bluuebunny/crossref_metadata_2025_split huggingface dataset:
An ecological study of socioeconomic predictors in detection of COVID-19 cases across neighborhoods in New York City
Authors: Whittle Richard S. , Diaz-Artiles Ana 
Published: September 2020

Abstract
Background
New York City was the first major urban center of the COVID-19 pandemic in the USA. Cases are clustered in the city, with certain neighborhoods experiencing more cases than others. We investigate whether potential socioeconomic factors can explain between-neighborhood variation in the COVID-19 test positivity rate.

Methods
Data were collected from 177 Zip Code Tabulation Areas (ZCTA) in New York City (99.9% of the population). We fit multiple Bayesian Besag-York-Mollié (BYM) mixed models using positive COVID-19 tests as the outcome, a set of 11 representative demographic, economic, and health-care associated ZCTA-level parameters as potential predictors, and the total number of COVID-19 tests as the exposure. The BYM model includes both spatial and nonspatial random effects to account for clustering and overdispersion.

Results
Multiple regression approaches indicated a consistent, statistically significant association between detected COVID-19 cases and dependent children (under 18 years old), population density, median household income, and race. In the final model, we found that an increase of only 5% in young population is associated with a 2.3% increase in COVID-19 positivity rate (95% confidence interval (CI) 0.4 to 4.2%, p=0.021). An increase of 10,000 people per km2 is associated with a 2.4% (95% CI 0.6 to 4.2%, p=0.011) increase in positivity rate. A decrease of $10,000 median household income is associated with a 1.6% (95% CI 0.7 to 2.4%, p<0.001) increase in COVID-19 positivity rate. With respect to race, a decrease of 10% in White population is associated with a 1.8% (95% CI 0.8 to 2.8%, p<0.001) increase in positivity rate, while an increase of 10% in Black population is associated with a 1.1% (95% CI 0.3 to 1.8%, p<0.001) increase in positivity rate. The percentage of Hispanic (p=0.718), Asian (p=0.966), or Other (p=0.588) populations were not statistically significant factors.

Conclusions
Our findings indicate associations between neighborhoods with a large dependent youth population, densely populated, low-income, and predominantly black neighborhoods and COVID-19 test positivity rate. The study highlights the importance of public health management during and after the current COVID-19 pandemic. Further work is warranted to fully understand the mechanisms by which these factors may have affected the positivity rate, either in terms of the true number of cases or access to testing.
Exploring the use of leucine zippers for the generation of a new class of inclusion bodies for pharma and biotechnological applications
Authors: Roca-Pinilla Ramon , Fortuna Sara , Natalello Antonino , Sánchez-Chardi Alejandro , Ami Diletta , Arís Anna , Garcia-Fruitós Elena 
Published: September 2020

Abstract
Background
Inclusion bodies (IBs) are biologically active protein aggregates forming natural nanoparticles with a high stability and a slow-release behavior. Because of their nature, IBs have been explored to be used as biocatalysts, in tissue engineering, and also for human and animal therapies. To improve the production and biological efficiency of this nanomaterial, a wide range of aggregation tags have been evaluated. However, so far, the presence in the IBs of bacterial impurities such as lipids and other proteins coexisting with the recombinant product has been poorly studied. These impurities could strongly limit the potential of IB applications, being necessary to control the composition of these bacterial nanoparticles. Thus, we have explored the use of leucine zippers as alternative tags to promote not only aggregation but also the generation of a new type of IB-like protein nanoparticles with improved physicochemical properties.

Results
Three different protein constructs, named GFP, J-GFP-F and J/F-GFP were engineered. J-GFP-F corresponded to a GFP flanked by two leucine zippers (Jun and Fos); J/F-GFP was formed coexpressing a GFP fused to Jun leucine zipper (J-GFP) and a GFP fused to a Fos leucine zipper (F-GFP); and, finally, GFP was used as a control without any tag. All of them were expressed in Escherichia coli and formed IBs, where the aggregation tendency was especially high for J/F-GFP. Moreover, those IBs formed by J-GFP-F and J/F-GFP constructs were smaller, rougher, and more amorphous than GFP ones, increasing surface/mass ratio and, therefore, surface for protein release. Although the lipid and carbohydrate content were not reduced with the addition of leucine zippers, interesting differences were observed in the protein specific activity and conformation with the addition of Jun and Fos. Moreover, J-GFP-F and J/F-GFP nanoparticles were purer than GFP IBs in terms of protein content.

