bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epstein-Barr Virus gp350 Can Functionally Replace the Rhesus Lymphocryptovirus Major Membrane Glycoprotein and Does Not Restrict Infection of Rhesus Macaques
Authors: Herrman Marissa , Mühe Janine , Quink Carol , Wang Fred 
Published: November 2015

ABSTRACT

Primary Epstein-Barr virus (EBV) infection is the most common cause of infectious mononucleosis, and persistent infection is associated with multiple cancers. EBV vaccine development has focused on the major membrane glycoprotein, gp350, since it is the major target for antibodies that neutralize infection of B cells. However, EBV has tropism for both B cells and epithelial cells, and it is unknown whether serum neutralizing antibodies against B cell infection will provide sufficient protection against virus infection initiated at the oral mucosa. This could be stringently tested by passive antibody transfer and oral virus challenge in the rhesus macaque model for EBV infection. However, only neutralizing monoclonal antibodies (MAbs) against EBV are available, and EBV is unable to infect rhesus macaques because of a host range restriction with an unknown mechanism. We cloned the prototypic EBV-neutralizing antibody, 72A1, and found that recombinant 72A1 did not neutralize rhesus lymphocryptovirus (rhLCV) infection of macaque B cells. Therefore, we constructed a chimeric rhLCV in which the native major membrane glycoprotein was replaced with EBV gp350. This chimeric rhLCV became sensitive to neutralization by the 72A1 MAb, efficiently immortalized macaque B cells
in vitro
, and successfully established acute and persistent infection after oral inoculation of rhesus macaques. Thus, EBV gp350 can functionally replace rhLCV gp350 and does not restrict rhLCV infection
in vitro
or
in vivo
. The chimeric rhLCV enables direct use of an EBV-specific MAb to investigate the effects of serum neutralizing antibodies against B cell infection on oral viral challenge in rhesus macaques.

IMPORTANCE
This study asked whether the EBV major membrane glycoprotein could functionally replace the rhLCV major membrane glycoprotein. We found that an rhLCV humanized with EBV gp350 is capable of efficiently immortalizing monkey B cells
in vitro
and reproduces acute and persistent infection after oral inoculation of macaques. These results advance our understanding of why EBV cannot infect rhesus macaques by proving that viral attachment through gp350 is not the mechanism for EBV host range restriction. Humanization of rhLCV with EBV gp350 also confers susceptibility to a potent EBV-neutralizing MAb and provides a novel and significant enhancement to the rhesus macaque animal model where both the clinical utility and biological role of neutralizing MAbs against B cell or epithelial cell infection can now be directly tested in the most accurate animal model for EBV infection.
Self-rated chronic conditions and 2-week prevalence in adults in Zhongshan, China: an epidemiological survey
Authors: Zhu Chunyan , Sun Xiaomin , Geng Qingshan , Fu Rong , Yang Hongling , Jiang Wei 
Published: November 2015

ObjectiveTo examine the association between behavioural factors and the risk of chronic conditions and 2-week prevalence.DesignThis was a cross-sectional survey.SettingThe study was conducted in Zhongshan, China.ParticipantsA multistage clustering sampling method was used to select a representative sample of residents from the household registration system between July and September 2011. The overall sample replacement rate was 9.4%, and the final sample included 43 028 individuals.Outcome measuresChronic conditions and 2-week prevalence.Results4979 (11.6%) of the participants reported having at least one chronic condition, 1067 (2.5%) had two or more concurrent chronic conditions, and 6830 (15.9%) reported having at least one disease in a 2-week recall period. The most common chronic condition was primary hypertension, which was reported by 6.8% of participants. Logistic regression models demonstrated that the main factors for having a chronic condition and 2-week prevalence were older age (≥65 years of age; OR 44.91, 95% CI 33.05 to 61.03; and OR 12.71, 95% CI 10.44 to 15.46, respectively), obesity (OR 3.00, 95% CI 2.63 to 3.42; and OR 2.50, 95% CI 2.22 to 2.82, respectively) and being a former smoker (OR 3.02, 95% CI 2.54 to 3.58; and OR 3.24, 95% CI 2.74 to 3.82, respectively).ConclusionsThis study suggests that older age, obesity and unhealthy behaviours are high-risk factors for poorer health status among the residents of Zhongshan, China. The present findings highlight the importance of recognising and managing harmful behaviours in order to improve health.
Testing a model of facilitated reflection on network feedback: a mixed method study on integration of rural mental healthcare services for older people
Authors: Fuller Jeffrey , Oster Candice , Muir Cochrane Eimear , Dawson Suzanne , Lawn Sharon , Henderson Julie , O'Kane Deb , Gerace Adam , McPhail Ruth , Sparkes Deb , Fuller Michelle , Reed Richard L 
Published: November 2015

