bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human microtubule‐associated protein tau mediates targeted killing of CD30+ lymphoma cells in vitro and inhibits tumour growth in vivo
Authors: Hristodorov Dmitrij , Nordlohne Johannes , Mladenov Radoslav , Huhn Michael , Fischer Rainer , Thepen Theo , Barth Stefan 
Published: October 2013

SummaryHodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL) are rare lymphoproliferative cancer types. Although most HL patients can be cured by chemo‐ and radio‐therapy, 4–50% of patients relapse and have a poor prognosis. The need for improved therapeutic options for patients with relapsed or refractory disease has been addressed by CD30‐specific antibody‐based immunotherapeutics. However, available CD30‐specific monoclonal antibodies (mAbs), antibody drug conjugates (ADCs) or chimeric immunotoxins suffer from the requirement of a functional host immunity, undesirable immune reactions or heterogeneity and instability, respectively. Here, we present a new fusion protein comprised of the CD30‐specific antibody single‐chain fragment Ki4(scFv) and the human pro‐apoptotic effector protein, microtubule‐associated protein tau (MAPT). Ki4(scFv)‐MAP selectively induced apoptosis in rapidly proliferating L540cy, L428, and Karpas 299 cells in a dose‐dependent manner. Tubulin polymerization assays confirmed that Ki4(scFv)‐MAP stabilizes microtubules, suggesting a mechanism for its pro‐apoptotic action. Dose‐finding experiments proved that Ki4(scFv)‐MAP is well tolerated in mice compared to the previously reported Ki4(scFv)‐ETA'. Ki4(scFv)‐MAP significantly inhibited growth of subcutaneous L540cy xenograft tumours in mice. Our data present a novel approach for the treatment of CD30+ lymphomas, combining the binding specificity of a target‐specific antibody fragment with the selective cytotoxicity of MAPT towards proliferating lymphoma cells.
Implementing the use of nomograms by choosing threshold points in predictive models: 2012 updated Partin Tables vs a European predictive nomogram for organ‐confined disease in prostate cancer
Authors: Borque Ángel , Rubio‐Briones Jose , Esteban Luis M. , Sanz Gerardo , Domínguez‐Escrig Jose , Ramírez‐Backhaus Miguel , Calatrava Ana , Solsona Eduardo 
Published: October 2013

Objectives
To implement the use of nomograms in clinical practice showing how to choose thresholds in nomograms’ predictions to select risk groups.
To validate and compare the predictive ability and clinical utility of the Hospital Universitario ‘Miguel Servet’ (HUMS) and the updated Partin Tables 2012 (PT‐2012) nomograms to predict organ‐confined disease (OCD) after radical prostatectomy (RP).
Patients and Methods
Cohort of 1285 patients with prostate cancer treated with RP at Instituto Valenciano de Oncología (IVO) between 1986 and 2011.
The predictive value of the nomograms was assessed by means of calibration curves, discrimination ability (area under the receiver operating characteristic (ROC) curve (AUC) and probability density functions).
The clinical utility was evaluated through Vickers’ decision curves and thresholds were chosen through probability density functions.
Results
The calibration curves showed a minimal underestimation in low probabilities (<20%), a minimal overestimation in high probabilities (>50%) in the HUMS nomogram and a regular minimal overestimation in the PT‐2012. Their AUC of 0.7285 (95% confidence interval [CI] 0.7010–0.7559) and 0.7288 (95%CI 0.7013–0.7562) respectively, show an adequate discrimination ability for both predictive models in the IVO cohort.
The decision curves show similar net benefits for both models.
In this study we advocate for a threshold of 53% for the identification of OCD.
Conclusions
The HUMS‐nomogram and the PT‐2012 predictions of OCD confirm their utility in a contemporary cohort of patients.
Patients with a probability of OCD >53% should be classified as OCD, helping physicians to better counsel their patients.
A selection of adequate thresholds, as presented in this paper, makes nomograms more accessible tools.
Immigrant Settlement Work in Canada: Limits and Possibilities for Professionalization
Authors: Türegün Adnan 
Published: October 2013

