bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of proline in the treatment of menopause
Authors: Nam Sun-Young , Yoou Myoung-Schook , Kim Hyung-Min , Jeong Hyun-Ja 
Published: February 2016

The amino acids in the placenta have multiple functions; however, the therapeutic effects of proline remain poorly for relief postmenopausal symptoms. The aim of present study was to evaluate the effects of proline in the treatment of menopause using in vitro and in vivo models. We assessed the therapeutic effects and regulatory mechanisms of proline by using MCF-7 estrogen-dependent cells, MG63 osteoblast cells, and ovariectomized mice model. An in vivo study was carried out in eight-week-old sham and ovariectomized group. The ovariectomized mouse was further subdivided into two groups administered orally with 17β-estradiol or proline (10 mg/kg/day) for eight weeks. Proline significantly increased cell proliferation and Ki-67 levels in MCF-7 cells and enhanced cell proliferation, alkaline phosphatase activity, extracellular signal-regulated kinase phosphorylation, and glutamyl-prolyl-tRNA synthetase activation in MG63 cells. The estrogen receptor-β and estrogen-response elements luciferase activity were significantly increased by proline in MCF-7 and MG63 cells. In ovariectomized mice, oral administration of proline (10 mg/kg/day) for eight weeks significantly reduced body and vaginal weights. Proline also significantly increased serum estradiol and alkaline phosphatase levels, whereas serum luteinizing hormone was decreased by proline. In addition, detailed microcomputed tomography analysis showed that the proline notably enhanced bone mineral density, trabecular bone volume, and trabecular number in ovariectomized mice. Those findings implied that proline can be a promising candidate for the treatment of menopause.
Portal hypertension is associated with modulation of regulatory T cells
Authors: Adar Tomer , Edden Yair , Shteingart Shimon , Ben Ya’acov Ami , Mahamid Mahmud , Broide Ellen , Shmorak Shimrit , Bar-Gil Shitrit Ariella , Reinus Constantin , Goldin Eran 
Published: February 2016

Background: Portal hypertension is a complication of liver cirrhosis. The portal vein drains the spleen and the intestines, which are both rich in inflammatory mediators. Portal hypertension- induced stress within these organs that may result in pro-inflammatory changes. The association of these changes with regulatory T cells was not addressed before. Aim: Our aim is to investigate the involvement of some subsets of regulatory T cells in portal hypertension. Methods: In the current study we used the partial portal vein ligation model to demonstrate differences in the distribution of regulatory T cells within the portal vein and the inferior vena cava associated with portal hypertension. Results: We show that CD4+CD25+FoxP3+ regulatory T cells are significantly ( P <0.05) increased only in the inferior vena cava of partial portal vein ligation-rats. The development of portal hypertension was associated with the reversal of the distribution patterns in the portal vein and inferior vena cava for both CD4+ and CD8+ cells. We further show that in naïve rats CD4+IL17+ cells were significantly ( P <0.05) and specifically enriched in inferior vena cava compared to the portal vein. Conclusions: These novel findings support the involvement of regulatory T cells in the inflammatory signals accompanied with acute portal hypertension.
Inpatient illness severity surveys provide essential data for planning capacity and managing patient flow in the acute hospital setting
Authors: Garland Adam , Ashton-Cleary David , Sinclair Ray 
Published: February 2016

