bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimal timing of primaquine to reduce Plasmodium falciparum gametocyte carriage when co-administered with artemether–lumefantrine
Authors: Shekalaghe Seif , Mosha Dominic , Hamad Ali , Mbaga Thabit A. , Mihayo Michael , Bousema Teun , Drakeley Chris , Abdulla Salim 
Published: January 2020

Abstract
Background
Primaquine is an important gametocytocidal drug that is combined with conventional malaria treatment for prevention of Plasmodium falciparum malaria transmission. Primaquine has been administered together on the first or the last day of conventional treatment but the impact of primaquine timing has never been examined. This study aimed to assess safety, efficacy and optimal timing of single full-dose (0.75 mg/kg) primaquine when added to a standard 6-dose regimen of artemether–lumefantrine (AL).

Methods
In an individual-level randomized controlled trial, enrolled participants who were G6PD normal and had uncomplicated P. falciparum malaria were randomly assigned to receive: AL only; AL and a single 0.75 mg/kg primaquine dose on the first day of AL (day 1); or AL and single 0.75 mg//kg primaquine on the last day of AL (day 3). On days 2, 3, 4, 8, 11 and 15, gametocytes were assessed and quantified by microscope and quantitative nuclear acid sequence based quantification (QT-NASBA).

Results
Overall, 111 participants aged between 3 and 17 years were randomly allocated to receive AL only (36) or combined with primaquine on day 1 (38), or primaquine on day 3 (37). Day 4 gametocyte prevalence in AL + day 1 primaquine was half the level seen in either AL + day 3 primaquine or AL only arm (11% [4/35] vs 26% [8/31] and 27% [8/30], respectively) albeit not statistically significant. A similar trend of lower gametocyte in the AL + day 1 primaquine verses AL + day 3 primaquine or AL only arm was observed in mean gametocyte density. Mean (sd) haemoglobin level in AL + day 3 primaquine arm recovered from -0.42(1.2) g/dl on day 2 to 0.35 (1.5) g/dl on day 15 of follow up. This was not the case in AL only and AL + day 1 primaquine arms during the same follow-up period, although the difference was not statistically significant (p = 318). No serious adverse events reported in the study. Across arms, 23% (26/111) of participants reported a total of 31 mild adverse events and the difference was not statistically significant (p = 0.477).

Conclusion
Primaquine administration on the first day of AL is well tolerated and as safe as later administration. Whilst the World Health Organization currently recommends a lower dose of primaquine (0.25 mg/kg), the findings are supportive of early primaquine administration when combined with artemisinin-combination therapy.
ClinicalTrials.gov Registration NCT01906788
Elaboration of a multimodal MRI-based radiomics signature for the preoperative prediction of the histological subtype in patients with non-small-cell lung cancer
Authors: Tang Xing , Xu Xiaopan , Han Zhiping , Bai Guoyan , Wang Hong , Liu Yang , Du Peng , Liang Zhengrong , Zhang Jian , Lu Hongbing , Yin Hong 
Published: January 2020

Abstract
Background
Non-invasive discrimination between lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) subtypes of non-small-cell lung cancer (NSCLC) could be very beneficial to the patients unfit for the invasive diagnostic procedures. The aim of this study was to investigate the feasibility of utilizing the multimodal magnetic resonance imaging (MRI) radiomics and clinical features in classifying NSCLC. This retrospective study involved 148 eligible patients with postoperative pathologically confirmed NSCLC. The study was conducted in three steps: (1) feature extraction was performed using the online freely available package with the multimodal MRI data; (2) feature selection was performed using the Student’s t test and support vector machine (SVM)-based recursive feature elimination method with the training cohort (n = 100), and the performance of these selected features was evaluated using both the training and the validation cohorts (n = 48) with a non-linear SVM classifier; (3) a Radscore model was then generated using logistic regression algorithm; (4) Integrating the Radscore with the semantic clinical features, a radiomics–clinical nomogram was developed, and its overall performance was evaluated with both cohorts.

