bluuebunny/crossref_metadata_2025_split huggingface dataset:
Draft Genome Sequence of Biocontrol Bacterium Brevibacillus brevis Strain FJAT-0809-GLX
Authors: Che Jianmei , Liu Bo , Lin Yingzhi , Tang Weiqi , Tang Jianyang 
Published: April 2013

ABSTRACT

Brevibacillus brevis
strain FJAT-0809-GLX had significant inhibition on many plant and animal pathogens. The draft genome sequence of
B. brevis
FJAT-0809-GLX is 6 Mb in size and consists of 5,677 genes (protein-coding sequences [CDS]), with an average length of 933 bp and a G+C content of 47.30%. Compared with the published
B. brevis
strain NBRC 100599, 618 specific genes were identified in the strain FJAT-0809-GLX.
Critical factors for the prevention of low back pain in elite junior divers
Authors: Narita Takaya , Kaneoka Koji , Takemura Masahiro , Sakata Yoshihiro , Nomura Takamichi , Miyakawa Shumpei 
Published: April 2013

Background/AimDuring competitive diving, divers jump up from 1 to 3 m springboards or 5 to 10 m platforms and dive into the water. The impact forces are very large in the water entry phase, and, as such, microtraumatic injuries are common due to the tremendous physical stress placed on the diver. Low-back pain (LBP) is the most frequently reported symptom in divers. This study aimed to extract possible risk factors related to LBP from physical and technical characteristics in Japanese elite junior divers.MethodsEighty-three elite junior divers (42 men and 41 women) in Japan were included in this study. LBP was assessed by a questionnaire, interview and physical examination during a national training camp. Morphological data, physical fitness and diving skills were also evaluated. The factors related to LBP were extracted by using logistic-regression analysis and the forward-selection method (likelihood ratio).ResultsA total of 37.3% (31 reports) of back pain occurred in the lumbar region. Shoulder flexibility (OR 0.919; 95% CI 0.851 to 0.992) and age (OR 0.441; 95% CI 0.239 to 0.814) were recognised as factors related to LBP in male-elite junior divers, whereas only age (OR 0.536; 95% CI 0.335 to 0.856) was a factor in female-elite junior divers.ConclusionsOur results suggest that shoulder flexibility is important for preventing LBP in elite-male junior divers, since they require full shoulder flexion during the water entry phase. Limited shoulder flexibility could cause lumbar hyperextension when adjusting for the angle of water entry.
Speaking the same language? International variations in the safety information accompanying top-selling prescription drugs
Authors: Kesselheim Aaron S , Franklin Jessica M , Avorn Jerry , Duke Jon D 
Published: April 2013

BackgroundThe official prescribing information document distributed with a prescription drug is a key source of safety information, but it may include excessive or insufficient details.ObjectivesTo compare prescribing information approved by the US Food and Drug Administration with the UK, Canada and Australia to identify content differences in safety warnings.MethodsFor 20 top-selling prescription drugs, we used an automated natural language processing tool to calculate the number and severity of reported adverse drug reactions (ADRs). We fit hierarchical Poisson models and included fixed effects for other prescribing information characteristics. Separately, we analysed the appearance and content of ‘black box’ warnings.ResultsThere was substantial variation in safety content of approved prescribing information. Canada had the highest median ADRs per drug (138 (IQR 86–234)) and the UK had the lowest (84 (IQR 51–111)). The number of ADRs reported was on average 50% higher in Canada compared with the USA (ratio of ADRs/document: 1.5, 95% CI 1.4 to 1.6, p<0.001). By contrast, there were on average 15% fewer ADRs listed in the UK compared with the USA (ratio of ADRs/document 0.85 (95% CI 0.78 to 0.93, p<0.001), and 21% fewer ADRs listed in Australia compared with the USS (ratio of ADRs/document 0.79, 95% CI 0.74 to 0.85, p<0.001). There were no variations in ADR severity. The presence and qualitative content of boxed warnings also showed substantial diversity.ConclusionsInternational variations exist in the presentation of safety data in drug prescribing information, which may have important implications for patient safety. Better international coordination is necessary to enhance use of this information for patient decision-making.
Triassic pterosaurs
Authors: Vecchia Fabio M. Dalla 
Published: April 2013