Cet article dépeint l’émergence du travail d’établissement auprès des immigrants au Canada et explore les perspectives d'avenir de celui‐ci en tant que profession. À l'heure actuelle, le travail d'établissement comprend trois formes de pratique : (1) un travail aux contours flous; (2) une spécialité du travail social; et (3) une profession en émergence. Cet article soutient que le travail d'établissement aura probablement un avenir professionnel. Cependant, la question de savoir s'il devient une profession indépendante dépend en grande partie du régime de financement du secteur des services d'établissement. Si le régime de financement fédéral et à court terme continue d'exister, le travail d'établissement cherchera encore sa définition au sein du domaine général du travail de service social. S'il émerge un régime de financement provincial et à long terme, les perspectives d'un travail d'établissement professionnel et indépendant s'amélioreront.This paper portrays the emergence of Canadian settlement work with immigrants and explores its prospects as an occupation. Currently, settlement work includes three forms of practice: (1) a loose occupation; (2) a specialty of social work; and (3) an emerging profession. The paper argues that settlement work is likely to have a professional future. However, whether or not it will become an independent profession depends largely on the funding regime of the settlement service sector. If the existing federal and short‐term funding regime continues, settlement work will still be trying to define itself in the broader field of social service work. If a provincial and long‐term funding regime emerges, prospects for an independent professional settlement work will improve.
CXCL1 is a negative regulator of mast cell chemotaxis to airway smooth muscle cell products in vitro
Authors: Alkhouri H. , Moir L. M. , Armour C. L. , Hughes J. M. 
Published: October 2013

SummaryBackgroundActivated mast cells (MC) numbers on airway smooth muscle (ASM) are increased in eosinophilic asthma. In vitro, asthmatic cytokine‐stimulated ASM cell‐conditioned medium (CM) induces more MC chemotaxis than CM from nonasthmatic ASM cells. Intriguingly the nonasthmatic ASM CM inhibits MC chemotaxis to the asthmatic ASM CM. However, the inhibitory factor(s) in the nonasthmatic ASM CM is still to be identified.ObjectiveTo identify the factor(s) released by nonasthmatic ASM cells that inhibits MC chemotaxis.MethodsConfluent, serum‐starved ASM cells from donors with and without asthma were stimulated with IL‐1β and T‐helper (Th)1 (TNFα and IFNγ) or Th2 (IL‐4, IL‐13) cytokines, or left unstimulated. CM samples were collected after 24 h, and a potential inhibitory factor identified using cytokine protein arrays. Its production was assessed using ELISA and RT‐PCR and inhibitory role investigated in MC chemotaxis and Ca2+ mobilization assays.ResultsOnly CXCL1 was produced in greater amounts by nonasthmatic than asthmatic ASM cells following Th1 and Th2 cytokine stimulation. CXCL1 mRNA expression was also increased. Exogenous rh‐CXCL1 significantly inhibited MC intracellular Ca2+ mobilization and chemotaxis to either CXCL10, CXCL8 or CM collected from asthmatic ASM cells following Th1 or Th2 cytokine stimulation. Neutralizing CXCL1 in nonasthmatic ASM CM or blocking its receptor significantly promoted MC chemotaxis.ConclusionsCXCL1 was a major factor regulating MC chemotaxis in vitro. Its differential release by ASM cells may explain the differences observed in MC localization to the ASM of people with and without asthma.Clinical RelevanceCXCL1 inhibition of MC recruitment to the ASM may lead to new targets to limit asthma pathophysiology.
Profile of ocular trauma in the Solomon Islands
Authors: Baker Michelle L , Painter Geoffrey , Hewitt Alex W , Amirul Islam F M , Szetu John , Qalo Mundi , Keeffe Jill 
Published: October 2013

AbstractBackgroundThe objective of this study was to characterize the causes of ocular trauma and determine the risk factors for infection and vision loss following ocular trauma in the Solomon Islands.DesignA prospective clinic‐based study.ParticipantsA total of 507 patients with ocular trauma who were reviewed at the National Referral Hospital in Honiara or one of five provincial eye clinics were included.MethodsAn interview‐based questionnaire to determine the circumstances of ocular trauma, and an ocular examination to elicit the trauma sustained, infectious sequelae and the visual outcome.Main Outcome MeasureVisual acuity.ResultsMales were significantly more likely to have ocular trauma than females (P = 0.01). The major cause of ocular trauma in young boys and girls was being poked by a stick, followed by lime burns in young boys. For both genders, physical violence resulted in most injuries across all adult age groups. Microbial keratitis complicated 4.4% of ocular trauma. Monocular vision impairment (<6/18) occurred in 5.5% of participants and was more likely to occur if female (P = 0.02).ConclusionsOcular trauma is a significant cause of visual morbidity in the Solomon Islands. The results from this prospective study provide a basis for planning blindness prevention programmes in the Western Pacific.
Curcumin Suppresses Malignant Glioma Cells Growth and Induces Apoptosis by Inhibition of SHH/GLI1 Signaling Pathway in Vitro and Vivo
Authors: Du Wen‐Zhong , Feng Yan , Wang Xiao‐Feng , Piao Xing‐Yin , Cui Yu‐Qiong , Chen Ling‐Chao , Lei Xu‐Hui , Sun Xu , Liu Xing , Wang Han‐Bing , Li Xian‐Feng , Yang Dong‐Bo , Sun Ying , Zhao Zhe‐Feng , Jiang Tao , Li Yong‐Li , Jiang Chuan‐Lu 
Published: October 2013

