bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathologically Relevant Mouse Models for Epstein–Barr Virus–Associated B Cell Lymphoma
Authors: Huang Shiyu , Yasuda Tomoharu
Published: February 2021

The Epstein–Barr virus (EBV) is endemic in humans and can efficiently transform infected B cells under some circumstances. If an EBV carrier experiences immune suppression, EBV+ B cells can turn into lymphoblasts and exhibit growth expansion that may cause lymphoproliferative diseases which often develop into lymphoma. Our immune system conducts surveillance for EBV+ B cells in order to block spontaneous tumor formation. Here, we summarize the EBV products involved in tumorigenesis, EBV-associated lymphomas, and pathologically relevant mouse models. Preclinical mouse models for a range of EBV-associated diseases not only clear the path to new therapeutic approaches but also aid in our understanding of the nature of lymphomagenesis and immune surveillance.
Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies
Authors: Ricke Darrell O.
Published: February 2021

COVID-19 (SARS-CoV-2) disease severity and stages varies from asymptomatic, mild flu-like symptoms, moderate, severe, critical, and chronic disease. COVID-19 disease progression include lymphopenia, elevated proinflammatory cytokines and chemokines, accumulation of macrophages and neutrophils in lungs, immune dysregulation, cytokine storms, acute respiratory distress syndrome (ARDS), etc. Development of vaccines to severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome coronavirus (MERS-CoV), and other coronavirus has been difficult to create due to vaccine induced enhanced disease responses in animal models. Multiple betacoronaviruses including SARS-CoV-2 and SARS-CoV-1 expand cellular tropism by infecting some phagocytic cells (immature macrophages and dendritic cells) via antibody bound Fc receptor uptake of virus. Antibody-dependent enhancement (ADE) may be involved in the clinical observation of increased severity of symptoms associated with early high levels of SARS-CoV-2 antibodies in patients. Infants with multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 may also have ADE caused by maternally acquired SARS-CoV-2 antibodies bound to mast cells. ADE risks associated with SARS-CoV-2 has implications for COVID-19 and MIS-C treatments, B-cell vaccines, SARS-CoV-2 antibody therapy, and convalescent plasma therapy for patients. SARS-CoV-2 antibodies bound to mast cells may be involved in MIS-C and multisystem inflammatory syndrome in adults (MIS-A) following initial COVID-19 infection. SARS-CoV-2 antibodies bound to Fc receptors on macrophages and mast cells may represent two different mechanisms for ADE in patients. These two different ADE risks have possible implications for SARS-CoV-2 B-cell vaccines for subsets of populations based on age, cross-reactive antibodies, variabilities in antibody levels over time, and pregnancy. These models place increased emphasis on the importance of developing safe SARS-CoV-2 T cell vaccines that are not dependent upon antibodies.
Performance of Saliva Samples for COVID-19 Diagnosis by Using the AllplexTM 2019-nCoV Assay Kit
Authors: Tapia Cecilia V. , Marcia Campos , Ivone Mora , Nadia Pozas , Lesly Morales , Camila Guzmán , Valentina Aguilera , Paula Ibarra , Fabien Magne
Published: February 2021

Background: Although the nasopharyngeal swab (NPS) is the reference sampling method for the detection of SARS-Cov-2, it is not always possible to collect NPS in some patients. Saliva represents an interesting sampling method because it is less invasive and more convenient in patients with nasal or pharyngeal lesions.

Objective: To compare the RT-qPCR test performances of saliva samples with nasal mid-turbinate swab (NMTS) and NPS samples in a cohort of ambulatory patients suspected of having COVID-19.

Study Design: For each of the 112 enrolled patients, NPS, NMTS, and saliva samples were collected and tested for SARS-Cov-2 detection using three different target genes (RdRP, N and E genes) by RT-qPCR.

Results: Among the positive samples (56/112), saliva samples showed a lower percentage of SARS-Cov-2 detection compared to NPS samples, (85.7 vs. 96.4%), while still a lower percentage was observed for NMTS samples (78.6%). In average, saliva samples showed higher Ct values for all tested target genes, compared to those from NPS and NMTS samples.

Conclusions: By using the AllplexTM 2019-nCoV Assay Kit, saliva samples showed lower sensitivity for SARS CoV-2 compared to NPS samples; however, the not detected cases had lower viral burden in NPS samples (CT values >33) representing an interesting alternative sampling method in patients in which it is not possible to take a NPS sample.
Local Geomorphological Gradients and Land Use Patterns Play Key Role on the Soil Bacterial Community Diversity and Dynamics in the Highly Endemic Indigenous Afrotemperate Coastal Scarp Forest Biome
Authors: Ogola Henry Joseph Oduor , Selvarajan Ramganesh , Tekere Memory
Published: February 2021

