bluuebunny/crossref_metadata_2025_split huggingface dataset:
MD‐2 is involved in the stimulation of matrix metalloproteinase‐1 expression by interferon‐γ and high glucose in mononuclear cells – a potential role of MD‐2 in Toll‐like receptor 4‐independent signalling
Authors: Lu Zhongyang , Li Yanchun , Samuvel Devadoss J. , Jin Junfei , Zhang Xiaoming , Lopes‐Virella Maria F. , Huang Yan 
Published: June 2013

SummaryWe reported recently that treatment of diabetic apolipoprotein E‐deficient mice with the Toll‐like receptor 4 (TLR4) antagonist Rs‐LPS, a lipopolysaccharide isolated from Rhodobacter sphaeroides, inhibited atherosclerosis. Since it is known that Rs‐LPS antagonizes TLR4 by targeting TLR4 co‐receptor MD‐2, this finding indicates that MD‐2 is a potential target for the treatment of atherosclerosis. In this study, we determined if MD‐2 is involved in the gene expression regulated by signalling pathways independent of TLR4. Given that interferon‐γ (IFNγ) and hyperglycaemia play key roles in atherosclerosis, we determined if MD‐2 is involved in IFN‐γ and high‐glucose‐regulated gene expression in mononuclear cells. Results showed that IFN‐γ and high glucose synergistically stimulated matrix metalloproteinase 1 (MMP‐1), a proteinase essential for vascular tissue remodelling and atherosclerosis, in U937 mononuclear cells, but Rs‐LPS inhibited the MMP‐1 stimulation. To provide more evidence for a role of MD‐2 in IFN‐γ‐stimulated MMP‐1, studies using antibodies and small interfering RNA demonstrated that MD‐2 blockade or knockdown attenuated the effect of IFN‐γ on MMP‐1. Furthermore, studies using PCR arrays showed that MD‐2 blockade had a similar effect as IFN‐γ receptor blockade on the inhibition of IFN‐γ‐stimulated pro‐inflammatory molecules. Although these findings indicate the involvement of MD‐2 in IFN‐γ signalling, we also observed that MD‐2 was up‐regulated by IFN‐γ and high glucose. We found that MD‐2 up‐regulation by IFN‐γ played an essential role in the synergistic effect of IFN‐γ and LPS on MMP‐1 expression. Taken together, these findings indicate that MD‐2 is involved in IFN‐γ signalling and IFN‐γ‐augmented MMP‐1 up‐regulation by LPS.
Does experiencing homelessness affect women's motivation to change alcohol or drug use?
Authors: Upshur Carole C. , Weinreb Linda , Cheng Debbie M. , Kim Theresa W. , Samet Jeffrey H. , Saitz Richard 
Published: June 2013

Background and ObjectivesHomeless women are at high risk of drug and alcohol dependence and may receive less opportunity for treatment. Our objective was to examine the association between experiencing homelessness and motivation to change drug or alcohol use.MethodsWomen (n = 154) participants in a study of substance dependence at an urban medical center (69 with some homeless days in the last 90 days; 85 continuously housed at baseline) completed six items rating motivation to change alcohol or drug use (ie, importance, readiness, and confidence) at baseline and in 3‐, 6‐, and 12‐month follow‐up interviews. Unadjusted and longitudinal analyses controlling for covariates (eg, demographics, insurance status, substance use consequences, mental health status, and participation in treatment) were conducted.ResultsThere were no significant differences between women experiencing homeless days versus continuously housed women in the odds of reporting high motivation to change alcohol or drug use, either in unadjusted baseline analyses or longitudinal analyses adjusted for covariates. Covariates that were significantly associated with high importance, readiness or confidence to change behavior were higher life time consequences of substance use, and participation in 12‐step programs.Discussion and ConclusionsThe findings suggest that clinicians should not make assumptions that homeless women have low motivation to change their substance use.Scientific Significance and Future DirectionsThe same opportunities for addiction treatment should be offered to homeless as to housed women. (Am J Addict 2014;23:76–83)
Associations between Post‐Traumatic Stress Symptoms, Stimulant Use, and Treatment Outcomes: A Secondary Analysis of NIDA's Women and Trauma Study
Authors: Ruglass Lesia M. , Hien Denise A. , Hu Mei‐Chen , Campbell Aimee N.C. 
Published: June 2013

