bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns in Benthic Microbial Community Structure Across Environmental Gradients in the Beaufort Sea Shelf and Slope
Authors: Walker Alexis M. , Leigh Mary Beth , Mincks Sarah L.
Published: January 2021

The paradigm of tight pelagic-benthic coupling in the Arctic suggests that current and future fluctuations in sea ice, primary production, and riverine input resulting from global climate change will have major impacts on benthic ecosystems. To understand how these changes will affect benthic ecosystem function, we must characterize diversity, spatial distribution, and community composition for all faunal components. Bacteria and archaea link the biotic and abiotic realms, playing important roles in organic matter (OM) decomposition, biogeochemical cycling, and contaminant degradation, yet sediment microbial communities have rarely been examined in the North American Arctic. Shifts in microbial community structure and composition occur with shifts in OM inputs and contaminant exposure, with implications for shifts in ecological function. Furthermore, the characterization of benthic microbial communities provides a foundation from which to build focused experimental research. We assessed diversity and community structure of benthic prokaryotes in the upper 1 cm of sediments in the southern Beaufort Sea (United States and Canada), and investigated environmental correlates of prokaryotic community structure over a broad spatial scale (spanning 1,229 km) at depths ranging from 17 to 1,200 m. Based on hierarchical clustering, we identified four prokaryotic assemblages from the 85 samples analyzed. Two were largely delineated by the markedly different environmental conditions in shallow shelf vs. upper continental slope sediments. A third assemblage was mainly comprised of operational taxonomic units (OTUs) shared between the shallow shelf and upper slope assemblages. The fourth assemblage corresponded to sediments receiving heavier OM loading, likely resulting in a shallower anoxic layer. These sites may also harbor microbial mats and/or methane seeps. Substructure within these assemblages generally reflected turnover along a longitudinal gradient, which may be related to the quantity and composition of OM deposited to the seafloor; bathymetry and the Mackenzie River were the two major factors influencing prokaryote distribution on this scale. In a broader geographical context, differences in prokaryotic community structure between the Beaufort Sea and Norwegian Arctic suggest that benthic microbes may reflect regional differences in the hydrography, biogeochemistry, and bathymetry of Arctic shelf systems.
kernInt: A Kernel Framework for Integrating Supervised and Unsupervised Analyses in Spatio-Temporal Metagenomic Datasets
Authors: Ramon Elies , Belanche-Muñoz Lluís , Molist Francesc , Quintanilla Raquel , Perez-Enciso Miguel , Ramayo-Caldas Yuliaxis
Published: January 2021

The advent of next-generation sequencing technologies allowed relative quantification of microbiome communities and their spatial and temporal variation. In recent years, supervised learning (i.e., prediction of a phenotype of interest) from taxonomic abundances has become increasingly common in the microbiome field. However, a gap exists between supervised and classical unsupervised analyses, based on computing ecological dissimilarities for visualization or clustering. Despite this, both approaches face common challenges, like the compositional nature of next-generation sequencing data or the integration of the spatial and temporal dimensions. Here we propose a kernel framework to place on a common ground the unsupervised and supervised microbiome analyses, including the retrieval of microbial signatures (taxa importances). We define two compositional kernels (Aitchison-RBF and compositional linear) and discuss how to transform non-compositional beta-dissimilarity measures into kernels. Spatial data is integrated with multiple kernel learning, while longitudinal data is evaluated by specific kernels. We illustrate our framework through a single point soil dataset, a human dataset with a spatial component, and a previously unpublished longitudinal dataset concerning pig production. The proposed framework and the case studies are freely available in the kernInt package at https://github.com/elies-ramon/kernInt.
Root Nodule Rhizobia From Undomesticated Shrubs of the Dry Woodlands of Southern Africa Can Nodulate Angolan Teak Pterocarpus angolensis, an Important Source of Timber
Authors: Bünger Wiebke , Sarkar Abhijit , Grönemeyer Jann Lasse , Zielinski Janina , Revermann Rasmus , Hurek Thomas , Reinhold-Hurek Barbara
Published: January 2021

Pterocarpus angolensis, a leguminous tree native to the dry woodlands of Southern Africa, provides valuable timber, but is threatened by land conversion and overharvesting while showing limited natural regeneration. Nitrogen-fixing root nodule symbionts that could improve establishment of young seedlings have not yet been described. Therefore, we investigated the ability of P. angolensis to form nodules with a diverse range of rhizobia. In drought-prone areas under climate change with higher temperatures, inoculants that are heat-tolerant and adapted to these conditions are likely to be of advantage. Sources of bacterial isolates were roots of P. angolensis from nurseries in the Kavango region, other shrubs from this area growing near Pterocarpus such as Indigofera rautanenii, Desmodium barbatum, Chamaecrista sp., or shrubs from drought-prone areas in Namaqualand (Wiborgia monoptera, Leobordea digitata) or Kalahari (Indigofera alternans). Only slight protrusions were observed on P. angolensis roots, from which a non-nodulating Microbacterium sp. was isolated. Rhizobia that were isolated from nodules of other shrubs were affiliated to Bradyrhizobium ripae WR4T, Bradyrhizobium spp. (WR23/WR74/WR93/WR96), or Ensifer/Mesorhizobium (WR41/WR52). As many plant growth-promoting rhizobacteria (PGPR), nodule isolates produced siderophores and solubilized phosphate. Among them, only the Bradyrhizobium strains nodulated P. angolensis under controlled conditions in the laboratory. Isolates were further characterized by multilocus sequence analysis and were found to be distant from known Bradyrhizobium species. Among additional reference species tested for nodulation on P. angolensis, Bradyrhizobium vignae 7-2T and Bradyrhizobium namibiense 5-10T from the Kavango region of Namibia as well as Bradyrhizobium elkanii LMG6234T and Bradyrhizobium yuanmingense LMG21728T induced nitrogen-fixing nodules, while Bradyrhizobium diazoefficiens USDA110T and Bradyrhizobium tropiciagri SEMIA6148T did not. This suggests a broad microsymbiont range from Bradyrhizobium japonicum and B. elkanii lineages. Phylogenetic analysis of nodC genes indicated that nodulating bradyrhizobia did not belong to a specific symbiovar. Also, for I. rautanenii and Wiborgia, nodule isolates B. ripae WR4T or Mesorhizobium sp. WR52, respectively, were authenticated. Characterization of symbionts inducing effective root nodules in P. angolensis and other shrubs from Subsahara Africa (SSA) give insights in their symbiotic partners for the first time and might help in future to develop bioinoculants for young seedlings in nurseries, and for reforestation efforts in Southern Africa.
Mfd Affects Global Transcription and the Physiology of Stressed Bacillus subtilis Cells
Authors: Martin Holly Anne , Sundararajan Anitha , Ermi Tatiana S. , Heron Robert , Gonzales Jason , Lee Kaiden , Anguiano-Mendez Diana , Schilkey Faye , Pedraza-Reyes Mario , Robleto Eduardo A.
Published: January 2021