Purpose We aimed to determine if Modified Early Warning Score could be used as a surrogate for the Association of United Kingdom University Hospitals dependency scoring in improving patient flow into higher areas of care. In particular, focus was to be placed on the impact of Critical Care expansion on the size of the populations of patients being managed outside of Critical Care with an Association of United Kingdom University Hospitals requirement of Level 2. Materials and Methods We conducted snapshot assessments of illness severity using Modified Early Warning Score and Association of United Kingdom University Hospitals dependency scores on all inpatients in a large, rural acute hospital during two five-day periods. Results A total of 3850 patients were reviewed: 1854 in Study Period 1 and 1996 during Study Period 2. A total of 3113 (80.9%) patients had an Association of United Kingdom University Hospitals care level of 0. There was no statistically significant difference between the patients reviewed in each study period when analysed by Association of United Kingdom University Hospitals care level ( p = 0.575). Eighty-nine patients required Level 2 care (inclusive of those in Critical Care). Study Period 1 had 32 Level 2 patients managed on the ward. Study Period 2 demonstrated a statistically significant increase in the proportion of these patients cared for in a Critical Care environment (37.3%–68.4% ( p = 0.0036)). This was facilitated by an expansion in Critical Care capacity between the two study periods as a result of the findings in Study Period 1. Conclusion We have shown that hospital inpatient data on illness severity are an essential tool in bed management and Critical Care capacity planning. We were able to demonstrate a fall in the number of Level 2 patients managed on a general ward environment following an expansion in Critical Care bed capacity. We also demonstrated that a Modified Early Warning Score of greater than 4 was associated with an increase in assessed care level requirement.
The prevalence and clinical characteristics associated with Diagnostic and Statistical Manual Version-5-defined anxious distress specifier in adults with major depressive disorder: results from the International Mood Disorders Collaborative Project
Authors: McIntyre Roger S. , Woldeyohannes Hanna O. , Soczynska Joanna K. , Vinberg Maj , Cha Danielle S. , Lee Yena , Gallaugher Laura A. , Dale Roman S. , Alsuwaidan Mohammad T. , Mansur Rodrigo B. , Muzina David J. , Carvalho Andre , Kennedy Sidney 
Published: February 2016

Objectives: The aim of the study was to evaluate the prevalence of and illness characteristics in adults with major depressive disorder (MDD) with anxious distress specifier (ADS) enrolled in the International Mood Disorders Collaborative Project, which is a collaborative research platform at the Mood Disorders Psychopharmacology Unit, University of Toronto, Canada and the Cleveland Clinic, Cleveland, Ohio, USA. Methods: Data from participants who met criteria for a current major depressive episode as part of MDD ( n = 830) were included in this post hoc analysis. Diagnostic and Statistical Manual Version-5-defined ADS was operationalized as the presence of at least two out of three proxy items instead of two out of five specifiers. Results: A total of 464 individuals (i.e. 56%) met criteria for ADS. There were no between-group differences in sociodemographic variables (e.g. gender, employment, marital status). Greater severity of illness was observed in adults with ADS as evidenced by a higher number of hospitalizations, higher rates of suicidal ideation, greater depressive symptom severity, greater workplace impairment, decreased quality of life, and greater self-reported cognitive impairment. Conclusions: Our findings underscore the importance of evaluating ADS in adults with MDD as its presence identifies a subpopulation with greater illness-associated burden and hazards.
Profiling of Alzheimer’s disease patients in Puerto Rico: A comparison of two distinct socioeconomic areas
Authors: Camacho-Mercado Clara L , Figueroa Raúl , Acosta Heriberto , Arnold Steven E , Vega Irving E 
Published: February 2016

Objective: The Latino/Hispanic community in the United States is at higher risk of developing Alzheimer’s disease than other ethnic groups. Specifically, Caribbean Hispanics showed a more severe Alzheimer’s disease symptomatology than any other ethnic group. In a previous study, we demonstrated that the mortality rate associated with Alzheimer’s disease in Puerto Rico is higher than that reported in the United States. Moreover, the mortality rate associated with Alzheimer’s disease was higher among Puerto Rican living in Puerto Rico than those in the mainland United States. There is also a differential geographical distribution of mortality rate associated with Alzheimer’s disease in Puerto Rico, which may be associated with differential socioeconomic status and/or access to healthcare. However, there is no information regarding the clinical profile of Alzheimer’s disease patients in Puerto Rico. Methods: Here, we present the results of a retrospective study directed to profile Alzheimer’s disease patients clustered into two groups based on areas previously determined with low (Metro Region) and high (Northwest-Central Region) mortality rate associated with Alzheimer’s disease in Puerto Rico. Results: Significant difference in the age-at-diagnosis and years of education was found among patients within the two studied regions. Despite these differences, both regions showed comparable levels of initial and last Mini Mental State Examination scores and rate of cognitive decline. Significant difference was also observed in the occurance of co-morbidities associated with Alzheimer’s disease. Conclusions: The differential profile of Alzheimer’s disease patients correlated with differences in socioeconomic status between these two regions, suggesting that covariant associated with social status may contribute to increased risk of developing Alzheimer’s disease. Further studies should be conducted to determine the role of socioeconomic factors and healthy living practices as risk factors for Alzheimer’s disease.
A meta-analysis of low-molecular-weight heparin to prevent pregnancy loss in women with inherited thrombophilia
Authors: Skeith Leslie , Carrier Marc , Kaaja Risto , Martinelli Ida , Petroff David , Schleußner Ekkehard , Laskin Carl A. , Rodger Marc A. 
Published: February 2016

