bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of transcriptome analysis to investigate the effects of long-term low temperature stress on liver function in the tiger puffer (Takifugu rubripes)
Authors: Liu Zhifeng , Zhu Liguang , Wang Xinan , Liu Shiying , Ma Aijun , Chang Haowen , Sun Zhibin , Xu Fei , Zhao Haichi
Published: November 2022

The tiger puffer (Takifugu rubripes) is an important economic fish species in northern China. However, it is a warm-temperature species, and low winter temperatures can result in high mortality in aquaculture. Understanding the mechanisms of cold resistance in tiger puffers will thus provide critical information to help cope with winter cold. In this study, we performed transcriptome analysis of livers from puffer fish kept at different temperatures (18°C, 13°C, and 8°C) to identify the key pathways and genes involved in the response to low-temperature stress. We also detected serum levels of proteases, arginine, and proline to obtain further information on the response to cold adaption. Totals of 51, 942, and 195 differentially expressed genes were identified in the 18°C vs 13°C, 18°C vs 8°C, and 13°C vs 8°C groups, respectively. Pathway analysis showed that significantly enriched pathways were mainly related to digestion, metabolism, and environmental adaptation. Most genes in the pathways related to digestion and metabolism were down-regulated, while most genes in the pathways related to environmental adaptation were up-regulated. Serum levels of proteases were significantly lower in the low-temperature groups (13°C and 8°C) compared with the control group (18°C), while arginine and proline levels were significantly higher in the 8°C group compared with the other two groups. These results suggest that low temperature caused digestive and metabolic disorders, as well as adaptive changes to low temperature in tiger puffers. On this premise, we found that some up-regulated genes in the pancreatic secretion pathway, arginine and proline metabolism pathway, and circadian rhythm pathway played important roles in the survival, growth, and development of tiger puffers under low-temperature stress. The accumulation of arginine and proline can maintain metabolism and circulation and resist cold stress. The circadian rhythm is closely related to digestion and metabolism, which is an adaptive change and plays a positive role in the resistance to low temperature. The results of this study provide new insights and a theoretical basis for the study of cold tolerance in tiger puffers.
Perioperative prothrombin complex concentrate and fibrinogen administration are associated with thrombotic complications after liver transplant
Authors: Dehne Sarah , Riede Carlo , Klotz Rosa , Sander Anja , Feisst Manuel , Merle Uta , Mieth Markus , Golriz Mohammad , Mehrabi Arianeb , Büchler Markus W. , Weigand Markus A. , Larmann Jan
Published: November 2022

Background

Use of intraoperative prothrombin complex concentrates (PCC) and fibrinogen concentrate administration has been linked to thrombotic events. However, it is unknown if its use is associated with thrombotic events after liver transplant.

Methods and analysis

We conducted a post hoc analysis of a prospectively conducted registry database study on patients who underwent liver transplant between 2004 and 2017 at Heidelberg University Hospital, Heidelberg, Germany. Univariate and multivariate analyses were used to determine the association between PCC and fibrinogen concentrate administration and thrombotic complications.

Results

Data from 939 transplantations were included in the analysis. Perioperative PCC or fibrinogen administration was independently associated with the primary composite endpoint Hepatic artery thrombosis (HAT), Portal vein thrombosis (PVT), and inferior vena cava thrombosis [adjusted HR: 2.018 (1.174; 3.468), p = 0.011]. PCC or fibrinogen administration was associated with the secondary endpoints 30-day mortality (OR 4.225, p < 0.001), graft failure (OR 3.093, p < 0.001), intraoperative blood loss, red blood cell concentrate, fresh frozen plasma and platelet transfusion, longer hospitalization, and longer length of stay in intensive care units (ICUs) (all p < 0.001). PCC or fibrinogen administration were not associated with pulmonary embolism, myocardial infarction, stroke, or deep vein thrombosis within 30 days after surgery.

Conclusion

A critical review of established strategies in coagulation management during liver transplantation is warranted. Perioperative caregivers should exercise caution when administering coagulation factor concentrate during liver transplant surgery. Prospective randomized controlled trials are needed to establish causality for the relationship between coagulation factors and thrombotic events in liver transplantation. Further studies should be tailored to identify patient subgroups that will likely benefit from PCC or fibrinogen administration.
Cuproptosis key gene FDX1 is a prognostic biomarker and associated with immune infiltration in glioma
Authors: Lu Hanwen , Zhou Liwei , Zhang Bingchang , Xie Yuanyuan , Yang Huiyin , Wang Zhanxiang
Published: November 2022

Recent studies have found that the protein encoded by the FDX1 gene is involved in mediating Cuproptosis as a regulator of protein lipoylation and related to immune response process of tumors. However, the specific biological function of FDX1 in glioma is currently unclear. To explore the potential function of FDX1, this study explored the correlation between the expression of FDX1 in cancers and survival prognosis by analyzing the public databases of GEPIA and Cbioportal. Immune infiltration was analyzed by the TIMER2.0 database in tumors. The possible biological processes and functions of FDX1-related in glioma were annotated through gene enrichment. Relationship between Cuproptosis and autophagy was explored through gene co-expression studies. Summary and conclusions of this study: (1) FDX1 is highly expressed in gliomas and associated with poor prognosis in low-grade gliomas (LGG). (2) Gene annotation indicates that FDX1 is mainly involved in the tumor protein lipoylation and cell death. (3) FDX1 expression is positively correlated with the infiltration of immune cells. (4) LIPT2 and NNAT, two other genes involved in lipoylation, may be unidentified marker gene for Cuproptosis. And the Cuproptosis genes related to FDX1 were positively correlated with the expression of autophagy marker genes Atg5, Atg12, and BECN-1. This evidence suggests that there may be some interaction between FDX1 mediated Cuproptosis and autophagy. In summary, FDX1 may serve as a potential immunotherapy target and prognostic marker for Glioma.
Comparison of machine learning and deep learning-based methods for locomotion mode recognition using a single inertial measurement unit
Authors: Vu Huong Thi Thu , Cao Hoang-Long , Dong Dianbiao , Verstraten Tom , Geeroms Joost , Vanderborght Bram
Published: November 2022

