bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aging With Multiple Sclerosis: Age-Related Factors and Socioeconomic Risks
Authors: Wandall-Holm Malthe Faurschou , Andersen Mads Albrecht , Buron Mathias Due , Magyari Melinda 
Published: March 2022

BackgroundStudies have demonstrated an increasing mean age of the population with multiple sclerosis (MS). The association between increased age and socioeconomic outcomes has been investigated sparsely.ObjectiveThe purpose of this study is to describe the demographic and socioeconomic status of the current Danish population of patients with MS according to age and to assess the age-related risks of no income or losing all income from earnings or receiving disability pension.MethodsThe nationwide population-based Danish Multiple Sclerosis Registry provided data linked with the Danish Income Statistics Register and the Danish Rational Economic Agents Model (DREAM) database. The prevalence of socioeconomic milestones of the current MS population was compared with healthy controls and the risks of reaching socioeconomic milestones were assessed using cause-specific Cox models and cumulative incidence functions compared to healthy controls.ResultsThe current Danish population of patients with MS of working age (18–65 years of age) consists of 11,287 patients, of which 29.3% was older than 55 years. In 2018, 38.0% of all patients and 18.9% of controls had no income from earnings, whereas 30.5% of all patients and 7.7% of controls received disability pension. The risk of losing all income from earnings was higher for patients with MS with a hazard ratio (HR) peaking at of 4.0 (95% CI, 3.8–4.2) for the ages of 45–54 years. The risk of receiving disability pension was much higher for patients with MS peaking at a HR of 22.6 (95% CI, 20.9–24.4) for the ages of 25–34 years. Likewise, the absolute risks of both outcomes were higher for the patients with MS at all ages.ConclusionDanish patients with MS are at a higher risk of losing all income from earnings and at a much higher risk of receiving disability pension compared with healthy controls.
Do All Roads Lead to Rome? Genes Causing Dravet Syndrome and Dravet Syndrome-Like Phenotypes
Authors: Ding Jiangwei , Wang Lei , Jin Zhe , Qiang Yuanyuan , Li Wenchao , Wang Yangyang , Zhu Changliang , Jiang Shucai , Xiao Lifei , Hao Xiaoyan , Hu Xulei , Li Xinxiao , Wang Feng , Sun Tao 
Published: March 2022

BackgroundDravet syndrome (DS) is a severe epileptic encephalopathy mainly caused by haploinsufficiency of the gene SCN1A, which encodes the voltage-gated sodium channel NaV1. 1 in the brain. While SCN1A mutations are known to be the primary cause of DS, other genes that may cause DS are poorly understood. Several genes with pathogenic mutations result in DS or DS-like phenotypes, which may require different drug treatment approaches. Therefore, it is urgent for clinicians, especially epilepsy specialists to fully understand these genes involved in DS in addition to SCN1A. Particularly for healthcare providers, a deep understanding of these pathogenic genes is useful in properly selecting and adjusting drugs in a more effective and timely manner.ObjectiveThe purpose of this study was to identify genes other than SCN1A that may also cause DS or DS-like phenotypes.MethodsA comprehensive search of relevant Dravet syndrome and severe myoclonic epilepsy in infancy was performed in PubMed, until December 1, 2021. Two independent authors performed the screening for potentially eligible studies. Disagreements were decided by a third, more professional researcher or by all three. The results reported by each study were narratively summarized.ResultsA PubMed search yielded 5,064 items, and other sources search 12 records. A total of 29 studies published between 2009 and 2021 met the inclusion criteria. Regarding the included articles, seven studies on PCDH19, three on SCN2A, two on SCN8A, five on SCN1B, two on GABRA1, three on GABRB3, three on GABRG2, and three on STXBP1 were included. Only one study was recorded for CHD2, CPLX1, HCN1 and KCNA2, respectively. It is worth noting that a few articles reported on more than one epilepsy gene.ConclusionDS is not only identified in variants of SCN1A, but other genes such as PCDH19, SCN2A, SCN8A, SCN1B, GABRA1, GABRB3, GABRG2, KCNA2, CHD2, CPLX1, HCN1A, STXBP1 can also be involved in DS or DS-like phenotypes. As genetic testing becomes more widely available, more genes associated with DS and DS-like phenotypes may be identified and gene-based diagnosis of subtypes of phenotypes in this spectrum may improve the management of these diseases in the future.
Integration of an Independent Monitor Unit Check for High-Magnetic-Field MR-Guided Radiation Therapy System
Authors: Yang Jie , Zhang Pengpeng , Tyagi Neelam , Scripes Paola Godoy , Subashi Ergys , Liang Jiayi , Lovelock Dale , Mechalakos James , Li Anyi , Lim Seng B. 
Published: March 2022

