bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Trial Evaluating the Clinical and Biologic Effects of Bevacizumab in Unresectable Hepatocellular Carcinoma
Authors: Siegel Abby B. , Cohen Emil I. , Ocean Allyson , Lehrer Deborah , Goldenberg Alec , Knox Jennifer J. , Chen Helen , Clark-Garvey Sean , Weinberg Alan , Mandeli John , Christos Paul , Mazumdar Madhu , Popa Elizabeta , Brown Robert S. , Rafii Shahin , Schwartz Jonathan D. 
Published: June 2008

Purpose To determine the clinical and biologic effects of bevacizumab, an anti–vascular endothelial growth factor (VEGF) monoclonal antibody, in unresectable hepatocellular carcinoma (HCC). Patients and Methods Adults with organ-confined HCC, Eastern Cooperative Oncology Group performance status of 0 to 2, and compensated liver disease were eligible. Patients received bevacizumab 5 mg/kg (n = 12) or 10 mg/kg (n = 34) every 2 weeks until disease progression or treatment-limiting toxicity. The primary objective was to determine whether bevacizumab improved the 6-month progression-free survival (PFS) rate from 40% to 60%. Secondary end points included determining the effects of bevacizumab on arterial enhancement and on plasma cytokine levels and the capacity of patients' plasma to support angiogenesis via an in vitro assay. Results The study included 46 patients, of whom six had objective responses (13%; 95% CI, 3% to 23%), and 65% were progression free at 6 months. Median PFS time was 6.9 months (95% CI, 6.5 to 9.1 months); overall survival rate was 53% at 1 year, 28% at 2 years, and 23% at 3 years. Grade 3 to 4 adverse events included hypertension (15%) and thrombosis (6%, including 4% with arterial thrombosis). Grade 3 or higher hemorrhage occurred in 11% of patients, including one fatal variceal bleed. Bevacizumab was associated with significant reductions in tumor enhancement by dynamic contrast-enhanced magnetic resonance imaging and reductions in circulating VEGF-A and stromal-derived factor-1 levels. Functional angiogenic activity was associated with VEGF-A levels in patient plasma. Conclusion We observed significant clinical and biologic activity for bevacizumab in nonmetastatic HCC and achieved the primary study end point. Serious bleeding complications occurred in 11% of patients. Further evaluation is warranted in carefully selected patients.
Benjamin Franklin and the Limits of Secular Civil Society
Authors: Glazener Nancy 
Published: June 2008

Assessments of Benjamin Franklin have often been implicit assessments of civil society, whose double character of facilitating market transactions and promoting more expansive forms of public reflection have fueled competing accounts of Franklin. This essay explores Franklin's reliance on the conception of self-interest as a way of managing conflicting beliefs about the world. Taking Franklin as an influential early proponent of “interest-thinking”—the view that a self automatically or naturally possesses interests that fit an economic model, even if the interests are not solely economic in nature—the essay examines the failure of interest-thinking to capture the most important features of conviction or belief (religious or not). To the extent that secular civil society relies on interest-thinking to manage conflicting beliefs, secularism as we know it may be limited and compromised.
Franklin's writings offer a particular, wryly humorous way of wearing interests that is important to understand, however. The historical emergence of an interest-bearing self was facilitated, especially in America, by the fact that the doctrine of self-interest circulated not only (maybe even not primarily) as an abstract theory of the human but in satirical, self-ironic writings such as Franklin's. Franklin's satires of religious hypocrisy and public posing were an important way in which the interest-bearing self was absorbed into American public culture.
Management Strategies for Premenstrual Syndrome/Premenstrual Dysphoric Disorder
Authors: Jarvis Courtney I , Lynch Ann M , Morin Anna K 
Published: June 2008

