bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Extracellular Vesicles Isolated From Osteoblasts of Patients With Cox-Arthrosis and/or Osteoporosis on Metabolism and Osteogenic Differentiation of BMSCs
Authors: Niedermair Tanja , Lukas Christoph , Li Shushan , Stöckl Sabine , Craiovan Benjamin , Brochhausen Christoph , Federlin Marianne , Herrmann Marietta , Grässel Susanne 
Published: December 2020

Background:Studies with extracellular vesicles (EVs), including exosomes, isolated from mesenchymal stem cells (MSC) indicate benefits for the treatment of musculoskeletal pathologies as osteoarthritis (OA) and osteoporosis (OP). However, little is known about intercellular effects of EVs derived from pathologically altered cells that might influence the outcome by counteracting effects from “healthy” MSC derived EVs. We hypothesize, that EVs isolated from osteoblasts of patients with hip OA (coxarthrosis/CA), osteoporosis (OP), or a combination of both (CA/OP) might negatively affect metabolism and osteogenic differentiation of bone-marrow derived (B)MSCs.Methods:Osteoblasts, isolated from bone explants of CA, OP, and CA/OP patients, were compared regarding growth, viability, and osteogenic differentiation capacity. Structural features of bone explants were analyzed via μCT. EVs were isolated from supernatant of naïve BMSCs and CA, OP, and CA/OP osteoblasts (osteogenic culture for 35 days). BMSC cultures were stimulated with EVs and subsequently, cell metabolism, osteogenic marker gene expression, and osteogenic differentiation were analyzed.Results:Trabecular bone structure was different between the three groups with lowest number and highest separation in the CA/OP group. Viability and Alizarin red staining increased over culture time in CA/OP osteoblasts whereas growth of osteoblasts was comparable. Alizarin red staining was by trend higher in CA compared to OP osteoblasts after 35 days and ALP activity was higher after 28 and 35 days. Stimulation of BMSC cultures with CA, OP, and CA/OP EVs did not affect proliferation but increased caspase 3/7-activity compared to unstimulated BMSCs. BMSC viability was reduced after stimulation with CA and CA/OP EVs compared to unstimulated BMSCs or stimulation with OP EVs. ALP gene expression and activity were reduced in BMSCs after stimulation with CA, OP, and CA/OP EVs. Stimulation of BMSCs with CA EVs reduced Alizarin Red staining by trend.Conclusion:Stimulation of BMSCs with EVs isolated from CA, OP, and CA/OP osteoblasts had mostly catabolic effects on cell metabolism and osteogenic differentiation irrespective of donor pathology and reflect the impact of tissue microenvironment on cell metabolism. These catabolic effects are important for understanding differences in effects of EVs on target tissues/cells when harnessing them as therapeutic drugs.
Focusing on Emotional and Social Intelligence Stimulation of People With Dementia by Playing a Serious Game—Proof of Concept Study
Authors: Berenbaum Rakel , Tziraki Chariklia , Baum Reem , Rosen Adi , Reback Tuvia , Abikhzer Judith , Naparstek Daphna , Ben-David Boaz M. 
Published: December 2020

Context: Dementia is one of the top five chronic diseases, which has an overwhelming impact on patients' life quality, family, and caregivers. Currently, research relating to people with dementia (PwD) focuses on the deterioration of cognitive abilities. A more innovative approach, and the one taken by this paper, is focusing on methods to maintain and improve functionality, communication and quality of life of PwD by building on remaining capacities in the yet unexplored domain of emotional and social intelligence (ESI). The use of serious games for PwD (SG4D) aimed at building social and emotional capacity is a budding field of research.Objectives: Proof of concept that the, low cost, easy to deploy SG4D, called “My Brain Works” (MBW), co-designed with PwD, enhances ESI, based on the Bar-On ESI model.Methods: 27 PwD, clients at MELABEV dementia day center, participated in a mixed methods 12 weeks pilot, proof of concept study using a tablet SG4D co-designed with PwD. Quantitative performance data was collected automatically by the tablet during game sessions. In this paper we focus on the analysis of the qualitative and quantitative data related to ESI, observed by 10 different researchers, during each game session.Results: Quantitative data revealed: both the PwD with high and low MoCA scores had similar average ESI scores. Qualitative analysis revealed that the PwD demonstrated 9 sub-components of the Bar-On ESI Model.Conclusion: While there is no drug to stop cognitive decline associated with dementia, interventions related to ESI, on the other hand, may improve functioning and quality of life. Despite declines in cognitive abilities, our study shows that a tablet based SG4D can stimulate their ESI and evoke responses in self-awareness, empathy, social and communication capacities. Using SG4D to exercise and maintain social skills is an area that may be promising in the future and may help counter the negative effects of social isolation and loneliness. Such games, while not focusing on cognitive improvement, may also impact on cognitive functioning and help bridge the gap between caregiver and PwD. More research is needed with larger sample sizes.
Effects of Obesity and Thrombophilia on the Risk of Abortion in Women Undergoing In Vitro Fertilization
Authors: Candeloro Matteo , Di Nisio Marcello , Ponzano Adalisa , Tiboni Gian Mario , Potere Nicola , Tana Marco , Rutjes Anne W. S. , Porreca Ettore 
Published: December 2020

