bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two Novel PDE11A Genetic Variants Increase Tau Phosphorylations in Early-onset Alzheimer's Disease
Authors: qin wei , Zhou Aihong , Zuo Xiumei , Jia Longfei , Wei Cuibai , Tang Yi , Wang Fen , Li Fangyu , Wang Qi , Li Ying , Wei Yiping , Zhao Lina , Jin Hongmei , cruchaga Carlos , Benitez Bruno A. , Jia jianping 
Published: August 2020

Abstract
Background: Alzheimer’s disease (AD) is a leading cause of dementia in the elderly and has become a major health issue. However, a large number of genetic risk factors remain undiscovered. Methods: To identify novel risk genes and better understand the molecular pathway underlying AD, whole-exome sequencing (WES) was performed in 215 early-onset AD (EOAD) patients and 55 unrelated healthy controls of Han Chinese ethnicity. Subsequent direct sequencing was performed in 4962 individuals to validate the selected rare mutations. Computational annotation and in vitro functional studies were performed to evaluate the role of candidate mutations in EOAD and the underlying mechanisms.Results: We identified two rare missense mutations in the phosphodiesterase 11A (PDE11A) gene, resulting in p.Arg202His, and p.Leu756Gln, in individuals with EOAD. Both mutations are located in evolutionarily highly conserved amino acids, are predicted to alter the protein conformation, and classified as pathogenic. Furthermore, we found significantly decreased protein levels of PDE11A in brain samples of AD patients. Expression of PDE11A variants and knockdown experiments with specific short hairpin RNA (shRNA) for PDE11A both resulted in an increase of AD-associated Tau hyperphosphorylation at T181, S404, S202, S416, S214, S396 and AT8 epitopes in vitro. PDE11A variants or PDE11A shRNA also caused increased cAMP levels, protein kinase A (PKA) activation, and cAMP response element-binding protein (CREB) phosphorylation. Additionally, pretreatment with a PKA inhibitor (H89) suppressed PDE11A mutation-induced p-Tau formation.Conclusions: Our results demonstrate that both PDE11A mutations and PDE11A knockdown increase Tau phosphorylation through the cAMP/PKA pathway, suggesting that PDE11A is a novel risk gene for AD. This study provides insight into the involvement of Tau phosphorylation via the cAMP/PKA pathway in EOAD pathogenesis and provides a potential new target for intervention.
Light-responsive self-assembly of semi-conducting nanoplatelets
Authors: ARIAS Yesica FLORES , PLAMONT Rémi , Huang He , Ryabchun Alexander , Katsonis Nathalie , fleury Benoit 
Published: August 2020

Abstract
CdSe nanoplatelets are a recently discovered class of colloidal semiconducting nanocrystals. Atomic control over their thickness allows achieving control over quantum size effects, and in particular, these platelets exhibit monochromatic light emission because of the confinement of photo-generated excitons only in their thickness. These nanoplatelets can self-organize into supra-particular polymers, depending on their environment, which means that their shape anisotropy can be expressed at the microscale. Here, the self-assembly of semiconducting nanoplatelets is controlled remotely by light, in a dynamic nanoparticulate system that integrates light-responsive molecular switches covalently. Azobenzene ligands were thus designed to (i) be grafted on the nanoplatelets (ii) ensure their colloidal stability in chloroform when confined on their surface in the E-configuration. Upon irradiation, the ligands isomerize into their Z-configuration, leading to a modification of the dipolar moment of the particles and to the formation of one-dimensional stacks. The self-assembly is reversible, as thermal relaxation of the ligands yields the initial dispersion back. This reversible hybrid system can be used in the design of responsive optical systems, as illustrated by photo-patterning experiments leading to controlled spatial resolution of the luminescence intensity in thin films.
Non-small lung cancer cells-derived exosome miR-3157-3p primes pre-metastatic niche by inducing angiogenesis and vascular permeability
Authors: Ma Zijian , Wei Ke , Yang Fengming , Guo Zizhang , Pan Chunfeng , He Yaozhou , Wang Jun , Li Zhihua , Chen Liang , Xia Yang , Chen Yijiang 
Published: August 2020

