bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunoporosis: Role of immune system in the pathophysiology of different types of osteoporosis
Authors: Zhang Weidong , Gao Ruihan , Rong Xing , Zhu Siqi , Cui Yajun , Liu Hongrui , Li Minqi 
Published: September 2022

Osteoporosis is a skeletal system disease characterized by low bone mass and altered bone microarchitecture, with an increased risk of fractures. Classical theories hold that osteoporosis is essentially a bone remodeling disorder caused by estrogen deficiency/aging (primary osteoporosis) or secondary to diseases/drugs (secondary osteoporosis). However, with the in-depth understanding of the intricate nexus between both bone and the immune system in recent decades, the novel field of “Immunoporosis” was proposed by Srivastava et al. (2018, 2022), which delineated and characterized the growing importance of immune cells in osteoporosis. This review aimed to summarize the response of the immune system (immune cells and inflammatory factors) in different types of osteoporosis. In postmenopausal osteoporosis, estrogen deficiency-mediated alteration of immune cells stimulates the activation of osteoclasts in varying degrees. In senile osteoporosis, aging contributes to continuous activation of the immune system at a low level which breaks immune balance, ultimately resulting in bone loss. Further in diabetic osteoporosis, insulin deficiency or resistance-induced hyperglycemia could lead to abnormal regulation of the immune cells, with excessive production of proinflammatory factors, resulting in osteoporosis. Thus, we reviewed the pathophysiology of osteoporosis from a novel insight-immunoporosis, which is expected to provide a specific therapeutic target for different types of osteoporosis.
Modified Qing’ e Pills exerts anti-osteoporosis effects and prevents bone loss by enhancing type H blood vessel formation
Authors: Lu Junjie , Hu Desheng , Ma Chen , Xu Xiaojuan , Shen Lin , Rong Jianhui , Zhao Jia , Shuai Bo 
Published: September 2022

ObjectiveTo explore whether the modified Qing’ e Pills (MQEP) exerts anti-osteoporotic effects and prevents bone loss by enhancing angiogenesis.MethodsNetwork pharmacology was used to assess whether MQEP has a pro-angiogenic capacity and to predict its potential targets. Human umbilical vein endothelial cells were treated with glucocorticoids and MQEP to assess cell viability. The expression of angiotensin II type 1 receptor, angiotensin II type 2 receptor, and angiotensin converting enzyme, which are associated with the activation of the renin-angiotensin-aldosterone system, and the expression of vascular endothelial growth factor and hypoxia-inducible factor 1 alpha, which are associated with the formation of type H blood vessels, were examined by western blot and RT-qPCR. Thereafter, the glucocorticoid-induced osteoporosis model was established and intervened with MQEP. Femur scanning was performed with micro-computed tomography; trabecular spacing, trabecular thickness, and trabecular number were observed and calculated; the expression of nuclear factor-kappa B ligand and osteoprotegerin was detected by ELISA, and the ratio was calculated to evaluate the degree of bone resorption. Finally, type H blood vessels that were highly coupled to osteogenic cells were identified by immunohistochemistry staining and flow cytometry.ResultsThis is the first study to reveal and confirm that MQEP could prevent bone loss in glucocorticoid-induced osteoporosis by promoting the expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor, which are highly associated with type H blood vessel formation. In vitro experiments confirmed that MQEP could effectively promote the proliferation of vascular endothelial cells and alleviate glucocorticoids-induced activation of the renin-angiotensin-aldosterone system, thereby reducing vascular injury.ConclusionMQEP exerts anti-osteoporosis effects and prevents bone loss by alleviating vascular injury caused by renin-angiotensin-aldosterone system activation and promoting type H blood vessel formation.
Identification of signaling pathways associated with achaete-scute homolog 1 in glioblastomas through ChIP-seq data bioinformatics
Authors: Zhang Na , Zhang Jie , Liu Zhihong , Li Tushuai 
Published: September 2022

