bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ornithosuchidae: a group of Triassic archosaurs with a unique ankle joint
Authors: Baczko M. Belén von , Ezcurra Martín D. 
Published: January 2013

Abstract

The ornithosuchids were a group of archosaurs with body lengths ranging from 2 to 4 m recorded from Upper Triassic beds in Argentina and Scotland. The group was defined as a node-based clade including
Ornithosuchus longidens
,
Riojasuchus tenuisceps
,
Venaticosuchus rusconii
and all descendants of their most recent common ancestor. The ornithosuchids are diagnosed by the following apomorphies observed in the three known species of the clade: downturned premaxilla; premaxilla–maxilla contact with a diastema in the alveolar margin equal in length to two teeth; palatine–pterygoid fenestra; and orbit with a distinct ventral point surrounded by ‘V’-shaped dorsal processes of the jugal. The most remarkable postcranial apomorphy of the group is the presence of the so-called crocodile reversed ankle joint, a condition that seems to be unique for the ornithosuchids among amniotans. The systematic history of Ornithosuchidae is complex and
Ornithosuchus
was allied with dinosaurs or phytosaurs prior to the implementation of numerical phylogenetic analyses. Currently, there is consensus that Ornithosuchidae is positioned within Pseudosuchia, but their phylogenetic position within the group remains strongly debated. Nevertheless, all hypotheses agree in inferring an extremely long ghost lineage at the base of the clade. The presence of derived pseudosuchians in the late Olenekian produces a ghost lineage of
c.
16–18 millions of years for Ornithosuchidae, indicating that only the late evolutionary history of the clade is currently sampled in the fossil record.
Phase I Study of GRN1005 in Recurrent Malignant Glioma
Authors: Drappatz Jan , Brenner Andrew , Wong Eric T. , Eichler April , Schiff David , Groves Morris D. , Mikkelsen Tom , Rosenfeld Steve , Sarantopoulos John , Meyers Christina A. , Fielding Robert M. , Elian Kelly , Wang Xiaolin , Lawrence Betty , Shing Mona , Kelsey Stephen , Castaigne Jean Paul , Wen Patrick Y. 
Published: January 2013

Abstract
Purpose: GRN1005 is a peptide–drug conjugate with the ability to penetrate the blood–brain barrier (BBB) and tumor cells by targeting the low-density lipoprotein receptor–related protein-1. We conducted a first-in-human phase I trial of GRN1005 in patients with recurrent glioma.
Methods: Patients received GRN1005 by intravenous infusion every 3 weeks. Doses were escalated using a modified Fibonacci scheme. Study objectives included safety, tolerability, identification of the maximum tolerated dose (MTD), pharmacokinetics, and preliminary evidence of efficacy. Tumor extracted from patients undergoing surgery following administration of GRN1005 was analyzed to determine whether therapeutic concentrations of GRN1005 were achieved.
Results: Sixty-three patients received GRN1005 at doses of 30 to 700 mg/m2 every 3 weeks. Therapy was well tolerated with neutropenia, leucopenia, and fatigue as the most frequent drug-associated grade 3/4 or higher toxicities. The MTD was 650 mg/m2 every 3 weeks. Dose-limiting toxicities were grade 3 mucositis and grade 4 neutropenia. There was no evidence of central nervous system toxicity or antibody production. Pharmacokinetic analysis showed that exposure to GRN1005 was dose proportional. We observed one complete and two partial responses. Eight of 27 patients dosed ≥420 mg/m2 had stable disease, which lasted a median of 51 days. Therapeutic concentrations of GRN1005 and free paclitaxel were shown in tumor tissue of surgical patients dosed with ≥200 mg/m2.
Conclusion: GRN1005 delivers paclitaxel across the BBB and achieves therapeutic concentrations in tumor tissue. It has similar toxicity to paclitaxel and appears to have activity in recurrent glioma. The recommended phase II dose is 650 mg/m2 every 3 weeks. Clin Cancer Res; 19(6); 1567–76. ©2013 AACR.
Experimental Pediatric Arterial Ischemic Stroke Model Reveals Sex-specific Estrogen Signaling
Authors: Herson Paco S. , Bombardier Chris G. , Parker Susan M. , Shimizu Takeru , Klawitter Jost , Klawitter Jelena , Quillinan Nidia , Exo Jennifer L. , Goldenberg Neil A. , Traystman Richard J. 
Published: January 2013

Background and Purpose—
Pediatric stroke, birth to 18 years, is a significant cause of long-term disability in the United States; however, there is currently little experimental data on the pathophysiology of childhood stroke owing to lack of animal models. We developed a novel mouse model of experimental childhood-onset arterial ischemic stroke to characterize the sex-specific response of the adolescent brain to cerebral ischemia and assess the neuroprotective effect of estrogen at this developmental stage.

