bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting chromatin binding regulation of constitutively active AR variants to overcome prostate cancer resistance to endocrine-based therapies
Authors: Chan Siu Chiu , Selth Luke A. , Li Yingming , Nyquist Michael D. , Miao Lu , Bradner James E. , Raj Ganesh V. , Tilley Wayne D. , Dehm Scott M. 
Published: April 2015

Abstract
Androgen receptor (AR) variants (AR-Vs) expressed in prostate cancer (PCa) lack the AR ligand binding domain (LBD) and function as constitutively active transcription factors. AR-V expression in patient tissues or circulating tumor cells is associated with resistance to AR-targeting endocrine therapies and poor outcomes. Here, we investigated the mechanisms governing chromatin binding of AR-Vs with the goal of identifying therapeutic vulnerabilities. By chromatin immunoprecipitation and sequencing (ChIP-seq) and complementary biochemical experiments, we show that AR-Vs display a binding preference for the same canonical high-affinity androgen response elements (AREs) that are preferentially engaged by AR, albeit with lower affinity. Dimerization was an absolute requirement for constitutive AR-V DNA binding and transcriptional activation. Treatment with the bromodomain and extraterminal (BET) inhibitor JQ1 resulted in inhibition of AR-V chromatin binding and impaired AR-V driven PCa cell growth in vitro and in vivo. Importantly, this was associated with a novel JQ1 action of down-regulating AR-V transcript and protein expression. Overall, this study demonstrates that AR-Vs broadly restore AR chromatin binding events that are otherwise suppressed during endocrine therapy, and provides pre-clinical rationale for BET inhibition as a strategy for inhibiting expression and chromatin binding of AR-Vs in PCa.
A Randomized, Double-blinded Trial of a “Rule of Threes” Algorithm versus Continuous Infusion of Oxytocin during Elective Cesarean Delivery
Authors: Kovacheva Vesela P. , Soens Mieke A. , Tsen Lawrence C. 
Published: April 2015

AbstractAbstract
In 60 women randomized to treatment at cesarean delivery, a single intravenous bolus of 3 IU at delivery was as effective as continuous, wide-open infusion of oxytocin, 30 IU/500 ml despite less total oxytocin delivered. Groups did not differ in side effects associated with oxytocin.

Background:
The administration of uterotonic agents during cesarean delivery is highly variable. The authors hypothesized a “rule of threes” algorithm, featuring oxytocin 3 IU, timed uterine tone evaluations, and a systematic approach to alternative uterotonic agents, would reduce the oxytocin dose required to obtain adequate uterine tone.

Methods:
Sixty women undergoing elective cesarean delivery were randomized to receive a low-dose bolus or continuous infusion of oxytocin. To blind participants, the rule group simultaneously received intravenous oxytocin (3 IU/3 ml) and a “wide-open” infusion of 0.9% normal saline (500 ml); the standard care group received intravenous 0.9% normal saline (3 ml) and a “wide-open” infusion of oxytocin (30 IU in 0.9% normal saline/500 ml). Uterine tone was assessed at 3, 6, 9, and 12 min, and if inadequate, additional uterotonic agents were administered. Uterine tone, total dose and timing of uterotonic agent use, maternal hemodynamics, side effects, and blood loss were recorded.

Results:
Adequate uterine tone was achieved with lower oxytocin doses in the rule versus standard care group (mean, 4.0 vs. 8.4 IU; point estimate of the difference, 4.4 ± 1.0 IU; 95% CI, 2.60 to 6.15; P < 0.0001). No additional oxytocin or alternative uterotonic agents were needed in either group after 6 min. No differences in the uterine tone, maternal hemodynamics, side effects, or blood loss were observed.