ObjectiveTo test a management model of facilitated reflection on network feedback as a means to engage services in problem solving the delivery of integrated primary mental healthcare to older people.DesignParticipatory mixed methods case study evaluating the impact of a network management model using organisational network feedback (through social network analysis, key informant interviews and policy review).InterventionA model of facilitated network reflection using network theory and methods.SettingA rural community in South Australia.Participants32 staff from 24 services and 12 senior service managers from mental health, primary care and social care services.ResultsHealth and social care organisations identified that they operated in clustered self-managed networks within sectors, with no overarching purposive older people's mental healthcare network. The model of facilitated reflection revealed service goal and role conflicts. These discussions helped local services to identify as a network, and begin the problem-solving communication and referral links. A Governance Group assisted this process. Barriers to integrated servicing through a network included service funding tied to performance of direct care tasks and the lack of a clear lead network administration organisation.ConclusionsA model of facilitated reflection helped organisations to identify as a network, but revealed sensitivity about organisational roles and goals, which demonstrated that conflict should be expected. Networked servicing needed a neutral network administration organisation with cross-sectoral credibility, a mandate and the resources to monitor the network, to deal with conflict, negotiate commitment among the service managers, and provide opportunities for different sectors to meet and problem solve. This requires consistency and sustained intersectoral policies that include strategies and funding to facilitate and maintain health and social care networks in rural communities.
A multilevel study on the association of observer-assessed working conditions with depressive symptoms among female eldercare workers from 56 work units in 10 care homes in Denmark
Authors: Jakobsen Louise M , Jorgensen Anette F B , Thomsen Birthe L , Greiner Birgit A , Rugulies Reiner 
Published: November 2015

ObjectivesEldercare workers in Denmark have a higher prevalence of poor psychological health than other occupational groups. We examined the association between working conditions assessed by trained observers and depressive symptoms assessed by self-report in a study of female Danish eldercare workers.MethodsWorking conditions were observed based on action regulation theory and defined as (1) regulation requirements, a workplace resource providing opportunity for decision-making and skill development and (2) barriers for task completion. We examined the associations of individual and work unit averaged working conditions with depressive symptoms in a sample of 95 individually observed eldercare workers. Further, we examined the association of work unit averaged working conditions with depressive symptoms in a sample of 205 care workers, including both observed and non-observed individuals. We used regression models that allowed for correlations within work units and care homes and adjusted these models for demographics, job characteristics and stressful life events.ResultsHigher levels of regulation requirements were associated with lower depressive symptoms at the individual level (p=0.04), but not at the workplace level. Barriers were not associated with depressive symptoms at the individual level. At the workplace level, a higher number of qualitatively different barriers (p=0.04) and a higher number of barriers for equipment use (p=0.03) were associated with lower levels of depressive symptoms in the age and cohabitation adjusted model, however statistical significance was lost in the fully adjusted model.ConclusionsLow level of regulation requirements was associated with a high level of depressive symptoms. The study highlights the importance of examining both individual and workplace levels of working conditions.
Current-reported outcome domains in studies of adults with a focus on the treatment of tinnitus: protocol for a systematic review
Authors: Hall Deborah A , Szczepek Agnieszka J , Kennedy Veronica , Haider Haúla 
Published: November 2015