Conclusions
This study proved that the use of leucine zippers strategy allows the formation of IBs with an increased aggregation ratio and protein purity, as we observed with the J/F-GFP approach, and the formation of IBs with a higher specific activity, in the case of J-GFP-F IBs. Thus, overall, the use of leucine zippers seems to be a good system for the production of IBs with more promising characteristics useful for pharma or biotech applications.
Plasmodium falciparum gametocyte-induced volatiles enhance attraction of Anopheles mosquitoes in the field
Authors: Debebe Yared , Hill Sharon Rose , Birgersson Göran , Tekie Habte , Ignell Rickard 
Published: September 2020

Abstract
Background
Plasmodium parasites manipulate the interaction between their mosquito and human hosts. Patients infected with gametocytes attract anopheline mosquitoes differentially compared to healthy individuals, an effect associated with an increased release of attractive volatile cues. This odour-driven manipulation is partly mediated by the gametocyte-specific metabolite, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), which induces increased release of select aldehydes and terpenes from red blood cells and results in the enhanced attraction of host-seeking mosquitoes, which are vectors of malaria. This study investigates the effect of the HMBPP-induced volatiles on the attraction of wild Anopheles mosquitoes to humans under field conditions.

Methods
The efficacy of the HMBPP-induced odour blend to attract Anopheles was evaluated in a 4 × 6 Latin rectangular study design indoors using baited Suna traps. Furthermore, to assess the efficacy of the HMBPP-induced odour blend in (1) augmenting the attractiveness of human odour, and (2) attracting Anopheles mosquitoes in the absence of human odour, a two-choice assay using host decoy traps (HDTs) was used and evaluated using binomial generalized regression.

Results
Traps baited with the HMBPP-induced odour blend attracted and caught both Anopheles arabiensis and Anopheles pharoensis females in a dose-dependent manner in the presence of background human odour, up to 2.5 times that of an unbaited trap. Given a choice between human odour and human odour laden with the HMBPP-induced odour blend, mosquitoes differentially preferred traps augmented with the HMBPP-induced odour blend, which caught twice as many female An. arabiensis. Traps baited with the HMBPP-induced odour blend but lacking the background of human odour were not effective in attracting and catching mosquitoes.

Conclusion
The findings of the present study revealed that the HMBPP-induced odour blend, when augmented with human body odour, is attractive to anopheline mosquitoes and could be used as a complementary vector control tool along with existing strategies.
Trends in adolescent first births in sub-Saharan Africa: a tale of increasing inequity?
Authors: Neal Sarah , Channon Andrew Amos , Chandra-Mouli Venkatraman , Madise Nyovani 
Published: September 2020

Abstract
Background
Single aggregate figures for adolescent pregnancy may fail to demonstrate particular population groups where rates are very high, or where progress has been slow. In addition, most indicators fail to separate younger from older adolescents. As there is some evidence that the disadvantages faced by adolescent mothers are greatest for those at the younger end of the spectrum, this is an important omission. This paper provides information on levels and trends of adolescent first births in 22 countries (at national and regional level) disaggregated by age (< 16 years, 16/17 years and 18/19 years), socio-economic status and place of residence. It highlights differences and similarities between countries in the characteristics of women who experience first birth during adolescence, as well as providing information on trends to identify groups where progress in reducing adolescent first births is poor.

Methodology
In this descriptive and trend analysis study we used data from 22 low- and middle-income countries from sub-Saharan Africa that have at least three Demographic and Health Surveys (DHS) since 1990, with the most recent carried out after 2005. Adolescent first births from the most recent survey are analysed by age, wealth, and residence by country and region for women aged 20–24 years at time of survey. We also calculated annual percentage rates of change (using both short- and longer-term data) for adolescent first births disaggregated by age, family wealth and residence and examined changes in concentration indices (CI).

