bluuebunny/crossref_metadata_2025 huggingface dataset:
PredictiveNetwork: predictive gene network estimation with application to gastric cancer drug response-predictive network analysis
Authors: Park Heewon , Imoto Seiya , Miyano Satoru
Published: August 2022

Background

Gene regulatory networks have garnered a large amount of attention to understand disease mechanisms caused by complex molecular network interactions. These networks have been applied to predict specific clinical characteristics, e.g., cancer, pathogenicity, and anti-cancer drug sensitivity. However, in most previous studies using network-based prediction, the gene networks were estimated first, and predicted clinical characteristics based on pre-estimated networks. Thus, the estimated networks cannot describe clinical characteristic-specific gene regulatory systems. Furthermore, existing computational methods were developed from algorithmic and mathematics viewpoints, without considering network biology.

Results

To effectively predict clinical characteristics and estimate gene networks that provide critical insights into understanding the biological mechanisms involved in a clinical characteristic, we propose a novel strategy for predictive gene network estimation. The proposed strategy simultaneously performs gene network estimation and prediction of the clinical characteristic. In this strategy, the gene network is estimated with minimal network estimation and prediction errors. We incorporate network biology by assuming that neighboring genes in a network have similar biological functions, while hub genes play key roles in biological processes. Thus, the proposed method provides interpretable prediction results and enables us to uncover biologically reliable marker identification. Monte Carlo simulations shows the effectiveness of our method for feature selection in gene estimation and prediction with excellent prediction accuracy. We applied the proposed strategy to construct gastric cancer drug-responsive networks.

Conclusion

We identified gastric drug response predictive markers and drug sensitivity/resistance-specific markers,AKR1B10,AKR1C3,ANXA10, andZNF165, based on GDSC data analysis. Our results for identifying drug sensitive and resistant specific molecular interplay are strongly supported by previous studies. We expect that the proposed strategy will be a useful tool for uncovering crucial molecular interactions involved a specific biological mechanism, such as cancer progression or acquired drug resistance.
Antimicrobial resistance, virulence genes, and phylogenetic characteristics of pathogenic Escherichia coli isolated from patients and swine suffering from diarrhea
Authors: Do Kyung-Hyo , Seo Kwangwon , Lee Wan-Kyu
Published: August 2022

Background

Escherichia (E.) coli causes colibacillosis in swine and humans, and is frequently associated with antimicrobial resistance. In this study we aimed to compare antimicrobial resistance, O-serogroups, virulence genes, and multi-locus sequence type of E. coli between isolates from pigs and patients suffering from diarrhea, and the most prevalent pathogenic E. coli strain from swine isolates in Korea.

Methods

We tested 64 and 50 E. coli strains from pigs and patients suffering from diarrhea for antimicrobial susceptibility test, virulence genes, O-serogroups, and multi-locus sequence typing.

Results

We confirmed that isolates from swine showed significantly higher resistance than from those from patients, especially to fluoroquinolone (ciprofloxacin: 37.5 and 10.0%; norfloxacin: 29.7 and 8.0%, respectively). Stx1 (46.0%) was most frequently detected in patients followed by stx2 (38.0%). There was no significant difference in stx2 (swine: 23.4%, patients: 38.0%). In isolates from patients, O157 (12.0%) was the most prevalent O-serogroup, and two isolates (3.1%) from pigs were confirmed to have O157. Additionally, sequence type (ST) 10 (swine: 6 isolates, patients: 2 isolates) and ST 88 (swine: 2 isolates, patients: 1 isolate) were simultaneously detected.

Conclusions

We found that both isolates from swine and human had the stx2 gene, which could cause severe disease. Moreover, antimicrobial resistance was significantly higher in pigs than in patients. These results suggest that pig could act as a reservoir in human infection and antimicrobial resistance could be transferred to human from pigs.
Transcriptomic analysis reveals the regulatory role of quorum sensing in the Acinetobacter baumannii ATCC 19606 via RNA-seq
Authors: Xiong Li , Yi Fanli , Yu Qiuju , Huang Xiyue , Ao Keping , Wang Yuanfang , Xie Yi
Published: August 2022

Background

Acinetobacter baumannii has emerged as the major opportunistic pathogen in healthcare-associated infections with high-level antibiotic resistance and high mortality. Quorum sensing (QS) system is a cell-to-cell bacterial communication mediated by the synthesis, secretion, and binding of auto-inducer signals. It is a global regulatory system to coordinate the behavior of individual bacteria in a population. The present study focused on the QS system, aiming to investigate the regulatory role of QS in bacterial virulence and antibiotic resistance.

Method

The auto-inducer synthase gene abaI was deleted using the A. baumannii ATCC 19606 strain to interrupt the QS process. The RNA-seq was performed to identify the differentially expressed genes (DEGs) and pathways in the mutant (△abaI) strain compared with the wild-type (WT) strain.

Results

A total of 380 DEGs [the adjusted P value < 0.05 and the absolute value of log2(fold change) > log21.5] were identified, including 256 upregulated genes and 124 downregulated genes in the △abaI strain. The enrichment analysis indicated that the DEGs involved in arginine biosynthesis, purine metabolism, biofilm formation, and type VI secretion system (T6SS) were downregulated, while the DEGs involved in pathways related to fatty acid metabolism and amino acid metabolism were upregulated. Consistent with the expression change of the DEGs, a decrease in biofilm formation was observed in the △abaI strain compared with the WT strain. On the contrary, no obvious changes were found in antimicrobial resistance following the deletion of abaI.

