bluuebunny/crossref_metadata_2025 huggingface dataset:
Stepping out of the ‘Difference’: Discerning the Dalit Female Standpoint in Bama’s Sangati
Authors: Yogisha  , Kumar Nagendra
Published: April 2020

The term Dalit carries, within itself, a structural negativity since its inception in every sphere of life be it political, social or economic. It encapsulates the trials and tribulations of a crushed and suppressed community, which is known as the ‘Dalit community’. Dalit literature is a manifestation of the life of Dalit community, which is nothing but a painful saga of an endless suffering. Initially, it was viewed as an all-male affair, but in recent times we have seen the emergence of very powerful narratives by Dalit females. Thus, paving the way for Dalit feminist literature with a new perspective and new ideology which can be termed as ‘Dalit female standpoint’. It unravels some hidden territories of Dalit females’ lives and talks about their situation, location and experiences. Sangati, a very powerful novel written by Bama, a Dalit female writer, stands testimony to the things mentioned above as it presents the agency and audacity of the Dalit women who question their subjugation and raise a step against the biased society. Their knowledge towards the outer world gives them a new outlook and fresh perspective on life as they re-examine gender relations as fundamental to the broader ideologies of caste. The present article seeks to explore the life conditions of Dalit females as they are caught in the vortex of caste, gender and class and their grit and resolve to survive despite all odds by harping on their oppositional consciousness.
Pulsed radiofrequency on the occipital nerve for treatment of short-lasting unilateral neuralgiform headache: A case report
Authors: Gonzalez Fatima López , Blasco Isabel Beltrán , Ferri Cesar Margarit
Published: April 2020

Short-lasting unilateral neuralgiform headache (Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing (SUNCT)/Short-lasting Unilateral Neuralgiform headache attacks with Autonomic Symptoms) is a trigeminal autonomic cephalalgia with difficult treatment and its management is based on neuromodulator drugs and sometimes ablative procedures on the trigeminal nerve. A positive response to occipital anesthetic blocks and peripheral and deep neurostimulation has also been described. We present the case of a patient with criteria of left SUNCT and transient response to occipital anesthetic blocks, satisfactorily controlled with pulsed radiofrequency (PRF) of the occipital nerve. Upon examination, the patient had tenderness in the left greater occipital nerve (GON). Blockade was performed with anesthetic and corticosteroid, obtaining a highly positive but transient response. After several nerve blocks, the patient was referred to the Pain Unit where pulsed radiofrequency on the left GON was performed. After two sessions, more than 90% of reduction of pain was achieved, maintained for 12 months. There haven’t been found data in the literature on the use of GON PRF for the treatment of SUNCT, while there are descriptions for other types of cranial pain. The intention of our case is to make this procedure to be considered as an alternative for the treatment of this entity in patients who respond to anesthetic blocks.
Varicose Veins: A Local or Systemic Hemodynamic Disorder?
Authors: Kalinin Roman E. , Suchkov Igor A. , Laut Marina V. , Mzhavanadze Nina D. , Shanaev Ivan N.
Published: April 2020

Objective:

To determine the capabilities of a sonographic examination to evaluate local and systemic hemodynamic disorders in patients with varicose disease.

Materials and Methods:

This study included 583 patients with varicose veins, among whom 348 had trophic disorders. All subjects underwent lower limb duplex sonography and superficial, perforator, and deep venous diameter measurements, as well as had a calculated velocity for antegrade and reflux flow. Peripheral resistive index (RI) in the arteries, accompanying perforator veins (PVs), was analyzed. In addition, echocardiography was performed on 46 of the participants.

Results:

A statistically significant difference in the diameter of the great saphenous vein was obtained between class C2 and C4 varicose veins ( P < .05). Similar findings were obtained for the diameter of the PVs and the velocity reflux flow through PVs. Arteries in the perforator bundles demonstrated low RI, which may be attributed to the presence of arteriovenous shunts. Varicose veins were associated with an increased incidence of nonrestrictive type of blood flow through the tricuspid valve.

