bluuebunny/crossref_metadata_2025_split huggingface dataset:
Checkpoint inhibition in combination with an immunoboost of external beam radiotherapy in solid tumors (CHEERS): study protocol for a phase 2, open-label, randomized controlled trial
Authors: Spaas Mathieu , Sundahl Nora , Hulstaert Eva , Kruse Vibeke , Rottey Sylvie , De Maeseneer Daan , Surmont Veerle , Meireson Annabel , Brochez Lieve , Reynders Dries , Goetghebeur Els , Van den Begin Robbe , Van Gestel Dirk , Renard Vincent , Dirix Piet , Mestdagh Pieter , Ost Piet 
Published: May 2021

Abstract
Background
While the introduction of checkpoint inhibitors (CPIs) as standard of care treatment for various tumor types has led to considerable improvements in clinical outcome, the majority of patients still fail to respond. Preclinical data suggest that stereotactic body radiotherapy (SBRT) could work synergistically with CPIs by acting as an in situ cancer vaccine, thus potentially increasing response rates and prolonging disease control. Though SBRT administered concurrently with CPIs has been shown to be safe, evidence of its efficacy from large randomized trials is still lacking. The aim of this multicenter randomized phase II trial is to assess whether SBRT administered concurrently with CPIs could prolong progression-free survival as compared to standard of care in patients with advanced solid tumors.

Methods/design
Ninety-eight patients with locally advanced or metastatic disease will be randomized in a 1:1 fashion to receive CPI treatment combined with SBRT (Arm A) or CPI monotherapy (Arm B). Randomization will be stratified according to tumor histology (melanoma, renal, urothelial, head and neck squamous cell or non-small cell lung carcinoma) and disease burden (≤ or > 3 cancer lesions). The recommended SBRT dose is 24Gy in 3 fractions, which will be administered to a maximum of 3 lesions and is to be completed prior to the second or third CPI cycle (depending on CPI treatment schedule). The study’s primary endpoint is progression-free survival as per iRECIST. Secondary endpoints include overall survival, objective response, local control, quality of life and toxicity. Translational analyses will be performed using blood, fecal and tissue samples. Discussion: The CHEERS trial will provide further insights into the clinical and immunological impact of SBRT when combined with CPIs in patients with advanced solid tumors. Furthermore, study results will inform the design of future immuno-radiotherapy trials.

Trial registration
Clinicaltrials.gov identifier: NCT03511391. Registered 17 April 2018.
Thoracic radiotherapy and concurrent almonertinib for unresectable stage III EGFR-mutated non-small-cell lung cancer: a phase 2 study
Authors: ZHU Lucheng , Zou Changlin , Zhang Zhanchun , Wang Jianfang , Yang Li , Rao Chuangzhou , Yang Zhiping , Liang Jiafeng , Xia Bing , Shenglin M. A. 
Published: May 2021

Abstract
Background
Concurrent chemo-radiotherapy remains the standard treatment in unresectable stage III non-small-cell lung cancer (NSCLC) patients. Several studies have shown a potential value of concurrent epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) with thoracic radiotherapy in EGFR-mutated population, but a high risk of radiation pneumonitis raised a major concern. This study intends to explore the safety and efficacy of concurrent almonertinib, a new third-generation EGFR-TKI, with radiotherapy in locally advanced EGFR-mutated NSCLC patients.

Methods
Locally advanced NSCLC patients harboring sensitive EGFR mutation will be included in this study. A radiotherapy plan will be made for each patient before treatment, and the lung V20 will be calculated. Patients with lung V20 ≥ 28% were enrolled in induction group (arm A), which almonertinib was given for 2 months followed by concurrent radiotherapy; patients with lung V20 < 28% were enrolled in concurrent group (arm B), which almonertinib was given concurrent with thoracic radiotherapy. The primary endpoint is the incidence of grade ≥ 3 radiation pneumonitis within 6 months post-radiotherapy, and the secondary endpoints are local control rate, progression-free survival, and overall survival.

Discussion
The safety and efficacy of third-generation EGFR-TKI concurrent with thoracic radiotherapy in locally advanced EGFR-mutated NSCLC is still unknown. We propose to conduct this phase 2 study evaluating the safety especially the radiation pneumonitis within 6 months post-radiotherapy. This trial protocol has been approved by the Ethics committee of Hangzhou cancer hospital. The ethics number is HZCH-2020-030.

