bluuebunny/crossref_metadata_2025_split huggingface dataset:
Search and Characterization of ITM2A as a New Potential Target for Brain Delivery
Authors: Cegarra Céline , Chaves Catarina , Déon Catherine , Do Tuan Minh , Dumas Bruno , Frenzel André , Kuhn Philip , Roudieres Valérie , Guillemot Jean-Claude , Lesuisse Dominique 
Published: December 2021

Abstract
Background

Integral membrane protein 2A (ITM2A) is a transmembrane protein whose function is not well described. This target was identified as highly enriched in human brain vs peripheral endothelial cells by transcriptomic and proteomic studies during the European Collaboration on the Optimization of Macromolecular Pharmaceutical Innovative Medicines Initiative (COMPACT IMI) consortium. The object of the present paper is to report the work we have undertaken to characterize this protein as a potential brain delivery target.
Methods

A series of ITM2A constructs, cell lines and specific anti-human and mouse ITM2A antibodies were generated. Binding and internalization in Human Embryonic Kidney 293 (HEK293) cells overexpressing ITM2A and in brain microvascular endothelial cells from mouse and non-human primate (NHP) were performed with these tools. The best antibody was evaluated in an in vitro human blood brain barrier (BBB) model and in a mouse in vivo pharmacokinetic study to validate blood brain barrier crossing.
Results

Antibodies specifically recognizing extracellular parts of ITM2A or tags inserted in its extracellular domain showed selective binding and uptake in ITM2A-expressing cells. However, despite high RNA expression in mouse and human microvessels, this protein, is rapidly downregulated upon endothelial cells culture, probably explaining why transcytosis could not be evidenced in vitro. An attempt to directly demonstrate in vivo transcytosis in mice turned out unconvincing, using a cross reactive anti ITM2A antibody on one hand and in vivo phage panning of an anti ITM2A phage library on the other hand.
Conclusions

The present article describes the work we have undertaken to explore the potential of ITM2A as target to mediate transcytosis through BBB. This work highlights the multiple challenges linked to the identification of new brain delivery targets.
A New Strategy for Specific Qualities of Waxy Rice Breeding by Analyzing Physicochemical Properties Between Five Waxy Mutants and Corresponding Their Wild Types
Authors: Fu Yuhao , Luo Tingting , Zhu Zizhong , Liu Yiping , Liu Xu , Zhang Baoli , Liu Rui , Zhu Jun 
Published: December 2021

Abstract
Waxy rice is an essential mutant type of rice, which quality is controlled by amylopectin fine structure and apparent amylose content (AAC). The influence of amylopectin structure and AAC on quality and the waxy rice can be obtained by editing the Waxy (Wx) gene have been elucidated. However, the quality of waxy rice cannot be predicted before breeding, especially how to determine the quality of waxy (wx) mutants by wild types (WT) quality remains unclear. Herein, the quality of waxy rice has been successfully predicted through analyzing the association in physicochemical properties before and after Wx gene knockout. We demonstrated that the higher amylose WT would obtain higher amylose wx mutants, and wx mutants were endowed gelatinization temperature, amylopectin chain ratio and agronomic traits similar to WT. These data indicate that the quality of wild varieties played a decisive role in waxy rice breeding. Overall, we provide a new strategy for the specific quality breeding of waxy rice, which can get waxy rice of prescribed quality and contribute to expanding the particular type of waxy rice germplasm resources.
Dissecting the Single-Cell Transcriptome Network in Superficial/Deep Tumor Tissues of Diffuse Gastric Cancer
Authors: Ren Yili , Zhang Beibei , Xu Chenkai , Zhang Lei 
Published: December 2021

