bluuebunny/crossref_metadata_2025 huggingface dataset:
eSVD-DE: cohort-wide differential expression in single-cell RNA-seq data using exponential-family embeddings
Authors: Lin Kevin Z. , Qiu Yixuan , Roeder Kathryn
Published: March 2024

Background

Single-cell RNA-sequencing (scRNA) datasets are becoming increasingly popular in clinical and cohort studies, but there is a lack of methods to investigate differentially expressed (DE) genes among such datasets with numerous individuals. While numerous methods exist to find DE genes for scRNA data from limited individuals, differential-expression testing for large cohorts of case and control individuals using scRNA data poses unique challenges due to substantial effects of human variation, i.e., individual-level confounding covariates that are difficult to account for in the presence of sparsely-observed genes.

Results

We develop the eSVD-DE, a matrix factorization that pools information across genes and removes confounding covariate effects, followed by a novel two-sample test in mean expression between case and control individuals. In general, differential testing after dimension reduction yields an inflation of Type-1 errors. However, we overcome this by testing for differences between the case and control individuals’ posterior mean distributions via a hierarchical model. In previously published datasets of various biological systems, eSVD-DE has more accuracy and power compared to other DE methods typically repurposed for analyzing cohort-wide differential expression.

Conclusions

eSVD-DE proposes a novel and powerful way to test for DE genes among cohorts after performing a dimension reduction. Accurate identification of differential expression on the individual level, instead of the cell level, is important for linking scRNA-seq studies to our understanding of the human population.
The association between inflammation, arterial stiffness, oxidized LDL and cardiovascular disease in Finnish men with metabolic syndrome – a 15-year follow-up study
Authors: Saarinen Harri Juhani , Lahtela Jorma , Mähönen Päivi , Palomäki Ari ,   for the Hämeenlinna Metabolic Syndrome Research Program Study Group, Pohjantähti-Maaroos Hanna , Husgafvel Sari , Knuth Timo , Laitinen Ruth , Oksanen Kalevi , Vesterinen Kai , Wallenius Marja
Published: March 2024

Background

All-cause mortality and cardiovascular disease are increased in subjects with metabolic syndrome (MetS). Risk scores are used to predict individual risk of heart disease. We performed a long-term follow-up study to investigate whether risk scores and cardiovascular risk factors such as arterial stiffness, high-sensitive C-reactive protein (hs-CRP) and oxidized LDL (OxLDL) can be used to predict cardiovascular events in Finnish men with MetS.

Methods

After baseline measurements we followed 105 Finnish men aged 30 to 65 years with MetS for a mean period of 16.4 years. The primary outcome of the study was a composite of myocardial infarction, stroke, symptomatic vascular disease diagnosed with invasive angiography, coronary or peripheral revascularization, amputation due to peripheral vascular disease, cardiovascular death and non-cardiovascular death. The endpoints were retrieved from electronic medical records.

Results

The number of acute myocardial infarctions and strokes during the first 10 years was lower than estimated by FINRISK score but SCORE predicted cardiovascular death correctly. During the whole follow-up period, 27 of 105 participants (25.8%) had 30 endpoint events. The incidence of the primary composite outcome was significantly lower in subjects with hs-CRP < 1.0 mg/L than in subjects with hs-CRP ≥ 1.0 mg/L (6 of 41 subjects [14.6%] vs. 21 of 64 subjects [32.8%]; p = 0.036). The incidence of the primary composite outcome was higher among subjects with large artery elasticity classified as borderline compared to subjects with normal large artery elasticity (5 of 10 subjects [50%] vs. 22 of 93 subjects [24%]; p = 0.05). There was no difference in the incidence of primary composite outcome in groups with different degrees of small artery elasticity or different level of oxLDL.

