readers obtain the truth about all research, especially reports of randomised trials, which hold a special place in answering what works best for patients.

Failure to publish the findings of all studies, especially randomised trials, seriously distorts the evidence base for clinical decision making. A recent systematic review of reboxetine for treating depression found that almost three quarters of included patients were in unpublished trials.2 Of 904 completed trials of interventions for acute ischaemic stroke (1955-2008), a fifth were not properly published, “several of which may be large enough to influence clinical practice and the findings of systematic reviews and meta-analyses.”3

Bad as non-publication is, incomplete or misleading publications cause greater problems. Results of clinical trials published in peer reviewed publications may differ from what was previously submitted to regulatory agencies,4 5 6 with the published data being more positive. The primary outcome often differs from what the researchers had stated in the trial protocol7 8 or …
Tamoxifen Induces Expression of Immune Response–Related Genes in Cultured Normal Human Mammary Epithelial Cells
Authors: Laura J. Schild-Hay, Tarek A. Leil, Rao L. Divi, Ofelia A. Olivero, Ainsley Weston, Miriam C. Poirier
Journal: Cancer Research (2009)

Abstract Use of tamoxifen is associated with a 50% reduction in breast cancer incidence and an increase in endometrial cancer incidence. Here, we documented tamoxifen-induced gene expression changes in cultured normal human mammary epithelial cells (strains 5, 16, and 40), established from tissue taken at reduction mammoplasty from three individuals. Cells exposed to 0, 10, or 50 μmol/L of tamoxifen for 48 hours were evaluated for (E)-α-(deoxyguanosine-N2-yl)-tamoxifen (dG-N2-TAM) adduct formation using TAM-DNA (DNA modified with dG-N2-TAM) chemiluminescence immunoassay, gene expression changes using National Cancer Institute DNA-oligonucleotide microarray, and real-time PCR. At 48 hours, cells exposed to 10 and 50 μmol/L of tamoxifen were 85.6% and 48.4% viable, respectively, and there were no measurable dG-N2-TAM adducts. For microarrays, cells were exposed to 10 μmol/L of tamoxifen and genes with expression changes of &amp;gt;3-fold were as follows: 13 genes up-regulated and 1 down-regulated for strain 16; 17 genes up-regulated for strain 5, and 11 genes up-regulated for strain 40. Interferon-inducible genes (IFITM1, IFIT1, MXI, and GIP3), and a potassium ion channel (KCNJ1) were up-regulated in all three strains. No significant expression changes were found for genes related to estrogen or xenobiotic metabolism. Real-time PCR revealed the up-regulation of IFNA1 and confirmed the tamoxifen-induced up-regulation of the five other genes identified by microarray, with the exception of GIP3 and MX1, which were not up-regulated in strain 40. Induction of IFN-related genes in the three normal human mammary epithelial cell strains suggests that, in addition to hormonal effects, tamoxifen exposure may enhance immune response in normal breast tissue. [Cancer Res 2009;69(3):1150–5]
A randomised 4-arm multicentre study of interferon alfa-2b plus ribavirin in the treatment of patients with chronic hepatitis C not responding to interferon alone
Authors: G. Saracco, A. Ciancio, A. Olivero, A. Smedile, L. Roffi, G. Croce, C. Colletta, G. Cariti, M. Andreoni, A. Biglino, G. Calleri, G. Maggi, G.F. Tappero, P.G. Orsi, N. Terreni, A. Macor, A. Di Napoli, E. Rinaldi, G. Ciccone, M. Rizzetto
Journal: Journal of Hepatology (2001)
Coverage for High‐Cost Specialty Drugs for Rheumatoid Arthritis in Medicare Part D
Authors: Jinoos Yazdany, R. Adams Dudley, Randi Chen, Grace A. Lin, Chien‐Wen Tseng
Journal: Arthritis & Rheumatology (2015)