Conclusions

The present study demonstrated the transcriptomic profile of A. baumannii after the deletion of abaI, revealing an important regulatory role of the QS system in bacterial virulence. The deletion of abaI suppressed the biofilm formation in A. baumannii ATCC 19606, leading to decreased pathogenicity. Further studies on the role of abaR, encoding the receptor of auto-inducer in the QS circuit, are required for a better understanding of the regulation of bacterial virulence and pathogenicity in the QS network.
Integrative analysis of transcriptome and metabolome reveals flavonoid biosynthesis regulation in Rhododendron pulchrum petals
Authors: Xia Xi , Gong Rui , Zhang Chunying
Published: August 2022

Background

Color is the major ornamental feature of theRhododendron genus, and it is related to the contents of flavonoid in petals. However, the regulatory mechanism of flavonoid biosynthesis inRhododendron pulchrumremains unknown. The transcriptome and metabolome analysis ofRhododendron pulchrumwith white, pink and purple color in this study aimed to reveal the mechanism of flavonoid biosynthesis and to provide insight for improving the petal color.

Results

Flavonoids and flavonols are the major components of flavonoid metabolites inR.pulchrum, such as laricitrin, apigenin, tricin, luteolin, isoorientin, isoscutellarein, diosmetin and their glycosides derivatives. With transcriptome and metabolome analysis, we foundCHS, FLS, F3’H, F3′5’H, DFR, ANS,GT, FNS,IFRandFAOMTgenes showed significantly differential expression in cultivar ‘Zihe'.FNS and IFRwere discovered to be associated with coloration inR.pulchrumfor the first time. TheFNSgene existed in the form ofFNSI.TheIFRgene and its related metabolites of medicarpin derivatives were highly expressed in purple petal. In cultivar ‘Fenhe', up-regulation ofF3’HandF3′5’Hand down-regulation of4CL, DFR, ANS,andGTwere associated with pink coloration. With the transcription factor analysis, a subfamily ofDREBswas found to be specifically enriched in pink petals. This suggested that theDREBfamily play an important role in pink coloration. In cultivars ‘Baihe', flavonoid biosynthesis was inhibited by low expression ofCHS, while pigment accumulation was inhibited by low expression ofF3′5'H, DFR, andGT, which led to a white coloration.

Conclusions

By analyzing the transcriptome and metabolome ofR.pulchrum, principal differential expression genes and metabolites of flavonoid biosynthesis pathway were identified. Many novel metabolites, genes, and transcription factors associated with coloration have been discovered. To reveal the mechanism of the coloration of different petals, a model of the flavonoid biosynthesis pathway ofR.pulchrumwas constructed. These results provide in depth information regarding the coloration of the petals and the flavonoid metabolism ofR.pulcherum. The study of transcriptome and metabolome profiling gains insight for further genetic improvement inRhododendron.
Burn related injuries: a nationwide analysis of adult inter-facility transfers over a six-year period in the United States
Authors: Evans Christopher S. , Hart Kimberly , Self Wesley H. , Nikpay Sayeh , Thompson Callie M. , Ward Michael J.
Published: August 2022

Background

US emergency department (ED) visits for burns and factors associated with inter-facility transfer are unknown and described in this manuscript.

Methods

We conducted a retrospective analysis of burn-related injuries from 2009–2014 using the Nationwide Emergency Department Sample (NEDS), the largest sample of all-payer datasets. We included all ED visits by adults with a burn related ICD-9 code and used a weighted multivariable logistic regression model to predict transfer adjusting for covariates.

Results

Between 2009–2014, 3,047,701 (0.4%) ED visits were for burn related injuries. A total of 108,583 (3.6%) burn visits resulted in inter-facility transfers occurred during the study period, representing approximately 18,097 inter-facility transfers per year. Burns with greater than 10% total body surface area (TBSA) resulted in a 10-fold increase in the probability of transfer, compared to burn visits with less than 10% TBSA burns. In the multivariable model, male sex (adjusted odds ratio [aOR] 2.4, 95% CI 2.3–2.6) was associated with increased odds of transfer. Older adults were more likely to be transferred compared to all other age groups. Odds of transfer were increased for Medicare and self-pay patients (vs. private pay) but there was a significant interaction of sex and payer and the effect of insurance varied by sex.

Conclusions

In a national sample of ED visits, burn visits were more than twice as likely to have an inter-facility transfer compared to the general ED patient population. Substantial sex differences exist in U.S. EDs that impact the location of care for patients with burn injuries and warrants further investigation.
Interpretation of white blood cell counts in the cerebrospinal fluid of neonates with traumatic lumbar puncture: a retrospective cohort study
Authors: García-De la Rosa Gema , De las Heras-Flórez Silvia , Rodríguez-Afonso Jorge , Carretero-Pérez Mercedes
Published: August 2022

Background

Difficulty in interpreting white blood cell (WBC) counts in cerebrospinal fluid (CSF) complicates the diagnosis of neonatal meningitis in traumatic lumbar punctures (LP). The aim of our study was to determine the correction factor for WBC counts in traumatic LP that offers the greatest diagnostic efficacy in meningitis.

Methods

We conducted a retrospective observational study of LP in neonates between January 2014 and December 2020. Traumatic LP was defined as a red blood cell (RBC) count ≥ 1,000 cells/mm3 CSF and pleocytosis as WBCs ≥ 20 cells/mm3 CSF. The CSF RBC:WBC ratio was analyzed by linear regression to determine a new correction factor. Cell count adjustments were also studied using the 500:1, the 1,000:1 ratio method, and the peripheral blood RBC:WBC ratio, using ROC curves and studies of accuracy (sensitivity and specificity).