IntroductionObesity is associated with a higher risk of abortion in women undergoing in vitro fertilization (IVF). Whether thrombophilia amplifies this risk is currently unclear. The aim of this study was to evaluate the effects of thrombophilia on the risk of abortion in obese women treated with IVF.MethodsPatient characteristics, presence of inherited or acquired thrombophilia, and comorbidities were prospectively collected before the procedure in consecutive women undergoing IVF. The primary outcome was the incidence of abortion among women who achieved a clinical pregnancy.ResultsA total of 633 non-obese and 49 obese Caucasian women undergoing IVF were included. 204 (32%) women achieved clinical pregnancy, of whom six had an ectopic pregnancy and 63 experienced an abortion. The incidence of abortion was higher in obese women compared to non-obese women after adjusting for age (64.3% vs. 29.3%, odds ratio [OR] 4.41; 95% CI 1.41 to 13.81). Women with one or more thrombophilia were at increased risk of abortion relative to those without thrombophilia (OR 2.70; 95% CI 1.34 to 5.45), and the risk seemed to be higher with hereditary (OR 5.12; 95% CI 1.77 to 14.8) than acquired thrombophilia (OR 1.92; 95% CI 0.52 to 5.12; p for interaction 0.194). Among obese women, the presence of one or more thrombophilia seemed associated with a substantially increased risk of abortion (unadjusted OR 14.00; 95% CI 0.94 to 207.6).ConclusionsObese women undergoing IVF have a high risk of abortion which seems further amplified by the concomitant presence of thrombophilia.
Case Report: Humanized Selective CD19CAR-T Treatment Induces MRD-Negative Remission in a Pediatric B-ALL Patient With Primary Resistance to Murine-Based CD19CAR-T Therapy
Authors: Wang Kai , Zhao Yu , Wang Xuan , Wang Bin , Qin Maoquan , Zhu Guanghua , Wu Huantong , Liu Zhongfeng , Zheng Xueling , Zheng Huyong , Chen Zhiguo 
Published: December 2020

BackgroundCD19 chimeric antigen receptor T cell (CD19CAR-T) has shown great potential to treat acute B cell lymphoblastic leukemia (B-ALL) and B cell lymphoma, and most of anti-CD19 scFv are derived from murine antibody sequences. However, about 10–20% of B-ALL patients exhibit primary resistance to murine-based CD19CAR-T (CD19mCAR-T). Herein, we report that a humanized selective CD19CAR-T (CD19hsCAR-T) may offer a solution to this problem.Case DescriptionA 10-year old boy was diagnosed with high-risk B-ALL in Mar., 2013, and relapsed in Oct., 2018, after he underwent haplo-identical hematopoietic stem cell transplantation (HSCT) in 2017. The patient then received haplo-identical CD19mCAR-T infusions twice following induction chemotherapy with Vincristine, Dexamethasone and Asparaginase (VDL), but no response was observed. We further treated this patient with CD19hsCAR-T following chemotherapy with Vindesine, Idarubicin, Dexamethasone, and Pegylated Asparaginase (VDLD) plus bortezomib. The patient achieved minimal residual disease-negative (MRDneg) complete remission with incomplete hematopoietic recovery (CRi), and remained in CRi for more than 8 months with manageable side effect. The patient, unfortunately, died of unidentified pulmonary infection on Jan. 25 2020.ConclusionCD19hsCAR-T may have the potential to induce remission in patients who are primarily refractory to CD19mCAR-T.
Texture Analysis in the Diagnosis of Primary Breast Cancer: Comparison of High-Resolution Dedicated Breast Positron Emission Tomography (dbPET) and Whole-Body PET/CT
Authors: Satoh Yoko , Hirata Kenji , Tamada Daiki , Funayama Satoshi , Onishi Hiroshi 
Published: December 2020

