bluuebunny/crossref_metadata_2025_split huggingface dataset:
IRF4-mediated Treg phenotype switching can aggravate hyperoxia-induced alveolar epithelial cell injury
Authors: Langyue He , Ying Zhu , Jianfeng Jiang , Yue Zhu , Huici Yao , Hongyan Lu 
Published: March 2024

AbstractBronchopulmonary dysplasia (BPD) is characterized by alveolar dysplasia, and evidence indicates that interferon regulatory factor 4 (IRF4) is involved in the pathogenesis of various inflammatory lung diseases. Nonetheless, the significance and mechanism of IRF4 in BPD remain unelucidated. Consequently, we established a mouse model of BPD through hyperoxia exposure, and ELISA was employed to measure interleukin-17 A (IL-17 A) and interleukin-6 (IL-6) expression levels in lung tissues. Western blotting was adopted to determine the expression of IRF4, surfactant protein C (SP-C), and podoplanin (T1α) in lung tissues. Flow cytometry was utilized for analyzing the percentages of FOXP3+ regulatory T cells (Tregs) and FOXP3+RORγt+ Tregs in CD4+ T cells in lung tissues to clarify the underlying mechanism. Our findings revealed that BPD mice exhibited disordered lung tissue structure, elevated IRF4 expression, decreased SP-C and T1α expression, increased IL-17 A and IL-6 levels, reduced proportion of FOXP3+ Tregs, and increased proportion of FOXP3+RORγt+ Tregs. For the purpose of further elucidating the effect of IRF4 on Treg phenotype switching induced by hyperoxia in lung tissues, we exposed neonatal mice with IRF4 knockout to hyperoxia. These mice exhibited regular lung tissue structure, increased proportion of FOXP3+ Tregs, reduced proportion of FOXP3+RORγt+ Tregs, elevated SP-C and T1α expression, and decreased IL-17 A and IL-6 levels. In conclusion, our findings demonstrate that IRF4-mediated Treg phenotype switching in lung tissues exacerbates alveolar epithelial cell injury under hyperoxia exposure.
Clinical characteristics and outcome of lung cancer in patients with fibrosing interstitial lung disease
Authors: Han Soo Jin , Kim Hyeon Hwa , Hyun Dong-gon , Ji Wonjun , Choi Chang-Min , Lee Jae Cheol , Kim Ho Cheol 
Published: March 2024

Abstract
Background
Lung cancer (LC) is an important comorbidity of interstitial lung disease (ILD) and has a poor prognosis. The clinical characteristics and outcome of each ILD subtype in LC patients have not been sufficiently investigated. Therefore, this study aimed to evaluate the difference between idiopathic pulmonary fibrosis (IPF) and non-IPF ILD as well as prognostic factors in patients with ILD-LC.

Methods
The medical records of 163 patients diagnosed with ILD-LC at Asan Medical Center from January 2018 to May 2023 were retrospectively reviewed. Baseline characteristics and clinical outcomes were compared between the IPF-LC and non-IPF ILD-LC groups, and prognostic factors were analyzed using the Cox proportional-hazard model.

Results
The median follow-up period was 11 months after the cancer diagnosis. No statistically significant differences were observed in clinical characteristics and mortality rates (median survival: 26 vs. 20 months, p = 0.530) between the groups. The independent prognostic factors in patients with ILD-LC were higher level of Krebs von den Lungen-6 (≥ 1000 U/mL, hazard ratio [HR] 1.970, 95% confidence interval [CI] 1.026-3.783, p = 0.025) and advanced clinical stage of LC (compared with stage I, HR 3.876 for stage II, p = 0.025, HR 5.092 for stage III, p = 0.002, and HR 5.626 for stage IV, p = 0.002). In terms of treatment, surgery was the significant factor for survival (HR 0.235; 95% CI 0.106-0.520; p < 0.001).

Conclusions
No survival difference was observed between IPF-LC and non-IPF ILD-LC patients. A higher level of Krebs von den Lungen-6 may act as a prognostic marker in ILD-LC patients.
Derivation of a novel antimicrobial peptide from the Red Sea Brine Pools modified to enhance its anticancer activity against U2OS cells
Authors: Elradi Mona , Ahmed Ahmed I. , Saleh Ahmed M. , Abdel-Raouf Khaled M. A. , Berika Lina , Daoud Yara , Amleh Asma 
Published: March 2024