Methods—

Postnatal day 20 to 25 mice were subjected to 90 minutes experimental stroke via the intraluminal filament middle cerebral artery occlusion model and ischemic damage assessed 22 hours after reperfusion. Real-time quantitative real-time polymerase chain reaction was performed 22 hours after middle cerebral artery occlusion to determine the effects of ischemia and estrogen treatment on the proapoptotic gene
Bax
.

Results—

Ischemic injury did not differ between male and female juvenile (postnatal day 20–25) mice after middle cerebral artery occlusion. However, estrogen reduced ischemic injury in female mice, whereas having no effect in juvenile males. No differences in estrogen receptor expression were observed on postnatal day between 20 males and females. In contrast, estrogen minimized the ischemia-induced increase in the proapoptotic gene
Bax
in female mice, whereas having no effect on Bax induction in the male brain.

Conclusions—
Focal ischemia has fundamentally different effects in the juvenile brain compared with the adult, as evidenced by the lack of sex difference in ischemic injury in the murine postnatal day 20 to 25 middle cerebral artery occlusion model and the sexually dimorphic response to estrogen neuroprotection.
Comprehensiveness and usability of tools for assessment of energy saving measures in schools
Authors: Smith Greta Caruana , Mumovic Dejan , Curtis Lee 
Published: January 2013

Having in mind constantly changing regulatory frameworks which demand both carbon emission reduction and improvement of the quality of internal environment, this paper analyses strengths and limitations of available design tools of various complexity: Annex 36 Energy Concept Advisor Tool and an approved Dynamic Simulation Model. As a platform for discussion, two representative school buildings in North London were selected and modelled using both tools. Discussion integrates views of 76 building industry professionals on applicability of various school retrofit options in practice. Using the available statistics on total number of schools and floor space in each category, a simple extrapolation was applied to roughly quantify potential for carbon emission reduction of the school building stock in England and Wales. Practical applications: More than 70% of approximately 25,000 maintained and independent primary and secondary schools in England and Wales were built before the introduction of thermal regulations in 1970s, offering a significant opportunity to reduce carbon emission of the school building stock. In terms of construction, they could be divided in two major categories: pre 1919 solid wall construction and post war masonry cavity school buildings. This paper reviews capabilities of the less-known Energy Concept Advisor which offers designers, architects and decision makers the opportunity of assessing the performance of a particular building and comparing possible retrofitting measures quickly.
Resource Utilization in Primary Repair of Cleft Lip
Authors: Owusu James A. , Liu Meixia , Sidman James D. , Scott Andrew R. 
Published: January 2013

ObjectiveTo determine national variations in resource utilization for primary repair of cleft lip, identify patient and institutional factors associated with high resource use, and estimate the current incidence of cleft lip in the United States.Study DesignRetrospective analysis of a national, pediatric database (2009 Kids’ Inpatient Database [KID]).MethodsPatients aged 1 year and younger were selected using international classification of disease codes for cleft lip and procedure codes for cleft lip repair. A number of demographic variables were analyzed, and hospital charges were considered as a measure of resource utilization.ResultsThere were 1318 patients identified. The national incidence was 0.09%, with a male to female ratio of 1.8:1. Regional incidence varied from 0.07% (Northeast) to 0.10% (West). The mean age at surgery was 4.2 months. The average length of stay was 1.4 days. The national average hospital charge was $20,147, ranging from $14,635 (South) to $23,663 (West). Teaching hospitals charge an average of $9764 higher than nonteaching hospitals. The strongest predictor of charge was length of stay, increasing charge by $8102 for every additional hospital day (P <. 01).ConclusionRegional variations exist in resource utilization for primary cleft lip repair. Resource use is higher in the West and among teaching hospitals.
The proteasome inhibitor lactacystin exerts its therapeutic effects on glioma via apoptosis: An in vitro and in vivo study
Authors: Wang Haifeng , Zhang Shuyan , Zhong Jiateng , Zhang Jizhou , Luo Yinan , Ge Pengfei 
Published: January 2013