Conclusions:

Sonography demonstrated that additional factors rather than hemodynamics may be attributable to the development of venous ulcers. The most informative parameters of cardiac function, in a patient with varicose veins, are the indicators of diastolic function in both ventricles.
Facilitating Efficiency and Flexibility Ambidexterity in Project-Based Organizations: An Exploratory Study of Organizational Antecedents
Authors: Sun Xiuxia , Zhu Fangwei , Sun Mouxuan , Müller Ralf , Yu Miao
Published: April 2020

Through an exploratory multiple-case study in the context of project-based organizations in China, this study aims to identify the antecedents that facilitate three prevalent types of ambidexterity, namely, structural, sequential, and contextual ambidexterity. To understand and theorize on this phenomenon, seven case studies with 76 qualitative interviews were held. The results show that unpredictable and changing environments set the enabling context for ambidexterity, whereas design choices involving dimensions of structure, processes, empowerment, rewards, and human resource policies serve as structural antecedents. The managers and employees who respectively behave in supportive and initiative ways ultimately trigger different types of ambidexterity.
HLA loci predisposing to immune TTP in Japanese: potential role of the shared ADAMTS13 peptide bound to different HLA-DR
Authors: Sakai Kazuya , Kuwana Masataka , Tanaka Hidenori , Hosomichi Kazuyoshi , Hasegawa Atsushi , Uyama Hiroki , Nishio Kenji , Omae Takashi , Hishizawa Masakatsu , Matsui Masashi , Iwato Koji , Okamoto Akinao , Okuhiro Kazuki , Yamashita Yukiko , Itoh Masataka , Kumekawa Hanae , Takezako Naoki , Kawano Noriaki , Matsukawa Toshihiro , Sano Haruna , Ohshiro Kazuiku , Hayashi Kunio , Ueda Yasunori , Mushino Toshiki , Ogawa Yoshiyuki , Yamada Yuji , Murata Mitsuru , Matsumoto Masanori
Published: April 2020

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare autoimmune disorder caused by neutralizing anti-ADAMTS13 autoantibodies. In white individuals, HLA allele DRB1*11 is a predisposing factor for iTTP, whereas DRB1*04 is a protective factor. However, the role of HLA in Asians is unclear. In this study, we analyzed 10 HLA loci using next-generation sequencing in 52 Japanese patients with iTTP, and the allele frequency in the iTTP group was compared with that in a Japanese control group. We identified the following HLA alleles as predisposing factors for iTTP in the Japanese population: DRB1*08:03 (odds ratio [OR], 3.06; corrected P [Pc] = .005), DRB3/4/5*blank (OR, 2.3; Pc = .007), DQA1*01:03 (OR, 2.25; Pc = .006), and DQB1*06:01 (OR,: 2.41; Pc = .003). The estimated haplotype consisting of these 4 alleles was significantly more frequent in the iTTP group than in the control group (30.8% vs 6.0%; Pc < .001). DRB1*15:01 and DRB5*01:01 were weak protective factors for iTTP (OR, 0.23; Pc = .076; and OR, 0.23, Pc = .034, respectively). On the other hand, DRB1*11 and DRB1*04 were not associated with iTTP in the Japanese. These findings indicated that predisposing and protective factors for iTTP differ between Japanese and white individuals. HLA-DR molecules encoded by DRB1*08:03 and DRB1*11:01 have different peptide-binding motifs, but interestingly, bound to the shared ADAMTS13 peptide in an in silico prediction model.
Coexpression of FOXP3 and a Helios isoform enhances the effectiveness of human engineered regulatory T cells
Authors: Seng Amara , Krausz Kelsey L. , Pei Dong , Koestler Devin C. , Fischer Ryan T. , Yankee Thomas M. , Markiewicz Mary A.
Published: April 2020