Locomotion mode recognition provides the prosthesis control with the information on when to switch between different walking modes, whereas the gait phase detection indicates where we are in the gait cycle. But powered prostheses often implement a different control strategy for each locomotion mode to improve the functionality of the prosthesis. Existing studies employed several classical machine learning methods for locomotion mode recognition. However, these methods were less effective for data with complex decision boundaries and resulted in misclassifications of motion recognition. Deep learning-based methods potentially resolve these limitations as it is a special type of machine learning method with more sophistication. Therefore, this study evaluated three deep learning-based models for locomotion mode recognition, namely recurrent neural network (RNN), long short-term memory (LSTM) neural network, and convolutional neural network (CNN), and compared the recognition performance of deep learning models to the machine learning model with random forest classifier (RFC). The models are trained from data of one inertial measurement unit (IMU) placed on the lower shanks of four able-bodied subjects to perform four walking modes, including level ground walking (LW), standing (ST), and stair ascent/stair descent (SA/SD). The results indicated that CNN and LSTM models outperformed other models, and these models were promising for applying locomotion mode recognition in real-time for robotic prostheses.
Machine learning-based identification of the novel circRNAs circERBB2 and circCHST12 as potential biomarkers of intracerebral hemorrhage
Authors: Bai Congxia , Hao Xiaoyan , Zhou Lei , Sun Yingying , Song Li , Wang Fengjuan , Yang Liu , Liu Jiayun , Chen Jingzhou
Published: November 2022

Background

The roles and potential diagnostic value of circRNAs in intracerebral hemorrhage (ICH) remain elusive.

Methods

This study aims to investigate the expression profiles of circRNAs by RNA sequencing and RT–PCR in a discovery cohort and an independent validation cohort. Bioinformatics analysis was performed to identify the potential functions of circRNA host genes. Machine learning classification models were used to assess circRNAs as potential biomarkers of ICH.

Results

A total of 125 and 284 differentially expressed circRNAs (fold change > 1.5 and FDR < 0.05) were found between ICH patients and healthy controls in the discovery and validation cohorts, respectively. Nine circRNAs were consistently altered in ICH patients compared to healthy controls. The combination of the novel circERBB2 and circCHST12 in ICH patients and healthy controls showed an area under the curve of 0.917 (95% CI: 0.869–0.965), with a sensitivity of 87.5% and a specificity of 82%. In combination with ICH risk factors, circRNAs improved the performance in discriminating ICH patients from healthy controls. Together with hsa_circ_0005505, two novel circRNAs for differentiating between patients with ICH and healthy controls showed an AUC of 0.946 (95% CI: 0.910–0.982), with a sensitivity of 89.1% and a specificity of 86%.

Conclusion

We provided a transcriptome-wide overview of aberrantly expressed circRNAs in ICH patients and identified hsa_circ_0005505 and novel circERBB2 and circCHST12 as potential biomarkers for diagnosing ICH.
Microstructural organization of the corpus callosum in young endurance athletes: A global tractography study
Authors: Tarumi Takashi , Fukuie Marina , Yamabe Takayuki , Kimura Ryota , Zhu David C. , Ohyama-Byun Keigo , Maeda Seiji , Sugawara Jun
Published: November 2022

Introduction

Aerobic exercise training has been shown to improve microstructural organization of the corpus callosum (CC); however, evidence of this topographic effect is limited.

Purpose

To compare the CC microstructural organization between endurance athletes and sedentary adults using a white-matter fiber tractography approach.

Materials and methods

Diffusion tensor imaging (DTI) and T1-weighted structural data were collected from 15 male young endurance athletes and 16 age- and sex-matched sedentary adults. DTI data were analyzed with a global probabilistic tractography method based on neighborhood anatomical information. Fractional anisotropy (FA) and mean, radial (RD), and axial diffusivities were measured in the eight CC tracts: rostrum, genu, splenium, and body’s prefrontal, premotor, central, parietal, and temporal tracts. Cortical thickness of the CC tract endpoints and the CC tract length and volume were also measured. Physical activity level was assessed by metabolic equivalents (METs).

Results

The athlete group had an average VO2max of 69.5 ± 3.1 ml/kg/min, which is above 90%ile according to the American College of Sports Medicine guideline. Compared with the sedentary group, the athlete group had higher FA in the CC body’s premotor and parietal tracts and the CC splenium. These tracts showed lower RD in the athlete compared with sedentary group. The voxelwise analysis confirmed that the athlete group had higher FA in the CC and other white matter regions than the sedentary group, including the corona radiata, internal capsule, and superior longitudinal fasciculus. Cortical thickness of the CC tract endpoints and the CC tract lengths and volumes were similar between the two groups. Physical activity levels were positively correlated with FA in the CC body’s parietal (r = 0.486, p = 0.006) and temporal (r = 0.425, p = 0.017) tracts and the CC splenium (r = 0.408, p = 0.023).

