bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ginsenosides, potential TMPRSS2 inhibitors, a trade-off between the therapeutic combination for anti-PD-1 immunotherapy and the treatment of COVID-19 infection of LUAD patients
Authors: Meng Mei , Gao Rui , Liu Zixue , Liu Fengxiang , Du Shiyu , Song Yizhi , He Jian 
Published: March 2023

Background: Acting as a viral entry for coronavirus to invade human cells, TMPRSS2 has become a target for the prevention and treatment of COVID-19 infection. Before this, TMPRSS2 has presented biological functions in cancer, but the roles remain controversial and the mechanism remains unelucidated. Some chemicals have been reported to be inhibitors of TMPRSS2 and also demonstrated other pharmacological properties. At this stage, it is important to discover more new compounds targeting TMPRSS2, especially from natural products, for the prevention and treatment of COVID-19 infection.Methods: We analyzed the correlation between TMPRSS2 expression, methylation level, overall survival rate, clinical parameters, biological process, and determined the correlation between TMPRSS2 and tumor-infiltrating lymphocytes in the tumor and adjacent normal tissue of adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) respectively by using various types of bioinformatics approaches. Moreover, we determined the correlation between TMPRSS2 protein level and the prognosis of LUAD and LUSC cohorts by immunohistochemistry assay. Furthermore, the cancer immunome atlas (TCIA) database was used to predict the relationship between the expression of TMPRSS2 and response to programmed cell death protein 1 (PD-1) blocker immunotherapy in lung cancer patients. Finally, the putative binding site of ginsenosides bound to TMPRSS2 protein was built from homology modeling to screen high-potency TMPRSS2 inhibitors.Results: We found that TMPRSS2 recruits various types of immunocytes, including CD8+, CD4+ T cells, B cells and DCs both in LUAD and LUSC patients, and the correlation between TMPRSS2 expression and CD8+ and CD4+ T cells are stronger in LUAD rather than in LUSC, but excludes macrophages and neutrophils in LUAD patient cohorts. These might be the reason that higher mRNA and protein levels of TMPRSS2 are associated with better prognosis in LUAD cohorts rather than in LUSC cohorts. Furthermore, we found that TMPRSS2 was positively correlated with the prognosis in patient nonresponse to anti-PD-1 therapy. Therefore, we made an inference that increasing the expression level of TMPRSS2 may improve the anti-PD-1 immunotherapy efficacy. Finally, five ginsenosides candidates with high inhibition potency were screened from the natural chemical library to be used as TMPRSS2 inhibitors.Conclusion: All these may imply that TMPRSS2 might be a novel prognostic biomarker and serve as a potential immunomodulator target of immunotherapy combination therapies in LUAD patients nonresponse to anti-PD-1 therapy. Also, these findings may suggest we should pay more attention to LUAD patients, especially those infected with COVID-19, who should avoid medicating TMPRSS2 inhibitors, such as ginsenosides to gain prophylactic and therapeutic benefits against COVID-19.
Ginaton reduces M1-polarized macrophages in hypertensive cardiac remodeling via NF-κB signaling
Authors: Wang Jie , Cai Enze , An Xiangbo , Wang Junjie 
Published: March 2023

