bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic resources and marker validation for diploid and polyploid Veronica (Plantaginaceae) from New Zealand and Europe
Authors: Mayland‐Quellhorst Eike , Meudt Heidi M. , Albach Dirk C. 
Published: October 2016

Premise of the study:Polyploidy may generate novel variation, leading to adaptation and species diversification. An excellent natural system to study polyploid evolution in a comparative framework is Veronica (Plantaginaceae), which comprises several parallel, recently evolved polyploid series.Methods:Over 105 million Illumina paired‐end sequence reads were generated from cDNA libraries of leaf tissue from eight individuals representing three European and four New Zealand species. Forty‐eight simple sequence repeat (SSR) and 48 low‐copy nuclear (LCN) markers were developed and validated with Fluidigm microfluidic PCR and Illumina MiSeq amplicon sequencing on 48 different individuals each.Results:Individual Trinity assemblies were similar regarding annotated transcripts (13,009–14,271), mean contig length (635–742 bp), N50 value (916–1133 bp), E90N50 value (1099–1308 bp), contigs with positive BLAST hits (42–63%), and gene ontology terms. Analyses of 29,738 single‐nucleotide polymorphisms (8746 phylogenetically informative) mined from these transcriptomes plus two outgroups (Picrorhiza kurrooa and Plantago ovata) showed moderate to high bootstrap support for all branches and reticulation among sampled European Veronica.Discussion:The transcriptome sequences themselves, as well as the validated SSR (40/48) and LCN (11/48) markers derived from them, show inter‐ and intraspecific genetic variation. These resources will be invaluable for future population genetic, phylogenetic, and functional genetic investigations in polyploid Veronica.
Myeloid Cell–Derived HIF-1α Promotes Control of Leishmania major
Authors: Schatz Valentin , Strüssmann Yannic , Mahnke Alexander , Schley Gunnar , Waldner Maximilian , Ritter Uwe , Wild Jens , Willam Carsten , Dehne Nathalie , Brüne Bernhard , McNiff Jennifer M. , Colegio Oscar R. , Bogdan Christian , Jantsch Jonathan 
Published: October 2016

Abstract
Hypoxia-inducible factor-1α (HIF-1α), which accumulates in mammalian host organisms during infection, supports the defense against microbial pathogens. However, whether and to what extent HIF-1α expressed by myeloid cells contributes to the innate immune response against Leishmania major parasites is unknown. We observed that Leishmania-infected humans and L. major–infected C57BL/6 mice exhibited substantial amounts of HIF-1α in acute cutaneous lesions. In vitro, HIF-1α was required for leishmanicidal activity and high-level NO production by IFN-γ/LPS-activated macrophages. Mice deficient for HIF-1α in their myeloid cell compartment had a more severe clinical course of infection and increased parasite burden in the skin lesions compared with wild-type controls. These findings were paralleled by reduced expression of type 2 NO synthase by lesional CD11b+ cells. Together, these data illustrate that HIF-1α is required for optimal innate leishmanicidal immune responses and, thereby, contributes to the cure of cutaneous leishmaniasis.
Programmed Death Ligand 1 Plays a Neuroprotective Role in Experimental Autoimmune Neuritis by Controlling Peripheral Nervous System Inflammation of Rats
Authors: Ding Yanan , Han Ranran , Jiang Wei , Xiao Jinting , Liu Haijie , Chen Xiuju , Li Xiaowen , Hao Junwei 
Published: October 2016