Abstract
We performed a meta-analysis of randomized controlled trials comparing low-molecular-weight heparin (LMWH) vs no LMWH in women with inherited thrombophilia and prior late (≥10 weeks) or recurrent early (<10 weeks) pregnancy loss. Eight trials and 483 patients met our inclusion criteria. There was no significant difference in livebirth rates with the use of LMWH compared with no LMWH (relative risk, 0.81; 95% confidence interval, 0.55-1.19; P = .28), suggesting no benefit of LMWH in preventing recurrent pregnancy loss in women with inherited thrombophilia.
Impact of imputation methods on the amount of genetic variation captured by a single-nucleotide polymorphism panel in soybeans
Authors: Xavier A. , Muir William M. , Rainey Katy M. 
Published: February 2016

Abstract
Background
Success in genome-wide association studies and marker-assisted selection depends on good phenotypic and genotypic data. The more complete this data is, the more powerful will be the results of analysis. Nevertheless, there are next-generation technologies that seek to provide genotypic information in spite of great proportions of missing data. The procedures these technologies use to impute genetic data, therefore, greatly affect downstream analyses. This study aims to (1) compare the genetic variance in a single-nucleotide polymorphism panel of soybean with missing data imputed using various methods, (2) evaluate the imputation accuracy and post-imputation quality associated with these methods, and (3) evaluate the impact of imputation method on heritability and the accuracy of genome-wide prediction of soybean traits. The imputation methods we evaluated were as follows: multivariate mixed model, hidden Markov model, logical algorithm, k-nearest neighbor, single value decomposition, and random forest. We used raw genotypes from the SoyNAM project and the following phenotypes: plant height, days to maturity, grain yield, and seed protein composition.

Results
We propose an imputation method based on multivariate mixed models using pedigree information. Our methods comparison indicate that heritability of traits can be affected by the imputation method. Genotypes with missing values imputed with methods that make use of genealogic information can favor genetic analysis of highly polygenic traits, but not genome-wide prediction accuracy. The genotypic matrix captured the highest amount of genetic variance when missing loci were imputed by the method proposed in this paper.

Conclusions
We concluded that hidden Markov models and random forest imputation are more suitable to studies that aim analyses of highly heritable traits while pedigree-based methods can be used to best analyze traits with low heritability. Despite the notable contribution to heritability, advantages in genomic prediction were not observed by changing the imputation method. We identified significant differences across imputation methods in a dataset missing 20 % of the genotypic values. It means that genotypic data from genotyping technologies that provide a high proportion of missing values, such as GBS, should be handled carefully because the imputation method will impact downstream analysis.
Non-T cell activation linker (NTAL) proteolytic cleavage as a terminator of activatory intracellular signals
Authors: Arbulo-Echevarria Mikel M , Muñoz-Miranda Juan Pedro , Caballero-García Andrés , Poveda-Díaz José L , Fernández-Ponce Cecilia , Durán-Ruiz Mª Carmen , Miazek Arkadiusz , García-Cózar Francisco , Aguado Enrique 
Published: February 2016

