bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brd4‐Brd2 isoform switching coordinates pluripotent exit and Smad2‐dependent lineage specification
Authors: Fernandez‐Alonso Rosalia , Davidson Lindsay , Hukelmann Jens , Zengerle Michael , Prescott Alan R , Lamond Angus , Ciulli Alessio , Sapkota Gopal P , Findlay Greg M 
Published: June 2017

AbstractPluripotent stem cells (PSCs) hold great clinical potential, as they possess the capacity to differentiate into fully specialised tissues such as pancreas, liver, neurons and cardiac muscle. However, the molecular mechanisms that coordinate pluripotent exit with lineage specification remain poorly understood. To address this question, we perform a small molecule screen to systematically identify novel regulators of the Smad2 signalling network, a key determinant of PSC fate. We reveal an essential function for BET family bromodomain proteins in Smad2 activation, distinct from the role of Brd4 in pluripotency maintenance. Mechanistically, BET proteins specifically engage Nodal gene regulatory elements (NREs) to promote Nodal signalling and Smad2 developmental responses. In pluripotent cells, Brd2‐Brd4 occupy NREs, but only Brd4 is required for pluripotency gene expression. Brd4 downregulation facilitates pluripotent exit and drives enhanced Brd2 NRE occupancy, thereby unveiling a specific function for Brd2 in differentiative Nodal‐Smad2 signalling. Therefore, distinct BET functionalities and Brd4‐Brd2 isoform switching at NREs coordinate pluripotent exit with lineage specification.
Salt‐inducible kinase induces cytoplasmic histone deacetylase 4 to promote vascular calcification
Authors: Abend Alon , Shkedi Omer , Fertouk Michal , Caspi Lilac H , Kehat Izhak 
Published: June 2017

AbstractA pathologic osteochondrogenic differentiation of vascular smooth muscle cells (VSMCs) promotes arterial calcifications, a process associated with significant morbidity and mortality. The molecular pathways promoting this pathology are not completely understood. We studied VSMCs, mouse aortic rings, and human aortic valves and showed here that histone deacetylase 4 (HDAC4) is upregulated early in the calcification process. Gain‐ and loss‐of‐function assays demonstrate that HDAC4 is a positive regulator driving this pathology. HDAC4 can shuttle between the nucleus and cytoplasm, but in VSMCs, the cytoplasmic rather than the nuclear activity of HDAC4 promotes calcification, and a nuclear‐localized mutant of HDAC4 fails to promote calcification. The cytoplasmic location and function of HDAC4 is controlled by the activity of salt‐inducible kinase (SIK). Pharmacologic inhibition of SIK sends HDAC4 to the nucleus and inhibits the calcification process in VSMCs, aortic rings, and in vivo. In the cytoplasm, HDAC4 binds and its activity depends on the adaptor protein ENIGMA (Pdlim7) to promote vascular calcification. These results establish a cytoplasmic role for HDAC4 and identify HDAC4, SIK, and ENIGMA as mediators of vascular calcification.
Male Infertility Is Responsible for Nearly Half of the Extinction Observed in the Mouse Collaborative Cross
Authors: Shorter John R , Odet Fanny , Aylor David L , Pan Wenqi , Kao Chia-Yu , Fu Chen-Ping , Morgan Andrew P , Greenstein Seth , Bell Timothy A , Stevans Alicia M , Feathers Ryan W , Patel Sunny , Cates Sarah E , Shaw Ginger D , Miller Darla R , Chesler Elissa J , McMillian Leonard , O’Brien Deborah A , Villena Fernando Pardo-Manuel de 
Published: June 2017