Conclusion

Young endurance athletes have higher microstructural organization of the CC tracts connected the sensorimotor and visual cortices than the age- and sex-matched sedentary adults.
Attenuated effective connectivity of large-scale brain networks in children with autism spectrum disorders
Authors: Wei Lei , Zhang Yao , Zhai Wensheng , Wang Huaning , Zhang Junchao , Jin Haojie , Feng Jianfei , Qin Qin , Xu Hao , Li Baojuan , Liu Jian
Published: November 2022

Introduction

Understanding the neurological basis of autism spectrum disorder (ASD) is important for the diagnosis and treatment of this mental disorder. Emerging evidence has suggested aberrant functional connectivity of large-scale brain networks in individuals with ASD. However, whether the effective connectivity which measures the causal interactions of these networks is also impaired in these patients remains unclear.

Objects

The main purpose of this study was to investigate the effective connectivity of large-scale brain networks in patients with ASD during resting state.

Materials and methods

The subjects were 42 autistic children and 127 age-matched normal children from the ABIDE II dataset. We investigated effective connectivity of 7 large-scale brain networks including visual network (VN), default mode network (DMN), cerebellum, sensorimotor network (SMN), auditory network (AN), salience network (SN), frontoparietal network (FPN), with spectral dynamic causality model (spDCM). Parametric empirical Bayesian (PEB) was used to perform second-level group analysis and furnished group commonalities and differences in effective connectivity. Furthermore, we analyzed the correlation between the strength of effective connectivity and patients’ clinical characteristics.

Results

For both groups, SMN acted like a hub network which demonstrated dense effective connectivity with other large-scale brain network. We also observed significant causal interactions within the “triple networks” system, including DMN, SN and FPN. Compared with healthy controls, children with ASD showed decreased effective connectivity among some large-scale brain networks. These brain networks included VN, DMN, cerebellum, SMN, and FPN. In addition, we also found significant negative correlation between the strength of the effective connectivity from right angular gyrus (ANG_R) of DMN to left precentral gyrus (PreCG_L) of SMN and ADOS-G or ADOS-2 module 4 stereotyped behaviors and restricted interest total (ADOS_G_STEREO_BEHAV) scores.

Conclusion

Our research provides new evidence for the pathogenesis of children with ASD from the perspective of effective connections within and between large-scale brain networks. The attenuated effective connectivity of brain networks may be a clinical neurobiological feature of ASD. Changes in effective connectivity of brain network in children with ASD may provide useful information for the diagnosis and treatment of the disease.
Ingenuity pathway analysis of α-synuclein predicts potential signaling pathways, network molecules, biological functions, and its role in neurological diseases
Authors: Suthar Sharad Kumar , Lee Sang-Yoon
Published: November 2022

Despite the knowledge that mutation, multiplication, and anomalous function of α-synuclein cause progressive transformation of α-synuclein monomers into toxic amyloid fibrils in neurodegenerative diseases, the understanding of canonical signaling, interaction network molecules, biological functions, and role of α-synuclein remains ambiguous. The evolution of artificial intelligence and Bioinformatics tools have enabled us to analyze a vast pool of data to draw meaningful conclusions about the events occurring in complex biological systems. We have taken the advantage of such a Bioinformatics tool, ingenuity pathway analysis (IPA) to decipher the signaling pathways, interactome, biological functions, and role of α-synuclein. IPA of the α-synuclein NCBI gene dataset revealed neuroinflammation, Huntington’s disease, TREM1, phagosome maturation, and sirtuin signaling as the key canonical signaling pathways. IPA further revealed Parkinson’s disease (PD), sumoylation, and SNARE signaling pathways specific to the toxicity of α-synuclein. A frequency distribution analysis of α-synuclein-associated genes from the NCBI dataset that appeared in the predicted canonical pathways revealed that NFKB1 was the most populated gene across the predicted pathways followed by FOS, PRKCD, TNF, GSK3B, CDC42, IL6, MTOR, PLCB1, and IL1B. Overlapping of the predicted top-five canonical signaling pathways and the α-synuclein NCBI gene dataset divulged that neuroinflammation signaling was the most overlapped pathway, while NFKB1, TNF, and CASP1 were the most shared molecules among the pathways. The major diseases associated with α-synuclein were predicted to be neurological diseases, organismal injury and abnormalities, skeletal and muscular disorders, psychological disorders, and hereditary disorders. The molecule activity predictor (MAP) analysis of the principal interaction network of α-synuclein gene SNCA revealed that SNCA directly interacts with APP, CLU, and NEDD4, whereas it indirectly communicates with CALCA and SOD1. Besides, IPA also predicted amyloid plaque forming APP, cytokines/inflammatory mediators IL1B, TNF, MIF, PTGS2, TP53, and CCL2, and kinases of MAPK family Mek, ERK, and P38 MAPK as the top upstream regulators of α-synuclein signaling cascades. Taken together, the first IPA analysis of α-synuclein predicted PD as the key toxicity pathway, neurodegeneration as the major pathological outcome, and inflammatory mediators as the critical interacting partners of α-synuclein.
Differential influences of serum vitamin C on blood pressure based on age and sex in normotensive individuals
Authors: Huang Rui , Song Linhua , Zhao Jingbo , Lei Yuhua , Li Tian
Published: November 2022

Aim

Hypertension is among the most prevalent chronic diseases with diverse etiology, affecting over 1 billion people globally. In numerous studies, vitamin C inversely correlated with blood pressure and was suspected to have antihypertensive properties. Currently, there is conflicting evidence regarding the relationship between vitamin C and blood pressure, with most studies being conducted on hypertensive subjects. The principal objective of this project was to investigate the relationship between vitamin C and blood pressure in normotensive adult subjects.

