bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large‐scale comparative analyses of immunomarkers for diagnostic subtyping of non‐small‐cell lung cancer biopsies
Authors: Warth Arne , Muley Thomas , Herpel Esther , Meister Michael , Herth Felix J F , Schirmacher Peter , Weichert Wilko , Hoffmann Hans , Schnabel Philipp A 
Published: May 2012

Warth A, Muley T, Herpel E, Meister M, Herth F J F, Schirmacher P, Weichert W, Hoffmann H & Schnabel P A  (2012) Histopathology Large‐scale comparative analyses of immunomarkers for diagnostic subtyping of non‐small‐cell lung cancer biopsiesAims:  Patient stratification according to histological subtype is important for non‐small‐cell lung cancer (NSCLC) therapy. For specimens with uncertain histomorphology, rational and material‐saving algorithms for specific and sensitive immunotyping need to be established.Methods and results:  One thousand one hundred and forty‐five NSCLCs were immunohistochemically investigated for the expression of cytokeratin 5/6 (CK5/6), CK7, thyroid transcription factor‐1 (TTF‐1), p63, napsin‐A, and desmocollin‐3. Overall, napsin‐A and desmocollin‐3 were the most specific markers (specificity of each, 99%), and CK7 and CK5/6 the most sensitive markers (sensitivity, 96% and 94%) for adenocarcinomatous and squamous differentiation, respectively. However, for NSCLC not otherwise specified (NOS) cases, TTF‐1, p63, CK5/6 and CK7 were found to be the most reliable markers. On the basis of morphology alone, approximately two‐thirds of all NSCLCs could be reliably diagnosed in biopsy specimens. Immunohistochemistry further reduced the NOS fraction to 10%.Conclusions:  When morphology alone is not reliable, the use of selected markers and marker panels is highly sensitive and specific, and allows reliable distinction between squamous cell carcinoma and adenocarcinoma. Considering the impact of typing for the selection of molecular testing and treatment response, one must be aware of immunomarker expression patterns in NSCLC and their diagnostic value, in order to optimize typing and thereby maximize patient benefit from chemotherapy.
Pivotal factors interfering in 24‐hour blood pressure fluctuation and arterial stiffness in a community of Chinese elderly hypertensive patients
Authors: Zang Xiao‐Ying , Zhang Hua , Cheng Shu‐Ling , Gao Ya‐Jie , Cao Yong‐Jun , Zhao Yue , Mårtensson Jan 
Published: May 2012

Aims and objectives.  To explore which sociodemographic and clinical factors could interfere in the parameters of ambulatory blood pressure monitoring and determine the affecting factors of Ambulatory Arterial Stiffness Index.Background.  Although the clinical relevance of ambulatory blood pressure monitoring and Ambulatory Arterial Stiffness Index have been studied, the explanation of their role and related interfering factors remains controversial in patients with different disease or age, etc.Design.  Cross‐sectional study.Methods.  The study was carried out between October 2008–October 2009. A convenience sample of hypertensive patients over 60 years old was recruited in China. Twenty‐four hour ambulatory blood pressure monitoring was carried out on the non‐dominant arm using an oscillometric device.Results.  (1) All 95 patients completed the study and their ages ranged from 60–76 years. (2) There were statistical differences for certain parameters of ambulatory blood pressure monitoring between different characteristics of patients. Financial status was an important factor interfering in patients’ BP fluctuation, especially daytime and 24 hours systolic pressure. The higher body mass index the patients had, the higher the pressure was. (3) Multiple variants logistic analysis of Ambulatory Arterial Stiffness Index showed statistical differences only in coefficient variation of 24‐hour diastolic pressure and daytime systolic blood pressure.Conclusions.  There are more factors that interfered with systolic pressure and diastolic pressure during the day than nigh. Patients who have less nocturnal dipping may have a higher night time systolic pressure and diastolic pressure. The coefficient of variation of 24 hours diastolic pressure and daytime systolic pressure contribute more to Ambulatory Arterial Stiffness Index which should arouse practitioners’ attention.Relevance to clinical practice.  Ambulatory blood pressure monitoring should be used as a routine procedure, as well as Ambulatory Arterial Stiffness Index calculated for older hypertensive patients. The findings may be used to guide community health providers to pay more attention to the factors that may influence BP fluctuation and Ambulatory Arterial Stiffness Index according to individual’s characteristics.
Assessment of body fluid status in hemodialysis patients using the body composition monitor measurement technique
Authors: Mamat Rafidah , Kong Norella CT , Ba’in Arbai’yah , Shah Shamsul A , Cader Rizna , Wong Vincent , Mohd Rozita , Abdul Gafor Abdul Halim , Ismail Rahimah 
Published: May 2012

