bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR141–CXCL1–CXCR2 Signaling–Induced Treg Recruitment Regulates Metastases and Survival of Non–Small Cell Lung Cancer
Authors: Lv Mingming , Xu Yujun , Tang Ruijing , Ren Jing , Shen Sunan , Chen Yueqiu , Liu Baorui , Hou Yayi , Wang Tingting 
Published: October 2014

AbstractPatients with non–small cell lung cancer (NSCLC) with malignant pleural effusion (MPE) have a short median survival time and increased regulatory T cells (Treg). However, it is unclear whether some specific factors in MPE are involved in Treg recruitment in the progression of NSCLC. Here, we found that Treg population was increased in MPE and inversely correlated with patient survival (P &lt; 0.001). Increased level of CXCL1 in MPE was associated with recruitment of Tregs (P &lt; 0.01). Moreover, miR141 regulated expression of CXCL1 in lung cancer cells, whereas the luciferase test confirmed that CXCL1 is a target of miR141. Chemotaxis assay showed that the miR141–CXCL1–CXCR2 pathway regulates migration of Tregs into MPE. Furthermore, miR141 significantly inhibited tumor growth and metastasis in an immune-competent mouse model. This suppressive function was mediated by the CXCL1–CXCR2 pathway and recruitment of Tregs. Our study uncovered a causative link between microRNA and development of MPE. Mechanistically, decreased expressions of miR141, associated with the survival of patients with NSCLC with MPE, resulted in the increased production of CXCL1 and recruitment of Tregs to promote immune escape of tumor. Mol Cancer Ther; 13(12); 3152–62. ©2014 AACR.
Combined CDKN1A/TP53 Mutation in Bladder Cancer Is a Therapeutic Target
Authors: Liu Yang , Kwiatkowski David J. 
Published: October 2014

AbstractInvasive bladder cancer has high morbidity and nearly uniform mortality when metastatic, with no therapeutic improvement in many years. Although chemotherapy combined with Chk1 inhibition has been investigated in several cancer types in which TP53 mutation is seen, this combination treatment approach has not been studied in bladder cancer. Recently, cancer genome sequencing efforts have identified CDKN1A (p21) mutations at 14% frequency in invasive bladder cancer, co-occurring half the time with TP53 mutations. We hypothesized that combined CDKN1A–TP53 loss would make bladder cancer sensitive to combined treatment with gemcitabine and Chk1 inhibitor. Here, we show that TP53–CDKN1A double-mutant bladder cancer cell lines, 647V and RT-112, have a remarkable increase in p-Chk1 levels and G2–M arrest in response to gemcitabine treatment, with a heightened sensitivity to combination treatment with gemcitabine and either Chk1 inhibitor PF477736 or AZD7762, in comparison with other bladder cancer cell lines (either TP53 or p21 deficient). In addition, CDKN1A restoration in p21-deficient bladder cancer cells significantly reduced their sensitivity to combined treatment by protecting them from DNA damage and apoptosis. Furthermore, xenograft studies using RT-112 showed a significant synergistic effect of combined gemcitabine–PF477736 treatment on tumor growth. Our findings suggest that TP53/CDKN1A double-mutant bladder cancer cells have a unique dependence on Chk1 activity for the G2–M cell-cycle checkpoint in response to chemotherapy-induced DNA damage. This combination or others involving genotoxic agents and Chk kinase inhibitors is a promising therapeutic approach for bladder cancer with these mutations. Mol Cancer Ther; 14(1); 174–82. ©2014 AACR.
Responses of the Western North Pacific Subtropical High to Global Warming under RCP4.5 and RCP8.5 Scenarios Projected by 33 CMIP5 Models: The Dominance of Tropical Indian Ocean–Tropical Western Pacific SST Gradient
Authors: He Chao , Zhou Tianjun 
Published: October 2014

