bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human dental pulp stem cells (hDPSCs) promote the lipofibroblast transition in the early stage of a fibro-inflammatory process
Authors: Pisciotta Alessandra , Di Tinco Rosanna , Bertani Giulia , Orlandi Giulia , Bertoni Laura , Pignatti Elisa , Orciani Monia , Sena Paola , Bertacchini Jessika , Salvarani Carlo , Carnevale Gianluca 
Published: May 2023

Introduction: In autoimmune diseases, particularly in systemic sclerosis and chronic periaortitis, a strict correlation between chronic inflammation and fibrosis exists. Since the currently used drugs prove mostly effective in suppressing inflammation, a better comprehension of the molecular mechanisms exerted by cell types implicated in fibro-inflammation is needed to develop novel therapeutic strategies. Mesenchymal stromal/stem cells (MSCs) are being matter of deep investigation to unveil their role in the evolution of fibrogenetic process. Several findings pointed out the controversial implication of MSCs in these events, with reports lining at a beneficial effect exerted by external MSCs and others highlighting a direct contribution of resident MSCs in fibrosis progression. Human dental pulp stem cells (hDPSCs) have demonstrated to hold promise as potential therapeutic tools due to their immunomodulatory properties, which strongly support their contribution to tissue regeneration.Methods: Our present study evaluated hDPSCs response to a fibro-inflammatory microenvironment, mimicked in vitro by a transwell co-culture system with human dermal fibroblasts, at early and late culture passages, in presence of TGF-β1, a master promoter of fibrogenesis.Results and Discussion: We observed that hDPSCs, exposed to acute fibro-inflammatory stimuli, promote a myofibroblast-to-lipofibroblast transition, likely based on BMP2 dependent pathways. Conversely, when a chronic fibro-inflammatory microenvironment is generated, hDPSCs reduce their anti-fibrotic effect and acquire a pro-fibrotic phenotype. These data provide the basis for further investigations on the response of hDPSCs to varying fibro-inflammatory conditions.
Protective effect of ursodeoxycholic acid on COVID-19 in patients with chronic liver disease
Authors: Li Yanyan , Zhu Na , Cui Xinyu , Lin Yingying , Li Xin 
Published: May 2023

ObjectiveUrsodeoxycholic acid (UDCA) may reduce susceptibility to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection by downregulating angiotensin-converting enzyme 2 (ACE2), based on recent experimental investigation. This study aimed to determine the potential protective effect of UDCA against SARS-CoV-2 infection in patients with chronic liver disease.MethodsPatients with chronic liver disease receiving UDCA (taking UDCA ≥1 month) at Beijing Ditan Hospital between January 2022 and December 2022 were consecutively enrolled. These patients were matched in a 1:1 ratio to those with liver disease not receiving UDCA during the same period by using a propensity score matching analysis with nearest neighbor matching algorithm. We conducted a phone survey of coronavirus disease 2019 (COVID-19) infection during the early phase of the pandemic liberation (from 15 December 2022 to 15 January 2023). The risk of COVID-19 was compared in two matched cohorts of 225 UDCA users and 225 non-UDCA users based on patient self-report.ResultsIn the adjusted analysis, the control group was superior to the UDCA group in COVID-19 vaccination rates and liver function indicators, including γ-glutamyl transpeptidase and alkaline phosphatase (p &lt; 0.05). UDCA was associated with a lower incidence of SARS-CoV-2 infection (UDCA 85.3% vs. control 94.2%, p = 0.002), more mild cases (80.0% vs. 72.0%, p = 0.047), and shorter median time from infection to recovery (5 vs. 7 days, p &lt; 0.001). Logistic regression analysis showed that UDCA was a significant protective factor against COVID-19 infection (OR: 0.32, 95%CI: 0.16–0.64, p = 0.001). Furthermore, diabetes mellitus (OR: 2.48, 95%CI: 1.11–5.54, p = 0.027) and moderate/severe infection (OR: 8.94, 95%CI: 1.07–74.61, p = 0.043) were more likely to prolong the time from infection to recovery.ConclusionUDCA therapy may be beneficial in reducing COVID-19 infection risk, alleviating symptoms, and shortening the recovery time in patients with chronic liver disease. However, it should be emphasized that the conclusions were based on patient self-report rather than classical COVID-19 detection by experimental investigations. Further large clinical and experimental studies are needed to validate these findings.
Multi-omics analysis of Siglec family genes in cutaneous melanoma
Authors: Li Kezhu , Xu Nan , Guo Shu 
Published: May 2023

