bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salivary cortisol in healthy dogs: a randomized cross-over study to evaluate different saliva stimulation methods and their effects on saliva volume and cortisol concentration
Authors: Meunier Solène , Groessl Michael , Reusch Claudia , Boretti Felicitas , Sieber-Ruckstuhl Nadja 
Published: May 2021

Abstract
Background
Salivary cortisol collected at home is a useful test to diagnose and monitor Cushing’s syndrome in humans. The main problem in dogs is to retrieve a sufficient amount of saliva. The aim of this study was to evaluate different salivary collection methods and compare their effects on volume, pH and cortisol concentration of saliva. Sixteen healthy Beagles were used in a 4 × 4 randomized crossover study with a washout period of 1 week between each of the following collection methods: 1. Salimetrics® cotton swab dipped in ginger powder (ginger group); 2. beef-flavored Salimetrics® (bouillon group); 3. Salivette® cotton swab with an enclosed treat (treat group); 4. plain Salimetrics® (control group). First, baseline saliva (plain cotton swab, S0) and, 2 min later, experimental saliva (according to group allocation above, SExp) were collected. Saliva was gathered by holding the swabs in the animal’s mouth for 2 min. After the cross-over study, another saliva sample was collected from all dogs by the ginger method, using a 30 s sampling time (30s-ginger method). Cortisol concentrations were measured by liquid chromatography tandem mass spectrometry.

Results
All three stimulation methods increased saliva production significantly (S0 compared to SExp: ginger p = 0.0005; bouillon p = 0.009; treat p = 0.007). Only ginger stimulation, however, generated a significantly higher amount of saliva (SExp) compared to the control group (p = 0.00001; median (range) amount of saliva for SExp: ginger 1200 ul (600–1700), bouillon 650 ul (200–1900), treat 700 ul (300–1000), control 400 ul (0–1100)). The amount of saliva retrieved by the 30s-ginger method was still higher than that from the control group (p = 0.0004). Bouillon and treat stimulation led to decreased pH values (bouillon, p = 0.0028; treat, 0.0018). Excitement was higher in the ginger group (p = 0.01). Chewing was intensified in the ginger and treat group (ginger, p = 0.003; treat, 0.0009). The cortisol concentration SExp was higher compared to that of S0 in the ginger and treat group (p = 0.02, 0.003). The experimental cortisol concentrations (SExp) were not different between groups.

Conclusions
The 30s-ginger method could prove useful in evaluating or monitoring dogs with Cushing’s syndrome, as sampling at home for 30 s by the owner seems feasible.
Health and physical fitness profiling of working population: Sport4Health 2021
Authors: Todorovic Nikola , Stajer Valdemar , Harrison Bojana , Korovljev Darinka , Maksimovic Nebojsa , van Heel John , Pintar Damjan , Ibric Hasan , Kralski Milko , Jukic Igor , Kekic Sophie , Ostojic Sergej M. 
Published: May 2021

AbstractSport4Health Network (SPORT4H) is a multidisciplinary project co-funded by the European Union Erasmus+ programme aimed to encourage participation in physical activity in working population. SPORT4H includes educational and instructional activities that provide top-notch knowledge on various physical activities that may have an additional benefit to improve healthy lifestyle behaviours across workforce. The aims of Sport4Health 2021 e-symposium organized from 22nd to 23th March 2021 were to: (1) summarize data collected during this project through evaluation of health and fitness profiles for over 40,000 employees from all Sport4HealthNet countries (Belgium, Bulgaria, Croatia, Netherlands, Serbia and Slovenia); (2) discuss the applicability of user-friendly guidelines for physical activity at workplace and e-learning module that includes multicomponent interventions with innovative activities; (3) share experiences from different partners about the effects of educational interventions in specific working environment; and, (4) overview challenges identified during the implementation of interventions at work settings. The Sport4Health 2021 e-symposium facilitated networking between partner institutions, provided practical information for extensive public education that advances physical activity at workplace, and capacitated interaction and recruitment of end-users through e-learning modules and guidelines.
Bacillus subtilis revives conventional antibiotics against Staphylococcus aureus osteomyelitis
Authors: Zhang Fan , Wang Bowei , Liu Shiluan , Chen Yuhui , Lin Yihuang , Liu Zixian , Zhang Xianrong , Yu Bin 
Published: May 2021

