bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of the gut-microbiome-brain axis in metabolic remodeling amongst children with cerebral palsy and epilepsy
Authors: Peng Ye , Chiu Annie T. G. , Li Vivien W. Y. , Zhang Xi , Yeung Wai L. , Chan Sophelia H. S. , Tun Hein M. 
Published: February 2023

BackgroundEpilepsy-associated dysbiosis in gut microbiota has been previously described, but the mechanistic roles of the gut microbiome in epileptogenesis among children with cerebral palsy (CP) have yet to be illustrated.MethodsUsing shotgun metagenomic sequencing coupled with untargeted metabolomics analysis, this observational study compared the gut microbiome and metabolome of eight children with non-epileptic cerebral palsy (NECP) to those of 13 children with cerebral palsy with epilepsy (CPE). Among children with CPE, 8 had drug-sensitive epilepsy (DSE) and five had drug-resistant epilepsy (DRE). Characteristics at enrollment, medication history, and 7-day dietary intake were compared between groups.ResultsAt the species level, CPE subjects had significantly lower abundances of Bacteroides fragilis and Dialister invisus but higher abundances of Phascolarctobacterium faecium and Eubacterium limosum. By contrast, DRE subjects had a significantly higher colonization of Veillonella parvula. Regarding microbial functional pathways, CPE subjects had decreased abundances of pathways for serine degradation, quinolinic acid degradation, glutamate degradation I, glycerol degradation, sulfate reduction, and nitrate reduction but increased abundances of pathways related to ethanol production. As for metabolites, CPE subjects had higher concentrations of kynurenic acid, 2-oxindole, dopamine, 2-hydroxyphenyalanine, 3,4–dihydroxyphenylglycol, L-tartaric acid, and D-saccharic acid; DRE subjects had increased concentrations of indole and homovanilic acid.ConclusionsIn this study, we found evidence of gut dysbiosis amongst children with cerebral palsy and epilepsy in terms of gut microbiota species, functional pathways, and metabolites. The combined metagenomic and metabolomic analyses have shed insights on the potential roles of B. fragilis and D. invisus in neuroprotection. The combined analyses have also provided evidence for the involvement of GMBA in the epilepsy-related dysbiosis of kynurenine, serotonin, and dopamine pathways and their complex interplay with neuroimmune and neuroendocrinological pathways.
The comparison of manual and mechanical anastomosis after total pharyngolaryngoesophagectomy
Authors: Wang Kexi , He Xiaotian , Wu Duoguang , Wang Kefeng , Li Yuquan , Wang Wenjian , Hu Xueting , Lei Kai , Tan Binghua , Liang Ruihao , Cai Qian , Wang Minghui 
Published: February 2023

BackgroundTotal pharyngolaryngoesophagectomy (TPLE) is considered as a curative treatment for hypopharynx cancer and cervical esophageal carcinomas (HPCECs). Traditional pharyngo-gastric anastomosis is usually performed manually, and postoperative complications are common. The aim of this study was to introduce a new technique for mechanical anastomosis and to evaluate perioperative outcomes and prognosis.MethodsFrom May 1995 to Nov 2021, a series of 75 consecutive patients who received TPLE for a pathological diagnosis of HPCECs at Sun Yat-sen Memorial Hospital were evaluated. Mechanical anastomosis was performed in 28 cases and manual anastomosis was performed in 47 cases. The data from these patients were retrospectively analyzed.ResultsThe mean age was 57.6 years, and 20% of the patients were female. The rate of anastomotic fistula and wound infection in the mechanical group were significantly lower than that in the manual group. The operation time, intraoperative blood loss and postoperative hospital stays were significantly higher in the manual group than that in the mechanical group. The R0 resection rate and the tumor characteristics were not significantly different between groups. There was no significant difference in overall survival and disease-free survival between the two groups.ConclusionThe mechanical anastomosis technology adopted by this study was shown to be a safer and more effective procedure with similar survival comparable to that of manual anastomosis for the HPCECs patients.
The gene regulatory molecule GLIS3 in gastric cancer as a prognostic marker and be involved in the immune infiltration mechanism
Authors: Ding Yi , Wang Zehua , Chen Chen , Wang Chenxu , Li Dongyu , Qin Yanru 
Published: February 2023