Aims and objectives.  The main objective of the study was to correlate the target dry weight in haemodialysis (HD) patients as assessed clinically by nephrologists to those measured by the Body Composition Monitor (BCM – Fresenius) machine. The second objective was to compare pre and postdialysis changes of extracellular fluid and clinical parameters.Background.  Clinical assessment of target dry weight in HD patients remains problematic. Inaccurate dry weight resulted in hypovolaemic or overhydration states. The BCM (Fresenius) utilises bioimpedance technology for body fluid monitoring and has been extensively validated.Design.  This was a prospective cross‐sectional study on consecutive patients who underwent HD and gave informed consent.Methods.  The target dry weights of these patients were first assessed by their attending nephrologists and appropriate ultrafiltration prescribed. Their body fluid statuses were then measured with the BCM before and after HD treatment.Results.  Eighty HD patients (37 men, 43 women) with a mean age of 55 ± 13 years and a mean duration on HD of 71 ± 56 months were studied. The dry weight measured by BCM significantly correlated with dry weight assessed by the nephrologists. The mean dry weight was higher when assessed by the nephrologists compared to that by BCM. Only systolic blood pressure and not other components of blood pressure reduced after HD treatments.Conclusion.  The BCM is a rapid and easy‐to‐use tool that can help HD nursing staffs to adjust patients’ dry weights between nephrologists’ reviews thus optimising HD therapy and patient outcomes.Relevance to clinical practice.  We propose that experienced HD nursing staff be trained in the use of the BCM or other simple bioimpedance machines to help monitor patient overhydration and approximate dry weight in consultation with the nephrologists responsible for the care of these patients so as to obviate excessive residual overhydration between nephrology reviews.
Genetic assessment of population structure and connectivity in the threatened Mediterranean coral Astroides calycularis (Scleractinia, Dendrophylliidae) at different spatial scales
Authors: CASADO‐AMEZÚA P. , GOFFREDO S. , TEMPLADO J. , MACHORDOM A. 
Published: May 2012

AbstractUnderstanding dispersal patterns, population structure and connectivity among populations is helpful in the management and conservation of threatened species. Molecular markers are useful tools as indirect estimators of these characteristics. In this study, we assess the population genetic structure of the orange coral Astroides calycularis in the Alboran Sea at local and regional scale, and at three localities outside of this basin. Bayesian clustering methods, traditional F‐statistics and Dest statistics were used to determine the patterns of genetic structure. Likelihood and coalescence approaches were used to infer migration patterns and effective population sizes. The results obtained reveal a high level of connectivity among localities separated by as much as 1 km and moderate levels of genetic differentiation among more distant localities, somewhat corresponding with a stepping‐stone model of gene flow and connectivity. These data suggest that connectivity among populations of this coral is mainly driven by the biology of the species, with low dispersal abilities; in addition, hydrodynamic processes, oceanographic fronts and the distribution of rocky substrate along the coastline may influence larval dispersal.
Induction of jasmonate signalling regulators MaMYC2s and their physical interactions with MaICE1 in methyl jasmonate‐induced chilling tolerance in banana fruit
Authors: ZHAO MING‐LEI , WANG JUN‐NING , SHAN WEI , FAN JIA‐GENG , KUANG JIAN‐FEI , WU KE‐QIANG , LI XUE‐PING , CHEN WEI‐XIN , HE FANG‐YUAN , CHEN JIAN‐YE , LU WANG‐JIN 
Published: May 2012

ABSTRACTMYC2, a basic helix‐loop‐helix (bHLH) transcription factor, is a key regulator in the activation of jasmonate (JA) response. However, the molecular details of MYC2 involving in methyl jasmonate (MeJA)‐induced chilling tolerance of fruit remain largely unclear. In the present work, two MYC2 genes, MaMYC2a and MaMYC2b, and one homolog of the inducer of the C‐repeat‐binding factor (CBF) gene, MaICE1 were isolated and characterized from banana fruit. MaMYC2s and MaICE1 were found to be all localized in the nucleus. In addition, the proline‐rich domain (PRD) and the acidic domain (AD) in the N‐terminus were important for the transcriptional activation of MaMYC2 in yeast cells. Unlike MaICE1's constitutive expression, MaMYC2a and MaMYC2b were induced rapidly following MeJA treatment during cold storage. Moreover, protein–protein interaction analysis confirmed that MaMYC2s interacted with MaICE1. The expression of ICE‐CBF cold‐responsive pathway genes including MaCBF1, MaCBF2, MaCOR1, MaKIN2, MaRD2 and MaRD5 was also significantly induced by MeJA. Taken together, our work provides strong evidence that MaMYC2 is involved in MeJA‐induced chilling tolerance in banana fruit through physically interacting and likely functionally coordinating with MaICE1, revealing a novel mechanism for ICE1 in response to cold stress as well as during development of induced chilling tolerance.
Consumer perspectives about weight management services in a community pharmacy setting in NSW, Australia
Authors: Um Irene S. , Armour Carol , Krass Ines , Gill Timothy , Chaar Betty B. 
Published: May 2012

