bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using the Multiphase Optimization Strategy (MOST) framework to test intervention delivery strategies: a study protocol
Authors: Broder-Fingert Sarabeth , Kuhn Jocelyn , Sheldrick Radley Christopher , Chu Andrea , Fortuna Lisa , Jordan Megan , Rubin Dana , Feinberg Emily 
Published: December 2019

Abstract
Background
Delivery of behavioral interventions is complex, as the majority of interventions consist of multiple components used either simultaneously, sequentially, or both. The importance of clearly delineating delivery strategies within these complex interventions—and furthermore understanding the impact of each strategy on effectiveness—has recently emerged as an important facet of intervention research. Yet, few methodologies exist to prospectively test the effectiveness of delivery strategies and how they impact implementation. In the current paper, we describe a study protocol for a large randomized controlled trial in which we will use the Multiphase Optimization Strategy (MOST), a novel framework developed to optimize interventions, i.e., to test the effectiveness of intervention delivery strategies using a factorial design. We apply this framework to delivery of Family Navigation (FN), an evidence-based care management strategy designed to reduce disparities and improve access to behavioral health services, and test four components related to its implementation.

Methods/design
The MOST framework contains three distinct phases: Preparation, Optimization, and Evaluation. The Preparation phase for this study occurred previously. The current study consists of the Optimization and Evaluation phases. Children aged 3-to-12 years old who are detected as “at-risk” for behavioral health disorders (n = 304) at a large, urban federally qualified community health center will be referred to a Family Partner—a bicultural, bilingual member of the community with training in behavioral health and systems navigation—who will perform FN. Families will then be randomized to one of 16 possible combinations of FN delivery strategies (2 × 2 × 2× 2 factorial design). The primary outcome measure will be achieving a family-centered goal related to behavioral health services within 90 days of randomization. Implementation data on the fidelity, acceptability, feasibility, and cost of each strategy will also be collected. Results from the primary and secondary outcomes will be reviewed by our team of stakeholders to optimize FN delivery for implementation and dissemination based on effectiveness, efficiency, and cost.

Discussion
In this protocol paper, we describe how the MOST framework can be used to improve intervention delivery. These methods will be useful for future studies testing intervention delivery strategies and their impact on implementation.

Trial registration
ClinicalTrials.gov, NCT03569449. Registered on 26 June 2018.
Efficacy of chlorthalidone and hydrochlorothiazide in combination with amiloride in multiple doses on blood pressure in patients with primary hypertension: a protocol for a factorial randomized controlled trial
Authors: Martins Vítor Magnus , Helal Lucas , Ferrari Filipe , Bottino Leonardo Grabinski , Fuchs Sandra Costa , Fuchs Flávio Danni 
Published: December 2019

Abstract
Background
Thiazide diuretics have demonstrated favorable blood pressure lowering efficacy, but the equivalent doses of their more common agents, chlorthalidone and hydrochlorothiazide, are still unclear. Further, concerns exist regarding adverse metabolic effects, which may be attenuated with the concomitant administration of a potassium-sparing diuretic, such as amiloride. This trial aims to investigate the efficacy of chlorthalidone and hydrochlorothiazide, in combination with amiloride at different doses, for initial management of patients with primary hypertension.

Methods/design
This is a factorial (2 × 2) randomized double-blinded clinical trial comparing the association of a thiazide diuretic (chlorthalidone 25 mg/day or hydrochlorothiazide 50 mg/day) with a potassium-sparing diuretic (amiloride 10 mg/day or amiloride 20 mg/day) in patients with primary hypertension. The primary outcome will be the mean change from baseline in 24-h systolic and diastolic blood pressure measured by ambulatory blood pressure monitoring. The secondary outcomes will be the mean change from baseline in daytime and nighttime systolic and diastolic blood pressure measured by ambulatory blood pressure monitoring, mean change from baseline in systolic and diastolic blood pressure measured by office blood pressure, incidence of adverse events, variation of laboratory parameters, and proportion of patients who achieved blood pressure control. The follow-up will last 12 weeks. For a P alpha of 0.05, power of 80%, standard deviation of 9 mmHg, and absolute difference of 6 mmHg on systolic blood pressure on 24-h ambulatory blood pressure monitoring, it will be necessary to study a total of 76 patients. The sample size will be increased by 10% to compensate for losses, resulting in 84 patients being randomized.