Results
Thirteen optimal features achieved favorable discrimination performance with both cohorts, with area under the curve (AUC) of 0.819 and 0.824, respectively. The radiomics–clinical nomogram integrating the Radscore with the independent clinical predictors exhibited more favorable discriminative power, with AUC improved to 0.901 and 0.872 in both cohorts, respectively. The Hosmer–Lemeshow test and decision curve analysis results furtherly showed good predictive precision and clinical usefulness of the nomogram.

Conclusion
Non-invasive histological subtype stratification of NSCLC can be done favorably using multimodal MRI radiomics features. Integrating the radiomics features with the clinical features could further improve the performance of the histological subtype stratification in patients with NSCLC.
Complete resolution of urinary incontinence with treatment improved the health-related quality of life of children with functional daytime urinary incontinence: a prospective study
Authors: Ikeda Hirokazu , Oyake Chisato , Oonuki Yuta , Fuyama Masaki , Watanabe Tsuneki , Kyoda Takashi , Tamura Setuko 
Published: January 2020

Abstract
Background
To assess the health-related quality of life (HRQOL) of children with daytime urinary incontinence (DUI) based on pre- and post-treatment self-reports and parent proxy-reports.

Methods
The study population comprised 117 children with at least one episode of DUI per week and their caregivers as well as 999 healthy children (control group). The Pediatric Quality of Life Inventory 4.0 (PedsQL) questionnaire was administered to assess the HRQOL of children. To assess the degree of improvement in HRQOL, we categorized children into two groups: group A achieved complete response (CR) to treatment within 12 months and group B did not achieve CR within 12 months. CR was defined as the complete resolution of symptoms or alleviation of symptoms to < 1 DUI episode/month.

Results
Valid responses were collected from 84 children [53 boys and 31 girls; mean age: 7.9 ± 1.5 years (range, 6–12)]. Sixty-two patients (73.8%) were classified into group A and 22 (26.1%) into group B. Based on self-reports, significant post-treatment improvement was observed in the scores of all PedsQL items (mean total score: 82.2 ± 11.3 vs. 87.2 ± 9.8; P = 0.003). Group A showed significant improvement in the scores of all PedsQL items after achievement of CR based on child self-reports; however, this was improvement not observed in group B.

Conclusions
To the best of our knowledge, this is the first study to demonstrate the complete resolution of DUI with treatment for improving the HRQOL of these children.
Designing clinical practice feedback reports: three steps illustrated in Veterans Health Affairs long-term care facilities and programs
Authors: Landis-Lewis Zach , Kononowech Jennifer , Scott Winifred J. , Hogikyan Robert V. , Carpenter Joan G. , Periyakoil V. S. , Miller Susan C. , Levy Cari , Ersek Mary , Sales Anne 
Published: January 2020

Abstract
Background
User-centered design (UCD) methods are well-established techniques for creating useful artifacts, but few studies illustrate their application to clinical feedback reports. When used as an implementation strategy, the content of feedback reports depends on a foundational audit process involving performance measures and data, but these important relationships have not been adequately described. Better guidance on UCD methods for designing feedback reports is needed. Our objective is to describe the feedback report design method for refining the content of prototype reports.

Methods
We propose a three-step feedback report design method (refinement of measures, data, and display). The three steps follow dependencies such that refinement of measures can require changes to data, which in turn may require changes to the display. We believe this method can be used effectively with a broad range of UCD techniques.

Results
We illustrate the three-step method as used in implementation of goals of care conversations in long-term care settings in the U.S. Veterans Health Administration. Using iterative usability testing, feedback report content evolved over cycles of the three steps. Following the steps in the proposed method through 12 iterations with 13 participants, we improved the usability of the feedback reports.

Conclusions
UCD methods can improve feedback report content through an iterative process. When designing feedback reports, refining measures, data, and display may enable report designers to improve the user centeredness of feedback reports.
The scale affects our view on the identification and distribution of microbial communities in ticks
Authors: Pollet Thomas , Sprong Hein , Lejal Emilie , Krawczyk Aleksandra I. , Moutailler Sara , Cosson Jean-Francois , Vayssier-Taussat Muriel , Estrada-Peña Agustín 
Published: January 2020