AbstractBackground  Obesity is a public health challenge faced worldwide. Community pharmacists may be well placed to manage Australia’s obesity problem owing to their training, accessibility and trustworthiness. However, determining consumers’ needs is vital to the development of any new services or the evaluation of existing services.Objective  To explore Australian consumers’ perspectives regarding weight management services in the community pharmacy setting, including their past experiences and willingness to pay for a specific pharmacy‐based service.Design  An online cross‐sectional consumer survey was distributed through a marketing research company. The survey instrument comprised open‐ended and closed questions exploring consumers’ experiences of and preferences for weight management services in pharmacy. It also included an attitudinal measure, the Consumer Attitude to Pharmacy Weight Management Services (CAPWMS) scale.Setting and participants  A total of 403 consumers from New South Wales, Australia, completed the survey.Results  The majority of respondents had previously not sought a pharmacist’s advice regarding weight management. Those who had previously consulted a pharmacist were more willing to pay for and support pharmacy‐based services in the future. Most consumers considered pharmacists’ motivations to provide advice related to gaining profit from selling a product and expressed concerns about the perceived conflicts of interest. Participants also perceived pharmacists as lacking expertise and time.Conclusion  Although Australian consumers were willing to seek pharmacists’ advice about weight management, they perceived several barriers to the provision of weight management services in community pharmacy. If barriers are addressed, community pharmacies could be a viable and accessible setting to manage obesity.
High serum levels of free cortisol indicate severity of cirrhosis in hemodynamically stable patients
Authors: Thevenot Thierry , Dorin Richard , Monnet Elisabeth , Qualls Clifford R , Sapin Remy , Grandclement Emilie , Borot Sophie , Sheppard Frances , Weil Delphine , Degand Thibault , Di Martino Vincent , Kazlauskaite Rasa 
Published: May 2012

AbstractBackground and Aim:  We investigated: (i) the association between severity of cirrhosis and serum levels of free cortisol (SFC) and total cortisol (STC), measured before and 30 min after (T30) the low‐dose 1‐µg short synacthen test (LD‐SST); and (ii) the prognostic value of SFC and STC.Methods:  Consecutive, hemodynamically stable, cirrhotic patients (34 Child–Pugh class A, 29B, and 32C) underwent the LD‐SST. Patients were followed for at least 12 months to assess non‐transplant‐related mortality.Results:  Child–Pugh class C patients had significantly higher basal levels of SFC than Child–Pugh class A or B patients. Prevalence of suspected adrenal dysfunction ranged between 7.4% (T0 STC < 138 nmol/L) and 49.4% (change in STC < 250 nmol/L) according to the threshold used. In receiver–operator curve analysis, the area‐under‐the‐curve values were 0.67 for T30 SFC (0.51–0.79), 0.81 for Child–Pugh score (0.70–0.88), and 0.79 for albumin level (0.63–0.88). During the follow‐up period, 16 patients with high T30 SFC (≥ 78.9 nmol/L) (26.2%) and one patient with low T30 SFC (< 78.9 nmol/L) (3.4%) died (P = 0.027 for high vs low T30 SFC, log–rank test). Albeit not statistically significant, the risk of death for patients with T30 SFC ≥ 78.9 nmol/L was fivefold higher than for patients with lower levels after adjusting for cirrhosis severity and level of albumin.Conclusions:  One‐year, non‐transplant‐related mortality is high among patients with T30 levels of SFC ≥ 78.9 nmol/L (26.2%). These findings might result from latent inflammatory stress in hemodynamically stable cirrhotic patients, detected by adrenal testing.
Effect of intravenous proton pump inhibitor regimens and timing of endoscopy on clinical outcomes of peptic ulcer bleeding
Authors: Liu Na , Liu Lili , Zhang HongBo , Gyawali Prakash Chandra , Zhang Dexin , Yao Liping , Yang Yan , Wu KaiChun , Ding Jie , Fan DaiMing 
Published: May 2012