Regulatory T cells (Tregs) are a subset of immune cells that suppress the immune response. Treg therapy for inflammatory diseases is being tested in the clinic, with moderate success. However, it is difficult to isolate and expand Tregs to sufficient numbers. Engineered Tregs (eTregs) can be generated in larger quantities by genetically manipulating conventional T cells to express FOXP3. These eTregs can suppress in vitro and in vivo but not as effectively as endogenous Tregs. We hypothesized that ectopic expression of the transcription factor Helios along with FOXP3 is required for optimal eTreg immunosuppression. To test this theory, we generated eTregs by retrovirally transducing total human T cells (CD4+ and CD8+) with FOXP3 alone or with each of the 2 predominant isoforms of Helios. Expression of both FOXP3 and the full-length isoform of Helios was required for eTreg-mediated disease delay in a xenogeneic graft-versus-host disease model. In vitro, this corresponded with superior suppressive function of FOXP3 and full-length Helios-expressing CD4+ and CD8+ eTregs. RNA sequencing showed that the addition of full-length Helios changed gene expression in cellular pathways and the Treg signature compared with FOXP3 alone or the other major Helios isoform. Together, these results show that functional human CD4+ and CD8+ eTregs can be generated from total human T cells by coexpressing FOXP3 and full-length Helios.
Modulating the rate of fibrin formation and clot structure attenuates microvascular thrombosis in systemic inflammation
Authors: Valladolid Christian , Martinez-Vargas Marina , Sekhar Nitin , Lam Fong , Brown Cameron , Palzkill Timothy , Tischer Alexander , Auton Mathew , Vijayan K. Vinod , Rumbaut Rolando E. , Nguyen Trung C. , Cruz Miguel A.
Published: April 2020

Systemic inflammation can lead to coagulopathy and disseminated intravascular coagulation (DIC). In prior studies, the recombinant A2 domain of human von Willebrand factor (VWF; A2 protein) attenuated DIC and decreased mortality in lipopolysaccharide (LPS)-treated mice. Here, we performed studies to dissect the mechanism by which the A2 protein moderates DIC. We used confocal microscopy to analyze the fibrin clot structure in plasma from healthy humans and endotoxemic mice, turbidity assays to examine fibrin polymerization, and a murine model for LPS-induced DIC and introduced a loss-of-function mutation into the A2 protein for fibrin. The mutation of the residue E1567 located in the α2 helix of the folded A2 domain of VWF inhibited binding activity for fibrin, possibly mapping a novel region containing a putative binding site for fibrin. The A2 protein increased the initial rate of change of fibrin polymerization, intercalated into the fibrin network, and modified the resultant clot structure in vitro. Furthermore, ex vivo experiments using plasma from mice with endotoxemia treated with the A2 protein revealed an increased rate of fibrin formation and an altered clot structure as compared with plasma from nontreated sick animals. Moreover, and in contrast to the A2 mutant, the A2 protein improved survival and reduced fibrin deposition and microvascular thrombosis in mice with endotoxemia-induced DIC. Importantly, in vivo and in vitro studies indicated that the A2 protein did not affect experimental thrombosis. Thus, we provide evidence for a novel treatment to attenuate systemic inflammation-induced coagulopathy/DIC via targeting fibrin formation, without an increased risk for bleeding.
The possible use of surian tree (Toona sinensis Roem) branches as an alternative raw material in the production of composite boards
Authors: Alamsyah Eka Mulya , Sutrisno  , Sumardi Ihak , Darwis Atmawi , Suhaya Yoyo , Hidayat Yayat
Published: April 2020

The current research focuses on the utilization of branches and twigs of surian as raw material for making composite boards in an effort to utilize the waste part of surian stem wood waste. The types of particle board and oriented strand board were bonded with phenol formaldehyde (PF) of 10% resin content. Variations of board density and board types were focused in this research. The boards were evaluated based on Japanese Industrial Standard (JIS). The results showed that the density of the board affected the physical and mechanical properties of the composite board. Strand boards were better than particle boards with regard to mechanical properties. Physical properties that met the testing standards were moisture content, density, water absorption and thickness swell for both after soaking 2 h in water, while for the mechanical properties test, only modulus of elasticity (MOE) met the standards. However, for further study, it seemed that generally this initial study informed that it was possible to make composite boards from the raw materials, both branches and twigs, with the additional treatment such as changing the size of particles and strands that could improve the properties of the board.
Application of Chemically Exfoliated Boron Nitride Nanosheets Doped with Co to Remove Organic Pollutants Rapidly from Textile Water
Authors: Hassan J. , Ikram M. , Ul-Hamid A. , Imran M. , Aqeel M. , Ali S.
Published: April 2020