Abstract
The goal of the Collaborative Cross (CC) project was to generate and distribute over 1000 independent mouse recombinant inbred strains derived from eight inbred founders. With inbreeding nearly complete, we estimated the extinction rate among CC lines at a remarkable 95%, which is substantially higher than in the derivation of other mouse recombinant inbred populations. Here, we report genome-wide allele frequencies in 347 extinct CC lines. Contrary to expectations, autosomes had equal allelic contributions from the eight founders, but chromosome X had significantly lower allelic contributions from the two inbred founders with underrepresented subspecific origins (PWK/PhJ and CAST/EiJ). By comparing extinct CC lines to living CC strains, we conclude that a complex genetic architecture is driving extinction, and selection pressures are different on the autosomes and chromosome X. Male infertility played a large role in extinction as 47% of extinct lines had males that were infertile. Males from extinct lines had high variability in reproductive organ size, low sperm counts, low sperm motility, and a high rate of vacuolization of seminiferous tubules. We performed QTL mapping and identified nine genomic regions associated with male fertility and reproductive phenotypes. Many of the allelic effects in the QTL were driven by the two founders with underrepresented subspecific origins, including a QTL on chromosome X for infertility that was driven by the PWK/PhJ haplotype. We also performed the first example of cross validation using complementary CC resources to verify the effect of sperm curvilinear velocity from the PWK/PhJ haplotype on chromosome 2 in an independent population across multiple generations. While selection typically constrains the examination of reproductive traits toward the more fertile alleles, the CC extinct lines provided a unique opportunity to study the genetic architecture of fertility in a widely genetically variable population. We hypothesize that incompatibilities between alleles with different subspecific origins is a key driver of infertility. These results help clarify the factors that drove strain extinction in the CC, reveal the genetic regions associated with poor fertility in the CC, and serve as a resource to further study mammalian infertility.
Best Fed Beginnings: A Nationwide Quality Improvement Initiative to Increase Breastfeeding
Authors: Feldman-Winter Lori , Ustianov Jennifer , Anastasio Julius , Butts-Dion Sue , Heinrich Patricia , Merewood Anne , Bugg Kimarie , Donohue-Rolfe Sarah , Homer Charles J. 
Published: June 2017

BACKGROUND AND OBJECTIVE:
In response to a low number of Baby-Friendly–designated hospitals in the United States, the Centers for Disease Control and Prevention funded the National Institute for Children’s Health Quality to conduct a national quality improvement initiative between 2011 and 2015. The initiative was entitled Best Fed Beginnings and enrolled 90 hospitals in a nationwide initiative to increase breastfeeding and achieve Baby-Friendly designation.

METHODS:
The intervention period lasted from July 2012 to August 2014. During that period, data on process indicators aligned with the Ten Steps to Successful Breastfeeding and outcome measures (overall and exclusively related to breastfeeding) were collected. In addition, data on the Baby-Friendly designation were collected after the end of the intervention through April 2016. Hospitals assembled multidisciplinary teams that included parent partners and community representatives. Three in-person learning sessions were interspersed with remote learning and tests of change, and a Web-based platform housed resources and data for widespread sharing.

RESULTS:
By April 2016, a total of 72 (80%) of the 90 hospitals received the Baby-Friendly designation, nearly doubling the number of designated hospitals in the United States. Participation in the Best Fed Beginnings initiative had significantly high correlation with designation compared with hospital applicants not in the program (Pearson’s r [235]: 0.80; P &lt; .01). Overall breastfeeding increased from 79% to 83% (t = 1.93; P = .057), and exclusive breastfeeding increased from 39% to 61% (t = 9.72; P &lt; .001).

CONCLUSIONS:
A nationwide initiative of maternity care hospitals accomplished rapid transformative changes to achieve Baby-Friendly designation. These changes were accompanied by a significant increase in exclusive breastfeeding.
Região Norte, política de formação de professores e avaliação de polos do sistema Universidade Aberta do Brasil
Authors: Pantoja Antunes Graciete 
Published: June 2017

No presente texto se tem por objetivo apresentar, em linhas gerais, a região norte e suas políticas de formação de professores implementadas nos últimos 5 anos, localizando neste quadro a importância do sistema Universidade Aberta do Brasil e de seus polos de apoio presencial, conforme metodologia de pesquisa vinculada ao projeto “Institucionalização da EaD no Brasil”. Maior ênfase será dada aos dados dos estados do Acre e Pará, haja vista que duas autoras do presente texto atuam como coordenadoras dos polos de apoio presencial do Sistema Universidade Aberta do Brasil nestes estados. Concebemos o texto, com base em depoimento de coordenadores de polos que participaram da pesquisa participativa,realizada pelo Grupo de Pesquisa “Formação docente e tecnologias de informação e comunicação”, LANTE/UFF. Objetivamos também identificar a estrutura e o funcionamento dos Polos de Apoio presencial da UAB da região Norte, assim como o instrumento de avaliação dos polos aplicado nessa região.
POLO UAB DE CACHOEIRO DE ITAPEMIRIM – ES: DA INSTITUCIONALIZAÇÃO A FORMAÇÃO DE SERVIDORES MUNICIPAIS
Authors: Cellin Joelma 
Published: June 2017

