bluuebunny/crossref_metadata_2025_split huggingface dataset:
Testing strategies for couple engagement in prevention of mother-to-child transmission of HIV and family health in Kenya: study protocol for a randomized controlled trial
Authors: Kwena Zachary , Kimbo Liza , Darbes Lynae A. , Hatcher Abigail M. , Helova Anna , Owino George , Thirumurthy Harsha , Bukusi Elizabeth A. , Braun Thomas , Kilgore Meredith , Pisu Maria , Tamhane Ashutosh , Nghiem Van T. , Agot Kawango , Neilands Torsten B. , Turan Janet M. 
Published: January 2021

Abstract
Background
HIV-related maternal deaths and HIV infection among infants remain unacceptably high across sub-Saharan Africa despite increased antenatal care attendance and provision of antiretroviral therapy to pregnant women. In the Jamii Bora (“Better Family” in Swahili) Study, we seek to test the efficacy of an interdependence theory-based couple intervention. The intervention reaches pregnant women and male partners through home visits by male-female pairs of lay health workers. The aim is to increase access to home-based couples’ HIV testing and counseling services to improve family health.

Methods
This is a three-arm randomized control trial among 1080 pregnant women 15 years of age or older, living with their male partners, and who have not undergone couples’ HIV testing and counseling in Kisumu and Migori Counties in Kenya. Couples will be randomized into three groups: home-based couple visits, HIV self-testing kits for couple use, or standard care (male partner clinic invitation letters). Participants will be followed up to 18 months postpartum. The study has three aims: in aim 1, we will determine the effects of the intervention on our primary outcome of couple HIV testing, compared to HIV self-testing kits and standard care; in aim 2, we will examine the intervention impact on HIV prevention behaviors, facility delivery, and postnatal healthcare utilization, as well as secondary health outcomes of maternal viral suppression and HIV-free child survival up to 18 months for couples living with HIV; and in aim 3, we will compare the cost-effectiveness of the home-based couple intervention to the less resource-intensive strategies used in the other two study arms. Assessments with couples are conducted at baseline, late pregnancy, and at months 3, 6, 12, and 18 after birth.

Discussion
The results from this study will inform decision-makers about the cost-effective strategies to engage pregnant couples in the prevention of mother-to-child transmission and family health, with important downstream benefits for maternal, paternal, and infant health.

Trial registration
ClinicalTrials.gov NCT03547739. Registered on May 9, 2018
An exercise trial for adults undergoing neoadjuvant chemoradiotherapy for rectal cancer proves not feasible: recommendations for future trials
Authors: Brunet Jennifer , Price Jenson , Delluc Céline 
Published: January 2021

Abstract
Background
The aim of this paper is to share the methodological problems of an unsuccessful prospective single-arm feasibility trial conducted to evaluate the safety and feasibility of a 12-week progressive exercise intervention for adults undergoing neoadjuvant chemoradiotherapy for rectal cancer, as well as offer recommendations for future trials.

Methods
The initial plan was to recruit adults diagnosed with rectal cancer and scheduled for neoadjuvant chemoradiotherapy over a 12-month period. The exercise intervention was to consist of supervised exercise sessions delivered three times per week by a trained exercise specialist. Feasibility (i.e., recruitment, adherence, and compliance rates) and safety (i.e., adverse events) were to be assessed throughout the trial, and patient-reported and physical health outcomes were to be assessed pre- and post-intervention. After 8 months of open recruitment, we had been unable to successfully enroll patients into our trial. We therefore modified our eligibility criteria to increase the number of patients that could be recruited into our trial, and in turn increase our recruitment rate. We also amended our recruitment procedures to ensure we could reach patients who were either awaiting treatment, receiving treatment, or had completed treatments in the past 5 years. In doing so, we added a research objective, namely to determine the optimal timing of conducting an exercise intervention with adults diagnosed with rectal cancer (i.e., during neoadjuvant treatment, after surgery, during adjuvant treatment, or post-treatment).

Results
Many problems continued to hinder the progress of our trial, particularly the low recruitment rate and the failure to enroll the required sample size that would make our results reliable.

