bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and up‐conversion of Er3+ and Yb3+ Co‐doped LiY(MoO4)2@SiO2 for optical thermometry applications
Authors: Feng Xiaohui , Wang Le , Wei Ran , Wang Ziyan
Published: August 2019

Non‐contact temperature sensors based on the fluorescence intensity ratio (FIR) have been widely investigated owing to their high sensitivity and reliable real‐time monitoring. Herein, the SiO2‐coated LiY(MoO4)2@SiO2:Er3+,Yb3+ phosphor was investigated as an optical thermometry material, which was synthesized using the conventional solid state reaction and coated by a facile wet chemical route. The effect of surface modification on FIR was systematically characterized by structural analyses and spectral measurements and the temperature‐dependent up‐conversion FIR was investigated from 303 to 603 K under a 980 nm laser excitation. The results showed that the FIR value was thermally stable and the SiO2 coating led to a higher FIR sensitivity as well as a higher saturation threshold. This work would pave a way to design interesting optical thermometry materials in up‐conversion phosphors with better properties.
Insights into the direct formation of [Ca24Al28O64]4+(4e−) and its electrical characterization
Authors: Li Fan , Zhang Xin , Liu Hongliang
Published: August 2019

C12A7:e−electrides are potentially useful in various technological applications. However, it usually needs to be synthesized through a complicated multistep process under severe conditions. Therefore, the search is on for a more facile and direct process that occurs under milder conditions. Here, a facile and efficient synthesis strategy has been developed for the rapid production of highly conductive C12A7:e−directly from commercially available chemical ingredients of CaO, Al2O3, and Al powders at 1200°C in a 10−2 Pa vacuum for 20 minutes using SPS process. The electron concentration in the as‐prepared C12A7:e−was enhanced up to 2.13 × 1021 cm−3by simply regulating the addition amounts of Al, covering IM transition. The electronic structure results indicated the formation of homogeneous trapped electrons in the lattice. Further thermal analyses illustrated that Al made a dual function of reducing agent and and reaction promoter, which remarkably reduced the formation temperature of mayenite structure. This study fills in the gaps of direct formation mechanisms of conductive mayenite phase, and provides a new perspective to regulate the resultantNe.
Inclusive management for social entrepreneurs with intellectual disabilities: “how they act”
Authors: Caldwell Kate , Parker Harris Sarah , Renko Maija
Published: August 2019

Background

Social entrepreneurship is a growing trend that reflects a shift in contemporary policy towards entrepreneurship and self‐employment as viable employment option for people with disabilities. Entrepreneurship is intended to promote autonomy and reduce dependence on entitlement‐based services as well as reduce employment disparities while stimulating business and job creation.However, it is not well understood what exactly this means for people with intellectual disabilities (ID) involved in social entrepreneurial ventures.

Methods

Dyadic interviews were conducted with people with ID participating in social entrepreneurship (n = 7) as well as with the person they identified as instrumental in providing support (n = 7). Interviews focused on understanding the management processes used by people with ID, or “how they act” in negotiating between formal and informal systems of services and supports and barriers encountered.

Results

Themes that emerged include the main barriers they experienced, how their businesses are organized; and the use of formal and informal services and supports.

Conclusions

This research expands upon our understanding of social entrepreneurship and the management processes involved in customized employment for people with ID. It offers new insights and information for practitioners, policymakers, and researchers to inform the expectations we set for entrepreneurship as a sustainable employment option, from the perspective of social entrepreneurs with ID themselves.
Network‐ and distance‐based methods in bioregionalization processes at regional scale: An application to the terrestrial mammals of Iran
Authors: Yusefi Gholam Hosein , Safi Kamran , Brito José Carlos
Published: August 2019

Aim

In recent years, novel approaches have been proposed to improve current bioregionalization methods, but these have not been thoroughly compared. We assessed the applicability of the recently developed network‐based clustering method (Infomap algorithm) in bioregionalization analysis at regional spatial scales and compared the results with commonly used distance‐based methods (hierarchical clustering algorithm). We also identified climate regions by using a model‐based cluster analysis (Gaussian algorithm). Finally, we quantified the representation of climate regions and bioregions in current protected areas (PAs).

Location

Iran.

Taxa

Terrestrial mammals.

Methods

To define bioregions we used the Infomap algorithm and distance‐based clustering methods based on species distribution data (over 14,000 occurrence records for 188 species). The Infomap algorithm was applied using the interactive web application “INFOMAP BIOREGIONS” and the distance‐based clustering was based on unweighted pair‐group method using arithmetic averages (UPGMA). To identify climate regions we used principal components analysis and a model‐based cluster analysis both based on 15 climatic variables as well as a terrain ruggedness index.

Results

The Infomap algorithm detected nine biogeographical units: seven bioregions and two transition zones. The distance‐based method suggested five bioregions. The identified bioregions differed between methods with some consistent spatial patterns across methods. Temperature and precipitation explained 85.8% of the environmental variation. Eight climate regions were identified. In general, climate variation and bioregional patterns are currently poorly represented in PAs (<25% coverage).

