bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adding eptinezumab to brief patient education to treat chronic migraine and medication-overuse headache: Protocol for RESOLUTION—A phase 4, multinational, randomized, double-blind, placebo-controlled study
Authors: Jensen Rigmor H. , Schytz Henrik Winther , Tassorelli Cristina , Terwindt Gisela M. , Carlsen Louise N. , Mittoux Aurélia , Østerberg Ole , Lipton Richard B. , Tepper Stewart J. , Blumenfeld Andrew , Lundqvist Christofer 
Published: February 2023

IntroductionMigraine is a highly prevalent and disabling neurological disease. Excessive use of acute medications can lead to medication-overuse headache (MOH), occurring when a patient experiences an increasing number of headache and migraine days, despite taking greater amounts of acute medication. To treat MOH, a preventive migraine treatment and/or withdrawal of the overused medication(s) are advised. Brief Educational Intervention (BEI) has been shown to be an effective tool with promising results for MOH. Here, we report the design of a clinical trial that aims to evaluate the efficacy of eptinezumab, an anti-calcitonin gene-related peptide preventive migraine treatment, as an add-on to BEI for treatment of MOH in those with chronic migraine.Methods and analysisRESOLUTION will be a phase 4, multi-national, randomized, double-blind, placebo-controlled study. This study will enroll approximately 570 participants with dual diagnoses of chronic migraine and MOH. Eligible patients will be randomly allocated to one of two treatment groups, BEI and eptinezumab (100 mg; n = 285) or BEI and placebo (n = 285), in a 1:1 ratio. The primary endpoint is the change from baseline in monthly migraine days over weeks 1–4. Secondary and exploratory endpoints will assess monthly migraine days over weeks 1–12, MOH remission, transition from chronic to episodic migraine, health-related quality of life, work productivity, and the safety and tolerability of eptinezumab in this patient population.Ethics and disseminationThis study will be conducted in accordance with good clinical practice. All patients will be fully informed about the study, including the risks and benefits of participation, and all participants will provide informed consent for participation in the trial and dissemination of results.
Ascertaining the optimal myoelectric signal recording duration for pattern recognition based prostheses control
Authors: Asogbon Mojisola Grace , Samuel Oluwarotimi Williams , Nsugbe Ejay , Li Yongcheng , Kulwa Frank , Mzurikwao Deogratias , Chen Shixiong , Li Guanglin 
Published: February 2023

IntroductionElectromyogram-based pattern recognition (EMG-PR) has been widely considered an essentially intuitive control method for multifunctional upper limb prostheses. A crucial aspect of the scheme is the EMG signal recording duration (SRD) from which requisite motor tasks are characterized per time, impacting the system’s overall performance. For instance, lengthy SRD inevitably introduces fatigue (that alters the muscle contraction patterns of specific limb motions) and may incur high computational costs in building the motion intent decoder, resulting in inadequate prosthetic control and controller delay in practical usage. Conversely, relatively shorter SRD may lead to reduced data collection durations that, among other advantages, allow for more convenient prosthesis recalibration protocols. Therefore, determining the optimal SRD required to characterize limb motion intents adequately that will aid intuitive PR-based control remains an open research question.MethodThis study systematically investigated the impact and generalizability of varying lengths of myoelectric SRD on the characterization of multiple classes of finger gestures. The investigation involved characterizing fifteen classes of finger gestures performed by eight normally limb subjects using various groups of EMG SRD including 1, 5, 10, 15, and 20 s. Two different training strategies including Between SRD and Within-SRD were implemented across three popular machine learning classifiers and three time-domain features to investigate the impact of SRD on EMG-PR motion intent decoder.ResultThe between-SRD strategy results which is a reflection of the practical scenario showed that an SRD greater than 5 s but less than or equal to 10 s (&gt;5 and &lt; = 10 s) would be required to achieve decent average finger gesture decoding accuracy for all feature-classifier combinations. Notably, lengthier SRD would incur more acquisition and implementation time and vice-versa. In inclusion, the study’s findings provide insight and guidance into selecting appropriate SRD that would aid inadequate characterization of multiple classes of limb motion tasks in PR-based control schemes for multifunctional prostheses.
Evolution and clinical significance of HER2-low status after neoadjuvant therapy for breast cancer
Authors: Shang Jiuyan , Sun Xuemei , Xu Zihang , Cai Lijing , Liu Chang , Wu Si , Liu Yueping 
Published: February 2023