PurposeCommercial independent monitor unit (IMU) check systems for high-magnetic-field MR-guided radiation therapy (RT) systems are lacking. We investigated the feasibility of adopting an existing treatment planning system (TPS) as an IMU check for online adaptive radiotherapy using 1.5-Tesla MR-Linac.MethodsThe 7-MV flattening filter free (FFF) beam and multi-leaf collimator (MLC) models of a 1.5-T Elekta Unity MR-Linac within Monte Carlo-based Monaco TPS were used to generate an optimized beam model in Eclipse TPS. The MLC dosimetric leaf gap of the beam in Eclipse was determined by matching the dose distribution of Eclipse-generated intensity-modulated radiation therapy (IMRT) plans using the Analytical Anisotropic Algorithm (AAA) algorithm to Monaco plans. The plans were automatically adjusted for different source-to-axis distances (SADs) between the two systems. For IMU check, the treatment plans developed in Monaco were transferred to Eclipse to recalculate the dose using AAA. A plug-in within Eclipse was created to perform a 2D gamma analysis of the AAA and Monte Carlo dose distribution on a beam’s eye view parallel plane. Monaco dose distribution was shifted laterally by 2 mm during gamma analysis to account for the impact of magnetic field on electron trajectories. Eclipse doses for posterior beams were corrected for both the Unity couch and the posterior MR coil attenuation. Thirteen patients, each with 4–5 fractions for a variety of tumor sites (pancreas, rectum, and prostate), were tested.ResultsAfter thorough commissioning, the method was implemented as part of the standard clinical workflow. A total of 62 online plans, each with approximately 15 beams, were evaluated. The average per-beam gamma (3%/3 mm) pass rate for plans was 97.9% (range, 95.9% to 98.8%). The average pass rate per beam for all 932 beams used in these plans was 97.9% ± 1.9%, with the lowest per-beam gamma pass rate at 88.4%. The time for the process was within 3.2 ± 0.9 min.ConclusionThe use of a second planning system provides an efficient way to perform IMU checks with clinically acceptable accuracy for online adaptive plans on Unity MR-Linac. This is essential for meeting the safety requirements for second checks as outlined in American Association of Physicists in Medicine Task Group (AAPM TG) reports 114 and 219.
Evaluation of Deep Learning-Based Automated Detection of Primary Spine Tumors on MRI Using the Turing Test
Authors: Ouyang Hanqiang , Meng Fanyu , Liu Jianfang , Song Xinhang , Li Yuan , Yuan Yuan , Wang Chunjie , Lang Ning , Tian Shuai , Yao Meiyi , Liu Xiaoguang , Yuan Huishu , Jiang Shuqiang , Jiang Liang 
Published: March 2022

BackgroundRecently, the Turing test has been used to investigate whether machines have intelligence similar to humans. Our study aimed to assess the ability of an artificial intelligence (AI) system for spine tumor detection using the Turing test.MethodsOur retrospective study data included 12179 images from 321 patients for developing AI detection systems and 6635 images from 187 patients for the Turing test. We utilized a deep learning-based tumor detection system with Faster R-CNN architecture, which generates region proposals by Region Proposal Network in the first stage and corrects the position and the size of the bounding box of the lesion area in the second stage. Each choice question featured four bounding boxes enclosing an identical tumor. Three were detected by the proposed deep learning model, whereas the other was annotated by a doctor; the results were shown to six doctors as respondents. If the respondent did not correctly identify the image annotated by a human, his answer was considered a misclassification. If all misclassification rates were &gt;30%, the respondents were considered unable to distinguish the AI-detected tumor from the human-annotated one, which indicated that the AI system passed the Turing test.ResultsThe average misclassification rates in the Turing test were 51.2% (95% CI: 45.7%–57.5%) in the axial view (maximum of 62%, minimum of 44%) and 44.5% (95% CI: 38.2%–51.8%) in the sagittal view (maximum of 59%, minimum of 36%). The misclassification rates of all six respondents were &gt;30%; therefore, our AI system passed the Turing test.ConclusionOur proposed intelligent spine tumor detection system has a similar detection ability to annotation doctors and may be an efficient tool to assist radiologists or orthopedists in primary spine tumor detection.
Knockdown of AKR1C3 Promoted Sorafenib Sensitivity Through Inhibiting the Phosphorylation of AKT in Hepatocellular Carcinoma
Authors: Zheng Jia , Yang Zhihong , Li Yanlei , Yang Li , Yao Ruili 
Published: March 2022