Conclusions

Men with MetS who had hs-CRP ≥ 1.0 mg/L had higher risk for CVD and all-cause mortality than those with hs-CRP of < 1.0 mg/L. This also applies to subjects with borderline decreased large artery elasticity. The amount of OxLDL had no predictive value on the incidence of CVD and all-cause mortality. Men with MetS participating in the Hämeenlinna Metabolic Syndrome Research Program without lifestyle or drug intervention had better outcome for myocardial infarction or stroke than estimated by the FINRISK score.

Trial registration

ClinicalTrials.gov NCT01119404 retrospectively registered 07/05/2010.
Association of lymphocyte subsets with the efficacy and prognosis of PD‑1 inhibitor therapy in advanced gastric cancer: results from a monocentric retrospective study
Authors: Wang Xinyan , Liu Xiaoling , Dai Huwei , Jia Junmei
Published: March 2024

Purpose

This retrospective study aimed to investigate the changes in peripheral blood lymphocyte subsets before and after immunotherapy in patients with advanced gastric cancer and their relationship n with the therapeutic efficacy and clinical prognosis.

Methods

Peripheral blood lymphocyte subsets, including CD4 + T cells, CD8 + T cells, CD4+/CD8 + ratio, NK cells, Treg cells, and B cells, were collected from 195 patients with advanced gastric cancer who were admitted to the First Hospital of Shanxi Medical University with immunotherapy from January 2020 to October 2021, at the time of diagnosis of advanced gastric cancer, before immunotherapy and after 3 cycles of immunotherapy. T-tests were used to examine the factors influencing the patients’ peripheral blood lymphocyte subsets and the changes after immunotherapy. To examine the relationship between lymphocyte subsets and treatment outcomes, ROC curves were plotted using a logistic regression. Kaplan–Meier curve was drawn, and the Log Rank test was carried out to compare the differences in PFS between the different groups. Cox proportional hazards regression model was used to analyze the factors affecting PFS after calibration of other variables.

Results

The proportion of peripheral blood lymphocyte subsets in patients with advanced gastric cancer was affected by age and PD-L1 level. Compared to the baseline, the treatment effective group had higher proportions of CD4 + T cells, a higher CD4+/CD8 + ratio, NK cells and Treg cells, and lower proportions of CD8 + T cells and B cells in the peripheral blood after three cycles of immunotherapy. In the treatment-naive group, there were no significant differences in the lymphocyte subsets. With cut-off values of 30.60% and 18.00%, baseline CD4 + T cell and NK cell ratios were independent predictors of immunotherapy efficacy and PFS. Treg cell ratio, gender, PD-L1 levels, and MMR status all predicted PFS independently.

Conclusion

The proportion of peripheral blood lymphocyte subsets was modified in patients who responded to PD-1 inhibitors. Different lymphocyte subpopulation levels can be used as biomarkers to predict immunotherapy efficacy and clinical prognosis in patients with advanced gastric cancer.
The relationship between sarcopenia and metabolic dysfunction-associated fatty liver disease among the young and middle-aged populations
Authors: Feng Ziyan , Zhao Fanrong , Wang Ziyao , Tang Xinyi , Xie Yan , Qiu Li
Published: March 2024

Background

Metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed as a new term for diagnosing fatty liver disease, which is considered to be a multi-systemic disease with multiple extrahepatic manifestations, including sarcopenia. The link between sarcopenia and MAFLD remains uncertain, especially among young and middle-aged adults. Thus, we examined the relationship between MAFLD and sarcopenia in young and middle-aged individuals in this study.

Methods

A total of 2214 individuals with laboratory tests, dual-energy X-ray absorptiometry and ultrasound transient elastography from NHANES 2017–2018 were selected for this study. MAFLD was diagnosed as fatty liver disease with any one of the situations: overweight/obesity, diabetes mellitus, presence of metabolic dysregulation. Sarcopenia was defined by appendicular lean mass adjusted for body mass index (BMI). Multivariable logistic regression and restricted cubic spline (RCS) model were applied to explore the relationship between MAFLD and sarcopenia, and the mediation analyses were also conducted. Moreover, subgroup analyses stratified by BMI and lifestyles were done.