SummaryAimsTo study the role of curcumin on glioma cells via the SHH/GLI1 pathway in vitro and vivo.MethodsThe effects of curcumin on proliferation, migration, apoptosis, SHH/GLI1 signaling, and GLI1 target genes expression were evaluated in multiple glioma cell lines in vitro. A U87‐implanted nude mice model was used to study the role of curcumin on tumor volume and the suppression efficacy of GLI1.ResultsCurcumin showed cytotoxic effects on glioma cell lines in vitro. Both mRNA and protein levels of SHH/GLI1 signaling (Shh, Smo, GLI1) were downregulated in a dose‐ and time‐dependent manner. Several GLI1‐dependent target genes (CyclinD1, Bcl‐2, Foxm1) were also downregulated. Curcumin treatment prevented GLI1 translocating into the cell nucleus and reduced the concentration of its reporter. Curcumin suppressed cell proliferation, colony formation, migration, and induced apoptosis which was mediated partly through the mitochondrial pathway after an increase in the ratio of Bax to Bcl2. Intraperitoneal injection of curcumin in vivo reduced tumor volume, GLI1 expression, the number of positively stained cells, and prolonged the survival period compared with the control group.ConclusionThis study shows that curcumin holds a great promise for SHH/GLI1 targeted therapy against gliomas.
Enhancing ex vivo expansion of cord blood‐derived unrestricted somatic stem cells for clinical applications
Authors: Demerdash Z. , El Baz H. , Mahmoud F. , Mohamed S. , Maher K. , Gaafar T. , Shawky S. , Hassan M. , Abdelhady D. , Taha T. 
Published: October 2013

AbstractObjectivesTo study effects of serum‐containing medium (SCM) versus serum‐free medium (SFM) and influence of seeding density, on rate of expansion of cord blood (CB) unrestricted somatic stem cells (USSCs), as a prerequisite for evaluating their therapeutic potential in ongoing clinical trials.Material and methodsIsolation, propagation and characterization of USSCs from CB samples were performed and followed by their passage 3 culture in SCM and SFM, at cell densities of 5, 50, 500 and 5000 cells/cm2.ResultsThe cells were CD44+, CD90+, CD73+, CD105+, CD34−, CD45−, and HLA‐DR, with Oct4 & Sox2 gene expression; they were differentiated into osteoblasts and adipocytes. USSCs cultured in SCM had significantly higher population doubling levels (P < 0.01) than those cultured in SFM. Those cultured in SCM at 5 cells/cm2 and those cultured in SFM at 50 cells/cm2 had significantly higher population doubling (P < 0.01) levels than those cultured at higher cell densities.ConclusionsFor scaling up of USSCs from 106 (?) to 1012 (?) in 6 weeks, culturing of CB‐derived cells of early passage (≤P3) in SCM at low cell seeding density (5 cells/cm2) is suggested for increasing cell count with lower passaging frequency, followed by culture of expanded USSCs at 50 cells/cm2 in SFM, to avoid undesirable effects of bovine serum in clinical applications.
Sildenafil Increases Muscle Protein Synthesis and Reduces Muscle Fatigue
Authors: Sheffield‐Moore Melinda , Wiktorowicz John E. , Soman Kizhake V. , Danesi Christopher P. , Kinsky Michael P. , Dillon Edgar L. , Randolph Kathleen M. , Casperson Shannon L. , Gore Dennis C. , Horstman Astrid M. , Lynch James P. , Doucet Barbara M. , Mettler Joni A. , Ryder Jeffrey W. , Ploutz‐Snyder Lori L. , Hsu Jean W. , Jahoor Farook , Jennings Kristofer , White Gregory R. , McCammon Susan D. , Durham William J. 
Published: October 2013

