bluuebunny/crossref_metadata_2025 huggingface dataset:
Complex Involvement of Interleukin-26 in Bacterial Lung Infection
Authors: Che Karlhans F. , Paulsson Magnus , Piersiala Krzysztof , Sax Jakob , Mboob Ibrahim , Rahman Mizanur , Rekha Rokeya S. , Säfholm Jesper , Adner Mikael , Bergman Peter , Cardell Lars-Olaf , Riesbeck Kristian , Lindén Anders
Published: October 2021

Pneumonia is a global cause of mortality, and this provides a strong incentive to improve the mechanistic understanding of innate immune responses in the lungs. Here, we characterized the involvement of the cytokine interleukin (IL)-26 in bacterial lung infection. We observed markedly increased concentrations of IL-26 in lower airway samples from patients with bacterial pneumonia and these correlated with blood neutrophil concentrations. Moreover, pathogen-associated molecular patterns (PAMPs) from both Gram-negative and -positive bacteria increased extracellular IL-26 concentrations in conditioned media from human models of alveolar epithelial cells, macrophages, and neutrophils in vitro. Stimulation with IL-26 inhibited the inherent release of neutrophil elastase and myeloperoxidase in unexposed neutrophils. This stimulation also inhibited the expression of activity makers in neutrophils exposed to Klebsiella pneumoniae. In addition, priming of human lung tissue ex vivo with exogenous IL-26 potentiated the endotoxin-induced increase in mRNA for other cytokines involved in the innate immune response, including the master Th17-regulator IL-23 and the archetype inhibitory cytokine IL-10. Finally, neutralization of endogenous IL-26 clearly increased the growth of Klebsiella pneumoniae in the macrophage culture. These findings suggest that IL-26 is involved in bacterial lung infection in a complex manner, by modulating critical aspects of innate immune responses locally and systemically in a seemingly purposeful manner and by contributing to the killing of bacteria in a way that resembles an antimicrobial peptide. Thus, IL-26 displays both diagnostic and therapeutic potential in pneumonia and deserves to be further evaluated in these respects.
Comprehensive Analysis of Differentially Expressed mRNA, Non-coding RNA, and Their Competitive Endogenous RNA Network of Pacific Oyster Crassostrea gigas With Different Glycogen Content Between Different Environments
Authors: Wang Xue , Wang Weijun , Li Zan , Sun Guohua , Xu Tao , Xu Xiaohui , Feng Yanwei , Luo Qihao , Li Bin , Yang Jianmin
Published: October 2021

Glycogen content is a quantitative trait, its phenotype differences are found between individual oysters due to genetic effects and environmental factors which were including food, water temperature, salinity, and so on. In this study, a full sibling family of Pacific oyster Crassostrea gigas showed different phenotypes with high and low glycogen content between South Huanghai Sea (Rizhao offshore area, RZ) and North Huanghai Sea (Kongtong Dao area, KTD), respectively. At the same time, the content of 11 glucogenic amino acids and 13 fatty acids were also significant differences between RZ and KTD. RNA-seq and small RNA-seq technologies were used for transcriptome sequencing and functional enrichment analysis of differentially expressed RNA were used by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. A total of 2,084 mRNAs, 1,080 long non-coding RNAs (lncRNAs), 34 circular RNAs (circRNAs), and 7 microRNAs (miRNAs) were differentially expressed. Based on these differentially expressed genes (DEGs), miRNA target interactions (lncRNA/circRNA–miRNA pairs and miRNA–mRNA pairs) were predicted using the miRanda software. The differentially expressed mRNAs in this network were mainly shown to be involved in calcium signaling pathway and insulin signaling pathway. These findings could help to speculate that environmental factors may be epigenetically regulated by non-coding RNA in C. gigas, thereby further affecting glycogen content.
Tracing the Atmospheric Input of Seawater-Dissolvable Pb Based on the Budget of 210Pb in the East Sea (Japan Sea)
Authors: Seo Hojong , Kim Guebuem , Kim Young-Il , Kim Intae
Published: October 2021

In order to determine the atmospheric input of 210Pb and seawater-dissolvable Pb in the East Sea (Japan Sea), we measured the concentrations of total 210Pb and dissolved Pb (<0.2 μm) in seawater and 210Pb and 226Ra in sinking particles. The East Sea is deep (∼3700 m) and enclosed by surrounding continents except for the shallow sills (<150 m). Since the East Sea is located off the East Asian continent under the westerlies, the concentrations of 210Pb and dissolved Pb in this sea are significantly affected by terrestrial sources through the atmosphere. The vertical profiles of total 210Pb and dissolved Pb generally showed a surface maximum and then decreased with depth. The concentrations of dissolved Pb in the surface water were 2 and 3 times higher than those in the North Pacific and North Atlantic Oceans, respectively. Using an independent box model (upper 1000 m or 2000 m), we estimate the atmospheric input of 210Pb to be 1.46 ± 0.25 dpm cm−2 y −1, which is within the range of published results from the land-based sites (0.44–4.40 dpm cm−2 y −1) in South Korea, China, and Japan. Based on this flux, the residence time of total 210Pb in the East Sea is calculated to be approximately 7.1 ± 1.6 years, which is twice lower than the previous estimation. Combining the residence time of 210Pb and the inventory of dissolved Pb, the atmospheric input of seawater-dissolvable Pb is estimated to be 0.98 ± 0.28 nmol cm−2 y −1. This flux is approximately 25% of the Pb flux through the wet deposition (acid-leachable fraction). Thus, our results suggest that the flux and fate of atmospheric Pb in the ocean can be successfully determined using an accurate mass balance model of naturally occurring 210Pb.
Angiogenesis Pathway in Kidney Renal Clear Cell Carcinoma and Its Prognostic Value for Cancer Risk Prediction
Authors: Che Xiangyu , Su Wenyan , Li Xiaowei , Liu Nana , Wang Qifei , Wu Guangzhen
Published: October 2021

