bluuebunny/crossref_metadata_2025_split huggingface dataset:
Going beyond the mean: economic benefits of myocardial infarction secondary prevention
Authors: von Wyl Viktor , Ulyte Agne , Wei Wenjia , Radovanovic Dragana , Grübner Oliver , Brüngger Beat , Bähler Caroline , Blozik Eva , Dressel Holger , Schwenkglenks Matthias 
Published: December 2020

AbstractBackgroundUsing the example of secondary prophylaxis of myocardial infarction (MI), our aim was to establish a framework for assessing cost consequences of compliance with clinical guidelines; thereby taking cost trajectories and cost distributions into account.MethodsSwiss mandatory health insurance claims from 1840 persons with hospitalization for MI in 2014 were analysed. Included persons were predominantly male (74%), had a median age of 73 years, and 71% were pre-exposed to drugs for secondary prophylaxis, prior to index hospitalization. Guideline compliance was defined as being prescribed recommended 4-class drug prophylaxis including drugs from the following four classes: beta-blockers, statins, aspirin or P2Y12inhibitors, and angiotension-converting enzyme inhibitors or angiotensin receptor blockers. Health care expenditures (HCE) accrued over 1 year after index hospitalization were compared by compliance status using two-part regression, trajectory analysis, and counterfactual decomposition analysis.ResultsOnly 32% of persons received recommended 4-class prophylaxis. Compliant persons had lower HCE (− 4865 Swiss Francs [95% confidence interval − 8027; − 1703]) and were more likely to belong to the most favorable HCE trajectory (with 6245 Swiss Francs average annual HCE and comprising 78% of all studied persons). Distributional analyses showed that compliance-associated HCE reductions were more pronounced among persons with HCE above the median.ConclusionsCompliance with recommended prophylaxis was robustly associated with lower HCE and more favorable cost trajectories, but mainly among persons with high health care expenditures. The analysis framework is easily transferrable to other diseases and provides more comprehensive information on HCE consequences of non-compliance than mean-based regressions alone.
Layered double hydroxide nanoparticles as an adjuvant for inactivated foot-and-mouth disease vaccine in pigs
Authors: Wu Peng , Zhang Yunfeng , Yin Xinyue , He Yanhua , Zhang Qian , Chen Chuangfu 
Published: December 2020

AbstractBackgroundFoot-and-mouth disease (FMD) is a highly transmissible disease that leads to vast economic losses in many countries. Prevention using inactivated vaccines is one effective measure used to control FMD. Unfortunately, inactivated FMD vaccines provide only short-term protection and require a cold-chain system. In recent years, many studies have shown that layered double metal hydroxides (LDHs) carrying antigens can be used to strongly induce immune responses. In this study, LDH nanoparticles (NPs) were prepared by hydrothermal synthesis. LDH particle size, electric potential, and morphology were measured and observed. The adsorption capacity of LDH NPs to FMDV was tested. The effects of LDH as an adjuvant on inactivated FMDV vaccines were further evaluated and compared with commercial FMDV Montanide ISA-206 in BALB/C female mice and Yorkshire pigs.ResultsLDH NPs were successfully prepared with a uniform particle size of ~ 87.21 nm, regular edges, a loose hexagonal shape and positive zeta charge of 32 mV. The maximum absorption concentration was 0.16–0.31 μg FMDV/μg LDH. In the mouse experiment, antibody levels in group LDH + FMDV were significantly higher compared to group saline + FMDV (P < 0.01) from days 42–98 and were significantly higher to group ISA-206 + FMDV on day 56 post-immunization (P < 0.05). After day 14 post-immunization, IFN-γ content was significantly increased (P < 0.05). In the pig experiment, antibody levels in both the ISA-206 + FMDV and LDH + FMDV were positive and were significantly higher compared with the PBS group on day 7 (P < 0.005). Antibody levels in 90% pigs were positive on day 56 in the LDH group. The neutralizing antibody levels in the LDH and ISA-206 groups were significantly higher from days 7–28 compared to the PBS control group (P < 0.05). Thus, LDH NPs were effective at inducing an immune response against FMDV.ConclusionsLDHs with a loose hexagonal shape and a positive charge were prepared and evaluated as adjuvant for FMD vaccine. It was demonstrated that LDHs can induce immune responses in mice and pigs. In addition, the LDHs produced antibodies continuously which may indicate a slow-release effect. The study shows that LDHs may act as a potentially useful FMDV adjuvant.
Peritumoral plasmacytoid dendritic cells predict a poor prognosis for intrahepatic cholangiocarcinoma after curative resection
Authors: Hu Zhi-Qiang , Zhou Zheng-Jun , Luo Chu-Bin , Xin Hao-Yang , Li Jia , Yu Song-Yang , Zhou Shao-Lai 
Published: December 2020

Abstract
Background
Plasmacytoid dendritic cells (pDCs) are present in various primary and metastatic human neoplasms; however, their clinical significance in intrahepatic cholangiocarcinoma is not clear.