Abstract
Background: Cancer-derived exosomes are considered to be the main driving force for cancer-induced metastasis niche formation at foreign sites, but the mechanism is unclear.Methods: Identification of differentially expressed miRNAs in exosomes by miRNA sequencing. Through a series of in vitro and in vivo experiments, it was studied that the tumor-derived exosome miR-3157-3p can be taken up by the endothelium and exert biological functions. The molecular mechanism of miR-3157-3p was confirmed by Western blot, luciferase test and rescue experiment. Finally, real-time fluorescence quantitative PCR and RNA in situ hybridization were used to evaluate the clinical relevance of miR-3157-3p expression.Result: In metastatic NSCLC patients, the expression level of miR-3157-3p in circulating exosomes was significantly higher than that of non-metastatic NSCLC patients. Here, we found that miR-3157-3p can be transferred from NSCLC cells to vascular endothelial cells through exosomes. Exosome miR-3157-3p has regulated the expression of VEGF / MMP2 / MMP9 and occludin in endothelial cells by targeting TIMP / KLF2, thereby promoted angiogenesis and increased vascular permeability. In addition, exosome miR-3157-3p from NSCLC cells enhances NSCLC metastasis in mouse lungs.Conclusion: Our work indicates that exosome miR-3157-3p is involved in the formation of pre-metastatic niche and may be used as a blood-based biomarker for NSCLC metastasis.
NF-κB-Mediated lncRNA AC007271.3 as A ceRNA Promotes Carcinogenesis of Oral Squamous Cell Carcinoma by Regulating Slug
Authors: Zheng Ze-nan , Huang Guang-zhao , Wu Qing-qing , Ye Heng-yu , Zeng Wei-sen , Lv Xiao-zhi 
Published: August 2020

Abstract
Background: Oral squamous cell carcinoma (OSCC) is the most common oral cancer. Our previous studies confirmed that dysregulation function of long non-coding RNA (lncRNA) AC007271.3 was associated with a poor prognosis and overexpression of AC007271.3 promoted cell proliferation, migration, invasion and inhibited cell apoptosis in vitro, and promoted tumor growth in vivo. However, the underlying mechanisms of AC007271.3 dysregulation remained obscure.Methods: Bioinformatics databases were used to predicted the potential down-stream targeted of AC007271.3 and verified by dual luciferase reporter assay. Core promoter region of AC007271.3 was identified by luciferase activity assay and the potential transcription factor on it was verified by ChIP assay. Western blot and qRT-PCR were performed to detect the protein and messenger RNA (mRNA) levels, respectively. Animal experiments confirmed the metastatic ability in vivo.Results: AC007271.3 functioned as competing endogenous RNA (ceRNA) by binding to miR-125b-2-3p and upregulated the expression of Slug, which is a direct target of miR-125b-2-3p. AC007271.3 enhanced the expression of Slug and inhibited the expression of E-cadherin to promote the migration and invasion in OSCC cells. The expression of AC007271.3 was promoted by canonical nuclear factor-κB (NF-κB) pathway. Conclusion: Our study showed that the classical NF-κB pathway-activated AC007271.3 regulates EMT by miR-125b-2-3p / Slug / E-cadherin axis to promote the development of OSCC, implicating it as a novel potential target for therapeutic intervention in this disease.
Effect of the timing of stay-at-home orders on COVID-19 infections in the United States of America
Authors: Trivedi Megh , Das Anirudha 
Published: August 2020

Abstract
The current COVID-19 pandemic has sparked growing global interest in understanding the spread and outcome of the virus. From previous pandemics, we have learned that several demographic, geographic, and socio-economic factors may play a role in increasing risk of infection. Our objective was to examine the association of timing of mandated stay-at-home orders at the county-level with COVID-19 cases, daily case rate and mortality in the United States of America (USA). Publicly available data were used to perform a cross-sectional study of USA counties with > 100,000 population, and at least 50 confirmed cases per 100,000 people as of May 24, 2020. The three outcome variables were: total cases/100,000, daily case rate (DCR), and total deaths/100,000. Out of 3142 USA counties, 569 met the inclusion criteria. Of all variables, the timing of state-mandated stay-at-home order had the most significant effect on all three outcomes after adjusting for multiple socio-demographic, geographic and health related factors. Additional factors with significant association with increased cases and deaths include population density, housing problem, unemployment, African American race, and age > 65. Policymakers at the local level must take this into consideration while planning for interventions to prevent the spread of COVID-19.
Measuring PrEP Preferences Among At-Risk Military&nbsp;Populations: Results of an&nbsp;Adaptive Choice Based Conjoint Analysis Study
Authors: Gutierrez Jose I , Dubov Alex , Altice Frederick , Vlahov David 
Published: August 2020