Results

Overall, 41.0% of the 1,053 LPs included in the study were traumatic. The best results for effective WBC correction were the method based on the peripheral blood ratio (sensitivity = 1.0 and specificity = 0.9 for bacterial meningitis and sensitivity = 0.8 and specificity = 0.9 for viral meningitis) and the 400:1 ratio (sensitivity = 1.0 and specificity = 0.8 for bacterial meningitis and sensitivity = 0.8 and specificity = 0.8 for viral meningitis) obtained from linear regression (95% CI 381.7–427.4; R2 = 0.7).

Conclusion

Both the peripheral blood correction and the 400:1 correction reduce the number of neonates classified with pleocytosis who were not eventually diagnosed with meningitis. Both methods might be a useful tool to clarify the neonatal meningitis diagnosis, offering neonatologists the possibility to assess the WBC count in traumatic LP.
A survey regarding orthodontic treatment among contemporary college freshmen in China
Authors: Wang Tianyi , Li Haolin , Fan Xi , Guo Yongwen
Published: August 2022

Background

A growing number of Chinese residents are seeking orthodontic treatment. The aim of the study was to investigate rates of orthodontic publicity, orthodontic treatment history and related factors among college freshmen in China, to preliminarily understand the current situation of orthodontic publicity and treatment in China, especially after the 2020s.

Methods

Referred to previous studies, a self-designed online questionnaire of Chinese college freshmen was conducted. The questionnaire was divided into two parts, after collecting basic information, we investigated orthodontic publicity rate and orthodontic treatment history with starting age, relapse phenomenon, satisfaction score and willingness to re-treatment. Factors hindering first-time and second-time treatment were also collected. The statistical analysis was performed using the Chi-square test, t-test, Kruskal–Wallis test and logistic regression analysis.

Results

The response rate was 100% and 3308 responses were included. The male to female ratio was 1524:1784 with a mean age of 18.43 years (SD 0.91 years). Statistically significant of economic administrative regions, age, major and orthodontics engagement of relatives or friends were found on prevalence and rate of orthodontic treatment (P < 0.05). Average opinion on orthodontic treatment was “satisfied” and most claimed a phenomenon of relapse (slight relapse: 38.22%, obvious relapse: 23.12%), where age, major and orthodontics engagement of relatives or friends showed statistically significant. Retreatment willingness was correlation with start age and relapse phenomenon. For those who refused first-time treatment, except for good tooth arrangement condition, pain, long-time span, and cost weighted, while for those who refused re-treatment, the fair of discomfort and long-time span ranked at the top.

Conclusions

In contemporary China, the prevalence and rate of orthodontic treatment had been greatly promoted. Earlier age for receiving orthodontic treatment was also discovered. Subjective factors regarding psychology, self-requirement affected the need of orthodontic treatment. Contemporary Chinese college freshmen had a high ability of judging dental alignment, while improve of overall orthodontic care level is still required.
Antimalarial activity of solvent fractions of a leaf of Eucalyptus globulus labill against Plasmodium berghei infected mice
Authors: Ayalew Mihret , Atnafie Seyfe Asrade , Bekele Azmeraw
Published: August 2022

Introduction

The leaf of Eucalyptus globulus is commonly used in the traditional management of malaria. However, the efficacy of solvent fractions are didn’t study yet scientifically. Thus, this study aimed to investigate the antimalarial efficacy of the solvent fractions of the leaf of Eucalyptus globulus in mice against P.berghei.

Methods

The antimalarial activity of the fractions was tested in a 4-day suppressive test, Rane’s test, and prophylactic test models within P.berghei infected mice. The results were analyzed using a one-way analysis of variance (ANOVA) followed by a post hoc Tukey’s test in version 20 SPSS.

Results

All fractions at all test doses in the three test models suppressed parasitemia (p < 0.001) compared to the negative controls. In addition, the CF and EA at all three test doses and the AF at 400 mg/kg in three antimalarial test models showed 50% and above parasitemia suppression. In compliance with this, all fractions at all test doses in all test models prolonged the mean survival time of the mice greater than 12 days, except the AF at a lower dose. All fractions at 400 mg/kg in the three test models prevented (p < 0.001) loss of body weight and rectal temperature compared to the negative controls. Furthermore, all fractions in all test models and doses prevented packed cell volume reduction (p < 0.05 to p < 0.001) compared to the negative controls..

Conclusion

The findings of this study showed that CF and EAF had greater antimalarial activity compared to AF. This could be attributed to the presence of few phytochemicals in the AF in contrast to the CF and EAF. Overall, the results of this study further support the in vitro antimalarial activity study and the traditional use of the leaf in the management of malaria.
The Swedish father/non-birthing parent visit: evaluating implementation fidelity among child health nurses one year after voluntary implementation
Authors: Odonde Rahel-Ochido Ibilola , Aronson Olov , Wells Michael B.
Published: August 2022

Swedish child health centres (CHCs) have created a series of visits for fathers/non-birthing parents. The primary aim was to assess child health nurses’ implementation fidelity of the father/non-birthing parent visits, with a secondary aim of exploring predictor variables for fidelity. In 2017, nurses voluntarily implemented a series of father/non-birthing parent visits in Region Stockholm. Nurses (n = 122) completed baseline and 8—12 month follow-up surveys. Multiple imputation was used for missing data. Register data on the number of fathers attending the three-to-five month visit was used. Frequencies of nurses reporting good overall adherence to the home visit, three-to-five week visit, and three-to-five month visit were 86%, 76%, and 68%, respectively. A total of 3,609 fathers attended the three-to-five month visit in 2018, where over half of the visits were at 14 of the 134 CHCs. Multiple linear regression showed that working for a private CHC, seeing more fathers, and nurses’ perceptions of receiving enough support predicted higher three-to-five month visit adherence. After nurses saw eight fathers, they were more likely to adhere to the guidelines.
Medium- and longer-term cardiovascular effects of e-cigarettes in adults making a stop-smoking attempt: a randomized controlled trial
Authors: Klonizakis Markos , Gumber Anil , McIntosh Emma , Brose Leonie S.
Published: August 2022

Background

Smoking is a major risk factor for cardiovascular disease and smoking cessation reduces excess risk. E-cigarettes are popular for smoking cessation but there is little evidence on their cardiovascular health effect. Our objective was to compare the medium- and longer-term cardiovascular effects in smokers attempting to quit smoking using e-cigarettes with or without nicotine or prescription nicotine replacement therapy (NRT).