BackgroundSorafenib, which can induce ferroptosis, is a multikinase inhibitor for enhancing survival in advanced hepatocellular carcinoma (HCC). However, a considerable challenge for the treatment of HCC is sorafenib resistance. Therefore, targeting the relationship between sorafenib resistance and ferroptosis genes may provide a novel approach for the treatment of HCC.Materials and MethodsWe analyzed the gene expression and clinicopathological factors from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) databases (GSE109211/GSE62813). The statistical analysis was conducted in R. Cell proliferation was assayed by MTT, cell colony-forming assay, and wound healing assay. Immunofluorescence assay and Western blot were used to evaluate the expression of AKT.ResultsMany ferroptosis-related genes were upregulated in the sorafenib-resistant group. Aldo-keto reductase 1C3 (AKR1C3) was highly expressed in sorafenib-resistant patients, and the high expression of AKR1C3 was associated with the poor prognosis of patients from the TCGA and ICGC databases. MTT and colony-forming assays showing AKR1C3 overexpression enhanced the proliferation of HCC cells and acute sorafenib resistance. Knockdown of AKR1C3 inhibited the proliferation of HCC cells and increased the drug sensitivity of sorafenib. Immunofluorescence assay and Western blot proved that AKR1C3 promoted the phosphorylation of AKT.ConclusionAKR1C3 can induce sorafenib resistance through promoting the phosphorylation of AKT in HCC. AKR1C3 inhibitors may be used in conjunction with sorafenib to become a better therapeutic target for HCC.
Clinical Evaluation of an Auto-Segmentation Tool for Spine SBRT Treatment
Authors: Chen Yingxuan , Vinogradskiy Yevgeniy , Yu Yan , Shi Wenyin , Liu Haisong 
Published: March 2022

PurposeSpine SBRT target delineation is time-consuming due to the complex bone structure. Recently, Elements SmartBrush Spine (ESS) was developed by Brainlab to automatically generate a clinical target volume (CTV) based on gross tumor volume (GTV). The aim of this project is to evaluate the accuracy and efficiency of ESS auto-segmentation.MethodsTwenty spine SBRT patients with 21 target sites treated at our institution were used for this retrospective comparison study. Planning CT/MRI images and physician-drawn GTVs were inputs for ESS. ESS can automatically segment the vertebra, split the vertebra into 6 sectors, and generate a CTV based on the GTV location, according to the International Spine Radiosurgery Consortium (ISRC) Consensus guidelines. The auto-segmented CTV can be edited by including/excluding sectors of the vertebra, if necessary. The ESS-generated CTV contour was then compared to the clinically used CTV using qualitative and quantitative methods. The CTV contours were compared using visual assessment by the clinicians, relative volume differences (RVD), distance of center of mass (DCM), and three other common contour similarity measurements such as dice similarity coefficient (DICE), Hausdorff distance (HD), and 95% Hausdorff distance (HD95).ResultsQualitatively, the study showed that ESS can segment vertebra more accurately and consistently than humans at normal curvature conditions. The accuracy of CTV delineation can be improved significantly if the auto-segmentation is used as the first step. Conversely, ESS may mistakenly split or join different vertebrae when large curvatures in anatomy exist. In this study, human interactions were needed in 7 of 21 cases to generate the final CTVs by including/excluding sectors of the vertebra. In 90% of cases, the RVD were within ±15%. The RVD, DCM, DICE, HD, and HD95 for the 21 cases were 3% ± 12%, 1.9 ± 1.5 mm, 0.86 ± 0.06, 13.34 ± 7.47 mm, and 4.67 ± 2.21 mm, respectively.ConclusionESS can auto-segment a CTV quickly and accurately and has a good agreement with clinically used CTV. Inter-person variation and contouring time can be reduced with ESS. Physician editing is needed for some occasions. Our study supports the idea of using ESS as the first step for spine SBRT target delineation to improve the contouring consistency as well as to reduce the contouring time.
Efficacy of Intermittent, Oral Famciclovir Prophylaxis for Bortezomib-Induced Herpes Zoster in Multiple Myeloma Patients
Authors: Zheng Gaofeng , Guan Fangshu , Han Xiaoyan , Yang Li , Zhao Yi , Yang Yang , Zhang Enfang , He Jingsong , He Donghua , Wu Wenjun , Huang He , Cai Zhen 
Published: March 2022

