bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of four tools to identify painful new osteoporotic vertebral fractures in the postmenopausal population in Beijing
Authors: Guo SiJia , An Ning , Lin JiSheng , Fan ZiHan , Meng Hai , Yang Yong , Fei Qi 
Published: November 2022

ObjectivesTo validate and compare four tools, the Fracture Risk Assessment Tool (FRAX) without bone mineral density (BMD), Beijing Friendship Hospital Osteoporosis Screening Tool (BFH-OST), Osteoporosis Self-Assessment Tool for Asians (OSTA), and BMD, to identify painful new osteoporotic vertebral fractures (PNOVFs).MethodsA total of 2874 postmenopausal women treated from June 2013 to June 2022 were enrolled and divided into two groups: patients with PNOVFs who underwent percutaneous vertebroplasty (PNOVFs group, n = 644) and community-enrolled females (control group, n = 2230). Magnetic resonance and X-ray imaging were used to confirm the presence of PNOVFs. Dual-energy X-ray absorptiometry was performed to calculate the BMD T-scores. Osteoporosis was diagnosed according to WHO Health Organization criteria. Data on the clinical and demographic risk factors were self-reported using a questionnaire. The ability to identify PNOVFs using FRAX, BFH-OST, OSTA, and BMD scores was evaluated using receiver operating characteristic (ROC) curves. For this evaluation, we calculated the areas under the ROC curves (AUCs), sensitivity, specificity, and optimal cut-off points.ResultsThere were significant differences in FRAX (without BMD), BFH-OST, OSTA, and BMD T-scores (total hip, femoral neck, and lumbar spine) between the PNOVFs and control groups. Compared with BFH-OST, OSTA, and BMD, the FRAX score had the best identifying value for PNOVFs; the AUC of the FRAX score (optimal cutoff =3.6%) was 0.825, while the sensitivity and specificity were 82.92% and 67.09%, respectively.ConclusionFRAX may be the preferable tool for identifying PNOVFs in postmenopausal women, while BFH-OST and OSTA can be applied as more simple screening tools for PNOVFs.
Ceritinib (LDK378) prevents bone loss via suppressing Akt and NF-κB-induced osteoclast formation
Authors: He Wenxin , Cao Xiankun , Kong Keyu , Rong Kewei , Han Shuai , Qin An 
Published: November 2022

BackgroundCeritinib is used for the treatment of patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC), who are at the risk of developing bone metastasis. During bone metastasis, tumor cells release factors that induce osteoclast formation, resulting in osteolysis. However, the effect of ceritinib on osteoclast formation remains unclear.MethodsOsteoclastogenesis was induced to assess the effect of ceritinib on osteoclast formation and osteoclast-specific gene expression. Western blotting was used to examine the molecular mechanisms underlying the effect of ceritinib on osteoclast differentiation. An in vivo ovariectomized mouse model was established to validate the effect of ceritinib in suppressing osteoclast formation and preventing bone loss.ResultsThe differentiation of osteoclasts and the expression of osteoclast-specific genes were inhibited upon ceritinib stimulation. Ceritinib suppressed Akt and p65 phosphorylation during the receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis. The administration of ceritinib to ovariectomized mice ameliorated trabecular bone loss by inhibiting osteoclast formation.ConclusionsCeritinib is beneficial in preventing bone loss by suppressing osteoclastic Akt and nuclear factor κB (NF-κB) signaling.
Research and analysis of the effect between the power level and economy on the lead-based modular nuclear power reactor
Authors: Lei Lou , Lianjie Wang , Bingyan Zhou , Chen Zhao , Bin Zhang , Mingyu Yan , Ce Zhang , Hongzhi Xiang , Yun Cai , Xingbo Wang , Zifan Zhao , Nan Zhou , Jiayi Liu 
Published: November 2022