Main conclusions

The network‐based method allowed identifying bioregions at regional scale and was apparently more sensitive than the conventional distance‐based method. The detection of transition zones by the Infomap algorithm was an advantage, and stressed the fact that the distribution of Iranian mammalian fauna is complex, especially in the south‐eastern part where contact areas between several bioregions are found. The identified bioregions (especially the distance‐based bioregions) and climate regions tended to match well with previous bioregionalization studies and the global terrestrial ecoregions. When thoroughly compared and understood, bioregions and climate regions provide a framework for regional biodiversity conservation planning.
NCBP1 promotes the development of lung adenocarcinoma through up‐regulation of CUL4B
Authors: Zhang Huijun , Wang An , Tan Yulong , Wang Shaohua , Ma Qinyun , Chen Xiaofeng , He Zelai
Published: August 2019

Lung cancer is the most frequent cancer type and is the leading cause of tumour‐associated deaths worldwide. Nuclear cap‐binding protein 1 (NCBP1) is necessary for capped RNA processing and intracellular localization. It has been reported that silencing of NCBP1 resulted in cell growth reduction in HeLa cells. Nevertheless, its clinical significance and underlying molecular mechanisms in non–small‐cell lung cancer remain unclear. In this study, we found that NCBP1 was significantly overexpressed in lung cancer tissues and several lung cancer cell lines. Through knockdown and overexpression experiments, we showed that NCBP1 promoted lung cancer cell growth, wound healing ability, migration and epithelial‐mesenchymal transition. Mechanistically, we found that cullin 4B (CUL4B) was a downstream target gene of NCBP1 in NSCLC. NCBP1 up‐regulated CUL4B expression via interaction with nuclear cap‐binding protein 3 (NCBP3). CUL4B silencing significantly reversed NCBP1‐induced tumorigenesis in vitro. Based on these findings, we propose a model involving the NCBP1‐NCBP3‐CUL4B oncoprotein axis, providing novel insight into how CUL4B is activated and contributes to LUAD progression.
The Clinical Course after Long‐Term Acute Care Hospital Admission among Older Medicare Beneficiaries
Authors: Makam Anil N. , Tran Thu , Miller Michael E. , Xuan Lei , Nguyen Oanh Kieu , Halm Ethan A.
Published: August 2019

Objectives

Long‐term acute care (LTAC) hospitals provide extended complex post–acute care to more than 120 000 Medicare beneficiaries annually, with the goal of helping patients to regain independence and recover. Because little is known about patients’ long‐term outcomes, we sought to examine the clinical course after LTAC admission.

Design

Nationally representative 5‐year cohort study using 5% Medicare data from 2009 to 2013.

Setting

LTAC hospitals.

Participants

Hospitalized Medicare fee‐for‐service beneficiaries 65 years of age or older who were transferred to an LTAC hospital.

Measurements

Mortality, recovery (defined as achieving 60 consecutive days alive without inpatient care), time spent in an inpatient facility following LTAC hospital admission, receipt of an artificial life‐prolonging procedure (feeding tube, tracheostomy, hemodialysis), and palliative care physician consultation.

Results

Of 14 072 hospitalized older adults transferred to an LTAC hospital, median survival was 8.3 months, and 1‐ and 5‐year survival rates were 45% and 18%, respectively. Following LTAC admission, 53% never achieved a 60‐day recovery. The median time of their remaining life a patient spent as an inpatient after LTAC admission was 65.6% (interquartile range = 21.4%‐100%). More than one‐third (36.9%) died in an inpatient setting, never returning home after the LTAC admission. During the preceding hospitalization and index LTAC admission, 30.9% received an artificial life‐prolonging procedure, and 1% had a palliative care physician consultation.

Conclusion

Hospitalized older adults transferred to LTAC hospitals have poor survival, spend most of their remaining life as an inpatient, and frequently undergo life‐prolonging procedures. This prognostic understanding is essential to inform goals of care discussions and prioritize healthcare needs for hospitalized older adults admitted to LTAC hospitals. Given the exceedingly low rates of palliative care consultations, future research is needed to examine unmet palliative care needs in this population. J Am Geriatr Soc 67:2282–2288, 2019
GBSS‐BINDING PROTEIN, encoding a CBM48 domain‐containing protein, affects rice quality and yield
Authors: Wang Wei , Wei Xiangjin , Jiao Guiai , Chen Wenqiang , Wu Yawen , Sheng Zhonghua , Hu Shikai , Xie Lihong , Wang Jiayu , Tang Shaoqing , Hu Peisong
Published: August 2019

The percentage of amylose in the endosperm of rice (Oryza sativa) largely determines grain cooking and eating qualities. Granule‐bound starch synthase I (GBSSI) and GBSSII are responsible for amylose biosynthesis in the endosperm and leaf, respectively. Here, we identified OsGBP, a rice GBSS‐binding protein that interacted with GBSSI and GBSSII in vitro and in vivo. The total starch and amylose contents in osgbp mutants were significantly lower than those of wild type in leaves and grains, resulting in reduced grain weight and quality. The carbohydrate‐binding module 48 (CBM48) domain present in the C‐terminus of OsGBP is crucial for OsGBP binding to starch. In the osgbp mutant, the extent of GBSSI and GBSSII binding to starch in the leaf and endosperm was significantly lower than wild type. Our data suggest that OsGBP plays an important role in leaf and endosperm starch biosynthesis by mediating the binding of GBSS proteins to developing starch granules. This elucidation of the function of OsGBP enhances our understanding of the molecular basis of starch biosynthesis in rice and contributes information that can be potentially used for the genetic improvement of yield and grain quality.
Placental mesenchymal dysplasia with a good outcome: A case report
Authors: Oide Shiho , Kuwata Tomoyuki , Wang Liangcheng , Imai Ken , Chikazawa Kenro , Takagi Kenjiro
Published: August 2019

