bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness and cost-effectiveness analysis of nimotuzumab for the radiotherapy of locoregionally advanced nasopharyngeal carcinoma
Authors: Fei Zhaodong , Xu Ting , Li Mengying , Chen Taojun , Li Li , Qiu Xiufang , Chen Chuanben 
Published: October 2020

Abstract
Background
This study aimed to assess the effectiveness and cost-effectiveness of nimotuzumab in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC).

Methods
LA-NPC patients treated between October 2013 and December 2016 were retrospectively reviewed. A well-balanced cohort of patients who received nimotuzumab in addition to standard treatment (n = 50) and patients who did not receive nimotuzumab (n = 100) was selected using propensity score-matching method (1:2 ratio) for the cost-effectiveness analysis.

Results
Compared with concurrent chemoradiotherapy (CCRT) alone, addition of nimotuzumab to CCRT significantly improved the 3-year overall survival (OS) (98.00% vs. 91.00%, P = 0.032). On multivariate analysis, nimotuzumab (hazard ratio = 0.124, 95% confidence interval: 0.017–0.902, P = 0.039) showed prognostic significance for OS. No serious treatment-related adverse events were observed in the nimotuzumab group (P > 0.05). Cost-effectiveness analysis revealed that addition of nimotuzumab increased the average treatment costs by $14,364.63. The additional cost for every one percent increase in OS rate was $ 2,052.09.

Conclusion
Addition of nimotuzumab to CCRT for LA-NPC confers significant survival benefits; however, it is not cost-effective.
Impact of cervical sagittal parameters on axial neck pain in patients with cervical kyphosis
Authors: Li Jia , Zhang Di , Shen Yong 
Published: October 2020

Abstract
Background
Cervical sagittal alignment (CSA) is closely related with cervical disk degeneration and impacts the spinal function, especially in the setting of cervical kyphosis (CK). In this study, we evaluated the influence of cervical sagittal parameters on the development of axial neck pain (ANP) in patients with CK.

Methods
Data pertaining to 263 patients with CK who visited the outpatient department of our hospital between January 2012 and December 2018 were retrospective analyzed. The most common symptoms of ANP were neck pain, stiffness, or dullness. Visual analog scale (VAS) was used to evaluate ANP. The following radiographic parameters were evaluated: CK types, C2-7 sagittal vertical axis (SVA), thoracic inlet angle (TIA), T1 slope, neck tilt (NT), cranial tilt, and cervical tilt. Sagittal alignment of CK was classified into 2 types: global and regional type. Multivariate logistic regression analysis was performed to identify risk factors for ANP.

Results
Patients who complained of ANP were categorized as ANP group (VAS score ≥ 3; n = 92), while those without ANP were categorized as non-ANP group (VAS score < 3; n = 171). There was no significant between-group difference with respect to age (P = 0.196), gender (P = 0.516), TIA (P = 0.139), NT (P = 0.676), CK type (P = 0.533), cranial tilt (P = 0.332), cervical tilt (P = 0.585), or cervical disk degeneration (P = 0.695). The T1 slope and C2-7 SVA in the ANP group were significantly greater than that in the non-ANP group (P < 0.05). On multivariate logistic regression, C2-7 SVA [
odds ratio (OR) 2.318, 95% confidence interval 1.373–4.651, P = 0.003) and T1 slope (OR 2.563, 95% CI 1.186–4.669, P = 0.028) were identified as risk factors for ANP.

Conclusions
Our findings suggest a significant effect of cervical sagittal parameters on the occurrence of ANP in patients with CK. Greater T1 slope and larger C2-7 SVA may lead to the development of neck pain.
Challenging behavior in mucopolysaccharidoses types I–III and day-to-day coping strategies: a cross sectional explorative study
Authors: Hoffmann Frederik , Hoffmann Susanne , Kunzmann Kevin , Ries Markus 
Published: October 2020

Abstract
Background
Challenging behavior represents a core symptom in neuropathological mucopolysaccharidoses (MPS) and puts major strain on affected families. Although multimodal approaches including behavioral strategies to treatment could be valuable, there is lack of research to the effectiveness of specific measures. This explorative, cross-sectional study is aimed at the collection of parental experiences regarding effective day-to-day measures against challenging behavior in MPS and focuses on 4 major research questions: First: What is challenging behavior in MPS? Second: Which strategies are helpful in the day-to-day coping with challenging behavior? Third: How strong is parental acceptance of illness and the disorder’s impact on family relationships? Fourth: What are beneficial personal and interfamilial strategies for generally coping with the disorder?