IntroductionIn Europe alone, over 70 million people experience tinnitus. Despite its considerable socioeconomic relevance, progress in developing successful treatments has been limited. Clinical effectiveness is judged according to change in primary outcome measures, but because tinnitus is a subjective condition, the definition of outcomes is challenging and it remains unclear which distinct aspects of tinnitus (ie, ‘domains’) are most relevant for assessment. The development of a minimum outcome reporting standard would go a long way towards addressing these problems. In 2006, a consensus meeting recommended using 1 of 4 questionnaires for tinnitus severity as an outcome in clinical trials, in part because of availability in different language translations. Our initiative takes an approach motivated by clinimetrics, first by determining what to measure before seeking to determine how to measure it. Agreeing on the domains that contribute to tinnitus severity (ie, ‘what’) is the first step towards achieving a minimum outcome reporting standard for tinnitus that has been reached via a methodologically rigorous and transparent process.Methods and analysisDeciding what should be the core set of outcomes requires a great deal of discussion and so lends itself well to international effort. This protocol lays out the first-step methodology in defining a Core Domain Set for clinical trials of tinnitus by establishing existing knowledge and practice with respect to which outcome domains have been measured and which instruments used in recent registered and published clinical trials.Ethics and disseminationNo ethical issues are foreseen. Findings will be reported at national and international ear, nose and throat (ENT) and audiology conferences and in a peer-reviewed journal, using PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analysis) guidelines.Trial registration numberThe systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525.
Vascular endothelial growth factor as a predictive marker for POEMS syndrome treatment response: retrospective cohort study
Authors: Misawa S , Sato Y , Katayama K , Hanaoka H , Sawai S , Beppu M , Nomura F , Shibuya K , Sekiguchi Y , Iwai Y , Watanabe K , Amino H , Ohwada C , Takeuchi M , Sakaida E , Nakaseko C , Kuwabara S 
Published: November 2015

ObjectivePOEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome is a rare multisystem disease characterised by plasma cell dyscrasia and overproduction of vascular endothelial growth factor (VEGF). VEGF is assumed to be useful in monitoring disease activity, because VEGF levels usually decrease after treatment. However, there is no study to investigate whether the extent of decrease in VEGF correlates with clinical outcome. We tested the predictive efficacy of serum VEGF levels in POEMS syndrome.MethodThis was an institutional review board approved retrospective observational cohort study of 20 patients with POEMS monitored regularly for more than 12 months (median follow-up, 87 months) after treatment onset using our prospectively accumulated database of POEMS from 1999 to 2015. Patients were treated by autologous peripheral blood stem cell transplantation or thalidomide administration. Serum VEGF was measured by ELISA. Outcome measures included clinical and laboratory findings and relapse-free survival.ResultsSerum VEGF levels decreased rapidly after treatment, and stabilised by 6 months post treatment. Patients with normalised serum VEGF levels (<1040 pg/mL) at 6 months showed prolonged relapse-free survival (HR=12.81, 95% CI 2.691 to 90.96; p=0.0001) and greater later clinical improvement. The rate of serum VEGF reduction over the first 6 months post treatment correlated with increased grip strength, serum albumin levels, and compound muscle action potential amplitudes at 12 months.ConclusionsSerum VEGF level at 6 months post treatment is a predicative biomarker for disease activity and prognosis in POEMS syndrome. Serum VEGF could be used as a surrogate endpoint for relapse-free survival or clinical or laboratory improvement of POEMS syndrome for clinical trials.
The association between green space and depressive symptoms in pregnant women: moderating roles of socioeconomic status and physical activity
Authors: McEachan R R C , Prady S L , Smith G , Fairley L , Cabieses B , Gidlow C , Wright J , Dadvand P , van Gent D , Nieuwenhuijsen M J 
Published: November 2015

