bluuebunny/crossref_metadata_2025_split huggingface dataset:
Focal vibrations enhance somatosensory facilitation in healthy subjects: A pilot study on Equistasi® and high-frequency oscillations
Authors: Cruciani Alessandro , Lanzone Jacopo , Musumeci Gabriella , Di Lazzaro Vincenzo , Marano Massimo 
Published: November 2022

BackgroundEquistasi® is a vibrotactile device composed of nanotechnology fibers that converts temperature change into mechanical energy by self-producing a focal vibration. It is used in non-pharmacological rehabilitation in patients with movement disorders and multiple sclerosis sequelae. Nonetheless, the mechanism underlying such an improvement in motor functions is still poorly understood.ObjectivesWe designed a small uncontrolled pilot trial to explore the effect of Equistasi® on the somatosensory pathway through the analysis of high-frequency oscillations (HFOs).MethodsFor all the included subjects, we recorded somatosensory-evoked potentials (SEPs) at the baseline (T0) and at 60 min after the application of Equistasi® (T1) on the seventh cervical vertebra level and at the forearm over each flexor carpi radialis, bilaterally. Then, we extracted the HFOs from the N20 signal and compared the HFO duration and area under the curve pre- and post-Equistasi® application.ResultsIn a head-to-head comparison of T0 to T1 data, there was a statistically significant reduction in the total HFO area (p &lt; 0.01), which was prominent for the late component (p = 0.025). No statistical differences have been found between T0 and T1 HFO duration (p &gt; 0.05). We further evaluated the N20 amplitude from the onset to the N20 peak to avoid possible interpretational bias. No statistical differences have been found between T0 and T1 (p = 0.437).ConclusionOur clinical hypothesis, supported by preliminary data, is that vibrotactile afference delivered by the device could work by interfering with the somatosensory processing, rather than by peripheral effects.
Predictions of task using neural modeling
Authors: Fox Elizabeth L. , Ugolini Margaret , Houpt Joseph W. 
Published: November 2022

IntroductionA well-designed brain-computer interface (BCI) can make accurate and reliable predictions of a user's state through the passive assessment of their brain activity; in turn, BCI can inform an adaptive system (such as artificial intelligence, or AI) to intelligently and optimally aid the user to maximize the human-machine team (HMT) performance. Various groupings of spectro-temporal neural features have shown to predict the same underlying cognitive state (e.g., workload) but vary in their accuracy to generalize across contexts, experimental manipulations, and beyond a single session. In our work we address an outstanding challenge in neuroergonomic research: we quantify if (how) identified neural features and a chosen modeling approach will generalize to various manipulations defined by the same underlying psychological construct, (multi)task cognitive workload.MethodsTo do this, we train and test 20 different support vector machine (SVM) models, each given a subset of neural features as recommended from previous research or matching the capabilities of commercial devices. We compute each model's accuracy to predict which (monitoring, communications, tracking) and how many (one, two, or three) task(s) were completed simultaneously. Additionally, we investigate machine learning model accuracy to predict task(s) within- vs. between-sessions, all at the individual-level.ResultsOur results indicate gamma activity across all recording locations consistently outperformed all other subsets from the full model. Our work demonstrates that modelers must consider multiple types of manipulations which may each influence a common underlying psychological construct.DiscussionWe offer a novel and practical modeling solution for system designers to predict task through brain activity and suggest next steps in expanding our framework to further contribute to research and development in the neuroergonomics community. Further, we quantified the cost in model accuracy should one choose to deploy our BCI approach using a mobile EEG-systems with fewer electrodes—a practical recommendation from our work.
Association between blood selenium levels and gestational diabetes mellitus: A systematic review and meta-analysis
Authors: Yan Shuai , Su Han , Xia Yang , Yan Zixuan , Gao Yitao , Shi Mengyuan , Liu Huiyuan , Wen Yu , Zhao Yuhong , Chang Qing 
Published: November 2022