Conclusion:
A “rule of threes” algorithm using oxytocin 3 IU results in lower oxytocin doses when compared with continuous-infusion oxytocin in women undergoing elective cesarean delivery.
A Comprehensive Review of Randomized Placebo‐Controlled Pharmacological Clinical Trials in Children With Functional Abdominal Pain Disorders
Authors: Saps Miguel , Biring Harman S. , Pusatcioglu Cenk K. , Mintjens Stijn , Rzeznikiewiz Damian 
Published: April 2015

ABSTRACTObjectives:Abdominal pain–predominant functional gastrointestinal disorders (AP‐FGIDs) are the most common cause of consultation to pediatric gastroenterology; however, no medications have been approved to treat this group of disorders in children. The Food and Drug Administration have published recommendations for clinical trials on AP‐FGIDs in adults but not in children. The lack of methodological guidelines and accepted primary endpoints for clinical trials in children hampers the progress of the field, making the approval of new medications difficult. A necessary first step to determine the feasibility of clinical trials in children and provide recommendations on the best design for future trials is to review the methods, ability to recruit, attrition rate, and results of previous clinical trials. We designed a comprehensive review of pharmacological clinical trials in AP‐FGIDs in children focused on study design.Methods:Study eligibility was randomized controlled trials (RCTs) evaluating the efficacy of pharmacological interventions compared with that of placebo in children and adolescents with AP‐FGIDs.Results:There is no evidence to support the use of most commonly used drugs in children. Only 7 pharmacological RCTs on AP‐FGIDs in children were found. Most studies were single center based and had a small sample size. The methods and outcomes were heterogeneous. Primary endpoints varied widely among studies. Many of the RCTs did not show a consistently significant benefit of the drug over placebo in some or all of the outcomes. We found a considerable risk of bias in most studies. None of the studies have considered minimal clinically important differences in their selection of primary endpoints.Conclusions:Few randomized clinical trials have been conducted. Most studies have methodological limitations and small sample size. There is an urgent need for well‐designed randomized clinical trials using age‐appropriate validated outcome measures.
Metagenome-assembled genomes uncover a global brackish microbiome
Authors: Hugerth Luisa W. , Larsson John , Alneberg Johannes , Lindh Markus V. , Legrand Catherine , Pinhassi Jarone , Andersson Anders F. 
Published: April 2015

AbstractMicrobes are main drivers of biogeochemical cycles in oceans and lakes, yet surprisingly few bacterioplankton genomes have been sequenced, partly due to difficulties in cultivating them. Here we used automatic binning to reconstruct a large number of bacterioplankton genomes from a metagenomic time-series from the Baltic Sea. The genomes represent novel species within freshwater and marine clades, including clades not previously genome-sequenced. Their seasonal dynamics followed phylogenetic patterns, but with fine-grained lineage specific adaptations. Signs of streamlining were evident in most genomes, and estimated genome sizes correlated with abundance variation across filter size fractions. Comparing the genomes with globally distributed aquatic metagenomes suggested the existence of a global brackish metacommunity whose populations diverged from freshwater and marine relatives >100,000 years ago, hence long before the Baltic Sea was formed (8000 years). This markedly contrasts to most Baltic Sea multicellular organisms that are locally adapted populations of fresh- or marine counterparts.
Studies on the Tempo of Bubble Formation in Recently Cavitated Vessels: A Model to Predict the Pressure of Air Bubbles
Authors: Wang Yujie , Pan Ruihua , Tyree Melvin T. 
Published: April 2015

Abstract
A cavitation event in a vessel replaces water with a mixture of water vapor and air. A quantitative theory is presented to argue that the tempo of filling of vessels with air has two phases: a fast process that extracts air from stem tissue adjacent to the cavitated vessels (less than 10 s) and a slow phase that extracts air from the atmosphere outside the stem (more than 10 h). A model was designed to estimate how water tension (T) near recently cavitated vessels causes bubbles in embolized vessels to expand or contract as T increases or decreases, respectively. The model also predicts that the hydraulic conductivity of a stem will increase as bubbles collapse. The pressure of air bubbles trapped in vessels of a stem can be predicted from the model based on fitting curves of hydraulic conductivity versus T. The model was validated using data from six stem segments each of Acer mono and the clonal hybrid Populus 84K (Populus alba × Populus glandulosa). The model was fitted to results with root mean square error less than 3%. The model provided new insight into the study of embolism formation in stem tissue and helped quantify the bubble pressure immediately after the fast process referred to above.
The bidirectional CSR investment – economic performance relationship
Authors: Nakamura Eri 
Published: April 2015