Placental mesenchymal dysplasia (PMD), characterized by an enlarged and thickened placenta with multiple hypoechoic cystic spaces, frequently leads to a poor infantile/fetal outcome. Here, we describe a case of PMD involving an infant delivered at term with a good outcome. The fetus was male, and the proportion of the PMD lesion to the entire placenta remained constant: the PMD lesion did not enlarge. Given what is known about the pathogenesis of PMD with its association with vascular endothelial growth factor‐D (VEGF‐D) encoded by an X‐linked gene and androgenetic/biparental mosaicism, which is consistent with female dominancy and a poor outcome, we suggest that a male sex of the fetus and non‐progressing PMD may have been associated with this good outcome.
Bronchiolitis at a specialist paediatric centre: The electronic medical record helps to evaluate low‐value care
Authors: Lawrence Joanna G , Andrew Lauren , Bracken Jenny , Voskoboynik Alice , Oakley Ed , South Mike , Middleton Katherine , Scanlan Barry , Marshall Tim , Hiscock Harriet
Published: August 2019

Aim

Low‐value care (LVC) is common. We aimed, using infants presenting to a major tertiary paediatric hospital with bronchiolitis between April 2016 and July 2018, to: (i) assess rates of chest X‐ray (CXR) and medication use; (ii) identify associated factors; and (iii) measure the harm of not performing these practices.

Methods

We extracted data from the electronic medical record for all children aged 1–12 months given a diagnosis of bronchiolitis in the emergency department. Factors potentially associated with LVC practices were extracted, including patient demographics, ordering physician characteristics, order indication, medications prescribed and admission ward. To assess for harm, a radiologist, blinded to CXR indication, reviewed all CXRs ordered over the winter of 2017 for infants with bronchiolitis.

Results

A CXR was ordered for 439 (11.2%) infants, most commonly to rule out consolidation and collapse (65%). CXRs were more likely to be ordered for admitted infants (40.9% admitted to the general medical ward), and 62% were ordered by emergency department staff. Salbutamol was prescribed for 9.3% (n = 199). Amongst those who had a CXR, 28% were prescribed an antibiotic compared to 2.1% for those who did not. In an audit of 98 CXRs ordered over the winter of 2017, there were no CXR findings that meaningfully affected patient outcomes.

Conclusion

Using electronic medical record data, we found that CXR and medication use in bronchiolitis were higher than expected given our hospital guideline advice. Future research needs to understand why and develop interventions to reduce LVC.
USF2 enhances the osteogenic differentiation of PDLCs by promoting ATF4 transcriptional activities
Authors: Liu Fan , Wang Xiaohong , Zheng Bowen , Li Danni , Chen Cen , Lee In‐seop , Zhong Jialin , Li Duo , Liu Yi
Published: August 2019

Objective

Our study aimed to elucidate the regulatory molecules related to the osteogenic differentiation of periodontal ligament cells (PDLCs).

Background

Periodontal ligament cells are a favorable source for cell‐based therapy in periodontal bone engineering and regeneration due to their potential multilineage differentiation ability. However, the molecular mechanism and signaling pathways related to the osteogenic differentiation of PDLCs are still unclear.

Methods

Osteoblast‐specific protein expression levels were examined by ELISA in osteogenic‐induced PDLCs (induced‐PDLC group). A microarray assay and a bioinformatics analysis were carried out to reveal significantly expressed genes and the related pathways in induced‐PDLCs, and these findings were then confirmed by qRT‐PCR and a luciferase reporter assay. Finally, overexpressing and silencing gene systems were established to identify the specific transcriptional relationship and function of the target genes on the osteogenic differentiation of PDLCs.

Results

Osteogenically differentiated PDLCs with high levels of osteoblast‐specific proteins were established. The upstream stimulatory factor 2 (USF2) and activating transcription factor 4 (ATF4) mRNA levels were upregulated the most through the MAPK signaling pathway in the induced‐PDLC group. USF2 could bind to the transcriptional initiation region of ATF4 and regulate its transcriptional activities. Additionally, the overexpression of USF2 promoted osteoblast‐specific gene expression and the Alizarin red staining of PDLCs, while simultaneously overexpressing USF2 and silencing ATF4 reversed the favorable osteogenic effect of the induced‐PDLCs by reducing osteoblast‐specific gene expression and the Alizarin red staining level.

Conclusion

Our study demonstrated that USF2 could enhance the osteogenic differentiation of PDLCs by regulating ATF4 transcriptional activities, which provides a new strategy to utilize USF2 and ATF4 as potential target molecules for periodontal bone regeneration.
Evaluation of a hepatitis C virus core antigen assay from venepuncture and dried blood spot collected samples: A cohort study
Authors: Catlett Beth , Lamoury Francois M. J. , Bajis Sahar , Hajarizadeh Behzad , Martinez Danica , Mowat Yasmin , Cunningham Philip H. , Jacka Brendan P. , Cloherty Gavin A , Marks Philippa , Dore Gregory J. , Grebely Jason , Applegate Tanya L.
Published: August 2019