IntroductionThe association between blood (serum or plasma) selenium concentrations and gestational diabetes mellitus (GDM) has been evaluated in some studies. However, the reported findings are debatable, and only case-control and cross-sectional studies were included.ObjectiveThis research aimed to assess the association between blood selenium levels and GDM by analyzing existing literature. To provide a reference for the prevention and treatment of GDM, we included prospective studies which are not included in previous studies to collate more high-quality evidence and better test the etiological hypothesis between blood Se concentrations and GDM.MethodsThe PubMed, EMBASE, and Web of Science databases were retrieved for literature up to September 2022, and relevant references were manually searched. Raw data from relevant studies were extracted, and a random effect model was adopted for meta-analysis. The total effects were reported as weighted mean differences. All data were analyzed using Stata 16.0 software.ResultsFourteen studies involving 890 pregnant women with GDM and 1618 healthy pregnant women were incorporated in the meta-analysis. Pregnancies with GDM had significantly lower blood selenium levels than those with normal glucose tolerance (weighted mean difference = −8.11; 95% confidence interval: −12.68 to −3.54, P = 0.001). Subgroup analyses showed that the association between blood selenium levels and GDM was consistent in the residents of Asia and Africa, but not in European. This trend was significant in the second and third trimester subgroups, but not in the first trimester subgroup. Articles published in 2006–2015 also showed this trend, but those published before 2005 and 2016–2019 did not show significant results. This difference was evident in non-prospective studies, but not significant in prospective studies. Studies using the Carpenter and Coustan diagnostic criteria were consistent with this trend, whereas studies using other diagnostic criteria found no differences. In addition, in terms of blood selenium measurement methods, atomic absorption spectrometry showed more significant differences than other methods. In the subgroup analysis based on the sample size of included studies and the quality of the studies, each subgroup showed statistical differences.ConclusionLower blood selenium concentrations are associated with GDM as shown in our study. Therefore, supplementing an appropriate amount of selenium may be helpful for GDM prevention and treatment.
Phase I trial of pembrolizumab plus vemurafenib and cobimetinib in patients with metastatic melanoma
Authors: Shaikh Saba S. , Zang Yan , Hanmer Janel , Wang Hong , Lin Yan , Davar Diwakar , Zarour Hassane M. , Kirkwood John M. , Najjar Yana G. 
Published: November 2022

BackgroundPreclinical and translational evidence suggest BRAF/MEK inhibitors modulate the tumor microenvironment (TME), providing rationale for combination with immunotherapy.MethodsThis investigator-initiated, phase I trial evaluated pembrolizumab, vemurafenib, and cobimetinib in patients with untreated, BRAFV600E/K mutant advanced melanoma. The first 4 patients received vemurafenib with pembrolizumab, and the next 5 patients received vemurafenib and cobimetinib with pembrolizumab. Primary endpoints: safety and maximum tolerated dose of the triplet.Secondary endpointsobjective response rate (ORR), progression-free survival (PFS), overall survival (OS), and quality of life (QoL). The trial was closed after enrollment of 9 (planned 30) patients due to dose-limiting toxicity (DLT). Study NCT02818023 was approved by the IRB, and all patients provided informed consent.ResultsPatients received a median of 6 cycles of therapy. 8 of 9 experienced drug-related grade 3/4 AEs. DLTs included dermatitis (n=8), hepatitis (n=1), QTc prolongation (n=1), and arthralgias (n=1 each). QoL assessments identified a clinically significant decrease in self assessed QoL at 1 year compared to baseline (0.38 v 0.43). Median PFS was 20.7 months and median OS was 23.8 months for vemurafenib with pembrolizumab. Median PFS and OS were not reached for patients receiving triple therapy. ORR in the overall cohort was 78% (7/9). 2 patients experienced a complete response, 5 had a partial response, 1 had stable disease, and 1 had progressive disease. 4 patients had ongoing responses at data analysis. Peripheral blood flow cytometry identified significantly decreased PD1 expression on CD4+ T-cells at 3 and 9 weeks compared to baseline, not corresponding to clinical response.ConclusionsTriple therapy with vemurafenib, cobimetinib and pembrolizumab is associated with high response rates but significant adverse events, leading to early study closure.
A novel prognostic model based on cellular senescence-related gene signature for bladder cancer
Authors: Luo Lianmin , Li Fenghua , Gong Binbin , Xi Ping , Xie Wenjie 
Published: November 2022

