bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison of the accuracy of clinical decisions based on full-text articles and on journal abstracts alone: a study among residents in a tertiary care hospital
Authors: Marcelo Alvin , Gavino Alex , Isip-Tan Iris Thiele , Apostol-Nicodemus Leilanie , Mesa-Gaerlan Faith Joan , Firaza Paul Nimrod , Faustorilla John Francis , Callaghan Fiona M , Fontelo Paul 
Published: July 2012

BackgroundMany clinicians depend solely on journal abstracts to guide clinical decisions.ObjectivesThis study aims to determine if there are differences in the accuracy of responses to simulated cases between resident physicians provided with an abstract only and those with full-text articles. It also attempts to describe their information-seeking behaviour.MethodsSeventy-seven resident physicians from four specialty departments of a tertiary care hospital completed a paper-based questionnaire with clinical simulation cases, then randomly assigned to two intervention groups—access to abstracts-only and access to both abstracts and full-text. While having access to medical literature, they completed an online version of the same questionnaire.FindingsThe average improvement across departments was not significantly different between the abstracts-only group and the full-text group (p=0.44), but when accounting for an interaction between intervention and department, the effect was significant (p=0.049) with improvement greater with full-text in the surgery department. Overall, the accuracy of responses was greater after the provision of either abstracts-only or full-text (p<0.0001). Although some residents indicated that ‘accumulated knowledge’ was sufficient to respond to the patient management questions, in most instances (83% of cases) they still sought medical literature.ConclusionsOur findings support studies that doctors will use evidence when convenient and current evidence improved clinical decisions. The accuracy of decisions improved after the provision of evidence. Clinical decisions guided by full-text articles were more accurate than those guided by abstracts alone, but the results seem to be driven by a significant difference in one department.
Qualities of sessile serrated adenoma/polyp/lesion and its borderline variant in the context of synchronous colorectal carcinoma
Authors: Mohammadi Mahin , Kristensen Michael Holmsgaard , Nielsen Hans Jørgen , Bonde Jesper Hansen , Holck Susanne 
Published: July 2012

AimsAlthough much data have accumulated on sessile serrated adenoma/polyp/lesion (SSA/P/L) in general, its characteristics in specified contexts are less well elucidated. This lack of knowledge is even more conspicuous concerning its borderline counterpart, referred to as BSSA/P/L. The previous histological observations of the authors on SSA/P/L and BSSA/P/L in general are here extended to encompass attributes of these polyps in the context of synchronous colorectal carcinoma (SCRC), with a focus on the place of BSSA/P/L in the spectrum of non-dysplastic serrated polyps.Methods219 SSA/P/Ls, 206 BSSA/P/Ls and 170 hyperplastic polyps (HPs) were examined for SCRC. Demographics, polyp details (size, site, BRAF(V600E)) and advanced synchronous conventional adenomas were recorded.ResultsSCRC was present in 12.3% of SSA/P/Ls, 7.1% of HPs (p=0.09) and 8.3% of BSSA/P/Ls. Patients' ages were comparable. Gender distribution of SSA/P/L and BSSA/P/L was equal, which differed, albeit insignificantly, from a male predominance of HPs. More SSA/P/Ls and BSSA/P/Ls than HPs exceeded 4 mm (p≤0.0001). A proximal site characterised SSA/P/L compared with BBSA/P/L and HP (p<0.0001).BRAFmutation was more prevalent in SSA/P/Ls and BSSA/P/Ls, which further coexisted with advanced synchronous conventional adenomas less commonly than HPs.ConclusionsBSSA/P/L was like SSA/P/L in most respects. The lower SCRC prevalence of BSSA/P/L could fit the idea of BSSA/P/L as a precursor to SSA/P/L, a notion that deserves attention when formulating guidelines for CRC screening.
Dynamics of bovine herpesvirus type 1 infection in Estonian dairy herds with and without a control programme
Authors: Raaperi K. , Aleksejev A. , Orro T. , Viltrop A. 
Published: July 2012

