bluuebunny/crossref_metadata_2025_split huggingface dataset:
The inter-chamber differences in the contractile function between left and right atrial cardiomyocytes in atrial fibrillation in rats
Authors: Butova Xenia , Myachina Tatiana , Simonova Raisa , Kochurova Anastasia , Mukhlynina Elena , Kopylova Galina , Shchepkin Daniil , Khokhlova Anastasia 
Published: August 2023

IntroductionThe left and right atria (LA, RA) work under different mechanical and metabolic environments that may cause an intrinsic inter-chamber diversity in structure and functional properties between atrial cardiomyocytes (CM) in norm and provoke their different responsiveness to pathological conditions. In this study, we assessed a LA vs. RA difference in CM contractility in paroxysmal atrial fibrillation (AF) and underlying mechanisms.MethodsWe investigated the contractile function of single isolated CM from LA and RA using a 7-day acetylcholine (ACh)-CaCl2 AF model in rats. We compared auxotonic force, sarcomere length dynamics, cytosolic calcium ([Ca2+]i) transients, intracellular ROS and NO production in LA and RA CM, and analyzed the phosphorylation levels of contractile proteins and actin-myosin interaction using an in vitro motility assay.ResultsAF resulted in more prominent structural and functional changes in LA myocardium, reducing sarcomere shortening amplitude, and velocity of sarcomere relengthening in mechanically non-loaded LA CM, which was associated with the increased ROS production, decreased NO production, reduced myofibrillar content, and decreased phosphorylation of cardiac myosin binding protein C and troponin I. However, in mechanically loaded CM, AF depressed the auxotonic force amplitude and kinetics in RA CM, while force characteristics were preserved in LA CM.DiscussionThus, inter-atrial differences are increased in paroxysmal AF and affected by the mechanical load that may contribute to the maintenance and progression of AF.
Health risk assessment following exposure of operators to backpack-sprayed prothioconazole and its major metabolite in wheat fields in China
Authors: Li Shuang , Mei Chenghan , Wu Xuemin , Li Xuefeng , Pang Sen 
Published: August 2023

Introduction: Prothioconazole is a triazolinthione fungicide widely used to control diseases on various crops caused by Ascomycetes, Basidiomycetes, and Imperfecti fungi. However, in view of the rapid transformation of parent prothioconazole to its major metabolite prothioconazole-desthio during application and the fact that the latter is of higher toxicity, prothioconazole poses a potential threat to the health of operators in direct contact with it. Currently, very few studies have been carried out regarding prothioconazole and prothioconazole-desthio exposure.Methods: Therefore, a typical exposure scenario from wheat-planting provinces in China was chosen, and a motorized backpack-type sprayer was used as the application equipment. The actual exposure doses of prothioconazole and prothioconazole-desthio for mixers/loaders and applicators under different exposure routes were determined, and a tiered risk assessment was conducted considering different conditions.Results: The results of this study indicated that the exposure risk to operators after spraying with 30% prothioconazole oil dispersion was unacceptable in the primary risk assessment, while the risk was acceptable with integrated risk quotients less than 1 at a better level of protection. Moreover, the upper legs and hands were regarded as the most contaminated sections during the mixing/loading process, and legs were the most contaminated sections during spraying. Good protection equipment, such as hats, long-sleeve shirts, long pants, socks, shoes, and rubber or nitrile gloves, was effective at alleviating prothioconazole and prothioconazole-desthio exposure. This study aims to provide important references for the safe use and risk management of prothioconazole.
Immune cell type signature discovery and random forest classification for analysis of single cell gene expression datasets
Authors: Aybey Bogac , Zhao Sheng , Brors Benedikt , Staub Eike 
Published: August 2023