The fast reactor is gradually being paid attention to in nuclear power due to a better breeding effect, and its economy is also directly followed. Due to the restriction of the core power density, the core power level is directly related to the volume of the core active area. When the power level and the volume of the core gradually increase, the mass of uranium and 235U in the core at the beginning of life will gradually increase on the basis of a critical uranium inventory. At the same time, due to the gradual increase in the breeding effect, the utilization rate of uranium resources at the end of life will gradually increase. Due to the characteristics of the large critical uranium mass and high breeding effect, the mass of uranium and 235U in the low power level core at the beginning of life cannot be further reduced because of the critical uranium inventory. The lifetime of the high power level core should be extended to use the wealthy reactivity of the core because of the improvement in the breeding effect. However, due to the requirements of the nuclear power refuel time and the limitation to fuel consumption, the breeding effect brought by the improvement in the core power level and the size of the active zone may be less effective. In this article, the power level and economy of lead-based modular nuclear power are analyzed, and the economy of different power level fast reactors with 2,000 EFPD lifetime such as 100 MWt, 300 MWt, 500 MWt, 700 MWt, and 1000 MWt thermal power is designed and analyzed. By analyzing the invention of uranium and 235U and the fuel utilization of different core schemes, the best economic analysis of the single reactor power of the current lead-based modular reactor is proposed and the foundation of the lead-based modular nuclear power is provided.
Multifactor dimensionality reduction reveals the effect of interaction between ERAP1 and IFIH1 polymorphisms in psoriasis susceptibility genes
Authors: Zhang Chang , Qin Qin , Li Yuanyuan , Zheng Xiaodong , Chen Weiwei , Zhen Qi , Li Bao , Wang Wenjun , Sun Liangdan 
Published: November 2022

Background: Psoriasis is a common immune-mediated hyperproliferative skin dysfunction with known genetic predisposition. Gene–gene interaction (e.g., between HLA-C and ERAP1) in the psoriasis context has been reported in various populations. As ERAP1 has been recognized as a psoriasis susceptibility gene and plays a critical role in antigen presentation, we performed this study to identify interactions between ERAP1 and other psoriasis susceptibility gene variants.Methods: We validated psoriasis susceptibility gene variants in an independent cohort of 5,414 patients with psoriasis and 5,556 controls. Multifactor dimensionality reduction (MDR) analysis was performed to identify the interaction between variants significantly associated with psoriasis in the validation cohort and ERAP1 variants. We then conducted a meta-analysis of those variants with datasets from exome sequencing, target sequencing, and validation analyses and used MDR to identify the best gene–gene interaction model, including variants that were significant in the meta-analysis and ERAP1 variants.Results: We found that 19 of the replicated variants were identified with p &lt; 0.05 and detected six single-nucleotide polymorphisms of psoriasis susceptibility genes in the meta-analysis. MDR analysis revealed that the best predictive model was that between the rs27044 polymorphism of ERAP1 and the rs7590692 polymorphism of IFIH1 (cross-validation consistency = 9/10, test accuracy = 0.53, odds ratio = 1.32 (95% CI, 1.09–1.59), p &lt; 0.01).Conclusion: Our findings suggest that the interaction between ERAP1 and IFIH1 affects the development of psoriasis. This hypothesis needs to be tested in basic biological studies.
The prevalence of germline pathogenic variants in Estonian colorectal cancer patients: results from routine clinical setting 2016–2021
Authors: Roht Laura , Tooming Mikk , Rekker Kadri , Roomere Hanno , Toome Kadri , Murumets Ülle , Šamarina Ustina , Õunap Katrin , Kahre Tiina 
Published: November 2022

Background: Colorectal cancer (CRC) is the third most common cancer in Estonia in both women and men. According to the Estonian National Institute for Health Development, in 2017, there were 357 new colon cancer only cases in women and 282 in men. For colorectal cancer, the number for men and women altogether was 1040 in the same year. In 2018, there were over 1.8 million new cases worldwide. The Mayo Clinic found in a prospective, two-year multi-site study of CRC patients that 15.5% of patients carried pathogenic germline variants (PGV), using an &gt;80 gene Next Generation Sequencing (NGS) panel.Material and methods: This retrospective study aimed to analyse the estimated prevalence of pathogenic/likely pathogenic germline variants in Estonian colorectal cancer patients using NGS in a routine clinical setting. We gathered five-year data (July 2016-July 2021) of colorectal cancer patients (mostly not selected for age or family history) tested with either Illumina TruSight Cancer (94 genes) or TruSight Hereditary Cancer (113 genes) NGS panels.Results: Three hundred and fourteen NGS analyses were performed due to either CRC or polyposis in anamnesis and/or family anamnesis, including 126 CRC cases and 44 colorectal polyposis cases, while 144 were either healthy family members or had other types of cancers. While a known disease-causing variant was identified in 16.4% of all cancer patients tested, we found that 21.4% of CRC patients had such a variant. Among the 44 colorectal polyps cases MLH1, gene was the most affected one (25%), the second and third most affected genes were MSH2 and CHEK2. Other genes with disease-causing variants found in CRC patients included APC, BLM, BMPR1A, BRCA1, FANCM, MSH6, MUTYH, PMS2, SMAD4, SPINK1 and VHL.Conclusion: Our result give an overview of genetic testing of CRC patients, the prevalence of disease-causing variants and their landscape in Estonia. According to Estonian data, only 2.7–6.1% of CRC patients are genetically tested, which is around ten times less frequently than breast cancer patients and their family members. The diagnostic yield of CRC patients is 21.4%, suggesting that genetic testing will likely improve timely diagnosis and outcomes.
Probiotics modulate gastrointestinal microbiota after Helicobacter pylori eradication: A multicenter randomized double-blind placebo-controlled trial
Authors: He Cong , Xie Yong , Zhu Yin , Zhuang Kun , Huo Lijuan , Yu Yong , Guo Qiang , Shu Xu , Xiong Zhijuan , Zhang Zhenyu , Lyu Bin , Lu Nonghua 
Published: November 2022

