bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co-circulation of coxsackieviruses A-6, A-10, and A-16 causes hand, foot, and mouth disease in Guangzhou city, China
Authors: Xie Jia , Yang Xiao-Han , Hu Si-Qi , Zhan Wen-Li , Zhang Chang-Bin , Liu Hong , Zhao Hong-Yu , Chai Hui-Ying , Chen Ke-Yi , Du Qian-Yi , Liu Pan , Yin Ai-Hua , Luo Ming-Yong 
Published: April 2020

Abstract
Background
Hand, foot, and mouth disease (HFMD) is a common infectious disease occurring in children under 5 years of age worldwide, and Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CVA-16) are identified as the predominant pathogens. In recent years, Coxsackievirus A6 (CVA-6) and Coxsackievirus A10 (CVA-10) have played more and more important role in a series of HFMD outbreaks. This study aimed to understand the epidemic characteristics associated with HFMD outbreak in Guangzhou, 2018.

Methods
The clinical and laboratory data of 1220 enterovirus-associated HFMD patients in 2018 were analysed in this study. Molecular diagnostic methods were performed to identify its serotypes. Phylogenetic analyses were depicted based on the complete VP1 gene.

Results
There were 21 enterovirus serotypes detected in Guangzhou in 2018. Three serotypes of enterovirus, CVA-6 (364/1220, 29.8%), CVA-10 (305/1220, 25.0%), and CVA-16 (397/1220, 32.5%), were identified as the causative pathogens and accounted for 87.3% among all 1220 HFMD patients. In different seasons, CVA-6 was the predominant pathogen of HFMD during autumn, and CVA-10 as well as CVA-16 were more prevalent in summer. Patients infected by CVA-6, CVA-10 or CVA-16 showed similar clinical features and laboratory characteristics, and the ratios of severe HFMD were 5.8, 5.9, and 1.5% in the three serotypes. Phylogenetic analyses of VP1 sequences showed that the CVA-6, CVA-10, and CVA-16 sequences belonged to the sub-genogroup E2, genogroup E, and genogroup B1, respectively.

Conclusions
CVA-6, CVA-10, and CVA-16 were the predominant and co-circulated serotypes in Guangzhou China, 2018, which should be the new target for prevention and control of HFMD. Our findings provide useful information for diagnosis, treatment, and prevention of HFMD.
Multidrug-resistant HIV viral rebound during early syphilis: a case report
Authors: Giacomelli Andrea , Micheli Valeria , Cattaneo Dario , Mancon Alessandro , Gervasoni Cristina 
Published: April 2020

Abstract
Background
Syphilis has been associated with an increase in HIV RNA and a temporary decline in CD4 T cell counts in people living with HIV who are not receiving antiretroviral treatment (ART), and may be associated with a transient HIV RNA rebound in those who are receiving ART. Our case is the first to highlight the risk of a multidrug-resistant HIV viral rebound during the course of early syphilis even if antiretroviral drug concentrations are within the therapeutic range.

Case presentation
This 50-year-old HIV-1-positive male patient with concomitant early syphilis presented with an HIV RNA rebound (8908 copies/mL) during a scheduled visit to our clinic. He was receiving a stable ART regimen consisting of darunavir/cobicistat plus dolutegravir, and had a 15-year history of viral suppression. Good short-term drug adherence could be inferred as liquid chromatography tandem mass spectrometry showed that his trough antiretroviral drug concentrations were within the therapeutic range: darunavir 2353 ng/mL (minimum effective concentration > 500 ng/mL) and dolutegravir 986 ng/mL (minimum effective concentration > 100 ng/mL). A plasma RNA genotype resistance test revealed wild-type virus in the integrase region and protease region (PR), but extensive resistance in the reverse transcriptase (RT) region (M41L, E44D, D67N, K70R, M184V, L210W and T215Y). Phylogenetic analysis of next-generation sequences (used to investigate the presence of minor viral variants), the PR and RT sequences from plasma HIV RNA and pro-viral DNA extracted from peripheral blood mononuclear cells during the viral rebound, and a Sanger sequence obtained during a previous virological failure suggested clonal viral expression because the previous PR resistance mutations had been lost or had not been archived in pro-viral DNA.

