bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between dipstick proteinuria and hearing impairment in health check-ups among Japanese workers: a cross-sectional study
Authors: Umesawa Mitsumasa , Hara Mikako , Sairenchi Toshimi , Haruyama Yasuo , Nagao Masanori , Matsushita Munehiro , Kobashi Gen 
Published: May 2018

ObjectivePrevention of hearing impairment is important because it is difficult to recover from it. Epidemiological studies have examined the risk factors for hearing impairment; however, the association between dipstick proteinuria and hearing impairment has not been previously examined. This study aimed to clarify the association between dipstick proteinuria and hearing impairment.DesignCross-sectional study.SettingOffice and factory workers from all over Japan.ParticipantsThe total number of subjects was 7005. All were employees of the same company. Of these, we recruited 6192 subjects who underwent dipstick urine test and hearing test by audiometry in annual health check-ups (mean age 44.9 years, men 88.3%).Primary outcomesHearing tests were performed at two frequencies (1 kHz, 4 kHz) as prescribed by law in Japan. We defined the inability of subjects to respond to 30 dB at 1 kHz and/or 40 dB at 4 kHz as overall moderate hearing impairment. In addition, we defined moderate hearing impairment at 1 kHz (4 kHz) as an abnormal finding at 1 kHz (4 kHz). We examined the associations between degree of dipstick proteinuria and hearing impairment after adjustment for age, sex, body mass index, hypertension, diabetes mellitus, serum creatinine level and history of noisy work environment.ResultsOverall moderate hearing impairment was noted in 324 subjects (5.2%). Of these, 107 subjects (1.7%) had moderate hearing impairment at 1 kHz and 278 subjects (4.5%) at 4 kHz. Dipstick proteinuria was significantly associated with overall moderate hearing impairment, as well as moderate hearing impairment at both 1 kHz and 4 kHz. The prevalence of overall moderate hearing impairment among subjects with proteinuria ≥2+ was 23.5%, while that among subjects without proteinuria was 5.2% (p<0.01).ConclusionsDipstick proteinuria was associated with moderate hearing impairment in Japanese workers.
How effective and cost-effective are behaviour change interventions in improving the prescription and use of antibiotics in low-income and middle-income countries? A protocol for a systematic review
Authors: Batura Neha , Cuevas Carla , Khan Mishal , Wiseman Virginia 
Published: May 2018

IntroductionAntibiotic resistance endangers effective prevention and treatment of infections, and places significant burden on patients, families, communities and healthcare systems. Low-income and middle-income countries (LMICs) are especially vulnerable to antibiotic resistance, owing to high infectious disease burden, and limited resources for treatment. High prevalence of antibiotic prescription and use due to lack of provider’s knowledge, prescriber’s habits and perceived patient needs further exacerbate the situation. Interventions implemented to address the inappropriate prescription and use of antibiotics in LMICs must address different determinants of antibiotic resistance through sustainable and scalable interventions. The aim of this protocol is to provide a comprehensive overview of the methods that will be used to identify and appraise evidence on the effectiveness and cost-effectiveness of behaviour change interventions implemented in LMICs to improve the prescription and use of antibiotics.Methods and analysisTwo databases (Web of Science and PubMed) will be searched based on a strategy developed in consultation with an essential medicines and health systems researcher. Additional studies will be identified using the same search strategy in Google Scholar. To be included, a study must describe a behaviour change intervention and use an experimental design to estimate effectiveness and/or cost-effectiveness in an LMIC. Following systematic screening of titles, abstracts and keywords, and full-text appraisal, data will be extracted using a customised extraction form. Studies will be categorised by type of behaviour change intervention and experimental design. A meta-analysis or narrative synthesis will be conducted as appropriate, along with an appraisal of quality of studies using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) checklist.Ethics and disseminationNo individual patient data are used, so ethical approval is not required. The systematic review will be disseminated in a peer-reviewed journal and presented at a relevant international conference.PROSPERO registration numberCRD42017075596
Assessment of thyroid cancer risk associated with radiation dose from personal diagnostic examinations in a cohort study of US radiologic technologists, followed 1983–2014
Authors: Little Mark P , Lim Hyeyeun , Friesen Melissa C , Preston Dale L , Doody Michele M , Sigurdson Alice J , Neta Gila , Alexander Bruce H , Chang Lienard A , Cahoon Elizabeth K , Simon Steven L , Linet Martha S , Kitahara Cari M 
Published: May 2018