Methods
To evaluate pDCs’ distributions in and around tumors as well as their potential function and predictive value for prognosis in patients undergoing curative resection, we performed immunohistochemistry to examine the expression of pDC marker BDCA2, and CD3, CD4, CD8 and Foxp3 in intratumoral and peritumoral tissues from 359 patients with intrahepatic cholangiocarcinoma and compared with prognostic and clinicopathologic factors.

Results
Results showed that patients with high numbers of BDCA2+ pDCs in peritumoral tissues were more likely to have elevated levels of carbohydrate antigen 19-9 and gamma-glutamyl transferase, larger and more tumors, advanced tumor-node-metastasis staging, more vascular/bile duct invasion, and lymphatic metastasis in association with greater chance of recurrence and shorter overall survival. Peritumoral tissues with larger numbers of pDCs also showed increased Foxp3+ regulatory T cell infiltration, both of which were found to be independent factors for predicting time to recurrence and overall survival. By contrast, patient outcomes were not associated with the presence of intratumoral pDCs.

Conclusions
Peritumoral pDC infiltration may indicate an immune tolerogenic peritumor microenvironment and can be used to predict a poor prognosis for patients undergoing curative resection for intrahepatic cholangiocarcinoma.
Molecular surveillance of the Plasmodium vivax multidrug resistance 1 gene in Peru between 2006 and 2015
Authors: Villena Fredy E. , Maguiña Jorge L. , Santolalla Meddly L. , Pozo Edwar , Salas Carola J. , Ampuero Julia S. , Lescano Andres G. , Bishop Danett K. , Valdivia Hugo O. 
Published: December 2020

Abstract
Background
The high incidence of Plasmodium vivax infections associated with clinical severity and the emergence of chloroquine (CQ) resistance has posed a challenge to control efforts aimed at eliminating this disease. Despite conflicting evidence regarding the role of mutations of P. vivax multidrug resistance 1 gene (pvmdr1) in drug resistance, this gene can be a tool for molecular surveillance due to its variability and spatial patterns.

Methods
Blood samples were collected from studies conducted between 2006 and 2015 in the Northern and Southern Amazon Basin and the North Coast of Peru. Thick and thin blood smears were prepared for malaria diagnosis by microscopy and PCR was performed for detection of P. vivax monoinfections. The pvmdr1 gene was subsequently sequenced and the genetic data was used for haplotype and diversity analysis.

Results
A total of 550 positive P. vivax samples were sequenced; 445 from the Northern Amazon Basin, 48 from the Southern Amazon Basin and 57 from the North Coast. Eight non-synonymous mutations and three synonymous mutations were analysed in 4,395 bp of pvmdr1. Amino acid changes at positions 976F and 1076L were detected in the Northern Amazon Basin (12.8%) and the Southern Amazon Basin (4.2%) with fluctuations in the prevalence of both mutations in the Northern Amazon Basin during the course of the study that seemed to correspond with a malaria control programme implemented in the region. A total of 13 pvmdr1 haplotypes with non-synonymous mutations were estimated in Peru and an overall nucleotide diversity of π = 0.00054. The Northern Amazon Basin was the most diverse region (π = 0.00055) followed by the Southern Amazon and the North Coast (π = 0.00035 and π = 0.00014, respectively).