BackgroundMelanoma is widely recognized as the most aggressive and fatal type of skin cancer; however, effective prognostic markers are lacking. The sialic acid-binding immunoglobulin-type lectin (Siglec) gene family plays an important role in the development of tumors and immune escape, but its prognostic role in melanoma remains unknown.ResultsSiglec genes have a high mutation frequency, with up to 8% in SIGLEC7. High expression levels of Siglecs in tumor bulk suggests a better prognosis. Siglecs also show a high degree of synergistic expression. Immunohistochemistry was used to analyze the expression of SIGLEC9 in tumor tissue microarray. The expression of SIGLEC9 in tumor tissue without metastasis was higher than that in tumor tissue with metastasis. We used unsupervised clustering to create a high expression of Siglec (HES) cluster and a low expression of Siglec (LES) cluster. The HES cluster correlated with high overall survival and increased expression levels of Siglec genes. The HES cluster also showed significant immune cell infiltration and activation of immune signaling pathways. We used least absolute shrinkage and selection operator (LASSO) regression analysis to reduce the dimensionality of Siglec cluster-related genes and constructed a prognostic model composed of SRGN and GBP4, which can risk-stratify patients in both the training and test datasets.ConclusionWe conducted a multi-omics analysis of the Siglec family genes in melanoma and found that Siglecs play an important role in the occurrence and development of melanoma. Typing constructed using Siglecs can show risk stratification and derived prognostic models can predict a patient’s risk score. In summary, Siglec family genes are potential targets for melanoma treatment as well as prognostic markers that can direct individualized treatments and improve overall survival.
Unique genotype-phenotype correlations within LAMA2-related limb girdle muscular dystrophy in Chinese patients
Authors: Huang Xiuli , Tan Dandan , Zhang Zaiqiang , Ge Lin , Liu Jieyu , Ding Juan , Yang Haipo , Wei Cuijie , Chang Xingzhi , Yuan Yun , Yan Chuanzhu , Xiong Hui 
Published: May 2023

BackgroundLAMA2-related limb girdle muscular dystrophy (LGMD R23) is rare. The detailed clinical phenotypes and genetic information associated with LGMD R23 are unknown.MethodsWe conducted a retrospective cross-sectional and longitudinal study on 19 LGMD R23 patients.ResultsNormal early motor development was observed in 84.2% patients. Mild orthopedic complications were observed in 42.1% patients. 36.8% patients had seizures, which is unusually frequent in LGMD. Epilepsy was eventually diagnosed in 26.3% patients. 46.7% patients presented with motor neuropathy. Genetic analysis identified 29 pathogenic variants, with missense and frameshift variants being the most common. The mutant sites were mainly distributed in the N-terminal and G-like domains of laminin. The missense variants are distributed near the N-terminus (exons 3–11), whereas frameshift variants are distributed in exons 12–65. Five patients were diagnosed with epilepsy and all of them harbor at least one missense variants in exon 4. 71.4% variants of patients with motor neuropathy located in the LN domain.ConclusionsMissense variants in exon 4 maybe correlated with epilepsy and variants in the LN domain maybe correlated with motor neuropathy in Chinese patients. Our study expands the clinical and genetic spectrum caused by LAMA2 variations and provides novel genotype-phenotype correlations of LGMD R23.
Dermoglandular advancement-rotation flap for conservative treatment of breast cancer – description of technique, objective and subjective assessments
Authors: Soliani Bastos Maria Carolina , Bagnoli Fábio , Rinaldi José Francisco , João Thais Businaro Fernandes , de Oliveira Vilmar Marques 
Published: May 2023

Objectiveto describe and evaluate the dermoglandular advancement-rotation flap with no contralateral surgery as a technique for the conservative treatment of breast cancer when skin or a large proportion of gland requires resection.Patients/Methods14 patients with breast tumors with a mean size of 4.2 cm and need for skin resection. The resection area is included within an isosceles triangle, with its apex located on the areola, which is the pivot for rotation of a dermoglandular flap released through a lateral extension along that triangle base. Symmetry before and after radiotherapy was objectively assessed by authors using the BCCT.core software, as well as subjectively by three experts and patients themselves using the Harvard scale.ResultsExperts considered the breast symmetry results to be excellent/good for 85.7% of patients in the early post-operative period and 78.6% in the late post-operative period. Excellent/good ratings provided by BCCT.core software amounted to 78.6% of cases in the early post-operative period and 92.9% in the late post-operative period. Symmetry was rated as excellent/good by 100% of patients.ConclusionDermoglandular advancement-rotation flap technique with no contralateral surgery provides good symmetry when a large proportion of skin or gland requires resection on breast conservative cancer treatment.
TYROBP-positive endothelial cell-derived TWEAK as a promoter of osteosarcoma progression: insights from single-cell omics
Authors: Wei Zhi-qiang , Ding Sheng , Yang Yan-cai 
Published: May 2023

