bluuebunny/crossref_metadata_2025_split huggingface dataset:
An engagement and access model for healthcare delivery to adolescents with mood and anxiety concerns
Authors: Ross Erin , Vingilis Evelyn , Osuch Elizabeth 
Published: December 2011

AbstractAim: Mood and anxiety disorders typically begin during adolescence or early adulthood. Yet services targeting this population are frequently lacking. This study implemented an outreach, access and assessment programme for youth with these concerns. The data reported constitute an evaluation of this mental healthcare delivery approach.Methods: This evaluation included specification of both programme and implementation theories through causal and programme logic models and formative (process) evaluation. Outreach focused on access points for youth such as schools and family physicians' offices. Concerned youth were encouraged to self‐refer. Participants completed a semi‐structured clinical interview and symptom and function questionnaire package.Results: Engagement sessions were conducted and results involved 93 youth. The majority of youth self‐referred, a process not possible in traditional physician‐referral healthcare systems. Interestingly, almost half had received prior treatment and over half had tried a psychiatric medication. Yet participants had significant symptomatology: 81% reported moderate to severe depressive symptoms; 95% reported high levels of trait‐anxiety. Functional impairment was substantial: on average, participants missed 2.6 days of school/work and functioned at reduced levels on 4.2 days in the week prior to assessment. Demographic details are presented.Conclusion: This study evaluated a mental healthcare delivery system that identified individuals with significant distress and functional impairment from mood/anxiety concerns and previous unsuccessful treatment attempts, verifying that they were in need of mental health services. This approach provides a model for outreach and assessment in this population, where earlier intervention has the potential to prevent chronic mental illness and disability.
Significance of human papillomavirus 16/18 infection in association with p53 mutation in lung carcinomas
Authors: Yu Yan , Yang Aimin , Hu Senke , Zhang Jinghua , Yan Hong 
Published: December 2011

AbstractIntroduction:  The role of high‐risk human papillomavius (HPV) 16/18 in the development of lung cancer has recently been explored, and p53 mutation is a finding in lung cancer; however, its association with HPV infection is not well studied.Objectives:  To investigate HPV 16/18 infection and p53 mutation in lung carcinomas and their association with tumor behavior.Methods and Results:  We expanded our prior study to include 107 squamous cell carcinoma (SCC), 63 adenocarcinoma (AC) and 91 non‐cancer control cases of lung from a population of Western China. The results confirmed that HPV infection is more prevalent in SCC (59.8%) comparing with that of AC (17.5%) and the control cases (23.1%) (P < 0.001), and genotyping demonstrated predominant HPV 16/18 infection in the carcinomas and HPV 6 in the control cases. By immunohistochemistry, p53 mutation was detected in 67.3% of SCC and 60.3% of AC, in comparison with 9.9% in the control (P < 0.001). Within the group of SCC, the p53 mutation rate is significantly higher in those with HPV infection (78.1%) than that of the non‐infected carcinomas (51.2%, P = 0.004). However, this difference is not proven to be significant in the groups of AC and the controls. Clinicopathological analysis demonstrated that the coexistence of p53 mutation and HPV infection was associated with lymph node metastasis (P = 0.001) and high‐clinical TNM stage of SCC (P = 0.001). As there was no sequencing data, the evidence for HPV 16/18 E6 induced p53 mutation is still indirect.Conclusion:  This study indicates that p53 mutation and HPV 16/18 infection might coordinate in the development of lung squamous cell carcinomas, and their coexistence is associated with poor prognosis.Please cite this paper as: Yu Y, Yang A, Hu S, Zhang J and Yan H. Significance of human papillomavirus 16/18 infection in association with p53 mutation in lung carcinomas. Clin Respir J 2013; 7: 27–33.
Dynamic Energy Budget theory meets individual‐based modelling: a generic and accessible implementation
Authors: Martin Benjamin T. , Zimmer Elke I. , Grimm Volker , Jager Tjalling 
Published: December 2011