Conclusion
This led us to conclude that our trial was not feasible and that it is advisable to consider some elements carefully (e.g., recruitment strategies, communication, and trial location) before designing and conducting future trials. If one or more of these elements still proves to be problematic, trial results risk being compromised and alternative approaches should be considered.

Trial registration
ClinicalTrials.gov NCT03049124. Registered on 02 September 2017
ICan, an Internet-based intervention to reduce cannabis use: study protocol for a randomized controlled trial
Authors: Olthof Marleen I. A. , Blankers Matthijs , van Laar Margriet W. , Goudriaan Anna E. 
Published: January 2021

Abstract
Background
Heavy cannabis use is associated with adverse physical and mental health effects. Despite available effective treatments, the majority of heavy cannabis users does not seek professional help. Web-based interventions can provide an alternative for cannabis users who are reluctant to seek professional help. Several web-based cannabis interventions are effective in reducing cannabis use; however, the effect sizes are typically small and attrition rates are typically high. This suggests that web-based programs can be an effective cannabis use intervention for some, while others may need additional substance use treatment after completing a web-based intervention. Therefore, it is important that web-based interventions do not solely focus on reducing cannabis use, but also on improving attitudes towards substance use treatment. The Screening Brief Intervention and Referral to Treatment (SBIRT) approach appears to be well suited for the purpose of reducing cannabis use and improving substance use treatment utilization. Based on the SBIRT approach—and based on cognitive behavioral therapy (CBT) and motivational interviewing (MI)—we developed the Internet-based cannabis reduction intervention ICan.

Methods/design
This protocol paper presents the design of a randomized controlled trial (RCT) in which we evaluate the effectiveness of the ICan intervention compared to four online modules of educational information on cannabis in a sample of Dutch frequent cannabis users. The primary outcome measure is frequency of cannabis use. Secondary outcome measures include the quantity of cannabis used (grams), the attitudes towards seeking help and the number of participants who enter specialized treatment services for cannabis use-related problems.

Discussion
To the best of our knowledge, ICan is the first Internet-based intervention for cannabis users that combines screening, a brief intervention—based on CBT and MI—and referral to treatment options.

Trial registration
The study is registered in the Netherlands Trial Register; identifier NL7668. Registered on 17 April 2019.
Bioprospecting of microbial strains for biofuel production: metabolic engineering, applications, and challenges
Authors: Adegboye Mobolaji Felicia , Ojuederie Omena Bernard , Talia Paola M. , Babalola Olubukola Oluranti 
Published: January 2021

AbstractThe issues of global warming, coupled with fossil fuel depletion, have undoubtedly led to renewed interest in other sources of commercial fuels. The search for renewable fuels has motivated research into the biological degradation of lignocellulosic biomass feedstock to produce biofuels such as bioethanol, biodiesel, and biohydrogen. The model strain for biofuel production needs the capability to utilize a high amount of substrate, transportation of sugar through fast and deregulated pathways, ability to tolerate inhibitory compounds and end products, and increased metabolic fluxes to produce an improved fermentation product. Engineering microbes might be a great approach to produce biofuel from lignocellulosic biomass by exploiting metabolic pathways economically. Metabolic engineering is an advanced technology for the construction of highly effective microbial cell factories and a key component for the next-generation bioeconomy. It has been extensively used to redirect the biosynthetic pathway to produce desired products in several native or engineered hosts. A wide range of novel compounds has been manufactured through engineering metabolic pathways or endogenous metabolism optimizations by metabolic engineers. This review is focused on the potential utilization of engineered strains to produce biofuel and gives prospects for improvement in metabolic engineering for new strain development using advanced technologies.
Chimeric cellobiohydrolase I expression, activity, and biochemical properties in three oleaginous yeast
Authors: Alahuhta Markus , Xu Qi , Knoshaug Eric P. , Wang Wei , Wei Hui , Amore Antonella , Baker John O. , Vander Wall Todd , Himmel Michael E. , Zhang Min 
Published: January 2021