BackgroundEndothelial cells (ECs) play a vital role in promoting the progression of malignant cells, and they exhibit heterogeneity in their phenotypic characteristics. We aimed to explore the initiating cells of ECs in osteosarcoma (OS) and investigate their potential interaction with malignant cells.MethodWe obtained scRNA-seq data from 6 OS patients, and datasets were batch-corrected to minimize variations among samples. Pseudotime analysis was performed to investigate the origin of differentiation of ECs. CellChat was employed to examine the potential communication between endothelial cells and malignant cells, and gene regulatory network analysis was performed to identify transcription factor activity changes during the conversion process. Importantly, we generated TYROBP-positive ECs in vitro and investigated its role in OS cell lines. Finally, we explored the prognosis of specific ECs cluster and their impact on the tumor microenvironment (TME) at the bulk transcriptome level.ResultsThe results showed that TYROBP-positive ECs may play a crucial role in initiating the differentiation of ECs. TYROBOP-positive endothelial cells (ECs) exhibited the strongest crosstalk with malignant cells, likely mediated by TWEAK, a multifunctional cytokine. TYROBP-positive ECs exhibited significant expression of TME-related genes, unique metabolic and immunological profiles. Importantly, OS patients with low enrichment of TYROBP-positive ECs had better prognoses and a lower risk of metastasis. Finally, vitro assays confirmed that TWEAK was significantly increased in ECs-conditioned medium (ECs-CM) when TYROBP was over-expressed in EC cells, and could promote the proliferation and migration of OS cells.ConclusionWe concluded that TYROBP-positive ECs may be the initiating cells and play a crucial role in the promotion of malignant cell progression. TYROBP-positive ECs have a unique metabolic and immunological profile and may interact with malignant cells through the secretion of TWEAK.
Animal venoms: a novel source of anti-Toxoplasma gondii drug candidates
Authors: Yang Dongqian , Liu Xiaohua , Li Jing , Xie Jing , Jiang Liping 
Published: May 2023

Toxoplasma gondii (T. gondii) is a nucleated intracellular parasitic protozoan with a broad host selectivity. It causes toxoplasmosis in immunocompromised or immunodeficient patients. The currently available treatments for toxoplasmosis have significant side effects as well as certain limitations, and the development of vaccines remains to be explored. Animal venoms are considered to be an important source of novel antimicrobial agents. Some peptides from animal venoms have amphipathic alpha-helix structures. They inhibit the growth of pathogens by targeting membranes to produce lethal pores and cause membrane rupture. Venom molecules generally possess immunomodulatory properties and play key roles in the suppression of pathogenic organisms. Here, we summarized literatures of the last 15 years on the interaction of animal venom peptides with T. gondii and attempt to explore the mechanisms of their interaction with parasites that involve membrane and organelle damage, immune response regulation and ion homeostasis. Finally, we analyzed some limitations of venom peptides for drug therapy and some insights into their development in future studies. It is hoped that more research will be stimulated to turn attention to the medical value of animal venoms in toxoplasmosis.
Combined associations of vitamin D and cognitive function with all-cause mortality among older adults in Chinese longevity areas: A prospective cohort study
Authors: Dai Miao , Song Quhong , Wang Xiang , Li Ying , Lin Taiping , Liang Rui , Jiang Tingting , Shu Xiaoyu , Ge Ning , Yue Jirong 
Published: May 2023

