bluuebunny/crossref_metadata_2025_split huggingface dataset:
High incidence of hospitalisation due to infectious gastroenteritis in older people associated with poor self-rated health
Authors: Chen Yingxi , Liu Bette C , Glass Kathryn , Kirk Martyn D 
Published: December 2015

ObjectivesTo estimate the incidence and risk factors for gastroenteritis-related hospitalisations in older adults.DesignLongitudinal cohort study.ParticipantsThe 45 and Up Study is a large-scale Australian prospective study of adults aged ≥45 years (mean 62.7 years) at recruitment in 2006–2009. Self-reported demographic, health and dietary information at recruitment from 265 440 participants were linked to infectious gastroenteritis hospitalisation data.Outcome measuresWe estimated the incidence of hospitalisation for infectious gastroenteritis, and calculated HRs using Cox regression, adjusting for sociodemographic, health and behavioural variables, with age as the underlying time variable.ResultsThere were 6077 incident infectious gastroenteritis admissions over 1 111 000 person-years. Incidence increased exponentially with increasing age; from 2.4 per 1000 (95% CI 2.2 to 2.5) in individuals aged 45–54 years to 9.5 per 1000 (95% CI 9.2 to 9.8) in those aged 65+ years. After adjustment, hospitalisation due to infectious gastroenteritis was significantly more common in those reporting use of proton pump inhibitors (HR 1.6, 95% CI 1.5 to 1.7), and those with poorer self-rated health (HR 4.2, 95% CI 3.6 to 4.9).ConclusionsInfectious gastroenteritis results in hospitalisation of approximately 1% of people ≥65 years old each year. Early recognition and supportive treatment of diarrhoea in older patients with poorer self-rated health may prevent subsequent hospitalisation.
Assessing the impact of a Carer Support Needs Assessment Tool (CSNAT) intervention in palliative home care: a stepped wedge cluster trial
Authors: Grande Gunn Eli , Austin Lynn , Ewing Gail , O'Leary Neil , Roberts Chris 
Published: December 2015

ObjectivesTo test the impact on family carers of a Carer Support Needs Assessment Tool (CSNAT) intervention to facilitate carer-led assessment and support during end of life care.MethodMixed method, part-randomised, stepped wedge cluster trial with 6 palliative home care services comparing carers receiving the intervention with those receiving standard care. Postal survey with carers 4–5 months postbereavement measured adequacy of end of life support, current mental and physical health (Short Form 12 Health Survey SF-12), level of grief (Texas Revised Inventory of Grief, TRIG) and distress (Distress Thermometer, DT), place of death and carer satisfaction with place of death.ResultsSurveys were sent to 3260 (76%) carers of 4311 deceased patients; 681 (21%) were returned (N=333 control, N=348 intervention). Compared with controls, intervention carers had significantly lower levels of early grief, better psychological and physical health, were more likely to feel the place of death was right, and patients were more likely to die at home. However, differences were small and process measures showed low level of implementation, indicating differences may partially relate to increased awareness of carer issues rather than a direct impact of the intervention.ConclusionsCarers had better outcomes in the intervention condition, albeit modest. If this can be achieved through low level implementation and awareness raising of carers’ needs from implementation activities, substantial impact should be possible if the CSNAT intervention can be fully implemented with a majority of carers. The study illustrates challenges of implementing and testing a complex intervention in real-life practice and of achieving comprehensive carer assessment and support in line with government recommendations.
2-Deoxy-Glucose Downregulates Endothelial AKT and ERK via Interference with N-Linked Glycosylation, Induction of Endoplasmic Reticulum Stress, and GSK3β Activation
Authors: Kovács Krisztina , Decatur Christina , Toro Marcela , Pham Dien G. , Liu Huaping , Jing Yuqi , Murray Timothy G. , Lampidis Theodore J. , Merchan Jaime R. 
Published: December 2015