Introduction: Macrophages play a critical role in cardiac remodeling, and dysregulated macrophage polarization between the proinflammatory M1 and anti-inflammatory M2 phenotypes promotes excessive inflammation and cardiac damage. Ginaton is a natural extract extracted from Ginkgo biloba. Because of its anti-inflammatory properties, it has long been used to treat a variety of diseases. However, the role of Ginaton in modulating the diverse macrophage functional phenotypes brought on by Ang II-induced hypertension and cardiac remodeling is unknown.Methods: In the present study, we fed C57BL/6J mice in the age of eight weeks with Ginaton (300 mg/kg/day) or PBS control, and then injected Ang II (1000 ng/kg/min) or saline for 14 days to investigate the specific efficacy of Ginaton. Systolic blood pressure was recorded, cardiac function was detected by echocardiography, and pathological changes in cardiac tissue were assessed by histological staining. Different functional phenotypes of the macrophages were assessed by immunostaining. The mRNA expression of genes was assessed by qPCR analysis. Protein levels were detected by immunoblotting.Results: Our results showed that Ang II infusion significantly enhanced the activation and infiltration of macrophages with hypertension, cardiac insufficiency, myocardial hypertrophy, fibrosis and M1 phenotype macrophages compared with the saline group. Instead, Ginaton attenuated these effects. In addition, in vitro experiments showed that Ginaton inhibited Ang II-induced activation, adhesion and migration of M1 phenotype macrophages.Conclusion: Our study showed that Ginaton treatment inhibits Ang II-induced M1 phenotype macrophage activation, macrophage adhesion, and mitigation, as well as the inflammatory response leading to impaired and dysfunctional hypertension and cardiac remodeling. Gianton may be a powerful treatment for heart disease.
Efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of recurrent and refractory ovarian cancer: A systematic review and a meta-analysis
Authors: Zeng Siyuan , Liu Daju , Yu Yongai , Zou Lei , Jin Xianyu , Liu Bing , Liu Lifeng 
Published: March 2023

Objective: To explore the efficacy and safety of PD-1/PD-L1 inhibitors in treating recurrent/refractory ovarian cancer (OC).Methods: The online databases, including PubMed, Embase and Cochrane Library, were searched for relevant literatures on exploring the efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of recurrent/refractory OC. The keywords are as follows: Ovarian neoplasms, programmed death receptor, PD-1, PD-L1, immunotherapy, and immune checkpoint inhibitor. Furthermore, qualified studies were screened for further meta-analysis.Results: In this study, 11 studies (990 patients) were analyzed to evaluate the efficacy of PD-1/PD-L1 inhibitors in the treatment of recurrent/refractory OC. The combined results proved that the objective response rate (ORR) was 6.7%, 95% CI (4.6%,9.2%), disease control rate (DCR) was 37.9%, 95% CI (33.0%, 42.8%), median overall survival (OS) was 10.70 months, 95% CI (9.23, 12.17), and median progression free survival (PFS) was 2.24 months, 95% CI (2.05, 2.43). In addition, in terms of the safety of patients suffering from recurrent/refractory OC and receiving PD-1/PD-L1 inhibitors, the combined treatment related adverse events (TRAEs) were 70.9% (61.7%–80.2%), and the combined immune related adverse events (iAEs) were 29%, 95% CI (14.7%, 43.3%).Conclusion: In patients with recurrent/refractory OC, PD-1/PD-L1 inhibitors were used alone and there was no obvious evidence of improved efficacy and survival. As for safety, the incidences of TRAEs and iAEs are high, so PD1/PD-L1 inhibitors should be applied according to individual conditions.Clinical Trial Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=367525, identifier CRD42022367525.
Cortex-specific transcriptome profiling reveals upregulation of interferon-regulated genes after deeper cerebral hypoperfusion in mice
Authors: Zhang Zengyu , Guo Zimin , Tu Zhilan , Yang Hualan , Li Chao , Hu Mengting , Zhang Yuan , Jin Pengpeng , Hou Shuangxing 
Published: March 2023