ObjectiveTo assess whether personal medical diagnostic procedures over life, but particularly those associated with exposure in adulthood, were associated with increased thyroid cancer risk.DesignParticipants from the US Radiologic Technologists Study, a large, prospective cohort, were followed from the date of first mailed questionnaire survey completed during 1983–1989 to the earliest date of self-reported diagnosis of thyroid cancer or of any other cancer than non-melanoma skin cancer (NMSC) in any of three subsequent questionnaires up to the last in 2012–2014.SettingUS nationwide, occupational cohort.ParticipantsUS radiologic technologists with exclusion of: those who reported a previous cancer apart from NMSC on the first questionnaire; those who reported a cancer with an unknown date of diagnosis on any of the questionnaires; and those who did not respond to both the first questionnaire and at least one subsequent questionnaire.Primary outcome measureWe used Cox proportional hazards models with age as timescale to compute HRs and 95% CI for thyroid cancer in relation to cumulative 5-year lagged diagnostic thyroid dose.ResultsThere were 414 self-reported thyroid cancers (n=275 papillary) in a cohort of 76 415 persons. Cumulative thyroid dose was non-significantly positively associated with total (excess relative risk/Gy=2.29 (95% CI −0.91 to 7.01, p=0.19)) and papillary thyroid cancer (excess relative risk/Gy=4.15 (95% CI −0.39, 11.27, p=0.08)) risk. These associations were not modified by age at, or time since, exposure and were independent of occupational exposure.ConclusionOur study provides weak evidence that thyroid dose from diagnostic radiation procedures over the whole of life, in particular associated with exposure in adulthood, influences adult thyroid cancer risk.
Marathon Kids UK: study design and protocol for a mixed methods evaluation of a school-based running programme
Authors: Chalkley Anna E , Routen Ash C , Harris Jo P , Cale Lorraine A , Gorely Trish , Sherar Lauren B 
Published: May 2018

IntroductionSchools are promising settings for physical activity promotion; however, they are complex and adaptive systems that can influence the quality of programme implementation. This paper presents an evaluation of a school-based running programme (Marathon Kids). The aims of this study are (1) to identify the processes by which schools implement the programme, (2) identify and explain the contextual factors affecting implementation and explications of effectiveness and (3) examine the relationship between the level of implementation and perceived outcomes.MethodsUsing a realist evaluation framework, a mixed method single-group before-and-after design, strengthened by multiple interim measurements, will be used. Year 5 (9–10 years old) pupils and their teachers will be recruited from six state-funded primary schools in Leicestershire, UK.Data will be collected once prior to implementation, at five discrete time points during implementation and twice following implementation. A weekly implementation log will also be used. At time point 1 (TP1) (September 2016), data on school environment, teacher and pupil characteristics will be collected. At TP1 and TP6 (July 2017), accelerometry, pupil self-reported physical activity and psychosocial data (eg, social support and intention to be active) will be collected. At TP2, TP3 and TP5 (January, March and June 2017), observations will be conducted. At TP2 and TP5, there will be teacher interviews and pupil focus groups. Follow-up teacher interviews will be conducted at TP7 and TP8 (October 2017 and March 2018) and pupil focus group at TP8. In addition, synthesised member checking will be conducted (June 2018) with a mixed sample of schools.Ethics and disseminationEthical approval for this study was obtained through Loughborough University Human Participants Ethics Subcommittee (R16-P032 & R16-P116). Findings will be disseminated via print, online media and dissemination events as well as practitioner and/or research journals.
Developing a complex intervention to support timely engagement with palliative care for patients with advanced cancer in primary and secondary care in the UK: a study protocol
Authors: Hackett Julia , Bekker Hilary , Bennett Michael I , Carder Paul , Gallagher Jean , Henry Claire , Kite Suzanne , Taylor Sally , Velikova Galina , Ziegler Lucy 
Published: May 2018