Methods
A semi structured questionnaire was designed de novo in cooperation with affected families. 37/268 questionnaires were returned (rate: 13.8%), of which 34 (MPS I: n = 8, MPS II: n = 8; MPS III: n = 18) could be included in data analysis in accordance with inclusion criteria. Assessment of challenging symptoms was based on perceived frequency, parent- and child stress. Exploration of possible coping strategies for challenging behavior and general illness-related strain included the evaluation of perceived effectiveness. Questionnaires were completed by patient’s relatives and analyzed for strategies to cope with challenging behavior and the disorder’s impact. STROBE criteria were respected.

Results
MPS I was reported to show lower frequency and better perceived manageability of challenging behavior than MPS II and -III. Sleep disturbance, hyperactivity, agitation, aggression and orality seemed relevant symptoms regarding frequency and/or parent stress. Reported measures were manifold, worthwhile approaches against challenging behavior appeared to be aiming at distraction, relief and environmental changes. Medication and non-medication approaches were rated similarly effective. Social exchange, private space and networking with other affected families seemed highly important for personal and interfamilial well-being.

Conclusions
Multimodal mentoring for affected families could be based on the following equivalent pillars: (1) Medication therapy for challenging behavior including evaluation of cost and benefit (2) Guided implementation and re-evaluation of specific behavioral measures against challenging behavior. (3) Psychosocial support of MPS-families, including options for strengthening parental well-being and family functioning.
Trial registration This study was registered at clinicaltrials.gov prior to study start (NCT-Number: NCT03161171, Date: 2017/05/19).
The role of TRPV1 ion channels in the suppression of gastric cancer development
Authors: Gao Nannan , Yang Feng , Chen Siyuan , Wan Hanxing , Zhao Xiaoyan , Dong Hui 
Published: October 2020

Abstract
Background
Although the aberrant expression and function of most Ca2+-permeable channels are known to promote gastrointestinal tumors, the association between transient receptor potential vanilloid receptor 1 (TRPV1) channels and gastric cancer (GC) has not yet been explored. Herein, we sought to determine the role of TRPV1 channels in the development of GC and to elucidate the underlying molecular mechanisms involved therein.

Methods
Immunohistochemistry, qPCR, Western blot, immunofluorescence assays were used to detect the mRNA and protein expression of TRPV1 in GC cells and tissues, and the clinical significance of TRPV1 in GC was also studied by clinicopathologic analysis. CCK8, colony formation, flow cytometry assays were used to detect the proliferation and survival of GC cells, while transwell assay was used to detect migration and invasion of GC cells in vitro. Tumor xenograft and peritoneal dissemination assays in nude mice were used to examine the role of TRPV1 in GC development in vivo.

Results
TRPV1 expression was significantly downregulated in human primary GC tissues compared to their adjacent tissues. The decreased expression of TRPV1 proteins in GC tissues was positively correlated with tumor size, histological grade, lymphatic metastasis, clinical stage, and was strongly correlated with poor prognosis of GC patients. Moreover, the expression of TRPV1 was closely correlated with Ki67, VEGFR, and E-cadherin, all of which are the well-known cancer markers for proliferation and metastasis. TRPV1 proteins were predominately expressed on the plasma membrane in several GC cell lines. TRPV1 overexpression blocked cell cycle at G1 phase to inhibit GC cell proliferation and attenuated migration and invasion of GC cells in vitro, but TRPV1 knockdown increased these parameters. TRPV1 significantly reduced gastric tumor size, number and peritoneal dissemination in vivo. Mechanistically, TRPV1 overexpression in GC cells increased [Ca2+]i, activated CaMKKβ and AMPK phosphorylation, and decreased expression of cyclin D1 and MMP2, while TRPV1 knockdown induced the opposite effects.

