bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of the NEDD8-Activating Enzyme Inhibitor MLN4924 on Lytic Reactivation of Kaposi's Sarcoma-Associated Herpesvirus
Authors: Chang Pey-Jium , Chen Lee-Wen , Chen Li-Yu , Hung Chien-Hui , Shih Ying-Ju , Wang Shie-Shan 
Published: July 2017

ABSTRACT

The switch of Kaposi's sarcoma-associated herpesvirus (KSHV) from latency to lytic replication is a key event for viral dissemination and pathogenesis. MLN4924, a novel neddylation inhibitor, reportedly causes the onset of KSHV reactivation but impairs later phases of the viral lytic program in infected cells. Thus far, the molecular mechanism involved in the modulation of the KSHV lytic cycle by MLN4924 is not yet fully understood. Here, we confirmed that treatment of different KSHV-infected primary effusion lymphoma (PEL) cell lines with MLN4924 substantially induces viral lytic protein expression. Due to the key role of the virally encoded ORF50 protein in the latent-to-lytic switch, we investigated its transcriptional regulation by MLN4924. We found that MLN4924 activates the ORF50 promoter (ORF50p) in KSHV-positive cells (but not in KSHV-negative cells), and the RBP-Jκ-binding elements within the promoter are critically required for MLN4924 responsiveness. In KSHV-negative cells, reactivation of the ORF50 promoter by MLN4924 requires the presence of the latency-associated nuclear antigen (LANA). Under such a condition, LANA acts as a repressor to block the ORF50p activity, whereas MLN4924 treatment relieves LANA-mediated repression. Importantly, we showed that LANA is a neddylated protein and can be deneddylated by MLN4924. On the other hand, we revealed that MLN4924 exhibits concentration-dependent biphasic effects on 12-
O
-tetradecanoylphorbol-13-acetate (TPA)- or sodium butyrate (SB)-induced viral reactivation in PEL cell lines. In other words, low concentrations of MLN4924 promote activation of TPA- or SB-mediated viral reactivation, whereas high concentrations of MLN4924, conversely, inhibit the progression of TPA- or SB-mediated viral lytic program.

IMPORTANCE
MLN4924 is a neddylation (NEDD8 modification) inhibitor, which currently acts as an anti-cancer drug in clinical trials. Although MLN4924 has been reported to trigger KSHV reactivation, many aspects regarding the action of MLN4924 in regulating the KSHV lytic cycle are not fully understood. Since the KSHV ORF50 protein is the key regulator of viral lytic reactivation, we focus on its transcriptional regulation by MLN4924. We here show that activation of the ORF50 gene by MLN4924 involves the relief of LANA-mediated transcriptional repression. Importantly, we find that LANA is a neddylated protein. To our knowledge, this is the first report showing that neddylation occurs in viral proteins. Additionally, we provide evidence that different concentrations of MLN4924 have opposite effects on TPA-mediated or SB-mediated KSHV lytic cycle activation. Therefore, in clinical application, we propose that MLN4924 needs to be used with caution in combination therapy to treat KSHV-positive subjects.
What determines treatment satisfaction of patients with type 2 diabetes on insulin therapy? An observational study in eight European countries
Authors: Boels Anne Meike , Vos Rimke C , Hermans Tom G T , Zuithoff Nicolaas P A , Müller Nicolle , Khunti Kamlesh , Rutten Guy E H M 
Published: July 2017