Background and ObjectivesTo examine the associations between post‐traumatic stress disorder (PTSD) symptoms, stimulant use, and treatment outcomes among dually diagnosed women.MethodsParticipants were 141 women who participated in a multisite clinical trial of group treatments for PTSD and addictions.ResultsGeneralized linear models indicated Seeking Safety (SS; a cognitive‐behavioral intervention) was significantly more effective than Women's Health Education (WHE; a control group intervention) in reducing stimulant use at follow‐up among women who were heavy stimulant users at pre‐treatment and who showed improvements in PTSD symptoms. There were no significant differences between the interventions among women who were light stimulant users at treatment entry.Conclusions and Scientific SignificanceThese findings suggest that integrated treatment of co‐occurring PTSD and addictions may be more effective than general health education approaches for heavy stimulant users. Assessment of frequency of stimulant use among individuals with PTSD symptoms may inform treatment selection for this population. (Am J Addict 2014;23:90–95)
Expression of Keratin Proteins in Deeply Invasive Basal and Squamous Cell Carcinoma: An Immunohistochemical Study
Authors: ROBINSON JUNE K. 
Published: June 2013

Abstract. The expression of certain classes of keratin is associated with cell maturation and differentiation. During cell transformation and tumor development, the cell specificity of intermediate filament, keratin, is largely conserved. Taking advantage of this, we utilized monoclonal antikeratin immunohistochemical techniques to examine basal and squamous cell carcinomas as they became deeply invasive.Dyskeratotic keratinocytes and keratin pearls in squamous cell carcinomas (SCCs) stain with antikeratin anti‐sera to larger keratins (65–67 Kd). At the deep tumor margins, SCCs no longer express larger keratins but retain expression of 50, 58 Kd, which are markers of keratinocytes derived from stratified squamous epithelial cells. This selective loss of expression of keratin polypeptide markers of differentiation in SCC is associated with progressively more aggressive biologic behavior as the tumor invades deeper structures such as muscle and bone.Recurrent basal cell carcinoma (BCC) which was of the nodular type when first excised, shows features of morphea‐like BCC and of aggressive growth patterns at the deep invasive margin. At these deep margins, some tumors express markers of keratinization (65–67 Kd).While tumor cells retain the specificity of the intermediate filament, keratin, the individual cells express products of differentiation as measured by keratin expression independently of their cytologic atypia. At the deeper invasive margin of the tumor, the neoplastic cells synthesize keratin proteins in an unpredictable fashion.
Pharmacokinetics, pharmacodynamics, safety and tolerability of 4 weeks' treatment with empagliflozin in Japanese patients with type 2 diabetes mellitus
Authors: Kanada Shigeto , Koiwai Kazuki , Taniguchi Atsushi , Sarashina Akiko , Seman Leo , Woerle Hans J 
Published: June 2013

AbstractIntroductionTo evaluate the pharmacodynamics, pharmacokinetics, safety and tolerability of empagliflozin in Japanese patients with type 2 diabetes mellitus.Materials and methodsIn this 4‐week, multiple dose, randomized, parallel‐group, double‐blind, placebo‐controlled trial, patients (n = 100) were randomized to receive 1, 5, 10 or 25 mg of empagliflozin, or placebo once daily. Key end‐points were urinary glucose excretion (UGE), fasting plasma glucose (FPG) and eight‐point glucose profile.ResultsData are presented for 1, 5, 10, 25 mg of empagliflozin and placebo groups, respectively. Adjusted mean changes from baseline to day 27 in UGE were 40.8, 77.1, 80.9, 93.0 and −2.1 g (P < 0.0001 for all empagliflozin groups vs placebo). Adjusted mean changes from baseline to day 28 in FPG were −1.56, −1.96, −2.31, −2.37 and −0.86 mmol/L (P < 0.01 for all empagliflozin groups vs placebo). Adjusted mean changes from baseline to day 27 in eight‐point glucose profile were −1.96, −2.21, −2.42, −2.54 and −0.97 mmol/L (P < 0.01 for all empagliflozin groups vs placebo). Empagliflozin reached peak plasma concentration 1.5–2 h after dosing. Mean steady state terminal elimination half‐lives ranged from 13.2 to 18.0 h. Of 100 patients, 25 experienced an adverse event, occurring more frequently for empagliflozin (29.1%) than placebo (9.5%); frequency was not dose related.ConclusionsIn Japanese patients with type 2 diabetes mellitus, empagliflozin at doses up to 25 mg once daily for 4 weeks was well tolerated and resulted in significant improvements in glycemic control compared with placebo. This trial was registered with	ClinicalTrials.gov (no. NCT00885118).
Potential predictors of disease progression for main‐duct intraductal papillary mucinous neoplasms of the pancreas
Authors: Ogura Takeshi , Masuda Daisuke , Kurisu Yoshitaka , Edogawa Shoko , Imoto Akira , Hayashi Michihiro , Uchiyama Kazuhisa , Higuchi Kazuhide 
Published: June 2013