The global scale‐up of hepatitis C virus (HCV) diagnosis requires simplified and affordable HCV diagnostic pathways. This study evaluated the sensitivity and specificity of the HCV Architect core antigen (HCVcAg) assay for detection of active HCV infection in plasma and capillary whole blood dried blood spots (DBS) compared with HCV RNA testing in plasma (Abbott RealTime HCV Viral Load). Samples were collected from participants in an observational cohort enrolled at three sites in Australia (two‐drug treatment and alcohol clinics and one homelessness service). Of 205 participants, 200 had results across all samples and assay types and 186 were included in this analysis (14 participants receiving HCV therapy were excluded). HCV RNA was detected in 29% of participants ([95% CI: 22.6‐36.1], 54 of 186). The sensitivity of HCVcAg for detection of active HCV infection in plasma was 98.1% (95% CI: 90‐100) and 100% (95% CI: 93‐100) when compared to HCV RNA thresholds of ≥12 and ≥1000 IU/mL, respectively. The sensitivity of the HCVcAg assay for detection of active HCV infection in DBS was 90.7% (95% CI: 80‐97) and 92.5% (95% CI: 82‐98) when compared to HCV RNA thresholds of ≥12 and ≥1000 IU/mL, respectively. The specificity of HCV core antigen for detection of active infection was 100% (95% CI: 97‐100) for all samples and RNA thresholds. These data indicate that the detection of HCVcAg is a useful tool for determining active HCV infection; to facilitate enhanced testing, linkage to care and treatment particularly when testing plasma samples are collected by venepuncture.
Consistent high prevalence of undiagnosed blood‐borne virus infection in patients attending large urban emergency departments in England
Authors: Hopkins Mark J. , Todd Stacy , Beadsworth Mike , Anderson Charlotte , Mohamed Zameer , Muir David , Vivancos Roberto , Brown Ashley S. , Ruf Murad , Chawla Anu
Published: August 2019

Understanding local viral hepatitis and HIV epidemiology is essential if WHO elimination targets are to be achieved. We demonstrate a consistently high prevalence of undiagnosed active infection in urban emergency department attendees in England, with variations in local risk groups crucial to informing targeted testing initiatives.
Comparative study of nutritional mode and mycorrhizal fungi in green and albino variants of Goodyera velutina, an orchid mainly utilizing saprotrophic rhizoctonia
Authors: Suetsugu Kenji , Yamato Masahide , Matsubayashi Jun , Tayasu Ichiro
Published: August 2019

The majority of chlorophyllous orchids form mycorrhizal associations with so‐called rhizoctonia fungi, a phylogenetically heterogeneous assemblage of predominantly saprotrophic fungi in Ceratobasidiaceae, Tulasnellaceae, and Serendipitaceae. It is still a matter of debate whether adult orchids mainly associated with rhizoctonia species are partially mycoheterotrophic. Here, we investigated the nutritional modes of green and albino variants of Goodyera velutina, an orchid species considered to be mainly associated with Ceratobasidium spp., by measuring their 13C and 15N abundances, and by molecular barcoding of their mycorrhizal fungi. Molecular analysis revealed that both green and albino variants of G. velutina harbored a similar range of mycobionts, mainly saprotrophic Ceratobasidium spp., Tulasnella spp., and ectomycorrhizal Russula spp. In addition, stable isotope analysis revealed that albino variants were significantly enriched in 13C but not so greatly in 15N, suggesting that saprotrophic Ceratobasidium spp. and Tulasnella spp. are their main carbon source. However, in green variants, 13C levels were depleted and those of 15N were indistinguishable from the co‐occurring autotrophic plants. Therefore, we concluded that the albino G. velutina variants are fully mycoheterotrophic plants whose C derives mainly from saprotrophic rhizoctonia, while the green G. velutina variants are mainly autotrophic plants, at least at our study site, in spite of their additional associations with ectomycorrhizal fungi. This is the first report demonstrating that adult nonphotosynthetic albino variants can obtain their nutrition mainly from nonectomycorrhizal rhizoctonia.
Broad learning for nonparametric spatial modeling with application to seismic attenuation
Authors: Kuok Sin‐Chi , Yuen Ka‐Veng
Published: August 2019

Spatial modeling is a core element in geographical information science. It incorporates geographic information to construct the relationship for interpreting the behavior of spatial phenomena. In this paper, a broad learning framework for nonparametric spatial modeling is presented. Broad learning overcomes the obstacle of expensive computational consumption in deep learning and provides a powerful computationally efficient alternative. In contrast to the deep learning architecture that is configured with stacks of hierarchical layers, broad learning networks are established in a flat manner that can be flexibly reconfigured with the inherited information from the trained network. To develop the broad learning network, a simple prototype network is established as the initial trial and it is modified incrementally to enhance its data fitting capacity. Consequently, complex relationship of unstructured spatial data can be modeled efficiently. To demonstrate the efficacy and applicability of the broad learning framework, we will present a simulated example and a real application using the strong ground motion records on the 2008 great Wenchuan earthquake.
Periocular infantile hemangiomas: Characteristics, ocular sequelae, and outcomes
Authors: Zhao Jiawei , Huang Amy H. , Rainer Barbara M. , Kryatova Maria S. , Eghrari Allen O. , Wang Jiangxia , Puttgen Katherine B. , Cohen Bernard A.
Published: August 2019

Objectives

To identify clinical factors associated with complications of periocular infantile hemangioma (IH) and monitor improvement in complication rates post‐treatment.

Methods

Retrospective cohort study. Eighty‐nine patients diagnosed with periocular IH at a pediatric dermatology clinic of a tertiary care center between 2001 and 2013 were included with parental approval. Parents were interviewed by telephone between July and September of 2015, then again in January 2018 to inquire about ophthalmologic follow‐up. Electronic medical records were reviewed from January 2001 through January 2018.

Results

Sixty percent of patients demonstrated ocular sequelae, including astigmatism (33%), visual axis obstruction (29%), nasolacrimal duct obstruction (7%), ptosis (4%), amblyopia (3%), and strabismus (1%). Compared with superficial IH, deep and mixed IH had higher odds, 3.4 (P = 0.025) and 3.8 (P = 0.034), respectively, of developing ocular sequelae. All patients with astigmatism prior to involution of IH received systemic therapy, with a significant post‐treatment decrease in the proportion of patients with astigmatism (40% to 18%, P = 0.027). Three‐quarters of patients experienced complete IH involution by time of enrollment in kindergarten. Fifty‐one (57.3%) patients received formal ophthalmologic evaluation confirmed through chart review or phone interview, with average follow‐up duration of 51.2 months (range: 1.9, 99.3).

