bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting the Lung Adenocarcinoma and Its Biomarkers by Integrating Gene Expression and DNA Methylation Data
Authors: Qiu Wang-Ren , Qi Bei-Bei , Lin Wei-Zhong , Zhang Shou-Hua , Yu Wang-Ke , Huang Shun-Fa
Published: June 2022

The early symptoms of lung adenocarcinoma patients are inapparent, and the clinical diagnosis of lung adenocarcinoma is primarily through X-ray examination and pathological section examination, whereas the discovery of biomarkers points out another direction for the diagnosis of lung adenocarcinoma with the development of bioinformatics technology. However, it is not accurate and trustworthy to diagnose lung adenocarcinoma due to omics data with high-dimension and low-sample size (HDLSS) features or biomarkers produced by utilizing only single omics data. To address the above problems, the feature selection methods of biological analysis are used to reduce the dimension of gene expression data (GSE19188) and DNA methylation data (GSE139032, GSE49996). In addition, the Cartesian product method is used to expand the sample set and integrate gene expression data and DNA methylation data. The classification is built by using a deep neural network and is evaluated on K-fold cross validation. Moreover, gene ontology analysis and literature retrieving are used to analyze the biological relevance of selected genes, TCGA database is used for survival analysis of these potential genes through Kaplan-Meier estimates to discover the detailed molecular mechanism of lung adenocarcinoma. Survival analysis shows that COL5A2 and SERPINB5 are significant for identifying lung adenocarcinoma and are considered biomarkers of lung adenocarcinoma.
In silico Identification of miRNAs and Their Targets in Cluster Bean for Their Role in Development and Physiological Responses
Authors: Chaudhary Vrantika , Jangra Sumit , Yadav Neelam R.
Published: June 2022

Cluster bean popularly known as “guar” is a drought-tolerant, annual legume that has recently emerged as an economically important crop, owing to its high protein and gum content. The guar gum has wide range of applications in food, pharma, and mining industries. India is the leading exporter of various cluster bean-based products all across the globe. Non-coding RNAs (miRNAs) are involved in regulating the expression of the target genes leading to variations in the associated pathways or final protein concentrations. The understanding of miRNAs and their associated targets in cluster bean is yet to be used to its full potential. In the present study, cluster bean EST (Expressed Sequence Tags) database was exploited to identify the miRNA and their predicted targets associated with metabolic and biological processes especially response to diverse biotic and abiotic stimuli using in silico approach. Computational analysis based on cluster bean ESTs led to the identification of 57 miRNAs along with their targets. To the best of our knowledge, this is the first report on identification of miRNAs and their targets using ESTs in cluster bean. The miRNA related to gum metabolism was also identified. Most abundant miRNA families predicted in our study were miR156, miR172, and miR2606. The length of most of the mature miRNAs was found to be 21nt long and the range of minimal folding energy (MFE) was 5.8–177.3 (−kcal/mol) with an average value of 25.4 (−kcal/mol). The identification of cluster bean miRNAs and their targets is predicted to hasten the miRNA discovery, resulting in better knowledge of the role of miRNAs in cluster bean development, physiology, and stress responses.
Role of ADAM10 and ADAM17 in the Regulation of Keratinocyte Adhesion in Pemphigus Vulgaris
Authors: Kugelmann Daniela , Anders Maresa , Sigmund Anna M. , Egu Desalegn T. , Eichkorn Ramona A. , Yazdi Amir S. , Sárdy Miklós , Hertl Michael , Didona Dario , Hashimoto Takashi , Waschke Jens
Published: June 2022