ObjectivePatients with type 2 diabetes (T2DM) on insulin therapy are less satisfied with their diabetes treatment than those on oral hypoglycaemic therapies or lifestyle advice only. Determinants of satisfaction in patients with T2DM on insulin therapy are not clearly known. The aim of this study was to determine the association of treatment satisfaction with demographic and clinical characteristics of patients with T2DM.DesignFor this study we used data from the GUIDANCE (Guideline Adherence to Enhance Care) study, a cross-sectional study among 7597 patients with T2DM patients from Belgium, France, Germany, Ireland, Italy, Sweden, the Netherlands and the UK. The majority of patients were recruited from primary care. Treatment satisfaction was assessed by the Diabetes Treatment Satisfaction Questionnaire (DTSQ, score 0–36; higher scores reflecting higher satisfaction). To determine which patient characteristics and laboratory values were independently associated with treatment satisfaction, a linear mixed model analysis was used.ParticipantsIn total, 1984 patients on insulin were analysed; the number of included patients per country ranged from 166 (the Netherlands) to 384 (Italy).ResultsThe mean DTSQ score was 28.50±7.52 and ranged from 25.93±6.57 (France) to 30.11±5.09 (the Netherlands). Higher DTSQ scores were associated with having received diabetes education (β 1.64, 95% CI 0.95 to 2.32), presence of macrovascular complications (β 0.76, 95% CI 0.21 to 1.31) and better health status (β 0.08 for every one unit increase on a 0–100 scale, 95% CI 0.07 to 0.10). Lower DTSQ scores were associated with more frequently perceived hyperglycaemia (β −0.32 for every 1 unit increase on a seven-point Likert scale, 95% CI −0.50 to −0.13), and higher glycated haemoglobin (β −0.52 for every percentage increase, 95% CI −0.75 to −0.29).ConclusionsA number of factors including diabetes education, perceived and actual hyperglycaemia and macrovascular complications are associated with treatment satisfaction. Self-management education programmes should incorporate these factors for ongoing support in patients with T2DM.
Protecting study participants in emergency research: is community consultation before trial commencement enough?
Authors: Henry Blair , Perez Adic , Trpcic Sandy , Rizoli Sandro , Nascimento Barto 
Published: July 2017

BackgroundThis article presents the results of a community consultation (CC) process completed in Toronto, Ontario, using a random digit dialling technique, on the attitudes and perceptions of the public toward the use of exception from informed consent when conducting emergency research involving the use of massive blood transfusions.MethodsIn 2012, our hospital conducted a CC, using a random digit dialling technique, to elicit the attitudes and perceptions of the public toward the use of an exemption from informed consent for an upcoming clinical trial. A total of 500 participants from high violent crime areas were interviewed as part of this consultation.ResultsThe response rate for the telephone survey was 54%. Participants indicated a personal acceptance rate of 76%, acceptance of the justification for the exception to consent at 81%, thatthe study would meet the best interest of patients and the community at 81% and that youth (between 15 and 18 years) could be enrolled at 71%. When offered, no participant requested an opt-out wrist band to avoid being enrolled in this study.DiscussionThe use of violent crime neighborhoods to locate at risk communities was not effective in identifying the appropriate community of interest for this study. Though only representing a small subpopulation from a large Canadian city, the attitudes noted here is suggestive that Canadians may have a similar level of acceptance as the US based on published studies. However, given the resources needed to undertake this process and that in the end it did not elicit any useful feedback or recommendations for enhancing the safety of participants, the future use of phone surveys as a means of engaging communities should be reconsidered.Level of evidence (Level V)This is a retrospective subanalysis of a CC using a randomized phone dialling technique from a site prior to the start of the Pragmatic Randomized Optimal Platelet and Plasma Ratios Trial. The CC was not designed specifically for research purposes and as such reflect only a case study from a single center.Trial registration numberPre-result,NCT01545232.
Deviation maps for robust and informed indoor positioning services
Authors: Blunck Henrik , Prentow Thor S. , Temme Sylvie , Thom Andreas , Vahrenhold Jan 
Published: July 2017

The ability to position and track people and assets has become increasingly widespread and important in business and personal life. The prevalent means for such tasks is signal-strength-based, prominently WiFi-based, positioning, together with GNSS positioning. The latter, however, is insufficient for the majority of indoor environments in which most of our work and personal lives takes place. Signal-strength-based positioning, though, too, is error-prone in real-life building environments, suffering from large biases induced by the often many and complex attenuating elements in the environment. Additionally, in the prevalent signal-strength-based positioning methods, which rely solely on signal pattern matching, such biases and errors are hard to assess and thus positioning quality and glitches hard to predict.
We present an approach for assessing, visualizing, and counter-acting positioning biases and impairments in signal-strength-based positioning. This approach, centered around the notion of deviation maps, aim at improving positioning quality and predictability/reliability and, at the same time, at gaining knowledge and understanding of tracking quality. We seek to understand how the tracking quality is influenced by both positioning installation and building environment, and how the former may be altered to better suit the latter. We discuss results from applying our approach in a real-world large-scale work environment, a major hospital spanning 160,000 square meters, as well as lessons learned from the underlying experimentation-driven and use-centric design process. From these lessons we also derive directions for future work.
Relationship Between Myocardial Function, Body Mass Index, and Outcome After ST-Segment–Elevation Myocardial Infarction
Authors: Joyce Emer , Hoogslag Georgette E. , Kamperidis Vasileios , Debonnaire Philippe , Katsanos Spyridon , Mertens Bart , Marsan Nina Ajmone , Bax Jeroen J. , Delgado Victoria 
Published: July 2017

