bluuebunny/crossref_metadata_2025_split huggingface dataset:
Herpesvirus saimiri MicroRNAs Preferentially Target Host Cell Cycle Regulators
Authors: Guo Yang Eric , Oei Theresa , Steitz Joan A. 
Published: August 2015

ABSTRACT

In latently infected marmoset T cells,
Herpesvirus saimiri
(HVS) expresses six microRNAs (known as miR-HSURs [
H. saimiri
U-rich RNAs]). The viral miR-HSURs are processed from chimeric primary transcripts, each containing a noncoding U-rich RNA (HSUR) and a pre-miRNA hairpin. To uncover the functions of miR-HSURs, we identified mRNA targets in infected cells using high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP). HITS-CLIP revealed hundreds of robust Argonaute (Ago) binding sites mediated by miR-HSURs that map to the host genome but few in the HVS genome. Gene ontology analysis showed that several pathways regulating the cell cycle are enriched among cellular targets of miR-HSURs. Interestingly, miR-HSUR4-3p represses expression of the p300 transcriptional coactivator by binding the open reading frame of its mRNA. miR-HSUR5-3p directly regulates BiP, an endoplasmic reticulum (ER)-localized chaperone facilitating maturation of major histocompatibility complex class I (MHC-I) and the antiviral response. miR-HSUR5-3p also robustly downregulates WEE1, a key negative regulator of cell cycle progression, leading to reduced phosphorylation of its substrate, cyclin-dependent kinase (Cdk1). Consistently, inhibition of miR-HSUR5-3p in HVS-infected cells decreases their proliferation. Together, our results shed light on the roles of viral miRNAs in cellular transformation and viral latency.

IMPORTANCE
Viruses express miRNAs during various stages of infection, suggesting that viral miRNAs play critical roles in the viral life cycle. Compared to protein-coding genes, the functions of viral miRNAs are not well understood. This is because it has been challenging to identify their mRNA targets. Here, we focused on the functions of the recently discovered HVS miRNAs, called miR-HSURs. HVS is an oncogenic gammaherpesvirus that causes acute T-cell lymphomas and leukemias in New World primates and transforms human T cells. A better understanding of HVS biology will help advance our knowledge of virus-induced oncogenesis. Because numerous cellular miRNAs play crucial roles in cancer, viral miRNAs from the highly oncogenic HVS might also be important for transformation. Here, we found that the miR-HSURs preferentially modulate expression of host cell cycle regulators, as well as antiviral response factors. Our work provides further insight into the functions of herpesviral miRNAs in virus-induced oncogenesis and latency.
A randomized controlled trial comparing treatment with oral agents and basal insulin in elderly patients with type 2 diabetes in long-term care facilities
Authors: Pasquel Francisco J , Powell Winter , Peng Limin , Johnson Theodore M , Sadeghi-Yarandi Shadi , Newton Christopher , Smiley Dawn , Toyoshima Marcos T , Aram Pedram , Umpierrez Guillermo E 
Published: August 2015

BackgroundManaging hyperglycemia and diabetes is challenging in geriatric patients admitted to long-term care (LTC) facilities.MethodsThis randomized control trial enrolled patients with type 2 diabetes (T2D) with blood glucose (BG) >180 mg/dL or glycated hemoglobin >7.5% to receive low-dose basal insulin (glargine, starting dose 0.1 U/kg/day) or oral antidiabetic drug (OAD) therapy as per primary care provider discretion for 26 weeks. Both groups received supplemental rapid-acting insulin before meals for BG >200 mg/dL. Primary end point was difference in glycemic control as measured by fasting and mean daily glucose concentration between groups.ResultsA total of 150 patients (age: 79±8 years, body mass index: 30.1±6.5 kg/m2, duration of diabetes mellitus: 8.2±5.1 years, randomization BG: 194±97 mg/dL) were randomized to basal insulin (n=75) and OAD therapy (n=75). There were no differences in the mean fasting BG (131±27 mg/dL vs 123±23 mg/dL, p=0.06) between insulin and OAD groups, but patients treated with insulin had greater mean daily BG (163±39 mg/dL vs 138±27 mg/dL, p<0.001) compared to those treated with OADs. There were no differences in the rate of hypoglycemia (<70 mg/dL) between insulin (27%) and OAD (31%) groups, p=0.58. In addition, there were no differences in the number of hospital complications, emergency room visits, and mortality between treatment groups.ConclusionsThe results of this randomized study indicate that elderly patients with T2D in LTC facilities exhibited similar glycemic control, hypoglycemic events and complications when treated with either basal insulin or with oral antidiabetic drugs.Trial registration numberClinicalTrials.gov Identifier:NCT01131052.
Socioeconomic inequalities in functional somatic symptoms by social and material conditions at four life course periods in Sweden: a decomposition analysis
Authors: San Sebastian Miguel , Hammarström Anne , Gustafsson Per E 
Published: August 2015

