tbuckley/cabot-search huggingface dataset:
How to Get All Trials Reported: Audit, Better Data, and Individual Accountability
Authors: Ben Goldacre
Journal: PLoS Medicine (2015)

In this week's PLOS Medicine, the World Health Organization (WHO) publishes a landmark position statement, requiring all trials to make their methods and results available [1].This represents important progress on a long-standing and global structural problem that has a clear, negative impact on patient care.The best currently available evidence shows that the methods and results of clinical trials are routinely withheld from doctors, researchers, and patients [2-5], undermining our best efforts at informed decision making.From this point forward, whenever the methods and results of a trial are withheld, doctors, patients, researchers, campaigners, and health care providers will be able to point at an unambiguous statement from WHO.Delivering definitive change, however, will require more than positive statements and good intentions.The first quantitative data demonstrating publication bias in clinical trials-and clear call for trial registries-was published in 1986 [6].Anyone withholding the methods and results of a clinical trial is already in breach of multiple codes and regulations, including the Declaration of Helsinki, various promises from industry and professional bodies, and, in many cases, the United States Food and Drug Administration (FDA) Amendment Act of 2007.Indeed, a recently published cohort study of trials in clinicaltrials.govfound that more than half had failed to post results; and even though the FDA is entitled to issue fines of $10,000 a day for transgressions, no such fines have ever been levied [3].In the face of such slow progress, this commentary sets out some practical suggestions for auditing, performance tables, accountability, codes of conduct, and better data that should help to drive up standards and prevent trial reports being withheld from those who need them most.
The Translational Research Working Group Developmental Pathway for Interventive Devices
Authors: Gary S. Dorfman, Theodore S. Lawrence, Lynn M. Matrisian
Journal: Clinical Cancer Research (2008)

Abstract The interventive device pathway refers to one of six pathways developed by the Translational Research Working Group (TRWG) that, together, describe the core domains of early translational cancer research. This pathway focuses on the development of devices (as classified by the Food and Drug Administration), designed for local ablation of cancer or precancerous lesions (e.g., radiation therapy, microwave, radiofrequency ablation, and high-intensity focused ultrasound systems). This article describes the distinctive features of the pathway and issues that are encountered in the real-world development of interventive devices for the treatment of cancer. The interventive device pathway is envisioned to be a general guideline of the steps required for effective development, optimization, testing, and validation of developing devices, to be dynamic and adaptable, and to form a framework for discussions focused on improving the efficiency and effectiveness of new device development.
The isoprostane, 8-epi-PGF2α, is accumulated in coronary arteries isolated from patients with coronary heart disease
Authors: M Reza Mehrabi
Journal: Cardiovascular Research (1999)

In the present study we wanted to know whether 8-epi-PGF2 alpha, which belongs to the class of isoprostanes formed by free radical-mediated peroxidation of arachidonic acid and arachidonyl-containing phospholipids, is enriched in isolated coronary arteries of patients suffering from coronary heart disease (CHD, n = 23) who received allograft heart transplants as compared to vessels derived from patients with dilative cardiomyopathy (CMP, n = 19) or from healthy heart donors (controls, n = 6).Sections from the isolated coronary arteries were analysed by semiquantitative immunohistochemistry by determining the area and intensity of positive reaction for 8-epi-PGF2 alpha in the vascular intima and media. In addition, the 8-epi-PGF2 alpha content was determined using a specific immunoassay after extraction and purification.The immunohistochemical results indicated that 8-epi-PGF2 alpha is significantly enriched in arteries from patients suffering from CHD as compared to CMP (P < 0.0001). In controls, significantly less immunostaining was observed. Furthermore, a significant positive correlation between semiquantitative immunohistochemistry and radioimmunological determination was observed too.From our findings we conclude that 8-epi-PGF2 alpha is especially accumulated in coronary arteries from CHD patients and therefore is likely to be involved in atherogenesis.
Chemosensitization of Androgen-Independent Prostate Cancer with Neutral Endopeptidase
Authors: Makoto Sumitomo, Tomohiko Asano, Junichi Asakuma, Takako Asano, David M. Nanus, Masamichi Hayakawa
Journal: Clinical Cancer Research (2004)