Angiogenesis, a process highly regulated by pro-angiogenic and anti-angiogenic factors, is disrupted and dysregulated in cancer. Despite the increased clinical use of angiogenesis inhibitors in cancer therapy, most molecularly targeted drugs have been less effective than expected. Therefore, an in-depth exploration of the angiogenesis pathway is warranted. In this study, the expression of angiogenesis-related genes in various cancers was explored using The Cancer Genome Atlas datasets, whereupon it was found that most of them were protective genes in the patients with kidney renal clear cell carcinoma (KIRC). We divided the samples from the KIRC dataset into three clusters according to the mRNA expression levels of these genes, with the enrichment scores being in the order of Cluster 2 (upregulated expression) > Cluster 3 (normal expression) > Cluster 1 (downregulated expression). The survival curves plotted for the three clusters revealed that the patients in Cluster 2 had the highest overall survival rates. Via a sensitivity analysis of the drugs listed on the Genomics of Drug Sensitivity in Cancer database, we generated IC50 estimates for 12 commonly used molecularly targeted drugs for KIRC in the three clusters, which can provide a more personalized treatment plan for the patients according to angiogenesis-related gene expression. Subsequently, we investigated the correlation between the angiogenesis pathway and classical cancer-related genes as well as that between the angiogenesis score and immune cell infiltration. Finally, we used the least absolute shrinkage and selection operator (LASSO)–Cox regression analysis to construct a risk score model for predicting the survival of patients with KIRC. According to the areas under the receiver operating characteristic (ROC) curves, this new survival model based on the angiogenesis-related genes had high prognostic prediction value. Our results should provide new avenues for the clinical diagnosis and treatment of patients with KIRC.
Odisha Revisited: A Personal Account
Authors: Serjeant Graham R. , Kulozik Andreas E. , Serjeant Beryl E.
Published: October 2021

In 1986, a paper in the Lancet was the first to collate hematology, molecular findings, and clinical features of homozygous sickle cell (SS) disease in India. The paper came from the group organized by Professor Bimal Kar in Burla Medical College, Sambalpur University, in western Odisha. Although widely quoted, few readers will be aware of the history of this work that is now attached in an informal summary.
The Spectrum of Manifestations of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) Infection in Children: What We Can Learn From Multisystem Inflammatory Syndrome in Children (MIS-C)
Authors: Panaro Salvatore , Cattalini Marco
Published: October 2021

Multisystem Inflammatory Syndrome in Children (MIS-C) is defined as a clinically serious condition requiring hospitalization with fever, multi-system organ disfunction, inflammatory biomarkers increase. The syndrome develops in the context of a probable or ascertained Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2) infection, but other possible etiologies should be ruled out for definitive diagnosis. On the clinical side, along with the multi-system involvement, myocarditis with heart failure and shock is the most striking feature. Capillary leak is another fundamental feature of MIS-C. In fact, shock and hemodynamic compromise in MIS-C can occur also in the absence of laboratory evidence of myocardial inflammation, with preserved cardiac function and rapid reversibility. Since the first observations of MIS-C patients, it was evident that there is a delay between the peak of adult cases of Coronavirus disease 19 (COVID-19) and the MIS-C peak. Moreover, SARS-Cov2 isolation in children with MIS-C is not always possible, due to low viral load, while positive serology is far more commonly observed. These observations lead to the interpretation of MIS-C as a post-infectious disease. Although the exact pathogenesis of MIS-C is far from being elucidated, it is clear that it is a hyperinflammatory disease with a different inflammatory response as compared to what is seen in acute SARS-CoV-2 infection and that the disease shares some, but not all, immunological features with Macrophage Activation Syndrome (MAS), Kawasaki Disease (KD), Hemophagocytic Lymphohistiocytosis (HLH), and Toxic Shock Syndrome (TSS). Different mechanisms have been hypothesized as being responsible, from molecular mimicry to antibody dependent enhancement (ADE). Some evidence has also been collected on the immunological profile of patients with MIS-C and their difference from COVID-19. This review is focused on critical aspects of MIS-C clinical presentation and pathogenesis, and different immunological profiles. We propose a model where this hyperinflammatory disease represents one manifestation of the SARS-CoV2 spectrum in children, going from asymptomatic carriers to the post-infectious MIS-C, through symptomatic children, a low number of which may suffer from a severe infection with hyperinflammation (pediatric Hyper-COVID).
Profiling Tryptophan Catabolites of Human Gut Microbiota and Acute-Phase Protein Levels in Neonatal Dried Blood Specimens
Authors: Aust Anne-Christine , Benesova Eliska , Vidova Veronika , Coufalikova Katerina , Smetanova Sona , Borek Ivo , Janku Petr , Budinska Eva , Klanova Jana , Thon Vojtech , Spacil Zdenek
Published: October 2021

