bluuebunny/crossref_metadata_2025_split huggingface dataset:
TMIGD2 as a potential therapeutic target in glioma patients
Authors: Boulhen Chaimae , AIT SSI Saadia , Benthami Hamza , Razzouki Ibtissam , Lakhdar Abdelhakim , Karkouri Mehdi , Badou Abdallah 
Published: May 2023

IntroductionAmong all types of central nervous system cancers, glioma remains the most frequent primary brain tumor in adults. Despite significant advances in immunomodulatory therapies, notably immune checkpoint inhibitors, their effectiveness remains constrained due to glioma resistance. The discovery of TMIGD2 (Transmembrane and Immunoglobulin Domain Containing 2) as an immuno-stimulatory receptor, constitutively expressed on naive T cells and most natural killer (NK) cells, has emerged as an attractive immunotherapy target in a variety of cancers. The expression profile of TMIGD2 and its significance in the overall survival of glioma patients remains unknown.MethodsIn the present study, we first assessed TMIGD2 mRNA expression using the Cancer Genome Atlas (TCGA) glioma transcriptome dataset (667 patients), followed by validation with the Chinese Glioma Genome Atlas (CGGA) cohort (693 patients). Secondly, we examined TMIGD2 protein staining in a series of 25 paraffin-embedded blocks from Moroccan glioma patients. The statistical analysis was performed using GraphPad Prism 8 software.ResultsTMIGD2 expression was found to be significantly higher in astrocytoma, IDH-1 mutations, low-grade, and young glioma patients. TMIGD2 was expressed on immune cells and, surprisingly, on tumor cells of glioma patients. Interestingly, our study demonstrated that TMIGD2 expression was negatively correlated with angiogenesis, hypoxia, G2/M checkpoint, and epithelial to mesenchymal transition signaling pathways. We also demonstrated that dendritic cells, monocytes, NK cells, gd T cells, and naive CD8 T cell infiltration correlates positively with TMIGD2 expression. On the other hand, Mantel-Cox analysis demonstrated that increased expression of TMIGD2 in human gliomas is associated with good overall survival. Cox multivariable analysis revealed that TMIGD2 is an independent predictor of a good prognosis in glioma patients.DiscussionTaken together, our results highlight the tight implication of TMIGD2 in glioma progression and show its promising therapeutic potential as a stimulatory target for immunotherapy.
A network analysis of psychological flexibility, coping, and stigma in dermatology patients
Authors: Vasiliou Vasilis S. , Russell Hellen , Cockayne Sarah , Coelho Gabriel Lins de Holanda , Thompson Andrew R. 
Published: May 2023

IntroductionDespite the negative effects of stigma in individuals with skin conditions, interventions to address its effects are rare. This might be in part due to a continued lack of understanding as to how individuals respond to stigma.MethodsIn this study, we employed a step-case analytic method, using traditional regression, moderation, and network analyses, to examine the role of psychological flexibility (PF) with stigmatized experiences, and stigma-related outcomes. We run a cross-sectional study (n = 105 individuals with various skin conditions) and analyzed stigma-related variables. We included variables examining perceived stigmatization (PSQ), anxiety (GAD-7), depression (PHQ-9), well-being (EQ5D5L), and variables stemming from the PF model (CompACT), presented as three coping with stigma responses, namely “open,” “aware,” and “active.”.ResultsUsing network analysis, the most influential or central variables that contributed to stigma were generalized anxiety, perceived stigmatization, and valued actions. In relation to PF, being open to the experience of stigma (as opposed to avoidance), keeping a distance from stigmatized thoughts (as opposed to self-stigmatizing), and bringing attention to value-based committed actions (as opposed to passivity) were all found to contribute to less stigmatized experiences.DiscussionThe results indicate that two of the three skills of the PF model (“open” and “active”) may be important targets for interventions targeting stigma in people living with skin conditions.
Risk factors and outcomes of inpatients with carbapenem-resistant Pseudomonas aeruginosa bloodstream infections in China: a 9-year trend and multicenter cohort study
Authors: Yuan Qing , Guo Lei , Li Bin , Zhang Sheng , Feng Haiting , Zhang Yan , Yu Meihong , Hu Hangbin , Chen Hongchao , Yang Qing , Qu Tingting 
Published: May 2023

