bluuebunny/crossref_metadata_2025_split huggingface dataset:
Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration
Authors: Pui Ching-Hon , Yang Jun J. , Hunger Stephen P. , Pieters Rob , Schrappe Martin , Biondi Andrea , Vora Ajay , Baruchel André , Silverman Lewis B. , Schmiegelow Kjeld , Escherich Gabriele , Horibe Keizo , Benoit Yves C.M. , Izraeli Shai , Yeoh Allen Eng Juh , Liang Der-Cherng , Downing James R. , Evans William E. , Relling Mary V. , Mullighan Charles G. 
Published: August 2015

Purpose To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents. Methods A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article was reviewed and revised by the committee chairs of the major ALL study groups. Results With long-term survival rates for ALL approaching 90% and the advent of high-resolution genome-wide analyses, several international study groups or consortia were established to conduct collaborative research to further improve outcome. As a result, treatment strategies have been improved for several subtypes of ALL, such as infant, MLL-rearranged, Philadelphia chromosome–positive, and Philadelphia chromosome–like ALL. Many recurrent genetic abnormalities that respond to tyrosine kinase inhibitors and multiple genetic determinants of drug resistance and toxicities have been identified to help develop targeted therapy. Several genetic polymorphisms have been recognized that show susceptibility to developing ALL and that help explain the racial/ethnic differences in the incidence of ALL. Conclusion The information gained from collaborative studies has helped decipher the heterogeneity of ALL to help improve personalized treatment, which will further advance the current high cure rate and the quality of life for children and adolescents with ALL.
Trebananib (AMG 386) in Combination With Sunitinib in Patients With Metastatic Renal Cell Cancer: An Open-Label, Multicenter, Phase II Study
Authors: Atkins Michael B. , Gravis Gwenaelle , Drosik Kazimierz , Demkow Tomasz , Tomczak Piotr , Wong Shirley S. , Michaelson M. Dror , Choueiri Toni K. , Wu Benjamin , Navale Lynn , Warner Douglas , Ravaud Alain 
Published: August 2015

Purpose Trebananib, an investigational recombinant peptide-Fc fusion protein, neutralizes the receptor-ligand interaction between Tie2 and angiopoietin-1/2. This phase II study was conducted to evaluate trebananib plus sunitinib, a vascular endothelial growth factor receptor inhibitor, in patients with metastatic clear cell renal cell carcinoma. Patients and Methods Adults with metastatic renal cell carcinoma were enrolled sequentially onto two cohorts that received sunitinib 50 mg once per day for 4 weeks on and 2 weeks off and intravenous trebananib once per week at a dose of 10 mg/kg in cohort A or 15 mg/kg in cohort B. The primary end points were incidences of adverse events (AEs) and dose interruptions of sunitinib during the first 12 weeks of treatment. Secondary end points included objective response rate and progression-free survival. Results Eighty-five patients were enrolled: 43 in cohort A, and 42 in cohort B. During the first 12 weeks of treatment, 58% and 57% of patients in cohorts A and B, respectively, had sunitinib dose interruptions (dose decrease, withholding, or withdrawal). The most frequent AEs were diarrhea (cohort A, 74%; cohort B, 67%), mucosal inflammation (cohort A, 49%; cohort B, 60%), and hypertension (cohort A, 52%; cohort B, 45%). AEs of grade 3 or greater occurred in 58% of patients in cohort A and in 69% of patients in cohort B. The objective response rate was 58% and 63% in cohorts A and B, respectively. The median progression-free survival time was 13.9 months (95% CI, 10.4 to 19.2) and 16.3 months (95% CI, 13.1 to 21.4) in cohorts A and B, respectively. The median overall survival time was 36 months (95% CI, 25.2 to not estimable) in cohort A and was not estimable (median follow-up, 25 months) in cohort B. Conclusion Trebananib plus sunitinib seemed to increase toxicity at the tested doses. Efficacy results suggest a potential benefit for the addition of trebananib to sunitinib.
Electroacupuncture Versus Gabapentin for Hot Flashes Among Breast Cancer Survivors: A Randomized Placebo-Controlled Trial
Authors: Mao Jun J. , Bowman Marjorie A. , Xie Sharon X. , Bruner Deborah , DeMichele Angela , Farrar John T. 
Published: August 2015

