bluuebunny/crossref_metadata_2025_split huggingface dataset:
Applicability of duplex real time and lateral flow strip reverse-transcription recombinase aided amplification assays for the detection of Enterovirus 71 and Coxsackievirus A16
Authors: Li Xin-na , Shen Xin-xin , Li Ming-hui , Qi Ju-ju , Wang Rui-huan , Duan Qing-xia , Zhang Rui-qing , Fan Tao , Bai Xue-ding , Fan Guo-hao , Xie Yao , Ma Xue-jun 
Published: December 2019

AbstractBackgroundEnterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the two main etiological agents of Hand, Foot and Mouth Disease (HFMD). Simple and rapid detection of EV71 and CA16 is critical in resource-limited settings.MethodsDuplex real time reverse-transcription recombinase aided amplification (RT-RAA) assays incorporating competitive internal amplification controls (IAC) and visible RT-RAA assays combined with lateral flow strip (LFS) for detection of EV71 and CA16 were developed respectively. Duplex real time RT-RAA assays were performed at 42 °C within 30 min using a portable real-time fluorescence detector, while LFS RT-RAA assays were performed at 42 °C within 30 min in an incubator. Recombinant plasmids containing conserved VP1 genes were used to analyze the sensitivities of these two methods. A total of 445 clinical specimens from patients who were suspected of being infected with HFMD were used to evaluate the performance of the assays.ResultsThe limit of detection (LoD) of the duplex real time RT-RAA for EV71 and CA16 was 47 copies and 38 copies per reaction, respectively. The LoD of the LFS RT-RAA for EV71 and CA16 were both 91 copies per reaction. There was no cross reactivity with other enteroviruses. Compared to reverse transcription-quantitative PCR (RT-qPCR), the clinical diagnostic sensitivities of the duplex real time RT-RAA assay were 92.3% for EV71 and 99.0% for CA16, and the clinical diagnostic specificities were 99.7 and 100%, respectively. The clinical diagnostic sensitivities of the LFS RT-RAA assay were 90.1% for EV71 and 94.9% for CA16, and the clinical diagnostic specificities were 99.7 and 100%, respectively.ConclusionsThe developed duplex real time RT-RAA and LFS RT-RAA assays for detection of EV71 and CA16 are potentially suitable in primary clinical settings.
Marburg virus pathogenesis – differences and similarities in humans and animal models
Authors: Shifflett Kyle , Marzi Andrea 
Published: December 2019

AbstractMarburg virus (MARV) is a highly pathogenic virus associated with severe disease and mortality rates as high as 90%. Outbreaks of MARV are sporadic, deadly, and often characterized by a lack of resources and facilities to diagnose and treat patients. There are currently no approved vaccines or treatments, and the chaotic and infrequent nature of outbreaks, among other factors, makes testing new countermeasures during outbreaks ethically and logistically challenging. Without field efficacy studies, researchers must rely on animal models of MARV infection to assess the efficacy of vaccines and treatments, with the limitations being the accuracy of the animal model in recapitulating human pathogenesis. This review will compare various animal models to the available descriptions of human pathogenesis and aims to evaluate their effectiveness in modeling important aspects of Marburg virus disease.
Implementation strategies for infection prevention and control promotion for nurses in Sub-Saharan Africa: a systematic review
Authors: Barrera-Cancedda Amy Elizabeth , Riman Kathryn A. , Shinnick Julianna E. , Buttenheim Alison M. 
Published: December 2019