AbstractBackground and Aim:  The most effective schedule of proton pump inhibitor (PPI) administration and the optimal timing of endoscopy in acute peptic ulcer bleeding remain uncertain. The aim of this study was to determine the most efficient PPI regimen and optimal timing of endoscopy.Methods:  Consecutive patients with suspected bleeding peptic ulcers were enrolled and randomized to receive either a standard regimen or a high‐dose intensive intravenous regimen. Only patients with bleeding peptic ulcers diagnosed at initial endoscopy continued the study. High‐risk patients received endoscopic hemostasis. The primary outcome measure of recurrent bleeding was compared between the two dosage regimens and between early and late endoscopy. Secondary outcome measures compared included need for endoscopic treatment, blood transfusion, hospital stay, surgery and mortality.Results:  A total of 875 patients completed the study. Recurrent bleeding occurred in 11.0% in the standard regimen group, statistically higher than that in the intensive regimen group (6.4%, P = 0.02). Mean units of blood transfused and duration of hospital stay were also higher in the standard regimen group (P < 0.001 for each compared to intensive regimen group). However, no significant differences were noted between the two groups in the need for endoscopic hemostasis, need for surgery, and mortality. Recurrence of bleeding was similar between the early and late endoscopy groups. Units of blood transfused and length of hospital stay were both significantly reduced with early endoscopy.Conclusion:  High‐dose PPI infusion is more efficacious in reducing rebleeding rate, blood transfusion requirements and hospital stay. Early endoscopy is safe and more effective than late endoscopy.
Are European social safety nets tight enough? Coverage and adequacy of Minimum Income schemes in 14 EU countries
Authors: Figari Francesco , Matsaganis Manos , Sutherland Holly 
Published: May 2012

Figari F, Matsaganis M, Sutherland H. Are European social safety nets tight enough? Coverage and adequacy of Minimum Income schemes in 14 EU countriesThis study explored and compared the effectiveness of Minimum Income (MI) schemes for persons of working age in the European Union (EU). Using the European microsimulation model EUROMOD, we estimated indicators of coverage and adequacy of MI schemes in 14 EU countries. In terms of coverage, we found that in several countries, some individuals are ineligible for MI even when they fall below a poverty line set at 40 per cent of median income. With respect to adequacy, we show that in certain countries, a large fraction of those entitled to MI remain at very low levels of income even when MI benefit is added. Overall, our findings suggest that MI schemes in Europe remain divergent, and that their clustering may be more complex than has hitherto been allowed for.Key Practitioner Message:•The ability of European welfare states to fight poverty is a key policy question, especially at times of crisis;•Adequacy and coverage of Minimum Income schemes are crucial aspects of the answer;•Microsimulation allows us to separate the effectiveness of MI schemes ‘by design’, from issues of benefit administration, targeting errors and so forth.
Calcyon, a mammalian specific NEEP21 family member, interacts with adaptor protein complex 3 (AP‐3) and regulates targeting of AP‐3 cargoes
Authors: Muthusamy Nagendran , Faundez Victor , Bergson Clare 
Published: May 2012

AbstractCalcyon is a neural enriched, single transmembrane protein that interacts with clathrin light chain and stimulates clathrin assembly and clathrin‐mediated endocytosis. A similar property is shared by the heterotetrameric adaptor protein (AP) complexes AP‐1, AP‐2, and AP‐3 which recruit cargoes for insertion into clathrin coated transport vesicles. Here we report that AP medium (μ) subunits interact with a YXXØ‐type tyrosine motif located at residues 133–136 in the cytoplasmic domain of calcyon. Site specific mutagenesis of the critical tyrosine and bulky hydrophobic residues tyrosine 133 and methionine 136 preferentially abrogated binding of the ubiquitous and neuronal isoforms of μ3, and also impacted μ1 and μ2 binding to a lesser degree. The relevance of these interactions was explored in vivo using mice harboring null alleles of calcyon. As seen in the mutagenesis studies, calcyon deletion in mice preferentially altered the subcellular distribution of AP‐3 suggesting that calcyon could regulate membrane‐bound pools of AP‐3 and AP‐3 function. To test this hypothesis, we focused on the hilar region of hippocampus, where levels of calcyon, AP‐3, and AP‐3 cargoes are abundant. We analyzed brain cryosections from control and calcyon null mice for zinc transporter 3 (ZnT3), and phosphatidylinositol‐4‐kinase type II alpha (PI4KIIα), two well‐defined AP‐3 cargoes. Confocal microscopy indicated that ZnT3 and PI4KIIα are significantly reduced in the hippocampal mossy fibers of calcyon knock‐out brain, a phenotype previously described in AP‐3 deficiencies. Altogether, our data suggest that calcyon directly interacts with μ3A and μ3B, and regulates the subcellular distribution of AP‐3 and the targeting of AP‐3 cargoes.
Pharmacological comparison of novel synthetic fenamate analogues with econazole and 2‐APB on the inhibition of TRPM2 channels
Authors: Chen Gui‐Lan , Zeng Bo , Eastmond Sarah , Elsenussi Sandra E , Boa Andrew N , Xu Shang‐Zhong 
Published: May 2012

