bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of belimumab for the treatment of refractory childhood-onset systemic lupus erythematosus: A single-center, real-world, retrospective study
Authors: Wang Dahai , Shan Chunrong , Liu Jia , Zhang Ranran , Zhu Guohao , Gao Tingting , Chang Hong , Gao Shan , Bai Cui , Nie Nana , Zhang Qiuye , Lin Yi 
Published: December 2022

ObjectiveThis study aimed to investigate the efficacy and safety of belimumab for treating children with refractory childhood-onset systemic lupus erythematosus (cSLE).MethodsTwenty-six cSLE patients who received belimumab treatment in our hospital from January 2020 to September 2021 (23 of them for more than 52 weeks) were enrolled in this study. Their clinical and laboratory data, assessment of disease activity, glucocorticoid dosage, and treatment-emergent adverse events (TEAEs) were retrieved for analysis. The paired samples t-test and the nonparametric test were used to compare the baseline and post-treatment data.ResultsThe mean age of onset was 10.3 ± 2.4 years old; the mean disease duration was 41.6 ± 37.4 months; the median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score was 10 (P25, P75: 3, 17); and the mean Physician’s Global Assessment (PGA) score at baseline was 1.9 ± 1.0. Compared with the baseline values, there was a significant decrease in the 24-h urine protein quantifications at 24 and 52 weeks of treatment (P&lt;0.05) as well as an elevated complement (C) 3 and C4 levels at 4, 12, 24, and 52 weeks of treatment. In addition, the SLEDAI-2K and PGA scores as well as the percentage of CD19+ B cells were significantly decreased at 12, 24, and 52 weeks of treatment compared with the baseline values (P&lt;0.05). The dosage of glucocorticoid at 4, 12, 24, and 52 weeks of treatment was significantly less than that at baseline or the previous follow-up (P&lt;0.05). At 52 weeks, 14 subjects (53.8%) achieved Lupus Low Disease Activity State (LLDAS), and 4 subjects (15.4%) reached clinical remission (CR). At the last follow-up, 16 subjects (61.5%) achieved LLDAS, and 10 subjects (38.5%) reached CR.ConclusionsBelimumab treatment can significantly improve laboratory indicators, reduce disease activity, and decrease the dosage of glucocorticoid required in children with cSLE. Moreover, it has a good safety profile.
New insights into β-glucan-enhanced immunity in largemouth bass Micropterus salmoides by transcriptome and intestinal microbial composition
Authors: Zhang Yuexing , Guo Mingyu , Li Ning , Dong Zhiyong , Cai Linwei , Wu Bowen , Xie Jianjun , Liu Liang , Ren Lina , Shi Bo 
Published: December 2022

β-glucan is widely used in aquaculture due to its immunostimulatory effects, but the specific effect and potential regulatory mechanism on largemouth bass (Micropterus salmoides) are still unclear. Here, we evaluated the effects of β-glucan on growth, resistance to Aeromonas schubertii, intestinal health, and transcriptome of largemouth bass to reveal the potential regulators, metabolic pathways, and altered differential microbiota. Four experimental diets were designed with β-glucan supplementation levels of 0 (control), 100 (LA-100), 200 (MA-200), and 300 (HA-300) mg kg-1, and each diet was fed to largemouth bass (79.30 ± 0.50 g) in triplicate for 70 days, followed by a 3-day challenge experiment. Results showed that different β-glucan supplementations had no significant effects on growth performance and whole-body composition. Fish fed a diet with 300 mg kg-1 β-glucan significantly increased the activity of lysozyme than those fed diets with 0 and 100 mg kg-1 β-glucan. In addition, the survival rate of largemouth bass in β-glucan supplementation groups was significantly higher than the control group at 12- and 24-h challenge by Aeromonas schubertii. Transcriptome analysis showed that a total of 1,245 genes were differentially expressed [|log2(fold change)| ≥1, q-value ≤0.05], including 109 immune-related differentially expressed genes (DEGs). Further analysis revealed that significantly upregulated and downregulated DEGs associated with immunity were mapped into 12 and 24 pathways, respectively. Results of intestinal microflora indicated that fish fed a diet with 300 mg kg-1 β-glucan had higher bacterial richness and diversity as evaluated by Sobs, Chao, Ace, and Simpson indices, but no significant differences were found in the comparison groups. Furthermore, 300 mg kg-1 β-glucan significantly increased the relative abundance of Mycoplasma and decreased Proteobacteria (mainly Escherichia-Shigella and Escherichia coli) and Bacillus anthracis in largemouth bass intestinal microflora. The findings of this study provided new insights that will be valuable in future studies to elucidate the mechanism of immunity enhancement by β-glucan.
Livestock-associated methicillin-resistant Staphylococcus aureus epidemiology, genetic diversity, and clinical characteristics in an urban region
Authors: Konstantinovski Maria M. , Schouls Leo M. , Witteveen Sandra , Claas Eric C. J. , Kraakman Margriet E. , Kalpoe Jayant , Mattson Eva , Hetem David J. , van Elzakker Erika P. M. , Kerremans Jos , Hira Vishal , Bosch Thijs , Gooskens Jairo 
Published: December 2022