Abstract
Non-T cell activation linker is an adaptor protein that is tyrosine phosphorylated upon cross-linking of immune receptors expressed on B lymphocytes, NK cells, macrophages, basophils, or mast cells, allowing the recruitment of cytosolic mediators for downstream signaling pathways. Fas receptor acts mainly as a death receptor, and when cross-linked with Fas ligand, many proteins are proteolytically cleaved, including several signaling molecules in T and B cells. Fas receptor triggering also interferes with TCR intracellular signals, probably by means of proteolytic cleavage of several adaptor proteins. We have previously found that the adaptor linker for activation of T cells, evolutionarily related to non-T cell activation linker, is cleaved upon proapoptotic stimuli in T lymphocytes and thymocytes, in a tyrosine phosphorylation-dependent fashion. Here, we describe non-T cell activation linker proteolytic cleavage triggered in human B cells and monocytes by Fas cross-linking and staurosporine treatment. Non-T cell activation linker is cleaved, producing an N-terminal fragment of ∼22 kDa, and such cleavage is abrogated in the presence of caspase 8/granzyme B and caspase 3 inhibitors. Moreover, we have identified an aspartic acid residue at which non-T cell activation linker is cleaved, which similar to linker for activation of T cells, this aspartic acid residue is located close to tyrosine and serine residues, suggesting an interdependence of phosphorylation and proteolytic cleavage. Consistently, induction of non-T cell activation linker phosphorylation by pervanadate inhibits its cleavage. Interestingly, the truncated isoform of non-T cell activation linker, generated after cleavage, has a decreased signaling ability when compared with the full-length molecule. Altogether, our results suggest that cleavage of transmembrane adaptors constitutes a general mechanism for signal termination of immune receptors.
Translational Breast Cancer Research Consortium (TBCRC) 022: A Phase II Trial of Neratinib for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases
Authors: Freedman Rachel A. , Gelman Rebecca S. , Wefel Jeffrey S. , Melisko Michelle E. , Hess Kenneth R. , Connolly Roisin M. , Van Poznak Catherine H. , Niravath Polly A. , Puhalla Shannon L. , Ibrahim Nuhad , Blackwell Kimberly L. , Moy Beverly , Herold Christina , Liu Minetta C. , Lowe Alarice , Agar Nathalie Y.R. , Ryabin Nicole , Farooq Sarah , Lawler Elizabeth , Rimawi Mothaffar F. , Krop Ian E. , Wolff Antonio C. , Winer Eric P. , Lin Nancy U. 
Published: February 2016

Purpose Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)–positive breast cancer in the CNS are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4, with promising activity in HER2-positive breast cancer; however, its activity in the CNS is unknown. We evaluated the efficacy of treatment with neratinib in patients with HER2-positive breast cancer brain metastases in a multicenter, phase II open-label trial. Patients and Methods Eligible patients were those with HER2-positive brain metastases (≥ 1 cm in longest dimension) who experienced progression in the CNS after one or more line of CNS-directed therapy, such as whole-brain radiotherapy, stereotactic radiosurgery, and/or surgical resection. Patients received neratinib 240 mg orally once per day, and tumors were assessed every two cycles. The primary endpoint was composite CNS objective response rate (ORR), requiring all of the following: ≥50% reduction in volumetric sum of target CNS lesions and no progression of non-target lesions, new lesions, escalating corticosteroids, progressive neurologic signs/symptoms, or non-CNS progression—the threshold for success was five of 40 responders. Results Forty patients were enrolled between February 2012 and June 2013; 78% of patients had previous whole-brain radiotherapy. Three women achieved a partial response (CNS objective response rate, 8%; 95% CI, 2% to 22%). The median number of cycles received was two (range, one to seven cycles), with a median progression-free survival of 1.9 months. Five women received six or more cycles. The most common grade ≥ 3 event was diarrhea (occurring in 21% of patients taking prespecified loperamide prophylaxis and 28% of those without prophylaxis). Patients in the study experienced a decreased quality of life over time. Conclusion Although neratinib had low activity and did not meet our threshold for success, 12.5% of patients received six or more cycles. Studies combining neratinib with chemotherapy in patients with CNS disease are ongoing.
Prognostic Effect of Tumor Lymphocytic Infiltration in Resectable Non–Small-Cell Lung Cancer
Authors: Brambilla Elisabeth , Le Teuff Gwénaël , Marguet Sophie , Lantuejoul Sylvie , Dunant Ariane , Graziano Stephen , Pirker Robert , Douillard Jean-Yves , Le Chevalier Thierry , Filipits Martin , Rosell Rafael , Kratzke Robert , Popper Helmut , Soria Jean-Charles , Shepherd Frances A. , Seymour Lesley , Tsao Ming Sound 
Published: February 2016