For several decades, Mfd has been studied as the bacterial transcription-coupled repair factor. However, recent observations indicate that this factor influences cell functions beyond DNA repair. Our lab recently described a role for Mfd in disulfide stress that was independent of its function in nucleotide excision repair and base excision repair. Because reports showed that Mfd influenced transcription of single genes, we investigated the global differences in transcription in wild-type and mfd mutant growth-limited cells in the presence and absence of diamide. Surprisingly, we found 1,997 genes differentially expressed in Mfd– cells in the absence of diamide. Using gene knockouts, we investigated the effect of genetic interactions between Mfd and the genes in its regulon on the response to disulfide stress. Interestingly, we found that Mfd interactions were complex and identified additive, epistatic, and suppressor effects in the response to disulfide stress. Pathway enrichment analysis of our RNASeq assay indicated that major biological functions, including translation, endospore formation, pyrimidine metabolism, and motility, were affected by the loss of Mfd. Further, our RNASeq findings correlated with phenotypic changes in growth in minimal media, motility, and sensitivity to antibiotics that target the cell envelope, transcription, and DNA replication. Our results suggest that Mfd has profound effects on the modulation of the transcriptome and on bacterial physiology, particularly in cells experiencing nutritional and oxidative stress.
Integrated Proteomic and Transcriptomic Analyses Reveal the Roles of Brucella Homolog of BAX Inhibitor 1 in Cell Division and Membrane Homeostasis of Brucella suis S2
Authors: Zhang Guangdong , Zhong Fangli , Chen Lei , Qin Peipei , Li Junmei , Zhi Feijie , Tian Lulu , Zhou Dong , Lin Pengfei , Chen Huatao , Tang Keqiong , Liu Wei , Jin Yaping , Wang Aihua
Published: January 2021

BAX inhibitor 1 (BI-1) is an evolutionarily conserved transmembrane protein first identified in a screening process for human proteins that suppress BAX-induced apoptosis in yeast cells. Eukaryotic BI-1 is a cytoprotective protein that suppresses cell death induced by multiple stimuli in eukaryotes. Brucella, the causative agent of brucellosis that threatens public health and animal husbandry, contains a conserved gene that encodes BI-1-like protein. To explore the role of the Brucella homolog of BI-1, BrBI, in Brucella suis S2, we constructed the brbI deletion mutant strain and its complemented strain. brbI deletion altered the membrane properties of Brucella suis S2 and decreased its resistance to acidic pH, H2O2, polymyxin B, and lincomycin. Additionally, deleting brbI led to defective growth, cell division, and viability in Brucella suis S2. We then revealed the effect of brbI deletion on the physiological characteristics of Brucella suis S2 via integrated transcriptomic and proteomic analyses. The integrated analysis showed that brbI deletion significantly affected the expression of multiple genes at the mRNA and/or protein levels. Specifically, the affected divisome proteins, FtsB, FtsI, FtsL, and FtsQ, may be the molecular basis of the impaired cell division of the brbI mutant strain, and the extensively affected membrane proteins and transporter-associated proteins were consistent with the phenotype of the membrane properties’ alterations of the brbI mutant strain. In conclusion, our results revealed that BrBI is a bacterial cytoprotective protein involved in membrane homeostasis, cell division, and stress resistance in Brucella suis S2.
Baicalin Induces Apoptosis and Suppresses the Cell Cycle Progression of Lung Cancer Cells Through Downregulating Akt/mTOR Signaling Pathway
Authors: Sui Xinbing , Han Xuemeng , Chen Peng , Wu Qibiao , Feng Jiao , Duan Ting , Chen Xiaying , Pan Ting , Yan Lili , Jin Ting , Xiang Yu , Gao Quan , Wen Chengyong , Ma Weirui , Liu Wencheng , Zhang Ruonan , Chen Bi , Zhang Mingming , Yang Zuyi , Kong Na , Xie Tian , Ding Xia
Published: January 2021

