bluuebunny/crossref_metadata_2025 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

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

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

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

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

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

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

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

Introduction

Adolescents’ 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).

Method

Using 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.

Result

The 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.

Conclusion

Service 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

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

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.
Mechanosensitive channel of large conductance enhances the mechanical stretching-induced upregulation of glycolysis and oxidative metabolism in Schwann cells
Authors: Shan Fangzhen , Zhang Nannan , Yao Xiaoying , Li Yi , Wang Zihao , Zhang Chuanji , Wang Yuzhong
Published: February 2024

Background

Physical exercise directly stretching the peripheral nerve promotes nerve regeneration; however, its action mechanism remains elusive. Our present study aimed to investigate the effects of mechanosensitive channel of large conductance (MscL) activated by mechanical stretching on the cultured Schwann cells (SCs) and explore the possible mechanism.

Methods

Primary SCs from neonatal mice at 3–5 days of age were derived and transfected with the lentivirus vector expressing a mutant version of MscL, MscL-G22S. We first detected the cell viability and calcium ion (Ca2+) influx in the MscL-G22S-expressing SCs with low-intensity mechanical stretching and the controls. Proteomic and energy metabolomics analyses were performed to investigate the comprehensive effects of MscL-G22S activation on SCs. Measurement of glycolysis- and oxidative phosphorylation-related molecules and ATP production were respectively performed to further validate the effects of MscL-G22S activation on SCs. Finally, the roles of phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway in the mechanism of energy metabolism modulation of SCs by MscL-G22S activation was investigated.

Results

Mechanical stretching-induced MscL-G22S activation significantly increased the cell viability and Ca2+ influx into the SCs. Both the proteomic and targeted energy metabolomics analysis indicated the upregulation of energy metabolism as the main action mechanism of MscL-G22S-activation on SCs. MscL-G22S-activated SCs showed significant upregulation of glycolysis and oxidative phosphorylation when SCs with stretching alone had only mild upregulation of energy metabolism than those without stimuli. MscL-G22S activation caused significant phosphorylation of the PI3K/AKT/mTOR signaling pathway and upregulation of HIF-1α/c-Myc. Inhibition of PI3K abolished the MscL-G22S activation-induced upregulation of HIF-1α/c-Myc signaling in SCs and reduced the levels of glycolysis- and oxidative phosphorylation-related substrates and mitochondrial activity.

Conclusion

Mechanical stretching activates MscL-G22S to significantly promote the energy metabolism of SCs and the production of energic substrates, which may be applied to enhance nerve regeneration via the glia-axonal metabolic coupling.
Effects of a dietary intervention with lacto-ovo-vegetarian and Mediterranean diets on apolipoproteins and inflammatory cytokines: results from the CARDIVEG study
Authors: Pagliai Giuditta , Tristan Asensi Marta , Dinu Monica , Cesari Francesca , Bertelli Alessia , Gori Anna Maria , Giusti Betti , Marcucci Rossella , Sofi Francesco , Colombini Barbara
Published: February 2024

Background

Apolipoproteins have been recently proposed as novel markers of cardiovascular disease (CVD) risk. However, evidence regarding effects of diet on apolipoproteins is limited.

Aim

To compare the effects of Mediterranean diet (MD) and lacto-ovo vegetarian diet (VD) on apolipoproteins and traditional CVD risk factors in participants with low-to-moderate CVD risk.

Methods

Fifty-two participants (39 women; 49.1 ± 12.4 years), followed MD and VD for 3 months each. Medical and dietary information was collected at the baseline. Anthropometric parameters and blood samples were obtained at the beginning and the end of interventions.

Results

MD and VD resulted in significant improvement in anthropometric and lipid profiles. Both diets led to a reduction in most of the inflammatory parameters. As for apolipoproteins, a significant change was observed for ApoC-I after VD (+ 24.4%; p = 0.020). MD led to a negative correlation between ApoC-III and carbohydrates (R = − 0.29; p = 0.039) whereas VD between ApoD and saturated fats (R = − 0.38; p = 0.006). A positive correlation emerged after VD between HDL and ApoD (R = 0.33; p = 0.017) and after MD between plasma triglycerides and ApoC-I (R = 0.32; p = 0.020) and ApoD (R = 0.30; p = 0.031). IL-17 resulted to be positively correlated with ApoB after MD (R = 0.31; p = 0.028) and with ApoC-III after VD (R = 0.32; p = 0.019). Subgroup analysis revealed positive effects on apolipoproteins from both diets, especially in women, individuals older than 50 years-old or with < 3 CVD risk factors.