Abstract
Interference with endothelial cell metabolism is a promising, yet unexploited strategy for angiogenesis inhibition. We reported that the glucose analogue 2-deoxy-D-glucose (2-DG) inhibits angiogenesis at significantly lower concentrations than those required for tumor cytotoxicity. Here, we found that hypersensitivity to 2-DG in endothelial cells is not associated with enhanced drug uptake compared with tumor cells, but with time-dependent, endothelial-selective inhibition of AKT and ERK phosphorylation. Downregulation of these critical survival pathways is shown to be due to 2-DG's interference with N-linked glycosylation, leading to alterations in VEGFR2 (and downstream signaling) as well as induction of endoplasmic reticulum (ER) stress, GSK3β activation, and apoptosis. In vivo, periocular administration of 2-DG in LHBETATAG mice was associated with significant reduction of newly formed (CD105+) tumor capillaries, ER stress (GRP 78 expression), and endothelial apoptosis (TUNEL). These findings uniquely link N-linked glycosylation inhibition, ER stress, and ERK/AKT downregulation in endothelial cells, and provide a novel drug development strategy to overcome resistance mechanisms to currently available antiangiogenic agents. Mol Cancer Ther; 15(2); 264–75. ©2015 AACR.
Targeted Photodynamic Virotherapy Armed with a Genetically Encoded Photosensitizer
Authors: Takehara Kiyoto , Tazawa Hiroshi , Okada Naohiro , Hashimoto Yuuri , Kikuchi Satoru , Kuroda Shinji , Kishimoto Hiroyuki , Shirakawa Yasuhiro , Narii Nobuhiro , Mizuguchi Hiroyuki , Urata Yasuo , Kagawa Shunsuke , Fujiwara Toshiyoshi 
Published: December 2015

Abstract
Photodynamic therapy (PDT) is a minimally invasive antitumor therapy that eradicates tumor cells through a photosensitizer-mediated cytotoxic effect upon light irradiation. However, systemic administration of photosensitizer often makes it difficult to avoid a photosensitive adverse effect. The red fluorescent protein KillerRed generates reactive oxygen species (ROS) upon green light irradiation. Here, we show the therapeutic potential of a novel tumor-specific replicating photodynamic viral agent (TelomeKiller) constructed using the human telomerase reverse transcriptase (hTERT) promoter. We investigated the light-induced antitumor effect of TelomeKiller in several types of human cancer cell lines. Relative cell viability was investigated using an XTT assay. The in vivo antitumor effect was assessed using subcutaneous xenografted tumor and lymph node metastasis models. KillerRed accumulation resulted in ROS generation and apoptosis in light-irradiated cancer cells. Intratumoral injection of TelomeKiller efficiently delivered the KillerRed protein throughout the tumors and exhibited a long-lasting antitumor effect with repeated administration and light irradiation in mice. Moreover, intratumorally injected TelomeKiller could spread into the regional lymph node area and eliminate micrometastasis with limited-field laser irradiation. Our results suggest that KillerRed has great potential as a novel photosensitizer if delivered with a tumor-specific virus-mediated delivery system. TelomeKiller-based PDT is a promising antitumor strategy to efficiently eradicate tumor cells. Mol Cancer Ther; 15(1); 199–208. ©2015 AACR.
Optimization of RGD-Containing Cyclic Peptides against αvβ3 Integrin
Authors: Wang Yan , Xiao Wenwu , Zhang Yonghong , Meza Leah , Tseng Harry , Takada Yoshikazu , Ames James B. , Lam Kit S. 
Published: December 2015

Abstract
We have previously reported the use of one-bead-one-compound (OBOC) combinatorial technology to develop a disulfide cyclic, Arg-Gly-Asp–containing octapeptide LXW7 (cGRGDdvc), that targets αvβ3 integrin with high affinity and specificity. αvβ3 integrin is known to be overexpressed in many cancers and in tumor vasculature, and it has been established as a cancer therapeutic target. To further optimize LXW7, we have performed systematic structure–activity relationship studies. On the basis of the results, two highly focused OBOC peptide libraries were designed, synthesized, and screened against αvβ3 integrin–transfected K562 cells. One of the best ligands, LXW64, was found to have 6.6-fold higher binding affinity than LXW7, and showed preferential binding to cells expressing αvβ3 integrin. In addition to binding strongly to U-87MG glioblastoma cells in vitro, LXW64 also targets U-87MG xenografts implanted in nude mice, indicating that it is an excellent vehicle for the delivery of cytotoxic payload to tumors and tumor blood vessels that overexpress αvβ3 integrin. Mol Cancer Ther; 15(2); 232–40. ©2015 AACR.
Influence of Obesity on Breast Density Reduction by Omega-3 Fatty Acids: Evidence from a Randomized Clinical Trial
Authors: Sandhu Narinder , Schetter Susann E. , Liao Jason , Hartman Terryl J. , Richie John P. , McGinley John , Thompson Henry J. , Prokopczyk Bogdan , DuBrock Cynthia , Signori Carina , Hamilton Christopher , Calcagnotto Ana , Trushin Neil , Aliaga Cesar , Demers Laurence M. , El-Bayoumy Karam , Manni Andrea 
Published: December 2015

