bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rethinking informed consent in the time of COVID-19: An exploratory survey
Authors: De Sutter Evelien , Lalova-Spinks Teodora , Borry Pascal , Valcke Peggy , Kindt Els , Negrouk Anastassia , Verhenneman Griet , Derèze Jean-Jacques , Storme Ruth , Huys Isabelle 
Published: September 2022

BackgroundOwing to the infectious nature of COVID-19, alternative solutions, such as electronic informed consent (eIC), needed to be implemented to inform research participants about study-related information and to obtain their consent. This study aimed to investigate stakeholders’ experiences with alternative consenting methods as well as their views on any regulatory or legal guidelines for eIC implementation in clinical research. Results may serve as the cornerstone to rethink the informed consent process in clinical research.Materials and methodsThis study consisted of an online survey among three stakeholder groups across European Union (EU) Member States and the United Kingdom. The stakeholder groups included (i) investigators, (ii) data protection officers (DPOs) or legal experts working in the pharmaceutical industry, academia, and academic biobanks, and (iii) ethics committee (EC) members. Data collection occurred between April and December 2021. The data collected were analyzed using descriptive and inferential statistics.ResultsThe online survey was completed by 191 respondents, of whom 52% were investigators. Respondents were active in 24 out of the 27 EU Member States and the United Kingdom. The majority of each stakeholder group considered validated electronic methods moderately or extremely useful to re-consent previously enrolled research participants upon study amendments or to obtain consent from COVID-19 patients. Nevertheless, this exploratory survey identified that only 13% of DPOs/legal experts, 26% of investigators, and 41% of EC members had experience with eIC. In addition, results suggest that the legal acceptance of eIC across EU Member States and the United Kingdom is variable and that a definition of eIC, issued by national law or policy, is rarely available. The results also showed that the COVID-19 pandemic brought additional challenges to inform participants and to obtain their consent; for example, related to travel restrictions.ConclusionA number of alternative consenting methods were recommended, for example by the European Medicines Agency, to ensure clinical study continuation during the COVID-19 pandemic. Although stakeholders support the use of eIC in clinical research, it seems that the experience with eIC is low. To harmonize eIC practices as much as possible, further investments in multi-stakeholder, multi-national guidance are needed.
Are preoperative phase-contrast CSF flow parameters ideal for predicting the outcome of shunt surgery in patients with idiopathic normal pressure hydrocephalus?
Authors: He Wen-Jie , Zhang Xie-jun , Xu Qi-Zhong , Bai Run-tao , Chen Jia-kuan , Zhou Xi , Xia Jun 
Published: September 2022

PurposePhase-contrast magnetic resonance (PC-MR) is widely used in patients with idiopathic normal pressure hydrocephalus (iNPH), but its role in predicting prognosis remains controversial. To evaluate the effectiveness of preoperative PC-MR CSF flow measurement in predicting the clinical response to shunt surgery in patients with iNPH.MethodsForty-six patients with definite iNPH were included between January 2018 and January 2022. PC-MR was used to evaluate CSF peak velocity (PV), average velocity, aqueductal stroke volume (ASV), net ASV, and net flow. The modified Rankin Scale (mRS), iNPH grading scale (iNPHGS), Mini-Mental State Examination (MMSE), and Timed 3-m Up and Go Test (TUG) were used for clinical assessment. The primary endpoint was the improvement in the mRS score 1 year after surgery, and the secondary endpoints were the iNPHGS, MMSE, and TUG scores at 1 year. Differences between shunt improvement and non-improvement groups, based on the clinical outcomes, were compared using the Mann-Whitney U-test, logistic regression models, and receiver operating characteristic curves. Correlations between CSF flow parameters and the baseline clinical outcomes were assessed using Spearman's correlation coefficient.ResultsNo CSF parameters significantly differed between shunt improvement and non-improvement groups based on mRS and secondary outcomes. And all CSF parameters showed significant overlap in both shunt improvement and non-improvement groups based on mRS and secondary outcomes. Significant correlations between the mRS and iNPHGS scores, and PV, ASV, and net ASV were observed.ConclusionWhile some preoperative PC-MR CSF flow parameters reflected the symptom severity of iNPH to a certain extent, they alone might not be ideal markers of shunt responsiveness.
A rise in saliva and urine pH in children with SCN1A-related epilepsy: An exploratory prospective controlled study
Authors: Lu Qian , Wang Yang-Yang , Chen Hui-Min , Wang Qiu-Hong , Yang Xiao-Yan , Zou Li-Ping 
Published: September 2022