Background: Chronic cerebral hypoperfusion (CCH) is commonly accompanied by brain injury and glial activation. In addition to white matter lesions, the intensity of CCH greatly affects the degree of gray matter damage. However, little is understood about the underlying molecular mechanisms related to cortical lesions and glial activation following hypoperfusion. Efforts to investigate the relationship between neuropathological alternations and gene expression changes support a role for identifying novel molecular pathways by transcriptomic mechanisms.Methods: Chronic cerebral ischemic injury model was induced by the bilateral carotid artery stenosis (BCAS) using 0.16/0.18 mm microcoils. Cerebral blood flow (CBF) was evaluated using laser speckle contrast imaging (LSCI) system. Spatial learning and memory were assessed by Morris water maze test. Histological changes were evaluated by Hematoxylin staining. Microglial activation and neuronal loss were further examined by immunofluorescence staining. Cortex-specific gene expression profiling analysis was performed in sham and BCAS mice, and then validated by quantitative RT-PCR and immunohistochemistry (IHC).Results: In our study, compared with the sham group, the right hemisphere CBF of BCAS mice decreased to 69% and the cognitive function became impaired at 4 weeks postoperation. Besides, the BCAS mice displayed profound gray matter damage, including atrophy and thinning of the cortex, accompanied by neuronal loss and increased activated microglia. Gene set enrichment analysis (GSEA) revealed that hypoperfusion-induced upregulated genes were significantly enriched in the pathways of interferon (IFN)-regulated signaling along with neuroinflammation signaling. Ingenuity pathway analysis (IPA) predicted the importance of type I IFN signaling in regulating the CCH gene network. The obtained RNA-seq data were validated by qRT-PCR in cerebral cortex, showing consistency with the RNA-seq results. Also, IHC staining revealed elevated expression of IFN-inducible protein in cerebral cortex following BCAS-hypoperfusion.Conclusion: Overall, the activation of IFN-mediated signaling enhanced our understanding of the neuroimmune responses induced by CCH. The upregulation of IFN-regulated genes (IRGs) might exert a critical impact on the progression of cerebral hypoperfusion. Our improved understanding of cortex-specific transcriptional profiles will be helpful to explore potential targets for CCH.
Adaptations to the stressful combination of serpentine soils and Mediterranean climate drive plant functional groups and trait richness
Authors: Hidalgo-Triana Noelia , Pérez-Latorre Andrés V. , Adomou Aristide Cossi , Rudner Michael , Thorne James H. 
Published: March 2023

IntroductionPlant functional traits (FTs) are important for understanding plant ecological strategies (e.g., drought avoidance), especially in the nutrient-poor soils of serpentine ecosystems. In the Mediterranean areas, such ecosystems are characterized by climatic factors (e.g., summer drought) that exert a filtering effect.Material and MethodsIn our study, we analyzed 24 species with varying serpentine affinity, from strictly serpentine plants to generalist plants, from two ultramafic shrublands in southern Spain, considering four FTs: plant height (H), leaf area (LA), specific leaf area (SLA), and stem specific density (SSD). Additionally, we also identified the species’ dominant strategies to avoid drought and those strategies’ relationship to serpentine affinity. We used principal component analysis to identify combinations of FTs, and cluster analysis to define Functional Groups (FGs).Results and DiscussionWe defined eight FGs, which suggests that such Mediterranean serpentine shrublands are composed of species with wide-ranging of FTs. Indicator traits explained 67–72% of the variability based on four strategies: (1) lower H than in other Mediterranean ecosystems; (2) middling SSD; (3) low LA; and (4) low SLA due to thick and/or dense leaves, which contribute to long leaf survival, nutrient retention, and protection from desiccation and herbivory. Generalist plants had higher SLA than obligate serpentine plants, whereas the obligate serpentine plants showed more drought avoidance mechanisms than the generalists. Although most plant species inhabiting Mediterranean serpentine ecosystems have shown similar ecological adaptations in response to the Mediterranean environment, our results suggest that serpentine obligate plant species could present greater resilience to climate change. Given greater number and more pronounced drought avoidance mechanisms in these species compared with generalists, and the high number of FGs identified, the serpentine plants have shown adaptation to severe drought.
Investigation on sleep-related cognition of Chinese health care workers during the first wave of COVID-19 pandemic
Authors: Wang Wei , Ji Xincan , Guo Hao-Yang , Tao Mengjun , Jin Lairun , Chen Miao , Yuan Hui , Peng Hui 
Published: March 2023