Southern Afrotemperate forests are small multi-layered and highly fragmented biodiversity rich biomes that support unique flora and fauna endemism. However, little is known about the microbial community and their contribution to these ecosystems. In this study, high throughput sequencing analysis was used to investigate the soil bacterial community structure and function, and understand the effect of local topography/geomorphological formations and land use patterns on a coastal scarp forest. Soil samples were collected from three forest topography sites: upper (steeper gradients, 30–55°; open canopy cover, <30%), mid (less steep, 15–30°; continuous forest canopy, >80%), and lower (flatter gradient, <15°; open canopy cover, 20–65%), and from the adjacent sugarcane farms. Results indicated that forest soils were dominated by members of phyla Proteobacteria (mainly members of α-proteobacteria), Actinobacteria, Acidobacteria, Firmicutes, and Planctomycetes, while Actinobacteria and to a lesser extent β-proteobacteria and γ-proteobacteria dominated SC soils. The core bacterial community clustered by habitat (forest vs. sugarcane farm) and differed significantly between the forest topography sites. The Rhizobiales (genera Variibacter, Bradyrhizobium, and unclassified Rhizobiales) and Rhodospirallales (unclassified Rhodospirillum DA111) were more abundant in forest mid and lower topographies. Steeper forest topography (forest_upper) characterized by the highly leached sandy/stony acidic soils, low in organic nutrients (C and N) and plant densities correlated to significant reduction of bacterial diversity and richness, associating significantly with members of order Burkholderiales (Burkholderia-Paraburkholderia, Delftia, and Massilia) as the key indicator taxa. In contrast, changes in the total nitrogen (TN), soil organic matter (SOM), and high acidity (low pH) significantly influenced bacterial community structure in sugarcane farm soils, with genus Acidothermus (Frankiales) and uncultured Solirubrobacterales YNFP111 were the most abundant indicator taxa. Availability of soil nutrients (TN and SOM) was the strongest driver of metabolic functions related to C fixation and metabolism, N and S cycling; these processes being significantly abundant in forest than sugarcane farm soils. Overall, these results revealed that the local topographical/geomorphological gradients and sugarcane farming affect both soil characteristics and forest vegetation (canopy coverage), that indirectly drives the structure and composition of bacterial communities in scarp forest soils.
Insights Into Insect Vector Transmission and Epidemiology of Plant-Infecting Fijiviruses
Authors: Zhang Lu , Wu Nan , Ren Yingdang , Wang Xifeng
Published: February 2021

Viruses in genus Fijivirus (family Reoviridae) have caused serious damage to rice, maize and sugarcane in American, Asian, European and Oceanian countries, where seven plant-infecting and two insect-specific viruses have been reported. Because the planthopper vectors are the only means of virus spread in nature, their migration and efficient transmission of these viruses among different crops or gramineous weeds in a persistent propagative manner are obligatory for virus epidemics. Understanding the mechanisms of virus transmission by these insect vectors is thus key for managing the spread of virus. This review describes current understandings of main fijiviruses and their insect vectors, transmission characteristics, effects of viruses on the behavior and physiology of vector insects, molecular transmission mechanisms. The relationships among transmission, virus epidemics and management are also discussed. To better understand fijivirus-plant disease system, research needs to focus on the complex interactions among the virus, insect vector, insect microbes, and plants.
Exogenous Alpha-Synuclein Evoked Parkin Downregulation Promotes Mitochondrial Dysfunction in Neuronal Cells. Implications for Parkinson’s Disease Pathology
Authors: Wilkaniec Anna , Lenkiewicz Anna M. , Babiec Lidia , Murawska Emilia , Jęśko Henryk M. , Cieślik Magdalena , Culmsee Carsten , Adamczyk Agata
Published: February 2021

Aberrant secretion and accumulation of α-synuclein (α-Syn) as well as the loss of parkin function are associated with the pathogenesis of Parkinson’s disease (PD). Our previous study suggested a functional interaction between those two proteins, showing that the extracellular α-Syn evoked post-translational modifications of parkin, leading to its autoubiquitination and degradation. While parkin plays an important role in mitochondrial biogenesis and turnover, including mitochondrial fission/fusion as well as mitophagy, the involvement of parkin deregulation in α-Syn-induced mitochondrial damage is largely unknown. In the present study, we demonstrated that treatment with exogenous α-Syn triggers mitochondrial dysfunction, reflected by the depolarization of the mitochondrial membrane, elevated synthesis of the mitochondrial superoxide anion, and a decrease in cellular ATP level. At the same time, we observed a protective effect of parkin overexpression on α-Syn-induced mitochondrial dysfunction. α-Syn-dependent disturbances of mitophagy were also shown to be directly related to reduced parkin levels in mitochondria and decreased ubiquitination of mitochondrial proteins. Also, α-Syn impaired mitochondrial biosynthesis due to the parkin-dependent reduction of PGC-1α protein levels. Finally, loss of parkin function as a result of α-Syn treatment induced an overall breakdown of mitochondrial homeostasis that led to the accumulation of abnormal mitochondria. These findings may thus provide the first compelling evidence for the direct association of α-Syn-mediated parkin depletion to impaired mitochondrial function in PD. We suggest that improvement of parkin function may serve as a novel therapeutic strategy to prevent mitochondrial impairment and neurodegeneration in PD (thereby slowing the progression of the disease).
Computed-Tomography-Structured Reporting in Middle Ear Opacification: Surgical Results and Clinical Considerations From a Large Retrospective Analysis
Authors: Cavaliere Michele , Di Lullo Antonella Miriam , Russo Camilla , Mesolella Massimo , Cantone Elena , Di Lorenzo Giuseppe , Motta Gaetano , Elefante Andrea
Published: February 2021

Purpose: The aim of the study is to compare the accuracy of unstructured preoperative Computed Tomography (CT) reports from non-tertiary diagnostic centers with intraoperative findings in a large cohort of patients with Chronic Otitis Media (COM) undergone surgery.

Methods: From 2012 to 2019, a total number of 301 patients were considered for our purposes. All patients with clinical evidence of COM had preoperative non-contrast high resolution CT scan of the temporal bone in non-tertiary diagnostic centers, performed within 3 months before surgery.