AbstractBackground and AimThe evidence for main pancreatic duct intraductal papillary mucinous neoplasms (MPD‐IPMN) malignancy is based predominantly on investigation of resected cases, and the natural history is still unclear. The aim of the present study is to investigate the natural history of MPD‐IPMN and examine potential predictors of disease progression in MPD‐IPMN patients who conformed to “high‐risk stigmata” criteria.MethodsThis study included consecutive 20 follow‐up patients and 19 surgical patients with “high‐risk stigmata” MPD‐IPMN, in whom the diameter of the MPD was > 10 mm, branch duct was < 5 mm, and who underwent clinical follow up for ≥ 2 years.ResultsAmong surgical patients, mural nodules and MPD diameter of invasive patients were significantly different compared with non‐invasive patients. On the other hand, among follow‐up patients, univariate analysis revealed the following potential predictors for disease progression: diameter of MPD ≥ 15 mm (hazard ratio [HR], 20.9; 95% confidence interval [CI], 2.59–173.4; P < 0.01); and diffuse lesions of MPD‐IPMN (HR, 4.46; 95% CI, 1.10–18.0; P = 0.04). On the other hand, multivariate analysis identified only diameter of MPD ≥ 15 mm (HR, 19.2; 95%CI, 1.87–198.5; P = 0.01) as a potential predictor of disease progression.ConclusionIf MPD‐IPMN patients have other severe complications or reasons for not undergoing surgical treatment, MPD diameter < 15 mm, negative cytology, and no mural nodules, conservative clinical follow up for several years may be an option.
Is the double‐guidewire technique superior to the pancreatic duct guidewire technique in cases of pancreatic duct opacification?
Authors: Tanaka Reina , Itoi Takao , Sofuni Atsushi , Itokawa Fumihide , Kurihara Toshio , Tsuchiya Takayoshi , Tsuji Shujiro , Ishii Kentaro , Ikeuchi Nobuhito , Umeda Junko , Tonozuka Ryosuke , Honjo Mitsuyoshi , Mukai Shuntaro , Moriyasu Fuminori 
Published: June 2013

AbstractBackground and AimsPancreatic duct guidewire placement (P‐GW) techniques include both the injection cannulation technique with a contrast medium and wire‐guided cannulation without contrast injection for selective biliary cannulation; the latter is the so‐called “double‐guidewire technique” (D‐GW). The aim of this study was to compare the outcomes between P‐GW and D‐GW for biliary cannulation.MethodsThe procedures for biliary cannulation with a naïve papilla were performed in a total of 363 cases. We divided the patients chronologically, according to the time period during which the procedures were performed, into two groups: group A, P‐GW performed from March 2008 to June 2009; and group B, D‐GW performed from July 2009 to December 2010. The success rates and complication rates were evaluated in each group.ResultsBiliary cannulation was successful in 31 (81.6%) patients in the P‐GW group and 34 patients (82.9%) in the D‐GW group. The onsets of postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) occurred in the P‐GW and D‐GW groups were four (10.5%) and three (7.3%) patients, respectively, and all were mild cases (P = 0.616). The frequency of hyperamylasemia and the serum amylase level tended to be lower in the D‐GW group than in the P‐GW group (P = 0.213). There was a statistically significant difference on the onsets of PEP in the GW and non‐GW groups (P = 0.04, 8.9% and 1.1%, respectively).ConclusionsBoth the D‐GW and P‐GW techniques were equally effective for difficult biliary cannulation. Furthermore, the complication rates, including PEP, were similar in both techniques. A prospective randomized trial is warranted.
Effect of probiotic bacteria on the intestinal microbiota in irritable bowel syndrome
Authors: Ng Siew Chien , Lam Emma F C , Lam Tommy T Y , Chan Yawen , Law Wendy , Tse Pete C H , Kamm Michael A , Sung Joseph J Y , Chan Francis K L , Wu Justin C Y 
Published: June 2013

