bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison between neoadjuvant and adjuvant gemcitabine plus cisplatin chemotherapy for muscle‐invasive bladder cancer
Authors: Matsubara Nobuaki , Mukai Hirofumi , Naito Yoichi , Nezu Masahiko , Itoh Kuniaki 
Published: November 2012

AbstractAimRadical cystectomy plus platinum‐based perioperative chemotherapy is a standard treatment for patients with clinically localized muscle‐invasive bladder cancer. The standard perioperative chemotherapy is methotrexate, vinblastine, doxorubicin and cisplatin (MVAC). However, no prospective randomized trial has been published that compares neoadjuvant and adjuvant chemotherapy for bladder cancer. Moreover, the efficacy of perioperative chemotherapy with gemcitabine plus cisplatin (GC) has not been clarified. In this study we have compared the clinical outcomes between neoadjuvant and adjuvant chemotherapy in patients receiving GC.MethodsWe retrospectively reviewed the records of patients who were scheduled to be treated with a radical cystectomy plus perioperative chemotherapy with GC from 2005 to 2010 at our institution. The primary outcome measure was recurrence‐free survival (RFS).ResultsA total of 42 patients received perioperative chemotherapy with GC (25 neoadjuvant, 17 adjuvant). The median number of cycles of GC administered to the two groups was not significantly different. The median duration of follow up was 28.6 months. During the follow‐up period, recurrence was observed in nine and three patients in the neoadjuvant and adjuvant groups, respectively. The RFS rate at median follow up was 67 and 76% in the neoadjuvant and adjuvant groups, respectively. No significant difference in RFS at median follow up was observed between the two groups (P = 0.124).ConclusionOur results showed no statistically significant difference in RFS between neoadjuvant and adjuvant GC chemotherapy for muscle‐invasive bladder cancer. We expect to validate these findings in a prospective randomized trial.
Levels of satisfaction with current chronic constipation treatment options in Europe – an internet survey
Authors: Müller‐Lissner S. , Tack J. , Feng Y. , Schenck F. , Specht Gryp R. 
Published: November 2012

SummaryBackgroundData on treatment satisfaction in European men and women with chronic constipation are limited.AimTo assess satisfaction with current treatment among European men and women with chronic constipation.MethodsAn internet‐based survey was conducted in 2009 in 10 European countries: Austria, Germany, France, Ireland, Italy, Spain, Switzerland, the UK, Belgium and the Netherlands. Participants had self‐reported chronic constipation (<3 bowel movements/week and ≥1 symptoms for ≥6 months of: pain during defecation; lumpy/hard faeces; and feeling of incomplete evacuation). Demographic data and disease history were collected. For participants using laxatives, drug name/class, satisfaction with treatment and interest in other treatments were collected.ResultsOf the 1941 participants screened, 1355 had chronic constipation and met the inclusion criteria (chronic constipation population). The majority of the chronic constipation population who disclosed their sex (n = 811) were women (82%). Sixty‐eight per cent of respondents (n = 855/1255) reported using laxatives, with the proportion of laxative users differing between subsets. Twenty‐eight per cent (n = 225/793) were (very) satisfied with their treatment, whereas 44% (n = 345/793) were neutral and 28% (n = 223/793) (very) dissatisfied. There was no relationship between type of laxative and degree of (dis)satisfaction. Interest in other treatments was high with 83% (n = 686/827) of respondents ‘absolutely’ or ‘probably’ interested. Respondents dissatisfied with their treatment were more likely to be interested in other treatments.ConclusionsLaxative‐use is common for chronic constipation. In this large survey, 28% of participants were dissatisfied with their treatment, with the majority interested in other treatments.
Useful and convenient procedure for intermittent vascular occlusion in laparoscopic hepatectomy
Authors: Okuda Yukihiro , Honda Goro , Kurata Masanao , Kobayashi Shin 
Published: November 2012