Abstract

Pterosaurs are a clade of highly specialized, volant archosauromorphs recorded from the Upper Triassic to the uppermost Cretaceous. Problematic remains referred to the Pterosauria are reported from the Triassic of Europe and both North and South America, but unequivocal pterosaur specimens are only known from the Alps (Italy, Austria and Switzerland:
Preondactylus buffarinii
,
Austriadactylus cristatus
,
Peteinosaurus zambellii
,
Eudimorphodon ranzii
,
Carniadactylus rosenfeldi
,
Caviramus schesaplanensis
and
Raeticodactylus filisurensis
) and Greenland (‘
Eudimorphodon’ cromptonellus
). Pterosaurs are diagnosed mostly by features associated with the advent of powered flight. They are generally considered to be archosaurians more closely related to dinosaurs than to crocodilians, but non-archosaurian positions have also been proposed. There is a lack of general agreement about ingroup relationships, particularly among the basal pterosaurs. Triassic pterosaurs differ from other non-pterodactyloid pterosaurs in features of the dentition and caudal vertebral column. A ‘Big Bang’ model for their early history fits better with the fossil record: the earliest unequivocal pterosaurs show a sudden and geographically limited appearance in the fossil record, as well as a relatively high burst of diversity and considerable morphologic disparity. Absence of pterosaur remains from deposits where they are expected to be found suggests that they had not yet evolved in pre-Norian times.
ATM Kinase Inhibition Preferentially Sensitizes p53-Mutant Glioma to Ionizing Radiation
Authors: Biddlestone-Thorpe Laura , Sajjad Muhammad , Rosenberg Elizabeth , Beckta Jason M. , Valerie Nicholas C.K. , Tokarz Mary , Adams Bret R. , Wagner Alison F. , Khalil Ashraf , Gilfor Donna , Golding Sarah E. , Deb Sumitra , Temesi David G. , Lau Alan , O'Connor Mark J. , Choe Kevin S. , Parada Luis F. , Lim Sang Kyun , Mukhopadhyay Nitai D. , Valerie Kristoffer 
Published: April 2013

Abstract
Purpose: Glioblastoma multiforme (GBM) is the most lethal form of brain cancer with a median survival of only 12 to 15 months. Current standard treatment consists of surgery followed by chemoradiation. The poor survival of patients with GBM is due to aggressive tumor invasiveness, an inability to remove all tumor tissue, and an innate tumor chemo- and radioresistance. Ataxia–telangiectasia mutated (ATM) is an excellent target for radiosensitizing GBM because of its critical role in regulating the DNA damage response and p53, among other cellular processes. As a first step toward this goal, we recently showed that the novel ATM kinase inhibitor KU-60019 reduced migration, invasion, and growth, and potently radiosensitized human glioma cells in vitro.
Experimental Design: Using orthotopic xenograft models of GBM, we now show that KU-60019 is also an effective radiosensitizer in vivo. Human glioma cells expressing reporter genes for monitoring tumor growth and dispersal were grown intracranially, and KU-60019 was administered intratumorally by convection-enhanced delivery or osmotic pump.
Results: Our results show that the combined effect of KU-60019 and radiation significantly increased survival of mice 2- to 3-fold over controls. Importantly, we show that glioma with mutant p53 is much more sensitive to KU-60019 radiosensitization than genetically matched wild-type glioma.
Conclusions: Taken together, our results suggest that an ATM kinase inhibitor may be an effective radiosensitizer and adjuvant therapy for patients with mutant p53 brain cancers. Clin Cancer Res; 19(12); 3189–200. ©2013 AACR.
Clinical Activity and Safety of Combination Therapy with Temsirolimus and Bevacizumab for Advanced Melanoma: A Phase II Trial (CTEP 7190/Mel47)
Authors: Slingluff Craig L. , Petroni Gina R. , Molhoek Kerrington R. , Brautigan David L. , Chianese-Bullock Kimberly A. , Shada Amber L. , Smolkin Mark E. , Olson Walter C. , Gaucher Alison , Chase Cheryl Murphy , Grosh William W. , Weiss Geoffrey R. , Wagenseller Aubrey G. , Olszanski Anthony J. , Martin Lainie , Shea Sofia M. , Erdag Gulsun , Ram Prahlad , Gershenwald Jeffrey E. , Weber Michael J. 
Published: April 2013