Background—
Better survival for overweight and obese patients after ST-segment–elevation myocardial infarction (STEMI) has been demonstrated. The association between body mass index (BMI), outcome, and left ventricular (LV) structure and function after STEMI, including LV longitudinal strain (global longitudinal strain), was evaluated.

Methods and Results—

First patients with STEMI undergoing primary percutaneous coronary intervention (n=1604; mean age, 61±12 years; 75% men) had BMI measured on admission, and 2-dimensional transthoracic echocardiography performed within 48 hours. Patients were categorized based on standard criteria (normal/underweight, BMI<25 kg/m
2
[n=486]; overweight, 25≤BMI<30 kg/m
2
[n=820]; obese, BMI≥30 kg/m
2
[n=298]). LV global longitudinal strain was measured using speckle-tracking analysis. Primary outcome measure was all-cause mortality. Compared with normal/underweight patients, obese patients were younger and more likely to have diabetes mellitus, hypertension, and hyperlipidemia and have higher discharge blood pressures. Despite no significant differences in infarct size, obese patients had significantly more impaired LV global longitudinal strain (−13.7±3.8 versus −15.0±4.2% and −15.0±4.1%;
P
<0.001) compared with normal/underweight and overweight patients, respectively. Although normal/underweight patients had the worst overall survival (log-rank
P
=0.04) after STEMI during a median follow-up of 5.2 (3.6, 6.9) years on Kaplan–Meier analysis, a significant nonlinear association between BMI and all-cause mortality across the range of BMI was seen, persisting after adjustment for age and sex.

Conclusions—
Obese patients demonstrate greater adverse LV remodeling and more impaired LV deformation after STEMI compared with those with normal BMI, amid similar infarct characteristics. Normal weight patients continue to demonstrate the worst survival, suggesting that the potential nonadverse effect of higher BMI in this population is independent of LV function.
Geographic Variations in Cardiovascular Disease Mortality Among Asian American Subgroups, 2003–2011
Authors: Pu Jia , Hastings Katherine G. , Boothroyd Derek , Jose Powell O. , Chung Sukyung , Shah Janki B. , Cullen Mark R. , Palaniappan Latha P. , Rehkopf David H. 
Published: July 2017

Background

There are well‐documented geographical differences in cardiovascular disease (
CVD
) mortality for non‐Hispanic whites. However, it remains unknown whether similar geographical variation in
CVD
mortality exists for Asian American subgroups. This study aims to examine geographical differences in
CVD
mortality among Asian American subgroups living in the United States and whether they are consistent with geographical differences observed among non‐Hispanic whites.

Methods and Results

Using US death records from 2003 to 2011 (n=3 897 040
CVD
deaths), age‐adjusted
CVD
mortality rates per 100 000 population and age‐adjusted mortality rate ratios were calculated for the 6 largest Asian American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, and Vietnamese) and compared with non‐Hispanic whites. There were consistently lower mortality rates for all Asian American subgroups compared with non‐Hispanic whites across divisions for
CVD
mortality and ischemic heart disease mortality. However, cerebrovascular disease mortality demonstrated substantial geographical differences by Asian American subgroup. There were a number of regional divisions where certain Asian American subgroups (Filipino and Japanese men, Korean and Vietnamese men and women) possessed no mortality advantage compared with non‐Hispanic whites. The most striking geographical variation was with Filipino men (age‐adjusted mortality rate ratio=1.18; 95%
CI
, 1.14–1.24) and Japanese men (age‐adjusted mortality rate ratio=1.05; 95%
CI
: 1.00–1.11) in the Pacific division who had significantly higher cerebrovascular mortality than non‐Hispanic whites.