AbstractAs treatment of Staphylococcus aureus (S. aureus) osteomyelitis is often hindered by the development of antibiotic tolerance, novel antibacterial therapeutics are required. Here we found that the cell-free supernatant of Bacillus subtilis (B. subtilis CFS) killed planktonic and biofilm S. aureus, and increased S. aureus susceptibility to penicillin and gentamicin as well. Further study showed that B. subtilis CFS suppressed the expression of the genes involved in adhesive molecules (Cna and ClfA), virulence factor Hla, quorum sensing (argA, argB and RNAIII) and biofilm formation (Ica and sarA) in S. aureus. Additionally, our data showed that B. subtilis CFS changed the membrane components and increased membrane permeabilization of S. aureus. Finally, we demonstrated that B. subtilis CFS increased considerably the susceptibility of S. aureus to penicillin and effectively reduced S. aureus burdens in a mouse model of implant-associated osteomyelitis. These findings support that B. subtilis CFS may be a potential resistance-modifying agent for β-lactam antibiotics against S. aureus.
miR-129-5p inhibits clear cell renal cell carcinoma cell proliferation, migration and invasion by targeting SPN
Authors: Gao Bin , Wang Lijuan , Zhang Na , Han Miaomiao , Zhang Yubo , Liu Huancai , Sun Dongli , Xiao Xiaolong , Liu Yifei 
Published: May 2021

Abstract
Objective
Our study aims to investigate the mechanism of the miR-129-5p/SPN axis in clear cell renal cell carcinoma (ccRCC), providing a novel direction for the targeted therapy of ccRCC.

Methods
Bioinformatics methods were implemented to find the differentially expressed genes (DEGs) associated with ccRCC from TCGA database. qRT-PCR was performed to detect miR-129-5p and SPN mRNA expression, while western bot was carried out for the detection of protein expression of SPN. Bioinformatics analysis was used to predict the binding sites of miR-129-5p on SPN 3’UTR, while dual-luciferase assay was conducted to verify their binding relationship. CCK-8 assay, colony formation assay, wound healing assay and Transwell assay were employed to measure ccRCC cell proliferative ability, cell formation ability, cell migratory and invasive abilities. Flow cytometry was implemented to assess cell cycle and apoptosis.

Results
miR-129-5p exhibited a significantly down-regulated expression level in ccRCC, while SPN showed a remarkably up-regulated expression level. Overexpressed miR-129-5p inhibited ccRCC cell proliferative, invasive and migratory capacities while induced cell cycle arrest in G0/G1 phase and promoted cell apoptosis. Dual-luciferase assay confirmed that there was a binding relationship between miR-129-5p and SPN. Moreover, overexpressed miR-129-5p remarkably reduced SPN expression in cancer cells, weakened the promoting effect of SPN on cell proliferation, migration, invasion and cell cycle progress, and led to enhanced cell apoptotic activity.

Conclusions
Our study proves the regulatory effect of the miR-129-5p/SPN axis in ccRCC, and provides a novel potential target for precise treatment of patients with ccRCC.
Mismatch repair-deficient hormone receptor-positive breast cancers: Biology and pathological characterization
Authors: Sajjadi Elham , Venetis Konstantinos , Piciotti Roberto , Invernizzi Marco , Guerini-Rocco Elena , Haricharan Svasti , Fusco Nicola 
Published: May 2021

AbstractThe clinical outcome of patients with a diagnosis of hormone receptor (HR)+ breast cancer has improved remarkably since the arrival of endocrine therapy. Yet, resistance to standard treatments is a major clinical challenge for breast cancer specialists and a life-threatening condition for the patients. In breast cancer, mismatch repair (MMR) status assessment has been demonstrated to be clinically relevant not only in terms of screening for inherited conditions such as Lynch syndrome, but also for prognostication, selection for immunotherapy, and early identification of therapy resistance. Peculiar traits characterize the MMR biology in HR+ breast cancers compared to other cancer types. In these tumors, MMR genetic alterations are relatively rare, occurring in ~3 % of cases. On the other hand, modifications at the protein level can be observed also in the absence of gene alterations and vice versa. In HR+ breast cancers, the prognostic role of MMR deficiency has been confirmed by several studies, but its predictive value remains a matter of controversy. The characterization of MMR status in these patients is troubled by the lack of tumor-specific guidelines and/or companion diagnostic tests. For this reason, precise identification of MMR-deficient breast cancers can be problematic. A deeper understanding of the MMR biology and clinical actionability in HR+ breast cancer may light the path to effective tumor-specific diagnostic tools. For a precise MMR status profiling, the specific strengths and limitations of the available technologies should be taken into consideration. This article aims at providing a comprehensive overview of the current state of knowledge of MMR alterations in HR+ breast cancer. The available armamentarium for MMR testing in these tumors is also examined along with possible strategies for a tailored pathological characterization.
Factors associated with the use of insecticide-treated nets: analysis of the 2018 Burkina Faso Malaria Indicator Survey
Authors: Tassembedo Mahamadi , Coulibaly Soumaila , Ouedraogo Boukary 
Published: May 2021