Abstract
Background and purpose: Gastric cancer is a type of highly heterogeneous malignant tumor and the prognosis of gastric cancer is hard to be improved due to limited knowledge on the molecular mechanism of heterogeneity. Single-cell sequencing technology is recently widely used for the investigation of both inter-tumoral heterogeneity and intra-tumoral heterogeneity. The present study aims to explore the potential oncogene by analyzing the single-cell data in the GSE167297 dataset.Methods: The GSE167297 dataset was downloaded from the GEO database, followed by quality control to remove data with lower quality. The division on cell subtypes was determined by the characteristic marker expressed in each cell subpopulation. Wilcoxon rank-sum test was used to screen out differentially expressed genes. Survival analysis was performed to evaluate the prognostic value of G-protein subunit g 11 (GNG11) gene which was significantly overexpressed in deep tumor tissues of diffuse gastric cancer.Results: In both normal tissues and tumor tissues, subtypes of immune cells and stromal cells were identified, with a higher proportion of infiltrated macrophages observed in deep tumor tissues. EPCAM was found significantly highly expressed in a cell subpopulation from gastric tumor tissues. 515 differentially expressed genes (| log2FC | > 2 and FDR < 1e-5) were screened out between normal tissues and tumor tissues. 86 differentially expressed genes (| log2FC | > 1 and FDR < 0.01) were screened out between superficial and deep tumor tissues, in which GNG11 was most highly expressed in deep tumor tissues (mean expression value: 0.1247, FC value: 52.2109). Disease-specific survival analysis on GNG11 results showed that the HR [95%CI] in the constructed univariate Cox proportional risk model was 4.419 [1.399-13.96] and the P-value in the log-rank test was 0.0056.Conclusion: Differentially expression profiles were provided both extratumorally and intratumorally, indicating a higher infiltration of macrophages in deep tumor tissues. Additionally,GNG11 was screened out to be a significant risk factor in STAD patients.
Association Between Maternal Weight Gain in Different Periods of Pregnancy and the Risk of Venous Thromboembolism: A Retrospective Matched Case-Control Study
Authors: Wu Yuelin , Pei Jindan , Dong Lingling , Zhou Zheying , Zhou Tianfan , Zhao Xiaobo , Che Ronghua , Han Zhimin , Hua Xiaolin 
Published: December 2021

Abstract
Background Although the rate of maternal mortality has declined over the past few decades, pulmonary embolus (PE) remains an important cause of maternal deaths. Little is known about the associations of specific periods of gestational weight gain with detailed PE and deep venous thrombosis (DVT). We explored the incidence of pregnancy-related venous thromboembolism (VTE) in China and assessed the associations of maternal weight gain in different periods of pregnancy with VTE.Methods In a retrospective case-control study conducted in in Shanghai First Maternity and Infant Hospital from January 1st, 2017 to July 31th, 2021, 151 cases (11.7 per 10000) of venous thromboembolism (VTE) within pregnancy or the first 6 postnatal weeks were identified. 302 controls without VTE who gave birth at the same time as the cases were selected. Maternal pre-pregnancy weight, weight in early, mid and late pregnancy and other maternal pregnancy and newborn characteristics were obtained. GWG was standardized into gestational age-specific z-scores stratified by body mass index (BMI) and categorized as low (z score <-1), normal (-1 to 1), and high (>1). The adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated through log-binomial regression models. Interaction effects between gestational weight gain (GWG) and some other adjustment factors were tested, further stratified analyses were performed separately where interaction terms were significant. Results There were 65.6% (99 of 151) of pulmonary embolus (PE) alone and 34.4% (52 of 151) of deep venous thrombosis (DVT) alone or combined with PE. For all pre-pregnancy BMI categories (underweight, normal weight, overweight and obese), there was no statistical association between maternal weight gain of all gestational intervals and DVT or all VTE in this study. However, for PE, there was observed protective effects of low weight gain (aOR 0.79; 95% CI 0.37–1.68) and significantly increased risks of high weight gain (aOR=1.47; 95% CI: 1.03-2.09) among normal-weight women in early pregnancy. Similarly, a tendency towards decreased risk at lower weight gain throughout pregnancy (aOR 0.79; 95% CI 0.37–1.68) and significantly increased risk at higher values (aOR=1.52; 95% CI: 1.01-2.31) for PE was observed in normal-weight women. As for underweight and overweight women, results from the categorical model for early, late or total pregnancy weight gain indicated an increased risk in PE at both low and high weight gain, but confidence intervals were wide.Conclusion Chinese women have a higher risk of PE than the foreigner counterparts. Maternal weight gain in total or early pregnancy is an important risk factor for PE. In order to effectively improve maternal and child outcomes, intensive weight management that continues through pregnancy may be indispensable.
Does Latent Tuberculosis Lead to a Spurious Correlation between BCG and COVID-19 Mortality?
Authors: Raham Tareef Fadhil 
Published: December 2021