Abstract
Programmed death 1 (PD-1; CD279), a member of the CD28 family, is an inhibitory receptor on T cells and is responsible for T cell dysfunction in infectious diseases and cancers. The ligand for PD-1, programmed death ligand 1 (PD-L1; also known as B7-H1, CD274), is a member of the B7 family. The engagement of PD-1 with programmed death ligand can downregulate autoreactive T cells that participate in multiple autoimmune diseases. Experimental autoimmune neuritis (EAN) is an animal model of Guillain–Barré syndrome, and the pathogenesis of EAN is mediated principally through T cells and macrophages. In this study, we investigated the effects of PD-L1 in EAN rats. For preventative and therapeutic management, we administered PD-L1, which successfully decreased the severity of EAN; it alleviated the neurologic course of EAN, as well as inhibited the infiltration of inflammatory cells and demyelination of sciatic nerves. Our data revealed that PD-L1 treatment inhibited lymphocyte proliferation and altered T cell differentiation by inducing decreases in IFN-γ+CD4+ Th1 cells and IL-17+CD4+ Th17 cells and increases in IL-4+CD4+ Th2 cells and Foxp3+CD4+ regulatory T cells. The expression levels of p-STAT3 and Foxp3 were significantly different in PD-L1–treated groups compared with the control group. Additionally, PD-L1 regulated the expression of Foxp3 and p-STAT3 in EAN, probably by inhibiting PI3K/AKT/mTOR signaling expression. In summary, PD-L1 is a potentially useful agent for the treatment of EAN because of its anti-inflammatory and neuroprotective effects.
Plasmodium falciparum Resistance to Artemisinin Derivatives and Piperaquine: A Major Challenge for Malaria Elimination in Cambodia
Authors: Duru Valentine , Witkowski Benoit , Ménard Didier 
Published: October 2016

Abstract
Artemisinin-based combination therapies (ACTs) are the cornerstone of current strategies for fighting malaria. Over the last decade, ACTs have played a major role in decreasing malaria burden. However, this progress is being jeopardized by the emergence of artemisinin-resistant Plasmodium falciparum parasites. Artemisinin resistance was first detected in western Cambodia in 2008 and has since been observed in neighboring countries in southeast Asia. The problem of antimalarial drug resistance has recently worsened in Cambodia, with reports of parasites resistant to piperaquine, the latest generation of partner drug used in combination with dihydroartemisinin, leading to worrying rates of clinical treatment failure. The monitoring and the comprehension of both types of resistance are crucial to prevent the spread of multidrug-resistant parasites outside southeast Asia, and particularly to Africa, where the public health consequences would be catastrophic. To this end, new tools are required for studying the biological and molecular mechanisms underlying resistance to antimalarial drugs and for monitoring the geographic distribution of the resistant parasites. In this review, we detail the major advances in our understanding of resistance to artemisinin and piperaquine and define the challenges that the malaria community will have to face in the coming years.
Epidemiological and Clinical Features of Severe Fever with Thrombocytopenia Syndrome During an Outbreak in South Korea, 2013–2015
Authors: Park Sun-Whan , Ryou Jungsang , Choi Woo-Young , Han Myung-Guk , Lee Won-Ja 
Published: October 2016

Abstract
Since the first reported case of severe fever with thrombocytopenia syndrome (SFTS) in South Korea in 2013, between 2013 and 2015, we collected 1,697 serum samples from suspected patients who experienced symptoms of SFTS. We performed reverse transcriptase polymerase chain reaction using total RNA extracted from the patients' sera. When viral RNA was detected in the sera, SFTS was diagnosed. Among the 1,697 samples, 170 were positive for SFTS virus. We then analyzed the epidemiologic features of these 170 cases. As a result, we found that the annual number of cases increased steadily. However, the annual case fatality rate exhibited a downward trend. The majority of patients were aged ≥ 60 years, and most cases occurred during May–October in the eastern and southern parts of the country. These results may be useful for effective SFTS control by describing the clinical and epidemiologic features of the disease in South Korea.
Comparison of Babesia microti Real-Time Polymerase Chain Reaction Assays for Confirmatory Diagnosis of Babesiosis
Authors: Souza Samaly S. , Bishop Henry S. , Sprinkle Patrick , Qvarnstrom Yvonne 
Published: October 2016