Results

The prevalence of MAFLD was 47.85%, and nearly 8.05% of participants had sarcopenia. The prevalence of sarcopenia was higher in participants with MAFLD (12.75%; 95% CI 10.18–15.31%) than in the non-MAFLD (3.73%; 95% CI 2.16–5.31%). MAFLD was significantly positively associated with sarcopenia after adjustments [OR = 2.87 (95% CI: 1.62–5.09)]. Moreover, significant positive associations were observed between liver fibrosis and sarcopenia prevalence in MAFLD patients (OR = 2.16; 95% CI 1.13–4.15). The RCS curve revealed that MAFLD was linearly associated with sarcopenia. The relationship between the MAFLD and sarcopenia were mediated by C-reactive protein (mediation proportion: 15.9%) and high-density lipoprotein cholesterol (mediation proportion: 18.9%). Subgroup analyses confirmed the association between MAFLD and sarcopenia differed in different lifestyle groups.

Conclusions

Both MAFLD prevalence and severity was significantly associated with sarcopenia. Thus, clinicians should advise comorbidity screening and lifestyle changes to young and middle-aged patients.
Exploring the lived experiences of women with multiple gestations in Iran: a phenomenological study
Authors: Banafshi Zhina , Khatony Alireza , Jalali Amir , Jalali Rostam
Published: March 2024

Background

Multiple gestations present numerous physical, psychological, social, and economic challenges for women. Understanding the problem-solving experiences of pregnant women carrying multiple can be invaluable. This study aimed to explore the experiences of Iranian women with multiple gestations.

Methods

This descriptive phenomenological study utilized purposive sampling and continued until data saturation. Data collection involved in-depth semi-structured interviews, with analysis performed using Colaizzi’s 7-step method. MAXQDA software was employed for data management.

Results

This study involved 12 women with multiple gestations. The average age of the participants was 33.76 ± 6.22 years, and 9 were pregnant with triplets. The data were categorized into four primary themes: the paradox of emotions, the pregnancy prison, immersion in fear, and the crystallization of maternal love, encompassing 17 sub-themes.

Conclusion

Pregnant women with multiple gestations undergo various changes and experience conflicting emotions. Enhancing their ability to adapt to and accept numerous pregnancies can be achieved through supportive, personalized, and family-centered care, along with improvements and revisions in care policies for multiple gestations.
Effect of topical bromfenac on intraretinal cystoid lesion in simultaneous cataract and idiopathic epiretinal membrane surgery
Authors: Kim EunAh , Kwon Han Jo , Park Sung Who , Byon Iksoo
Published: March 2024

Purpose

To investigate the effect of topical nonsteroidal anti-inflammatory drugs (NSAIDs,) bromfenac on the intraretinal cystic lesions (IRC) when performing simultaneous cataract and idiopathic epiretinal membrane (iERM) surgery.

Methods

This study included patients with iERM who had been followed up for 6 months after vitrectomy, membrane removal, and concurrent cataract surgery. Eyes were treated with topical bromfenac or not. The baseline fluorescein angiography (FA) was obtained to assess the microvascular leakage (ML). Structural changes of macula, including IRC and central macular thickness (CMT) were assessed using optical coherence tomography (OCT). The main outcome measures were changes in IRCs and best-corrected visual acuity (BCVA) regarding FA findings.

Results

One hundred eighteen eyes were included. IRC and ML were observed in 51 eyes (43.2%) and 63 eyes (53.4%), respectively. The IRC did not show any association with the ML. Of total, 29 eyes (24.6%) were treated with topical bromfenac (Group A). Compared to Group B, topical bromfenac did not show beneficial effects in aspect of preventions for the newly developed IRC and treatment for pre-existed IRC. Whether the ML existed or not, topical bromfenac did not show any different effect on the changes in BCVA and IRC.

