bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor Decelerating and Chemo-Potentiating Action of Methyl Jasmonate on a T Cell Lymphoma In Vivo: Role of Altered Regulation of Metabolism, Cell Survival, Drug Resistance, and Intratumoral Blood Flow
Authors: Goel Yugal , Yadav Saveg , Pandey Shrish Kumar , Temre Mithlesh Kumar , Maurya Babu Nandan , Verma Ashish , Kumar Ajay , Singh Sukh Mahendra
Published: February 2021

Methyl jasmonate (MJ), a natural oxylipin, possesses a broad spectrum of antineoplastic potential in vitro. However, its tumor growth impeding and chemo-potentiating action has not been adequately investigated in vivo. Using a murine thymus-derived tumor named Dalton’s Lymphoma (DL), in the present study, we examined if intra-tumoral administration of MJ can cause tumor growth impedance. We also explored the associated molecular mechanisms governing cell survival, carbohydrate & lipid metabolism, chemo-potentiation, and angiogenesis. MJ administration to tumor-transplanted mice caused deceleration of tumor growth accompanying prolonged survival of the tumor-bearing mice. MJ-dependent tumor growth retardation was associated with the declined blood supply in tumor milieu, cell cycle arrest, augmented induction of apoptosis and necrosis, deregulated glucose and lipid metabolism, enhanced membrane fragility of tumor cells, and altered cytokine repertoire in the tumor microenvironment. MJ administration modulated molecular network implicating Hsp70, Bcl-2, TERT, p53, Cyt c, BAX, GLUT-1, HK 2, LDH A, PDK-1, HIF-1α, ROS, MCT-1, FASN, ACSS2, SREBP1c, VEGF, cytokine repertoire, and MDR1, involved in the regulation of cell survival, carbohydrate and fatty acid metabolism, pH homeostasis, and drug resistance. Thus, the present study unveils novel molecular mechanisms of the tumor growth decelerating action of MJ. Besides, this preclinical study also establishes the adjunct therapeutic potential of MJ. Hence, the present investigation will help to design novel anti-cancer therapeutic regimens for the treatment of hematological malignancies.
Hypomethylating Agents and Immunotherapy: Therapeutic Synergism in Acute Myeloid Leukemia and Myelodysplastic Syndromes
Authors: Wong Kah Keng , Hassan Rosline , Yaacob Nik Soriani
Published: February 2021

Decitabine and guadecitabine are hypomethylating agents (HMAs) that exert inhibitory effects against cancer cells. This includes stimulation of anti-tumor immunity in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients. Treatment of AML and MDS patients with the HMAs confers upregulation of cancer/testis antigens (CTAs) expression including the highly immunogenic CTA NY-ESO-1. This leads to activation of CD4+ and CD8+ T cells for elimination of cancer cells, and it establishes the feasibility to combine cancer vaccine with HMAs to enhance vaccine immunogenicity. Moreover, decitabine and guadecitabine induce the expression of immune checkpoint molecules in AML cells. In this review, the accumulating knowledge on the immunopotentiating properties of decitabine and guadecitabine in AML and MDS patients are presented and discussed. In summary, combination of decitabine or guadecitabine with NY-ESO-1 vaccine enhances vaccine immunogenicity in AML patients. T cells from AML patients stimulated with dendritic cell (DC)/AML fusion vaccine and guadecitabine display increased capacity to lyse AML cells. Moreover, decitabine enhances NK cell-mediated cytotoxicity or CD123-specific chimeric antigen receptor-engineered T cells antileukemic activities against AML. Furthermore, combination of either HMAs with immune checkpoint blockade (ICB) therapy may circumvent their resistance. Finally, clinical trials of either HMAs combined with cancer vaccines, NK cell infusion or ICB therapy in relapsed/refractory AML and high-risk MDS patients are currently underway, highlighting the promising efficacy of HMAs and immunotherapy synergy against these malignancies.
PD-L2 Is Constitutively Expressed in Normal and Malignant Urothelium
Authors: Dowell Alexander C. , Munford Haydn , Goel Anshita , Gordon Naheema S. , James Nicholas D. , Cheng K. K. , Zeegers Maurice P. , Ward Douglas G. , Bryan Richard T.
Published: February 2021

The use of immune checkpoint blockade, in particular PD-1 and PD-L1 inhibitors, is now commonplace in many clinical settings including the treatment of muscle-invasive bladder cancer (MIBC). Notwithstanding, little information exists regarding the expression of the alternative PD-1 ligand, PD-L2 in urothelial bladder cancer (UBC). We therefore set out to characterise the expression of PD-L2 in comparison to PD-L1. Firstly, we assessed PD-L2 expression by immunohistochemistry and found widespread expression of PD-L2 in UBC, albeit with reduced expression in MIBC. We further investigated these findings using RNA-seq data from a cohort of 575 patients demonstrating that PDCD1LG2 (PD-L2) is widely expressed in UBC and correlated with CD274 (PD-L1). However, in contrast to our immunohistochemistry findings, expression was significantly increased in advanced disease. We have also provided detailed evidence of constitutive PD-L2 expression in normal urothelium and propose a mechanism by which PD-L2 is cleaved from the cell surface in MIBC. These data provide a comprehensive assessment of PD-L2 in UBC, showing PD-L2 is abundant in UBC and, importantly, constitutively present in normal urothelium. These data have implications for future development of immune checkpoint blockade, and also the understanding of the function of the immune system in the normal urinary bladder.
New Approaches in Oncology for Repositioning Drugs: The Case of PDE5 Inhibitor Sildenafil
Authors: Cruz-Burgos Marian , Losada-Garcia Alberto , Cruz-Hernández Carlos D. , Cortés-Ramírez Sergio A. , Camacho-Arroyo Ignacio , Gonzalez-Covarrubias Vanessa , Morales-Pacheco Miguel , Trujillo-Bornios Samantha I. , Rodríguez-Dorantes Mauricio
Published: February 2021