Abstract
Babesiosis is an emerging tick-borne disease caused by apicomplexan parasites of the genus Babesia. Most human infections in the United States are caused by Babesia microti, but other infection-causing Babesia parasites have been documented as well. Polymerase chain reaction (PCR)–based methods can be used to identify this parasite to the species level. In this study, published real-time PCR assays for the specific detection of B. microti were evaluated against conventional PCR for their analytical performance. All evaluated real-time PCR assays had comparable dynamic range and amplification efficiency, but the sensitivity and specificity varied. The best performing test, a TaqMan assay targeting the 18S ribosomal RNA gene, was further evaluated for diagnostic performance using blood specimens submitted to the Centers for Disease Control and Prevention for parasite detection and was found to have 100% sensitivity and specificity. In conclusion, the 18S TaqMan real-time PCR assay is a sensitive, specific, and rapid method for identification of B. microti among cases of babesiosis in the United States.
Family Cluster Analysis of Severe Fever with Thrombocytopenia Syndrome Virus Infection in Korea
Authors: Yoo Jeong Rae , Heo Sang Taek , Park Dahee , Kim Hyemin , Fukuma Aiko , Fukushi Shuetsu , Shimojima Masayuki , Lee Keun Hwa 
Published: October 2016

Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is tick-borne viral disease that was first suspected in China in 2009. The causative virus (SFTSV) was isolated in 2009 and reported in 2011, and SFTSV expanded its geographic distribution in 2012–2013, from China to South Korea and Japan. Most SFTSV infections occur through Haemaphysalis longicornis. However, SFTSV infection can also occur between family members, and nosocomial transmission of SFTSV is also possible through close contact with a patient. In this study, we first analyzed clinical, epidemiological, and laboratory data for SFTS patients and family members of an index patient in Korea. The S segment of SFTSV was amplified from the sera of three patients, and the S segment of SFTSV and IgG specific to SFTSV were detected in the serum from one family member; although this individual had no history of exposure to H. longicornis, she frequently had close contact with the index patient. In Korea, SFTSV infection among family members does not have to be reported, and we suggest that person-to-person transmission of SFTSV among family members is possible in Korea.
The Lack of Association of Eosinophilia and Neurocysticercosis at Clinical Presentation: A Retrospective Analysis of Cases Seen at the National Institutes of Health, 1985–2015
Authors: Ware JeanAnne M. , Nash Theodore E. 
Published: October 2016

Abstract
Eosinophilia is a common laboratory finding in helminth infections but whether it is suggestive of neurocysticercosis (NCC) is controversial and inadequately studied. We determined the presence of eosinophilia (≥ 500 eosinophils/mm3) at clinical presentation in 72 patients with a proven or probable diagnosis of NCC and who had not received corticosteroids within 2 weeks of evaluation and complete blood count. Only two persons whose last possible endemic exposures to NCC were 7 and 6 years earlier had eosinophilia of 500 eosinophils/mm3 and both had a positive antibody serology to strongyloidiasis. In the one subject where a follow-up assessment was possible, the eosinophilia resolved. The likely cause for eosinophilia in both was strongyloidiasis. Therefore, none of the subjects with newly diagnosed NCC had significant eosinophilia. Eosinophilia in newly diagnosed symptomatic NCC subjects who had remote exposure is unusual and should prompt a search for another process or infection.
Application of the full spectrum inversion algorithm to simulated airborne GPS radio occultation signals
Authors: Adhikari Loknath , Xie Feiqin , Haase Jennifer S. 
Published: October 2016