Abstract
Using the outputs of 33 coupled models that participated in phase 5 of the Coupled Model Intercomparison Project (CMIP5), the changes of the western North Pacific subtropical high (WNPSH) in the 2050–99 period under representative concentration pathway 4.5 and 8.5 (RCP4.5 and RCP8.5) scenarios relative to the 1950–99 period are analyzed. Under both scenarios, the projected changes in the WNPSH intensity are approximately zero in the multimodel ensemble mean (MME), and large intermodel spread is seen. About half of the models project an enhanced WNPSH and about half of the models project a weakened WNPSH under both scenarios. As revealed by both diagnostic studies and numerical simulations, the projected change in the WNPSH intensity is dominated by the change in the zonal sea surface temperature (SST) gradient between the tropical Indian Ocean (TIO) and the tropical western Pacific (TWP). A stronger (weaker) warming in the TIO is in favor of an enhanced (weakened) WNPSH, and a weaker (stronger) warming over the TWP is also in favor of an enhanced (weakened) WNPSH. The projected change of the WNPSH modulates the climate change over eastern China. Under both RCP4.5 and RCP8.5 scenarios, all of the models with a significantly increased (decreased) WNPSH intensity are associated with a significant increase in the precipitation over the northern (southern) part of eastern China and an enhanced (weakened) southerly wind.
Changes in U.S. East Coast Cyclone Dynamics with Climate Change
Authors: Marciano Christopher G. , Lackmann Gary M. , Robinson Walter A. 
Published: October 2014

Abstract
Previous studies investigating the impacts of climate change on extratropical cyclones have primarily focused on changes in the frequency, intensity, and distribution of these events. Fewer studies have directly investigated changes in the storm-scale dynamics of individual cyclones. Precipitation associated with these events is projected to increase with warming owing to increased atmospheric water vapor content. This presents the potential for enhancement of cyclone intensity through increased lower-tropospheric diabatic potential vorticity generation. This hypothesis is tested using the Weather Research and Forecasting Model to simulate individual wintertime extratropical cyclone events along the United States East Coast in present-day and future thermodynamic environments. Thermodynamic changes derived from an ensemble of GCMs for the IPCC Fourth Assessment Report (AR4) A2 emissions scenario are applied to analyzed initial and lateral boundary conditions of observed strongly developing cyclone events, holding relative humidity constant. The perturbed boundary conditions are then used to drive future simulations of these strongly developing events. Present-to-future changes in the storm-scale dynamics are assessed using Earth-relative and storm-relative compositing. Precipitation increases at a rate slightly less than that dictated by the Clausius–Clapeyron relation with warming. Increases in cyclone intensity are seen in the form of minimum sea level pressure decreases and a strengthened 10-m wind field. Amplification of the low-level jet occurs because of the enhancement of latent heating. Storm-relative potential vorticity diagnostics indicate a strengthening of diabatic potential vorticity near the cyclone center, thus supporting the hypothesis that enhanced latent heat release is responsible for this regional increase in future cyclone intensity.
Is implementation of the 2013 Australian treatment guidelines for posttraumatic stress disorder cost-effective compared to current practice? A cost-utility analysis using QALYs and DALYs
Authors: Mihalopoulos Cathrine , Magnus Anne , Lal Anita , Dell Lisa , Forbes David , Phelps Andrea 
Published: October 2014

Objective: To assess, from a health sector perspective, the incremental cost-effectiveness of three treatment recommendations in the most recent Australian Clinical Practice Guidelines for posttraumatic stress disorder (PTSD). The interventions assessed are trauma-focused cognitive behavioural therapy (TF-CBT) and selective serotonin reuptake inhibitors (SSRIs) for the treatment of PTSD in adults and TF-CBT in children, compared to current practice in Australia. Method: Economic modelling, using existing databases and published information, was used to assess cost-effectiveness. A cost-utility framework using both quality-adjusted life-years (QALYs) gained and disability-adjusted life-years (DALYs) averted was used. Costs were tracked for the duration of the respective interventions and applied to the estimated 12 months prevalent cases of PTSD in the Australian population of 2012. Simulation modelling was used to provide 95% uncertainty around the incremental cost-effectiveness ratios. Consideration was also given to factors not considered in the quantitative analysis but could determine the likely uptake of the proposed intervention guidelines. Results: TF-CBT is highly cost-effective compared to current practice at $19,000/QALY, $16,000/DALY in adults and $8900/QALY, $8000/DALY in children. In adults, 100% of uncertainty iterations fell beneath the $50,000/QALY or DALY value-for-money threshold. Using SSRIs in people already on medications is cost-effective at $200/QALY, but has considerable uncertainty around the costs and benefits. While there is a 13% chance of health loss there is a 27% chance of the intervention dominating current practice by both saving dollars and improving health in adults. Conclusion: The three Guideline recommended interventions evaluated in this study are likely to have a positive impact on the economic efficiency of the treatment of PTSD if adopted in full. While there are gaps in the evidence base, policy-makers can have considerable confidence that the recommendations assessed in the current study are likely to improve the efficiency of the mental health care sector.
A questionnaire examining attitudes of collegiate athletes toward doping and pharmacists as information providers
Authors: Malek Scott , Taylor Jeff , Mansell Kerry 
Published: October 2014