Trial registration
clinicaltrials.gov, NCT04636593. Registered 19 November 2020 - Retrospectively registered
Different diagnostic performance of plasma fibrinogen and D-dimer in periprosthetic joint infection: a propensity score matched study
Authors: Chen Xi , Qian Wenwei , Weng Xisheng , Lin Jin , Jin Jin , Wang Yiou , Zhu Shibai 
Published: May 2021

Abstract
Background
Fibrinogen (Fbg) and D-dimer have been used as biomarkers for the diagnosis of periprosthetic joint infection (PJI). However, previous research has reported conflicting results on the diagnostic value of D-dimer in comparison to Fbg, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR).

Aim
This study aimed to: (1) determine the optimal threshold of plasma Fbg and D-dimer in the diagnosis of PJI and compare their diagnostic value to that of CRP and ESR; and (2) investigate whether Fbg and D-dimer perform differently than CRP and ESR as diagnostic indicators for different types of PJI.

Methods
A total of 115 revision cases after total hip arthroplasty (THA) and total knee arthroplasty (TKA) were identified. Based on demographic characteristics, 25 culture-positive cases were matched to 50 culture-negative cases using propensity score matching. Sensitivity, specificity, receiver operating characteristics (ROC), negative predictive value (NPV), and positive predictive value (PPV) were calculated and compared.

Results
The optimal thresholds were 2.72 mg/L for D-dimer, 3.655 g/L for Fbg, 12.64 mg/L for CRP, and 27 mm/h for ESR. Levels of plasma Fbg, D-dimer, CRP, and ESR were significantly higher in the culture-positive group than the culture-negative group. Fbg, D-dimer, CRP, and ESR showed sensitivity of 0.92, 0.56, 0.92, and 0.88, respectively, and showed specificity of 0.84, 0.96, 0.94, and 0.80, respectively. The ROC curve showed that CRP has the highest area under the curve (AUC) (0.94), followed by Fbg (0.90), ESR (0.87), and D-dimer (0.81).

Conclusions
Plasma Fbg exhibited a similar diagnostic performance compared to CRP and ESR in predicting culture-positive results in PJI. Plasma D-dimer showed high specificity but low sensitivity. In our study, Fbg and D-dimer did not show better diagnostic performance with different pathogens and different types of PJI. Further studies are required to investigate the difference between serum D-dimer and plasma D-dimer in the arthroplasty population.
Laminoplasty with selective fusion at unstable segment versus laminectomy with fusion for multilevel cervical myelopathy: a case‐control study
Authors: Du Lin , Gao Yanzheng , Zhao Changqing , Zhou Tangjun , Tian Haijun , Zhang Kai , Zhao Jie 
Published: May 2021

Abstract
Background
Segmental cervical instability is a risk factor for the progression of osteophytic bone spurs and development of myelopathy, and is treated as a relative contraindication of cervical laminoplasty. The aim of this study was to compare laminoplasty with selective fixation (LPSF) versus laminectomy with fusion (LCF) in patients with multilevel cervical myelopathy accompanied by segmental instability.

Methods
A case-control study was conducted by reviewing data from 63 patients who underwent LPSF (n = 30) or LCF (n = 33). Cervical alignment, range of motion (ROM), neurologic status and axial symptom severity pre-operation, 3-days after operation, and at the final follow-up (minimum 24 months) were measured and compared between groups.

Results
Postoperation, patients in the LPSF group lost 31.1 ± 17.3 % of cervical lordosis and 43.2 ± 10.9 % cervical ROM while patients in the LCF group lost 5.7 ± 8.2 % and 67.9 ± 15.5 %, respectively. Both LPSF and LCF groups significantly improved neurologic status and axial symptom severity at the final follow-up with similar between-group results(P > 0.05). Blood loss, operation time, hospital stay, and medical cost in the LPSF group were significantly less than in the LCF group(P < 0.05).

Conclusions
In 2 years of clinical observation, LPSF was effective in maintaining the stability of the cervical spine with less sacrifice of mobility and surgical trauma for multilevel myelopathy with segmental instability compared to LCF.
Multiple intravenous tranexamic acid doses in total knee arthroplasty in patients with rheumatoid arthritis: a randomized controlled study
Authors: Kang Bing-xin , Xu Hui , Gao Chen-xin , Zhong Sheng , Zhang Jing , Xie Jun , Sun Song-tao , Ma Ying-hui , Xu Xi-rui , Zhao Chi , Zhai Wei-tao , Xiao Lian-bo , Gao Xiao-jun 
Published: May 2021

Abstract
Background
We aimed to determine the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) on perioperative blood loss in patients with rheumatoid arthritis (RA) who had undergone primary unilateral total knee arthroplasty (TKA).