More than 1 in 4 Medicare beneficiaries with rheumatoid arthritis use high-cost biologic disease-modifying antirheumatic drugs (DMARDs), and spending for these drugs has risen sharply for Medicare Part D. Our aim was to conduct the first systematic, national investigation of how Part D plans cover biologic DMARDs and to determine patients' financial burden under current cost-sharing structures.We performed a cross-sectional analysis of Part D plan formularies (n = 2,737) in 50 states and Washington, DC using the January 2013 Centers for Medicare and Medicaid Services Prescription Drug Plan Formulary and Pharmacy Network Files. We calculated the percentage of plans covering each DMARD as well as the percentage requiring prior authorization and/or coinsurance. We also compared biologic drug coverage in Medicare Advantage prescription drug plans to that in Medicare Part D stand-alone plans.All plans covered at least 1 biologic DMARD, but the vast majority required prior authorizations (95%). Nearly all plans (81-100%) required patients to pay a coinsurance percentage (averaging 29.6% of drug costs) rather than a fixed dollar copayment. This translated into mean out-of-pocket costs of $2,712-$2,774 before reaching the catastrophic phase of coverage, during which beneficiaries pay 5% of drug costs. Medicare Advantage prescription drug plans covered more individual biologic DMARDs (55-100%) than did Medicare Part D stand-alone plans (22-100%), but Medicare Advantage prescription drug plans required higher average coinsurance (31.1% versus 29.0%). In contrast, 6 of 9 nonbiologic DMARDs were covered by nearly all plans without prior authorizations at fixed copayments averaging $5-$10/month.Nationally, nearly all Part D plans cover at least 1 biologic DMARD, but the vast majority require cost sharing sufficiently high to risk significant financial burden to patients.
Interleukin-12 Enhances the Sensitivity of Human Osteosarcoma Cells to 4-Hydroperoxycyclophosphamide by a Mechanism Involving the Fas/Fas-Ligand Pathway
Authors: Xiaoping Duan, Zhichao Zhou, Shu-Fang Jia, Michael Colvin, Elizabeth A. Lafleur, Eugenie S. Kleinerman
Journal: Clinical Cancer Research (2004)

Abstract Cyclophosphamide (CY) and its derivative ifosfamide are alkylating agents used to treat osteosarcoma (OS). The purpose of these studies was to determine whether alkylating agents affect the expression of Fas ligand (FasL) and whether interleukin 12 enhances the sensitivity of human OS cells to alkylating agents. 4-Hydroperoxycyclophosphamide (4-HC), the preactivated CY compound, and 4-hydroperoxydidechlorocloclophosphamide (4-HDC), its nonalkylating analogue, human OS LM6 cells, and a clone of cells derived by transfection with the interleukin 12 gene (LM6-#6) were used for these studies. Incubation of LM6 and LM6-#6 with 10 μm 4-HC increased the expression of FasL mRNA (2.5- and 3.0-fold, respectively). By contrast, 4-HDC, Adriamycin (ADR), cisplatin (CDP), and methotrexate (MTX) had no effect on FasL mRNA expression. Increased FasL expression after treatment with 4-HC was also demonstrated by immunohistochemistry and flow cytometry. Drug-induced FasL was functional and mediated cell death. We examined the effect of FasL up-regulation by 4-HC on LM6 and LM6-#6 cells. Flow cytometry showed that LM6-#6 cells expressed 2.2-fold more Fas than LM6 cells. Cytotoxicity of 4-HC, 4-HDC, ADR, CDP, and MTX on LM6, LM6-neo, and LM6-#6 were quantified. Colony-forming assay revealed an IC50 of 2.10 μm for 4-HC in LM6-neo cells compared with 0.41 μm in LM6-#6 cells. The IC50 for 4-HDC, ADR, CDP, and MTX were not significantly different between the two cell lines. We concluded that the increased expression of Fas enhanced LM6-#6 sensitivity to 4-HC. These data indicate that Fas/FasL may be involved in the cytotoxic pathway of CY. Combining biological agents with chemotherapeutic agents that have complementary Fas/FasL pathway actions may offer new therapeutic alternatives.
Funding Opportunities for Investigators in the Early Stages of Career Development
Authors: C. Amelia Sumandea, C. William Balke
Journal: Circulation (2009)