Abstract Purpose: We investigated whether neutral endopeptidase (NEP) could augment chemosensitivity to anticancer drugs by promoting protein kinase C (PKC)δ-mediated mitochondrial apoptosis in prostate cancer (PC) cells. Experimental Design: Human PC cell lines LNCaP and PC-3, and a normal prostate epithelial cell line (PrEC) were used. The protein expression was detected by Western blot analysis, and the protein turnover was determined by pulse-chase assay. Apoptotic ratio was measured by annexin V staining. Results: Western blot analyses and pulse-chase assays showed that the specific NEP inhibitor CGS24592 decreased PKCδ protein expression by promoting PKCδ protein degradation in NEP-expressing LNCaP cells. Conversely, recombinant NEP (rNEP) increased PKCδ protein expression by delaying PKCδ protein degradation in NEP-negative PC-3 cells. Apoptosis assays showed that rNEP promoted anticancer drug-induced apoptosis in PC-3 cells specifically through PKCδ activity that mediated anticancer drug-induced mitochondrial change such as cytochrome-c release and caspase-9 activation. Of note, rNEP was able to increase PKCδ protein expression predominantly in PC-3 cells rather than in PrEC cells. Treatment with rNEP before subtoxic concentrations of etoposide (0.1 μm) significantly promoted mitochondrial apoptosis compared with only etoposide in PC-3 cells (P &amp;lt; 0.01) but not in PrEC cells. Conclusions: These results suggest that NEP enzyme activity contributes to anticancer drug-induced PC cell apoptosis dependent on PKCδ-mediated mitochondrial events. More importantly, the combination of NEP with anticancer drugs may be a promising therapeutic modality because rNEP is able to augment chemosensitivity in androgen-independent PC with minimal toxicity in normal tissues.
PCR detection of Streptococcus pneumoniae DNA in serum samples for pneumococcal pneumonia diagnosis
Authors: J. Domínguez, N. Galí, L. Matas, P. Pedroso, S. Blanco, M. Giménez, C. Prat, N. Sopena, M. Sabrià, V. Ausina
Journal: Clinical Microbiology and Infection (2001)
Positive Selection during the Evolution of the Blood Coagulation Factors in the Context of Their Disease-Causing Mutations
Authors: Pavithra M. Rallapalli, Christine A. Orengo, Romain A. Studer, Stephen J. Perkins
Journal: Molecular Biology and Evolution (2014)

Blood coagulation occurs through a cascade of enzymes and cofactors that produces a fibrin clot, while otherwise maintaining hemostasis.The 11 human coagulation factors (FG, FII-FXIII) have been identified across all vertebrates, suggesting that they emerged with the first vertebrates around 500 Ma.Human FVIII, FIX, and FXI are associated with thousands of disease-causing mutations.Here, we evaluated the strength of selective pressures on the 14 genes coding for the 11 factors during vertebrate evolution, and compared these with human mutations in FVIII, FIX, and FXI.Positive selection was identified for fibrinogen (FG), FIII, FVIII, FIX, and FX in the mammalian Primates and Laurasiatheria and the Sauropsida (reptiles and birds).This showed that the coagulation system in vertebrates was under strong selective pressures, perhaps to adapt against blood-invading pathogens.The comparison of these results with disease-causing mutations reported in FVIII, FIX, and FXI showed that the number of disease-causing mutations, and the probability of positive selection were inversely related to each other.It was concluded that when a site was under positive selection, it was less likely to be associated with disease-causing mutations.In contrast, sites under negative selection were more likely to be associated with disease-causing mutations and be destabilizing.A residue-by-residue comparison of the FVIII, FIX, and FXI sequence alignments confirmed this.This improved understanding of evolutionary changes in FVIII, FIX, and FXI provided greater insight into disease-causing mutations, and better assessments of the codon sites that may be mutated in applications of gene therapy.
Prospective Study of Zinc Intake and Risk of Type 2 Diabetes in Women
Authors: Qi Sun, Rob M. van Dam, Walter C. Willett, Frank B. Hu
Journal: Diabetes Care (2009)

OBJECTIVE The aim of this study is to investigate the intake of zinc in relation to risk of type 2 diabetes in U.S. women. RESEARCH DESIGN AND METHODS Dietary intakes of zinc and other nutrients were assessed and updated using a validated food frequency questionnaire from 1980 to 2002 among 82,297 women who were aged 33–60 years at baseline in 1980 and followed up to 2004 in the Nurses' Health Study. RESULTS During the 24 years of follow-up, 6,030 incident cases of type 2 diabetes were ascertained. After adjustment of lifestyle and dietary risk factors, the relative risks (RRs) (95% CI) of type 2 diabetes comparing the highest with the lowest quintiles were 0.90 (0.82–0.99) (Ptrend = 0.04) for total zinc intake and 0.92 (0.84–1.00) (Ptrend = 0.009) for dietary zinc intake from food sources, respectively. We further found an inverse association for dietary zinc to heme iron ratio. After multivariate adjustment of covariates, the RRs (95% CI) across quintiles of this ratio were 1.0 (reference), 0.93 (0.86–1.01), 0.86 (0.79–0.94), 0.82 (0.75–0.90), and 0.72 (0.66–0.80), respectively (Ptrend &amp;lt; 0.0001). CONCLUSIONS Higher zinc intake may be associated with a slightly lower risk of type 2 diabetes in women. More studies are warranted to confirm this association and to explore potential mechanisms.
In Vitro Evidence for an Intracellular Site of Angiotensin Action
Authors: Julia L. Cook, Zhuo Zhang, Richard N. Re
Journal: Circulation Research (2001)