Abstract
Preclinical data indicate that omega-3 fatty acids (n-3FA) potentiate the chemopreventive effect of the antiestrogen (AE) tamoxifen against mammary carcinogenesis. The role of n-3FA in breast cancer prevention in humans is controversial. Preclinical and epidemiologic data suggest that n-3FA may be preferentially protective in obese subjects. To directly test the protective effect of n-3FA against breast cancer, we conducted a 2-year, open-label randomized clinical trial in 266 healthy postmenopausal women (50% normal weight, 30% overweight, 20% obese) with high breast density (BD; ≥25%) detected on their routine screening mammograms. Eligible women were randomized to one of the following five groups (i) no treatment, control; (ii) raloxifene 60 mg; (iii) raloxifene 30 mg; (iv) n-3FA lovaza 4 g; and (v) lovaza 4 g plus raloxifene 30 mg. The 2-year change in BD, a validated biomarker of breast cancer risk, was the primary endpoint of the study. In subset analysis, we tested the prespecified hypothesis that body mass index (BMI) influences the relationship between plasma n-3FA on BD. While none of the interventions affected BD in the intention-to-treat analysis, increase in plasma DHA was associated with a decrease in absolute breast density but only in participants with BMI &gt;29. Our results suggest that obese women may preferentially experience breast cancer risk reduction from n-3FA administration. Cancer Prev Res; 9(4); 275–82. ©2015 AACR.
Biomechanical Evaluation of a Bed Feature to Assist in Turning and Laterally Repositioning Patients
Authors: Wiggermann Neal 
Published: December 2015

Objective: This study investigated the effects of hospital bed features on the biomechanical stresses experienced by nurses when turning and laterally repositioning patients. Turn Assist, a common feature in ICU beds that helps to rotate patients, and side rail orientation were evaluated. Background: Manual patient handling is a risk factor for musculoskeletal injury, and turning patients is one of the most common patient handling activities. No known studies have evaluated bed attributes such as the Turn Assist feature and side rail orientation that may affect the stresses experienced by the nurse. Method: Nine female nurses laterally repositioned and turned a 63-kg and 123-kg subject on an ICU bed while motion capture, ground reaction forces, and hand force data were recorded. Loading of the spine and shoulder was modeled using 3D Static Strength Prediction Program (3DSSPP). Results: Spine compression and shear forces did not exceed recommended limits when turning or laterally repositioning. However, the mean pull forces required to manually laterally reposition even the 63-kg subject was 340 Newtons, more than 50% greater than limits established in psychophysical testing. Turn Assist considerably reduced spine loading and pull forces for both turning and laterally repositioning. Lowering side rails reduced spinal compression by 11% when turning patients. Conclusion: Laterally repositioning patients as part of turning may pose an injury risk to caregivers. Turn Assist reduces physical loading on nurses when turning and repositioning patients. Application: Caregivers should consider using Turn Assist and other aids such as mechanical lifts or sliding sheets especially when turning patients requires lateral repositioning.
Derived importance-performance analysis and diagonal model in a Spanish municipality
Authors: Ortigueira-Sánchez Luis Camilo , Ortigueira-Bouzada Manuel , Gómez-Selemeneva Dinaidys 
Published: December 2015