Abstract
Background: Many factors have been suggested to confound coronavirus disease 2019 (COVID-19) studies, and BCG studies have been criticized for not adjusting for many confounders. We conducted this study to analyze the presumed effectiveness of the Bacillus Calmette–Guérin (BCG) vaccine in decreasing the COVID-19 mortality rate, and to answer the question of whether this is confounded by latent tuberculosis (LTB) prevalence.Materials and methods: We chose sixty-nine malaria-free countries with different BCG vaccination policies. TB prevalence was considered as a proxy for LTB. The BCG, TB prevalence, and COVID-19 mortality data are publically available. Contingency coefficients (C.C.) and a ROC analysis were used to assess the relationship between TB prevalence and BCG status, and identify cutoff points in each BCG group category. A stem–leaf plot was also used to explore the data’s apparent behavior concerning COVID-19 in relation to the BCG groups.Results: TB prevalence was significantly associated with BCG status. The BCG vaccination status apparently had a relationship with BCG status.Conclusions: TB is suggested to have a confounding effect on BCG results, leading to a spurious correlation between BCG and COVID-19 mortality.
Delayed Tuberculosis Diagnosis in a Low Incidence Country and its Effect on Cost of Care
Authors: O'Connell James , Reidy Niamh , McNally Cora , Stanistreet Debbi , de Barra Eoghan , McConkey Samuel 
Published: December 2021

Abstract
Background

Tuberculosis elimination (TB) is a global priority that requires high-quality timely care to be achieved. In low TB incidence countries such as Ireland, delayed diagnosis is common. Despite cost being central to policy making, it is not known if delayed care affects care cost among TB patients in a low-incidence setting.
Methods

Health care records of patients with signs and symptoms of TB evaluated by a tertiary service in Ireland between July 1st 2018 and December 31st 2019 were reviewed to measure and determine predictors of patient-related delays, health care-provider related delay and the cost of TB care. Benchmarks against which the outcomes were compared were derived from the literature.
Results

Thirty-seven patients were diagnosed with TB and 51% (19/37) had pulmonary TB (PTB). The median patient-related delay was 60 days among those with PTB, greater than the benchmark derived from the literature (38 days). The median health care provider-related delay among patients with PTB was 16 days and, although similar to the benchmark (median 22 days, minimum 11 days, maximum 36 days) could be improved. The health care-provider related delay among patients with EPTB was 66 days, greater than the benchmark (42 days). The cost of care was €8298, and while similar to that reported in the literature (median €9,319, minimum €6,486, maximum €14,750) could be improved. Patient-related delay among those with PTB predicted care costs.
Conclusion

Patient-related and health care-related delays in TB diagnosis in Ireland must be reduced. Initiatives to do so should be resourced.
Tracking Recent DDT Contamination in a Northern New England Watershed
Authors: May Amanda , Doner Lisa , Duncan Jeremiah , Hill Stephen 
Published: December 2021

Abstract
Research on declines in loon populations at Squam Lake, New Hampshire, U.S.A., point to multiple potential causes since 2005, including dichlorodiphenyltrichloroethane (DDT). This study narrows down sources of DDT in a small sub-watershed by focusing mainly on collecting and analyzing soil and sediment samples, achieving rapid source area determination of DDT. We find presence of p,p’ isomers of DDT and DDE in the Bennett Brook sub-watershed arising from long-term soil and sediment storage of applications 60 years ago, plus a concentrated and current source area at a former barn. Highest concentrations, 723 μg/kg p,p’-DDT and 721 μg/kg p,p’-DDE, occur in the soils adjacent to the barn’s foundation remnants. DDT exceeds that of the metabolite, DDE, in many soils around Bennett Brook, including but not limited to the barn site. In soils where DDT>DDE, we infer mechanisms that delayed breakdown of DDT over the last 60 years. A Pb-210 dated lake sediment core, collected near the outlet of Bennet Brook, shows continuous accumulation of p,p’-DDE and p,p-DDD after 1951. These residuals likely derived from multiple sources within the sub-watershed, including orchard soils, the barn site, and from mobilized sediment deposits following extreme floods in the watershed. Although the DDT residues fall below mandatory soil remediation levels for the State of New Hampshire, Bennett Brook sediments exceed sediment quality guidelines for protection of aquatic life. Crayfish collected in Bennett Brook have significantly higher concentrations of p,p’-DDE than crayfish collected elsewhere in Squam Lake.
Multimodal Optimization with the Local Optimum Ranking 2 Algorithm
Authors: Duarte Francisco Daniel Filip 
Published: December 2021