Purpose– This paper aims to investigate the following two research questions: Do corporate social responsibility (CSR) investments enhance a firm’s economic performance? Does the firm’s economic performance influence CSR investments? That is, the bidirectional relationship between CSR investments and economic performance.Design/methodology/approach– This paper analyzes three types of CSR investments (environmental, labor-related and social investments) using a simultaneous equations model with a data set of 185 Japanese firms.Findings– Environmental investments reduce economic performance, labor-related investments do not significantly affect economic performance and social investments increase economic performance. Moreover, strong economic performance decreases environmental investments but increases social investments. Labor-related investments are chosen considering economic performance in both the present and previous terms.Practical implications– For managers, environmental and labor-related investments are not effective for improving economic performance. However, eradicating them completely might harm corporate reputation. In contrast, social investments have now become important. For policymakers, different approaches may be adopted to encourage firms to increase CSR investments. In some cases, policymakers can rely on firm initiatives instead of regulating or encouraging CSR activities.Originality/value– First, the authors empirically examine the bidirectional relationship between CSR investments and economic performance. Second, they clarify the determinants of CSR by specifying the investment function of each type of CSR. Third, they consider three types of CSR investments, with interrelations among them allowed in the model, and determine how each type affects firm performance.
Exploring the link between corporate social responsibility and health and safety in the mines
Authors: Amponsah-Tawiah Kwesi , Mensah Justice 
Published: April 2015

Purpose– The aim of this paper is to set a baseline understanding of the corporate social responsibility (CSR) concept amongst the different stakeholders in the mining industry in Ghana and further examine their appreciation of issues of occupational health and safety. It explored the integration of issues of health and safety of employees into the broader CSR agenda through a stakeholder analysis.Design/methodology/approach– The study population comprised various stakeholders operating in the mining industry of Ghana. The purposive sampling technique was used in the selection of the organisations/institutions that participated in the study. In all, 35 people were interviewed, and the interview data were analysed using thematic-content analysis.Findings– The findings provide an insight into how the various stakeholders in the mining industry in Ghana understood the CSR concept and how they went about practising it. Appreciation of issues health and safety by the various stakeholders also received considerable attention. All the stakeholders equated CSR to community relations. In all the cases, respondents referred to the local community as their focal point when discussing the concept.Originality/value– On the basis of this paper, it appears that mining companies in Ghana have looked upon the concept as a strategic challenge and not as a series of high-profile initiatives aimed at ensuring a responsible business practice. This paper adds to the literature by providing a perspective on how CSR associates with health and safety.
Interest Rate Volatility and Business Cycle Expectations
Authors: Martínez‐Serna María‐Isabel , Navarro Eliseo 
Published: April 2015

AbstractOne explanation for the usefulness of financial variables as tools for economic forecasting is that they embody individual and firm expectations of future economic conditions. In this paper, we analyse whether interest rate volatility contains information on agent expectations which are directly measured by confidence indicators. For the sake of robustness, we use several different expectation indicators for the two countries we analyse, the US and Germany. We propose using a forward‐looking measure of volatility: the implied volatility of one year cap options. We find that implied volatility adds explanatory power to the yield spread and to changes in the short rate, which are typical predictors of the business cycle, and outperforms realized volatility.
Utilisation of MR spectroscopy and diffusion weighted imaging in predicting and monitoring of breast cancer response to chemotherapy
Authors: Leong Kin Men , Lau Peter , Ramadan Saadallah 
Published: April 2015

SummaryNeoadjuvant chemotherapy (NACT) is the standard treatment option for breast cancer as more data shows that pathologic complete response (pCR) after NACT correlates with improved prognosis. MRI is accepted as the best imaging modality for evaluating the response to NACT in many studies as compared with clinical examination and other imaging modalities. In vivo magnetic resonance spectroscopy (MRS) and diffusion‐weighted imaging (DWI) studies have both emerged as potential tools to provide early response indicators based on the changes in the metabolites and the apparent diffusion coefficient (ADC) respectively. In this review article, we aim to discuss the strength and limitations of MRS and DWI in monitoring of early response breast cancer to NACT.
Clinical contraindications to allergen immunotherapy: an EAACI position paper
Authors: Pitsios C. , Demoly P. , Bilò M. B. , Gerth van Wijk R. , Pfaar O. , Sturm G. J. , Rodriguez del Rio P. , Tsoumani M. , Gawlik R. , Paraskevopoulos G. , Ruëff F. , Valovirta E. , Papadopoulos N. G. , Calderón M. A. 
Published: April 2015