Methods

This was a single-center, pragmatic three-arm randomized (1:1:1) controlled trial, which recruited adult smokers (≥ 10 cigarettes/day), who were willing to attempt to stop smoking with support (n = 248).

Participants were randomized to receive behavioral support with either (a) e-cigarettes with 18 mg/ml nicotine, (b) e-cigarettes without nicotine, and (c) NRT.

Flow-mediated dilation (%FMD) and peak cutaneous vascular conductance (CVCmax) responses to acetylcholine (ACh) and sodium nitroprusside (SNP), mean arterial pressure (MAP), and other outcomes were recorded at baseline, 3, and 6 months after stopping smoking. Data were analyzed using generalized estimating equations (GEE).

Results

At 3- and 6-month follow-up, %FMD showed an improvement over baseline in all three groups (e.g., p < 0.0001 at 6 months). Similarly, ACh, SNP, and MAP improved significantly over baseline in all groups both at 3 and 6 months (e.g., ACh: p = 0.004, at 6 months).

Conclusions

Smokers attempting to quit experienced positive cardiovascular impact after both a 3- and 6-month period. None of the groups (i.e., nicotine-containing and nicotine-free e-cigarettes or NRT) offered superior cardiovascular benefits to the others.

Trial registration

ClinicalTrials.gov NCT03061253. Registered on 17 February 2017.
A randomised controlled trial to assess the antithrombotic effects of aspirin in type 1 diabetes: role of dosing and glycaemic control
Authors: Parker William A. E. , Sagar Rebecca , Kurdee Zeyad , Hawkins Fladia , Naseem Khalid M. , Grant Peter J. , Storey Robert F. , Ajjan Ramzi A.
Published: August 2022

Background

The enhanced thrombotic milieu in diabetes contributes to increased risk of vascular events. Aspirin, a key antiplatelet agent, has inconsistent effects on outcomes in diabetes and the best dosing regimen remains unclear. This work investigated effects of aspirin dose and interaction with glycaemia on both the cellular and protein components of thrombosis.

Methods

A total of 48 participants with type 1 diabetes and 48 healthy controls were randomised to receive aspirin 75 or 300 mg once-daily (OD) in an open-label crossover study. Light transmittance aggregometry and fibrin clot studies were performed before and at the end of each treatment period.

Results

Aspirin demonstrated reduced inhibition of collagen-induced platelet aggregation (PA) in participants with diabetes compared with controls, although the higher dose showed better efficacy. Higher aspirin dose facilitated clot lysis in controls but not individuals with diabetes. Collagen-induced PA correlated with glycaemic control, those in the top HbA1c tertile having a lesser inhibitory effect of aspirin. Threshold analysis suggested HbA1c levels of > 65 mmol/mol and > 70 mmol/mol were associated with poor aspirin response to 75 and 300 mg daily doses, respectively. Higher HbA1c was also associated with longer fibrin clot lysis time.

Conclusions

Patients with diabetes respond differently to the antiplatelet and profibrinolytic effects of aspirin compared with controls. In particular, those with elevated HbA1c have reduced inhibition of PA with aspirin. Our findings indicate that reducing glucose levels improves the anti-thrombotic action of aspirin in diabetes, which may have future clinical implications.

Trial registration

EudraCT, 2008-007875-26, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2008-007875-26.
Hormonal regulation of telomerase activity and hTERT expression in steroid-regulated tissues and cancer
Authors: Taheri Mohammad , Ghafouri-Fard Soudeh , Najafi Sajad , Kallenbach Julia , Keramatfar Elmira , Atri Roozbahani Golnaz , Heidari Horestani Mehdi , Hussen Bashdar Mahmud , Baniahmad Aria
Published: August 2022

Naturally, in somatic cells chromosome ends (telomeres) shorten during each cell division. This process ensures to limit proliferation of somatic cells to avoid malignant proliferation; however, it leads to proliferative senescence. Telomerase contains the reverse transcriptase TERT, which together with the TERC component, is responsible for protection of genome integrity by preventing shortening of telomeres through adding repetitive sequences. In addition, telomerase has non-telomeric function and supports growth factor independent growth. Unlike somatic cells, telomerase is detectable in stem cells, germ line cells, and cancer cells to support self-renewal and expansion. Elevated telomerase activity is reported in almost all of human cancers. Increased expression of hTERT gene or its reactivation is required for limitless cellular proliferation in immortal malignant cells. In hormonally regulated tissues as well as in prostate, breast and endometrial cancers, telomerase activity and hTERT expression are under control of steroid sex hormones and growth factors. Also, a number of hormones and growth factors are known to play a role in the carcinogenesis via regulation of hTERT levels or telomerase activity. Understanding the role of hormones in interaction with telomerase may help finding therapeutical targets for anticancer strategies. In this review, we outline the roles and functions of several steroid hormones and growth factors in telomerase regulation, particularly in hormone regulated cancers such as prostate, breast and endometrial cancer.
Dual roles of interleukin-33 in cognitive function by regulating central nervous system inflammation
Authors: Rao Xiuqin , Hua Fuzhou , Zhang Lieliang , Lin Yue , Fang Pu , Chen Shoulin , Ying Jun , Wang Xifeng
Published: August 2022