Abstract
BACKGROUNDPre-exposure prophylaxis (PrEP) effectively prevents HIV infection, yet its uptake remains low among U.S. military men who have sex with men (MSM). Research shows that health services matching preferences produce favorable outcomes. Therefore, an early step for planning program design is to characterize and identify preferences for improved PrEP delivery within this population. METHODSHIV-negative military MSM were recruited through a closed, LGBT military social media group. Participants completed an anonymous survey presenting five experimentally varied attributes of interest related to PrEP administration (dosing method, provider type, visit location, lab work evaluation location, and dispensing venue). Relative importance and part-worth utility scores were generated using Hierarchical Bayes (HB) estimation, and the randomized first choice model was used to examine participation interest across eight possible PrEP program scenarios. RESULTSAmong the 429 participants and the eight scenarios that varied the five attributes into delivery profiles, the most preferred scenario (69.9%) featured a daily pill or long-term PrEP injection, military provider, smartphone/telehealth visit, lab evaluation on-base, and on-base medication pick-up. Responses indicated the need for providers to familiarize themselves with PrEP prescription knowledge and to provide interactions sensitive to sexual identity, mental health, and decision autonomy. CONCLUSIONThese results suggest that a military setting is preferred over a civilian or off-site one, yet more importantly, it points to a high value placed on the quality of clinical interactions. High interest in long-acting implants and injections also suggest potential markets for future PrEP engagement.
Identification of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma Based on Multi-Omics Analysis
Authors: Yin Lu , Zhou Liuzhi , Xu Rujun 
Published: August 2020

Abstract
Background: We aimed to explore the tumor mutational burden (TMB) and immune infiltration in HCC and investigate new biomarkers for immunotherapy.Methods: Transcriptome and gene mutation data were downloaded from the GDC portal, including 374 HCC samples and 50 matched samples. Furthermore, we divided the samples into high and low TMB groups, and analyzed the differential genes between them with GO, KEGG, and GSEA. Cibersort was used to assess the immune cell infiltration in the samples. Finally, univariate and multivariate Cox regression analyses were performed to identify differential genes related to TMB and immune infiltration, and a risk prediction model was constructed.Results: We found 10 frequently mutated genes, including TP53, TTN, CTNNB1, MUC16, ALB, PCLO, MUC, APOB, RYR2, and ABCA. Pathway analysis indicated that these TMB-related differential genes were mainly enriched in PI3K-AKT. Cibersort analysis showed that memory B cells (P=0.02), CD8+ T cells (P=0.09), CD4+ memory activated T cells (P=0.07), and neutrophils (P=0.06) demonstrated a difference in immune infiltration between high and low TMB groups. On multivariate analysis, GABRA3 (P=0.05), CECR7 (P<0.001), TRIM16 (P=0.003), and IL7R (P=0.04) were associated with TMB and immune infiltration. The risk prediction model had an area under the curve (AUC) of 0.69, suggesting that patients with low risk had better survival outcomes.Conclusions: Our study demonstrated for the first time that CECR7, GABRA3, IL7R, and TRIM16L mutations were associated with TMB and promoted antitumor immunity in HCC.
Numerical modelling of FC bacteria using a dynamic and variable mortality rate
Authors: Mohammadi Siavash , Kashefipour Seyed Mahmood 
Published: August 2020