Purpose Tumor lymphocytic infiltration (TLI) has differing prognostic value among various cancers. The objective of this study was to assess the effect of TLI in lung cancer. Patients and Methods A discovery set (one trial, n = 824) and a validation set (three trials, n = 984) that evaluated the benefit of platinum-based adjuvant chemotherapy in non–small-cell lung cancer were used as part of the LACE-Bio (Lung Adjuvant Cisplatin Evaluation Biomarker) study. TLI was defined as intense versus nonintense. The main end point was overall survival (OS); secondary end points were disease-free survival (DFS) and specific DFS (SDFS). Hazard ratios (HRs) and 95% CIs associated with TLI were estimated through a multivariable Cox model in both sets. TLI-histology and TLI-treatment interactions were explored in the combined set. Results Discovery and validation sets with complete data included 783 (409 deaths) and 763 (344 deaths) patients, respectively. Median follow-up was 4.8 and 6 years, respectively. TLI was intense in 11% of patients in the discovery set compared with 6% in the validation set (P < .001). The prognostic value of TLI in the discovery set (OS: HR, 0.56; 95% CI, 0.38 to 0.81; P = .002; DFS: HR, 0.59; 95% CI, 0.42 to 0.83; P = .002; SDFS: HR, 0.56; 95% CI, 0.38 to 0.82; P = .003) was confirmed in the validation set (OS: HR, 0.45; 95% CI, 0.23 to 0.85; P = .01; DFS: HR, 0.44; 95% CI, 0.24 to 0.78; P = .005; SDFS: HR, 0.42; 95% CI, 0.22 to 0.80; P = .008) with no heterogeneity across trials (P ≥ .38 for all end points). No significant predictive effect was observed for TLI (P ≥ .78 for all end points). Conclusion Intense lymphocytic infiltration, found in a minority of tumors, was validated as a favorable prognostic marker for survival in resected non–small-cell lung cancer.
Comparative Effectiveness of Minimally Invasive Hysterectomy for Endometrial Cancer
Authors: Wright Jason D. , Burke William M. , Tergas Ana I. , Hou June Y. , Huang Yongmei , Hu Jim C. , Hillyer Grace Clarke , Ananth Cande V. , Neugut Alfred I. , Hershman Dawn L. 
Published: February 2016

Purpose Despite the potential benefits of minimally invasive hysterectomy for uterine cancer, population-level data describing the procedure’s safety in unselected patients are lacking. We examined the use of minimally invasive surgery and the association between the route of the procedure and long-term survival. Methods We used the SEER-Medicare database to identify women with stage I-III uterine cancer who underwent hysterectomy from 2006 to 2011. Patients who underwent abdominal hysterectomy were compared with those who had minimally invasive hysterectomy (laparoscopic and robot-assisted). Perioperative morbidity, use of adjuvant therapy, and long-term survival were examined after propensity score balancing. Results We identified 6,304 patients, including 4,139 (65.7%) who underwent abdominal hysterectomy and 2,165 (34.3%) who underwent minimally invasive hysterectomy; performance of minimally invasive hysterectomy increased from 9.3% in 2006 to 61.7% in 2011. Robot-assisted procedures accounted for 62.3% of the minimally invasive operations. Compared with women who underwent abdominal hysterectomy, minimally invasive hysterectomy was associated with a lower overall complication rate (22.7% v 39.7%; P < .001), and lower perioperative mortality (0.6% v 1.1%), but these women were more likely to receive adjuvant pelvic radiotherapy (34.3% v 31.3%) and brachytherapy (33.6% v 31.0%; P < .05). The complication rate was higher after robot-assisted hysterectomy compared with laparoscopic hysterectomy (23.7% v 19.5%; P = .03). There was no association between the use of minimally invasive hysterectomy and either overall (HR, 0.89; 95% CI, 0.75 to 1.04) or cancer-specific (HR, 0.83; 95% CI, 0.59 to 1.16) mortality. Conclusion Minimally invasive hysterectomy does not appear to compromise long-term survival for women with endometrial cancer.