bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Lisbon Cohort of men who have sex with men
Authors: Meireles Paula , Lucas Raquel , Martins Ana , Carvalho Ana Cláudia , Fuertes Ricardo , Brito João , Campos Maria José , Mendão Luís , Barros Henrique 
Published: May 2015

PurposeNewly diagnosed HIV infections among men who have sex with men (MSM) are rising in many European countries. Surveillance tools must be tailored to the current state of the epidemic, and include decentralised prospective monitoring of HIV incidence and behavioural changes in key populations. In this scenario, an open prospective cohort study was assembled—The Lisbon Cohort of MSM—aiming to dynamically monitor the frequency of disease and its predictors.ParticipantsThe Lisbon Cohort of MSM is an ongoing observational prospective study conducted at a community-based voluntary HIV counselling and testing centre in Lisbon, Portugal (CheckpointLX). Men testing negative for HIV, aged 18 or over and reporting having had sex with men are invited to follow-up visits every 6 months. At each evaluation, a face-to-face interview using a structured questionnaire is conducted, and HIV and syphilis rapid tests are performed by trained peer counsellors. From April 2011 to February 2014, 3106 MSM were eligible to the cohort of whom 923 (29.7%) did not participate. The remaining 2183 (70.3%) MSM were enrolled and 804 had at least one follow-up evaluation, for a total of 893 person-years of observation.Future plansThe study findings will be disseminated in peer-reviewed journals and presented at national and international conferences. The follow-up of this cohort of HIV-negative MSM will be a valuable tool for monitoring HIV incidence in a setting where limited prospective information existed. Moreover, it will allow for a deeper analytical approach to the study of population time trends and individual changes in risk factors that currently shape the HIV epidemic among MSM.
Racial ethnic differences in type 2 diabetes treatment patterns and glycaemic control in the Boston Area Community Health Survey
Authors: Goonesekera Sunali D , Yang May H , Hall Susan A , Fang Shona C , Piccolo Rebecca S , McKinlay John B 
Published: May 2015

ObjectivesNumerous studies continue to report poorer glycaemic control, and a higher incidence of diabetes-related complications among African–Americans and Hispanic–Americans as compared with non-Hispanic Caucasians with type 2 diabetes. We examined racial/ethnic differences in receipt of hypoglycaemic medications and glycaemic control in a highly insured Massachusetts community sample of individuals with type 2 diabetes.SettingCommunity-based sample from Boston, Massachusetts, USA.Participants682 patients with physician-diagnosed diabetes from the third wave of the Boston Area Community Health Survey (2010–2012). The study included approximately equal proportions of African–Americans, Hispanics and Caucasians.MethodsWe examined racial/ethnic disparities in diabetes treatment by comparing proportions of individuals on mutually exclusive diabetes treatment regimens across racial/ethnic subgroups. Using multivariable linear and logistic regression, we also examined associations between race/ethnicity and glycaemic control in the overall population, and within treatment regimens, adjusting for age, gender, income, education, health insurance, health literacy, disease duration, diet and physical activity.ResultsAmong those treated (82%), the most commonly prescribed antidiabetic regimens were biguanides only (31%), insulin only (23%), and biguanides and insulin (16%). No overall racial/ethnic differences in treatment or glycaemic control (per cent difference for African–Americans: 6.18, 95% CI −1.00 to 13.88; for Hispanic–Americans: 1.01, 95% CI −10.42 to 12.75) were observed. Within regimens, we did not observe poorer glycaemic control for African–Americans prescribed biguanides only, insulin only or biguanides combined with insulin/sulfonylureas. However, African–Americans prescribed miscellaneous regimens had higher risk of poorer glycaemic control (per cent difference=23.37, 95% CI 7.25 to 43.33). There were no associations between glycaemic levels and Hispanic ethnicity overall, or within treatment regimens.ConclusionsFindings suggest a lack of racial/ethnic disparities in diabetes treatment patterns and glycaemic control in this highly insured Massachusetts study population. Future studies are needed to understand impacts of increasing insurance coverage on racial/ethnic disparities in treatment patterns and related outcomes.
What caused the outbreak of ESBL-producingKlebsiella pneumoniaein a neonatal intensive care unit, Germany 2009 to 2012? Reconstructing transmission with epidemiological analysis and whole-genome sequencing
Authors: Haller Sebastian , Eller Christoph , Hermes Julia , Kaase Martin , Steglich Matthias , Radonić Aleksandar , Dabrowski Piotr Wojtek , Nitsche Andreas , Pfeifer Yvonne , Werner Guido , Wunderle Werner , Velasco Edward , Abu Sin Muna , Eckmanns Tim , Nübel Ulrich 
Published: May 2015