Baicalin, as a natural active ingredient extracted and isolated from the traditional Chinese medicine Scutellaria baicalensis Georgi., has been potentially used in various areas for its antioxidative, antitumor, anti-inflammatory, and anti-proliferative activities. Although several studies have reported the antitumor effects of baicalin against various cancer types, its beneficial effects on lung cancer have not yet been elucidated. Therefore, the therapeutic effects and molecular mechanisms of baicalin on lung cancer cell lines H1299 and H1650 were investigated. Here, the results of its antitumor activity were shown. We found that Akt/mTOR pathway inhibition was the essential determinant in baicalin-induced cell cycle arrest. Furthermore, when the Akt Agonist SC79 or Akt plasmid transfection was performed, the antitumor effect of baicalin was significantly abrogated in both H1299 and H1650 cells. In conclusion, we found that baicalin exerted its antitumor activity mainly by inducing Akt-dependent cell cycle arrest and promoting apoptosis, which show great potential for developing a new drug for lung cancer treatment.
Evolution of Apathy in Early Parkinson's Disease: A 4-Years Prospective Cohort Study
Authors: Ou Ruwei , Lin Junyu , Liu Kuncheng , Jiang Zheng , Wei Qianqian , Hou Yanbing , Zhang Lingyu , Cao Bei , Zhao Bi , Song Wei , Shang Huifang
Published: January 2021

Objective: We investigated the prevalence, evolution, associated factors, and risk factors of apathy in a cohort of patients with early-stage Parkinson's disease (PD), who underwent a 4-years prospective follow-up.

Methods: This study included 188 patients with PD (baseline disease duration <3 years) who underwent an annual evaluation using the Lille Apathy Rating Scale (LARS). Based on the cut-off value of −21 observed on the LARS, patients were categorized as PD with and without apathy. The generalized estimating equations (GEE) model was utilized to determine the factors associated with apathy, and the Cox proportional-hazards regression model was used to determine the predictors of apathy.

Results: Apathy increased from a baseline rate of 18.6–28.8% after 4 years; notably, this rate was not persistent across patients' visits. The LARS score was independently associated with the male sex (B 8.131, p = 0.009), low Frontal Assessment Battery (FAB) scores (B 0.567, p = 0.011), low attention scores on the Montreal Cognitive Assessment (MOCA) test (B 0.217, p = 0.026), high Hamilton Depression Rating Scale (HDRS) scores (B 1.362, p < 0.001), high Unified Parkinson's Disease Rating Scale (UPDRS) part III scores (B 1.147, p < 0.001), and prolonged follow-up time (B 1.785, p = 0.048). A high HDRS score was the only predictor of apathy in PD [hazard ratio (HR) 1.043, p = 0.026].

Conclusions: The risk of apathy is higher in men with progressive PD accompanied by disease-specific motor and non-motor symptoms. Depression during early-stage PD is a primary risk factor for apathy in PD.
Diagnosing Autism Spectrum Disorder Without Expertise: A Pilot Study of 5- to 17-Year-Old Individuals Using Gazefinder
Authors: Tsuchiya Kenji J. , Hakoshima Shuji , Hara Takeshi , Ninomiya Masaru , Saito Manabu , Fujioka Toru , Kosaka Hirotaka , Hirano Yoshiyuki , Matsuo Muneaki , Kikuchi Mitsuru , Maegaki Yoshihiro , Harada Taeko , Nishimura Tomoko , Katayama Taiichi
Published: January 2021

Atypical eye gaze is an established clinical sign in the diagnosis of autism spectrum disorder (ASD). We propose a computerized diagnostic algorithm for ASD, applicable to children and adolescents aged between 5 and 17 years using Gazefinder, a system where a set of devices to capture eye gaze patterns and stimulus movie clips are equipped in a personal computer with a monitor. We enrolled 222 individuals aged 5–17 years at seven research facilities in Japan. Among them, we extracted 39 individuals with ASD without any comorbid neurodevelopmental abnormalities (ASD group), 102 typically developing individuals (TD group), and an independent sample of 24 individuals (the second control group). All participants underwent psychoneurological and diagnostic assessments, including the Autism Diagnostic Observation Schedule, second edition, and an examination with Gazefinder (2 min). To enhance the predictive validity, a best-fit diagnostic algorithm of computationally selected attributes originally extracted from Gazefinder was proposed. The inputs were classified automatically into either ASD or TD groups, based on the attribute values. We cross-validated the algorithm using the leave-one-out method in the ASD and TD groups and tested the predictability in the second control group. The best-fit algorithm showed an area under curve (AUC) of 0.84, and the sensitivity, specificity, and accuracy were 74, 80, and 78%, respectively. The AUC for the cross-validation was 0.74 and that for validation in the second control group was 0.91. We confirmed that the diagnostic performance of the best-fit algorithm is comparable to the diagnostic assessment tools for ASD.
Endovascular Treatment of Ruptured Wide-Necked Anterior Communicating Artery Aneurysms Using a Low-Profile Visualized Intraluminal Support (LVIS) Device
Authors: Xue Gaici , Liu Peng , Xu Fengfeng , Fang Yibin , Li Qiang , Hong Bo , Xu Yi , Liu Jianmin , Huang Qinghai
Published: January 2021

Objective:To evaluate the safety and efficacy of low-profile visualized intraluminal support (LVIS) stent-assisted coiling for the treatment of ruptured wide-necked anterior communicating artery (ACoA) aneurysms.

Methods:The clinical and angiographic data of 31 acutely ruptured wide-necked ACoA aneurysms treated with LVIS stent-assisted coiling between January 2014 and December 2018 were retrospectively reviewed.