Objective: To evaluate the current nonpharmacologic and pharmacologic treatment options for symptoms of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). Data Sources: Literature was obtained through searches of MEDLINE Ovid (1950–March week 3, 2008) and EMBASE Drugs and Pharmacology (all years), as well as a bibliographic review of articles identified by the searches. Key terms included premenstrual syndrome, premenstrual dysphoric disorder, PMS, PMDD, and treatment. Study Selection/Data Extraction: All pertinent clinical trials, retrospective studies, and case reports in human subjects published in the English language were identified and evaluated for the safety and efficacy of pharmacologic and nonpharmacologic treatments of PMS/PMDD. Data from these studies and information from review articles were included in this review. Data Synthesis: Selective serotonin-reuptake inhibitors (SSRIs) have been proven safe and effective for the treatment of PMDD and are recommended as first-line agents when pharmacotherapy is warranted. Currently fluoxetine, controlled-release paroxetine, and sertraline are the only Food and Drug Administration-approved agents (or this indication. Suppression of ovulation using hormonal therapies is an alternative approach to treating PMDD when SSRIs or second-line psychotropic agents are ineffective; however, adverse effects limit their use. Anxiolytics, spironolactone, and nonsteroidal antiinflammatory drugs can be used as supportive care to relieve symptoms. Despite lack of specific evidence, lifestyle modifications and exercise are first-line recommendations for all women with PMS/PMDD and may be all that is needed to treat mild-to-moderate symptoms. Herbal and vitamin supplementation and complementary and alternative medicine have been evaluated for use in PMS/PMDD and have produced unclear or conflicting results. More controlled clinical trials are needed to determine their safety and efficacy and potential for drug interactions. Conclusions: Healthcare providers need to be aware of the symptoms of PMS and PMDD and the treatment options available. Treatment selection should be based on Individual patient symptoms, concomitant medical history, and need for contraception.
Increase in counselling communication skills after basic and advanced microskills training
Authors: Kuntze Jeroen , van der Molen Henk T. , Born Marise P. 
Published: June 2008

Background Mastering counselling communication skills is one of the requirements that lead to the diploma of a registered European psychologist. The microcounseling method proves to be effective in training these skills.Aim Research into the effectiveness of the microcounseling method often reports overall effect sizes only. The aim of this study was to investigate the adequate use of separate counselling communication skills (seven basic skills: minimal encouragements; asking questions; paraphrasing; reflection of feeling; concreteness; summarizing; and situation clarification and five advanced skills: advanced accurate empathy; confrontation; positive relabelling; examples of one's own; and directness) after respectively a basic and an advanced training in these skills.Sample Participants were 583 first year or second year bachelor students in psychology who took the counselling communication skills progress test (CSPT). The participants are divided in a group of freshmen, who had not received any training in counselling communication skills; first year students, who had received a training in basic skills; second year students who had followed a training in advanced skills and a control group.Method A between‐subject design, a within‐subject design and a pre‐test–post‐test‐control group design were used to examine the scores on these skills.Results Seven basic skills and four advanced skills had large effect sizes. One advanced skill had a moderate effect size.Conclusio The microcounseling method is very effective on the level of separate microskills. However, students perform better on the basic skills than on the advanced skills. More training seems to be needed in the latter to achieve the same level of mastery.
Improving self‐regulated learning of preschool children: Evaluation of training for kindergarten teachers
Authors: Perels Franziska , Merget‐Kullmann Miriam , Wende Milena , Schmitz Bernhard , Buchbinder Carla 
Published: June 2008

Background In the context of lifelong learning, self‐regulated learning is an important competence. Children between 4 and 6 years of age are at a crucial step in their life to develop self‐regulatory competence. That is why their kindergarten teachers play an important role as instructors as well as role models.Aim This study tested the effects of self‐regulation training for kindergarten teachers concerning their own self‐regulation and methods to foster self‐regulation in children at preschool age whom they were teaching.Sample In this study, 35 German kindergarten teachers and 97 children participated. All adult participants were graduated kindergarten teachers.Method The kindergarten teachers were tested with a questionnaire 2 weeks before and after the training. At the same time, the preschoolers were interviewed. A waiting control group design was applied.Results and conclusions The results obtained by means of analyses of variance show that the self‐regulation of the kindergarten teachers as well as the self‐regulated learning of preschoolers whose kindergarten teachers took part in the training improved significantly. The results indicate that it is possible to improve self‐regulated learning of preschool children by a training programme for kindergarten teachers.
4 Months, 3 Weeks and 2 Days: The Corruption of Intimacy
Authors: Uricaru Ioana 
Published: June 2008