BackgroundCellular senescence plays crucial role in the progression of tumors. However, the expression patterns and clinical significance of cellular senescence-related genes in bladder cancer (BCa) are still not clearly clarified. This study aimed to establish a prognosis model based on senescence-related genes in BCa.MethodsThe transcriptional profile data and clinical information of BCa were downloaded from TCGA and GEO databases. The least absolute shrinkage and selection operator (LASSO), univariate and multivariate Cox regression analyses were performed to develop a prognostic model in the TCGA cohort. The GSE13507 cohort were used for validation. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and single-sample gene set enrichment analysis (ssGSEA) were performed to investigate underlying mechanisms.ResultsA six-gene signature (CBX7, EPHA3, STK40, TGFB1I1, SREBF1, MYC) was constructed in the TCGA databases. Patients were classified into high risk and low risk group in terms of the median risk score. Survival analysis revealed that patients in the higher risk group presented significantly worse prognosis. Receiver operating characteristic (ROC) curve analysis verified the moderate predictive power of the risk model based on the six senescence-related genes signature. Further analysis indicated that the clinicopathological features analysis were significantly different between the two risk groups. As expected, the signature presented prognostic significance in the GSE13507 cohort. Functional analysis indicated that immune-related pathways activity, immune cell infiltration and immune-related function were different between two risk groups. In addition, risk score were positively correlated with multiple immunotherapy biomarkers.ConclusionOur study revealed that a novel model based on senescence-related genes could serve as a reliable predictor of survival for patients with BCa.
Preoperative differentiation of hepatocellular carcinoma with peripheral rim-like enhancement from intrahepatic mass-forming cholangiocarcinoma on contrast-enhanced MRI
Authors: Zhang Sisi , Huo Lei , Feng Yayuan , Zhang Juan , Wu Yuxian , Liu Yiping , Lu Lun , Jia Ningyang , Liu Wanmin 
Published: November 2022

PurposeThe present study aimed to determine the reliable imaging features to distinguish atypical hepatocellular carcinoma (HCC) with peripheral rim-like enhancement from intrahepatic mass-forming cholangiocarcinoma (IMCC) on contrast-enhanced magnetic resonance imaging (MRI).MethodsA total of 168 patients (130 male, 57.10 ± 10.53 years) pathological confirmed HCC or IMCC who underwent contrast-enhanced MRI between July 2019 and February 2022 were retrospectively included. Univariate and multivariate logistic regression analyses were used to determine independent differential factors for distinguishing HCC from IMCC, and the model was established. Bootstrap resampling 1000 times was used to verify the model, which was visualized by nomograms. The predictive performance of the model was evaluated based on discrimination, calibration, and clinical utility.ResultsRadiological capsule (OR 0.024, 95% CI: 0.006, 0.095, P&lt;0.001), heterogeneous signal intensity (SI) on T1WI (OR 0.009, 95%CI: 0.001,0.056, P&lt;0.001) were independent differential factors for predicting HCC over IMCC. A lobulated contour (OR 11.732, 95%CI: 2.928,47.007, P = 0.001), target sign on DP (OR 14.269, 95%CI: 2.849,82.106, P = 0.007), bile duct dilatation (OR 12.856, 95%CI: 2.013, P = 0.001) were independent differential factors for predicting IMCCs over HCCs. The independent differential factors constituted a model to distinguish atypical HCCs and IMCCs. The area under receiver operating characteristic (ROC) curve, sensitivity, and specificity values of the model were 0.964(0.940,0.987), 0.88, and 0.906, indicating that the model had an excellent differential diagnostic performance. The decision curve analysis (DCA) curve showed that the model obtained a better net clinical benefit.ConclusionThe present study identified reliable imaging features for distinguishing atypical HCCs with peripheral rim-like enhancement from IMCCs on contrast-enhanced MRI. Our findings may help radiologists provide clinicians with more accurate preoperative imaging diagnoses to select appropriate treatment options.
Population pharmacokinetics and dosing optimization of unbound teicoplanin in Chinese adult patients
Authors: Fu Wen-Qian , Tian Ting-Ting , Zhang Min-Xin , Song Hong-Tao , Zhang Li-Li 
Published: November 2022