The use of already-approved drugs to treat new or alternative diseases has proved to be beneficial in medicine, because it reduces both drug development costs and timelines. Most drugs can be used to treat different illnesses, due their mechanisms of action are not restricted to one molecular target, organ or illness. Diverging from its original intent offers an opportunity to repurpose previously approved drugs to treat other ailments. This is the case of sildenafil (Viagra), a phosphodiesterase-5 (PDE5) inhibitor, which was originally designed to treat systemic hypertension and angina but is currently commercialized as erectile dysfunction treatment. Sildenafil, tadalafil, and vardenafil are PDE5 inhibitors and potent vasodilators, that extend the physiological effects of nitric oxide and cyclic guanosine monophosphate (cGMP) signaling. Although most of the biological implications of these signaling regulations remain unknown, they offer a large therapeutic potential for several diseases. In addition, some PDE5 inhibitors’ molecular effects seem to play a key role in different illnesses such as kidney disease, diabetes mellitus, and cancer. In this review, we discuss the molecular effects of PDE5 inhibitors and their therapeutic repurposing in different types of cancer.
RNA N6-Methyladenosine Regulator-Mediated Methylation Modifications Pattern and Immune Infiltration Features in Glioblastoma
Authors: Pan Yimin , Xiao Kai , Li Yue , Li Yuzhe , Liu Qing
Published: February 2021

Glioblastoma (GBM) is a group of intracranial neoplasms with intra-tumoral heterogeneity. RNA N6-methyladenosine (m6A) methylation modification reportedly plays roles in immune response. The relationship between the m6A modification pattern and immune cell infiltration in GBM remains unknown. Utilizing expression data of GBM patients, we thoroughly explored the potential m6A modification pattern and m6A-related signatures based on 21 regulators. Thereafter, the m6A methylation modification-based prognostic assessment pipeline (MPAP) was constructed to quantitatively assess GBM patients’ clinical prognosis combining the Robustness and LASSO regression. Single-sample gene-set enrichment analysis (ssGSEA) was used to estimate the specific immune cell infiltration level. We identified two diverse clusters with diverse m6A modification characteristics. Based on differentially expressed genes (DEGs) within two clusters, m6A-related signatures were identified to establish the MPAP, which can be used to quantitatively forecast the prognosis of GBM patients. In addition, the relationship between 21 m6A regulators and specific immune cell infiltration was demonstrated in our study and the m6A regulator ELAVL1 was determined to play an important role in the anticancer response to PD-L1 therapy. Our findings indicated the relationship between m6A methylation modification patterns and tumor microenvironment immune cell infiltration, through which we could comprehensively understand resistance to multiple therapies in GBM, as well as accomplish precise risk stratification according to m6A-related signatures.
Development, Validation, and Visualization of A Web-Based Nomogram for Predicting the Recurrence-Free Survival Rate of Patients With Desmoid Tumors
Authors: Liu Haotian , Huang Kai , Li Tao , Yang Tielong , Liao Zhichao , Zhang Chao , Xiang Lijie , Chen Yong , Yang Jilong
Published: February 2021

Background

Surgery is an important treatment option for desmoid tumor (DT) patients, but how to decrease and predict the high recurrence rate remains a major challenge.

Methods

Desmoid tumor patients diagnosed and treated at Tianjin Cancer Institute & Hospital were included, and a web-based nomogram was constructed by screening the recurrence-related risk factors using Cox regression analysis. External validation was conducted with data from the Fudan University Shanghai Cancer Center.

Results

A total of 385 patients were identified. Finally, after excluding patients without surgery, patients who were lost to follow-up, and patients without complete resection, a total of 267 patients were included in the nomogram construction. Among these patients, 53 experienced recurrence, with a recurrence rate of 19.85%. The 3-year and 5-year recurrence-free survival (RFS) rates were 82.5% and 78%, respectively. Age, tumor diameter, admission status, location, and tumor number were correlated with recurrence in univariate Cox analysis. In multivariate Cox analysis, only age, tumor diameter and tumor number were independent risk factors for recurrence and were then used to construct a web-based nomogram to predict recurrence. The concordance index (C-index) of the nomogram was 0.718, and the areas under the curves (AUCs) of the 3-year and 5-year receiver operating characteristic (ROC) curves were 0.751 and 0.761, respectively. In the external validation set, the C-index was 0.706, and the AUCs of the 3-year and 5-year ROC curves are 0.788 and 0.794, respectively.

