bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteoblasts are “educated” by crosstalk with metastatic breast cancer cells in the bone tumor microenvironment
Authors: Kolb Alexus D. , Shupp Alison B. , Mukhopadhyay Dimpi , Marini Frank C. , Bussard Karen M. 
Published: February 2019

AbstractIntroductionIn a cancer-free environment in the adult, the skeleton continuously undergoes remodeling. Bone-resorbing osteoclasts excavate erosion cavities, and bone-depositing osteoblasts synthesize osteoid matrix that forms new bone, with no net bone gain or loss. When metastatic breast cancer cells invade the bone, this balance is disrupted. Patients with bone metastatic breast cancer frequently suffer from osteolytic bone lesions that elicit severe bone pain and fractures. Bisphosphonate treatments are not curative. Under ideal circumstances, osteoblasts would synthesize new matrix to fill in erosion cavities caused by osteoclasts, but this is not what occurs. Our prior evidence demonstrated that osteoblasts are diverted from laying down bone matrix to producing cytokines that facilitate breast cancer cell maintenance in late-stage disease. Here, we have new evidence to suggest that there are subpopulations of osteoblasts in the tumor niche as evidenced by their protein marker expression that have distinct roles in tumor progression in the bone.MethodsTumor-bearing tibia of mice was interrogated by immunofluorescent staining for the presence of osteoblasts and alterations in niche protein expression. De-identified tissue from patients with bone metastatic breast cancer was analyzed for osteoblast subpopulations via multi-plex immunofluorescent staining. Effects of breast cancer cells on osteoblasts were recapitulated in vitro by osteoblast exposure to breast cancer-conditioned medium. Triple-negative and estrogen receptor-positive breast cancer proliferation, cell cycle, and p21 expression were assessed upon contact with “educated” osteoblasts.ResultsA subpopulation of osteoblasts was identified in the bone tumor microenvironment in vivo of both humans and mice with bone metastatic breast cancer that express RUNX2/OCN/OPN but is negative for IL-6 and alpha-smooth muscle actin. These tumor “educated” osteoblasts (EOs) have altered properties compared to “uneducated” osteoblasts and suppress both triple-negative and estrogen receptor-positive breast cancer cell proliferation and increase cancer cell p21 expression. EO effects on breast cancer proliferation were mediated by NOV and decorin. Importantly, the presence of EO cells in the tibia of mice bearing tumors led to increased amounts of alkaline phosphatase and suppressed the expression of inflammatory cytokines in vivo.ConclusionsOur work reveals that there is a subpopulation of osteoblasts in the bone tumor microenvironment that demonstrate a functional role in retarding breast cancer cell growth.
Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma: Results From the Phase IIIb/IV CheckMate 511 Trial
Authors: Lebbé Celeste , Meyer Nicolas , Mortier Laurent , Marquez-Rodas Ivan , Robert Caroline , Rutkowski Piotr , Menzies Alexander M. , Eigentler Thomas , Ascierto Paolo A. , Smylie Michael , Schadendorf Dirk , Ajaz Mazhar , Svane Inge Marie , Gonzalez Rene , Rollin Linda , Lord-Bessen Jennifer , Saci Abdel , Grigoryeva Elena , Pigozzo Jacopo 
Published: February 2019

PURPOSE Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1+IPI3) is approved for first-line treatment of patients with advanced melanoma in several countries. We conducted a phase IIIb/IV study (CheckMate 511) to determine if nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (NIVO3+IPI1) improves the safety profile of the combination. PATIENTS AND METHODS Patients (N = 360) age 18 years or older with previously untreated, unresectable stage III or IV melanoma were randomly assigned 1:1 to NIVO3+IPI1 or NIVO1+IPI3 once every 3 weeks for four doses. After 6 weeks, all patients received NIVO 480 mg once every 4 weeks until disease progression or unacceptable toxicity. The primary end point was a comparison of the incidence of treatment-related grade 3 to 5 adverse events (AEs) between groups. Secondary end points included descriptive analyses of objective response rate, progression-free survival, and overall survival. The study was not designed to formally demonstrate noninferiority of NIVO3+IPI1 to NIVO1+IPI3 for efficacy end points. RESULTS At a minimum follow-up of 12 months, incidence of treatment-related grade 3 to 5 AEs was 34% with NIVO3+IPI1 versus 48% with NIVO1+IPI3 ( P = .006). In descriptive analyses, objective response rate was 45.6% in the NIVO3+IPI1 group and 50.6% in the NIVO1+IPI3 group, with complete responses in 15.0% and 13.5% of patients, respectively. Median progression-free survival was 9.9 months in the NIVO3+IPI1 group and 8.9 months in the NIVO1+IPI3 group. Median overall survival was not reached in either group. CONCLUSION The CheckMate 511 study met its primary end point, demonstrating a significantly lower incidence of treatment-related grade 3-5 AEs with NIVO3+IPI1 versus NIVO1+IPI3. Descriptive analyses showed that there were no meaningful differences between the groups for any efficacy end point, although longer follow up may help to better characterize efficacy outcomes.
Clinical Use of Epidermal Growth Factor Receptor Testing in Patients With Advanced Lung Cancer by Physicians: Survey of US and International Patterns
Authors: Peters Matthew , Kim Edward S. , Hirsch Vera 
Published: February 2019

