bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolomics and transcriptomics of embryonic livers reveal hypoxia adaptation of Tibetan chickens
Authors: Xue Mingming , Yu Runjie , Yang Lixian , Xie Fuyin , Fang Meiying , Tang Qiguo 
Published: February 2024

Abstract
Background
Exploring the hypoxia adaptation mechanism of Tibetan chicken is of great significance for revealing the survival law of Tibetan chicken and plateau animal husbandry production. To investigate the hypoxia adaptation of Tibetan chickens (TBCs), an integrative metabolomic-transcriptomic analysis of the liver on day 18 of embryonic development was performed. Dwarf laying chickens (DLCs), a lowland breed, were used as a control.

Results
A total of 1,908 metabolites were identified in both TBCs and DLCs. Energy metabolism and amino acid metabolism related differentially regulated metabolites (DRMs) were significantly enriched under hypoxia. Important metabolic pathways including the TCA cycle and arginine and proline metabolism were screened; PCK1, SUCLA2, and CPS1 were found to be altered under hypoxic conditions. In addition, integrated analysis suggested potential differences in mitochondrial function, which may play a crucial role in the study of chicken oxygen adaptation.

Conclusions
These results suggest that hypoxia changed the gene expression and metabolic patterns of embryonic liver of TBCs compared to DLCs. Our study provides a basis for uncovering the molecular regulation mechanisms of hypoxia adaptation in TBCs with the potential application of hypoxia adaptation research for other animals living on the Qinghai-Tibet plateau, and may even contribute to the study of diseases caused by hypoxia.
Implementing and evaluating a fully functional AI-enabled model for chronic eye disease screening in a real clinical environment
Authors: Skevas Christos , de Olaguer Nicolás Pérez , Lleó Albert , Thiwa David , Schroeter Ulrike , Lopes Inês Valente , Mautone Luca , Linke Stephan J. , Spitzer Martin Stephan , Yap Daniel , Xiao Di 
Published: February 2024

Abstract
Background
Artificial intelligence (AI) has the potential to increase the affordability and accessibility of eye disease screening, especially with the recent approval of AI-based diabetic retinopathy (DR) screening programs in several countries.

Methods
This study investigated the performance, feasibility, and user experience of a seamless hardware and software solution for screening chronic eye diseases in a real-world clinical environment in Germany. The solution integrated AI grading for DR, age-related macular degeneration (AMD), and glaucoma, along with specialist auditing and patient referral decision. The study comprised several components: (1) evaluating the entire system solution from recruitment to eye image capture and AI grading for DR, AMD, and glaucoma; (2) comparing specialist’s grading results with AI grading results; (3) gathering user feedback on the solution.

Results
A total of 231 patients were recruited, and their consent forms were obtained. The sensitivity, specificity, and area under the curve for DR grading were 100.00%, 80.10%, and 90.00%, respectively. For AMD grading, the values were 90.91%, 78.79%, and 85.00%, and for glaucoma grading, the values were 93.26%, 76.76%, and 85.00%. The analysis of all false positive cases across the three diseases and their comparison with the final referral decisions revealed that only 17 patients were falsely referred among the 231 patients. The efficacy analysis of the system demonstrated the effectiveness of the AI grading process in the study’s testing environment. Clinical staff involved in using the system provided positive feedback on the disease screening process, particularly praising the seamless workflow from patient registration to image transmission and obtaining the final result. Results from a questionnaire completed by 12 participants indicated that most found the system easy, quick, and highly satisfactory. The study also revealed room for improvement in the AMD model, suggesting the need to enhance its training data. Furthermore, the performance of the glaucoma model grading could be improved by incorporating additional measures such as intraocular pressure.

Conclusions
The implementation of the AI-based approach for screening three chronic eye diseases proved effective in real-world settings, earning positive feedback on the usability of the integrated platform from both the screening staff and auditors. The auditing function has proven valuable for obtaining efficient second opinions from experts, pointing to its potential for enhancing remote screening capabilities.