AbstractIntroductionWhile the amount of blood loss during laparoscopic hepatectomy tends to be smaller than that during open hepatectomy, intermittent vascular occlusion to control hepatic inflow can diminish blood loss during laparoscopic hepatectomy. Described herein is a useful and convenient method for intermittent vascular occlusion, which was standardized for laparoscopic hepatectomy.MethodsA tourniquet system consisting of cloth tape and a 20‐cm catheter was used for intermittent vascular occlusion. This was placed through a hole in the abdominal wall from which a 5‐mm trocar had been extracted. By operating this tourniquet system outside the patient's body, we were easily able to repeat intermittent vascular occlusion. Twenty‐three patients underwent laparoscopic hepatectomy using this system.ResultsThe mean time of operation and vascular occlusion were 311.6 and 83.6 min, respectively. The mean blood loss was 215.0 mL. There were no intraoperative blood transfusions or critical postoperative complications. The average length of postoperative hospital stay was 6.5 days. The mean time to place this system was 354 s, and there were no complications caused by this system.ConclusionDuring totally laparoscopic hepatectomy, surgeons can perform intermittent vascular occlusion safely by using this method.
Should Women Care Less? Intrinsic Motivation and Gender Inequality
Authors: Folbre Nancy 
Published: November 2012

AbstractGendered values, norms and preferences shape the intrinsic motivation to provide care for others. This article situates an analysis of this motivation within the broader literature on gender inequality, explaining why it has costly consequences for women in both the home and the labour market, even as it provides considerable personal satisfaction and social benefit. Further movement towards gender equality may depend on the success of political and cultural efforts to ‘de‐gender’ normative obligations to care.
Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients
Authors: Xie Cen , Zhou Jialan , Guo Zitao , Diao Xingxing , Gao Zhiwei , Zhong Dafang , Jiang Haoyuan , Zhang Lijia , Chen Xiaoyan 
Published: November 2012

Background and PurposeFamitinib is a novel multi‐targeted receptor tyrosine kinase inhibitor under development for cancer treatment. This study aims to characterize the metabolic and bioactivation pathways of famitinib.Experimental ApproachThe metabolites in human plasma, urine and feces were identified via ultra‐high performance liquid chromatography‐quadrupole‐time of flight‐mass spectrometry and confirmed using synthetic standards. Biotransformation and bioactivation mechanisms were investigated using microsomes, recombinant metabolic enzymes and hepatocytes.Key ResultsFamitinib was extensively metabolized after repeated oral administrations. Unchanged famitinib was the major circulating material, followed by N‐desethylfaminitib (M3), whose steady‐state exposure represented 7.2 to 7.5% that of the parent drug. Metabolites in the excreta were mainly from oxidative deamination (M1), N‐desethylation (M3), oxidative defluorination (M7), indolylidene hydroxylation (M9‐1 and M9‐5) and secondary phase‐II conjugations. CYP3A4/5 was the major contributor to M3 formation, CYP3A4/5 and aldehyde dehydrogenase to M1 formation and CYP1A1/2 to M7, M9‐1 and M9‐5 formations. Minor cysteine conjugates were observed in the plasma, urine and feces, implying the formation of reactive intermediate(s). In vitro microsomal studies proved that famitinib was bioactivated through epoxidation at indolylidene by CYP1A1/2 and spontaneously defluorinated rearrangement to afford a quinone‐imine species. A correlation between famitinib hepatotoxicity and its bioactivation was observed in the primary human hepatocytes.Conclusion and ImplicationsFamitinib is well absorbed and extensively metabolized in cancer patients. Multiple enzymes, mainly CYP3A4/5 and CYP1A1/2, are involved in famitinib metabolic clearance. The quinone‐imine intermediate formed through bioactivation may be associated with famitinib hepatotoxicity. Co‐administered CYP1A1/2 inducers or inhibitors may potentiate or suppress its hepatotoxicity.
The correlation between T helper type 17 cells and clinical characters in Chinese paediatric patients with chronic hepatitis B
Authors: Zhu S , Zhang H , Dong Y , Xu Z , Chen D , Wang L , Gan Y , Wang F , Wang Y , Xing X , Hu S , Li Z , Long L , Liu L , Zhong Y 
Published: November 2012