Purpose Hot flashes are a common and debilitating symptom among survivors of breast cancer. This study aimed at evaluating the effects of electroacupuncture (EA) versus gabapentin (GP) for hot flashes among survivors of breast cancer, with a specific focus on the placebo and nocebo effects. Patients and Methods We conducted a randomized controlled trial involving 120 survivors of breast cancer experiencing bothersome hot flashes twice per day or greater. Participants were randomly assigned to receive 8 weeks of EA or GP once per day with validated placebo controls (sham acupuncture [SA] or placebo pills [PPs]). The primary end point was change in the hot flash composite score (HFCS) between SA and PP at week 8, with secondary end points including group comparisons and additional evaluation at week 24 for durability of treatment effects. Results By week 8, SA produced significantly greater reduction in HFCS than did PP (−2.39; 95% CI, −4.60 to −0.17). Among all treatment groups, the mean reduction in HFCS was greatest in the EA group, followed by SA, GP, and PP (−7.4 v −5.9 v −5.2 v −3.4; P = < .001). The pill groups had more treatment-related adverse events than did the acupuncture groups: GP (39.3%), PP (20.0%), EA (16.7%), and SA (3.1%), with P = .005. By week 24, HFCS reduction was greatest in the EA group, followed by SA, PP, and GP (−8.5 v −6.1 v −4.6 v −2.8; P = .002). Conclusion Acupuncture produced larger placebo and smaller nocebo effects than did pills for the treatment of hot flashes. EA may be more effective than GP, with fewer adverse effects for managing hot flashes among breast cancer survivors; however, these preliminary findings need to be confirmed in larger randomized controlled trials with long-term follow-up.
Equivalence Ratio for Daunorubicin to Doxorubicin in Relation to Late Heart Failure in Survivors of Childhood Cancer
Authors: Feijen Elizabeth A.M. , Leisenring Wendy M. , Stratton Kayla L. , Ness Kirsten K. , van der Pal Helena J.H. , Caron Huib N. , Armstrong Gregory T. , Green Daniel M. , Hudson Melissa M. , Oeffinger Kevin C. , Robison Leslie L. , Stovall Marilyn , Kremer Leontien C.M. , Chow Eric J. 
Published: August 2015

Purpose Cumulative anthracycline dose is one of the strongest predictors of heart failure (HF) after cancer treatment. However, the differential risk for cardiotoxicity between daunorubicin and doxorubicin has not been rigorously evaluated among survivors of childhood cancer. These risks, which are based on hematologic toxicity, are currently assumed to be approximately equivalent. Patients and Methods Data from 15,815 survivors of childhood cancer who survived at least 5 years were used. Survivors were from the Emma Children's Hospital/Academic Medical Center (n = 1,349), the National Wilms Tumor Study (n = 364), the St Jude Lifetime Cohort Study (n = 1,695), and the Childhood Cancer Survivor Study (n = 12,407). The hazard ratio (HR) for clinical HF through age 40 years for doses of daunorubicin and doxorubicin (per 100-mg/m2 increments) was estimated by using Cox regression adjusted for sex, age at diagnosis, treatment with other anthracycline agents and chest radiation, and cohort membership. Results In total, 5,144 (32.5%) patients received doxorubicin as part of their cancer treatment, whereas 2,243 (14.7%) received daunorubicin. On the basis of 271 occurrences of HF during a median follow-up time after cohort entry of 17.3 years (range, 0.0 to 35.0 years), the cumulative incidence of HF at age 40 years was 3.2% (95% CI, 2.8% to 3.7%). The average ratio of HRs for daunorubicin to doxorubicin was 0.45 (95% CI, 0.23 to 0.73). A similar ratio was obtained by using a linear dose-response model, which yielded an HR of 0.49 (95% CI, 0.28 to 0.70). Conclusion Compared with doxorubicin, daunorubicin was less cardiotoxic among survivors of childhood cancer than most current guidelines suggest. This may have implications for follow-up guidelines. The feasibility of substitution of doxorubicin with daunorubicin in childhood cancer treatment protocols to reduce cardiotoxicity should be additionally investigated.
Activin A Increases Human Trophoblast Invasion by Inducing SNAIL-Mediated MMP2 Up-Regulation Through ALK4
Authors: Li Yan , Klausen Christian , Zhu Hua , Leung Peter C. K. 
Published: August 2015

Context:
Activin A increases matrix metalloproteinase (MMP) 2 expression and cell invasion in human trophoblasts, but whether the expression of MMP2 is essential for the proinvasive effect of activin A has yet to be determined. Moreover, the identity of the activin receptor-like kinase (ALK; TGF-β type I receptors) and downstream transcription factors (eg, SNAIL and SLUG) mediating the effects of activin on MMP2 expression and trophoblast cell invasion remains unknown.

Objective:
To elucidate the role of MMP2 in activin A-induced human trophoblast cell invasion as well as the involvement of ALK4 and SNAIL.