Results: The accuracy of CT reports was analyzed in terms of nature, anatomical site, disease extension, bony erosion, vascular structures abnormalities relevant to surgical planning, and Eustachian tube patency. Compared to post-surgical findings, CT reporting critical analysis revealed a tendency to overestimation of bony erosion, coupled to underestimated description of facial canal/lateral semi-circular canal, vascular structures, and Eustachian tube.

Conclusion: Discrepancies between CT reports and surgical findings in middle ear opacification can be at least in part due to limited expertise of general radiologists in ENT neuroimaging. To limit this lack of information and the limited accuracy of middle ear structures depiction, here we propose a structured checklist to adopt in the case of a temporal bone CT scan for COM, in order to optimize the communication with surgeons and provide all the crucial information for an accurate surgical planning.
Long-Term Outcomes of the Minimally Invasive Ponto Surgery vs. Linear Incision Technique With Soft Tissue Preservation for Installation of Percutaneous Bone Conduction Devices
Authors: Strijbos Ruben M. , Straatman Louise V. , Calon Tim G. A. , Johansson Martin L. , de Bruijn Arthur J. G. , van den Berge Herbert , Wagenaar Mariette , Eichhorn Edwin , Janssen Miranda , Jonhede Sofia , van Tongeren Joost , Holmberg Marcus , Stokroos Robert
Published: February 2021

Objective: Comparing the surgical outcomes of the Minimally Invasive Ponto Surgery (MIPS) technique with the linear incision technique with soft tissue preservation (LITT-P) for bone conduction devices after a follow-up of 22 months.

Methods: In this multicenter randomized controlled trial, there was the inclusion of 64 adult patients eligible for unilateral surgery. There was 1:1 randomization to the MIPS (test) or the LITT-P (control) group. The primary outcome was an (adverse) soft tissue reaction. Secondary outcomes were pain, loss of sensibility, soft tissue height/overgrowth, skin sagging, implant loss, Implant Stability Quotient measurements, cosmetic scores, and quality of life questionnaires.

Results: Sixty-three subjects were analyzed in the intention-to-treat population. No differences were found in the presence of (adverse) soft tissue reactions during complete follow-up. Also, there were no differences in pain, wound dehiscence, skin level, soft tissue overgrowth, and overall quality of life. Loss of sensibility (until 3-month post-surgery), cosmetic scores, and skin sagging outcomes were better in the MIPS group. The Implant Stability Quotient was higher after the LITT-P for different abutment lengths at various points of follow-up. Implant extrusion was nonsignificantly higher after the MIPS (15.2%) compared with LITT-P (3.3%).

Conclusion: The long-term results show favorable outcomes for both techniques. The MIPS is a promising technique with some benefits over the LITT-P. Concerns regarding nonsignificantly higher implant loss may be overcome with future developments and research.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT02438618.
Fine Tuning of Traumatic Brain Injury Management in Neurointensive Care—Indicative Observations and Future Perspectives
Authors: Svedung Wettervik Teodor M. , Lewén Anders , Enblad Per
Published: February 2021

Neurointensive care (NIC) has contributed to great improvements in clinical outcomes for patients with severe traumatic brain injury (TBI) by preventing, detecting, and treating secondary insults and thereby reducing secondary brain injury. Traditional NIC management has mainly focused on generally applicable escalated treatment protocols to avoid high intracranial pressure (ICP) and to keep the cerebral perfusion pressure (CPP) at sufficiently high levels. However, TBI is a very heterogeneous disease regarding the type of injury, age, comorbidity, secondary injury mechanisms, etc. In recent years, the introduction of multimodality monitoring, including, e.g., pressure autoregulation, brain tissue oxygenation, and cerebral energy metabolism, in addition to ICP and CPP, has increased the understanding of the complex pathophysiology and the physiological effects of treatments in this condition. In this article, we will present some potential future approaches for more individualized patient management and fine-tuning of NIC, taking advantage of multimodal monitoring to further improve outcome after severe TBI.
Predictors of Adherence Among Patients With Multiple Sclerosis Using the BETACONNECT® Autoinjector: A Prospective Observational Cohort Study
Authors: Köhler Wolfgang , Bayer-Gersmann Kirsten , Neußer Thomas , Schürks Markus , Ziemssen Tjalf
Published: February 2021

Background: In patients with multiple sclerosis (MS), non-adherence to disease-modifying drug therapy is associated with an increased rate of MS relapses. Early identification of patients at risk of non-adherence would allow provision of timely and individualized support. The aim of the BETAPREDICT study was to investigate potential predictors of adherence in patients with MS in Germany treated with interferon β-1b (IFNβ-1b) using the BETACONNECT® autoinjector.

Methods: BETAPREDICT was a national, multi-center, prospective, non-interventional, single-arm, 24-month cohort study of patients with relapsing–remitting MS or clinically isolated syndrome receiving IFNβ-1b via the BETACONNECT® autoinjector (ClinicalTrials.gov: NCT02486640). Injection data were captured by the autoinjector. The primary objective was to determine baseline predictors of compliance, persistence, and adherence to IFNβ-1b treatment after 12- and 24 months using multivariable-adjusted regression. Secondary objectives included evaluation of satisfaction with the autoinjector, injection site pain, vitamin and nutrient supplementation, clinical course, and patient-related outcome measures.