Conclusions

There was substantial geographical variation in Asian American subgroup mortality for cerebrovascular disease when compared with non‐Hispanic whites. It deserves increased attention to prioritize prevention and treatment in the Pacific division where approximately 80% of Filipinos
CVD
deaths and 90% of Japanese
CVD
deaths occur in the United States.
Characterizing the Exponential Law Under Laplace Order Domination
Authors: Mitra Murari , Basu Sujit K. , Bhattacharjee M. C. 
Published: July 2017

Interesting characterizations of the exponential distribution have been obtained in classes of life distributions important in reliability theory. The results strengthen some of the analogous conclusions already existing in the literature. AMS (1991) Subject Classification No. Primary 62NOS: Secondaey 90825. 60F99.
Bacteriology of Chronic Sinusitis after Amoxicillin‐Clavulanate Potassium Therapy
Authors: Jiang Rong‐San , Jang Jinq‐Wen , Hsu Chen‐Yi 
Published: July 2017

The bacteriology of chronic sinusitis was studied after amoxicillin‐clavulanate potassium therapy. Patients with chronic sinusitis were randomly divided into 2 groups. In the study group, 90 patients were given a 2‐week course of amoxicillin‐clavulanate potassium before functional endoscopic sinus surgery. In the control group, 113 patients did not take any antibiotics within 2 weeks before the surgery. Swab specimens were taken from the maxillary and ethmoid sinuses during surgery and sent for aerobic and anaerobic culture. In the study group, the culture rates of maxillary and ethmoid sinuses were 45.6% and 28.9%, respectively. In the control group, the culture rates of maxillary and ethmoid sinuses were 53.1% and 34.5%, respectively. The culture rates between the control group and the study group were not significantly different, either for the maxillary sinus or the ethmoid sinus. This showed that treatment with amoxicillin‐clavulanate potassium did not change the bacteriology of chronic sinusitis.
Studies on the Osteogenic Potential of Vascularized Periosteum: Behavior of Periosteal Flaps Transferred onto Soft Tissues
Authors: Burstein Fernando D. , Canalis Rinaldo F. 
Published: July 2017

We investigated the basic properties of vascularized periosteal autografts. A pleuroperiosteal flap based on the intercostal vessels was developed In a canine model. Fourteen animals had vascularized periosteal flaps rotated onto the soft tissues of the chest wall. These animals were killed at intervals of 7 to 90 days and the flaps were studied by tetracycline labeling and light microscopy. Four other animals had similar flaps transplanted onto the soft tissues of the neck by microvascular techniques. All harvested flaps showed periosteal bone production, leading to the following observations: (1) Osteogenesis begins as early as 7 days after grafting; (2) the rate and extent of periosteal osteogenesis Is proportional to the vascular supply; (3) bone formation starts in small foci of active osteoblasts that grow and become confluent; and (4) Intimate bony periosteal contact Is not necessary for periosteal osteogenesis to take place, but it appears to influence the rate and amount of bone formation.
Facial Nerve Evoked Potentials
Authors: Metson Ralph , Nuwer Marc , Hanson David G. , Honrubia Vicente 
Published: July 2017

Evoked potentials representing both intracranial and extracranial activity have been recorded from the canine scalp after retrograde stimulation of peripheral facial nerve branches. A negative electrode at the vertex and a positive electrode at the ipsilaterai mastoid (grounded at the contralateral mastoid) show a monophasic negative stylomastoid evoked potential that appears to be generated from the facial nerve trunk at the stylomastoid foramen. When the positive electrode is moved from the mastoid to the posterior scalp (overlying the foramen magnum), a similar potential with a latency 1.5 msec greater is obtained. This brain stem evoked potential is generated from fibers in the vicinity of the root entry zone and the initial trajectory into the brain stem. A potential of similar latency but greater magnitude is recorded with the positive electrode in the cerebrospinal fluid of the posterior fossa.
Third Place — Resident Clinical Science Award 1994: Recovery of Eustachian Tube Function and Hearing Outcome in Patients with Cleft Palate
Authors: Smith Timothy L. , Diruggiero Douglas C. , Jones Kim R. 
Published: July 2017