AbstractBackground and AimIn irritable bowel syndrome (IBS), the gut microbiota may be altered. Probiotic bacteria appear to be therapeutically effective. We characterized the mucosa‐associated microbiota, and determined the clinical and microbiological effects of orally administered probiotic bacteria, in patients with IBS.MethodsMucosal microbiota from rectal biopsies of IBS patients and controls were assessed on the V1 and V2 variable regions of the 16S ribosomal RNA gene amplified using 454 pyrosequencing. Clinical symptoms and changes in mucosal microbiota were assessed in IBS patients before and after 4 weeks of treatment with probiotic mix VSL#3.ResultsTen IBS subjects (eight female; mean age 46 years) were included. At week 4 of probiotic therapy, six patients showed symptom improvement on global symptom assessment compared with baseline (P = 0.031). Before therapy, intestinal microbiota of IBS subjects differed significantly from that of healthy controls, with less diversity and evenness than controls (n = 9; P < 0.05), increased abundance of Bacteroidetes (P = 0.014) and Synegitestes (P = 0.017), and reduced abundance of Actinobacteria (P = 0.004). The classes Flavobacteria (P = 0.028) and Epsilonproteobacteria (P = 0.017) were less enriched in IBS. Abundance differences were largely consistent from the phylum to genus level. Probiotic treatment in IBS patients was associated with a significant reduction of the genus Bacteroides (all taxonomy levels; P < 0.05) to levels similar to that of controls.ConclusionIn this pilot study, global and deep molecular analysis demonstrates an altered mucosal microbiota composition in IBS. Probiotic leads to detectable changes in the microbiota. These effects of probiotic bacteria may contribute to their therapeutic benefit.
Achievement of 10‐year survival: A case of pubic bone recurrence as the primary failure site of chemo‐refractory ovarian clear cell carcinoma
Authors: Akashi Daisuke , Todo Yukiharu , Okamoto Kazuhira , Minobe Shinichiro , Kato Hidenori 
Published: June 2013

AbstractClear cell carcinoma of the ovary tends to have a poor response to conventional platinum‐based chemotherapy. Bone recurrence from ovarian cancer is rare and prognosis of patients with such a condition is poor. We report a patient with chemo‐refractory ovarian clear cell carcinoma who developed pubic bone recurrence and subsequent para‐aortic node recurrence. The patient achieved long‐term survival after salvage surgery twice in spite of these inauspicious conditions. Surgical treatment should be taken into consideration for skeletal recurrence from ovarian clear cell carcinoma.
Recurrent cervical cancer in a patient who was compound heterozygous for UGT1A1*6 and UGT1A1*28 presenting with serious adverse events during irinotecan hydrochloride/nedaplatin therapy
Authors: Takatori Eriko , Shoji Tadahiro , Miura Yuki , Takeuchi Satoshi , Yoshizaki Akira , Sugiyama Toru 
Published: June 2013

AbstractThere have been no case reports of the risk of serious adverse events associated with the administration of irinotecan hydrochloride (CPT‐11) in patients with gynecologic cancer who are compound heterozygous for UGT1A1*6 and UGT1A1*28. A 71‐year‐old patient presented with recurrent stage IIIb cervical cancer. Combined chemotherapy was initiated with CPT‐11 (60 mg/m2 on days 1 and 8) plus nedaplatin (NDP; 80 mg/m2 on day 1), with each cycle lasting for 28 days. The patient was a compound heterozygote for UGT1A1*6 and UGT1A1*28. Hematotoxic adverse events observed during the chemotherapy were grade 4 neutropenia, grade 3 anemia, and grade 4 thrombocytopenia, and the non‐hematotoxic adverse events were grade 3 diarrhea and grade 3 fatigue. The findings in this patient indicate that CPT‐11 should be administered with great care, even at a dose of 60 mg/m2, in patients receiving combined therapy with CPT‐11 and NDP who are compound heterozygous for UGT1A1*6 and UGT1A1*28.
Does postoperative pain predict the outcome of endometrial ablation?
Authors: Yuan Xi , Richmond Michael N. , Leng Yan , Li Tin‐Chiu 
Published: June 2013

AbstractAimIn this article, we hypothesized that significant pain in the immediate postoperative period is due to a deeper degree of thermal ablation, down to the myometrial layer, and consequently an increased likelihood of successful outcome.Material and MethodsWe retrospectively reviewed the medical records of 87 subjects who underwent thermal balloon endometrial ablation as the sole procedure under general anesthesia, administered by the same anesthetist using a standard protocol over a 10‐year period from 2000 to 2010 at Thornbury Hospital, Sheffield, UK. All the cases were performed by the same surgeon in one hospital.ResultsTwenty‐eight (32.2%) subjects experienced severe or intractable pain within 1 h after the thermal balloon endometrial ablation procedure, while 26 (29.9%) subjects required morphine injection in the postoperative period. Overall, more than 70% of women experienced significant reduction in their menstrual flow. There was no difference in the clinical outcome between those who did or did not experience severe pain or between those who did or did not require morphine injection in the postoperative period.ConclusionThe amount of postoperative pain did not predict the outcome of thermal balloon endometrial ablation.
Body mass index, smoking, age and cancer mortality among women: A classification tree analysis
Authors: Kitsantas Panagiota , Wu Huichuan 
Published: June 2013