BackgroundThe emergence of HER2 antibody-drug conjugates provides new treatment decisions for breast cancer patients, especially those with HER2-low expression. In order to explore the biological characteristics of breast cancer with HER2-low expression, the HER2-low category in primary breast cancer and residual tumor after neoadjuvant therapy was investigated to reflect the evolution of HER2 expression.MethodsHER2 was assessed according to the latest ASCO/CAP guidelines. The cut-off value for staining of HER2-positive cells was &gt;10%. HER2-negative cases were divided into HER2-low (IHC=1+/2+ and no ISH amplification) and HER2-zero (IHC-0), and the clinicopathological characteristics of the cases were collected.ResultsThis study included 1140 patients with invasive breast cancer who received preoperative neoadjuvant therapy from 2018 to 2021, of which 365 patients achieved pCR and 775 were non-pCR. In the non-pCR cohort, HER2-low cases accounted for 59.61% of primary tumors and 55.36% of residual tumors. Among HER2-negative cases, HR-positive tumors had a higher incidence of low HER2 expression compared with triple-negative tumors (80.27% vs 60.00% in primary tumors and 72.68% vs 50.77% in residual tumors). The inconsistency rate of HER2 expression was 21.42%, mainly manifested as the conversion of HER2-low cases to HER2-zero (10.19%) and the conversion of HER2-zero to HER2-low (6.45%). Among the HER2-negative cases in the primary tumor, the HER2 discordance rate of HR-positive cases was lower than that of triple-negative cases (23.34% VS 36.92%). This difference was mainly caused by the case switching from HER2-low to HER2-zero. Compared with HER2-zero cases, there were statistically significant differences in RCB grade, MP grade and the number of metastatic lymph nodes in HER2-low cases. Patients with low HER2 expression had a lower pathological response rate and a higher number of metastatic lymph nodes.ConclusionHER2-low breast cancer is highly unstable during disease evolution and has certain biological characteristics. HER2-low breast cancer is not only correlated with positive HR, but also has a certain correlation with positive AR. Re-detection of HER2 in breast cancer after neoadjuvant therapy may lead to new treatment opportunities for a certain proportion of patients.
(20R)-panaxadiol improves obesity by promoting white fat beigeing
Authors: Lv Yuqian , Lv Xiaoyan , Feng Jianshu , Cheng Fanghui , Yu Zhiyi , Guan Fengying , Chen Li 
Published: February 2023

Introduction: Obesity is an important cause of a range of metabolic diseases. However, the complex mechanisms of obesity and its related diseases make some weight loss methods ineffective or have safety issues. Ginseng, a specialty of Jilin Province in China with both edible and medicinal value, contains mainly ginsenosides and other components. In order to study the anti-obesity effect of ginseng, network pharmacology was used to predict and screen the active ingredients, action targets and signaling pathways of ginseng. We found (20R)-panaxadiol (PD) is a more desirable active ingredient due to its high drug-like properties and high bioavailability. Moreover, it is closely related to cAMP pathway which is more important in metabolism regulation. The corresponding pharmacodynamic targets of PD include ADRB2 (the gene encoding the β2-adrenoceptor receptor). Our study aimed to investigate whether Panaxadiol can promote white adipocyte beigeing and increase thermogenesis through modulating the β2/cAMP pathway to exert anti-obesity effects.Methods:In vivo, we established high-fat feeding obesity model, genotypically obese mice (ob/ob) model, and administered PD (10 mg/kg). PD treatment in ob/ob mice along with β2 receptor inhibitor ICI118551. In vitro, differentiated mature 3T3-L1 cells were given palmitate (PA) to induce hypertrophy model along with PD (20 μM).Results: The results of this study demonstrated that PD significantly reduced body weight, improved glucose tolerance and lipid levels in high-fat-induced obese mice and ob/ob mice, and also reduced lipid droplet size in PA-treated hypertrophic adipocytes in vitro. Molecular biology assays confirmed that cAMP response element binding protein (CREB) phosphorylation was increased after PD administration, and the expression of thermogenesis-related proteins UCP1, PRDM16 and mitochondrial biosynthesis-related proteins PGC-1α, TFAM and NRF1 were increased. Molecular docking results showed a low binding energy between β2 receptors and PD, indicating an affinity between the β2 receptor and PD. In addition, the β2 receptor inhibition, reversed the anti-obesity effect of PD on the body weight, lipid droplets, the expression of thermogenesis-related proteins and CREB phosphorylation in ob/ob mice.Discussion: These results suggest that PD may promote the expression of thermogenic proteins through phosphorylation of CREB via β2 receptor activation, and thus exert anti-obesity effects.
Differences in bioavailability and cognitive-enhancing activity exerted by different crystal polymorphs of latrepirdine (Dimebon®)
Authors: Gorin Boris I. , Tukhovskaya Elena A. , Ismailova Alina M. , Slashcheva Gulsara A. , Lenina Oksana A. , Petrov Konstantin A. , Kazeev Ilya V. , Murashev Arkady N. 
Published: February 2023