Objective To examine the effect and underlying mechanism of action of the proteasome inhibitor lactacystin on glioma, in vitro and in vivo. Methods Rat C6 glioma cells were cultured with or without lactacystin. Cell proliferation, apoptosis and mitochondrial membrane potential were determined. A glioma xenograft model was established in mice and animals were treated with 0, 1 or 5 µg/20 g body weight lactacystin for 7 days. Animals were sacrificed on day 17 after completion of treatment. Apoptosis in tumour tissue was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Levels of B cell lymphoma 2 (Bcl-2), and Bcl2-associated X protein (Bax) protein and mRNA, were determined in C6 cells and tumour tissues. Results Lactacystin significantly inhibited the proliferation of C6 cells, increased apoptosis and reduced mitochondrial membrane potential in vitro, and suppressed tumour growth in vivo. Lactacystin increased the ratio of Bax to Bcl-2 at the mRNA and protein levels, both in vitro and in vivo. Conclusions The effects of lactacystin are associated with apoptosis induction. Proteasome inhibition may represent an effective treatment option for glioma.
Understanding the sleep problems of people with dementia and their family caregivers
Authors: Gibson Rosemary H , Gander Philippa H , Jones Linda M 
Published: January 2013

Sleep disturbances are common with dementia and can adversely affect waking function. However, the perspectives of people with dementia and their family caregivers concerning their sleep are under-researched. We conducted three focus groups with 12 community-dwelling pairs (a person with dementia and their family caregiver). Discussions addressed sleep disturbances, coping strategies, and beliefs and attitudes surrounding sleep. Thematic analysis indicated that dementia-related sleep disturbances were common, including confused awakenings and dementia-related behaviors at night, changes to sleep timing, and nightmares. Common issues for caregivers included being woken at night, having problems getting back to sleep, trips to the bathroom, and daytime sleepiness. Participants often normalized their sleeping problems and had developed a number of coping strategies. These findings highlight the impact that sleep disturbances can have on people living with dementia. Their experiences and beliefs need to be considered for developing effective interventions to improve sleep, waking function, and wellbeing.
Intermediate and Long-Term Outcomes of the Suture Bridge Technique for the Management of Insertional Achilles Tendinopathy
Authors: Greenhagen Robert M. , Shinabarger Andrew B. , Pearson Kyle T. , Burns Patrick R. 
Published: January 2013

Introduction. Insertional Achilles tendinopathy is a problem frequently encountered by the foot and ankle surgeon. Conservative care yields mixed results, and this condition is often treated surgically. Our hypothesis is that the suture bridge technique through a central posterior incision allows adequate visualization for thorough debridement and exostectomy and provides a stable tendon-to-bone interface for healing. Material and Methods. The medical records of 35 patients who underwent surgical treatment for insertional Achilles tendinopathy with the suture bridge technique, by a single surgeon, between 2006 and 2012 were retrospectively reviewed. American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot instruments as well as a subjective questionnaire were utilized. Results. In all, 30 individuals who met the inclusion criteria for the treatment of insertional Achilles tendinopathy were evaluated at a mean follow-up of 28.93 ± 16.99 months. We included 10 men and 20 women, with a mean age of 49.1 ± 9.2 years. The mean preoperative AOFAS score was 56.6 ± 14.0. The average postoperative AOFAS score significantly increased to 91.7 ± 10.4 (P < .0001). One participant required revisional surgery, consisting of a flexor hallucis longus transfer performed by another physician. There were no wound complications or infections. Overall, there was a 97% (28/29) satisfaction rate. Conclusion. The central incision with complete detachment of the Achilles tendon and reattachment with the suture bridge technique for the treatment of insertional Achilles tendinopathy provides an effective treatment with good to excellent clinical outcomes in 97% of patients, with a mean follow-up of 29 months. Levels of Evidence: Therapeutic, Level IV, Retrospective case series
Action in the Event Tent! Medical-Legal Issues Facing the Volunteer Event Physician
Authors: Ross David S. , Ferguson Alishia , Herbert David L. 
Published: January 2013