ObjectiveBacteremia caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) has high mortality, threatening the healthcare quality worldwide. Analysis is required to update the epidemiological data of CRPA bloodstream infections (BSI) and evaluate the prevalent strains in China. Moreover, it is necessary to clarify the risk factors associated with the development and mortality of CRPA bacteremia.MethodsThis is a 9-year multicenter retrospective study, enrolling 137 patients with CRPA BSI and 137 carbapenem-susceptible P. aeruginosa (CSPA) BSI during January 2012 and December 2020. Antimicrobials susceptibility between the two groups were compared. Risk factors of CRPA BSI were identified by binary logistic regression for development and cox regression for mortality. The Kaplan–Meier method was used to compare time to mortality. CRPA and difficult-to-treat resistant P. aeruginosa (DTRPA) detection rate was analyzed year-by-year in ZYH.ResultsA total of 7,384 P. aeruginosa clinical samples were cultured in ZYH during 9  years, and notable increase of CRPA and DTRPA detection rate in P. aeruginosa BSI was identified (from 17 to 60%; from 2.1 to 25%). Multivariate analysis revealed that prior ICU hospitalization, immunosuppressive therapy and exposure to carbapenems were independent risk factors for development of CRPA BSI. The 30-day crude mortality of 137 CRPA BSI was 39%. A total of 46 DTRPA were identified, and the 30-day mortality for patients infected by DTRPA was 50%. The 30-day crude mortality of CRPA BSI was independently associated with multiple organ failure and higher Pitt bacteremia score, whereas receipt appropriate therapy improved prognosis.ConclusionA significant increase in the detection rate of CRPA and DTRPA in P. aeruginosa BSI was identified. Strict policies for carbapenems usage, cautious decisions regarding the usage of immunosuppressive agent and standard care for patients with prior ICU hospitalization are necessary for CRPA BSI management.
Physiological and pathophysiological mechanisms of the molecular and cellular biology of angiogenesis and inflammation in moyamoya angiopathy and related vascular diseases
Authors: Dorschel Kirsten B. , Wanebo John E. 
Published: May 2023

RationaleThe etiology and pathophysiological mechanisms of moyamoya angiopathy (MMA) remain largely unknown. MMA is a progressive, occlusive cerebrovascular disorder characterized by recurrent ischemic and hemorrhagic strokes; with compensatory formation of an abnormal network of perforating blood vessels that creates a collateral circulation; and by aberrant angiogenesis at the base of the brain. Imbalance of angiogenic and vasculogenic mechanisms has been proposed as a potential cause of MMA. Moyamoya vessels suggest that aberrant angiogenic, arteriogenic, and vasculogenic processes may be involved in the pathophysiology of MMA. Circulating endothelial progenitor cells have been hypothesized to contribute to vascular remodeling in MMA. MMA is associated with increased expression of angiogenic factors and proinflammatory molecules. Systemic inflammation may be related to MMA pathogenesis.ObjectiveThis literature review describes the molecular mechanisms associated with cerebrovascular dysfunction, aberrant angiogenesis, and inflammation in MMA and related cerebrovascular diseases along with treatment strategies and future research perspectives.Methods and resultsReferences were identified through a systematic computerized search of the medical literature from January 1, 1983, through July 29, 2022, using the PubMed, EMBASE, BIOSIS Previews, CNKI, ISI web of science, and Medline databases and various combinations of the keywords “moyamoya,” “angiogenesis,” “anastomotic network,” “molecular mechanism,” “physiology,” “pathophysiology,” “pathogenesis,” “biomarker,” “genetics,” “signaling pathway,” “blood-brain barrier,” “endothelial progenitor cells,” “endothelial function,” “inflammation,” “intracranial hemorrhage,” and “stroke.” Relevant articles and supplemental basic science articles almost exclusively published in English were included. Review of the reference lists of relevant publications for additional sources resulted in 350 publications which met the study inclusion criteria. Detection of growth factors, chemokines, and cytokines in MMA patients suggests the hypothesis of aberrant angiogenesis being involved in MMA pathogenesis. It remains to be ascertained whether these findings are consequences of MMA or are etiological factors of MMA.ConclusionsMMA is a heterogeneous disorder, comprising various genotypes and phenotypes, with a complex pathophysiology. Additional research may advance our understanding of the pathophysiology involved in aberrant angiogenesis, arterial stenosis, and the formation of moyamoya collaterals and anastomotic networks. Future research will benefit from researching molecular pathophysiologic mechanisms and the correlation of clinical and basic research results.
Brain function effects of exercise interventions for cognitive decline: a systematic review and meta-analysis
Authors: Karamacoska Diana , Butt Ali , Leung Isabella H. K. , Childs Ryan L. , Metri Najwa-Joelle , Uruthiran Vithya , Tan Tiffany , Sabag Angelo , Steiner-Lim Genevieve Z. 
Published: May 2023