AbstractCancer associated drug resistance is a major cause for cancer aggravation, particularly as conventional therapies have presented limited efficiency, low specificity, resulting in long term deleterious side effects. Peptide based drugs have emerged as potential alternative cancer treatment tools due to their selectivity, ease of design and synthesis, safety profile, and low cost of manufacturing. In this study, we utilized the Red Sea metagenomics database, generated during AUC/KAUST Red Sea microbiome project, to derive a viable anticancer peptide (ACP). We generated a set of peptide hits from our library that shared similar composition to ACPs. A peptide with a homeodomain was selected, modified to improve its anticancer properties, verified to maintain high anticancer properties, and processed for further in-silico prediction of structure and function. The peptide’s anticancer properties were then assessed in vitro on osteosarcoma U2OS cells, through cytotoxicity assay (MTT assay), scratch-wound healing assay, apoptosis/necrosis detection assay (Annexin/PI assay), RNA expression analysis of Caspase 3, KI67 and Survivin, and protein expression of PARP1. L929 mouse fibroblasts were also assessed for cytotoxicity treatment. In addition, the antimicrobial activity of the peptide was also examined on E coli and S. aureus, as sample representative species of the human bacterial microbiome, by examining viability, disk diffusion, morphological assessment, and hemolytic analysis. We observed a dose dependent cytotoxic response from peptide treatment of U2OS, with a higher tolerance in L929s. Wound closure was debilitated in cells exposed to the peptide, while annexin fluorescent imaging suggested peptide treatment caused apoptosis as a major mode of cell death. Caspase 3 gene expression was not altered, while KI67 and Survivin were both downregulated in peptide treated cells. Additionally, PARP-1 protein analysis showed a decrease in expression with peptide exposure. The peptide exhibited minimal antimicrobial activity on critical human microbiome species E. coli and S. aureus, with a low inhibition rate, maintenance of structural morphology and minimal hemolytic impact. These findings suggest our novel peptide displayed preliminary ACP properties against U2OS cells, through limited specificity, while triggering apoptosis as a primary mode of cell death and while having minimal impact on the microbiological species E. coli and S. aureus.
Comparative analysis of stress distribution in residual roots with different canal morphologies: evaluating CAD/CAM glass fiber and other post-core materials
Authors: Huang Minghao , Wang Biyao , Zhang Kaige , Yan Xu , Chen Zhiyu , Zhang Xinwen 
Published: March 2024

Abstract
Background
The selection of post-core material holds significant importance in endodontically treated teeth, influencing stress distribution in the dental structure after restoration. The use of computer-aided design/computer-aided manufacturing (CAD/CAM) glass fiber post-core possesses a better adaptation for different root canal morphologies, but whether this results in a more favorable stress distribution has not been clearly established.

Materials and methods
This study employed finite element analysis to establish three models of post-core crown restoration with normal, oversized, and dumbbell-shaped root canals. The three models were restored using three different materials: CAD/CAM glass fiber post-core (CGF), prefabricated glass fiber post and resin core (PGF), and cobalt-chromium integrated metal post-core (Co-Cr), followed by zirconia crown restoration. A static load was applied and the maximum equivalent von Mises stress, maximum principal stress, stress distribution plots, and the peak of maximum displacement were calculated for dentin, post-core, crown, and the cement acting as the interface between the post-core and the dentin.

Results
In dentin of three different root canal morphology, it was observed that PGF exhibited the lowest von Mises stresses, while Co-Cr exhibited the highest ones under a static load. CGF showed similar stress distribution to that of Co-Cr, but the stresses were more homogeneous and concentrated apically. In oversized and dumbbell-shaped root canal remnants, the equivalent von Mises stress in the cement layer using CGF was significantly lower than that of PGF.

Conclusions
In oversized root canals and dumbbell-shaped root canals, CGF has shown good performance for restoration of endodontically treated teeth.

Clinical relevance
This study provides a theoretical basis for clinicians to select post-core materials for residual roots with different root canal morphologies and should help to reduce the occurrence of complications such as root fracture and post-core debonding.
Female genital mutilation/cutting among girls aged 0–14: evidence from the 2018 Mali Demographic and Health Survey data
Authors: Ahinkorah Bright Opoku , Budu Eugene , Seidu Abdul-Aziz , Agbaglo Ebenezer , Adu Collins , Ameyaw Edward Kwabena , Ajayi Anthony Idowu , Yaya Sanni 
Published: March 2024

Abstract
Background
Female genital mutilation/cutting (FGM/C) is considered a social norm in many African societies, with varying prevalence among countries. Mali is one of the eight countries with very high prevalence of FGM/C in Africa. This study assessed the individual and contextual factors associated with female FGM/C among girls aged 0–14 years in Mali.