ObjectiveSocioeconomic inequalities in health are deemed a worldwide public health problem, but current research is lacking on key points including determinants of socioeconomic differences in health, and not the least variations of these determinants over the life course. Using a 26-year prospective Swedish community-based cohort, we aim at decomposing socioeconomic inequalities in functional somatic symptoms by social and material life circumstances, at 4 periods of the life course.DesignRepeated cross-sectional study.SettingParticipants came from the Northern Swedish Cohort (n=1001), who completed questionnaires about occupational class, social and material living conditions, and symptoms at ages 16, 21, 30 and 42. Socioeconomic inequalities were estimated and decomposed using the Blinder-Oaxaca decomposition analysis.ResultsInequalities in symptoms between blue-collar and white-collar socioeconomic groups increased along the life course in the sample. In the decomposition analysis, a high proportion of the gap between socioeconomic groups could be explained by social and material living conditions at ages 16 (84% explained), 30 (45%) and 42 (68%), but not at age 21. Specific social (parental illness at age 16 and violence at ages 30 and 42) and material (parental unemployment at age 16, and own unemployment and financial strain at ages 30 and 42) factors contributed jointly to the health gaps.ConclusionsSocioeconomic inequalities in functional somatic symptoms increased along the life course in this Swedish cohort. A considerable portion of the social gaps in health was explained by concurrent social and material conditions, and the importance of specific adversities was dependent on the life course stage. Our findings suggest that socioeconomic inequalities in functional somatic symptoms may be reduced by addressing both social and material living conditions of disadvantaged families, and also that the life course stage needs to be taken into consideration.
Feasibility and acceptability of advance care planning in elderly Italian and Greek speaking patients as compared to English-speaking patients: an Australian cross-sectional study
Authors: Detering Karen , Sutton Elizabeth , Fraser Scott , Wallis Kasey , Silvester William , Mawren Daveena , Whiteside Kathryn 
Published: August 2015

ObjectivesTo assess the feasibility and acceptability of facilitated advance care planning (ACP) discussions in elderly Italian and Greek-speaking inpatients compared to English-speaking inpatients.Design, setting and participantsThis cross-sectional study with convenience sampling was conducted in Melbourne, Australia, and recruited hospital inpatients with medical decision-making capacity, aged 65 years or above, who spoke Greek (25 patients), Italian (24 patients) or English (63 patients).InterventionFacilitated ACP was offered, aiming to assists patients to consider and discuss their goals, values, beliefs and future treatment wishes with their family and doctor; to help them consider how they would like healthcare decisions made in the future if they become unable to do this for themselves; and to complete advance care directives.Main outcome measuresThe completion of ACP discussions, their duration, advance care directive completion and utilisation of interpreters.ResultsOf 112 patients, 109 (97%) had at least one discussion, 63 (54%) completed advance care directives, either nominating a substitute decision-maker, documenting their wishes or both, and 76 (68%) included family in discussions. The median duration of discussions for all patients was slightly more than 1 h, over two visits. There were no differences between the Greek-speaking and the Italian-speaking patients, or between the Non-English speaking and the English-speaking patients in any of these measures. Only 14 non-English speaking patients, (30%) utilised interpreters, but when utilised, patients were much more likely (p<0.005) to complete advance care directives.ConclusionsFacilitated ACP in elderly Italian and Greek-speaking patients is feasible, acceptable and is similar to that for English-speaking patients.
Enhanced Antitumor Activity of an Anti-5T4 Antibody–Drug Conjugate in Combination with PI3K/mTOR inhibitors or Taxanes
Authors: Shor Boris , Kahler Jennifer , Dougher Maureen , Xu Jane , Mack Michelle , Rosfjord Ed , Wang Fang , Melamud Eugene , Sapra Puja 
Published: August 2015

