bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smooth muscle cells-specific loss of OCT4 accelerates neointima formation after acute vascular injury
Authors: Shin Junchul , Tkachenko Svyatoslav , Gomez Delphine , Tripathi Rupande , Owens Gary K. , Cherepanova Olga A. 
Published: October 2023

IntroductionThere is growing evidence that smooth muscle cell (SMC) phenotypic transitions play critical roles during normal developmental and tissue recovery processes and in pathological conditions such as atherosclerosis. However, the molecular mechanisms responsible for these transitions are not well understood. Recently, we found that the embryonic stem cell/induced pluripotent stem cell (iPSC) factor OCT4, which was believed to be silenced in somatic cells, plays an atheroprotective role in SMC, and regulates angiogenesis after corneal alkali burn and hindlimb ischemia by mediating microvascular SMC and pericyte migration. However, the kinetics of OCT4 activation in arterial SMC and its role in acute pathological conditions are still unknown.Methods and ResultsHere, using an Oct4-IRES-GFP reporter mouse model, we found that OCT4 is reactivated in the carotid artery 18 hours post-acute ligation-induced injury, a common in vivo model of the SMC phenotypic transitions. Next, using a tamoxifen-inducible Myh11-CreERT2 Oct4 knockout mouse model, we found that the loss of OCT4, specifically in SMC, led to accelerated neointima formation and increased tunica media following carotid artery ligation, at least in part by increasing SMC proliferation within the media. Bulk RNA sequencing analysis on the cultured SMC revealed significant down-regulation of the SMC contractile markers and dysregulation of the genes belonging to the regulation of cell proliferation and, positive and negative regulation for cell migration ontological groups following genetic inactivation of Oct4. We also found that loss of Oct4 resulted in suppression of contractile SMC markers after the injury and in cultured aortic SMC. Further mechanistic studies revealed that OCT4 regulates SMC contractile genes, ACTA2 and TAGLN, at least in part by direct binding to the promoters of these genes.ConclusionThese results demonstrate that the pluripotency factor OCT4 is quickly activated in SMC after the acute vascular injury and inhibits SMC hyperproliferation, which may be protective in preventing excessive neointima formation.
Adalimumab biosimilar ABP 501 is equally effective and safe in long-term management of inflammatory bowel diseases patients when used as first biologic treatment or as replace of the ADA originator for a non-medical reason
Authors: Mocci Giammarco , Cingolani Arianna , Orrù Giorgia , Felice Carla , Onidi Francesca Maria , Lombardi Gianmarco , Checchin Davide , Colucci Raffaele , Grossi Laurino , Ferronato Antonio , Rocchi Chiara , Ascolani Marta , Satta Paolo Usai , Fanini Lucia , Pilati Stefano , Tursi Antonio 
Published: October 2023

ObjectiveBiosimilars represent a new opportunity for inflammatory bowel disease (IBD) treatment and economic sustainability of therapies. This study aimed to evaluate the efficacy and long-term safety of the adalimumab biosimilar ABP 501 in biologic-naïve vs. biologic-switched IBD patients.MethodsA retrospective observational study was conducted using a database of patients with IBD treated with ABP 501, biologic-naïve or switched from the original, at eight IBD centers. We included adult patients with at least one year of follow-up. The primary objective of this study was to assess the efficacy (persistence) and safety (adverse event rate) of ABP 501 therapy.ResultsA total of 118 patients with IBD were included in the analysis: 84 patients with Crohn’s disease (CD) (39 women, 45 men, mean age 40.4 ± 14.3 years; 33% biologic-naïve) and 34 patients with ulcerative Colitis (UC) (16 women, 18 men, mean age 38.9 ± 14.9 years; 61.8% biologic-naïve). Regarding the primary endpoint, no difference was observed in the efficacy between biologic-naïve patients and patients with Adalimumab (ADA) originator replacement for non-medical reasons in terms of long-term persistence. However, ABP 501 showed a higher percentage of sustained clinical remission at 2 years in patients with CD (64 patients, 77%) than in those with UC (15 patients, 45.5%; p=0.00091). Nine patients (six with CD and three with UC) experienced adverse events that led to drug discontinuation in three.ConclusionsAPB 501 showed a good safety and efficacy profile in maintaining clinical response at 2 years in patients with IBD, both as a treatment-naïve and as a replacement for ADA originator for non-medical reasons.
Gender-based roles, psychosocial variation, and power relations during delivery and postnatal care: a qualitative case study in rural Ethiopia
Authors: Shibeshi Ketema , Lemu Yohannes , Gebretsadik Lakew , Gebretsadik Abebe , Morankar Sudhakar 
Published: October 2023