PURPOSE Guidelines recommend testing for EGFR mutation at diagnosis of advanced non–small-cell lung cancer to guide treatment. Two surveys, 18 months apart, aimed to identify changes in EGFR mutation testing and treatment practices in non–small-cell lung cancer. METHODS The first survey of 562 physicians from Canada, France, Germany, Italy, Japan, South Korea, Spain, Taiwan, the United Kingdom, and the United States was conducted between December 2014 and January 2015. The second, between July and August 2016, surveyed 707 physicians in the same countries with the addition of China; China was excluded from year-on-year comparisons. RESULTS Globally (excluding China), physicians requested EGFR mutation testing in 80% (excluding China; 2015: 81%) of patients before first-line therapy. In 2016, 18% of results were not received before initiating treatment, a significant improvement over 2015 (23%). Reasons for not testing included tumor histology, insufficient tissue, poor performance status, and long turnaround time, although this had significantly improved in 2016 from 2015. Prolonging of survival/extending life was deemed the most important therapy goal in first-line treatment of both cohorts. CONCLUSION Improvements in availability of test results before first-line therapy were seen, but incomplete implementation of guidelines is still observed, resulting in a large proportion of patients not receiving tyrosine kinase inhibitor treatment on the basis of mutation status. The reasons for not testing remained the same, year-on-year: tumor histology, insufficient tissue, poor performance status, and long test turnaround time. Receiving timely results must be addressed, if treatment parity for eligible patients can be achieved. Physician education and closer guideline concordance are key steps to improve outcomes.
Kwisin in Chosŏn Literati Writings: Multilayered Recognition, Cultural Sensibility, and Imagination
Authors: Choe Keysook 
Published: February 2019

Abstract
This paper investigates Confucian literati’s multilayered recognition of kwisin in the Chosŏn dynasty by focusing on three distinct genres: philosophical writings, ritual writings, and fictionalized writings. Multifaceted concepts of kwisin in these three genres are analyzed through interpretive lenses such as philosophical thought, cultural sensibilities, and literary imagination. In the context of philosophy, Chosŏn literati developed the traditional concept of kwisin as spiritual beings in accordance with the Confucian paradigms. In the context of empirical cultural fields, however, sadaebu collected fantastic stories as contemporary cultural research with the aim of publishing encyclopedic collections. In such works, Chosŏn intelligentsia exhibited a dual position: one criticizing the worship of kwisin by the lower classes, the other recognizing such as a cultural tradition. Although literati criticized fictional stories containing ghosts, they penned their own versions with female apparitions, maintaining their patriarchal Confucian ideology by “otherizing” these ghosts of unclear familial lineage. Fictional narratives in which kwisin appeared fostered communication across ideology, folk knowledge, and experiential sensibility and embraced the metaphysical recognition and everyday sense of kwisin. Gendered kwisin stories played the cultural roles of criticizing and reflecting social paradox and received a wide range of social sympathy, from the elite class to commoners.
Leishmania amazonensis hijacks host cell lysosomes involved in plasma membrane repair to induce invasion in fibroblasts
Authors: Cavalcante-Costa Victor Soares , Costa-Reginaldo Mariana , Queiroz-Oliveira Thamires , Oliveira Anny C. S. , Couto Natália Fernanda , dos Anjos Danielle Oliveira , Lima-Santos Jane , Andrade Luciana Oliveira , Horta Maria Fátima , Castro-Gomes Thiago 
Published: February 2019