AbstractBackgroundDespite impressive reductions in infectious disease burden within Sub-Saharan Africa (SSA), half of the top ten causes of poor health or death in SSA are communicable illnesses. With emerging and re-emerging infections affecting the region, the possibility of healthcare-acquired infections (HAIs) being transmitted to patients and healthcare workers, especially nurses, is a critical concern. Despite infection prevention and control (IPC) evidence-based practices (EBP) to minimize the transmission of HAIs, many healthcare systems in SSA are challenged to implement them. The purpose of this review is to synthesize and critique what is known about implementation strategies to promote IPC for nurses in SSA.MethodsThe databases, PubMed, Ovid/Medline, Embase, Cochrane, and CINHAL, were searched for articles with the following criteria: English language, peer-reviewed, published between 1998 and 2018, implemented in SSA, targeted nurses, and promoted IPC EBPs. Further, 6241 search results were produced and screened for eligibility to identify implementation strategies used to promote IPC for nurses in SSA. A total of 61 articles met the inclusion criteria for the final review. The articles were evaluated using the Joanna Briggs Institute’s (JBI) quality appraisal tools. Results were reported using PRISMA guidelines.ResultsMost studies were conducted in South Africa (n = 18, 30%), within the last 18 years (n = 41, 67%), and utilized a quasi-experimental design (n = 22, 36%). Few studies (n = 14, 23%) had sample populations comprising nurses only. The majority of studies focused on administrative precautions (n = 36, 59%). The most frequent implementation strategies reported were education (n = 59, 97%), quality management (n = 39, 64%), planning (n = 33, 54%), and restructure (n = 32, 53%). Penetration and feasibility were the most common outcomes measured for both EBPs and implementation strategies used to implement the EBPs. The most common MAStARI and MMAT scores were 5 (n = 19, 31%) and 50% (n = 3, 4.9%) respectively.ConclusionsAs infectious diseases, especially emerging and re-emerging infectious diseases, continue to challenge healthcare systems in SSA, nurses, the keystones to IPC practice, need to have a better understanding of which, in what combination, and in what context implementation strategies should be best utilized to ensure their safety and that of their patients. Based on the results of this review, it is clear thatimplementationof IPC EBPs in SSA requires additional research from an implementation science-specific perspective to promote IPC protocols for nurses in SSA.
Comparative photon and proton dosimetry for patients with mediastinal lymphoma in the era of Monte Carlo treatment planning and variable relative biological effectiveness
Authors: Tseng Yolanda D. , Maes Shadonna M. , Kicska Gregory , Sponsellor Patricia , Traneus Erik , Wong Tony , Stewart Robert D. , Saini Jatinder 
Published: December 2019

Abstract
Background
Existing pencil beam analytical (PBA) algorithms for proton therapy treatment planning are not ideal for sites with heterogeneous tissue density and do not account for the spatial variations in proton relative biological effectiveness (vRBE). Using a commercially available Monte Carlo (MC) treatment planning system, we compared various dosimetric endpoints between proton PBA, proton MC, and photon treatment plans among patients with mediastinal lymphoma.

Methods
Eight mediastinal lymphoma patients with both free breathing (FB) and deep inspiration breath hold (DIBH) CT simulation scans were analyzed. The original PBA plans were re-calculated with MC. New proton plans that used MC for both optimization and dose calculation with equivalent CTV/ITV coverage were also created. A vRBE model, which uses a published model for DNA double strand break (DSB) induction, was applied on MC plans to study the potential impact of vRBE on cardiac doses. Comparative photon plans were generated on the DIBH scan.

Results
Re-calculation of FB PBA plans with MC demonstrated significant under coverage of the ITV V99 and V95. Target coverage was recovered by re-optimizing the PT plan with MC with minimal change to OAR doses. Compared to photons with DIBH, MC-optimized FB and DIBH proton plans had significantly lower dose to the mean lung, lung V5, breast tissue, and spinal cord for similar target coverage. Even with application of vRBE in the proton plans, the putative increase in RBE at the end of range did not decrease the dosimetric advantages of proton therapy in cardiac substructures.

Conclusions
MC should be used for PT treatment planning of mediastinal lymphoma to ensure adequate coverage of target volumes. Our preliminary data suggests that MC-optimized PT plans have better sparing of the lung and breast tissue compared to photons. Also, the potential for end of range RBE effects are unlikely to be large enough to offset the dosimetric advantages of proton therapy in cardiac substructures for mediastinal targets, although these dosimetric findings require validation with late toxicity data.
Antithrombotic drugs do not increase intraoperative blood loss in emergency gastrointestinal surgery: a single-institution propensity score analysis
Authors: Matsuoka Tadashi , Kobayashi Kenji , Lefor Alan Kawarai , Sasaki Junichi , Shinozaki Hiroharu 
Published: December 2019

Abstract
Background
The use of antithrombotic drugs is increasing with the aging population. Prior to elective procedures, antithrombotic drugs are often discontinued. For emergency procedures in patients taking antithrombotic drugs, their effect cannot be attenuated which may lead to an increased risk of hemorrhagic events. However, there are few studies showing increased intraoperative blood loss in patients taking antithrombotic drugs who undergo emergency gastrointestinal surgery. The aim of this study is to determine whether the use of antithrombotic agents increases intraoperative blood loss in emergency gastrointestinal surgery.

Methods
A retrospective review of patients who underwent emergency abdominal surgery between January 2013 and December 2017 was conducted. The primary outcome measure was intraoperative blood loss. Patients were divided into the antithrombotic drug group and a control group, and a propensity score was developed using multivariate logistic regression. We use 1:1 propensity score matching analysis to compare outcomes between the two groups.