Methods
We obtained data from the 2018 Mali Demographic and Health Survey. The prevalence of FGM/C in girls was presented using percentages while a multilevel binary logistic regression analysis was conducted to assess the predictors of FGM/C and the results were presented using adjusted odds ratios with associated 95% confidence intervals (CIs).

Results
The results indicate that more than half (72.7%, 95% CI = 70.4–74.8) of women in Mali with daughters had at least one daughter who has gone through circumcision. The likelihood of circumcision of girls increased with age, with women aged 45–49 having the highest odds compared to those aged 15–19 (aOR = 17.68, CI = 7.91–31.79). A higher likelihood of FGM/C in daughters was observed among women who never read newspaper/magazine (aOR = 2.22, 95% CI = 1.27–3.89), compared to those who read newspaper/magazine at least once a week. Compared to women who are not circumcised, those who had been circumcised were more likely to have their daughters circumcised (aOR = 53.98, 95% CI = 24.91–117.00).

Conclusion
The study revealed the age of mothers, frequency of reading newspaper/magazine, and circumcision status of mothers, as factors associated with circumcision of girls aged 0–14 in Mali. It is, therefore, imperative for existing interventions and new ones to focus on these factors in order to reduce FGM/C in Mali. This will help Mali to contribute to the global efforts of eliminating all harmful practices, such as child, early and forced marriage and female genital mutilation by 2030.
Evaluation of bias and gender/racial concordance based on sentiment analysis of narrative evaluations of clinical clerkships using natural language processing
Authors: Bhanvadia Sonali , Radha Saseendrakumar Bharanidharan , Guo Joy , Spadafore Maxwell , Daniel Michelle , Lander Lina , Baxter Sally L. 
Published: March 2024

AbstractThere is increasing interest in understanding potential bias in medical education. We used natural language processing (NLP) to evaluate potential bias in clinical clerkship evaluations. Data from medical evaluations and administrative databases for medical students enrolled in third-year clinical clerkship rotations across two academic years. We collected demographic information of students and faculty evaluators to determine gender/racial concordance (i.e., whether the student and faculty identified with the same demographic). We used a multinomial log-linear model for final clerkship grades, using predictors such as numerical evaluation scores, gender/racial concordance, and sentiment scores of narrative evaluations using the SentimentIntensityAnalyzer tool in Python. 2037 evaluations from 198 students were analyzed. Statistical significance was defined as P < 0.05. Sentiment scores for evaluations did not vary significantly by student gender, race, or ethnicity (P = 0.88, 0.64, and 0.06, respectively). Word choices were similar across faculty and student demographic groups. Modeling showed narrative evaluation sentiment scores were not predictive of an honors grade (odds ratio [OR] 1.23, P = 0.58). Numerical evaluation average (OR 1.45, P < 0.001) and gender concordance between faculty and student (OR 1.32, P = 0.049) were significant predictors of receiving honors. The lack of disparities in narrative text in our study contrasts with prior findings from other institutions. Ongoing efforts include comparative analyses with other institutions to understand what institutional factors may contribute to bias. NLP enables a systematic approach for investigating bias. The insights gained from the lack of association between word choices, sentiment scores, and final grades show potential opportunities to improve feedback processes for students.
Utilization of 3D evaluation for assessing selective caries removal practice in pre-clinical dental students: a pilot study
Authors: Romalee Worachate , Suksudaj Nattira , Doungkom Patchayaporn , Wang Ding-Han , Hsu Ming-Lun , Panpisut Piyaphong 
Published: March 2024

Abstract
Background
Practicing and assessment of selective caries removal techniques in dental students remain challenges in many dental schools. The aim of this study was to utilize a 3D assessment technique, within a designated acceptable range of deviation, to evaluate the tendency of dental students in performing selective caries removal (SCR). The correlation between 3D assessment results and the conventional rubric rated by an instructor was also determined.

Methods
Fifth-year dental students (n = 61) performed the SCR task on 3D-printed teeth containing simulated deep caries lesions in occlusal and proximal surfaces. One instructor assessed the results using a conventional analytic rubric. The excavated teeth were additionally evaluated using 3D analysis software with the designated acceptable range of deviations (± 0.5 mm) from the standard cavities. The average root mean square (RMS) value, representing the deviation between student-prepared cavities and the predefined standard cavities, was recorded. A tendency towards over-excavation was defined for RMS values > 0.5 mm, and towards under-excavation for RMS values < 0.5 mm.