Conclusions
This case shows that early syphilis may cause an HIV RNA rebound in patients under stable virological control with the potential of transmitting an extensively drug-resistant virus.
Assessing Gammapapillomavirus infections of mucosal epithelia with two broad-spectrum PCR protocols
Authors: Bolatti Elisa M. , Hošnjak Lea , Chouhy Diego , Casal Pablo E. , Re-Louhau María F. , Bottai Hebe , Komloš Kristina Fujs , Poljak Mario , Giri Adriana A. 
Published: April 2020

Abstract
Background
Human papillomaviruses (HPVs) have been divided into mucosal and cutaneous types according to their primary epithelial tissue tropism. However, recent studies showed the presence of several cutaneous types in mucosal lesions and healthy mucosa from different anatomical sites.

Methods
Here, the HPV prevalence and type-specific distribution were assessed in a variety of mucosal samples from 435 individuals using a combination of two established broad-spectrum primer systems: Gamma-PV PCR and CUT PCR.

Results
Overall HPV prevalence in anal canal swabs, cervical cancer biopsies, genital warts and oral swabs was 85, 47, 62 and 4%, respectively. In anal canal swabs, Alpha-PVs were most frequently found (59%), followed by Gamma- (37%) and Beta-PVs (4%). The prevalence and persistence of HPV infection in the anal canal of 226 individuals were further explored. Overall HPV, Gamma-PVs and multiple HPV infections were significantly higher in men vs. women (p = 0.034, p = 0.027 and p = 0.003, respectively); multiple HPV infections were more common in individuals ≤40 years (p = 0.05), and significantly higher prevalence of Gamma-PVs and multiple HPV infections was observed in HIV-1-positive vs. HIV-1-negative individuals (p = 0.003 and p = 0.04, respectively). Out of 21 patients with follow-up anal swabs, only one persistent infection with the same type (HPV58) was detected.

Conclusions
Our findings suggest that Gamma-PVs (except species Gamma-6) are ubiquitous viruses with dual muco-cutaneous tissue tropism. Anal canal Gamma-PV infections may be associated with sexual behavior and the host immune status. This study expands the knowledge on Gamma-PVs’ tissue tropism, providing valuable data on the characteristics of HPV infection in the anal canal.
Drug resistance occurred in a newly characterized preclinical model of lung cancer brain metastasis
Authors: Shah Neal , Liu Zhongwei , Tallman Rachel M. , Mohammad Afroz , Sprowls Samuel A. , Saralkar Pushkar A. , Vickers Schuyler D. , Pinti Mark V. , Gao Weimin , Lockman Paul R. 
Published: April 2020

AbstractBackgroundCancer metastasis and drug resistance have traditionally been studied separately, though these two lethal pathological phenomena almost always occur concurrently. Brain metastasis occurs in a large proportion of lung cancer patients (~ 30%). Once diagnosed, patients have a poor prognosis surviving typically less than 1 year due to lack of treatment efficacy.MethodsHuman metastatic lung cancer cells (PC-9-Br) were injected into the left cardiac ventricle of female athymic nude mice. Brain lesions were allowed to grow for 21 days, animals were then randomized into treatment groups and treated until presentation of neurological symptoms or when moribund. Prior to tissue collection mice were injected with Oregon Green and14C-Aminoisobutyric acid followed by an indocyanine green vascular washout. Tracer accumulation was determined by quantitative fluorescent microscopy and quantitative autoradiography. Survival was tracked and tumor burden was monitored via bioluminescent imaging. Extent of mutation differences and acquired resistance was measured in-vitro through half-maximal inhibitory assays and qRT-PCR analysis.ResultsA PC-9 brain seeking line (PC-9-Br) was established. Mice inoculated with PC-9-Br resulted in a decreased survival time compared with mice inoculated with parental PC-9. Non-targeted chemotherapy with cisplatin and etoposide (51.5 days) significantly prolonged survival of PC-9-Br brain metastases in mice compared to vehicle control (42 days) or cisplatin and pemetrexed (45 days). Further in-vivo imaging showed greater tumor vasculature in mice treated with cisplatin and etoposide compared to non-tumor regions, which was not observed in mice treated with vehicle or cisplatin and pemetrexed. More importantly, PC-9-Br showed significant resistance to gefitinib by in-vitro MTT assays (IC50 > 2.5 μM at 48 h and 0.1 μM at 72 h) compared with parental PC-9 (IC50: 0.75 μM at 48 h and 0.027 μM at 72 h). Further studies on the molecular mechanisms of gefitinib resistance revealed that EGFR and phospho-EGFR were significantly decreased in PC-9-Br compared with PC-9. Expression of E-cadherin and vimentin did not show EMT in PC-9-Br compared with parental PC-9, and PC-9-Br had neither a T790M mutation nor amplifications of MET and HER2 compared with parental PC-9.ConclusionOur study demonstrated that brain metastases of lung cancer cells may independently prompt drug resistance without drug treatment.
Endogenous Endophthalmitis: yield of the diagnostic evaluation
Authors: Regan Kathleen A. , Radhakrishnan Nila S. , Hammer Jon D. , Wilson Benjamin D. , Gadkowski Lara Beth , Iyer Siva S. R. 
Published: April 2020