AbstractTicks transmit the highest variety of pathogens impacting human and animal health worldwide. It is now well established that ticks also harbour a microbial complex of coexisting symbionts, commensals and pathogens. With the development of high throughput sequencing technologies, studies dealing with such diverse bacterial composition in tick considerably increased in the past years and revealed an unexpected microbial diversity. These data on diversity and composition of the tick microbes are increasingly available, giving crucial details on microbial communities in ticks and improving our knowledge on the tick microbial community. However, consensus is currently lacking as to which scales (tick organs, individual specimens or species, communities of ticks, populations adapted to particular environmental conditions, spatial and temporal scales) best facilitate characterizing microbial community composition of ticks and understanding the diverse relationships among tick-borne bacteria. Temporal or spatial scales have a clear influence on how we conduct ecological studies, interpret results, and understand interactions between organisms that build the microbiome. We consider that patterns apparent at one scale can collapse into noise when viewed from other scales, indicating that processes shaping tick microbiome have a continuum of variability that has not yet been captured. Based on available reports, this review demonstrates how much the concept of scale is crucial to be considered in tick microbial community studies to improve our knowledge on tick microbe ecology and pathogen/microbiota interactions.
MicroRNA-126 protects against vascular injury by promoting homing and maintaining stemness of late outgrowth endothelial progenitor cells
Authors: Pei Chong Zhe , Liu Bo , Li Ye Ting , Fang Lu , Zhang Yi , Li Yi Gang , Meng Shu 
Published: January 2020

Abstract
Background
Endothelial progenitor cells (EPCs) contribute to reendothelialization and neovascularization and protect against vascular injury and ischemia of various organs. We have previously shown downregulation of microRNA (miR)-126 in EPCs from diabetic patients, which contributes to dysfunction of EPCs including impaired migratory ability. The aims of the present study were to examine (1) in vitro the effects of miR-126 on the homing and stemness of late outgrowth EPCs (LOCs), along with relevant signaling pathways, and (2) in vivo the effects of modulating LOCs by manipulating miR-126 expression on LOC homing and reendothelialization of injured arteries in GK rats (a non-obese diabetes model).

Methods
Rat bone marrow-derived LOCs were transfected with miR-126 inhibitor or lentiviral vectors expressing miR-126. LOC migration was determined by transwell migration assay. CXCR4 expression was measured by real-time PCR, Western blotting, and confocal microscopy while related signaling pathway proteins were measured by Western Blotting. Stemness gene expression, and gene and protein expression and promoter activity of KLF-8 were also measured. LOCs transfected with lenti-miR-126 or miR-126 inhibitor were injected into GK rats with carotid artery injury, and then vascular reendothelialization and the extent of intimal hyperplasia were examined.

Results
Lenti-miR-126 increased while miR-126 inhibitor decreased LOC migration and CXCR4 expression on LOCs. miR-126 positively regulated p-ERK, VEGF, p-Akt, and eNOS protein expression, and inhibitors of these proteins blocked miR-126-induced CXCR4 expression and also reduced LOC migration. Overexpression of miR-126 promoted while inhibition of miR-126 suppressed stemness gene expression in LOCs. miR-126 also inhibited gene and protein expression and promoter activity of KLF-8 while shRNA-mediated knockdown of KLF-8 increased stemness gene expression. Upregulation of stemness gene expression by miR-126 overexpression was completely abrogated by co-transfection of lenti-KLF-8 and lenti-miR-126 into LOCs. In GK rats, transplantation of LOCs overexpressing miR-126 enhanced LOC homing and reendothelialization and decreased intimal hyperplasia of injured arteries.

Conclusion
Our results indicate that miR-126 protects against vascular injury by promoting CXCR4 expression and LOC homing via ERK/VEGF and Akt/eNOS signaling pathways and maintaining stemness via targeting KLF-8.
LncRNA-NEAT1 from the competing endogenous RNA network promotes cardioprotective efficacy of mesenchymal stem cell-derived exosomes induced by macrophage migration inhibitory factor via the miR-142-3p/FOXO1 signaling pathway
Authors: Chen Hanbin , Xia Wenzheng , Hou Meng 
Published: January 2020