BackgroundThe current study explored the association between green space and depression in a deprived, multiethnic sample of pregnant women, and examined moderating and mediating variables.Method7547 women recruited to the ‘Born in Bradford’ cohort completed a questionnaire during pregnancy. A binary measure of depressive symptoms was calculated using a validated survey. Two green space measures were used: quintiles of residential greenness calculated using the normalised difference vegetation index for three neighbourhood sizes (100, 300 and 500 m buffer zones around participant addresses); access to major green spaces estimated as straight line distance between participant address and nearest green space (>0.5 hectares). Logistic regression analyses examined relationships between green space and depressive symptoms, controlling for ethnicity, demographics, socioeconomic status (SES) and health behaviours. Multiplicative interactions explored variations by ethnic group, SES or activity levels. Mediation analysis assessed indirect effects via physical activity.ResultsPregnant women in the greener quintiles were 18–23% less likely to report depressive symptoms than those in the least green quintile (for within 100 m of green space buffer zone). The green space-depressive symptoms association was significant for women with lower education or who were active. Physical activity partially mediated the association of green space, but explained only a small portion of the direct effect.ConclusionsHigher residential greenness was associated with a reduced likelihood of depressive symptoms. Associations may be stronger for more disadvantaged groups and for those who are already physically active. Improving green space is a promising intervention to reduce risk of depression in disadvantaged groups.
Haemorrhoids: modern diagnosis and treatment
Authors: Hollingshead J R F , Phillips R K S 
Published: November 2015

AbstractHaemorrhoids present often to primary and secondary care, and haemorrhoidal procedures are among the most common carried out. They may co-exist with more serious pathology, and correct evaluation is important. In most cases a one-off colonoscopy in patients aged 50 or above with flexible sigmoidoscopy in younger patients is reasonable. Many people with haemorrhoids do not require treatment. Topical remedies provide no more than symptomatic relief—and even evidence for this is poor. Bulk laxatives alone may improve symptoms of both bleeding and prolapse and seem as effective as injection sclerotherapy. Rubber band ligation is effective in 75% of patients in the short term, but does not treat prolapsed haemorrhoids or those with a significant external component. Conventional haemorrhoidectomy remains the most effective treatment in the long term, the main limitation being post-operative pain. Metronidazole, topical sphincter relaxants and operative technique have all been shown to reduce pain. Stapled haemorrhoidectomy and haemorrhoidal artery ligation techniques are probably less effective but less painful. Long-term data are poor for all procedures, with many studies reporting only 1–3 years of follow-up data. Haemorrhoids are common in pregnancy, occurring in 40% of women. They can usually be treated conservatively during pregnancy, with any treatment delayed until after delivery. Acutely strangulated haemorrhoids may be treated either conservatively or operatively. There is an increased risk of anal stenosis after acute surgery, but the risks of sepsis and sphincter damage are less significant than previously thought. The majority of patients who are treated conservatively will still require definitive treatment at a later date.
Glacial history of Mt Chelmos, Peloponnesus, Greece
Authors: Pope R. J. , Hughes P. D. , Skourtsos E. 
Published: November 2015

Abstract

Mt Chelmos in the Peloponnesus was glaciated by a plateau ice field during the most extensive Pleistocene glaciation. Valley glaciers radiated out from an ice field over the central plateau of the massif. The largest glaciations are likely to be Middle Pleistocene in age. Smaller valley and cirque glaciers formed later and boulders on the moraines of these glacial phases have been dated using
36
Cl terrestrial cosmogenic nuclide exposure dating. These ages indicate a Late Pleistocene age with glacier advance/stabilization at 40–30 ka, glacier retreat at 23–21 ka and advance/stabilization at 13–10 ka. This indicates that the glacial maximum of the last cold stage occurred during Marine Isotope Stage 3, several thousand years before the global Last Glacial Maximum (Marine Isotope Stage 2). The last phase of moraine-building occurred at the end of the Pleistocene, possibly during the Younger Dryas.
Neuropilin-2 Regulates Endosome Maturation and EGFR Trafficking to Support Cancer Cell Pathobiology
Authors: Dutta Samikshan , Roy Sohini , Polavaram Navatha S. , Stanton Marissa J. , Zhang Heyu , Bhola Tanvi , Hönscheid Pia , Donohue Terrence M. , Band Hamid , Batra Surinder K. , Muders Michael H. , Datta Kaustubh 
Published: November 2015