Results
The mean (min-max) of RMS was 0.27 (0.18–0.40) for occlusal and 0.29 (0.20–0.57)for proximal cavities. A tendency of dental students toward over-excavation was observed in both occlusal (74%) and proximal cavities (87%). There was a moderate negative correlation between the RMS values and the traditional rubric scores for both occlusal (R2 = 0.148, P = 0.002) and proximal cavities (R2 = 0.107, P = 0.010).

Conclusions
The 3D evaluation technique effectively revealed specific tendencies in dental students’ caries removal skills. The integration of computerized assessments with traditional methods could potentially assist the instructors in delivering more objective and specific feedback to students. Further research is encouraged to investigate the impact of this assessment technique on improving student performance in selective caries removal skills.
Application of advanced very high-resolution radiometer (AVHRR)-based vegetation health indices for modelling and predicting malaria in Northern Benin, West Africa
Authors: Gbaguidi Gouvidé Jean , Idrissou Mouhamed , Topanou Nikita , Filho Walter Leal , Ketoh Guillaume K. 
Published: March 2024

Abstract
Background
Vegetation health (VH) is a powerful characteristic for forecasting malaria incidence in regions where the disease is prevalent. This study aims to determine how vegetation health affects the prevalence of malaria and create seasonal weather forecasts using NOAA/AVHRR environmental satellite data that can be substituted for malaria epidemic forecasts.

Methods
Weekly advanced very high-resolution radiometer (AVHRR) data were retrieved from the NOAA satellite website from 2009 to 2021. The monthly number of malaria cases was collected from the Ministry of Health of Benin from 2009 to 2021 and matched with AVHRR data. Pearson correlation was calculated to investigate the impact of vegetation health on malaria transmission. Ordinary least squares (OLS), support vector machine (SVM) and principal component regression (PCR) were applied to forecast the monthly number of cases of malaria in Northern Benin. A random sample of proposed models was used to assess accuracy and bias.

Results
Estimates place the annual percentage rise in malaria cases at 9.07% over 2009–2021 period. Moisture (VCI) for weeks 19–21 predicts 75% of the number of malaria cases in the month of the start of high mosquito activities. Soil temperature (TCI) and vegetation health index (VHI) predicted one month earlier than the start of mosquito activities through transmission, 78% of monthly malaria incidence.

Conclusions
SVM model D is more effective than OLS model A in the prediction of malaria incidence in Northern Benin. These models are a very useful tool for stakeholders looking to lessen the impact of malaria in Benin.
Microsatellites reveal high polymorphism and high potential for use in anti-malarial efficacy studies in areas with different transmission intensities in mainland Tanzania
Authors: Ishengoma Deus S. , Mandara Celine I. , Madebe Rashid A. , Warsame Marian , Ngasala Billy , Kabanywanyi Abdunoor M. , Mahende Muhidin K. , Kamugisha Erasmus , Kavishe Reginald A. , Muro Florida , Mandike Renata , Mkude Sigsbert , Chacky Frank , Njau Ritha , Martin Troy , Mohamed Ally , Bailey Jeffrey A. , Fola Abebe A. 
Published: March 2024

AbstractBackgroundTanzania is currently implementing therapeutic efficacy studies (TES) in areas of varying malaria transmission intensities as per the World Health Organization (WHO) recommendations. In TES, distinguishing reinfection from recrudescence is critical for the determination of anti-malarial efficacy. Recently, the WHO recommended genotyping polymorphic coding genes, merozoite surface proteins 1 and 2(msp1 and msp2), and replacing the glutamate-rich protein (glurp) gene with one of the highly polymorphic microsatellites inPlasmodium falciparumto adjust the efficacy of antimalarials in TES. This study assessed the polymorphisms of six neutral microsatellite markers and their potential use in TES, which is routinely performed in Tanzania.MethodsPlasmodium falciparumsamples were obtained from four TES sentinel sites, Kibaha (Pwani), Mkuzi (Tanga), Mlimba (Morogoro) and Ujiji (Kigoma), between April and September 2016. Parasite genomic DNA was extracted from dried blood spots on filter papers using commercial kits. Genotyping was done using six microsatellites (Poly-α, PfPK2, TA1, C3M69, C2M34 and M2490) by capillary method, and the data were analysed to determine the extent of their polymorphisms and genetic diversity at the four sites.ResultsOverall, 83 (88.3%) of the 94 samples were successfully genotyped (with positive results for ≥ 50.0% of the markers), and > 50.0% of the samples (range = 47.6–59.1%) were polyclonal, with a mean multiplicity of infection (MOI) ranging from 1.68 to 1.88 among the four sites. There was high genetic diversity but limited variability among the four sites based on mean allelic richness (RS = 7.48, range = 7.27–8.03, for an adjusted minimum sample size of 18 per site) and mean expected heterozygosity (He = 0.83, range = 0.80–0.85). Cluster analysis of haplotypes using STRUCTURE, principal component analysis, and pairwise genetic differentiation (FST) did not reveal population structure or clustering of parasites according to geographic origin. Of the six markers, Poly-α was the most polymorphic, followed by C2M34, TA1 and C3M69, while M2490 was the least polymorphic.ConclusionMicrosatellite genotyping revealed high polyclonality and genetic diversity but no significant population structure. Poly-α, C2M34, TA1 and C3M69 were the most polymorphic markers, and Poly-α alone or with any of the other three markers could be adopted for use in TES in Tanzania.
Hypoxia preconditioning of adipose stem cell-derived exosomes loaded in gelatin methacryloyl (GelMA) promote type H angiogenesis and osteoporotic fracture repair
Authors: Li Xiaoqun , Fang Shuo , Wang Shaohai , Xie Yang , Xia Yan , Wang Panfeng , Hao Zichen , Xu Shuogui , Zhang Yuntong 
Published: March 2024