Results
Of 1555 patients included in this study, 1184 patients, including 170 patients taking antithrombotic drugs, were eligible for propensity score matching analysis. A 1:1 matching yielded 117 well-balanced pairs. There was no statistically significant difference in intraoperative blood loss (antithrombotic drug group vs control group, median (interquartile): 60 (225–10) vs 100 (243–10) ml, p = 0.43).

Conclusions
This study suggests that antithrombotic drugs do not increase intraoperative blood loss in patients undergoing emergency gastrointestinal surgery. Emergency gastrointestinal surgery for patients currently taking antithrombotic drugs can be performed safely, and the use of antithrombotic drugs is not a reason to delay surgical intervention.
Targeting T cell malignancies using CAR-based immunotherapy: challenges and potential solutions
Authors: Fleischer Lauren C. , Spencer H. Trent , Raikar Sunil S. 
Published: December 2019

AbstractChimeric antigen receptor (CAR) T cell therapy has been successful in treating B cell malignancies in clinical trials; however, fewer studies have evaluated CAR T cell therapy for the treatment of T cell malignancies. There are many challenges in translating this therapy for T cell disease, including fratricide, T cell aplasia, and product contamination. To the best of our knowledge, no tumor-specific antigen has been identified with universal expression on cancerous T cells, hindering CAR T cell therapy for these malignancies. Numerous approaches have been assessed to address each of these challenges, such as (i) disrupting target antigen expression on CAR-modified T cells, (ii) targeting antigens with limited expression on T cells, and (iii) using third party donor cells that are either non-alloreactive or have been genome edited at the T cell receptor α constant (TRAC) locus. In this review, we discuss CAR approaches that have been explored both in preclinical and clinical studies targeting T cell antigens, as well as examine other potential strategies that can be used to successfully translate this therapy for T cell disease.
Musashi2 contributes to the maintenance of CD44v6+ liver cancer stem cells via notch1 signaling pathway
Authors: Wang Xiju , Wang Ronghua , Bai Shuya , Xiong Si , Li Yawen , Liu Man , Zhao Zhenxiong , Wang Yun , Zhao Yuchong , Chen Wei , Billiar Timothy R. , Cheng Bin 
Published: December 2019

AbstractBackgroundLiver cancer stem cells (LCSCs) contribute to hepatocellular carcinoma (HCC) development, metastasis, and drug resistance. MSI2 and Notch1 signaling are involved in the maintenance of CSCs. However, it is unknown whether MSI2 and Notch1 are involved in the maintenance of CD44v6+ LCSCs. Therefore, we investigated the clinical significance and function of MSI2 and its relationship with Notch1 signaling in the maintenance of stemness properties in CD44v6+ LCSCs.MethodsThe expression of MSI2 and CD44v6 were detected by fresh specimens and a HCC tissue microarray. The tissue microarray containing 82 HCC samples was used to analyze the correlation between CD44v6 and MSI2. CD44v6+/− cells were isolated using microbeads sorting. We explored the roles of MSI2 and Notch1 signaling in CD44v6+ LCSCs by sphere formation assay, transwell assay, clone formation assay in vitro, and xenograft tumor models in vivo. A Notch RT2PCR Array, Co-immunoprecipitation, and RNA-immunoprecipitation were used to further investigate the molecular mechanism of MSI2 in activating Notch1 signaling.ResultsHere, we found MSI2 expression was positively correlated with high CD44v6 expression in HCC tissues, and further correlated with tumor differentiation. CD44v6+ cells isolated from HCC cell lines exhibited increased self-renewal, proliferation, migration and invasion, resistance to Sorafenib and tumorigenic capacity. Both MSI2 and Notch1 signaling were elevated in sorted CD44v6+ cells than CD44v6- cells and played essential roles in the maintenance of stemness of CD44v6+ LCSCs. Mechanically, MSI2 directly bound to Lunatic fringe (LFNG) mRNA and protein, resulting in Notch1 activation.ConclusionsOur results demonstrated that MSI2 maintained the stemness of CD44v6+ LCSCs by activating Notch1 signaling through the interaction with LFNG, which could be a potential molecular target for stem cell-targeted therapy for liver cancer.
Does virtual reality reduce pain in pediatric patients? A systematic review
Authors: Iannicelli Anna Maria , Vito Daniele , Dodaro Concetta Anna , De Matteo Pasquale , Nocerino Rita , Sepe Angela , Raia Valeria 
Published: December 2019