Abstract
Neuropilin-2 (NRP2) is a non-tyrosine kinase receptor frequently overexpressed in various malignancies, where it has been implicated in promoting many protumorigenic behaviors, such as imparting therapeutic resistance to metastatic cancer cells. Here, we report a novel function of NRP2 as a regulator of endocytosis, which is enhanced in cancer cells and is often associated with increased metastatic potential and drug resistance. We found that NRP2 depletion in human prostate and pancreatic cancer cells resulted in the accumulation of EEA1/Rab5-positive early endosomes concomitant with a decrease in Rab7-positive late endosomes, suggesting a delay in early-to-late endosome maturation. NRP2 depletion also impaired the endocytic transport of cell surface EGFR, arresting functionally active EGFR in endocytic vesicles that consequently led to aberrant ERK activation and cell death. Mechanistic investigations revealed that WD-repeat– and FYVE-domain–containing protein 1 (WDFY1) functioned downstream of NRP2 to promote endosome maturation, thereby influencing the endosomal trafficking of EGFR and the formation of autolysosomes responsible for the degradation of internalized cargo. Overall, our results indicate that the NRP2/WDFY1 axis is required for maintaining endocytic activity in cancer cells, which supports their oncogenic activities and confers drug resistance. Therefore, therapeutically targeting endocytosis may represent an attractive strategy to selectively target cancer cells in multiple malignancies. Cancer Res; 76(2); 418–28. ©2015 AACR.
Evaluation of a 5-Marker Blood Test for Colorectal Cancer Early Detection in a Colorectal Cancer Screening Setting
Authors: Werner Simone , Krause Friedemann , Rolny Vinzent , Strobl Matthias , Morgenstern David , Datz Christian , Chen Hongda , Brenner Hermann 
Published: November 2015

Abstract
Purpose: In initial studies that included colorectal cancer patients undergoing diagnostic colonoscopy, we had identified a serum marker combination able to detect colorectal cancer with similar diagnostic performance as fecal immunochemical test (FIT). In this study, we aimed to validate the results in participants of a large colorectal cancer screening study conducted in the average-risk, asymptomatic screening population.
Experimental Design: We tested serum samples from 1,200 controls, 420 advanced adenoma patients, 4 carcinoma in situ patients, and 36 colorectal cancer patients with a 5-marker blood test [carcinoembryonic antigen (CEA)+anti-p53+osteopontin+seprase+ferritin]. The diagnostic performance of individual markers and marker combinations was assessed and compared with stool test results.
Results: AUCs for the detection of colorectal cancer and advanced adenomas with the 5-marker blood test were 0.78 [95% confidence interval (CI), 0.68–0.87] and 0.56 (95% CI, 0.53–0.59), respectively, which now is comparable with guaiac-based fecal occult blood test (gFOBT) but inferior to FIT. With cutoffs yielding specificities of 80%, 90%, and 95%, the sensitivities for the detection of colorectal cancer were 64%, 50%, and 42%, and early-stage cancers were detected as well as late-stage cancers. For osteopontin, seprase, and ferritin, the diagnostic performance in the screening setting was reduced compared with previous studies in diagnostic settings while CEA and anti-p53 showed similar diagnostic performance in both settings.
Conclusions: Performance of the 5-marker blood test under screening conditions is inferior to FIT even though it is still comparable with the performance of gFOBT. CEA and anti-p53 could contribute to the development of a multiple marker blood-based test for early detection of colorectal cancer. Clin Cancer Res; 22(7); 1725–33. ©2015 AACR.