Discussion
Diuretics are pivotal drugs for the treatment of hypertension. Chlorthalidone and hydrochlorothiazide, in combination with amiloride in multiple doses, will be tested in terms of blood pressure lowering efficacy and safety. Since the intensity of blood pressure reduction is the major determinant of reduction in cardiovascular risk in hypertensive patients, this study will help to determine which combination of diuretics represents the most appropriate treatment for this population.

Trial registration
ClinicalTrials.gov, NCT03928145. Registered on 25 April 2019. Last update on 29 April 2019.
Genome shuffling enhances stress tolerance of Zymomonas mobilis to two inhibitors
Authors: Wang Weiting , Wu Bo , Qin Han , Liu Panting , Qin Yao , Duan Guowei , Hu Guoquan , He Mingxiong 
Published: December 2019

Abstract
Background
Furfural and acetic acid are the two major inhibitors generated during lignocellulose pretreatment and hydrolysis, would severely inhibit the cell growth, metabolism, and ethanol fermentation efficiency of Zymomonas mobilis. Effective genome shuffling mediated by protoplast electrofusion was developed and then applied to Z. mobilis.

Results
After two rounds of genome shuffling, 10 different mutants with improved cell growth and ethanol yield in the presence of 5.0 g/L acetic acid and 3.0 g/L furfural were obtained. The two most prominent genome-shuffled strains, 532 and 533, were further investigated along with parental strains in the presence of 7.0 g/L acetic acid and 3.0 g/L furfural. The results showed that mutants 532 and 533 were superior to the parental strain AQ8-1 in the presence of 7.0 g/L acetic acid, with a shorter fermentation time (30 h) and higher productivity than AQ8-1. Mutant 533 exhibited subtle differences from parental strain F34 in the presence of 3.0 g/L furfural. Mutations present in 10 genome-shuffled strains were identified via whole-genome resequencing, and the source of each mutation was identified as either de novo mutation or recombination of the parent genes.

Conclusions
These results indicate that genome shuffling is an efficient method for enhancing stress tolerance in Z. mobilis. The engineered strains generated in this study could be potential cellulosic ethanol producers in the future.
Prevalence and genetic characterization of Toxoplasma gondii in naturally infected backyard pigs intended for familial consumption in Romania
Authors: Paştiu Anamaria Ioana , Cozma-Petruț Anamaria , Mercier Aurélien , Balea Anamaria , Galal Lokman , Mircean Viorica , Pusta Dana Liana , Bogdan Liviu , Györke Adriana 
Published: December 2019

Abstract
Background
Foodborne toxoplasmosis in humans can be due to the exposure to tissue cysts of Toxoplasma gondii through the consumption of meat, including pork, of infected animals. Traditional Romanian food habits include pork as the preferred meat, while backyard pig rearing remains a common practice in many rural areas of Romania. The aims of the present study were to estimate the prevalence of T. gondii infection in naturally infected backyard pigs slaughtered for familial consumption and to genetically characterize the T. gondii strains obtained.

Methods
Paired blood and heart samples were collected from 94 backyard pigs, home slaughtered for private consumption. Serum samples were analyzed using the immunofluorescence antibody test (IFAT) for anti-T. gondii antibody detection. Heart samples were screened by polymerase chain reaction (PCR) targeting the 529-bp repeat region (REP529) for T. gondii detection. In addition, heart samples from IFAT positive animals were bioassayed in mice. The T. gondii isolates were genotyped by the analysis of 15 microsatellite markers.

Results
The results showed that almost half of the pigs investigated were T. gondii seropositive (46.8%, 95% confidence interval (CI): 36.4–57.4%) and in more than a quarter of the pigs (26.6%, 95% CI: 18.0–36.7%), the parasite was detected by PCR. Three (3/44) T. gondii strains were isolated from hearts of seropositive pigs and they all belonged to genotype II.