Bovine herpesvirus type 1 (BHV‐1) is an important bovine pathogen, exacerbating poor health and the productivity of cattle. The aims of this study were to detect the efficacy of vaccination programmes in lowering the seroprevalence of BHV‐1 gE within the dairy herd and to follow the dynamics of the infection in non‐vaccinated herds with uninfected heifers. A two‐year longitudinal study was carried out on seven herds that were vaccinated, and in five herds with uninfected heifers without applying a control programme. After the start of the vaccination programme, calves born remained free from the virus. However, in one herd, 7 per cent (95 per cent CI 2 to 18) of these animals showed antibodies to BHV‐1 two years after the first vaccination. A decline in BHV‐1 antibody prevalence was found in vaccinating herds. Among the five herds not under the control programme, one experienced active virus spread, although one herd experienced self‐clearance of the virus. In the herds with high BHV‐1 prevalence, vaccinating all cattle from three months of age twice a year with a commercial inactivated marker vaccine efficiently protected offspring from becoming infected, and lowered the prevalence of BHV‐1 within the herd. A small proportion of herds may experience self‐clearance of the virus.
A Phase I Dose-Escalation Trial of Trastuzumab and Alvespimycin Hydrochloride (KOS-1022; 17 DMAG) in the Treatment of Advanced Solid Tumors
Authors: Jhaveri Komal , Miller Kathy , Rosen Lee , Schneider Bryan , Chap Linnea , Hannah Alison , Zhong Ziyang , Ma Weining , Hudis Clifford , Modi Shanu 
Published: July 2012

Abstract
Purpose: We conducted a phase I dose-escalation study to define the maximum tolerated dose (MTD), pharmacokinetics (PK), and pharmacodynamics of alvespimycin (17-DMAG), a heat shock protein 90 (Hsp90) inhibitor, given in combination with trastuzumab.
Experimental Design: Patients were treated with trastuzumab followed by intravenous alvespimycin on a weekly schedule. Hsp90 client proteins were measured at baseline and serially in peripheral blood lymphocytes (PBL) during cycle 1. Patients with advanced solid tumors progressing on standard therapy were eligible.
Results: Twenty-eight patients (25, breast; 3, ovarian) were enrolled onto three dose cohorts: 60 (n = 9), 80 (n = 13), and 100 mg/m2 (n = 6). Dose-limiting toxicities (DLT) were: grade III left ventricular systolic dysfunction presenting as congestive heart failure in 1 patient (100 mg/m2), and reversible grade III keratitis in two patients (80 mg/m2). Drug-related grade III toxicity included one episode each of fatigue, diarrhea, myalgia, and back pain. Common mild to moderate toxicities included diarrhea, fatigue, myalgia, arthralgia, nausea, blurry vision, headache, back pain, and dry eyes. There was one partial response and seven cases of stable disease (range, 4–10 months), all in HER2+ MBC. In addition, an ovarian cancer patient had complete resolution of ascites and pleural effusion that lasted 24.8 months. There was no change in PK upon weekly dosing. Hsp70 effect continued to increase across four weeks and was most pronounced at 80 and 100 mg/m2.
Conclusion: The combination of alvespimycin and trastuzumab is safe and tolerable at MTD. Antitumor activity was seen in patients with refractory HER2+ MBC and ovarian cancer. The recommended dose of alvespimycin for further study in this combination is 80 mg/m2 weekly. Clin Cancer Res; 18(18); 5090–8. ©2012 AACR.
Peptidomimetic Src/Pretubulin Inhibitor KX-01 Alone and in Combination with Paclitaxel Suppresses Growth, Metastasis in Human ER/PR/HER2-Negative Tumor Xenografts
Authors: Anbalagan Muralidharan , Ali Alaa , Jones Ryan K. , Marsden Carolyn G. , Sheng Mei , Carrier Latonya , Bu Yahao , Hangauer David , Rowan Brian G. 
Published: July 2012

