bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia-cultured human adipose-derived mesenchymal stem cells are non-oncogenic and have enhanced viability, motility, and tropism to brain cancer
Authors: Feng Y , Zhu M , Dangelmajer S , Lee Y M , Wijesekera O , Castellanos C X , Denduluri A , Chaichana K L , Li Q , Zhang H , Levchenko A , Guerrero-Cazares H , Quiñones-Hinojosa A 
Published: December 2014

AbstractAdult human adipose-derived mesenchymal stem cells (hAMSCs) are multipotent cells, which are abundant, easily collected, and bypass the ethical concerns that plague embryonic stem cells. Their utility and accessibility have led to the rapid development of clinical investigations to explore their autologous and allogeneic cellular-based regenerative potential, tissue preservation capabilities, anti-inflammatory properties, and anticancer properties, among others. hAMSCs are typically cultured under ambient conditions with 21% oxygen. However, physiologically, hAMSCs exist in an environment of much lower oxygen tension. Furthermore, hAMSCs cultured in standard conditions have shown limited proliferative and migratory capabilities, as well as limited viability. This study investigated the effects hypoxic culture conditions have on primary intraoperatively derived hAMSCs. hAMSCs cultured under hypoxia (hAMSCs-H) remained multipotent, capable of differentiation into osteogenic, chondrogenic, and adipogenic lineages. In addition, hAMSCs-H grew faster and exhibited less cell death. Furthermore, hAMSCs-H had greater motility than normoxia-cultured hAMSCs and exhibited greater homing ability to glioblastoma (GBM) derived from brain tumor-initiating cells from our patients in vitro and in vivo. Importantly, hAMSCs-H did not transform into tumor-associated fibroblasts in vitro and were not tumorigenic in vivo. Rather, hAMSCs-H promoted the differentiation of brain cancer cells in vitro and in vivo. These findings suggest an alternative culturing technique that can enhance the function of hAMSCs, which may be necessary for their use in the treatment of various pathologies including stroke, myocardial infarction, amyotrophic lateral sclerosis, and GBM.
Functional expression cloning identifies COX-2 as a suppressor of antigen-specific cancer immunity
Authors: Göbel C , Breitenbuecher F , Kalkavan H , Hähnel P S , Kasper S , Hoffarth S , Merches K , Schild H , Lang K S , Schuler M 
Published: December 2014

AbstractThe efficacy of immune surveillance and antigen-specific cancer immunotherapy equally depends on the activation of a sustained immune response targeting cancer antigens and the susceptibility of cancer cells to immune effector mechanisms. Using functional expression cloning and T-cell receptor (TCR) transgenic mice, we have identified cyclooxygenase 2/prostaglandin-endoperoxide synthase 2 (COX-2) as resistance factor against the cytotoxicity induced by activated, antigen-specific T cells. Expressing COX-2, but not a catalytically inactive COX-2 mutant, increased the clonogenic survival of E1A-transformed murine cancer cells when cocultured with lymphocytes from St42Rag2−/− mice harboring a transgenic TCR directed against an E1A epitope. COX-2 expressing tumors established in immune-deficient mice were less susceptible to adoptive immunotherapy with TCR transgenic lymphocytes in vivo. Also, immune surveillance of COX-2-positive tumor cells in TCR transgenic mice was less efficient. The growth of murine MC-GP tumors, which show high endogenous COX-2 expression, in immunocompetent mice was effectively suppressed by treatment with a selective COX-2 inhibitor, celecoxib. Mechanistically, COX-2 expression blunted the interferon-gamma release of antigen-specific T cells exposed to their respective cellular targets, and increased the expression of interleukin-4 and indoleamine 2,3-dioxygenase by tumor cells. Addition of interferon-gamma sensitized COX-2 expressing cancer cells to tumor suppression by antigen-specific T cells. In conclusion, COX-2, which is frequently induced in colorectal cancer, contributes to immune evasion and resistance to antigen-specific cancer immunotherapy by local suppression of T-cell effector functions.
Exposure to endosulfan influences sperm competition in Drosophila melanogaster
Authors: Misra Snigdha , Kumar Ajay , Ratnasekhar Ch. , Sharma Vandana , Mudiam Mohana Krishna Reddy , Ram Kristipati Ravi 
Published: December 2014