National screening programs use dried blood specimens to detect metabolic disorders or aberrant protein functions that are not clinically evident in the neonatal period. Similarly, gut microbiota metabolites and immunological acute-phase proteins may reveal latent immune aberrations. Microbial metabolites interact with xenobiotic receptors (i.e., aryl hydrocarbon and pregnane-X) to maintain gastrointestinal tissue health, supported by acute-phase proteins, functioning as sensors of microbial immunomodulation and homeostasis. The delivery (vaginal or cesarean section) shapes the microbial colonization, which substantially modulates both the immune system’s response and mucosal homeostasis. This study profiled microbial metabolites of the kynurenine and tryptophan pathway and acute-phase proteins in 134 neonatal dried blood specimens. We newly established neonatal blood levels of microbial xenobiotic receptors ligands (i.e., indole-3-aldehyde, indole-3-butyric acid, and indole-3-acetamide) on the second day of life. Furthermore, we observed diverse microbial metabolic profiles in neonates born vaginally and via cesarean section, potentially due to microbial immunomodulatory influence. In summary, these findings suggest the supportive role of human gut microbiota in developing and maintaining immune system homeostasis.
The Visual Dictionary of Antimicrobial Stewardship, Infection Control, and Institutional Surveillance Data
Authors: Keizer Julia , Luz Christian F. , Sinha Bhanu , van Gemert-Pijnen Lisette , Albers Casper , Beerlage-de Jong Nienke , Glasner Corinna
Published: October 2021

Objectives: Data and data visualization are integral parts of (clinical) decision-making in general and stewardship (antimicrobial stewardship, infection control, and institutional surveillance) in particular. However, systematic research on the use of data visualization in stewardship is lacking. This study aimed at filling this gap by creating a visual dictionary of stewardship through an assessment of data visualization (i.e., graphical representation of quantitative information) in stewardship research.

Methods: A random sample of 150 data visualizations from published research articles on stewardship were assessed (excluding geographical maps and flowcharts). The visualization vocabulary (content) and design space (design elements) were combined to create a visual dictionary. Additionally, visualization errors, chart junk, and quality were assessed to identify problems in current visualizations and to provide improvement recommendations.

Results: Despite a heterogeneous use of data visualization, distinct combinations of graphical elements to reflect stewardship data were identified. In general, bar (n = 54; 36.0%) and line charts (n = 42; 28.1%) were preferred visualization types. Visualization problems comprised color scheme mismatches, double y-axis, hidden data points through overlaps, and chart junk. Recommendations were derived that can help to clarify visual communication, improve color use for grouping/stratifying, improve the display of magnitude, and match visualizations to scientific standards.

Conclusion: Results of this study can be used to guide data visualization creators in designing visualizations that fit the data and visual habits of the stewardship target audience. Additionally, the results can provide the basis to further expand the visual dictionary of stewardship toward more effective visualizations that improve data insights, knowledge, and clinical decision-making.
Bifidobacterial β-Galactosidase-Mediated Production of Galacto-Oligosaccharides: Structural and Preliminary Functional Assessments
Authors: Ambrogi Valentina , Bottacini Francesca , Mac Sharry John , van Breen Justin , O’Keeffe Ellen , Walsh Dan , Schoemaker Barry , Cao Linqiu , Kuipers Bas , Lindner Cordula , Jimeno Maria Luisa , Doyagüez Elisa G. , Hernandez-Hernandez Oswaldo , Moreno F. Javier , Schoterman Margriet , van Sinderen Douwe
Published: October 2021

In the current study the ability of four previously characterized bifidobacterial β-galactosidases (designated here as BgaA, BgaC, BgaD, and BgaE) to produce galacto-oligosaccharides (GOS) was optimized. Of these enzymes, BgaA and BgaE were found to be promising candidates for GOS production (and the corresponding GOS mixtures were called GOS-A and GOS-E, respectively) with a GOS concentration of 19.0 and 40.3% (of the initial lactose), respectively. GOS-A and GOS-E were partially purified and structurally characterized. NMR analysis revealed that the predominant (non-lactose) disaccharide was allo-lactose in both purified GOS preparations. The predominant trisaccharide in GOS-A and GOS-E was shown to be 3′-galactosyllactose, with lower levels of 6′-galactosyllactose and 4′-galactosyllactose. These three oligosaccharides have also been reported to occur in human milk. Purified GOS-A and GOS-E were shown to be able to support bifidobacterial growth similar to a commercially available GOS. In addition, GOS-E and the commercially available GOS were shown to be capable of reducing Escherichia coli adhesion to a C2BBe1 cell line. Both in vitro bifidogenic activity and reduced E. coli adhesion support the prebiotic potential of GOS-E and GOS-A.
Inflamma-MicroRNAs in Alzheimer’s Disease: From Disease Pathogenesis to Therapeutic Potentials
Authors: Liang Yuanyuan , Wang Lin
Published: October 2021

Alzheimer’s disease (AD) is the most common cause of senile dementia. Although AD research has made important breakthroughs, the pathogenesis of this disease remains unclear, and specific AD diagnostic biomarkers and therapeutic strategies are still lacking. Recent studies have demonstrated that neuroinflammation is involved in AD pathogenesis and is closely related to other health effects. MicroRNAs (miRNAs) are a class of endogenous short sequence non-coding RNAs that indirectly inhibit translation or directly degrade messenger RNA (mRNA) by specifically binding to its 3′ untranslated region (UTR). Several broadly expressed miRNAs including miR-21, miR-146a, and miR-155, have now been shown to regulate microglia/astrocytes activation. Other miRNAs, including miR-126 and miR-132, show a progressive link to the neuroinflammatory signaling. Therefore, further studies on these inflamma-miRNAs may shed light on the pathological mechanisms of AD. The differential expression of inflamma-miRNAs (such as miR-29a, miR-125b, and miR-126-5p) in the peripheral circulation may respond to AD progression, similar to inflammation, and therefore may become potential diagnostic biomarkers for AD. Moreover, inflamma-miRNAs could also be promising therapeutic targets for AD treatment. This review provides insights into the role of inflamma-miRNAs in AD, as well as an overview of general inflamma-miRNA biology, their implications in pathophysiology, and their potential roles as biomarkers and therapeutic targets.
Cerebral Microbleed Burden in Ischemic Stroke Patients on Aspirin: Prospective Cohort of Intracranial Hemorrhage
Authors: Xu Chong-xi , Xu Hui , Yi Tong , Yi Xing-yang , Ma Jun-peng
Published: October 2021

Objective: This investigation aimed at studying the prevalence of cerebral microbleeds (CMBs), including risk factors and the correlation of CMBs to ischemic stroke (IS) patient end results.