ObjectiveSCN1A, encoding the alpha 1 subunit of the sodium channel, is associated with a range of related epilepsy. This study aims to assess saliva and urine pH in children with SCN1A-related epilepsy.MethodsA prospective controlled observational study with a 1:1 ratio was conducted on seven patients with SCN1A-related epilepsy and seven healthy children of the same family, gender, and age but without a history of seizures. The pH of saliva and urine was measured by pH test paper. Parents of patients with epilepsy recorded seizures to compare the relationship between pH and seizures.ResultsThe fourteen participants were all males, aged 1 to 14 years. Seven patients had different pathogenic SCN1A variants. The pH of saliva and urine was monitored for 21–95 days. The pH of saliva and urine was higher in patients with SCN1A-related epilepsy than in the healthy group. The urine pH in Dravet syndrome patients was high compared with other epilepsy patients. The urine pH in patients with seizures was higher than that in patients without seizures, which occurred during the study.ConclusionsThe pH of saliva and urine was chronically high in patients with SCN1A-related epilepsy, and urine pH was higher in patients with seizures and with Dravet syndrome.
Natural history of carotid artery free-floating thrombus—A single center, consecutive cohort analysis
Authors: Müller Mandy D. , Raptis Nikolaos , Mordasini Pasquale , Z'Graggen Werner , Raabe Andreas , Schucht Philippe , Heldner Mirjam R. , Bervini David 
Published: September 2022

IntroductionCarotid free-floating thrombus (CFFT) is a rare cause of stroke and is thought to be associated with a high risk of recurrent cerebrovascular ischaemic events. The existing data on the natural history and optimal treatment modalities of CFFT is scanty and no clear recommendations exist.ObjectiveA retrospective analysis, single-center cohort of consecutive patients diagnosed with CFFT was conducted, investigating the risk for recurrent cerebrovascular ischaemic events.MethodsWe performed a single-center retrospective analysis including all patients presenting at our tertiary center between January 2005 and December 2020 with symptoms consistent with ischaemic stroke and/or transient ischaemic attack. Digital subtraction angiography (DSA), computed tomography angiography (CTA) or magnetic resonance angiography (MRA) were used to diagnose CFFT. In all included patients, CFFT was confirmed with a second imaging modality. CFFT was defined on imaging as a defect in contrast filling extending into the carotid lumen. We gathered information on vascular risk factors, diagnosis and follow-up methods, modality of treatment and neurological outcome. A survival analysis was performed, assessing the risk for recurrent cerebrovascular events.ResultsIn total, N = 62 patients presenting with symptomatic CFFT were included. Mean age was 68 years, 69% (43/62) of patients were male, 52% (32/62) current or previous smokers, 76% (47/62) suffered from arterial hypertension, 68% (42/62) from dyslipidaemia, and 31% (19/62) from diabetes mellitus. Overall, 71% (44/62) of patients received any kind of intervention [endovascular or surgical carotid thrombo-endartectomy (CEA)] at any time point during follow-up. Sixteen percent of patients (10/62) received intervention within 48 h after diagnosis of CFFT. The survival analysis and Kaplan-Meier model censoring patients at the time of intervention or last follow-up showed that the risk for any recurrent ischaemic stroke was 19.7% within the first 7 days and 27.4% within 3 months after diagnosis. No patients experienced a new ischaemic stroke beyond 11 days after diagnosis of CFTT (n = 17).ConclusionThe risk of recurrent ischaemic events in patients with CFFT is high, especially in the first week after diagnosis. Prospective studies are needed to further investigate the optimal management of these patients.
Psychiatric symptoms in adult patients with cerebral palsy: A cohort study
Authors: Pizzighello Silvia , Uliana Marianna , Michielotto Martina , Pellegri Alda , Vascello Matteo G. F. , Piccoli Sara , Martinuzzi Michela , Martinuzzi Andrea 
Published: September 2022