Conclusions

Age, tumor diameter, and tumor number were independent predictors of recurrence for DTs, and a web-based nomogram containing these three predictors could accurately predict RFS (https://stepforward.shinyapps.io/Desmoidtumor/).
The Role of EBV-Encoded LMP1 in the NPC Tumor Microenvironment: From Function to Therapy
Authors: Lo Angela Kwok-Fung , Dawson Christopher W. , Lung Hong Lok , Wong Ka-Leung , Young Lawrence S.
Published: February 2021

Nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr virus (EBV) infection. It is also characterized by heavy infiltration with non-malignant leucocytes. The EBV-encoded latent membrane protein 1 (LMP1) is believed to play an important role in NPC pathogenesis by virtue of its ability to activate multiple cell signaling pathways which collectively promote cell proliferation and survival, angiogenesis, invasiveness, and aerobic glycolysis. LMP1 also affects cell-cell interactions, antigen presentation, and cytokine and chemokine production. Here, we discuss how LMP1 modulates local immune responses that contribute to the establishment of the NPC tumor microenvironment. We also discuss strategies for targeting the LMP1 protein as a novel therapy for EBV-driven malignancies.
Specific and Sensitive Diagnosis of BCOR-ITD in Various Cancers by Digital PCR
Authors: Barets Doriane , Appay Romain , Heinisch Marie , Battistella Maxime , Bouvier Corinne , Chotard Guillaume , Le Loarer François , Macagno Nicolas , Perbet Romain , Pissaloux Daniel , Rousseau Audrey , Tauziède-Espariat Arnaud , Varlet Pascale , Vasiljevic Alexandre , Colin Carole , Fina Frédéric , Figarella-Branger Dominique
Published: February 2021

BCOR is an epigenetic regulator altered by various mechanisms including BCOR-internal tandem duplication (BCOR-ITD) in a wide range of cancers. Six different BCOR-ITD in the 3’-part of the coding sequence of exon 15 have been reported ranging from 89 to 114 bp in length. BCOR-ITD is a common genetic alteration found in clear cell sarcoma of the kidney and primitive myxoid mesenchymal tumor of infancy (PMMTI) and it characterizes a new type of central nervous system tumor: “CNS tumor with BCOR-ITD”. It can also be detected in undifferentiated round cell sarcoma (URCS) and in high-grade endometrial stromal sarcoma (HGESS). Therefore, it is of utmost importance to search for this genetic alteration in these cancers with the most frequent technique being RNA-sequencing. Here, we developed a new droplet PCR assay (dPCR) to detect the six sequences characterizing BCOR-ITD. To achieve this goal, we used a single colored probe to detect both the duplicated region and the normal sequence that acts as a reference. We first generated seven synthetic DNA sequences: ITD0 (the normal sequence) and ITD1 to ITD6 (the duplicated sequences described in the literature) and then we set up the optima dPCR conditions. We validated our assay on 19 samples from a representative panel of human tumors (9 HGNET-BCOR, 5 URCS, 3 HGESS, and 2 PMMTI) in which BCOR-ITD status was known using at least one other method including RNA sequencing, RT-PCR or DNA-methylation profiling for CNS tumors. Our results showed that our technique was 100% sensitive and specific. DPCR detected BCOR-ITD in 13/19 of the cases; in the remaining 6 cases additional RNA-sequencing revealed BCOR gene fusions. To conclude, in the era of histomolecular classification of human tumors, our modified dPCR assay is of particular interest to detect BCOR-ITD since it is a robust and less expensive test that can be applied to a broad spectrum of cancers that share this alteration.
G6PD-NF-κB-HGF Signal in Gastric Cancer-Associated Mesenchymal Stem Cells Promotes the Proliferation and Metastasis of Gastric Cancer Cells by Upregulating the Expression of HK2
Authors: Chen Bin , Cai Tuo , Huang Chao , Zang Xueyan , Sun Li , Guo Shuwei , Wang Qianqian , Chen Zhihong , Zhao Yuanyuan , Han Zhiqiang , Xu Rongman , Xu Wenrong , Wang Mei , Shen Bo , Zhu Wei
Published: February 2021

Background: Tumor-associated stromal cells have been widely recognized for their tumor-promoting capability involving paracrine signaling. However, the underlying mechanism and the effects of the molecules in the glycolysis pathway in gastric cancer-associated mesenchymal stem cells (GCMSCs) and gastric cancer cells on tumor progression remain unclear.

Methods: The expression of hepatocyte growth factor (HGF) in GCMSCs and bone marrow mesenchymal stem cells (BMMSCs) was detected by enzyme-linked immunosorbent assay (ELISA). The effect of HGF derived from GCMSCs on the proliferation, metastasis, and HK2 expression of gastric cancer cells was evaluated in vitro and in vivo. The effects of G6PD on the production of HGF in mesenchymal stem cells (MSCs) were analyzed by immunoblotting.

Results: HGF derived from GCMSCs promoted glycolysis, proliferation, and metastasis of gastric cancer by upregulating c-Myc-HK2 signal. The progression of the disease induced by GCMSCs decelerated in the absence of HK2. The expression of G6PD activated NF-κB signaling and stimulated the production of HGF in GCMSCs. Blocking HGF derived from GCMSCs decreased proliferation, metastasis, and angiogenesis of gastric cancer cells in vivo.

Conclusions: GCMSCs highly expressed G6PD and facilitated the progression of gastric cancer through the G6PD-NF-κB-HGF axis coordinates. Blocking HGF derived from GCMSCs is a potential new therapeutic target for the treatment of gastric cancer.
Thoracic Fluid Content (TFC) Measurement Using Impedance Cardiography Predicts Outcomes in Critically Ill Children
Authors: Sumbel Lydia , Wats Aanchal , Salameh Mohammed , Appachi Elumalai , Bhalala Utpal
Published: February 2021

Objective: Conventional methods of fluid assessment in critically ill children are difficult and/or inaccurate. Impedance cardiography has capability of measuring thoracic fluid content (TFC). There is an insufficient literature reporting correlation between TFC and conventional methods of fluid balance and whether TFC predicts outcomes in critically ill children. We hypothesized that TFC correlates with indices of fluid balance [FIMO (Fluid Intake Minus Output) and AFIMO (Adjusted Fluid Intake Minus Output)] and is a predictor of outcomes in critically ill children.