AbstractClinical indications for allergen immunotherapy (AIT) in respiratory and Hymenoptera venom allergy are well established; however, clinical contraindications to AIT are not always well documented. There are some discrepancies when classifying clinical contraindications for different forms of AIT as ‘absolute’ or ‘relative’. EAACI Task Force on ‘Contraindications to AIT’ was created to evaluate and review current literature on clinical contraindications, and to update recommendations for both sublingual and subcutaneous AIT for respiratory and venom immunotherapy. An extensive review of the literature was performed on the use of AIT in asthma, autoimmune disorders, malignant neoplasias, cardiovascular diseases, acquired immunodeficiencies and other chronic diseases (including mental disorders), in patients treated with β‐blockers, ACE inhibitors or monoamine oxidase inhibitors, in children under 5 years of age, during pregnancy and in patients with poor compliance. Each topic was addressed by the following three questions: (1) Are there any negative effects of AIT on this concomitant condition/disease? (2) Are more frequent or more severe AIT‐related side‐effects expected? and (3) Is AIT expected to be less efficacious? The evidence, for the evaluation of these clinical conditions as contraindications, was limited, and most of the conclusions were based on case reports. Based on an extended literature research, recommendations for each medical condition assessed are provided. The final decision on the administration of AIT should be based on individual evaluation of any medical condition and a risk/benefit assessment for each patient.
Pulmonary edema after laparoscopic hepatectomy in a patient with Budd–Chiari syndrome‐associated hepatocellular carcinoma
Authors: Hanaoka Marie , Hara Yoshiaki , Fujiogi Michimasa , Fujisawa Nobutaka , Kawakami Masayo , Shioiri Sadaaki , Tanaka Michio , Yasuno Masamichi 
Published: April 2015

AbstractAn 84‐year‐old man diagnosed with Budd–Chiari syndrome (BCS) developed a 20‐mm hepatocellular carcinoma. We performed laparoscopic hepatectomy without complications, but the patient's percutaneous oxygen saturation gradually worsened and pulmonary edema was detected 50 minutes after extubation. He was subsequently re‐intubated and received diuretic therapy. He was discharged on postoperative day 32. Patients with severe BCS have been reported to have an expanded plasma volume. In addition, pneumoperitoneum during laparoscopic surgery has been reported to decrease the venous flow in the portal vein and/or renal vein, the collateral pathways in BCS. The cause of pulmonary edema in the present case may have involved increased venous return following decompression of pneumoperitoneum pressure under the state of an expanded plasma volume. This case suggests that clinicians should pay special attention to achieving volume control in patients with BCS, particularly during laparoscopic surgery and minimizing the duration of pneumoperitoneum.
Thoracoscopic repair of a large neonatal congenital diaphragmatic hernia using Gerota's fascia
Authors: Fukuzawa Hiroaki , Tamaki Akihiko , Takemoto Jyunkichi , Morita Keiichi , Endo Kosuke , Iwade Tamaki , Yuichi Okata , Bitoh Yuko , Yokoi Akiko , Maeda Kosaku 
Published: April 2015

AbstractA large congenital diaphragmatic hernia needing patch repair has a high risk of recurrence. Thus, managing these large congenital diaphragmatic hernias under thoracoscopy has become a problem. Here, a large congenital diaphragmatic hernia that was repaired using Gerota's fascia under thoracoscopy is reported. In the present case, it was impossible to close the hernia directly under thoracoscopy because the hernia was too large. Gerota's fascia was raised up by the left kidney and used for the repair. The left colon adhering to Gerota's fascia was mobilized, and a large space was made under thoracoscopy. Gerota's fascia was fixed to the diaphragmatic defect. The patient's postoperative course was good, and there was no recurrence. This technique could be one option for repairing a large hernia under thoracoscopy.
Risk factors for mesh erosion after female pelvic floor reconstructive surgery: a systematic review and meta‐analysis
Authors: Deng Tuo , Liao Banghua , Luo Deyi , Shen Hong , Wang Kunjie 
Published: April 2015