To differentiate the relative effects of nuclear and cell surface angiotensin II (Ang II) receptors, we mutated the angiotensinogen cDNA by removing the signal sequence-encoding region to produce a nonsecreted form of angiotensinogen [Ang(-S)Exp]. Rat hepatoma cells (which produce renin and angiotensin-converting enzyme mRNAs) were stably transfected with Ang(-S)Exp/pSVL (or a corresponding control) expression plasmid, and mitotic indices were measured for stably transfected cell lines. Experimental clonal cell lines demonstrate an average of 33+/-4.4% (P<0.001) increase in percentage-labeled nuclei compared with control cell lines. The mitogenic effect is blocked by 10(-6) mol/L losartan and by 1 micromol/L renin antisense phosphorothioate oligomers but not by 10(-6) mol/L candesartan. In addition, phenylarsine oxide, which blocks angiotensin receptor internalization, abolishes the losartan inhibitory effect, suggesting that after cell-surface receptor-mediated endocytosis, losartan blocks Ang II nuclear receptors. PDGF mRNA levels are elevated 2.2-fold in Ang(-S)Exp transfected cell lines; addition of anti-PDGF antibodies to the culture medium partially blocks the mitogenic effect of Ang(-S)Exp, while anti-Ang II antibodies have no effect. These results suggest that the Ang(-S)Exp growth effect is due, in part, to autocrine/paracrine stimulation by secreted PDGF after Ang II/Ang II receptor intracellular interactions. We further demonstrate that these cells produce the alternative renin transcript, renin 1A, which apparently lacks a signal sequence and is maintained intracellularly. Collectively, these studies of cultured cells suggest that some cell types may possess components of the renin-angiotensin system that permit intracellular processing of angiotensinogen to Ang II and that Ang II generated intracellularly may be mitogenic.
Second metatarsal stress fracture in sport: comparative risk factors between proximal and non-proximal locations
Authors: B. Chuckpaiwong, C. Cook, R. Pietrobon, J. A Nunley
Journal: British Journal of Sports Medicine (2007)

Background: Stress fractures of the second metatarsal are common injuries in athletes and military recruits. There are two distinct areas in the second metatarsal where stress fractures develop: one proximal (at the base) and the other non-proximal (distal). Diagnosis can be difficult, and there is a difference in prognosis and treatment of the two types of stress fracture. Therefore differentiation of fracture location is warranted. Differences in risk factors and clinical outcomes between proximal and non-proximal stress fractures have not been studied. Objective: To determine whether different risk factors and/or clinical outcomes associated with proximal and non-proximal stress fractures of the second metatarsal exist. Methods: Patients diagnosed with proximal stress fractures of the second metatarsal were included in the study. Retrospectively, an age-matched control group with a non-proximal stress fracture was selected for comparison. Statistical analysis involved bivariate comparisons of demographic variables and clinical measurement between the two groups. Results: Patients with proximal stress fractures were more likely to be chronically affected, usually exhibited an Achilles contracture, showed differences in length of first compared with second metatarsal, were more likely to experience multiple stress fractures, and exhibited low bone mass. In addition, a high degree of training slightly increased the risk of a non-proximal fracture, whereas low training volume was associated with a proximal stress fracture. Conclusion: The signs, symptoms and clinical findings associated with proximal metatarsal stress fractures are different from those of non-proximal stress fractures.
Differentiation of ventricular tachyarrhythmias.
Authors: K M Ropella, J M Baerman, A V Sahakian, S Swiryn
Journal: Circulation (1990)