Results: Of 165 patients enrolled, 153 were available for analysis (120 with autoinjector data). Seventy-two patients left the study prematurely. Compliance (N = 120), persistence (N = 153), and adherence (N = 120) at 24 months were 89.1, 53.6, and 41.7%, respectively. Compliance at 12- and 24 months was predicted by intake of vitamin D supplements and absence of specific injection site reactions. Positive predictors of persistence included age (at 12- and 24 months) and previous duration of treatment (at 12 months), while intake of vitamins/nutrients other than vitamin D was a negative predictor (at 12 months). Positive predictors of adherence at 24 months were age and being experienced with IFNβ-1b. Higher scores in specific SF-36 subscales were positive predictors of medication-taking behavior at 24 months. Satisfaction with the autoinjector was high at baseline and 24 months (median score: 9 out of 10).

Conclusions: Compliance with IFNβ-1b treatment among participants still under observation remained high over a 24-month period, while persistence and adherence continuously declined. Multiple factors affected medication-taking behavior, including patient characteristics, treatment history, injection site reactions, patients' perception of their health and support programs. The importance of these factors may differ among patients according to their individual situation.
Epileptic High-Frequency Oscillations in Intracranial EEG Are Not Confounded by Cognitive Tasks
Authors: Boran Ece , Stieglitz Lennart , Sarnthein Johannes
Published: February 2021

Rationale: High-frequency oscillations (HFOs) in intracranial EEG (iEEG) are used to delineate the epileptogenic zone during presurgical diagnostic assessment in patients with epilepsy. HFOs are historically divided into ripples (80–250 Hz), fast ripples (FR, >250 Hz), and their co-occurrence (FRandR). In a previous study, we had validated the rate of FRandRs during deep sleep to predict seizure outcome. Here, we ask whether epileptic FRandRs might be confounded by physiological FRandRs that are unrelated to epilepsy.

Methods: We recorded iEEG in the medial temporal lobe MTL (hippocampus, entorhinal cortex, and amygdala) in 17 patients while they performed cognitive tasks. The three cognitive tasks addressed verbal working memory, visual working memory, and emotional processing. In our previous studies, these tasks activated the MTL. We re-analyzed the data of these studies with the automated detector that focuses on the co-occurrence of ripples and FRs (FRandR).

Results: For each task, we identified those channels in which the HFO rate was modulated during the task condition compared to the control condition. However, the number of these channels did not exceed the chance level. Interestingly, even during wakefulness, the HFO rate was higher for channels within the seizure onset zone (SOZ) than for channels outside the SOZ.

Conclusion: Our prospective definition of an epileptic HFO, the FRandR, is not confounded by physiological HFOs that might be elicited by our cognitive tasks. This is reassuring for the clinical use of FRandR as a biomarker of the EZ.
Correcting for Non-stationarity in BOLD-fMRI Connectivity Analyses
Authors: Davey Catherine E. , Grayden David B. , Johnston Leigh A.
Published: February 2021

In this work fMRI BOLD datasets are shown to contain slice-dependent non-stationarities. A model containing slice-dependent, non-stationary signal power is proposed to address time-varying signal power during BOLD data acquisition. The impact of non-stationary power on functional MRI connectivity is analytically derived, establishing that pairwise connectivity estimates are scaled by a function of the time-varying signal power, with magnitude upper bound by 1, and that the variance of sample correlation is increased, thereby inducing spurious connectivity. Consequently, we make the observation that time-varying power during acquisition of BOLD timeseries has the propensity to diminish connectivity estimates. To ameliorate the impact of non-stationary signal power, a simple correction for slice-dependent non-stationarity is proposed. Our correction is analytically shown to restore both signal stationarity and, subsequently, the integrity of connectivity estimates. Theoretical results are corroborated with empirical evidence demonstrating the utility of our correction. In addition, slice-dependent non-stationary variance is experimentally determined to be optimally characterized by an inverse Gamma distribution. The resulting distribution of a voxel's signal intensity is analytically derived to be a generalized Student's-t distribution, providing support for the Gaussianity assumption typically imposed by fMRI connectivity methods.
Diffusion Tensor Imaging Detects Acute Pathology-Specific Changes in the P301L Tauopathy Mouse Model Following Traumatic Brain Injury
Authors: Soni Neha , Medeiros Rodrigo , Alateeq Khawlah , To Xuan Vinh , Nasrallah Fatima A.
Published: February 2021

Traumatic brain injury (TBI) has been linked with tauopathy. However, imaging methods that can non-invasively detect tau-protein abnormalities following TBI need further investigation. This study aimed to investigate the potential of diffusion tensor imaging (DTI) to detect tauopathy following TBI in P301L mutant-tau-transgenic-pR5-mice. A total of 24 9-month-old pR5 mice were randomly assigned to sham and TBI groups. Controlled cortical injuries/craniotomies were performed for TBI/sham groups followed by DTI data acquisition on days 1 and 7 post-injury. DTI data were analyzed by using voxelwise analysis and track-based spatial statistics for gray matter and white matter. Further, immunohistochemistry was performed for total-tau and phosphorylated-tau, astrocytes, and microglia. To detect the association of DTI with these pathological markers, a correlation analysis was performed between DTI and histology findings. At day 1 post-TBI, DTI revealed a widespread reduction in fractional anisotropy (FA) and axial diffusivity (AxD) in the TBI group compared to shams. On day 7, further reduction in FA, AxD, and mean diffusivity and increased radial diffusivity were observed. FA was significantly increased in the amygdala and cortex. Correlation results showed that in the ipsilateral hemisphere FA reduction was associated with increased phosphorylated-tau and glial-immunoreactivity, whereas in the contralateral regions, the FA increase was associated with increased immunostaining for astrocytes. This study is the first to exploit DTI to investigate the effect of TBI in tau-transgenic mice. We show that alterations in the DTI signal were associated with glial activity following TBI and would most likely reflect changes that co-occur with/without phosphorylated-tau. In addition, FA may be a promising measure to identify discrete pathological processes such as increased astroglia activation, tau-hyperphosphorylation or both in the brain following TBI.
Identification of Immune-Related Therapeutically Relevant Biomarkers in Breast Cancer and Breast Cancer Stem Cells by Transcriptome-Wide Analysis: A Clinical Prospective Study
Authors: Wang Linbang , Liu Wei , Liu Jingkun , Wang Yuanyuan , Tai Jiaojiao , Yin Xuedong , Tan Jinxiang
Published: February 2021