Abstract
Background
Endogenous endophthalmitis is an infection of the eye secondary to sepsis, occurring in 0.04–0.5% of bacteremia or fungemia. Risk factors include intravenous drug abuse (IVDA), diabetes, indwelling catheters, and immune suppression. Many patients have known or suspected bacteremia or fungemia; however, culture yield is reported to be low (approximately 50%). The purpose of this study is to elucidate the yield of diagnostic evaluation including microbial cultures over a 6.5 year period at an academic center in the United States.

Methods
Retrospective chart review of patients with endogenous endophthalmitis at the University of Florida from June 2011 to February 2018.

Results
Included are 40 eyes of 35 patients. Endophthalmitis was secondary to an endogenous source in 23.5% of all endophthalmitis cases observed. Intraocular culture positivity was 28.6% overall but was 0% after initiation of systemic antibiotics. Most commonly identified organisms from the eye were coagulase-negative Staphylococcus and Candida. Blood culture positivity was 48.6%, most commonly Staphylococcus. IVDA was noted with increasing frequency as a risk factor. Diagnosis of endophthalmitis upon hospital admission was associated with a higher intraocular culture positivity (P = 0.040) and a shorter hospital stay (P = 0.035). Computed tomography (CT) and magnetic resonance imaging (MRI) were the highest yield imaging modalities; X-ray and non-ocular ultrasound were less diagnostically useful. Echocardiogram was positive by transesophageal route (TEE) in 22% and in 9% by transthoracic (TTE) testing. Following discharge from the hospital, 48.4% of patients failed to follow up with outpatient ophthalmology.

Conclusions
Based on the results of this study, the interdisciplinary team should consider directed imaging, eye cultures prior to antimicrobial administration, thorough history for IVDA, and caution with premature discharge from the hospital.
Comparing the trueness of seven intraoral scanners and a physical impression on dentate human maxilla by a novel method
Authors: Nagy Zsolt , Simon Botond , Mennito Anthony , Evans Zachary , Renne Walter , Vág János 
Published: April 2020

Abstract
Backgrounds
Intraoral scanner (IOS) accuracy is commonly evaluated using full-arch surface comparison, which fails to take into consideration the starting position of the scanning (scan origin). Previously a novel method was developed, which takes into account the scan origin and calculates the deviation of predefined identical points between references and test models. This method may reveal the error caused by stitching individual images during intraoral scan. This study aimed to validate the novel method by comparing the trueness of seven IOSs (Element 1, Element 2, Emerald, Omnicam, Planscan, Trios 3, CS 3600) to a physical impression digitized by laboratory scanner which lacks linear stitching problems.

Methods
Digital test models of a dentate human cadaver maxilla were made by IOSs and by laboratory scanner after polyvinylsiloxane impression. All scans started on the occlusal surface of the tooth #15 (universal notation, scan origin) and finished at tooth #2. The reference model and test models were superimposed at the scan origin in GOM Inspect software. Deviations were measured between identical points on three different axes, and the complex 3D deviation was calculated. The effect of scanners, tooth, and axis was statistically analyzed by the generalized linear mixed model.

Results
The deviation gradually increased as the distance from scan origin increased for the IOSs but not for the physical impression. The highest deviation occurred mostly at the apico-coronal axis for the IOSs. The mean deviation of the physical impression (53 ± 2 μm) was not significantly different from the Trios 3 (156 ± 8 μm) and CS 3600 (365 ± 29 μm), but it was significantly lower than the values of Element 1 (531 ± 26 μm), Element 2 (246 ± 11 μm), Emerald (317 ± 13 μm), Omnicam (174 ± 11 μm), Planscan (903 ± 49 μm).

Conclusions
The physical impression was superior compared to the IOSs on dentate full-arch of human cadaver. The novel method could reveal the stitching error of IOSs, which may partly be caused by the difficulties in depth measurement.
Technology at the service of surgery in a new technique of autotransplantation by guided surgery: a case report
Authors: Mena-Álvarez J. , Riad-Deglow E. , Quispe-López N. , Rico-Romano C. , Zubizarreta-Macho A. 
Published: April 2020

Abstract
Background
The aim of this case report was to use a surgical technique for autotransplantation of tooth using virtually planned 3D printed surgical templates for guided osteotomy preparation of the recipient of donor tooth.