ObjectivesWhile both vitamin D deficiency and cognitive impairment have individually been linked to a greater risk of all-cause mortality, the combined effects of these two different conditions have not previously been explored in this context. We aimed to investigate the combined impact of vitamin D concentration and cognitive impairment on all-cause mortality in older adults.MethodsThe analyzed data were collected from community-dwelling adults ≥65 years of age that were enrolled in the Chinese Longitudinal Healthy Longevity Survey (n = 1,673). The Mini-Mental Status Examination (MMSE) was used to assess cognitive function, while the plasma 25-hydroxyvitamin D [25(OH)D] test was used to assess vitamin D status. The associations between vitamin D concentration, cognitive function, and all-cause mortality were assessed with Cox proportional hazards models. We used restricted cubic splines to examine the dose–response relationship between vitamin D and the risk of all-cause mortality and used joint effect testing to explore interactions between vitamin D concentration and cognitive function.ResultsDuring a mean (SD) follow-up of 3.8 (1.9) years, 899 (53.7%) deaths occurred. A negative dose–response relationship was observed between 25(OH)D concentration and cognition impairment at baseline, as well as the odds of all-cause mortality during follow-up. Similarly, cognitive impairment was significantly related to all-cause mortality risk (HR 1.81, 95% CI: 1.54 to 2.12). The combined analyses showed positive associations, with the highest mortality risk observed in older adults with both low vitamin D and cognitive impairment (HR 3.04, 95% CI: 2.40 to 3.86). Moreover, the interaction between 25(OH)D concentration and cognitive function was found to be significant in relation to the risk of mortality (p for interaction &lt;0.001).ConclusionLower plasma 25(OH)D and cognitive impairment were, respectively, associated with increased all-cause mortality risks. The 25(OH)D concentration and cognitive impairment exhibited a combined additive effect on all-cause mortality among older Chinese adults.
Recombinant mycobacterium tuberculosis fusion protein for diagnosis of mycobacterium tuberculosis infection: a short-term economic evaluation
Authors: Liu Zheng , Diao Sha , Zeng Linan , Liu Dan , Jiao Xuefeng , Chen Zhe , Cheng Xiao , Ni Xiaofeng , He Siyi , Wu Bin , Kang Deying , Wan Chaomin , Zhao Rongsheng , Wang Huiqing , Zhang Lingli 
Published: May 2023

ObjectivesRecombinant Mycobacterium tuberculosis fusion protein (EC) was anticipated to be used for the scale-up of clinical application for diagnosis of Mycobacterium tuberculosis infection in China, but it lacked a head-to-head economic evaluation based on the Chinese population. This study aimed to estimate the cost-utility and the cost-effectiveness of both EC and tuberculin pure protein derivative (TB-PPD) for diagnosis of Mycobacterium tuberculosis infection in the short term.MethodsFrom a Chinese societal perspective, both cost-utility analysis and cost-effectiveness analysis were performed to evaluate the economics of EC and TB-PPD for a one-year period based on clinical trials and decision tree model, with quality-adjusted life years (QALYs) as the utility-measured primary outcome and diagnostic performance (including the misdiagnosis rate, the omission diagnostic rate, the number of patients correctly classified, and the number of tuberculosis cases avoided) as the effective-measured secondary outcome. One-way and probabilistic sensitivity analyses were performed to validate the robustness of the base-case analysis, and a scenario analysis was conducted to evaluate the difference in the charging method between EC and TB-PPD.ResultsThe base-case analysis showed that, compared with TB-PPD, EC was the dominant strategy with an incremental cost-utility ratio (ICUR) of saving 192,043.60 CNY per QALY gained, and with an incremental cost-effectiveness ratio (ICER) of saving 7,263.53 CNY per misdiagnosis rate reduction. In addition, there was no statistical difference in terms of the omission diagnostic rate, the number of patients correctly classified, and the number of tuberculosis cases avoided, and EC was a similar cost-saving strategy with a lower test cost (98.00 CNY) than that of TB-PPD (136.78 CNY). The sensitivity analysis showed the robustness of cost-utility and cost-effectiveness analysis, and the scenario analysis indicated cost-utility in EC and cost-effectiveness in TB-PPD.ConclusionThis economic evaluation from a societal perspective showed that, compared to TB-PPD, EC was likely to be a cost-utility and cost-effective intervention in the short term in China.
Associations of long-term exposure to air pollution, physical activity with blood pressure and prevalence of hypertension: the China Health and Retirement Longitudinal Study
Authors: Zhang Jinglong , Zhang Fen , Xin Chao , Duan Zhizhou , Wei Jing , Zhang Xi , Han Shichao , Niu Zhiping 
Published: May 2023