Conclusions
TRPV1 uniquely suppresses GC development through a novel Ca2+/CaMKKβ/AMPK pathway and its downregulation is correlated with poor survival of human GC patients. Thus, TRPV1 upregulation and its downstream signaling may represent a promising target for GC prevention and therapy.
The MUK eight protocol: a randomised phase II trial of cyclophosphamide and dexamethasone in combination with ixazomib, in relapsed or refractory multiple myeloma (RRMM) patients who have relapsed after treatment with thalidomide, lenalidomide and a proteasome inhibitor
Authors: Hinsley Samantha , Walker Katrina , Sherratt Debbie , Bailey Lucy , Reed Sadie , Flanagan Louise , McKee Sophie , Brudenell Straw Fiona , Dawkins Bryony , Meads David , Auner Holger W. , Kaiser Martin F. , Cook Mark , Brown Sarah , Cook Gordon ,   on behalf of the Myeloma UK Clinical Trials Network
Published: October 2020

Abstract
Background
Multiple myeloma is a plasma cell tumour with approximately 5500 new cases in the UK each year. Ixazomib is a next generation inhibitor of the 20S proteasome and is thought to be an effective treatment for those who have relapsed from bortezomib. The combination of cyclophosphamide and dexamethasone (CD) is a recognised treatment option for patients with relapsed refractory multiple myeloma (RRMM) who have relapsed after treatment with bortezomib and lenalidomide, whilst also often being combined with newer proteasome inhibitors. The most apparent combination for ixazomib is therefore with CD.

Methods
MUK eight is a randomised, controlled, open, parallel group, multi-centre phase II trial that will recruit patients with RRMM who have relapsed after treatment with thalidomide, lenalidomide, and a proteasome inhibitor. The primary objective of the trial is to evaluate whether ixazomib in combination with cyclophosphamide and dexamethasone (ICD) has improved clinical activity compared to CD in terms of progression-free survival (PFS). Secondary objectives include comparing toxicity profiles and the activity and cost-effectiveness of both treatments. Since opening, the trial has been amended to allow all participants who experience disease progression (as per the IMWG criteria) on the CD arm to subsequently switch to receive ICD treatment, once progression has been confirmed with two clinical members of the Trial Management Group (TMG). This ‘switch’ phase of the study is exploratory and will assess second progression-free survival measured from randomisation to second disease progression (PFS2) and progression-free survival from the point of switching to second disease progression (PFS Switch) in participants who switch from CD to ICD treatment.

Discussion
Development of ixazomib offers the opportunity to further investigate the value of proteasome inhibition through oral administration in the treatment of RRMM. Previous studies investigating the safety and efficacy of ICD in patients with RRMM demonstrate a toxicity profile consistent with ixazomib in combination with lenalidomide and dexamethasone, whilst the combination showed possible activity in RRMM patients. Further investigation of the anti-tumour effect of this drug in RRMM patients is therefore warranted, especially since no trials comparing CD with ICD have been completed at present.

Trial registration
ISRCTN number: ISRCTN58227268. Registered on 26 August 2015.
Flywheel squats versus free weight high load squats for improving high velocity movements in football. A randomized controlled trial
Authors: Sagelv Edvard H. , Pedersen Sigurd , Nilsen Lars Petter R. , Casolo Andrea , Welde Boye , Randers Morten B. , Pettersen Svein Arne 
Published: October 2020

Abstract
Background
High load (HL: > 85% of one repetition maximum (1RM)) squats with maximal intended velocity contractions (MIVC) combined with football sessions can be considered a relevant and time-efficient practice for maintaining and improving high velocity movements in football. Flywheel (FW) resistance exercise (RE) have recently emerged with promising results on physical parameters associated with football performance.

Methods
In this randomized controlled trial over 6 weeks, 38 recreationally active male football players randomly performed RE with MIVCs two times per week as either 1) FW squats (n = 13) or 2) barbell free weight (BFW) HL squats (n = 13), where a third group served as controls (n = 12). All three groups conducted 2–3 football sessions and one friendly match a week during the intervention period. Pre- to post changes in 10-m sprint, countermovement jump (CMJ) and 1RM partial squat were assessed with univariate analyses of variance.

Results
The FW and BFW group equally improved their 10-m sprint time (2 and 2%, respectively, within group: both p < 0.001) and jump height (9 and 8%, respectively, within group: both p < 0.001), which was superior to the control group’s change (between groups: both p < 0.001). The BFW group experienced a larger increase (46%) in maximal squat strength than the FW group (17%, between groups: p < 0.001), which both were higher than the control group’s change (both p < 0.001).

Conclusion
Squats carried out with FWs or BFWs where both are performed with MIVCs and combined with football sessions, were equally effective in improving sprint time and jump height in football players. The BFW group experienced a more than two-fold larger increase in maximal partial squat strength than the FW group in maximal partial squat strength. This presents FW RE as an alternative to BFW HL RE for improving high velocity movements in football.