BackgroundThe COVID pandemic has brought tremendous negative effects on the mental health of health care workers, such as anxiety, depression, and sleep disorders. We conducted this study to evaluate the sleep-related cognition of Chinese health care workers (HCWs) during the first wave of COVID-19 pandemic and analyze its association with sleep quality, so as to provide scientific reference for improving sleep of HCWs.Patients and methodsA total of 404 HCWs from Yijishan Hospital of Wuhu City, China were enrolled in the study, selected by randomized cluster sampling in May 2020. We made a questionnaire to collect the general demographic information of the participants. The Pittsburgh Sleep Quality Index (PSQI) and a brief version of Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS-16) were used to measure sleep quality and sleep-related cognition, respectively.ResultsThe results showed that 312 HCWs (77.2%) had false beliefs and attitudes about sleep, while only 92 HCWs (22.8%) had correct beliefs about sleep. In addition, we found that those HCWs who were older, married, with a bachelor’s degree or higher, nurses, more daily working hours (&gt; 8 h) and monthly night shifts (≥ 5 times), had higher DBAS-16 scores (all p &lt; 0.05). However, we did not find significant differences between men and women in DBAS-16 scores. According to the definition of PSQI, a total of 1/4 of the HCWs are poor sleepers and their DBAS-16 score was higher than good sleepers (t = 7.622, p &lt; 0.001). In the end, we confirmed a positive correlation between sleep cognition and sleep quality (r = 0.392, p &lt; 0.01).ConclusionOur study revealed false beliefs and attitudes about sleep were prevalent among HCWs during the first wave of COVID-19 pandemic, and these false beliefs about sleep were closely correlated to sleep quality. We recommend fighting against these false beliefs about sleep.
The role of substance use in the lives of incarcerated older adults: A qualitative study
Authors: Avieli Hila 
Published: March 2023

BackgroundThe prevalence of drug abuse among older adults has grown over the last decade. Despite the expanding development of a body of research dedicated to studying this phenomenon, drug abuse by incarcerated older adults has been marginalized. Thus, the aim of the present study was to explore drug abuse patterns in the lives of incarcerated older adults.MethodSemi-structured interviews were conducted with 28 incarcerated older adults, and an interpretive analysis was used to analyze the participants’ narratives.FindingsFour themes emerged: (1) Growing up around drugs; (2) Prison onset; (3) Professionals, and (4) Lifelong substance abuse.ConclusionThe study findings reveal a unique typology of drug-related themes in the lives of incarcerated older adults. This typology sheds light on the interplay between aging, drug use, and incarceration and the way these three socially marginalized positions may intersect.
Electroconvulsive therapy knowledge and attitudes among patients and caregivers in South China: A preliminary study
Authors: Deng Can-Jin , Nie Sha , Mai Jian-Xin , Huang Xiong , Huang Xing-Bing , Zheng Wei 
Published: March 2023

BackgroundElectroconvulsive therapy (ECT) is a safe and effective therapy for individuals suffering from major psychiatric disorders, but attitudes towards ECT among patients and caregivers have not been well studied. This study was conducted to elucidate patient and caregiver knowledge and attitudes concerning ECT in South China.MethodsThe sample comprised 92 patients diagnosed with major psychiatric disorders and their caregivers (n = 92). Participants completed questionnaire measures of knowledge and attitudes related to ECT.ResultsInformation before ECT was inadequately provided to both caregivers and patients (55.4% versus 37.0%, p &lt; 0.05). Caregivers reported receiving more adequate information about the therapeutic effects (50.0% versus 44.6%), side effects (67.4% versus 41.3%), and risks (55.4% versus 20.7%) of ECT when compared to patients (all p &lt; 0.05). However, less than half of patients and caregivers believed that ECT was effective (43.5% versus 46.7%, p &gt; 0.05), while more than half of them believed that ECT was beneficial (53.3% versus 71.7%, p &lt; 0.05), and approximately half of them believed that ECT was safe (50.0% versus 51.1%, p &gt; 0.05). A total of 32.6% of patients and 55.4% of caregivers (p &lt; 0.05) reported that ECT was used only for critically ill patients. A total of 62.0% of patients experienced side effects, with memory impairment being the most commonly reported.ConclusionClinicians should develop a systematic health education program before ECT treatment and ensure that patients and caregivers have an accurate understanding of ECT, particularly the treatment process, its therapeutic effects and potential side effects prior to administering this treatment.
Network analysis of somatic symptoms in Chinese patients with depressive disorder
Authors: Li Yang , Jia Shoumei , Cao Baohua , Chen Li , Shi Zhongying , Zhang Hao 
Published: March 2023