Conclusion

Deep and mixed IH were more likely to demonstrate ocular complications than superficial IH. Rate of astigmatism decreased with systemic therapy. Our study suggests that patients with periocular IH have a lower rate of amblyopia now compared with the prepropranolol era and emphasizes the importance of early treatment of periocular IH to prevent permanent visual sequelae.
Sharing Quality‐Distribution Information for the Selective Assembly of Intermediary Components in the Automotive Industry
Authors: Clottey Toyin , Benton W. C.
Published: August 2019

This study investigates the value of a supplier sharing information about the quality‐distribution (i.e., dimensional mean or variance) of components with an assembler who matches such parts with the selective assembly of an intermediary component. Selective assembly is a strategy that is widely used by high‐precision manufacturing companies to gain a competitive advantage in product quality. The use of inexpensive intermediary components (e.g., bearings) to ensure that all mating components are matched with acceptable clearance is a contemporary way of reducing shortage and surplus component costs associated with the traditional fixed‐bin selective assembly process. We develop and analyze a Bayesian model for information sharing in this environment, with results indicating that substantial savings occur with the use of shared information from the supplier in a fixed‐bin selective assembly of an intermediary‐component (FBSAI) context. However, there is a hierarchy regarding benefits, whereas the sharing of information which includes the process mean is most beneficial, and the sharing of only process variance information is least beneficial. The savings can assist the assembler in determining the investment required to create and maintain a profitable quality‐distribution information‐sharing network of suppliers, thus making the shared information advantageous for both the buying and selling organization.
A pre‐adaptive approach for tropical forest restoration during climate change using naturally occurring genetic variation in response to water limitation
Authors: Axelsson E. Petter , Grady Kevin C. , Lardizabal Maria L. T. , Nair Ignatius B. S. , Rinus Daideth , Ilstedt Ulrik
Published: August 2019

Effective reforestation of degraded tropical forests depends on selecting planting material suited to the stressful environments typical at restoration sites that can be exacerbated by increased duration and intensity of dry spells expected with climate change. While reforestation efforts in nontropical systems are incorporating drought‐adapted genotypes into restoration programs to cope with drier conditions, such approaches have not been tested or implemented in tropical forests. As the first effort to examine genetic variation in plant response to drought in a tropical wet forest, we established a watering experiment using five replicated maternal lines (i.e. seedlings from different maternal trees) of five dipterocarp species native to Borneo. Apart from the expected species level variation in growth and herbivory (3‐fold variation in both cases), we also found intraspecific variation so that growth in some cases varied 2‐fold, and herbivory 3‐fold, among genetically different maternal lines. In two species we found that among‐maternal line variation in growth rate was negatively correlated with tolerance to water limitation, that is, the maternal lines that performed the best in the high water treatment lost proportionally more of their growth during water limitation. We argue that selection for tolerance to future drier conditions is not only likely to impact population genetics of entire forests, but likely extends from forest trees to the communities of canopy arthropods associated with these trees. In tropical reforestation efforts where increased drought is predicted from climate change, including plant material resilient to drier conditions may improve restoration effectiveness.
Inclusion of Time-Varying Covariates in Cure Survival Models with an Application in Fertility Studies
Authors: Lambert Philippe , Bremhorst Vincent
Published: August 2019

Cure survival models are used when we desire to acknowledge explicitly that an unknown proportion of the population studied will never experience the event of interest. An extension of the promotion time cure model enabling the inclusion of time-varying covariates as regressors when modelling (simultaneously) the probability and the timing of the monitored event is presented. Our proposal enables us to handle non-monotone population hazard functions without a specific parametric assumption on the baseline hazard. This extension is motivated by and illustrated on data from the German Socio-Economic Panel by studying the transition to second and third births in West Germany.
A Hidden Semi-Markov Model for Characterizing Regime Shifts in Ocean Density Variability
Authors: Economou Theodoros , Menary Matthew B.
Published: August 2019

Societally important decadal predictions of temperature and precipitation over Europe are largely affected by variability in the North Atlantic Ocean. Within this region, the Labrador Sea is of particular importance because of its link between surface-driven density variability and the Atlantic meridional overturning circulation. Using physical justifications, we propose a statistical model to describe the temporal variability of ocean density in terms of salinity-driven and temperature-driven density. This is a hidden semi-Markov model that allows for either a salinity-driven or a temperature-driven ocean density regime, such that the persistence in each regime is governed probabilistically by a semi-Markov chain. The model is fitted in the Bayesian framework, and a reversible jump Markov chain Monte Carlo algorithm is proposed to deal with a single-regime scenario. The model is first applied to a reanalysis data set, where model checking measures are also proposed. Then it is applied to data from 43 climate models to investigate whether and how ocean density variability differs between them and also the reanalysis data. Parameter estimates relating to the mean holding time for each regime are used to establish a link between regime behaviour and the Atlantic meridional overturning circulation.
Association of CTLA‐4, TNF alpha and IL 10 polymorphisms with susceptibility to hepatocellular carcinoma
Authors: Wang Jia‐jia , Wang Zhi‐bin , Tan Tai‐chang
Published: August 2019