Conclusions

Both diets seem to improve CVD risk, however, MD showed a greater positive effect on apolipoproteins in some subgroups, thus suggesting how diet may influence new potential markers of CVD risk.

Trial registration: registered at clinicaltrials.gov (identifier: NCT02641834) on December 2015.
METTL16 promotes liver cancer stem cell self-renewal via controlling ribosome biogenesis and mRNA translation
Authors: Xue Meilin , Dong Lei , Zhang Honghai , Li Yangchan , Qiu Kangqiang , Zhao Zhicong , Gao Min , Han Li , Chan Anthony K. N. , Li Wei , Leung Keith , Wang Kitty , Pokharel Sheela Pangeni , Qing Ying , Liu Wei , Wang Xueer , Ren Lili , Bi Hongjie , Yang Lu , Shen Chao , Chen Zhenhua , Melstrom Laleh , Li Hongzhi , Timchenko Nikolai , Deng Xiaolan , Huang Wendong , Rosen Steven T. , Tian Jingyan , Xu Lin , Diao Jiajie , Chen Chun-Wei , Chen Jianjun , Shen Baiyong , Chen Hao , Su Rui
Published: February 2024

Background

While liver cancer stem cells (CSCs) play a crucial role in hepatocellular carcinoma (HCC) initiation, progression, recurrence, and treatment resistance, the mechanism underlying liver CSC self-renewal remains elusive. We aim to characterize the role of Methyltransferase 16 (METTL16), a recently identified RNA N6-methyladenosine (m6A) methyltransferase, in HCC development/maintenance, CSC stemness, as well as normal hepatogenesis.

Methods

Liver-specific Mettl16 conditional KO (cKO) mice were generated to assess its role in HCC pathogenesis and normal hepatogenesis. Hydrodynamic tail-vein injection (HDTVi)-induced de novo hepatocarcinogenesis and xenograft models were utilized to determine the role of METTL16 in HCC initiation and progression. A limiting dilution assay was utilized to evaluate CSC frequency. Functionally essential targets were revealed via integrative analysis of multi-omics data, including RNA-seq, RNA immunoprecipitation (RIP)-seq, and ribosome profiling.

Results

METTL16 is highly expressed in liver CSCs and its depletion dramatically decreased CSC frequency in vitro and in vivo. Mettl16 KO significantly attenuated HCC initiation and progression, yet only slightly influenced normal hepatogenesis. Mechanistic studies, including high-throughput sequencing, unveiled METTL16 as a key regulator of ribosomal RNA (rRNA) maturation and mRNA translation and identified eukaryotic translation initiation factor 3 subunit a (eIF3a) transcript as a bona-fide target of METTL16 in HCC. In addition, the functionally essential regions of METTL16 were revealed by CRISPR gene tiling scan, which will pave the way for the development of potential inhibitor(s).

Conclusions

Our findings highlight the crucial oncogenic role of METTL16 in promoting HCC pathogenesis and enhancing liver CSC self-renewal through augmenting mRNA translation efficiency.
Epidemiology of Bartonella henselae infection in pet and stray cats in Croatia with risk factors analysis
Authors: Stepanić Maja , Duvnjak Sanja , Reil Irena , Hađina Suzana , Kempf Volkhard A. J. , Špičić Silvio , Mihaljević Željko , Beck Relja
Published: February 2024

Background

Cats are the primary reservoirs of the bacterium Bartonella henselae, the main cause of cat-scratch disease in humans. The main vector of the bacterium is the cat flea, Ctenocephalides felis. In southeastern Europe, data are lacking on the prevalence of B. henselae infection in cats, the strains of B. henselae involved and the risk factors associated with the infection.

Methods

Blood samples collected in ethylenediaminetetraacetic acid-containing tubes from 189 domestic cats (156 pet cats and 33 stray cats) from Zagreb, the capital city of Croatia, and 10 counties throughout Croatia were cultured for Bartonella spp. Following culture, bacterial isolates were genotyped at eight loci after using PCR to amplify 16S ribosomal RNA (rRNA) and the internal transcribed spacer region between the 16S and 23S rRNA sequences. Univariate and multivariate logistic regression were used to identify risk factors for B. henselae infection in cats.