Introduction: Pharmacokinetic characteristics as well as cognitive-enhancing nootropic activity of latrepirdine (Dimebon®) in relationship with its polymorphic forms have been studied in SD and Wistar rats.Methods: The pharmacokinetics of six polymorphs (A, B, C, D, E, F) of latrepirdine were studied in male SD rats after 7 days of oral administration in corn oil at a dose of 10 mg/kg once a day. Blood and brain samples were taken on the 7th day of administration at 15 min, 30 min, 60 min and 120 min after administration and analyzed for latrepirdine content by LC-MS. The cognitive-enhancing nootropic effect was studied in male and female Wistar rats after 9 days of oral administration in corn oil at a dose of 10 mg/kg, after prior administration of scopolamine, an agent that causes memory impairment similar to that in Alzheimer’s disease. The animals’ cognitive function was studied in the passive avoidance test.Results: When studying the pharmacokinetics, the highest bioavailability both in the blood and in the brain was demonstrated by polymorph E, whose AUC was the highest relative to other polymorphs. In the study of the cognitive-enhancing nootropic effect, polymorph E also showed the highest activity, whose values of the latent period of entering the dark chamber did not differ from control animals, and differed from other polymorphs.Conclusion: Thus, the crystal structure has been shown to play a key role in the bioavailability and efficacy of latrepirdine, and polymorph E has also been shown to be a promising drug for the treatment of neurodegenerative diseases associated with memory impairment, such as Alzheimer’s disease.
Identification of angiogenesis-related subtypes, the development of prognostic models, and the landscape of tumor microenvironment infiltration in colorectal cancer
Authors: Zhang Chen , Liu Tao , Yun Zhennan , Liang Bin , Li Xue , Zhang Jiantao 
Published: February 2023

Background: Angiogenesis is one of the most prominent markers of cancer progression and contributes to tumor metastasis and prognosis. Anti-angiogenic drugs have proven effective in treating metastatic colorectal cancer. However, there is some uncertainty regarding the potential role of angiogenesis-related genes in the tumor microenvironment.Methods: We analyzed 1,214 colorectal cancer samples to identify alterations in angiogenesis-related genes (ARGs), and then correlated angiogenesis with clinical features, prognosis, and TME. The ARGs expression profiles in colorectal cancer were analyzed using three computational methods (CIBERSORT, ssGSEA, and MCPcounter) and provided a systematic immune landscape. Patients with CRC were classified into two subtypes based on consensus clustering analysis of angiogenesis-related genes. The revealed differentially expressed genes between the two subtypes were used to create and validate ARGscore prognostic models. In addition, we collected eight colorectal cancer patient specimens and performed RT-qPCR to validate the signature gene expression.Results: We assessed the expression patterns of ARGs in colorectal cancer. We identified two molecular subtypes and confirmed that the expression of ARGs was associated with prognosis and TME characteristics. Based on differentially expressed genes between subtypes, we constructed ARGscore and evaluated their predictive power for the survival of colorectal cancer patients. We also developed an accurate nomogram to make the ARGscore more clinically useful. In addition, ARGscore was significantly correlated with microsatellite instability, cancer stem cells, and chemotherapeutic drug sensitivity. Patients with ARGscore-low characterized by immune activation and microsatellite instability high had a better prognosis.Conclusion: ARGs expression influenced the prognosis, clinicopathological features, and tumor stromal immune microenvironment in colorectal cancer. We developed a new risk model, ARGscore, for the treatment and prognosis of CRC patients and validated its promising predictive power. These findings will enable us to understand colorectal cancer better, assess prognoses, and develop more effective treatment options.
Repeated measurements of Adaptive Force: Maximal holding capacity differs from other maximal strength parameters and preliminary characteristics for non-professional strength vs. endurance athletes
Authors: Schaefer Laura V. , Carnarius Friederike , Dech Silas , Bittmann Frank N. 
Published: February 2023