Background: Doping in sport has become an increasingly prominent topic. The decision to take part in doping practices is multifactorial and often based on many different information sources of varying reliability. This study sought to determine the attitudes of athletes at a Canadian Interuniversity Sport (CIS) university toward doping and to discover if pharmacists are perceived to be a valid information source on medication usage for these athletes. Methods: CIS athletes competing in at least 1 of 8 sports were asked to complete a questionnaire. Participants were asked various questions regarding their perceptions of doping, medication use, information available to them regarding doping and the role of pharmacists in providing advice on medication usage. Results: In total, 92.7% (307/331) of questionnaires were at least partially completed. Generally, these athletes did not feel pressured to dope or that it was prevalent or necessary. The fear of doping violations largely did not alter the use of medications and supplements. The online doping education program administered by the Canadian Centre for Ethics in Sport was the most used information source (74.5%); pharmacists were used 37.7% of the time. Pharmacists were perceived to be a good source of information about banned substances by 75.6% (223/295) of participants, although only 35% (104/297) consulted a pharmacist each time they purchased a nonprescription medication. Conclusions: It appears that doping is neither prevalent nor worth the risk for these CIS athletes. There also appears to be an opportunity for pharmacists to play a more prominent role in providing advice on medication use to high-performance athletes.
Infection control intervention on meticillin resistant Staphylococcus aureus transmission in residential care homes for the elderly
Authors: Chuang Vivien WM , Tsang Iris HL , Keung Jessica PY , Leung June YY , Yuk Janet MT , Wong Doris KW , Au Sui-sum , Tam Rebekah KY , Lam Wendy WY , Kwan Martin CT , Wong Andrew TY 
Published: October 2014

Background: The objectives were to evaluate the effectiveness of an infection control bundle in controlling the meticillin resistant Staphylococcus aureus (MRSA) transmission in residential care homes for the elderly (RCHEs) in Hong Kong. Methods: This was a two-arm cluster randomised controlled trial. Infection control bundles focused on hand hygiene (HH), environmental hygiene, and modified contact precautions were applied to the intervention arm. Nasal swabs from residents; staff HH compliance and effectiveness; and environmental hygiene were assessed by microbiological sampling or observation at the baseline and quarterly after the intervention. Results: A total of 2776 residents from 36 RCHEs were recruited. The overall MRSA prevalence was 20.4% (95% confidence interval, 18.9%−21.9%). The intervention elicited an immediate effect of 2.4% absolute decrease in the prevalence and 3.7% in the intra-facility transmission, though the difference between the two arms was insignificant. Staff HH compliance increased substantially from 5.9% to 45.6% post-intervention ( p < 0.001). Conclusions: We initiated the infection control culture into the RCHEs and gained their acceptance. However, this behavioural change takes time to emerge. Our study shows that relying on the bundle alone could not bring sustainable MRSA reduction. Administrative control for strengthening infection control infrastructure is important for continuous compliance and improvement.
A novel recurrent NPM1-TYK2 gene fusion in cutaneous CD30-positive lymphoproliferative disorders
Authors: Velusamy Thirunavukkarasu , Kiel Mark J. , Sahasrabuddhe Anagh A. , Rolland Delphine , Dixon Catherine A. , Bailey Nathanael G. , Betz Bryan L. , Brown Noah A. , Hristov Alexandra C. , Wilcox Ryan A. , Miranda Roberto N. , Medeiros L. Jeffrey , Jeon Yoon K. , Inamdar Kedar V. , Lim Megan S. , Elenitoba-Johnson Kojo S. J. 
Published: October 2014

Key Points
Whole-transcriptome sequencing reveals NPM1-TYK2 gene fusion in cutaneous CD30-positve lymphoproliferative disorders. NPM1-TYK2 activates STAT signaling and is a therapeutic target in a subset of cutaneous CD30-positive lymphoproliferative disorders.
Preparation of periodic surface structures on doped poly(methyl metacrylate) films by irradiation with KrF excimer laser
Authors: Kalachyova Yevgeniya , Lyutakov Oleksiy , Slepicka Petr , Elashnikov Roman , Svorcik Vaclav 
Published: October 2014