Abstract
Faecal coliform (FC) microorganisms are one of the most important indicators in water quality management, since their presence reveals the possibility of existence of other dangerous microorganisms, leading to higher health risks. An accurate estimate of the concentration of this indicator helps better evaluation of the water pollution in riverine basins; thus, it is essential for future developments. The FC mortality rate depends on the physical, chemical, and biological processes in rivers. These processes are generally affected by environmental conditions. In this study, the decay coefficient (K) or mortality rate are related to the environmental parameters such as temperature, turbidity, pH, and salinity by an empirical equation. The results showed that turbidity and temperature are the most effective parameters. Moreover, an empirical equation was developed utilizing numerical model calibration, which describes the relationship of the mortality rate (K) with water temperature and turbidity. This equation was then added to the water quality module of the FASTER numerical model. Comparison of the measured FC concentrations with the predicted values obtained from the numerical model showed that the model accuracy significantly improved for the dynamic and variable decay coefficient.
Variability of water, sanitation, and hygiene conditions and the potential infection risk following cesarean delivery in rural Rwanda
Authors: Robb Katharine Ann , Habiyakare Caste , Kateera Fredrick , Nkurunziza Theoneste , Dusabe Leila , Kubwimana Marthe , Powell Brittany , Koch Rachel , Gruendl Magdalena , Ngamije Patient , Riviello Robert , Hedt-Gauthier Bethany 
Published: August 2020

Abstract
Safe water, sanitation, and hygiene (WASH) is critical for the prevention of postpartum infections. The aim of this study was to characterize the WASH conditions women are exposed to following cesarean section in rural Rwanda. We assessed the variability of WASH conditions in the postpartum ward of a district hospital over two months, the WASH conditions at the women's homes, and the association between WASH conditions and suspected surgical site infection (SSI). Piped water flowed more consistently during the rainy month, which increased availability of water for drinking and handwashing (p &lt; 0.05 for all). Latex gloves and hand-sanitizer were more likely to be available on weekends versus weekdays (p &lt; 0.05 for both). Evaluation for suspected SSI after cesarean section was completed for 173 women. Women exposed to a day or more without running water in the hospital were 2.6 times more likely to develop a suspected SSI (p = 0.027). 92% of women returned home to unsafe WASH environments, with notable shortfalls in handwashing supplies and sanitation. The variability in hospital WASH conditions and the poor home WASH conditions may be contributing to SSIs after cesarean section. These relationships must be further explored to develop appropriate interventions to improve mothers’ outcomes.
Allergen Homologues, Pathogenesis-Related 1, Polygalacturonase, and Pectin Methyl Esterase from a Japanese Hop
Authors: Jang Seok Woo , Jeong Kyoung Yong , Yuk Ji Eun , Lee Jongsun , Park Kyung Hee , Park Jung-Won 
Published: August 2020

Background:
Japanese hop is an important cause of weed pollinosis in East Asia. Its
pollen is abundant in autumn. This pollen is known to be the cause of many allergic diseases. However,
molecular characteristics of its allergens have not been elucidated.

Objective:
In this study, we produced recombinant proteins of allergen homologues from Japanese
hop by the analysis of expressed sequence tags (EST), and evaluated its allergenicity.

Methods:
cDNA library was constructed using as little as 50 ng of total RNA from Japanese hop
pollen. Allergen homologues were identified by the initial screening of 963 EST clones. Recombinant
proteins were overexpressed in the E. coli expression system and purified using Ni-nitrilotriacetic
acid-agarose. Purified proteins were analyzed by ELISA.

Results:
Japanese hop pathogenesis-related 1 protein (PR-1) shares 37.0 to 44.4%
of amino acid sequence identity with Art v 2, Cuc m 3, and Cyn d 24. Pectin methyl esterase (PME)
shows 23.2 to 50.2% of identities to Act d 7, Ole e 11, and Sal k 1. Polygalacturonase (PGs)
shows 16.7 to 19.3% of identities to Phl p 13, Cry j 2, Cha o 2, Jun a 2, Pla a 2, and Pla or 2. IgE
antibodies from Japanese hop allergy patients’ sera recognized PR-1 (3.4%), PME (13.8%), PGs
(3.7%), and profilin (13.8%), respectively.

Conclusion:
Novel allergenic components were identified, even though low IgE reactivity was displayed
reflecting the low degree of cross-reactivity with other pollen allergens. We believe that these
molecules have worth further studies.
Insights into the Structural Features, Conformational Stability and Functional Activity of the Olneya tesota PF2 Lectin
Authors: Acedo-Espinoza Edgar , Lagarda-Diaz Irlanda , Cabrera Rosina , Guzman-Partida Ana M. , Maldonado-Arce Amir , Ortega-Nieblas María M. , Chan-Chan Lerma , Vázquez-Moreno Luz 
Published: August 2020

Background:
The O. tesota lectin PF2 is a tetrameric protein with subunits of 33 kDa
that recognizes only complex carbohydrates, resistant to proteolytic enzymes and has insecticidal
activity against Phaseolus beans pest.