AbstractConsolidated bioprocessing using oleaginous yeast is a promising modality for the economic conversion of plant biomass to fuels and chemicals. However, yeast are not known to produce effective biomass degrading enzymes naturally and this trait is essential for efficient consolidated bioprocessing. We expressed a chimeric cellobiohydrolase I gene in three different oleaginous, industrially relevant yeast: Yarrowia lipolytica, Lipomyces starkeyi, and Saccharomyces cerevisiae to study the biochemical and catalytic properties and biomass deconstruction potential of these recombinant enzymes. Our results showed differences in glycosylation, surface charge, thermal and proteolytic stability, and efficacy of biomass digestion. L. starkeyi was shown to be an inferior active cellulase producer compared to both the Y. lipolytica and S. cerevisiae enzymes, whereas the cellulase expressed in S. cerevisiae displayed the lowest activity against dilute-acid-pretreated corn stover. Comparatively, the chimeric cellobiohydrolase I enzyme expressed in Y. lipolytica was found to have a lower extent of glycosylation, better protease stability, and higher activity against dilute-acid-pretreated corn stover.
Phlebotomus (Adlerius) simici NITZULESCU, 1931: first record in Austria and phylogenetic relationship with other Adlerius species
Authors: Kniha Edwin , Dvořák Vít , Milchram Markus , Obwaller Adelheid G. , Köhsler Martina , Poeppl Wolfgang , Antoniou Maria , Chaskopoulou Alexandra , Paronyan Lusine , Stefanovski Jovana , Mooseder Gerhard , Volf Petr , Walochnik Julia 
Published: January 2021

Abstract
Background
Phlebotomine sand flies are the principal vectors of Leishmania spp. (Kinetoplastida: Trypanosomatidae). Information on sand flies in Central Europe is scarce and, to date, in Austria, only Phlebotomus mascittii has been recorded. In 2018 and 2019, entomological surveys were conducted in Austria with the aim to further clarify sand fly distribution and species composition.

Results
In 2019, a Ph. simici specimen was trapped in Austria for the first time. Analyses of two commonly used marker genes, cytochrome c oxidase I (coxI) and cytochrome b (cytb), revealed high sequence identity with Ph. simici specimens from North Macedonia and Greece. Phylogenetic analyses showed high intraspecific distances within Ph. simici, thereby dividing this species into three lineages: one each from Europe, Turkey and Israel. Low interspecific distances between Ph. simici, Ph. brevis and an as yet unidentified Adlerius sp. from Turkey and Armenia highlight how challenging molecular identification within the Adlerius complex can be, even when standard marker genes are applied.

Conclusion
To our knowledge, this study reports the first finding of Ph. simici in Austria, representing the northernmost recording of this species to date. Moreover, it reveals valuable insights into the phylogenetic relationships among species within the subgenus Adlerius. Phlebotomus simici is a suspected vector of L. infantum and therefore of medical and veterinary importance. Potential sand fly expansion in Central Europe due to climatic change and the increasing import of Leishmania-infected dogs from endemic areas support the need for further studies on sand fly distribution in Austria and Central Europe in general.

Graphic abstract
Fluralaner as a novel treatment for sarcoptic mange in the bare-nosed wombat (Vombatus ursinus): safety, pharmacokinetics, efficacy and practicable use
Authors: Wilkinson Vicky , Takano Kotaro , Nichols David , Martin Alynn , Holme Roz , Phalen David , Mounsey Kate , Charleston Michael , Kreiss Alexandre , Pye Ruth , Browne Elizabeth , Næsborg-Nielsen Christina , Richards Shane A. , Carver Scott 
Published: January 2021