Results

Bartonella spp. was detected in 31 cats (16.4%), and subsequent genotyping at the eight loci revealed B. henselae in all cases. Thirty complete multilocus sequence typing profiles were obtained, and the strains were identified as four sequence types that had been previously reported, namely ST5 (56.7%), ST6 (23.3%), ST1 (13.3%) and ST24 (3.3%), as well as a novel sequence type, ST33 (3.3%). The univariate analysis revealed a significantly higher risk of B. henselae infection in cats residing in coastal areas of Croatia (odds ratio [OR] 2.592, 95% confidence interval [CI] 1.150–5.838; P = 0.0191) and in cats with intestinal parasites (OR 3.207, 95% CI 1.088–9.457; P = 0.0279); a significantly lower risk was identified in cats aged > 1 year (OR 0.356, 95% CI 0.161–0.787; P = 0.0247) and in cats sampled between April and September (OR 0.325, 95% CI 0.147–0.715; P = 0.005). The multivariate analysis that controlled for age showed a positive association with the presence of intestinal parasites (OR 4.241, 95% CI 1.243–14.470; P = 0.0119) and coastal residence (OR 2.567, 95% CI 1.114–5.915; P = 0.0216) implying increased risk of infection, and a negative association with sampling between April and September (OR 0.379, 95% CI 0.169–0.848; P = 0.018) implying a decreased risk of infection. After controlling for the season, an increased risk of infection remained for the coastal region (OR 2.725, 95% CI 1.200–6.186; P = 0.012).

Conclusions

Bartonella henselae is prevalent throughout Croatia and is a public health threat. Environmental and host factors can significantly affect the risk of infection, and these should be explored in more detail. The presence of intestinal parasites highlights the need to eliminate the flea vector, Ctenocephalides felis, as the most effective approach to control infections in cats and humans.

Graphical Abstract
Macrophage heterogeneity and its interactions with stromal cells in tumour microenvironment
Authors: Cao Liren , Meng Xiaoyan , Zhang Zhiyuan , Liu Zhonglong , He Yue
Published: February 2024

Macrophages and tumour stroma cells account for the main cellular components in the tumour microenvironment (TME). Current advancements in single-cell analysis have revolutionized our understanding of macrophage diversity and macrophage–stroma interactions. Accordingly, this review describes new insight into tumour-associated macrophage (TAM) heterogeneity in terms of tumour type, phenotype, metabolism, and spatial distribution and presents the association between these factors and TAM functional states. Meanwhile, we focus on the immunomodulatory feature of TAMs and highlight the tumour-promoting effect of macrophage–tumour stroma interactions in the immunosuppressive TME. Finally, we summarize recent studies investigating macrophage-targeted therapy and discuss their therapeutic potential in improving immunotherapy by alleviating immunosuppression.
Minimal clinically important change of knee flexion in people with knee osteoarthritis after non-surgical interventions using a meta-analytical approach
Authors: Silva M. Denika C. , Woodward Andrew P. , Fearon Angela M. , Perriman Diana M. , Spencer Trevor J. , Couldrick Jacqui M. , Scarvell Jennie M.
Published: February 2024

Background

Minimal clinically important change (MCIC) represents the minimum patient-perceived improvement in an outcome after treatment, in an individual or within a group over time. This study aimed to determine MCIC of knee flexion in people with knee OA after non-surgical interventions using a meta-analytical approach.

Methods

Four databases (MEDLINE, Cochrane, Web of Science and CINAHL) were searched for studies of randomised clinical trials of non-surgical interventions with intervention duration of ≤ 3 months that reported change in (Δ) (mean change between baseline and immediately after the intervention) knee flexion with Δ pain or Δ function measured using tools that have established MCIC values. The risk of bias in the included studies was assessed using version 2 of the Cochrane risk-of-bias tool for randomised trials (RoB 2). Bayesian meta-analytic models were used to determine relationships between Δ flexion with Δ pain and Δ function after non-surgical interventions and MCIC of knee flexion.

Results

Seventy-two studies (k = 72, n = 5174) were eligible. Meta-analyses included 140 intervention arms (k = 61, n = 4516) that reported Δ flexion with Δ pain using the visual analog scale (pain-VAS) and Δ function using the Western Ontario and McMaster Universities Osteoarthritis Index function subscale (function-WOMAC). Linear relationships between Δ pain at rest-VAS (0–100 mm) with Δ flexion were − 0.29 (− 0.44; − 0.15) (β: posterior median (CrI: credible interval)). Relationships between Δ pain during activity VAS and Δ flexion were − 0.29 (− 0.41, − 0.18), and Δ pain-general VAS and Δ flexion were − 0.33 (− 0.42, − 0.23). The relationship between Δ function-WOMAC (out of 100) and Δ flexion was − 0.15 (− 0.25, − 0.07). Increased Δ flexion was associated with decreased Δ pain-VAS and increased Δ function-WOMAC. The point estimates for MCIC of knee flexion ranged from 3.8 to 6.4°.