IntroductionThe World Health Organization (WHO) strongly encouraged men to support women in receiving maternal healthcare. However, especially in developing countries, maternal healthcare has traditionally been viewed as an issue in women, with men making little or no contribution, even though sexuality and children are shared products. The study aims to understand how gender-based roles, psychosocial variation, and power relations are related to child delivery and postnatal care (PNC) services.MethodsThe study was conducted in three rural districts of Oromia regional state, Jimma Zone, Ethiopia. An in-depth interview and focus group discussion were held with carefully chosen health professionals, health extension workers, community health development armies, and religious leaders. The data was collected, translated, and transcribed by experienced men and women qualitative researchers. For data analysis, ATLAS.ti version 9 was used. The data were coded and categorized concerning delivery and PNC service utilization. Independent and shared gender-based roles were identified as a means to improve maternal healthcare service delivery.ResultsThe result obtained three categories, namely, gender-based roles, psychosocial variation, and power relations. Men can persuade pregnant women to use delivery services and PNC. The place of delivery is determined by the levels of gender-based power relations at the household level, but women are usually the last decision-makers. The belief of the community that giving birth in a health facility makes women look clean and neat, as opposed to home delivery, increases their intention to use maternal healthcare services.DiscussionThe study contributes that the role of a man as a husband is crucial in mobilizing others to carry pregnant women to health facilities, contributing to early intervention during labor. The decision-making capacity of women has improved over time, with men accepting their right to make decisions about their health and fetuses. Home delivery and men not being present during delivery are perceived as signs of backwardness, whereas giving birth in health institutes is seen as a sign of modernization and the rights of women.
Pembrolizumab combined with anlotinib improves therapeutic efficacy in pulmonary sarcomatoid carcinoma with TMB-H and PD-L1 expression: a case report and literature review
Authors: Wu Shugui , Wu Shanlian , Liao Xiaohong , Zhou Chaoming , Qiu Feng , Wang Chen , Zhong Wenjuan 
Published: October 2023

BackgroundPulmonary sarcomatoid carcinoma (PSC) is a unique subtype of non-small cell lung cancer (NSCLC) with a high degree of malignancy and poor therapeutic effects. With the widespread use of immune checkpoint inhibitors (ICIs) in recent years, few studies have reported that immunotherapy is effective against PSC. As a multi-target anti-vascular targeting agent, anlotinib showed a better anti-tumor effect in various cancer species. The paper reported the therapeutic and side effects of pembrolizumab combined with anlotinib in a patient with advanced PSC.Case presentationThis is a 73 year old female patient who underwent thoracoscopy right upper lobectomy and was diagnosed as locally advanced PSC. However, the patient experienced tumor recurrence and metastasis 7 weeks after surgery and was unable to tolerate chemoradiotherapy. Moreover, she detected TP53 mutation and found that tumor mutation burden (TMB) and PD-L1 were high expression. Therefore, the patient received pembrolizumab combined with anlotinib treatment. After 15 cycles of treatment, the tumor significantly shrank with no tumor activity. The evaluation of tumor efficacy is partial response (PR). During the treatment period, she experienced one-degree thyroid-stimulating hormone elevation and two-degree hand-foot syndrome. Pembrolizumab and anlotinib was continued for two years as a maintenance treatment. The patient had a good quality of life and no disease progression was observed. Currently, the patient is still alive without tumor progression and has overall survival exceeding 45 months and toxic side effects were tolerable.ConclusionsCombining ICIs and anti-angiogenic targeted therapy has brought new hope in treating advanced PSC. Additionally, TMB and PD-L1 expression could be potential predictive biomarkers of the efficacy in advanced PSC with immunotherapy.
The causal relationship between gut microbiota and bone mineral density: a Mendelian randomization study
Authors: Wang Ying , Zhang Xuejian , Tang Guangjun , Deng Pin , Qin Yuyan , Han Jinglu , Wang Shulong , Sun Xiaojie , Li Dongxiao , Chen Zhaojun 
Published: October 2023