AbstractPurpose: Targeted treatment of solid or liquid tumors with antibody–drug conjugates (ADCs) can lead to promising clinical benefit. The aim of the study is to investigate combination regimens of auristatin-based ADCs in preclinical models of cancer.Experimental Design: An auristatin-based anti-5T4 antibody conjugate (5T4-ADC) and auristatin payloads were combined with the dual PI3K/mTOR catalytic site inhibitor PF-05212384 (PF-384) or taxanes in a panel of tumor cell lines. Drug interactions in vitro were evaluated using cell viability assays, apoptosis induction, immunofluorescence, mitotic index, and immunoblotting. Breast cancer cells treated with auristatin analogue or 5T4-ADC were profiled by total- and phospho-proteomics. Antitumor efficacy of selected combinations was evaluated in 5T4-positive human breast or lung tumor xenografts in vivo.Results: In vitro, auristatin-based agents displayed strong synergistic or additive activity when combined with PF-384 or taxanes, respectively. Further, treatment of 5T4-ADC plus PF-384 resulted in stronger induction of apoptosis and cell line–specific attenuation of pAKT and pGSK. Interestingly, proteomic analysis revealed unique effects of auristatins on multiple components of mRNA translation. Addition of PF-384 further amplified effects of 5T4-ADC on translational components, providing a potential mechanism of synergy between these drugs. In human tumor xenografts, dual targeting with 5T4-ADC/PF-384 or 5T4-ADC/paclitaxel produced substantially greater antitumor effects with longer average survival as compared with monotherapy treatments.Conclusions: Our results provide a biologic rationale for combining 5T4-ADC with either PI3K/mTOR pathway inhibitors or taxanes and suggest that mechanisms underlying the synergy may be attributed to cellular effects of the auristatin payload. Clin Cancer Res; 22(2); 383–94. ©2015 AACR.
Wind Measurements from Arc Scans with Doppler Wind Lidar
Authors: Wang H. , Barthelmie R. J. , Clifton A. , Pryor S. C. 
Published: August 2015

AbstractDefining optimal scanning geometries for scanning lidars for wind energy applications remains an active field of research. This paper evaluates uncertainties associated with arc scan geometries and presents recommendations regarding optimal configurations in the atmospheric boundary layer. The analysis is based on arc scan data from a Doppler wind lidar with one elevation angle and seven azimuth angles spanning 30° and focuses on an estimation of 10-min mean wind speed and direction. When flow is horizontally uniform, this approach can provide accurate wind measurements required for wind resource assessments in part because of its high resampling rate. Retrieved wind velocities at a single range gate exhibit good correlation to data from a sonic anemometer on a nearby meteorological tower, and vertical profiles of horizontal wind speed, though derived from range gates located on a conical surface, match those measured by mast-mounted cup anemometers. Uncertainties in the retrieved wind velocity are related to high turbulent wind fluctuation and an inhomogeneous horizontal wind field. The radial velocity variance is found to be a robust measure of the uncertainty of the retrieved wind speed because of its relationship to turbulence properties. It is further shown that the standard error of wind speed estimates can be minimized by increasing the azimuthal range beyond 30° and using five to seven azimuth angles.
Prevalence and risk factors for violent behavior in young people presenting with first-episode psychosis in Hong Kong: A 3-year follow-up study
Authors: Chang Wing Chung , Chan Sherina Suet In , Hui Christy Lai Ming , Chan Sherry Kit Wa , Lee Edwin Ho Ming , Chen Eric Yu Hai 
Published: August 2015