ObjectiveWe aimed to retrospectively reconstruct the timing of transmission events and pathways in order to understand why extensive preventive measures and investigations were not sufficient to prevent new cases.MethodsWe extracted available information from patient charts to describe cases and to compare them to the normal population of the ward. We conducted a cohort study to identify risk factors for pathogen acquisition. We sequenced the available isolates to determine the phylogenetic relatedness ofKlebsiella pneumoniaeisolates on the basis of their genome sequences.ResultsThe investigation comprises 37 cases and the 10 cases with ESBL (extended-spectrum beta-lactamase)-producingK. pneumoniaebloodstream infection. Descriptive epidemiology indicated that a continuous transmission from person to person was most likely. Results from the cohort study showed that ‘frequent manipulation’ (a proxy for increased exposure to medical procedures) was significantly associated with being a case (RR 1.44, 95% CI 1.02 to 2.19). Genome sequences revealed that all 48 bacterial isolates available for sequencing from 31 cases were closely related (maximum genetic distance, 12 single nucleotide polymorphisms). Based on our calculation of evolutionary rate and sequence diversity, we estimate that the outbreak strain was endemic since 2008.ConclusionsEpidemiological and phylogenetic analyses consistently indicated that there were additional, undiscovered cases prior to the onset of microbiological screening and that the spread of the pathogen remained undetected over several years, driven predominantly by person-to-person transmission. Whole-genome sequencing provided valuable information on the onset, course and size of the outbreak, and on possible ways of transmission.
Classification of accelerometer wear and non-wear events in seconds for monitoring free-living physical activity
Authors: Zhou Shang-Ming , Hill Rebecca A , Morgan Kelly , Stratton Gareth , Gravenor Mike B , Bijlsma Gunnar , Brophy Sinead 
Published: May 2015

ObjectiveTo classify wear and non-wear time of accelerometer data for accurately quantifying physical activity in public health or population level research.DesignA bi-moving-window-based approach was used to combine acceleration and skin temperature data to identify wear and non-wear time events in triaxial accelerometer data that monitor physical activity.SettingLocal residents in Swansea, Wales, UK.Participants50 participants aged under 16 years (n=23) and over 17 years (n=27) were recruited in two phases: phase 1: design of the wear/non-wear algorithm (n=20) and phase 2: validation of the algorithm (n=30).MethodsParticipants wore a triaxial accelerometer (GeneActiv) against the skin surface on the wrist (adults) or ankle (children). Participants kept a diary to record the timings of wear and non-wear and were asked to ensure that events of wear/non-wear last for a minimum of 15 min.ResultsThe overall sensitivity of the proposed method was 0.94 (95% CI 0.90 to 0.98) and specificity 0.91 (95% CI 0.88 to 0.94). It performed equally well for children compared with adults, and females compared with males. Using surface skin temperature data in combination with acceleration data significantly improved the classification of wear/non-wear time when compared with methods that used acceleration data only (p<0.01).ConclusionsUsing either accelerometer seismic information or temperature information alone is prone to considerable error. Combining both sources of data can give accurate estimates of non-wear periods thus giving better classification of sedentary behaviour. This method can be used in population studies of physical activity in free-living environments.
Effects of an internet-based cognitive behavioural therapy intervention on preventing major depressive episodes among workers: a protocol for a randomised controlled trial
Authors: Imamura Kotaro , Kawakami Norito , Furukawa Toshi A , Matsuyama Yutaka , Shimazu Akihito , Kasai Kiyoto 
Published: May 2015

