bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ex vivo haemostatic capacity of plasma upon thawing and beyond: a comparison between fresh frozen plasma (FFP) and frozen plasma prepared from whole blood stored at room temperature up to 24 hours postcollection (RTFP24)
Authors: Ang Ai Leen , Wong Wan Hui , Tan Jeslyn , Ng Heng Joo , Tan Chuen Wen , Kuperan Ponnudurai , Lam Sally , Tan Hwee Huang , Chua Sze Sze 
Published: February 2019

Background/objectivesWe compared the ex vivo haemostatic capacity of RTFP24 with FFP upon thawing and >24 h post‐thaw. We included thrombin generation (TG) as few studies had compared global haemostatic function, and most did not directly compare RTFP24 with FFP >24 h post‐thaw.Materials/methodsTwenty units each of RTFP24 and FFP were measured for coagulation factors and thrombin generation upon thawing (D0) and 4 days post‐thaw (D4). Labile factors were also measured from D1 to D3. 10 single cryoprecipitate units were each prepared from FFP and RTFP24, and measured for FXIII, FVIII and fibrinogen at D0.ResultsAt D0, RTFP24 was comparable to FFP except for lower FV, protein S, endogenous thrombin potential (ETP) and higher FXIII. These differences were likely clinically insignificant since 95% and 80% of RTFP24 met our laboratory's reference ranges for FV/protein S and ETP, respectively. There were no differences between RTFP24‐ and FFP‐derived cryoprecipitate.At D4, RTFP24 was comparable to FFP except for lower FV, ETP, and higher FXI and FXIII. More RTFP24 than FFP had ETP lower than our laboratory's reference range (45% vs 15%). Multiple coagulation factors and all TG parameters declined from their respective baselines. The percentage declines were comparable or less in RTFP24, except for protein C, fibrinogen and time to peak.ConclusionRTFP24 and FFP, and their derived cryoprecipitate have comparable haemostatic capacity upon thawing. RTFP24 has poorer TG potential than FFP >24 h post‐thaw, not supporting universal extension of RTFP24's shelf life except to facilitate urgent transfusions for massive haemorrhage.
Provider trends in paediatric and adult transfusion reaction reporting
Authors: Vossoughi Sarah , Parker‐Jones Sylvia , Schwartz Joseph , Stotler Brie 
Published: February 2019

Background and ObjectivesPassive transfusion reaction reporting systems fail to capture a significant number of reactions, and no data exist on provider reporting trends. The aim of this study was to describe transfusion reaction reporting patterns by adult and paediatric providers.Materials and MethodsThis is a multihospital study on transfusion reaction reporting over a 7‐year period. Reports were categorized according to transfusion location and assigned to either a transfusion reaction or nonreaction group according to Centers for Disease Control imputability guidelines. Included in the reaction group (RXN) were definite, probable or possible reaction categories; with the remainder assigned as nonreactions (NORXN). Rates were calculated per 100,000 components transfused using chi‐square comparison.ResultsThere were 1092 reports generated from 363 437 transfusions; 230 reports from 69 311 paediatric and 862 reports from 294 126 adult treatment areas. The reporting rate per 100 000 components transfused was 332 for paediatric and 293 for adult (P = 0·09). The per 100 000 components transfused rates were as follows: 237 for paediatric and 169 for adult (P < 0·01) in the RXN group; with 95 paediatric and 124 adult rates in the NORXN group (P = 0·04).ConclusionThe total number of reports generated by paediatric and adult providers was not significantly different, suggesting that both provider groups engage the passive reporting system equally. However, paediatric providers reported more true reactions compared to adult providers. Robust hemovigilance systems will further the understanding of these trends and may aid in the development of targeted provider education programmes.
Using lean thinking to improve hypertension in a community health centre: a quality improvement report
Authors: Lee Patrick , Pham Linhchi , Oakley Stephen , Eng Kimberly , Freydin Elena , Rose Tayla , Ruiz Alyssa , Reen Joyce , Suleyman Deborah , Altman Vanna , Keating Bench Kara , Lee Alice , Mahaniah Kiame 
Published: February 2019