ObjectivesWhile Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA), defined as CC398, is a well-known pathogen among those working with livestock, there are indications that LA-MRSA prevalence among the general population is increasing. However, the clinical impact in urban areas remains unknown. The aim of this study was to assess the genetic epidemiology and clinical characteristics of LA-MRSA in an urban area with a limited livestock population.MethodsIn this retrospective study, we evaluated LA-MRSA strains that were collected between 2014 and 2018 from patients who received clinical care in a single urban area in Netherlands. Patient files were assessed for livestock exposure data, clinical findings, and contact tracing information. Next-generation sequencing (NGS) analysis in combination with wgMLST was conducted to assess genetic diversity and relatedness and to detect virulence and resistance genes.ResultsLA-MRSA strains were cultured from 81 patients, comprising 12% of all the MRSA strains found in seven study laboratories between 2014 and 2018. No livestock link was found in 76% of patients (n = 61), and 28% of patients (n = 23) had an infection, mostly of the skin or soft tissue. Contact tracing had been initiated in 14 cases, leading to the identification of two hospital transmissions: a cluster of 9 cases and one of 2 cases. NGS data were available for 91% (n = 75) of the patients. wgMLST confirmed the clusters detected via contact tracing (n = 2) and identified 5 additional clusters without a known epidemiological link. Relevant resistance and virulence findings included the PVL virulence gene (3 isolates) and tetracycline resistance (79 isolates).ConclusionLA-MRSA may cause a relevant burden of disease in urban areas. Surprisingly, most infections in the present study occurred in the absence of a livestock link, suggesting inter-human transmission. These findings and the presence of PVL and other immune evasive complex virulence genes warrant future surveillance and preventative measures.
Case Report: Deep brain stimulation improves tremor in FGF-14 associated spinocerebellar ataxia
Authors: Loeffler Moritz A. , Synofzik Matthis , Cebi Idil , Klocke Philipp , Hormozi Mohammad , Gasser Thomas , Gharabaghi Alireza , Weiss Daniel 
Published: December 2022

ObjectivesSpinocerebellar ataxia 27 (SCA 27) is a rare heredodegenerative disorder caused by mutations in the fibroblast growth factor 14 (FGF14) and characterized by early-onset tremor and progressive ataxia later during the disease course. We investigated the effect of deep brain stimulation (DBS) of the ventralis intermedius nucleus of the thalamus (VIM) and subthalamic projections on tremor and ataxia.MethodsAt baseline, we studied the effects of high-frequency VIM stimulation and low-frequency stimulation of subthalamic projections on tremor and ataxia. The patient then adopted the best individual high-frequency stimulation programme at daytime and either 30 Hz-stimulation of the subthalamic contacts or StimOFF at night during two separate 5-weeks follow-up intervals. Both patient and rater were blinded to the stimulation settings.ResultsHigh-frequency stimulation of the VIM effectively attenuated tremor. At follow-up, intermittent 30 Hz-stimulation at night resulted in a superior tremor response compared to StimOFF at night. Ataxia was not affected.DiscussionStimulation of the VIM and adjacent subthalamic projections effectively attenuated tremor in a patient with confirmed SCA 27. Cycling between daytime high-frequency and night-time low-frequency stimulation led to a more sustained tremor response. This suggests to study in future if low-frequency stimulation of the subthalamic projection fibers may help overcome tolerance of tremor that is observed as a long-term limitation of VIM-DBS.
Endovascular treatment of acute ischemic stroke with a fully radiopaque retriever: A randomized controlled trial
Authors: Zhang Yongxin , Liu Pei , Li Zifu , Peng Ya , Chen Wenhuo , Zhang Liyong , Chu Jianfeng , Kuai Dong , Chen Zhen , Wu Wei , Xu Yun , Zhang Yong , Zhou Bin , Geng Yu , Yin Congguo , Li Jiang , Wang Ming , Zhai Naichi , Peng Xiaoxiang , Ji Zhong , Xiao Yaping , Zhu Xingen , Cai Xueli , Zhang Lei , Hong Bo , Xing Pengfei , Shen Hongjian , Zhang Yongwei , Li Minghua , Shang Meixia , Liu Jianmin , Yang Pengfei 
Published: December 2022