IntroductionExercise is recognized as a modifiable lifestyle factor that can mitigate cognitive decline and dementia risk. While the benefits of exercise on cognitive aging have been reported on extensively, neuronal effects in adults experiencing cognitive decline have not been systematically synthesized. The aim of this systematic review was to assess the effects of exercise on cognition and brain function in people with cognitive decline associated with dementia risk.MethodA systematic search was conducted for randomized controlled trials of ≥ 4 weeks exercise (aerobic, resistance, or mind-body) that assessed cognition and brain function using neuroimaging and neurophysiological measures in people with subjective or objective cognitive decline. Study characteristics and brain function effects were narratively synthesized, while domain-specific cognitive performance was subjected to meta-analysis. Study quality was also assessed.Results5,204 records were identified and 12 unique trials met the eligibility criteria, representing 646 adults classified with cognitive frailty, mild or vascular cognitive impairment. Most interventions involved 40-minute sessions conducted 3 times/week. Exercise improved global cognition (g = −0.417, 95% CI, −0.694 to −0.140, p = 0.003, I2 = 43.56%), executive function (g = −0.391, 95% CI, −0.651 to −0.131, p = 0.003, I2 = 13.28%), but not processing speed or general short-term memory (both p &gt;0.05). Across fMRI and ERP studies, significant neuronal adaptations were found with exercise cf. control throughout the brain and were linked with improved global cognition, memory, and executive function. Cerebral blood flow was also found to improve with 24 weeks of exercise, but was not linked with cognitive changes.DiscussionThe cognitive improvements associated with exercise are likely driven by increased metabolic activity, cerebrovascular mechanisms, and neuroplasticity throughout the brain. Our paper shows the promise in, and need for, high-quality trials integrating cognitive and brain function measures to elucidate the functional relationship between exercise and brain health in populations with a high risk of dementia.Systematic review registrationPROSPERO, identifier: CRD42022291843.
BRCA2 mutation in advanced lung squamous cell carcinoma treated with Olaparib and a PD-1 inhibitor: a case report
Authors: Chen Zhujun , Wang Kang , Zhao Lintao , Gong Liang 
Published: May 2023

BackgroundMutations in the human breast cancer susceptibility gene 2 (breast cancer 2, BRCA2) increase the risk of breast, ovarian and other cancers. Olaparib, an oral poly[adenosine diphosphate (ADP)–ribose] polymerase (PARP) inhibitor, is usually prescribed to treat BRCA mutated tumors, especially breast and ovarian cancers. Programmed cell death-1 (PD-1) inhibitors have revolutionized the treatment of lung cancer and many other cancers by destroying the interaction between receptors with ligands in the tumor-immune microenvironment and enabling T cells to recognize and attack cancer cells.Case descriptionIn our study, we report a patient with advanced BRCA2 lung squamous cell carcinoma who received platinum-based chemotherapy combined with paclitaxel. Seven months later, the disease progressed. BRCA2 mutations were detected in peripheral blood by next-generation sequencing. After 2 months of treatment with Olaparib combined with Cindilimab, the patient was in partial remission and the progression-free survival (PFS) lasted for 6 months, but the patient developed immune renal damage.ConclusionsThis study adds to the clinical data for the treatment of BRCA2 mutant non-small cell lung cancer by demonstrating that lung squamous cell carcinoma has a good response to PARP inhibitors. It also serves as a reminder that there may still be some negative effects from targeted superimposed immunotherapy.
Clinical characteristics and prostate-cancer-specific mortality of competitive risk nomogram in the second primary prostate cancer
Authors: Xu Chaojie , Pei Dongchen , Liu Yi , Guo Jianhua , Liu Nan , Wang Qian , Yu Yang , Kang Zhengjun 
Published: May 2023