AbstractBackgroundSarcoptic mange causes significant animal welfare and occasional conservation concerns for bare-nosed wombats (Vombatus ursinus) throughout their range. To date,in situchemotherapeutic interventions have involved macrocytic lactones, but their short duration of action and need for frequent re-administration has limited treatment success. Fluralaner (Bravecto®; MSD Animal Health), a novel isoxazoline class ectoparasiticide, has several advantageous properties that may overcome such limitations.MethodsFluralaner was administered topically at 25 mg/kg (n= 5) and 85 mg/kg (n= 2) to healthy captive bare-nosed wombats. Safety was assessed over 12 weeks by clinical observation and monitoring of haematological and biochemical parameters. Fluralaner plasma pharmacokinetics were quantified using ultra-performance liquid chromatography and tandem mass spectrometry. Efficacy was evaluated through clinical assessment of response to treatment, including mange and body condition scoring, for 15 weeks after topical administration of 25 mg/kg fluralaner to sarcoptic mange-affected wild bare-nosed wombats (n= 3). Duration of action was determined through analysis of pharmacokinetic parameters and visual inspection of study subjects for ticks during the monitoring period. Methods for diluting fluralaner to enable ‘pour-on’ application were compared, and an economic and treatment effort analysis of fluralaner relative to moxidectin was undertaken.ResultsNo deleterious health impacts were detected following fluralaner administration. Fluralaner was absorbed and remained quantifiable in plasma throughout the monitoring period. For the 25 mg/kg and 85 mg/kg treatment groups, the respective means for maximum recorded plasma concentrations (Cmax) were 6.2 and 16.4 ng/ml; for maximum recorded times to Cmax, 3.0 and 37.5 days; and for plasma elimination half-lives, 40.1 and 166.5 days. Clinical resolution of sarcoptic mange was observed in all study animals within 3–4 weeks of treatment, and all wombats remained tick-free for 15 weeks. A suitable product for diluting fluralaner into a ‘pour-on’ was found. Treatment costs were competitive, and predicted treatment effort was substantially lower relative to moxidectin.ConclusionsFluralaner appears to be a safe and efficacious treatment for sarcoptic mange in the bare-nosed wombat, with a single dose lasting over 1–3 months. It has economic and treatment-effort-related advantages over moxidectin, the most commonly used alternative. We recommend a dose of 25 mg/kg fluralaner and, based on the conservative assumption that at least 50% of a dose makes dermal contact, Bravecto Spot-On for Large Dogs as the most appropriate formulation for adult bare-nosed wombats.Graphical abstract
A novel fluorescence immunochromatographic assay strip for the diagnosis of schistosomiasis japonica
Authors: Shen Yuanxi , Ji Rongyi , Chai Rui , Yuan Nana , Zhang Jiyue , Jing Yi , Yang Man , Zhang Lanqi , Hong Yang , Lin Jiaojiao , Zhu Chuangang 
Published: January 2021

AbstractBackgroundSchistosomiasis japonica is a severe zoonosis. Domestic animals are the primary source of infection and play an important role in disease transmission. Surveillance and diagnosis play key roles in schistosomiasis control; however, current techniques for the surveillance and diagnosis of the disease have limitations. In this study, we developed a novel fluorescence immunochromatographic assay (FICA) strip to detect anti-Schistosoma japonicumantibodies in host serum.MethodsA FICA strip was developed for the diagnosis ofSchistosoma japonicumin domestic animals. Streptococcus protein G (SPG) and soluble egg antigen (SEA) were transferred onto a nitrocellulose (NC) membrane to form the control line (C) and the test line (T), respectively. With fluorescence activity as well as binding activity to multispecies IgG, the recombinant protein rSPG-RFP was expressed and employed as an antibody indicator in the FICA strips.ResultsThe dual gene fusion plasmid was verified by PCR and restriction enzyme digestion. The expressed recombinant protein was 39.72 kDa in size, which was consistent with the predicted molecular weight. The western blot results showed binding activity between rSPG-RFP and IgGs from different hosts. Fluorescence microscopy also showed the fluorescence activity of the protein present. The affinity constant (Ka) values of rSPG-RFP with rabbit, donkey, mouse and goat IgG were 1.9 × 105, 4.1 × 105, 1.7 × 105and 5.4 × 105, respectively. Moreover, based on the recombinant protein, the test strip for detectingS. japonicumin buffaloes could distinguish positive from negative serum. The lower limit of detection of the FICA strip was 1:10,000. Compared with ELISA, the FICA strips exhibited similar results in the diagnosis of infection in clinical bovine serum samples, with a kappa value of 0.9660 andP < 0.01. The cross-reactivities of the FICA strips withHaemonchus contortusandSchistosoma turkestanicum(30.15% and 91.66%, respectively) were higher than those of ELISA (26.98% and 87.5%, respectively).ConclusionsBased on the rSPG-RFP protein that we developed, strip detection can be completed within 15 min. Heightened sensitivity allows the strip to accurately identify schistosome antibodies in serum. In conclusion, this method is convenient, feasible, rapid and effective for detectingS. japonicum.Graphical Abstract
Spatio-temporal variations of emerging sites infested with schistosome-transmitting Oncomelania hupensis in Hunan Province, China, 1949–2016
Authors: Li Shengming , Shi Ying , Deng Weicheng , Ren Guanghui , He Hongbin , Hu Benjiao , Li Chunlin , Zhang Na , Zheng Yingyan , Wang Yingjian , Dong Shurong , Chen Yue , Jiang Qingwu , Zhou Yibiao 
Published: January 2021