RESUMO O presente artigo apresenta a institucionalização do Polo de Apoio Presencial da Universidade Aberta do Brasil - UAB do Município de Cachoeiro de Itapemirim- ES e oportuniza uma reflexão quanto à contribuição desta Instituição na formação e capacitação dos profissionais do quadro da educação e dos servidores administrativos da Prefeitura local. Apresenta ainda, a experiência de onze anos na Educação a Distância do Estado do Espírito Santo, que se inicia no ano de 2001, com a Universidade Federal do Espírito Santo, através dos Centros Regionais de Educação a Distância - cre@ads e que perpassa pela implantação do Sistema Universidade Aberta do Brasil – UAB. Demonstra que a implementação do Polo UAB de Cachoeiro é positiva, através da oferta dos cursos de graduação, especialização e aperfeiçoamento, por meio das Instituições de Ensino Superior credenciadas no Ministério da Educação, a saber: Universidade Federal do Espírito Santo - UFES e o Instituto Federal do Espírito Santo - IFES. Descritores: Universidade Aberta do Brasil; Polos; Institucionalização.
A influência das percepções de benefícios, resultados e dificuldades dos grupos de pesquisa sobre as interações com empresas
Authors: Araujo Veneziano de Castro , Mascarini Suelene , Santos Emerson Gomes dos , Costa Ariana Ribeiro 
Published: June 2017

O presente trabalho tem por objetivo investigar como as percepções dos grupos de pesquisa acadêmica sobre resultados, benefícios e dificuldades esperados das interações influenciam o número de interações que eles realizam com empresas, com base em um survey sobre as relações universidade-empresa no Brasil. Para tanto, por meio da Teoria de Resposta ao Item não Paramétrico (TRIN), foram criados agrupamentos não ad hoc a partir de padrões de resposta de pesquisadores para as percepções analisadas. A partir dos agrupamentos, foi estimado um modelo para identificar como essas percepções influenciam o número de interações dos grupos. Os resultados apontam que os grupos de pesquisa que percebem benefícios intangíveis e resultados de conhecimentos como mais importantes tendem a apresentar maior número de interações com empresas. Além disso, as dificuldades transacionais implicam menos interações com empresas. Por fim, são tecidos alguns desdobramentos para políticas públicas.
Bisphosphonate Use and the Risk of Undergoing Total Knee Arthroplasty in Osteoporotic Patients with Osteoarthritis
Authors: Fu Shau-Huai , Wang Chen-Yu , Yang Rong-Sen , Wu Fe-Lin Lin , Hsiao Fei-Yuan 
Published: June 2017

Background:
The use of bisphosphonates has been reported to have potential beneficial effects on knee osteoarthritis, but existing studies have limitations. The purpose of this study was to examine the association of bisphosphonate use with the risk of undergoing total knee arthroplasty and with the consumption of pain medication among osteoporotic patients with knee osteoarthritis.

Methods:
We identified patients who were newly diagnosed with knee osteoarthritis among a cohort of patients with osteoporosis from 2009 to 2012 in the National Health Insurance Research Database in Taiwan. We further categorized these patients into 2 groups: those who were treated with bisphosphonates (bisphosphonate users) and those who were not treated with any anti-osteoporosis drug (nonusers). Bisphosphonate treatment adherence was calculated by the medication possession ratio (MPR) as the proportion of days of bisphosphonate treatment within a fixed duration; an MPR of ≥80% was considered high adherence. The primary and secondary outcomes of interest were undergoing total knee arthroplasty and the use of pain medication, respectively. Analyses using Cox proportional hazard models with propensity-score adjustment were performed to estimate the association between bisphosphonate use and the risk of undergoing total knee arthroplasty. The incremental change in the mean accumulated defined daily doses of pain medications among both bisphosphonate users and nonusers was calculated.