BACKGROUND AND PURPOSE Fenamate analogues, econazole and 2‐aminoethoxydiphenyl borate (2‐APB) are inhibitors of transient receptor potential melastatin 2 (TRPM2) channels and are used as research tools. However, these compounds have different chemical structures and therapeutic applications. Here we have investigated the pharmacological profile of TRPM2 channels by application of newly synthesized fenamate analogues and the existing channel blockers.EXPERIMENTAL APPROACH Human TRPM2 channels in tetracycline‐regulated pcDNA4/TO vectors were transfected into HEK293 T‐REx cells and the expression was induced by tetracycline. Whole cell currents were recorded by patch‐clamp techniques. Ca2+ influx or release was monitored by fluorometry.KEY RESULTS Flufenamic acid (FFA), mefenamic acid (MFA) and niflumic acid (NFA) concentration‐dependently inhibited TRPM2 current with potency order FFA > MFA = NFA. Modification of the 2‐phenylamino ring by substitution of the trifluoromethyl group in FFA with –CH3, –F, –CF3, –OCH3, –OCH2CH3, –COOH, and –NO2 at various positions, reduced channel blocking potency. The conservative substitution of 3‐CF3 in FFA by –CH3 (3‐MFA), however, gave the most potent fenamate analogue with an IC50 of 76 µM, comparable to that of FFA, but unlike FFA, had no effect on Ca2+ release. 3‐MFA and FFA inhibited the channel intracellularly. Econazole and 2‐APB showed non‐selectivity by altering cytosolic Ca2+ movement. Econazole also evoked a non‐selective current.CONCLUSION AND IMPLICATIONS The fenamate analogue 3‐MFA was more selective than other TRPM2 channel blockers. FFA, 2‐APB and econazole should be used with caution as TRPM2 channel blockers, as these compounds can interfere with intracellular Ca2+ movement.
Competence and Governance in Strategic Collaboration: The Differential Effect of Network Structure on the Creation of Core and Noncore Technology
Authors: Vanhaverbeke Wim , Gilsing Victor , Duysters Geert 
Published: May 2012

Whereas most of the literature on the benefits of alliances for learning and innovation has taken on a competence perspective, this paper provides an alternative integrated framework based on both a competence and governance point of view. The former focuses on the role of knowledge flows as means to access new knowledge, whereas the latter is centered around the core concepts of opportunism and freeridership in knowledge exchange situations. Although it has generally been acknowledged that competence‐based benefits of collaboration may come at a price of elevated risks due to knowledge spillovers and freeridership, such a governance view remains understudied. This paper explains how a firm's alliance network structure affects benefits as well as risks of collaboration in the context of the creation of core and noncore technology. In the case of core technology, firms attach more value to reducing governance‐based risks relative to obtaining competence‐based benefits. The opposite is found when firms develop noncore technology. This paper contributes to the existing literature by going beyond the common idea that competence and governance perspectives are either complementary or competing. Instead, this study shows that for technology‐based collaboration, they can both apply at the same time, implying a trade‐off in some cases and offering synergy in other cases.Based on an empirical test in three different industries (pharmaceuticals, chemicals, and automotive), there is support for most of our hypotheses. Direct ties have an invertedU‐shaped effect on both core and noncore technology, and the effect is relatively stronger for the former. The results furthermore show that indirect ties play a positive role in noncore technology development and that this effect is not hampered by the number of direct ties a firm has. In contrast, indirect ties seem to hamper core competence development when companies have a lot of direct ties. Finally, firms are found to benefit from nonredundancy in their alliance network in their efforts to strengthen their core technology. The joint effect of these three network characteristics leads to optimal results for core and noncore technologies under quite different alliance network structures. This poses a problem for the ambidexterity of companies, when they simultaneously try to strengthen core and noncore technologies.