Abstract
Background
Sleeping under an ITN reduces contact with mosquitoes through the combination of a physical barrier and an insecticidal effect, which reduces the incidence of malaria. The 2016–2020 Burkina Faso National Malaria Strategic Plan aims to have at least 90% of the population, 100% of children under age 5, and 100% of pregnant women sleep under an ITN.

Methods
The analysis examines individual, household, and community-level factors associated with ITN usage. According to the 2017–18 Burkina Faso MIS, 58% of individuals in households that own at least one ITN reported that they slept under an ITN on the night before the survey.

Results
The use of ITNs was significantly associated with individual, household, and community-level variables that included age, gender, age of household head, number of sleeping rooms, wealth, malaria prevalence, residence, and region.

Conclusions
The results highlight areas of intervention at the individual, household, and community levels that can increase ITN use.
Inhibition of mutant KRAS-driven overexpression of ARF6 and MYC by an eIF4A inhibitor drug improves the effects of anti-PD-1 immunotherapy for pancreatic cancer
Authors: Hashimoto Ari , Handa Haruka , Hata Soichiro , Tsutaho Akio , Yoshida Takao , Hirano Satoshi , Hashimoto Shigeru , Sabe Hisataka 
Published: May 2021

AbstractMany clinical trials are being conducted to clarify effective combinations of various drugs for immune checkpoint blockade (ICB) therapy. However, although extensive studies from multiple aspects have been conducted regarding treatments for pancreatic ductal adenocarcinoma (PDAC), there are still no effective ICB-based therapies or biomarkers for this cancer type. A series of our studies have identified that the small GTPase ARF6 and its downstream effector AMAP1 (also called ASAP1/DDEF1) are often overexpressed in different cancers, including PDAC, and closely correlate with poor patient survival. Mechanistically, the ARF6-AMAP1 pathway drives cancer cell invasion and immune evasion, via upregulating β1-integrins and PD-L1, and downregulating E-cadherin, upon ARF6 activation by external ligands. Moreover, the ARF6-AMAP1 pathway enhances the fibrosis caused by PDAC, which is another barrier for ICB therapies. KRAS mutations are prevalent in PDACs. We have shown previously that oncogenic KRAS mutations are the major cause of the aberrant overexpression of ARF6 and AMAP1, in which KRAS signaling enhances eukaryotic initiation factor 4A (eIF4A)-dependent ARF6 mRNA translation and eIF4E-dependent AMAP1 mRNA translation. MYC overexpression is also a key pathway in driving cancer malignancy. MYC mRNA is also known to be under the control of eIF4A, and the eIF4A inhibitor silvestrol suppresses MYC and ARF6 expression. Using a KPC mouse model of human PDAC (LSL-Kras(G12D/+); LSL-Trp53(R172H/+)); Pdx-1-Cre), we here demonstrate that inhibition of the ARF6-AMAP1 pathway by shRNAs in cancer cells results in therapeutic synergy with an anti-PD-1 antibody in vivo; and furthermore, that silvestrol improves the efficacy of anti-PD-1 therapy, whereas silvestrol on its own promotes tumor growth in vivo. ARF6 and MYC are both essential for normal cell functions. We demonstrate that silvestrol substantially mitigates the overexpression of ARF6 and MYC in KRAS-mutated cells, whereas the suppression is moderate in KRAS-intact cells. We propose that targeting eIF4A, as well as mutant KRAS, provides novel methods to improve the efficacy of anti-PD-1 and associated ICB therapies against PDACs, in which ARF6 and AMAP1 overexpression, as well as KRAS mutations of cancer cells are biomarkers to identify patients with drug-susceptible disease. The same may be applicable to other cancers with KRAS mutations.
Mir-139-5p inhibits glioma cell proliferation and progression by targeting GABRA1
Authors: Wang Lei , Liu Yan , Yu Zhengtao , Gong Jianwu , Deng Zhiyong , Ren Nianjun , Zhong Zhe , Cai Hao , Tang Zhi , Cheng Haofeng , Chen Shuai , He Zhengwen 
Published: May 2021