IntroductionThe aim of this study is to examine the effects of an internet-based cognitive behavioural therapy (iCBT) program on decreasing the risk of major depressive episodes (MDEs) among workers employed in a private corporate group in Japan, using a randomised controlled trial design.Methods and analysisAll of the workers in a corporate group (n=20 000) will be recruited through an invitation email. Participants who fulfil the inclusion criteria will be randomly allocated to intervention or control groups (planned N=4050 for each group). They will be allowed to complete the six lessons of the iCBT program within 10 weeks after the baseline survey. Those in the control group will receive the same iCBT after 12 months. The program includes several CBT skills: self-monitoring, cognitive restructuring, assertiveness, problem-solving and relaxation. The primary outcome measure is no new onset of MDE (using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)/DSM-5 criteria) during the 12-month follow-up. Assessment will use the web version of the WHO Composite International Diagnostic Interview V.3.0 depression section.Ethics and disseminationThe Research Ethics Review Board of Graduate School of Medicine, the University of Tokyo (No. 3083-(2)), approved the study procedures.Trial registration numberThe study protocol is registered at the UMIN Clinical Trials Registry (UMIN-CTR; ID=UMIN000014146).
Exploratory clinical trial of combination wound therapy with a gelatin sheet and platelet-rich plasma in patients with chronic skin ulcers: study protocol
Authors: Morimoto Naoki , Kakudo Natsuko , Matsui Makoto , Ogura Tsunetaka , Hara Tomoya , Suzuki Kenji , Yamamoto Masaya , Tabata Yasuhiko , Kusumoto Kenji 
Published: May 2015

IntroductionChronic skin ulcers, such as diabetic ulcers, venous leg ulcers and pressure ulcers, are intractable and increasing in prevalence, representing a costly problem in healthcare. We developed a combination therapy with a gelatin sheet, capable of providing sustained release of platelet-rich plasma (PRP). The objective of this study is to investigate the safety and efficacy of autologous PRP covered with a hydrocolloid dressing and PRP covered with a gelatin sheet in the treatment of chronic skin ulcers.Methods and analysisThirty patients with chronic skin ulcers who have not healed with conventional therapy for at least 1 month are being recruited. The patients will receive PRP after debridement, and the wounds will be covered with a hydrocolloid dressing or gelatin sheet. The efficacy will be evaluated according to the time from the beginning of PRP application to secondary healing or the day on which wound closure is achieved with a relatively simple surgical procedure, such as skin grafting or suturing. All patients will be followed up until 6 weeks after application to observe adverse events related to the application of PRP and the dressings. This study was designed to address and compare the safety and efficacy of PRP covered with a hydrocolloid dressing versus a gelatin sheet. If successful, this combination therapy may be an alternative to bioengineered skin substitutes containing living cells and lead to substantial progress in the management of chronic skin ulcers.Ethics and disseminationThe study protocol was approved by the Institutional Review Board of Kansai Medical University (KMU Number 0649-1, 4 August 2014: V.1.0). The findings of this trial will be disseminated through peer-reviewed journals, and national and international scientific meetings as well as to the patients.Trial registration numberUMIN000015689.
The association of folds and fractures and the link between folding, fracturing and fluid flow during the evolution of a fold–thrust belt: a brief review
Authors: Cosgrove J. W. 
Published: May 2015

Abstract
Because of the importance of understanding the association of folds and fractures in the hydrocarbon and mining industry, a considerable amount of work has been undertaken to establish the geometric relationship between these structures. The structures are linked in a variety of ways. Sometimes, as for example in the formation of fractures in the inner and outer arcs of the hinge zones of single-layer folds or of accommodation thrusts in the hinge regions of multilayer folds, it is the process of folding that generates the fractures. At other times, as in the formation of a fault-bend fold and other types of forced folds, the reverse is true. In this paper an attempt is made to look briefly at the various types of fold-fracture associations found in nature and, by considering the evolution of a typical fold–thrust belt, obtain an insight into the controls on the temporal and spatial organization of the different types of folds and their associated fractures that form in this tectonic regime. The role of fluids in the initiation of both folds and thrusts is considered, as is the subsequent impact of these structures on fluid migration. It is shown that understanding the links between stress, fluid pressure, fracturing and folding provides a clear insight into the fluid mechanics operating in an active fold–thrust belt.
Breast Cancer Mortality in African-American and Non-Hispanic White Women by Molecular Subtype and Stage at Diagnosis: A Population-Based Study
Authors: Tao Li , Gomez Scarlett Lin , Keegan Theresa H.M. , Kurian Allison W. , Clarke Christina A. 
Published: May 2015