AbstractAimsExtracellular vesicles, especially exosomes, have emerged as key mediators of intercellular communication with the potential to improve cardiac function as part of cell-based therapies. We previously demonstrated that the cardioprotective factor, macrophage migration inhibitory factor (MIF), had an optimizing effect on mesenchymal stem cells (MSCs). The aim of this study was to determine the protective function of exosomes derived from MIF-pretreated MSCs in cardiomyocytes and to explore the underlying mechanisms.Methods and resultsExosomes were isolated from control MSCs (exosome) and MIF-pretreated MSCs (exosomeMIF), and delivered to cardiomyocytes subjected to H2O2in vitro. Regulatory long non-coding RNAs (lncRNAs) activated by MIF pretreatment were explored using genomics approaches. ExosomeMIFprotected cardiomyocytes from H2O2-induced apoptosis. Mechanistically, we identified lncRNA-NEAT1 as a mediator of exosomeMIFby regulating the expression of miR-142-3p and activating Forkhead class O1 (FOXO1). The cardioprotective effects of exosomeMIFwere consistently abrogated by depletion of lncRNA-NEAT1, by overexpression of miR-142-3p, or by FOXO1 silencing. Furthermore, exosomeMIFinhibited H2O2-induced apoptosis through modulating oxidative stress.ConclusionsExosomes obtained from MIF-pretreated MSCs have a protective effect on cardiomyocytes. The lncRNA-NEAT1 functions as an anti-apoptotic molecule via competitive endogenous RNA activity towards miR-142-3p. LncRNA-NEAT1/miR-142-3p/FOXO1 at least partially mediates the cardioprotective roles of exosomeMIFin protecting cardiomyocytes from apoptosis.
The emerging specialty of perioperative medicine: a UK survey of the attitudes and behaviours of anaesthetists
Authors: Partridge J. S. L. , Rogerson A. , Joughin A. L. , Walker D. , Simon J. , Swart M. , Dhesi J. K. 
Published: January 2020

Abstract
Background
In 2014, the Royal College of Anaesthetists (RCoA) launched the Perioperative Medicine Programme to facilitate the delivery of best preoperative, intraoperative and postoperative care through implementation of evidence-based medicine to reduce variation and improve postoperative outcomes. However, variation exists in the establishment of perioperative medicine services in the UK. This survey explored attitudes and behaviours of anaesthetists towards perioperative medicine, described current anaesthetic-led perioperative medicine services across the UK and explored barriers to anaesthetic involvement in perioperative medicine.

Methods
Survey content based on the RCoA vision document was refined and validated using an expert panel. An anonymous electronic survey was then sent by email to the members of the RCoA.

Results
Seven hundred fifty-eight UK anaesthetists (4.5% of the RCoA mailing list) responded to the survey. Of these, 64% considered themselves a perioperative doctor, with 65% having changed local services in response to the RCoA vision. Barriers to developing perioperative medicine included insufficient time (75%) and inadequate training (51%). Three quarters of respondents advocate anaesthetists leading the development of perioperative medicine.

Conclusions
Despite evidence of emerging services, this survey describes barriers to ongoing development of perioperative medicine. Facilitators may include increased clinical exposure, targeted education and training and collaborative working with other specialties.
Experimental Investigation on Flexural Behavior of Reinforced Ultra High Performance Concrete Low-Profile T-Beams
Authors: Qiu Minghong , Shao Xudong , Wille Kay , Yan Banfu , Wu Jiajia 
Published: January 2020

AbstractThe flexural behavioral properties of ultra high performance concrete (UHPC) low-profile T-beams reinforced with a combination of steel fibers and steel reinforcing bars were investigated in this paper. Five large scale T-beams were tested and analyzed regarding their deflection, ductility, strain, curvature, load capacity and crack development. The experimental variables include the reinforcement ratio, the slenderness (length to diameter ratio) of the fiber reinforcements, and the fiber type. The experiments showed that all specimens exhibit flexural failure with the yielding of steel bars and excessive expansion of flexural crack, and the compression zone in the reinforced UHPC low-profile T-beam is not crushed because of the ultra high compressive strength and area of UHPC. In addition, it was concluded that using hooked-end fibers can effectively increase the specimen’s durability-based cracking load in comparison to straight fibers of same slenderness, whereas the reinforcement ratio and the slenderness of the fibers have little influence on this. Increasing the reinforcement ratio and using hooked-end instead of straight fibers increase the load capacity and bending stiffness of the specimen, as well as reduces the crack width at comparable applied load. A model was established to compute the ultimate capacity of UHPC low-profile T-beams and the prediction agrees well with the experimental results in the present and published investigations.
Energetic performance index improvement after Glenn and Damus-Kaye-Stansel procedure using vector flow mapping analysis: a case report
Authors: Kainuma Atsushi , Akiyama Koichi , Naito Yoshifumi , Hayase Kazuma , Hongu Hisayuki , Itatani Keiichi , Yamagishi Masaaki , Sawa Teiji 
Published: January 2020