Trial registration
Institutional Review Board of the Hamburg Medical Chamber (Ethik-Kommission der Ärztekammer Hamburg): 2021-10574-BO-ff.
Prevalence and factors associated with inter-arm systolic and diastolic blood pressure differences: results from the baseline Fasa Adult’s Cohort Study (FACS)
Authors: Mouseli Ali , Sharafi Mehdi , Amiri Zahra , Dehghan Azizallah , Haghjoo Elham , Mohsenpour Mohammad Ali , Eftekhari Mohammad Hassan , Fatemian Hossein , Keshavarzian Omid 
Published: February 2024

Abstract
Background
One of the modifiable risk factors for cardiovascular diseases is the inter-arm blood pressure difference (IAD), which can be easily measured. This study aimed to determine the prevalence and factors related to the Iranian population’s inter-arm differences in systolic and diastolic blood pressure.

Method
This cross-sectional study was conducted on the baseline data of participants who had Iranian nationality, were at least 1 year of residence in the area, aged within the age range of 35–70 years, and willed to participate from the Fasa Persian Adult Cohort Study (FACS). IAD for systolic and diastolic blood pressure was measured and categorized into two groups of difference < 10 and ≥ 10 mmHg. Logistic regression was used to model the association between independent variables and IAD.

Results
The prevalence of systolic and diastolic IAD ≥ 10 mmHg was 16.34% and 10.2%, respectively, among 10,124 participants. According to the multivariable logistic regression models, age (adjusted odds ratio (aOR): 1.019 [95% CI: 1.013, 1.025]), body mass index (BMI) (aOR: 1.112 [95% CI: 1.016, 1.229]), having type 2 diabetes (aOR Yes/No: 1.172 [95% CI: 1.015, 1.368]), having chronic headaches (aOR Yes/No: 1.182 [95% CI: 1.024, 1.365]), and pulse rate (aOR: 1.019 [95% CI: 1.014, 1.024]) significantly increased the odds of systolic IAD ≥ 10 mmHg. Additionally, high socio-economic status decreased the odds of systolic IAD ≥ 10 mmHg (aOR High/Low: 0.854 [95% CI: 0.744, 0.979]). For diastolic IAD, age (aOR: 1.112 [95% CI: 1.015, 1.210]) and pulse rate (aOR: 1.021 [95% CI: 1.015, 1.027]) significantly increased the odds of diastolic IAD ≥ 10 mmHg. Moreover, high socioeconomic status decreased the odds of diastolic IAD ≥ 10 mmHg (aOR High/Low: 0.820 [95% CI: 0.698, 0.963]).

Conclusion
The noticeable prevalence of systolic and diastolic IAD in general population exhibits health implications due to its’ association with the risk of cardiovascular events. Sociodemographic and medical history assessments have potentials to be incorporated in IAD risk stratification and preventing programs.
Deep orange gene editing triggers temperature-sensitive lethal phenotypes in Ceratitis capitata
Authors: Sollazzo Germano , Nikolouli Katerina , Gouvi Georgia , Aumann Roswitha A. , Schetelig Marc F. , Bourtzis Kostas 
Published: February 2024

Abstract
Background
The Mediterranean fruit fly, Ceratitis capitata, is a significant agricultural pest managed through area-wide integrated pest management (AW-IPM) including a sterile insect technique (SIT) component. Male-only releases increase the efficiency and cost-effectiveness of SIT programs, which can be achieved through the development of genetic sexing strains (GSS). The most successful GSS developed to date is the C. capitata VIENNA 8 GSS, constructed using classical genetic approaches and an irradiation-induced translocation with two selectable markers: the white pupae (wp) and temperature-sensitive lethal (tsl) genes. However, currently used methods for selecting suitable markers and inducing translocations are stochastic and non-specific, resulting in a laborious and time-consuming process. Recent efforts have focused on identifying the gene(s) and the causal mutation(s) for suitable phenotypes, such as wp and tsl, which could be used as selectable markers for developing a generic approach for constructing GSS. The wp gene was recently identified, and efforts have been initiated to identify the tsl gene. This study investigates Ceratitis capitata deep orange (Ccdor) as a tsl candidate gene and its potential to induce tsl phenotypes.

Results
An integrated approach based on cytogenetics, genomics, bioinformatics, and gene editing was used to characterize the Ccdor. Its location was confirmed on the right arm of chromosome 5 in the putative tsl genomic region. Knock-out of Ccdor using CRISPR/Cas9-NHEJ and targeting the fourth exon resulted in lethality at mid- and late-pupal stage, while the successful application of CRISPR HDR introducing a point mutation on the sixth exon resulted in the establishment of the desired strain and two additional strains (dor 12del and dor 51dup), all of them expressing tsl phenotypes and presenting no (or minimal) fitness cost when reared at 25 °C. One of the strains exhibited complete lethality when embryos were exposed at 36 °C.