Many sources of advice and guidance are available to the early career investigator. Generally, mentors serve as the primary source of information, although program and review officers are the most underutilized resources. This article organizes these opportunities to enable early career investigators to plot a rational trajectory for career success. A list of the major agencies that provide grant support for early career investigators is included. In addition, funding opportunities are organized on the basis of the stage in career development pathway and the type of terminal degree.
<i>In vivo</i>Optical Coherence Tomography Imaging of Preinvasive Bronchial Lesions
Authors: Stephen Lam, Beau Standish, Corisande Baldwin, Annette McWilliams, Jean leRiche, Adi Gazdar, Alex I. Vitkin, Victor Yang, Norihiko Ikeda, Calum MacAulay
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Optical coherence tomography (OCT) is an optical imaging method that can visualize cellular and extracellular structures at and below tissue surface. The objective of the study was to determine if OCT could characterize preneoplastic changes in the bronchial epithelium identified by autofluorescence bronchoscopy. Experimental Design: A 1.5-mm fiberoptic probe was inserted via a bronchoscope into the airways of 138 volunteer heavy smokers participating in a chemoprevention trial and 10 patients with lung cancer to evaluate areas that were found to be normal or abnormal on autofluorescence bronchoscopy. Radial scanning of the airways was done to generate OCT images in real time. Following OCT imaging, the same sites were biopsied for pathologic correlation. Results: A total of 281 OCT images and the corresponding bronchial biopsies were obtained. The histopathology of these areas includes 145 normal/hyperplasia, 61 metaplasia, 39 mild dysplasia, 10 moderate dysplasia, 6 severe dysplasia, 7 carcinoma in situ, and 13 invasive carcinomas. Quantitative measurement of the epithelial thickness showed that invasive carcinoma was significantly different than carcinoma in situ (P = 0.004) and dysplasia was significantly different than metaplasia or hyperplasia (P = 0.002). In addition, nuclei of the cells corresponding to histologic results became more discernible in lesions that were moderate dysplasia or worse compared with lower-grade lesions. Conclusion: Preliminary data suggest that autofluorescence bronchoscopy–guided OCT imaging of bronchial lesions is technically feasible. OCT may be a promising nonbiopsy tool for in vivo imaging of preneoplastic bronchial lesions to study their natural history and the effect of chemopreventive intervention.
Pulmonary artery compression by haemorrhage from the aorta simulating pulmonary embolism
Authors: D. H. Franklin, J. Jacques
Journal: Thorax (1974)

<b>Franklin, D. H., and Jacques, J. (1974).</b><i>Thorax</i>, <b>29</b>, 142-144. <b>Pulmonary artery compression by haemorrhage from the aorta simulating pulmonary embolism.</b> A case is presented in which pulmonary embolism was simulated by compression of the pulmonary artery by haematoma during an episode of acute bacterial endocarditis occurring 18 months after aortic valve replacement.
Decision Making in Patients with Pulmonary Nodules
Authors: David E. Ost, Michael K. Gould
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Section:ChooseTop of pageAbstract <<Updating the Definition o...Estimating the Probabilit...Conceptual Framework for ...Management StrategiesClinical AlgorithmSummaryReferencesCITING ARTICLES
Is Schizophrenia a Progressive Neurodevelopmental Disorder? Toward a Unitary Pathogenetic Mechanism
Authors: Bryan T. Woods
Journal: American Journal of Psychiatry (1998)

The author 1) reassesses the case against a neuronal degeneration hypothesis for schizophrenia; 2) demonstrates that the hypothesis that schizophrenia is a disorder caused by early (i.e., pre- or perinatal) and static (i.e., fixed, nonprogressive) damage to the brain is unsatisfactory because it cannot readily account for brain imaging results from schizophrenic patients and lacks both satisfactory clinical examples and experimental models of early, static developmental disorders resulting in the late spontaneous functional deterioration that characterizes schizophrenia; and 3) offers an alternative pathogenetic hypothesis for schizophrenia that is consistent with the available imaging and neuropathological data.Published data on schizophrenia and relevant clinical and experimental studies of neurodevelopment and its disorders are reviewed.The neuropathological studies provide strong evidence against a classic neurodegenerative pathogenesis of schizophrenia and moderate support for prenatal developmental abnormalities. The imaging data provide strong evidence that excessive brain volume loss occurs after maximum brain volume expansion and equivocal evidence that it continues after onset of overt illness. The available clinical and experimental models of late deterioration after static, early brain lesions are unconvincing. A progressive developmental mechanism can reconcile the neuropathological and imaging data, while being compatible with both early onset and late deterioration.It matters whether the pathogenetic agent in schizophrenia is static or progressive, since if it is the latter it is worthwhile to search not only for means of prevention but also for interventions that will arrest progression as early as possible.
Balanced T cell subsets for good health
Authors: Hema Bashyam
Journal: The Journal of Experimental Medicine (2008)

![Graphic][1] 

The naive RORγt+ T cell population (green) includes Foxp3-expressing regulatory T cells (arrowheads). On page 