BackgroundHelicobacter pylori (H. pylori) eradication has been reported to cause short-term disruption of gut microbiota. It is acknowledged that probiotics supplementation mitigates side effects induced by H. pylori eradication, yet its role on alleviating dysbiosis of microbiota is obscure.ObjectivesTo evaluate the impact of probiotics on gastrointestinal microbiota after eradication therapy.MethodsThis was a multicenter, double-blinded, randomized trial done at seven centers in China. A total of 276 treatment-naïve H. pylori-positive patients were randomly assigned to receive 14-day bismuth-containing quadruple therapy (esomeprazole, bismuth, amoxicillin, furazolidone) combined with probiotics (Bifidobacterium Tetragenous viable Bacteria Tablets) (n=140) or placebo (n=136) for 28 days. Saliva, gastric mucosa and fecal samples were collected before and after therapy for 16S rRNA gene sequencing.ResultsThe incidence of gastrointestinal adverse events was lower in probiotics group compared to placebo group (23.6% vs 37.7%, p=0.016), while there was no significant difference in eradication rate. We found dramatic perturbations of gut microbiota immediately following eradication, with the predominance of Proteobacteria in replacement of commensal Firmicutes and Bacteroidetes, and gradually restored after two weeks. The reduction of gut Bacteroidetes caused by eradication drugs was neutralized with probiotics supplementation. The gastric microbiota was completely reconstituted with H. pylori depleted and other taxa flourished. Of note, patients treated with probiotics showed smaller fluctuations of gastric microbiota compared to those with placebo. We also observed changes of saliva microbiota after H. pylori eradication, illustrated by the overgrowth of Neisseria and depletion of Streptococcus. The expansion of some pathogenic genera, including Porphyromonas, Leptotrichia, in the mouth was suppressed by probiotics.ConclusionThis study not only demonstrated the beneficial effect of probiotics implementation on side events during H. pylori eradication but also provided a comprehensive profile of microbiome alterations along gastrointestinal tract that modulated by probiotics.
Delamanid suppresses CXCL10 expression via regulation of JAK/STAT1 signaling and correlates with reduced inflammation in tuberculosis patients
Authors: Qiao Min , Li Shanshan , Yuan Jinfeng , Ren Weicong , Shang Yuanyuan , Wang Wei , Liu Rongmei , Zhang Fuzhen , Li Qing , Wu Xiao , Lu Jie , Gao Mengqiu , Pang Yu 
Published: November 2022

BackgroundApart from bactericidal effects, anti-tuberculosis drugs can interfere with the host’s immune system. In this study, we analyzed the role of delamanid (DLM), an inhibitor of mycolic acid synthesis of mycobacterial cell wall, on human macrophages.MethodsBased on a cohort of multidrug-resistant tuberculosis (MDR-TB) patients treated with DLM, the levels of C-reaction protein (CRP) and cytokines in the plasma were monitored using immunoturbidimetric assay and flow cytometry, respectively. We investigated the role of DLM on CXCL10 expression in U937 cell model using the following methods: cell viability assay, reverse transcription-quantitative polymerase chain reaction, enzyme linked immunosorbent assay, immunoblot, and transwell co-culture assay.ResultsA total of 23 MDR-TB patients were included, comprising of 13 patients treated with optimized background therapeutic regimen (OBR) plus DLM regimen (OBR+DLM) and 10 patients treated with OBR plus placebo. DLM administration was associated with a significant reduce in circulating CRP level. Correspondingly, after treatment, the level of CXCL10 in patients treated with OBR+DLM was significantly lower than that with control. Using cell model, DLM dramatically suppressed CXCL10 expression, which majorly depended on inhibiting the JAK/STAT pathway, and impaired the migration of PBMCs.ConclusionOur data firstly demonstrate that DLM suppresses CXCL10 expression via regulation of JAK2/STAT1 signaling and correlates with reduced inflammation in MDR-TB patients. DLM could be used as a potential drug for immunotherapy of patients with overactive immune response due to CXCL10.
Inflammatory profile of incident cases of late-onset compared with young-onset rheumatoid arthritis: A nested cohort study
Authors: Mena-Vázquez Natalia , Lisbona-Montañez Jose Manuel , Redondo-Rodriguez Rocío , Mucientes Arkaitz , Manrique-Arija Sara , Rioja José , Garcia-Studer Aimara , Ortiz-Márquez Fernando , Cano-García Laura , Fernández-Nebro Antonio 
Published: November 2022