BackgroundGastric cancer is the most prevalent solid tumor form. Even after standard treatment, recurrence and malignant progression are nearly unavoidable in some cases of stomach cancer. GLIS Family Zinc Finger 3 (GLIS3) has received scant attention in gastric cancer research. Therefore, we sought to examine the prognostic significance of GLIS3 and its association with immune infiltration in gastric cancer.MethodUsing public data from The Cancer Genome Atlas (TCGA), we investigated whether GLIS3 gene expression was linked with prognosis in patients with stomach cancer (STAD). The following analyses were performed: functional enrichment analysis (GSEA), quantitative real-time PCR, immune infiltration analysis, immunological checkpoint analysis, and clinicopathological analysis. We performed functional validation of GLIS3 in vitro by plate cloning and CCK8 assay. Using univariate and multivariate Cox regression analyses, independent prognostic variables were identified. Additionally, a nomogram model was built. The link between OS and subgroup with GLIS3 expression was estimated using Kaplan-Meier survival analysis. Gene set enrichment analysis utilized the TCGA dataset.ResultGLIS3 was significantly upregulated in STAD. An examination of functional enrichment revealed that GLIS3 is related to immunological responses. The majority of immune cells and immunological checkpoints had a positive correlation with GLIS3 expression. According to a Kaplan-Meier analysis, greater GLIS3 expression was related to adverse outcomes in STAD. GLIS3 was an independent predictive factor in STAD patients, as determined by Cox regression (HR = 1.478, 95%CI = 1.478 (1.062-2.055), P=0.02)ConclusionGLIS3 is considered a novel STAD patient predictive biomarker. In addition, our research identifies possible genetic regulatory loci in the therapy of STAD.
Clinicopathological characteristics and treatment outcome of resectable gastric cancer patients with small para-aortic lymph node
Authors: Yao Zhendan , Yang Hong , Cui Ming , Xing Jiadi , Zhang Chenghai , Zhang Nan , Chen Lei , Tan Fei , Xu Kai , Liu Maoxing , Su Xiangqian 
Published: February 2023

BackgroundResectable gastric cancer (GC) patients with small para-aortic lymph node (smaller than 10mm in diameter, sPAN) were seldom reported, and existing guidelines did not provide definite treatment recommendation for them.MethodsA total of 667 consecutive resectable GC patients were enrolled. 98 patients were in the sPAN group, and 569 patients without enlarged para-aortic lymph node were in the nPAN group. Standard D2 lymphadenectomy was performed. Neoadjuvant and adjuvant chemotherapy were administrated according to the cTNM and pTNM stage, respectively. Clinicopathological features and prognosis were compared between these two groups.ResultsThe median size of sPAN was 6 (range, 2−9) mm and the distribution was prevalent in No. 16b1. cN stage (p=0.001) was significantly related to the presence of sPAN. sPAN was both independent risk factor for OS (p=0.031) and RFS (p=0.046) of all patients. The prognosis of patients with sPAN was significantly worse than that of patients with nPAN (OS: p=0.008; RFS: p=0.007). Preoperative CEA and CA19-9 were independent risk factors for prognosis of patients with sPAN. Furthermore, patients in the sPAN group with normal CEA and CA19-9 exhibited acceptable prognosis (5-year OS: 67%; RFS: 64%), while those with elevated CEA or CA19-9 suffered significantly poorer prognosis (5-year OS: 17%; RFS: 17%) than patients in the nPAN group (5-year OS: 64%; RFS 62%) (both p &lt; 0.05).ConclusionsStandard D2 lymphadenectomy should be considered a valid approach for GC patients with sPAN associate to normal preoperative CEA and CA19-9 levels. Patients with sPAN associated to elevated CEA or CA19-9 levels could benefit from a multimodal approach: neoadjuvant chemotherapy; radical surgery with D2 plus lymph nodal dissection extended to No. 16 station.
Integrative population pharmacokinetic/pharmacodynamic analysis of nemonoxacin capsule in Chinese patients with community-acquired pneumonia
Authors: Chen Yuancheng , Wu Xiaojie , Tsai Chengyuan , Chang Liwen , Yu Jicheng , Cao Guoying , Guo Beining , Shi Yaoguo , Zhu Demei , Hu Fupin , Yuan Jinyi , Liu Yang , Zhao Xu , Zhang Yingyuan , Wu Jufang , Zhang Jing 
Published: February 2023