Context: Physicians need to consider medical-legal issues when volunteering their time to assist with community mass-participation and athletic events. This article also reviews medical-legal aspects of the volunteer physician’s out-of-state practice. Seven cases illustrate the importance of expertise and planning to avoid legal issues for the volunteer event physician. Evidence Acquisition: Relevant studies, expert opinion, medical-legal legislation, and medical-legal cases were reviewed. Results: Physicians typically make 4 common assumptions regarding these types of events: Good Samaritan legislation, event liability insurance, personal liability insurance, and waivers. We discuss the intent of these assumptions and the reality of how, or how not, they provide any protection to the volunteer event physician. Conclusion: The intent of this article is to make physicians aware of medial-legal issues when volunteering their time for community and athletic events.
Association of thymidylate synthase gene 3'-untranslated region polymorphism with sensitivity of non-small cell lung cancer to pemetrexed treatment: TS gene polymorphism and pemetrexed sensitivity in NSCLC
Authors: Wang Xia , Wang Yadi , Wang Yue , Cheng Jian , Wang Yanyun , Ha Minwen 
Published: January 2013

Abstract

Background
Thymidylate synthase (TS) is a key enzyme responsible for DNA synthesis and repair. Altered expression of TS protein or TS gene polymorphisms has been associated with cancer progression and treatment response. This study investigated the expressions of TS and its gene SNPs in non-small cell lung cancer (NSCLC), and then its association with sensitivity to pemetrexed treatment. Immunohistochemistry and qRT-PCR were performed on 160 resected NSCLC specimens and corresponding normal tissues to assess the expressions of TS protein and TS mRNA, and for associations with clinicopathological data. Blood samples of 106 lung adenocarcinoma patients were examined for polymorphisms of the TS gene 3’-UTR 1494del 6 bp, which was then investigated for associations with responses of the patients to pemetrexed treatment and survival.

Results
Expression of both TS protein and its mRNA was elevated in NSCLC tissues compared with matched normal tissues, and significantly higher in lung squamous cell carcinoma than in lung adenocarcinoma. TS expression was associated with poor tumor differentiation. Furthermore, the genotyping data showed that 56% of lung adenocarcinoma patients had the TS gene 3’-UTR 1494 bp (−6 bp/-6 bp) genotype and the rest had TS gene 3’-UTR 1494 bp (−6 bp/+6 bp). There was no TS 3’-UTR 1494 bp (+6 bp/+6 bp) genotype in any patients. Statistical analysis revealed that gender, tumor stage, and TS 3’-UTR 1494del 6 bp polymorphism were significant prognostic factors after short-term pemetrexed treatment. Log-rank analysis revealed that patients with the (−6 bp/-6 bp) genotype had significantly better progression-free and overall survival than patients with (−6 bp/+6 bp).

Conclusions
This study showed that TS protein is highly expressed in NSCLC and that polymorphisms of TS 3’-UTR 1494del 6 bp are associated with sensitivity of lung adenocarcinoma patients to pemetrexed treatment. This suggests that TS gene polymorphisms should be further evaluated as prognostic markers for personalized therapy in lung adenocarcinoma.
Enhanced cognitive function and antidepressant-like effects after krill oil supplementation in rats
Authors: Wibrand Karin , Berge Kjetil , Messaoudi Michaël , Duffaud Anaïs , Panja Debabrata , Bramham Clive R , Burri Lena 
Published: January 2013