BackgroundRobust immune cell gene expression signatures are central to the analysis of single cell studies. Nearly all known sets of immune cell signatures have been derived by making use of only single gene expression datasets. Utilizing the power of multiple integrated datasets could lead to high-quality immune cell signatures which could be used as superior inputs to machine learning-based cell type classification approaches.ResultsWe established a novel workflow for the discovery of immune cell type signatures based primarily on gene-versus-gene expression similarity. It leverages multiple datasets, here seven single cell expression datasets from six different cancer types and resulted in eleven immune cell type-specific gene expression signatures. We used these to train random forest classifiers for immune cell type assignment for single-cell RNA-seq datasets. We obtained similar or better prediction results compared to commonly used methods for cell type assignment in independent benchmarking datasets. Our gene signature set yields higher prediction scores than other published immune cell type gene sets in random forest-based cell type classification. We further demonstrate how our approach helps to avoid bias in downstream statistical analyses by re-analysis of a published IFN stimulation experiment.Discussion and conclusionWe demonstrated the quality of our immune cell signatures and their strong performance in a random forest-based cell typing approach. We argue that classifying cells based on our comparably slim sets of genes accompanied by a random forest-based approach not only matches or outperforms widely used published approaches. It also facilitates unbiased downstream statistical analyses of differential gene expression between cell types for significantly more genes compared to previous cell classification algorithms.
Wearable teleoperation controller with 2-DoF robotic arm and haptic feedback for enhanced interaction in virtual reality
Authors: Zhang Zheyuan , Qian Chen 
Published: August 2023

IntroductionTeleoperation is an essential component in fields such as medicine and manufacturing, enabling human operators to interact with remote robotic systems. A wearable device has been designed and manufactured to enhance sensitivity, wearability, and synchronization, providing users with the ability to experience the sensation of grasping virtual objects.MethodsThe device incorporates a 2-DoF robotic arm, haptic sensors for finger gestures, and a Unity-powered virtual scene system. Its effectiveness was evaluated through user experiments, where participants were asked to rank the weights of three virtual balls and identify the direction of force applied to a virtual ball in separate tests. Additionally, the device's ability to render various shapes was also examined.ResultsThe experiments showed that 73.3% of participants accurately ranked the balls by mass, and an overall correctness rate of 87.3% was achieved for force direction identification. For shape rendering, the device yielded more accurate results for simple objects like spheres, whereas rendering more complex objects such as cups and cones was challenging.DiscussionThe findings indicate that this wearable device has potential applications in haptic feedback and virtual reality contexts. Despite the challenges with complex shape rendering, the device shows promising capability in enhancing the user's immersive experience in virtual environments.
Effect of clinical features on antiseizure medication doses in patients with newly diagnosed epilepsy
Authors: Hersi Hire , Peltola Jukka , Raitanen Jani , Saarinen Jukka T. 
Published: August 2023

ObjectiveWe evaluate the effect of distinct clinical features on anti-seizure medication (ASM) doses in seizure-free and not seizure-free patients aged ≥16 years with new-onset epilepsy.Materials and methodsThis study included 459 patients with a validated diagnosis of epilepsy. The most prescribed ASMs were oxcarbazepine (OXC; n = 307), followed by valproic acid (VPA; n = 115), carbamazepine (CBZ; n = 81), and lamotrigine (LTG; n = 67). The seizure freedom rate with their first or subsequent ASM was 88.0%. A retrospective analysis of patient records was performed to determine any association between doses of ASMs and patient characteristics.ResultsThe median OXC dose in seizure-free patients aged &gt;60 years was 600 mg compared to 900 mg in younger patients. When controlling for age but not in an unadjusted model, the median dose of OXC was lower (300 mg, p = 0.018) for seizure-free patients compared to non-seizure-free patients, and the median dose of OXC was also 300 mg lower among older patients aged &gt;60 years (p &lt; 0.001). The median OXC doses for men aged ≤60 years were 300 mg higher than for women aged &gt;60 years (900 mg vs. 600 mg, p = 0.021). The median dose of VPA was 400 mg higher in men than in women (p &lt; 0.001) and 400 mg higher in not seizure-free patients compared to seizure-free patients only when adjusting for sex (p &lt; 0.001). Higher median doses for CBZ were registered with FAS compared with FBTCS (difference in median doses of 200 mg; p = 0.017).ConclusionSignificant OXC dose differences were detected between age groups, whereas VPA dosing was different in men and women. Moreover, CBZ doses were dependent on some seizure types. These data allow for the individualization of the initial target dosing based on key clinical characteristics.
Assessing ‘no evidence of disease activity’ status in patients with relapsing–remitting multiple sclerosis: a long-term follow-up
Authors: Zilli Chiara , Scribani Rossi Pietro , Di Stadio Arianna , Fratino Mariangela , Giuliani Giada , Annecca Rosanna , Russo Gaetano , Di Piero Vittorio , Altieri Marta 
Published: August 2023

IntroductionMultiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS with an autoimmune pathogenesis. Over the years, numerous disease-modifying therapies (DMTs) have proven effective in disease control; to date, there is a need to identify a personalized treatment effective in ensuring disease-free status or no evidence of disease activity (NEDA).Objectiveidentify clinical, demographic and treatment approach characteristics that affect the maintenance of NEDA-3 and the occurrence of clinical relapses during a 6-years follow-up.Materials and methoda retrospective study was conducted on a cohort of MS patients followed up with six-year period. All participants were treated with first- or second-line MS drugs.Clinical relapse, NEDA-3 at 6 years and sustained EDSS were assessed as disease activity outcomes. Patients with follow-up of less than 6 years and insufficient clinical and radiological data were excluded from the study.ResultsTwo-hundred-eighty naive patients (mean age was 49.8 years, SD ± 11.35 years, 23–76, F/M 182/98), with MS were followed up for 6 years.The mean age at diagnosis was 34.3 years (SD ±11.5, 14–62 years), the mean EDSS score at the onset was 1.9 (±1.3), 76.8% of patients had an EDSS below or equal to 2.5 at diagnosis.In the cohort 37 (13.2%) directly received second-line treatment, 243 (86.8%) received first-line drugs.The analysis showed that second-line treatment from beginning had a protective effect for the achievement of NEDA-3 (p = 0.029), on the prevention of clinical relapse (p = 0.018) and on number of relapses (p = 0.010); this finding was confirmed by logistic regression analysis (p = 0.04) and Kaplan–Meier analysis (p = 0.034).ConclusionThe results of this study demonstrate the efficacy of targeted and early intervention so as to act in the right time window, ensuring a favorable outcome in both clinical and radiological terms; this could be decisive in reducing clinical relapse, disease progression and related disability. Therefore, prescribing highly effective drug in the early stages of the disease represents a leading strategy with the most favorable cost–benefit ratio.
The efficacy and safety of first-line anti-seizure medications as substitution therapy for children with drug-resistant epilepsy: a randomized controlled trial protocol
Authors: Perdani Roro Rukmi Windi , Arozal Wawaimuli , Mangunatmadja Irawan , Kaswandani Nastiti , Handryastuti Setyo , Medise Bernie Endyarni , Hardi Harri , Thandavarayan Rajarajan Amirthalingam , Oswari Hanifah 
Published: August 2023

Although many anti-seizure medications (ASMs) are available, treatment failure, known as drug-resistant epilepsy (DRE), still occurs in around 30% of children with epilepsy. Second-line ASMs are usually used as substitution therapy in DRE to control seizures, although international consensus is not available yet. Previous studies focus on comparing the ASMs, whether as add-on or substitution therapy, mainly conducted in newly diagnosed epilepsy. However, the study that investigated first-line ASMs as substitution therapy compared to second-line ones, particularly among DRE children, is still lacking. A randomized controlled trial (RCT) enrolling 102 participants, aged 1–18, at three referral hospitals in Indonesia will be conducted, dividing them into intervention and control groups. The intervention group will be treated with first-line ASMs as the substitution therapy, while the other in the control group will get second-line ASMs. The primary outcome measure is the proportion difference of responders between groups who get first-line and second-line ASMs in 14 weeks of intervention.Clinical trial registration: ClinicalTrials.gov, identifier NCT05697614.
Huntingtin-associated protein 1 ameliorates neurological function rehabilitation by facilitating neurite elongation through TrKA-MAPK pathway in mice spinal cord injury
Authors: Miao Li , Qing Sun Wan , Tao Lu 
Published: August 2023