Methods: Four hundred and fifty-nine acute IS cases were recruited between April 2014 and December 2016. Cerebral microbleeds were analyzed using susceptibility-weighted imaging (SWI) brain MRI scan. The enrolled patients with acute IS were followed up for 12–24 months, with a median follow-up time of 19 months. The follow-up endpoint events including recurrent ischemic stroke (RIS), intracranial hemorrhage (ICH), transient ischemic attack (TIA), mortality, and cardiovascular events. The associations between vascular risk factors and CMBs in IS patients were analyzed using univariate and multivariate logistic regression analysis. Cox regression model was employed for evaluating CMB impact on clinical outcome.

Results: Among 459 enrolled patients, 187 (40.7%) had CMBs and 272 (59.2%) had no CMB. In comparison with patients with no CMBs, age was higher and hypertension was more frequent in patients with CMBs. Multivariate logistic regression analyses revealed age and hypertension were independently associated with the presence of CMBs. Among the patient cohort, 450 cases completed the follow-up. During the follow-up period, 22 (4.9%) of patients developed ICH, 12 (2.7%) developed TIA, 68 (15.1%) developed RIS, cardiovascular events occurred in 20 (4.44%), and 13 (2.89%) cases were mortalities. Compared with patients without CMBs, IS patients with CMBs have an increased prevalence of ICH (p < 0.05). However, no statistically valid variations regarding other outcome incidences between both groups was identified (p > 0.05). The incidence of ICH was elevated in tandem with elevations in number of CMBs. Following adjusting for age, multivariate Cox proportional-hazards regression analysis revealed that CMBs ≥10 were independent predictors of ICH in acute IS patients.

Conclusion: Age and hypertension are independently associated with the presence of CMBs. Intracranial hemorrhage incidence rate was increased with the number of CMBs, and the number of CMBs ≥10 were independent predictors of ICH in acute stroke patients.
Corticospinal Excitability of the Lower Limb Muscles During the Anticipatory Postural Adjustments: A TMS Study During Dart Throwing
Authors: Matsumoto Amiri , Liang Nan , Ueda Hajime , Irie Keisuke
Published: October 2021

Objective: To investigate whether the changes in the corticospinal excitability contribute to the anticipatory postural adjustments (APAs) in the lower limb muscles when performing the ballistic upper limb movement of the dart throwing.

Methods: We examined the primary motor cortex (M1) excitability of the lower limb muscles [tibialis anterior (TA) and soleus (SOL) muscles] during the APA phase by using transcranial magnetic stimulation (TMS) in the healthy volunteers. The surface electromyography (EMG) of anterior deltoid, triceps brachii, biceps brachii, TA, and SOL muscles was recorded and the motor evoked potential (MEP) to TMS was recorded in the TA muscle along with the SOL muscle. TMS at the hotspot of the TA muscle was applied at the timings immediately prior to the TA onset. The kinematic parameters including the three-dimensional motion analysis and center of pressure (COP) during the dart throwing were also assessed.

Results: The changes in COP and EMG of the TA muscle occurred preceding the dart throwing, which involved a slight elbow flexion followed by an extension. The correlation analysis revealed that the onset of the TA muscle was related to the COP change and the elbow joint flexion. The MEP amplitude in the TA muscle, but not that in the SOL muscle, significantly increased immediately prior to the EMG burst (100, 50, and 0 ms prior to the TA onset).

Conclusion: Our findings demonstrate that the corticospinal excitability of the TA muscle increases prior to the ballistic upper limb movement of the dart throwing, suggesting that the corticospinal pathway contributes to the APA in the lower limb in a muscle-specific manner.
Functional Connectivity and Networks Underlying Complex Tool-Use Movement in Assembly Workers: An fMRI Study
Authors: Taniguchi Seira , Higashi Yuichiro , Kataoka Hirotaka , Nakajima Hiroshi , Shimokawa Tetsuya
Published: October 2021