Cancer stem cells (CSCs) represent a subset of tumor cells that are responsible for recurrence and metastasis of tumors. These cells are resistant to radiotherapy and chemotherapy. Immunotherapeutic strategies that target CSCs specifically have provided initial results; however, the mechanism of action of these strategies is unclear. The data were requested from The Cancer Genome Atlas and Genotype-Tissue Expression, followed with the survival analysis and weighted gene co-expression network analysis to detect survival and stemness related genes. Patients were divided into three groups based on their immune status by applying single sample GSEA (ssGSEA) with proven dependability by ESTIMATE analysis. The filtered key genes were analyzed using oncomine, GEPIA, HPA, qRT-PCR, and functional analysis. Patients in a group with a higher stemness and a lower immune infiltration showed a worse overall survival probability, stemness and immune infiltration characteristics of breast cancer progressed in a non-linear fashion. Thirteen key genes related to stemness and immunity were identified and the functional analysis indicated their crucial roles in cell proliferation and immune escape strategies. The qRT-PCR results showed that the expression of PIMREG and MTFR2 differed in different stages of patients. Our study revealed a promising potential for CSC-target immunotherapy in the early stage of cancer and a probable value for PIMREG and MTFR2 as biomarkers and targets for immunotherapy.
The Current Role of Adjuvant Chemotherapy in Locally Advanced Nasopharyngeal Carcinoma
Authors: Su Lin , She Lei , Shen Liangfang
Published: February 2021

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors of the head and neck, and it originates from the mucous epithelium of the nasopharynx. Because it is “hidden”, the symptoms of NPC can easily be missed, and more than 70% of patients present with locally advanced disease at diagnosis. Concurrent radiation therapy with chemotherapy can significantly improve regional control of NPC. At present, distant metastasis is the main cause of treatment failure. At the end of the 20th century, clinical trial No. IG0099 in the United States confirmed the effectiveness of adjuvant chemotherapy (AC) for the first time. However, in the past 20 years, various clinical trials and meta-analyses conducted globally have yielded contradictory results regarding the effect of AC on locally advanced NPC. AC has changed from category 1 to the current category 2A in the National Comprehensive Cancer Network (NCCN) guidelines, and it remains controversial whether AC can significantly improve the survival of NPC patients. Here, we comprehensively analyzed the role of AC in locally advanced NPC by comparing some treatment methods. We conclude the role of AC in treating locally advanced NPC, based on the studies presented, remains undefined but is associated with increased toxicity.
Associations of P Score With Real-World Survival Improvement Offered by Adjuvant Chemotherapy in Stage II Colon Cancer: A Large Population-Based Longitudinal Cohort Study
Authors: Liu Qi , Shan Zezhi , Luo Dakui , Zhang Sheng , Li Qingguo , Li Xinxiang
Published: February 2021

Background

Based on a prognostic scoring system (P score) proposed by us recently, this retrospective large population-based and propensity score-matched (PSM) study focused on predicting the survival benefit of adjuvant CT in stage II disease.

Methods

Patients diagnosed with stage II colon cancer (N = 73397) were identified from the Surveillance, Epidemiology, and End Results database between January 1, 1988 and December 31, 2005 and divided into the CT and non-CT groups. PSM balanced the patient characteristics between the CT and non-CT groups.

Results

The magnitude of CSS improvement among patients treated with adjuvant CT was significantly associated with the P score, score 8 [hazard ratio (HR) = 0.580, 95% confidence interval (CI) = 0.323–1.040, P = 0.067] was associated with a much higher increased CSS benefit among patients treated with adjuvant CT as compared to score 2* (*, including scores 0, 1, and 2; HR = 1.338, 95% CI = 1.089–1.644, P = 0.006).

Conclusions

High P scores were demonstrated to be associated with superior survival benefit of adjuvant CT. Therapy decisions of adjuvant CT in stage II colon cancer could be tailored on the basis of tumor biology, patient characteristics and the P score.
DNAJC12 as a Mediator Between ESR1 and ERBB4 in Breast Carcinoma Cells
Authors: Lin Mianjie , Wang Ya-Nan , Ye Yixin , Xiong Zhelei , Guo Fengbiao , Chen Haibin
Published: February 2021

Mutation of the DNAJC12 gene is typically associated with non-progressive Parkinsonism, but is also detectable in breast carcinoma where its contribution and mechanisms are unexplored. In breast carcinoma, ESR1 was positively correlated with DNAJC12 and ERBB4, and DNAJC12 was positively correlated with ERBB4. We used the GEO2R tool to compare differential gene expression of MCF-7 cells, following ESR1 knockdown (GEO database, E-GEOD-27473 array), and found decreased expression of DNAJC12 and ERBB4 in ESR1-silenced MCF-7 cells. The number of identical genes having correlativity with ESR1, DNAJC12, or ERBB4 was 12,165 (66.41%). These results suggest that ESR1 can promote the expression of DNAJC12 and ERBB4, and DNAJC12 can enhance the expression of ERBB4 in MCF-7 cells, implying that there may be a regulatory network among these three genes.
RBM10 Regulates Tumor Apoptosis, Proliferation, and Metastasis
Authors: Cao Yingshu , Di Xin , Zhang Qinghua , Li Ranwei , Wang Ke
Published: February 2021