Our aim was to evaluate the association of genetic polymorphisms of immunoregulatory molecules with susceptibility to hepatocellular carcinoma (HCC). The polymorphisms in CTLA‐4 (−318 T/C, CT60 G/A), TNF (−238 G/A, −308 G/A) and IL10 (−592 C/A, −819 C/T) were genotyped by PCR and DNA sequencing. The functional relevance of the polymorphisms was examined by ELISAs, in vitro lymphocyte proliferation assay and cytotoxic assay. The CTLA‐4 −318 TC/TT, CTLA‐4 CT60 GG, IL10 −592 CA and −819 CT/TT variants, CTLA‐4 −318 T and IL 10 −819 T alleles were positively associated with HCC risk (P < .05). While TNF −238 AA variant, TNF −238 A allele were associated with decreased risk of HCC (P < .05). Furthermore, combinations of CTLA‐4 −318 TC/TT and TNF −238 GG/GA; CTLA‐4 −318 TC/TT and IL 10 −819 CC; CTLA‐4 −318 CC and IL 10 −819 CT/TT in patients with HCC were statistically significant (P < .05). Peripheral blood mononuclear cells (PBMCs) carrying −318 TC/TT genotypes exhibited significantly lower proliferation rates, decreased IL‐2, IL‐4 levels, fewer cytolytic activities and elevated TGF‐β levels. For IL 10 −819 C/T, the CC genotype was significantly associated with higher proliferation rate, decreased TGF‐β, IL‐10 levels and higher cytolytic activities (P < .05). For TNF −238 G/A, the AA genotype only had association with serum IL‐2, IL‐4 (P < .05). In addition, we also found that CTLA‐4 −318 T/C, IL‐10 −819 T/C variants, combinations of CTLA‐4 −318 CC with IL 10 −819 CT or TT, CTLA‐4 −318 TC or TT with IL 10 −819 CT or TT were associated with the severity of HCC. These findings suggest that CTLA‐4 −318 TC/TT and IL 10 −819 CT/TT could promote the pathogenesis of HCC, which might be related with down‐regulation of Th1/Th2‐type cytokines and/or up‐regulation of Th3‐type cytokines.
Characterization of an HLA‐B*55:01:01 variant, HLA‐B*55:01:01:14, identified in a Brazilian individual
Authors: Vianna Romulo , Porto Luís Cristóvão
Published: August 2019

Characterization of an HLA‐B*55:01:01 variant, called HLA‐B*55:01:01:14.
Successful management and recovery following severe prolonged starvation in a dog
Authors: Khoo Alison Wui Sing , Taylor Susan M. , Owens Tammy J.
Published: August 2019

Objective

To describe the successful management of a dog following a period of prolonged food deprivation.

Case Summary

A 7‐year‐old, intact male Labrador Retriever presented with profound weakness and loss of nearly 50% of his body weight due to severe prolonged starvation after being trapped in a well for 27 days. Electrolyte concentrations were managed with intensive intravenous supplementation during refeeding. The dog's electrolyte abnormalities resolved, wounds healed, and strength returned during the first 3 weeks of treatment. During the next 3 months, body condition score normalized and muscle mass improved.

New or Unique Information Provided

This report describes the management of a severely malnourished dog during refeeding, and highlights treatment considerations that may be important in the prevention of refeeding syndrome in such cases.
Combining anti‐IgM and IgG immunoassays for comprehensive chikungunya virus diagnostic testing
Authors: Mendoza Emelissa J. , Robinson Alyssia , Dimitrova Kristina , Mueller Nicole , Holloway Kimberly , Makowski Kai , Wood Heidi
Published: August 2019

Chikungunya virus (CHIKV) is a mosquito‐borne pathogen that causes CHIKV fever. Definitive diagnosis is crucial for patients experiencing symptoms similar to other arboviral diseases because they can vary in clinical consequences. An increasing number of patients experience long‐term rheumatic effects of CHIKV infection, but these cases may not be optimally detected by molecular assays and anti‐CHIKV IgM ELISAs (M‐ELISAs) used for confirmation and screening, respectively. The subsequent confirmatory serological test, the plaque reduction neutralization test (PRNT), is laborious and time‐consuming. In this study, we evaluated a new diagnostic algorithm in which the M‐ELISA is conducted in parallel with an anti‐CHIKV IgG ELISA (G‐ELISA) and observed that the Euroimmun M‐ELISA combined with the Euroimmun G‐ELISA or the Abcam G‐ELISA exhibited excellent sensitivity and specificity for CHIKV. The combinations demonstrated perfect and near perfect inter‐rater agreement with the PRNT, respectively, suggesting their potential to be used as alternatives to the confirmatory serological PRNT assay for CHIKV.
Diguanylate Cyclases and Phosphodiesterases Required for Basal-Level c-di-GMP in
Pseudomonas aeruginosa
as Revealed by Systematic Phylogenetic and Transcriptomic Analyses
Authors: Wei Qing , Leclercq Sebastien , Bhasme Pramod , Xu Anming , Zhu Bin , Zhang Yuhuan , Zhang Miaokun , Wang Shiwei , Ma Luyan Z.
Published: August 2019