Case presentation
An 18-year-old male patient received autotransplantation of the right mandibular third molar to replace an included right second molar. This procedure was based on guided implant surgery methods by superimposition of DICOM files and 3D data sets of the jaws. In order to design a 3D-printed template with the aid of a fully digital workflow; the third molar was conserved in PRGF during the surgical procedure and the tooth socket was prepared with a template and the help of a 3D-printed donor tooth copy in order to prevent iatrogenic damage to the donor tooth. This template and replica were manufactured using 3D-printing techniques. The transplanted tooth was placed in infra-occlusion and fixed with a suture splint and root canal therapy was performed 15 days later. The intervention was be accomplished by performing preplanned virtual transplantations with guided osteotomies to ensure accurate donor tooth placement in the new recipient site. The 24 months follow-up showed physiological clinical and radiologic results compatible with healing periradicular tissues.

Conclusions
This approach enables the planning and production of a 3D printed surgical template using the latest diagnostic methods and techniques of guided implant surgery. These accurate virtually predesigned surgical templates and printed analogues of the donor tooth could facilitate autotransplantation, ensuring an atraumatic surgical protocol.
How are pay-for-performance schemes in healthcare designed in low- and middle-income countries? Typology and systematic literature review
Authors: Kovacs Roxanne J. , Powell-Jackson Timothy , Kristensen Søren R. , Singh Neha , Borghi Josephine 
Published: April 2020

Abstract
Background
Pay for performance (P4P) schemes provide financial incentives to health workers or facilities based on the achievement of pre-specified performance targets and have been widely implemented in health systems across low and middle-income countries (LMICs). The growing evidence base on P4P highlights that (i) there is substantial variation in the effect of P4P schemes on outcomes and (ii) there appears to be heterogeneity in incentive design. Even though scheme design is likely a key determinant of scheme effectiveness, we currently lack systematic evidence on how P4P schemes are designed in LMICs.

Methods
We develop a typology to classify the design of P4P schemes in LMICs, which highlights different design features that are a priori likely to affect the behaviour of incentivised actors. We then use results from a systematic literature review to classify and describe the design of P4P schemes that have been evaluated in LMICs. To capture academic publications, Medline, Embase, and EconLit databases were searched. To include relevant grey literature, Google Scholar, Emerald Insight, and websites of the World Bank, WHO, Cordaid, Norad, DfID, USAID and PEPFAR were searched.

Results
We identify 41 different P4P schemes implemented in 29 LMICs. We find that there is substantial heterogeneity in the design of P4P schemes in LMICs and pinpoint precisely how scheme design varies across settings. Our results also highlight that incentive design is not adequately being reported on in the literature – with many studies failing to report key design features.

Conclusions
We encourage authors to make a greater effort to report information on P4P scheme design in the future and suggest using the typology laid out in this paper as a starting point.
What will it take? Using an implementation research framework to identify facilitators and barriers in implementing a school-based referral system for sexual health services
Authors: Leung Emily , Wanner Kathryn J. , Senter Lindsay , Brown Amanda , Middleton Dawn 
Published: April 2020

Abstract
Background
Across the United States, sexually transmitted infections and unintended pregnancy rates are alarmingly high among youth. Schools, due to their proximity and access to youth, can increase student access to sexual health services (SHS) by creating referral systems (RS) to link students to school- and community-based SHS. From 2013 to 2018, the Centers for Disease Control and Prevention’s Division of Adolescent and School Health funded 17 Local Education Agencies (LEA) to partner with priority schools and stakeholders to develop and implement RS to increase student access to SHS. Cicatelli Associates Inc. (CAI) was funded to provide capacity-building to LEA. In 2016–2017, CAI conducted case studies at two LEA, both large and urban sites, but representing different geographical and political contexts, to elucidate factors that influence RS implementation.

Methods
Nineteen LEA and community-based healthcare (CBH) staff were interviewed in the Southeastern (n = 9) and Western U.S. (n = 10). Key constructs (e.g., leadership engagement, resources, state and district policies) across the five domains of the Consolidated Framework for Implementation Research (CFIR) framework guided the methodology and analysis. Qualitative data was analyzed using the Framework Method and contextual factors and themes that led to RS implementation were identified.