AbstractGlioma is an extremely aggressive malignant neoplasm of the central nervous system. MicroRNA (miRNA) are known to bind to specific target mRNA to regulate post-transcriptional gene expression and are, therefore, currently regarded as promising biomarkers for glioma diagnosis and prognosis. The aim of the present study was to examine the pathogenesis and potential molecular markers of glioma by comparing the differential expression of miRNA and mRNA between glioma tissue and peritumor brain tissue. We explored the impact of screened core miRNA and mRNA on cell proliferation, invasion, and migration of glioma. An miRNA expression profile dataset (GSE90603) and a transcriptome profile dataset (GSE90598) were downloaded from combined miRNA-mRNA microarray chips in the Gene Expression Omnibus (GEO) database. Overall, 59 differentially expressed miRNAs (DEMs) and 419 differentially expressed genes (DEGs) were identified using the R limma software package. FunRich software was used to predict DEM target genes and miRNA-gene pairs, and Perl software was used to find overlapping genes between DEGs and DEM target genes. There were 129 overlapping genes regulated by nine miRNAs between target genes of the DEMs and DEGs. The Chinese Glioma Genome Atlas(CGGA) was analyzed in order to identify miRNAs with diagnostic and prognostic significance. MiR-139-5p, miR-137, and miR-338-3p were validated to be significantly linked to prognosis in glioma patients. Finally, we validated that miR-139-5p affected glioma malignant biological behavior via targeting gamma-aminobutyric acid A receptor alpha 1(GABRA1) through rescue experiments. Low miR-139-5p expression was correlated with survival probability and World Health Organization (WHO) grade. MiR-139-5p overexpression inhibited cell proliferation, migration, and invasion of glioma in vitro. GABRA1 was identified as a functional downstream target of miR-139-5p. Decreased GABRA1 expression was related to similar biological roles as miR-139-5p overexpression while upregulation of GABRA1 effectively reversed the inhibition effects of miR-139-5p. These results demonstrate a novel axis for miR-139-5p/GABRA1 in glioma progression and provide potential prognostic predictors and therapeutic target for glioma patients.
Sleep problems among children with Fetal Alcohol Spectrum Disorders (FASD)- an explorative study
Authors: Dylag Katarzyna Anna , Bando Bożena , Baran Zbigniew , Dumnicka Paulina , Kowalska Katarzyna , Kulaga Paulina , Przybyszewska Katarzyna , Radlinski Jakub , Roozen Sylvia , Curfs Leopold 
Published: May 2021

AbstractBackgroundFetal alcohol spectrum disorders (FASD) is a group of conditions resulting from prenatal alcohol exposure (PAE). Patients with FASD experience a variety of neuropsychological symptoms resulting from central nervous system impairment. Little is known about sleep disorders associated with PAE. The objective of this study was to investigate sleep problems related to FASD.MethodsForty patients (median age 8 years (6; 11)) diagnosed with FASD and forty typically developing children (median age 10 years (8; 13)) were recruited for the 1st phase of the study. In the 1st phase, the screening of sleep problems was performed with Child Sleep Habit Questionnaire (CSHQ) filled in by a caregiver. Those of the FASD group who scored above 41 points were qualified to the 2nd phase of the study and had an in-lab attended polysomnography (PSG) performed. The measurements consisted of electroencephalogram, electrooculograms, chin and tibial electromyogram, electrocardiogram, ventilatory monitoring, breathing effort, pulse oximetry, snoring and body position. Their results were compared to PSG laboratory reference data.ResultsThe number of participants with sleep disturbances was markedly higher in the FASD group as compared to typically developing children (55% vs. 20%). The age-adjusted odds ratio for a positive result in CSHQ was 4.31 (95% CI: 1.54–12.11;p = 0.005) for FASD patients as compared to the control group. Significant differences between the FASD as compared to the typically developing children were observed in the following subscales: sleep onset delay, night wakings, parasomnias, sleep disordered breathing, and daytime sleepiness. Children from the FASD group who underwent PSG experienced more arousals during the sleep as compared with the PSG laboratory reference data. The respiratory indices in FASD group appear higher than previously published data from typically developing children.ConclusionThe results support the clinical observation that sleep disorders appear to be an important health problem in individuals with FASD. In particular distorted sleep architecture and apneic/hypopneic events need further attention.
An atlas connecting shared genetic architecture of human diseases and molecular phenotypes provides insight into COVID-19 susceptibility
Authors: Wang Liuyang , Balmat Thomas J. , Antonia Alejandro L. , Constantine Florica J. , Henao Ricardo , Burke Thomas W. , Ingham Andy , McClain Micah T. , Tsalik Ephraim L. , Ko Emily R. , Ginsburg Geoffrey S. , DeLong Mark R. , Shen Xiling , Woods Christopher W. , Hauser Elizabeth R. , Ko Dennis C. 
Published: May 2021

Abstract
Background
While genome-wide associations studies (GWAS) have successfully elucidated the genetic architecture of complex human traits and diseases, understanding mechanisms that lead from genetic variation to pathophysiology remains an important challenge. Methods are needed to systematically bridge this crucial gap to facilitate experimental testing of hypotheses and translation to clinical utility.