ObjectiveTo explore the efficacy and safety of intermittent, oral famciclovir prophylaxis for bortezomib-induced herpes zoster in multiple myeloma patients.MethodWe retrospectively analyzed the incidence of bortezomib treatment-related varicella-zoster virus reactivation in 719 newly-diagnosed multiple myeloma patients receiving intermittent oral famciclovir prophylaxis, continuous oral acyclovir prophylaxis or no prophylaxis. The definition of intermittent oral famciclovir prophylaxis was oral famciclovir at a dose of 250mg twice daily for 9 days after finishing the last dose of bortezomib therapy every cycle. Age, gender, stage per the International Staging System, type of M protein, baseline of absolute lymphocyte count, absolute neutrophil count, and absolute monocyte count were analyzed to find the potential factors that could predispose to herpes zoster infections.ResultsVaricella-zoster virus infection occurred in 96 patients (13.4%) during bortezomib treatment. The incidence of herpes zoster was significantly higher in the non-prophylaxis group compared with the prophylaxis group (22.9% vs 8.2% P&lt;0.001), while the rate was similar between the intermittent oral famciclovir group and the continuous oral acyclovir group (8.4% vs 7.9% P=0.835). Hepatic and renal toxicity were observed in 12% and 2.8% of the patient respectively in the intermittent famciclovir group, which was similar in the continuous acyclovir group (18.1% and 4.2%). The prophylactic use of antiviral agents is a predictive factor for varicella-zoster virus reactivation.ConclusionIntermittent famciclovir prophylaxis is effective and safe in preventing herpes zoster development and can markedly reduce the duration of oral medicine treatment compared with continuous acyclovir prophylaxis.
Performance Comparison of Infection Prediction Scores in a South African Neonatal Unit: A Retrospective Case-Control Study
Authors: Lloyd Lizel Georgi , Dramowski Angela , Bekker Adrie , Malou Nada , Ferreyra Cecilia , Van Weissenbruch Mirjam Maria 
Published: March 2022

Background and objectivesInfection prediction scores are useful ancillary tests in determining the likelihood of neonatal hospital-acquired infection (HAI), particularly in very low birth weight (VLBW; &lt;1,500 g) infants who are most vulnerable to HAI and have high antibiotic utilization rates. None of the existing infection prediction scores were developed for or evaluated in South African VLBW neonates.MethodsWe identified existing infection prediction scores through literature searches and assessed each score for suitability and feasibility of use in resource-limited settings. Performance of suitable scores were compared using a retrospective dataset of VLBW infants (2016–2017) from a tertiary hospital neonatal unit in Cape Town, South Africa. Sensitivity, specificity, predictive values, and likelihood ratios were calculated for each score.ResultsEleven infection prediction scores were identified, but only five were suitable for use in resource-limited settings (NOSEP1, Singh, Rosenberg, and Bekhof scores). The five selected scores were evaluated using data from 841 episodes of HAI in 659 VLBW infants. The sensitivity for the scores ranged between 3% (NOSEP1 ≥14; proven and presumed infection), to a maximum of 74% (Singh score ≥1; proven infection). The specificity of these scores ranged from 31% (Singh score ≥1; proven and presumed infection) to 100% (NOSEP1 ≥11 and ≥14, NOSEP-NEW-1 ≥11; proven and presumed infection).ConclusionExisting infection prediction scores did not achieve comparable predictive performance in South African VLBW infants and should therefore only be used as an adjunct to clinical judgment in antimicrobial decision making. Future studies should develop infection prediction scores that have high diagnostic accuracy and are feasible to implement in resource-limited neonatal units.
Effects of Fuyou Formula on GnRH Secretion and Related Gene Expression in Treating Precocious Puberty
Authors: Zhang Yi , Sun Ning , Zhang Meng , Ding Qian , Wang Qian , Liang Yuguang , He Huan , Yang Yuxin , Guo Chunyan 
Published: March 2022