Conclusions

The estimated knee flexion MCIC values from this study are the first to be reported using a novel meta-analytical method. The novel meta-analytical method may be useful to estimate MCIC for other measures where anchor questions are problematic.

Systematic review registration

PROSPERO CRD42022323927.
Higher order $(n,m)$-Drazin normal operators
Authors: AlShammari Hadi Obaid
Published: February 2024

The purpose of this paper is to introduce and study the structure of p-tuple of $(n,m)$
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m
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Infinite system of nonlinear tempered fractional order BVPs in tempered sequence spaces
Authors: Rao Sabbavarapu Nageswara , Khuddush Mahammad , Msmali Ahmed Hussein , Ahmadini Abdullah Ali H.
Published: February 2024

This paper deals with the existence results of the infinite system of tempered fractional BVPs $$\begin{aligned}& {}^{\mathtt{R}}_{0}\mathrm{D}_{\mathrm{r}}^{\varrho , \uplambda} \mathtt{z}_{\mathtt{j}}(\mathrm{r})+\psi _{\mathtt{j}}\bigl(\mathrm{r}, \mathtt{z}(\mathrm{r})\bigr)=0,\quad 0< \mathrm{r}< 1, \\& \mathtt{z}_{\mathtt{j}}(0)=0,\qquad {}^{\mathtt{R}}_{0} \mathrm{D}_{ \mathrm{r}}^{\mathtt{m}, \uplambda} \mathtt{z}_{\mathtt{j}}(0)=0, \\& \mathtt{b}_{1} \mathtt{z}_{\mathtt{j}}(1)+\mathtt{b}_{2} {}^{ \mathtt{R}}_{0}\mathrm{D}_{\mathrm{r}}^{\mathtt{m}, \uplambda} \mathtt{z}_{\mathtt{j}}(1)=0, \end{aligned}$$

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The effects of educational robotics in STEM education: a multilevel meta-analysis
Authors: Ouyang Fan , Xu Weiqi
Published: February 2024

Educational robotics, as emerging technologies, have been widely applied in the field of STEM education to enhance the instructional and learning quality. Although previous research has highlighted potentials of applying educational robotics in STEM education, there is a lack of empirical evidence to investigate and understand the overall effects of using educational robotics in STEM education as well as the critical factors that influence the effects. To fill this gap, this research conducted a multilevel meta-analysis to examine the overall effect size of using educational robotics in STEM education under K-16 education based on 30 effect sizes from 21 studies published between 2010 and 2022. Furthermore, we examined the possible moderator variables of robot-assisted STEM education, including discipline, educational level, instructor support, instructional strategy, interactive type, intervention duration, robotic type, and control group condition. Results showed that educational robotics had the moderate-sized effects on students’ STEM learning compared to the non-robotics condition. Specifically, educational robotics had moderate-sized effects on students’ learning performances and learning attitudes, and insignificant effects on the improvement of computational thinking. Furthermore, we examined the influence of moderator variables in robot-assisted STEM education. Results indicated that the moderator variable of discipline was significantly associated with the effects of educational robotics on STEM learning. Based on the findings, educational and technological implications were provided to guide future research and practice in the application of educational robotics in STEM education.
Persona/scenario (P/S) toolkit enhancing inclusive fashion design education
Authors: Lee Jee Hyun , Lee Eunjee , Huh Jiwon , Kim Minji Lena , Kim Jieun
Published: February 2024