AbstractVirtual Reality (VR) as a tool for pain reduction is the research topic of several clinical trial for Randomized Controlled Trials despite its wide use in the daily clinical practice for non- pharmacological reduction of pain in some countries. At present, there are no published reviews of VR-efficacy of pain reduction in pediatric patients. That is why we made a systematic review of the efficacy of VR as a tool for pain reduction in children and adolescents. Electronic databases and gray literature published between 2014 and 2019 were analyzed. A total of 9 studies were eligible according to the established inclusion criteria. Results show that virtual reality is a valid tool for non-pharmacological pain reduction and that this approach is to be preferred to the standard reduction techniques currently in use. However, more studies using standardized experimental methodologies are needed to provide more systematic comparison and quantitative synthesis.
Defining benefit threshold for extracorporeal membrane oxygenation in children with sepsis—a binational multicenter cohort study
Authors:   on behalf of the Australian & New Zealand Intensive Care Society (ANZICS) Centre for Outcomes & Resource Evaluation (CORE) and the Australian & New Zealand Intensive Care Society (ANZICS) Paediatric Study Group, Schlapbach Luregn J. , Chiletti Roberto , Straney Lahn , Festa Marino , Alexander Daniel , Butt Warwick , MacLaren Graeme 
Published: December 2019

AbstractBackgroundThe surviving sepsis campaign recommends consideration for extracorporeal membrane oxygenation (ECMO) in refractory septic shock. We aimed to define the benefit threshold of ECMO in pediatric septic shock.MethodsRetrospective binational multicenter cohort study of all ICUs contributing to the Australian and New Zealand Paediatric Intensive Care Registry. We included patients < 16 years admitted to ICU with sepsis and septic shock between 2002 and 2016. Sepsis-specific risk-adjusted models to establish ECMO benefit thresholds with mortality as the primary outcome were performed. Models were based on clinical variables available early after admission to ICU. Multivariate analyses were performed to identify predictors of survival in children treated with ECMO.ResultsFive thousand sixty-two children with sepsis and septic shock met eligibility criteria, of which 80 (1.6%) were treated with veno-arterial ECMO. A model based on 12 clinical variables predicted mortality with an AUROC of 0.879 (95% CI 0.864–0.895). The benefit threshold was calculated as 47.1% predicted risk of mortality. The observed mortality for children treated with ECMO below the threshold was 41.8% (23 deaths), compared to a predicted mortality of 30.0% as per the baseline model (16.5 deaths; standardized mortality rate 1.40, 95% CI 0.89–2.09). Among patients above the benefit threshold, the observed mortality was 52.0% (13 deaths) compared to 68.2% as per the baseline model (16.5 deaths; standardized mortality rate 0.61, 95% CI 0.39–0.92). Multivariable analyses identified lower lactate, the absence of cardiac arrest prior to ECMO, and the central cannulation (OR 0.31, 95% CI 0.10–0.98,p = 0.046) as significant predictors of survival for those treated with VA-ECMO.ConclusionsThis binational study demonstrates that a rapidly available sepsis mortality prediction model can define thresholds for survival benefit in children with septic shock considered for ECMO. Survival on ECMO was associated with central cannulation. Our findings suggest that a fully powered RCT on ECMO in sepsis is unlikely to be feasible.
Prophylactic use of levosimendan in pediatric patients undergoing cardiac surgery: a prospective randomized controlled trial
Authors: Wang Anbiao , Cui Chaomei , Fan Yiou , Zi Jie , Zhang Jie , Wang Guanglai , Wang Fang , Wang Jun , Tan Qi 
Published: December 2019

Abstract
Background
The administration of levosimendan prophylactically to patients undergoing cardiac surgery remains a controversial practice, and few studies have specifically assessed the value of this approach in pediatric patients. This study therefore sought to explore the safety and efficacy of prophylactic levosimendan administration to pediatric patients as a means of preventing low cardiac output syndrome (LCOS) based upon hemodynamic, biomarker, and pharmacokinetic readouts.

Methods
This was a single-center, double-blind, randomized, placebo-controlled trial. Patients ≤ 48 months old were enrolled between July 2018 and April 2019 and were randomly assigned to groups that received either placebo or levosimendan infusions for 48 h post-surgery, along with all other standard methods of care. LCOS incidence was the primary outcome of this study.