Conclusions
Gene editing of the deep orange gene in Ceratitis capitata resulted in the establishment of temperature-sensitive lethal mutant strains. The induced mutations did not significantly affect the rearing efficiency of the strains. As deep orange is a highly conserved gene, these data suggest that it can be considered a target for the development of tsl mutations which could potentially be used to develop novel genetic sexing strains in insect pests and disease vectors.
Can medication-related osteonecrosis of the jaw be attributed to specific microorganisms through oral microbiota analyses? A preliminary study
Authors: Kim Heon-Young , Jung Young-Soo , Park Wonse , Choi Yoon Jeong , Kim Jun-Young 
Published: February 2024

Abstract
Background
Medication-related osteonecrosis of the jaw (MRONJ) can cause significant pain and loss of aesthetics and function if not treated properly. However, diagnosis still relies on detailed intraoral examinations and imaging. Prognosis varies even among patients with similar stages or conditions of MRONJ, emphasizing the need for a deeper understanding of its complex mechanisms. Thus, this study aimed to identify the oral microbiota of patients with MRONJ.

Methods
This single-center prospective cohort study included patients with confirmed MRONJ who visited the Department of Oral and Maxillofacial Surgery at Yonsei University Dental Hospital between 2021 and 2022. Oral swab samples were collected from the affected and unaffected sides of each patient. The composition and enumeration of the microbial communities were analyzed, and the diversity was compared to verify ecological changes in the groups using a next-generation sequencing-based 16S metagenomic analysis. A statistical analysis was performed using Wilcoxon signed-rank test with SPSS version 22, and values of P less than 0.05 were considered statistically significant.

Results
The final study sample included 12 patients. The mean age was 82.67 ± 5.73 (range, 72–90) years. Changes in microbial composition were observed at different taxonomic levels (phylum, genus, and species). The identified microorganisms were commonly associated with periodontitis, gingival disease, and endodontic infection, suggesting a multifactorial etiology of MRONJ.

Conclusions
Although this study is based on a small number of cases, it shows that MRONJ is not caused by a specific microorganism but can rather be caused by a variety of factors. By addressing these findings in large-scale studies, the significance of oral microbiome in pathogenesis can be further elucidated and can facilitate the development of effective therapeutic interventions for patients with MRONJ.
Phytochemical screening and antimicrobial activity of Polygala sadebeckiana Gürke extracts on bacterial isolates from Wound samples of patients with “Shimetere”
Authors: Zeleke Bereket , Mekonnen Zebene , Bireda Meskele , Yitbarek Melaku , Dendir Andamlak 
Published: February 2024

Abstract
Background
Modern medicine is not the choice of patients with “shimetere” in the Gurage community owing to their perception of ‘parenteral medication use severely aggravates the disease’. For this reason, the root part of Polygala sadebeckiana Gürke is commonly utilized as traditional medicine in the management of the disease. The aim of this study was to evaluate the antimicrobial activity of Polygala sadebeckiana Gürke extract on bacterial isolates from wound samples of patients with “Shimetere”.

Methods
The agar well diffusion method was used to evaluate antibacterial activity, and the agar dilution method was utilized to determine minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MICs). The crude extract was tested against isolated bacteria at concentrations of 25, 50, 75 and 100 mg/mL in triplicate (3x). The positive controls were azithromycin (15 µg) and cloxacillin disk (5 µg), and the negative control was dimethylsulfoxide (5%). The group mean comparisons were made using one-way ANOVA at a significance level of p < 0.05, and the results are presented as the mean ± standard deviation. The presence of secondary metabolites from crude extract was checked by standard testing procedures.

Results
S. aureus and S. pyrogen were the two identified bacteria from 9 (60%) and 3 (20%) wound samples, respectively. All identified bacterial strains were susceptible to the reference antibiotics. Tannins and saponins were the most abundant secondary metabolites found in the crude extracts. The average inhibition zones of the plant extracts with 100, 75, 50 and 25 mg/mL concentrations were 27, 20.33, 15.25, and 11.96 mm (p < 0.000) for S. aureus and 30.02, 24.50, 19.07, and 15.77 mm (p < 0.000) for S. pyrogen bacteria, respectively. The MIC and MBC of the crude extract were 1.67 and 10 mg/mL for S. aureus and 0.98 and 4 mg/mL for S. pyrogen.