Design: Retrospective chart review.

Setting: Pediatric intensive care unit of a tertiary care teaching hospital.

Patients: Children <21 years, admitted to our Pediatric Intensive Care Unit (PICU) between July- November 2018 with acute respiratory failure and/or shock and who were monitored for fluid status using ICON® monitor.

Interventions: None.

Measurements and Main Results: We collected demographic information, data on daily and cumulative fluid balance (CFB), ventilator, PICU and hospital days, occurrence of multi-organ dysfunction syndrome (MODS), and mortality. We calculated AFIMO using insensible fluid loss. We analyzed data using correlation coefficient, chi-square test and multiple linear regression analysis. We analyzed a total 327 recordings of TFC, FIMO and AFIMO as daily records of fluid balance in 61 critically ill children during the study period. The initial TFC, FIMO, and AFIMO in ml [median (IQR)] were 30(23, 44), 300(268, 325), and 21.05(−171.3, 240.2), respectively. The peak TFC, FIMO, and AFIMO in ml were 36(26, 24), 322(286, 334), and 108.8(−143.6, 324.4) respectively. The initial CFB was 1134.2(325.6, 2774.4). TFC did not correlate well with FIMO or AFIMO (correlation coefficient of 0.02 and −0.03, respectively), but a significant proportion of patients with high TFC exhibited pulmonary plethora on x-ray chest (as defined by increased bronchovascular markings and/or presence of pleural effusion) (p = 0.015). The multiple linear regression analysis revealed that initial and peak TFC and peak and mean FIMO and AFIMO predicted outcomes (ventilator days, length of PICU, and hospital days) in critically ill children (p < 0.05).

Conclusions: In our cohort of critically ill children with respiratory failure and/or shock, TFC did not correlate with conventional measures of fluid balance (FIMO/AFIMO), but a significant proportion of patients with high TFC had pulmonary plethora on chest x-ray. Both initial and peak TFC predicted outcomes in critically ill children.
Airway Remodeling Factors During Early-Life Rhinovirus Infection and the Effect of Premature Birth
Authors: XuChen Xilei , Weinstock Jered , Arroyo Maria , Salka Kyle , Chorvinsky Elizabeth , Abutaleb Karima , Aguilar Hector , Kahanowitch Ryan , Rodríguez-Martínez Carlos E. , Perez Geovanny F. , Gutierrez Maria J. , Nino Gustavo
Published: February 2021

Background: Early rhinovirus (RV) infection is a strong risk factor for asthma development. Airway remodeling factors play a key role in the progression of the asthmatic condition. We hypothesized that RV infection in young children elicits the secretion of growth factors implicated in airway remodeling and asthma progression.

Methods: We examined the nasal airway production of remodeling factors in children ( ≤ 2 years old) hospitalized due to PCR-confirmed RV infection. Airway remodeling proteins included: MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, TIMP-2, EGF, Angiopoietin-2, G-CSF, BMP-9, Endoglin, Endothelin-1, Leptin, FGF-1, Follistatin, HGF, HB-EGF, PLGF, VEGF-A, VEGF-C, VEGF-D, FGF-2, TGF-β1, TGF-β2, TGF-β3, PDGF AA, PDGF BB, SPARC, Periostin, OPN, and TGF-α.

Results: A total of 43 young children comprising RV cases (n = 26) and uninfected controls (n = 17) were included. Early RV infection was linked to (1) enhanced production of several remodeling factors (e.g., HGF, TGFα), (2) lower MMP-9/TIMP-2 and MMP-2/TIMP-2 ratios, and (3) increased MMP-10/TIMP-1 ratios. We also found that relative to term infants, severely premature children had reduced MMP-9/TIMP-2 ratios at baseline.

Conclusion: RV infection in young children elicits the airway secretion of growth factors implicated in angiogenesis, fibrosis, and extracellular matrix deposition. Our results highlight the potential of investigating virus-induced airway remodeling growth factors during early infancy to monitor and potentially prevent chronic progression of respiratory disorders in all ages.
Hypertrophic Cardiomyopathy in Children: Pathophysiology, Diagnosis, and Treatment of Non-sarcomeric Causes
Authors: Monda Emanuele , Rubino Marta , Lioncino Michele , Di Fraia Francesco , Pacileo Roberta , Verrillo Federica , Cirillo Annapaola , Caiazza Martina , Fusco Adelaide , Esposito Augusto , Fimiani Fabio , Palmiero Giuseppe , Pacileo Giuseppe , Calabrò Paolo , Russo Maria Giovanna , Limongelli Giuseppe
Published: February 2021

Hypertrophic cardiomyopathy (HCM) is a myocardial disease characterized by left ventricular hypertrophy not solely explained by abnormal loading conditions. Despite its rare prevalence in pediatric age, HCM carries a relevant risk of mortality and morbidity in both infants and children. Pediatric HCM is a large heterogeneous group of disorders. Other than mutations in sarcomeric genes, which represent the most important cause of HCM in adults, childhood HCM includes a high prevalence of non-sarcomeric causes, including inherited errors of metabolism (i.e., glycogen storage diseases, lysosomal storage diseases, and fatty acid oxidation disorders), malformation syndromes, neuromuscular diseases, and mitochondrial disease, which globally represent up to 35% of children with HCM. The age of presentation and the underlying etiology significantly impact the prognosis of children with HCM. Moreover, in recent years, different targeted approaches for non-sarcomeric etiologies of HCM have emerged. Therefore, the etiological diagnosis is a fundamental step in designing specific management and therapy in these subjects. The present review aims to provide an overview of the non-sarcomeric causes of HCM in children, focusing on the pathophysiology, clinical features, diagnosis, and treatment of these rare disorders.
Fisetin Rescues the Mice Brains Against D-Galactose-Induced Oxidative Stress, Neuroinflammation and Memory Impairment
Authors: Ahmad Sareer , Khan Amjad , Ali Waqar , Jo Myeung Hoon , Park Junsung , Ikram Muhammad , Kim Myeong Ok
Published: February 2021