Abstract. With a GPS receiver on board an airplane, the airborne radio occultation (ARO) technique provides dense lower-tropospheric soundings over target regions. Large variations in water vapor in the troposphere cause strong signal multipath, which could lead to systematic errors in RO retrievals with the geometric optics (GO) method. The spaceborne GPS RO community has successfully developed the full-spectrum inversion (FSI) technique to solve the multipath problem. This paper is the first to adapt the FSI technique to retrieve atmospheric properties (bending and refractivity) from ARO signals, where it is necessary to compensate for the receiver traveling on a non-circular trajectory inside the atmosphere, and its use is demonstrated using an end-to-end simulation system. The forward-simulated GPS L1 (1575.42 MHz) signal amplitude and phase are used to test the modified FSI algorithm. The ARO FSI method is capable of reconstructing the fine vertical structure of the moist lower troposphere in the presence of severe multipath, which otherwise leads to large retrieval errors in the GO retrieval. The sensitivity of the modified FSI-retrieved bending angle and refractivity to errors in signal amplitude and errors in the measured refractivity at the receiver is presented. Accurate bending angle retrievals can be obtained from the surface up to ∼ 250 m below the receiver at typical flight altitudes above the tropopause, above which the retrieved bending angle becomes highly sensitive to the phase measurement noise. Abrupt changes in the signal amplitude that are a challenge for receiver tracking and geometric optics bending angle retrieval techniques do not produce any systematic bias in the FSI retrievals when the SNR is high. For very low SNR, the FSI performs as expected from theoretical considerations. The 1 % in situ refractivity measurement errors at the receiver height can introduce a maximum refractivity retrieval error of 0.5 % (1 K) near the receiver, but the error decreases gradually to ∼ 0.05 % (0.1 K) near the surface. In summary, the ARO FSI successfully retrieves the fine vertical structure of the atmosphere in the presence of multipath in the lower troposphere.
SILICA GRAFTED WITH EPOXIDIZED LIQUID POLYBUTADIENES: ITS BEHAVIOR AS FILLER FOR TIRE TREAD COMPOUNDS
Authors: Braum Marcus V. , Jacobi Marly A. M. 
Published: October 2016

ABSTRACT
Achieving high polymer-filler interaction and lowering the energy consumption required to disperse precipitated silica in a rubber matrix have been the main motivations behind the recent interest in silica-coating processes. A simple, low-cost, and environmentally friendly process is available to graft epoxidized liquid polybutadienes onto a silica surface. The polymer-grafted silicas are applied as reinforcing fillers in typical car tire tread compounds. The processability, cure kinetics, and properties of the vulcanizates are greatly affected by the degree of epoxidation, molar mass, and microstructure of the epoxidized polybutadienes used for coating the silica surface. The dynamic-mechanical behavior is superior to that of the reference compound, using bis-[triethoxysilylpropyl] tetrasulfide as a coupling agent, in stiffness and hysteresis at low temperatures, which is indicative of superior performance in wet grip and emergency maneuvers (hard-handling). Thus, the use of this reinforcement system for high-performance car tires, for which safety features should be prioritized, is promising.
Measures for Pain and Function Assessments for Patients With Osteoarthritis
Authors: Saleh Khaled J. , Davis Aileen 
Published: October 2016

Introduction:
To develop an osteoarthritis (OA) quality measure that satisfies quality-reporting initiatives, a systematic review of the literature was undertaken to identify and evaluate measures of pain and function commonly used to assess outcomes in patients with upper and lower extremity OA.

Methods:
English-language systematic reviews and meta-analyses evaluating validity of pain and function instruments in OA patients published between 1995 and 2014 were considered for inclusion. The quality of all included studies was assessed using the Appraisal of Guidelines for Research and Evaluation II instrument (AGREE II).

Results:
More than 90 pain and/or functional assessment tools were evaluated within the 16 systematic reviews included in this analysis. Of the 16 systematic reviews, 6 articles had high-quality study designs; the remaining 10 reviews had moderate-quality study designs.

Conclusion:
There currently exists no OA pain and functional assessment tool capable of meeting the stringent requirements established by newer quality-reporting programs. The use of invalidated or unreliable patient-reported outcome measures may improperly estimate patient pain and functional status, which could affect treatment options, patient satisfaction, reimbursement, and/or quality of life.

Level of Evidence:
II
Respons en motivatiebronnen bij bedrijfsenquêtes
Authors: Torres van Grinsven Vanessa 
Published: October 2016

Respons en motivatiebronnen bij bedrijfsenquêtes
Bedrijven en andere organisaties ontvangen vaak veel enquêtes en klagen over de lastendruk hiervan. Tevens dalen responsaantallen en zijn er zorgen over de kwaliteit van de respons. In dit artikel wordt beschreven wat er gedaan kan worden om de motivatie van bedrijven en organisaties, en hun respondenten, te verhogen om daarmee bij organisatie- en bedrijfsenquêtes de responsaantallen en de responskwaliteit te verbeteren.
PrEP implementation research in Africa: what is new?
Authors: Cowan Frances M , Delany‐Moretlwe Sinead , Sanders Eduard J , Mugo Nelly R , Guedou Fernand A , Alary Michel , Behanzin Luc , Mugurungi Owen , Bekker Linda‐Gail 
Published: October 2016