Findings
Overall percentages of adolescent first births vary considerably between countries for all disaggregated age groups. The burden of first birth among adolescents is significant, including in the youngest age group: in some countries over 20% of women gave birth before 16 years of age (e.g. Mali and Niger). Adolescent first births are more common among women who are poorer, and live in rural areas; early adolescent first births before 16 years of age are particularly concentrated in these disadvantaged groups. Progress in reducing adolescent first births has also been particularly poor amongst these vulnerable groups, leading to increasing inequity.

Conclusions
Findings from this study show that adolescent births are concentrated among vulnerable groups where progress is often poorest. Strategies and programmes need to be developed to reduce adolescent pregnancies in marginalised young women in low- and middle-income countries.
Internal cross-linked polymeric nanoparticles with dual sensitivity for combination therapy of muscle-invasive bladder cancer
Authors: Zhu Guanchen , Wang Kaikai , Qin Haixiang , Zhao Xiaozhi , Chen Wei , Xu Linfeng , Cao Wenmin , Guo Hongqian 
Published: September 2020

Abstract
Background
Chemotherapy is a standard cancer treatment which uses anti-cancer drugs to destroy or slow the growth of cancer cells. However, chemotherapy has limited therapeutic effects in bladder cancer. One of the reasons of this resistance to chemotherapy is that higher levels of glutathione in invasive bladder cancer cells. We have fabricated nanoparticles that respond to high concentrations of glutathione and near-infrared laser irradiation in order to increase the drug accumulation at the tumor sites and combine chemotherapy with photothermal therapy to overcome the challenges of bladder cancer treatment.

Methods
The DOX&IR780@PEG-PCL-SS NPs were prepared by co-precipitation method. We investigated the tumor targeting capability of NPs in vitro and in vivo. The orthotopic bladder cancer model in C57BL/6 mice was established for in vivo study and the photothermal effects and therapeutic efficacy of NPs were evaluated.

Results
The DOX&IR780@PEG-PCL-SS NPs were synthesized using internal cross-linking strategy to increase the stability of nanoparticles. Nanoparticles can be ingested by tumor cells in a short time. The DOX&IR780@PEG-PCL-SS NPs have dual sensitivity to high levels of glutathione in bladder cancer cells and near-infrared laser irradiation. Glutathione triggers chemical structural changes of nanoparticles and preliminarily releases drugs, Near-infrared laser irradiation can promote the complete release of the drugs from the nanoparticles and induce a photothermal effect, leading to destroying the tumor cells. Given the excellent tumor-targeting ability and negligible toxicity to normal tissue, DOX&IR780@PEG-PCL-SS NPs can greatly increase the concentration of the anti-cancer drugs in tumor cells. The mice treated with DOX&IR780@PEG-PCL-SS NPs have a significant reduction in tumor volume. The DOX&IR780@PEG-PCL-SS NPs can be tracked by in vivo imaging system and have good tumor targeting ability, to facilitate our assessment during the experiment.

Conclusion
A nanoparticle delivery system with dual sensitivity to glutathione and near-infrared laser irradiation was developed for delivering IR780 and DOX. Chemo-photothermal synergistic therapy of both primary bladder cancer and their metastases was achieved using this advanced delivery system.
Establishing a reasonable price for an orphan drug
Authors: Berdud Mikel , Drummond Michael , Towse Adrian 
Published: September 2020

Abstract
Background
This paper addresses the question of what a reasonable price for an orphan drug is. The research proposes a way to adjust an established payer/HTA body incremental cost-effectiveness threshold (CET) to take account of differences in patient populations and costs of research and development in order to sustain prices that generate rates of return from investments in developing orphan drugs that are no greater than the industry average.

Methods
We investigated the cost of conducting research for orphan drugs as compared to non-orphan drugs, as well as patient population sizes targeted by orphans and non-orphans. We provided an empirical illustration based on novel drug approvals of orphan and non-orphan drugs of the FDA between 2011 and 2015 (N = 182).

Results
Using, for illustration, the NICE incremental CET (£20 K per QALY) as an anchor and adjusting by R&D costs and expected market revenue, we estimated the adjusted reasonable CET for orphan drugs to be £39.1 K per QALY at the orphan population cut-off and £78.3 K per QALY at the orphan population mid-point. For ultra-orphan drugs the adjusted CET was £937.1 K.