Methods

A total of 2,533 individuals aged 20 years and above were enrolled in the present study from the National Health and Nutrition Examination Survey (NHANES) 2017-2018. Outcome variables were systolic blood pressure (SBP) and diastolic blood pressure (DBP). Serum vitamin C was regarded as an independent variable. EmpowerStats software and R (version 3.4.3) were used to examine the association between vitamin C and SBP or DBP.

Results

Vitamin C was reversely correlated with both SBP (β = −0.02, 95% CI: −0.03 to −0.00, p = 0.0306) and DBP (β = −0.02, 95% CI: −0.04 to −0.01, p = <0.0011) after adjusting all covariates. This reverse relationship may be affected by a number of factors, including a person’s gender, age, race, and ethnicity. A U-shaped association between vitamin C and SBP in females and an inverted one between vitamin C and DBP in males were detected, respectively. We further calculated the inflection points at 90.3 μmol/L for females and 40 μmol/L for males. It is somewhat surprising that a reverse U-shaped distribution between vitamin C and SBP and DBP in people over 50 was detected, and the point of inflection of vitamin C were all located at 40 μmol/L.

Conclusion

Vitamin C was negatively correlated with both SBP and DBP in this cross-sectional analysis. However, a U-shaped relationship and an inverted one were also observed in certain people, which implied that, though vitamin C is considered a vital antioxidant, maintaining vitamin C at appropriate levels may be beneficial according to different populations.
Comparison of the efficacy and safety in the treatment strategies between chemotherapy combined with antiangiogenic and with immune checkpoint inhibitors in advanced non-small cell lung cancer patients with negative PD-L1 expression: A network meta-analysis
Authors: Li Jiaqi , Chen Yingjie , Hu Fan , Qiang Huiping , Chang Qing , Qian Jialin , Shen Yinchen , Cai Yong , Chu Tianqing
Published: November 2022

Background

In the first-line treatment of advanced non-small cell lung cancer (NSCLC), for those patients with negative PD-L1 expression, which treatment strategy has the better efficacy and safety between chemotherapy combined with antiangiogenic and with immune checkpoint inhibitors (ICIs) is still unclear due to the absence of head-to-head clinical trials. This study aims to answer the question by performing a systematic review and network meta-analysis (NMA).

Methods

Electronic databases (PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov) were systematically searched accordingly to extract eligible studies from inception to October 2022, as well as the abstracts from the most recent main oncology congresses (American Association for Cancer Research (AACR), American Society of Clinical Oncology (ASCO), World Conference on Lung Cancer (WCLC), and European Society for Medical Oncology (ESMO)). Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) of grades 3 to 5 were independently extracted and collected by two reviewers based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. We used Cochrane’s risk of bias tool for randomized controlled trials through RevMan 5.3 to ascertain the quality of the included studies. NMA with a Bayesian random-effects model was performed by R (version 4.0.4).

Results

According to the ranking list from OS-NMA, pembrolizumab combined with chemotherapy has the most effective ranking first (surface under the cumulative ranking (SUCRA) = 0.809844) (pooled HR = 0.65 [0.51–0.83]). On PFS, the triple combination of nivolumab/bevacizumab/chemotherapy ranks first (NMA estimate: HR = 0.35 [0.28–0.43]). On safety, in combination with chemotherapy, sintilimab has minimal toxicity, followed by pembrolizumab+chemo.

Conclusions

In advanced NSCLC patients with negative PD-L1 expression, pembrolizumab+chemo ranks first in the efficacy of OS and does not apparently increase the incidence of any grade ≥ 3 AE as compared with chemo alone. On PFS, pembrolizumab also has advantages, but for patients with squamous cell carcinoma, camrelizumab+chemo seems to be a better choice.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42021231441.
Improvements in survival for patients with stage IV adenocarcinoma in the lung, diagnosed between 2010 – 2020 - A population-based registry study from Norway
Authors: Børø Siri , Thoresen Steinar , Helland Åslaug
Published: November 2022

Objectives

We investigated how the prognosis for Norwegian patients with stage IV, adenocarcinoma (NSCLC) has developed during the last decade, to observe if increased survival coincides with the introduction of immunotherapy at a population level.

Materials and methods

Incidence data from the Cancer Registry of Norway are virtually complete and includes information about histological subtypes and biomarkers. The data was used to analyze median and relative survival for females and males diagnosed with stage IV NSCLC, divided by histological subgroups and age-groups.