BackgroundWith the development of early diagnosis and treatment, the second primary malignancy (SPM) attracts increasing attention. The second primary prostate cancer (spPCa) is an important class of SPM, but remains poorly understood.MethodsWe retrospectively analyzed 3,322 patients with spPCa diagnosed between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. Chi-square test was applied to compare demographic and clinical variables and analyze causes of death. Multivariate competitive risk regression model was used to identify risk factors associated with prostate-cancer-specific mortality (PCSM), and these factors were enrolled to build a nomogram of competitive risk. The C-index, calibration curve, and decision curve analysis (DCA) were employed to evaluate the discrimination ability of our nomogram.ResultsThe median follow-up (interquartile range, IQR) time was 47 (24–75) months, and the median (IQR) diagnosis interval between the first primary cancer (FPC) and spPCa was 32 (16–57) months. We found that the three most common sites of SPM were the urinary system, digestive system, and skin. Through multivariate competitive risk analysis, we enrolled race (p &lt; 0.05), tumor–node–metastasis (TNM) stage (p &lt; 0.001), Gleason score (p &lt; 0.05), surgery (p = 0.002), and radiotherapy (p = 0.032) to construct the model to predict the outcomes of spPCa. The C-index was 0.856 (95% CI, 0.813–0.899) and 0.905 (95% CI, 0.941–0.868) in the training and validation set, respectively. Moreover, both the calibration curve and DCA illustrated that our nomogram performed well in predicting PCSM.ConclusionIn conclusion, we identified four risk factors associated with the prognosis of spPCa and construct a competing risk nomogram, which performed well in predicting the 3-, 5-, and 10-year PCSM.
Long-term economic evaluation of the recombinant Mycobacterium tuberculosis fusion protein (EC) test for the diagnosis of Mycobacterium tuberculosis infection
Authors: Diao Sha , Liu Zheng , Liu Dan , Cheng Xiao , Zeng Linan , Jiao Xue-Feng , Chen Zhe , Ni Xiaofeng , He Siyi , Wu Bin , Kang Deying , Wan Chaomin , Zhao Rongsheng , Wang Huiqing , Zhang Lingli 
Published: May 2023

Background: Tuberculosis continues to be a significant global burden. Purified protein derivative of tuberculin (TB-PPD) is one type of tuberculin skin test (TST) and is used commonly for the auxiliary diagnosis of tuberculosis. The recombinant Mycobacterium tuberculosis fusion protein (EC) test is a new test developed in China.Objective: Evaluate the long-term economic implications of using the EC test compared with the TB-PPD test to provide a reference for clinical decision-making.Methods: The target population was people at a high risk persons of being infected with Mycobacterium tuberculosis. The outcome indicator was quality-adjusted life years (QALY). A cost–utility analysis was used to evaluate the long-term economic implications of using the EC test compared with the TB-PPD test. We employed a decision tree–Markov model from the perspective of the whole society within 77 years.Results: Compared with the TB-PPD test, the EC test had a lower cost but higher QALY. The incremental cost–utility ratio was −119,800.7381 CNY/QALY. That is, for each additional QALY, the EC test could save 119,800.7381 CNY: the EC test was more economical than the TB-PPD test.Conclusion: Compared with the TB-PPD test, the EC test would be more economical in the long term for the diagnosis of M. tuberculosis infection according our study.
Soluble receptors for advanced glycation end-products prevent unilateral ureteral obstruction-induced renal fibrosis
Authors: Kim Chan Ho , Kang Hye-Young , Kim Gyuri , Park Jimin , Nam Bo Young , Park Jung Tak , Han Seung Hyeok , Kang Shin-Wook , Yoo Tae-Hyun 
Published: May 2023