Conclusion
Polygala sadebeckiana Gürke contained significant tannins and saponins as secondary metabolites and had antibacterial activities against isolated bacteria (S. aureus and S. pyrogen) from “Shimetere”. The potential mechanism of antibacterial action of the plant extract was cell wall synthesis inhibition.
Perspectives of key informants before and after implementing UPSIDES peer support in mental health services: qualitative findings from an international multi-site study
Authors: Haun Maria , Adler Ben-Dor Inbar , Hall Cerdic , Kalha Jasmine , Korde Palak , Moran Galia , Müller-Stierlin Annabel S. , Niwemuhwezi Jackline , Nixdorf Rebecca , Puschner Bernd , Ramesh Mary , Charles Ashleigh , Krumm Silvia 
Published: February 2024

Abstract
Background
Peer support is an essential part of recovery-oriented care worldwide. Contextual factors have an impact on the implementation of peer support work. However, research has paid little attention to similarities and differences of implementation factors in settings varying by income-level and cultural values. The aim of this study is to assess the factors influencing the implementation of a peer support intervention across study sites in low-, middle- and high-income countries in line with the Consolidation Framework for Implementation Research (CFIR).

Method
6 focus groups with a total of 54 key informants with relevant contextual (organisational) knowledge regarding implementation facilitators and barriers were conducted at six study sites Ulm and Hamburg (Germany), Butabika (Uganda), Dar es Salaam (Tanzania), Be’er Sheva (Israel), and Pune (India) before and 1.5 years after the start of UPSIDES peer support. Transcripts were analysed using qualitative content analysis.

Results
Across study sites key informants reported benefits of peer support for service users and peer support workers as implementation facilitators. At study sites with lower resources, reduced workload for mental health workers and improved access to mental health services through peer support were perceived as implementation facilitators (CFIR Domain 1: Intervention characteristics). The degree of engagement of mental health workers (CFIR Domain 3: Inner Setting/Domain 4: Individuals involved) varied across study sites and was seen either as a barrier (low engagement) or a facilitator (high engagement). Across study sites, adequate training of peer support workers (CFIR Domain 5: Implementation process) was seen as animplementation facilitator, while COVID-19 as well as low resource availability were reported as implementation barriers (CFIR Domain 2: Outer setting).

Conclusions
This study highlights the importance of considering contextual factors when implementing peer support, including previous experience and perceived benefits. Particular attention should be given to organisational benefits such as workload reduction and the allocation of sufficient resources as key drivers in LMICs. In HICs, the potential of organisational benefits for successful implementation should be further investigated and promoted.
Barriers and facilitators to accessing adolescents’ mental health services in Karachi: users and providers perspectives
Authors: Mubeen Zainab , Fatmi Zafar , Hameed Waqas , Asim Muhammad 
Published: February 2024

AbstractIntroductionAdolescents’ Mental Healthcare (MHC) is influenced by numerous factors, and adolescents occasionally seek professional help for mental health (MH) issues. These factors become more complex within low-middle-income countries (LMICs); therefore, this study aims to understand barriers and facilitators to access mental health services among adolescents aged 10 to 19 years old from the perspective of users (parents) and providers (Mental Healthcare Providers - MHPs).MethodUsing a qualitative exploratory design, a semi-structured interview guide was developed using Andersen’s health service utilization model. In-depth interviews were conducted with MHPs (n = 21) and parents of adolescents (n = 19) in the psychiatry department of public and private hospitals in Karachi, from October—December 2021. Data was thematically analyzed using an inductive approach.ResultThe findings revealed a consensus of users and providers in all three categories of the Andersen model and referred the compulsion as the major driving force to MHC access and utilization rather than personal choices. Within pre-disposing, need, and enabling factors; the participants highlighted a unique perspective; users regarded frequent migration, daily wage loss, and women’s societal status as barriers while the need for marriage and patient willingness were stated as facilitators. Whereas, MHPs indicated societal tolerance, the burden on the health system, and the absence of Child and Adolescent Mental Health (CAMH) services as major gaps in service delivery.ConclusionService utilization is mainly facilitated by the severity of illness rather than healthy choices and beliefs, and accessibility and affordability. It is therefore imperative to prioritize adolescent MH through promotion and prevention approaches and address service delivery gaps to prevent treatment delays via task-shifting and capacity building of the health workforce.
BNIPL is a promising biomarker of laryngeal cancer: novel insights from bioinformatics analysis and experimental validation
Authors: Wang Rui , Gao Ying , Wen Shuxin , Guo Xiudong 
Published: February 2024