Results

During 2010 – 2020, 14472 patients were diagnosed with lung cancer in stage IV, in Norway. Among them 6351 patients (43%) were classified with adenocarcinoma. The median survival has increased for both sexes, but the largest increase is seen in females. From 2010 to 2020, median survival for females in the 0-69 group increased from 6.7 months to 12 months and from 3.7 months to 10 months for the 70+ age group. For the equivalent male age groups, we see an increase from 6.1 months to 7.7 months for the 0-69 group, and an increase from 3.8 months to 4.5 months for the 70+ group. When excluding patients with EGFR/ALK mutations from the survival analysis, the groups continue to display an increased survival from 2010 to 2020, although modest in the male 70+ group. The 1-year relative survival (RS) has increased for both sexes, from 32.4% to 51.2 in females and 25.4% to 44.5% in males. When EGFR/ALK positive patients were excluded from the analysis 1-year RS in females rose from 32.4% to 47.4% and for males from 25.4% to 41.8%.

Conclusion

A real-world patient population of stage IV, NSCLC adenocarcinoma have had a clinically meaningful increase in both median and relative survival from 2010 – 2020. The steepest survival increase has taken place after 2016, the time point where immunotherapy was implemented as a treatment option for the stage IV, adenocarcinoma population not harboring targetable mutations (EGFR/ALK).
What matters most to patients with multiple myeloma? A Pan-European patient preference study
Authors: Janssens Rosanne , Lang Tamika , Vallejo Ana , Galinsky Jayne , Morgan Kate , Plate Ananda , De Ronne Chris , Verschueren Margaux , Schoefs Elise , Vanhellemont Anneleen , Delforge Michel , Schjesvold Fredrik , Cabezudo Elena , Vandebroek Martina , Stevens Hilde , Simoens Steven , Huys Isabelle
Published: November 2022

Introduction

Given the rapid increase in novel treatments for patients with multiple myeloma (MM), this patient preference study aimed to establish which treatment attributes matter most to MM patients and evaluate discrete choice experiment (DCE) and swing weighting (SW) as two elicitation methods for quantifying patients’ preferences.

Methods

A survey incorporating DCE and SW was disseminated among European MM patients. The survey included attributes and levels informed by a previous qualitative study with 24 MM patients. Latent class and mixed logit models were used to estimate the DCE attribute weights and descriptive analyses were performed to derive SW weights. MM patients and patient organisations provided extensive feedback during survey development.

Results

393 MM patients across 21 countries completed the survey (Myears since diagnosis=6; Mprevious therapies=3). Significant differences (p<.01) between participants’ attribute weights were revealed depending on participants’ prior therapy experience, and their experience with side-effects and symptoms. Multivariate analyses showed that participants across the three MM patient classes identified via the latent class model differed regarding their past number of therapies (F=4.772, p=.009). Patients with the most treatments (class 1) and those with the least treatments (class 3) attached more value to life expectancy versus quality of life-related attributes such as pain, mobility and thinking problems. Conversely, patients with intermediary treatment experience (class 2) attached more value to quality of life-related attributes versus life expectancy. Participants highlighted the difficulty of trading-off between life expectancy and quality of life and between physical and mental health. Participants expressed a need for greater psychological support to cope with their symptoms, treatment side-effects, and uncertainties. With respect to patients’ preferences for the DCE or SW questions, 42% had no preference, 32% preferred DCE, and 25% preferred SW.

Conclusions

Quality of life-related attributes affecting MM patients’ physical, mental and psychological health such as pain, mobility and thinking problems were considered very important to MM patients, next to life expectancy. This underscores a need to include such attributes in decision-making by healthcare stakeholders involved in MM drug development, evidence generation, evaluation, and clinical practice. This study highlights DCE as the preferred methodology for understanding relative attribute weights from a patient’s perspective.
Unsuccessful external validation of the MAC-score for predicting increased MIB-1 index in patients with spinal meningiomas
Authors: El-Hajj Victor Gabriel , Fletcher-Sandersjöö Alexander , Pettersson-Segerlind Jenny , Edström Erik , Elmi-Terander Adrian
Published: November 2022

Objective

Recently, the MAC-spinal meningioma score (MAC-score) was proposed to preoperatively identify spinal meningioma patients with high MIB-1 indices. Risk factors were age ≥ 65 years, a modified McCormick score (mMCs) ≥ 2, and absence of tumor calcification. The aim of this study was to externally validate the MAC-score in an independent cohort.

Methods

Using the same inclusion and exclusion criteria as in the original study, we performed a retrospective, single-center, population-based, cohort study that included patients who had undergone surgical treatment for spinal meningiomas between 2005 – 2017. Data was collected from patient charts and radiographic images. Validation was performed by applying the MAC-score to our cohort and evaluating the area under the receiver operating characteristic curve (AUC).

Results

In total, 108 patients were included. Baseline and outcome data were comparable to the original development study. An increased MIB-1 index (≥5%) was observed in 56 (52%) patients. AUC of the MAC-score in our validation cohort was 0.61 (95% CI: 0.51 – 0.71), which corresponds to a poor discriminative ability.

Conclusion

The MAC-score showed poor discriminative ability for MIB-1 index prediction in patients with spinal meningiomas. Moreover, the MAC-score rests on a weak theoretical and statistical foundation. Consequently, we argue against its clinical implementation.
High expression of RARG accelerates ovarian cancer progression by regulating cell proliferation
Authors: Xiu Lin , Zhao Yuxi , Li Ning , Zeng Jia , Liu Jing , Fu Yongliang , Gao Qiao , Wu Lingying
Published: November 2022

Purpose

To explore the relationship between retinoic acid receptor gamma (RARG) and ovarian cancer (OC) cell proliferation and the prognosis of patients.