The aim of this study was to identify the functional connectivity and networks utilized during tool-use in real assembly workers. These brain networks have not been elucidated because the use of tools in real-life settings is more complex than that in experimental environments. We evaluated task-related functional magnetic resonance imaging in 13 assembly workers (trained workers, TW) and 27 age-matched volunteers (untrained workers, UTW) during a tool-use pantomiming task, and resting-state functional connectivity was also analyzed. Two-way repeated-measures analysis of covariance was conducted with the group as a between-subject factor (TW > UTW) and condition (task > resting) as a repeated measure, controlling for assembly time and accuracy as covariates. We identified two patterns of functional connectivity in the whole brain within three networks that distinguished TW from UTW. TW had higher connectivity than UTW between the left middle temporal gyrus and right cerebellum Crus II (false discovery rate correctedp-value,p-FDR = 0.002) as well as between the left supplementary motor area and the pars triangularis of the right inferior frontal gyrus (p-FDR = 0.010). These network integrities may allow for TW to perform rapid tool-use. In contrast, UTW showed a stronger integrity compared to TW between the left paracentral lobule and right angular gyrus (p-FDR = 0.004), which may reflect a greater reliance on sensorimotor input to acquire complex tool-use ability than that of TW. Additionally, the fronto-parietal network was identified as a common network between groups. These findings support our hypothesis that assembly workers have stronger connectivity in tool-specific motor regions and the cerebellum, whereas UTW have greater involvement of sensorimotor networks during a tool-use task.
Ipsilesional Mu Rhythm Desynchronization Correlates With Improvements in Affected Hand Grip Strength and Functional Connectivity in Sensorimotor Cortices Following BCI-FES Intervention for Upper Extremity in Stroke Survivors
Authors: Remsik Alexander B. , Gjini Klevest , Williams Leroy , van Kan Peter L. E. , Gloe Shawna , Bjorklund Erik , Rivera Cameron A. , Romero Sophia , Young Brittany M. , Nair Veena A. , Caldera Kristin E. , Williams Justin C. , Prabhakaran Vivek
Published: October 2021

Stroke is a leading cause of acquired long-term upper extremity motor disability. Current standard of care trajectories fail to deliver sufficient motor rehabilitation to stroke survivors. Recent research suggests that use of brain-computer interface (BCI) devices improves motor function in stroke survivors, regardless of stroke severity and chronicity, and may induce and/or facilitate neuroplastic changes associated with motor rehabilitation. The present sub analyses of ongoing crossover-controlled trial NCT02098265 examine first whether, during movements of the affected hand compared to rest, ipsilesional Mu rhythm desynchronization of cerebral cortical sensorimotor areas [Brodmann’s areas (BA) 1-7] is localized and tracks with changes in grip force strength. Secondly, we test the hypothesis that BCI intervention results in changes in frequency-specific directional flow of information transmission (direct path functional connectivity) in BA 1-7 by measuring changes in isolated effective coherence (iCoh) between cerebral cortical sensorimotor areas thought to relate to electrophysiological signatures of motor actions and motor learning. A sample of 16 stroke survivors with right hemisphere lesions (left hand motor impairment), received a maximum of 18–30 h of BCI intervention. Electroencephalograms were recorded during intervention sessions while outcome measures of motor function and capacity were assessed at baseline and completion of intervention. Greater desynchronization of Mu rhythm, during movements of the impaired hand compared to rest, were primarily localized to ipsilesional sensorimotor cortices (BA 1-7). In addition, increased Mu desynchronization in the ipsilesional primary motor cortex, Post vs. Pre BCI intervention, correlated significantly with improvements in hand function as assessed by grip force measurements. Moreover, the results show a significant change in the direction of causal information flow, as measured by iCoh, toward the ipsilesional motor (BA 4) and ipsilesional premotor cortices (BA 6) during BCI intervention. Significant iCoh increases from ipsilesional BA 4 to ipsilesional BA 6 were observed in both Mu [8–12 Hz] and Beta [18–26 Hz] frequency ranges. In summary, the present results are indicative of improvements in motor capacity and behavior, and they are consistent with the view that BCI-FES intervention improves functional motor capacity of the ipsilesional hemisphere and the impaired hand.
Suppressing of Power Line Artifact From Electroencephalogram Measurements Using Sparsity in Frequency Domain
Authors: Tan Jin-Lin , Liang Zhi-Feng , Zhang Rui , Dong You-Qiang , Li Guang-Hui , Zhang Min , Wang Hai , Xu Na
Published: October 2021

Electroencephalogram (EEG) plays an important role in brain disease diagnosis and research of brain-computer interface (BCI). However, the measurements of EEG are often exposed to strong interference of power line artifact (PLA). Digital notch filters (DNFs) can be applied to remove the PLA effectively, but it also results in severe signal distortions in the time domain. To address this problem, spectrum correction (SC) based methods can be utilized. These methods estimate harmonic parameters of the PLA such that compensation signals are produced to remove the noise. In order to ensure high accuracy during harmonic parameter estimations, a novel approach is proposed in this paper. This novel approach is based on the combination of sparse representation (SR) and SC. It can deeply mine the information of PLA in the frequency domain. Firstly, a ratio-based spectrum correction (RBSC) using rectangular window is employed to make rough estimation of the harmonic parameters of PLA. Secondly, the two spectral line closest to the estimated frequency are calculated. Thirdly, the two spectral lines with high amplitudes can be utilized as input of RBSC to make finer estimations of the harmonic parameters. Finally, a compensation signal, based on the extracted harmonic parameters, is generated to suppress PLA. Numerical simulations and actual EEG signals with PLA were used to evaluate the effectiveness of the improved approach. It is verified that this approach can effectively suppress the PLA without distorting the time-domain waveform of the EEG signal.
Comparing Biomarkers for Predicting Pathological Responses to Neoadjuvant Therapy in HER2-Positive Breast Cancer: A Systematic Review and Meta-Analysis
Authors: Zhao Fuxing , Huo Xingfa , Wang Miaozhou , Liu Zhen , Zhao Yi , Ren Dengfeng , Xie Qiqi , Liu Zhilin , Li Zitao , Du Feng , Shen Guoshuang , Zhao Jiuda
Published: October 2021

Introduction

The predictive strength and accuracy of some biomarkers for the pathological complete response (pCR) to neoadjuvant therapy for HER2-positive breast cancer remain unclear. This study aimed to compare the accuracy of the HER2-enriched subtype and the presence of PIK3CA mutations, namely, TILs, HRs, and Ki-67, in predicting the pCR to HER2-positive breast cancer therapy.