Abstract
Background
Laryngeal cancer (LC) is a malignant tumor with high incidence and mortality. We aim to explore key genes as novel biomarkers to find potential target of LC in clinic diagnosis and treatment.

Methods
We retrieved GSE143224 and GSE84957 datasets from the Gene Expression Omnibus database to screen the differentially expressed genes (DEGs). Hub genes were identified from protein-protein interaction networks and further determined using receiver operating characteristic curves and principal component analysis. The expression of hub gene was verified by quantitative real time polymerase chain reaction. The transfection efficiency of BCL2 interacting protein like (BNIPL) was measured by western blot. Proliferation, migration, and invasion abilities were detected by Cell Counting Kit-8, wound-healing, and transwell assays, respectively.

Results
Total 96 overlapping DEGs were screened out from GSE143224 and GSE84957 datasets. Six hub genes (BNIPL, KRT4, IGFBP3, MMP10, MMP3, and TGFBI) were identified from PPI network. BNIPL was selected as the target gene. The receiver operating characteristic curves of BNIPL suggested that the false positive rate was 18.5% and the true positive rate was 81.5%, showing high predictive values for LC. The expression level of BNIPL was downregulated in TU212 and TU686 cells. Additionally, overexpression of BNIPL suppressed the proliferation, migration, and invasion of TU212 and TU686 cells.

Conclusion
BNIPL is a novel gene signature involved in LC progression, which exerts an inhibitory effect on LC development. These findings provide a novel insight into the pathogenesis of LC.
The value of machine learning approaches in the diagnosis of early gastric cancer: a systematic review and meta-analysis
Authors: Shi Yiheng , Fan Haohan , Li Li , Hou Yaqi , Qian Feifei , Zhuang Mengting , Miao Bei , Fei Sujuan 
Published: February 2024

Abstract
Background
The application of machine learning (ML) for identifying early gastric cancer (EGC) has drawn increasing attention. However, there lacks evidence-based support for its specific diagnostic performance. Hence, this systematic review and meta-analysis was implemented to assess the performance of image-based ML in EGC diagnosis.

Methods
We performed a comprehensive electronic search in PubMed, Embase, Cochrane Library, and Web of Science up to September 25, 2022. QUADAS-2 was selected to judge the risk of bias of included articles. We did the meta-analysis using a bivariant mixed-effect model. Sensitivity analysis and heterogeneity test were performed.

Results
Twenty-one articles were enrolled. The sensitivity (SEN), specificity (SPE), and SROC of ML-based models were 0.91 (95% CI: 0.87–0.94), 0.85 (95% CI: 0.81–0.89), and 0.94 (95% CI: 0.39–1.00) in the training set and 0.90 (95% CI: 0.86–0.93), 0.90 (95% CI: 0.86–0.92), and 0.96 (95% CI: 0.19–1.00) in the validation set. The SEN, SPE, and SROC of EGC diagnosis by non-specialist clinicians were 0.64 (95% CI: 0.56–0.71), 0.84 (95% CI: 0.77–0.89), and 0.80 (95% CI: 0.29–0.97), and those by specialist clinicians were 0.80 (95% CI: 0.74–0.85), 0.88 (95% CI: 0.85–0.91), and 0.91 (95% CI: 0.37–0.99). With the assistance of ML models, the SEN of non-specialist physicians in the diagnosis of EGC was significantly improved (0.76 vs 0.64).

Conclusion
ML-based diagnostic models have greater performance in the identification of EGC. The diagnostic accuracy of non-specialist clinicians can be improved to the level of the specialists with the assistance of ML models. The results suggest that ML models can better assist less experienced clinicians in diagnosing EGC under endoscopy and have broad clinical application value.