Background: Achaete-scute homolog 1 transcription factors were important in the differentiation of neuronal-like glioblastoma (GBM) cancer stem cells (CSCs). To gain a better understanding of the role of ASCL1 in GBM, chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) data can be analyzed to construct their gene transcription regulation network.Methods: GSE87618 was downloaded from the Gene Expression Omnibus, which is a famous database, in the field of biology. The filtered clean reads were mapped to the human genome utilizing the software of bowtie2. Then, differential peak analysis was performed by diffbind. Finally, the annotated gene functions and signaling pathways were investigated by Gene ontology function and kyoto encyclopedia of genes genomes (KEGG) pathway enrichment analysis. Moreover, the protein–protein interaction network (PPI) analysis of genes obtained from ASCL1 was carried out to explore the hub genes influenced by ASCL1.Results: A total of 516 differential peaks were selected. GO analysis of functions revealed that promoter, untranslated region (UTR), exon, intron, and intergenic genes were mainly enriched in biological pathways such as keratinization, regulation of cAMP metabolic process, blood coagulation, fibrin clot formation, midgut development, and synapse assembly. Genes were mainly enriched in KEGG pathways including pentose phosphate pathway, glycosphingolipid biosynthesis—globo and isoglobo series, ECM–receptor interaction, and adherens junction. In total, 244 nodes and 475 interaction pairs were included in the PPI network with the hub genes including EGFR, CTNNB1, and SPTAN1.Conclusion: EGFR, SPTAN1, and CTNN1B might be the potential down-stream genes of ASCL1 in GBM development, and CTNN1B might make contributions to GBM progression on regulating the cAMP pathway.
Phenotypic prevalence of obesity and metabolic syndrome among an underdiagnosed and underscreened population of over 50 million children and adults
Authors: Kim Eric GR , Kaelber David C 
Published: September 2022

Background: Metabolic syndrome is a phenotypic condition associated with a variety of genotypes. Studies of rare genotypes can be made more difficult by clinical underscreening of the population for the phenotypic traits that define metabolic syndrome to clinicians. Studies have demonstrated underdiagnosis of pediatric obesity, as well as reduced rates of pediatric screening for obesity related conditions, including conditions leading to a diagnosis of metabolic syndrome. If true, there may be a significant underdiagnosis of metabolic syndrome among the pediatric population compared to the adult population.Methods: Using Epic’s Cosmos Data Network aggregated, de-identified patient data collected from healthcare organizations using the Epic electronic health record (EHR), we examined obesity and metabolic syndrome rates among adult and pediatric patients. We also examined screening rates for obesity related conditions and metabolic syndrome among adult and pediatric patients across the United States. We also sought to compare rates between subgroups within the population including age, sex, and race.Results: In our population, 45% of adults and 27% of pediatric population were obese by age and gender specific BMI criteria. 38% of the obese adult population had an ICD-10 code associated with the diagnosis vs. 52% of the pediatric population. Of adults meeting obesity criteria, 36% had results for appropriate, guideline-based blood laboratory testing for insulin resistance, 40–42% for dyslipidemia, and 55% for hepatic steatosis. 36% of obese adult patients had none of the recommended blood laboratory testing. 31% of the adult population met diagnostic criteria for metabolic syndrome. Of pediatric patients meeting obesity criteria, 27% had results for appropriate blood laboratory testing for insulin resistance, 28% for dyslipidemia, and 33% for hepatic steatosis. 59% of obese pediatric patients had none of the recommended blood laboratory testing. 3% of the pediatric population met criteria for diagnosis of metabolic syndrome.Discussion: This study represents one of the largest multicenter national cohorts assembled for studying metabolic syndrome (over 50 million patients) and demonstrates the power of emerging aggregated EHR tools for research. Although obesity is better diagnosed in pediatric patients than in adult patients, significantly lower screening rates for obesity related conditions occurred in pediatric patients compared to adults. Statistically significant, but clinically negligible differences in screening rates were found by race and gender. These results support smaller prior studies that suggest that obesity is under-diagnosed and obesity related conditions underscreened in pediatric and adult populations, and additionally suggests underdiagnosis of metabolic syndrome among United States pediatric and adult patients.
Multi‑institutional development and validation of a nomogram to predict prognosis of early-onset gastric cancer patients
Authors: Liu Hongda , Li Zequn , Zhang Qun , Li Qingya , Zhong Hao , Wang Yawen , Yang Hui , Li Hui , Wang Xiao , Li Kangshuai , Wang Dehai , Kong Xiangrong , He Zhongyuan , Wang Weizhi , Wang Linjun , Zhang Diancai , Xu Hao , Yang Li , Chen Yuxin , Zhou Yanbing , Xu Zekuan 
Published: September 2022