ObjectiveThe Neurohawk retriever is a new fully radiopaque retriever. A randomized controlled non-inferiority trial was conducted to compare the Neurohawk and the Solitaire FR in terms of safety and efficacy. In order to evaluate the efficacy and safety of endovascular treatment in acute ischemic stroke (AIS) caused by intracranial atherosclerotic disease (ICAD) larger vessel occlusion (LVO), a sub-analysis was performed.MethodsAcute ischemic stroke patients aged 18–80 years with LVO in the anterior circulation were randomly assigned to undergo thrombectomy with either the Neurohawk or the Solitaire FR. The primary efficacy endpoint was successful reperfusion (mTICI 2b-3) rate by the allocated retriever. A relevant non-inferiority margin was 12.5%. Safety outcomes were symptomatic intracranial hemorrhage (sICH) and all-cause mortality within 90 days. Secondary endpoints included first-pass effect (FPE), modified FPE, and favorable outcomes at 90 days. In subgroup analysis, the patients were divided into the ICAD group and non-ICAD group according to etiology, and baseline characteristics, angiographic, and clinical outcomes were compared.ResultsA total of 232 patients were involved in this analysis (115 patients in the Neurohawk group and 117 in the Solitaire group). The rates of successful reperfusion with the allocated retriever were 88.70% in the Neurohawk group and 90.60% in the Solitaire group (95%CI of the difference, −9.74% to 5.94%; p = 0.867). There were similar results in FPE and mFPE in both groups. The rate of sICH seemed higher in the Solitaire group (13.16% vs. 7.02%, p = 0.124). All-cause mortality and favorable outcome rates were comparable as well. In subgroup analysis, 58 patients were assigned to the ICAD group and the remaining 174 to the non-ICAD group. The final successful reperfusion and favorable outcome rates showed no statistically significant differences in two groups. Mortality within 90 days was relatively lower in the ICAD group (6.90% vs. 17.24%; p = 0.054).ConclusionThe Neurohawk retriever is non-inferior to the Solitaire FR in the mechanical thrombectomy of large vessel occlusion-acute ischemic stroke (LVO-AIS). The sub-analysis suggested that endovascular treatment including thrombectomy with the retriever and essential rescue angioplasty is effective and safe in AIS patients with intracranial atherosclerotic disease-larger vessel occlusion (ICAD-LVO).Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04995757, number: NCT04995757.
Phase-dependent modulation of the vestibular–cerebellar network via combined alternating current stimulation influences human locomotion and posture
Authors: Nakazono Hisato , Taniguchi Takanori , Mitsutake Tsubasa , Takeda Akinori , Yamada Emi , Ogata Katsuya 
Published: December 2022