BackgroundPatients with cerebral palsy (CP) have an increased risk of developing mental health disorders.AimsThis paper is aimed to investigate the occurrence of psychiatric symptoms in adults with CP and to explore the relation between clinical and psychosocial variables.Methods and proceduresWe included 199 adults with a diagnosis of CP. The chi-square and the Mann-Whitney U tests were used to compare clinical and psychosocial variables, the level of perceived disability, and the type of observed parental style in patients with and without psychiatric symptoms. Logistic regression analysis was used to identify variables that could predict the occurrence of mental health disorders.Outcome and resultsAnxiety and psychosis were the most represented disorders. Age, living status, assumption of drugs, motor, manual, and global impairment were significantly different between patients with and without psychiatric symptoms. Similarly, a different parental style was observed between the two groups. Logistic regression indicated that living status, prescribed drugs, parental style, and the perceived disability in getting along with others predicted the occurrence of psychiatric symptoms.Conclusions and implicationsResults suggest that patients with and without psychiatric symptoms have different clinical and psychosocial characteristics. Some variables should be considered as potentially affecting the mental health of patients with CP.
Association between vitamin D3 levels and frailty in the elderly: A large sample cross-sectional study
Authors: Zheng Zitian , Xu Wennan , Wang Fei , Qiu Yudian , Xue Qingyun 
Published: September 2022

BackgroundFrailty is recognized as a cornerstone of geriatric medicine. Accurately screening and identifying frailty can promote better quality and personalized medical services for the elderly. Previous studies have shown that the association between vitamin D and frailty in the elderly population is still controversial. More research is needed to explore the association between them.Materials and methodsWe used three waves of data from the National Health and Nutrition Examination Survey (NHANES). Based on the widely accepted AAH FRAIL Scale, we measured and evaluated the participants’ frailty from five aspects: fatigue, resistance, ambulation, illness, and loss of weight. All possible relevant variables are included. Machine learning XGboost algorithm, the Least Absolute Shrinkage Selection Operator (LASSO) regression and univariate logistic regression were used to screen variables, and multivariate logistic regression and generalized additive model (GAM) were used to build the model. Finally, subgroup analysis and interaction test were performed to further confirm the association.ResultsIn our study, XGboost machine learning algorithm explored the relative importance of all included variables, which confirmed the close association between vitamin D and frailty. After adjusting for all significant covariates, the result indicated that for each additional unit of 25-hydroxyvitamin D3, the risk of frailty was reduced by 1.3% with a statisticaldifference. A smooth curve was constructed based on the GAM. It was found that there was a significant negative correlation between 25-hydroxyvitamin D3 and the risk of frailty.ConclusionThere may be a negative correlation between 25-hydroxyvitamin D3 and the risk of frailty. However, more well-designed studies are needed to verify this relationship.
PTEN loss promotes Warburg effect and prostate cancer cell growth by inducing FBP1 degradation
Authors: Song Changze , Zhang Jianong , Liu Xiao , Li Meilu , Wang Dejie , Kang Zhijian , Yu Jiaao , Chen Jiuwei , Pan Hongxin , Wang Honglei , Li Guangbin , Huang Haojie 
Published: September 2022

RationaleFructose-1,6-bisphosphatase (FBP1) is a tumor suppressor and a key enzyme negatively regulating Warburg effect in cancer. However, regulation of FBP1 protein expression and its exact role in prostate cancer (PCa) is largely unclear. Phosphatase and tensin homolog (PTEN) is one of the most frequently deleted tumor suppressor genes in human PCa. However, the role of PTEN loss in aberrant Warburg effect in cancer remains poorly understood.MethodsExpression of PTEN and FBP1 was analyzed in several PCa cell lines and prostate tumor tissues in mice. Western blot (WB) and RT-PCR approaches were used to examine how PTEN regulates FBP1 expression. Co-immunoprecipitation (co-IP) and in vivo ubiquitination assays were used to define the regulatory mechanisms. A PCa xenograft model was employed to determine the impact of PTEN regulation of FBP1 on PCa growth in vivo.ResultWe demonstrated that in a manner dependent of PI3K/AKT signal pathway PTEN regulated FBP1 expression in various PCa cell lines and tumors in mice. We confirmed that this regulation took place at the protein level and was mediated by SKP2 E3 ubiquitin ligase. Mechanistically, we showed that serine 271 phosphorylation of FBP1 by cyclin-dependent kinases (CDKs) was essential for SKP2-mediated degradation of FBP1 protein induced by PTEN loss. Most importantly, we further showed that loss of PTEN expression enhanced Warburg effect and PCa growth in mice in a manner dependent, at least partially on FBP1 protein degradation.ConclusionsOur results reveal a novel tumor-suppressive feature of PTEN in restraining FBP1 degradation and the Warburg effect. These results also suggest that prohibiting FBP1 protein degradation could be a viable therapeutic strategy for PTEN-deficient PCa.
Analysis and prediction of relative survival trends in patients with non-Hodgkin lymphoma in the United States using a model-based period analysis method
Authors: Xie Shuping , Yu Zhong , Feng Aozi , Zheng Shuai , Li Yunmei , Zeng You , Lyu Jun 
Published: September 2022