Implantable devices capable of several modes of therapy will require differentiation of various ventricular tachyarrhythmias. Three methods of arrhythmia analysis, magnitude-squared coherence, ventricular rate, and irregularity of cycle length were performed for 45 episodes of induced ventricular tachyarrhythmia in 15 patients. Differentiation of monomorphic ventricular tachycardia from polymorphic ventricular tachycardia and ventricular fibrillation was possible by mean magnitude-squared coherence, less possible by rate, and not possible by beat-to-beat irregularity. Faster monomorphic ventricular tachycardia overlapped with rates of polymorphic ventricular tachycardia and ventricular fibrillation. Differentiation of polymorphic ventricular tachycardia and ventricular fibrillation was not possible by rate or irregularity. A progressive decrease in mean magnitude-squared coherence from monomorphic ventricular tachycardia to polymorphic ventricular tachycardia to ventricular fibrillation strengthens previous observations that coherence is a measure of rhythm "organization."
KB-R7943 Block of Ca <sup>2+</sup> Influx Via Na <sup>+</sup> /Ca <sup>2+</sup> Exchange Does Not Alter Twitches or Glycoside Inotropy but Prevents Ca <sup>2+</sup> Overload in Rat Ventricular Myocytes
Authors: Hiroshi Satoh, Kenneth S. Ginsburg, Ke Qing, Hajime Terada, Hideharu Hayashi, Donald M. Bers
Journal: Circulation (2000)

Background —The Na + /Ca 2+ exchange (NCX) extrudes Ca 2+ from cardiac myocytes, but it can also mediate Ca 2+ influx, load the sarcoplasmic reticulum with Ca 2+ , and trigger Ca 2+ release from the sarcoplasmic reticulum. In ischemia/reperfusion or digitalis toxicity, increased levels of intracellular [Na + ] ([Na + ] i ) may raise levels of intracellular [Ca 2+ ] ([Ca 2+ ] i ) via NCX, leading to cell injury and arrhythmia. Methods and Results —We used KB-R7943 (KBR) to selectively block Ca 2+ influx via NCX to study the role of NCX-mediated Ca 2+ influx in intact rat ventricular myocytes. Removing extracellular Na + caused [Ca 2+ ] i to rise, due to Ca 2+ influx via NCX, and this was blocked by 90% with 5 μmol/L KBR. However, KBR did not alter [Ca 2+ ] i decline due to NCX. Thus, we used 5 μmol/L KBR to selectively block Ca 2+ entry but not efflux via NCX. Under control conditions, 5 μmol/L KBR did not alter steady-state twitches, Ca 2+ transients, Ca 2+ load in the sarcoplasmic reticulum, or rest potentiation, but it did prolong the late low plateau of the rat action potential. When Na + /K + ATPase was inhibited by strophanthidin, KBR reduced diastolic [Ca 2+ ] i and abolished the spontaneous Ca 2+ oscillations, but it did not prevent inotropy. Conclusions —In rat ventricular myocytes, Ca 2+ influx via NCX is not important for normal excitation-contraction coupling. Furthermore, the inhibition of Ca 2+ efflux alone (as [Na + ] i rises) may be sufficient to cause glycoside inotropy. In contrast, Ca 2+ overload and spontaneous activity at high [Na + ] i was blocked by KBR, suggesting that net Ca 2+ influx (not merely reduced efflux) via NCX is involved in potentially arrhythmogenic Ca 2+ overload.
Melanoma Computer-Aided Diagnosis
Authors: Marco Burroni, Rosamaria Corona, Giordana Dell’Eva, Francesco Sera, Riccardo Bono, Pietro Puddu, Roberto Perotti, Franco Nobile, Lucio Andreassi, Pietro Rubegni
Journal: Clinical Cancer Research (2004)

Abstract Background: Differential diagnosis of melanoma from melanocytic nevi is often not straightforward. Thus, a growing interest has developed in the last decade in the automated analysis of digitized images obtained by epiluminescence microscopy techniques to assist clinicians in differentiating early melanoma from benign skin lesions. Purpose: The aim of this study was to evaluate diagnostic accuracy provided by different statistical classifiers on a large set of pigmented skin lesions grabbed by four digital analyzers located in two different dermatological units. Experimental Design: Images of 391melanomas and 449 melanocytic nevi were included in the study. A linear classifier was built by using the method of receiver operating characteristic curves to identify a threshold value for a fixed sensitivity of 95%. A K-nearest-neighbor classifier, a nonparametric method of pattern recognition, was constructed using all available image features and trained for a sensitivity of 98% on a large exemplar set of lesions. Results: On independent test sets of lesions, the linear classifier and the K-nearest-neighbor classifier produced a mean sensitivity of 95% and 98% and a mean specificity of 78% and of 79%, respectively. Conclusions: In conclusion, our study suggests that computer-aided differentiation of melanoma from benign pigmented lesions obtained with DB-Mips is feasible and, above all, reliable. In fact, the same instrumentations used in different units provided similar diagnostic accuracy. Whether this would improve early diagnosis of melanoma and/or reducing unnecessary surgery needs to be demonstrated by a randomized clinical trial.
A Conformal, Bio-Interfaced Class of Silicon Electronics for Mapping Cardiac Electrophysiology
Authors: Jonathan Viventi, Dae-Hyeong Kim, Joshua D. Moss, Yun-Soung Kim, Justin A. Blanco, Nicholas Annetta, Andrew Hicks, Jianliang Xiao, Younggang Huang, David J. Callans, John A. Rogers, Brian Litt
Journal: Science Translational Medicine (2010)