Herein, we have evaluated the protective potentials of Fisetin against d-galactose-induced oxidative stress, neuroinflammation, and memory impairment in mice. d-galactose (D-gal) causes neurological impairment by inducing reactive oxygen species (ROS), neuroinflammation, and synaptic dysfunction, whereas fisetin (Fis) is a natural flavonoid having potential antioxidant effects, and has been used against different models of neurodegenerative diseases. Here, the normal mice were injected with D-gal (100 mg/kg/day for 60 days) and fisetin (20 mg/kg/day for 30 days). To elucidate the protective effects of fisetin against d-galactose induced oxidative stress-mediated neuroinflammation, we conducted western blotting, biochemical, behavioral, and immunofluorescence analyses. According to our findings, D-gal induced oxidative stress, neuroinflammation, synaptic dysfunctions, and cognitive impairment. Conversely, Fisetin prevented the D-gal-mediated ROS accumulation, by regulating the endogenous anti-oxidant mechanisms, such as Sirt1/Nrf2 signaling, suppressed the activated p-JNK/NF-kB pathway, and its downstream targets, such as inflammatory cytokines. Hence, our results together with the previous reports suggest that Fisetin may be beneficial in age-related neurological disorders.
Dietary Trivalent Chromium Exposure Up-Regulates Lipid Metabolism in Coral Trout: The Evidence From Transcriptome Analysis
Authors: Wei Lu , Li Yu , Ye Hengzhen , Xiao Juan , Hogstrand Christer , Green Iain , Guo Zhiqiang , Han Dong
Published: February 2021

Diet quality greatly affects an animal’s performance and metabolism. Despite the fact that trivalent chromium [Cr(III)] is considered an essential element and is widely used in nutritional supplements for animals and humans, the potential toxicity of Cr(III) is unclear. Here, liver transcriptome sequencing was performed on coral trout (Plectropomus leopardus) exposed to 200 mg kg–1 of dietary organic Cr(III) [as chromium picolinate (CrPic)] for 8 weeks. One-hundred-and thirteen differentially expressed genes (DEGs) were identified in response to Cr(III) stress, in comparison to the control, including 31 up-regulated and 82 down-regulated DEGs. Clusters of Orthologous Groups of proteins (COG) classifies DEGs into 15 functional categories, with the predominant category being related to lipid transport and metabolism (9.73%). The Kyoto Encyclopedia of Genes and Genomes (KEGG) assigned DEGs to six major categories with robust DEGs as part of the lipid metabolism pathway (18.58%). Moreover, KEGG functional enrichment analysis showed that these DEGs are primarily related to steroid biosynthesis, terpenoid backbone biosynthesis, and steroid hormone biosynthesis pathways, of which steroid biosynthesis was the most significant pathway, and 12 key up-regulated DEGs (dhcr7, dhcr24, ebp, lss, msmo1, sqle, cyp51, tm7sf2, sc5dl, fdft1, nsdhl, and hsd17b7) were found for steroid biosynthesis pathways. To validate the RNA sequencing data using quantitative real-time PCR (qRT-PCR), qRT-PCR results indicate that the expression of genes encoding HMGCR, TM7SF2, TRYP2, CTRL, EBP, LSS, and CYP51 were induced, while those encoding THRSP, LCE, and MCM5 were reduced, consistent with RNA-seq results. This findings provides the first evidence that a long-term high dose of Cr(III) intake causes lipid metabolism disorder and potential toxicity in fish. Cautious health risk assessment of dietary Cr(III) intake is therefore highly recommended for the commercial and/or natural diets of aquatic animals, which has previously largely been ignored.
A High-Precision Machine Learning Algorithm to Classify Left and Right Outflow Tract Ventricular Tachycardia
Authors: Zheng Jianwei , Fu Guohua , Abudayyeh Islam , Yacoub Magdi , Chang Anthony , Feaster William W. , Ehwerhemuepha Louis , El-Askary Hesham , Du Xianfeng , He Bin , Feng Mingjun , Yu Yibo , Wang Binhao , Liu Jing , Yao Hai , Chu Huimin , Rakovski Cyril
Published: February 2021

Introduction

Multiple algorithms based on 12-lead ECG measurements have been proposed to identify the right ventricular outflow tract (RVOT) and left ventricular outflow tract (LVOT) locations from which ventricular tachycardia (VT) and frequent premature ventricular complex (PVC) originate. However, a clinical-grade machine learning algorithm that automatically analyzes characteristics of 12-lead ECGs and predicts RVOT or LVOT origins of VT and PVC is not currently available. The effective ablation sites of RVOT and LVOT, confirmed by a successful ablation procedure, provide evidence to create RVOT and LVOT labels for the machine learning model.