Abstract
Src kinase is elevated in breast tumors that are ER/PR negative and do not overexpress HER2, but clinical trials with Src inhibitors have shown little activity. The present study evaluated preclinical efficacy of a novel peptidomimetic compound, KX-01 (KX2-391), that exhibits dual action as an Src and pretubulin inhibitor. KX-01 was evaluated as a single-agent and in combination with paclitaxel in MDA-MB-231, MDA-MB-157, and MDA-MB-468 human ER/PR/HER2-negative breast cancer cells. Treatments were evaluated by growth/apoptosis, isobologram analysis, migration/invasion assays, tumor xenograft volume, metastasis, and measurement of Src, focal adhesion kinase (FAK), microtubules, Ki67, and microvessel density. KX-01 inhibited cell growth in vitro and in combination with paclitaxel resulted in synergistic growth inhibition. KX-01 resulted in a dose-dependent inhibition of MDA-MB-231 and MDA-MB-157 tumor xenografts (1 and 5 mg/kg, twice daily). KX-01 inhibited activity of Src and downstream mediator FAK in tumors that was coincident with reduced proliferation and angiogenesis and increased apoptosis. KX01 also resulted in microtubule disruption in tumors. Combination of KX-01 with paclitaxel resulted in significant regression of MDA-MB-231 tumors and reduced metastasis to mouse lung and liver. KX-01 is a potently active Src/pretubulin inhibitor that inhibits breast tumor growth and metastasis. As ER/PR/HER2-negative patients are candidates for paclitaxel therapy, combination with KX-01 may potentiate antitumor efficacy in management of this aggressive breast cancer subtype. Mol Cancer Ther; 11(9); 1936–47. ©2012 AACR.
Pioglitazone, a PPARγ Agonist, Suppresses CYP19 Transcription: Evidence for Involvement of 15-Hydroxyprostaglandin Dehydrogenase and BRCA1
Authors: Subbaramaiah Kotha , Howe Louise R. , Zhou Xi Kathy , Yang Peiying , Hudis Clifford A. , Kopelovich Levy , Dannenberg Andrew J. 
Published: July 2012

Abstract
Estrogen synthesis is catalyzed by cytochrome P450 aromatase, which is encoded by the CYP19 gene. In obese postmenopausal women, increased aromatase activity in white adipose tissue is believed to contribute to hormone-dependent breast cancer. Prostaglandin E2 (PGE2) stimulates the cAMP→protein kinase A (PKA) pathway leading to increased CYP19 transcription and elevated aromatase activity in inflamed white adipose tissue. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) plays a major role in the catabolism of PGE2. Here, we investigated the mechanism by which pioglitazone, a ligand of the nuclear receptor PPARγ suppressed aromatase expression. Treatment of human preadipocytes with pioglitazone suppressed Snail, a repressive transcription factor, resulting in elevated levels of 15-PGDH and reduced levels of PGE2 in the culture medium. Pioglitazone also inhibited cAMP→PKA signaling leading to reduced interaction between phosphorylated cAMP responsive element–binding protein, p300, and CYP19 I.3/II promoter. BRCA1, a repressor of CYP19 transcription, was induced by pioglitazone. Consistent with these in vitro findings, treatment of mice with pioglitazone activated PPARγ, induced 15-PGDH and BRCA1 while suppressing aromatase levels in the mammary gland. Collectively, these results indicate that the activation of PPARγ induces BRCA1 and suppresses the PGE2→cAMP→PKA axis leading to reduced levels of aromatase. PPARγ agonists may have a role in reducing the risk of hormone-dependent breast cancer in obese postmenopausal women. Cancer Prev Res; 5(10); 1183–94. ©2012 AACR.
Selective Activation of Oxygen-Deprived Tumor-Infiltrating Lymphocytes through Local Intratumoral Delivery of CD137 Monoclonal Antibodies
Authors: Melief Cornelis J.M. 
Published: July 2012

Abstract
Summary: Hypoxia-inducing transcription factor-1α (HIF-1α) in hypoxic tumors induces the TNF receptor family member CD137 on tumor-infiltrating lymphocytes. This can be exploited for intratumoral low-dose injection of effective systemic immunotherapy with agonist CD137-specific monoclonal antibodies that induce circulation of systemic tumor-specific effector T cells capable of eradicating distant metastases. Cancer Discov; 2(7); 586–7. ©2012 AACR.
Commentary on Palazón et al., p. 608.
ADAMTS13 exerts a thrombolytic effect in microcirculation
Authors: Demers Melanie , Voorhees Jaymie R. , Wong Siu , Ho-Tin-Noé Benoit , Crescente Marilena , Thomas Grace M. , Wagner Denisa D. 
Published: July 2012