Methods

The transcriptome and clinical information of 379 OC and 88 normal ovarian samples were downloaded from the Cancer Genome Atlas (TCGA) database and the Genotype Tissue Expression (GTEx) database. We compared the mRNA level of RARG between ovrian normal and tumor tissues with the Wilcoxon rank sum test.The R package “limma” was used to analyze the differences in RARG expression between different clinical subgroups. Kaplan−Meier analysis was applied to evaluate the correlation between RARG and prognosis of patients. A nomogram was established to predict the effect of RARG on prognosis of OC patients. Immunohistochemistry and qRT−PCR experiments were conducted to determine the differential expression of RARG between ovarian normal and tumor tissues. Finally, we altered RARG expression using specific siRNA and lentiviral expression vectors to explore the function of RARG by CCK-8, cell cycle, colony formation, and xenograft assays in nude mice.

Results

RARG was highly expressed in ovarian tumors and was an independent predictor of poor overall survival outcomes. Subgroup analysis showed the high expression of RARG was related to FIGO stage III-IV (P=0.027), overall survival time <5 years (P=0.013) and dead status (P=0.041). The Kaplan-Meier curve indicated that patients with high RARG expression level had poor prognosis. The area under the curve (AUC) of RAGR expression for predicting patient survival rates at 1, 5 and 9 years were 0.659, 0.616 and 0.627, respectively. The GSEA enrichment analysis revealed that RARG was involved in ovarian cancer progression through multiple pathways. In cellular experiments in vitro, downregulation of RARG expression significantly suppressed the proliferation and colony formation capacity of OC cells. In cellular experiments in vivo, knockdown of RARG significantly reduced tumor growth in nude mice, decreased expression levels of Ki-67 and proliferation cell nuclear antigen (PCNA).

Conclusions

High expression of RARG could promote OC cell proliferation and was an independent predictor of poor prognosis. RARG might work as a potential molecular target and biomarker for individualized diagnosis and treatment in OC patients.
Targeting the chemerin/CMKLR1 axis by small molecule antagonist α-NETA mitigates endometriosis progression
Authors: Yu Ming , Yang Yali , Zhao Hao , Li Mengxia , Chen Jie , Wang Baobei , Xiao Tianxia , Huang Chen , Zhao Huashan , Zhou Wei , Zhang Jian V.
Published: November 2022

Endometriosis is a common gynecological disease, characterized by the presence of endometrial-like lesions outside the uterus. This debilitating disease causes chronic pelvic pain and infertility with limited therapeutics. Chemerin is a secretory protein that acts on CMKLR1 (Chemokine-Like Receptor 1) to execute functions vital for immunity, adiposity, and metabolism. Abnormal chemerin/CMKLR1 axis underlies the pathological mechanisms of certain diseases including cancer and inflammatory diseases, but its role in endometriosis remains unknown. Herein, our results showed that chemerin and CMKLR1 are up-regulated in endometriotic lesions by analyzing the human endometriosis database and murine model. Knockdown of chemerin or CMKLR1 by shRNA led to mesenchymal-epithelial transition (MET) along with compromised viability, migration, and invasion of hEM15A cells. Most importantly, 2-(α-naphthoyl) ethyltrimethylammonium iodide (α-NETA), a small molecule antagonist for CMKLR1, was evidenced to exhibit profound anti-endometriosis effects (anti-growth, anti-mesenchymal features, anti-angiogenesis, and anti-inflammation) in vitro and in vivo. Mechanistically, α-NETA exhibited a dual inhibition effect on PI3K/Akt and MAPK/ERK signaling pathways in hEM15A cells and murine endometriotic grafts. This study highlights that the chemerin/CMKLR1 signaling axis is critical for endometriosis progression, and targeting this axis by α-NETA may provide new options for therapeutic intervention.
Energy metabolic shift contributes to the phenotype modulation of maturation stage ameloblasts
Authors: Arai Haruno , Inaba Akira , Ikezaki Shojiro , Kumakami-Sakano Mika , Azumane Marii , Ohshima Hayato , Morikawa Kazumasa , Harada Hidemitsu , Otsu Keishi
Published: November 2022

Maturation stage ameloblasts (M-ABs) are responsible for terminal enamel mineralization in teeth and undergo characteristic cyclic changes in both morphology and function between ruffle-ended ameloblasts (RA) and smooth-ended ameloblasts (SA). Energy metabolism has recently emerged as a potential regulator of cell differentiation and fate decisions; however, its implication in M-ABs remains unclear. To elucidate the relationship between M-ABs and energy metabolism, we examined the expression pattern of energy metabolic enzymes in M-ABs of mouse incisors. Further, using the HAT7 cell line with M-AB characteristics, we designed experiments to induce an energy metabolic shift by changes in oxygen concentration. We revealed that RA preferentially utilizes oxidative phosphorylation, whereas SA depends on glycolysis-dominant energy metabolism in mouse incisors. In HAT7 cells, hypoxia induced an energy metabolic shift toward a more glycolytic-dominant state, and the energy metabolic shift reduced alkaline phosphatase (ALP) activity and calcium transport and deposition with a change in calcium-related gene expression, implying a phenotype shift from RA to SA. Taken together, these results indicate that the energy metabolic state is an important determinant of the RA/SA phenotype in M-ABs. This study sheds light on the biological significance of energy metabolism in governing M-ABs, providing a novel molecular basis for understanding enamel mineralization and elucidating the pathogenesis of enamel hypomineralization.
Hyperspectral imaging with machine learning for non-destructive classification of Astragalus membranaceus var. mongholicus, Astragalus membranaceus, and similar seeds
Authors: Xu Yanan , Wu Weifeng , Chen Yi , Zhang Tingting , Tu Keling , Hao Yun , Cao Hailu , Dong Xuehui , Sun Qun
Published: November 2022