[1381][2], Lochner et al. expose the promiscuity of a transcription factor that was previously thought to be exclusive to inflammatory T helper (Th) 17 cells
Hypoxia-inducible factor-1 mediates the biological effects of oxygen on human trophoblast differentiation through TGFβ3
Authors: Isabella Caniggia, Homa Mostachfi, Jennifer Winter, Max Gassmann, Stephen J. Lye, Maciej Kuliszewski, Martin Post
Journal: Journal of Clinical Investigation (2000)

During early pregnancy, placentation occurs in a relatively hypoxic environment that is essential for appropriate embryonic development. Intervillous blood flow increases around 10 to 12 weeks of gestation and results in exposure of trophoblast cells to increased oxygen tension. Before this time, low oxygen appears to prevent trophoblast differentiation toward an invasive phenotype. Using human villous explants of 5–8 weeks’ gestation, we found that low oxygen tension triggered trophoblast proliferation, fibronectin synthesis, α5 integrin expression, and gelatinase A activity. These biochemical markers were barely detectable under oxic conditions. We therefore examined the placental expression of hypoxia-inducible factor-1 (HIF-1), a master regulator of oxygen homeostasis, and determined that expression of HIF-1α subunit during the first trimester of gestation parallels that of TGFβ3, an inhibitor of extravillous trophoblast differentiation. Expression of both molecules is high in early pregnancy and falls around 9 weeks of gestation, when placental pO2 levels are believed to increase. Increasing oxygen tension induced a similar decrease in expression in cultured explants. Moreover, antisense inhibition of HIF-1α expression in hypoxic explants inhibited expression of TGFβ3, arrested cell proliferation, decreased α5 expression and gelatinase A activity, and triggered biochemical markers of an invasive trophoblast phenotype such as α1 integrin and gelatinase B expression. These data suggest that the oxygen-regulated early events of trophoblast differentiation are in part mediated by TGFβ3 through HIF-1 transcription factors.
Hypersensitivity to Apple and Carrot Can Be Reliably Detected with Fresh Material
Authors: Arto Lahti, Matti Hannuksela
Journal: Allergy (1978)

Hypersensitivity to birch pollen was linked with allergy to apple and carrot, apple seeds and carrot seeds and also with their fractions, Skin reactions among other atopics were rare, and non‐atopic patient; showed no reactions to fresh fruits and vegetables. Apple and carrot as well as apple seeds and carrot seeds were fractionated using column chromatography. Two major fractions were obtained, one with sugar and proteins, and one with proteins, the tatter giving skin reactions more often than the former. The correlation between clinical symptoms and skin lest results with the fractionated material was somewhat lower than that obtained with the non‐fractionated fresh material. The allergens of fruits and vegetables might be proteins (enzymes).
Changes in practice with a coeliac disease dietician led clinic over a 30 year period, should we be measuring vitamin D?
Authors: R. R. Keld, E. Shuttleworth, S. Burden, S. Campbell
Journal: Gut (2011)

<h3>Introduction</h3> Morbidity surrounding Coeliac disease is usually a consequence of malabsorbtion of minerals and vitamins leading to anaemia and metabolic bone disease. In January 2002 a Dietetic led clinic was introduced at Manchester Royal Infirmary to improve patient care. We conducted an audit to compare the practice of the initial management of Coeliac disease to assess the introduction of the Dietetic led clinic. Practice was compared to the current 2010 BSG guidelines. <h3>Methods</h3> We chose 50 cases at random from the dietician led Coeliac clinic, 25 patients were diagnosed prior to 2002 and 25 cases selected after 2002. We focused our audit on the time from diagnosis to 4 years follow up. Date of diagnosis ranged from 1976 to 2010. Age, symptom control, antibody, duodenal pathology, body weight, haemoglobin, vitamin D level, DEXA T and Z scores, fracture history, calcium and bisphosphonate prescriptions were all recorded. <h3>Results</h3> Average age at diagnosis was similar, 42.5 (SD 19) (pre 2002) and 45.9 years (SD 18.6) (post 2002). Females accounted for 64% and 84% respectively. Antibody results were available in 48% and 76%, positive in 92% and 100% respectively. Diagnostic duodenal biopsies were available in 52% and 84% respectively. Body weight was recorded in 52% and 92% and haemoglobin levels recorded in 56% and 85%. Weight, symptoms and Haemoglobin improved in both groups. Initial bone densitometry was performed in 28% and 64% and repeated at 4 years in 50% and 67% respectively. Bone density reduced slightly over the 4 year follow up. Vitamin D levels were measured in 20% and 50% at the time of diagnosis and levels increased over a 4 year period (pre 2002: 17.8 (SD11.6) to 25.4 (SD 8.8); post 2002: 16.9 (SD 12.6) to 24.3 (SD 10.3)). Bisphosphonates were prescribed appropriately in 33% and 100% in the respective groups. Fractures were present in 10% of all patients. <h3>Conclusion</h3> A Dietetic led service has led to favourable changes in practice. Disease response measured by symptoms, weight and haemoglobin improved in both groups; in the post 2002 cohort, more data is available and this may indicate improved clinic attendance at the Dietetic led clinic. The fracture incidence of 10% is comparable to the general population incidence, much lower than studies of previous UK and South American Coeliac cohorts. This low fracture incidence may be to be due the judicious use of bone density assessment and treatment with calcium and vitamin D. Vitamin D is not in the BSG 2010 guidelines, the low fracture incidence in this cohort may partly be reflected by the correction of vitamin D levels. This raises questions whether routine measurement vitamin D should be advocated?
Incretin-Based Drugs and the Risk of Congestive Heart Failure
Authors: Oriana Hoi Yun Yu, Kristian B. Filion, Laurent Azoulay, Valerie Patenaude, Agnieszka Majdan, Samy Suissa
Journal: Diabetes Care (2014)