The Adaptive Force (AF) reflects the neuromuscular capacity to adapt to external loads during holding muscle actions and is similar to motions in real life and sports. The maximal isometric AF (AFisomax) was considered to be the most relevant parameter and was assumed to have major importance regarding injury mechanisms and the development of musculoskeletal pain. The aim of this study was to investigate the behavior of different torque parameters over the course of 30 repeated maximal AF trials. In addition, maximal holding vs. maximal pushing isometric muscle actions were compared. A side consideration was the behavior of torques in the course of repeated AF actions when comparing strength and endurance athletes. The elbow flexors of n = 12 males (six strength/six endurance athletes, non-professionals) were measured 30 times (120 s rest) using a pneumatic device. Maximal voluntary isometric contraction (MVIC) was measured pre and post. MVIC, AFisomax, and AFmax (maximal torque of one AF measurement) were evaluated regarding different considerations and statistical tests. AFmax and AFisomax declined in the course of 30 trials [slope regression (mean ± standard deviation): AFmax = −0.323 ± 0.263; AFisomax = −0.45 ± 0.45]. The decline from start to end amounted to −12.8% ± 8.3% (p &lt; 0.001) for AFmax and −25.41% ± 26.40% (p &lt; 0.001) for AFisomax. AF parameters declined more in strength vs. endurance athletes. Thereby, strength athletes showed a rather stable decline for AFmax and a plateau formation for AFisomax after 15 trials. In contrast, endurance athletes reduced their AFmax, especially after the first five trials, and remained on a rather similar level for AFisomax. The maximum of AFisomax of all 30 trials amounted 67.67% ± 13.60% of MVIC (p &lt; 0.001, n = 12), supporting the hypothesis of two types of isometric muscle action (holding vs. pushing). The findings provided the first data on the behavior of torque parameters after repeated isometric–eccentric actions and revealed further insights into neuromuscular control strategies. Additionally, they highlight the importance of investigating AF parameters in athletes based on the different behaviors compared to MVIC. This is assumed to be especially relevant regarding injury mechanisms.
Evaluation of depression and obesity indices based on applications of ANOVA, regression, structural equation modeling and Taguchi algorithm process
Authors: Mohamed Nur Anisah , Alanzi Ayed R. A. , Azizan Noor Azlinna , Azizan Suzana Ariff , Samsudin Nadia , Jenatabadi Hashem Salarzadeh 
Published: February 2023

IntroductionDepression and obesity are the main threat among women which have been considered by many research scholars in psychology studies. In their analysis for measuring and estimating obesity and depression they were involving statistical functions.MethodsRegression, Analysis of Variance (ANOVA), and in the last two decades Structural Equation Modeling are the most familiar statistical methods among research scholars. Taguchi algorism process is one the statistical methods which mostly have been applying in engineering studies. In this study we are looking at two main objectives. The first one is to introduce Taguchi algorism process and apply it in a case study in psychology area. The second objective is challenging among four statistical techniques include ANOVA, regression, SEM, and Taguchi technique in a same data. To achieve those aims we involved depression and obesity indices with other familiar indicators contain socioeconomic, screen time, sleep time, and usage fitness and nutrition mobile applications.Results and discussionOutputs proved that Taguchi technique is able to analyze some correlations which are not achieved by applying ANOVA, regression, and SEM. Moreover, SEM has a special capability to estimate some hidden correlations which are not possible to evaluate them by using ANOVA, regression, and even Taguchi method. In the last, we found that some correlations are significant by SEM, however, in the same data with regression those correlation were not significant. This paper could be a warning for psychology research scholars to be more careful with involving statistical methods for measuring and estimating of their research variables.
Part-time or full-time teleworking? A systematic review of the psychosocial risk factors of telework from home
Authors: Antunes Evelise Dias , Bridi Leonardo Rodrigues Thomaz , Santos Marta , Fischer Frida Marina 
Published: February 2023