Introduction: The receptor for advanced glycation end products (RAGE) and its ligands, such as high-mobility group protein box 1 (HMGB1), play an important role in the accumulation of extracellular matrix in chronic kidney diseases with tubulointerstitial fibrosis. Blocking RAGE signaling with soluble RAGE (sRAGE) is a therapeutic candidate for renal fibrosis.Methods: NRK-52E cells were stimulated with or without HMGB1 and incubated with sRAGE in vitro. Sprague-Dawley rats were intraperitoneally treated with sRAGE after unilateral ureteral obstruction (UUO) operation in vivo.Results: HMBG1-stimulated NRK-52E cells showed increased fibronectin expression, type I collagen, α-smooth muscle actin, and connective tissue growth factor, which were attenuated by sRAGE. The mitogen-activated protein kinase (MAPK) pathway and nuclear translocation of nuclear factor kappa B (NF-κB) were enhanced in NRK-52E cells exposed to HMBG1, and sRAGE treatment alleviated the activation of the MAPK and NF-κB pathways. In the UUO rat models, sRAGE significantly ameliorated the increased renal fibronectin, type I collagen, and α-smooth muscle actin expressions. Masson’s trichrome staining confirmed the anti-fibrotic effect of sRAGE in the UUO rat model. RAGE also significantly attenuated the activation of the MAPK pathway and NF-κB, as well as the increased number of infiltrated macrophages within the tubulointerstitium in the kidney of the UUO rat models.Conclusion: These findings suggest that RAGE plays a pivotal role in the pathogenesis of renal fibrosis and that its inhibition by sRAGE may be a potential therapeutic approach for renal fibrosis.
Masculinity, sexism and populist radical right support
Authors: Coffe Hilde , Fraile Marta , Alexander Amy , Fortin-Rittberger Jessica , Banducci Susan 
Published: May 2023

IntroductionThe gender gap in populist radical right voting—with women being less likely to support populist radical right parties than men—is well-established. Much less is known about the interplay between gender, masculinity and populist radical right voting. This study investigates the extent to which masculinity affects women and men's likelihood of supporting populist radical right parties. Focusing on sexism as a link between masculinity and populist radical right support, we put forward two mechanisms that operate at once: a mediating effect of sexism (sexism explains the association between masculinity and populist radical right voting) and a moderating effect of sexism (the impact of masculinity is stronger among citizens scoring high on sexism compared with citizens with low levels of sexist attitudes).MethodsWe draw on an original dataset collected in Spain at the end of 2020 to investigate support for the Spanish populist radical right party VOX.ResultsWe find support for hypothesized mechanisms, mediation and moderation, chiefly among men. First, sexism explains about half of the link between masculinity and populist radical right support for this group, confirming the hypothesized mediation effect. Second, masculinity has a significantly stronger impact on the likelihood of supporting VOX among men scoring high on sexism, which in turn substantiates the presence of a moderation effect.DiscussionExisting research so far has examined the empirical connections between how individuals perceive their levels of masculinity, sexism, and PRR voting separately. Our study offers a first step in unpacking the relationship between masculinity and PRR support by focusing specifically on how sexism relates to both these variables.
Suprachiasmatic nucleus functional connectivity related to insomnia symptoms in adolescents with major depressive disorder
Authors: Cao Lingling , Feng Ruohan , Gao Yingxue , Bao Weijie , Zhou Zilin , Liang Kaili , Hu Xinyue , Li Hailong , Zhang Lianqing , Li Yang , Zhuo Lihua , Huang Guoping , Huang Xiaoqi 
Published: May 2023

BackgroundInsomnia is a commonly seen symptom in adolescents with major depressive disorder (MDD). The suprachiasmatic nucleus (SCN), which is the circadian rhythm regulation center, plays a crucial role in the regulation of sleep-wake circulation. Nevertheless, how SCN function contributes to the exact neural mechanisms underlying the associations between insomnia and depressive symptoms has not been explored in adolescents. In the current study, we aimed to explore the relationship between SCN functional connectivity (FC) and insomnia symptoms in adolescents with MDD using a seed-based FC method.MethodsIn the current study, we recruited sixty-eight first-episode drug-naïve adolescents with MDD and classified them into high insomnia (MDD-HI) and low insomnia (MDD-LI) groups according to the sleep disturbance subscale of the Hamilton Depression Rating Scale (HAMD-S). Forty-three age/gender-matched healthy controls (HCs) were also recruited. SCN FC maps were generally for all subjects and compared among three groups using one-way ANOVA with age, gender and adjusted HAMD score as covariates. We used partial correlations to explore associations between altered FC and clinical symptoms, including sleep quality scores.ResultsAdolescents with MDD showed worse sleep quality, which positively correlated with the severity of depression. Compared to MDD-LI and HCs, MDD-HI adolescents demonstrated significantly decreased FC between the right SCN and bilateral precuneus, and there was no significant difference between the MDD-LI and HC groups. The HAMD-S scores were negatively correlated with bilateral SCN-precuneus connectivity, and the retardation factor score of HAMD was negatively correlated with right SCN-precuneus connectivity.ConclusionThe altered FC between the SCN and precuneus may underline the neural mechanism of sleep-related symptoms in depressive adolescents and provide potential targets for personalized treatment strategies.