Abstract
Background
Echocardiography vector flow mapping can assess dynamic flow to treat congenital heart diseases. We evaluated intracardiac flow, energy loss, left ventricular output kinetic energy, and energetic performance index using vector flow mapping during Glenn and Damus-Kaye-Stansel procedures in order to assess the efficacy of the surgery.

Case presentation
A 9-month-old boy underwent Glenn and Damus-Kaye-Stansel procedures. The energy loss depends on the left ventricular preload; therefore, energy loss decreased after the Glenn procedure. After the Damus-Kaye-Stansel procedure, the kinetic energy would increase owing to the integrated systemic outflow; however, in our case, kinetic energy decreased, which was potentially explained by the fact that kinetic energy also depends on the left ventricular preload. After the Glenn and Damus-Kaye-Stansel procedures, we detected an improvement in energetic performance index, indicating that the cardiac workload improved as well.

Conclusion
We revealed the efficiency of the Glenn and Damus-Kaye-Stansel procedures using vector flow mapping.
Phase IB/II Trial of Lenvatinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma, Endometrial Cancer, and Other Selected Advanced Solid Tumors
Authors: Taylor Matthew H. , Lee Chung-Han , Makker Vicky , Rasco Drew , Dutcus Corina E. , Wu Jane , Stepan Daniel E. , Shumaker Robert C. , Motzer Robert J. 
Published: January 2020

PURPOSE Modulation of vascular endothelial growth factor–mediated immune suppression via angiogenesis inhibition may augment the activity of immune checkpoint inhibitors. We report results from the dose-finding and initial phase II expansion of a phase Ib/II study of lenvatinib plus pembrolizumab in patients with selected advanced solid tumors. METHODS Eligible patients had metastatic renal cell carcinoma (RCC), endometrial cancer, squamous cell carcinoma of the head and neck (SCCHN), melanoma, non–small-cell lung cancer (NSCLC), or urothelial cancer. The primary objective of phase Ib was to determine the maximum tolerated dose (MTD) for lenvatinib plus pembrolizumab (200 mg intravenously every 3 weeks). In the preplanned phase II cohort expansion, the primary objective was objective response rate at week 24 (ORRweek 24) at the recommended phase II dose. RESULTS Overall, 137 patients were enrolled during phase Ib (n = 13) and the initial phase II expansion (n = 124). Two dose-limiting toxicities (DLTs; grade 3 arthralgia and grade 3 fatigue) were reported in the initial dose level (lenvatinib 24 mg/d plus pembrolizumab). No DLTs were observed in the subsequent dose–de-escalation cohort, establishing the MTD and recommended phase II dose at lenvatinib 20 mg/d plus pembrolizumab. ORRweek24 was as follows: RCC, 63% (19/30; 95% CI, 43.9% to 80.1%); endometrial cancer, 52% (12/23; 95% CI, 30.6% to 73.2%); melanoma, 48% (10/21; 95% CI, 25.7% to 70.2%); SCCHN, 36% (8/22; 95% CI, 17.2% to 59.3%); NSCLC, 33% (7/21; 95% CI, 14.6% to 57.0%); and urothelial cancer 25% (5/20; 95% CI, 8.7% to 49.1%). The most common treatment-related adverse events were fatigue (58%), diarrhea (52%), hypertension (47%), and hypothyroidism (42%). CONCLUSION Lenvatinib plus pembrolizumab demonstrated a manageable safety profile and promising antitumor activity in patients with selected solid tumor types.