BackgroundAchieving better care at lower cost in the US healthcare safety net will require federally qualified health centres (FQHC) to implement new models of team-based population healthcare. Lean thinking may offer a way to reduce the financial risk of practice transformation while increasing the likelihood of sustained improvement.ObjectiveTo demonstrate system-level improvement in hypertension control in a large FQHC through the situational use of lean thinking and statistical process control.SettingLynn Community Health Center, the third largest FQHC in Massachusetts, USA.Participants4762 adult patients with a diagnosis of hypertension.InterventionFirst, we created an organisation-wide focus on hypertension. Second, we implemented a multicomponent hypertension care pathway. The lean tools of strategy deployment, standardised work, job instruction, Plan-Do-Study-Adjust, 5S and visual control were used to overcome specific obstacles in the implementation.MeasurementsThe primary outcome was hypertension control, defined as last measured blood pressure <140/90. Statistical process control was used to establish baseline performance and assess special cause variation resulting from the two-step intervention.ResultsHypertension control improved by 11.6% from a baseline of 66.8% to a 6 month average of 78.2%.LimitationsDurability of system changes has not been demonstrated beyond the 14-month period of the intervention. The observed improvement may underestimate the effect size of the full hypertension care pathway, as two of the five steps have only been partially implemented.ConclusionsSuccess factors included experienced improvement leaders, a focus on engaging front-line staff, the situational use of lean principles to make the work easier, better, faster and cheaper (in that order of emphasis), and the use of statistical process control to learn from variation. The challenge of transforming care delivery in the safety net warrants a closer look at the principles, relevance and potential impact of lean thinking in FQHCs.
Interprofessional simulation training’s impact on process and outcome team efficacy beliefs over time
Authors: Kerry Matthew James , Ander Douglas S , Davis Beth P 
Published: February 2019

IntroductionRecent findings suggest that process and outcome-based efficacy beliefs are factorially distinct with differential effects for team performance. This study extends this work by examining process and outcome efficacy (TPE, TOE) of interprofessional (IP) care teams over time.MethodsA within-team, repeated measures design with survey methodology was implemented in a sample of prelicensure IP care teams performing over three consecutive clinical simulation scenarios. TPE and TOE were assessed before and after each performance episode.ResultsInitial baseline results replicated the discriminant validity for TPE and TOE separate factors. Further findings from multilevel modelling indicated significant time effects for TPE convergence, but not TOE convergence. However, a cross-level interaction effect of ‘TOE(Start-Mean)×Time’ strengthened TOE convergence over time. A final follow-up analysis of team agreement’s substantive impact was conducted using independent faculty-observer ratings of teams’ final simulation.ConclusionIndependent sample t-tests of high/low-agreement teams indicated support for agreement’s substantive impact, such that high-agreement teams were rated as significantly better performers than low-agreement teams during the final simulation training. We discuss the substantive merit of methodological within-team agreement as an indicator of team functionality within IP and greater healthcare-simulation trainings at-large.
Increasing adolescent girls’ ability to identify STI-risk characteristics of sexual partners: a pilot study within an alternative disciplinary school
Authors: Richardson Eric , Komro Kelli A , Samarah Esaa , Staras Stephanie A S 
Published: February 2019

ObjectivesWe evaluated the feasibility of conducting a 9-week long sexually transmitted infection (STI) prevention intervention,Angels in Action,within an alternative disciplinary school for adolescent girls.MethodsAll girls who were 16–18 years old, enrolled in the school and did not have plans to transfer from the school were eligible to participate. We measured process feasibility with recruitment, retention and participant enjoyment. Using a pretest-post-test design with a double post-test, we used χ² tests to estimate the intervention effect on participants’ sexual partner risk knowledge, intentions to reduce partner risk and sexual activities in the past 60 days with three behavioural surveys: prior to, immediately following and 3 months after the intervention.ResultsAmong the 20 girls who were eligible, 95% (19/20) of parents consented and all girls (19/19) agreed to participate. Survey participation was 100% (19/19) prior to, 76% (13/17) immediately following and 53% (9/17) 3 months after the intervention. The intervention was administered twice and a total 17 girls participated. Session attendance was high (89%) and most participants (80%) reported enjoying the intervention. The intervention increased the percentage of girls who could identify partner characteristics associated with increased STI risk: 38% before, 92% immediately following and 100% 3 months after the intervention (p=0.01). Girls also increased their intentions to find out four of the most highly associated partner characteristics (partner’s age, recent sexual activity and STI or jail history): 32% before to 75% immediately following (p=0.02) and 67% 3 months after the intervention (p=0.09).ConclusionsThis pilot study suggests girls at alternative disciplinary schools participated in and enjoyed a 9-week STI preventive intervention. Within alternative disciplinary schools, it is potentially feasible to increase girls’ consideration of partner risk characteristics as a means to enhance their STI prevention skills.
New Hardware Architecture for Self-Organizing Map Used for Color Vector Quantization
Authors: Khalifa Khaled Ben , Blaiech Ahmed Ghazi , Abadi Mehdi , Bedoui Mohamed Hedi 
Published: February 2019