Methods
For this single-center, single-blind randomized controlled clinical trial, 10 male and 87 female participants with RA, aged 50–75 years, who underwent unilateral primary TKA were recruited. The patients received one dose of 1 g IV-TXA 10 min before skin incision, followed by articular injection of 1.5 g tranexamic acid after cavity suture during the surgery. The patients were randomly assigned (1:1) into two groups and received an additional single dose of IV-TXA (1 g) for 3 h (group A) or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group B) postoperatively. Primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and maximum hemoglobin (Hb) level decrease. Secondary outcomes were transfusion rate and D-dimer levels. All parameters were measured postoperatively during inpatient hospital stay.

Results
The mean TBL, HBL, and maximum Hb level decrease in group B (506.1 ± 227.0 mL, 471.6 ± 224.0 mL, and 17.5 ± 7.7 g/L, respectively) were significantly lower than those in group A (608.8 ± 244.8 mL, P = 0.035; 574.0 ± 242.3 mL, P = 0.033; and 23.42 ± 9.2 g/L, P = 0.001, respectively). No episode of transfusion occurred. The D-dimer level was lower in group B than in group A on postoperative day 1 (P <  0.001), and the incidence of thromboembolic events was similar between the groups (P > 0.05).

Conclusion
In patients with RA, three doses of postoperative IV-TXA further facilitated HBL and Hb level decrease without increasing the incidence of adverse events in a short period after TKA.

Trial registration
The trial was registered in the Chinese Clinical Trial Registry (ChiCTR1900025013).
Electromyographic features and efficacy of orofacial myofunctional treatment for skeletal anterior open bite in adolescents: an exploratory study
Authors: Hong Hong , Zeng Yue , Chen Xiaomin , Peng Caixia , Deng Jianqing , Zhang Xueqin , Deng Lidi , Xie Yongjian , Wu Liping 
Published: May 2021

AbstractBackgroundDue to the multifactorial aetiology and unpredictable long-term stability, skeletal anterior open bite (SAOB) is one of the most intractable conditions for orthodontists. The abnormal orofacial myofunctional status (OMS) may be a major risk factor contributing to the development and relapse of SAOB. This study is aimed at evaluating the OMS and the efficacy of orofacial myofunctional therapy (OMT) alone for SAOB subjects.MethodsEighteen adolescents with SAOB (4 males, 14 females; age: 12–18 years) and eighteen adolescents with normal occlusion (2 males, 16 females; age: 12–18 years) were selected. The electromyographic activity (EMGA) associated with mastication and closed mouth state was measured. Lateral cephalography was used to evaluate craniofacial morphology. Wilcoxon signed rank tests and t-tests were performed to evaluate myofunctional and morphological differences. Pearson or Spearman correlation analysis was used to investigate the correlations between EMGA and morphological characteristics. SAOB subjects were given OMT for 3 months, and the EMGA was compared between before and after OMT.ResultsDuring rest, anterior temporalis activity (TAA) and mentalis muscle activity (MEA) increased in SAOB subjects, but TAA and masseter muscle activity (MMA) decreased in the intercuspal position (ICP); and upper orbicularis activity (UOA) and MEA significantly increased during lip sealing and swallowing (P < 0.05). Morphological evaluation revealed increases in the FMA, GoGn-SN, ANS-Me, N-Me, L1-MP, U6-PP, and L6-MP and decreases in the angle of the axis of the upper and lower central incisors and OB in SAOB subjects (P < 0.05). TAA, MMA and anterior digastric activity (DAA) in the ICP were negatively correlated with vertical height and positively correlated to incisor protrusion. MEA was positively correlated with vertical height and negatively correlated with incisor protrusion; and the UOA showed a similar correlation in ICP, during sealing lip and swallowing. After SAOB subjects received OMT, MEA during rest and TAA, MMA and DAA in the ICP increased, while UOA and MEA decreased (P < 0.05).ConclusionSAOB subjects showed abnormal OMS features including aberrant swallowing patterns and weak masticatory muscles, which were interrelated with the craniofacial dysmorphology features including a greater anterior facial height and incisor protrusion. Furthermore, OMT contributes to OMS harmonization, indicating its therapeutic prospect in SAOB.
Variability of risk factors and diabetes complications
Authors: Ceriello Antonio , Prattichizzo Francesco 
Published: May 2021