BackgroundSurvival rates are usually used to evaluate the effect of cancer treatment and prevention. This study aims to analyze the 5-year relative survival of non-Hodgkin lymphoma (NHL) in United States using population-based cancer registry data.MethodsA period analysis was used to evaluate the improvement in long-term prognosis of patients with NHL from 2004 to 2018, and a generalized linear model was developed to predict the 5-year relative survival rates of patients during 2019–2023 based on data from the SEER database stratified by age, sex, race and subtype.ResultsIn this study, relative survival improved for all NHL, although the extent of improvement varied by sex, age group and lymphoma subtype. Survival improvement was also noted for NHL subtypes, although the extent varied, with marginal-zone lymphoma having the highest 5-year relative survival rate (92.5%) followed by follicular lymphoma (91.6%) and chronic lymphocytic leukemia/small lymphocytic lymphoma (87.3%). Across all subtypes, survival rates were slightly higher in females than in males. Survival rates are lower in the elderly than in the young. Furthermore, the study demonstrated that black patients had lower NHL survival rates than white patients. Survival rates for NHL were higher in rural areas than in urban areas. Patients with extra-nodal NHL had a higher survival rate than patients with nodal NHL.ConclusionOverall, patient survival rates for NHL gradually improved during 2004–2018. The trend continues with a survival rate of 75.2% for the period 2019–2023. Analysis by NHL subtype and subgroups indicating that etiology and risk factors may differ by subtype. Identification of population-specific prevention strategies and treatments for each subtype can be aided by understanding these variations.
bub1 as a potential oncogene and a prognostic biomarker for neuroblastoma
Authors: Song Jingjing , Ni Chao , Dong Xubin , Sheng Chenang , Qu Yue , Zhu Libin 
Published: September 2022

BackgroundNeuroblastoma is the most common malignant extracranial tumor for children. Molecular mechanisms underpinning the pathogenesis of this disease are yet to be fully clarified. This study aimed to identify a novel oncogene that could be used as a biomarker informing the prognosis of neuroblastoma, and to predict its biological functions, using bioinformatics and molecular biology tools.MethodsThree data sets from the TARGET, GSE62564, and GSE85047 databases were used for analysis. Survivals of patients with high or low expression of bub1 were compared, using the Kaplan-Meier curve and log-rank test. Immune infiltration was evaluated using ESTIMATE and MCP-counter algorithms. Synthetic small interfering RNAs (siRNAs) were employed to silence bub1 expression in neuroblastoma cell lines SH-SY5Y and SK-N-SH, in order to characterize its biological functions. Gene enrichment analyses of bub1 were carried out, using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.ResultsExpression of bub1 was found to significantly affect overall survival and event-free survival of patients with neuroblastoma, positively correlate with the expressions of tpx2 and the ASPM gene, and negatively correlate with host immune infiltration. Expression of bub1 was elevated in patients with neuroblastoma. Silencing bub1 expression using siRNAs in SH-SY5Y and SK-N-SH resulted in decreased cell growth (p &lt; 0.05), reduced migration (p &lt; 0.05), and increased apoptosis (p &lt; 0.05). Function analysis of bub1 revealed cancer-promoting effects, probably via regulating several important downstream molecules, including that related to the apoptosis process and epithelial-mesenchymal transition.ConclusionWe identified a potential tumor-promoting gene bub1 for neuroblastoma that could also serve as a prognostic biomarker.
Accurate classification of pain experiences using wearable electroencephalography in adolescents with and without chronic musculoskeletal pain
Authors: Teel Elizabeth F. , Ocay Don Daniel , Blain-Moraes Stefanie , Ferland Catherine E. 
Published: September 2022