Conclusions
The present study showed the presence of T. gondii infection in backyard pigs in Romania, which suggests that consumption of pork from animals reared and slaughtered at home may pose a potential threat to human health and should be given attention. In addition, to our knowledge, this is the first study to provide data concerning T. gondii strains circulating in pigs from Romania.
B lymphocyte stimulator modulates number and function of endothelial progenitor cells in systemic lupus erythematosus
Authors: Spinelli Francesca Romana , Barbati Cristiana , Cecarelli Fulvia , Morello Francesca , Colasanti Tania , Vomero Marta , Massaro Laura , Orefice Valeria , Alessandri Cristiano , Valesini Guido , Conti Fabrizio 
Published: December 2019

Abstract
Background
Circulating endothelial progenitor cells (EPCs) are biologic markers of endothelial function. In patients with systemic lupus erythematosus (SLE), the numerical reduction and functional impairment of EPCs contribute to the endothelial dysfunction.
Through ex vivo and in vitro studies, we aimed at evaluating the effects of B lymphocyte stimulator (BLyS) on EPC colonies and endothelial cells and also investigating BLyS receptor expression on these cells.

Methods
EPCs were isolated from peripheral blood mononuclear cells (PBMC). In order to evaluate their ability to form colonies, EPCs were cultured on fibronectin-coated dishes and incubated with BlyS alone or BlyS and belimumab. Apoptosis of EPCs and endothelial cell line EA.hy926 was evaluated after 6, 12, and 24 h of incubation with BLyS and after 6 h with BLyS and belimumab. The expression of B cell activating factor-receptor (BAFF-R), B cell maturation antigen (BCMA), and transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI) on EPCs and EA.hy926 was analyzed by cytofluorimetry.

Results
The number of EPC colonies was lower in patients than in controls. Moreover, the colonies from SLE patients were poorly organized compared to controls; the addition of belimumab restored the colony structure. Incubation with BLyS induced apoptosis of EPCs and EA.hy926 that was inhibited by the co-incubation with belimumab. BAFF-R and BCMA were expressed on both EPCs and EA.hy926, while TACI was expressed only on EPCs.

Conclusions
EPCs and endothelial cells preferentially express BAFF-R which could be involved in the pro-apoptotic effect of BlyS. Belimumab administration seems to restore the quantitative and qualitative changes of EPC colonies both ex vivo and in vitro.
Comparison of different technologies for the decipherment of the whole genome sequence of Campylobacter jejuni BfR-CA-14430
Authors: Epping Lennard , Golz Julia C. , Knüver Marie-Theres , Huber Charlotte , Thürmer Andrea , Wieler Lothar H. , Stingl Kerstin , Semmler Torsten 
Published: December 2019

AbstractBackgroundCampylobacter jejuniis a zoonotic pathogen that infects the human gut through the food chain mainly by consumption of undercooked chicken meat, raw chicken cross-contaminated ready-to-eat food or by raw milk. In the last decades,C. jejunihas increasingly become the most common bacterial cause for food-born infections in high income countries, costing public health systems billions of euros each year. Currently, different whole genome sequencing techniques such as short-read bridge amplification and long-read single molecule real-time sequencing techniques are applied for in-depth analysis of bacterial species, in particular, Illumina MiSeq, PacBio and MinION.ResultsIn this study, we analyzed a recently isolatedC. jejunistrain from chicken meat by short- and long-read data from Illumina, PacBio and MinION sequencing technologies. For comparability, this strain is used in the German PAC-CAMPY research consortium in several studies, including phenotypic analysis of biofilm formation, natural transformation and in vivo colonization models. The complete assembled genome sequence most likely consists of a chromosome of 1,645,980 bp covering 1665 coding sequences as well as a plasmid sequence with 41,772 bp that encodes for 46 genes. Multilocus sequence typing revealed that the strain belongs to the clonal complex CC-21 (ST-44) which is known to be involved inC. jejunihuman infections, including outbreaks. Furthermore, we discovered resistance determinants and a point mutation in the DNA gyrase (gyrA) that render the bacterium resistant against ampicillin, tetracycline and (fluoro-)quinolones.ConclusionThe comparison of Illumina MiSeq, PacBio and MinION sequencing and analyses with different assembly tools enabled us to reconstruct a complete chromosome as well as a circular plasmid sequence of theC. jejunistrain BfR-CA-14430. Illumina short-read sequencing in combination with either PacBio or MinION can substantially improve the quality of the complete chromosome and epichromosomal elements on the level of mismatches and insertions/deletions, depending on the assembly program used.
Association of metabolic and genetic heterogeneity in head and neck squamous cell carcinoma with prognostic implications: integration of FDG PET and genomic analysis
Authors: Choi Jinyeong , Gim Jeong-An , Oh Chiwoo , Ha Seunggyun , Lee Howard , Choi Hongyoon , Im Hyung-Jun 
Published: December 2019

Abstract
Purpose
The linkage between the genetic and phenotypic heterogeneity of the tumor has not been thoroughly evaluated. Herein, we investigated how the genetic and metabolic heterogeneity features of the tumor are associated with each other in head and neck squamous cell carcinoma (HNSC). We further assessed the prognostic significance of those features.