Introduction: Nemonoxacin is an innovative quinolone antibiotic for treatment of community-acquired pneumonia (CAP). As more data are available from clinical studies, it is necessary to perform an integrative pharmacokinetic/pharmacodynamic (PK/PD) analysis to support and justify the optimal dosing regimen of nemonoxacin in clinical practice.Methods and Results: We developed a population PK model using non-linear mixed effect model based on the data of 195 Chinese subjects receiving nemonoxacin in phase I to III clinical trials. The base model was a standard two-compartment PK model defined by clearance (12 L/h) and central volume of distribution (86 L). Covariates included creatinine clearance (CLcr), body weight (BW), sex, disease status and food. Compared to the subject with BW 60 kg, Cmax and AUC0‐24, ss reduced by 24% and 19% in the subject with BW 80 kg, respectively. Compared to the subject with CLcr 150 ml/min, AUC0‐24, ss and T1/2 increased by 28% and 24%, respectively in the subject with CLcr 30 ml/min. Compared to the fasted status, Tmax of nemonoxacin increased by 1.2 h in the subject with fed status. Effects of sex and disease status on PK parameters were small (change of PK parameters ≤19%). AUC0–24/MIC and %T &gt; MIC were identified as the optimal PK/PD indices for predicting clinical efficacy. The AUC0-24/MIC target was 63.3, 97.8, and 115.7 against Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae, respectively. The %T &gt; MIC target was 7.96% against Klebsiella pneumoniae. Monte Carlo simulation showed that treatment with nemonoxacin 500 mg q24 h could attain a PK/PD cutoff value higher than the MIC90 against S. pneumoniae and S. aureus. The corresponding cumulative fraction of response (CFR) was greater than 93%, while nemonoxacin 750 mg q24 h would provide higher PK/PD cutoff value against Haemophilus parainfluenzae, and higher CFR (83%) than 500 mg q24 h.Conclusion: Integrative PK/PD analysis justifies the reliable clinical and microbiological efficacy of nemonoxacin 500 mg q24 h in treating CAP caused by S. pneumoniae, S. aureus, and K. pneumoniae, irrespective of patient sex, mild renal impairment, empty stomach or not. However, nemonoxacin 750 mg q24 h would provide better efficacy than 500 mg q24 h for the CAP caused by H. parainfluenzae in terms of CFR.
Studies of different kernel functions in nuclear mass predictions with kernel ridge regression
Authors: Wu X. H. 
Published: February 2023

The kernel ridge regression (KRR) approach has been successfully applied in nuclear mass predictions. Kernel function plays an important role in the KRR approach. In this work, the performances of different kernel functions in nuclear mass predictions are carefully explored. The performances are illustrated by comparing the accuracies of describing experimentally known nuclei and the extrapolation abilities. It is found that the accuracies of describing experimentally known nuclei in the KRR approaches with most of the adopted kernels can reach the same level around 195 keV, and the performance of the Gaussian kernel is slightly better than other ones in the extrapolation validation for the whole range of the extrapolation distances.
The effect of Tabata-style functional high-intensity interval training on cardiometabolic health and physical activity in female university students
Authors: Lu Yining , Wiltshire Huw D. , Baker Julien Steven , Wang Qiaojun , Ying Shanshan 
Published: February 2023

Introduction: The increasing prevalence of metabolic syndrome and physical inactivity enhances exposure to cardiometabolic risk factors in university students. High-intensity interval training (HIIT) improved cardiometabolic health in clinical adults but the evidence in the university setting is limited. Furthermore, few studies examined the effect of low-volume HIIT on habitual physical activity (PA). Therefore, the primary aim of this study was to evaluate the efficacy of 12-week Tabata-style functional HIIT for improving multiple cardiometabolic health outcomes and habitual PA. We also investigated whether changes in habitual PA over the intervention period had an impact on exercise-induced health outcomes.Methods: 122 female freshmen were randomized into the Tabata group (n = 60) and the control (n = 62). The Tabata training protocol involved 8 × 20 s maximal repeated functional exercises followed by 10 s rest with a frequency of 3 times per week for 12 weeks. Body composition, maximal oxygen uptake (VO2max), blood pressure (BP), blood lipids, fasting glucose and insulin, C-reactive protein and PA were objectively measured using standardized methods. Dietary intake was measured using a valid food frequency questionnaire. All variables were measured pre- and post-intervention.Results: Mixed linear modelling results showed that there were large intervention effects on VO2max (p &lt; 0.001, d = 2.53, 95% CI: 2.03 to 3.00 for relative VO2max; p &lt; 0.001, d = 2.24, 95% CI: 1.76 to 2.68 for absolute VO2max), resting heart rate (p &lt; 0.001, d = −1.82, 95% CI: −2.23 to −1.37), systolic BP (p &lt; 0.001, d = −1.24, 95% CI: −1.63 to −0.84), moderate-to-vigorous intensity physical activity (MVPA) (p &lt; 0.001, d = 2.31, 95% CI: 1.83 to 2.77), total PA (p &lt; 0.001, d = 1.98, 95% CI: 1.53 to 2.41); moderate effects on %BF (p &lt; 0.001, d = -1.15, 95% CI: −1.53 to −0.75), FM (p &lt; 0.001, d = −1.08, 95% CI: −1.46 to −0.69), high-density lipoprotein (HDL) (p &lt; 0.001, d = 1.04, 95% CI: 0.65 to 1.42), total cholesterol (p = 0.001, d = −0.64, 95% CI: −1.00 to −0.26); small effects on BMI (p = 0.011, d = −0.48, 95% CI: −0.84 to 0.11), WC (p = 0.043, d = −0.37, 95% CI: −0.74 to −0.01), low-density lipoprotein (p = 0.003, d = −0.57, 95% CI: −0.93 to −0.19), HOMA-IR (p = 0.026, d = −0.42, 95% CI: −0.78 to −0.05) and fasting insulin (p = 0.035, d = −0.40, 95% CI: −0.76 to −0.03). Regression analysis showed that only the percentage change of HDL was associated with the change of MVPA (b = 0.326, p = 0.015) and TPA (b = 0.480, p = 0.001).Conclusion: From the findings of the study we can conclude that 12-week low-volume Tabata-style functional HIIT was highly effective for university female students to improve cardiorespiratory fitness, body fat, some cardiometabolic health outcomes and habitual PA.
A real-time and convex model for the estimation of muscle force from surface electromyographic signals in the upper and lower limbs
Authors: Shirzadi Mehdi , Marateb Hamid Reza , Rojas-Martínez Mónica , Mansourian Marjan , Botter Alberto , Vieira dos Anjos Fabio , Martins Vieira Taian , Mañanas Miguel Angel 
Published: February 2023