IntroductionOf the two million new HIV infections in adults in 2014, 70% occurred in sub‐Saharan Africa. Several African countries have already approved guidelines for pre‐exposure prophylaxis (PrEP) for individuals at substantial risk of HIV as part of combination HIV prevention but key questions remain about how to identify and deliver PrEP to those at greatest need. Throughout the continent, individuals in sero‐discordant relationships, and members of key populations (sex workers, men who have sex with men (MSM), transgender women and injection drug users) are likely to benefit from the availability of PrEP. In addition, adolescent girls and young women (AGYW) are at substantial risk in some parts of the continent. It has been estimated that at least three million individuals in Africa are likely to be eligible for PrEP according to WHO's criteria. Tens of demonstration projects are planned or underway across the continent among a range of countries, populations and delivery settings.DiscussionIn each of the target populations, there are overarching issues related to (i) creating demand for PrEP, (ii) addressing supply‐side issues and (iii) providing appropriate and tailored adherence support. Critical for creating demand for PrEP is the normalization of HIV prevention. Community‐level interventions which engage opinion leaders as well as empowerment interventions for those at highest risk will be key. Critical to supply of PrEP is that services are accessible for all, including for stigmatized populations. Establishing accessible integrated services provides the opportunity to address other public health priorities including the unmet need for HIV testing, contraception and sexually transmitted infections treatment. National policies need to include minimum standards for training and quality assurance for PrEP implementation and to address supply chain issues. Adherence support needs to recognize that social and structural factors are likely to have an important influence. Combining interventions that build self‐efficacy, empowerment and social cohesion, with evidence‐based individualized adherence support for PrEP, are most likely to be effective.ConclusionsEfficacy of tenfovir‐based PrEP is proven but many issues related to implementation remain unclear. Here, we have summarized some of the important implementation questions that need to be assessed as PrEP is rolled out across Africa.
Implementation of pre‐exposure prophylaxis for human immunodeficiency virus infection: progress and emerging issues in research and policy
Authors: Cáceres Carlos F , Borquez Annick , Klausner Jeffrey D , Baggaley Rachel , Beyrer Chris 
Published: October 2016

BackgroundIn this article, we present recent evidence from studies focused on the implementation, effectiveness and cost‐effectiveness of pre‐exposure prophylaxis (PrEP) for HIV infection; discuss PrEP scale‐up to date, including the observed levels of access and policy development; and elaborate on key emerging policy and research issues to consider for further scale‐up, with a special focus on lower‐middle income countries.DiscussionThe 2015 WHO Early Release Guidelines for HIV Treatment and Prevention reflect both scientific evidence and new policy perspectives. Those guidelines present a timely challenge to health systems for the scaling up of not only treatment for every person living with HIV infection but also the offer of PrEP to those at substantial risk. Delivery and uptake of both universal antiretroviral therapy (ART) and PrEP will require nation‐wide commitment and could reinvigorate health systems to develop more comprehensive “combination prevention” programmes and support wider testing linked to both treatments and other prevention options for populations at highest risk who are currently not accessing services. Various gaps in current health systems will need to be addressed to achieve strategic scale‐up of PrEP, including developing prioritization strategies, strengthening drug regulations, determining cost and funding sources, training health providers, supporting user adherence and creating demand.ConclusionsThe initial steps in the scale‐up of PrEP globally suggest feasibility, acceptability and likely impact. However, to prevent setbacks in less well‐resourced settings, countries will need to anticipate and address challenges such as operational and health systems barriers, drug cost and regulatory policies, health providers’ openness to prescribing PrEP to populations at substantial risk, demand and legal and human rights issues. Emerging problems will require creative solutions and will continue to illustrate the complexity of PrEP implementation.