Abstract
Background
Constant emerging sites infested with Oncomelania hupensis (O. hupensis) impede the goal realization of eliminating schistosomiasis. The study assessed the spatial and temporal distributions of new Oncomelania snail habitats in Hunan Province from 1949 to 2016.

Methods
We used the data from annual snail surveys throughout Hunan Province for the period from 1949 to 2016. Global Moran’s I, Anselin local Moran’s I statistics (LISA) and a retrospective space-time permutation model were applied to determine the spatial and temporal distributions of emerging snail-infested sites.

Results
There were newly discovered snail-infested sites almost every year in 1949–2016, except for the years of 1993, 2009 and 2012. The number of emerging sites varied significantly in the five time periods (1949–1954, 1955–1976, 1977–1986, 1986–2003 and 2004–2016) (H = 25.35, p < 0.05). The emerging sites lasted 37.52 years in marshlands, 30.04 years in hills and 24.63 at inner embankments on average, with the values of Global Moran’s I being 0.52, 0.49 and 0.44, respectively. High-value spatial clusters (HH) were mainly concentrated along the Lishui River and in Xiangyin County. There were four marshland clusters, two hill clusters and three inner embankment clusters after 1976.

Conclusions
Lower reaches of the Lishui River and the Dongting Lake estuary were the high-risk regions for new Oncomelania snail habitats with long durations. Snail surveillance should be strengthened at stubborn snail-infested sites at the inner embankments. Grazing prohibition in snail-infested grasslands should be a focus in marshlands. The management of bovines in Xiangyin County is of great importance.

Graphical Abstract
Serotonin stimulates Echinococcus multilocularis larval development
Authors: Herz Michaela , Brehm Klaus 
Published: January 2021

AbstractBackgroundSerotonin is a phylogenetically ancient molecule that is widely distributed in most metazoans, including flatworms. In addition to its role as a neurotransmitter, serotonin acts as a morphogen and regulates developmental processes. Although several studies have focused on the serotonergic nervous system in parasitic flatworms, little is known on the role of serotonin in flatworm development.MethodsTo study the effects of serotonin on proliferation and development of the cestodeEchinococcus multilocularis, we cloned the genes encoding theE. multilocularisserotonin transporter (SERT) and tryptophan hydroxylase (TPH), analyzed gene expression by transcriptome analysis and whole mountin situhybridization (WMISH) and performed cell culture experiments.ResultsWe first characterized orthologues encoding the SERT and TPH, the rate-limiting enzyme in serotonin biosynthesis. WMISH and transcriptomic analyses indicated that the genes for both SERT and TPH are expressed in the parasite nervous system. Long-term treatment of parasite stem cell cultures with serotonin stimulated development towards the parasite metacestode stage. Mature metacestode vesicles treated with serotonin showed increased rates of incorporation of the thymidine analogue 5-ethynyl-2′-deoxyuridine (EdU), indicating stimulated cell proliferation. In contrast, treatment with the selective serotonin reuptake inhibitor paroxetine strongly affected the viability of parasite cells. Paroxetine also caused structural damage in metacestode vesicles, suggesting that serotonin transport is crucial for the integrity of parasite vesicles.ConclusionsOur results indicate that serotonin plays an important role inE. multilocularisdevelopment and proliferation, providing evidence that theE. multilocularisSERT and TPH are expressed in the nervous system of the protoscolex. Our results further suggest that theE. multilocularisSERT has a secondary role outside the nervous system that is essential for parasite integrity and survival. Since serotonin stimulatedE. multilocularismetacestode development and proliferation, serotonin might also contribute to the formation and growth of the parasite in the liver.Graphical Abstract