Surface electromyography (sEMG) is a signal consisting of different motor unit action potential trains and records from the surface of the muscles. One of the applications of sEMG is the estimation of muscle force. We proposed a new real-time convex and interpretable model for solving the sEMG—force estimation. We validated it on the upper limb during isometric voluntary flexions-extensions at 30%, 50%, and 70% Maximum Voluntary Contraction in five subjects, and lower limbs during standing tasks in thirty-three volunteers, without a history of neuromuscular disorders. Moreover, the performance of the proposed method was statistically compared with that of the state-of-the-art (13 methods, including linear-in-the-parameter models, Artificial Neural Networks and Supported Vector Machines, and non-linear models). The envelope of the sEMG signals was estimated, and the representative envelope of each muscle was used in our analysis. The convex form of an exponential EMG-force model was derived, and each muscle’s coefficient was estimated using the Least Square method. The goodness-of-fit indices, the residual signal analysis (bias and Bland-Altman plot), and the running time analysis were provided. For the entire model, 30% of the data was used for estimation, while the remaining 20% and 50% were used for validation and testing, respectively. The average R-square (%) of the proposed method was 96.77 ± 1.67 [94.38, 98.06] for the test sets of the upper limb and 91.08 ± 6.84 [62.22, 96.62] for the lower-limb dataset (MEAN ± SD [min, max]). The proposed method was not significantly different from the recorded force signal (p-value = 0.610); that was not the case for the other tested models. The proposed method significantly outperformed the other methods (adj. p-value &lt; 0.05). The average running time of each 250 ms signal of the training and testing of the proposed method was 25.7 ± 4.0 [22.3, 40.8] and 11.0 ± 2.9 [4.7, 17.8] in microseconds for the entire dataset. The proposed convex model is thus a promising method for estimating the force from the joints of the upper and lower limbs, with applications in load sharing, robotics, rehabilitation, and prosthesis control for the upper and lower limbs.
Effects of two-week machine massage on muscle properties in adolescent wrestlers
Authors: Qu Guangcai , Wang Hongbo , Zhou Guohai , Liu Haiping 
Published: February 2023