Methods

We randomly sampled training, validation, and testing data sets from 420 patients who underwent successful catheter ablation (CA) to treat VT or PVC, containing 340 (81%), 38 (9%), and 42 (10%) patients, respectively. We iteratively trained a machine learning algorithm supplied with 1,600,800 features extracted via our proprietary algorithm from 12-lead ECGs of the patients in the training cohort. The area under the curve (AUC) of the receiver operating characteristic curve was calculated from the internal validation data set to choose an optimal discretization cutoff threshold.

Results

The proposed approach attained the following performance: accuracy (ACC) of 97.62 (87.44–99.99), weighted F1-score of 98.46 (90–100), AUC of 98.99 (96.89–100), sensitivity (SE) of 96.97 (82.54–99.89), and specificity (SP) of 100 (62.97–100).

Conclusions

The proposed multistage diagnostic scheme attained clinical-grade precision of prediction for LVOT and RVOT locations of VT origin with fewer applicability restrictions than prior studies.
Cerebrovascular Reactivity Measurement Using Magnetic Resonance Imaging: A Systematic Review
Authors: Sleight Emilie , Stringer Michael S. , Marshall Ian , Wardlaw Joanna M. , Thrippleton Michael J.
Published: February 2021

Cerebrovascular reactivity (CVR) magnetic resonance imaging (MRI) probes cerebral haemodynamic changes in response to a vasodilatory stimulus. CVR closely relates to the health of the vasculature and is therefore a key parameter for studying cerebrovascular diseases such as stroke, small vessel disease and dementias. MRI allows in vivo measurement of CVR but several different methods have been presented in the literature, differing in pulse sequence, hardware requirements, stimulus and image processing technique. We systematically reviewed publications measuring CVR using MRI up to June 2020, identifying 235 relevant papers. We summarised the acquisition methods, experimental parameters, hardware and CVR quantification approaches used, clinical populations investigated, and corresponding summary CVR measures. CVR was investigated in many pathologies such as steno-occlusive diseases, dementia and small vessel disease and is generally lower in patients than in healthy controls. Blood oxygen level dependent (BOLD) acquisitions with fixed inspired CO2 gas or end-tidal CO2 forcing stimulus are the most commonly used methods. General linear modelling of the MRI signal with end-tidal CO2 as the regressor is the most frequently used method to compute CVR. Our survey of CVR measurement approaches and applications will help researchers to identify good practice and provide objective information to inform the development of future consensus recommendations.
Precipitation Changes Regulate Plant and Soil Microbial Biomass Via Plasticity in Plant Biomass Allocation in Grasslands: A Meta-Analysis
Authors: Zhang Chunhui , Xi Nianxun
Published: February 2021

In theory, changes in the amount of rainfall can change plant biomass allocation and subsequently influence coupled plant-soil microbial processes. However, testing patterns of combined responses of plants and soils remains a knowledge gap for terrestrial ecosystems. We carried out a comprehensive review of the available literature and conducted a meta-analysis to explore combined plant and soil microbial responses in grasslands exposed to experimental precipitation changes. We measured the effects of experimental precipitation changes on plant biomass, biomass allocation, and soil microbial biomass and tested for trade-offs between plant and soil responses to altered precipitation. We found that aboveground and belowground plant biomass responded asynchronically to precipitation changes, thereby leading to shifts in plant biomass allocation. Belowground plant biomass did not change under precipitation changes, but aboveground plant biomass decreased in precipitation reduction and increased in precipitation addition. There was a trade-off between responses of aboveground plant biomass and belowground plant biomass to precipitation reduction, but correlation wasn't found for precipitation addition. Microbial biomass carbon (C) did not change under the treatments of precipitation reduction. Increased root allocation may buffer drought stress for soil microbes through root exudations and neutralize microbial responses to precipitation reduction. However, precipitation addition increased microbial biomass C, potentially reflecting the removal of water limitation for soil microbial growth. We found that there were positive correlations between responses of aboveground plant biomass and microbial biomass C to precipitation addition, indicating that increased shoot growth probably promoted microbial responses via litter inputs. In sum, our study suggested that aboveground, belowground plant biomass and soil microbial biomass can respond asynchronically to precipitation changes, and emphasizes that testing the plant-soil system as a whole is necessary for forecasting the effects of precipitation changes on grassland systems.
Conserved Residues in the C-Terminal Domain Affect the Structure and Function of CYP38 in Arabidopsis
Authors: Shi Lujing , Du Lele , Wen Jingru , Zong Xiumei , Zhao Wene , Wang Juan , Xu Min , Wang Yuhua , Fu Aigen
Published: February 2021

Arabidopsis cyclophilin38 (CYP38) is a thylakoid lumen protein critial for PSII assembly and maintenance, and its C-terminal region serves as the target binding domain. We hypothesized that four conserved residues (R290, F294, Q372, and F374) in the C-terminal domain are critical for the structure and function of CYP38. In yeast two-hybrid and protein pull-down assays, CYP38s with single-sited mutations (R290A, F294A, Q372A, or F374A) did not interact with the CP47 E-loop as the wild-type CYP38. In contrast, CYP38 with the R290A/F294A/Q372A/F374A quadruple mutation could bind the CP47 E-loop. Gene transformation analysis showed that the quadruple mutation prevented CYP38 to efficiently complement the mutant phenotype of cyp38. The C-terminal domain half protein with the quadruple mutation, like the wild-type one, could interact with the N-terminal domain or the CP47 E-loop in vitro. The cyp38 plants expressing CYP38 with the quadruple mutation showed a similar BN-PAGE profile as cyp38, but distinct from the wild type. The CYP38 protein with the quadruple mutation associated with the thylakoid membrane less efficiently than the wild-type CYP38. We concluded that these four conserved residues are indispensable as changes of all these residues together resulted in a subtle conformational change of CYP38 and reduced its intramolecular N-C interaction and the ability to associate with the thylakoid membrane, thus impairing its function in chloroplast.
A Maize Male Gametophyte-Specific Gene Encodes ZmLARP6c1, a Potential RNA-Binding Protein Required for Competitive Pollen Tube Growth
Authors: Zhou Lian , Vejlupkova Zuzana , Warman Cedar , Fowler John E.
Published: February 2021