The RNA-binding motif protein 10 (RBM10) is involved in alternative splicing and modifies mRNA post-transcriptionally. RBM10 is abnormally expressed in the lung, breast, and colorectal cancer, female genital tumors, osteosarcoma, and other malignant tumors. It can inhibit proliferation, promote apoptosis, and inhibit invasion and metastasis. RBM10 has long been considered a tumor suppressor because it promotes apoptosis through the regulation of the MDM2-p53 negative feedback loop, Bcl-2, Bax, and other apoptotic proteins and inhibits proliferation through the Notch signaling and rap1a/Akt/CREB pathways. However, it has been recently demonstrated that RBM10 can also promote cancer. Given these different views, it is necessary to summarize the research progress of RBM10 in various fields to reasonably analyze the underlying molecular mechanisms, and provide new ideas and directions for the clinical research of RBM10 in various cancer types. In this review, we provide a new perspective on the reasons for these opposing effects on cancer biology, molecular mechanisms, research progress, and clinical value of RBM10.
Extracellular Matrix Stiffness: New Areas Affecting Cell Metabolism
Authors: Ge Heming , Tian Mengxiang , Pei Qian , Tan Fengbo , Pei Haiping
Published: February 2021

In recent years, in-depth studies have shown that extracellular matrix stiffness plays an important role in cell growth, proliferation, migration, immunity, malignant transformation, and apoptosis. Most of these processes entail metabolic reprogramming of cells. However, the exact mechanism through which extracellular matrix stiffness leads to metabolic reprogramming remains unclear. Insights regarding the relationship between extracellular matrix stiffness and metabolism could help unravel novel therapeutic targets and guide development of clinical approaches against a myriad of diseases. This review provides an overview of different pathways of extracellular matrix stiffness involved in regulating glucose, lipid and amino acid metabolism.
A Nomogram Predicting the Prognosis of Children With Biliary Atresia After Hepatoportoenterostomy
Authors: Liu Jin-qiao , Chen Wen-juan , Zhou Meng-jie , Li Wen-feng , Tang Ju , Zhou Qi-chang
Published: February 2021

Background: Although Kasai portoenterostomy (KPE) is performed timely for most children with biliary atresia (BA), the native liver survival (NLS) is still poor due to the progressive liver fibrosis. Many children have to receive liver transplantation (LT) within 2 years after KPE. Early prediction of the prognosis permits the implementation of prophylactic treatments for BA children. However, studies about the prediction are limited.

Objective: The purpose of this study is to establish a nomogram to predict the prognosis of BA children within 2 years after KPE.

Methods: The follow-up data of 151 BA children were retrospectively reviewed, and were randomly divided into a training cohort for constructing a nomogram (n = 103) and a validation cohort (n = 48). In the training cohort, patients were divided into Group A and Group B according to whether death or LT were observed within 2 years post-KPE. Multivariate Cox regression based on the baseline characteristics, liver function indicators and LSM (liver stiffness measurement) values at KPE and 3 months after KPE was utilized for the establishment of the nomogram in predicting the prognosis of BA within 2 years after KPE. The discrimination and calibration of the nomogram were internally and externally validated.

Results: Fifty-six BA children were included in Group A and 47 were included in group B. Age at KPE, METAVIR score F4, LSM at 3 months, first onset of cholangitis within 3 months, and jaundice clearance time were the independent predictors for the prognosis of BA children within 2 years after KPE (all P < 0.05). The developed nomogram based on these independent predictors showed good discrimination and calibration by the internal and external validation. Its performance was better than each predictor in predicting the prognosis (all P < 0.05).

Conclusions: The established nomogram based on the indicators from the first 3 months after KPE may be useful for predicting the prognosis of BA children within 2 years post-KPE and helpful for the consideration of LT.
The Role of Cold Inducible RNA-Binding Protein in Cardiac Physiology and Diseases
Authors: Zhong Peng , Peng Jianye , Bian Zhouyan , Huang He
Published: February 2021

Cold-inducible RNA-binding protein (CIRP) is an intracellular stress-response protein that can respond to various stress conditions by changing its expression and regulating mRNA stability. As an RNA-binding protein, CIRP modulates gene expression at the post-transcriptional level, including those genes involved in DNA repair, cellular redox metabolism, circadian rhythms, telomere maintenance, and cell survival. CIRP is expressed in a large variety of tissues, including testis, brain, lung, kidney, liver, stomach, bone marrow, and heart. Recent studies have observed the important role of CIRP in cardiac physiology and diseases. CIRP regulates cardiac electrophysiological properties such as the repolarization of cardiomyocytes, the susceptibility of atrial fibrillation, and the function of the sinoatrial node in response to stress. CIRP has also been suggested to protect cardiomyocytes from apoptosis under various stress conditions, including heart failure, high glucose conditions, as well as during extended heart preservation under hypothermic conditions. This review summarizes the findings of CIRP investigations in cardiac physiology and diseases and the underlying molecular mechanism.
Differential Brain and Muscle Tissue Oxygenation Responses to Exercise in Tibetans Compared to Han Chinese
Authors: Fan Jui-Lin , Wu Tian Yi , Lovering Andrew T. , Nan Liya , Bang Wang Liang , Kayser Bengt
Published: February 2021