IntroductionSince the start of the COVID-19 pandemic thousands of people have experienced teleworking and this practice is becoming increasingly commonplace. This review aims to highlight the differences in exposure to psychosocial risk factors for health between part-time and full-time teleworking from home.MethodsThe protocol of the systematic review of the literature was registered on PROSPERO 2020 platform according to the PRISMA statement guidelines. The key words “telework” and “frequency” (“part-time” or “full-time”), together with their synonyms and variations, were searched. Independent researchers conducted the systematic search of 7 databases: Scopus, SciELO, PePSIC; PsycInfo, PubMed, Applied Social Sciences Index and Abstracts (ASSIA) and Web of Science. Of the 638 articles identified from 2010 to June 2021, 32 were selected for data extraction. The authors evaluated the risk of bias and quality of evidence of the studies included using the Mixed Methods Appraisal Tool. Main themes categorized include 7 dimensions of psychosocial risk factors: work intensity and working hours; emotional demands; autonomy; social relationships at work; conflict of values, work insecurity and home/work interface.ResultsThe results revealed scant practice of full-time teleworking prior to the pandemic. Regarding the psychosocial risk factors found, differences were evident before and during the COVID-19 pandemic. For part-time and full-time telework prior to the pandemic, the dimensions of intensification of work and working hours, social relationships at work, and the home-work interface were the most prominent factors. However, studies performed during the COVID-19 pandemic where teleworking was mostly performed full-time, there was an increase in focus on emotional demands and the home-work interface, and a reduction in the other dimensions.DiscussionFull-time telework brings important changes in working conditions and has the potential to affect living and health conditions of teleworkers. Part-time teleworking may have positive impact on psychosocial risk factors, favoring work-home balance, communication, and social relationships.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=191455, PROSPERO 2020 CRD4202019 1455.
The association between grandparents as caregivers and overdose mortality in Appalachia and non-Appalachia counties
Authors: Beatty Kate E. , Mathis Stephanie M. , McCurry Abby R. , Francisco Margaret M. , Meit Michael , Wahlquist Amy E. 
Published: February 2023

ObjectiveTo assess the association of drug overdose mortality with grandparents serving as caregivers of children in Appalachia and non-Appalachia in the U.S.MethodsThis study used a cross-sectional design, with percent of grandparents as caregivers and overdose mortality rates being of primary interest. County-level data were combined, and descriptive, bivariate, and multivariable statistics were applied. Multiple sociodemographic and geographic variables were included: median age of the population, percent of the population that is uninsured, percent of the population that is non-Hispanic white, teen birth rate, percent of high school dropouts, and rurality.ResultsThe percent of grandparents as caregivers increased as the overdose mortality rate increased (p &lt; 0.01). For every 1% increase in the overdose mortality rate, the percent of grandparents as caregivers increased by 56% in Appalachian counties compared to 24% in non-Appalachian counties. After adjusting for sociodemographic characteristics, the interaction between overdose mortality and Appalachian vs. non-Appalachian counties was no longer significant (p = 0.3).ConclusionsCounties with higher overdose mortality rates had greater rates of grandparents as caregivers, with Appalachian counties experiencing greater rates of grandparents as caregivers than non-Appalachian counties. Sociodemographic characteristics that are often more prevalent in Appalachia may be driving the observed differences.Policy implicationsPolicies and programs are needed to support grandparents providing caregiving for children impacted by substance use disorders including reform to federal child welfare financing to support children, parents, and grandparent caregivers such as kinship navigation, substance use treatment and prevention services, mental health services and in-home supports.