Members of the La-related protein family (LARPs) contain a conserved La module, which has been associated with RNA-binding activity. Expression of the maize gene GRMZM2G323499/Zm00001d018613, a member of the LARP family, is highly specific to pollen, based on both transcriptomic and proteomic assays. This suggests a pollen-specific RNA regulatory function for the protein, designated ZmLARP6c1 based on sequence similarity to the LARP6 subfamily inArabidopsis. To test this hypothesis, aDs-GFPtransposable element insertion in theZmLarp6c1gene (tdsgR82C05) was obtained from the Dooner/Du mutant collection. Sequencing confirmed that theDs-GFPinsertion is in an exon, and thus likely interferes with ZmLARP6c1 function. Tracking inheritance of the insertion via its endosperm-expressed GFP indicated that the mutation was associated with reduced transmission from a heterozygous plant when crossed as a male (ranging from 0.5 to 26.5% transmission), but not as a female. Furthermore, this transmission defect was significantly alleviated when less pollen was applied to the silk, reducing competition between mutant and wild-type pollen. Pollen grain diameter measurements and nuclei counts showed no significant differences between wild-type and mutant pollen. However,in vitro, mutant pollen tubes were significantly shorter than those from sibling wild-type plants, and also displayed altered germination dynamics. These results are consistent with the idea that ZmLARP6c1 provides an important regulatory function during the highly competitive progamic phase of male gametophyte development following arrival of the pollen grain on the silk. The conditional, competitive nature of theZmlarp6c1::Dsmale sterility phenotype (i.e., reduced ability to produce progeny seed) points toward new possibilities for genetic control of parentage in crop production.
Crop Performance Evaluation of Chickpea and Dry Pea Breeding Lines Across Seasons and Locations Using Phenomics Data
Authors: Zhang Chongyuan , McGee Rebecca J. , Vandemark George J. , Sankaran Sindhuja
Published: February 2021

The Pacific Northwest is an important pulse production region in the United States. Currently, pulse crop (chickpea, lentil, and dry pea) breeders rely on traditional phenotyping approaches to collect performance and agronomic data to support decision making. Traditional phenotyping poses constraints on data availability (e.g., number of locations and frequency of data acquisition) and throughput. In this study, phenomics technologies were applied to evaluate the performance and agronomic traits in two pulse (chickpea and dry pea) breeding programs using data acquired over multiple seasons and locations. An unmanned aerial vehicle-based multispectral imaging system was employed to acquire image data of chickpea and dry pea advanced yield trials from three locations during 2017–2019. The images were analyzed semi-automatically with custom image processing algorithm and features were extracted, such as canopy area and summary statistics associated with vegetation indices. The study demonstrated significant correlations (P < 0.05) between image-based features (e.g., canopy area and sum normalized difference vegetation index) with yield (r up to 0.93 and 0.85 for chickpea and dry pea, respectively), days to 50% flowering (r up to 0.76 and 0.85, respectively), and days to physiological maturity (r up to 0.58 and 0.84, respectively). Using image-based features as predictors, seed yield was estimated using least absolute shrinkage and selection operator regression models, during which, coefficients of determination as high as 0.91 and 0.80 during model testing for chickpea and dry pea, respectively, were achieved. The study demonstrated the feasibility to monitor agronomic traits and predict seed yield in chickpea and dry pea breeding trials across multiple locations and seasons using phenomics tools. Phenomics technologies can assist plant breeders to evaluate the performance of breeding materials more efficiently and accelerate breeding programs.
The Relationship of Reading Abilities With the Underlying Cognitive Skills of Math: A Dimensional Approach
Authors: Bernabini Luca , Bonifacci Paola , de Jong Peter F.
Published: February 2021

Math and reading are related, and math problems are often accompanied by problems in reading. In the present study, we used a dimensional approach and we aimed to assess the relationship of reading and math with the cognitive skills assumed to underlie the development of math. The sample included 97 children from 4th and 5th grades of a primary school. Children were administered measures of reading and math, non-verbal IQ, and various underlying cognitive abilities of math (counting, number sense, and number system knowledge). We also included measures of phonological awareness and working memory (WM). Two approaches were undertaken to elucidate the relations of the cognitive skills with math and reading. In the first approach, we examined the unique contributions of math and reading ability, as well as their interaction, to each cognitive ability. In the second approach, the cognitive abilities were taken to predict math and reading. Results from the first set of analyses showed specific effects of math on number sense and number system knowledge, whereas counting was affected by both math and reading. No math-by-reading interactions were observed. In contrast, for phonological awareness, an interaction of math and reading was found. Lower performing children on both math and reading performed disproportionately lower. Results with respect to the second approach confirmed the specific relation of counting, number sense, and number system knowledge to math and the relation of counting to reading but added that each math-related marker contributed independently to math. Following this approach, no unique effects of phonological awareness on math and reading were found. In all, the results show that math is specifically related to counting, number sense, and number system knowledge. The results also highlight what each approach can contribute to an understanding of the relations of the various cognitive correlates with reading and math.
Autobiographical Meaning Making Protects the Sense of Self-Continuity Past Forced Migration
Authors: Camia Christin , Zafar Rida
Published: February 2021