Objective:
To explore PF2 lectin features at different protein structural levels and to evaluate the effect
of temperature and pH on its functionality and conformational stability.

Methods:
PF2 lectin was purified by affinity chromatography. Its primary structure was resolved
by mass spectrometry and analyzed by bioinformatic tools, including its tertiary structure homology
modeling. The effect of temperature and pH on its conformational traits and stability was addressed
by dynamic light scattering, circular dichroism, and intrinsic fluorescence. The hemagglutinating
activity was evaluated using a suspension of peripheral blood erythrocytes.

Results:
The proposed PF2 folding comprises a high content of beta sheets. At pH 7 and 25°C, the
hydrodynamic diameter (Dh) was found to be 12.3 nm which corresponds to the oligomeric native
state of PF2 lectin. Dh increased under the other evaluated pH and temperature conditions, suggesting
protein aggregation. At basic pH, PF2 exhibited low conformational stability. The native PF2
(pH 7) retained its full hemagglutinating activity up to 45°C and exhibited one transition state with
a melting temperature of 76.8°C.

Conclusion:
PF2 showed distinctive characteristics found in legume lectins. The pH influences the
functionality and conformational stability of the protein. PF2 lectin displayed a relatively narrow
thermostability to the loss of secondary structure and hemagglutinating activity.
Identification and Characterization of SNP Mutation in Genes Related to Non-small Cell Lung Cancer
Authors: Dayananda P. , Hiremath Neelambika B. 
Published: August 2020

Background and Objective:
The advent of Next Generation Sequencing (NGS) has created a high throughput
platform, to identify disease traits and phenotypic characteristics using RNASeq Sequencing analysis in humans. Non-small
cell lung cancer (NSCLC), a lethal disease accounts for 85 percent of most lung cancers with very small window ofsurvival
rate. The decision of tumour image bio marker impression can be improved by gene profile. Hence there is a need to
characterise the variants in the disease manifestation.

Methods:
To understand the SNP’s in the major genes responsible for NSCLC, RNASeq data of patients aged above 50
years, were downloaded from SRA database. The quality matrix analysis is mapped to Genome reference consortium human
build 38 (GRCh38) to call the variants and identify SNP’s with the tuxedo protocol.

Results:
The SNPs and the patterns of variants were analysed to see the comparison between healthy
individuals and NSCLC patients, and in between patients of different age. Oncogenes commonly associated
with the NSCLC like KRAS, EGFR, ALK, BRAF and HER2 were mainly analysed to see
the SNPs and their characterisations with respect to the functional change done.

Conclusion:
The SNPs with the greater quality scores belonging to the above-said genes were identified,
which gives us a baseline to understand the NSCLC at the Genomic level. Further fold change
of these genes to the frequency of variants can be mapped to understand the NSCLC at a greater
depth.
Vulnerability to Child Maltreatment and Neglect in Italy: A Proposal of an Indicator
Authors: Cardinali Paola , Badalassi Giovanna , Emmi Valeria , Gentile Federica , Migliorini Laura 
Published: August 2020

Background:
Child maltreatment and neglect is a significant social problem. Present work addresses the important issue of quantifying the vulnerability to child maltreatment and neglect, proposing the application in the Italian context of a new General Index on Vulnerability to Maltreatment and Neglect to achieve a more comprehensive understanding of this phenomenon.

Methods:
The paper presents the first findings of the vulnerability among Italian minors, obtained through the new General Index, based on a set of 65 indicators that already existed at the regional and national levels.

Results:
The General Index summarizes both the weaknesses of territory in terms of risk factors and its ability to react according to the policies and public services. A global index could be useful for allocating resources and monitoring progress. To understand and ensure the effectiveness of preventive interventions, it is essential to build both an overall picture at the national and regional levels.

Conclusion:
This new index could give policymakers information on where to direct their efforts to prevent child maltreatment.