Objectives: To develop a population pharmacokinetic (PopPK) model describing unbound teicoplanin concentrations in Chinese adult patients and perform Monte Carlo simulations to optimize the dosing regimens.Methods: The raw data for PopPK analysis in this study were collected from Chinese adult patients. A PopPK model of unbound teicoplanin was developed and Monte Carlo simulations were used to optimize the dosing regimens. The trough concentrations of unbound teicoplanin were targeted at 0.75 mg/L and 1.13 mg/L for most infection induced by Gram-positive bacteria and endocarditis or severe infections, respectively.Results: A total of 103 teicoplanin unbound concentrations were collected from 72 Chinese adult patients. A one-compartment pharmacokinetic model with first-order elimination was established. The typical values of clearance and the volume of distribution were 11.7 L/h and 811 L, respectively. The clearance and volume of distribution of unbound teicoplanin were positively correlated with estimated glomerular filtration rate (eGFR) and serum albumin concentrations, respectively. Dosing simulation results showed that standard dosing regimens were unable to meet the treatment needs of all patients, and the dosing regimen need optimize based on eGFR and serum albumin concentrations. The high eGFR and serum albumin concentration were associated with reduced probability of achieving target unbound trough concentrations.Conclusion: We successfully characterized the pharmacokinetics of unbound teicoplanin in Chinese adult patients. Importantly, we further highlight the importance of guiding dosing through unbound drugs. To achieve safe and effective treatment, the dosing regimens need to be adjusted according to eGFR and serum albumin concentrations.
Apol9a regulates myogenic differentiation via the ERK1/2 pathway in C2C12 cells
Authors: Jiang Xuan , Ji Siyu , Cui Siyuan , Wang Rong , Wang Wei , Chen Yongquan , Zhu Shenglong 
Published: November 2022

Background: The rising prevalence of obesity and its complications is a big challenge for the global public health. Obesity is accompanied by biological dysfunction of skeletal muscle and the development of muscle atrophy. The deep knowledge of key molecular mechanisms underlying myogenic differentiation is crucial for discovering novel targets for the treatment of obesity and obesity-related muscle atrophy. However, no effective target is currently known for obesity-induced skeletal muscle atrophy.Methods: Transcriptomic analyses were performed to identify genes associated with the regulation of myogenic differentiation and their potential mechanisms of action. C2C12 cells were used to assess the myogenic effect of Apol9a through immunocytochemistry, western blotting, quantitative polymerase chain reaction, RNA interference or overexpression, and lipidomics.Results: RNA-seq of differentiated and undifferentiated C2C12 cells revealed that Apol9a expression significantly increased following myogenic differentiation and decreased during obesity-induced muscle atrophy. Apol9a silencing in these C2C12 cells suppressed the expression of myogenesis-related genes and reduced the accumulation of intracellular triglycerides. Furthermore, RNA-seq and western blot results suggest that Apol9a regulates myogenic differentiation through the activation of extracellular signal-regulated kinase 1/2 (ERK1/2). This assumption was subsequently confirmed by intervention with PD98059.Conclusion: In this study, we found that Apol9a regulates myogenic differentiation via the ERK1/2 pathway. These results broaden the putative function of Apol9a during myogenic differentiation and provide a promising therapeutic target for intervention in obesity and obesity-induced muscle atrophy.
Remarkable consistency of spinal cord microvasculature in highly adapted diving odontocetes
Authors: Miller Megan L. , Glandon Hillary L. , Tift Michael S. , Pabst D. Ann , Koopman Heather N. 
Published: November 2022