Pseudomonas aeruginosa
is an opportunistic pathogen that can cause infections in animals, humans, and plants. The formation of biofilms by
P. aeruginosa
is the central mode of action to persist in hosts and evade immune and antibiotic attacks. Cyclic-di-GMP (c-di-GMP) is an important second messenger involved in the regulation of biofilm formation. In
P. aeruginosa
PAO1 strain, there are around 40 genes that encode enzymes for making and breaking this dinucleotide. A major missing piece of information in this field is the phylogeny and expression profile of those genes. Here, we took a systemic approach to investigate this mystery. We found that among 40 c-di-GMP metabolizing genes, 5 have well-conserved phylogenetic distribution and invariable expression profiles, suggesting that there are enzymes required for the basal level of c-di-GMP in
P. aeruginosa
. This study thus provides putative therapeutic targets against
P. aeruginosa
infections.
Violet-Blue Light Arrays at 405 Nanometers Exert Enhanced Antimicrobial Activity for Photodisinfection of Monomicrobial Nosocomial Biofilms
Authors: Halstead F. D. , Hadis M. A. , Marley N. , Brock K. , Milward M. R. , Cooper P. R. , Oppenheim B. , Palin W. M.
Published: August 2019

This study reports the efficacy of VBL and blue light (BL) and their antimicrobial activity against mature biofilms of a range of important nosocomial pathogens. While this study investigated the antibacterial activity of a range of wavelengths of between 375 and 450 nm and identified a specific wavelength region (∼405 nm) with increased antibacterial activity, decontamination was dependent on the bacterial species, strain, irradiation parameters, and experimental conditions. Further research with controlled experiments that ameliorate the heating effects and improve the optical properties are required to optimize the dosing parameters to advance the successful clinical translation of this technology.
Tyr82 Amino Acid Mutation in PB1 Polymerase Induces an Influenza Virus Mutator Phenotype
Authors: Naito Tadasuke , Shirai Kazumasa , Mori Kotaro , Muratsu Hidetaka , Ushirogawa Hiroshi , Ohniwa Ryosuke L. , Hanada Kousuke , Saito Mineki
Published: August 2019

Influenza A virus rapidly acquires antigenic changes and antiviral drug resistance, which limit the effectiveness of vaccines and drug treatments, primarily owing to its high rate of evolution. Virus populations formed by quasispecies can contain resistance mutations even before a selective pressure is applied. To study the effects of the viral mutation spectrum and quasispecies, high- and low-fidelity variants have been isolated for several RNA viruses. Here, we report the discovery of a low-fidelity RdRp variant of influenza A virus that contains a substitution at Tyr82 in PB1. Viruses containing the PB1-Y82C substitution showed growth kinetics and viral RNA synthesis levels similar to those of the wild-type virus in cell culture; however, they had significantly attenuated phenotypes in a chicken egg infection experiment. These data demonstrated that decreased RdRp fidelity attenuates influenza A virus
in vivo
, which is a desirable feature for the development of safer live attenuated vaccine candidates.
Avian Flavivirus Infection of Monocytes/Macrophages by Extensive Subversion of Host Antiviral Innate Immune Responses
Authors: Ma Yong , Liang Yumeng , Wang Nana , Cui Lu , Chen Zhijie , Wu Hanguang , Zhu Chenyang , Wang Zhitao , Liu Shengwang , Li Hai
Published: August 2019

Mosquito-borne flaviviruses include a group of pathogenic viruses that cause serious diseases in humans and animals, including dengue, West Nile, and Japanese encephalitis viruses. These flaviviruses are zoonotic and use animals, including birds, as amplifying and reservoir hosts. Avian Tembusu virus (TMUV) is an emerging mosquito-borne flavivirus that is pathogenic for many avian species and can infect cells derived from mammals and humans
in vitro
. Although not currently pathogenic for primates, the infection of duck industry workers and the potential risk of TMUV infection in immunocompromised individuals have been highlighted. Thus, the prevention of TMUV in flocks is important for both avian and mammalian health. Our study reveals the escape of TMUV from the first line of the host defense system in the arthropod-borne transmission route of arboviruses, possibly helping to extend our understanding of flavivirus infection in birds and refine the design of anti-TMUV therapeutics.
Biological Characterization of Conserved Residues within the Cytoplasmic Tail of the Pichinde Arenaviral Glycoprotein Subunit 2 (GP2)
Authors: Shao Junjie , Huang Qinfeng , Liu Xiaoying , Di Da , Dileepan Mythili , Brisse Morgan , Ly Hinh , Liang Yuying
Published: August 2019

Several arenaviruses, such as Lassa virus (LASV), can cause severe and lethal hemorrhagic fever diseases with high mortality and morbidity, for which no FDA-approved vaccines or therapeutics are available. Viral entry is mediated by the arenavirus GP complex, which consists of the stable signal peptide (SSP), the receptor-binding subunit GP1, and the transmembrane subunit GP2. The cytoplasmic tail (CT) of GP2 is highly conserved among arenaviruses, but its functional role in viral replication is not completely understood. Using a reverse genetics system of a prototypic arenavirus, Pichinde virus (PICV), we show that the GP2 CT contains certain conserved residues that are essential for virus replication, implicating it as a potentially good target for developing antivirals and live-attenuated viral vaccines against deadly arenavirus pathogens.
Strong
In Vivo
Inhibition of HIV-1 Replication by Nullbasic, a Tat Mutant
Authors: Jin Hongping , Sun Yifan , Li Dongsheng , Lin Min-Hsuan , Lor Mary , Rustanti Lina , Harrich David
Published: August 2019