The severe autoimmune blistering disease Pemphigus vulgaris (PV) is mainly caused by autoantibodies (IgG) against desmoglein (Dsg) 3 and Dsg1. The mechanisms leading to the development of blisters are not fully understood, but intracellular signaling seems to play an important role. Sheddases ADAM10 and ADAM17 are involved in the turnover of the desmosomal cadherin Dsg2 and ADAM10 has been shown to contribute to acantholysis in a murine pemphigus model. In the present study, we further examined the role of ADAM10 and ADAM17 both in keratinocyte adhesion and in the pathogenesis of PV. First, we found that inhibition of ADAM10 enhanced adhesion of primary human keratinocytes but not of immortalized keratinocytes. In dissociation assays, inhibition of ADAM10 shifted keratinocyte adhesion towards a hyperadhesive state. However, ADAM inhibition did neither modulate protein levels of Dsg1 and Dsg3 nor activation of EGFR at Y1068 and Y845. In primary human keratinocytes, inhibition of ADAM10, but not ADAM17, reduced loss of cell adhesion and fragmentation of Dsg1 and Dsg3 immunostaining in response to a PV1-IgG from a mucocutaneous PV patient. Similarly, inhibition of ADAM10 in dissociation assay decreased fragmentation of primary keratinocytes induced by a monoclonal antibody against Dsg3 and by PV-IgG from two other patients both suffering from mucosal PV. However, such protective effect was not observed in both cultured cells and ex vivo disease models, when another mucocutaneous PV4-IgG containing more Dsg1 autoantibodies was used. Taken together, ADAM10 modulates both hyperadhesion and PV-IgG-induced loss of cell adhesion dependent on the autoantibody profile.
Natural Killer Cells in SARS-CoV-2 Infection: Pathophysiology and Therapeutic Implications
Authors: Di Vito Clara , Calcaterra Francesca , Coianiz Nicolò , Terzoli Sara , Voza Antonio , Mikulak Joanna , Della Bella Silvia , Mavilio Domenico
Published: June 2022

Natural Killer (NK) cells are lymphocytes of the innate immunity that play a crucial role in the control of viral infections in the absence of a prior antigen sensitization. Indeed, they display rapid effector functions against target cells with the capability of direct cell killing and antibody-dependent cell-mediated cytotoxicity. Furthermore, NK cells are endowed with immune-modulatory functions innate and adaptive immune responses via the secretion of chemokines/cytokines and by undertaking synergic crosstalks with other innate immune cells, including monocyte/macrophages, dendritic cells and neutrophils. Recently, the Coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally. Although the specific role of NK cells in COVID-19 pathophysiology still need to be explored, mounting evidence indicates that NK cell tissue distribution and effector functions could be affected by SARS-CoV-2 infection and that a prompt NK cell response could determine a good clinical outcome in COVID-19 patients. In this review, we give a comprehensive overview of how SARS-CoV-2 infection interferes with NK cell antiviral effectiveness and their crosstalk with other innate immune cells. We also provide a detailed characterization of the specific NK cell subsets in relation to COVID-19 patient severity generated from publicly available single cell RNA sequencing datasets. Finally, we summarize the possible NK cell-based therapeutic approaches against SARS-CoV-2 infection and the ongoing clinical trials updated at the time of submission of this review. We will also discuss how a deep understanding of NK cell responses could open new possibilities for the treatment and prevention of SARS-CoV-2 infection.
Immune-Mediated Hepatitis During Immune Checkpoint Inhibitor cancer Immunotherapy: Lessons From Autoimmune Hepatitis and Liver Immunology
Authors: Hercun Julian , Vincent Catherine , Bilodeau Marc , Lapierre Pascal
Published: June 2022