The Tibetans’ better aerobic exercise capacity at altitude remains ill-understood. We tested the hypothesis that Tibetans display better muscle and brain tissue oxygenation during exercise in hypoxia. Using near-infrared spectrometry (NIRS) to provide indices of tissue oxygenation, we measured oxy- and deoxy-hemoglobin ([O2Hb] and [HHb], respectively) responses of the vastus lateralis muscle and the right prefrontal cortex in ten Han Chinese and ten Tibetans during incremental cycling to exhaustion in a pressure-regulated chamber at simulated sea-level (air at 1 atm: normobaric normoxia) and 5,000 m (air at 0.5 atm: hypobaric hypoxia). Hypoxia reduced aerobic capacity by ∼22% in both groups (d= 0.8,p< 0.001 vs. normoxia), while Tibetans consistently outperformed their Han Chinese counterpart by ∼32% in normoxia and hypoxia (d= 1.0,p= 0.008). We found cerebral [O2Hb] was higher in Tibetans at normoxic maximal effort compared Han (p= 0.001), while muscle [O2Hb] was not different (p= 0.240). Hypoxic exercise lowered muscle [O2Hb] in Tibetans by a greater extent than in Han (interaction effect:p< 0.001 vs. normoxic exercise). Muscle [O2Hb] was lower in Tibetans when compared to Han during hypoxic exercise (d= 0.9,p= 0.003), but not during normoxic exercise (d= 0.4,p= 0.240). Muscle [HHb] was not different between the two groups during normoxic and hypoxic exercise (p= 0.778). Compared to Han, our findings revealed a higher brain tissue oxygenation in Tibetans during maximal exercise in normoxia, but lower muscle tissue oxygenation during exercise in hypoxia. This would suggest that the Tibetans privileged oxygenation of the brain at the expense of that of the muscle.
Neutral Ceramidase Is Required for the Reproduction of Brown Planthopper, Nilaparvata lugens (Stål)
Authors: Shi Xiao-Xiao , Zhu Mu-Fei , Wang Ni , Huang Yuan-Jie , Zhang Min-Jing , Zhang Chao , Ali Soomro A. , Zhou Wen-Wu , Zhang Chuanxi , Mao Cungui , Zhu Zeng-Rong
Published: February 2021

Ceramides are bioactive sphingolipids that have been implicated in insect development; however, their role in insect reproduction remains poorly understood. Here, we report the pivotal role of neutral ceramidase (NCER) in the female reproduction of the brown planthopper (BPH), Nilaparvata lugens (Stål), a significant pest in rice cultivation in Asia. LC-MS/MS demonstrated that, among different developmental stages of BPH, the levels of ceramides were highest in 1st instar nymphs and lowest in adults. The transcription of NCER was negatively correlated with the levels of ceramides at different developmental stages of BPH, in that the transcript levels of NCER were the highest, whereas ceramides levels were the lowest in BPH adults. Knocking down NCER through RNA interference (RNAi) increased the levels of ceramides in BPH females and ovaries, which resulted in a delay in oocyte maturation, a reduction in oviposition and egg hatching rate, as well as the production of vulnerable offspring. Transmission electron microscopy (TEM) analysis and TdT-mediated dUTP Nick-End Labeling (TUNEL) assays showed mitochondrial deficiency and apoptosis in NCER-deficient oocytes. Taken together, these results suggest that NCER plays a crucial role in female reproduction in BPH, likely by regulating the levels of ceramides.
A Novel Model Based on Spatial and Morphological Domains to Predict the Origin of Premature Ventricular Contraction
Authors: He Kaiyue , Sun Jian , Wang Yiwen , Zhong Gaoyan , Yang Cuiwei
Published: February 2021

Pace mapping is commonly used to locate the origin of ventricular arrhythmias, especially premature ventricular contraction (PVC). However, this technique relies on clinicians’ ability to rapidly interpret ECG data. To avoid time-consuming interpretation of ECG morphology, some automated algorithms or computational models have been explored to guide the ablation. Inspired by these studies, we propose a novel model based on spatial and morphological domains. The purpose of this study is to assess this model and compare it with three existing models. The data are available from the Experimental Data and Geometric Analysis Repository database in which three in vivo PVC patients are included. To measure the hit rate (A hit occurs when the predicted site is within 15 mm of the target) of different algorithms, 47 target sites are tested. Moreover, to evaluate the efficiency of different models in narrowing down the target range, 54 targets are verified. As a result, the proposed algorithm achieves the most hits (37/47) and fewest misses (9/47), and it narrows down the target range most, from 27.62 ± 3.47 mm to 10.72 ± 9.58 mm among 54 target sites. It is expected to be applied in the real-time prediction of the origin of ventricular activation to guide the clinician toward the target site.
Genome-Wide Identification and Low Temperature Responsive Pattern of Actin Depolymerizing Factor (ADF) Gene Family in Wheat (Triticum aestivum L.)
Authors: Xu Ke , Zhao Yong , Zhao Sihang , Liu Haodong , Wang Weiwei , Zhang Shuhua , Yang Xueju
Published: February 2021