IntroductionNetwork theory conceptualizes somatic symptoms as a network of individual symptoms that are interconnected and influenced by each other. In this conceptualization, the network's central symptoms have the strongest effect on other symptoms. Clinical symptoms of patients with depressive disorders are largely determined by their sociocultural context. To our knowledge, no previous study has investigated the network structure of somatic symptoms among Chinese patients with depressive disorders. The aim of this study was to characterize the somatic symptoms network structure in patients with depressive disorders in Shanghai, China.MethodA total of 177 participants were recruited between October 2018 and June 2019. The Chinese version of the Patient Health Questionnaire-15 was used to assess somatic symptoms. In order to quantify the somatic symptom network structure, indicators of “closeness,” “strength,” and “betweenness” were employed as identifiers for network-central symptoms.ResultThe symptoms of “feeling your heart pound or race,” “shortness of breath,” and “back pain” had the highest centrality values, indicating that these symptoms were central to the somatic symptom networks. Feeling tired or mentally ill had the strongest positive correlation with insomnia or other sleep problems (r = 0.419), followed by chest pain and breathlessness (r = 0.334), back pain, and limb or joint pain (r = 0.318).DiscussionPsychological and neurobiological research that offers insights into somatic symptoms may focus on these central symptoms as targets for treatment and future research.
Mobile Application to identify and recognize emotions for children with autism: A systematic review
Authors: Al-Saadi Abdelrahman Mohammed , Al-Thani Dena 
Published: March 2023

IntroductionEmotions are a vital component of human interaction. Children with Autism Spectrum Disorder (ASD) face severe difficulties in sensing and interpreting the emotions of others, as well as responding emotionally appropriately. Developers are producing many mobile applications to assist ASD children in improving their facial expression detection and reaction abilities and increasing their independence.ObjectiveThis systematic review aims to explore the mobile application in helping children with ASD to identify and express their feeling.MethodsThe inclusion and exclusion articles for our analysis were mapped using the PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analysis diagram. The studies were retrieved from the following four databases: Google Scholar, Scopus, Association for Computing Machinery (ACM), and Institute of Electrical and Electronics Engineers (IEEE). Additionally, two screening processes were used to determine relevant literature. Reading the title and abstract was the initial step, followed by reading the complete content. Finally, the authors display the results using a narrative synthesis.ResultsFrom four electronic databases, we retrieved 659 articles. six studies that met our inclusion criteria were included in the systematic review. More details about inclusion and exclusion criteria can be found in the Eligibility criteria.ConclusionThis systematic review sheds light on current research that employed mobile applications to improve emotion detection and expression in children with ASD. This smartphone application has the potential to empower autistic children by assisting them in expressing their emotions and enhancing their ability to recognize emotions. However, it is currently deemed essential to assess the effectiveness of mobile applications for remediation through more rigorous methodological research. For example, most included studies were quantitative and focused on statical measurements. However, there is an immediate need for more incredible research in this area to include qualitative research and to consider large samples, control groups and placebo, prolonged treatment durations, and follow-up to see whether improvements are sustainable and to ensure the effectiveness of applications.