AimsHuntingtin-associated protein 1 (HAP1) is a neuronal protein closely associated with microtubules and might facilitate neurological function rehabilitation. This study aimed to investigate the effects of HAP1 on SCI and the underlying mechanisms.Methodsthe spinal cord injury (SCI) mouse model was induced by Allen’s method. Then recombinant-HAP1 (r-HAP1) was administrated by intrathecal injection, and the BMS, Thermal nociceptive thresholds, tactile nociceptive thresholds, and neurofibrillary regeneration were identified to inspect the therapy outcome. Then NSCs were isolated from mice on embryonic day 14.5 and induced to differentiate into neurons. The efficiency of axon growth was calculated. Signaling pathway array was conducted to examine the signaling pathways in NSCs treated with r-HAP1. Antagonists and activators of TrkA were used to confirm the role of TrkA of HAP1 intervention both in vitro and in vivo.Resultsr-HAP1 ameliorates the neurological function rehabilitation after SCI, and benefits the regain of Tuj in injury spinal cord. Also significantly enhances neurite growth during neuronal differentiation of NSCs; Signaling pathway array and Western blot revealed that r-HAP1 significantly activates the phosphorylation of TrkA-MAPK/ERK in NSCs. TrkA selective inhibitor GW441756 blocks r-HAP1 on TrkA-MAPK/ERK signaling pathway and detracts from axonal growth after neuronal differentiation. TrkA selective activator gambogic amide can mimic the function of r-HAP1 by activating the foregoing pathway. ERK activator U-46619 reverses the blocking effect of GW441756 on r-HAP1.ConclusionHAP1 activates the TrkA-MAPK signaling pathway and is conducive to neurite elongation during NSC neuronal differentiation; by which to improve the prognosis of spinal cord injury in mice.
Comprehensive analysis of ferroptosis-related genes in immune infiltration and prognosis in multiple myeloma
Authors: Wang Quanqiang , Zhao Misheng , Zhang Tianyu , Zhang Bingxin , Zheng Ziwei , Lin Zhili , Zhou Shujuan , Zheng Dong , Chen Zixing , Zheng Sisi , Zhang Yu , Lin Xuanru , Dong Rujiao , Chen Jingjing , Qian Honglan , Hu Xudong , Zhuang Yan , Zhang Qianying , Jiang Songfu , Ma Yongyong 
Published: August 2023

Background: One particular type of cellular death that is known as ferroptosis is caused by the excessive lipid peroxidation. It is a regulated form of cell death that can affect the response of the tumor cells. Currently, it is not known if the presence of this condition can affect the prognosis of patients with multiple myeloma (MM).Methods: In this study, we studied the expression differences and prognostic value of ferroptosis-related genes (FRGs) in MM, and established a ferroptosis risk scoring model. In order to improve the prediction accuracy and clinical applicability, a nomogram was also established. Through gene enrichment analysis, pathways closely related to high-risk groups were identified. We then explored the differences in risk stratification in drug sensitivity and immune patterns, and evaluated their value in prognostic prediction and treatment response. Lastly, we gathered MM cell lines and samples from patients to confirm the expression of marker FRGs using quantitative real-time PCR (qRT-PCR).Results: The ability to predict the survival of MM patients is a challenging issue. Through the use of a risk model derived from ferroptosis, we were able to develop a more accurate prediction of the disease’s prognosis. They were then validated by a statistical analysis, which showed that the model is an independent factor in the prognosis of MM. Patients of high ferroptosis risk scores had a much worse chance of survival than those in the low-risk groups. The calibration and power of the nomogram were also strong. We noted that the link between the ferroptosis risk score and the clinical treatment was suggested by the FRG’s significant correlation with the immune checkpoint genes and the medication sensitivity. We validated the predictive model using qRT-PCR.Conclusion: We demonstrated the association between FRGs and MM, and developed a new risk model for prognosis in MM patients. Our study sheds light on the potential clinical relevance of ferroptosis in MM and highlights its potential as a therapeutic target for patients with this disease.
Design, synthesis and antitumour activity evaluation of novel dolutegravir derivatives
Authors: Hou Xi-Xi , Mao Long-Fei , Guo Yajie , Lou Chaoxuan , Wang Lan , Li Rui-Fang , Wang Huili , Li San-Qiang , Yang Jian-Xue 
Published: August 2023

Based on the modification of the structure of dolutegravir, we introduced 1,2,3-triazole moieties with different substituted groups and obtained a lot of novel dolutegravir derivatives. The activity of A549 cells treated with the derivatives was examined, and most compounds showed good inhibitory effects. Among them, compounds 4b and 4g were the most effective, and inhibited the growth of A549 cells with IC50 values of 8.72 ± 0.11 μM and 12.97 ± 0.32 μM, respectively. In addition, compound 4g induced apoptosis and clonal suppression in A549 tumor cells. Compound 4g also activated the LC3 signaling pathway to induce autophagy in tumor cells, and activated the γ-H2AX signaling pathway to induce DNA damage in tumor cells.
Hemodynamic responses to handgrip and metaboreflex activation are exaggerated in individuals with metabolic syndrome independent of resting blood pressure, waist circumference, and fasting blood glucose
Authors: Stavres Jon , Aultman Ryan A. , Brandner Caleb F. , Newsome Ta’Quoris A. , Vallecillo-Bustos Anabelle , Wise Havens L. , Henderson Alex , Stanfield Diavion , Mannozzi Joseph , Graybeal Austin J. 
Published: August 2023