The actin depolymerizing factor (ADF) gene family, which is conserved in eukaryotes, is important for plant development, growth, and stress responses. Cold stress restricts wheat growth, development, and distribution. However, genome-wide identification and functional analysis of the ADF family in wheat is limited. Further, because of the promising role of ADF genes in cold response, there is need for an understanding of the function of this family on wheat under cold stress. In this study, 25 ADF genes (TaADFs) were identified in the wheat genome and they are distributed on 15 chromosomes. The TaADF gene structures, duplication events, encoded conversed motifs, and cis-acting elements were investigated. Expression profiles derived from RNA-seq data and real-time quantitative PCR analysis revealed the tissue- and temporal-specific TaADF expression patterns. In addition, the expression levels of TaADF13/16/17/18/20/21/22 were significantly affected by cold acclimation or freezing conditions. Overexpression of TaADF16 increased the freezing tolerance of transgenic Arabidopsis, possibly because of enhanced ROS scavenging and changes to the osmotic regulation in cells. The expression levels of seven cold-responsive genes were up-regulated in the transgenic Arabidopsis plants, regardless of whether the plants were exposed to low temperature. These findings provide fundamental information about the wheat ADF genes and may help to elucidate the regulatory effects of the encoded proteins on plant development and responses to low-temperature stress.
Effects of Nitrogen and Intercropping on the Occurrence of Wheat Powdery Mildew and Stripe Rust and the Relationship With Crop Yield
Authors: Luo Chaosheng , Ma Liankun , Zhu Jinhui , Guo Zengpeng , Dong Kun , Dong Yan
Published: February 2021

Wheat powdery mildew (Blumeria graminis f. sp. tritici) and stripe rust (Puccinia striiformis Westend f. sp. tritici) restrict wheat production in southwest China. Nitrogen fertilizers may influence outbreaks of these wheat diseases where wheat/faba beans are intercropped. To clarify how intercropping and varying nitrogen levels influence wheat powdery mildew and stripe rust and their relationship with crop yield, two consecutive field experiments were conducted from 2015 to 2017. Three cropping regimens (monocropped wheat, monocropped faba beans, and intercropped wheat/faba beans) and four nitrogen levels [N0 (0 kg⋅ha–1), N1 (90 kg⋅ha–1), N2 (180 kg⋅ha–1), and N3 (270 kg⋅ha–1)] were evaluated. In two consecutive planting seasons, the incidence and disease index of powdery mildew and stripe rust increased, while the disease index was more affected by nitrogen levels than their incidence. Both diseases were most prevalent at the N3 level. Compared with monocropping, intercropping (N0–N3 levels) reduced the incidence of powdery mildew by 2.8–37.0% and disease index by 15.5–47.4%, increased the relative control effect by 10.7–56.2 and 16.3–47.2%, reduced the incidence of stripe rust by 2.9–42.7% and disease index by 8.3–42.2%, and increased the relative control effect by 5.9–43.7 and 8.8–42.1%. The relative control efficacy of intercropping was most affected by N2 level. Intercropping yield increased with increasing nitrogen by 25.0–46.8%, and overall land equivalent ratio (LER) was 1.30–1.39. The correlation coefficient between disease index and wheat yield for both diseases was −0.7429 to −0.9942, a significant negative correlation, most significant at N1. Nitrogen regulation in intercropped wheat/faba beans can control powdery mildew and stripe rust, and optimize wheat yield. Intercropping at 180 kg ha–1 N2 resulted in the highest yield.
Influence of Social Distance Expressed by Driving Support Agent’s Utterance on Psychological Acceptability
Authors: Miyamoto Tomoki , Katagami Daisuke , Shigemitsu Yuka , Usami Mayumi , Tanaka Takahiro , Kanamori Hitoshi , Yoshihara Yuki , Fujikake Kazuhiro
Published: February 2021

In this study, we discuss the psychological acceptability of an utterance strategy used by the Driving Support Agent (DSA). Previous literature regarding DSA suggests that the adoption of a small robot as a form will increase acceptability. However, the agent’s utterance has been reported as a problem faced by the user. Therefore, in this study, we designed the agent’s utterance using politeness strategy as described by Brown and Levinson’s famous sociolinguistics and pragmatics theory and analyzed its acceptability through a participant-based experiment. In this experiment, we used positive and negative politeness strategies (PPS and NPS, respectively). In general, PPS is utilized to reflect the desire to be liked/recognized by others, whereas NPS is utilized to reflect the need for not wanting to be disturbed by others. Based on our results, PPS was rated high compared to NPS (n = 197). Therefore, many participants highly evaluated PPS. However, there was a group of participants who appreciated NPS. There were also participants who evaluated the two strategies equally. The number of participants in these three groups was observed at 4:1:1. This result contributes as an index on the utterance design of the DSA.
How Cognitive Strengths Compensate Weaknesses Related to Specific Learning Difficulties in Fourth-Grade Children
Authors: Huijsmans Marije D. E. , Kleemans Tijs , Kroesbergen Evelyn H.
Published: February 2021

The goal of the present study was to investigate whether children’s cognitive strengths can compensate the accompanied weaknesses related to their specific learning difficulties. A Bayesian multigroup mediation SEM analysis in 281 fourth-grade children identified a cognitive compensatory mechanism in children with mathematical learning difficulties (n= 36): Children with weak number sense, but strong rapid naming performed slightly better on mathematics compared to peers with weak rapid naming. In contrast, a compensatory mechanism was not identified for children with a comorbid mathematical and reading difficulty (n= 16). One explanation for the latter finding could relate to the lack of ability to compensate, because of the difficulties these children experience in both academic domains. These findings lead to a new direction in research on learning difficulties in mathematics and/or reading by suggesting that children with a learning disability each have a unique profile of interrelated cognitive strengths and weaknesses. Children might compensate with these strengths for their weaknesses, which could lead to (small) learning gains in the affected domain.