IntroductionFor patients with advanced cancer, timely access to palliative care can improve quality of life and enable patients to participate in decisions about their end-of-life care. However, in a UK population of 2500 patients who died from cancer, one-third did not receive specialist palliative care, and of those who did, the duration of involvement was too short to maximise the benefits. Initiating a conversation about palliative care is challenging for some health professionals and patients often have unmet information needs and misconceptions about palliative care. We will work closely with patients and health professionals to develop a patient decision aid and health professional training module designed to facilitate a timely and informed conversation about palliative care.Methods and analysisThis study is being conducted over 24 months from November 2017 to October 2019 and follows the UK Medical Research Council framework for developing complex interventions and the International Patient Decision Aids Guideline. The Ottawa Decision Support Framework underpins the study. The Supporting Timely Engagement with Palliative care (STEP) intervention will be developed though an iterative process informed by interviews and focus groups with patients with advanced cancer, oncologists, general practitioners and palliative care doctors. An expert panel will also review each iteration. The expert panel will consist of a patient representative with experience of palliative care, health professionals who are involved in advanced cancer care decision-making, a medical education expert and the National Council for Palliative Care director of transformation. The feasibility and acceptability of the decision aid and doctor training will be tested in oncology and general practice settings.Ethics and disseminationEthical approval for the study has been granted by the Office for Research Ethics Committees Northern Ireland (ORECNI), approval reference 17/NI/0249. Dissemination and knowledge transfer will be conducted via publications, national bodies and networks, and patient and family groups.
Intense Exercise for Survival among Men with Metastatic Castrate-Resistant Prostate Cancer (INTERVAL-GAP4): a multicentre, randomised, controlled phase III study protocol
Authors: Newton Robert U , Kenfield Stacey A , Hart Nicolas H , Chan June M , Courneya Kerry S , Catto James , Finn Stephen P , Greenwood Rosemary , Hughes Daniel C , Mucci Lorelei , Plymate Stephen R , Praet Stephan F E , Guinan Emer M , Van Blarigan Erin L , Casey Orla , Buzza Mark , Gledhill Sam , Zhang Li , Galvão Daniel A , Ryan Charles J , Saad Fred 
Published: May 2018

IntroductionPreliminary evidence supports the beneficial role of physical activity on prostate cancer outcomes. This phase III randomised controlled trial (RCT) is designed to determine if supervised high-intensity aerobic and resistance exercise increases overall survival (OS) in patients with metastatic castrate-resistant prostate cancer (mCRPC).Methods and analysisParticipants (n=866) must have histologically documented metastatic prostate cancer with evidence of progressive disease on androgen deprivation therapy (defined as mCRPC). Patients can be treatment-naïve for mCRPC or on first-line androgen receptor-targeted therapy for mCRPC (ie, abiraterone or enzalutamide) without evidence of progression at enrolment, and with no prior chemotherapy for mCRPC. Patients will receive psychosocial support and will be randomly assigned (1:1) to either supervised exercise (high-intensity aerobic and resistance training) or self-directed exercise (provision of guidelines), stratified by treatment status and site. Exercise prescriptions will be tailored to each participant’s fitness and morbidities. The primary endpoint is OS. Secondary endpoints include time to disease progression, occurrence of a skeletal-related event or progression of pain, and degree of pain, opiate use, physical and emotional quality of life, and changes in metabolic biomarkers. An assessment of whether immune function, inflammation, dysregulation of insulin and energy metabolism, and androgen biomarkers are associated with OS will be performed, and whether they mediate the primary association between exercise and OS will also be investigated. This study will also establish a biobank for future biomarker discovery or validation.Ethics and disseminationValidation of exercise as medicine and its mechanisms of action will create evidence to change clinical practice. Accordingly, outcomes of this RCT will be published in international, peer-reviewed journals, and presented at national and international conferences. Ethics approval was first obtained at Edith Cowan University (ID: 13236 NEWTON), with a further 10 investigator sites since receiving ethics approval, prior to activation.Trial registration numberNCT02730338.
Closure of large bore 9 F arterial puncture sites with the AngioSeal STS device in acute stroke patients after intravenous recombinant tissue plasminogen activator (rt-PA)
Authors: Janssen Hendrik , Killer-Oberpfalzer Monika , Lange Ruediger 
Published: May 2018