AbstractSeveral studies suggest that, together with glucose variability, the variability of other risk factors, as blood pressure, plasma lipids, heart rate, body weight, and serum uric acid, might play a role in the development of diabetes complications. Moreover, the variability of each risk factor, when contemporarily present, may have additive effects. However, the question is whether variability is causal or a marker. Evidence shows that the quality of care and the attainment of the target impact on the variability of all risk factors. On the other hand, for some of them causality may be considered. Although specific studies are still lacking, it should be useful checking the variability of a risk factor, together with its magnitude out of the normal range, in clinical practice. This can lead to an improvement of the quality of care, which, in turn, could further hesitate in an improvement of risk factors variability.
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and cardiac arrhythmias: a systematic review and meta-analysis
Authors: Li Hang-Long , Lip Gregory Y. H. , Feng Qi , Fei Yue , Tse Yi-Kei , Wu Mei-zhen , Ren Qing-wen , Tse Hung-Fat , Cheung Bernard-M. Y. , Yiu Kai-Hang 
Published: May 2021

Abstract
Background
Cardiac arrhythmias are associated with poorer outcomes in patients with heart failure (HF), diabetes mellitus (DM), and chronic kidney disease (CKD). Previous studies have shown inconsistent conclusions regarding the association between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and the risk of developing arrhythmias. This study aims to investigate the association of SGLT2i treatment with arrhythmia outcomes in clinical trials of patients with HF, DM, or CKD.

Methods
MEDLINE, EMBASE, and ClinicalTrials.gov were searched from inception up to 27 August 2020. Randomized controlled trials that randomized patients with DM, CKD, or HF to SGLT2i or placebo were included. The outcomes of interest include atrial fibrillation (AF), embolic stroke, atrial flutter (AFL), AF/AFL, ventricular tachycardia (VT), and cardiac arrest. Relative risks (RRs) and 95% confidence intervals (CI) were pooled using a random-effects model.

Results
Out of 4,532 citations, 22 trials with altogether 52,115 patients were included (mean age 63.2 years; 33,747 [64.8%] of participants were men). SGLT2i were associated with a lower risk of AF (RR 0.82, 95% CI 0.70–0.96), embolic stroke (RR 0.32, 95% CI 0.12–0.85), AF/AFL (RR 0.82, 95% CI 0.71–0.95), and VT (RR 0.73, 95% CI 0.53–0.99), while the risk reductions in AFL (RR 0.83, 95% CI 0.58–1.17) and cardiac arrest (RR 0.83, 95% CI 0.61–1.14) did not reach statistical significance. The associations appeared to be consistent across different baseline conditions (DM vs CKD vs HF; atherosclerotic cardiovascular disease [ASCVD] vs no ASCVD) and the SGLT2i used.

Conclusions
SGLT2i reduced the risk of cardiac arrhythmias. Our study provides further evidence for recommending the use of SGLT2i in patients with DM, CKD, and HF. Further research is needed to fully elucidate the mechanism by which SGLT2i protect against arrhythmias.
Identification and validation of a hypoxia-related prognostic and immune microenvironment signature in bladder cancer
Authors: Sun Xianchao , Zhou Zhen , Zhang Ying , Wang Jinyou , Zhao Xiaofeng , Jin Liang , Zhai Tingshuai , Liu Xiang , Zhang Jiaxin , Mei Wangli , Zhang Bihui , Luo Ming , Yao Xudong , Ye Lin 
Published: May 2021

Abstract
Background
Bladder cancer is the leading causes of cancer-associated mortality and seriously affects population health. Hypoxia plays a key role in tumor development and immune escape, which contributes to malignant behaviors.

Methods
In this study, we analyzed the RNA-seq and clinical information of bladder cancer patients from The Cancer Genome Atlas (TCGA) database. To investigate the hypoxia-related prognostic and immune microenvironment in bladder cancer, we constructed a hypoxia-related risk model for overall survival (OS). The RNA-seq and clinical data of bladder cancer patients from the Gene Expression Omnibus (GEO) database were used as validation sets.

Results
The hypoxia-related risk signature was significantly correlated with clinical outcomes and could independently predict OS outcomes. Furthermore, the hypoxia-related risk signature could effectively reflected the levels of immune cell type fractions and the expression of critical immune checkpoint genes were higher in the high-risk group compared to the low-risk group. We also validated the expression levels of the prognostic genes in bladder cancer and paracancerous tissue samples through qRT-PCR analysis.