Two-dimensional layered materials doped with transition metals exhibit enhanced magnetization and improved catalytic stability during water treatment leading to potential environmental applications across several industrial sectors. In the present study, cobalt (Co)-doped boron nitride nanosheets (BN-NS) were explored for such an application. Chemical exfoliation process was used to exfoliate BN-NS and the hydrothermal route was adopted to incorporate Co dopant in various concentrations (e.g., 2.5, 5, 7.5, and 10 wt%). X-ray diffraction (XRD) study indicated that crystallinity improved upon doping with the formation of a hexagonal phase of the synthesized material. Selected area electron diffraction (SAED) confirmed enhanced crystallinity, which corroborates XRD results. Interlayer spacing was evaluated through a high-resolution transmission electron microscope (HR-TEM) equipped with Gatan digital micrograph software. Compositional and functional group analysis was undertaken with energy dispersive X-ray (EDS) and Fourier transform infrared (FTIR) spectroscopy, respectively. Field emission scanning electron microscope (FE-SEM) and HR-TEM were utilized to probe surface morphologies of prepared samples. Bonding modes in the sample were identified through Raman analysis. Optical properties were examined using UV-vis spectroscopy. Photoluminescence spectra were acquired to estimate the separation and recombination of excitons. Magnetic properties were studied by means of hysteresis loop acquired using VSM measurements. Methylene blue dye was degraded with as-prepared host and doped nanosheets used as catalysts and investigated through absorption spectra ranging from 250 to 800 nm. The experimental results of this study indicate that Co-doped BN-NS showed enhanced magnetic properties and can be used to degrade dyes present as an effluent in industrial wastewater.
Exposure to low-dose nanopolystyrene induces the response of neuronal JNK MAPK signaling pathway in nematode Caenorhabditis elegans
Authors: Qu Man , Li Dan , Zhao Yunli , Yuan Yujie , Wang Dayong
Published: April 2020

Background

The response of organisms to nanoplastic exposure has gradually received the attention. Nevertheless, the role of neurons in response to nanoplastic exposure and the underlying mechanism are still largely unclear. We here examined the role of neuronal JNK MAPK signaling in response to low-dose of polystyrene (100 nm) in Caenorhabditis elegans.

Results

Exposure to nanopolystyrene in the range of μg/L could increase the expression of genes (jkk-1, mek-1, and jnk-1) encoding JNK MAPK signaling pathway. Meanwhile, RNAi knockdown of any of these genes induced a susceptibility to nanopolystyrene toxicity. In the neurons, SNB-1/synaptobrevin was identified as the downstream target of JNK-1/JNK, suggesting the alteration in neurotransmitter signals in nanopolystyrene-exposed nematodes. In nanopolystyrene-exposed nematodes, JNK-1 modulated TBH-1-mediated octopamine signal and CAT-2-mediated dopamine signal. TBH-1 and CAT-2 further regulated the response to nanopolystyrene by affecting the function of corresponding intestinal octopamine receptors (SER-6 and OCTR-1) and intestinal dopamine receptor (DOP-1). In the intestine, DOP-1 regulated the response to nanopolystyrene by activating the downstream signaling cascade in p38 MAPK signaling pathway.

Conclusions

Exposure to low-dose of nanopolystyrene could induce the response of neuronal JNK MAPK signaling pathway in nematodes. Our data further highlight the crucial role of neuronal JNK MAPK signaling-activated alteration in octopamine and dopamine signals in regulating the response to nanopolystyrene in organisms.
Which factors affect willingness-to-pay for automated vehicle services? Evidence from public road deployment in Stockholm, Sweden
Authors: Chee Pei Nen Esther , Susilo Yusak O. , Wong Yiik Diew , Pernestål Anna
Published: April 2020

Introduction

Travel demand and travel satisfaction of a transport service are affected by user perceptions of the service quality attributes, and such perceptions should be included in studying user willingness-to-pay (WTP) for automated vehicle (AV) services. This study applied structural equation modelling with service quality attribute perceptions as latent variables affecting WTP.