The roots of Astragalus membranaceus var. mongholicus (AMM) and A. membranaceus (AM) are widely used in traditional Chinese medicine. Although AMM has higher yields and accounts for a larger market share, its cultivation is fraught with challenges, including mixed germplasm resources and widespread adulteration of commercial seeds. Current methods for distinguishing Astragalus seeds from similar (SM) seeds are time-consuming, laborious, and destructive. To establish a non-destructive method, AMM, AM, and SM seeds were collected from various production areas. Machine vision and hyperspectral imaging (HSI) were used to collect morphological data and spectral data of each seed batch, which was used to establish discriminant models through various algorithms. Several preprocessing methods based on hyperspectral data were compared, including multiplicative scatter correction (MSC), standard normal variable (SNV), and first derivative (FD). Then selection methods for identifying informative features in the above data were compared, including successive projections algorithm (SPA), uninformative variable elimination (UVE), and competitive adaptive reweighted sampling (CARS). The results showed that support vector machine (SVM) modeling of machine vision data could distinguish Astragalus seeds from SM with >99% accuracy, but could not satisfactorily distinguish AMM seeds from AM. The FD-UVE-SVM model based on hyperspectral data reached 100.0% accuracy in the validation set. Another 90 seeds were tested, and the recognition accuracy was 100.0%, supporting the stability of the model. In summary, HSI data can be applied to discriminate among the seeds of AMM, AM, and SM non-destructively and with high accuracy, which can drive standardization in the Astragalus production industry.
Early damage enhances compensatory responses to herbivory in wild lima bean
Authors: Bustos-Segura Carlos , González-Salas Raúl , Benrey Betty
Published: November 2022

Damage by herbivores can induce various defensive responses. Induced resistance comprises traits that can reduced the damage, while compensatory responses reduce the negative effects of damage on plant fitness. Timing of damage may be essential in determining the patterns of induced defenses. Here, we tested how timing and frequency of leaf damage affect compensatory responses in wild lima bean plants in terms of growth and seed output, as well as their effects on induced resistance to seed beetles. To this end, we applied mechanical damage to plants at different ontogenetical stages, at one time point (juvenile stage only) or two time points (seedling and juvenile stage or juvenile and reproductive stage). We found that plants damaged at the seedling/juvenile stage showed higher compensatory growth, and seed output compared to plants damaged only at the juvenile stage or juvenile/reproductive stage. Seeds from plants damaged at the juvenile and juvenile/reproductive stages had fewer beetles than seeds from undamaged plants, however this was driven by a density dependent effect of seed abundance rather than a direct effect of damage treatments. We did not find differences in parasitism rate by parasitoid wasps on seed beetles among plant treatments. Our results show that damage at the seedling stage triggers compensatory responses which implies that tolerance to herbivory is enhanced or primed by early damage. Herbivory often occurs at several time points throughout plant development and this study illustrates that, for a full understanding of the factors associated with plant induced responses in a dynamic biotic environment, it is important to determine the multitrophic consequences of damage at more than one ontogenetical stage.
Commercial scale genetic transformation of mature seed embryo explants in maize
Authors: Ye Xudong , Shrawat Ashok , Williams Edward , Rivlin Anatoly , Vaghchhipawala Zarir , Moeller Lorena , Kumpf Jennifer , Subbarao Shubha , Martinell Brian , Armstrong Charles , Saltarikos M. Annie , Somers David , Chen Yurong
Published: November 2022

A novel, efficient maize genetic transformation system was developed using Agrobacterium-mediated transformation of embryo explants from mature seeds. Seeds from field grown plants were sterilized and crushed to isolate embryo explants consisting of the coleoptile, leaf primordia, and shoot apical meristem which were then purified from the ground seed bulk preparation. The infection of relevant tissues of seed embryo explants (SEEs) by Agrobacterium was improved by the centrifugation of the explants. Transgenic plants were obtained by multiple bud induction on high cytokinin media, followed by plant regeneration on hormone-free medium. Three different selectable markers (cp4 epsps, aadA, and nptII) were successfully used for producing transgenic plants. Stable integration of transgenes in the maize genome was demonstrated by molecular analyses and germline transmission of the inserted transgenes to the next generation was confirmed by pollen segregation and progeny analysis. Phenotypic evidence for chimeric transgenic tissue was frequently observed in initial experiments but was significantly reduced by including a second bud induction step with optimized cytokinin concentration. Additional improvements, including culturing explants at an elevated temperature during bud induction led to the development of a revolutionary system for efficient transgenic plant production and genome editing. To our knowledge, this is the first report of successful transgenic plant regeneration through Agrobacterium-mediated transformation of maize mature SEEs. This system starts with mature seed that can be produced in large volumes and the SEEs explants are storable. It has significant advantages in terms of scalability and flexibility over methods that rely on immature explants.
E2Fs co-participate in cadmium stress response through activation of MSHs during the cell cycle
Authors: Zheng Wen-Jie , Li Wang-Qing , Peng Yan , Shao Ye , Tang Li , Liu Ci-Tao , Zhang Dan , Zhang Lan-Jing , Li Ji-Huan , Luo Wu-Zhong , Yuan Zhi-Cheng , Zhao Bing-Ran , Mao Bi-Gang
Published: November 2022