PurposeThis retrospective analysis was performed to evaluate whether large bore 9 F puncture sites can be safely closed with the 8 F AngioSeal STS device after endovascular stroke procedures in patients who did or did not receive recombinant tissue plasminogen activator (rt-PA).MethodsOut of 161 consecutive endovascular stroke procedures we identified 72 patients who met the inclusion criteria, of whom 46 received rt-PA before the endovascular procedure and 26 did not. All groin complications such as major haemorrhage, failure of the device to close the puncture site, delayed haemorrhage, acute lower extremity ischaemia or necessary vascular surgery as well as infections were recorded.ResultsOnly one patient had delayed groin haemorrhage after closure of the 9 F puncture site with the AngioSeal STS device. There was no significant difference in complications between patients with or without rt-PA treatment.ConclusionThe 8 F AngioSeal STS seems to be safe and efficient to close 9 F femoral artery puncture sites, even under active rt-PA thrombolysis.
Diabetes mellitus and latent tuberculosis infection: baseline analysis of a large UK cohort
Authors: Jackson Charlotte , Southern Jo , Lalvani Ajit , Drobniewski Francis , Griffiths Chris J , Lipman Marc , Bothamley Graham H , Deeks Jonathan J , Imran Ambreen , Kon Onn Min , Mpofu Sithembinkosi , Nikolayevskyy Vladyslav , Rees-Roberts Melanie , Sitch Alice , Sridhar Saranya , Tsou Chuen-Yan , Whitworth Hilary , Abubakar Ibrahim 
Published: May 2018

We conducted a cross-sectional analysis of baseline data from a UK cohort study which enrolled participants at risk of latent tuberculosis infection (LTBI, defined as a positive result for either of the two interferon gamma release assays). Binomial regression with a log link was used to estimate crude and adjusted prevalence ratios (PRs) and 95% CIs for the relationship between diabetes mellitus (DM) and LTBI. Adjusted for age, sex, ethnicity, body mass index and the presence of other immunocompromising conditions, DM was associated with a 15% higher prevalence of LTBI (adjusted PR=1.15, 95% CI 1.02 to 1.30, p=0.025).Trial registration numberPREDICT is registered on clinicaltrials.gov (NCT01162265)
Magmatism and extension rates at rifted margins
Authors: Lundin Erik R. , Doré Anthony G. , Redfield Thomas F. 
Published: May 2018

Rifted margins are commonly classified as either magma-rich or magma-poor. Magma-poor margins are often implicitly related to ultraslow–slow extension. Conversely, therefore, magma-rich margins should represent more rapid extension. Although supported by numerical modelling, these relationships are based on limited data and depend on a perhaps spurious comparison between continental margins and spreading ridges. Three case studies from the Atlantic margins are therefore presented here as a local, by no means complete, examination of this concept.
Extension rates for magma-poor margins are mainly derived from offshore Iberia, while the best documented rates on magma-rich margins are probably those in the NE Atlantic. Particularly for the NE Atlantic, there is a dependence on the initial oceanic spreading rate as pre-break-up rates are very difficult to quantify. Our two southerly examples, the Central Atlantic and southern South Atlantic, are both magma-rich in parts and have been described as opening during ultraslow–slow plate separation. Both would therefore seem to contradict the positive ‘rate-magmatism’ correlation. However, on closer examination, a wide range of initial extension rates are actually possible. This is largely due to poor constraints on break-up ages. The assumption that break-up is synchronous with flood basalt extrusion is flawed, and may have caused initial extension rates to have been significantly underestimated. Additionally, averaging between widely spaced oceanic magnetic anomalies allows for a wide range of extension rates. New, well-constrained ages and event chronologies from critical areas of conjugate margins are needed to determine whether this relationship has global validity.
Fibrin Stiffness Mediates Dormancy of Tumor-Repopulating Cells via a Cdc42-Driven Tet2 Epigenetic Program
Authors: Liu Yuying , Lv Jiadi , Liang Xiaoyu , Yin Xiaonan , Zhang Le , Chen Degao , Jin Xun , Fiskesund Roland , Tang Ke , Ma Jingwei , Zhang Huafeng , Dong Wenqian , Mo Siqi , Zhang Tianzhen , Cheng Feiran , Zhou Yabo , Xie Jing , Wang Ning , Huang Bo 
Published: May 2018