BackgroundHuman locomotion induces rhythmic movements of the trunk and head. Vestibular signaling is relayed to multiple regions in the brainstem and cerebellum, and plays an essential role in maintaining head stability. However, how the vestibular–cerebellar network contributes to the rhythmic locomotor pattern in humans is unclear. Transcranial alternating current stimulation (tACS) has been used to investigate the effects of the task-related network between stimulation regions in a phase-dependent manner. Here, we investigated the relationship between the vestibular system and the cerebellum during walking imagery using combined tACS over the left cerebellum and alternating current galvanic vestibular stimulation (AC-GVS).MethodsIn Experiment 1, we tested the effects of AC-GVS alone at around individual gait stride frequencies. In Experiment 2, we then determined the phase-specificity of combined stimulation at the gait frequency. Combined stimulation was applied at in-phase (0° phase lag) or anti-phase (180° phase lag) between the left vestibular and left cerebellar stimulation, and the sham stimulation. We evaluated the AC-GVS-induced periodic postural response during walking imagery or no-imagery using the peak oscillatory power on the angular velocity signals of the head in both experiments. In Experiment 2, we also examined the phase-locking value (PLV) between the periodic postural responses and the left AC-GVS signals to estimate entrainment of the postural response by AC-GVS.ResultsAC-GVS alone induced the periodic postural response in the yaw and roll axes, but no interactions with imagery walking were observed in Experiment 1 (p &gt; 0.05). By contrast, combined in-phase stimulation increased yaw motion (0.345 ± 0.23) compared with sham (−0.044 ± 0.19) and anti-phase stimulation (−0.066 ± 0.18) during imaginary walking (in-phase vs. other conditions, imagery: p &lt; 0.05; no-imagery: p ≥ 0.125). Furthermore, there was a positive correlation between the yaw peak power of actual locomotion and in-phase stimulation in the imagery session (imagery: p = 0.041; no-imagery: p = 0.177). Meanwhile, we found no imagery-dependent effects in roll peak power or PLV, although in-phase stimulation enhanced roll motion and PLV in Experiment 2.ConclusionThese findings suggest that combined stimulation can influence vestibular–cerebellar network activity, and modulate postural control and locomotion systems in a temporally sensitive manner. This novel combined tACS/AC-GVS stimulation approach may advance development of therapeutic applications.
Decreased circulating branched-chain amino acids are associated with development of Alzheimer’s disease in elderly individuals with mild cognitive impairment
Authors: Ikeuchi Takeshi , Kanda Mayuka , Kitamura Hitomi , Morikawa Fumiyoshi , Toru Shuta , Nishimura Chika , Kasuga Kensaku , Tokutake Takayoshi , Takahashi Tetsuya , Kuroha Yasuko , Miyazawa Nobuhiko , Tanaka Shin , Utsumi Kumiko , Ono Kenjiro , Yano Satoshi , Hamano Tadanori , Naruse Satoshi , Yajima Ryuji , Kawashima Noriko , Kaneko Chikako , Tachibana Hisatsugu , Yano Yuki , Kato Yumiko , Toue Sakino , Jinzu Hiroko , Kitamura Akihiko , Yokoyama Yuri , Kaneko Eiji , Yamakado Minoru , Nagao Kenji 
Published: December 2022

BackgroundNutritional epidemiology has shown that inadequate dietary protein intake is associated with poor brain function in the elderly population. The plasma free amino acid (PFAA) profile reflects nutritional status and may have the potential to predict future changes in cognitive function. Here, we report the results of a 2-year interim analysis of a 3-year longitudinal study following mild cognitive impairment (MCI) participants.MethodIn a multicenter prospective cohort design, MCI participants were recruited, and fasting plasma samples were collected. Based on clinical assessment of cognitive function up to 2 years after blood collection, MCI participants were divided into two groups: remained with MCI or reverted to cognitively normal (“MCI-stable,” N = 87) and converted to Alzheimer’s disease (AD) (“AD-convert,” N = 68). The baseline PFAA profile was compared between the two groups. Stratified analysis based on apolipoprotein E ε4 (APOE ε4) allele possession was also conducted.ResultsPlasma concentrations of all nine essential amino acids (EAAs) were lower in the AD-convert group. Among EAAs, three branched-chain amino acids (BCAAs), valine, leucine and isoleucine, and histidine (His) exhibited significant differences even in the logistic regression model adjusted for potential confounding factors such as age, sex, body mass index (BMI), and APOE ε4 possession (p &lt; 0.05). In the stratified analysis, differences in plasma concentrations of these four EAAs were more pronounced in the APOE ε4-negative group.ConclusionThe PFAA profile, especially decreases in BCAAs and His, is associated with development of AD in MCI participants, and the difference was larger in the APOE ε4-negative population, suggesting that the PFAA profile is an independent risk indicator for AD development. Measuring the PFAA profile may have importance in assessing the risk of AD conversion in the MCI population, possibly reflecting nutritional status.Clinical trial registration[https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000025322], identifier [UMIN000021965].
Antioxidant, anti-inflammatory and immunomodulatory effects of spirulina in exercise and sport: A systematic review
Authors: Calella Patrizia , Cerullo Giuseppe , Di Dio Mirella , Liguori Fabrizio , Di Onofrio Valeria , Gallè Francesca , Liguori Giorgio 
Published: December 2022