This article presents and discusses empirical research into citizen satisfaction, conducted to measure the performance and management of local public policies. The object of the research is to evaluate the public safety policy of a Spanish city through a survey measuring citizen satisfaction with the local public services. Regression and ‘importance-performance analysis’ (IPA) were applied to the views expressed by a sample of citizens. One objective of the study reported is to use different derived importance values, from correlation and regression analysis, to compare the results of two ‘importance-performance analyses’. The concept of variant and invariant weights and the three-factor theory of customer satisfaction were also considered for the research. Results confirm that the ‘fire service’ is seen as a ‘dissatisfier’, a basic or flat attribute; they suggest that negative coefficient values could be associated with ‘dissatisfiers’ and that inherent discontinuity is only partly resolved in the partition importance-performance grid. The findings show that the results of the two IPAs differ using the traditional IPA grid but are similar with diagonal models of the partition IPA grid. Points for practitioners One of the main problems for political decision-makers in recent years has been the reconfiguration of the budget for the entity managed, such as a municipality, in the current situation of economic crisis. This article contributes to improving decision-making on the reallocation of money and resources in the face of restrictions and financial cuts.
Chondrogenic induction of mesenchymal stromal/stem cells from Wharton’s jelly embedded in alginate hydrogel and without added growth factor: an alternative stem cell source for cartilage tissue engineering
Authors: Reppel Loïc , Schiavi Jessica , Charif Naceur , Leger Léonore , Yu Hao , Pinzano Astrid , Henrionnet Christel , Stoltz Jean-François , Bensoussan Danièle , Huselstein Céline 
Published: December 2015

Abstract
Background
Due to their intrinsic properties, stem cells are promising tools for new developments in tissue engineering and particularly for cartilage tissue regeneration. Although mesenchymal stromal/stem cells from bone marrow (BM-MSC) have long been the most used stem cell source in cartilage tissue engineering, they have certain limits. Thanks to their properties such as low immunogenicity and particularly chondrogenic differentiation potential, mesenchymal stromal/stem cells from Wharton’s jelly (WJ-MSC) promise to be an interesting source of MSC for cartilage tissue engineering.

Methods
In this study, we propose to evaluate chondrogenic potential of WJ-MSC embedded in alginate/hyaluronic acid hydrogel over 28 days. Hydrogels were constructed by the original spraying method. Our main objective was to evaluate chondrogenic differentiation of WJ-MSC on three-dimensional scaffolds, without adding growth factors, at transcript and protein levels. We compared the results to those obtained from standard BM-MSC.

Results
After 3 days of culture, WJ-MSC seemed to be adapted to their new three-dimensional environment without any detectable damage. From day 14 and up to 28 days, the proportion of WJ-MSC CD73+, CD90+, CD105+ and CD166+ decreased significantly compared to monolayer marker expression. Moreover, WJ-MSC and BM-MSC showed different phenotype profiles. After 28 days of scaffold culture, our results showed strong upregulation of cartilage-specific transcript expression. WJ-MSC exhibited greater type II collagen synthesis than BM-MSC at both transcript and protein levels. Furthermore, our work highlighted a relevant result showing that WJ-MSC expressed Runx2 and type X collagen at lower levels than BM-MSC.

Conclusions
Once seeded in the hydrogel scaffold, WJ-MSC and BM-MSC have different profiles of chondrogenic differentiation at both the phenotypic level and matrix synthesis. After 4 weeks, WJ-MSC, embedded in a three-dimensional environment, were able to adapt to their environment and express specific cartilage-related genes and matrix proteins. Today, WJ-MSC represent a real alternative source of stem cells for cartilage tissue engineering.
Chemokine interaction with synergy-inducing molecules: fine tuning modulation of cell trafficking
Authors: Cecchinato Valentina , D’Agostino Gianluca , Raeli Lorenzo , Uguccioni Mariagrazia 
Published: December 2015