Summary
Interleukin (IL)-17-mediated immune response has been shown to play a critical role in inflammation-associated disease. However, its role in the pathogenesis of chronic hepatitis B virus (HBV) in paediatric patients remains unknown. We investigated the frequency of T helper type 17 (Th17) cells and evaluated the association between the Th17 and clinical characters in paediatric patients with chronic hepatitis B (CHB). The frequency of Th17 cells was detected by flow cytometry analyses from 65 paediatric patients with CHB and nine healthy controls. The degree of hepatic inflammation was graded using the histological activity index (HAI). Compared with healthy controls, the frequency of Th17 cells in peripheral blood was significantly higher in paediatric patients with CHB. The proportion of Th17 cells was higher in the patients with higher HAI score (G2–G3) compared to those subjects with lower HAI score (G0–G1), but the frequency of Th17 cells had no correlation with serum HBV DNA loads or alanine aminotransferase levels. Compared with the younger age group (age 1–6 years), Th17 cell frequency was higher in the older age group (age 7–18 years). Peripheral Th17 cell frequency is associated closely with inflammation activity of liver tissues in paediatric patients with CHB.
Refugee species: which historic baseline should inform conservation planning?
Authors: Kuemmerle Tobias , Hickler Thomas , Olofsson Jörgen , Schurgers Guy , Radeloff Volker C. 
Published: November 2012

AbstractUnderstanding species' historical ranges can provide important information for conservation planning in the face of environmental change. Cromsigt et al. (this issue) comment on our recent European bison (Bison bonasus) range reconstruction, suggesting that bison were already 8000 years ago a refugee species (i.e. restricted to marginal habitat due to past human pressure) and that species distribution models (SDM) are generally of limited use for refugee species conservation. While we welcome this discussion, we find no evidence for the claim that human pressure prior to 8000 BP determined where bison occurred. More importantly, as human pressure is generally high and increasing, attempts to restore species across their former range may fail where the factors that relegated species into refugee status are still at play or where their optimal habitat has vanished. Identifying areas where human pressure is low and where refugee species have persisted over the last millennia is crucial, and SDM based on historical data are important for doing so. Refugee species suffer from the shifting baseline syndrome, but careful reality checks are needed and all available data should be considered before determining the baseline that should inform conservation planning.
Intensification of diabetes medication and risk for 30‐day readmission
Authors: Wei N. J. , Wexler D. J. , Nathan D. M. , Grant R. W. 
Published: November 2012

AbstractAimTo examine the association of in‐hospital diabetes regimen intensification with subsequent 30‐day risk for unplanned readmission/emergency department admission.MethodsWe retrospectively studied 1949 adults with Type 2 diabetes receiving primary care within an academic health network admitted to the hospital between January 2007 and December 2009. Glucose therapy intensification was defined as new start of insulin or oral hypoglycaemic agents, or addition of prandial insulin or insulin mixtures. The association of glucose therapy intensification with subsequent 30‐day risk for unplanned readmission/emergency department admission was examined, with focus on medicine service patients with poorly controlled glycaemia (baseline HbA1c ≥ 64 mmol/mol).ResultsOne in six patients (324/1949, 17%) had early readmission/emergency department admission. Compared with patients without early readmission, readmitted patients were more often male (58 vs. 52%, P = 0.03), had higher Charlson co‐morbidity score [mean (sd) 3.0 (2.0) vs. 2.8 (1.8), P = 0.02], longer length of stay [5 (4.4) vs. 3.9 (3.3) days, P < 0.01] and were more often discharged home with nursing services (38 vs. 32%, P = 0.03). Overall, glucose therapy intensification was not associated with early hospital readmission/emergency department admission (odds ratio 0.94, 95% CI 0.64–1.37, P = 0.74). However, among medicine service patients with baseline HbA1c ≥ 64 mmol/mol (8%), glucose therapy intensification was associated with a significantly decreased early readmission risk (adjusted odds ratio 0.33, 95% CI 0.12–0.88, P = 0.03) and lower post‐discharge HbA1c {mean decrease (sd): 20 (26) mmol/mol [1.8 (2.4)%] vs. 7 (15) mmol/mol [0.6 (1.4)%], P < 0.01}.ConclusionsDiabetes medical regimen intensification during hospitalization was not associated with early readmission. Among patients with elevated HbA1c, glucose therapy intensification was associated with a decreased 30‐day readmission/emergency department admission risk and lower outpatient HbA1c levels. Our findings support the safety and durable impact of diabetes regimen optimization during hospital admission.
The impact of regional deprivation and individual socio‐economic status on the prevalence of Type 2 diabetes in Germany. A pooled analysis of five population‐based studies
Authors: Maier W. , Holle R. , Hunger M. , Peters A. , Meisinger C. , Greiser K. H. , Kluttig A. , Völzke H. , Schipf S. , Moebus S. , Bokhof B. , Berger K. , Mueller G. , Rathmann W. , Tamayo T. , Mielck A. ,   for the DIAB‐CORE Consortium
Published: November 2012