With the advent of an aging society, the incidence of dementia is increasing, resulting in a vast burden on society. It is increasingly acknowledged that neuroinflammation is implicated in various neurological diseases with cognitive dysfunction such as Alzheimer’s disease, multiple sclerosis, ischemic stroke, traumatic brain injury, and central nervous system infections. As an important neuroinflammatory factor, interleukin-33 (IL-33) is highly expressed in various tissues and cells in the mammalian brain, where it plays a role in the pathogenesis of a number of central nervous system conditions. Reams of previous studies have shown that IL-33 has both pro- and anti-inflammatory effects, playing dual roles in the progression of diseases linked to cognitive impairment by regulating the activation and polarization of immune cells, apoptosis, and synaptic plasticity. This article will summarize the current findings on the effects IL-33 exerts on cognitive function by regulating neuroinflammation, and attempt to explore possible therapeutic strategies for cognitive disorders based on the adverse and protective mechanisms of IL-33.
Discovery and validation of tissue-specific DNA methylation as noninvasive diagnostic markers for colorectal cancer
Authors: Li Dapeng , Zhang Lei , Fu Jinming , Huang Hao , Liu Yanlong , Zhu Lin , Sun Hongru , Sun Simin , Zhang Ding , Tian Tian , Wang Fan , Hu Fulan , Peng Xiaolin , Li Gairui , Zhao Liyuan , Zheng Ting , Wang Xuan , Cui Binbin , Zhao Yashuang
Published: August 2022

Background

Noninvasive diagnostic markers that are capable of distinguishing patients with colorectal cancer (CRC) from healthy individuals or patients with other cancer types are lacking. We report the discovery and validation of a panel of methylation-based markers that specifically detect CRC.

Methods

This was a large-scale discovery study based on publicly available datasets coupled with a validation study where multiple types of specimens from six cohorts with CRC, other cancer types, and healthy individuals were used to identify and validate the tissue-specific methylation patterns of CRC and assess their diagnostic performance.

Results

In the discovery and validation cohort (N = 9307), ten hypermethylated CpG sites located in three genes, C20orf194, LIFR, and ZNF304, were identified as CRC-specific markers. Different analyses have suggested that these CpG sites are CRC-specific hypermethylated and play a role in transcriptional silencing of corresponding genes. A random forest model based on ten markers achieved high accuracy rates between 85.7 and 94.3% and AUCs between 0.941 and 0.970 in predicting CRC in three independent datasets and a low misclassification rate in ten other cancer types. In the in-house validation cohort (N = 354), these markers achieved consistent discriminative capabilities. In the cfDNA pilot cohort (N = 14), hypermethylation of these markers was observed in cfDNA samples from CRC patients. In the cfDNA validation cohort (N = 155), the two-gene panel yielded a sensitivity of 69.5%, specificity of 91.7%, and AUC of 0.806.

Conclusions

Hypermethylation of the ten CpG sites is a CRC-specific alteration in tissue and has the potential use as a noninvasive cfDNA marker to diagnose CRC.
Nonnegative solution of a class of double phase problems with logarithmic nonlinearity
Authors: Aberqi Ahmed , Benslimane Omar , Elmassoudi Mhamed , Ragusa Maria Alessandra
Published: August 2022

This manuscript proves the existence of a nonnegative, nontrivial solution to a class of double-phase problems involving potential functions and logarithmic nonlinearity in the setting of Sobolev space on complete manifolds. Some applications are also being investigated. The arguments are based on the Nehari manifold and some variational techniques.
Existence of infinitely many solutions of nonlinear fourth-order discrete boundary value problems
Authors: Chen Yanshan , Zhou Zhan
Published: August 2022

The fourth-order discrete Dirichlet boundary value problem is also a discrete elastic beam problem. In this paper, the existence of infinitely many solutions to this problem is investigated through the critical point theory. By an important inequality we established and the oscillatory behavior of f either near the origin or at infinity, we obtain the existence of infinitely many solutions, which either converge to zero or unbounded. In the end, two examples are presented to illustrate our results.
CircRNA 0009043 suppresses non-small-cell lung cancer development via targeting the miR-148a-3p/DNAJB4 axis
Authors: She Kelin , Yu Shaoqi , He Shushuai , Wang Wen , Chen Biao
Published: August 2022

Background

Circular RNAs (circRNAs) are important regulators of the development and progression of non-small-cell lung cancer (NSCLC) and many other malignancies. The functional importance of circ_0009043 in NSCLC, however, has yet to be established.

Methods

The expression of circ_0009043, miR-148a-3p, and DnaJ heat shock protein family (Hsp40) member B4 (DNAJB4) in NSCLC cells was assessed via qPCR. The proliferative activity of these cells was examined through EdU uptake and CCK-8 assays, while flow cytometry approaches were used to examine apoptotic cell death rates. Protein expression was measured through Western immunoblotting. Interactions between miR-148a-3p and circ_0009043 or DNAJB4 were detected through RNA immunoprecipitation (RIP) and dual-luciferase reporter assays. The in vivo importance of circ_0009043 as a regulator of oncogenic activity was assessed using murine xenograft models.