Abstract
Purpose: A CTEP-sponsored phase II trial was conducted to evaluate safety and clinical activity of combination therapy with CCI-779 (temsirolimus) and bevacizumab in patients with advanced melanoma.
Experimental Design: Patients with unresectable stage III to IV melanoma were treated intravenously with temsirolimus 25 mg weekly and bevacizumab 10 mg every 2 weeks. Adverse events were recorded using CTCAE v3.0. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors and overall survival was recorded. Correlative studies measured protein kinases and histology of tumor biopsies and immune function in peripheral blood.
Results: Seventeen patients were treated. Most patients tolerated treatment well, but 2 had grade 4 lymphopenia and 1 developed reversible grade 2 leukoencephalopathy. Best clinical response was partial response (PR) in 3 patients [17.7%, 90% confidence interval (CI) 5, 0–39.6], stable disease at 8 weeks (SD) in 9 patients, progressive disease (PD) in 4 patients, and not evaluable in 1 patient. Maximal response duration for PR was 35 months. Ten evaluable patients had BRAFWT tumors, among whom 3 had PRs, 5 had SD, and 2 had PD. Correlative studies of tumor biopsies revealed decreased phospho-S6K (d2 and d23 vs. d1, P &lt; 0.001), and decreased mitotic rate (Ki67+) among melanoma cells by d23 (P = 0.007). Effects on immune functions were mixed, with decreased alloreactive T-cell responses and decreased circulating CD4+FoxP3+ cells.
Conclusion: These data provide preliminary evidence for clinical activity of combination therapy with temsirolimus and bevacizumab, which may be greater in patients with BRAFwt melanoma. Mixed effects on immunologic function also support combination with immune therapies. Clin Cancer Res; 19(13); 3611–20. ©2013 AACR.
MPT0B098, a Novel Microtubule Inhibitor That Destabilizes the Hypoxia-Inducible Factor-1α mRNA through Decreasing Nuclear–Cytoplasmic Translocation of RNA-Binding Protein HuR
Authors: Cheng Yun-Ching , Liou Jing-Ping , Kuo Ching-Chuan , Lai Wen-Yang , Shih Kuang-Hsing , Chang Chi-Yen , Pan Wen-Yu , Tseng Joseph T. , Chang Jang-Yang 
Published: April 2013

Abstract
Microtubule inhibitors have been shown to inhibit hypoxia-inducible factor-1α (HIF-1α) expression through inhibition translation or enhancing protein degradation. Little is known of the effect of microtubule inhibitors on the stability of HIF-1α mRNA. We recently discovered a novel indoline–sulfonamide compound, 7-aryl-indoline-1-benzene-sulfonamide (MPT0B098), as a potent microtubule inhibitor through binding to the colchicine-binding site of tubulin. MPT0B098 is active against the growth of various human cancer cells, including chemoresistant cells with IC50 values ranging from 70 to 150 nmol/L. However, normal cells, such as human umbilical vein endothelial cells (HUVEC), exhibit less susceptibility to the inhibitory effect of MPT0B098 with IC50 of 510 nmol/L. Similar to typical microtubule inhibitors, MPT0B098 arrests cells in the G2–M phase and subsequently induces cell apoptosis. In addition, MPT0B098 effectively suppresses VEGF-induced cell migration and capillary-like tube formation of HUVECs. Distinguished from other microtubule inhibitors, MPT0B098 not only inhibited the expression levels of HIF-1α protein but also destabilized HIF-1α mRNA. The mechanism of causing unstable of HIF-1α mRNA by MPT0B098 is through decreasing RNA-binding protein, HuR, translocation from the nucleus to the cytoplasm. Notably, MPT0B098 effectively suppresses tumor growth and microvessel density of tumor specimens in vivo. Taken together, our results provide a novel mechanism of inhibiting HIF-1α of a microtubule inhibitor MPT0B098. MPT0B098 is a promising anticancer drug candidate with potential for the treatment of human malignancies. Mol Cancer Ther; 12(7); 1202–12. ©2013 AACR.
Targeted Phosphotyrosine Profiling of Glycoprotein VI Signaling Implicates Oligophrenin-1 in Platelet Filopodia Formation
Authors: Bleijerveld Onno B. , van Holten Thijs C. , Preisinger Christian , van der Smagt Jasper J. , Farndale Richard W. , Kleefstra Tjitske , Willemsen Marjolein H. , Urbanus Rolf T. , de Groot Philip G. , Heck Albert J.R. , Roest Mark , Scholten Arjen 
Published: April 2013

Objective—

Platelet adhesion to subendothelial collagen is dependent on the integrin α
2
β
1
and glycoprotein VI (GPVI) receptors. The major signaling routes in collagen-dependent platelet activation are outlined; however, crucial detailed knowledge of the actual phosphorylation events mediating them is still limited. Here, we explore phosphotyrosine signaling events downstream of GPVI with site-specific detail.