Results:All stents were successfully deployed. The immediate angiographic results were modified Raymond-Roy class I in 27 cases, modified Raymond-Roy class II in 2 cases, and modified Raymond-Roy class IIIa in 2 cases. Intraoperative thrombosis and postoperative aneurysmal rebleeding occurred in one case each. Two patients (6.5%) who were admitted due to poor clinical grade conditions died during hospital admission as a result of initial bleeding. Angiographic follow-up (mean: 12.9 months) was performed for 26 patients, the results of which demonstrated that 25 aneurysms were completely occluded and one was class II. The last clinical follow-up (mean: 25.3 months) outcomes demonstrated that 27 patients had favorable clinical outcomes and two had poor clinical outcomes.

Conclusion:LVIS stent-assisted coiling for ruptured wide-necked ACoA aneurysms was safe and effective, with a relatively low rate of perioperative complications and a high rate of complete occlusion at follow-up.
Cognitive Impairment Impacts Exercise Effects on Cognition in Multiple Sclerosis
Authors: Rademacher Annette , Joisten Niklas , Proschinger Sebastian , Bloch Wilhelm , Gonzenbach Roman , Kool Jan , Langdon Dawn , Bansi Jens , Zimmer Philipp
Published: January 2021

Purpose:Exercise training reveals high potential to beneficially impact cognitive performance in persons with multiple sclerosis (pwMS). Research indicates that high-intensity interval training (HIIT) has potentially higher effects on physical fitness and cognition compared to moderate continuous exercise. This study (i) compares the effects of a 3-week HIIT and moderate continuous exercise training on cognitive performance and cardiorespiratory fitness of pwMS in an overall analysis and (ii) investigates potential effects based on baseline cognitive status in a subgroup analysis.

Methods:Seventy-five pwMS were randomly assigned to an intervention (HIIT: 5 × 1.5-min intervals at 95–100% HRmax, 3 ×/week) or active control group (CG: 24 min continuous exercise at 65% HRmax, 3 ×/week). Cognitive performance was assessed pre- and post-intervention with the Brief International Cognitive Assessment for MS (BICAMS). (I) To examine potential within (time) and interaction (time × group) effects in the overall analysis, separate analyses of covariance (ANCOVA) were conducted. (II) For the subgroup analysis, participants were divided into two groups [intact cognition or impaired cognition (>1.5 standard deviation (SD) compared to healthy, age-matched norm data in at least one of the three tests of the BICAMS]. Potential impacts of cognitive status and intervention were investigated with multivariate analyses of variance (MANOVA).

Results:Overall analysis revealed significant time effects for processing speed, verbal learning, rel. VO2peak, and rel. power output. A time*group interaction effect was observed for rel. power output. Subgroup analysis indicated a significant main effect for cognition (impaired cognition vs. intact cognition). Subsequentpost-hocanalysis showed significant larger effects on verbal learning in pwMS with impaired cognition.

Conclusion:Current results need to be confirmed in a powered randomized controlled trial with cognitive performance as primary endpoint and eligibility based on cognitive performance that is assessed prior to study inclusion.
Virtual Rehabilitation of the Paretic Hand and Arm in Persons With Stroke: Translation From Laboratory to Rehabilitation Centers and the Patient's Home
Authors: Fluet Gerard , Qiu Qinyin , Patel Jigna , Mont Ashley , Cronce Amanda , Yarossi Mathew , Merians Alma , Adamovich Sergei
Published: January 2021

The anatomical and physiological heterogeneity of strokes and persons with stroke, along with the complexity of normal upper extremity movement make the possibility that any single treatment approach will become the definitive solution for all persons with upper extremity hemiparesis due to stroke unlikely. This situation and the non-inferiority level outcomes identified by many studies of virtual rehabilitation are considered by some to indicate that it is time to consider other treatment modalities. Our group, among others, has endeavored to build on the initial positive outcomes in studies of virtual rehabilitation by identifying patient populations, treatment settings and training schedules that will best leverage virtual rehabilitation's strengths. We feel that data generated by our lab and others suggest that (1) persons with stroke may adapt to virtual rehabilitation of hand function differently based on their level of impairment and stage of recovery and (2) that less expensive, more accessible home based equipment seems to be an effective alternative to clinic based treatment that justifies continued optimism and study.
Determinants of Neural Plastic Changes Induced by Motor Practice
Authors: Dai Wen , Nakagawa Kento , Nakajima Tsuyoshi , Kanosue Kazuyuki
Published: January 2021

Short-term motor practice leads to plasticity in the primary motor cortex (M1). The purpose of this study is to investigate the factors that determine the increase in corticospinal tract (CST) excitability after motor practice, with special focus on two factors; “the level of muscle activity” and “the presence/absence of a goal of keeping the activity level constant.” Fifteen healthy subjects performed four types of rapid thumb adduction in separate sessions. In the “comfortable task” (C) and “forceful task” (F), the subjects adducted their thumb using comfortable and strong forces. In the “comfortable with a goal task” (CG) and “forceful with a goal task” (FG), subjects controlled the muscle activity at the same level as in the C and F, respectively, by adjusting the peak electromyographic amplitude within the target ranges. Paired associative stimulation (PAS), which combines peripheral nerve (median nerve) stimulation and transcranial magnetic stimulation (TMS), with an inter-stimulus interval of 25 ms (PAS25) was also done. Before and after the motor tasks and PAS25, TMS was applied to the M1. None of the four tasks showed any temporary changes in behavior, meaning no learning occurred. Motor-evoked potential (MEP) amplitude increased only after the FG and it exhibited a positive correlation with the MEP increase after PAS25, suggesting that FG and PAS25 share at least similar plasticity mechanisms in the M1. Resting motor threshold (RMT) decreased only after FG, suggesting that FG would also be associated with the membrane depolarization of M1 neurons. These results suggest task-dependent plasticity from the synergistic effect of forceful muscle activity and of setting a goal of keeping the activity level constant.
Test-Retest Reliability of Neural Correlates of Response Inhibition and Error Monitoring: An fMRI Study of a Stop-Signal Task
Authors: Korucuoglu Ozlem , Harms Michael P. , Astafiev Serguei V. , Golosheykin Semyon , Kennedy James T. , Barch Deanna M. , Anokhin Andrey P.
Published: January 2021