Abstract
In optimization tasks, it is interesting to achieve a set of efficient solutions instead of one single output, in the case the best solution is not suitable. Many niching methods offer a diversified response, yet some important problems are common: (1) The most interesting solutions of each local optimum are not identified. Thus, the output is the overall population of solutions, which increases the work of the designer in verifying which solution is the most interesting. (2) Existing niching algorithms tend to distribute the solutions on the most promising regions, over-populating some local optima and sub-populating others, which leads to poor optimization.To solve these challenges, a novel niching method is presented, named local optimum ranking 2 (LOR2). This sorting methodology favors the exploration of a defined number of local optima and ranks each local population by objective value within each local optimum. Thus, is performed a multi-focus exploration, with an equalized number of solutions on each local optimum, while identifying which solutions are the local apices. To exemplify its application, the LOR2 algorithm is applied in the design optimization of a metallic cantilever beam. It achieves a set of efficient and diverse design configurations, offering both performance and diversity for structural design challenges.In addition, a second experiment describes how the algorithm can be applied to segment the domain of any function, into a mesh of similar sized or custom-sized elements. Thus, it can significantly simplify metamodels and reduce their computation time.
Water quality impacts of young green roofs in a tropical city: a case study from Singapore
Authors: Lim H. S. , Segovia E. , Ziegler A. D. 
Published: December 2021

Abstract
This study examined the effects of two substrates (SOIL and COMMERCIAL) and grass on the green roof runoff quality in Singapore. Ten events were sampled over a 9-month period. Rainfall and green roof runoff from grass and bare experimental configurations were tested for total organic carbon (TOC), nitrogen and phosphorus nutrients (NO3−-N and PO43−-P), cations/anions and trace metals (Fe, Cu, Zn, Cd and Pb). All configuration units neutralised acid rainfall and removed metals except Fe despite their proximity to an industrial area. Concentrations decrease over the monitoring period for most water quality variables. The COMMERCIAL (COM) configurations elevated Cl− (3.8–10.8 ppm), SO42− (1.5–32.4 ppm), NO3−-N (7.8–75.6 ppm) and NH4+-N (22.0–53.1 ppm) concentrations in the runoff. Concentrations of NO3−-N (4.5–67.7 ppm) and NH4+-N (14.7–53.0 ppm) remained high at the end of the monitoring period for the COMgrass configuration, even with dilution from monsoon rainfall, making it suitable as an irrigation water source and a fertiliser substitute. The SOIL substrate retained N-nutrients, TOC and trace metals with concentrations comparable or below rainfall inputs. This substrate is suitable for widespread green roof applications in Singapore and other tropical cities. We recommend substrate testing before their approval for use on green roofs and encourage the long-term monitoring of these systems.
Prediction of flood quantiles at ungauged catchments for the contiguous USA using Artificial Neural Networks
Authors: Filipova Valeriya , Hammond Anthony , Leedal David , Lamb Rob 
Published: December 2021

Abstract
In this study, we utilise Artificial Neural Network (ANN) models to estimate the 100- and 1500-year return levels for around 900,000 ungauged catchments in the contiguous USA. The models were trained and validated using 4,079 gauges and several selected catchment descriptors out of a total of 25 available. The study area was split into 15 regions, which represent major watersheds. ANN models were developed for each region and evaluated by calculating several performance metrics such as root-mean-squared error (RMSE), coefficient of determination (R2) and absolute percent error. The availability of a large dataset of gauges made it possible to test different model architectures and assess the regional performance of the models. The results indicate that ANN models with only one hidden layer are sufficient to describe the relationship between flood quantiles and catchment descriptors. The regional performance depends on climate type as models perform worse in arid and humid continental climates. Overall, the study suggests that ANN models are particularly applicable for predicting ungauged flood quantiles across a large geographic area. The paper presents recommendations about future application of ANN in regional flood frequency analysis.
Removal of antibiotic resistance genes in secondary effluent by slow filtration-NF process
Authors: Sun Lihua , Ma Yao , Ding Yu , Mei Xiaoyu , Liu Yehui , Feng Cuimin 
Published: December 2021