Results:
We identified 16,276 bisphosphonate users and 123,791 nonusers of any anti-osteoporosis drug among the patients with osteoporosis who were newly diagnosed with osteoarthritis. Bisphosphonate use was significantly associated with a decreased risk of total knee arthroplasty (adjusted hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.69 to 0.83; p < 0.001). In patients with a follow-up period of ≥24 months and an MPR of ≥80%, the effect size was significantly greater (adjusted HR, 0.66; p = 0.048). Over the 5 years of follow-up, we found a significantly greater decrease in the use of pain medication among bisphosphonate users than among nonusers (p < 0.001; Chow test).

Conclusions:
Among patients with osteoporosis and osteoarthritis, bisphosphonate use was associated with a significantly lower risk of total knee arthroplasty, especially in patients with high adherence and longer treatment duration. A lower consumption of pain medication was also found for bisphosphonate users among the patients with osteoporosis and osteoarthritis.

Level of Evidence:
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Familial Clustering Identified in Periprosthetic Joint Infection Following Primary Total Joint Arthroplasty
Authors: Anderson Mike B. , Curtin Karen , Wong Jathine , Pelt Christopher E. , Peters Christopher L. , Gililland Jeremy M. 
Published: June 2017

Background:
It is estimated that the cost to treat periprosthetic joint infection in the United States will approach $1.62 billion by 2020. Thus, the need to better understand the pathogenesis of periprosthetic joint infection is evident. We performed a population-based, retrospective cohort study to determine if familial clustering of periprosthetic joint infection was observed.

Methods:
Analyses were conducted using software developed at the Utah Population Database (UPDB) in conjunction with the software package R. The cohort was obtained by querying the UPDB for all patients undergoing total joint arthroplasty and for those patients who had subsequent periprosthetic joint infection. The magnitude of familial risk was estimated by hazard ratios (HRs) from Cox regression models to assess the relative risk of periprosthetic joint infection in relatives and spouses. Using percentiles for age strata, we adjusted for sex, body mass index (BMI) of ≥30 kg/m2, and a history of smoking, diabetes, and/or end-stage renal disease. Additionally, we identified families with excess clustering of periprosthetic joint infection above that expected in the population using the familial standardized incidence ratio.

Results:
A total of 66,985 patients underwent total joint arthroplasty and 1,530 patients (2.3%) had a periprosthetic joint infection. The risk of periprosthetic joint infection following total joint arthroplasty was elevated in first-degree relatives (HR, 2.16 [95% confidence interval (CI), 1.29 to 3.59]) and combined first and second-degree relatives (HR, 1.79 [95% CI, 1.22 to 2.62]). Further, 116 high-risk pedigrees with a familial standardized incidence ratio of >2 and a p value of <0.05 were identified and 9 were selected for genotyping studies based on the observed periprosthetic joint infection/total joint arthroplasty ratio and visual inspection of the pedigrees for lack of excessive comorbidities.

Conclusions:
Although preliminary, these data may help to guide further genetic research associated with periprosthetic joint infections. An understanding of familial risks could lead to new discoveries in creating patient-centered pathways for infection prevention in patients at risk.

Level of Evidence:
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Energy implications of the millennium drought on urban water cycles in Southeast Australian cities
Authors: Lam K. L. , Lant P. A. , Kenway S. J. 
Published: June 2017