Results
Here, we leveraged cross-phenotype associations to identify traits with shared genetic architecture, using linkage disequilibrium (LD) information to accurately capture shared SNPs by proxy, and calculate significance of enrichment. This shared genetic architecture was examined across differing biological scales through incorporating data from catalogs of clinical, cellular, and molecular GWAS. We have created an interactive web database (interactive Cross-Phenotype Analysis of GWAS database (iCPAGdb)) to facilitate exploration and allow rapid analysis of user-uploaded GWAS summary statistics. This database revealed well-known relationships among phenotypes, as well as the generation of novel hypotheses to explain the pathophysiology of common diseases. Application of iCPAGdb to a recent GWAS of severe COVID-19 demonstrated unexpected overlap of GWAS signals between COVID-19 and human diseases, including with idiopathic pulmonary fibrosis driven by the DPP9 locus. Transcriptomics from peripheral blood of COVID-19 patients demonstrated that DPP9 was induced in SARS-CoV-2 compared to healthy controls or those with bacterial infection. Further investigation of cross-phenotype SNPs associated with both severe COVID-19 and other human traits demonstrated colocalization of the GWAS signal at the ABO locus with plasma protein levels of a reported receptor of SARS-CoV-2, CD209 (DC-SIGN). This finding points to a possible mechanism whereby glycosylation of CD209 by ABO may regulate COVID-19 disease severity.

Conclusions
Thus, connecting genetically related traits across phenotypic scales links human diseases to molecular and cellular measurements that can reveal mechanisms and lead to novel biomarkers and therapeutic approaches. The iCPAGdb web portal is accessible at http://cpag.oit.duke.edu and the software code at https://github.com/tbalmat/iCPAGdb.
A model-agnostic approach for understanding heart failure risk factors
Authors: Miran Seyed M. , Nelson Stuart J. , Zeng-Treitler Qing 
Published: May 2021

Abstract
Objective
Understanding the risk factors for developing heart failure among patients with type 2 diabetes can contribute to preventing deterioration of quality of life for those persons. Electronic health records (EHR) provide an opportunity to use sophisticated machine learning models to understand and compare the effect of different risk factors for developing HF. As the complexity of the model increases, however, the transparency of the model often decreases. To interpret the results, we aimed to develop a model-agnostic approach to shed light on complex models and interpret the effect of features on developing heart failure. Using the HealthFacts EHR database of the Cerner EHR, we extracted the records of 723 patients with at least 6 yeas of follow up of type 2 diabetes, of whom 134 developed heart failure. Using age and comorbidities as features and heart failure as the outcome, we trained logistic regression, random forest, XGBoost, neural network, and then applied our proposed approach to rank the effect of each factor on developing heart failure.

Results
Compared to the “importance score” built-in function of XGBoost, our proposed approach was more accurate in ranking the effect of the different risk factors on developing heart failure.
Blue light inactivation of the enveloped RNA virus Phi6
Authors: Vatter Petra , Hoenes Katharina , Hessling Martin 
Published: May 2021

Abstract
Objective
Ultraviolet radiation is known for its antimicrobial properties but unfortunately, it could also harm humans. Currently, disinfection techniques against SARS-CoV-2 are being sought that can be applied on air and surfaces and which do not pose a relevant thread to humans. In this study, the bacteriophage phi6, which like SARS-CoV-2 is an enveloped RNA virus, is irradiated with visible blue light at a wavelength of 455 nm.

Results
For the first time worldwide, the antiviral properties of blue light around 455 nm can be demonstrated. With a dose of 7200 J/cm2, the concentration of this enveloped RNA virus can be successfully reduced by more than three orders of magnitude. The inactivation mechanism is still unknown, but the sensitivity ratio of phi6 towards blue and violet light hints towards an involvement of photosensitizers of the host cells. Own studies on coronaviruses cannot be executed, but the results support speculations about blue-susceptibility of coronaviruses, which might allow to employ blue light for infection prevention or even therapeutic applications.