BackgroundThe gut microbiota has emerged as an intriguing and potentially influential factor in regulating bone health. However, the causal effect of the gut microbiota on bone mineral density (BMD) appears to differ throughout various life stages.MethodsWe conducted a Mendelian randomization (MR) analysis to investigate the potential causal relationship between gut microbiota and BMD in five distinct age groups: 0–15, 15–30, 30–45, 45–60, and 60 years and older. The analysis employed three different methods, namely MR-Egger, weighted median, and Inverse-variance weighting, to ensure the robustness of our findings, a series of sensitivity analyses were also conducted, such as horizontal pleiotropy tests, heterogeneity tests, and leave-one-out sensitivity tests.ResultsIn the age group of 0–15 years, Eubacterium_fissicatena_group and Eubacterium_hallii_group were identified as risk factors for BMD. During the 15–30 age group, Phascolarctobacterium, Roseburia, and Ruminococcaceae_UCG_003 were found to be protective factors for BMD. In the 30–45 age group, Lachnospira genus demonstrated a protective effect on BMD, while Barnesiella and Lactococcus were identified as risk factors for BMD. Moving on to the 45–60 age group, Eubacterium_ventriosum_group, Lachnospiraceae_UCG_004, and Subdoligranulum were observed to be protective factors for BMD, while Eubacterium_coprostanoligenes_group, Fusicatenibacter, and Lactococcus were associated with an increased risk of BMD. In individuals aged 60 years and older, Fusicatenibacter and Ruminococcaceae_UCG_002 were also noted as risk factors for BMD. Conversely, Eubacterium_ruminantium_group, Ruminococcus_gauvreauii_group, Alistipes, and Coprococcus_3 were found to be protective factors for BMD, whereas Barnesiella and Sellimonas were identified as risk factors for BMD.ConclusionA robust causal relationship between gut microbiota and bone mineral density (BMD) exists throughout all stages of life, with Firmicutes phylum being the primary group associated with BMD across age groups. Gut microbiota linked with BMD primarily belong to the Firmicutes phylum across age groups. The diversity of gut microbiota phyla associated with BMD depicts relatively stable patterns during the ages of 0–45 years. However, for individuals aged 45 years and above, there is an observed increase in the number of gut microbiota species linked with BMD, and by the age of 60 years, a trend toward an increase in the Bacteroidetes phylum categories is proposed.
Predicting mild cognitive impairment among Chinese older adults: a longitudinal study based on long short-term memory networks and machine learning
Authors: Huang Yucheng , Huang Zishuo , Yang Qingren , Jin Haojie , Xu Tingke , Fu Yating , Zhu Yue , Zhang Xiangyang , Chen Chun 
Published: October 2023

BackgroundMild cognitive impairment (MCI) is a transitory yet reversible stage of dementia. Systematic, scientific and population-wide early screening system for MCI is lacking. This study aimed to construct prediction models using longitudinal data to identify potential MCI patients and explore its critical features among Chinese older adults.MethodsA total of 2,128 participants were selected from wave 5–8 of Chinese Longitudinal Healthy Longevity Study. Cognitive function was measured using the Chinese version of Mini-Mental State Examination. Long- short-term memory (LSTM) and three machine learning techniques, including 8 sociodemographic features and 12 health behavior and health status features, were used to predict individual risk of MCI in the next year. Performances of prediction models were evaluated through receiver operating curve and decision curve analysis. The importance of predictors in prediction models were explored using Shapley Additive explanation (SHAP) model.ResultsThe area under the curve values of three models were around 0.90 and decision curve analysis indicated that the net benefit of XGboost and Random Forest were approximate when threshold is lower than 0.8. SHAP models showed that age, education, respiratory disease, gastrointestinal ulcer and self-rated health are the five most important predictors of MCI.ConclusionThis screening method of MCI, combining LSTM and machine learning, successfully predicted the risk of MCI using longitudinal datasets, and enables health care providers to implement early intervention to delay the process from MCI to dementia, reducing the incidence and treatment cost of dementia ultimately.
Temporal dynamics of isolation calls emitted by pups in environmental and genetic mouse models of autism spectrum disorder
Authors: Gal Ayelet , Raykin Eynav , Giladi Shaked , Lederman Dror , Kofman Ora , Golan Hava M. 
Published: October 2023