BackgroundEarly-onset gastric cancer (EOGC, ≤45 years old) is characterized with increasing incidence and more malignant phenotypes compared with late-onset gastric cancer, which exhibits remarkable immune cell infiltration and is potential immunotherapeutic population. Till now, restricted survival information of EOGC is available due to limited case numbers. This study established a novel nomogram to help evaluate cancer-specific survival (CSS) of EOGC patients who underwent gastrectomy, and may provide evidence for predicting patients’ survival.MethodsWe retrospectively enrolled a cohort containing 555 EOGC cases from five independent medical centers in China, among which 388 cases were randomly selected into a training set while the other 167 cases were assigned into the internal validation set. Asian or Pacific Islander (API) patients diagnosed with EOGC during 1975-2016 were retrieved from the SEER database (n=299) and utilized as the external validation cohort. Univariate and multivariate analyses were conducted to test prognostic significances of clinicopathological factors in the training set. Accordingly, two survival nomogram models were established and compared by concordance index (C-index), calibration curve, receiver operating characteristics (ROC) curves and decision curve analyses (DCA).ResultsThe 5-year CSS rate of training cohort was 61.3% with a median survival time as 97.2 months. High consistency was observed on calibration curves in all three cohorts. Preferred nomogram was selected due to its better performance on ROC and DCA results. Accordingly, a novel predicative risk model was introduced to better stratify high-risk EOGC patients with low-risk patients. In brief, the 5-year CSS rates for low-risk groups were 92.9% in training set, 83.1% in internal validation set, 89.9% in combined NQSQS cohort, and 85.3% in SEER-API cohort. In contrast, the 5-year CSS rates decreased to 38.5%, 44.3%, 40.5%, and 36.9% in the high-risk groups of the four cohorts above, respectively. The significant survival difference between high-risk group (HRG) and low-risk group (LRG) indicated the precise accuracy of our risk model. Furthermore, the risk model was validated in patients with different TNM stages, respectively. Finally, an EOGC web-based survival calculator was established with public access, which can help predict prognosis.ConclusionsOur data provided a precise nomogram on predicting CSS of EOGC patients with potential clinical applicability.
Longitudinal profiles of plasma gelsolin, cytokines and antibody expression predict COVID-19 severity and hospitalization outcomes
Authors: Asare-Werehene Meshach , McGuinty Michaeline , Vranjkovic Agatha , Galipeau Yannick , Cowan Juthaporn , Cameron Bill , Cooper Curtis L. , Langlois Marc-André , Crawley Angela M. , Tsang Benjamin K. 
Published: September 2022

BackgroundPrognostic markers for COVID-19 disease outcome are currently lacking. Plasma gelsolin (pGSN) is an actin-binding protein and an innate immune marker involved in disease pathogenesis and viral infections. Here, we demonstrate the utility of pGSN as a prognostic marker for COVID-19 disease outcome; a test performance that is significantly improved when combined with cytokines and antibodies compared to other conventional markers such as CRP and ferritin.MethodsBlood samples were longitudinally collected from hospitalized COVID-19 patients as well as COVID-19 negative controls and the levels of pGSN in μg/mL, cytokines and anti- SARS-CoV-2 spike protein antibodies assayed. Mean ± SEM values were correlated with clinical parameters to develop a prognostic platform.ResultspGSN levels were significantly reduced in COVID-19 patients compared to healthy individuals. Additionally, pGSN levels combined with plasma IL-6, IP-10 and M-CSF significantly distinguished COVID-19 patients from healthy individuals. While pGSN and anti-spike IgG titers together strongly predict COVID-19 severity and death, the combination of pGSN and IL-6 was a significant predictor of milder disease and favorable outcomes.ConclusionTaken together, these findings suggest that multi-parameter analysis of pGSN, cytokines and antibodies could predict COVID-19 hospitalization outcomes with greater certainty compared with conventional clinical laboratory markers such as CRP and ferritin. This research will inform and improve clinical management and health system interventions in response to SARS-CoV-2 infection.
Diagnostic and predictive values of serum metabolic profiles in sudden sensorineural hearing loss patients
Authors: Wang Xiangsheng , Gao Yan , Jiang Ruirui 
Published: September 2022