Approach and Results—

Immunoprecipitations of phosphotyrosine-modified peptides from protein digests of GPVI-activated and resting human platelets were compared by stable isotope-based quantitative mass spectrometry. We surveyed 214 unique phosphotyrosine sites over 2 time points, of which 28 showed a significant increase in phosphorylation on GPVI activation. Among these was Tyr370 of oligophrenin-1 (OPHN1), a Rho GTPase–activating protein. To elucidate the function of OPHN1 in platelets, we performed an array of functional platelet analyses within a small cohort of patients with rare oligophrenia. Because of germline mutations in the
OPHN1
gene locus, these patients lack OPHN1 expression entirely and are in essence a human knockout model. Our studies revealed that among other unaltered properties, patients with oligophrenia show normal P-selectin exposure and α
IIb
β
3
activation in response to GPVI, as well as normal aggregate formation on collagen under shear conditions. Finally, the major difference in OPHN1-deficient platelets turned out to be a significantly reduced collagen-induced filopodia formation.

Conclusions—
In-depth phosphotyrosine screening revealed many novel signaling recipients downstream of GPVI activation uncovering a new level of detail within this important pathway. To illustrate the strength of such data, functional follow-up of OPHN1 in human platelets deficient in this protein showed reduced filopodia formation on collagen, an important parameter of platelet hemostatic function.
Autoregulation of Cerebral Blood Flow is Preserved in Primary Intracerebral Hemorrhage
Authors: Gould Bronwen , McCourt Rebecca , Asdaghi Negar , Dowlatshahi Dariush , Jeerakathil Thomas , Kate Mahesh , Coutts Shelagh B. , Hill Michael D. , Demchuk Andrew M. , Shuaib Ashfaq , Emery Derek , Butcher Kenneth 
Published: April 2013

Background and Purpose—
Treatment of acute hypertension after intracerebral hemorrhage (ICH) is controversial. In the context of disrupted cerebral autoregulation, blood pressure (BP) reduction may cause decreased cerebral blood flow (CBF). We used serial computed tomography perfusion to test the hypothesis that CBF remains stable after BP reduction.

Methods—
Patients recruited within 72 hours of ICH were imaged with computed tomography perfusion before and after BP treatment. Change in perihematoma relative (r) CBF after BP treatment was the primary end point.

Results—

Twenty patients were imaged with computed tomography perfusion at a median (interquartile range) time from onset of 20.2 (25.7) hours and reimaged 2.1 (0.5) hours later, after BP reduction. Mean systolic BP in treated patients (n=16; 4 untreated as BP<target at baseline) decreased significantly between the first (168±21 mm Hg) and second (141±19 mm Hg;
P
<0.0001) computed tomography perfusion scans. The primary end point of rCBF was not affected by BP reduction (pretreatment=0.89±0.11; post-treatment=0.87±0.11 mL/100 g per minute;
P
=0.37). Linear regression showed no relationship between changes in systolic BP and perihematoma rCBF (β=0.001 [−0.002 to 0.003];
P
=0.63).

Conclusions—
CBF remained stable after acute BP reduction, suggesting some preservation of cerebral autoregulation.
Adjustment of ionized calcium concentration for serum pH is not a valid marker of calcium homeostasis: implications for identifying individuals at risk of calcium metabolic disorders
Authors: Lam Virginie , Dhaliwal Satvinder S , Mamo John C 
Published: April 2013

Background Ionized calcium (iCa) is the biologically active form of this micronutrient. Serum determination of iCa is measured via ion-electrode potentiometry (IEP) and reporting iCa relative to pH 7.4 is normally utilized to avoid the potential confounding effects of ex vivo changes to serum pH. Adjustment of iCa for pH has not been adequately justified. Methods In this study, utilizing carefully standardized protocols for blood collection, the preparation of serum and controlling time of collection-to-analysis, we determined serum iCa and pH utilizing an IEP-analyser hosted at an accredited diagnostic laboratory. Results Regression analysis of unadjusted-iCa (iCaraw) concentration versus pH was described by linear regression and accounted for 37% of serum iCaraw variability. iCaraw was then expressed at pH 7.4 by either adjusting iCaraw based on the linear regression equation describing the association of iCa with serum pH (iCaregr) or using IEP coded published normative equations (iCapub). iCaregr was comparable to iCaraw, indicating that blood collection and processing methodologies were sound. However, iCapub yielded values that were significantly lower than iCaraw. iCapub did not identify 15% subjects who had greater than desirable serum concentration of iCa based on iCaraw. Sixty percent of subjects with low levels of iCaraw were also not detected by iCapub. Determination of the kappa value measure of agreement for iCaraw versus iCapub showed relatively poor concordance ( κ = 0.42). Conclusions With simple protocols that avoid sampling artefacts, expressing iCaraw is likely to be a more valid and physiologically relevant marker of calcium homeostasis than is iCapub.
Differences in perfusion CT parameter values with commercial software upgrades: a preliminary report about algorithm consistency and stability
Authors: Mazzei Maria Antonietta , Squitieri Nevada Cioffi , Sani Eleonora , Guerrini Susanna , Imbriaco Giusi , Di Lucia Duccio , Guasti Andrea , Mazzei Francesco Giuseppe , Volterrani Luca 
Published: April 2013