AbstractDwindling male fertility due to xenobiotics is of global concern. Accordingly, male reproductive toxicity assessment of xenobiotics through semen quality analysis in exposed males and examining progeny production of their mates is critical. These assays, in part, are biased towards monogamy. Females soliciting multiple male partners (polyandry) is the norm in many species. Polyandry incites sperm competition and allows females to bias sperm use. However, consequences of xenobiotic exposure to the sperm in the light of sperm competition remain to be understood. Therefore, we exposed Drosophila melanogaster males to endosulfan and evaluated their progeny production as well as the ability of their sperm to counter rival control sperm in the storage organs of females sequentially mated to control/exposed males. Endosulfan (2 μg/ml) had no significant effect on progeny production and on the expression of certain genes associated with reproduction. However, exposed males performed worse in sperm competition, both as 1st and 2nd male competitors. These findings indicate that simple non-competitive measures of reproductive ability may fail to demonstrate the harmful effects of low-level exposure to xenobiotics on reproduction and advocate consideration of sperm competition, as a parameter, in the reproductive toxicity assessment of xenobiotics to mimic situations prevailing in the nature.
Synthetic approach toward complexity of sialic acid-containing glycans
Authors: Ando Hiromune 
Published: December 2014

Abstract
The biological relevance of sialic acid-containing glycans (sialo-glycans) to various interactions at the cell surface has increased the demand for the supply of structurally defined sialo-glycans. Due to their unique structures, the stereoselective synthesis of glycosides of sialic acid is inherently difficult, which makes the synthetic approach to synthesize diverse and complex sialo-glycans far from successful. However, the gap between the chemical and natural synthesis of complex sialo-glycans is narrowing through the emergence of synthetic methods. This review highlights recent progress made in the synthesis of complex sialo-glycans via cutting-edge synthetic methods.
Different Angiotensin-Converting Enzyme Inhibitors and the Associations With Overall and Cause-Specific Mortalities in Patients With Hypertension
Authors: Chang Chia-Hsuin , Lin Jou-Wei , Caffrey James L. , Wu Li-Chiu , Lai Mei-Shu 
Published: December 2014

BACKGROUND
Angiotensin-converting enzyme (ACE) inhibitors have been widely used in the treatment of hypertension, but the comparative effectiveness in reducing mortality among different drugs is seldom reported.

METHODS
We identified hypertensive patients who started captopril, enalapril, lisinopril, fosinopril, perindopril, ramipril, or imidapril therapy from Taiwan’s National Health Insurance database between 1 January 2004 and 31 December 2009. Overall and cause-specific mortalities were ascertained through a linkage to Taiwan’s National Death Registry. Patients were followed from the initiation of ACE inhibitors to death, disenrollment, or study termination (31 December 2010). A Cox proportional hazard regression model was used to calculate the hazard ratio (HR) and 95% confidence interval (CI), using ramipril as the reference group.

RESULTS
A total of 989,489 hypertensive patients were included, with a mean follow-up ranging from 3.5 years for imidapril to 4.5 years for enalapril. Captopril initiators had the highest overall mortality rate (117.8 per 1,000,000 person–days) as compared to other ACE inhibitors (54.3–79.4 per 1,000,000 person–days). Patients who started captopril therapy had a significantly increased risk of overall mortality (HR: 1.28, 95% CI: 1.24–1.31) when compared with ramipril. Enalapril (HR: 1.08, 95% CI: 1.05–1.11) and fosinopril (HR: 1.08, 95% CI: 1.05–1.12) were also associated with a modestly increased risk. No difference in mortality was found for lisinopril, perindopril, and imidapril, as compared with ramipril.

CONCLUSIONS
There are differences in the mortality risk associated with different ACE inhibitors. However, potential residual confounding effects might still exist.
Stage I Lung SBRT Clinical Practice Patterns
Authors: Corso Christopher D. , Park Henry S. , Moreno Amy C. , Kim Anthony W. , Yu James B. , Husain Zain A. , Decker Roy H. 
Published: December 2014

Objectives:
Stereotactic body radiation therapy (SBRT) has become increasingly utilized over the last decade in the treatment of inoperable stage I non–small cell lung cancer (NSCLC) patients, although no standardized dosing guidelines exist. In this retrospective study, we investigated the dose prescription pattern use in the United States for patients receiving SBRT.