Summary1. Dynamic Energy Budget (DEB) theory was designed to understand the dynamics of biological systems from cells to populations and ecosystems via a mass balance approach of individuals. However, most work so far has focused on the level of the individual. To encourage further use of DEB theory in a population context, we developed DEB‐IBM, a generic individual‐based model (IBM) that is based on DEB theory.2. The generic IBM is implemented as a computer program using NetLogo, a free software platform that is accessible to biologists with little programming background. The IBM uses DEB to represent assimilation, maintenance, growth and reproduction of individuals. The model description follows the overview, design and details (ODD) protocol, a generic format for describing IBMs, and thereby provides a novel and accessible introduction to DEB theory and how it works in a population context.3. Dynamic Energy Budget‐individual‐based model can be used to explore properties of both individual life‐history traits and population dynamics, which emerge from the set of DEB parameters of a species, and their interaction with environmental variables such as food density. Furthermore, DEB‐IBM can be adapted to address specific research questions, for example by including spatial effects. A user manual explains how this can be done.4. Dynamic Energy Budget‐individual‐based model is designed to both facilitate use and testing DEB theory in a population context and to advance individual‐based modelling by basing the representation of individuals on well‐tested physiological principles.
phytools: an R package for phylogenetic comparative biology (and other things)
Authors: Revell Liam J. 
Published: December 2011

Summary1. Here, I present a new, multifunctional phylogenetics package, phytools, for the R statistical computing environment.2. The focus of the package is on methods for phylogenetic comparative biology; however, it also includes tools for tree inference, phylogeny input/output, plotting, manipulation and several other tasks.3. I describe and tabulate the major methods implemented in phytools, and in addition provide some demonstration of its use in the form of two illustrative examples.4. Finally, I conclude by briefly describing an active web‐log that I use to document present and future developments for phytools. I also note other web resources for phylogenetics in the R computational environment.
Mitochondrial DNA Sequence Variation and Risk of Pancreatic Cancer
Authors: Lam Ernest T. , Bracci Paige M. , Holly Elizabeth A. , Chu Catherine , Poon Annie , Wan Eunice , White Krystal , Kwok Pui-Yan , Pawlikowska Ludmila , Tranah Gregory J. 
Published: December 2011

Abstract
Although the mitochondrial genome exhibits high mutation rates, common mitochondrial DNA (mtDNA) variation has not been consistently associated with pancreatic cancer. Here, we comprehensively examined mitochondrial genomic variation by sequencing the mtDNA of participants (cases = 286, controls = 283) in a San Francisco Bay Area pancreatic cancer case–control study. Five common variants were associated with pancreatic cancer at nominal statistical significance (P &lt; 0.05) with the strongest finding for mt5460g in the ND2 gene [OR = 3.9; 95% confidence interval (CI), 1.5–10; P = 0.004] which encodes an A331T substitution. Haplogroup K was nominally associated with reduced pancreatic cancer risk (OR = 0.32; 95% CI, 0.13–0.76; P = 0.01) when compared with the most common haplogroup, H. A total of 19 haplogroup-specific rare variants yielded nominal statistically significant associations (P &lt; 0.05) with pancreatic cancer risk, with the majority observed in genes involved in oxidative phosphorylation. Weighted-sum statistics were used to identify an aggregate effect of variants in the 22 mitochondrial tRNAs on pancreatic cancer risk (P = 0.02). While the burden of singleton variants in the HV2 and 12S RNA regions was three times higher among European haplogroup N cases than controls, the prevalence of singleton variants in ND4 and ND5 was two to three times higher among African haplogroup L cases than in controls. Together, the results of this study provide evidence that aggregated common and rare variants and the accumulation of singleton variants are important contributors to pancreatic cancer risk. Cancer Res; 72(3); 686–95. ©2011 AACR.
Modulation of NOXA and MCL-1 as a Strategy for Sensitizing Melanoma Cells to the BH3-Mimetic ABT-737
Authors: Lucas Keryn M. , Mohana-Kumaran Nethia , Lau Diana , Zhang Xu Dong , Hersey Peter , Huang David C. , Weninger Wolfgang , Haass Nikolas K. , Allen John D. 
Published: December 2011