Sudden sensorineural hearing loss (SSNHL) is an otologic emergency, and metabolic disturbance is involved in its pathogenesis. This study recruited 20 SSNHL patients and 20 healthy controls (HCs) and collected their serum samples. Serum metabolites were detected by liquid chromatography-mass spectrometry, and metabolic profiles were analyzed. All patients were followed up for 3 months and categorized into recovery and non-recovery groups. The distinctive metabolites were assessed between two groups, and their predictive values for hearing recovery were evaluated. Analysis results revealed that SSNHL patients exhibited significantly characteristic metabolite signatures compared to HCs. The top 10 differential metabolites were further analyzed, and most of them showed potential diagnostic values based on receiver operator characteristic (ROC) curves. Finally, 14 SSNHL patients were divided into the recovery group, and six patients were included in the non-recovery group. Twelve distinctive metabolites were observed between the two groups, and ROC curves demonstrated that N4-acetylcytidine, p-phenylenediamine, sphingosine, glycero-3-phosphocholine, and nonadecanoic acid presented good predictabilities in the hearing recovery. Multivariate analysis results demonstrated that serum N4-Acetylcytidine, sphingosine and nonadecanoic acid levels were associated with hearing recovery in SSNHL patients. Our results identified that SSNHL patients exhibited distinctive serum metabolomics signatures, and several serum biomarkers were proved to be potential in predicting hearing recovery. The discriminative metabolites might contribute to illustrating the mechanisms of SSNHL and provide possible clues for its treatments.
The Charlotte Project: Recommendations for patient-reported outcomes and clinical parameters in Dravet syndrome through a qualitative and Delphi consensus study
Authors: Aledo-Serrano Ángel , Mingorance Ana , Villanueva Vicente , García-Peñas Juan José , Gil-Nagel Antonio , Boronat Susana , Aibar JoséÁngel , Cámara Silvia , Yániz María José , Aras Luis Miguel , Blanco Bárbara , Sánchez-Carpintero Rocío 
Published: September 2022

ObjectiveThe appropriate management of patients with Dravet Syndrome (DS) is challenging, given the severity of symptoms and the burden of the disease for patients and caregivers. This study aimed to identify, through a qualitative methodology and a Delphi consensus-driven process, a set of recommendations for the management of DS to guide clinicians in the assessment of the clinical condition and quality of life (QoL) of DS patients, with a special focus on patient- and caregiver-reported outcomes (PROs).MethodsThis study was conducted in five phases, led by a multidisciplinary scientific committee (SC) including pediatric neurologists, epileptologists, a neuropsychologist, an epilepsy nurse, and members of DS patient advocates. In phases 1 and 2, a questionnaire related to patients' QoL was prepared and answered by caregivers and the SC. In phase 3, the SC generated, based on these answers and on a focus group discussion, a 70-item Delphi questionnaire, covering six topic categories on a nine-point Likert scale. In phase 4, 32 panelists, from different Spanish institutions and with a multidisciplinary background, answered the questionnaire. Consensus was obtained and defined as strong or moderate if ≥80% and 67–79% of panelists, respectively, rated the statement with ≥7. Phase 5 consisted of the preparation of the manuscript.ResultsThe panelists agreed on a total of 69 items (98.6%), 54 (77.14%), and 15 (21.43%) with strong and moderate consensus, respectively. The experts' recommendations included the need for frequent assessment of patient and caregivers QoL parameters. The experts agreed that QoL should be assessed through specific questionnaires covering different domains. Likewise, the results showed consensus regarding the regular evaluation of several clinical parameters related to neurodevelopment, attention, behavior, other comorbidities, and sudden unexpected death in epilepsy (SUDEP). A consensus was also reached on the instruments, specific parameters, and caregivers' education in the routine clinical management of patients with DS.ConclusionsThis consensus resulted in a set of recommendations for the assessment of clinical and QoL parameters, including PROs, related to the general evaluation of QoL, neurodevelopment, attention, behavior, other comorbidities affecting QoL, SUDEP, and QoL of caregivers/relatives and patients with DS.
Prospective evaluation of the role of imaging techniques and TMPRSS2:ERG mutation for the diagnosis of clinically significant prostate cancer
Authors: Lazzeri Massimo , Fasulo Vittorio , Lughezzani Giovanni , Benetti Alessio , Soldà Giulia , Asselta Rosanna , De Simone Ilaria , Paciotti Marco , Avolio Pier Paolo , Contieri Roberto , Saitta Cesare , Saita Alberto , Hurle Rodolfo , Guazzoni Giorgio , Buffi Nicolò Maria , Casale Paolo 
Published: September 2022