Results
A total of 187 patients were enrolled, of whom 94 and 93 received levosimendan and placebo, respectively. LCOS incidence did not differ significantly between the levosimendan and placebo groups (10 [10.6%] versus 18 [19.4%] patients, respectively; 95% confidence interval [CI] 0.19–1.13; p = 0.090) nor did 90-day mortality (3 [3.2%] versus 4 [4.3%] patients, CI 0.14–3.69, p = 0.693), duration of mechanical ventilation (median, 47.5 h and 39.5 h, respectively; p = 0.532), ICU stay (median, 114.5 h and 118 h, respectively; p = 0.442), and hospital stay (median, 20 days and 20 days, respectively; p = 0.806). The incidence of hypotension and cardiac arrhythmia did not differ significantly between the groups. Levels of levosimendan fell rapidly without any plateau in plasma concentrations during infusion. A multiple logistic regression indicated that randomization to the levosimendan group was a predictor of LCOS.

Conclusions
Prophylactic levosimendan administration was safe in pediatric patients and had some benefit to postoperative hemodynamic parameters, but failed to provide significant benefit with respect to LCOS or 90-day mortality relative to placebo.

Trial registration
Name of the registry: Safety evaluation and therapeutic effect of levosimendan on the low cardiac output syndrome in patients after cardiopulmonary bypass. Trial registration number: ChiCTR1800016594. Date of registration: 11 June 2018. URL of trial registry record: http://www.chictr.org.cn/index.aspx
Lasting s-ketamine block of spreading depolarizations in subarachnoid hemorrhage: a retrospective cohort study
Authors: Santos Edgar , Olivares-Rivera Arturo , Major Sebastian , Sánchez-Porras Renán , Uhlmann Lorenz , Kunzmann Kevin , Zerelles Roland , Kentar Modar , Kola Vasilis , Aguilera Adrian Hernández , Herrera Mildred Gutierrez , Lemale Coline L. , Woitzik Johannes , Hartings Jed A. , Sakowitz Oliver W. , Unterberg Andreas W. , Dreier Jens P. 
Published: December 2019

Abstract
Objective
Spreading depolarizations (SD) are characterized by breakdown of transmembrane ion gradients and excitotoxicity. Experimentally, N-methyl-d-aspartate receptor (NMDAR) antagonists block a majority of SDs. In many hospitals, the NMDAR antagonist s-ketamine and the GABAA agonist midazolam represent the current second-line combination treatment to sedate patients with devastating cerebral injuries. A pressing clinical question is whether this option should become first-line in sedation-requiring individuals in whom SDs are detected, yet the s-ketamine dose necessary to adequately inhibit SDs is unknown. Moreover, use-dependent tolerance could be a problem for SD inhibition in the clinic.

Methods
We performed a retrospective cohort study of 66 patients with aneurysmal subarachnoid hemorrhage (aSAH) from a prospectively collected database. Thirty-three of 66 patients received s-ketamine during electrocorticographic neuromonitoring of SDs in neurointensive care. The decision to give s-ketamine was dependent on the need for stronger sedation, so it was expected that patients receiving s-ketamine would have a worse clinical outcome.

Results
S-ketamine application started 4.2 ± 3.5 days after aSAH. The mean dose was 2.8 ± 1.4 mg/kg body weight (BW)/h and thus higher than the dose recommended for sedation. First, patients were divided according to whether they received s-ketamine at any time or not. No significant difference in SD counts was found between groups (negative binomial model using the SD count per patient as outcome variable, p = 0.288). This most likely resulted from the fact that 368 SDs had already occurred in the s-ketamine group before s-ketamine was given. However, in patients receiving s-ketamine, we found a significant decrease in SD incidence when s-ketamine was started (Poisson model with a random intercept for patient, coefficient − 1.83 (95% confidence intervals − 2.17; − 1.50), p < 0.001; logistic regression model, odds ratio (OR) 0.13 (0.08; 0.19), p < 0.001). Thereafter, data was further divided into low-dose (0.1–2.0 mg/kg BW/h) and high-dose (2.1–7.0 mg/kg/h) segments. High-dose s-ketamine resulted in further significant decrease in SD incidence (Poisson model, − 1.10 (− 1.71; − 0.49), p < 0.001; logistic regression model, OR 0.33 (0.17; 0.63), p < 0.001). There was little evidence of SD tolerance to long-term s-ketamine sedation through 5 days.

Conclusions
These results provide a foundation for a multicenter, neuromonitoring-guided, proof-of-concept trial of ketamine and midazolam as a first-line sedative regime.