Methods

We screened studies that included pCR predicted by one of the following biomarkers: the HER2-enriched subtype and the presence of PIK3CA mutations, TILs, HRs, or Ki-67. We then calculated the pooled sensitivity, specificity, positive and negative predictive values (PPVs and NPVs, respectively), and positive and negative likelihood ratios (LRs). Summary receiver operating characteristic (SROC) curves and areas under the curve (AUCs) were used to estimate the diagnostic accuracy.

Results

The pooled estimates of sensitivity and specificity for the HER2-enriched subtype and the presence of PIK3CA mutations, namely, TILs, HRs, and Ki-67, were 0.66 and 0.62, 0.85 and 0.27, 0.49 and 0.61, 0.54 and 0.64, and 0.68 and 0.51, respectively. The AUC of the HER2-enriched subtype was significantly higher (0.71) than those for the presence of TILs (0.59, p = 0.003), HRs (0.65, p = 0.003), and Ki-67 (0.62, p = 0.005). The AUC of the HER2-enriched subtype had a tendency to be higher than that of the presence of PIK3CA mutations (0.58, p = 0.220). Moreover, it had relatively high PPV (0.58) and LR+ (1.77), similar NPV (0.73), and low LR− (0.54) compared with the other four biomarkers.

Conclusions

The HER2-enriched subtype has a moderate breast cancer diagnostic accuracy, which is better than those of the presence of PIK3CA mutations, TILs, HRs, and Ki-67.
Prognostic Role of the C-Reactive Protein/Albumin Ratio in Patients With Gynecological Cancers: A Meta-Analysis
Authors: Fang Yingji , Zheng Tingting , Zhang Chengling
Published: October 2021

Background

Many studies have investigated the prognostic role of the C-reactive protein/albumin ratio (CRP/Alb ratio) in patients with gynecological cancers; however, there is lack of consensus owing to conflicting results across studies. We performed a meta-analysis to determine the prognostic role of the CRP/Alb ratio in gynecological cancers.

Methods

We searched the PubMed, Embase, the Web of Science, Cochrane Library, China National Knowledge Infrastructure, and Wanfang electronic databases since inception to April 2021. Combined hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the prognostic effect of the CRP/Alb ratio in gynecological cancers. Pooled odds ratios (ORs) and 95% CIs were used to investigate the association between the CRP/Alb ratio and clinicopathological features.

Results

The meta-analysis included seven studies with 1,847 patients. The pooled results showed that a high pretreatment CRP/Alb ratio was associated with poor overall survival (HR, 1.84; 95% CI, 1.41–2.40; p < 0.001) and progression-/disease-free survival (HR, 2.58; 95% CI, 1.42–4.68; p = 0.002). Additionally, a high CRP/Alb ratio was significantly associated with stages III–IV disease (the International Federation of Gynecology and Obstetrics classification) (OR, 2.98; 95% CI, 1.45–6.14; p = 0.003). However, we observed a non-significant correlation between the CRP/Alb ratio and lymph node metastasis, tumor size, and histopathological grade.

Conclusions

The CRP/Alb ratio is a convenient and accurate predictor of survival outcomes in gynecological cancers. A high CRP/Alb ratio also predicts tumor progression.
KDM4 Involvement in Breast Cancer and Possible Therapeutic Approaches
Authors: Varghese Benluvankar , Del Gaudio Nunzio , Cobellis Gilda , Altucci Lucia , Nebbioso Angela
Published: October 2021

Breast cancer (BC) is the second leading cause of cancer death in women, although recent scientific and technological achievements have led to significant improvements in progression-free disease and overall survival of patients. Genetic mutations and epigenetic modifications play a critical role in deregulating gene expression, leading to uncontrolled cell proliferation and cancer progression. Aberrant histone modifications are one of the most frequent epigenetic mechanisms occurring in cancer. In particular, methylation and demethylation of specific lysine residues alter gene accessibility via histone lysine methyltransferases (KMTs) and histone lysine demethylases (KDMs). The KDM family includes more than 30 members, grouped into six subfamilies and two classes based on their sequency homology and catalytic mechanisms, respectively. Specifically, the KDM4 gene family comprises six members, KDM4A-F, which are associated with oncogene activation, tumor suppressor silencing, alteration of hormone receptor downstream signaling, and chromosomal instability. Blocking the activity of KDM4 enzymes renders them “druggable” targets with therapeutic effects. Several KDM4 inhibitors have already been identified as anticancer drugs in vitro in BC cells. However, no KDM4 inhibitors have as yet entered clinical trials due to a number of issues, including structural similarities between KDM4 members and conservation of the active domain, which makes the discovery of selective inhibitors challenging. Here, we summarize our current knowledge of the molecular functions of KDM4 members in BC, describe currently available KDM4 inhibitors, and discuss their potential use in BC therapy.
18F-PSMA-1007 PET/CT Performance on Risk Stratification Discrimination and Distant Metastases Prediction in Newly Diagnosed Prostate Cancer
Authors: Wang Zhuonan , Zheng Anqi , Li Yunxuan , Dong Weixuan , Liu Xiang , Yuan Wang , Gao Fan , Duan Xiaoyi
Published: October 2021

Objective

To evaluate the prediction performance of 18F-PSMA-1007 PET/CT and clinicopathologic characteristics on prostate cancer (PCa) risk stratification and distant metastatic prediction.