ObjectivesTo test the hypothesis of a relationship between a specific genetic lesion (T2:ERG) and imaging scores, such as PI-RADS and PRI-MUS, and to test the effectiveness of these parameters for the diagnosis of prostate cancer (PCa) and clinically significant PCa (csPCa).Materials and methodsThis is a prospective study of men with suspected PCa enrolled between 2016 and 2019 at a high-volume tertiary hospital. Patients underwent systematic US-guided biopsy, plus targeted biopsy if they were presenting with &gt;=1 suspicious lesion (PI-RADS&gt;2) at mpMRI or PR-IMUS &gt;2 at micro-ultrasound assessment. For each patient, one core from the highest PI-RADS or PRI-MUS lesion was collected for T2:ERG analysis. Multivariable logistic regression models (LRMs) were fitted for csPCa with a clinical model (age, total PSA, previous biopsy, family history for PCa), a clinical plus PI-RADS, clinical plus T2:ERG, clinical plus PI-RADS plus T2:ERG, and T2:ERG plus PI-RADS alone.ResultsThe cohort consists of 158 patients: 83.5% and 66.2% had respectively a diagnosis of PCa and csPCa after biopsy. A T2:ERG fusion was found in 37 men and 97.3% of these patients harbored PCa, while 81.1% were diagnosed with csPCa. SE of T2:ERG assay for csPCa was 28.8%, SP 87.0%, NPV 38.8%, and PPV 81.1%. Of 105 patients who performed mpMRI 93.% had PIRADS ≥3. SE of mpMRI for csPCa was 98.5%, SP was 12.8%, NPV was 83.3%, and PPV was 65.7%. Among 67 patients who were subjected to micro-US, 90% had a PRI-MUS ≥3. SE of micro-US for csPCa was 89.1%, SP was 9.52%, NPV was 28.6%, and PPV was 68.3%. At univariable LRM T2:ERG was confirmed as independent of mpMRI and micro-US result (OR 1.49, p=0.133 and OR 1.82, p=0.592, respectively). At multivariable LRM the clinical model alone had an AUC for csPCa of 0.74 while the clinical model including PI-RADS and T2:ERG achieved an AUC of 0.83.ConclusionsT2:ERG translocation and imaging results are independent of each other, but both are related csPCa. To evaluate the best diagnostic work-up for PCa and csPCa detection, all available tools (T2:ERG detection and imaging techniques) should be employed together as they appear to have a complementary role.
microRNA-145-5p inhibits prostate cancer bone metastatic by modulating the epithelial-mesenchymal transition
Authors: Luo Bingfeng , Yuan Yuan , Zhu Yifei , Liang Songwu , Dong Runan , Hou Jian , Li Ping , Xing Yaping , Lu Zhenquan , Lo Richard , Kuang Guan-Ming 
Published: September 2022

ObjectiveTo investigate the effects of miRNA-145-5p on the tumor development and progression of prostate cancer (Pca) bone metastasis.MethodsLevels of miRNA-145-5p were assessed by real-time quantitative PCR in PC3 (bone metastatic Pca cells), 22RV1 (non-metastatic Pca cells), RWPE-1 (non-cancerous prostate epithelial cells) and Pca tissues collected from patients with and without bone metastases. The impact of miRNA-145-5p on cell proliferation was tested by CCK8 assay, colony formation assay and flow cytometric cell cycle analysis. Effects on invasion and migration of PC3 cells were determined by Transwell and wound healing assays. Western blotting, enzyme-linked immunosorbent assay, and flow cytometry apoptosis analyses were also performed to assess roles in metastasis.ResultsLevels of miRNA-145-5p were decreased in Pca bone metastases and miRNA-145-5p inhibited cell proliferation, migration and invasion. miRNA-145-5p inhibited the expression of basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF) and transforming growth factor-β (TGF-β) in PC3 cells. miR-145-5p increased the expression of the epithelial marker E-cadherin and reduced the expression of matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9). It was found that miRNA-145-5p mediated the epithelial-mesenchymal transition (EMT) and induced apoptosis.ConclusionsmiRNA-145-5p negatively regulated the EMT, inhibited Pca bone metastasis and promoted apoptosis in Pca bone metastasis. Mimicry of miRNA-145-5p action raises the possibility of a novel target for treating Pca with bone metastases.