OBJECTIVE To determine whether the use of incretin-based drugs, including GLP-1 analogs and dipeptidyl peptidase-4 inhibitors, is associated with an increased risk of congestive heart failure (CHF) among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS The U.K. Clinical Practice Research Datalink, linked to the Hospital Episode Statistics database, was used to conduct a cohort study with a nested case-control analysis among patients newly prescribed antidiabetic drugs between 1 January 2007 and 31 March 2012 and no prior history of CHF. Case subjects were defined as patients hospitalized for a first CHF and matched with up to 20 control subjects on age, duration of treated diabetes, calendar year, and time since cohort entry. Conditional logistic regression was used to estimate odds ratios (ORs) with corresponding 95% CIs of incident CHF comparing current use of incretin-based drugs with current use of two or more oral antidiabetic drugs. RESULTS The cohort consisted of 57,737 patients followed for a mean 2.4 years, during which time 1,118 incident cases of hospitalized CHF were identified (incidence rate 8.1/1,000 person-years). Current use of incretin-based drugs was not associated with an increased risk of CHF (adjusted OR 0.85 [95% CI 0.62–1.16]). Secondary analyses revealed no duration-response relationship (P trend = 0.39). CONCLUSIONS In our population-based study, incretin-based drug use was not associated with an increased risk of CHF among patients with type 2 diabetes. These findings provide some reassurance, but will need to be replicated in other large-scale studies.
The use of clonidine with diuretic therapy in the treatment of refractory ascites in patients with cirrhosis awaiting liver transplantation
Authors: J. M. Hutchinson, M. H. Davies
Journal: Gut (2011)

We have read the comprehensive review article by Cardenas and Gines that details the management of ascites, hyponatraemia, hepatorenal syndrome, bacterial infections, hepatic encephalopathy and variceal bleeding in patients with decompensated chronic liver disease.1 It is well recognised that such conditions alter pre-, peri- and post-orthotopic liver transplant (OLT) outcomes. However, there is one important issue around …
Chronic diseases influence major life changing decisions: a new domain in quality of life research
Authors: ZU Bhatti, MS Salek, AY Finlay
Journal: Journal of the Royal Society of Medicine (2011)

The purpose of this review is to identify knowledge about the influence of chronic disease on major life changing decisions (MLCDs). This review was carried out in three stages: identification of key search terms; selection of databases and searching parameters; and evaluation of references. Only two articles matched the main search term ‘major life changing decisions’. No article reviewed or measured the influence of chronic disease on major life changing decisions. However, 76 articles and various sections of seven books were identified that provided insight into this area and these are reviewed in detail. This literature review has brought together previously scattered information on chronic disease impact on important patient life decisions. These include decisions related to having children, marriage and divorce, job and career choice, social life, holidays, travelling and education. Lifestyle decisions viewed by patients as major decisions are also documented. The influence of cancer on life decisions is discussed, as are affected life decisions of other family members. Very little information is available about the long-term impact of chronic disease on patients' lives and methodology to assess long-term impact is incomplete. This review points to a novel dimension to health-related outcome research, the impact of chronic disease on major life changing decisions, and its possible implication for patients' future health.