Materials and Methods

A retrospective analysis was performed on 101 consecutively patients with biopsy or radical prostatectomy proved PCa who underwent 18F-PSMA-1007 PET/CT. The semi-quantitative analysis provided minimum, maximum and mean standardized uptake (SUVmin, SUVmax and SUVmean) of PCa. Association between clinicopathologic characteristics (total prostate-specific antigen, tPSA and Gleason Score, GS) and PET/CT indexes were analyzed. The diagnostic performance of distant metastatic on PET/CT parameters, tPSA and GS was evaluated using logistic regression analyses. A path analysis was conducted to evaluate the mediating effect of tPSA level on the relation between semi-quantitative parameters of primary tumors and metastatic lesions.

Results

The PET/CT parameters were all higher in high risk stratification subgroups (tPSA>20 ng/mL, GS ≥ 8, and tPSA>20 ng/mL and/or GS ≥ 8, respectively) with high sensitivity (86.89%, 90.16% and 83.61%, respectively). The SUVmax, tPSA and GS could effectively predict distant metastatic with high sensitivity of SUVmax (90.50%) compared with tPSA (57.14%) and GS (55.61%). With a cutoff value of 29.01ng/mL for tPSA, the detection rate of distant metastasis between low and high prediction tPSA group had statistical differences (50.00% vs. 76.60%, respectively; P = 0.006) which was not found on guideline tPSA level (P>0.05). 6/15 (40%) patients tPSA between 20ng/mL to 29.01ng/mL without distant metastases may change the risk stratification. Finally, tPSA had a partial mediating effect on SUVmax of primary tumors and metastases lesions.

Conclusion

The 18F-PSMA-1007 PET/CT SUVmax has a higher sensitivity and can be an “imaging biomarker” for primary PCa risk stratification. The prediction tPSA level (29.01 ng/mL) is more conducive to the assessment of distant metastasis and avoid unnecessary biopsy.
Pediatric Simplified Acute Physiology Score II: Establishment of a New, Repeatable Pediatric Mortality Risk Assessment Score
Authors: Irschik Stefan , Veljkovic Jelena , Golej Johann , Schlager Gerald , Brandt Jennifer B. , Krall Christoph , Hermon Michael
Published: October 2021

Objectives:In critical care it is crucial to appropriately assess the risk of mortality for each patient. This is especially relevant in pediatrics, with its need for accurate and repeatable scoring. Aim of this study was to evaluate an age-adapted version of the expanded Simplified Acute Physiology Score II; (p-SAPS II), a repeatable, newly-designed scoring system compared to established scores (Pediatric Sequential Organ Failure Assessment Score/pSOFA, Pediatric Logistic Organ Dysfunction Score-2/PELOD-2 and Pediatric Index of Mortality 3/PIM3).

Design:This retrospective cohort pilot study included data collected from patients admitted to the Pediatric Intensive Care Unit (PICU) at the Medical University of Vienna between July 2017 through December 2018.

Patients:231 admissions were included, comprising neonates (gestational age of ≥ 37 weeks) and patients up to 18 years of age with a PICU stay longer than 48 h.

Main Outcomes:Mortality risk prediction and discrimination between survivors and non-survivors were the main outcomes of this study. The primary statistical methods for evaluating the performance of each score were the area under the receiver operating characteristic curve (AUROC) and goodness-of-fit test.

Results:Highest AUROC curve was calculated for p-SAPS II (AUC = 0.86; 95% CI: 0.77–0.96;p< 0.001). This was significantly higher than the AUROCs of PELOD-2/pSOFA but not of PIM3. However, in a logistic regression model including p-SAPS II and PIM3 as covariates, p-SAPS II had a significant effect on the accuracy of prediction (p= 0.003). Nevertheless, according to the goodness-of-fit test for p-SAPS II and PIM3, p-SAPS II overestimated the number of deaths, whereas PIM3 showed acceptable estimations. Repeatability testing showed increasing AUROC values for p-SAPS II throughout the clinical stay (0.96 at day 28) but still no significant difference to PIM 3. The prediction accuracy, although improved over the days and even exceeded PIM 3.

Conclusions:The newly-created p-SAPS II performed better than the established PIM3 in terms of discriminating between survivors and non-survivors. Furthermore, p-SAPS II can be assessed repeatably throughout a patient's PICU stay what improves mortality prediction. However, there is still a need to optimize calibration of the score to accurately predict mortality sooner throughout the clinical stay.
Bleeding Outcomes After Dental Extraction in Patients Under Direct-Acting Oral Anticoagulants vs. Vitamin K Antagonists: A Systematic Review and Meta-Analysis
Authors: Hua Wenbing , Huang Zhengmei , Huang Zhuoli
Published: October 2021

Background: The current systematic review aimed to compare bleeding outcomes in dental extraction patients receiving uninterrupted Direct-acting oral anticoagulant (DOAC) or Vitamin K antagonists (VKAs) for various systemic diseases.

Methods: PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar databases were searched for randomized controlled trials, controlled clinical trials, prospective and retrospective cohort studies, and case control studies, conducted on adult patients undergoing dental extraction under uninterrupted DOAC or VKAs therapy and reporting bleeding outcomes. The search was conducted up to March 31, 2021. We pooled data to calculate risk ratios (RR) with 95% confidence intervals (CI) in a random-effects model.