Immune checkpoint inhibitors (ICI) are being increasingly used to successfully treat several types of cancer. However, due to their mode of action, these treatments are associated with several immune-related adverse events (irAEs), including immune-mediated autoimmune-like hepatitis in 5 to 10% of cases. The specific immune mechanism responsible for the development of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI) is currently unknown. This review summarizes the current knowledge on hepatic irAEs during cancer immunotherapy. It also addresses the clinical management of ILICI and how it is becoming an increasingly important clinical issue. Clinical, histological, and laboratory features of autoimmune hepatitis (AIH) and ILICI are compared, and their shared and distinctive traits are discussed in an effort to better understand the development of hepatic irAEs. Finally, based on the current knowledge of liver immunology and AIH pathogenesis, we propose a series of events that could trigger the observed liver injury in ICI-treated patients. This model could be useful in the design of future studies aiming to identify the specific immune mechanism(s) at play in ILICI and improve immune checkpoint inhibitor cancer immunotherapy.
Seroconversion Rate After SARS-CoV-2 Infection and Two Doses of Either ChAdOx1-nCOV COVISHIELD™ or BBV-152 COVAXIN™ Vaccination in Renal Allograft Recipients: An Experience of Two Public and Private Tertiary Care Center
Authors: Prasad Narayan , Bansal Shyam Bihari , Yadav Brijesh , Manhas Neha , Yadav Deependra , Gautam Sonam , Kushwaha Ravishankar , Singh Ankita , Bhadauria Dharmendra , Yachha Monika , Behera Manas Ranjan , Kaul Anupama
Published: June 2022

Introduction

Vaccination is an effective strategy for preventing SARS-CoV-2 infection and associated mortality. Renal Transplant Recipients (RTRs) are vulnerable to acquiring infection and high mortality due to their immunocompromised state. Varying responses to the different vaccines, depending on types of vaccines and population, have been reported. Vaccines supply is also limited. The current study evaluated the seroconversion rate after SARS-CoV-2 infection and 2 doses of either COVAXIN™ or COVISHIELD™ vaccination in RTR.

Methods

The serum anti-SARS-CoV-2 spike protein neutralizing antibody titer was measured in 370 RTRs who acquired SARS-CoV-2 infection (n=172), yet not vaccinated; and those vaccinated with COVAXIN™ (n=78), and COVISHIELD™ (n=120) by chemiluminescence microparticle immunoassay methods from serum.

Result

Overall, the seroconversion rate either after vaccination or infection was 85.13% (315/370). The vaccine-associated seroconversion was 80.30% (159/198). SARS-CoV-2 infection-associated seroconversion was 90.69% (156/172), COVISHIELD™ associated seroconversion was 79.2% (95/120), and COVAXIN™ associated seroconversion was 82.05% (64/78). The median IgG titer in the SARS-CoV-2 infection group was 646.50 AU/ml (IQR: 232.52-1717.42), in the COVAXIN™ group was 1449.75 AU/ml (IQR: 400.0-3068.55), and the COVISHIELD™ vaccination group was 1500.51 AU/ml (IQR: 379.47-4938.50). The seroconversion rate and antibody titers were similar irrespective of the place of sampling. Patient’s age-associated seroconversion in <45 years was 88.01% (213/242), 45.1-60 years was 83.18% (94/113), and > 60 years was 58.3% (7/12).

Conclusions

Both infection and vaccination induce robust antibody formation in RTRs. The seroconversion rate after SARS-CoV-2 infection was higher but with a lower antibody titer than vaccines. The vaccines, COVAXIN™ and COVISHIELD™, induce more elevated antibody titers than natural infection. The seroconversion rate and antibody titer in Indian RTRs appears to be better than in the western population, irrespective of their vaccination status.
Epigenetic Aspects and Prospects in Autoimmune Hepatitis
Authors: Czaja Albert J.
Published: June 2022