Conclusions
We propose one general method for establishing a reasonable price for an orphan drug, based on the proposition that rates of return for investments in developing orphan drugs should not be greater than the industry average. More research is required on data and assumptions, but with the data and assumptions we use, we find that in order to secure such a reasonable price for an orphan drug, the CET for orphans would need to be higher. This could be one approach for establishing the maximum allowable price society should be willing to pay, although decision-makers may still wish to negotiate a lower price, or refuse to pay such a premium over the value-based price in order to treat these groups of patients.
Estimating completeness of national and subnational death reporting in Brazil: application of record linkage methods
Authors: Costa Luiz Fernando Lima , de Mesquita Silva Montenegro Marli , Rabello Neto Dacio de Lyra , de Oliveira Antonio Tadeu Ribeiro , Trindade Jose Eduardo de Oliveira , Adair Tim , Marinho Maria de Fatima 
Published: September 2020

Abstract
Background
In Brazil, both the Civil Registry (CR) and Ministry of Health (MoH) Mortality Information System (SIM) are sources of routine mortality data, but neither is 100% complete. Deaths from these two sources can be linked to facilitate estimation of completeness of mortality reporting and measurement of adjusted mortality indicators using generalized linear modeling (GLM).

Methods
The 2015 and 2016 CR and SIM data were linked using deterministic methods. GLM with covariates of the deceased’s sex, age, state of residence, cause of death and place of death, and municipality-level education decile and population density decile, was used to estimate total deaths and completeness nationally, subnationally and by population sub-group, and to identify the characteristics of unreported deaths. The empirical completeness method and Global Burden of Disease (GBD) 2017 estimates were comparators at the national and state level.

Results
Completeness was 98% for SIM and 95% for CR. The vast majority of deaths in Brazil were captured by either system and 94% were reported by both sources. For each source, completeness was lowest in the north. SIM completeness was consistently high across all sub-groups while CR completeness was lowest for deaths at younger ages, outside facilities, and in the lowest deciles of municipality education and population density. There was no clear municipality-level relationship in SIM and CR completeness, suggesting minimal dependence between sources. The empirical completeness method model 1 and GBD completeness estimates were each, on average, less than three percentage points different from GLM estimates at the state level. Life expectancy was lowest in the northeast and 7.5 years higher in females than males.

Conclusions
GLM using socio-economic and demographic covariates is a valuable tool to accurately estimate completeness from linked data sources. Close scrutiny of the quality of variables used to link deaths, targeted identification of unreported deaths in poorer, northern states, and closer coordination of the two systems will help Brazil achieve 100% death reporting completeness. The results also confirm the validity of the empirical completeness method.
Alpha-1 antitrypsin deficient individuals have circulating extracellular vesicles with profibrogenic cargo
Authors: Khodayari Nazli , Oshins Regina , Holliday L. Shannon , Clark Virginia , Xiao Qiang , Marek George , Mehrad Borna , Brantly Mark 
Published: September 2020

Abstract
Background
Alpha-1 antitrypsin deficiency (AATD)-mediated liver disease is a toxic “gain-of-function” inflammation in the liver associated with intracellular retention of mutant alpha-1 antitrypsin. The clinical presentation of the disease includes fibrosis, cirrhosis and liver failure. However, the pathogenic mechanism of AATD-mediated liver disease is not well understood. Here, we investigated the role of plasma extracellular vesicles (EVs) in progression of AATD-mediated liver disease.

Methods
EVs were isolated from plasma of AATD individuals with liver disease and healthy controls. Their cytokines and miRNA content were examined by multiplex assay and small RNA sequencing. The bioactivity of EVs was assessed by qPCR, western blot analysis and immunofluorescent experiments using human hepatic stellate cells (HSCs) treated with EVs isolated from control or AATD plasma samples.

Results
We have found that AATD individuals have a distinct population of EVs with pathological cytokine and miRNA contents. When HSCs were cultured with AATD plasma derived-EVs, the expression of genes related to the development of fibrosis were significantly amplified compared to those treated with healthy control plasma EVs.