Flexible electronics and sensors that adhere to the surfaces of living, moving tissues allow detailed mapping of cardiac electrical activity in a porcine animal model.
CARCINOMA IN BENIGN MUCOUS MEMBRANE PEMPHIGOID (OCULAR PEMPHIGUS).
Authors: H. W. CHADFIELD, C. R. KANAGASUNDARAM
Journal: British Journal of Dermatology (1962)

Journal Article CARCINOMA IN BENIGN MUCOUS MEMBRANE PEMPHIGOID (OCULAR PEMPHIGUS). Get access H. W. CHADFIELD, M.R.C.P.(Ed.), H. W. CHADFIELD, M.R.C.P.(Ed.) Consultant Dermatologist, The Royal Hospital, Wolverhampton Search for other works by this author on: Oxford Academic Google Scholar C. R. KANAGASUNDARAM, M.B., B.S., D.O. C. R. KANAGASUNDARAM, M.B., B.S., D.O. Senior Registrar, Eye Infirmary, Wolverhampton.* Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 74, Issue 12, 1 December 1962, Pages 458–461, https://doi.org/10.1111/j.1365-2133.1962.tb13446.x Published: 01 December 1962
A1.33 LY6C resident monocytes with osteoclastogenic potential arise before clinical onset of arthritis
Authors: A Puchner, V Saferding, E Goncalves-Alves, H Leiss, JS Smolen, K Redlich, S Blüml
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Introduction</h3> Bone erosions and systemic bone loss in rheumatoid arthritis patients results from an increased activity of osteoclast, which are derived from precursor cells of the myeloid lineage. Although there is much known about the mechanisms regulating the formation and activation of mature osteoclasts, the identity of an osteoclast precursor population in and its regulation by inflammatory cytokines during arthritis is poorly understood. <h3>Methods</h3> HTNFtg mice were clinically scored once per week for grip strength and swelling. In addition, blood was collected every week starting on week 4. Mice were sacrificed at week 10 - blood, spleen and bone marrow were collected for flow cytometry analysis. CCR2<sup>-/-</sup> mice were crossed into hTNFtg mice and histological analysis was performed. Different monocyte subsets were Facs-sorted and cultured in the presence of RANKL and MCSF to induce osteoclasts. <h3>Results</h3> We show that during TNF-driven arthritis CD11b<sup>+</sup>CD115<sup>+</sup> cells are elevated in blood before the onset of clinical symptoms and remain elevated throughout. These cells are also elevated in spleen and bone marrow during arthritis. In blood, these cells can be separated by their expression of Ly6C into inflammatory monocytes (CD115<sup>+</sup>Ly6C<sup>high</sup>) and resident monocytes (CD115<sup>+</sup><sup>L</sup>y6C<sup>low</sup>). Interestingly, especially resident monocytes are elevated preclinical. Upon sorting resident and inflammatory monocyes from blood, we demonstrate that only resident monocytes are able to form multinucleated TRAP+ osteoclasts, but inflammatory monocytes do not. In order to further investigate the role of these monocyte subsets in the development of arthritic bone destruction and osteoclast formation we used CCR2 deficient mice, which lack circulating inflammatory monocytes and crossed them into hTNFtg animals. In line with our <i>in vitro</i> data, hTNFtg mice lacking CCR2 (i.e. inflammatory monocytes) showed no reduction in the amount of joint destruction but even enhanced local bone erosion and osteoclast generation. <h3>Conclusion</h3> CD115<sup>+</sup> CD11b<sup>+</sup> cells, especially Ly6C- resident monocytes with osteoclastogenic potential, increase during inflammatory arthritis. Elevated numbers of these cells can be detected before clinical onset of disease and therefore may provide a biomarker for erosive inflammatory arthritis and even a possible target for therapeutically intervention.