The Fuyou (Fy) formula is an in-hospital preparation consisting of traditional Chinese medicine (TCM) that has been used for treating precocious puberty (PP) for more than 20 years. In this study, we aimed to clarify the effect of the Fy formula and its major components on PP. To confirm the effect of the Fy formula on the release of hypothalamic gonadotropin-releasing hormone (GnRH), GT1-7 cells were treated with estrogen to build the model group and subsequently treated with the Fy formula and its major components to explore their effects on the secretion of GnRH. The level of GnRH in GT1-7 cells was determined using enzyme-linked immunosorbent assay. The results illustrated that, compared to the model group, the Fy formula inhibited the release of GnRH. In addition, the expression levels of proteins related to GnRH secretion, including GnRH, gonadotropin-releasing hormone receptor (GnRHR), Kiss-1 metastasis-suppressor (Kiss1), G-protein coupled receptor 54 (GPR54), estrogen receptor α (ERα), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-1 receptor (IGF-1R), were detected by real-time polymerase chain reaction (RT-qPCR). The results demonstrated that the Fy formula significantly reduced the level of GnRH secretion in the GT1-7 cell lines compared with the model group. Moreover, it significantly downregulated the expression of GnRH, GnRHR, Kiss1, GPR54, ERα, IGF-1, and IGF-1R. In summary, our results indicate that the Fy formula and its major components may inhibit the effects of estrogen, which alleviates PP through transcriptional regulation of target genes.
A Qualitative Study on Coping Strategies of Chinese Women With Metastatic Breast Cancer Undergoing Chemotherapy
Authors: Guo Yi-Qiang , Ju Qing-Mei , You Miaoning , Yusuf Azlina , Wu Ying , Soon Lean Keng 
Published: March 2022

ObjectivesWomen who underwent chemotherapy (CT) for metastatic breast cancer (MBC) used both adaptive and maladaptive coping strategies but had low implementation levels. The present study explores the qualitative experience of coping strategies for women with MBC undergoing CT in Beijing.MethodsA hermeneutic phenomenological approach was employed on twenty Chinese MBC women undergoing CT. These interviews were transcribed verbatim, coded using thematic analysis, and analyzed using NVivo 11.ResultsThree themes are highlighted: Maintaining hope; Spiritual growth, and Self-perceived support resources.ConclusionThe present study results have led to a greater understanding of the tremendous impact of CT on MBC women’s lives. This research provides insight into the scope of maintaining hope. Spiritual growth and self-perceived support resources were crucial factors to coping strategies among MBC women to improve their quality of life.Clinical RelevanceBy attaining the adaptive coping strategies and further understanding about Chinese MBC women, health care professionals are encouraged to appraise MBC women’s specific problems and adopt effective interventions to improve MBC women’s psychosocial wellbeing.
Age-Related Performance in Using a Fully Immersive and Automated Virtual Reality System to Assess Cognitive Function
Authors: Tan Ngiap Chuan , Lim Jie En , Allen John Carson , Wong Wei Teen , Quah Joanne Hui Min , Muthulakshmi Paulpandi , Teh Tuan Ann , Lim Soon Huat , Malhotra Rahul 
Published: March 2022

IntroductionCognition generally declines gradually over time due to progressive degeneration of the brain, leading to dementia and eventual loss of independent functions. The rate of regression varies among the six cognitive domains (perceptual motor, executive function, complex attention, learning and memory, social cognition and language). Current modality of cognitive assessment using neuropsychological paper-and-pencil screening tools for cognitive impairment such as the Montreal Cognitive Assessment (MoCA) has limitations and is influenced by age. Virtual reality (VR) is considered as a potential alternative tool to assess cognition. A novel, fully immersive automated VR system (Cognitive Assessment using Virtual Reality, CAVIRE) has been developed to assess the six cognitive domains. As cognition is associated with age, VR performance is postulated to vary with age using this system.AimsThis is a feasibility study to evaluate the VR performance of cognitively healthy adults aged between 35 and 74 years old, based on the performance score and completion time using the CAVIRE system.MethodsConducted in a public primary care clinic in Singapore, 25 multi-ethnic Asian adults were recruited in each of the four age groups in years: (1) 35–44; (2) 45–54; (3) 55–64, and (4) 65–74. The eligibility criteria included a MoCA score of 26 or higher to reflect normal cognition and understanding English instructions. They completed common daily activities ranging from brushing teething to shopping, across 13 VR segments. Their performances scores and completion time were automatically computed by the CAVIRE system. These VR performance indices were compared across the four age groups using one-way ANOVA, F-test of the hypothesis, followed by pair-wise comparisons in the event of a significant F-test (p &lt; 0.05).ResultsOne participant dropped out from Group 1. The demographic characteristics of 99 participants were similar across the 4 age groups. Overall, younger participants in Groups 1 and 2 attained higher VR performance scores and shorter completion time, compared to those in Groups 3 and 4, in all six cognitive domains (all p &lt; 0.05).ConclusionThe CAVIRE VR performance scores and completion time significantly differ between the younger and older Asian participants with normal cognition. Enhancements to the system are needed to establish the age-group specific normal performance indices.