Methods:
Patients with stage I NSCLC treated with SBRT between 2004 and 2011 were identified within the National Cancer Database (NCDB). Trends in SBRT use and dose prescriptions were analyzed.

Results:
A total of 5246 patients met criteria as receiving SBRT. The overall mean and median BED10 were 134.5 and 132 Gy, respectively. Of these patients, 94.5% were prescribed a regimen with a BED10≥100 Gy. The most common prescriptions overall were 60 Gy in 3 fractions (24.1%), 48 Gy in 4 fractions (17.8%), 50 Gy in 5 fractions (13.0%), and 54 Gy in 3 fractions (12.8%). Analysis of prescription trends revealed decreased utilization of 54 to 60 Gy in 3 fractions (47.9% in 2006 to 27.9% in 2011, combined) and increased utilization of 50 Gy in 5 fractions (3.1% in 2006 to 20.4% in 2011).

Conclusions:
Our findings suggest increasing use of SBRT over the last decade with a majority of patients being treated with regimens employing a BED10≥100 Gy. Since 2006, there has been a decline in the use of 54 to 60 Gy in 3 fractions, with an increase in the use of 50 Gy in 5 fractions. Possible explanations include concern for increased toxicity with higher BED regimens and increasing treatment of centrally located tumors.
Lymph Node Burden as a Predictive Factor for Selective Chemoradiotherapy in Patients With Locally Advanced Gastric Cancer After a D2 Dissection
Authors: Li Qiwen , Li Guichao , Palmer Joshua D. , Zhang Zhen 
Published: December 2014

Objectives:
The role of adjuvant radiation in locally advanced gastric cancer after a D2 lymph node dissection is not well defined. The Adjuvant Chemoradiation Therapy in Stomach Cancer trial demonstrated a benefit in selected patients with positive lymph nodes. This study further defines lymph node burden as a predictive factor for adjuvant radiation in locally advanced gastric cancer after radical D2 lymph node dissection.

Materials and Methods:
One hundred eighty-six patients with locally advanced gastric cancer and D2 dissections were retrospectively investigated. Patients were divided into 2 equal and well-balanced groups based on clinicopathologic characteristics, with half receiving chemoradiation and the other half chemotherapy alone. Clinical outcomes and recurrence patterns were compared. Lymph node ratio (LNR) was defined as ratio of positive to examined nodes. Chemotherapies were fluorouracil-based regimens. Radiation was prescribed to 45 Gy (range, 45 to 50.4 Gy) using 3-dimensional conformal or intensity-modulated radiation therapy techniques.

Results:
There was no difference between patients treated with or without radiation in 3-year disease-free survival (DFS) (57.0% vs. 62.0%, P=0.30) or 3-year overall survival (72.8% vs. 77.4%, P=0.23). However, patients with LNR>0.65 or 3 to 6 positive nodes (N2) had improved 3-year DFS and 3-year distant metastasis-free survival (DMFS) in the chemoradiation group (LNR>0.65 vs. LNR≤0.65: 3-y DFS: 35.8% vs. 0%, P=0.052, 3-y DMFS: 75.2% vs. 0%, P=0.026; N2 vs. non-N2: 3-y DFS: 84.7% vs. 57.1%, P=0.046, 3-y DMFS: 100.0% vs. 65.3%, P=0.036).

Conclusions:
N2 or LNR>0.65 may be indications for adjuvant chemoradiotherapy. Further randomized studies are needed for validation.
Why We Should Not Be Indifferent to Specification Choices for Difference‐in‐Differences
Authors: Ryan Andrew M. , Burgess James F. , Dimick Justin B. 
Published: December 2014