SummaryRecombinant tissue plasminogen activator (r-tPA) is the drug of choice for thrombolysis, but it is associated with a significant risk of bleeding and is not always successful. By cleaving von Willebrand factor (VWF), the metalloprotease ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type I repeats-13) down-regulates thrombus formation in injured vessels. We investigated whether recombinant ADAMTS13 (r-ADAMTS13) induces thrombolysis in vivo in mice. Thrombosis was produced by ferric chloride-induced (FeCl3) injury in the venules of a dorsal skinfold chamber. Phosphate-buffered saline (PBS, vehicle), r-tPA or r-ADAMTS13, supplemented with hirudin (to stop ongoing thrombin generation), was directly applied onto the occluded vessel, and thrombus dissolution was evaluated by intravital microscopy. The incidence of blood flow restoration significantly increased 30 minutes (min) after r-ADAMTS13 vs. PBS treatment (60% vs. 0%, p<0.05) and 60 min after r-tPA treatment (75% vs. 17%, p<0.05). Both r-tPA and r-ADAMTS13 significantly reduced thrombus size 60 min after their superfusion (53.2% and 62.3% of the initial thrombus size, p<0.05 and p<0.01, respectively). Bleeding occurred in all r-tPA-treated chambers, while it was absent in mice treated with r-ADAMTS13 or PBS. We observed that, similar to r-tPA, r-ADAMTS13 can dissolve occlusive thrombi induced by FeCl3 injury in venules. In contrast to r-tPA, the in vivo thrombolytic effect of ADAMTS13 was not associated with any signs of haemorrhage. ADAMTS13 could represent a new therapeutic option for thrombolysis.
Levels of prolactin in relation to coagulation factors and risk of venous thrombosis
Authors: Debeij Jan , van Zaane Bregje , Dekkers Olaf M. , Smit Jan W. A. , Büller Harry R. , Rosendaal Frits R. , Gerdes Victor E. A. , Cannegieter Suzanne C. , Stuijver Danka J. F. 
Published: July 2012

SummaryThe pituitary hormone prolactin is thought to influence coagulation. We aimed to study the relation between prolactin levels, coagulation factors and risk of venous thrombosis (VT). We used data from a large population based case-control study into aetiology of first VT (MEGA-study). Prolactin levels were determined in 2,068 patients with VT and 2,785 age- and sex matched control subjects. The relation between levels of coagulation factors and prolactin was studied among the controls. In addition, odds ratios (OR) and 95% confidence intervals (95%CI) were calculated for the risk of VT for different cut-off points of prolactin levels based on percentiles determined in the controls. Restricted analysis was performed among cases in whom blood was sampled within six months after VT. We found a rise in factor VIII and von Willebrand factor with increasing levels of prolactin in the controls. An increased risk of VT was observed when blood was sampled within six months after thrombosis (OR 2.9, 95%CI 1.1–8.1) for prolactin levels above the 99th percentile (42.6 μg/l) relative to levels between the 20th to 80th percentile. When blood was sampled more than six months after VT no clear association could be observed (OR 1.3, 95%CI 0.7–2.3). In conclusion, we found a modest association between pro-lactin and symptomatic venous thromboembolism, particularly when blood was sampled close to the event. This may be explained by a causal relation or by prolactin being a marker of stress due to the thrombotic event.
Functional characterisation of Vizottin, the first factor Xa inhibitor purified from the leech Haementeria vizottoi
Authors: Oliveira Daniella , Alvarez-Flores Miryam , Lopes Adriana , Chudzinski-Tavassi Ana 
Published: July 2012

SummaryThe strategic position of factor Xa (FXa) in blood coagulation makes it a compelling target for the development of new anticoagulants. Bloodsucking animals have in their salivary glands mixtures of anticoagulants, which could be used for designing novel antithrombotic compounds. Herein, we describe Vizottin, the first FXa inhibitor from the salivary complex of the leech Haementeria vizottoi. Vizottin was purified by gel filtration and reverse-phase chromatography, and shown to have anticoagulant effects in human plasma, prolonging the recalcification time in a dose-dependent manner (IC50 40 nM). Vizottin induced blood incoagulability in FX-deficient plasma, whereas in normal and reconstituted plasma, Vizottin doubled the prothrombin time at 160 nM. This peptide competitively inhibited human FXa (Ki 2 nM) like FXa inhibitors from other leeches, albeit via a distinct mechanism of action. At high concentrations, vizottin inhibited the amidolytic activity of factor VIIa/tissue factor (IC50 96.4 nM). Vizottin inhibited FXa in the prothrombinase complex and Gla-domainless FXa. Moreover, vizottin did not interfere with FX activation induced by RVV-X, a known enzyme that requires the Gla-domain of FX for activation. Competition experiments in the presence of FXa and GGACK-FXa (active site blocked) demonstrated that the inhibition of FXa by vizottin is through binding to the active site rather than an exosite. This novel inhibitor appears to exert its inhibitory effects through direct binding to the active site of FXa in a time-dependent manner, but not involving a tight-binding model. In this context, vizottin is a promising model for designing novel anticoagulants for the treatment of thrombotic diseases.
New direct oral anticoagulants – current therapeutic options and treatment recommendations for bleeding complications
Authors: Seifried Erhard , Miesbach Wolfgang 
Published: July 2012