Objectives

We investigated how WTP AV services are affected by socio-demographic characteristics, knowledge and experiences with AV, existing travel modes and particularly, perceptions of the associated service quality attributes. The AV services are: 1) on-demand personalised AV (PAV) service, 2) demand responsive shared AV (SAV) service, and 3) first−/last-mile automated bus (AB) service.

Methods

The data were collected from 584 potential users of a first−/last-mile AB service trial operated in Kista, Stockholm.

Results

Results show people hold different expectations towards each type of AV service. These expectations act as the minimum requirements for people to pay for the AV services. Respondents are found to be willing to pay more for PAV service if it is safe, provides good ride comfort, and is competitively priced relative to the price travelling by metro and train over a same distance. Other than service quality attribute perceptions, income level, existing travel modes for daily trips, familiarity with automated driving technology and AB ride experience are important factors affecting WTP for the AV services.

Conclusion

The developed model can be applied to understand expectations of potential users towards a new AV service, and to identify user groups who are willing to pay the service. New AV services can thus be designed sensibly according to users’ actual needs.
ORdensity: user-friendly R package to identify differentially expressed genes
Authors: Martínez-Otzeta José María , Irigoien Itziar , Sierra Basilio , Arenas Concepción
Published: April 2020

Background

Microarray technology provides the expression level of many genes. Nowadays, an important issue is to select a small number of informative differentially expressed genes that provide biological knowledge and may be key elements for a disease. With the increasing volume of data generated by modern biomedical studies, software is required for effective identification of differentially expressed genes. Here, we describe an R package, called , that implements a recent methodology (Irigoien and Arenas, 2018) developed in order to identify differentially expressed genes. The benefits of parallel implementation are discussed.

Results

gives the user the list of genes identified as differentially expressed genes in an easy and comprehensible way. The experimentation carried out in an off-the-self computer with the parallel execution enabled shows an improvement in run-time. This implementation may also lead to an important use of memory load. Results previously obtained with simulated and real data indicated that the procedure implemented in the package is robust and suitable for differentially expressed genes identification.

Conclusions

The new package, , offers a friendly and easy way to identify differentially expressed genes, which is very useful for users not familiar with programming.

Availability
Using multiple reference genomes to identify and resolve annotation inconsistencies
Authors: Monnahan Patrick J. , Michno Jean-Michel , O’Connor Christine , Brohammer Alex B. , Springer Nathan M. , McGaugh Suzanne E. , Hirsch Candice N.
Published: April 2020

Background

Advances in sequencing technologies have led to the release of reference genomes and annotations for multiple individuals within more well-studied systems. While each of these new genome assemblies shares significant portions of synteny between each other, the annotated structure of gene models within these regions can differ. Of particular concern are split-gene misannotations, in which a single gene is incorrectly annotated as two distinct genes or two genes are incorrectly annotated as a single gene. These misannotations can have major impacts on functional prediction, estimates of expression, and many downstream analyses.

Results

We developed a high-throughput method based on pairwise comparisons of annotations that detect potential split-gene misannotations and quantifies support for whether the genes should be merged into a single gene model. We demonstrated the utility of our method using gene annotations of three reference genomes from maize (B73, PH207, and W22), a difficult system from an annotation perspective due to the size and complexity of the genome. On average, we found several hundred of these potential split-gene misannotations in each pairwise comparison, corresponding to 3–5% of gene models across annotations. To determine which state (i.e. one gene or multiple genes) is biologically supported, we utilized RNAseq data from 10 tissues throughout development along with a novel metric and simulation framework. The methods we have developed require minimal human interaction and can be applied to future assemblies to aid in annotation efforts.