IntroductionEnvironmental and genetic factors contribute to the increased risk for neurodevelopmental disorders, including deficits in the development of social communication. In the mouse, ultrasonic vocalizations emitted by the pup stimulate maternal retrieval and potentiate maternal care. Therefore, isolation induced ultrasonic vocalization emitted by pups provides a means to evaluate deficits in communication during early development, before other ways of communication are apparent. Previous studies in our labs showed that gestational exposure to the pesticide chlorpyrifos (CPF) and the Methylenetetrahydrofolate (Mthfr)-knock-out mice are associated with impaired social preference, restricted or repetitive behavior and altered spectral properties of pups’ ultrasonic vocalization. In this study, we explore the temporal dynamics of pups’ vocalization in these Autism spectrum disorder (ASD) models.MethodsWe utilized the maternal potentiation protocol and analyzed the time course of pup vocalizations following isolation from the nest. Two models of ASD were studied: gestational exposure to the pesticide CPF and the Mthfr-knock-out mice.ResultsVocalization emitted by pups of both ASD models were dynamically modified in quantity and spectral structure within each session and between the two isolation sessions. The first isolation session was characterized by a buildup of call quantity and significant effects of USV spectral structure variables, and the second isolation session was characterized by enhanced calls and vocalization time, but minute effect on USV properties. Moreover, in both models we described an increased usage of harmonic calls with time during the isolation sessions.DiscussionCommunication between two or more individuals requires an interplay between the two sides and depends on the response and the time since the stimulus. As such, the presence of dynamic changes in vocalization structure in the control pups, and the alteration observed in the pups of the ASD models, suggest impaired regulation of vocalization associated with the environmental and genetic factors. Last, we propose that temporal dynamics of ultrasonic vocalization communication should be considered in future analysis in rodent models of ASD to maximize the sensitivity of the study of vocalizations.
Diagnostic performance of CT scan–based radiomics for prediction of lymph node metastasis in gastric cancer: a systematic review and meta-analysis
Authors: HajiEsmailPoor Zanyar , Tabnak Peyman , Baradaran Behzad , Pashazadeh Fariba , Aghebati-Maleki Leili 
Published: October 2023

ObjectiveThe purpose of this study was to evaluate the diagnostic performance of computed tomography (CT) scan–based radiomics in prediction of lymph node metastasis (LNM) in gastric cancer (GC) patients.MethodsPubMed, Embase, Web of Science, and Cochrane Library databases were searched for original studies published until 10 November 2022, and the studies satisfying the inclusion criteria were included. Characteristics of included studies and radiomics approach and data for constructing 2 × 2 tables were extracted. The radiomics quality score (RQS) and Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) were utilized for the quality assessment of included studies. Overall sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated to assess diagnostic accuracy. The subgroup analysis and Spearman’s correlation coefficient was done for exploration of heterogeneity sources.ResultsFifteen studies with 7,010 GC patients were included. We conducted analyses on both radiomics signature and combined (based on signature and clinical features) models. The pooled sensitivity, specificity, DOR, and AUC of radiomics models compared to combined models were 0.75 (95% CI, 0.67–0.82) versus 0.81 (95% CI, 0.75–0.86), 0.80 (95% CI, 0.73–0.86) versus 0.85 (95% CI, 0.79–0.89), 13 (95% CI, 7–23) versus 23 (95% CI, 13–42), and 0.85 (95% CI, 0.81–0.86) versus 0.90 (95% CI, 0.87–0.92), respectively. The meta-analysis indicated a significant heterogeneity among studies. The subgroup analysis revealed that arterial phase CT scan, tumoral and nodal regions of interest (ROIs), automatic segmentation, and two-dimensional (2D) ROI could improve diagnostic accuracy compared to venous phase CT scan, tumoral-only ROI, manual segmentation, and 3D ROI, respectively. Overall, the quality of studies was quite acceptable based on both QUADAS-2 and RQS tools.ConclusionCT scan–based radiomics approach has a promising potential for the prediction of LNM in GC patients preoperatively as a non-invasive diagnostic tool. Methodological heterogeneity is the main limitation of the included studies.Systematic review registrationhttps://www.crd.york.ac.uk/Prospero/display_record.php?RecordID=287676, identifier CRD42022287676.
Next-generation sequencing identifies CDKN2A alterations as prognostic biomarkers in recurrent or metastatic head and neck squamous cell carcinoma predominantly receiving immune checkpoint inhibitors
Authors: Xue Liqiong , Tang Wenbo , Zhou Jiuli , Xue Junli , Li Qun , Ge Xiaoxiao , Lin Fengjuan , Zhao Wei , Guo Ye 
Published: October 2023