Abstract
Cristian Mungiu's 4 Months, 3 Weeks and 2 Days shares with other recent Romanian films, notably The Death of Mr. Lazarescu (2005) and 12:08 East of Bucharest (2006), a preoccupation with accessing large-scale phenomena (politics, history, society) through the narrow focus of meticulously observed individual stories.
4 Months, 3 Weeks and 2 Days: An “Abortion Movie”?
Authors: Wilson Emma 
Published: June 2008

Abstract
This essay situates Cristian Mungiu's film, 4 Months, 3 Weeks and 2 Days in relation to a number of films which deal with abortion. However, the argument is made that this film's chief concern is for problems of intimacy and distress pertaining to the central friendship between two women.
Late Ozu, Late Naruse
Authors: Mellen Joan 
Published: June 2008

Abstract
This essay reflects on the shared qualities of the late works of Yasujiro Ozu and Mikio Naruse. Both worked in the shomin-geki genre of middle-class life, depicting the often unhappy social conditions, notably among women, in post-war Japan. But while Ozu is tender and pitying, Naruse is agonized and outraged at injustice.
Tender is the Regard: I Don't Want to Sleep Alone and Still Life
Authors: Bíró Yvette 
Published: June 2008

Abstract
This essay compares Jia Zhang-ke's Still Life (set at the site of the construction of the Three Gorges Dam) and Tsai Ming-liang's I Don't Want to Sleep Alone (set among penniless worker in Kuala Lumpur), finding aesthetic similarities that are offset by contrasting sensibilities, Tsai practicing a certain Zen resignation, Jia more socially engaged.
Films of the Year, 2007
Authors: Naremore James 
Published: June 2008

Abstract
Prefaced by remarks about methodology, this article presents a survey of films (and one television show) released in the U.S. in 2007 which James Naremore evaluates to be the best of the year. The top three are: Pedro Costa's Colossal Youth, Pere Portabella's Cuadecuc-Vampir, and Abderrahmane Sissako's Bamako.
Coexpression of Gene Polymorphisms Involved in Bilirubin Production and Metabolism
Authors: Lin Zhili , Fontaine Jamie , Watchko Jon F. 
Published: June 2008

OBJECTIVE. The potential for genetically determined conditions to modulate the risk for developing neonatal hyperbilirubinemia is increasingly being recognized. The aims of this investigation were to (1) develop genotyping assays for an expanded panel of mutations and polymorphisms across 3 genes that are involved in bilirubin production and metabolism (glucose-6-phosphate dehydrogenase [G6PD], uridine diphosphate glucuronosyl transferase 1A1 [UGT1A1], and organic anion transporter polypeptide 1B1 [OATP1B1]) and (2) determine their allele frequencies in 450 anonymous DNA samples of US residents with ancestry from all of the major regions of the world.
METHODS. Genotyping assays were developed on the basis of allele-specific hybridization and melting peak analysis of the probe set and the match or mismatch template. Allele frequencies and the complexity of coinheritance of multiple genetic variants across G6PD, UGT1A1, and OATP1B1 genes in DNA samples from the DNA Polymorphism Discovery Resource of the National Human Genome Research Institute were determined by using this expanded panel.
RESULTS. Genetic polymorphisms of the UGT1A1 promoter, specifically the T-3279G phenobarbital responsive enhancer module and the (thymidine-adenine)7 dinucleotide repeat TATAA box variants, were common. Similarly, OATP1B1 coding sequence gene variants were frequently observed. Moreover, in more than three quarters of the samples, ≥2 variants were detected, reflecting a high degree of polymorphism coexpression across these genes, including those who carried the African A− G6PD mutation.
CONCLUSIONS. We conclude that this expanded panel of mutations and polymorphisms can serve as an effective instrument to study the genetic architecture of hyperbilirubinemia and speculate an important role for genetic polymorphism coinheritance in determining hyperbilirubinemia risk in newborns.
Effects of In Utero and Childhood Tobacco Smoke Exposure and β2-Adrenergic Receptor Genotype on Childhood Asthma and Wheezing
Authors: Wang Chengwei , Salam Muhammad T. , Islam Talat , Wenten Madé , Gauderman W. James , Gilliland Frank D. 
Published: June 2008