Trial registration
ClinicalTrials.gov Identifier: NCT04113031 (retrospectively registered, date: 02.10.2019).
Association of lysophosphatidic acids with cerebrospinal fluid biomarkers and progression to Alzheimer’s disease
Authors: Ahmad Shahzad , Orellana Adelina , Kohler Isabelle , Frölich Lutz , de Rojas Itziar , Gil Silvia , Boada Mercè , Hernández Isabel , Hausner Lucrezia , Bakker Margot H. M. , Cabrera-Socorro Alfredo , Amin Najaf , Ramírez Alfredo , Ruiz Agustín , Hankemeier Thomas , Van Duijn Cornelia M. 
Published: October 2020

Abstract
Background
Lysophosphatidic acids (LPAs) are bioactive signaling phospholipids that have been implicated in Alzheimer’s disease (AD). It is largely unknown whether LPAs are associated with AD pathology and progression from mild cognitive impairment (MCI) to AD.

Methods
The current study was performed on cerebrospinal fluid (CSF) and plasma samples of 182 MCI patients from two independent cohorts. We profiled LPA-derived metabolites using liquid chromatography-mass spectrometry. We evaluated the association of LPAs with CSF biomarkers of AD, Aβ-42, p-tau, and total tau levels overall and stratified by APOE genotype and with MCI to AD progression.

Results
Five LPAs (C16:0, C16:1, C22:4, C22:6, and isomer-LPA C22:5) showed significant positive association with CSF biomarkers of AD, Aβ-42, p-tau, and total tau, while LPA C14:0 and C20:1 associated only with Aβ-42 and alkyl-LPA C18:1, and LPA C20:1 associated with tau pathology biomarkers. Association of cyclic-LPA C16:0 and two LPAs (C20:4, C22:4) with Aβ-42 levels was found only in APOE ε4 carriers. Furthermore, LPA C16:0 and C16:1 also showed association with MCI to AD dementia progression, but results did not replicate in an independent cohort.

Conclusions
Our findings provide evidence that LPAs may contribute to early AD pathogenesis. Future studies are needed to determine whether LPAs play a role in upstream of AD pathology or are downstream markers of neurodegeneration.
Depression, stress, anxiety and their predictors in Iranian pregnant women during the outbreak of COVID-19
Authors: Effati-Daryani Fatemeh , Zarei Somayeh , Mohammadi Azam , Hemmati Elnaz , Ghasemi Yngyknd Sakineh , Mirghafourvand Mojgan 
Published: October 2020

Abstract
Background
Pregnancy as a sensitive period of a woman’s life can be affected by various psychological factors that can have adverse effects on the woman, her fetus and future baby. Since COVID-19 is a new phenomenon with limited information available, it may have adverse psychological effects on pregnant women. Therefore, this study was conducted to determine the status of depression, stress, anxiety and their predictors in Iranian pregnant women during the outbreak of COVID-19.

Methods
This descriptive-analytical cross-sectional study was performed on 205 pregnant women covered by Tabriz health centers in Iran. The sampling method used was cluster sampling. The data collection tool was the socio-demographic characteristics questionnaire and the DASS-21 (Depression, Anxiety and Stress Scale-21), which were completed online by pregnant women. The general linear model was used to determine the predictive factors of depression, anxiety and stress.

Results
The mean (SD) score of depression, stress, and anxiety were 3.91 (3.9), 6.22 (4.25), and 3.79 (3.39), respectively; the score range of 0 to 21. Depression, stress, and anxiety symptoms were observed in 32.7, 32.7, and 43.9% of the participants, respectively, with varying degrees from mild to very severe. Based on the adjusted general linear model, variables of education level, spouse’s job and marital life satisfaction were the predictors of depressive symptoms. Variables of spouse’s education level, spouse’s support, marital life satisfaction and the number of pregnancies were the predictive factors of anxiety symptoms and the variables of spouse’s education level, household income sufficiency, spouse’s support and marital life satisfaction were predictors of stress symptoms.