This study aimed to address the diversity issue in fashion design education by developing two prototypes for Inclusive Fashion Design (IFD) education. The prototypes were constructed based on the 3C3R model of Project-Based Learning (PBL) and incorporated the Persona/Scenario (P/S) toolkit for IFD. Additionally, the study examined the effectiveness of the FEA (Function, Expressive, and Aesthetics) self-checklist and the P/S toolkit in the IFD process. The experiments involved two design instructors, two teaching assistants, and 12 senior-level students divided into four teams. Thematic analysis was conducted on the interview data collected from the participants. The results revealed that FEA factors were highly considered in both education prototypes, regardless of the presence of the P/S toolkit. Maintaining consistency of the IFD concept throughout each stage of the process was found to be crucial, and the use of the P/S toolkit played a significant role in achieving this consistency. Team communication emerged as an essential factor in IFD education, as team collaboration using the P/S toolkit triggered diverse perspectives on targets, facilitated design expansion, and extended individual competences. Overall, this study contributes to the understanding of the diversity issue in fashion design education and promotes the adoption of the IFD education methodology, emphasizing the significance of consistent concept development, effective toolkits, and team collaboration in achieving inclusive design practices.
Elevated blood pressure among children born to women with obstructed labour in Eastern Uganda: a cohort study
Authors: Mukunya David , Musaba Milton W. , Nambozo Brendah , Oguttu Faith , Makoko Brian Tonny , Napyo Agnes , Nantale Ritah , Wani Solomon , Tumuhamye Josephine , Auma Prossy , Atim Ketty , Wamulugwa Joan , Nahurira Doreck , Okello Dedan , Ssegawa Lawrence , Wandabwa Julius , Kiguli Sarah , Chebet Martin
Published: February 2024

Background

Globally, high systolic blood pressure accounts for 10.8 million deaths annually. The deaths are disproportionately higher among black people. The reasons for this disparity are poorly understood, but could include a high burden of perinatal insults such as birth asphyxia. Therefore, we aimed to assess the incidence of elevated blood pressure and to explore associated factors among children born to women with obstructed labour.

Methods

We followed up children born to women with obstructed labour aged 25 to 44 months at Mbale regional referral hospital that had participated in the sodium bicarbonate trial ( Trial registration number PACTR201805003364421) between October 2021 and April 2022. Our primary outcome was elevated blood pressure defined as blood pressure (either systolic or diastolic or both) ≥ the 90th percentile for age, height, and sex in the reference population based on the clinical practice guideline for screening and management of high blood pressure in children and adolescents. We used logistic regression to estimate odds ratios between selected exposures and elevated blood pressure.

Results

The incidence of elevated blood pressure was (39/140, 27.9%: 95% (CI: 20.6–36.1)). Participants aged three years and above had twice the odds of elevated blood pressure as those aged less than three years (Adjusted odds ratio (AOR) 2.46: 95% CI (1.01–5.97). Female participants had 2.81 times the odds of elevated blood pressure as their male counterparts (AOR 2.81 95% CI (1.16–6.82). Participants with reduced estimated glomerular filtration rate had 2.85 times the odds of having elevated blood pressure as those with normal estimated glomerular filtration rate (AOR 2.85 95% CI (1.00–8.13). We found no association between arterial cord lactate, stunting, wealth index, exclusive breastfeeding, food diversity and elevated blood pressure.

Conclusion

Our findings show a high incidence of elevated blood pressure among children. We encourage routine checking for elevated blood pressure in the pediatric population particularly those with known risk factors.
Evaluation of brain white matter changes on MRI in patients newly diagnosed with obstructive sleep apnea compared with the control group
Authors: Khoroushi Farzaneh , Davoodi Yasmin , Fathabadi Amirhossein , Bakhshi Reihane , Sharifian Yasamin , Salehi Maryam , Ghofranyha Leila , Hassannejad Ehsan , Kharaghani Farnaz
Published: February 2024

Background

Obstructive sleep apnea (OSA) is nowadays introduced as a risk factor for white matter brain changes. Research on OSA and white matter changes provides contradictory evidence for the contextual link between the two conditions. This study aimed to determine the prevalence and severity of OSA and changes in the brain's white matter and the relationship between severity levels of both diseases.

Methods

This was a cross-sectional study in which 40 patients with OSA and 40 patients without OSA underwent polysomnography to determine the severity of OSA and MRI for detecting white matter changes. The severity of white matter changes was classified according to the age-related white matter change (ARWMC) score, and the severity of OSA based on the apnea–hypopnea index (AHI). To evaluate the independent effect of OSA on white matter changes, a multivariate regression model, including the severity of OSA and risk factors, was used.

Results

76.5% of affected people did not show any changes, and from 13 (32.5%) patients with OSA who experienced white matter changes, 10% were mild, and 22.5% were moderate to severe changes. The white matter changes score increased with increasing OSA severity. The univariate analysis also showed a significant positive correlation between OSA severity and ARWMC score.

Conclusion

Our major finding was that moderate to severe OSA was independently associated with the prevalence of white matter changes. We also observed a higher prevalence of moderate to severe OSA associated with increasing white matter changes, suggesting that the severity of the disease affects brain structural modification.