Design:
HTR8/SVneo immortalized human extravillous cytotrophoblast (EVT) cells and primary cultures of human first-trimester EVT cells were used as study models. Small interfering RNA (siRNA)-mediated knockdown approaches were used to investigate the molecular determinants of activin A-mediated functions.

Main Outcome Measures:
Levels of mRNA and protein were examined by reverse transcription-quantitative real-time PCR and Western blot, respectively. Cell invasiveness was measured by Matrigel-coated transwell assays.

Results:
Treatment of HTR8/SVneo cells with activin A increased the production of SNAIL, SLUG, and MMP2 without altering that of MMP9, TIMP1, TIMP2, TWIST, RUNX2, ZEB1, or ZEB2. Similarly, activin A up-regulated the mRNA and protein levels of SNAIL and MMP2 in primary EVT cells. Knockdown of SNAIL attenuated activin A-induced MMP2 up-regulation in HTR8/SVneo and primary EVT cells. In HTR8/SVneo cells, activin A-induced production of SNAIL and MMP2 was abolished by pretreatment with the TGF-β type I receptor (ALK4/5/7) inhibitor SB431542 or siRNA targeting ALK4, SMAD2/3, or common SMAD4. Likewise, knockdown of ALK4 or SMAD4 abolished the stimulatory effects of activin A on SNAIL and MMP2 expression in primary EVT cells. Importantly, activin A-induced HTR8/SVneo and primary EVT cell invasion were attenuated by siRNA-mediated depletion of ALK4 or MMP2.

Conclusion:
Activin A induces human trophoblast cell invasion by inducing SNAIL-mediated MMP2 expression through ALK4 in a SMAD2/3-SMAD4-dependent manner.
Identification of a Novel Coregulator, SH3YL1, That Interacts With the Androgen Receptor N-Terminus
Authors: Blessing Alicia M. , Ganesan Sathya , Rajapakshe Kimal , Ying Sung Ying , Reddy Bollu Lakshmi , Shi Yan , Cheung Edwin , Coarfa Cristian , Chang Jeffrey T. , McDonnell Donald P. , Frigo Daniel E. 
Published: August 2015

Abstract
Nuclear receptor (NR)-mediated transcriptional activity is a dynamic process that is regulated by the binding of ligands that induce distinct conformational changes in the NR. These structural alterations lead to the differential recruitment of coregulators (coactivators or corepressors) that control the expression of NR-regulated genes. Here, we show that a stretch of proline residues located within the N-terminus of androgen receptor (AR) is a bona fide coregulator binding surface, the disruption of which reduces the androgen-dependent proliferation and migration of prostate cancer (PCa) cells. Using T7 phage display, we identified a novel AR-interacting protein, Src homology 3 (SH3)-domain containing, Ysc84-like 1 (SH3YL1), whose interaction with the receptor is dependent upon this polyproline domain. As with mutations within the AR polyproline domain, knockdown of SH3YL1 attenuated androgen-mediated cell growth and migration. RNA expression analysis revealed that SH3YL1 was required for the induction of a subset of AR-modulated genes. Notable was the observation that ubinuclein 1 (UBN1), a key member of a histone H3.3 chaperone complex, was a transcriptional target of the AR/SH3YL1 complex, correlated with aggressive PCa in patients, and was necessary for the maximal androgen-mediated proliferation and migration of PCa cells. Collectively, these data highlight the importance of an amino-terminal activation domain, its associated coregulator, and downstream transcriptional targets in regulating cellular processes of pathological importance in PCa.
Tudo parou e não se podia dar o start: algo grave, muito grave, aconteceu!
Authors: Vieira Jailton Silva , Pereira de Araújo Maria Valéria 
Published: August 2015

Matheus é protagonista da modernização de toda a logística da empresa, que está abandonando o sistema de armazenagem, distribuição e transporte existentes por outro maior, melhor, mais lucrativo e competitivo. Mas uma falha compromete todo o projeto e cria um enorme problema. A partir da descoberta dessa falha, a competência logística da empresa é colocada à prova e começa uma corrida contra o tempo para reverter um quadro desastroso.
Som Livre: mudar ou morrer?
Authors: Trinta José Luiz , Altaf Joyce Gonçalves , Abdalla Márcio Moutinho , Troccoli Irene Raguenet 
Published: August 2015

O caso aborda as ações de mudança empreendidas pela gravadora Som Livre, dando ênfase ao seu novo modelo de negócios baseado na prestação de serviços. O principal foco é a necessidade da empresa de desenvolver um novo tipo de negócio, inteiramente distinto daquela que exercia há 35 anos.
Casa de Banho e o desafio da responsabilidade social em micro e pequenas empresas
Authors: Nogueira Fernando do Amaral , Costa Cristina de Miranda 
Published: August 2015