Methods
The mutant-allele tumor heterogeneity (MATH) score (n = 508), a genetic heterogeneity feature, and tumor glycolysis feature (GlycoS) (n = 503) were obtained from the HNSC dataset in the cancer genome atlas (TCGA). We identified matching patients (n = 33) who underwent 18F-fluorodeoxyglucose positron emission tomography (FDG PET) from the cancer imaging archive (TCIA) and obtained the following information from the primary tumor: metabolic, metabolic-volumetric, and metabolic heterogeneity features. The association between the genetic and metabolic features and their prognostic values were assessed.

Results
Tumor metabolic heterogeneity and metabolic-volumetric features showed a mild degree of association with MATH (n = 25, ρ = 0.4~0.5, P < 0.05 for all features). The patients with higher FDG PET features and MATH died sooner. Combination of MATH and tumor metabolic heterogeneity features showed a better stratification of prognosis than MATH. Also, higher MATH and GlycoS were associated with significantly worse overall survival (n = 499, P = 0.002 and 0.0001 for MATH and GlycoS, respectively). Furthermore, both MATH and GlycoS independently predicted overall survival after adjusting for clinicopathologic features and the other (P = 0.015 and 0.006, respectively).

Conclusion
Both tumor metabolic heterogeneity and metabolic-volumetric features assessed by FDG PET showed a mild degree of association with genetic heterogeneity in HNSC. Both metabolic and genetic heterogeneity features were predictive of survival and there was an additive prognostic value when the metabolic and genetic heterogeneity features were combined. Also, MATH and GlycoS were independent prognostic factors in HNSC; they can be used for precise prognostication once validated.
Immunosuppressive effects of a novel potassium channel toxin Ktx-Sp2 from Scorpiops Pocoki
Authors: Zhang Yubiao , Zhang Feng , Shi Shujuan , Liu Xinqiao , Cai Weisong , Han Guangtao , Ke Caihua , Long Siru , Di Zhiyong , Yin Shijin , Li Haohuan 
Published: December 2019

Abstract
Background
The cDNA Library of venomous animals could provide abundant bioactive peptides coding information and is an important resource for screening bioactive peptides that target and regulate disease-related ion channels. To further explore the potential medicinal usage of the transcriptome database of Scorpiops Pocoki’s venom gland, this research identified the function of a new potassium channel toxin Ktx-Sp2, whose gene was screened from the database by sequence alignment.

Results
The mature peptide of Ktx-Sp2 was obtained by genetic engineering. Whole-cell patch-clamp experiment showed that Ktx-Sp2 peptide could effectively block three types of exogenous voltage-gated potassium channels—Kv1.1, Kv1.2 and Kv1.3, among which, the blocking activity for Kv1.3 was relatively high, showing selectivity to some extent. Taking Jurkat T cells as the cell model, this study found that Ktx-Sp2 peptide could also effectively block endogenous Kv1.3, significantly reduce the free calcium concentration in Jurkat T cells, inhibit the activation of Jurkat T cells and reduce the release of inflammatory cytokines IL-2, showing a strong immunosuppressant effect.

Conclusions
This study further proves that the transcriptome database of the Scorpiops Pocoki venom gland is an important resource for discovery of novel bioactive polypeptide coding genes. The newly screened Kv1.3 channel blocker Ktx-Sp2 expanded the range of leading compounds for the treatment of autoimmune diseases and promoted the development and application of scorpion toxin peptides in the field of biomedicine.
The Israeli national population program of genetic carrier screening for reproductive purposes. How should it be continued?
Authors: Zlotogora Joël 
Published: December 2019