OBJECTIVE. Associations between single-nucleotide polymorphisms in the β2-adrenergic receptor gene and asthma and wheeze have been inconsistent. Recent studies indicated that tobacco smoke affects β2-adrenergic receptor gene expression and associations of β2-adrenergic receptor gene variants with asthma in adults. We aimed to investigate the joint effects of in utero and childhood secondhand tobacco smoke exposure and 2 well-characterized functional single-nucleotide polymorphisms (Arg16Gly and Glu27Gln) of β2-adrenergic receptor gene on asthma and wheezing in 3128 non-Hispanic and Hispanic white children of the Children's Health Study.
METHODS. We fitted logistic regression models to estimate odds ratios and 95% confidence intervals for the independent and joint effects of these single-nucleotide polymorphisms and in utero and secondhand tobacco smoke exposure on asthma and wheeze outcomes.
RESULTS. Exposures to in utero maternal smoking and secondhand tobacco smoke were associated with wheezing. Children who were homozygous for the Arg16 allele and were exposed to maternal smoking in utero were at a threefold increased risk for lifetime wheeze compared with children who were unexposed and had at least 1 Gly16 allele. We found similar joint effects of secondhand tobacco smoke and Arg16Gly with wheezing. The risk for lifetime, current, and nocturnal wheeze increased with the number of smokers at home among Arg16 homozygous children. The results were consistent in 2 cohorts of children recruited in 1993 and 1996. Diplotype-based analyses were consistent with the single-nucleotide polymorphism–specific results. No associations were found for Glu27Gln.
CONCLUSIONS. Both in utero and childhood exposure to tobacco smoke were associated with an increased risk for wheeze in children, and the risks were greater for children with the Arg16Arg genotype or 2 copies of the Arg16–Gln27 diplotype. Exposures to smoking need to be taken into account when evaluating the effects of β2-adrenergic receptor gene variants on respiratory health outcomes.
A ranking of European veterinary medicines based on environmental risks
Authors: Kools Stefan AE , Boxall Alistair BA , Moltmann Johann F , Bryning Gareth , Koschorreck Jan , Knacker Thomas 
Published: June 2008

Abstract
The most likely entry pathways of veterinary pharmaceuticals to the environment are via slurry or manure from intensively reared animals to soil and via dung or urine from animals grazing on pasture. These pathways may result in contamination of surface water via runoff or leaching and drainage. Direct entry into water may occur by defecation by pasture animals or by companion animals. In addition, application of medicines for aquaculture is important for a limited number of veterinary medicinal products. For a large number of veterinary medicinal products, consistent data on the environmental risk have never been generated. In this project, a simple risk-based ranking procedure was developed that should allow assessing the potential for environmental risks of active substances of veterinary medicinal products. In the European Union approximately 2000 products containing 741 active substances were identified. In the prescreening step and in agreement with the technical guidelines released by the European Medicines Agency, 294 natural substances, complex mixtures, and substances with low expected exposure were exempted from the ranking procedure. For 233 active substances, sufficient information was collated on 4 exposure scenarios: Intensively reared animals, pasture animals, companion animals, and aquaculture. The ranking approach was performed in 4 phases: 1) usage estimation; 2) characterization of exposure to soil, dung, surface water, and aquatic organisms depending on exposure scenarios; 3) characterization of effects based on therapeutical doses; and 4) risk characterization, which is the ratio of exposure to effects (risk index), and ranking. Generally, the top-ranked substances were from the antibiotic and parasiticide groups of veterinary medicines. Differences occurred in the ranking of substances in soil via application to either intensively reared or pasture animals. In intensive rearing, anticoccidia, for example, are used as feed-administered medicines (feed additives) in comparatively large doses over a long time. For pasture animals, these substances are used less, if at all, and therefore receive lower ranks. Besides that, the risk indices for the aquatic compartment are large for substances used in aquaculture or applied to companion animals. In conclusion, the ranking scheme developed for this project provided a scientifically based and pragmatic means of assessing the relative priority of veterinary medicines for further detailed risk assessment. The outcome of this project will support pharmaceutical industries and competent authorities when seeking authorization for market applications of veterinary pharmaceutical products.
High-Density Single Nucleotide Polymorphism Genome-Wide Linkage Scan for Susceptibility Genes for Diabetic Nephropathy in Type 1 Diabetes
Authors: Rogus John J. , Poznik G. David , Pezzolesi Marcus G. , Smiles Adam M. , Dunn Jonathon , Walker William , Wanic Krzysztof , Moczulski Dariusz , Canani Luis , Araki Shinichi , Makita Yuichiro , Warram James H. , Krolewski Andrzej S. 
Published: June 2008