Os microempresários Patrícia e Fernando precisam decidir se dão seqüência ao incipiente programa de responsabilidade social de sua empresa. O caso ilustra os processos de gestão típicos de uma microempresa e tem como principal objetivo possibilitar a discussão das características e desafios da implementação de programas de responsabilidade social em empresas desse porte. DOI: 10.12660/gvcasosv5n1c2http://dx.doi.org/10.12660/gvcasosv5n1c2
Der deutsche Beitrag zur internationalen immobilienwirtschaftlichen Forschung
Authors: Pfnür Andreas , Kämpf-Dern Annette 
Published: August 2015

Zusammenfassung
Der vorliegende Beitrag gibt eine Übersicht über die bisherigen Inhalte immobilienwirtschaftlicher Forschung in Deutschland. Der Beitrag zeigt sowohl die Schwerpunkte als auch die weißen Flecken dieser Forschung im Inland und im internationalen Vergleich auf. Mit Hilfe des Konzepts der Familienähnlichkeiten und Kommensurabilität von Verhaltensannahmen gleichartiger Akteure wurden Cluster immobilienwirtschaftlicher Forschung gebildet. In einer empirischen Studie wurden 14.124 Forschungsbeiträge internationaler Konferenzen der IRES und AREUEA katalogisiert und den Forschungsclustern zugeordnet, deren deutscher Anteil im Fokus dieses Beitrags steht. Es zeigt sich, dass immobilienwirtschaftliche Forschung vor allem aus der Investorenperspektive betrieben wurde, wohingegen Themen aus Sicht der Immobiliennutzung und der Immobilienproduktion/-dienstleistungen weit weniger häufig Gegenstand der deutschen Forschung waren. Die Verteilung der Konferenzbeiträge auf die Cluster immobilienwirtschaftlicher Forschung in Deutschland ist eng korreliert mit der weltweiten Verteilung. Die Bewertung der praktischen Relevanz oder der konzeptionellen Qualität der Beiträge kann und soll durch die Untersuchung nicht vorgenommen werden. Jedoch können anhand der Ergebnisse individuelle Forschungsagenden validiert und gezielt z. B. in Richtung Mainstream oder Nische weiterentwickelt werden. Der Beitrag liefert somit einen innovativen Vorschlag zur Clusterung immobilienwirtschaftlicher Forschung und stellt zum ersten Mal ein umfassendes empirisches Bild über deren inhaltliche Ausrichtung in Deutschland im weltweiten Vergleich dar.
Avaliação da qualidade da água subterrânea: estudo de caso de Vilhena – RO
Authors: Oliveira Gislayne Alves , Do Nascimento Elisabete Lourdes , Denardin da Rosa Ana Lúcia , Lauthartte Leidiane Caroline , Bastos Wanderley Rodrigues , Barros Calina Grazielli Dias , Cremonese Eloiza Ruschel , Bento Amanda Quinhones , Malm Olaf , Georgin Jordana , Corti Adrielen Moraes 
Published: August 2015

As águas subterrâneas do Aquífero Parecis (AP) representam a única fonte explorada para o abastecimento público de água potável do município de Vilhena - RO. Nesse sentido, a avaliação da qualidade da água determinada por análises físicas, químicas e microbiológicas, podem fornecer subsídios para a compreensão das condições da água consumida. No presente estudo, foram realizadas duas coletas de água subterrânea em 12 poços distribuídos na cidade: a primeira no período de estiagem (seca), em agosto de 2013; e a outra no período chuvoso, em dezembro de 2013. Os parâmetros analisados foram os constituintes iônicos (F<sup>-</sup>, Cl<sup>-</sup>, NO<sub>2</sub><sup>-</sup>,Br<sup>-</sup>,NO<sub>3</sub><sup>-</sup>,PO<sub>4</sub><sup>-3</sup>,SO<sub>4</sub><sup>-2</sup>,Na<sup>+</sup>,NH<sub>3</sub><sup>+</sup>, K<sup>+</sup>,Ca<sup>2+</sup> eMg<sup>2+</sup>), os quais foram quantificados pela técnica de cromatografia iônica, enquanto que para as análises microbiológicas, o método utilizado foi o de membranas filtrantes em meio cromogênico. Os parâmetros pH e turbidez foram medidos por meio de pHmetro e turbidimetro portáteis. Os resultados apresentaram valores abaixo dos limites estabelecidos pela Resolução CONAMA 396/2008 e Portaria do MS 2.914/2011 para a turbidez e praticamente todos os constituintes iônicos, com exceção do nitrato (6 poços) e de amônia (1 poço), além de um pH ácido. O período chuvoso apresentou maior contaminação por coliformes totais e <em>Escherichia coli</em> que o período de estiagem, podendo estar associado às más condições dos poços, além de ser um aquífero livre, facilitando o escoamento de possíveis contaminantes. Em função dos resultados, destaca-se a importância do monitoramento constante da qualidade da água nas comunidades usuárias de fontes alternativas, evitando problemas à saúde humana
Subclinical Cushing’s syndrome with bilateral adrenal tumours in a patient with gallbladder multiple stone: therapeutical options
Authors: Carsote Mara , Ghemigian Adina , Valea Ana , Dumitrascu Anda , Chirita Corina , Poiana Catalina 
Published: August 2015