SummaryTo date, clinical studies show that the incidence of spontaneous bleeding with new direct oral anticoagulants (DOAs) is comparable to that of established anticoagulants. However, unlike vitamin K antagonists, there are currently no clinically available antidotes or approved reversal agents for new DOAs. Restoring normal coagulation is important in many cases, such as emergency surgeries, serious bleedings, or anticoagulant overdosing. Attempts have been made to restore normal coagulation after treatment with new DOAs using compounds such as recombinant activated factor VII (rFVIIa), prothrombin complex concentrate (PCC), or FEIBA (factor eight inhibitor bypassing activity). Limited pre-clinical data and even less clinical evidence are available on the usefulness of these methods in restoring normal coagulation for the emergency management of critical bleeding episodes. Evaluating the utility of DOAs is further complicated by the fact that it is unknown how predictive established test systems are of the bleeding risks. Clinical practice requires further evaluation of the emergency management options for the new DOAs to define the agents and the doses that are most useful. Furthermore, patients receiving long-term treatment with a DOA are likely to undergo elective surgery at some point, and there is lack of evidence regarding perioperative treatment regimens under such conditions. This review summarises potential bleeding management options and available data on the new DOAs.
Should We Recommend Oral Anticoagulation Therapy in Patients With Atrial Fibrillation Undergoing Coronary Artery Stenting With a High HAS-BLED Bleeding Risk Score?
Authors: Ruiz-Nodar Juan M. , Marín Francisco , Roldán Vanessa , Valencia José , Manzano-Fernández Sergio , Caballero Luis , Hurtado José A. , Sogorb Francisco , Valdés Mariano , Lip Gregory Y.H. 
Published: July 2012

Background—

Recent European guidelines for the management of atrial fibrillation recommend oral anticoagulation (OAC) in patients with CHA
2
DS
2
-VASc score (congestive heart failure, hypertension, age ≥75 years, diabetes, history of previous stroke, vascular disease, age 65–74 years, and sex category [female]) ≥1. The HAS-BLED score (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly [>65 years], Drugs/alcohol concomitantly) has been suggested to assess bleeding risk in patients with atrial fibrillation (score ≥3 indicates high risk of bleeding). Despite the guidelines, this approach has never been tested in a cohort of patients with atrial fibrillation undergoing percutaneous coronary intervention with stent implantation.

Methods and Results—

We studied 590 consecutive patients with atrial fibrillation undergoing percutaneous coronary intervention/stenting and CHA
2
DS
2
-VASC score >1 (ie, OAC recommended). We compared patients with low-intermediate bleeding risk (HAS-BLED 0–2) and high risk (HAS-BLED ≥3), the relation between CHA
2
DS
2
-VASC and HAS-BLED, and the benefit and risks of the use of OAC in patients with high bleeding risk. The development of any bleeding episode, thromboembolism, mortality, cardiac events, and the composite major adverse cardiac events (ie, death, acute myocardial infarction, and/or target lesion revascularization) end point was recorded as well as the composite major adverse events (ie, major adverse cardiac events, major bleeding, or thromboembolism) end point at 1-year follow-up. Of the study cohort, 420 (71%) had a HAS-BLED score ≥3, and patients who were on OAC at discharge had lower mortality rate (9.3% versus 20.1%;
P
<0.01) and major adverse cardiac events (13.0% versus 26.4%;
P
<0.01) but with a similar major adverse event (20.5% versus 27.6%;
P
=0.11) and higher major bleeding rate (11.8% versus 4.0%;
P
<0.01). In a Cox multivariable analysis in patients with HAS-BLED ≥3, predictors of increased death were chronic renal failure and heart failure (both
P
<0.05), whereas OAC at discharge was associated with a reduced death rate (
P
<0.01). Predictors of major bleeding were chronic renal failure and the use of drug-eluting stents (both
P
<0.05).

Conclusions—
Most patients with atrial fibrillation undergoing percutaneous coronary intervention/stenting have a high risk for major bleeding (HAS-BLED score ≥3). Even in these patients, OAC improves prognosis in these patients (reduced mortality and major adverse cardiac events) with an increase in major bleeding.