Abstract
The challenges posed by delayed atrophic healing and nonunion stand as formidable obstacles in osteoporotic fracture treatment. The processes of type H angiogenesis and osteogenesis emerge as pivotal mechanisms during bone regeneration. Notably, the preconditioning of adipose-derived stem cell (ADSC) exosomes under hypoxic conditions has garnered attention for its potential to augment the secretion and functionality of these exosomes. In the present investigation, we embarked upon a comprehensive elucidation of the underlying mechanisms of hypo-ADSC-Exos within the milieu of osteoporotic bone regeneration. Our findings revealed that hypo-ADSC-Exos harboured a preeminent miRNA, namely, miR-21-5p, which emerged as the principal orchestrator of angiogenic effects. Through in vitro experiments, we demonstrated the capacity of hypo-ADSC-Exos to stimulate the proliferation, migration, and angiogenic potential of human umbilical vein endothelial cells (HUVECs) via the mediation of miR-21-5p. The inhibition of miR-21-5p effectively attenuated the proangiogenic effects mediated by hypo-ADSC-Exos. Mechanistically, our investigation revealed that exosomal miR-21-5p emanating from hypo-ADSCs exerts its regulatory influence by targeting sprouly1 (SPRY1) within HUVECs, thereby facilitating the activation of the PI3K/AKT signalling pathway. Notably, knockdown of SPRY1 in HUVECs was found to potentiate PI3K/AKT activation and, concomitantly, HUVEC proliferation, migration, and angiogenesis. The culminating stage of our study involved a compelling in vivo demonstration wherein GelMA loaded with hypo-ADSC-Exos was validated to substantially enhance local type H angiogenesis and concomitant bone regeneration. This enhancement was unequivocally attributed to the exosomal modulation of SPRY1. In summary, our investigation offers a pioneering perspective on the potential utility of hypo-ADSC-Exos as readily available for osteoporotic fracture treatment.

Graphical Abstract
Hypoxia promotes metastasis by relieving miR-598-3p-restricted glycolysis in gastric cancer
Authors: Zhou Wei , Tang Mengyuan , He Dan , Shen Yi , Huang Ziwei , Xia Wenxin , Wu Zhiyun , Wei Wenxiang , Zheng Hui , Wang Qi , Shi Weifeng , Jiang Jingting 
Published: March 2024

AbstractThe activation of glycolysis, particularly in the context of reprogrammed energy metabolism, is increasingly recognized as a significant characteristic of cancer. However, the precise mechanisms by which glycolysis is promoted in metastatic gastric cancer cells under normal oxygen conditions remain poorly understood. MicroRNAs (miRNAs) play a crucial role in the development of malignant phenotypes in gastric cancer. Nevertheless, our understanding of the specific involvement of miRNAs in hypoxia-induced metabolic shifting and the subsequent metastatic processes is limited. Hypoxia-induced downregulation of miR-598-3p mechanistically leads to the upregulation of RMP and IGF1r, thereby promoting glycolysis. Either overexpression of miR-598-3p or R406 treatment effectively suppresses the metastasis of gastric cancer cells both in vitro and in vivo. Collectively, the depletion of miR-598-3p alters glucose metabolism from oxidative phosphorylation to glycolysis, thereby exacerbating the malignancy of gastric cancer cells. The present findings indicate a potential target for the development of therapeutics against gastric cancers with increased miR-598-3p expression.