Response inhibition (RI) and error monitoring (EM) are important processes of adaptive goal-directed behavior, and neural correlates of these processes are being increasingly used as transdiagnostic biomarkers of risk for a range of neuropsychiatric disorders. Potential utility of these purported biomarkers relies on the assumption that individual differences in brain activation are reproducible over time; however, available data on test-retest reliability (TRR) of task-fMRI are very mixed. This study examined TRR of RI and EM-related activations using a stop signal task in young adults (n = 56, including 27 pairs of monozygotic (MZ) twins) in order to identify brain regions with high TRR and familial influences (as indicated by MZ twin correlations) and to examine factors potentially affecting reliability. We identified brain regions with good TRR of activations related to RI (inferior/middle frontal, superior parietal, and precentral gyri) and EM (insula, medial superior frontal and dorsolateral prefrontal cortex). No subcortical regions showed significant TRR. Regions with higher group-level activation showed higher TRR; increasing task duration improved TRR; within-session reliability was weakly related to the long-term TRR; motion negatively affected TRR, but this effect was abolished after the application of ICA-FIX, a data-driven noise removal method.
Dexmedetomidine and Netrin-1 Combination Therapy Inhibits Endoplasmic Reticulum Stress by Regulating the ERK5/MEF2A Pathway to Attenuate Cerebral Ischemia Injury
Authors: Yin Jiang-Wen , Li Jia , Ren Yi-Min , Li Yan , Wang Rui-Xue , Wang Sheng , Zuo Yun-Xia
Published: January 2021

The complexity of hard-to-treat diseases such as ischemic stroke strongly undermines the therapeutic potential of available treatment options. Therefore, current developments have gently shifted from a focus on monotherapy to combined or multiple therapies. Both dexmedetomidine and Netrin-1 have anti-neuronal apoptosis effects, but the mechanism is still unclear. The study aimed to estimate the efficacy of dexmedetomidine and Netrin-1 combination therapy against ERS-induced apoptosis after cerebral ischemia injuryin vivoandin vitro, and whether the mechanism is related to the ERK5/MEF2A pathway. Adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO)in vivo, 90 min ischemia and 24 h reperfusion. The hippocampus slices used to establish oxygen-glucose deprivation (OGD) injury modelin vitro. Neterin-1 and Dexmedetomidine were pretreated and post-treated, respectively, before and after the model establishment. MEF2A knockdown was performed by microinjection of AAV9-MEF2A RNAi vector. Orthodromic population spike (OPS) at the end of reoxygenation were recorded. Neurobehavioral tests, TTC staining, Nissl staining, TUNEL staining were performed to assess the effect of the drugs. The expression of CHOP, GRP78, MEF2A, ERK5, and p-ERK5 were investigated by Western blot and immunofluorescence staining. Neurological deficit score, infarct volume, the expression of GRP78, CHOP, and neural apoptotic rate of MCAO group increased markedly. Combination of dexmedetomidine and Netrin-1 resulted in lower infarct volumes and fewer neurological impairments, higher OPS recovery rate, and less damaged and apoptotic cells after cerebral ischemia injury. Furthermore, expression levels of GRP78 and CHOP decreased in the combination therapy group, and it was more effective than the single drug group. Meanwhile, Combination of dexmedetomidine and Netrin-1 increased MEF2A expression and promoted ERK5 phosphorylation. However, the protective effect of dexmedetomidine combined with Netrin-1 in improving neurological function was significantly eliminated by pre-knockdown MEF2A. The neuroprotective effects of dexmedetomidine combined with Netrin on cerebral ischemia-reperfusion injury and hippocampal hypoxia injury in terms of ERS. The synergistic effect of combination therapy is related to the activation of ERK5/MEF2A signaling pathway.
Survival After Treatable Hepatocellular Carcinoma Recurrence in Liver Recipients: A Nationwide Cohort Analysis
Authors: Ho Cheng-Maw , Lee Chih-Hsin , Lee Ming-Chia , Zhang Jun-Fu , Chen Chin-Hua , Wang Jann-Yuan , Hu Rey-Heng , Lee Po-Huang
Published: January 2021

Background

Survival after post-transplant recurrence of HCC is dismal, and almost all treatments for recurrent HCC are off-labeled, without an extensive large-scale analysis. We aimed to delineate their post-recurrence courses and define benchmarks for comparing future treatment effectiveness.

Methods

Three national databases, including health insurance, catastrophic illness, and the cause of death, were linked for cohort establishment and data collection during the period from 2005 to 2016. Patients with HCC recurrence ≥6 months after transplant surgery and under treatment were recruited for survival analysis. Selection of treatment strategies for HCC recurrence after liver transplant was based on the same criteria for those without liver transplant.

Results

Of 2,123 liver transplant recipients, 349 developed HCC recurrence ≥6 months after liver transplant, and the median recurrence time was 17.8 months post-transplant. Within 2 years of treatment, 61% patients showed recurrence (early recurrence group), and survival in these patients was poorer than in the late recurrence group. According to a multivariable analysis, the transplant era before 2008 and radiofrequency ablation were associated with good prognosis, whereas receiving sorafenib and radiotherapy was associated with poor prognosis. The effect of transplant era became insignificant after stratification by recently receiving pretransplant transarterial chemoembolization.