Conclusion

When performing simultaneous cataract and ERM surgery, topical NSAIDs, bromfenac did not show beneficial effects on the preventions and treatment of IRC in both eyes with and without the ML.
Artificial intelligence in age-related macular degeneration: state of the art and recent updates
Authors: Crincoli Emanuele , Sacconi Riccardo , Querques Lea , Querques Giuseppe
Published: March 2024

Age related macular degeneration (AMD) represents a leading cause of vision loss and it is expected to affect 288 million people by 2040. During the last decade, machine learning technologies have shown great potential to revolutionize clinical management of AMD and support research for a better understanding of the disease. The aim of this review is to provide a panoramic description of all the applications of AI to AMD management and screening that have been analyzed in recent past literature. Deep learning (DL) can be effectively used to diagnose AMD, to predict short term risk of exudation and need for injections within the next 2 years. Moreover, DL technology has the potential to customize anti-VEGF treatment choice with a higher accuracy than expert human experts. In addition, accurate prediction of VA response to treatment can be provided to the patients with the use of ML models, which could considerably increase patients’ compliance to treatment in favorable cases. Lastly, AI, especially in the form of DL, can effectively predict conversion to GA in 12 months and also suggest new biomarkers of conversion with an innovative reverse engineering approach.
Influence of families and other adult support on HIV prevention outcomes among black men who have sex with men
Authors: Boyd Donte T. , Ramos S. Raquel , Maragh-Bass Allysha C. , Dyer Typhanye V. , Zigah Edem Yaw , Abu-Ba’are Gamji Rabiu
Published: March 2024

Background

Prior research has consistently shown that the involvement of families plays a vital role in reducing risk behaviors, such as engaging in condomless sex, and promoting HIV prevention behaviors among young Black men who have sex with men (YBMSM). With the aim of expanding the existing knowledge, this study aimed to examine the specific influence of families and other supportive adults in facilitating casual condom use, partner condom use, HIV testing, and preexposure prophylaxis (PrEP) utilization among young Black MSM.

Methods

A sample of YBMSM aged 18–29 years (N = 400) was collected online. We used a path analysis to examine the influence of family factors on PrEP stigma and PrEP use. Respondents were recruited from December 1, 2021, to January 31, 2022. We used a path analysis to examine the direct and indirect effects of family factors on PrEP use through HIV testing and encouraging condom use.

Results

Among BMSM, other adult support was positive and directly associated with condom use by both casual partners (β = 0.04, p < .05) and partners (β = 0.17, p < .01). Condom use by casual partners was negative and was directly associated with HIV testing (β = − 0.15, p < .01).

Conclusion

The primary aim of this research was to examine the influence of family and adult support on HIV prevention behaviors among young Black MSM, including condom use, HIV testing, and PrEP use. Our findings highlight the significance of implementing interventions that incorporate families and other supportive adults to enhance the engagement of young Black MSM in HIV prevention behaviors.
The impact of caregiver burden on quality of life in family caregivers of patients with advanced cancer: a moderated mediation analysis of the role of psychological distress and family resilience
Authors: Cui Panpan , Yang Ming , Hu Hengyu , Cheng Chunyan , Chen Xinyi , Shi Jiaoxia , Li Shifeng , Chen Changying , Zhang Hongmei
Published: March 2024

Background

The caregiver burden frequently experienced by family members tending to advanced cancer patients significantly impacts their psychological well-being and quality of life (QoL). Although family resilience might function as a mitigating factor in this relationship, its specific role remains to be elucidated. This study aims to probe the mediating effect of psychological distress on the relationship between caregiver burden and QoL, as well as the moderating effect of family resilience.

Methods

A cross-sectional study was conducted between June 2020 and March 2021 in five tertiary hospitals in China. Data were collected on caregiver burden, family resilience, psychological distress (including anxiety and depression), and QoL. Moderated mediation analysis was performed.

Results

Data analysis included 290 caregivers. It confirmed the mediating role of psychological distress in the caregiver burden-QoL relationship (P < 0.001). Both overall family resilience and the specific dimension of family communication and problem-solving (FCPS) demonstrated significant moderating effects on the “psychological distress/anxiety—QoL” paths (P < 0.05). The utilization of social and economic resources (USER) significantly moderated the association between depression and QoL (P < 0.05).