ObjectiveWe assessed the potential of using EEG to detect cold thermal pain in adolescents with and without chronic musculoskeletal pain.MethodsThirty-nine healthy controls (15.2 ± 2.1 years, 18 females) and 121 chronic pain participants (15.0 ± 2.0 years, 100 females, 85 experiencing pain ≥12-months) had 19-channel EEG recorded at rest and throughout a cold-pressor task (CPT). Permutation entropy, directed phase lag index, peak frequency, and binary graph theory features were calculated across 10-second EEG epochs (Healthy: 292 baseline / 273 CPT epochs; Pain: 1039 baseline / 755 CPT epochs). Support vector machine (SVM) and logistic regression models were trained to classify between baseline and CPT conditions separately for control and pain participants.ResultsSVM models significantly distinguished between baseline and CPT conditions in chronic pain (75.2% accuracy, 95% CI: 71.4%–77.1%; p &lt; 0.0001) and control (74.8% accuracy, 95% CI: 66.3%–77.6%; p &lt; 0.0001) participants. Logistic regression models performed similar to the SVM (Pain: 75.8% accuracy, 95% CI: 69.5%–76.6%, p &lt; 0.0001; Controls: 72.0% accuracy, 95% CI: 64.5%–78.5%, p &lt; 0.0001). Permutation entropy features in the theta frequency band were the largest contributor to model accuracy for both groups.ConclusionsOur results demonstrate that subjective pain experiences can accurately be detected from electrophysiological data, and represent the first step towards the development of a point-of-care system to detect pain in the absence of self-report.
Analysing breast cancer survivors’ acceptance profiles for using an electronic pillbox connected to a smartphone application using Seintinelles, a French community-based research tool
Authors: Goetzinger Catherine , Alleaume Caroline , Schritz Anna , Vrijens Bernard , Préau Marie , Fagherazzi Guy , Huiart Laetitia 
Published: September 2022

Introduction: Up to 50% of breast cancer (BC) survivors discontinue their adjuvant endocrine therapy (AET) before the recommended 5 years, raising the issue of medication non-adherence. eHealth technologies have the potential to support patients to enhance their medication adherence and may offer an effective way to complement the healthcare. In order for eHealth technologies to be successfully implemented into the healthcare system, end-users need to be willing and accepting to use these eHealth technologies.Aim: This study aims to evaluate the current usability of eHealth technologiesin and to identify differences in BC SURVIVORS BC survivors accepting a medication adherence enhancing eHealth technology to support their AET to BC survivors that do not accept such a medication adherence enhancing eHealth technology.Methods: This study was conducted in 2020 including volunteering BC survivors belonging to the Seintinelles Association. Eligible participants were women, diagnosed with BC within the last 10 years, and been exposed to, an AET. Univariable and multivariable logistic regression analyses were performed to investigate medication adherence enhancing eHealth technology acceptance profiles among BC survivors. The dependent variable was defined as acceptance of an electronic pillbox connected to a smartphone application (hereafter: medication adherence enhancing eHealth technology).Results: Overall, 23% of the participants already use a connected device or health application on a regular basis. The mean age of the participants was 52.7 (SD 10.4) years. In total, 67% of 1268 BC survivors who participated in the survey declared that they would accept a medication adherence enhancing eHealth technology to improve their AET. BC survivors accepting a medication adherence enhancing eHealth technology for their AET, are younger (OR = 0.97, 95% CI [0.95; 0.98]), do take medication for other diseases (OR = 0.31, 95% CI [0.13; 0.68]), already use a medication adherence enhancing eHealth technology or technique (OR = 1.74, 95% CI [1.06; 2.94]) and are willing to possess or currently possess one or more connected devices or health applications (OR = 2.89, 95% CI [2.01; 4.19]).Conclusion: Understanding acceptance profiles of BC survivors is fundamental for conceiving an effective eHealth technology enhancing AET among BC survivors. Hence, such profiling will foster the development of personalized medication adherence enhancing eHealth technology.