Objective: This retrospective study aimed to compare the ability to classify tumor characteristics of breast cancer (BC) of positron emission tomography (PET)-derived texture features between dedicated breast PET (dbPET) and whole-body PET/computed tomography (CT).Methods: Forty-four BCs scanned by both high-resolution ring-shaped dbPET and whole-body PET/CT were analyzed. The primary BC was extracted with a standardized uptake value (SUV) threshold segmentation method. On both dbPET and PET/CT images, 38 texture features were computed; their ability to classify tumor characteristics such as tumor (T)-category, lymph node (N)-category, molecular subtype, and Ki67 levels was compared. The texture features were evaluated using univariate and multivariate analyses following principal component analysis (PCA). AUC values were used to evaluate the diagnostic power of the computed texture features to classify BC characteristics.Results: Some texture features of dbPET and PET/CT were different between Tis-1 and T2-4 and between Luminal A and other groups, respectively. No association with texture features was found in the N-category or Ki67 level. In contrast, receiver-operating characteristic analysis using texture features' principal components showed that the AUC for classification of any BC characteristics were equally good for both dbPET and whole-body PET/CT.Conclusions: PET-based texture analysis of dbPET and whole-body PET/CT may have equally good classification power for BC.
A Cohort Study of Liver Involvement in Patients With Adult-Onset Still's Disease: Prevalence, Characteristics and Impact on Prognosis
Authors: Chi Huihui , Wang Zhihong , Meng Jianfen , Han Pingyang , Zhai Limin , Feng Tienan , Teng Jialin , Sun Yue , Hu Qiongyi , Zhang Hao , Liu Honglei , Cheng Xiaobing , Ye Junna , Shi Hui , Wu Xinyao , Zhou Zhuochao , Jia Jinchao , Wan Liyan , Liu Tingting , Qiao Xin , Wang Mengyan , Wang Fan , Chen Xia , Yang Chengde , Su Yutong 
Published: December 2020

Objective: Adult-onset Still's disease (AOSD) is a systemic disorder commonly accompanied by liver involvement. This study aims to illustrate the detailed information of liver abnormalities in patients with AOSD and evaluate the impact on the prognosis.Methods: A total number of 128 hospitalized patients, who met the Yamaguchi criteria of AOSD in the Department of Rheumatology and Immunology, Ruijin Hospital from July 2016 to August 2019 were consecutively enrolled and followed up. The demographic characteristics, clinical features, laboratory tests, treatments and prognosis were recorded. Correlations of liver function tests (LFTs) with disease activity and laboratory parameters were analyzed by the Spearman test. Risk factors of the refractory AOSD were evaluated by multivariate logistic regression analysis.Results: Liver involvement was presented in 104 (81.3%) patients with AOSD. We observed that 34 (32.7%) patients were with mild elevation, 32 (30.8%) patients were with moderate elevation, and 38 (36.5%) patients were with severe elevation. The majority of elevated ALT, AST and ALP decreased to normal within the range of 2 months, except for GGT. Furthermore, the LFTs were found significantly correlated with disease activity. Besides, we found patients with higher levels of LFTs tended to require more intensive treatments and suffered from poorer prognosis. Multivariate logistic regression analysis showed ALP ≥ 141 IU/L and GGT ≥ 132 IU/L are independent risk factors of refractory AOSD.Conclusion: Liver involvement is common in patients with AOSD, the levels of LFTs are associated with disease activity and related to the treatment strategies and prognosis.
Efficacy of Postoperative FOLFOX Versus XELOX Chemotherapy for Gastric Cancer and Prognostic Value of Platelet–Lymphocyte Ratio in Patients Receiving XELOX
Authors: Yin Xin , Fang Tianyi , Wang Yimin , Li Chunfeng , Wang Yufei , Zhang Daoxu , Xue Yingwei 
Published: December 2020