Abstract
In this study, the combined process of slow filtration and low pressure nanofiltration (NF) has been used to deeply remove the antibiotic resistance genes (ARGs) in a secondary effluent, and the mechanism of ARGs removal has been subsequently explored. It is observed that the optimal filtration rate for the slow filtration without biofilm, slow filtration with the aerobic heterotrophic biofilm, slow filtration with the nitrification biofilm and slow filtration with the denitrification biofilm to remove tet A, tet W, sul I, sul II and DOC is 20 cm/h, and the slow filtration with the aerobic heterotrophic biofilm exhibits the highest removal amount. The slow filtration with biofilms removes a high extent of free ARGs. As compared with the direct NF of the secondary effluent and the slow filtration without biofilm-NF, the slow filtration with the aerobic heterotrophic biofilm-NF combined process exhibits the best ARGs removal effect. The microbial population structure and the high filtration rate in the aerobic heterotrophic biofilm promote the removal of ARGs. Strengthening the removal of 16S rDNA, intI 1 and DOC can improve the ARGs removal effect of the combined process. Overall, the slow filtration-NF combined process is a better process for removing ARGs.
CIDADANIA E O DIREITO À EDUCAÇÃO: UM ESTUDO A PARTIR DO PROCESSO PARTICIPATIVO DA CONFERÊNCIA DE DIREITOS HUMANOS
Authors: Fernandes Rômulo Magalhães , De Oliveira Azevedo Anna Carolina 
Published: December 2021

Este artigo tem como objetivo principal refletir sobre as propostas debatidas na IV Conferência Estadual de Direitos Humanos do Estado de Minas Gerais (2015) que estabeleçam relação entre o direito à educação e a cidadania, além de tecer considerações sobre como esse processo participativo pode incidir na formulação de políticas públicas sobre o direito à educação, no sentido amplo e múltiplo desse termo. Para tanto, adota-se como marco teórico os autores Leonardo Avritzer (2016) e Miguel G. Arroyo (2007), na medida em que ajudam a esclarecer os impasses da democracia diante do projeto de participação social historicamente construído no Brasil. Por último, a partir de uma metodologia qualitativa e documental, conclui-se pela importância dos mecanismos de participação e dos processos de constituição e de formação do povo como sujeito político na reivindicação de seus direitos e no avanço da democracia no Brasil.
A VINCULAÇÃO DO PROGRAMA DE METAS ELEITORAL AO CUMPRIMENTO DO PRINCÍPIO EFICIÊNCIA ADMINISTRATIVA E A CONSEQUÊNCIA DE SUA INOBSERVÂNCIA:
Authors: Serrano Antonio Carlos Alves Pinto 
Published: December 2021

O presente artigo tem por finalidade analisar o princípio da eficiência e da moralidade administrativa e sua aplicação na Administração Pública sob a vinculação do programa do governo apresentado durante as campanhas eleitorais e convertidos em programas de metas para a Administração Pública. Com destaque para o fundamento desta vinculação legal, seus meios de controle – interno e externo – e a consequência oriunda de seu descumprimento.
Palavras-chave: Princípio da Eficiência; Princípio da Moralidade; Administração Pública; Plano de Governo; Programa de Metas.
Soybean β-Conglycinin: Structure Characteristic, Allergenicity, Plasma
Lipid-Controlling, Prevention of Obesity and Non-alcoholic Fatty Liver
Disease
Authors: Shan Dandan , Yu Hansong , Lyu Bo , Fu Hongling 
Published: December 2021

:
Soybean has become an important world commodity because of its low price, good nutritional
value and recognized functional health benefits in recent years. β-conglycinin is one of the
major storage proteins in soybean. It has captured a growing interest recently because of its allergenicity
and potential health benefits, which continues to drive the research and commercial development
of β-conglycinin-based food products and ingredients. In this review, the structure, the amino
acid composition, extraction methods and electrophoretic pattern of β-conglycinin are briefly
summarized. Studies on β-conglycinin by allergenicity, plasma lipid-controlling, obesity and nonalcoholic
fatty liver disease are highlighted, critically discussing their main shortcomings and challenges
and identifying the research gaps. Studies to date have demonstrated the cultivation of β-conglycinin
with health benefits as functional ingredients and foodstuffs. The current research focuses
on proteins, mainly challenging the mechanisms of subunit/peptide effects interaction and identifying
and characterizing the hidden biological activities in the polypeptide chains. There is much
scope for further exploration into various aspects of β-conglycinin, such as the selection of mutant
strains and genetic engineering and prospects on targeted β-conglycinin exploitation in the nutraceutical
area. In addition, the safety evaluation of β-conglycinin and its stabilized emulsions deserve
more attention to food-related applications.