Conclusions

Split-gene misannotations occur at appreciable frequency in maize annotations. We have developed a method to easily identify and correct these misannotations. Importantly, this method is generic in that it can utilize any type of short-read expression data. Failure to account for split-gene misannotations has serious consequences for biological inference, particularly for expression-based analyses.
Morpho-physiological integrators, transcriptome and coexpression network analyses signify the novel molecular signatures associated with axillary bud in chrysanthemum
Authors: Ahmad Sagheer , Yuan Cunquan , Yang Qingqing , Yang Yujie , Cheng Tangren , Wang Jia , Pan Huitang , Zhang Qixiang
Published: April 2020

Background

Axillary bud is an important agronomic and economic trait in cut chrysanthemum. Bud outgrowth is an intricate process controlled by complex molecular regulatory networks, physio-chemical integrators and environmental stimuli. Temperature is one of the key regulators of bud’s fate. However, little is known about the temperature-mediated control of axillary bud at molecular levels in chrysanthemum. A comprehensive study was designed to study the bud outgrowth at normal and elevated temperature in cut chrysanthemum. Leaf morphology, histology, physiological parameters were studied to correlate the leaf activity with bud morphology, sucrose and hormonal regulation and the molecular controllers.

Results

Temperature caused differential bud outgrowth along bud positions. Photosynthetic leaf area, physiological indicators and sucrose utilization were changed considerable due to high temperature. Comparative transcriptome analysis identified a significant proportion of bud position-specific genes.Weighted Gene Co-expression Network Analysis (WGCNA) showed that axillary bud control can be delineated by modules of coexpressed genes; especially, MEtan3, MEgreen2 and MEantiquewhite presented group of genes specific to bud length. A comparative analysis between different bud positions in two temperatures revealed the morpho-physiological traits associated with specific modules. Moreover, the transcriptional regulatory networks were configured to identify key determinants of bud outgrowth. Cell division, organogenesis, accumulation of storage compounds and metabolic changes were prominent during the bud emergence.

Conclusions

RNA-seq data coupled with morpho-physiological integrators from three bud positions at two temperature regimes brings a robust source to understand bud outgrowth status influenced by high temperature in cut chrysanthemum. Our results provide helpful information for elucidating the regulatory mechanism of temperature on axillary bud growth in chrysanthemum.
Epidemiological characteristics and transmissibility of shigellosis in Hubei Province, China, 2005 – 2017
Authors: Chen Qi , Rui Jia , Hu Qingqing , Peng Ying , Zhang Hao , Zhao Zeyu , Tong Yeqing , Wu Yang , Su Yanhua , Zhao Benhua , Guan Xuhua , Chen Tianmu
Published: April 2020

Background

Shigellosis is one of the main diarrhea diseases in developing countries. However, the transmissibility of shigellosis remains unclear.

Methods

We used the dataset of shigellosis cases reported between January 2005 and December 2017, from Hubei Province, China. A mathematical model was developed based on the natural history and the transmission mechanism of the disease. By fitting the data using the model, transmission relative rate from person to person (b) and from reservoir to person (bw), and the effective reproduction number (Reff) were estimated. To simulate the contribution ofbandbwduring the transmission, we performed a “knock-out” simulation in four scenarios: A)b = 0 andbw = 0; B)b = 0; C)bw = 0; D) control (no intervention).

Results

A total of 130,770 shigellosis cases were reported in Hubei province, among which 13 cases were dead. The median annual incidence was 19.96 per 100,000 persons (range: 5.99 per 100,000 persons – 29.47 per 100,000 persons) with a decreased trend (trendχ2 = 25,470.27,P < 0.001). The mean values ofbandbwwere 0.0898 (95% confidence interval [CI]: 0.0851–0.0946) and 1.1264 × 10− 9(95% CI: 4.1123 × 10− 10–1.8416 × 10− 9), respectively. The “knock-out” simulation showed that the number of cases simulated by scenario A was almost the same as scenario B, and scenario C was almost the same as scenario D. The mean value ofReffof shigellosis was 1.19 (95% CI: 1.13–1.25) and decreased slightly with a Linear model until it decreased to an epidemic threshold of 0.99 (95% CI: 0.65–1.34) in 2029.

Conclusions

The incidence of shigellosis is still in high level. The transmissibility of the disease is low in Hubei Province. The transmission would be interrupted in the year of 2029.
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

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

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

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

Background

Cancer 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.

Methods

Human 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.

Results

A 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.

Conclusion

Our 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

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

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

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

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

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.