BackgroundLong-term exposure to air pollution and physical activity (PA) are linked to blood pressure and hypertension. However, the joint effect of air pollution and PA on blood pressure and hypertension are still unknown in Chinese middle-aged and older adults.MethodsA total of 14,622 middle-aged and older adults from the China Health and Retirement Longitudinal Study wave 3 were included in this study. Ambient air pollution [particulate matter with diameter ≤ 2.5 μm (PM2.5), or ≤10 μm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbonic oxide (CO)] were estimated using satellite-based spatiotemporal models. PA was investigated using International Physical Activity Questionnaire. Generalized linear models were used to examine the associations of air pollution, PA score with blood pressure [systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP)], and the prevalence of hypertension. Subgroup analysis was conducted to investigate the effects of air pollution on blood pressure and the prevalence of hypertension in different PA groups.ResultsThe results showed that for each inter-quartile range (IQR) increase in PM2.5 (25.45 μg/m3), PM10 (40.56 μg/m3), SO2 (18.61 μg/m3), NO2 (11.16 μg/m3), CO (0.42 mg/m3) and PA score (161.3 MET/h-week), the adjusted odd ratio (OR) of hypertension was 1.207 (95% confidence interval (CI): 1.137, 1.281), 1.189 (95%CI: 1.122, 1.260), 1.186 (95%CI: 1.112, 1.266), 1.186 (95%CI: 1.116, 1.260), 1.288 (95%CI: 1.223, 1.357), 0.948 (95%CI: 0.899, 0.999), respectively. Long-term exposure to PM2.5, PM10, SO2, NO2, and CO was associated with increased SBP, DBP, and MAP levels. For example, each IQR increase in PM2.5 was associated with 1.20 mmHg (95%CI: 0.69, 1.72) change in SBP, 0.66 mmHg (95%CI: 0.36, 0.97) change in DBP, and 0.84 mmHg (95%CI: 0.49, 1.19) change in MAP levels, respectively. Each IQR increase in PA score was associated with −0.56 mmHg (95%CI: −1.03, −0.09) change in SBP, −0.32 mmHg (95%CI: −0.59, −0.05) change in DBP, and −0.33 mmHg (95%CI: −0.64, −0.02) change in MAP levels, respectively. Subgroup analysis found that the estimated effects in the sufficient PA group were lower than that in the insufficient PA group.ConclusionLong-term exposure to air pollutants is associated with increased blood pressure and hypertension risk, while high-level PA is associated with decreased blood pressure and hypertension risk. Strengthening PA might attenuate the adverse effects of air pollution on blood pressure and hypertension risk.
Nitrous oxide: a unique official French addictovigilance national survey
Authors: Guerlais Marylène , Aquizerate Aurélie , Lionnet Arthur , Daveluy Amélie , Duval Mélanie , Gérardin Marie , Istvan Marion , Laforgue Edouard-Jules , Victorri-Vigneau Caroline ,   for French Addictovigilance Network
Published: May 2023

IntroductionNitrous oxide has become over the last few years a public health problem in many countries. France has a dedicated health monitoring system dedicated to the surveillance of the abuse, dependence and consequences associated with the use of psychoactive substances coordinated by the French National Agency for the Safety of Medicines and Health Products.We present the French national survey of nitrous oxide.Materials and methodsWe analyzed all the cases with nitrous oxide from 2012 to 2021: number of notifications, characteristics of the subjects and consumption, consequences reported and their evolutions over time. In addition, we have made a special focus on the four main complications reported.ResultsA total of 525 cases were received with an exponential increase since 2019. We observed changes in the characteristics of the notifications with an increase in the proportion of women [42.7% in 2021 vs. 30.8% in 2020 (p = 0.02)]; an increase in the quantities consumed (use of cylinders); a negative evolution of the contexts of use with a search for self-therapeutic effects and use in violent contexts; an increasing trend of the severity of cases [78.1% in 2021 vs. 70.0% in 2020 (p = 0.07)].The main effects were substance use disorders and/or associated criteria (82.5%), neurological disorders (75.4%), psychiatric symptoms (15.4%) and cardiovascular events (8.6%). In terms of evolution, we observed a significant increase in cases with a use disorder and an increase in neurological complications. Moreover, new serious effects, notably cardiovascular events were reported.DiscussionThe combination of high availability, varied effects from euphoria to relief of discomfort in a stressful global pandemic context and the development of dependence could explain the rapid growth of consumption and the seriousness of the cases.It must now be taken into account that (i) Substance use disorders are associated with nitrous oxide consumption; (ii) clinicians must consider “nitrous oxide” in young subjects presenting different types of manifestations; and (iii) stopping consumption is imperative and is the first treatment. In this context, an addictological assessment must also be carried out.