AbstractReductions in skeletal muscle function occur during the course of healthy aging as well as with bed rest or diverse diseases such as cancer, muscular dystrophy, and heart failure. However, there are no accepted pharmacologic therapies to improve impaired skeletal muscle function. Nitric oxide may influence skeletal muscle function through effects on excitation‐contraction coupling, myofibrillar function, perfusion, and metabolism. Here we show that augmentation of nitric oxide‐cyclic guanosine monophosphate signaling by short‐term daily administration of the phosphodiesterase 5 inhibitor sildenafil increases protein synthesis, alters protein expression and nitrosylation, and reduces fatigue in human skeletal muscle. These findings suggest that phosphodiesterase 5 inhibitors represent viable pharmacologic interventions to improve muscle function.
Pulmonary involvement in patients with thrombotic thrombocytopenic purpura
Authors: Nokes Timothy , George James N. , Vesely Sara K. , Awab Ahmed 
Published: October 2013

AbstractObjectivesTo determine the frequency of pulmonary involvement in patients with thrombotic thrombocytopenic purpura (TTP).MethodsThe experience of the Oklahoma TTP‐HUS (hemolytic–uremic syndrome) Registry, a population‐based cohort of consecutive patients without selection or referral bias, 1995–2012, was analyzed. Evidence for pulmonary involvement in patients with TTP was also documented with a systematic review of published reports.ResultsOnly one of 74 Registry patients with acquired severe ADAMTS13 deficiency (activity <10%) had clinically important pulmonary involvement (transient PaO2, 42 mm Hg; arterial O2 saturation, 78%; normal chest X‐ray). No clinically important pulmonary involvement occurred in the remaining 73 patients. The systematic review identified 144 articles with search terms for TTP and pulmonary involvement; seven, published 1978–2002, had evaluable individual patient data. Five articles described single patients; only one patient was documented to have severe acquired ADAMTS13 deficiency; in none of the five patients was pulmonary involvement clearly related to TTP. Two articles were case series of seven patients each; no patients had ADAMTS13 activity measured. Each of the 14 patients had potential etiologies other than TTP for pulmonary involvement.ConclusionsOnly one of 74 patients in the Oklahoma Registry had clinically important pulmonary involvement. A systematic review of published reports documented no clear evidence for pulmonary involvement resulting from TTP. Clinically important pulmonary involvement may be rare in patients with TTP because (i) pulmonary microvasculature may be inherently resistant to the formation of platelet thrombi and (ii) pulmonary function can be maintained in spite of multiple microvascular thrombi.
Short‐duration stimulation of the supplementary eye fields perturbs anti‐saccade performance while potentiating contralateral head orienting
Authors: Chapman Brendan B. , Corneil Brian D. 
Published: October 2013

AbstractMany forms of brain stimulation utilize the notion of state dependency, whereby greater influences are observed when a given area is more engaged at the time of stimulation. Here, by delivering intracortical microstimulation (ICMS) to the supplementary eye fields (SEF) of monkeys performing interleaved pro‐ and anti‐saccades, we show a surprising diversity of state‐dependent effects of ICMS‐SEF. Short‐duration ICMS‐SEF passed around cue presentation selectively disrupted anti‐saccades by increasing reaction times and error rates bilaterally, and also recruited neck muscles, favoring contralateral head turning to a greater degree on anti‐saccade trials. These results are consistent with the functional relevance of the SEF for anti‐saccades. The multiplicity of stimulation‐evoked effects, with ICMS‐SEF simultaneously disrupting anti‐saccade performance and facilitating contralateral head orienting, probably reflects both the diversity of cortical and subcortical targets of SEF projections, and the response of this oculomotor network to stimulation. We speculate that the bilateral disruption of anti‐saccades arises via feedback loops that may include the thalamus, whereas neck muscle recruitment arises via feedforward polysynaptic pathways to the motor periphery. Consideration of both sets of results reveals a more complete picture of the highly complex and multiphasic response to ICMS‐SEF that can play out differently in different effector systems.
Effects of forest degradation on butterfly communities in theGwangneungForest
Authors: Lee Cheol Min , Kwon Tae‐Sung , Kim Sung‐Soo , Sohn Jeong‐Dal , Lee Bong‐Woo 
Published: October 2013