AbstractAimOur objective was to test the hypothesis that the prevalence of Type 2 diabetes increases with increasing regional deprivation even after controlling for individual socio‐economic status.MethodsWe pooled cross‐sectional data from five German population‐based studies. The data set contained information on n = 11 688 study participants (men 50.1%) aged 45–74 years, of whom 1008 people had prevalent Type 2 diabetes (men 56.2%). Logistic multilevel regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI) for diabetes prevalence. We controlled for sex, age and lifestyle risk factors, individual socio‐economic status and regional deprivation, based on a new small‐area deprivation measure, the German Index of Multiple Deprivation.ResultsAdjusted for sex, age, body mass index (BMI), physical activity, smoking status and alcohol consumption, the prevalence of Type 2 diabetes showed a stepwise increase in risk with increasing area deprivation [OR 1.88 (95% CI 1.16–3.04) in quintile 4 and OR 2.14 (95% CI 1.29–3.55) in quintile 5 compared with the least deprived quintile 1], even after controlling for individual socio‐economic status. Focusing on individual socio‐economic status alone, the risk of having diabetes was significantly higher for low compared with medium or high educational level [OR 1.46 (95% CI 1.24–1.71)] and for the lowest compared with the highest income group [OR 1.53 (95% CI 1.18–1.99)].ConclusionRegional deprivation plays a significant part in the explanation of diabetes prevalence in Germany independently of individual socio‐economic status. The results of the present study could help to target public health measures in deprived regions.
CD14++CD16+ monocytes in patients with acute ischaemic heart failure
Authors: Wrigley Benjamin J. , Shantsila Eduard , Tapp Luke D. , Lip Gregory Y. H. 
Published: November 2012

AbstractBackgroundMonocytes play important roles in inflammation, angiogenesis and tissue repair and may contribute to the pathophysiology of heart failure (HF).ObjectivesWe examined differences in monocyte subset numbers and expression of cell surface markers of activation (CD14) and chemotaxis (CCR2) in patients with acute HF (AHF), stable HF (SHF), and controls and evaluated their impact on clinical outcomes.MethodsThree monocyte subsets [CD14++CD16−CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2) and CD14+CD16++CCR2− (Mon3)] were analysed by flow cytometry in 51 patients with AHF, 42 patients with SHF, 44 patients with stable coronary artery disease and without HF (CAD) and 40 healthy controls (HC). The prognostic impact of monocyte subsets was examined in AHF.ResultsPatients with AHF had significantly higher Mon1 counts compared to the three control groups (P < 0·001 for all). Similarly, Mon2 levels were increased in AHF compared to SHF (P = 0·004) and CAD (P < 0·001) and increased in SHF vs. CAD (P = 0·009). There were no differences in Mon3 counts between the groups. Twenty patients (39·2%) with AHF reached the primary end‐point of death or re‐hospitalisation, and after adjustment for confounders, Mon2 count remained negatively associated with a combined end‐point of death and re‐hospitalisation [hazard ratio (per 10 cells/μL): 0·79; confidence interval: 0·66–0·94; P = 0·009].ConclusionsMon2 counts are increased in patients with both acute and stable HF, with enhanced expression of surface markers of activation (CD14) and chemotaxis (CCR2). This subset was also associated with an adverse prognosis in patients with AHF.
Mitogen‐ and stress‐activated protein kinase 1 modulates photic entrainment of the suprachiasmatic circadian clock
Authors: Cao Ruifeng , Butcher Greg Q. , Karelina Kate , Arthur J. Simon , Obrietan Karl 
Published: November 2012