AbstractAimAlthough obesity is an established risk factor for cancer mortality among women, little is known about how body mass index (BMI) is interacting with certain lifestyle behaviors and sociodemographic characteristics to increase the risk of cancer mortality. The purpose of this study was to use classification trees to examine possible interactions between BMI, smoking, age, poverty level and marital status in identifying high‐risk subgroups for all‐cause cancer mortality in women.Material and MethodsData from the US National Health Interview Survey linked with the National Death Index from 1990–2004 were used in this study. The data were restricted to women with complete information on all risk factors considered in the analyses. The data were analyzed using descriptive statistics and classification trees.ResultsFindings revealed that younger women (41–50 years old) who smoked had higher cancer mortality if they were underweight. Even among 51–60‐year‐old never smokers, we observed an inverse relationship between BMI and mortality. High BMI, however, was not a protective factor in 51–60‐year‐old women who were not married and did not smoke.ConclusionClassification tree analysis confirms and extends current knowledge about the role of BMI and smoking on cancer mortality by providing preliminary risk profiles. The findings indicate that it is imperative for cancer‐related studies to examine BMI and smoking within age‐specific groups and in the context of several sociodemographic factors that are known to independently affect cancer mortality.
Patenting Activities and Firm Performance: Does Firm Size Matter?
Authors: Andries Petra , Faems Dries 
Published: June 2013

Whereas prior research has provided valuable insights into the willingness of small and medium‐sized enterprises (SMEs) and large firms to engage in patenting, a comparison of the performance implications of patenting activities across small and large firms is still lacking. This gap is important becauseSMEs and large firms, having different resources and capabilities, might benefit from patenting activities in different ways. In particular,SMEs can be expected to benefit less from patenting activities in terms of protection against imitators than large firms. On the other hand, the propensity and ability ofSMEs to license out their patents and generate additional revenue streams might be relatively higher than that of their large counterparts.This paper studies the impact of patenting on licensing, innovation, and financial performance for bothSMEs and large firms, using multiple‐group path analyses on a sample of 358 manufacturing firms. Contrary to expectations, this study demonstrates that not only large firms, but alsoSMEs benefit from patenting in terms of commercializing product innovations. Moreover, for bothSMEs and large firms, such increased innovation performance in turn contributes to higher profit margins. Patenting activities also increase the ability ofSMEs and large firms to license out knowledge to external parties, and this positive effect is significantly stronger for large firms. However, neither inSMEs nor in large firms, these outward licensing activities generate short‐term financial benefits. Finally, the study demonstrates that patenting activities do not trigger significant cost disadvantages for eitherSMEs or large firms.Jointly, these findings provide unique insights in the value‐generating and cost‐increasing effects of patenting, suggesting that not only large firms, but alsoSMEs should consider patenting as a viable strategy to fully reap commercial benefits from their innovation activities. At the same time, they temper open innovation scholars’ expectations regarding the financial benefits of licensing out knowledge. Overall, these findings point to opportunities for optimizing the intellectual property management of bothSMEs and large firms.
Urban behavioural adaptation
Authors: Garroway Colin J. , Sheldon Ben C. 
Published: June 2013

A large and growing proportion of the world is impacted directly by human activities; among the most extreme of these is the spread of urban environments. Environmental change associated with urbanization represents a potentially potent source of selection. While urban environments generally have lowered biodiversity, some clades seem to thrive in urban settings. For example, many members of the bird family Turdidae, known as the ‘true thrushes’ and the blackbird Turdus merula (Fig. 1) in particular, are familiar urban species. Indeed, the colonization of urban environments by blackbirds has become a textbook case study for our understanding of the many ways a wild species can deal with urbanization. In this issue, Mueller et al. (Molecular Ecology, 00, 2013, 00) add to that story by beginning to address the genetic nature of behavioural adaptation of blackbirds colonizing urban areas. They do this by testing for divergence between paired urban and rural samples at a suite of candidate genes with hypothesized effects on behaviours thought to be important for the colonization of urban environments. They find evidence for consistent patterns of divergence at an exonic microsatellite associated with the SERT gene. SERT has a number of hypothesized behavioural effects, including harm avoidance, which may be associated with tolerating the hustle and bustle of urban environments. This is among the first evidence that behavioural differences between urban and rural environments have a genetic basis and this work suggests that urban environments can in some cases exert homogeneous selection pressures.