Arthrospira platensis, also known as spirulina, is currently one of the most well-known algae supplements, mainly due to its high content of bioactive compounds that may promote human health. Some authors have hypothesized that spirulina consumption could protect subjects from exercise-induced oxidative stress, accelerate recovery by reducing muscle damage, and stimulate the immune system. Based on this, the main goal of this review was to critically analyze the effects of spirulina on oxidative stress, immune system, inflammation and performance in athletes and people undergoing exercise interventions. Of the 981 articles found, 428 studies were considered eligible and 13 met the established criteria and were included in this systematic review. Most recently spirulina supplementation has demonstrated ergogenic potential during submaximal exercise, increasing oxygen uptake and improving exercise tolerance. Nevertheless, spirulina supplementation does not seem to enhance physical performance in power athletes. Considering that data supporting benefits to the immune system from spirulina supplementation is still lacking, overall evidence regarding the benefit of spirulina supplementation in healthy people engaged in physical exercise is scarce and not consistent. Currently, spirulina supplementation might be considered in athletes who do not meet the recommended dietary intake of antioxidants. Further high-quality research is needed to evaluate the effects of spirulina consumption on performance, the immune system and recovery in athletes and active people.Systematic review registration[https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=262896], identifier [CRD42021262896].
Case Report: Bronchial artery embolization and chemoradiotherapy for central squamous cell lung carcinoma with rapid regression
Authors: Zhou Siqi , Zhang Jianxin , Meng Xue , Meng Yingtao , Han Xiao 
Published: December 2022

BackgroundInterventional embolization is a common treatment for hemoptysis, one of the complications of lung cancer. However, there are no official guidelines for the use of this method in antitumor therapy.Case DescriptionHerein, we describe a case of a patient who was pathologically diagnosed as central squamous cell lung cancer. The patient received chemotherapy, interventional embolization and radiotherapy successively. The tumor regressed rapidly within 48 hours of receipt of interventional embolization. Furthermore, the tumor decreased by more than 50% in size within 7 days during radiotherapy. Unfortunately, the patient has since developed lymph node metastases and remains under treatment.ConclusionsThus, finding the suitable blood vessel embolized may be a suitable option to reduce the local tumor load and can be considered as antitumor therapy in combination with other treatments. The patient’s theoretical hypoxia state after interventional therapy still produced a good tumor regression after radiotherapy. However, so far, no related studies have reported the changes of tumor immune microenvironment in human body after intervention and radiotherapy.
Plasma exosomal miR-320d, miR-4479, and miR-6763-5p as diagnostic biomarkers in epithelial ovarian cancer
Authors: Wang Shiwen , Song Xingguo , Wang Kangyu , Zheng Baibing , Lin Qinghai , Yu Miao , Xie Li , Chen Liang , Song Xianrang 
Published: December 2022

BackgroundExosomal miRNA had been proved as the promising biomarkers for multiple cancers including epithelial ovarian cancer (EOC). This study aimed to validate the diagnostic accuracy of exosomal miR-320d, miR-4479, and miR-6763-5p for EOC.Materials and methodsExosomes isolated from the plasma by ultracentrifugation were verified using TEM, qNano and western blot. MiRNAs sequencing was used to screen out the differential exosomal miRNAs and miR-320d, miR-4479, and miR-6763-5p were selected as candidates, which were further verified by RT-qPCR in 168 healthy donors and 161 primary EOC patients. Besides, the diagnostic accuracy of these three exosomal miRNAs were evaluated using the receiver operating characteristic curve (ROC).ResultsMiRNAs sequencing revealed 95 differential exosomal miRNAs between EOC patients and healthy donors. Subsequently, exosomal miR-320d, miR-4479, and miR-6763-5p were significantly down regulated in EOC patients compared with healthy controls and benign patients. More importantly, these three miRNAs could serve as circulating diagnostics biomarkers for EOC, possessing areas under the curve (AUC) of 0.6549, 0.7781, and 0.6834, respectively. Moreover, these three exosomal miRNAs levels were closely associated with lymph node metastasis, meanwhile exosomal miR-320d and miR-4479 expression was related to tumor stage.ConclusionExosomal miR-320d, miR-4479, and miR-6763-5p might serve as potential biomarkers for EOC.