AbstractBackgroundThe purpose of the study was to evaluate the effects of krill oil (KO) on cognition and depression-like behaviour in rats.MethodsCognition was assessed using the Aversive Light Stimulus Avoidance Test (ALSAT). The Unavoidable Aversive Light Stimulus (UALST) and the Forced Swimming Test (FST) were used to evaluate the antidepressant-like effects of KO. Imipramine (IMIP) was used as the antidepressant reference substance.ResultsAfter 7 weeks of KO intake, both males and females treated with KO were significantly better in discriminating between the active and the inactive levers in the ALSAT from day 1 of training (p<0.01). Both KO and IMIP prevented resignation/depression on the third day in the UALST. Similarly, a shorter immobility time was observed for the KO and IMIP groups compared to the control in the FST (p<0.001). These data support a robust antidepressant-like potential and beneficial cognitive effect of KO. Changes in expression of synaptic plasticity-related genes in the prefrontal cortex and hippocampus were also investigated. mRNA for brain-derived neurotrophic factor (Bdnf) was specifically upregulated in the hippocampus of female rats receiving 7 weeks of KO supplementation (p=0.04) and a similar trend was observed in males (p=0.08). Males also exhibited an increase in prefrontal cortex expression ofArcmRNA, a key protein in long-term synaptic plasticity (p=0.05). IMIP induced clear effects on several plasticity related genes includingBdnfandArc.ConclusionsThese results indicate that active components (eicosapentaenoic acid, docosahexaenoic acid and astaxanthin) in KO facilitate learning processes and provide antidepressant-like effects. Our findings also suggest that KO might work through different physiological mechanisms than IMIP.
Ganglioside-monosialic acid (GM1) prevents oxaliplatin-induced peripheral neurotoxicity in patients with gastrointestinal tumors
Authors: Zhu Yanyun , Yang Junlan , Jiao Shunchang , Ji Tiefeng 
Published: January 2013

AbstractBackgroundOxaliplatin, an effective antineoplastic agent againstgastrointestinal tumors, can cause severe peripheral neurotoxicity, which seriously limits its clinical application. To date, there are no effective treatments for this complication. Ganglioside-monosialic acid (GM1) has been shown to protect neurons against injuries and degeneration. The aim of this study was to evaluate the effects of GM1 on preventing oxaliplatin-induced neurotoxicity in patients with gastrointestinal tumors.MethodsIn this study, 120 patients with gastrointestinal tumors were enrolled, andthey received the treatment of XELOX (oxaliplatin and capecitabine) and FOLFOX4 (oxaliplatin, leukovolin and 5-fluorouracil). The patients were randomly divided into two groups, the experimental group and control group, with60 patients ineach. On the day chemotherapy was initiated, the experimental group received GM1 intravenously (100 mg once daily) for 3 days, while no neuroprotective agents were applied in the control group. The incidence rates and classification of neurotoxicity in the two groups were evaluated and the differences between the two groups were examined. Furthermore, whether GM1 affected the therapeutic effects of chemotherapy was also examined.ResultsThe grade of neurotoxicity in the experimental group was significantly lower than in the control group (P<0.05, Mann–Whitney U test). The probability of occurrence of low-grade neurotoxicity (grade 0 and 1) in the experimental group was higher than that in the control group (logistic ordinal regression); whereas the probability of occurrence of high-grade neurotoxicity (grade 2 and 3) in the experimental group was lower than in the control group (logistic ordinal regression).ConclusionThe data suggested that GM1 could reduce the grade of oxaliplatin-induced neurotoxicity and was an effective neuroprotective agent against oxaliplatin-induced high-grade neurotoxicity in patients with gastrointestinal tumors.
Health effects of exposure to nano-TiO2: a meta-analysis of experimental studies
Authors: Chang Xuhong , Zhang Yu , Tang Meng , Wang Bei 
Published: January 2013

Abstract
The paper is aimed to investigate the toxicity of nano-TiO2 and its potential harmful impact on human health using meta-analysis of in vitro and short-time animal studies. Data were retrieved according to included and excluded criteria from 1994 to 2011. The combined toxic effects of nano-TiO2 were calculated by the different endpoints by cell and animal models. From analysis of the experimental studies, more than 50% showed positive statistical significance except the apoptosis group, and the cytotoxicity was in a dose-dependent but was not clear in size-dependent manner. Nano-TiO2 was detained in several important organs including the liver, spleen, kidney, and brain after entering the blood through different exposure routes, but the coefficient of the target organs was altered slightly from animal models. It is possible that nano-TiO2 can induce cell damage related to exposure size and dose. Further studies will be needed to demonstrate that nanoparticles have toxic effects on human body, especially in epidemiological studies.