Introduction: Prior studies report conflicting evidence regarding exercise pressor and metaboreflex responses in individuals with metabolic syndrome (MetS).Purpose: To test the hypotheses that 1) exercise pressor and metaboreflex responses are exaggerated in MetS and 2) these differences may be explained by elevated resting blood pressure.Methods: Blood pressure and heart rate (HR) were evaluated in 26 participants (13 MetS) during 2 min of handgrip exercise followed by 3 min of post-exercise circulatory occlusion (PECO). Systolic (SBP), diastolic (DBP), and mean arterial pressure (MAP), along with HR and a cumulative blood pressure index (BPI), were compared between groups using independent samples t-tests, and analyses of covariance were used to adjust for differences in resting blood pressure, fasting blood glucose (FBG), and waist circumference (WC).Results: ΔSBP (∼78% and ∼54%), ΔMAP (∼67% and ∼55%), and BPI (∼16% and ∼20%) responses were significantly exaggerated in individuals with MetS during handgrip and PECO, respectively (all p ≤ 0.04). ΔDBP, ΔMAP, and BPI responses during handgrip remained significantly different between groups after independently covarying for resting blood pressure (p &lt; 0.01), and after simultaneously covarying for resting blood pressure, FBG, and WC (p ≤ 0.03). Likewise, peak SBP, DBP, MAP, and BPI responses during PECO remained significantly different between groups after adjusting for resting blood pressure (p ≤ 0.03), with peak SBP, MAP, and BPI response remaining different between groups after adjusting for all three covariates simultaneously (p ≤ 0.04).Conclusion: These data suggest that exercise pressor and metaboreflex responses are significantly exaggerated in MetS independent of differences in resting blood pressure, FBG, or WC.
Predicting the dyadic coping through self-esteem among infertile couples undergoing in vitro fertilization and embryo transfer: An actor-partner interdependence model
Authors: Zhang Lihong , Gu Wei , Jing Xiaoyu , Zhi Shihan , Zhou Nan , Zhang Lu , Wang Wenru , Jiang Ying 
Published: August 2023

BackgroundThe population of infertile couples receiving in vitro fertilization and embryo transfer in China is increasing gradually. The association of self-esteem and dyadic coping of infertile couples undergoing in vitro fertilization and embryo transfer has not been reported. This investigation aimed to examine the predictive effect of self-esteem of infertile couples undergoing in vitro fertilization and embryo transfer on coping strategies at the dyadic level.MethodsA cross-sectional study involving 283 infertile couples was conducted at the Reproductive Center of Northwest Women and Children’s Hospital in China. Participants were asked to complete two self-administered questionnaires, to assess self-esteem (Rosenberg Self-Esteem Scale) and dyadic coping (Dyadic Coping Inventory). Paired t-test and Pearson correlation were used to analyze the difference and correlation of variables between wife and husband. The actor-partner interdependence model was used to test the predictive effect of each individual’s self-esteem on their own and their partners’ dyadic coping.ResultsInfertile couples’ self-esteem and dyadic coping are in the medium range. The self-esteem of wives and husbands can fully predict their own dyadic coping. Meanwhile, the husband’s self-esteem can predict the wife’s stress communication (β = 0.135, p = 0.025), support dyadic coping (β = 0.142, p = 0.019), and negative dyadic coping (β = 0.133, p = 0.024), and the wife’s perceived partners’ supportive dyadic coping (β = 0.147, p = 0.014) and negative dyadic coping (β = 0.144, p = 0.016). Similarly, the wife’s self-esteem can predict the husband’s supportive dyadic coping (β = 0.195, p &lt; 0.001), and the husband’s perceived partners’ stress communication (β = 0.184, p = 0.003) and supportive dyadic coping (β = 0.180, p = 0.002).ConclusionThe actor-partner analyses revealed insight into how infertile couples undergoing in vitro fertilization and embryo transfer interact and highlighted the importance of self-esteem in dyadic coping styles. Future psychological interventions can enhance self-esteem as an effective way to improve dyadic coping of infertile couples.