ABSTRACT
Intracellular parasites of the genus Leishmania are the causative agents of leishmaniasis. The disease is transmitted by the bite of a sand fly vector, which inoculates the parasite into the skin of mammalian hosts, including humans. During chronic infection the parasite lives and replicates inside phagocytic cells, notably the macrophages. An interesting, but overlooked finding, is that other cell types and even non-phagocytic cells have been found to be infected by Leishmania spp. Nevertheless, the mechanisms by which Leishmania invades such cells had not been previously studied. Here, we show that L. amazonensis can induce their own entry into fibroblasts independently of actin cytoskeleton activity, and, thus, through a mechanism that is distinct from phagocytosis. Invasion involves subversion of host cell functions, such as Ca2+ signaling and recruitment and exocytosis of host cell lysosomes involved in plasma membrane repair.
This article has an associated First Person interview with the first author of the paper.
Reducing Unnecessary Treatment of Asymptomatic Elevated Blood Pressure with Intravenous Medications on the General Internal Medicine Wards: A Quality Improvement Initiative
Authors: Jacobs Zachary G , Najafi Nader , Fang Margaret C , Prasad Priya A , Abe‐Jones Yumiko , Auerbach Andrew D , Patel Sajan 
Published: February 2019

BACKGROUNDAsymptomatic elevated blood pressure (BP) is common in the hospital. There is no evidence supporting the use of intravenous (IV) antihypertensives in this setting.OBJECTIVETo determine the prevalence and effects of treating asymptomatic elevated BP with IV antihypertensives and to investigate the efficacy of a quality improvement (QI) initiative aimed at reducing utilization of these medications.DESIGNRetrospective cohort study.SETTINGUrban academic hospital.PATIENTSPatients admitted to the general medicine service, including the intensive care unit (ICU), with ≥1 episode of asymptomatic elevated BP (>160/90 mm Hg) during hospitalization.INTERVENTIONA two‐tiered, QI initiative.MEASUREMENTSThe primary outcome was the monthly proportion of patients with asymptomatic elevated BP treated with IV labetalol or hydralazine. We also analyzed median BP and rates of balancing outcomes (ICU transfers, rapid responses, cardiopulmonary arrests).RESULTSWe identified 2,306 patients with ≥1 episode of asymptomatic elevated BP during the 10‐month preintervention period, of which 251 (11%) received IV antihypertensives. In the four‐month postintervention period, 70 of 934 (7%) were treated. The odds of being treated were 38% lower in the postintervention period after adjustment for baseline characteristics, including length of stay and illness severity (OR = 0.62; 95% CI 0.47‐0.83; P = .001). Median SBP was similar between pre‐ and postintervention (167 vs 168 mm Hg; P = .78), as were the adjusted proportions of balancing outcomes.CONCLUSIONSHospitalized patients with asymptomatic elevated BP are commonly treated with IV antihypertensives, despite the lack of evidence. A QI initiative was successful at reducing utilization of these medications.
Deimplementation of Routine Chest X‐rays in Adult Intensive Care Units
Authors: Trumbo Silas P , Iams Wade T , Limper Heather M , Goggins Kathryn , Gibson Jayme , Oliver Lauren , Leverenz David L , Samuels Lauren R , Brady Donald W , Kripalani Sunil 
Published: February 2019

BACKGROUNDChoosing Wisely® is a national initiative to deimplement or reduce low‐value care. However, there is limited evidence on the effectiveness of strategies to influence ordering patterns.OBJECTIVEWe aimed to describe the effectiveness of an intervention to reduce daily chest X‐ray (CXR) ordering in two intensive care units (ICUs) and evaluate deimplementation strategies.DESIGNWe conducted a prospective, nonrandomized study with control data from a historical period. Qualitative evaluation was guided by the Consolidated Framework for Implementation Research.SETTINGThe study was performed in the medical intensive care unit (MICU) and cardiovascular intensive care unit (CVICU) of an academic medical center in the United States from October 2015 to June 2016.PARTICIPANTSThe initiative included the staff of the MICU and CVICU (physicians, surgeons, nurse practitioners, fellows, residents, medical students, and X‐ray technologists).INTERVENTION COMPONENTSWe utilized provider education, peer champions, and weekly data feedback of CXR ordering rates.MEASUREMENTSWe analyzed the CXR ordering rates and factors facilitating or inhibiting deimplementation.RESULTSSegmented linear time‐series analysis suggested a small but statistically significant decrease in CXR ordering rates in the CVICU (P < .001) but not in the MICU. Facilitators of deimplementation, which were more prominent in the CVICU, included engagement of peer champions, stable staffing, and regular data feedback. Barriers included the need to establish goal CXR ordering rates, insufficient intervention visibility, and waning investment among medical residents in the MICU due to frequent rotation and competing priorities.CONCLUSIONSIntervention modestly reduced CXRs ordered in one of two ICUs evaluated. Understanding why adoption differed between the two units may inform future interventions to deimplement low‐value diagnostic tests.
Improving Patient Flow: Analysis of an Initiative to Improve Early Discharge
Authors: Destino Lauren , Bennett Denise , Wood Matthew , Acuna Christy , Goodman Stephanie , Asch Steven M. , Platchek Terry 
Published: February 2019