Conclusion
AATD individuals have a distinct population of EVs with abnormal cytokine and miRNA contents and the capacity to activate HSCs and mediate fibrosis. Better understanding of the components which cause liver inflammation and fibrogenesis, leading to further liver injury, has the potential to lead to the development of new treatments or preventive strategies to prevent AATD-mediated liver disease.
Socioeconomic inequalities in effectiveness of and compliance to workplace health promotion programs: an individual participant data (IPD) meta-analysis
Authors: Coenen Pieter , Robroek Suzan J. W. , van der Beek Allard J. , Boot Cécile R. L. , van Lenthe Frank J. , Burdorf Alex , Oude Hengel Karen M. 
Published: September 2020

Abstract
Background
This individual patient data (IPD) meta-analysis aimed to investigate socioeconomic inequalities in effectiveness on healthy behavior of, and compliance to, workplace health promotion programs.

Methods
Dutch (randomized) controlled trials were identified and original IPD were retrieved and harmonized. A two-stage meta-analysis was conducted where linear mixed models were performed per study (stage 1), after which individual study effects were pooled (stage 2). All models were adjusted for baseline values of the outcomes, age and gender. Intervention effects were assessed on physical activity, diet, alcohol use, and smoking. Also, we assessed whether effects differed between participants with low and high program compliance and. All analyses were stratified by socioeconomic position.

Results
Data from 15 studies (n = 8709) were harmonized. Except for fruit intake (beta: 0·12 [95% CI 0·08 0·15]), no effects were found on health behaviors, nor did these effects differ across socioeconomic groups. Only participants with high compliance showed significant improvements in vigorous and moderate-to-vigorous physical activity, and in more fruit and less snack intake. There were no differences in compliance across socioeconomic groups.

Conclusions
Workplace health promotion programs were in general not effective. Neither effectiveness nor compliance differed across socioeconomic groups (operationalized by educational level). Even though stronger effects on health behavior were found for participations with high compliance, effects remained small. The results of the current study emphasize the need for new directions in health promotion programs to improve healthy behavior among workers, in particular for those in lower socioeconomic position.
Mass spectrometry-based analysis of formalin-fixed, paraffin-embedded distal cholangiocarcinoma identifies stromal thrombospondin-2 as a potential prognostic marker
Authors: Byrling Johannes , Kristl Theresa , Hu Dingyuan , Pla Indira , Sanchez Aniel , Sasor Agata , Andersson Roland , Marko-Varga György , Andersson Bodil 
Published: September 2020

Abstract
Background
Distal cholangiocarcinoma is an aggressive malignancy with a dismal prognosis. Diagnostic and prognostic biomarkers for distal cholangiocarcinoma are lacking. The aim of the present study was to identify differentially expressed proteins between distal cholangiocarcinoma and normal bile duct samples.

Methods
A workflow utilizing discovery mass spectrometry and verification by parallel reaction monitoring was used to analyze surgically resected formalin-fixed, paraffin-embedded samples from distal cholangiocarcinoma patients and normal bile duct samples. Bioinformatic analysis was used for functional annotation and pathway analysis. Immunohistochemistry was performed to validate the expression of thrombospondin-2 and investigate its association with survival.

Results
In the discovery study, a total of 3057 proteins were identified. Eighty-seven proteins were found to be differentially expressed (q < 0.05 and fold change ≥ 2 or ≤ 0.5); 31 proteins were upregulated and 56 were downregulated in the distal cholangiocarcinoma samples compared to controls. Bioinformatic analysis revealed an abundance of differentially expressed proteins associated with the tumor reactive stroma. Parallel reaction monitoring verified 28 proteins as upregulated and 18 as downregulated in distal cholangiocarcinoma samples compared to controls. Immunohistochemical validation revealed thrombospondin-2 to be upregulated in distal cholangiocarcinoma epithelial and stromal compartments. In paired lymph node metastases samples, thrombospondin-2 expression was significantly lower; however, stromal thrombospondin-2 expression was still frequent (72%). Stromal thrombospondin-2 was an independent predictor of poor disease-free survival (HR 3.95, 95% CI 1.09–14.3; P = 0.037).

Conclusion
Several proteins without prior association with distal cholangiocarcinoma biology were identified and verified as differentially expressed between distal cholangiocarcinoma and normal bile duct samples. These proteins can be further evaluated to elucidate their biomarker potential and role in distal cholangiocarcinoma carcinogenesis. Stromal thrombospondin-2 is a potential prognostic marker in distal cholangiocarcinoma.