Results

Both NSCLC cells and tissue samples were found to exhibit circ_0009043 upregulation, and lower circ_0009043 expression levels were found to be related to poorer NSCLC patient overall survival. Knocking down circ_0009043 resulted in the enhancement of NSCLC cell proliferative activity and the suppression of apoptotic tumor cell death in vitro, while also driving more rapid in vivo tumorigenesis. Mechanistically, circ_0009043 was found to function as a molecular sponge that sequestered miR-148a-3p, which was in turn able to directly suppress DNAJB4 expression. When miR-148a-3p was overexpressed, this reversed the impact of knocking down circ_0009043 on the apoptotic death and proliferation of NSCLC cells. Conversely, miR-148a-3p inhibition resulted in the suppression of NSCLC cell apoptosis and the enhancement of tumor cell growth, while the downregulation of DNAJB4 reversed these changes.

Conclusion

Circ_0009043 acts as a tumor suppressor in NSCLC cells, promoting DNAJB4 upregulation via the sequestration of miR-148a-3p.
Unlicensed driving among young drivers in North Carolina: a quasi-induced exposure analysis
Authors: Wang Yudan Chen , Foss Robert D. , Goodwin Arthur H.
Published: August 2022

Background

Little is known about the prevalence of driving among teenagers who have not yet obtained a license. The primary objective of the present study was to estimate the prevalence of unlicensed driving among young drivers using the quasi-induced exposure (QIE) approach and to determine whether unlicensed driving was more common among minority and lower-income teenagers. Additionally, we examined whether unlicensed driving among adolescents increased following the implementation of a graduated driver licensing (GDL) system and whether GDL differentially affected minority and low-income adolescents.

Methods

Using North Carolina crash and driver license data, we identified 90,267 two-vehicle crashes from 1991 through 2016 where only one driver was considered contributory and the non-contributory driver was a White or Black 16 or 17 years old. In the QIE approach, these non-contributory young drivers are assumed to be representative of all adolescents driving in the state during this time period. The prevalence of unlicensed driving among adolescents by age and year was estimated by identifying the proportion of non-contributory drivers who had never been licensed by the time of their involvement in these two-vehicle crashes. We further conducted logistic regression analyses to examine the likelihood of a non-contributory young driver being unlicensed as a function of race, neighborhood income level, and licensing era (prior to or after GDL was implemented).

Results

During the 26 years for which data were available, the mean annual prevalence of unlicensed driving was 1.2% for 16-year-olds and 1.7% among 17-year-olds. Young Black drivers and individuals living in lower-income neighborhoods were somewhat more likely to drive before obtaining a license, but the rates of unlicensed driving among these groups were also quite low. Unlicensed driving increased slightly for 17-year-olds following the implementation of GDL, but returned to previous levels after a few years.

Conclusion

Unlicensed driving among adolescents in North Carolina is substantially less common than suggested by previous self-report studies and analyses of fatal crash data.
Comparison of shadow models and their impact on precise orbit determination of BeiDou satellites during eclipsing phases
Authors: Zhang Yan , Wang Xiaoya , Xi Kewei , Li Zhen
Published: August 2022

Solar radiation pressure (SRP) is an extremely critical perturbative force that affects the GNSS satellites’ precise orbit determination (POD). Its imperfect modelling is one of the main error sources of POD, whose magnitude is even to10−9 m/s2. The shadow factor (i.e., eclipse factor) is one crucial parameter of SRP, generally estimated by the cylindrical model, the conical model, or shadow models considering the Earth’s oblateness and the atmospheric effect, such as the Perspective Projection Method atmosphere (PPMatm) model and Solar radiation pressure with Oblateness and Lower Atmospheric Absorption, Refraction, and Scattering Curve Fit (SOLAARS-CF) model. This paper applies the former four shadow models to determine the corresponding precise orbit using BeiDou satellites’ ground-based observation, and then compared and assessed the orbit accuracy through Satellite Laser Ranging (SLR) validation and Inter-Satellite Link (ISL) check. The results show that the PPMatm model’s accuracy is equivalent to the SOLAARS-CF model. Compared with the conical shadow model, SLR validations show the orbit accuracy from the PPMatm and SOLAARS-CF model can be generally improved by 2–10 mm; ISL range check shows that the Root Mean Square (RMS) can be decreased by 2–7 mm. These results show that the shadow model in GNSS POD should fully consider the Earth’s oblateness and the atmospheric effect, especially for the perturbative acceleration higher than 10–10 m/s2.

Graphical Abstract
Determinants of work and social participation in patients with psoriatic arthritis in the Netherlands: an observational study
Authors: van Hal Tamara W. , Mulder Michelle L. M. , Wenink Mark H. , Vriezekolk Johanna E.
Published: August 2022

Background

Psoriatic arthritis can cause pain, disability, and permanent joint damage. This can lead to impairments in work and social participation. Little is known about the extent of these impairments in routine practice. With this study, we aim to examine the extent of work and activity impairment in (subgroups of) Dutch patients with psoriatic arthritis (PsA), and to examine determinants associated with this impairment.

Methods

This is an observational study using data collected from the electronic health records of PsA patients treated at the Sint Maartenskliniek, the Netherlands. Data about work and activity impairment were collected via the Work Productivity and Activity Impairment questionnaire. To compare our PsA-cohort with the Dutch general population, we used age- and sex-matched data derived from the Central Bureau of Statistics. Regression analyses were performed to examine determinants of work and activity impairment.

Results

In total, 246 patients were included, of which 126 (51.2%) were female. Mean age (S.D.) was 55.7 (13.2) years. Compared with the Dutch general population, work for pay (WFP) was significantly lower in PsA (52.9% versus 62.6%, P < 0.001). In PsA, younger age and better physical function were associated with WFP status (P < 0.05). Higher disease activity, worse physical function, and worse mental health-related quality of life were associated with both more work and activity impairment (P < 0.05). Furthermore, reaching low disease activity status (LDA) according to Psoriatic ArthritiS Disease Activity Score (PASDAS; ≤ 3.2) was associated with less work and activity impairment than reaching LDA according to DAS28-CRP (≤ 2.9) (P < 0.05).