Abstract
Purpose: Drug resistance in melanoma is commonly attributed to ineffective apoptotic pathways. Inhibiting antiapoptotic BCL-2 and its relatives is an attractive strategy for sensitizing lymphoid malignancies to drugs but it has been largely unsuccessful for melanoma and other solid tumors. ABT-737, a small-molecule BH3-mimetic, selectively inhibits BCL-2, BCL-XL, and BCL-w and shows promise for treating leukemia, lymphoma, and small-cell lung cancer. Melanoma cells are insensitive to ABT-737, but MCL-1 inhibition reportedly increases the sensitivity of other tumors to the compound.
Experimental Design: The efficacy of MCL-1 and BFL-1 inhibition for sensitizing melanoma cells to ABT-737 was investigated by short hairpin RNA–mediated knockdown or overexpression of their antagonist NOXA in two-dimensional cell culture, a three-dimensional organotypic spheroid model, and an in vivo model.
Results: MCL-1 downregulation or NOXA overexpression strongly sensitized melanoma cells to ABT-737 in vitro. NOXA-inducing cytotoxic drugs also strongly sensitized melanomas to ABT-737 but, surprisingly, not vice versa. The drugs most suitable are not necessarily those normally used to treat melanoma. Resistance to ABT-737 occurred quickly in three-dimensional melanoma spheroids through reduced NOXA expression, although experiments with both xenografts and three-dimensional spheroids suggest that penetration of ABT-737 into tumor masses may be the principal limitation, which may be obviated through use of more diffusible BH3-mimetics.
Conclusion: Sensitization of tumors to BH3-mimetics by cytotoxic drugs that induce NOXA is a therapeutic strategy worth exploring for the treatment of melanoma and other solid cancers. Clin Cancer Res; 18(3); 783–95. ©2011 AACR.
SOD Mimetics: A Novel Class of Androgen Receptor Inhibitors That Suppresses Castration-Resistant Growth of Prostate Cancer
Authors: Thomas Rusha , Sharifi Nima 
Published: December 2011

AbstractAdvanced prostate cancer is the second leading cause of cancer-related deaths among American men. The androgen receptor (AR) is vital for prostate cancer progression, even in the face of castrate levels of serum testosterone following androgen ablation therapy, a mainstay therapy for advanced prostate cancer. Downregulation of superoxide dismutase 2 (SOD2), a major intracellular antioxidant enzyme, occurs progressively during prostate cancer progression to advanced states and is known to promote AR activity in prostate cancer. Therefore, this study investigated the effects of SOD mimetics on AR expression and function in AR-dependent LNCaP, CWR22Rv1, and LAPC-4AD prostate cancer cells. Treatment with Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), a SOD mimetic, not only lowered cellular superoxide levels but also concomitantly attenuated AR transcriptional activity and AR target gene expression in a dose- and time-dependent manner, in the presence and absence of dihydrotestosterone, the major endogenous AR agonist. Inhibition of AR by Tempol was mediated, in large part, by its ability to decrease AR protein via increased degradation, in the absence of any inhibitory effects on other nuclear receptors. Inhibitory effects of Tempol on AR were also reproducible with other SOD mimetics, MnTBAP and MnTMPyP. Importantly, effects of Tempol on AR function were accompanied by significant in vitro and in vivo reduction in castration-resistant prostate cancer (CRPC) survival and growth. Collectively, this study has shown for the first time that SOD mimetics, by virtue of their ability to suppress AR function, may be beneficial in treating the currently incurable CRPC, in which SOD2 expression is highly suppressed. Mol Cancer Ther; 11(1); 87–97. ©2011 AACR.
CHOP Silencing Reduces Acute Brain Injury in the Rat Model of Subarachnoid Hemorrhage
Authors: He Zhaohui , Ostrowski Robert P. , Sun Xiaochuan , Ma Qingyi , Huang Bing , Zhan Yan , Zhang John H. 
Published: December 2011

Background and Purpose—
Endoplasmic reticulum stress triggers apoptotic cascades in neurons of the central nervous system after subarachnoid hemorrhage. The aim of this work was to study the mechanism of neuroprotection conferred by targeting cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in the acute brain injury following subarachnoid hemorrhage.

Methods—
A total of 172 rats were used. Endovascular perforation induced subarachnoid hemorrhage. Two small interfering RNAs for CHOP were injected 24 hours before hemorrhage induction. At 24 or 72 hours, rats were neurologically evaluated and euthanized. The brains were recovered for molecular biology and histology studies.

Results—
Western blot analysis revealed effective silencing of CHOP associated with suppression of Bim-Caspase-3 apoptotic pathway. Moreover, the antiapoptotic Bcl2 was found upregulated with CHOP siRNA treatment. A reduced number of TUNEL-positive cells in the subcortex and in the hippocampus reflected histological protection. CHOP siRNA treatment ameliorated intracranial sequelae of and improved functional performance.