ObjectivesTo describe the characteristics of patients between late-onset rheumatoid arthritis (LORA) with young-onset (YORA), and analyze their association with cumulative inflammatory burden.MethodsWe performed a nested cohort study in a prospective cohort comprising 110 patients with rheumatoid arthritis (RA) and 110 age- and sex-matched controls. The main variable was cumulative inflammatory activity according to the 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR). High activity was defined as DAS28 ≥ 3.2 and low activity as DAS28 &lt; 3.2. The other variables recorded were inflammatory cytokines, physical function, and comorbid conditions. Two multivariate models were run to identify factors associated with cumulative inflammatory activity.ResultsA total of 22/110 patients (20%) met the criteria for LORA (≥ 60 years). Patients with LORA more frequently had comorbid conditions than patients with YORA and controls. Compared with YORA patients, more LORA patients had cumulative high inflammatory activity from onset [13 (59%) vs. 28 (31%);p= 0.018] and high values for CRP (p= 0.039) and IL-6 (p= 0.045). Cumulative high inflammatory activity in patients with RA was associated with LORA [OR (95% CI) 4.69 (1.49–10.71);p= 0.008], smoking [OR (95% CI) 2.07 (1.13–3.78);p= 0.017], anti–citrullinated peptide antibody [OR (95% CI) 3.24 (1.15–9.13);p= 0.025], average Health Assessment Questionnaire (HAQ) score [OR (95% CI) 2.09 (1.03–14.23);p= 0.034], and physical activity [OR (95% CI) 0.99 (0.99–0.99);p= 0.010]. The second model revealed similar associations with inflammatory activity in patients with LORA.ConclusionControl of inflammation after diagnosis is poorer and comorbidity more frequent in patients with LORA than in YORA patients and healthy controls.
Patients with inflammatory bowel disease have a higher chance of developing periodontitis: A systematic review and meta-analysis
Authors: Domokos Zsuzsanna , Uhrin Eszter , Szabó Bence , Czumbel Márk László , Dembrovszky Fanni , Kerémi Beáta , Varga Gábor , Hegyi Péter , Hermann Péter , Németh Orsolya 
Published: November 2022

Background and objectivePeriodontitis affects up to one billion people worldwide, and has been proven to be associated with several systemic inflammatory conditions. This study investigates the specific relationship between two multifactorial diseases: Inflammatory bowel disease (IBD) and periodontitis. To thoroughly explore this issue, we investigated separately whether IBD patients have a higher chance of developing periodontitis, and equally, whether patients with periodontitis have a higher chance of developing IBD.MethodsThe systematic search was performed in three databases: MEDLINE, Cochrane Trials, and Embase, up to 26 October 2021. The protocol was registered in PROSPERO. All eligible studies investigating the association between IBD and periodontitis from either direction were included. The Newcastle-Ottawa Scale was used to assess the risk of bias. As a primary outcome, we investigated the prevalence of IBD and periodontitis, and calculated the odds ratio (OR). Our secondary outcomes involved comparing the clinical periodontal outcomes of IBD patients to those of IBD-free patients.ResultsThe systematic search resulted in 1,715 records, 14 of which were eligible for qualitative synthesis and 8 for quantitative synthesis. On the basis of the results of the primary outcome, IBD diagnosis was associated with significantly higher odds of periodontitis: OR = 2.65 (CI: 2.09-3.36, I2 = 0 (CI: 0-0.75)). For subgroup analysis, we investigated separately the odds in Crohn’s disease (CD) patients: OR = 2.22 (CI: 1.49-3.31, I2 = 0.05 (CI: 0-0.76)) and in ulcerative colitis (UC) patients: OR = 3.52 (CI: 2.56 to 4.83, I2 = 0 (CI: 0-0.75)); the odds were significantly higher in all cases. Two studies investigated whether patients with periodontitis were more susceptible to IBD, and both found that periodontitis was significantly associated with the risk of subsequent UC, but not with subsequent CD. However, more studies are needed to prove an association.ConclusionOur analysis confirmed that IBD patients have a higher chance of developing periodontitis, and are a higher risk population in dentistry. Both dentists and gastroenterologists should be aware of this relationship and should emphasize the importance of prevention even more than in the healthy population.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021286161].
Blood monocyte counts as a prognostic biomarker and predictor in Chinese patients with idiopathic pulmonary fibrosis
Authors: Zhang Xinran , Ren Yanhong , Xie Bingbing , Ye Qiao , Ban Chenjun , Zhang Shu , Zhu Min , Liu Yan , Wang Shiyao , Geng Jing , He Xuan , Jiang Dingyuan , He Jiarui , Shu Shi , Luo Sa , Wang Xin , Song Dingyun , Fan Mingming , Sun Haishuang , Dai Huaping 
Published: November 2022