Conclusion
We established a 7 hypoxia-related gene (HRG) signature that can be used as an independent clinical predictor and provided a potential mechanism in bladder cancer immunotherapy.
Spatio-temporal associations of air pollutant concentrations, GP respiratory consultations and respiratory inhaler prescriptions: a 5-year study of primary care in the borough of Lambeth, South London
Authors:   on behalf of the STEAM project research group, Ashworth Mark , Analitis Antonis , Whitney David , Samoli Evangelia , Zafeiratou Sofia , Atkinson Richard , Dimakopoulou Konstantina , Beavers Sean , Schwartz Joel , Katsouyanni Klea 
Published: May 2021

Abstract
Background
Although the associations of outdoor air pollution exposure with mortality and hospital admissions are well established, few previous studies have reported on primary care clinical and prescribing data. We assessed the associations of short and long-term pollutant exposures with General Practitioner respiratory consultations and inhaler prescriptions.

Methods
Daily primary care data, for 2009–2013, were obtained from Lambeth DataNet (LDN), an anonymised dataset containing coded data from all patients (1.2 million) registered at general practices in Lambeth, an inner-city south London borough. Counts of respiratory consultations and inhaler prescriptions by day and Lower Super Output Area (LSOA) of residence were constructed. We developed models for predicting daily PM2.5, PM10, NO2 and O3 per LSOA. We used spatio-temporal mixed effects zero inflated negative binomial models to investigate the simultaneous short- and long-term effects of exposure to pollutants on the number of events.

Results
The mean concentrations of NO2, PM10, PM2.5 and O3 over the study period were 50.7, 21.2, 15.6, and 49.9 μg/m3 respectively, with all pollutants except NO2 having much larger temporal rather than spatial variability. Following short-term exposure increases to PM10, NO2 and PM2.5 the number of consultations and inhaler prescriptions were found to increase, especially for PM10 exposure in children which was associated with increases in daily respiratory consultations of 3.4% and inhaler prescriptions of 0.8%, per PM10 interquartile range (IQR) increase. Associations further increased after adjustment for weekly average exposures, rising to 6.1 and 1.2%, respectively, for weekly average PM10 exposure. In contrast, a short-term increase in O3 exposure was associated with decreased number of respiratory consultations. No association was found between long-term exposures to PM10, PM2.5 and NO2 and number of respiratory consultations. Long-term exposure to NO2 was associated with an increase (8%) in preventer inhaler prescriptions only.

Conclusions
We found increases in the daily number of GP respiratory consultations and inhaler prescriptions following short-term increases in exposure to NO2, PM10 and PM2.5. These associations are more pronounced in children and persist for at least a week. The association with long term exposure to NO2 and preventer inhaler prescriptions indicates likely increased chronic respiratory morbidity.
A new pathological classification of intrahepatic cholangiocarcinoma according to protein expression of SSTR2 and Bcl2
Authors: Yamashita Shoko , Morine Yuji , Imura Satoru , Ikemoto Tetsuya , Saito Yu , Takasu Chie , Yamada Shinichiro , Tokuda Kazunori , Okikawa Shohei , Miyazaki Katsuki , Oya Takeshi , Tsuneyama Koichi , Shimada Mitsuo 
Published: May 2021

Abstract
Background
No universal classification method for intrahepatic cholangiocarcinoma (IHCC) has been reported based on the embryological origin of biliary epithelial cells. The aim of this study was to classify IHCC according to protein expression levels of somatostatin receptor 2 (SSTR2) and b-cell leukemia/lymphoma 2 (Bcl2) and to elucidate the clinicopathological features of each group.

Methods
Fifty-two IHCC patients who underwent hepatic resection were enrolled in this study. Protein expression levels of SSTR2 and Bcl2 were examined using immunohistochemistry. Clinicopathological factors were compared between the three groups and prognostic factors were investigated.

Results
The patients were divided into three groups: SSTR2 positive and Bcl2 negative (p-Group H, n = 21), SSTR2 negative and Bcl2 positive (p-Group P, n = 14), and the indeterminate group (p-Group U, n = 17) for cases where SSTR2 and Bcl2 were both positive or both negative. All p-Group P cases displayed curability A or B. The 5-year survival rates of p-Group H and U patients were worse than those in p-Group P. p-Group H had higher T-factor, clinical stage, and incidence of periductal infiltration than p-Group P.

Conclusions
This method could be used to classify IHCC into peripheral and perihilar type by embryological expression patterns of SSTR2 and Bcl2.