Forced migration changes people’s lives and their sense of self-continuity fundamentally. One memory-based mechanism to protect the sense of self-continuity and psychological well-being is autobiographical meaning making, enabling individuals to explain change in personality and life by connecting personal experiences and other distant parts of life to the self and its development. Aiming to replicate and extend prior research, the current study investigated whether autobiographical meaning making has the potential to support the sense of self-continuity in refugees. We therefore collected life narratives from 31 refugees that were coded for autobiographical reasoning, self-event connections, and global narrative coherence. In line with prior research, results suggest that autobiographical meaning making relates to a higher sense of self-continuity and less psychological distress. Yet, if refugees experienced many continuing postdisplacement stressors in addition to their forced displacement, autobiographical meaning making was associated with higher self-discontinuity and greater psychological distress, especially with trauma-related symptoms such as memory intrusion and hyperarousal. Altogether, results indicate that autobiographical meaning making helps to compensate the effects of extreme biographical disruptions on the sense of self-continuity, as long as the stress caused by the biographical change is not overwhelming or too protracted.
Can Mindfulness Help to Alleviate Loneliness? A Systematic Review and Meta-Analysis
Authors: Teoh Siew Li , Letchumanan Vengadesh , Lee Learn-Han
Published: February 2021

Objective: Mindfulness-based intervention (MBI) has been proposed to alleviate loneliness and improve social connectedness. Several randomized controlled trials (RCTs) have been conducted to evaluate the effectiveness of MBI. This study aimed to critically evaluate and determine the effectiveness and safety of MBI in alleviating the feeling of loneliness.

Methods: We searched Medline, Embase, PsycInfo, Cochrane CENTRAL, and AMED for publications from inception to May 2020. We included RCTs with human subjects who were enrolled in MBI with loneliness as an outcome. The quality of evidence was assessed using Cochrane's Risk of Bias (ROB) tool and Grading of Recommendations Assessment, Development, and Evaluation (GRADE). A random-effects model was used for meta-analysis.

Results: Out of 92 articles identified, eight studies involving 815 participants were included in this study. Most (7/8) trials conducted a minimum of 8 weeks of MBI. Most of the trials (5/8) used UCLA-Loneliness Scale. A pooled analysis combining three trials and compared with wait-list showed significant improvement in loneliness score reduction using the UCLA-R scale with MD of −6.33 [95% confidence interval (CI): −9.39, −3.26]. Subgroup analysis with only two Cognitively-Based Compassion Training (CBCT) trials also showed similar MD of −6.05 (95% CI: −9.53, 2.58). The overall quality of evidence (GRADE) was low.

Conclusions: Mindfulness intervention with an average length of 8-week duration significantly improved the population's loneliness level with no mental health issue. However, this evidence had a low GRADE level.
An ERP Study on the Role of Phonological Processing in Reading Two-Character Compound Chinese Words of High and Low Frequency
Authors: Wang Yuling , Jiang Minghu , Huang Yunlong , Qiu Peijun
Published: February 2021

Unlike in English, the role of phonology in word recognition in Chinese is unclear. In this event-related potential experiment, we investigated the role of phonology in reading both high- and low-frequency two-character compound Chinese words. Participants executed semantic and homophone judgment tasks of the same precede-target pairs. Each pair of either high- or low-frequency words were either unrelated (control condition) or related semantically or phonologically (homophones). The induced P200 component was greater for low- than for high-frequency word-pairs both in semantic and phonological tasks. Homophones in the semantic judgment task and semantically-related words in the phonology task both elicited a smaller N400 than the control condition, word frequency-independently. However, for low-frequency words in the phonological judgment task, it was found that the semantically related pairs released a significantly larger P200 than the control condition. Thus, the semantic activation of both high- and low-frequency words may be no later than phonological activation.
Association Between Substance Use Behaviors, Developmental Assets and Mental Health: A Glance at Latin American Young College Students
Authors: Manrique-Millones Denisse , Wiium Nora , Pineda-Marín Claudia , Fernández-Arata Manuel , Alfonso-Murcia Diego , López-Martínez José Luis , Millones-Rivalles Rosa
Published: February 2021

Positive Youth Development (PYD) is an approach that promotes resilience and focuses on youth strengths rather than their weaknesses as done by the traditional deficit-based perspective. Research in Europe and North America show that developmental assets are associated with school success, psychological well-being, and lower health risks among youth and young adults. However, not much research has been done on these associations in Latin American contexts. The purpose of this research study is to assess the association between substance use behaviors, such as drunkenness and the use of illicit drugs, and mental health, together with the mediating role of developmental assets representing youth strengths (e.g., social competence) and contextual resources (e.g., social support at home or school). Cross-national data was collected from Colombian (n= 210; 70.4% females) and Peruvian(n= 349; 66.5% females) 1st year university students. Results shed light on the protective role of developmental assets regarding substance use behaviors and mental well-being. Specifically, the results showed direct negative associations between developmental assets and substance use behaviors and positive associations of developmental assets with mental health indicators. Internal assets appear to be a stronger predictor of social, emotional, and psychological well-being compared to external assets. We did not find any statistical significance in the association of substance use behavior and mental health. We discuss implications regarding research, policy, and practice.