Conclusion

Timing of recurrence and interventions used were associated with the outcomes of patients with post-transplant HCC recurrence. These data provide the benchmark and indicate the critical period and high-risk factors for further therapeutic trial consideration.
Pan-Cancer Molecular Characterization of m6A Regulators and Immunogenomic Perspective on the Tumor Microenvironment
Authors: Zhu Jie , Xiao Jiani , Wang Min , Hu Daixing
Published: January 2021

Purpose

N6-methyladenosine (m6A) methylation plays a critical role in diverse biological processes. However, knowledge regarding the constitution of m6A on tumor microenvironment (TME) and tumor-infiltrating lymphocytes (TILs) across cancer types is still lacking. We performed comprehensive immuno-genomic analyses to reveal molecular characterization of the m6A regulators and immune-related genes (IRGs) across TME and TIL heterogeneity.

Methods

We comprehensively analyzed the properties of m6A regulators in genomic profiles from The Cancer Genome Atlas (TCGA) according to expression perturbations of crucial IRGs, CD274, CD8A, GZMA, and PRF1. The four IRGs were proved to be reliable biomarkers of TILs and TME via CIBERSORT and ESTIMATE analyses, and their co-expression relationship was certified by TIMER analysis. Based on their median values, the samples from the pan-cancer tissues (N = 11,057) were classified into eight TME types. The RNA expression levels of 13 m6A regulators were compared across TME subtypes. Single-sample Gene Set Enrichment Analysis (ssGSEA) was also used to classify TME clusters, expression variants of IRGs and m6A regulators were verified among TME clusters. Meanwhile, the correlation between m6A regulators and tumor mutational burden (TMB) were tested. Finally, the impacts of IRGs and TME clusters in clinical characteristics and outcomes were revealed.

Results

CD274, CD8A, GZMA, and PRF1 showed similar TILs’ characteristics, of which the level of T cells CD8 and T cells CD4 memory activated are consistent with the expression levels of the four IRGs and higher immune infiltration. Besides, CD274, CD8A, GZMA, and PRF1 were positively correlated with the stromal score or immune score in almost all 33 tumor types. All of four IRGs showed impact between tumor pathological stages or clinical outcomes. Among TME type I to type IV, m6A regulators’ expression drift changed from high-level to low-level in ESCA, BLCA, HNSC, CESC, BRCA, and GBM. However among TME type V to type VIII, m6A regulators drew a shift from low-level to high-level expression in CESC, BLCA, ESCA, KIRP, HNSC, BRCA, KIRC, COAD, LAML, GBM, and KICH. In ssGSEA analyses, IRGs’ expression levels were elevated with the immune infiltration degree and m6A regulators’ expression level varied among three TIL subgroups. With different TMB levels, expression differences of m6A regulators were observed in BLCA, BRCA, COAD, LGG, LUAD, LUSC, STAD, THCA, and UCEC.

Conclusion

We identified four crucial IRGs affecting TILs, TME characteristics and clinical parameters. Expression variants of m6A regulators among the subgroups of TME types and ssGSEA clusters suggested that m6A regulators may be essential factors for phenotypic modifications of IRGs and thus affecting TME characteristics across multiple tumor types.
Non-invasive Cardiac Output Monitoring in Neonates
Authors: O'Neill Roisin , Dempsey Eugene M. , Garvey Aisling A. , Schwarz Christoph E.
Published: January 2021

Circulatory monitoring is currently limited to heart rate and blood pressure assessment in the majority of neonatal units globally. Non-invasive cardiac output monitoring (NiCO) in term and preterm neonates is increasing, where it has the potential to enhance our understanding and management of overall circulatory status. In this narrative review, we summarized 33 studies including almost 2,000 term and preterm neonates. The majority of studies evaluated interchangeability with echocardiography. Studies were performed in various clinical settings including the delivery room, patent ductus arteriosus assessment, patient positioning, red blood cell transfusion, and therapeutic hypothermia for hypoxic ischemic encephalopathy. This review presents an overview of NiCO in neonatal care, focusing on technical and practical aspects as well as current available evidence. We discuss potential goals for future research.
Outcomes of Preterm Infants With Congenital Heart Defects After Early Surgery: Defining Risk Factors at Different Time Points During Hospitalization
Authors: Cheung Po-Yin , Hajihosseini Morteza , Dinu Irina A. , Switzer Heather , Joffe Ari R. , Bond Gwen Y. , Robertson Charlene M. T.
Published: January 2021

Background: Compared with those born at term gestation, infants with complex congenital heart defects (CCHD) who were delivered before 37 weeks gestational age and received neonatal open-heart surgery (OHS) have poorer neurodevelopmental outcomes in early childhood. We aimed to describe the growth, disability, functional, and neurodevelopmental outcomes in early childhood of preterm infants with CCHD after neonatal OHS. Prediction models were evaluated at various timepoints during hospitalization which could be useful in the management of these infants.

Study Design: We studied all preterm infants with CCHD who received OHS within 6 weeks of corrected age between 1996 and 2016. The Western Canadian Complex Pediatric Therapies Follow-up Program completed multidisciplinary comprehensive neurodevelopmental assessments at 2-year corrected age at the referral-site follow-up clinics. We collected demographic and acute-care clinical data, standardized age-appropriate outcome measures including physical growth with calculated z-scores; disabilities including cerebral palsy, visual impairment, permanent hearing loss; adaptive function (Adaptive Behavior Assessment System-II); and cognitive, language, and motor skills (Bayley Scales of Infant and Toddler Development-III). Multiple variable logistic or linear regressions determined predictors displayed as Odds Ratio (OR) or Effect Size (ES) with 95% confidence intervals.