OBJECTIVE— Epidemiological and family studies have demonstrated that susceptibility genes play an important role in the etiology of diabetic nephropathy, defined as persistent proteinuria or end-stage renal disease (ESRD) in type 1 diabetes.
RESEARCH DESIGN AND METHODS— To efficiently search for genomic regions harboring diabetic nephropathy genes, we conducted a scan using 5,382 informative single nucleotide polymorphisms on 100 sibpairs concordant for type 1 diabetes but discordant for diabetic nephropathy. In addition to being powerful for detecting linkage to diabetic nephropathy, this design allows linkage analysis on type 1 diabetes via traditional affected sibpair (ASP) analysis. In weighing the evidence for linkage, we considered maximum logarithm of odds score (maximum likelihood score [MLS]) values and corresponding allelic sharing patterns, calculated and viewed graphically using the software package SPLAT.
RESULTS— Our primary finding for diabetic nephropathy, broadly defined, is on chromosome 19q (MLS = 3.1), and a secondary peak exists on chromosome 2q (MLS = 2.1). Stratification of discordant sibpairs based on whether disease had progressed to ESRD suggested four tertiary peaks on chromosome 1q (ESRD only), chromosome 20p (proteinuria only), and chromosome 3q (two loci 58 cm apart, one for ESRD only and another for proteinuria only). Additionally, analysis of 130 ASPs for type 1 diabetes confirmed the linkage to the HLA region on chromosome 6p (MLS = 9.2) and IDDM15 on chromosome 6q (MLS = 3.1).
CONCLUSIONS— This study identified several novel loci as candidates for diabetic nephropathy, none of which appear to be the sole genetic determinant of diabetic nephropathy in type 1 diabetes. In addition, this study confirms two previously reported type 1 diabetes loci.
Rapamycin Monotherapy in Patients With Type 1 Diabetes Modifies CD4+CD25+FOXP3+ Regulatory T-Cells
Authors: Monti Paolo , Scirpoli Miriam , Maffi Paola , Piemonti Lorenzo , Secchi Antonio , Bonifacio Ezio , Roncarolo Maria-Grazia , Battaglia Manuela 
Published: June 2008

OBJECTIVE—Rapamycin is an immunosuppressive drug currently used to prevent graft rejection in humans, which is considered permissive for tolerance induction. Rapamycin allows expansion of both murine and human naturally occurring CD4+CD25+FOXP3+ T regulatory cells (nTregs), which are pivotal for the induction and maintenance of peripheral tolerance. Preclinical murine models have shown that rapamycin enhances nTreg proliferation and regulatory function also in vivo. Objective of this study was to assess whether rapamycin has in vivo effects on human nTregs.
RESEARCH DESIGN AND METHODS—nTreg numbers and function were examined in a unique set of patients with type 1 diabetes who underwent rapamycin monotherapy before islet transplantation.
RESULTS—We found that rapamycin monotherapy did not alter the frequency and functional features, namely proliferation and cytokine production, of circulating nTregs. However, nTregs isolated from type 1 diabetic patients under rapamycin treatment had an increased capability to suppress proliferation of CD4+CD25− effector T-cells compared with that before treatment.
CONCLUSIONS—These findings demonstrate that rapamycin directly affects human nTreg function in vivo, which consists of refitting their suppressive activity, whereas it does not directly change effector T-cell function.