Conclusions—
We conclude that CHOP silencing alleviates early brain injury following subarachnoid hemorrhage via inhibiting apoptosis and that CHOP siRNA treatment has a clinical potential for patients with this type of hemorrhagic stroke.
Who May Have Durable Benefit From Robotic Gait Training?
Authors: Morone Giovanni , Iosa Marco , Bragoni Maura , De Angelis Domenico , Venturiero Vincenzo , Coiro Paola , Riso Raffaella , Pratesi Luca , Paolucci Stefano 
Published: December 2011

Background and Purpose—
Robotic-assisted walking training after stroke aims to enhance the odd of regaining independent gait. Recent studies have suggested that this approach is more effective than conventional therapy alone only in severely affected patients. We determined whether these results persist at long-term follow-up.

Methods—
Forty-eight nonambulant participants after subacute stroke were stratified by motricity index into high (<29) and low (≥29) motor impairment groups. Each arm was randomized to a robotic or control group at a mean of 20 days after stroke. All patients underwent 2 therapy sessions per day, 5 days per week, for 3 months. Robotic group subjects underwent 20 sessions of robotic-assisted gait training in the first 4 weeks of inpatient therapy and abbreviated conventional therapy, whereas control group patients received only conventional gait training. The primary outcome was Functional Ambulation Category, and secondary measures were the Rivermead Mobility Index and Barthel Index scores. The scales were administered before and after the inpatient stay and 2 years after discharge.

Results—

At follow-up, as at discharge, the low motricity robotic group improved more than the control group counterpart with regard to functional ambulation category (4.7±0.5 versus 3.1±1.5,
P
=0.002), Barthel Index (76.9±11.5 versus 64.7±14.0,
P
=0.024), and Rivermead Mobility Index (11.8±3.5 versus 7.0±3.6,
P
=0.010), whereas conventional and robotic therapies were equally effective in the high motricity groups.

Conclusions—
The higher efficacy of the combination of robotic therapy and conventional therapy versus conventional therapy alone that was observed at discharge only in patients with greater motor impairments was sustained after 2 years.
Synoptic-Scale Environments Conducive to Orographic Impacts on Cold-Season Surface Wind Regimes at Montreal, Quebec
Authors: Razy Alissa , Milrad Shawn M. , Atallah Eyad H. , Gyakum John R. 
Published: December 2011

AbstractOrographic wind channeling, defined as dynamically and thermally induced processes that force wind to blow along the axis of a valley, is a common occurrence along the St. Lawrence River Valley (SLRV) in Quebec, Canada, and produces substantial observed weather impacts at stations along the valley, including Montreal (CYUL). Cold-season observed north-northeast (n = 55) and south-southeast (n = 16) surface wind events at CYUL are identified from 1979 to 2002. The authors partition the north-northeast wind events into four groups using manual synoptic typing. Types A and D (“inland cyclone” and “northwestern cyclone”) are associated with strong lower-tropospheric geostrophic warm-air advection and near-surface pressure-driven channeling of cold air from the north-northeast, along the axis of the SLRV. Type C (“anticyclone”) shows no evidence of a surface cyclone and thus is the least associated with inclement weather at CYUL, whereas type B (“coastal cyclone”) is associated with predominantly forced wind channeling along the SLRV. Type D of the north-northeast wind events and all south-southeast wind events exhibit similar sea level pressure patterns. The respective magnitudes of the pressure gradients in the Lake Champlain Valley south of CYUL and the SLRV play a large role in determining the favored wind direction. Soundings of the various event types illustrate substantial differences in temperature structure, with a large near-surface temperature inversion particularly prevalent in north-northeast events. The results of this study may provide guidance in forecasting winds, temperatures, and observed weather in and around the SLRV, given certain synoptic-scale regimes.
A Brief Critique of a Theory Used to Interpret the Infrasound of Tornadic Thunderstorms
Authors: Schecter David A. 
Published: December 2011

AbstractIt has been proposed that the 0.5–10-Hz infrasound emitted by a severe storm is primarily generated by the axisymmetric oscillations of a tornado. This interpretation is challenged by a critical review of its theoretical foundation. A basic linear analysis shows that the principal axisymmetric oscillations of a subsonic, columnar vortex (axisymmetric Kelvin modes) cannot excite acoustic radiation. Numerical experiments further show that axisymmetric radiation is shaped primarily by the impulse that triggers the emission, not the properties of the vortex.
Suicide rates in the national and expatriate population in Dubai, United Arab Emirates
Authors: Dervic Kanita , Amiri Leena , Niederkrotenthaler Thomas , Yousef Said , Salem Mohamed O. , Voracek Martin , Sonneck Gernot 
Published: December 2011