Conclusion
This study showed a high variability in the frequencies of the 976F and 1076L polymorphisms in the Northern Amazon Basin between 2006 and 2015. The low and heterogeneous diversity of pvmdr1 found in this study underscores the need for additional research that can elucidate the role of this gene on P. vivax drug resistance as well as in vitro and clinical data that can clarify the extend of CQ resistance in Peru.
Integrin alpha-2 and beta-1 expression increases through multiple generations of the EDW01 patient-derived xenograft model of breast cancer—insight into their role in epithelial mesenchymal transition in vivo gained from an in vitro model system
Authors: Wafai Razan , Williams Elizabeth D. , de Souza Emma , Simpson Peter T. , McCart Reed Amy E. , Kutasovic Jamie R. , Waltham Mark , Snell Cameron E. , Blick Tony , Thompson Erik W. , Hugo Honor J. 
Published: December 2020

AbstractBackgroundBreast cancers acquire aggressive capabilities via epithelial to mesenchymal transition (EMT), in which various integrins/integrin-linked kinase signalling are upregulated.MethodsWe investigated this in two patient-derived xenografts (PDXs) developed from breast-to-bone metastases, and its functional significance in a breast cancer cell line system. ED03 and EDW01 PDXs were grown subcutaneously in immunocompromised SCID mice through 11 passages and 7 passages, respectively. Tumour tissue was assessed using immunohistochemistry (IHC) for oestrogen receptor (ER)-alpha, E-cadherin, vimentin, Twist1, beta-catenin, P120-RasGAP, CD44, CD24 and Ki67, and RT-qPCR of EMT-related factors (CDH1,VIM,CD44,CD24), integrins beta 1 (ITGB1), alpha 2 (ITGA2) andILK. Integrin andILKexpression in epidermal growth factor (EGF)-induced EMT of the PMC42-ET breast cancer cell line was assessed by RT-qPCR and Western blotting, as were the effects of their transient knockdown via small interfering RNA +/− EGF. Cell migration, changes in cell morphology and adhesion of siRNA-transfected PMC42-ET cells to various extracellular matrix (ECM) substrates was assessed.ResultsThe ED03 (ER+/PR−/HER2−/lobular) and EDW01 (ER+/PR−/HER2−/ductal) PDXs were both classified as molecular subtype luminal A. ED03 xenografts exhibited mutated E-cadherin with minimal expression, but remained vimentin-negative across all passages. In EDW01, the hypoxic indicator gene CAIX and Twist1 were co-ordinately upregulated at passages 4–5, corresponding with a decrease in E-cadherin. At passages 6–7,VIMwas upregulated along withITGB1andITGA2, consistent with an increasing EMT. The ED03 PDX displayed minimal change over passages in mice, for all genes examined.ILK,ITGB1andITGA2mRNAs were also increased in the EGF-induced EMT of PMC42-ET cells (in whichCDH1was downregulated) although siRNA against these targets revealed that this induction was not necessary for the observed EMT. However, their knockdown significantly reduced EMT-associated adhesion and Transwell migration.ConclusionOur data suggest that despite an increase inITGA2andITGB1gene expression in the EMT exhibited by EDW01 PDX over multiple generations, this pathway may not necessarily drive the EMT process.
Response to Brinkmann et al. “Re-assembly of 19th century smallpox vaccine genomes reveals the contemporaneous use of horsepox and horsepox-related viruses in the United States”
Authors: Duggan Ana T. , Holmes Edward C. , Poinar Hendrik N. 
Published: December 2020

AbstractWe thank Brinkmann and colleagues for their correspondence and their further investigation into these American Civil War Era vaccination strains. Here, we summarize the difficulties and caveats of work with ancient DNA.
Handwashing and disinfection precautions taken by U.S. adults to prevent coronavirus disease 2019, Spring 2020
Authors: Brown Laura G. , Hoover E. Rickamer , Barrett Catherine E. , Vanden Esschert Kayla L. , Collier Sarah A. , Garcia-Williams Amanda G. 
Published: December 2020

Abstract
Objectives
The objectives of this study were to assess self-reported hygiene precautions taken by U.S. adults during spring 2020 to prevent coronavirus disease 2019 (COVID-19) and to identify demographic characteristics associated with these hygiene precautions.

Results
We obtained data from Porter Novelli Public Services’s national survey, Spring ConsumerStyles, conducted March 19–April 9, 2020 among a nationally representative random sample of 6463 U.S. adults aged 18 years or older. We present data from the survey question: “What, if any, precautions are you taking to prevent coronavirus?”. Respondents replied yes or no to the following precautions: washing hands often with soap and water and disinfecting surfaces at home and work often. Most respondents reported taking hygiene-related precautions to prevent COVID-19; more respondents reported handwashing (93%) than disinfecting surfaces (74%). Men, younger respondents, those with lower income and education levels, and respondents in self-rated poor health had lower reported rates of both handwashing and disinfecting surfaces. Communications about hygiene precautions for COVID-19 prevention may need to target sub-populations with the greatest gaps in hygiene-related practices. Research identifying barriers to these practices and developing effective messaging could inform and improve these communications.
First pediatric electronic algorithm to stratify risk of penicillin allergy
Authors: Roberts Hannah , Soller Lianne , Ng Karen , Chan Edmond S. , Roberts Ashley , Kang Kristopher , Hildebrand Kyla J. , Wong Tiffany 
Published: December 2020