In this paper, we present a new generic architectural approach of a Self-Organizing Map (SOM). The proposed architecture, called the Diagonal-SOM (D-SOM), is described as an Hardware–Description-Language as an intellectual property kernel with easily adjustable parameters.The D-SOM architecture is based on a generic formalism that exploits two levels of the nested parallelism of neurons and connections. This solution is therefore considered as a system based on the cooperation of a distributed set of independent computations. The organization and structure of these calculations process an oriented data flow in order to find a better treatment distribution between different neuroprocessors. To validate the D-SOM architecture, we evaluate the performance of several SOM network architectures after their integration on a Xilinx Virtex-7 Field Programmable Gate Array support. The proposed solution allows the easy adaptation of learning to a large number of SOM topologies without any considerable design effort. [Formula: see text] SOM hardware is validated through FPGA implementation, where temporal performance is almost twice as fast as that obtained in the recent literature. The suggested D-SOM architecture is also validated through simulation on variable-sized SOM networks applied to color vector quantization.
lncRNA GAS5 restrains CCl4-induced hepatic fibrosis by targeting miR-23a through the PTEN/PI3K/Akt signaling pathway
Authors: Dong Zhiheng , Li Sha , Wang Xiaohui , Si Lengge , Ma Ruilian , Bao Lidao , Bo Agula 
Published: February 2019

Hepatic fibrosis is chronic liver damage with many causes that has a relatively high death rate. The current study showed that long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5), microRNA-23a (miR-23a), and phosphatase and tensin homolog (PTEN) play important roles in the pathological process of hepatic fibrosis but have a relatively unclear regulatory mechanism. This study aimed to investigate the roles of lncRNA GAS5, miR-23a, and PTEN in the pathological process of hepatic fibrosis and hepatic stellate cell (HSC) activation. We used carbon tetrachloride (CCl4) intraperitoneal injections to establish a rat hepatic fibrosis model and exogenous transforming growth factor-β1 to establish an HSC activation model. Quantitative RT-PCR, Western blot, dual-luciferase reporter system, and RNA pull-down assays were used to investigate which microRNAs and lncRNAs participate in the process of hepatic fibrosis and HSC activation. miR-23a expression increased significantly in hepatic fibrosis tissues and activated HSCs. miR-23a interaction with and degradation of PTEN further influenced the downstream signaling pathway phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin/Snail (PI3K/Akt/mTOR/Snail), causing E-cadherin expression levels to decrease and α-smooth muscle actin and collagen I expression levels to increase. lncRNA GAS5 can be used as a sponge platform for miR-23a to decrease miR-23a expression levels competitively. We revealed the role of the lncRNA GAS5/miR-23a/PTEN/PI3K/Akt/mTOR/Snail signaling pathway in hepatic fibrosis, providing molecular targets for the treatment of hepatic fibrosis. NEW & NOTEWORTHY This is the first study revealing that microRNA-23a (miR-23a) promotes hepatic fibrosis through the phosphatase and tensin homolog/phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin/Snail signaling pathway, and long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) can act as a sponge platform for miR-23a. Therefore, lncRNA GAS5/miR-23a may bring molecular targets for hepatic fibrosis therapy.
Docosahexaenoic acid reduces resting blood pressure but increases muscle sympathetic outflow compared with eicosapentaenoic acid in healthy men and women
Authors: Lee Jordan B. , Notay Karambir , Klingel Shannon L. , Chabowski Adrian , Mutch David M. , Millar Philip J. 
Published: February 2019