Abstract
During the Millennium Drought in Australia, a wide range of supply-side and demand-side water management strategies were adopted in major southeast Australian cities. This study undertakes a time-series quantification (2001–2014) and comparative analysis of the energy use of the urban water supply systems and sewage systems in Melbourne and Sydney before, during and after the drought, and evaluates the energy implications of the drought and the implemented strategies. In addition, the energy implications of residential water use in Melbourne are estimated. The research highlights that large-scale adoption of water conservation strategies can have different impacts on energy use in different parts of the urban water cycle. In Melbourne, the per capita water-related energy use reduction in households related to showering and clothes-washing alone (46% reduction, 580 kWhth/p/yr) was far more substantial than that in the water supply system (32% reduction, 18 kWhth/p/yr). This historical case also demonstrates the importance of balancing supply- and demand-side strategies in managing long-term water security and related energy use. The significant energy saving in water supply systems and households from water conservation can offset the additional energy use from operating energy-intensive supply options such as inter-basin water transfers and seawater desalination during dry years.
Negative Pressure Wound Therapy for Closed Surgical Wounds in Musculoskeletal Oncology Patients - A Case-Control Trial
Authors: Kong Roderick , Shields David , Bailey Oliver , Gupta Sanjay , Mahendra Ashish 
Published: June 2017

Following excision of musculoskeletal tumours, patients are at high risk of wound issues such as infection, dehiscence and delayed healing. This is due to a multitude of factors including the invasive nature of the disease, extensive soft tissue dissection, disruption to blood and lymphatic drainage, residual cavity and adjuvant therapies. The use of negative pressure wound therapy (NPWT) has a growing body of evidence on its beneficial effect of wound healing such as promoting cell differentiation, minimising oedema and thermoregulation. Traditionally, these dressings have been used for open or dehisced wounds; however recent research has investigated its role in closed wounds.Aim:To evaluate the effect of NPWT in patients with closed wounds, either primarily or with flap coverage, in our high risk group. Consecutive patients who had a NPWT dressing applied were selected, and a control group was established by a blinded researcher with matching for tissue diagnosis, surgical site, gender and age. The primary outcome measured was documented for wound complications, with secondary data collected on radiotherapy and wound drainage.Results:Patients were well matched between the intervention (n=9) and control (n=9) groups for gender, age and tissue diagnosis. Both groups had 1 patient who underwent preoperative radiotherapy. A total of 3 wound infections occurred in the control group and none in the NPWT group. Overall there was a trend towards lower drain output and statistically significantly reduced infection rate in the NPWT group.Conclusion:In this short series, despite the NPWT patients having more additional risk factors for wound issues, they resulted in fewer infections. The sample size is not sufficient to have statistically significant reduction. Further evaluation on the value of NPWT in this patient group should be prospectively evaluated.
A Novel Antibiotic Spacer for Significant Proximal Femoral Loss - Surgical Technique
Authors: Shields David , Kong Roderick , Gupta Sanjay , Mahendra Ashish 
Published: June 2017

Background:Infections of proximal femora with prosthetic implants in situ have long been a major concern in orthopedic surgery. The gold standard in the management of infected proximal femurs in the presence of prosthetic implants has traditionally been a two-stage revision. However, this is challenging in the setting of extensive bone loss.Methods:A 3 case series of such infections leading to extensive loss of the proximal femur is presented. We specifically describe our technique of debriding the infected segments as well as utilization of a trochanteric slide osteotomy to resect the femur.We also demonstrate preparation of the “pseudoacetabulum” and femoral component with an antibiotic spacer.Conclusion:The high cost of such a procedure is offset by reduction in time spent in hospital. The spacer also helps to allow mobilization by partial weight bearing on a stable femoral component and provide pain control which improves quality of life as compared to prolonged intravenous antimicrobial therapy.
The translation of texts from the tourist sector: textual conventions, cultural distance and other constraints
Authors: Kelly Dorothy 
Published: June 2017

The translation of texts in the tourist sector has receives little attention in works on translation, despite illustrating a wide-ranging series of challenges for the translator. This paper addresses some of those challenges, most particularly those related to differing reader expectations arising from differing textual conventions regarding content and style. La traducción de textos del sector turístico ha recibido poca atención en los estudios teóricos de la traducción, a pesar del hecho de que estos textos ilustren una amplia gama de desafíos para la traducción. En este artículo se pretende plantear algunos de esos desafíos, y muy especialmente los relacionados con las diferentes expectativas del/la lector/a del texto de origen y del texto de término surgidas de las diferentes convenciones textuales en cuanto a contenido y estilo.