ObjectivesWe sought to evaluate the prognostic value of blood routine parameters and biochemical parameters, especially inflammation-related biomarkers, and establish an inflammation-related prognostic model in Chinese patients with idiopathic pulmonary fibrosis (IPF).Material/methodsPatients diagnosed as IPF at Beijing Chaoyang Hospital and aged 40 years and older were consecutively enrolled from June 2000 to March 2015, and finally, a total of 377 patients were enrolled in the derivation cohort. The follow-up ended in December 2016. We used Cox proportional hazard model to calculate the hazard ratio (HR) and establish the prognostic model. The discrimination and calibration of the prognostic model were evaluated in an independent validation cohort enrolled from China-Japan Friendship Hospital between January 2015 and December 2019.ResultsMultivariate analysis revealed that patients with elevated monocyte-to-red blood cell count ratio (MRR) and monocyte counts showed increased risk of mortality. The clinical-physiological-biomarker (CPB) index and CPB stage we established in this study were a significant predictor, and the C-index for CPB index and CPB stage in the validation cohort was 0.635 (95% CI: 0.558–0.712) and 0.619 (95% CI: 0.544–0.694), respectively. Patients in CPB stage III had the poorest survival.ConclusionWe developed and validated a new inflammation-related prognostic model (CPB index and CPB stage) which was integration of age, gender, FVC (%, predicted), DLCO (%, predicted), Charlson Comorbidity Index, and blood monocyte counts. This prediction model exhibited strong ability in predicting mortality in Chinese patients with IPF.
Flexor carpi radialis H-reflex in different body positions in patients with post-stroke
Authors: Ma Jia-Yin , Wu Jia-Jia , Zheng Mou-Xiong , Hua Xu-Yun , Shan Chun-Lei , Xu Jian-Guang 
Published: November 2022

BackgroundSpinal stretch reflex (SSR) hyperexcitability reflected by the H-reflex has been reported in more strongly affected extremities after stroke. The H-reflex in the lower extremities is modulated by body position normally and alternatively modulated post-stroke.ObjectiveThis study aimed to preliminarily explore how upper extremity (UE) H-reflexes are modulated by body position after stroke, which remains unknown.Materials and methodsThree patients after stroke with hemiparesis/hemiplegia were included. Bilateral flexor carpi radialis (FCR) H-reflexes were examined in the supine position while standing. Other clinical evaluations include the modified Ashworth scale (MAS) and postural stability measurement.ResultsThe three cases herein showed that (1) SSR excitability was higher in more strongly affected UEs than less-affected UEs, (2) down-modulation of SSR excitability occurred in less-affected UEs in static standing compared with the supine position, but modulation of SSR excitability in more-affected UEs varied, and (3) bilateral UE SSR excitability in case 3 was down-modulated the most. Moreover, case 3 showed no difference in muscle tone of the more affected UE between supine and standing positions, and case 3 showed the best postural stability.ConclusionSpinal stretch reflex hyperexcitability in strongly affected UEs could commonly occur in different phases of recovery after stroke. Down-modulation of SSR excitability could occur in less-affected UEs in the standing position compared with the supine position, while modulation of SSR excitability might be altered in strongly affected UEs and vary in different phases of recovery. There could be some correlation between postural control and UE SSR hyperexcitability. The H-reflex may help to offer a new perspective on rehabilitation evaluation and interventions to promote UE motor control after stroke.