BackgroundSurgery combined with postoperative chemotherapy is an effective method for treating patients with gastric cancer (GC) in Asia. The important roles of systemic inflammatory response in chemotherapy have been gradually verified. The purpose of this study was to assess the difference in clinical effectiveness of FOLFOX (oxaliplatin + leucovorin + 5-fluorouracil) and XELOX (oxaliplatin + capecitabine), and the prognostic value of postoperative platelet–lymphocyte ratio (PLR) in the XELOX group.MethodsPatients who received radical gastrectomy combined with postoperative chemotherapy between 2004 and 2014 were consecutively selected into the FOLFOX and XELOX groups. Group bias was reduced through propensity score matching, which resulted in 278 patients in each group. Cut-off values of systemic immune inflammation (SII) score and PLR were obtained by receiver operating characteristic curve. Kaplan–Meier and Log-rank tests were used to analyze overall survival. The chi-square test was used to analyze the association between clinical characteristics and inflammatory indexes. Univariate and multivariate analyses based on Cox regression analysis showed independent risk factors for prognosis. The nomogram was made by R studio.ResultsPatients receiving XELOX postoperative chemotherapy had better survival than those receiving FOLFOX (P &lt; 0.001), especially for stage III GC (P = 0.002). Preoperative SII was an independent risk factor for prognosis in the FOLFOX group, and PLR of the second postoperative chemotherapy regimen in the XELOX group, combined with tumor size and pTNM stage, could construct a nomogram for evaluating recurrence and prognosis.ConclusionXELOX is better than FOLFOX for treatment of GC in Chinese patients, and a nomogram constructed by PLR, tumor size and pTNM stage can predict recurrence and prognosis.
Dyspnea in Patients Receiving Radical Radiotherapy for Non-Small Cell Lung Cancer: A Prospective Study
Authors: Sardaro Angela , McDonald Fiona , Bardoscia Lilia , Lavrenkov Konstantin , Singh Shalini , Ashley Sue , Traish Daphne , Ferrari Cristina , Meattini Icro , Asabella Artor Niccoli , Brada Michael 
Published: December 2020

Background and PurposeDyspnea is an important symptomatic endpoint for assessment of radiation-induced lung injury (RILI) following radical radiotherapy in locally advanced disease, which remains the mainstay of treatment at the time of significant advances in therapy including combination treatments with immunotherapy and chemotherapy and the use of local ablative radiotherapy techniques. We investigated the relationship between dose-volume parameters and subjective changes in dyspnea as a measure of RILI and the relationship to spirometry.Material and MethodsEighty patients receiving radical radiotherapy for non-small cell lung cancer were prospectively assessed for dyspnea using two patient-completed tools: EORTC QLQ-LC13 dyspnea quality of life assessment and dyspnea visual analogue scale (VAS). Global quality of life, spirometry and radiation pneumonitis grade were also assessed. Comparisons were made with lung dose-volume parameters.ResultsThe median survival of the cohort was 26 months. In the evaluable group of 59 patients there were positive correlations between lung dose-volume parameters and a change in dyspnea quality of life scale at 3 months (V30 p=0.017; V40 p=0.026; V50 p=0.049; mean lung dose p=0.05), and a change in dyspnea VAS at 6 months (V30 p=0.05; V40 p=0.026; V50 p=0.028) after radiotherapy. Lung dose-volume parameters predicted a 10% increase in dyspnea quality of life score at 3 months (V40; p=0.041, V50; p=0.037) and dyspnea VAS score at 6 months (V40; p=0.027) post-treatment.ConclusionsWorsening of dyspnea is an important symptom of RILI. We demonstrate a relationship between lung dose-volume parameters and a 10% worsening of subjective dyspnea scores. Our findings support the use of subjective dyspnea tools in future studies on radiation-induced lung toxicity, particularly at doses below conventional lung radiation tolerance limits.
Real-World Cost-Effectiveness Analysis of Gemcitabine and Cisplatin Compared to Docetaxel and Cisplatin Plus Fluorouracil Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma
Authors: Yang Jiangping , Han Jiaqi , He Jinlan , Duan Baofeng , Gou Qiheng , Ai Ping , Liu Lei , Li Yanchu , Ren Kexing , Wang Feng , Yao Min , Chen Nianyong 
Published: December 2020