BACKGROUNDDischarge delays adversely affect hospital bed availability and thus patient flow.OBJECTIVEWe aimed to increase the percentage of early discharges (EDCs; before 11 am). We hypothesized that obtaining at least 25% EDCs would decrease emergency department (ED) and postanesthesia care unit (PACU) hospital bed wait times.DESIGNThis study used a pre/postintervention retrospective analysis.SETTINGAll acute care units in a quaternary care academic children's hospital were included in this study.PATIENTSThe patient sample included all discharges from the acute care units and all hospital admissions from the ED and PACU from January 1, 2014, to December 31, 2016.INTERVENTIONA multidisciplinary team identified EDC barriers, including poor identification of EDC candidates, accountability issues, and lack of team incentives. A total of three successive interventions were implemented using Plan–Do‐Check‐Act (PDCA) cycles over 10 months between 2015 and 2016 addressing these barriers. Interventions included EDC identification and communication, early rounding on EDCs, and modest incentives.MEASUREMENTSCalendar month EDC percentage, ED (from time bed requested to the time patient left ED) and PACU (from time patient ready to leave to time patient left PACU) wait times were measured.RESULTSEDCs increased from an average 8.8% before the start of interventions (May 2015) to 15.8% after interventions (February 2016). Using an interrupted time series, both the jump and the slope increase were significant (3.9%, P = .02 and 0.48%, P < .01, respectively). Wait times decreased from a median of 221 to 133 minutes (P < .001) for ED and from 56 to 36 minutes per patient (P = .002) for PACU.CONCLUSIONA multimodal intervention was associated with more EDCs and decreased PACU and ED bed wait times.
Patient, Caregiver, and Clinician Perspectives on Expectations for Home Healthcare after Discharge: A Qualitative Case Study
Authors: Jones Christine D , Jones Jacqueline , Bowles Kathryn H , Schroeder Shara , Masoudi Frederick A , Coleman Eric A , Falvey Jason , Levy Cari R , Boxer Rebecca S 
Published: February 2019

BACKGROUNDPatients discharged from the hospital with skilled home healthcare (HHC) services have multiple comorbidities, high readmission rates, and multiple care needs. In prior work, HHC nurses described that patients often express expectations for services beyond the scope of skilled HHC.OBJECTIVEThe objective of this study is to evaluate and compare expectations for HHC from the patient, caregiver, and HHC perspectives after hospital discharge.DESIGN/PARTICIPANTSThis was a descriptive qualitative case study including HHC patients, caregivers, and clinicians. Patients were discharged from an academic medical center between July 2017 and February 2018.RESULTSThe sample (N = 27) included 11 HHC patients, eight caregivers, and eight HHC clinicians (five nurses and three physical therapists). Patient mean age was 66 years and the majority were female, white, and had Medicare. We observed main themes of clear and unclear expectations for HHC after discharge. Clear expectations occur when the patient and/or caregiver have expectations for HHC aligned with the services received. Unclear expectations occur when the patient and/or caregiver expectations are uncertain or misaligned with the services received. Patients and caregivers with clear expectations for HHC frequently described prior experiences with skilled HHC or work experience within the healthcare field. In most cases with unclear expectations, the patient and caregiver did not have prior experience with HHC.CONCLUSIONSTo improve HHC transitions, we recommend actively engaging both patients and caregivers in the hospital and HHC settings to provide education about HHC services, and assess and address additional care needs.
Clinical Guideline Highlights for the Hospitalist: The Use of Intravenous Fluids in the Hospitalized Adult
Authors: Gottenborg Emily , Pierce Read 
Published: February 2019