AbstractThis study was carried out to clarify the response of butterfly communities on forest degradation in theGwangneungForest,Korea. We monitored butterfly communities with varying degrees of human activities by conducting a line transect twice a month in 2011. A total of 70 species and 4676 individuals of butterflies were observed in four sites: natural forest (NR), two plantation forests, and theKoreanNationalArboretum (AR). The result on niche breadth, habitat breadth and habitat type of butterfly was not consistent with our predictions. Species richness of habitat type was only significantly different betweenNFandAR. Species diversity was significantly different among sites. Butterfly diversity associated with landscape patterns based on aerial photographs supported a mosaic concept. A forest management plan to conserve butterfly diversity in forests is necessary to maintain various habitats and to ensure that grasslands are protected.
An evaluation of hydrogen sulfide in orogenic gold fluids and the uncertainties associated with vapor‐rich inclusions
Authors: Mernagh T. P. , Bastrakov E. N. 
Published: October 2013

AbstractRaman spectroscopy has been used to obtain the concentration of H2S in individual fluid inclusions in the Archean Missouri gold deposit in Western Australia. These results indicated that the gas phase of Type III, vapor‐rich fluid inclusions from the Missouri gold deposit contained highly variable CO2/CH4 ratios and mole fractions of H2S up to 0.0018. There is good agreement between the calculated and empirically estimated H2S contents at 300°C and 200 MPa. The measured H2S concentrations can be explained by the proposed equilibrium with pyrite in the vicinity of or along the pyrite‐pyrrhotite sulfide buffer. In this study, optical methods were used for estimating the volume fractions of vapor and liquid (where observable) in inclusions at room temperature. To investigate the uncertainty associated with these measurements, where no aqueous phase was observed in an inclusion, we have calculated its bulk composition both without liquid water and also by assuming that there was a 0.5 μm film of liquid water on the walls of the inclusion. Calculations of bulk densities were found to be considerably higher for inclusions with liquid water when compared with vapor‐only inclusions. To investigate the error associated with undetected water in vapor‐rich inclusions, numerical experiments were completed for a number of fluid compositions in the H2O‐CH4‐CO2‐H2S compositional space, both for a regular compositional grid and for a set of specific fluid compositions derived from the visual observations and Raman measurements. Using this approach, the bulk compositions of fluid inclusions were calculated in equilibrium with the pyrite‐pyrrhotite buffer within the temperature‐pressure range of 270 to 360°C and approximately 40 to 260 MPa. The numerical modeling has also shown that variations in calculated H2S concentrations of up to two orders of magnitude may arise due to errors associated with visual estimates of volume fractions in vapor‐rich inclusions. To reduce this source of error, bulk inclusion compositions should be checked by other analytical methods, where possible.
Reduced Threshold for Inhibitory Homeostatic Responses in Migraine Motor Cortex? A tDCS/TMS Study
Authors: Cosentino Giuseppe , Brighina Filippo , Talamanca Simona , Paladino Piera , Vigneri Simone , Baschi Roberta , Indovino Serena , Maccora Simona , Alfonsi Enrico , Fierro Brigida 
Published: October 2013

Background and ObjectiveNeurophysiological studies in migraine have reported conflicting findings of either cortical hyper‐ or hypoexcitability. In migraine with aura (MwA) patients, we recently documented an inhibitory response to suprathreshold, high‐frequency repetitive transcranial magnetic stimulation (hf‐rTMS) trains applied to the primary motor cortex, which is in contrast with the facilitatory response observed in the healthy subjects. The aim of the present study was to support the hypothesis that in migraine, because of a condition of basal increased cortical responsivity, inhibitory homeostatic‐like mechanisms of cortical excitability could be induced by high magnitude stimulation. For this purpose, the hf‐rTMS trains were preconditioned by transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique able to modulate the cortical excitability state.MethodsTwenty‐two MwA patients and 20 patients with migraine without aura (MwoA) underwent trains of 5‐Hz repetitive transcranial magnetic stimulation at an intensity of 130% of the resting motor threshold, both at baseline and after conditioning by 15 minutes of cathodal or anodal tDCS. Motor cortical responses to the hf‐rTMS trains were compared with those of 14 healthy subjects.ResultsWe observed abnormal inhibitory responses to the hf‐rTMS trains given at baseline in both MwA and MwoA patients as compared with the healthy subjects (P < .00001). The main result of the study was that cathodal tDCS, which reduces the cortical excitability level, but not anodal tDCS, which increases it, restored the normal facilitatory response to the hf‐rTMS trains in both MwA and MwoA.ConclusionsThe present findings strengthen the notion that, in migraine with and without aura, the threshold for inducing inhibitory mechanisms of cortical excitability might be lower in the interictal period. This could represent a protective mechanism counteracting cortical hyperresponsivity. Our results could be helpful to explain some conflicting neurophysiological findings in migraine and to get insight into the mechanisms underlying recurrence of the migraine attacks.