Cadmium is one of the most common heavy metal contaminants found in agricultural fields. MutSα, MutSβ, and MutSγ are three different MutS-associated protein heterodimer complexes consisting of MSH2/MSH6, MSH2/MSH3, and MSH2/MSH7, respectively. These complexes have different mismatch recognition properties and abilities to support MMR. However, changes in mismatch repair genes (OsMSH2, OsMSH3, OsMSH6, and OsMSH7) of the MutS system in rice, one of the most important food crops, under cadmium stress and their association with E2Fs, the key transcription factors affecting cell cycles, are poorly evaluated. In this study, we systematically categorized six rice E2Fs and confirmed that OsMSHs were the downstream target genes of E2F using dual-luciferase reporter assays. In addition, we constructed four msh mutant rice varieties (msh2, msh3, msh6, and msh7) using the CRISPR-Cas9 technology, exposed these mutant rice seedlings to different concentrations of cadmium (0, 2, and 4 mg/L) and observed changes in their phenotype and transcriptomic profiles using RNA-Seq and qRT-PCR. We found that the difference in plant height before and after cadmium stress was more significant in mutant rice seedlings than in wild-type rice seedlings. Transcriptomic profiling and qRT-PCR quantification showed that cadmium stress specifically mobilized cell cycle-related genes ATR, CDKB2;1, MAD2, CycD5;2, CDKA;1, and OsRBR1. Furthermore, we expressed OsE2Fs in yeasts and found that heterologous E2F expression in yeast strains regulated cadmium tolerance by regulating MSHs expression. Further exploration of the underlying mechanisms revealed that cadmium stress may activate the CDKA/CYCD complex, which phosphorylates RBR proteins to release E2F, to regulate downstream MSHs expression and subsequent DNA damage repairment, thereby enhancing the response to cadmium stress.
Arbuscular mycorrhiza induces low oxidative burst in drought-stressed walnut through activating antioxidant defense systems and heat shock transcription factor expression
Authors: Ma Wen-Ya , Qin Qiu-Yun , Zou Ying-Ning , Kuča Kamil , Giri Bhoopander , Wu Qiang-Sheng , Hashem Abeer , Al-Arjani Al-Bandari Fahad , Almutairi Khalid F. , Abd_Allah Elsayed Fathi , Xu Yong-Jie
Published: November 2022

Arbuscular mycorrhizal fungi (AMF) have important roles in enhancing drought tolerance of host plants, but it is not clear whether and how AMF increase drought tolerance in walnut (Juglans regia). We hypothesized that AMF could activate antioxidant defense systems and heat shock transcription factors (Hsfs) transcription levels to alleviate oxidative damage caused by drought. The walnut variety ‘Liaohe No. 1’ was inoculated with Diversispora spurca and exposed to well-watered (WW, 75% of the maximum soil water capacity) and drought stress (DS, 50% of the maximum soil water capacity) for 6 weeks. Plant growth, antioxidant defense systems, and expressions of five JrHsfs in leaves were studied. Such drought treatment inhibited root mycorrhizal colonization, while plant growth performance was still improved by AMF inoculation. Mycorrhizal fungal inoculation triggered the increase in soluble protein, glutathione (GSH), ascorbic acid (ASC), and total ASC contents and ascorbic peroxidase and glutathione reductase activities, along with lower hydrogen peroxide (H2O2), superoxide anion radical (O2•−), and malondialdehyde (MDA) levels, compared with non-inoculation under drought. Mycorrhizal plants also recorded higher peroxidase, catalase, and superoxide dismutase activities than non-mycorrhizal plants under drought. The expression of JrHsf03, JrHsf05, JrHsf20, JrHsf22, and JrHsf24 was up-regulated under WW by AMF, while the expression of JrHsf03, JrHsf22, and JrHsf24 were up-regulated only under drought by AMF. It is concluded that D. spurca induced low oxidative burst in drought-stressed walnut through activating antioxidant defense systems and part Hsfs expressions.
The effect of ethical leadership on service recovery performance: A moderated mediation model of organizational virtuousness and trait mindfulness
Authors: Ma Ding , Wajid Nauman , Anser Muhammad Khalid , Anjum Zafar-Uz-Zaman , Jia Xiaoyun
Published: November 2022

In the present study, we first examined the relationship between ethical leadership and frontline employees’ (FLEs’) service recovery performance (SRP) and then tested the mediating role of organizational virtuousness in the relationship between ethical leadership and SRP in service contexts. Finally, we examined the moderating effect of FLE trait mindfulness on the direct relationship between ethical leadership and organizational virtuousness, as well as the indirect relationship between ethical leadership and SRP, via organizational virtuousness. Three-waved survey data collected from 273 supervisor-employee dyads in different service sector organizations supported our hypothesized relationships. In addition to important theoretical implications, the study carries useful practical implications, particularly for managers who are concerned about improving SRP in the service contexts.