ObjectiveTo evaluate the effects of specification choices on the accuracy of estimates in difference‐in‐differences (DID) models.Data SourcesProcess‐of‐care quality data from Hospital Compare between 2003 and 2009.Study DesignWe performed a Monte Carlo simulation experiment to estimate the effect of an imaginary policy on quality. The experiment was performed for three different scenarios in which the probability of treatment was (1) unrelated to pre‐intervention performance; (2) positively correlated with pre‐intervention levels of performance; and (3) positively correlated with pre‐intervention trends in performance. We estimated alternative DID models that varied with respect to the choice of data intervals, the comparison group, and the method of obtaining inference. We assessed estimator bias as the mean absolute deviation between estimated program effects and their true value. We evaluated the accuracy of inferences through statistical power and rates of false rejection of the null hypothesis.Principal FindingsPerformance of alternative specifications varied dramatically when the probability of treatment was correlated with pre‐intervention levels or trends. In these cases, propensity score matching resulted in much more accurate point estimates. The use of permutation tests resulted in lower false rejection rates for the highly biased estimators, but the use of clustered standard errors resulted in slightly lower false rejection rates for the matching estimators.ConclusionsWhen treatment and comparison groups differed on pre‐intervention levels or trends, our results supported specifications for DID models that include matching for more accurate point estimates and models using clustered standard errors or permutation tests for better inference. Based on our findings, we propose a checklist for DID analysis.
Practical recommendations for improvement of the physical health care of patients with severe mental illness
Authors: van Hasselt F. M. , Oud M. J. T. , Loonen A. J. M. 
Published: December 2014

ObjectiveHealth care for the physical health of patients with severe mental illness (SMI) needs to be improved. Therefore, we aimed to develop policy recommendations to improve this physical health care in the Netherlands based on consensus (general agreement) between the major stakeholders.MethodA modified Delphi was used to explore barriers and subsequently establish policy recommendations with all key stakeholders. Consensus was sought between patients with SMI, their family carers, general practitioners, and mental healthcare professionals – all experts in the everyday practice of health care.ResultsConsensus was reached on policy recommendations regarding (i) improvements in collaboration between healthcare professionals, (ii) the need for professional education on the specific medical risks of patients with SMI, and (iii) the distinguished responsibilities of general practitioners on the one hand and mental healthcare professionals on the other hand in taking care of patients' physical health.ConclusionThis article provides a range of policy recommendations that could lead to considerable improvements in the physical health of SMI patients.
mRNA Destabilizing Factors: Tristetraprolin Expression at the Porcine Maternal–Fetal Interface
Authors: Khalaj Kasra , Wessels Jocelyn M. , Kridli Rami T. , Bidarimath Mallikarjun , LaMarre Jonathan , Tayade Chandrakant 
Published: December 2014

ProblemTo evaluate the expression of the tristetraprolin family and their selected targets during porcine pregnancy.Method of studyUsing qPCR and Western blot, mRNA and protein levels were compared between endometrium and chorioallantoic membrane (CAM) associated with healthy and impaired conceptuses at gestation day (gd) 20 and gd50, respectively. Immunohistochemistry was performed to determine localization of TIS11 family members at gd20 and 50.ResultsMultiple significant differences (P < 0.05) in TIS11 family transcripts were observed in the aforementioned comparisons. GM‐CSF was significantly higher in healthy endometrium and CAM from impaired conceptus attachment sites. TNF‐α was elevated in CAM as compared to endometrium at gd50, regardless of conceptus health status. Immunohistochemical staining shows TIS11 family expressed in the glandular and luminal epithelium, as well as stromal cells in the uterus.ConclusionsThe shift in the expression of tristetraprolin (TTP) and TIS11D points to a potential role of these genes in regulating spontaneous fetal loss.
Investigation into the effect of infrastructure on fly‐in fly‐out mining workers
Authors: Perring Adam , Pham Kieu , Snow Steve , Buys Laurie 
Published: December 2014

AbstractObjectiveTo explore fly‐in fly‐out (FIFO) mining workers' attitudes towards the leisure time they spend in mining camps, the recreational and social aspects of mining camp culture, the camps' communal and recreational infrastructure and activities, and implications for health.DesignIn‐depth semistructured interviews.SettingIndividual interviews at locations convenient for each participant.ParticipantsA total of seven participants, one female and six males. The age group varied within 20–59 years. Marital status varied across participants.Main outcome measuresA qualitative approach was used to interview participants, with responses thematically analysed. Findings highlight how the recreational infrastructure and activities at mining camps impact participants' enjoyment of the camps and their feelings of community and social inclusion.ResultsThree main areas of need were identified in the interviews, as follows: (i) on‐site facilities and activities; (ii) the role of infrastructure in facilitating a sense of community; and (iii) barriers to social interaction.ConclusionRecreational infrastructure and activities enhance the experience of FIFO workers at mining camps. The availability of quality recreational facilities helps promote social interaction, provides for greater social inclusion and improves the experience of mining camps for their temporary FIFO residents. The infrastructure also needs to allow for privacy and individual recreational activities, which participants identified as important emotional needs. Developing appropriate recreational infrastructure at mining camps would enhance social interactions among FIFO workers, improve their well‐being and foster a sense of community. Introducing infrastructure to promote social and recreational activities could also reduce alcohol‐related social exclusion.
Quantitative or qualitative carbon dioxide monitoring for manual ventilation: a mannequin study
Authors: Hawkes GA , Kenosi M , Ryan CA , Dempsey EM 
Published: December 2014