AbstractBeta-lactam allergy is reported in 5–10% of children in North America, but up to 94–97% of patients are deemed not allergic after allergist assessment. The utility of standardized skin testing for penicillin allergy in the pediatric population has been recently questioned. Oral drug challenges when appropriate, are preferred over skin testing, and can definitively rule out immediate, IgE-mediated drug allergy. To our knowledge, this is the only pediatric study to assess the reliability of a penicillin allergy stratification tool using a paper and electronic clinical algorithm. By using an electronic algorithm, we identified 61 patients (of 95 deemed not allergic by gold standard allergist decision) as low risk for penicillin allergy, with no false negatives and without the need for allergist assessment or skin testing. In this study, we demonstrate that an electronic algorithm can be used by various pediatric clinicians when evaluating possible penicillin allergy to reliably identify low risk patients. We identified the electronic algorithm was superior to the paper version, capturing an even higher percentage of low risk patients than the paper version. By developing an electronic algorithm to accurately assess penicillin allergy risk based on appropriate history, without the need for diagnostic testing or allergist assessment, we can empower non-allergist health care professionals to safely de-label low risk pediatric patients and assist in alleviating subspecialty wait times for penicillin allergy assessment.
The pond snail Lymnaea stagnalis
Authors: Kuroda Reiko , Abe Masanori 
Published: December 2020

AbstractThe freshwater snail Lymnaea stagnalis has a long research history, but only relatively recently has it emerged as an attractive model organism to study molecular mechanisms in the areas of developmental biology and translational medicine such as learning/memory and neurodegenerative diseases. The species has the advantage of being a hermaphrodite and can both cross- and self-mate, which greatly facilitates genetic approaches. The establishment of body-handedness, or chiromorphogenesis, is a major topic of study, since chirality is evident in the shell coiling. Chirality is maternally inherited, and only recently a gene-editing approach identified the actin-related gene Lsdia1 as the key handedness determinant. This short article reviews the natural habitat, life cycle, major research questions and interests, and experimental approaches.
Regenerative capacity of the corneal transition zone for endothelial cell therapy
Authors: Sie Nicole Ming , Yam Gary Hin-Fai , Soh Yu Qiang , Lovatt Matthew , Dhaliwal Deepinder , Kocaba Viridiana , Mehta Jodhbir S. 
Published: December 2020

AbstractThe corneal endothelium located on the posterior corneal surface is responsible for regulating stromal hydration. This is contributed by a monolayer of corneal endothelial cells (CECs), which are metabolically active in a continuous fluid-coupled efflux of ions from the corneal stroma into the aqueous humor, preventing stromal over-hydration and preserving the orderly arrangement of stromal collagen fibrils, which is essential for corneal transparency. Mature CECs do not have regenerative capacity and cell loss due to aging and diseases results in irreversible stromal edema and a loss of corneal clarity. The current gold standard of treatment for this worldwide blindness caused by corneal endothelial failure is the corneal transplantation using cadaveric donor corneas. The top indication is Fuchs corneal endothelial dystrophy/degeneration, which represents 39% of all corneal transplants performed. However, the global shortage of transplantable donor corneas has restricted the treatment outcomes, hence instigating a need to research for alternative therapies. One such avenue is the CEC regeneration from endothelial progenitors, which have been identified in the peripheral endothelium and the adjacent transition zone. This review examines the evidence supporting the existence of endothelial progenitors in the posterior limbus and summarizes the existing knowledge on the microanatomy of the transitional zone. We give an overview of the isolation and ex vivo propagation of human endothelial progenitors in the transition zone, and their growth and differentiation capacity to the corneal endothelium. Transplanting these bioengineered constructs into in vivo models of corneal endothelial degeneration will prove the efficacy and viability, and the long-term maintenance of functional endothelium. This will develop a novel regenerative therapy for the management of corneal endothelial diseases.
Nutrient removal and carbohydrate production potential of indigenous Scenedesmus sp. grown in anaerobically digested brewery wastewater
Authors: Yirgu Zenebe , Leta Seyoum , Hussen Ahmed , Khan Mohammed Mazharuddin 
Published: December 2020