Results: Of 115 preterm infants (34 ± 2 weeks gestation, 2,339 ± 637 g, 64% males) with CCHD and OHS, there were 11(10%) deaths before first discharge and 21(18%) deaths by 2-years. Seven (6%) neonates had cerebral injuries, 7 had necrotizing enterocolitis; none had retinopathy of prematurity. Among 94 survivors, 9% had cerebral palsy and 6% had permanent hearing loss, with worse outcomes in those with syndromic diagnoses. Significant predictors of mortality included birth weight z-score [OR 0.28(0.11,0.72), P = 0.008], single-ventricle anatomy [OR 5.92(1.31,26.80), P = 0.021], post-operative ventilation days [OR 1.06(1.02,1.09), P = 0.007], and cardiopulmonary resuscitation [OR 11.58 (1.97,68.24), P = 0.007]; for adverse functional outcome in those without syndromic diagnoses, birth weight 2,000–2,499 g [ES −11.60(−18.67, −4.53), P = 0.002], post-conceptual age [ES −0.11(−0.22,0.00), P = 0.044], post-operative lowest pH [ES 6.75(1.25,12.25), P = 0.017], and sepsis [ES −9.70(−17.74, −1.66), P = 0.050].

Conclusions: Our findings suggest preterm neonates with CCHD and early OHS had significant mortality and morbidity at 2-years and were at risk for cerebral palsy and adverse neurodevelopment. This information may be important for management, parental counseling and the decision-making process.
Spider Venom Peptide Pn3a Inhibition of Primary Afferent High Voltage-Activated Calcium Channels
Authors: McArthur Jeffrey R. , Munasinghe Nehan R. , Finol-Urdaneta Rocio K. , Adams David J. , Christie Macdonald J.
Published: January 2021

Despite potently inhibiting the nociceptive voltage-gated sodium (Nav) channel, Nav1.7, µ-theraphotoxin Pn3a is antinociceptive only upon co-administration with sub-therapeutic opioid agonists, or by itself at doses >3,000-fold greater than its Nav1.7 IC50 by a yet undefined mechanism. Nav channels are structurally related to voltage-gated calcium (Cav) channels, Cav1 and Cav2. These channels mediate the high voltage-activated (HVA) calcium currents (ICa) that orchestrate synaptic transmission in nociceptive dorsal root ganglion (DRG) neurons and are fine-tuned by opioid receptor (OR) activity. Using whole-cell patch clamp recording, we found that Pn3a (10 µM) inhibits ∼55% of rat DRG neuron HVA-ICa and 60–80% of Cav1.2, Cav1.3, Cav2.1, and Cav2.2 mediated currents in HEK293 cells, with no inhibition of Cav2.3. As a major DRG ICa component, Cav2.2 inhibition by Pn3a (IC50 = 3.71 ± 0.21 µM) arises from an 18 mV hyperpolarizing shift in the voltage dependence of inactivation. We observed that co-application of Pn3a and µ-OR agonist DAMGO results in enhanced HVA-ICa inhibition in DRG neurons whereas co-application of Pn3a with the OR antagonist naloxone does not, underscoring HVA channels as shared targets of Pn3a and opioids. We provide evidence that Pn3a inhibits native and recombinant HVA Cavs at previously reportedly antinociceptive concentrations in animal pain models. We show additive modulation of DRG HVA-ICa by sequential application of low Pn3a doses and sub-therapeutic opioids ligands. We propose Pn3a's antinociceptive effects result, at least in part, from direct inhibition of HVA-ICa at high Pn3a doses, or through additive inhibition by low Pn3a and mild OR activation.
Spindle Architectural Features Must Be Considered Along With Cell Size to Explain the Timing of Mitotic Checkpoint Silencing
Authors: Bloomfield Mathew , Chen Jing , Cimini Daniela
Published: January 2021

Mitosis proceeds through a defined series of events that is largely conserved, but the amount of time needed for their completion can vary in different cells and organisms. In many systems, mitotic duration depends on the time required to satisfy and silence the spindle assembly checkpoint (SAC), also known as the mitotic checkpoint. Because SAC silencing involves trafficking SAC molecules among kinetochores, spindle, and cytoplasm, the size and geometry of the spindle relative to cell volume are expected to affect mitotic duration by influencing the timing of SAC silencing. However, the relationship between SAC silencing, cell size, and spindle dimensions is unclear. To investigate this issue, we used four DLD-1 tetraploid (4N) clones characterized by small or large nuclear and cell size. We found that the small 4N clones had longer mitotic durations than the parental DLD-1 cells and that this delay was due to differences in their metaphase duration. Leveraging a previous mathematical model for spatiotemporal regulation of SAC silencing, we show that the difference in metaphase duration, i.e., SAC silencing time, can be explained by the distinct spindle microtubule densities and sizes of the cell, spindle, and spindle poles in the 4N clones. Lastly, we demonstrate that manipulating spindle geometry can alter mitotic and metaphase duration, consistent with a model prediction. Our results suggest that spindle size does not always scale with cell size in mammalian cells and cell size is not sufficient to explain the differences in metaphase duration. Only when a number of spindle architectural features are considered along with cell size can the kinetics of SAC silencing, and hence mitotic duration, in the different clones be explained.
Phase Velocity of Facial Blood Volume Oscillation at a Frequency of 0.1 Hz
Authors: Yoshida Kenichiro , Nishidate Izumi
Published: January 2021