Abstract
Background: Higher breast cancer mortality rates for African-American than non-Hispanic White women are well documented; however, it remains uncertain if this disparity occurs in disease subgroups defined by tumor molecular markers and stage at diagnosis. We examined racial differences in outcome according to subtype and stage in a diverse, population-based series of 103,498 patients.
Methods: We obtained data for all invasive breast cancers diagnosed between January 1, 2005, and December 31, 2012, and followed through December 31, 2012, among 93,760 non-Hispanic White and 9,738 African-American women in California. Molecular subtypes were categorized according to tumor expression of hormone receptor (HR, based on estrogen and progesterone receptors) and human epidermal growth factor receptor 2 (HER2). Cox proportional hazards models were used to calculate relative hazard (RH) and 95% confidence intervals (CI) for breast cancer–specific mortality.
Results: After adjustment for patient, tumor, and treatment characteristics, outcomes were comparable by race for stage I or IV cancer regardless of subtype, and HR+/HER2+ or HR−/HER2+ cancer regardless of stage. We found substantially higher hazards of breast cancer death among African-American women with stage II/III HR+/HER2− (RH, 1.31; 95% CI, 1.03–1.65; and RH, 1.39; 95% CI, 1.10–1.75, respectively) and stage III triple-negative cancers relative to Whites.
Conclusions: There are substantial racial/ethnic disparities among patients with stages II/III HR+/HER2− and stage III triple-negative breast cancers but not for other subtype and stage.
Impact: These data provide insights to assess barriers to targeted treatment (e.g., trastuzumab or endocrine therapy) of particular subtypes of breast cancer among African-American patients. Cancer Epidemiol Biomarkers Prev; 24(7); 1039–45. ©2015 AACR.
TLR9-Targeted STAT3 Silencing Abrogates Immunosuppressive Activity of Myeloid-Derived Suppressor Cells from Prostate Cancer Patients
Authors: Hossain Dewan M. S. , Pal Sumanta K. , Moreira Dayson , Duttagupta Priyanka , Zhang Qifang , Won Haejung , Jones Jeremy , D'Apuzzo Massimo , Forman Stephen , Kortylewski Marcin 
Published: May 2015

Abstract
Purpose: Recent advances in immunotherapy of advanced human cancers underscored the need to address and eliminate tumor immune evasion. The myeloid-derived suppressor cells (MDSC) are important inhibitors of T-cell responses in solid tumors, such as prostate cancers. However, targeting MDSCs proved challenging due to their phenotypic heterogeneity.
Experimental Design: Myeloid cell populations were evaluated using flow cytometry on blood samples, functional assays, and immunohistochemical/immunofluorescent stainings on specimens from healthy subjects, localized and metastatic castration-resistant prostate cancer patients.
Results: Here, we identify a population of Lin−CD15HICD33LO granulocytic MDSCs that accumulate in patients' circulation during prostate cancer progression from localized to metastatic disease. The prostate cancer–associated MDSCs potently inhibit autologous CD8+ T cells' proliferation and production of IFNγ and granzyme-B. The circulating MDSCs have high levels of activated STAT3, which is a central immune checkpoint regulator. The granulocytic pSTAT3+ cells are also detectable in patients' prostate tissues. We previously generated an original strategy to silence genes specifically in Toll-like Receptor-9 (TLR9) positive myeloid cells using CpG-siRNA conjugates. We demonstrate that human granulocytic MDSCs express TLR9 and rapidly internalize naked CpG-STAT3siRNA, thereby silencing STAT3 expression. STAT3 blocking abrogates immunosuppressive effects of patients-derived MDSCs on effector CD8+ T cells. These effects depended on reduced expression and enzymatic activity of Arginase-1, a downstream STAT3 target gene and a potent T-cell inhibitor.
Conclusions: Overall, we demonstrate the accumulation of granulocytic MDSCs with prostate cancer progression and the feasibility of using TLR9-targeted STAT3siRNA delivery strategy to alleviate MDSC-mediated immunosuppression. Clin Cancer Res; 21(16); 3771–82. ©2015 AACR.
CD24+ Ovarian Cancer Cells Are Enriched for Cancer-Initiating Cells and Dependent on JAK2 Signaling for Growth and Metastasis
Authors: Burgos-Ojeda Daniela , Wu Rong , McLean Karen , Chen Yu-Chih , Talpaz Moshe , Yoon Euisik , Cho Kathleen R. , Buckanovich Ronald J. 
Published: May 2015