Background Computed tomographic perfusion (CTp) imaging is a promising technique that allows functional imaging, as an adjunct to a morphologic CT examination, that can be used as an aid to carefully evaluate the response to therapy in oncologic patients. Considering this statement, it could be desirable that the measurements obtained with the CT perfusion software, and their upgrades, are consistent and reproducible. Purpose To determine how commercial software upgrades impact on algorithm consistency and stability among the three version upgrades of the same platform in a preliminary study. Material and Methods Blood volume (BV), blood flow (BF), mean transit time (MTT), and permeability surface area product (PS) were calculated with repeated measurements ( n = 1119) while truncating the time density curve at different time values in six CT perfusion studies using CT perfusion software version 4D (CT Perfusion 4D), then repeated with the previous version (CT Perfusion 3.0 and CT Perfusion 4.0), using a fixed ROI both for arterial input and target lesion. The software upgrades were compared in pairs by applying a Kolmogorov-Smirnov test to all the parameters measured. Stability and reliability of the three versions were verified through the variation of the truncated parameters. Results The three software versions provided different parent distributions for approximately 80% of the 72 parameters measured. A complete agreement was found only for one patient in version 3.0 vs. 4.0 and 3.0 vs. 4D. Perfusion 4.0 vs. 4D: a complete agreement was found only in two cases. Parameters obtained with Perfusion 4D always showed the lowest standard deviation in all temporal intervals and also for all individual parameters. Conclusion The three versions of the same platform tested yield different perfusion measurements. Thus, our preliminary results show that Perfusion 4D version uses a stable deconvolution algorithm to provide more reliable measurements.
OK-432 Sclerotherapy for Malleolar Bursitis of the Ankle
Authors: Park Kwang Hwan , Lee Jongseok , Choi Woo Jin , Lee Jin Woo 
Published: April 2013

Background: The purpose of this study was to evaluate the clinical outcomes and usefulness of OK-432 (Picibanil) sclerotherapy as a new option in the conservative treatment of patients with malleolar bursitis of the ankle. Methods: Retrospectively, we reviewed a total of 20 consecutive patients (20 feet) in whom OK-432 sclerotherapy had been performed between March 2009 and June 2010. After aspiration of fluid in the malleolar bursal sac, 0.05 mg of OK-432 was injected into the malleolar bursal sac. We evaluated the clinical outcomes and side effects at the following time points: 2 weeks, 1 month, 3 months, 6 months, and 1 year after OK-432 sclerotherapy. The responses to the treatment were assessed according to the degree of fluctuation, shrinkage of the bursal sac, and soft tissue swelling. Results: Complete resolution was observed in 19 patients (95%) after the first or second application of OK-432 sclerotherapy, and a partial response was observed in 1 patient (5%) after a second application of OK-432 sclerotherapy. The physical component scores of SF-36 improved from 70.0 ± 6.8 to 76.5 ± 7.3 at the last follow-up ( P = .0002). Conclusion: OK-432 sclerotherapy was a useful procedure for patients not responding to the usual conservative treatment of malleolar bursitis of the ankle. Level of Evidence: Level IV, retrospective case series.
Partnership working and improved service delivery: views of staff providing sexual health services
Authors: Pow Janette , Elliott Lawrie , Raeside Robert , Themessl-Huber Markus , Claveirole Anne 
Published: April 2013

Objectives Successful partnership working has theoretically been linked to improvements in service delivery and is dependent on the strength of the partnership, trust, communication, professional roles and resource sharing. Empirical evidence to confirm the relationships between these factors and improved service provision, however, is lacking. Our aim was to assess the views of staff as to the conditions required for partnership working. Methods This study was a cross-sectional survey of 687 staff offering sexual health education, information or support to young people in the Healthy Respect intervention area in Scotland. Views of each variable were scored and structural equation modelling was used to assess the theoretical model. Results Responses were received from 284 (41%) staff. Greater strength of partnership was directly associated with increasing the number of referrals. Establishing professional roles between organizations was also associated with increasing the number of referrals. Strength of partnership was indirectly associated with working more effectively with young people and this relationship depended on clear communication, trust, established professional roles and shared resources. Effective partnership working depends on a number of interdependent relationships between organizations, which act synergistically to improve organizational outcomes. Conclusions Effective partnership working leads to improved service delivery though there is a need for better controlled studies which demonstrate the effect on health outcomes.