Abstract
In this work, we describe laser modification of poly(methyl methacrylate) films doped with Fast Red ITR, followed by dopant exclusion from the bulk polymer. By this procedure, the polymer can be modified under extremely mild conditions. Creation of surface ordered structure was observed already after application of 15 pulses and 12 mJ cm−2 fluence. Formation of grating begins in the hottest places and tends to form concentric semi-circles around them. The mechanism of surface ordered structure formation is attributed to polymer ablation, which is more pronounced in the place of higher light intensity. The smoothness of the underlying substrate plays a key role in the quality of surface ordered structure. Most regular grating structures were obtained on polymer films deposited on atomically ‘flat’ Si substrates. After laser patterning, the dopant was removed from the polymer by soaking the film in methanol.
Phase III Study of Iniparib Plus Gemcitabine and Carboplatin Versus Gemcitabine and Carboplatin in Patients With Metastatic Triple-Negative Breast Cancer
Authors: O'Shaughnessy Joyce , Schwartzberg Lee , Danso Michael A. , Miller Kathy D. , Rugo Hope S. , Neubauer Marcus , Robert Nicholas , Hellerstedt Beth , Saleh Mansoor , Richards Paul , Specht Jennifer M. , Yardley Denise A. , Carlson Robert W. , Finn Richard S. , Charpentier Eric , Garcia-Ribas Ignacio , Winer Eric P. 
Published: October 2014

Purpose There is a lack of treatments providing survival benefit for patients with metastatic triple-negative breast cancer (mTNBC), with no standard of care. A randomized phase II trial showed significant benefit for gemcitabine, carboplatin, and iniparib (GCI) over gemcitabine and carboplatin (GC) in clinical benefit rate, response rate, progression-free survival (PFS), and overall survival (OS). Here, we formally compare the efficacy of these regimens in a phase III trial. Patients and Methods Patients with stage IV/locally recurrent TNBC who had received no more than two previous chemotherapy regimens for mTNBC were randomly allocated to gemcitabine 1,000 mg/m2 and carboplatin area under the curve 2 (days 1 and 8) alone or GC plus iniparib 5.6 mg/kg (days 1, 4, 8, and 11) every 3 weeks. Random assignment was stratified by the number of prior chemotherapies. The coprimary end points were OS and PFS. Patients receiving GC could cross over to iniparib on progression. Results Five hundred nineteen patients were randomly assigned (261 GCI; 258 GC). In the primary analysis, no statistically significant difference was observed for OS (hazard ratio [HR] = 0.88; 95% CI, 0.69 to 1.12; P = .28) nor PFS (HR = 0.79; 95% CI, 0.65 to 0.98; P = .027). An exploratory analysis showed that patients in the second-/third-line had improved OS (HR = 0.65; 95% CI, 0.46 to 0.91) and PFS (HR = 0.68; 95% CI, 0.50 to 0.92) with GCI. The safety profile for GCI was similar to GC. Conclusion The trial did not meet the prespecified criteria for the coprimary end points of PFS and OS in the ITT population. The potential benefit with iniparib observed in second-/third-line subgroup warrants further evaluation.
Pharmacokinetic and Pharmacodynamic Properties of Calaspargase Pegol Escherichia coli L-Asparaginase in the Treatment of Patients With Acute Lymphoblastic Leukemia: Results From Children's Oncology Group Study AALL07P4
Authors: Angiolillo Anne L. , Schore Reuven J. , Devidas Meenakshi , Borowitz Michael J. , Carroll Andrew J. , Gastier-Foster Julie M. , Heerema Nyla A. , Keilani Taha , Lane Ashley R. , Loh Mignon L. , Reaman Gregory H. , Adamson Peter C. , Wood Brent , Wood Charlotte , Zheng Hao W. , Raetz Elizabeth A. , Winick Naomi J. , Carroll William L. , Hunger Stephen P. 
Published: October 2014