Supplementation with monounsaturated or ω-3 polyunsaturated fatty acids ( n-3 PUFA) can lower resting blood pressure (BP) and reduce the risk of cardiovascular events. The independent contributions of the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on BP, and the mechanisms responsible, are unclear. We tested whether EPA, DHA, and olive oil (OO), a source of monounsaturated fat, differentially affect resting hemodynamics and muscle sympathetic nerve activity (MSNA). Eighty-six healthy young men and women were recruited to participate in a 12-wk, randomized, double-blind trial examining the effects of orally supplementing ~3 g/day of EPA ( n = 28), DHA ( n = 28), or OO ( n = 30) on resting hemodynamics; MSNA was examined in a subset of participants ( n = 31). Both EPA and DHA supplements increased the ω-3 index ( P < 0.01). Reductions in systolic BP were greater [adjusted intergroup mean difference (95% confidence interval)] after DHA [−3.4 mmHg (−0.9, −5.9), P = 0.008] and OO [−3.0 mmHg (−0.5, −5.4), P = 0.01] compared with EPA, with no difference between DHA and OO ( P = 0.74). Reductions in diastolic BP were greater following DHA [−3.4 mmHg (−1.3,−5.6), P = 0.002] and OO [−2.2 mmHg (0.08,−4.3), P = 0.04] compared with EPA. EPA increased heart rate compared with DHA [4.2 beats/min (−0.009, 8.4), P = 0.05] and OO [4.2 beats/min, (0.08, 8.3), P = 0.04]. MSNA burst frequency was higher after DHA [4 bursts/min (0.5, 8.3), P = 0.02] but not OO [−3 bursts/min (−6, 0.6), P = 0.2] compared with EPA. Overall, DHA and OO evoked similar responses in resting BP; however, DHA, but not OO, increased peripheral vasoconstrictor outflow. These findings may have implications for fatty acid supplementation in clinical populations characterized by chronic high BP and sympathetic overactivation. NEW & NOTEWORTHY We studied the effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and olive oil supplementation on blood pressure (BP) and muscle sympathetic nerve activity (MSNA). After 12 wk of 3 g/day supplementation, DHA and olive oil were associated with lower resting systolic and diastolic BPs than EPA. However, DHA increased MSNA compared with EPA. The reductions in BP with DHA likely occur via a vascular mechanism and evoke a baroreflex-mediated increase in sympathetic activity.
EZH2 Inhibitor GSK126 Suppresses Antitumor Immunity by Driving Production of Myeloid-Derived Suppressor Cells
Authors: Huang Shuo , Wang Zhongyu , Zhou Jie , Huang Jiani , Zhou Li , Luo Jing , Wan Yisong Y. , Long Haixia , Zhu Bo 
Published: February 2019

Abstract

Enhancer of zeste homolog (EZH2) is a key epigenetic regulator of gene expression and is frequently overexpressed in various cancer types, suggesting a role in oncogenesis. The therapeutic potential of EZH2 inhibitors is currently being explored, but their effect on antitumor immunity is largely unknown. Here we report that suppressing EZH2 activity using EZH2 inhibitor GSK126 resulted in increased numbers of myeloid-derived suppressor cells (MDSC) and fewer CD4+ and IFNγ+CD8+ T cells, which are involved in antitumor immunity. Addition of a neutralizing antibody against the myeloid differentiation antigen GR-1 or gemcitabine/5-fluorouracil–depleted MDSCs alleviated MDSC-mediated immunosuppression and increased CD4+ and CD8+ T-cell tumor infiltration and GSK126 therapeutic efficacy. Mechanistically, we identified a novel pathway of MDSC production in cancer in which EZH2 inhibition directs myeloid differentiation from primitive hematopoietic progenitor cells. These findings suggest that modulating the tumor immune microenvironment may improve the efficacy of EZH2 inhibitors.

Significance:
This study uncovers a potential mechanism behind disappointing results of a phase I clinical trial of EZH2 inhibitor GSK126 and identifies a translatable combinational strategy to overcome it.
Upregulation of PD-L1 via HMGB1-Activated IRF3 and NF-κB Contributes to UV Radiation-Induced Immune Suppression
Authors: Wang Wei , Chapman Nicole M. , Zhang Bo , Li Mingqi , Fan Meiyun , Laribee R. Nicholas , Zaidi M. Raza , Pfeffer Lawrence M. , Chi Hongbo , Wu Zhao-Hui 
Published: February 2019

Abstract

Solar ultraviolet radiation (UVR) suppresses skin immunity, which facilitates initiation of skin lesions and establishment of tumors by promoting immune evasion. It is unclear whether immune checkpoints are involved in the modulation of skin immunity by UVR. Here, we report that UVR exposure significantly increased expression of immune checkpoint molecule PD-L1 in melanoma cells. The damage-associated molecular patterns molecule HMGB1 was secreted by melanocytes and keratinocytes upon UVR, which subsequently activated the receptor for advanced glycation endproducts (RAGE) receptor to promote NF-κB– and IRF3-dependent transcription of PD-L1 in melanocytes. UVR exposure significantly reduced the susceptibility of melanoma cells to CD8+ T-cell–dependent cytotoxicity, which was mitigated by inhibiting the HMGB1/TBK1/IRF3/NF-κB cascade or by blocking the PD-1/PD-L1 checkpoint. Taken together, our findings demonstrate that UVR-induced upregulation of PD-L1 contributes to immune suppression in the skin microenvironment, which may promote immune evasion of oncogenic cells and drive melanoma initiation and progression.