HIV-1 infection is effectively controlled by antiviral therapy that inhibits virus replication and reduces viral loads below detectable levels in patients. However, therapy interruption leads to viral rebound due to latently infected cells, which serve as a source of continued viral infection. Interest in strategies leading to a functional cure for HIV-1 infection by long-term or permanent viral suppression is growing. Here, we show that a mutant form of the HIV-1 Tat protein, referred to as Nullbasic, inhibits HIV-1 transcription in infected CD4
+
cells
in vivo
. Analysis shows that stable expression of Nullbasic in CD4
+
cells could lead to durable anti-HIV-1 activity. Nullbasic, as a gene therapy candidate, could be a part of a functional-cure strategy to suppress HIV-1 transcription and replication.
Interferon-Induced Protein 44 Interacts with Cellular FK506-Binding Protein 5, Negatively Regulates Host Antiviral Responses, and Supports Virus Replication
Authors: DeDiego Marta L. , Nogales Aitor , Martinez-Sobrido Luis , Topham David J.
Published: August 2019

Innate immune responses mediated by IFN and inflammatory cytokines are critical for controlling virus replication. Nevertheless, exacerbated innate immune responses could be detrimental for the host and feedback mechanisms are needed to maintain the cellular homeostasis. In this work, we describe a completely novel function for IFI44 in negatively modulating the innate immune responses induced after viral infections. We show that decreasing IFI44 expression by using small interfering RNAs (siRNAs) or by generating knockout (KO) cells impairs virus production and increases the levels of IFN responses. Moreover, we report a novel interaction of IFI44 with the cellular protein FKBP5, which in turn interacts with kinases essential for type I and III IFN induction and signaling, such as the inhibitor of nuclear factor kappa B (IκB) kinases IKKα, IKKβ, and IKKε. Our data indicate that binding of IFI44 to FKBP5 decreased the phosphorylation of IRF-3 and IκBα mediated by IKKε and IKKβ, respectively, providing a likely explanation for the function of IFI44 in negatively modulating IFN responses. These results provide new insights into the induction of innate immune responses and suggest that IFI44 is a new potential antiviral target for reducing virus replication.
Interaction of the Ankyrin H Core Effector of
Legionella
with the Host LARP7 Component of the 7SK snRNP Complex
Authors: Von Dwingelo Juanita , Chung Ivy Yeuk Wah , Price Christopher T. , Li Lei , Jones Snake , Cygler Miroslaw , Abu Kwaik Yousef
Published: August 2019

For intracellular pathogens to thrive in host cells, an environment that supports survival and replication needs to be established.
L. pneumophila
accomplishes this through the activity of the ∼330 effector proteins that are injected into host cells during infection. Effector functions range from hijacking host trafficking pathways to altering host cell machinery, resulting in altered cell biology and innate immunity. One such pathway is the host protein synthesis pathway. Five
L. pneumophila
effectors have been identified that alter host cell translation, and 2 effectors have been identified that indirectly affect host cell transcription. No pathogenic effectors have been described that directly interfere with host cell transcription. Here we show a direct interaction of the AnkH effector with a host cell transcription complex involved in transcriptional elongation. We identify a novel process by which AnkH interferes with host transcriptional elongation through interference with formation of a functional complex and show that this interference is required for pathogen proliferation.
Molecular Dating of the Emergence of Anaerobic Rumen Fungi and the Impact of Laterally Acquired Genes
Authors: Wang Yan , Youssef Noha H. , Couger Matthew Brian , Hanafy Radwa A. , Elshahed Mostafa S. , Stajich Jason E.
Published: August 2019

Anaerobic fungi living in the rumen of herbivorous mammals possess an extraordinary ability to degrade plant biomass. We examined the origin and genomic composition of these poorly characterized anaerobic gut fungi using both transcriptome and genomic data. Phylogenomics and molecular dating analyses found remarkable concurrence of the divergence times of the rumen fungi, the forage grasses, and the dietary shift of ancestral mammals from primarily insectivory to herbivory. Comparative genomics identified unique machinery in these fungi to utilize plant polysaccharides. The rumen fungi were also identified with the ability to code for three protein domains with putative functions in plant pectin degradation and microbial defense, which were absent from all other fungal organisms (examined over 1,000 fungal genomes). Two of these domains were likely acquired from rumen gut bacteria and animal hosts separately via horizontal gene transfer. The third one is a plant-like polysaccharide lyase, representing a unique fungal enzyme with potential pectin breakdown abilities.
Cetuximab associated dermal filler reaction
Authors: Pathmanathan Shivanshan , Dzienis Marcin
Published: August 2019

A 52-year-old male patient with hyaluronic acid-based dermal fillers injected in his cheeks was diagnosed with glossotonsillary malignancy, and managed with concurrent cetuximab (epidermal growth factor receptor inhibitor) and radiation therapy. He developed significant inflammation around the dermal filler sites after first cycle of cetuximab which improved with dissolution of the dermal fillers with hyaluronidase. This suggests that cetuximab can lead to inflammation around the dermal filler sites, which can be treated with dissolution of the filler.
Pulmonary cryptococcosis complicating interstitial lung disease in a patient with systemic lupus erythematosus
Authors: Gaiba Rahul , O’Neill Edward , Lakshmi Seetha
Published: August 2019

We report a case of primary pulmonary cryptococcosis in a 59-year-old female patient with a history of systemic lupus erythematosus, interstitial lung disease and glaucoma. She presented with a cough, severe fatigue, unintentional weight loss, shortness of breath (increase in home oxygen use from baseline) and pleuritic chest pain of 2 months duration. During these 2 months, her symptoms had worsened despite multiple hospital visits, empirical antibiotics and empirical increase of her steroid dosage. Cytopathology of the bronchoalveolar lavage fluid showed yeast cells with narrow-based budding and grewCryptococcus neoformanson fungal culture. She was treated with oral fluconazole 400 mg/day for 6 months with an improvement in cough, decrease in shortness of breath (return to baseline oxygen use) and resolution of pleuritic chest pain.