BackgroundAddition of gemcitabine and cisplatin (GP) or docetaxel and cisplatin plus fluorouracil (TPF) to concurrent chemoradiotherapy (CCRT) signiﬁcantly improved survival in locoregionally advanced nasopharyngeal carcinoma (NPC). However, an economic evaluation of these regimens remains unknown. The purpose of this study is to compare the cost-effectiveness of GP versus TPF regimen in the treatment of locoregionally advanced NPC in China.Materials and methodsA comprehensive Markov model was developed to evaluate the health and economic outcomes of GP versus TPF regimen for patients with locoregionally advanced NPC. Baseline and clinical outcome were derived from 158 patients with newly diagnosed stage III-IVA NPC between 2010 and 2015. We evaluated the quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs) from the perspective of the Chinese healthcare system. One-way sensitive analysis explored the impact of uncertainty in key model parameters on results, and probabilistic uncertainty was assessed through a Monte Carlo probabilistic sensitivity analysis.ResultsGP regimen provided an additional 0.42 QALYs with incremental cost of $3,821.99, resulting in an ICER of $9,099.98 per QALY versus TPF regimen at the real-world setting. One-way sensitivity analysis found that the results were most sensitive to the cost and proportion of receiving subsequent treatment in two groups. The probability that GP regimen being cost-effective compared with TPF regimen was 86.9% at a willingness-to-pay (WTP) of $31,008.16 per QALY.ConclusionUsing real-world data, GP regimen was demonstrated a cost-effective alternative to TFP regimen for patients with locoregionally advanced NPC in China. It provides valuable evidence for clinicians when making treatment decisions to improve the cost-effectiveness of treatment.
Stimulator of Interferon Genes-Associated Vasculopathy With Onset in Infancy: A Systematic Review of Case Reports
Authors: Dai YunFan , Liu XiuYun , Zhao ZhiPeng , He JianXin , Yin QingQin 
Published: December 2020

Objective: To summarize and analyze the manifestations of stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI).Methods: A systematic literature review was performed including cases from January 1, 2014, to February 1, 2020, using PubMed, OVID, CNKI, and WanFang. This included all the literature containing comparatively complete clinical data. Statistical analysis was performed using SPSS 20.0 to analyze the difference in age of onset, severity of skin lesions, and respiratory symptoms between SAVI patients with p.N154S and p.V155M mutations.Results: A total of 25 papers were included reporting on 51 individuals, of whom 17 had familiar inheritance of their mutation. Patients included 27 males and 24 females, and 8 fatal cases were observed. A total of 10 mutation sites have been reported in the STING gene, with p.V155M being the most prevalent. We identified SAVI as an early-onset disease with a median age of onset of 3 months after birth. Skin lesions were the most common symptoms of SAVI, found in 94.1% (48/51) of patients, while 76% (19/25) who had undergone a skin biopsy showed vasculopathy. Involvement of the lungs was identified in 68.6% (35/51) of patients, while only 22.2% (4/18) who had undergone a lung biopsy showed vasculopathy. Of 20 patients, 19 had increased immunoglobulin, mainly IgG. Furthermore, 45.1% (23/51) of patients had a positive low titer or were transiently positive for antinuclear antibodies. Of the 18 patients treated with JAK inhibitors, 6 relapsed and 2 died of acute respiratory failure caused by viral infection. Patients with p.N154S mutation had an earlier disease onset (p = 0.002) and more severe skin lesions (p &lt; 0.001) than those patients with p.V155M mutation.Conclusion: SAVI is an early-onset disease accompanied by skin and lung lesions whose clinical presentation varies among patients with different genotypes. Therapeutic effects of JAK inhibitors are unsatisfactory.
Implementation of a Compact Spot-Scanning Proton Therapy System in a GPU Monte Carlo Code to Support Clinical Routine
Authors: Gajewski Jan , Schiavi Angelo , Krah Nils , Vilches-Freixas Gloria , Rucinski Antoni , Patera Vincenzo , Rinaldi Ilaria 
Published: December 2020

The purpose of this work was to implement a fast Monte Carlo dose calculation tool, Fred, in the Maastro proton therapy center in Maastricht (Netherlands) to complement the clinical treatment planning system. Fred achieves high accuracy and computation speed by using physics models optimized for radiotherapy and extensive use of GPU technology for parallelization. We implemented the beam model of the Mevion S250i proton beam and validated it against data measured during commissioning and calculated with the clinical TPS. The beam exits the accelerator with a pristine energy of around 230 MeV and then travels through the dynamically extendable nozzle of the device. The nozzle contains the range modulation system and the multi-leaf collimator system named adaptive aperture. The latter trims the spots laterally over the 20 × 20 cm2 area at the isocenter plane. We use a single model to parameterize the longitudinal (energy and energy spread) and transverse (beam shape) phase space of the non-degraded beam in the default nozzle position. The range modulation plates and the adaptive aperture are simulated explicitly and moved in and out of the simulation geometry dynamically by Fred. Patient dose distributions recalculated with Fred were comparable with the TPS and met the clinical criteria. Calculation time was on the order of 10–15 min for typical patient cases, and future optimization of the simulation statistics is likely to improve this further. Already now, Fred is fast enough to be used as a tool for plan verification based on machine log files and daily (on-the-fly) dose recalculations in our facility.