Objective: The aim of the current study was to examine the rates of violence prior to and 3 years following treatment initiation, and predictors of post-treatment violence in Chinese young people presenting with first-episode psychosis (FEP). Method: Seven hundred patients aged 15–25 years consecutively enrolled in a territory-wide early intervention program for FEP in Hong Kong from July 2001 to August 2003 were studied. Socio-demographic, pre-treatment, baseline and 3-year follow-up variables were collected via systematic medical file review. Violent behavior was defined as physical aggression towards people and was further categorized at two levels of severity. Results: After onset of psychosis, 6.7% ( n = 47) patients exhibited violence before treatment. During 3-year treatment period, 9.4% ( n = 66) committed violent behavior and 4.3% ( n = 30) perpetrated serious violence. Two-fifths (40.4%) of patients who displayed pre-treatment violent behavior engaged in further act of violence after service contact. Multivariate regression analysis showed that previous violence, male gender and lower educational attainment were significantly associated with an increased risk of violence during 3-year follow-up. Comorbid substance, male gender, lower educational level and past history of violence were found to independently predict occurrence of serious violence after commencement of treatment for FEP. Conclusions: In a large representative cohort of Chinese young FEP patients, the rates of violent behavior before and after treatment were relatively lower than that reported in the literature. Risk factors for violence identified by the current study were comparable to the findings of previous research conducted in western populations. Close monitoring of patients with history of violence and specific treatments targeting at minimizing substance abuse may facilitate early identification and intervention of high-risk cases to reduce violence risk in the early course of illness.
Lateral Tibial Posterior Slope Is Increased in Patients With Early Graft Failure After Anterior Cruciate Ligament Reconstruction
Authors: Christensen Joshua J. , Krych Aaron J. , Engasser William M. , Vanhees Matthias K. , Collins Mark S. , Dahm Diane L. 
Published: August 2015

Background: The lateral tibial posterior slope (LTPS) has been reported in multiple studies to correlate with an increased risk for native anterior cruciate ligament (ACL) tearing. To date, no study has examined the effect of an increased LTPS as measured on magnetic resonance imaging (MRI) on the likelihood of ACL graft failure. Hypothesis: An increased LTPS as measured on MRI would correlate with an increased risk for ACL graft failure. Study Design: Case-control study; Level of evidence, 3. Methods: Fifty-eight patients were initially identified who experienced graft failure after primary ACL reconstruction and underwent revision between 1998 and 2009. Exclusion criteria were clinical follow-up of less than 4 years, graft failure occurring greater than 2 years after primary surgery, skeletal immaturity, deep infection, lack of available preoperative MRI, and history of trauma to the proximal tibia. This left 35 patients with early (within 2 years) failure of primary ACL reconstruction. These patients were matched to 35 control participants who had undergone ACL reconstruction with a minimum of 4 years of clinical follow-up and no evidence of graft failure. Patients were matched by age, sex, date of primary surgery, and graft type. The LTPS was then determined on MRI in a blinded fashion. Results: The mean time to failure in patients in the study group was 1 year (range, 0.6-1.4 years). The mean follow-up of those in the matched control group was 6.9 years (range, 4.0-13.9 years). The mean LTPS in the early ACL failure group was found to be 8.4°, which was significantly larger than that in the control group at 6.5° ( P = .012). The odds ratio for graft failure considering a 2° increase in the LTPS was 1.6 (95% CI, 1.1-2.2) and continued to increase to 2.4 (95% CI, 1.2-5.0) and 3.8 (95% CI, 1.3-11.3) with 4° and 6° increases in the LTPS, respectively. No significant association was identified between graft type and graft failure. Conclusion: An increased LTPS is associated with an increased risk for early ACL graft failure, regardless of graft type. Orthopaedic surgeons should consider measuring the LTPS as part of the preoperative assessment of ACL-injured patients.
Exploring a new method for the biological monitoring of plastic workers exposed to the vinyl chloride monomer
Authors: Azari Mansour Rezazadeh , Tayefeh-Rahimian Raana , Jafari Mohamad Javad , Souri Hamid , Shokoohi Yasser , Tavakol Alaheh , Yazdanbakhsh Zahra 
Published: August 2015