The master circadian clock in mammals, the suprachiasmatic nucleus (SCN), is under the entraining influence of the external light cycle. At a mechanistic level, intracellular signaling via the p42/44 mitogen‐activated protein kinase pathway appears to play a central role in light‐evoked clock entrainment; however, the precise downstream mechanisms by which this pathway influences clock timing are not known. Within this context, we have previously reported that light stimulates activation of the mitogen‐activated protein kinase effector mitogen‐stress‐activated kinase 1 (MSK1) in the SCN. In this study, we utilised MSK1−/− mice to further investigate the potential role of MSK1 in circadian clock timing and entrainment. Locomotor activity analysis revealed that MSK1 null mice entrained to a 12 h light/dark cycle and exhibited circadian free‐running rhythms in constant darkness. Interestingly, the free‐running period in MSK1 null mice was significantly longer than in wild‐type control animals, and MSK1 null mice exhibited a significantly greater variance in activity onset. Further, MSK1 null mice exhibited a significant reduction in the phase‐delaying response to an early night light pulse (100 lux, 15 min), and, using an 8 h phase‐advancing ‘jet‐lag’ experimental paradigm, MSK1 knockout animals exhibited a significantly delayed rate of re‐entrainment. At the molecular level, early night light‐evoked cAMP response element‐binding protein (CREB) phosphorylation, histone phosphorylation and Period1 gene expression were markedly attenuated in MSK1−/− animals relative to wild‐type mice. Together, these data provide key new insights into the molecular mechanisms by which MSK1 affects the SCN clock.
How Did the Spanish Financial System Survive the First Stage of the Global Crisis?
Authors: Royo Sebastián 
Published: November 2012

This article analyzed the impact of the global crisis on the Spanish financial system between 2008 and 2010. It shows that, overall, the performance of the largest Spanish financial institutions was positive. The article examined why, and outlined some lessons. It contendedthat this response was largely driven by institutional, political, and cultural factors. At the same time, the article showed that as the crisis intensified, Spain's banking sector could not escape its dramatic effects.Deteriorating economic conditions, the implosion of the real estate market, the dependence on wholesale funding, weaknesses in the regulatory framework, and the role of the Bank of Spain all helped to explain this reversal.Finally, the article considered the Spanish experience within the framework of the varieties of capitalism literature. It showed that differences among financial systems persist. Indeed, in Spain, the crisis has led to extensive regulatory intervention, reinforcing the preexisting model.
The British Nutrition Transition and its Histories
Authors: Otter Chris 
Published: November 2012

AbstractThis paper argues that food has become an increasingly important topic in British historiography. To frame this historiographical analysis, the paper focuses on the “nutrition transition” in Britain, which took place between around 1750 and 1950. This transition marked a shift towards a diet rich in refined wheat, sugar, dairy and meat. The paper explores various phenomena related to the nutrition transition, notably changes in the standard of living, the relationship between the state and the economy, the impact of war, and the development of globalization. These various historical developments have all become rich areas for historiographical analysis and debate. In general, we can observe a historiographical drift from “social” approaches to the history of food through “cultural” ones to today’s situation, which is one of methodological innovation and profusion. This situation suggests that some of the most interesting writing on British history is currently about food.
The Legal Status of Piracy in Medieval Europe
Authors: Tai Emily Sohmer 
Published: November 2012

AbstractThis article discusses the history of maritime theft, or piracy, in medieval Europe, not so much as a crime but rather as a case study in legal pluralism: the operation of competing systems of law across a common region. Although scholarship has often interpreted sources for medieval European piracy through the filter of early modern conditions, the parameters of how disputes over piracy were settled within the conflicting legal systems of medieval Europe may have heuristic implications for understanding twenty‐first century piracy. On the one hand, statutes of royal and civic polities across medieval Europe uniformly adhered to Roman legal precedents in condemning piracy as a capital crime. On the other hand, selective campaigns of maritime predation, referred to in the Latin sources as sailing ad piraticam or in cursum, (hence the term corsair), were sanctioned by medieval European polities when directed against political and economic rivals. Legal and narrative sources for maritime theft nevertheless indicate that piracy was often conflated with the operation of enemy corsairs in a manner that carried implications for the imposition of capital penalties on maritime marauders as well as for merchants who attempted to obtain compensation, or restitution, for cargo seized in a corsair raid from polities charged with authorizing their operations. Attempts to obtain restitution could also be complicated by commercial patterns subtly interwoven with maritime theft.