Odontocetes are breath-hold divers with a suite of physiological, anatomical, and behavioral adaptations that are highly derived and vastly different from those of their terrestrial counterparts. Because of these adaptations for diving, odontocetes were originally thought to be exempt from the harms of nitrogen gas embolism while diving. However, recent studies have shown that these mammals may alter their dive behavior in response to anthropogenic sound, leading to the potential for nitrogen supersaturation and bubble formation which may cause decompression sickness in the central nervous system (CNS). We examined the degree of interface between blood, gases, and neural tissues in the spinal cord by quantifying its microvascular characteristics in five species of odontocetes (Tursiops truncatus, Delphinus delphis, Grampus griseus, Kogia breviceps, and Mesoplodon europaeus) and a model terrestrial species (the pig-Sus scrofa domesticus) for comparison. This approach allowed us to compare microvascular characteristics (microvascular density, branching, and diameter) at several positions (cervical, thoracic, and lumbar) along the spinal cord from odontocetes that are known to be either deep or shallow divers. We found no significant differences (p &lt; 0.05 for all comparisons) in microvessel density (9.30–11.18%), microvessel branching (1.60–2.12 branches/vessel), or microvessel diameter (11.83–16.079 µm) between odontocetes and the pig, or between deep and shallow diving odontocete species. This similarity of spinal cord microvasculature anatomy in several species of odontocetes as compared to the terrestrial mammal is in contrast to the wide array of remarkable physio-anatomical adaptations marine mammals have evolved within their circulatory system to cope with the physiological demands of diving. These results, and other studies on CNS lipids, indicate that the spinal cords of odontocetes do not have specialized features that might serve to protect them from Type II DCS.
Yield and quality of alfalfa (Medicago sativa L.) in response to fertilizer application in China: A meta-analysis
Authors: Wan Weifan , Li Yuejin , Li Haigang 
Published: November 2022

IntroductionIn China, alfalfa (Medicago sativa L.) often grows in marginal land with poor soil fertility and suboptimal climate conditions. Alfalfa production cannot meet demands both in yield and quality. It is necessary to apply fertilizers to achieve high yields and produce high-quality alfalfa in China. However, there is no understanding on the impact of fertilizer application on alfalfa production and the possible optimal application rates across China.MethodsWe conducted a meta-analysis to explore the contribution of fertilizer application to the yield and quality of alfalfa based on a dataset from 86 studies published between 2004 and 2022.Results and DiscussionThe results showed that fertilizer application not only increased alfalfa yield by 19.2% but also improved alfalfa quality by increasing crude protein (CP) by 7.7% and decreasing acid detergent fibre by 2.9% and neutral detergent fibre by 1.8% overall compared to the non-fertilizer control levels. The combined nitrogen (N), phosphorus (P) and potassium (K) and combined NP fertilizer applications achieved the greatest yield and CP concentration increases of 27.0% and 13.5%, respectively. Considering both yield and quality, the optimal rate of fertilizer application ranged from 30 to 60 kg ha-1 for N, 120 to 150 kg ha-1 for P and less than 120 kg ha-1 for K. Meta-analysis further showed that the effect of fertilizer application on yield was greater in low soil organic matter (SOM) soils than in high SOM soils. In conclusion, fertilizer application is an effective strategy to improve the yield and quality of alfalfa in China, especially that grown in low SOM soils. This study is helpful for optimizing fertilization schedules of alfalfa in China.
How the European Union legislations are tackling the burden of diabetes mellitus: A legal surveillance study
Authors: Mahrouseh Nour , Lovas Szabolcs , Njuguna Diana Wangeshi , Nellamkuzhi Noel Johny , Soares Andrade Carlos Alexandre , Sackey Wilhelmina Egyirba , Irawan Anggi Septia , Varga Orsolya 
Published: November 2022

IntroductionSurveillance of the European Union's (EU) legislations on the prevention of diabetes mellitus (DM) is needed, to more effectively tackle the rising prevalence of DM.MethodsThis legal surveillance was carried out through a systematic search and screening, using EUR-Lex database to identify treaties, acts, and other legal documents for prevention of DM, non-communicable diseases (NCDs) and obesity, followed by their content analysis and assessment according to DM specific guidelines, target population and functional categories.Results and discussionWe found 22 legislations aimed at preventing DM, NCDs and obesity, but only 5 out of them specifically addressed preventing DM. The aims of legislations covered a broad spectrum of themes indicated by DM specific guidelines, mostly initiatives of life-course approach in preventing DM, NCDs and obesity from the area of energy intake. The target group of most legislations was the general population; high-risk subgroups such as pregnant women were hardly ever the primary target group. Our results prove that the EU has made cross-sectoral legislative efforts to reduce the disease burden and prevent DM but does not exhaust all possibilities. However, given its persistently rising DM prevalence, it is imperative to make sure that DM is a top health priority for various EU authorities and is incorporated into new initiatives, policies and laws.