GUIDELINE TITLEIntravenous Fluid Therapy in Adults in HospitalRELEASE DATEDecember, 2013PRIOR VERSIONNot ApplicableDEVELOPERMultidisciplinary Guideline Development Group within the United Kingdom's National Clinical Guideline CentreFUNDING SOURCENational Institute for Health and Care ExcellenceTARGET POPULATIONHospitalized adult patients
Response of supplemental cassava root sievate - cassava leaf meal based diets on carcass and cost benefits of kano brown goats Capra aegagrus
Authors: Obioha Ahaotu E. , Kennedy Okorie , Abayomi Akinfemi , Okechukwu Emeribe E. 
Published: February 2019

The experiment was conducted to determine the organ weight characteristics, carcass yield and cost benefits of Kano Brown goats fed cassava root sievate and cassava leaf meal (CRSCLM) based diets as supplement to (Pennisetum purpureum) using 36 Kano Brown goats of 8 to 10 months of age.Four diets T1, T2, T3,and T4, were formulated at the levels of 0%, 20%, 40% and 60% CRSCLM respectivelyin a completely randomized design. Each animal received a designated treatment diet in the morning for 97 days. Feed offered was based on 3.5% body weight per day; the animals in addition were fed a kg wilted chopped P. purpureum later in the day as basal diet to enhance rumination and fine chewing. Results on carcass indices showed significant (p<0.05) response on live weight at slaughter, empty carcass weight, warm carcass weight, dressing percentage, shoulder, leg, loin, end and shank with T4having relatively best results. The dressing percentage was numerically (49.59%) best at T4. On the offal weights, head and full guts were significantly (p<0.05) improved for T4and T1goats. The organ characteristic proved the safety of using CRSCLM through the significantly (p<0.05) lower organ weights at T4goats. Cost per kg feed, feed cost/weight gainand cost/benefit ratio were positively influenced (p<0.05) at T4with expected income of 4.79 / 1 invested. It could therefore be concluded that Kano Brown goats fed 60% CRSCLM had the best carcass and organ yields at a reduced feed cost. Keywords: Pennisetum purpureum, Kano brown goats, Cassava leaf meal, Cassava root sievate,
"Una mancha en el sol de Euclides": Hilbert y la teoría euclídea de las proporciones
Authors: Giovannini Eduardo N. 
Published: February 2019

El artículo examina una de las contribuciones más importantes a los fundamentos de la geometría euclídea elemental lograda por David Hilbert en su obra Fundamentos de la geometría (1899), a saber: la reconstrucción de la teoría euclídea de las proporciones y de los triángulos semejantes. Se argumenta que dicha reconstrucción no sólo estuvo motivada por la identificación de Hilbert de suposiciones implícitas en la teoría de Euclides, sino que además estuvo esencialmente ligada a la preocupación por la 'pureza del método'. Más aún, se afirma que, en este caso específico, el requerimiento de Hilbert por la pureza del método posee un carácter general o fundacional, esto es, no se refiere a la demostración de un teorema en particular, sino más bien es planteado respecto de la construcción axiomática de la teoría misma.
La construcción lógica de la Fenomenología del Espíritu de Hegel
Authors: López Diana María 
Published: February 2019

La Fenomenología del espíritu representa el punto de coronamiento de diversos proyectos elaborados por Hegel en los cursos de los años 1803-1807 del período de Jena. Así también, en algún sentido, la anticipación de su Lógica posterior. El artículo tiene como propósito dedicar algunas meditaciones básicas al origen de esta obra en relación con los cursos del período de Jena, la posible transformación conceptual de la Fenomenología durante el tiempo de su redacción y su contribución a la Ciencia de la lógica posterior.
¿En qué sentido es la Lógica de Hegel el dinero del espíritu? Interpretación del sistema hegeliano desde la génesis del dinero en El capital de Marx
Authors: Castiglioni Germán D. 
Published: February 2019

Es sabido que las obras de Marx, en sus distintas épocas, guardan siempre una relación conflictiva con Hegel. Pero, al mismo tiempo, esta relación se ve afectada continuamente por el propio desarrollo del pensamiento de Marx. Teniendo en cuenta este desarrollo, en el presente trabajo intentaremos brindar una interpretación marxiana del sistema hegeliano, tomando como punto de partida la frase juvenil de Marx que afirma que la Ciencia de la lógica de Hegel es "el dinero del espíritu". Sin embargo, bajo la premisa de que Marx está mucho más próximo a Hegel en su período de madurez que en su juventud, daremos un nuevo sentido a aquella frase juvenil a partir del tratamiento del dinero en la primera sección de El capital. Esto nos proporcionará nuevas herramientas conceptuales para interpretar la filosofía de Hegel, justificando esta interpretación en los propios textos hegelianos.