Vinyl chloride monomer (VCM) is widely used in the production of polyvinyl chloride (PVC) plastics. VCM is recognized as a confirmed human and animal carcinogenic compound. Recent studies have reported poor health of plastic workers, even having exposure at concentrations below the permissible limit to VCM. There has not been any study regarding exposed workers to VCM in Iran. Similarly, no information exists as to the biological monitoring of such workers. The main purpose of this study was to conduct a thorough occupational and biological monitoring of Iranian plastic workers exposed to VCM. A total of 100 workers from two plastic manufacturing plants (A and B) in Tehran along with 25 unexposed workers as controls were studied. The personal monitoring of all nonsmoking workers exposed to VCM at two plastic manufacturing plants (A and B) was performed in the morning shift (8 a.m. to 4 p.m.) according to the National Institute For Occupational Safety And Health method no. 1007. Biological monitoring of workers was carried out through collection of exhaled breath of all exposed and control workers in Tedlar bags and with a subsequent analysis using gas chromatography–flame ionization detector. Not only the mean occupational exposure of workers to VCM at plant A was higher than the respective threshold limit value but also the statistical significance was higher than workers at plant B. Similarly, VCM concentration in exhaled breath of workers at plant A was also statistically significantly higher than at plant B. Correlation of occupational exposure of all workers to vinyl chloride with its concentration in exhaled breath was statistically significant. This is the first study on biological monitoring for exposed plastic workers to VCM using exhaled breath. On the basis of the results in this study, a novel method of biological monitoring of plastic workers was proposed.
DNA damage assessment in the lymphocytes of construction painters by comet assay
Authors: Kianmehr Mojtaba , Amiri Mostafa , Ebrahimzadeh-bideskan Alireza , Hajavi Jafar 
Published: August 2015

Background: Exposure to chemicals is inevitable for certain occupational groups, particularly in industrial countries. Some cytogenetic tests such as comet assay are effectively utilized to screen genotoxic effects of these chemicals in humans. The purpose of this study has been to assess the DNA damage in construction painters’ lymphocytes using the comet assay. Methods: Fourteen male construction painters with 1 year of required work experience were randomly selected from the list of Painter Union in Gonabad city, Iran. In addition, 14 healthy male non-painters were randomly selected as controls. The DNA damage degree was determined using a fluorescence microscope and CometScore software. The obtained data were analyzed employing independent t-test using SPSS software v. 14 at the significant level of p < 0.05. Results: All participants were non-smokers and non-alcoholics. No significant differences were found between the two groups in terms of age, weight, height, body mass index, and systolic and diastolic blood pressure. The DNA damage in the painter group was significantly greater than that of the control group. Tail length (µm) was 12.63 ± 6.54 versus 2.90 ± 0.84, tail DNA (%) was 4.33 ± 1.84 versus 1.29 ± 0.43, and tail moment (µm) was 1.85 ± 0.98 versus 0.14 ± 0.20 in painter and control groups ( p < 0.001), respectively. Conclusion: The chemicals used in oil paint may increase the DNA damage in painter blood lymphocytes.
Methods of fertility control in cats
Authors: Murray Jane K , Mosteller Jill R , Loberg Jenny M , Andersson Maria , Benka Valerie A W 
Published: August 2015

Overview: Fertility control is important for population management of owned and unowned cats, provides health benefits at the individual level and can reduce unwanted sexually dimorphic behaviors such as roaming, aggression, spraying and calling. This article reviews the available evidence regarding European and American veterinarian, owner and pedigree cat breeder attitudes toward both surgical sterilization and non-surgical fertility control. It additionally presents new data on veterinarians’ and pedigree cat breeders’ use of, and attitudes toward, alternative modalities of fertility control. Proportion of cats that are neutered: Within the United States and Europe, the proportion of cats reported to be sterilized varies widely. Published estimates range from 27–93% for owned cats and 2–5% for cats trapped as part of a trap–neuter–return (TNR) program. In some regions and populations of cats, non-surgical fertility control is also used. Social context, cultural norms, individual preferences, economic considerations, legislation and professional organizations may all influence fertility control decisions for cats. Non-surgical methods of fertility control: Particularly in Europe, a limited number of non-surgical temporary contraceptives are available for cats; these include products with regulatory approval for cats as well as some used ‘off label’. Non-surgical methods remove the risk of complications related to surgery and offer potential to treat more animals in less time and at lower cost; they may also appeal to pedigree cat breeders seeking temporary contraception. However, concerns over efficacy, delivery methods, target species safety, duration and side effects exist with current non-surgical options. Research is under way to develop new methods to control fertility in cats without surgery. US and European veterinarians place high value on three perceived benefits of surgical sterilization: permanence, behavioral benefits and health benefits. Non-surgical options will likely need to share these benefits to be widely accepted by the veterinary community.