ObjectivesTo explore the risk factors for mesh erosion after female pelvic floor reconstructive surgery based on published literature.Materials and MethodsA systematic literature search of the PubMed, Embase, Cochrane Library, Chinese Biomedical Literature (CBM), China National Knowledge Infrastructure (CNKI) and Chinese Science and Technology Periodical (VIP) databases was performed to identify studies related to the risk factors for mesh erosion after female pelvic floor reconstruction published before December 2014. Summary unadjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of associations between the factors and mesh erosion.ResultsIn all, 25 studies containing 7 084 patients were included in our systematic review and meta‐analysis. Statistically significant differences in mesh erosion after female pelvic floor reconstruction were found in older vs younger patients (OR 0.96, 95% CI 0.94–0.98), more parities vs less parities (OR 1.27, 95% CI 1.07–1.51), the presence of premenopausal/oestrogen replacement therapy (ERT) (OR 1.36, 95% CI 1.03–1.79), diabetes mellitus (OR 1.87, 95% CI 1.35–2.57), smoking (OR 2.35, 95% CI 1.80–3.08), concomitant pelvic organ prolapse (POP) surgery (OR 0.37, 95% CI 0.16–0.84), concomitant hysterectomy (OR 1.46, 95% CI 1.03–2.07), preservation of the uterus at surgery (OR 0.22, 95% CI 0.08–0.63), and surgery performed by senior vs junior surgeons (OR 0.42, 95% CI 0.30–0.58).ConclusionOur study indicates that younger age, more parities, premenopausal/ERT, diabetes mellitus, smoking, concomitant hysterectomy, and surgery performed by a junior surgeon were significant risk factors for mesh erosion after female pelvic floor reconstructive surgery. Moreover, concomitant POP surgery and preservation of the uterus may be the potential protective factors for mesh erosion.
Bone Scan Index predicts outcome in patients with metastatic hormone‐sensitive prostate cancer
Authors: Poulsen Mads H. , Rasmussen Janne , Edenbrandt Lars , Høilund‐Carlsen Poul F. , Gerke Oke , Johansen Allan , Lund Lars 
Published: April 2015

ObjectiveTo evaluate the Bone Scan Index (BSI) for prediction of castration resistance and prostate cancer‐specific survival (PCSS). In this retrospective study, we used novel computer‐assisted software for automated detection/quantification of bone metastases by BSI. Patients with prostate cancer are M‐staged by whole‐body bone scintigraphy (WBS) and categorised as M0 or M1. Within the M1 group, there is a wide range of clinical outcomes. The BSI was introduced a decade ago providing quantification of bone metastases by estimating the percentage of bone involvement. Being too time consuming, it never gained widespread clinical use.Patients and MethodsIn all, 88 patients with prostate cancer awaiting initiation of androgen‐deprivation therapy due to metastases were included. WBS was performed using a two‐headed γ‐camera. BSI was obtained using the automated platform EXINI bone (EXINI Diagnostics AB, Lund, Sweden). In Cox proportional hazard models, time to castration‐resistant prostate cancer (CRPC) and PCSS were modelled as the dependent variables, whereas prostate‐specific antigen (PSA) level, Gleason score and BSI were used as explanatory factors. For Kaplan–Meier estimates, BSI groups were dichotomously split into: BSI <1 and BSI ≥1. Discrimination between prognostic models was explored using the concordance index (C‐index).ResultsThe mean (range) age of the patients was 72 (52–92) years, the median (range) PSA level was 73 (4–5 740) ng/mL, the mean (range) Gleason score was 7.7 (2–10), and the mean (range) BSI was 1.0 (0–9.2). During a mean (range) follow‐up of 26 (8–49) months, 48 patients became castration resistant and 15 had died; most (13) from prostate cancer. In multivariate analysis including PSA level, Gleason score and BSI, only prediction by BSI was statistically significant. This was true both for time to CRPC (hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.22–1.74; C‐index increase from 0.49 to 0.69) and for PCSS (HR 1.34, 95% CI 1.07–1.67; C‐index increase from 0.76 to 0.95).ConclusionBSI obtained using a novel automated computer‐assisted algorithm appears to be a useful predictor of outcome for time to CRPC and PCSS in patients with hormone‐sensitive metastatic prostate cancer.