Conclusions

The study corroborates psychological distress's mediation between caregiver burden and QoL and family resilience's moderation between psychological distress and QoL. It underscores the need for minimizing psychological distress and bolstering family resilience among caregivers of advanced cancer patients. Accordingly, interventions should be tailored, inclusive of psychological assistance and promotion of family resilience, particularly focusing on FCPS and USER, to augment the caregivers' well-being and QoL.
Relationship between physical activity and risk of depression in a married group
Authors: Ni Rong Jing , Yu Ying
Published: March 2024

Background

Currently, there are many different findings on the relationship between physical activity and depression, and there may be differences between genders. This study therefore focused on gender differences to understand the relationship between physical activity behaviour and the risk of depression in married individuals.

Methods

15607 married people in the China Family Panel Studies 2020 (CFPS 2020) were used to understand the relationship between physical activity and depression risk in different populations, and the chi-square test, Mann-Whitney U-test, and binary logistic regression were used to explore the relationship between physical activity and depression risk in the married population.

Results

527 (6.64%) women were at high risk of depression and 365 (4.76%) men were at high risk of depression; physical activity was associated with the risk of depression in the married population, but after incorporating demographic and relevant cognitive variables, physical activity was negatively associated with the risk of depression in women (OR = 0.94, P < 0.01) but not statistically significant with the risk of depression in men (OR = 0.96, P > 0.05).

Conclusion

Physical activity was directly related to the risk of depression in married women, but not in married men.
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

Bronchopulmonary 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

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

Cancer 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

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

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

There 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

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

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

Background

Tanzania 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.

Methods

Plasmodium 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.

Results

Overall, 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.

Conclusion

Microsatellite 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

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

The 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.
OralExplorer: a web server for exploring the mechanisms of oral inflammatory diseases
Authors: Lin Weiyin , Yang Hong , Lin Jiayu , Yang Xia , Liao Zhihao , Zheng Yifan , Luo Peng , Liu Chufeng
Published: March 2024

Background

Oral inflammatory diseases are localized infectious diseases primarily caused by oral pathogens with the potential for serious systemic complications. However, publicly available datasets for these diseases are underutilized. To address this issue, a web tool called OralExplorer was developed. This tool integrates the available data and provides comprehensive online bioinformatic analysis.

Methods

Human oral inflammatory disease-related datasets were obtained from the GEO database and normalized using a standardized process. Transcriptome data were then subjected to differential gene expression analysis, immune infiltration analysis, correlation analysis, pathway enrichment analysis, and visualization. The single-cell sequencing data was visualized as cluster plot, feature plot, and heatmaps. The web platform was primarily built using Shiny. The biomarkers identified in OralExplorer were validated using local clinical samples through qPCR and IHC.

Results

A total of 35 human oral inflammatory disease-related datasets, covering 6 main disease types and 901 samples, were included in the study to identify potential molecular signatures of the mechanisms of oral diseases. OralExplorer consists of 5 main analysis modules (differential gene expression analysis, immune infiltration analysis, correlation analysis, pathway enrichment analysis and single-cell analysis), with multiple visualization options. The platform offers a simple and intuitive interface, high-quality images for visualization, and detailed analysis results tables for easy access by users. Six markers (IL1β, SRGN, CXCR1, FGR, ARHGEF2, and PTAFR) were identified by OralExplorer. qPCR- and IHC-based experimental validation showed significantly higher levels of these genes in the periodontitis group.

Conclusions

OralExplorer is a comprehensive analytical platform for oral inflammatory diseases. It allows users to interactively explore the molecular mechanisms underlying the action and regression of these diseases. It also aids dental researchers in unlocking the potential value of transcriptomics data related to oral diseases. OralExplorer can be accessed athttps://smuonco.shinyapps.io/OralExplorer/ (Alternate URL:http://robinl-lab.com/OralExplorer).