Abstract
Ovarian cancer is known to be composed of distinct populations of cancer cells, some of which demonstrate increased capacity for cancer initiation and/or metastasis. The study of human cancer cell populations is difficult due to long requirements for tumor growth, interpatient variability, and the need for tumor growth in immune-deficient mice. We therefore characterized the cancer initiation capacity of distinct cancer cell populations in a transgenic murine model of ovarian cancer. In this model, conditional deletion of Apc, Pten, and Trp53 in the ovarian surface epithelium (OSE) results in the generation of high-grade metastatic ovarian carcinomas. Cell lines derived from these murine tumors express numerous putative stem cell markers, including CD24, CD44, CD90, CD117, CD133, and ALDH. We show that CD24+ and CD133+ cells have increased tumor sphere-forming capacity. CD133+ cells demonstrated a trend for increased tumor initiation while CD24+ cells versus CD24− cells had significantly greater tumor initiation and tumor growth capacity. No preferential tumor-initiating or growth capacity was observed for CD44+, CD90+, CD117+, or ALDH+ versus their negative counterparts. We have found that CD24+ cells, compared with CD24− cells, have increased phosphorylation of STAT3 and increased expression of STAT3 target Nanog and c-myc. JAK2 inhibition of STAT3 phosphorylation preferentially induced cytotoxicity in CD24+ cells. In vivo JAK2 inhibitor therapy dramatically reduced tumor metastases, and prolonged overall survival. These findings indicate that CD24+ cells play a role in tumor migration and metastasis and support JAK2 as a therapeutic target in ovarian cancer. Mol Cancer Ther; 14(7); 1717–27. ©2015 AACR.
Preexisting Levels of CD4 T Cells Expressing PD-1 Are Related to Overall Survival in Prostate Cancer Patients Treated with Ipilimumab
Authors: Kwek Serena S. , Lewis Jera , Zhang Li , Weinberg Vivian , Greaney Samantha K. , Harzstark Andrea L. , Lin Amy M. , Ryan Charles J. , Small Eric J. , Fong Lawrence 
Published: May 2015

Abstract
Cytotoxic T-lymphocyte–associated antigen-4 (CTLA-4) blockade can induce tumor regression and improved survival in cancer patients. This treatment can enhance adaptive immune responses without an exogenous vaccine, but the immunologic biomarkers associated with improved clinical outcome in cancer patients are not fully established. A phase Ib trial in patients with metastatic, castration-resistant prostate cancer was performed combining ipilimumab with sargramostim (GM-CSF). In addition to evaluating ipilimumab dose, patients were followed clinically for response and overall survival, and for immunomodulation of circulating T cells. PSA declines of ≥50% and radiographic responses were observed at doses of ≥3 mg/kg/dose. Timing of clinical responses could be either immediate or delayed. Durable responses were also observed off treatment. A subset of patients experienced long-term survival with or without objective clinical responses. The relationship between T-cell phenotype in peripheral blood and overall survival was examined retrospectively. We found that the treatment induced an increase in the levels of CD4+ effector T (Teff) cells, regulatory T cells, PD-1+ CD4 Teff cells, and PD-1+ CD8 T cells. However, these increased levels were not associated with overall survival. Instead, low pretreatment baseline levels of PD-1+ CD4 Teff cells were found to correlate with longer overall survival. Furthermore, baseline levels of PD-1+ CD4 Teff cells from patients with shorter overall survival were higher than from cancer-free male control subjects. These results suggest that preexisting expression of immunologic checkpoint marker PD-1 on CD4 Teff cells may help identify patients that may benefit from ipilimumab treatment. Cancer Immunol Res; 3(9); 1008–16. ©2015 AACR.