Purpose Asparaginase is a critical agent used to treat acute lymphoblastic leukemia (ALL). Pegaspargase (SS-PEG), a pegylated form of Escherichia coli L-asparaginase with a succinimidyl succinate (SS) linker, is the first-line asparaginase product used in Children's Oncology Group (COG) ALL trials. Calaspargase pegol (SC-PEG) replaces the SS linker in SS-PEG with a succinimidyl carbamate linker, creating a more stable molecule. COG AALL07P4 was designed to determine the pharmacokinetic and pharmacodynamic comparability of SC-PEG to SS-PEG in patients with newly diagnosed high-risk (HR) B-cell ALL. Patients and Methods A total of 165 evaluable patients were randomly assigned at a 2:1 ratio to receive SC-PEG at 2,100 (SC-PEG2100; n = 69) or 2,500 IU/m2 (SC-PEG2500; n = 42) versus SS-PEG 2,500 IU/m2 (SS-PEG2500; n = 54) as part of an otherwise identical chemotherapy regimen. The groups were similar demographically, except more female patients received SC-PEG2500. Results The mean half-life of plasma asparaginase activity for both SC-PEG doses was approximately 2.5× longer than that of SS-PEG2500. The total systemic exposure, as defined by induction area under the curve from time 0 to 25 days, was greater with SC-PEG2500 than with SS-PEG2500 or SC-PEG2100. The proportion of patients with plasma asparaginase activity ≥ 100 mIU/mL and ≥ 400 mIU/mL was higher in patients who received SC-PEG as compared with SS-PEG2500. After one dose of pegylated asparaginase on induction day 4, plasma asparagine was undetectable for 11 days for SS-PEG2500 and 18 days for both SC-PEG groups. Conclusion SC-PEG2500 achieves a significantly longer period of asparaginase activity above defined thresholds and asparagine depletion compared with SS-PEG2500 and has a comparable toxicity profile in children with HR B-cell ALL.
Non‐monophyly of Buglossoides (Boraginaceae: Lithospermeae): Phylogenetic and morphological evidence for the expansion of Glandora and reappraisal of Aegonychon
Authors: Cecchi Lorenzo , Coppi Andrea , Hilger Hartmut H. , Selvi Federico 
Published: October 2014

AbstractThe phylogeny of the small Old World genus Buglossoides and its position in tribe Lithospermeae was investigated using nrDNA and cpDNA sequences and morphology. Maximum parsimony and Bayesian analyses of ITS‐5.8S and trnL‐trnF IGS datasets consistently show that this group is close to Glandora and Lithospermum but not monophyletic. Of the seven species usually included, two were retrieved in the genus Glandora, i.e., B. goulandrisiorum from northern Greece and B. gastonii from the western Pyrenees. Based also on morphology and ecology, the placement of these two rare, rupicolous endemics in Glandora is here advocated and new combinations are made. The rest of Buglossoides includes two early‐diverging clades, one with annual taxa of section Buglossoides and one with the three perennials of section Margarospermum. Morphological, palynological and ecological data support the separation of these two groups in distinct genera, Buglossoides s.str. and the old but largely neglected Aegonychon. Within Buglossoides, two main clades correspond to the B. arvensis and B. incrassata complexes. These show a largely sympatric distribution from the south Mediterranean to central and northern Europe. Combined with their strong phenotypic polymorphism, this causes difficulties in the distinction between taxa of the two clades, especially without characteristic cotyledons or fruiting material. Molecular and morphological evidence clearly support the transfer of the west Mediterranean B. arvensis subsp. permixta to the B. incrassata complex.
The role of the Alzheimer's Society in hospital: evaluation of a new support service for patients and their carers
Authors: Woods Pernille , Tadros George 
Published: October 2014

In collaboration with third sector organisation Alzheimer's Society, a new initiative to support patients with memory problems in a general hospital has been launched. Alzheimer's Society support workers hold two weekly drop-in sessions at Heartlands hospital to provide information and plan community follow-up visits. A service evaluation was conducted with semi-structured staff and carer interviews regarding their views on the service, and attendance data to the Alzheimer's Society sessions were recorded. Between August and December 2013, 196 individuals visited the Alzheimer's Society in Heartlands hospital. Of these, 18 individuals received referrals to access community services, and carers recommended that a similar service should exist in other hospitals. Staff believed this service complements patients' care pathway, and can help to reduce carer burnout. Recommendations include expanding the service, and introducing dementia cafés. The evaluation should be repeated in 12 months to gather further results on attendance and service-user feedback.
Evaluating the efficacy of drama therapy in teaching social skills to children with Autism Spectrum Disorders
Authors: D’Amico Miranda , Lalonde Corinne , Snow Stephen 
Published: October 2014

Abstract
This article reviews a year-long study at the Centre for the Arts in Human Development at Concordia University (Montreal, Canada). It analyses the results of a specialized adaptation of drama therapy for a group of preadolescent children with high-functioning Autism Spectrum Disorders. The procedure aimed at improving social skills and problem behaviours. Statistical results of the study are promising in demonstrating the efficacy of drama therapy in this domain.