Results
Interviewees strongly believed that school-based RS can decrease STI, HIV and unintended pregnancy and increase students’ educational attainment. We identified the following contextual key factors that facilitate successful implementation and integration of an RS: enforcing state and district policies, strong LEA and CBH collaboration, positive school culture towards adolescent health, knowledgeable and supportive staff, leveraging of existing resources and staffing structures, and influential district and school building-level leadership and champions. Notably, this case study challenged our initial assumptions that RS are easily implemented in states with comprehensive SHS policies. Rather, our conversations revealed how districts and local-level policies can have significant impact and influence to impede or promote those policies.

Conclusions
Through the use of the CFIR framework, the interviews identified important contextual factors and themes associated with LEAs’ implementation barriers and facilitators. The study’s results present key recommendations that other LEA can consider to optimize integration of RS-related evidence-based practices, systems, and policies in their districts.
Sodium-glucose cotransporter 2 inhibitors antagonize lipotoxicity in human myeloid angiogenic cells and ADP-dependent activation in human platelets: potential relevance to prevention of cardiovascular events
Authors: Spigoni Valentina , Fantuzzi Federica , Carubbi Cecilia , Pozzi Giulia , Masselli Elena , Gobbi Giuliana , Solini Anna , Bonadonna Riccardo C. , Dei Cas Alessandra 
Published: April 2020

Abstract
Background
The clear evidence of cardiovascular benefits in cardiovascular outcome trials of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in type 2 diabetes might suggest an effect on atherosclerotic plaque vulnerability and/or thrombosis, in which myeloid angiogenic cells (MAC) and platelets (PLT) are implicated. We tested the effects of SGLT2i on inflammation and oxidant stress in a model of stearic acid (SA)-induced lipotoxicity in MAC and on PLT activation. The possible involvement of the Na+/H+ exchanger (NHE) was also explored.

Method
MAC and PLT were isolated from peripheral blood of healthy subjects and incubated with/without SGLT2i [empagliflozin (EMPA) and dapagliflozin (DAPA) 1–100 μM] to assess their effects on SA (100 μM)-induced readouts of inflammation, oxidant stress and apoptosis in MAC and on expression of PLT activation markers by flow-cytometry after ADP-stimulation. Potential NHE involvement was tested with amiloride (aspecific NHE inhibitor) or cariporide (NHE1 inhibitor). Differences among culture conditions were identified using one-way ANOVA or Friedman test.

Results
NHE isoforms (1,5–9), but not SGLT2 expression, were expressed in MAC and PLT. EMPA and DAPA (100 μM) significantly reduced SA-induced inflammation (IL1β, TNFα, MCP1), oxidant stress (SOD2, TXN, HO1), but not apoptosis in MAC. EMPA and DAPA (both 1 μM) reduced PLT activation (CD62p and PAC1 expression). SGLT2i effects were mimicked by amiloride, and only partially by cariporide, in MAC, and by both inhibitors in PLT.

Conclusions
EMPA and DAPA ameliorated lipotoxic damage in stearate-treated MAC, and reduced ADP-stimulated PLT activation, potentially via NHE-inhibition, thereby pointing to plaque stabilization and/or thrombosis inhibition as potential mechanism(s) involved in SGLT2i-mediated cardiovascular protection.
Increased production of periplasmic proteins in Escherichia coli by directed evolution of the translation initiation region
Authors: Mirzadeh Kiavash , Shilling Patrick J. , Elfageih Rageia , Cumming Alister J. , Cui Huanhuan L. , Rennig Maja , Nørholm Morten H. H. , Daley Daniel O. 
Published: April 2020

Abstract
Background
Recombinant proteins are often engineered with an N-terminal signal peptide, which facilitates their secretion to the oxidising environment of the periplasm (gram-negative bacteria) or the culture supernatant (gram-positive bacteria). A commonly encountered problem is that the signal peptide influences the synthesis and secretion of the recombinant protein in an unpredictable manner. A molecular understanding of this phenomenon is highly sought after, as it could lead to improved methods for producing recombinant proteins in bacterial cell factories.

Results
Herein we demonstrate that signal peptides contribute to an unpredictable translation initiation region. A directed evolution approach that selects a new translation initiation region, whilst leaving the amino acid sequence of the signal peptide unchanged, can increase production levels of secreted recombinant proteins. The approach can increase production of single chain antibody fragments, hormones and other recombinant proteins in the periplasm of E. coli.

Conclusions
The study demonstrates that signal peptide performance is coupled to the efficiency of the translation initiation region.