Significance:
These findings identify PD-L1 as a critical component of UV-induced immune suppression in the skin, which facilitates immunoevasion of oncogenic melanocytes and development of melanoma.
See related commentary by Sahu, p. 2805
A T-cell–engaging B7-H4/CD3-bispecific Fab-scFv Antibody Targets Human Breast Cancer
Authors: Iizuka Akira , Nonomura Chizu , Ashizawa Tadashi , Kondou Ryota , Ohshima Keiichi , Sugino Takashi , Mitsuya Koichi , Hayashi Nakamasa , Nakasu Yoko , Maruyama Kouji , Yamaguchi Ken , Akiyama Yasuto 
Published: February 2019

Abstract

Purpose:
The B7 homolog 4 (B7-H4, VTCN1) is an immune checkpoint molecule that negatively regulates immune responses and is known to be overexpressed in many human cancers. Previously, we generated a mouse anti-human B7-H4 mAb that did not have a significant antitumor effect in vivo probably because of molecule instability. In this study, we designed a B7-H4/CD3-bispecific antibody (BsAb) and investigated its antitumor activity in vitro and in vivo using a humanized mouse model.

Experimental Design:
cDNAs of the antibody-binding fragment (Fab)–single-chain variable fragment (scFv) and scFv-scFv of the anti-B7-H4/CD3 BsAb were synthesized, and the BsAb antibodies were produced in HEK293 cells. The antitumor activity against human breast cancer cells by human peripheral blood mononuclear cells (hPBMC) with BsAb was measured by lactate dehydrogenase release in vitro, and in vivo using hPBMC-transplanted MHC class I- and class II–deficient NOG mice.

Results:
hPBMCs with anti-B7-H4/CD3 BsAbs successfully lysed the human breast cancer cell line MDA-MB-468 (EC50: 0.2 ng/mL) and other B7-H4+ cell lines in vitro. When BsAb was injected in a humanized mouse model, there was an immediate and strong antitumor activity against MDA-MB-468, HCC-1954, and HCC-1569 tumors and CD8+ and granzyme B+ CTL infiltration into the tumor, and there were no adverse effects after long-term observation. CD8+ T-cell depletion by an anti-CD8 antibody mostly reduced the antitumor effect of BsAb in vivo.

Conclusions:
An anti-B7-H4/CD3 BsAb may be a good therapeutic tool for patients with B7-H4+ breast cancers.
Drugging RB1 Deficiency: Synthetic Lethality with Aurora Kinases
Authors: Dick Frederick A. , Li Shawn Shun-Cheng 
Published: February 2019

Abstract

Summary:
Two recent reports describe pharmacologic approaches to specifically treat RB1-mutant cancers. The basis of this approach is a synthetic lethal relationship between RB1 mutations and inhibition of Aurora kinases A or B.
See related article by Oser et al., p. 230.
See related article by Gong et al., p. 248.
Acoustic Discriminability of the Complex Phonation System in !Xóõ
Authors: Garellek Marc 
Published: February 2019

AbstractPhonation types, or contrastive voice qualities, are minimally produced using complex movements of the vocal folds, but may additionally involve constriction in the supraglottal and pharyngeal cavities. These complex articulations in turn produce a multidimensional acoustic output that can be modeled in various ways. In this study, I investigate whether the psychoacoustic model of voice by Kreiman et al. (2014) succeeds at distinguishing six phonation types of !Xóõ. Linear discriminant analysis is performed using parameters from the model averaged over the entire vowel as well as for the first and final halves of the vowel. The results indicate very high classification accuracy for all phonation types. Measures averaged over the vowel’s entire duration are closely correlated with the discriminant functions, suggesting that they are sufficient for distinguishing even dynamic phonation types. Measures from all classes of parameters are correlated with the linear discriminant functions; in particular, the “strident” vowels, which are harsh in quality, are characterized by their noise, changes in spectral tilt, decrease in voicing amplitude and frequency, and raising of the first formant. Despite the large number of contrasts and the time-varying characteristics of many of the phonation types, the phonation contrasts in !Xóõ remain well differentiated acoustically.