Background: Reports on suicide from the Gulf region are scarce. Dubai is a city with a large expatriate population. However, total and gender-specific suicide rates for the national and expatriate populations are not known. Aims: To investigate total and gender-specific suicide rates in the national and expatriate population in Dubai and to elicit socio-demographic characteristics of suicide victims. Methods: Registered suicides in Dubai from 2003 to 2009, and aggregated socio-demographic data of suicide victims were analysed. Suicide rates per 100,000 population were calculated. Results: Suicide rate among expatriates (6.3/100,000) was seven times higher than the rate among the nationals (0.9/100,000). In both groups, male suicide rate was more than three times higher than the female rate. Approximately three out of four expatriate suicides were committed by Indians. The majority of suicide victims were male, older than 30 years, expatriate, single and employed, with an education of secondary school level and below. Conclusion: Further research on risk factors for and protective factors against suicide, particularly among the expatriate population, is needed. Epidemiological monitoring of suicide trends at the national level and improvement of UAE suicide statistics would provide useful information for developing suicide prevention strategies.
Headache and prolonged dilatation of the middle meningeal artery by PACAP38 in healthy volunteers
Authors: Amin Faisal Mohammad , Asghar Mohammad Sohail , Guo Song , Hougaard Anders , Hansen Adam Espe , Schytz Henrik Winther , van der Geest Rob J , de Koning Patrick JH , Larsson Henrik BW , Olesen Jes , Ashina Messoud 
Published: December 2011

Aim: To explore a possible relationship between vasodilatation and delayed headache we examined the effect of pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) on the middle meningeal artery (MMA) and middle cerebral artery (MCA) using high resolution magnetic resonance angiography (MRA). Methods: In a double-blind, randomized, placebo-controlled study 14 healthy volunteers were scanned repeatedly after infusion (20 min) of 10 pmol/kg/min PACAP38 or placebo. In addition, four participants were scanned following subcutaneous sumatriptan (6 mg). Results: We found significant dilatation of the MMA (p = 0.00001), but not of the MCA (p = 0.50) after PACAP38. There was no change after placebo (p > 0.40). Vasodilatation (range 16–23%) lasted more than 5 h. Sumatriptan selectively contracted the MMA by 12.3% (p = 0.043). Conclusion: PACAP38-induced headache is associated with prolonged dilatation of the MMA but not of the MCA. Sumatriptan relieves headache in parallel with contraction of the MMA but not of the MCA.
Lack of drug interaction between the migraine drug MAP0004 (orally inhaled dihydroergotamine) and a CYP3A4 inhibitor in humans
Authors: Kellerman D , Kori S , Forst A , Chang J , Febbraro S , WuTann L , Thomas T , Taylor G , Dodick DW 
Published: December 2011

Background: Dihydroergotamine (DHE), a proven migraine treatment, currently has product labeling warning against concomitant use of CYP3A4 inhibitors because of potential drug interactions. However, no reported studies of such interactions with DHE administered by any route are available. Methods: The pharmacokinetics (PK) of MAP0004, an investigative inhaled DHE formulation, were assessed in human subjects with and without CYP3A4 inhibition by ketoconazole to evaluate the potential for drug interaction, elevation of DHE levels, and increased adverse effects. Results: After MAP0004 alone vs. MAP0004 plus ketoconazole, the DHE maximum concentrations (Cmax) and area-under-the-curve (AUC0–48 and AUC0–∞) were not statistically significantly different nor was the Cmax of the primary metabolite, 8’-OH-DHE. A difference in 8’-OH-DHE AUCs was observed between MAP0004 with and without ketoconazole; however, the concentrations were very low. MAP0004 was well tolerated after both treatments. Conclusions: This study demonstrated that CYP3A4 inhibition had little to no effect on DHE PK after MAP0004 administration, apparently because of its high systemic and low gastrointestinal bioavailability. CYP3A4 inhibition slowed elimination of the metabolite 8’-OH-DHE, but concentrations were too low to be pharmacologically relevant.