Objective: This study aimed to investigate the effect of a two-week machine massage on the physical properties of the erector spinae and serum biochemical indexes of adolescent athletes after training.Methods: Sixteen male adolescent wrestlers were recruited (age: 15 ± 1 year; height: 166 ± 7 cm; weight: 56 ± 7 kg) and randomly assigned to machine massage (MA, 8) and control (CO, 8) groups. Participants in the MA group received machine massage for 20 min after each wrestling training from Monday to Saturday (except on Thursday) for two weeks, while the participants in the CO group recovered naturally. Over the course of two weeks, all the participants underwent similar wrestling training program under the guidance of a professional coach. Before and after the intervention, serum urea and creatine kinase (CK) levels were measured in a fasting state. A Myoton Pro digital muscle evaluation system was used to measure the physical properties of the erector spinae, including the oscillation frequency, logarithmic decrement of a muscle’s natural oscillation, and dynamic stiffness.Results: After two weeks of machine massage treatment, the dynamic stiffness of the erector spinae in the MA group decreased by 12.90% and that in the CO group increased by 2.34%, indicating a significant difference between the two groups (p = 0.04, ƞ2 = 0.286). The decrease in the logarithmic decrement of a muscle’s natural oscillation value in the MA was significantly greater than that in the CO (p = 0.003, ƞ2 = 0.286). Moreover, the serum CK values decreased by 33.84% in the MA group and by 1.49% in the CO group, despite a trend of change between the groups (p = 0.062, ƞ2 = 0.084). No significant difference was found in the improvement in serum urea levels between the two groups after two weeks of treatment.Conclusion: Results of the present study indicated that a two-week machine massage had a positive effect on the improvement of the physical properties of the erector spinae of wrestlers during training.
VPS45 is required for both diffuse and tip growth of Arabidopsis thaliana cells
Authors: Mugume Yosia , Roy Rahul , Agbemafle William , Shepard Gabriella N. , Vue Yee , Bassham Diane C. 
Published: February 2023

IntroductionVPS45 belongs to the Sec1/Munc18 family of proteins, which interact with and regulate Qa-SNARE function during membrane fusion. We have shown previously that Arabidopsis thaliana VPS45 interacts with the SYP61/SYP41/VTI12 SNARE complex, which locates on the trans-Golgi network (TGN). It is required for SYP41 stability, and it functions in cargo trafficking to the vacuole and in cell expansion. It is also required for correct auxin distribution during gravitropism and lateral root growth.ResultsAs vps45 knockout mutation is lethal in Arabidopsis, we identified a mutant, vps45-3, with a point mutation in the VPS45 gene causing a serine 284-to-phenylalanine substitution. The VPS45-3 protein is stable and maintains interaction with SYP61 and SYP41. However, vps45-3 plants display severe growth defects with significantly reduced organ and cell size, similar to vps45 RNAi transgenic lines that have reduced VPS45 protein levels. Root hair and pollen tube elongation, both processes of tip growth, are highly compromised in vps45-3. Mutant root hairs are shorter and thicker than those of wild-type plants, and are wavy. These root hairs have vacuolar defects, containing many small vacuoles, compared with WT root hairs with a single large vacuole occupying much of the cell volume. Pollen tubes were also significantly shorter in vps45-3 compared to WT.DiscussionWe thus show that VPS45 is essential for proper tip growth and propose that the observed vacuolar defects lead to loss of the turgor pressure needed for tip growth.
Improving the efficacy of plant-made anti-HIV monoclonal antibodies for clinical use
Authors: Grandits Melanie , Grünwald-Gruber Clemens , Gastine Silke , Standing Joseph F. , Reljic Rajko , Teh Audrey Y-H. , Ma Julian K-C. 
Published: February 2023

IntroductionBroadly neutralising antibodies are promising candidates for preventing and treating Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS), as an alternative to or in combination with antiretroviral therapy (ART). These mAbs bind to sites on the virus essential for virus attachment and entry, thereby inhibiting entry into the host cell. However, the cost and availability of monoclonal antibodies, especially combinations of antibodies, hampers implementation of anti-HIV bNAb therapies in low- to middle- income countries (LMICs) where HIV-1 prevalence is highest.MethodsWe have produced three HIV broadly neutralizing antibodies (bNAbs), 10-1074, VRC01 and 3BNC117 in the Nicotiana benthamiana transient expression system. The impact of specific modifications to enhance potency and efficacy were assessed. To prolong half-life and increase bioavailability, a M252Y/S254T/T256E (YTE) or M428L/N434S (LS) mutation was introduced. To increase antibody dependent cellular cytotoxicity (ADCC), we expressed an afucosylated version of each antibody using a glycoengineered plant line.ResultsThe majority of bNAbs and their variants could be expressed at yields of up to 47 mg/kg. Neither the expression system nor the modifications impacted the neutralization potential of the bNAbs. Afucosylated bNAbs exhibit enhanced ability to bind to FcγRIIIa and trigger ADCC, regardless of the presence of Fc amino acid mutations. Lastly, we demonstrated that Fc-modified variants expressed in plants show enhanced binding to FcRn, which results in a favourable in vivo pharmacokinetic profile compared to their unmodified counterparts. ConclusionTobacco plants are suitable expression hosts for anti-HIV bNAbs with increased efficacy and an improved pharmacokinetic profile.