Facial blood flow, which typically exhibits distinctive oscillation at a frequency of around 0.1 Hz, has been extensively studied. Although this oscillation may include important information about blood flow regulation, its origin remains unknown. The spatial phase distribution of the oscillation is thus desirable. Therefore, we visualized facial blood volume oscillation at a frequency of around 0.1 Hz using a digital camera imaging method with an improved approximation equation, which enabled precise analysis over a large area. We observed a slow spatial movement of the 0.1-Hz oscillation. The oscillation phase was not synchronized, but instead moved slowly. The phase velocity varies with person, measurement location, and time. An average phase velocity of 3.8 mm/s was obtained for several subjects. The results are consistent with previous studies; however, the conventional explanation that the blood flow at a certain point oscillates independently of adjacent areas should be corrected. If the primary origin of the movement is myogenic activity, the movement may ascend along a blood vessel toward the upstream. Otherwise, the oscillation and its propagation can be considered to be related to Mayer waves. By determining the mechanism, some questions regarding Mayer waves can be answered. The direction of the wave (upstream or downstream) provides important information.
Biomarker Responses of Spanish Moss Tillandsia usneoides to Atmospheric Hg and Hormesis in This Species
Authors: Sun Xingyue , Li Peng , Zheng Guiling
Published: January 2021

Hg is an environmental pollutant with severe biotoxicity. Epiphytic Tillandsia species, especially Spanish moss T. usneoides, are widely used as the bioindicator of Hg pollution. However, the effects of different Hg concentrations on Tillandsia have been rarely studied and the occurrence of hormesis in Tillandsia species has not been determined. In this study, T. usneoides was subjected to stress induced by 15 concentrations of gaseous Hg ranging from 0 to 1.8 μg m–3 through a misting system and then Hg content and eight common biomarkers in leaves were measured. The results showed that leaf Hg content significantly increased with Hg concentration, showing a linear relationship. However, there were no obvious mortality symptoms, indicating that T. usneoides showed strong resistance to Hg. Conversely, there were no simple linear relationships between changes in various biomarkers following Hg treatment of T. usneoides and Hg concentration. With increasing Hg concentration, malondialdehyde (MDA) content did not change significantly, superoxide anion radical content decreased gradually, superoxide dismutase (SOD) content decreased to the bottom and then bounced back, electrical conductivity increased, and glutathione (GSH) and metallothionein (MT) content increased to the peak and then dropped. The coefficient of determination of the dose-effect curves between SOD, GSH, and MT contents and Hg concentration was high, and the dose-effect relationship varied with hormesis. The present study is first to confirm hormesis induced by heavy metal pollution in Tillandsia species.
The Effect of Traditional Opposition Games on University Students' Mood States: The Score and Group Type as Key Aspects
Authors: Cifo Izquierdo María Isabel , Alcaraz-Muñoz Verónica , Gea-García Gemma Maria , Yuste-Lucas Juan Luis , Alonso Roque José Ignacio
Published: January 2021

Playing traditional games has a direct impact on the mood states of the players, and this is the reason why physical education is an ideal setting for teaching how to recognize them and be aware about how they can swing. The objective of the study was to determine if participating in traditional opposition games causes changes to the participants' mood states. A total of 102 students participated. Each participant recorded the intensity of the mood state experienced at the beginning and at the end of the sessions, using the validated Profile of Mood States (POMS) instrument. The pedagogical experience was planned as 4 sessions with 6 and 5 opposition games each: (a) with competition in mixed groups, equally and unequally mixed; (b) without competition in mixed groups, equally and unequally mixed; (c) with competition in same-gender groups; and (d) without competition in same-gender groups. When comparing the different mood states according to session (with or without competition), the mood states of the depression, fatigue, and vigor dimensions were significantly different (p < 0.05), with higher scores in the sessions with competition for the mood states of vigor (Mcompetition = 7.27 and Mno_competition = 3.10) and fatigue (Mcompetition = 4.08 and Mno_competition = 1.80). Also, when comparing the mood states depending on session grouping and group type, the results showed differences in the scores obtained for the dimensions fatigue and anger, and general mood state (p < 0.05). These differences were found at the start of the session and at the end, with the dimension fatigue being the only one with differences in both situations when comparing the same-gender, equally-mixed, and unequally-mixed groups for the two types of traditional opposition games compared. In addition, after an analysis of the mood states depending on gender was performed, the results and therefore the significant differences found, were very similar to those obtained according to group type. Lastly, it was concluded that the type of group (equal, mixed & same gender), and gender were decisive, causing variations in the mood states of the students. This provides valuable information for teaching professionals about the structuring and organization of PE sessions, aiming to promoting positive motor experiences.
Opportunity Finding by Nascent Entrepreneurs: Accidental or Purposeful?
Authors: Zhou Rongji , Wu Sibin
Published: January 2021

Purpose

This research studies an important, but relatively unexplored entrepreneurial aspect: motivation and aspiration on opportunity finding/discovery.

Design/Methodology/Approach

This study surveyed 230 nascent entrepreneurs on their opportunity finding behavior. A poisson regression and a logistic analysis were conducted to discover the relationship between motivation/aspiration and opportunity search behavior.

Findings

Motivation and aspiration interact to influence active search in a positive way. However, only willingness to become an entrepreneur is found to search for opportunities purposefully.

Research Limitations/Implications

Participants of the research are from a Midwest state in United States. Future research may collect sample from more and larger areas.

Practical Implications

Bankers may use entrepreneurial opportunity search behavior as one criterion determining if to fund a person or not.

Originality/Value

This article answers the call to study motivation/aspiration on opportunity finding (Yitshaki and Kropp, 2018;Murnieks et al., 2020). It is one of the first studies to explore the above relationship.