AbstractThe Israeli population genetic screening program for reproductive purposes, is a population-specific screening that includes all known, severe diseases and relatively frequent in a specific population (carrier frequency at or above 1:60 and/or disease frequency at or above 1 in 15,000 live births). The carrier screening program is free of charge and offers testing according to disease frequency in the different groups within the population.The extraordinary technical changes that occurred in the last decade as well as the changes in the type of marriages within the Israeli population necessitate a revision in the basis of the program.The screening should include instead of only the relatively frequent variants, all the variants that were reported among patients causing a severe disease for which the natural history is well known without regard of their frequency. The population-specific screening that determine which variants are included according to the origin of the couple should be abandoned for a general screening including either all the Jewish population or all the Israeli Arab population.
Analysis of hidden terminal’s effect on the performance of vehicular ad-hoc networks
Authors: Kumar Saurabh , Choi Sunghyun , Kim HyungWon 
Published: December 2019

Abstract
Vehicular ad-hoc networks (VANETs) based on the IEEE 802.11p standard are receiving increasing attention for road safety provisioning. Hidden terminals, however, demonstrate a serious challenge in the performance of VANETs. In this paper, we investigate the effect of hidden terminals on the performance of one hop broadcast communication. The paper formulates an analytical model to analyze the effect of hidden terminals on the performance metrics such as packet reception probability (PRP), packet reception delay (PRD), and packet reception interval (PRI) for the 2-dimensional (2-D) VANET. To verify the accuracy of the proposed model, the analytical model-based results are compared with NS3 simulation results using 2-D highway scenarios. We also compare the analytical results with those from real vehicular network implemented using the commercial vehicle-to-everything (V2X) devices. The analytical results show high correlation with the results of both simulation and real network.
A hyperspectral image classification algorithm based on atrous convolution
Authors: Zhang Xiaoqing , Zheng Yongguo , Liu Weike , Wang Zhiyong 
Published: December 2019

AbstractHyperspectral images not only have high spectral dimension, but the spatial size of datasets containing such kind of images is also small. Aiming at this problem, we design the NG-APC (non-gridding multi-level concatenated Atrous Pyramid Convolution) module based on the combined atrous convolution. By expanding the receptive field of three layers convolution from 7 to 45, the module can obtain a distanced combination of the spectral features of hyperspectral pixels and solve the gridding problem of atrous convolution. In NG-APC module, we construct a 15-layer Deep Convolutional Neural Networks (DCNN) model to classify each hyperspectral pixel. Through the experiments on the Pavia University dataset, the model reaches 97.9% accuracy while the parameter amount is only 0.25 M. Compared with other CNN algorithms, our method gets the best OA (Over All Accuracy) and Kappa metrics, at the same time, NG-APC module keeps good performance and high efficiency with smaller number of parameters.
Fractional operators with generalized Mittag-Leffler k-function
Authors: Mubeen Shahid , Safdar Ali Rana 
Published: December 2019

AbstractIn this paper, our main aim is to deal with two integral transforms involving the Gauss hypergeometric functions as their kernels. We prove some composition formulas for such generalized fractional integrals with Mittag-Lefflerk-function. The results are established in terms of the generalized Wright hypergeometric function. The Euler integralk-transformation for Mittag-Lefflerk-functions has also been developed.
Reliability and capability based computation offloading strategy for vehicular ad hoc clouds
Authors: Li Bo , Peng Ziyi , Hou Peng , He Min , Anisetti Marco , Jeon Gwanggil 
Published: December 2019

AbstractIn the Internet of Vehicles (IoV), with the increasing demand for intelligent technologies such as driverless driving, more and more in-vehicle applications have been put into autonomous driving. For the computationally intensive task, the vehicle self-organizing network uses other high-performance nodes in the vehicle driving environment to hand over tasks to these nodes for execution. In this way, the computational load of the cloud alleviated. However, due to the unreliability of the communication link and the dynamic changes of the vehicle environment, lengthy task completion time may lead to the increase of task failure rate. Although the flooding algorithm can improve the success rate of task completion, the offloading expend will be large. Aiming at this problem, we design the partial flooding algorithm, which is a comprehensive evaluation method based on system reliability in the vehicle computing environment without infrastructure. Using V2V link to select some nodes with better performance for partial flooding offloading to reduce the task complete time, improve system reliability and cut down the impact of vehicle mobility on offloading. The results show that the proposed offloading strategy can not only improve the utilization of computing resources, but also promote the offloading performance of the system.