ABSTRACT
Introduction The field of Cushing syndrome is a various area; there are still subjects incompletely clarified as the subclinical pattern as well as cortisol producing bilateral adrenal tumours.
Case presentation The paper presents a 67-year old male case previously known with metabolic complications. He had an abdominal ultrasound done for unspecific complains and multiple gallbladder stones together with a right adrenal tumour were found. Later the computer tomography revealed bilateral adrenal tumours of almost 1.5 centimetres diameters (right larger than left) and a morning plasma cortisol level of 2.58 micrograms/ decilitre after low dose of dexametasone suppression test confirming the subclinical Cushing syndrome. After 6 months the endocrine and imagery profile was similar but the gallbladder patter aggravated so surgery was performed (together with right adrenalectomy) by a laparoscopic procedure. The blood pressure profile improved after surgery.
Conclusion Subclinical Cushing syndrome diagnosis is challenging especially if metabolic complications or bilateral adrenal tumours are presented. Based on our observations in this case unilateral adrenalectomy improved the metabolic pattern
Severe hepatocytolisis syndrome - a challenge in medical therapy of Cushing’s disease
Authors: Valea Ana , Carsote Mara , Ghemigian Adina , Morar Andra , Dumitru D.P. , Georgescu Carmen Emanuela 
Published: August 2015

ABSTRACT
Introduction Cushing’s disease is a rare endocrine disorder characterized by persistent hypercortisolism due to excessive, autonomous ACTH secretion by a pituitary adenoma. Transsphenoidal adenomectomy is the main therapeutic option in Cushing’s disease. When imaging studies are unable to demonstrate an obvious pituitary mass complete tumor resection is difficult and often encumbered by risk of relapse. Medical therapy is a second-line option or the first-line treatment for patients with high surgical risk, incomplete surgical resection or relapse. Rarely classic clinical manifestations limit the selection of medical therapy for Cushing’s disease. Case presentation We present the case of a male patient with Cushing’s disease complicated with diabetes mellitus and severe hepatocytolisis syndrome with no visible pituitary adenoma on MRI studies. In the absence of technical equipment petrosal sinus sampling could not be performed in order to improve surgery outcome
Conclusion The presence of unbalanced diabetes and severe hepatocytolisis syndrome made it impossible to use steroidogenesis inhibitors (mitotane, ketoconazole, metyrapone, etomidate) or inhibitors of ACTH secretion as pasireotide that represent a new option in achieving control of hypercortisolism
From headache to Rathke’s cleft cyst followed by diabetes insipidus with panhypopituitarism
Authors: Valea Ana , Marcusan Alexandra , Carsote Mara , Ghemigian Adina , Ghervan Cristina , Dumitrache C. 
Published: August 2015

ABSTRACT
Introduction The Rathke cyst represents an unusual benign tumour derived from Rathke’s cleft remnants. The diagnosis is potential seen at any age. The most frequent signs are mostly mass effects as headache, visual field defects and hypopituitarism.
Case presentation 30-year old female is admitted for persistent headache that was later associated with secondary amenorrhea and visual field defects for the last two years. The clinical data are consistent with high levels of serum prolactin, gonadotropes deficiency, as well as central hypothyroidism. The magnetic resonance imagery found a pituitary tumour of 2.7 centimetres with extrapituitary extension up to the optic chiasm. Surgery was performed in order to remove the tumour. The pathologic report confirmed a Rathke’s cleft cyst. Diabetes insipidus associated with panhypopituitarism was diagnosed and treated after the procedure. Close follow-up is necessary.
Conclusion This case highlights the fact that headache sometimes embraces a severe neoplasia diagnosis and that the iatrogenic complications after surgery are lifelong care demanding