AbstractAimTo compare the effectiveness of an in‐line EtCO2 detector (DET) and a quantitative EtCO2 detector (CAP), both attached to a t‐piece resuscitator, during PPV via a face mask.MethodsPaediatric trainees were randomly assigned to determine the method of PPV they commenced with (No device (ND), DET or CAP). Participants used each method for 2 min. Participants were video‐recorded to determine the amount of effective ventilations delivered with each method.ResultsTwenty‐three paediatric trainees provided a total of 6035 ventilations, and 91.2% were deemed effective. The percentages of median effective ventilations with the ND, the DET and the CAP were 91.0%, 93.0% and 94.0%, respectively. Fourteen (61%) of the trainees indicated a preference for the DET method, 8 (35%) for the CAP method, and 1 (4%) of the trainees indicated a preference for the ND method. Capnography was the most effective method per patient.ConclusionThere was no adverse effect with the addition of EtCO2 detectors. Trainees favoured methods of EtCO2 monitoring during ventilation. The NeoStat device was the preferred device by the majority. The greatest efficacy was achieved with the capnography device. Capnography may enhance face mask ventilation.
The genomic landscape of chronic lymphocytic leukaemia: biological and clinical implications
Authors: Strefford Jonathan C. 
Published: December 2014

SummaryChronic lymphocytic leukaemia (CLL) remains at the forefront of the genetic analysis of human tumours, principally due its prevalence, protracted natural history and accessibility to suitable material for analysis. With the application of high‐throughput genetic technologies, we have an unbridled view of the architecture of the CLL genome, including a comprehensive description of the copy number and mutational landscape of the disease, a detailed picture of clonal evolution during pathogenesis, and the molecular mechanisms that drive genomic instability and therapeutic resistance. This work has nuanced the prognostic importance of established copy number alterations, and identified novel prognostically relevant gene mutations that function within biological pathways that are attractive treatment targets. Herein, an overview of recent genomic discoveries will be reviewed, with associated biological and clinical implications, and a view into how clinical implementation may be facilitated.
Growth hormone secretion decreases with age in paediatric Prader‐Willi syndrome
Authors: Cohen M. , Harrington J. , Narang I. , Hamilton J. 
Published: December 2014

SummaryObjectiveGrowth hormone deficiency is a common feature of Prader‐Willi syndrome; however, biochemical deficiency is not uniformly demonstrated. Criteria for GH treatment in paediatric PWS vary with some countries requiring documentation of biochemical GH deficiency. Data regarding the significance of age in the interpretation of GH stimulation test results, particularly in infants, are lacking. We aimed to assess age‐related trends in the prevalence of biochemical GH deficiency in infants and children with PWS.DesignA retrospective chart review was conducted. Data from children with Prader‐Willi syndrome that had GH stimulation tests performed at the Hospital for Sick Children in Toronto between the years 2000 and 2012 were collected.PatientCharts of 47 children 0·4–15·5 years of age with PWS that had GH stimulation tests were reviewed.MeasurementsBiochemical GH status in relation to age and body mass index.ResultsThirty‐two of 47 patients (68%) were biochemically GH deficient. GH deficiency was significantly associated with older age (r = 0·45, P = 0·02) and higher body‐mass‐index z‐score (r = 0·45, P = 0·02). Biochemical GH deficiency was less prevalent up to 18 months of age (3/11 27%) compared with older children (29/36 [81%]; P = 0·001). A higher prevalence of GH deficiency was also detected in obese patients (14/16 [88%]) compared with nonobese patients (18/31 [58%]; P = 0·04).ConclusionsThe utility of performing GH stimulation tests as an indication of GH status under 18 months of age in Prader‐Willi syndrome is questionable. If performed, results should be carefully interpreted in the context of age.