Abstract
Dormancy is recognized as a critical biological event for tumorigenic cells surviving in an extremely harsh environment. Understanding the molecular process of dormancy can unlock novel approaches to tackle cancers. We recently reported that stem-like tumor-repopulating cells (TRC) sense mechanical signals and rapidly proliferate in a 90 Pa soft fibrin matrix. Here, we show that a stiff mechanical environment induces TRC dormancy via an epigenetic program initiated by translocation of Cdc42, a cytosolic regulator of mechanotransduction, into the nucleus, where it promotes transcription of hydroxymethylating enzyme Tet2. Tet2 epigenetically activated cell-cycle–inhibiting genes p21 and p27 to induce dormancy, but also caused downregulation of integrin β3 to maintain dormancy. This stiffness-mediated dormancy was recapitulated in mouse models for both murine and primary human melanoma TRCs. These data identify an epigenetic program directed by mechanics, which drives highly tumorigenic TRCs to enter dormancy in a stiff mechanical environment.
Significance: A mechanics-directed epigenetic program enables tumor-repopulating cells to enter dormancy in a stiff mechanical environment. Cancer Res; 78(14); 3926–37. ©2018 AACR.
LRRC15 Is a Novel Mesenchymal Protein and Stromal Target for Antibody–Drug Conjugates
Authors: Purcell James W. , Tanlimco Sonia G. , Hickson Jonathan , Fox Melvin , Sho Mien , Durkin Lisa , Uziel Tamar , Powers Rick , Foster Kelly , McGonigal Thomas , Kumar Subashri , Samayoa Josue , Zhang Dong , Palma Joann P. , Mishra Sasmita , Hollenbaugh Diane , Gish Kurt , Morgan-Lappe Susan E. , Hsi Eric D. , Chao Debra T. 
Published: May 2018

AbstractProgress in understanding tumor stromal biology has been constrained in part because cancer-associated fibroblasts (CAF) are a heterogeneous population with limited cell-type–specific protein markers. Using RNA expression profiling, we identified the membrane protein leucine-rich repeat containing 15 (LRRC15) as highly expressed in multiple solid tumor indications with limited normal tissue expression. LRRC15 was expressed on stromal fibroblasts in many solid tumors (e.g., breast, head and neck, lung, pancreatic) as well as directly on a subset of cancer cells of mesenchymal origin (e.g., sarcoma, melanoma, glioblastoma). LRRC15 expression was induced by TGFβ on activated fibroblasts (αSMA+) and on mesenchymal stem cells. These collective findings suggested LRRC15 as a novel CAF and mesenchymal marker with utility as a therapeutic target for the treatment of cancers with LRRC15-positive stromal desmoplasia or cancers of mesenchymal origin. ABBV-085 is a monomethyl auristatin E (MMAE)-containing antibody–drug conjugate (ADC) directed against LRRC15, and it demonstrated robust preclinical efficacy against LRRC15 stromal-positive/cancer-negative, and LRRC15 cancer-positive models as a monotherapy, or in combination with standard-of-care therapies. ABBV-085′s unique mechanism of action relied upon the cell-permeable properties of MMAE to preferentially kill cancer cells over LRRC15-positive CAF while also increasing immune infiltrate (e.g., F4/80+ macrophages) in the tumor microenvironment. In summary, these findings validate LRRC15 as a novel therapeutic target in multiple solid tumor indications and support the ongoing clinical development of the LRRC15-targeted ADC ABBV-085.Significance: These findings identify LRRC15 as a new marker of cancer-associated fibroblasts and cancers of mesenchymal origin and provide preclinical evidence for the efficacy of an antibody-drug conjugate targeting the tumor stroma. Cancer Res; 78(14); 4059–72. ©2018 AACR.