Conclusions

In PsA patients, worse physical function was associated with a lower likelihood of having WFP, and higher work and activity impairment. PASDAS LDA as a goal for treat to target, compared to DAS28-CRP, appears to favour the reduction of work and activity impairment.
Hands-on training in structural biology, a tool for sustainable development in Africa series 4
Authors: Ouologuem Dinkorma T. , Maiga Fatoumata O. , Dara Antoine , Djimdé Abdoulaye , Traore Daouda A. K. , Nji Emmanuel
Published: August 2022

Structural biology is an essential tool for understanding the molecular basis of diseases, which can guide the rational design of new drugs, vaccines, and the optimisation of existing medicines. However, most African countries do not conduct structural biology research due to limited resources, lack of trained persons, and an exodus of skilled scientists. The most urgent requirement is to build on the emerging centres in Africa – some well-established, others growing. This can be achieved through workshops that improve networking, grow skills, and develop mechanisms for access to light source beamlines for defining X-ray structures across the continent. These would encourage the growth of structural biology, which is central to understanding biological functions and developing new antimicrobials and other drugs. In this light, a hands-on training workshop in structural biology series 4 was organised by BioStruct-Africa and the Malaria Research and Training Center (MRTC) in Bamako, Mali, to help bridge this gap. The workshop was hosted by MRTC from the 25th to 28th of April 2022. Through a series of lectures and practicals, the workshop enlightened the participants on how structural biology can be utilised to find solutions to the prevalent diseases in Africa. The short training gave them an overview of target selection, protein production and purification, structural determination techniques, and analysis in combination with high-throughput, structure-guided, fragment-based drug design.
Transitions in development – an interview with Aman Husbands
Authors: Grewal Seema
Published: August 2022

Aman Husbands is the Mitchell J. Blutt and Margo Krody Blutt Presidential Assistant Professor of Biology at the University of Pennsylvania, USA. He set up his research group in January 2018 at Ohio State University, before moving across to the University of Pennsylvania. His work focuses on CLASS III HOMEODOMAIN LEUCINE ZIPPER (HD-ZIPIII) transcription factors and how they function in different contexts during plant development and evolution. We chatted with Aman to find out more about his career path and the challenges of becoming an independent group leader.
A multidimensional metabolomics workflow to image biodistribution and evaluate pharmacodynamics in adult zebrafish
Authors: Jackstadt Madelyn M. , Chamberlain Casey A. , Doonan Steven R. , Shriver Leah P. , Patti Gary J.
Published: August 2022

An integrated evaluation of the tissue distribution and pharmacodynamic properties of a therapeutic is essential for successful translation to the clinic. To date, however, cost-effective methods to measure these parameters at the systems level in model organisms are lacking. Here, we introduce a multidimensional workflow to evaluate drug activity that combines mass spectrometry-based imaging, absolute drug quantitation across different biological matrices, in vivo isotope tracing and global metabolome analysis in the adult zebrafish. As a proof of concept, we quantitatively determined the whole-body distribution of the anti-rheumatic agent hydroxychloroquine sulfate (HCQ) and measured the systemic metabolic impacts of drug treatment. We found that HCQ distributed to most organs in the adult zebrafish 24 h after addition of the drug to water, with the highest accumulation of both the drug and its metabolites being in the liver, intestine and kidney. Interestingly, HCQ treatment induced organ-specific alterations in metabolism. In the brain, for example, HCQ uniquely elevated pyruvate carboxylase activity to support increased synthesis of the neuronal metabolite, N-acetylaspartate. Taken together, this work validates a multidimensional metabolomics platform for evaluating the mode of action of a drug and its potential off-target effects in the adult zebrafish.

This article has an associated First Person interview with the first author of the paper.
Η κοινωνική διάσταση της Διοίκησης των Ανθρώπινων Πόρων στο πλαίσιο της Εταιρικής Κοινωνικής Ευθύνης
Authors: Κακουλίδης Κωνσταντίνος
Published: August 2022