BackgroundThis study aimed to identify potential biomarkers in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) and further probe the prognostic implications of CDKN2A mutations, particularly within a subset receiving immunotherapy.MethodsIn this retrospective single-center study, we evaluated the next-generation sequencing (NGS) data from Foundation Medicine (FM) for patients with recurrent or metastatic HNSCC between January 1, 2019, and December 31, 2021. Patients were stratified based on CDKN2A loss-of-function (LOF) versus wild-type (WT) categorizations, with a focused subgroup analysis on those administered immunotherapy.ResultsThe study encompassed 77 patients, of which 62 had undergone immunotherapy. The median duration of follow-up was 22.6 months. For the CDKN2A LOF group, the median overall survival (OS) was 16.5 months, contrasted with 30.0 months in the CDKN2A WT group (P=0.014). Notably, female gender (hazard ratio [HR]=4.526, 95% confidence interval [CI]: 1.934-10.180, P=0.0003) and CDKN2A LOF (HR=2.311, 95% CI: 1.156-4.748, P=0.019) emerged as independent risk factors for mortality in patients with recurrent or metastatic HNSCC. Within the immunotherapy subset, the median OS was 11.7 months for the CDKN2A LOF group, and 22.5 months for the CDKN2A WT group (P=0.017). Further, the female gender (HR=4.022, 95% CI: 1.417-10.710, P=0.006), CDKN2A LOF (HR=4.389, 95% CI: 1.782-11.460, P=0.002), and a combined positive score below 1 (HR=17.20, 95% CI: 4.134-79.550, P&lt;0.0001) were identified as significant predictors of mortality among patients with recurrent or metastatic HNSCC receiving immunotherapy.ConclusionAlterations manifesting as LOF in the CDKN2A gene stand as robust indicators of unfavorable survival outcomes in HNSCC patients, including the subset that underwent immunotherapy.
Case Report: Treatment and management of a child at high risk of caries
Authors: Fan Wen , Chen Qianjing , Zhang Yushan , Feng Jixian , Zhai Yuankun , He Baojie 
Published: October 2023

IntroductionCaries are at the forefront of childhood diseases. Although childhood caries is usually not life-threatening, it can affect children's dental–maxillofacial development and mental health and place significant financial and psychological burdens on parents. As the focus of childhood dental caries shifts to early diagnosis and prevention rather than restorative dentistry alone, screening children at a high risk of dental caries is urgent. Appropriate caries prevention measures and treatment sequences can effectively reduce the occurrence and development of dental caries in children.CaseWe report the case of a 7-year-old boy presenting with a high risk of dental caries involving multiple primary teeth and premature eruption of the permanent teeth. We shifted the caries status of the child from high to moderate likelihood. At the 9-month post-treatment follow-up, the patient had no new dental caries, and the length and width of the dental arch were effectively maintained.ConclusionOral health education, dental plaque removal in a regular basis, and fluoride application contribute to caries management.