Conclusions
Considering the role of marital life satisfaction, high level of spouse’s education and income in reducing symptoms of stress, anxiety, and depression in pregnant women in critical situations such as the prevalence of COVID-19, it seems that using strategies to promote marital life satisfaction and socio-economic status can play an effective role in controlling anxiety and reducing stress and depression in pregnant women.
Novel insights on targeting ferroptosis in cancer therapy
Authors: Zuo Sipeng , Yu Jie , Pan Hui , Lu Linna 
Published: October 2020

AbstractFerroptosis belongs to a novel form of regulated cell death. It is characterized by iron dependence, destruction of intracellular redox balance and non-apoptosis. And cellular structure and molecules level changes also occur abnormally during ferroptosis. It has been proved that ferroptosis exist widespreadly in many diseases, such as heart disease, brain damage or alzheimer disease. At the same time, the role of ferroptosis in cancer cannot be underestimated. More and more indications have told that ferroptosis is becoming a powerful weapon against cancer. In addition, therapies rely on ferroptosis have been applied to the clinic. Therefore, it is necessary to understand this newly discovered form of cell death and its connection with cancer. This review summarizes the mechanism of ferroptosis, ferroptosis inducers based on different targets and inspection methods. At last, we analyzed the relationship between ferroptosis and malignancies, in order to provide a novel theory basis for cancer treatment.
A novel method of constrained feature selection by the measurement of pairwise constraints uncertainty
Authors: Rostami Mehrdad , Berahmand Kamal , Forouzandeh Saman 
Published: October 2020

AbstractIn the past decades, the rapid growth of computer and database technologies has led to the rapid growth of large-scale datasets. On the other hand, data mining applications with high dimensional datasets that require high speed and accuracy are rapidly increasing. Semi-supervised learning is a class of machine learning in which unlabeled data and labeled data are used simultaneously to improve feature selection. The goal of feature selection over partially labeled data (semi-supervised feature selection) is to choose a subset of available features with the lowest redundancy with each other and the highest relevancy to the target class, which is the same objective as the feature selection over entirely labeled data. This method actually used the classification to reduce ambiguity in the range of values. First, the similarity values of each pair are collected, and then these values are divided into intervals, and the average of each interval is determined. In the next step, for each interval, the number of pairs in this range is counted. Finally, by using the strength and similarity matrices, a new constraint feature selection ranking is proposed. The performance of the presented method was compared to the performance of the state-of-the-art, and well-known semi-supervised feature selection approaches on eight datasets. The results indicate that the proposed approach improves previous related approaches with respect to the accuracy of the constrained score. In particular, the numerical results showed that the presented approach improved the classification accuracy by about 3% and reduced the number of selected features by 1%. Consequently, it can be said that the proposed method has reduced the computational complexity of the machine learning algorithm despite increasing the classification accuracy.
Human dosimetry of free 211At and meta-[211At]astatobenzylguanidine (211At-MABG) estimated using preclinical biodistribution from normal mice
Authors: Ukon Naoyuki , Zhao Songji , Washiyama Kohshin , Oriuchi Noboru , Tan Chengbo , Shimoyama Saki , Aoki Miho , Kubo Hitoshi , Takahashi Kazuhiro , Ito Hiroshi 
Published: October 2020

Abstract
Background
211At is one of the ideal nuclides for targeted radionuclide therapies (TRTs). Meta-[211At]astatobenzylguanidine (211At-MABG) has been proposed for the treatment of pheochromocytoma. To effectively use these radiopharmaceuticals, dosimetry must be performed. It is important to determine the absorbed doses of free 211At and 211At-MABG to determine the organs that may be at risk when using TRTs. The aim of this study was to estimate human dosimetry from preclinical biodistribution of free 211At and 211At-MABG in various organs in normal mice.

Methods
Male C57BL/6 N mice were administered 0.13 MBq of free 211At or 0.20 MBq of 211At-MABG by tail-vein injection. The mice were sacrificed at 5 min, and at 1, 3, 6, and 24 h after the injection (n = 5 for each group). The percentage of injected activity per mass in organs and blood (%IA/g) was determined. The human absorbed doses of free 211At and 211At-MABG were calculated using the Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA/EXM) version 2.0 and IDAC-Dose 2.1.

Results
High uptake of free 211At was observed in the lungs, spleen, salivary glands, stomach, and thyroid. The absorbed doses of free 211At in the thyroid and several tissues were higher than those of 211At-MABG. The absorbed doses of 211At-MABG in the adrenal glands, heart wall, and liver were higher than those of free 211At.

Conclusions
The absorbed doses of 211At-MABG in organs expressing the norepinephrine transporter were higher than those of free 211At. In addition, the biodistribution of free 211At was different from that of 211At-MABG. The absorbed dose of free 211At may help predict the organs potentially at risk during TRTs using 211At-MABG due to deastatination.