Results: Eight studies comparing 539 patients on DOAC therapy and 574 patients on VKAs were included. Meta-analysis indicated a statistically significant lower bleeding risk in patients under DOAC therapy (RR 0.68 95% CI 0.49, 0.95 I2 = 0%). However, on sensitivity analysis, the results were statistically non-significant after exclusion of any of the included studies. On pooled analysis of limited number of studies, we found no statistically significant difference in the risk of bleeding between apixaban (RR 0.85 95% CI 0.45, 1.60 I2 = 0%), rivaroxaban (RR 0.95 95% CI 0.36, 2.48 I2 = 45%), dabigatran (RR 0.49 95% CI 0.19, 1.28 I2 = 5%), edoxaban (RR 0.41 95% CI 0.13, 1.27 I2 = 0%) and VKAs.

Conclusion: The results of the first review comparing bleeding outcomes after dental extraction in patients on uninterrupted DOAC or VKA therapy indicates that patients on DOAC may have a reduced risk of hemorrhage. Current evidence is of very low-quality and should be interpreted with caution. Data on individual DOAC is scarce and at this point, the difference in the risk of bleeding between these drugs cannot be elucidated. Further studies with a large sample size shall supplement our conclusion.
The Role of the Inflammasome in Heart Failure
Authors: Wu Jimin , Dong Erdan , Zhang Youyi , Xiao Han
Published: October 2021

Inflammation promotes the development of heart failure (HF). The inflammasome is a multimeric protein complex that plays an essential role in the innate immune response by triggering the cleavage and activation of the proinflammatory cytokines interleukins (IL)-1β and IL-18. Blocking IL-1β with the monoclonal antibody canakinumab reduced hospitalizations and mortality in HF patients, suggesting that the inflammasome is involved in HF pathogenesis. The inflammasome is activated under various pathologic conditions that contribute to the progression of HF, including pressure overload, acute or chronic overactivation of the sympathetic system, myocardial infarction, and diabetic cardiomyopathy. Inflammasome activation is responsible for cardiac hypertrophy, fibrosis, and pyroptosis. Besides inflammatory cells, the inflammasome in other cardiac cells initiates local inflammation through intercellular communication. Some inflammasome inhibitors are currently being investigated in clinical trials in patients with HF. The current evidence suggests that the inflammasome is a critical mediator of cardiac inflammation during HF and a promising therapeutic target. The present review summarizes the recent advances in both basic and clinical research on the role of the inflammasome in HF.
Real Assessment of Maximum Oxygen Uptake as a Verification After an Incremental Test Versus Without a Test
Authors: Hebisz Paulina , Jastrzębska Agnieszka Danuta , Hebisz Rafał
Published: October 2021

The study was conducted to compare peak oxygen uptake (VO2peak) measured with the incremental graded test (GXT) (VO2peak) and two tests to verify maximum oxygen uptake, performed 15 min after the incremental test (VO2peak1) and on a separate day (VO2peak2). The aim was to determine which of the verification tests is more accurate and, more generally, to validate the VO2max obtained in the incremental graded test on cycle ergometer. The study involved 23 participants with varying levels of physical activity. Analysis of variance showed no statistically significant differences for repeated measurements (F = 2.28, p = 0.118, η2 = 0.12). Bland–Altman analysis revealed a small bias of the VO2peak1 results compared to the VO2peak (0.4 ml⋅min–1⋅kg–1) and VO2peak2 results compared to the VO2peak (−0.76 ml⋅min–1⋅kg–1). In isolated cases, it was observed that VO2peak1 and VO2peak2 differed by more than 5% from VO2peak. Considering the above, it can be stated that among young people, there are no statistically significant differences between the values of VO2peak measured in the following tests. However, in individual cases, the need to verify the maximum oxygen uptake is stated, but performing a second verification test on a separate day has no additional benefit.
Genetic Identity, Diversity, and Population Structure of CIP's Sweetpotato (I. batatas) Germplasm Collection
Authors: Anglin Noelle L. , Robles Ronald , Rossel Genoveva , Alagon Rocio , Panta Ana , Jarret Robert L. , Manrique Norma , Ellis David
Published: October 2021

The in trust sweetpotato collection housed by the International Center of Potato (CIP) is one of the largest assemblages of plant material representing the genetic resources of this important staple crop. The collection currently contains almost 6,000 accessions of Ipomoea batatas (cultivated sweetpotato) and over 1,000 accessions of sweetpotato crop wild relatives (CWRs). In this study, the entire cultivated collection (5,979 accessions) was genotyped with a panel of 20 simple sequence repeat (SSR) markers to assess genetic identity, diversity, and population structure. Genotyping and phenotyping of in vitro plantlets and mother plants were conducted simultaneously on 2,711 accessions (45% of the total collection) to identify and correct possible genetic identity errors which could have occurred at any time over the thirty plus years of maintenance in the in vitro collection. Within this group, 533 accessions (19.6%) had errors in identity. Field evaluations of morphological descriptors were carried out to confirm the marker data. A phylogenetic tree was constructed to reveal the intraspecific relationships in the population which uncovered high levels of redundancy in material from Peru and Latin America. These genotypic data were supported by morphological data. Population structure analysis demonstrated support for four ancestral populations with many of the accessions having lower levels of gene flow from the other populations. This was especially true of germplasm derived from Peru, Ecuador, and Africa. The set of 20 SSR markers was subsequently utilized to examine a subset of 189 accessions from the USDA sweetpotato germplasm collection and to identify and reconcile potential errors in the identification of clones shared between these collections. Marker analysis demonstrated that the USDA subset of material had 65 unique accessions that were not found in the larger CIP collection. As far as the authors are aware, this is the first report of genotyping an entire sweetpotato germplasm collection in its entirety.