Abstract
Background
The combination of nutrient removal using microalgae from wastewater with carbohydrate production has been considered as a promising approach for sustainable wastewater treatment and production of valuable products such as biofuels. In Ethiopia, urbanization and industrial development are not in tandem with wastewater treatment system The objective of this study was to evaluate nutrient removal and carbohydrate production potential of the indigenous microalgae Scenedesmus sp. grown in anaerobically digested brewery wastewater. The indigenous Scenedesmus sp. was grown in an anaerobically digested brewery effluent in different seasons of the year. The biomass was converted into carbohydrate using microwave, autoclave, and oven as pretreatment, followed by optimization for acid concentrations and hydrolysis time.

Result
The overall removal efficiencies for the indigenous Scenedesmus sp. based wastewater treatment system were over 99%, 92%, 63%, 65% and 75% for NH4+-N, TN, PO43− -P, TP and COD, respectively. The concentrations of final effluent quality of these parameters except for phosphorus nutrient were below the permissible discharge limit for brewery effluent standard set by Ethiopian Environmental Protection Authority. With regard to carbohydrate production, microwave-assisted acid hydrolysis with HCl produced a higher total sugar than that of autoclave and oven pretreatments. Among acid concentrations, HCl with 3 N produced a higher total sugar, which is significantly different (P < 0.05) to the other acid concentrations. The highest total sugar (233.89 mg g−1) was obtained from microalgal biomass during the 20 min hydrolysis time with 3 N HCl and 5% (w/v) biomass at 1000 watts and 1200C.

Conclusions
This study showed that there is an opportunity for using the indigenous microalgae for sustainable wastewater treatment and for carbohydrate production that uses as bioethanol source in Ethiopia.
Histopathological and microbiological study of porcine lymphadenitis: contributions to diagnosis and control of the disease
Authors: Cardoso-Toset Fernando , Gómez-Laguna Jaime , Gómez-Gascón Lidia , Rodríguez-Gómez Irene M. , Galán-Relaño Angela , Carrasco Librado , Tarradas Carmen , Vela Ana I. , Luque Inmaculada 
Published: December 2020

AbstractTuberculosis like lesions (TBL) in free-range pigs are characterised by presenting a marked heterogeneity in pathology and microbiology features, with a notorious role of Mycobacterium tuberculosis complex (MTC), Trueperella pyogenes and different Streptococcus species. However, the capacity of these microorganism to spread to different organic cavities leading to a generalised disease is unknown. Therefore, this study evaluated the organic distribution of these agents in free-range pig carcasses whole condemned due to generalised TBL.A total of 37 totally condemned animals were analysed, and samples of lymph nodes and organs were obtained (n = 262) and subjected to histopathological and microbiological examination. In addition, T. pyogenes and streptococci species were further characterised by PFGE analysis. Two different patterns were evidenced with lack or occasional lesions in superficial inguinal (SILN) and popliteal (PLN) lymph nodes and advanced lesions in submandibular (SLN) (35/36) and gastrohepatic (GHLN) (33/35) lymph nodes (stages III and IV). Early stage granulomas (stage I and II) prevailed in lungs (16/20), liver (14/31) and spleen (7/18). The microbiological analysis revealed that MTC, detected by qPCR, was present in 31 out of 37 animals and 90 (90/262) samples. In 26 out of the 31 pigs, MTC was detected from two or more organs. SLN (24/31) and GHLN (19/31) were the MTC+ organs most frequently detected, with 29 out of 31 MTC+ pigs detected as positive in one or both samples, which points out that both lymph nodes must be included in the sampling of surveillance programs. Other pathogens, such as T. pyogenes and Streptococcus spp., were also involved in generalised lymphadenitis, being frequently isolated from SLN and other organs, such as liver (T. pyogenes), tonsils or lung (Streptococcus spp.). A wide genetic diversity among streptococci was observed, showing the ubiquitous character of these pathogens, however, the isolation of a single clone of T. pyogenes from different organic locations from animals with generalised TBL was a common finding of this study, highlighting that the role of this pathogen in porcine lymphadenitis may be underestimated. These results should be considered in future studies on the pathogenesis and control of porcine lymphadenitis.