Abstract
Directed migration and arrest of leukocytes during homeostasis, inflammation, and tumor development is mediated by the chemokine system, which governs leukocyte migration and activities. Although we understand well the effects of different chemokines one by one, much less was known about the potential consequences of the concomitant expression of multiple chemokines or of their interaction with inflammatory molecules on leukocyte migration and functions. In the past 10 yr, several studies revealed the existence of additional features of chemokines: they can antagonize chemokine receptors or synergize with other chemokines, also by forming heterocomplexes. Moreover, recent data show that not only chemokines but also the alarmin high-mobility group box 1 can for a complex with CXCL12, enhancing its potency on CXCR4. The molecular mechanism underlying the effect of the heterocomplex has been partially elucidated, whereas its structure is a matter of current investigations. The present review discusses the current knowledge and relevance of the functions of heterocomplexes formed between chemokines or between the chemokine CXCL12 and the alarmin high-mobility group box 1. These studies highlight the importance of taking into account, when approaching innovative therapies targeting the chemokine system, also the fact that some chemokines and molecules released in inflammation, can considerably affect the activity of chemokine receptor agonists.
Human regulatory T cells control TCR signaling and susceptibility to suppression in CD4+ T cells
Authors: Chellappa Stalin , Lieske Nora V , Hagness Morten , Line Pål D , Taskén Kjetil , Aandahl Einar M 
Published: December 2015

Abstract
Human CD4+CD25hiFOXP3+ regulatory T cells maintain immunologic tolerance and prevent autoimmune and inflammatory immune responses. Regulatory T cells undergo a similar activation cycle as conventional CD4+ T cells upon antigen stimulation. Here, we demonstrate that T cell receptors and costimulation are required to activate the regulatory T cell suppressive function. Regulatory T cells suppressed the T cell receptor signaling in effector T cells in a time-dependent manner that corresponded with inhibition of cytokine production and proliferation. Modulation of the activation level and thereby the suppressive capacity of regulatory T cells imposed distinct T cell receptor signaling signatures and hyporesponsiveness in suppressed and proliferating effector T cells and established a threshold for effector T cell proliferation. The immune suppression of effector T cells was completely reversible upon removal of regulatory T cells. However, the strength of prior immune suppression by regulatory T cells and corresponding T cell receptor signaling in effector T cells determined the susceptibility to suppression upon later reexposure to regulatory T cells. These findings demonstrate how the strength of the regulatory T cell suppressive function determines intracellular signaling, immune responsiveness, and the later susceptibility of effector T cells to immune suppression and contribute to unveiling the complex interactions between regulatory T cells and effector T cells.
THE PREVALENCE OF ARTERIAL HYPERTENSION AND ITS RISK FACTORS TOWARD HIV-POSITIVE PERSONS IN FERGANA VALLEY
Authors: Mirsaydullaev Mirzoulugbek , Mamasaliev Nematjon 
Published: December 2015

Background: The data on the prevalence of arterial hypertension (AH) in patients with HIV/AIDS vary. Even though some authors have reported higher prevalence of high blood pressure and systemic arterial hypertension in this group, compared to the prevalence of AH in subjects without infection, other studies have found similar prevalence of AH between men and women with HIV and individuals without the infection. In Uzbekistan such researches were not conducted yet.Objective: Evaluate the prevalence of prevalence of arterial hypertension and its risk factors at the HIV-positive persons of Fergana Valley of Uzbekistan.Methods: A cross-sectional study aligned to a cohort of patients with HIV/AIDS. The study considered hypertension at levels ≥ 140/90 mmHg or use of antihypertensive drugs and pre-hypertension at levels > 120/80 mmHg.Results: Out of this total, 138 patients (48%) were male and 149 were female (52%); 65% of them were 40 years-old or younger, and other 35% were over 40 years of age. Among the individuals evaluated, 184 (64.1%) had blood pressure within the normal range, 62 (21.6%) were considered prehypertensive, and 41 (14.3%) were considered hypertensive. Twenty five patients (61%) knew they had hypertension, and 9 of them (36.0%) used antihypertensive medication on a continuous basis. The blood pressure levels were controlled in only 5 (20.0%) patients that knew that they were hypertensive.Conclusion: Among HIV-infected persons, 21.6% were considered prehypertensive, and 14.3% were considered hypertensive. It is important to warn clinicians who provide care to HIV/AIDS patients that such patients are not only individuals infected with a potentially fatal virus, but, despite the benefit of new antiretroviral therapies, they are also patients whose prognosis may be affected by comorbidities, such as hypertension.