Eustachian tube dysfunction is a nearly universal complication of cleft palate, resulting in chronic ear disease and conductive hearing loss. Cleft palate repair is thought to result in recovery of eustachian tube function, but the length of time between repair and recovery of eustachian tube function is not known. Furthermore, the efficacy of tympanostomy tubes in the treatment of eustachian tube dysfunction and hearing sequelae has not been examined in a systematic way. To answer these questions, we performed a retrospective study that used serial audiometric data and tympanometry on 81 patients with cleft palates (162 ears), with follow‐up ranging from 1 to 17.3 years. Average time to recovery of eustachian tube function was 6.0 years (range, 1.0 to 10.3 years) after cleft palate surgery. For children followed up for at least 6 years (longest follow‐up, 17.3 years), 70% (67 of 85) had normal eustachian tube function at their last follow‐up visit. Ears treated with Armstrong tympanostomy tubes required an average of 3.1 tubes per ear until recovery of eustachian tube function, whereas ears treated with Goode T tubes required only 1.1 tubes per ear (p < 0.05). Hearing evaluation revealed that 67% of ears had abnormal hearing thresholds (>20 dB) before tympanostomy tube placement, whereas only 7.5% of ears demonstrated this loss after tube placement. Furthermore more than 90% of ears maintained normal thresholds after recovery of eustachian tube function. These data indicate that most children with cleft palates eventually recover normal eustachian tube function after palatoplasty, but for the majority of children, this does not occur for many years. Furthermore, the hearing loss before tympanostomy tube placement and palatoplasty largely resolves after aeration of the middle ear and does not result in any significant permanent hearing deficit.
High Correlation with Survival of Proliferating Cell Nuclear Antigen Expression in Mucoepidermoid Carcinoma of the Parotid Gland
Authors: Frankenthaler Robert A. , El‐Naggar Adel K. , Ordonez Nelson G. , Miller Tina S. , Batsakis John G. 
Published: July 2017

We tested the hypothesis that proliferating cell nuclear antigen can predict survival in patients with mucoepidermoid carcinoma. Formalin‐fixed, paraffin‐embedded, tissue resected specimens from 43 patients with no prior treatment for mucoepidermoid carcinoma of the parotid gland were immunostained with the PC10 monoclonal antibody to proliferating cell nuclear antigen with the peroxidase/antiperoxidase method. Proliferating cell nuclear antigen levels were defined as the number of nuclei with strong immunostaining divided by the total cell count and were expressed as percentages. Both univariate and multivariate analyses were performed on 12 additional prognostic variables to determine the relative proliferating cell nuclear antigen level to predict survival. The median proliferating cell nuclear antigen level was 7. Five percent of patients with proliferating cell nuclear antigen levels less than 7 died of their disease compared with 48% of those with proliferating cell nuclear antigen levels of 7 or more. Multivariate analysis Indicates proliferating cell nuclear antigen to be the most Important parameter in predicting survival. Thus the measurement of proliferating cell nuclear antigen is a useful predictor of survival for patients with mucoepidermoid carcinoma of the parotid gland.
Psychological Characteristics of Problem Gamblers with and without Mood Disorder
Authors: Lister Jamey J , Milosevic Aleks , Ledgerwood David M 
Published: July 2017

Objective: Problem and pathological gamblers are significantly more likely to experience mood disorders, compared with the general population. Our study examined the relation of psychological characteristics (personality, trait impulsiveness, and gambling motives) to current co-occurring mood disorder (major depression and dysthymia) status among problem and pathological gamblers. Method: Problem and pathological gamblers ( N = 150) underwent a clinical interview to assess current co-occurring mood disorders; participants completed measures of problem gambling severity, personality, impulsiveness, and gambling motives. Results: Problem and pathological gamblers with a current co-occurring mood disorder were more likely to be female, older, and to report higher lifetime and past-year gambling severity. A co-occurring mood disorder was associated with higher personality scores for alienation and stress reaction, lower scores for well-being, social closeness, and control, as well as higher impulsiveness scores for urgency and lack of premeditation, and lower sensation seeking scores. Participants with a co-occurring mood disorder also reported higher coping motives for gambling. Multivariate logistic regression analyses demonstrated that personality factors (lower social closeness and higher alienation) contributed to the greatest likelihood of being diagnosed with a co-occurring mood disorder. Conclusions: Mood disorders frequently co-occur with problem and pathological gambling, and they are associated with greater gambling severity. These findings highlight that interpersonal facets of personality contribute substantially to co-occurring mood disorder status. Implications for treatment will be discussed.