Η επικρατούσα άποψη ότι η επιχειρηματικότητα περιορίζεται στην καταγραφή των νέων επιχειρήσεων που ιδρύονται στη πορεία του χρόνου, είναι εσφαλμένη λόγω του ότι πλέον, είναι ευρέως δεκτό, ότι η επιχειρηματικότητα, με την ευρεία της έννοια, εκφράζει, πάνω απ' όλα, "τρόπους σκέψης" και συμπεριφορές ατόμων ή ομάδων. Η Εταιρική Κοινωνική Ευθύνη (ΕΚΕ), υπό αυτή την έννοια, προδιαγράφει μια σύγχρονη αντίληψη διοίκησης που επηρεάζει δραστικά τις εταιρικές αξίες και αρχές, στο πλαίσιο της σύγχρονης επιχειρηματικής δράσης, και απευθύνεται κυρίως, στην κατεύθυνση της βιώσιμης ανάπτυξης και της κοινωνικής ευημερίας. Οι σύγχρονες κοινωνίες αποδέχονται πλέον την αναγκαιότητα να οργανώνονται και να λειτουργούν οι επιχειρήσεις στη κατεύθυνση δημιουργίας ισχυρών δεσμών με τις τοπικές κοινωνίες καλλιεργώντας και αναπτύσσοντας την ιδέα της Εταιρικής Κοινωνικής Ευθύνης (ΕΚΕ) και της Εταιρικής Ηθικής. Η Εταιρική Ηθική ή δεοντολογία συνδεόμενη με την ΕΚΕ έχει ευθεία αναφορά σε πρότυπα εσωτερικά και εξωτερικά και σε κώδικες συμπεριφοράς. Σημαντικό ανταγωνιστικό πλεονέκτημα των οργανισμών είναι το εργατικό δυναμικό, οι ανθρώπινοι πόροι, με υψηλές γνωστικές ικανότητες και πολλαπλές δεξιότητες. Διαχείριση Ανθρώπινων Πόρων (ΔΑΠ) ορίζεται η διαχείριση των ανθρώπων, που σε ατομικό αλλά και συλλογικό επίπεδο, συντελεί δραστικά στην υλοποίηση των επιχειρηματικών στόχων και στην ανάπτυξη εν γένει των επιχειρήσεων. Παράμετρος της αποτελεσματικότητας είναι η ευελιξία στην εργασία η οποία υπακούει στις διαρθρωτικές μεταβολές της αγοράς. Στην παρούσα διατριβή οριοθετήθηκε ο ερευνητικός στόχος με κεντρικό ζήτημα τη Δημόσια Επιχείρηση Ηλεκτρισμού (ΔΕΗ) Α.Ε. Τέθηκαν ζητήματα εκσυγχρονισμού ρυπογόνων παραγωγικών μονάδων, μετεγκατάσταση οικισμών, αποκατάσταση εδαφών και εδαφικού πλούτου, ανάπτυξη πολιτικής πράσινης ενέργειας, ανάπτυξη πολιτικών στο πεδίο της κοινωνικής και εταιρικής ευθύνης.
Kültürel Kavramsallaştırma Örneği: Eski Uygur Sivil Metinlerindeki Örü Kodı Bol- Yapısı Üzerine
Authors: AZILI Kenan
Published: August 2022

Eski Uygur sivil metinleri, diğer Eski Türkçe metinlerin aksine dinî içerikli tercüme yoluyla oluşturulmamış, hayatın içinde, halkın sosyal aktivitelerini gösterecek biçimde yazılmıştır. Bu anlamda metinler çok farklı düzeyde kültür kodlarını taşımaktadır. Bu metinlerde yer alan örü kodı bol- ifadesi, bugüne kadar yapılan çalışmalarda çeşitli anlamlandırma teklifleri yapılsa da tam anlamıyla özüme kavuşamamıştır. İfadenin dil bilimsel açıdan mukayeseli incelenmesinin yanında kültürel kavramsallaştırma yönünden dil ve kültür ilişkisi içinde yeniden ele alınması gerekmektedir. Çalışmada, söz konusu ifadenin dil bilimsel değerlendirmesi için öncelikle ifadeyi oluşturan örü kodı yapısı incelenecektir. Daha sonra formun yardımcı fiil ile oluşturulmuş son şekli, metinlerde tanıklanarak sentaktik dizilimin pragmatik sıralaması göz önünde bulundurulup diğer formlarla denkliği kurulacaktır. Bu evrede kurulan denklikler kültür dil bilimin kültürel kavramsallaştırma dalına göre değerlendirilecek ve kültürel kodları analiz edilecektir. Çalışmanın en önemli amacı, bazı dil formlarının sadece dil bilimsel izah ile çözülemeyeceği, dil kültür ilişkisi ile kültür dil bilim gibi farklı disiplinlerin yardımı ile çözmek gerektiğini göstermektir.
XI.-XII. Yüzyıllar Eski Türk Dili Söz Varlığının Divânu Lugâti’t-Türk’teki İfadesi
Authors: DADABAYEV Hamidulla
Published: August 2022

Tarihî karşılaştırmalı dil biliminin gelişiminde büyük önem arz eden Divânu Lugâti’t-Türk Karahanlılar dönemi Türkçesinin özelliklerini yansıtan nadir bir kaynaktır. Eserde Eski Türkçenin zengin söz varlığı, Türkçedeki dil bilimsel süreçlerin gelişimi, kelime yapımı özellikleri, anlam daralması, anlam genişlemesi, anlam karşıtlıkları gibi semantik değişimler, Türk boylarının söz varlığındaki benzerlik ve farklılıklar, kelimelerin etimolojisi, yer adları (toponimler), bazı kelimelerin ansiklopedik açıklamaları üzerinde durulmuştur. Makalenin temel amacı XI.-XII. yüzyıllar Eski Türk Dili söz varlığının Divânu Lugâti’t-Türk’teki yansımalarını araştırmaktır.
Turkey’s Security Policy towards Northern Syria and Iraq amid Regional Chaos (2011-2019)
Authors: SADRI ALIBABALU Sayyad
Published: August 2022

This study seeks to explain Turkey’s policies towards Iraq and Northern Syria in the context of regional geopolitical competition. The paper first explains the structure of the regional competitive system in the Middle East by taking into consideration the role and impact of Turkey, Iran and Saudi Arabia. Secondly, by focusing on the strategic goals of the regional actors, the paper contextualizes the logic of strategic rationality behind Turkey’s military and political engagements in Syria and Iraq. Finally, the research is addressing Turkey’s strategy for settling the Syrian
crisis. One of the most important threats against Turkey during this period has been the emergence of the YPG, the Syrian offshoot of the PKK terrorist organization, which became the central component of the counter-terrorism policy of the US against ISIS. With the deepening of the crises in Syria and then in Iraq, as well as the failed military coup in Turkey in 2016, the government has changed its strategy and has consolidated itself as one of the most effective players in the Syrian crisis. The overall assessment of this research is that Turkey has managed the emerged threats in northern Syria and Iraq by pursuing a twin pillar policy and relying on diplomatic and especially hard power capacities and eventually, has become a pole in resolving the Syrian crisis since
2016 when gradually moved away from the Western coalition.