The observed risk of autoimmune hepatitis exceeds its genetic risk, and epigenetic factors that alter gene expression without changing nucleotide sequence may help explain the disparity. Key objectives of this review are to describe the epigenetic modifications that affect gene expression, discuss how they can affect autoimmune hepatitis, and indicate prospects for improved management. Multiple hypo-methylated genes have been described in the CD4+and CD19+T lymphocytes of patients with autoimmune hepatitis, and the circulating micro-ribonucleic acids, miR-21 and miR-122, have correlated with laboratory and histological features of liver inflammation. Both epigenetic agents have also correlated inversely with the stage of liver fibrosis. The reduced hepatic concentration of miR-122 in cirrhosis suggests that its deficiency may de-repress the pro-fibroticprolyl-4-hydroxylase subunit alpha-1 gene. Conversely, miR-155 is over-expressed in the liver tissue of patients with autoimmune hepatitis, and it may signify active immune-mediated liver injury. Different epigenetic findings have been described in diverse autoimmune and non-autoimmune liver diseases, and these changes may have disease-specificity. They may also be responses to environmental cues or heritable adaptations that distinguish the diseases. Advances in epigenetic editing and methods for blocking micro-ribonucleic acids have improved opportunities to prove causality and develop site-specific, therapeutic interventions. In conclusion, the role of epigenetics in affecting the risk, clinical phenotype, and outcome of autoimmune hepatitis is under-evaluated. Full definition of the epigenome of autoimmune hepatitis promises to enhance understanding of pathogenic mechanisms and satisfy the unmet clinical need to improve therapy for refractory disease.
Immunogenic Cell Death and Role of Nanomaterials Serving as Therapeutic Vaccine for Personalized Cancer Immunotherapy
Authors: Catanzaro Elena , Feron Olivier , Skirtach André G. , Krysko Dmitri V.
Published: June 2022

Immunogenic cell death (ICD) is a rapidly growing research area representing one of the emerging therapeutic strategies of cancer immunotherapy. ICD is an umbrella term covering several cell death modalities including apoptosis, necroptosis, ferroptosis and pyroptosis, and is the product of a balanced combination of adjuvanticity (damage-associated molecular patterns and chemokines/cytokines) and antigenicity (tumor associated antigens). Only a limited number of anti-cancer therapies are available to induce ICD in experimental cancer therapies and even much less is available for clinical use. To overcome this limitation, nanomaterials can be used to increase the immunogenicity of cancer cells killed by anti-cancer therapy, which in themselves are not necessarily immunogenic. In this review, we outline the current state of knowledge of ICD modalities and discuss achievements in using nanomaterials to increase the immunogenicity of dying cancer cells. The emerging trends in modulating the immunogenicity of dying cancer cells in experimental and translational cancer therapies and the challenges facing them are described. In conclusion, nanomaterials are expected to drive further progress in their use to increase efficacy of anti-cancer therapy based on ICD induction and in the future, it is necessary to validate these strategies in clinical settings, which will be a challenging research area.
The Absence of STING Ameliorates Non-Alcoholic Fatty Liver Disease and Reforms Gut Bacterial Community
Authors: Zhang Qiang , Chen Qiongyun , Yan Changsheng , Niu Chunyan , Zhou Jingping , Liu Jingjing , Song Yang , Zhou Fei , Fan Yanyun , Ren Jianlin , Xu Hongzhi , Zhang Bangzhou
Published: June 2022

Non-alcoholic fatty liver disease (NAFLD) is one of the primary causes of cirrhosis and a major risk factor for hepatocellular carcinoma and liver-related death. It has been correlated with changes in the gut microbiota, which promote its development by regulating insulin resistance, bile acid and choline metabolism, and inflammation. Recent studies suggested a controversial role of the stimulator of interferon genes (STING) in the development of NAFLD. Here, we showed that as an immune regulator, STING aggravates the progression of NAFLD in diet-induced mice and correlated it with the changes in hepatic lipid metabolism and gut microbiota diversity. After feeding wild-type (WT) and STING deletion mice with a normal control diet (NCD) or a high-fat diet (HFD), the STING deletion mice showed decreased lipid accumulation and liver inflammation compared with WT mice fed the same diet. In addition, STING specifically produced this hepatoprotective effect by inhibiting the activation of CD8+ T cells. The gut microbiota analysis revealed significant differences in intestinal bacteria between STING deletion mice and WT mice under the same diet and environmental conditions; moreover, differential bacterial genera were associated with altered metabolic phenotypes and involved in related metabolic pathways. Overall, our findings reveal the important regulatory role that STING plays in the progression of NAFLD. In addition, the change in intestinal microbiota diversity may be the contributing factor.
Characteristics and Genomic Diversity of Measles Virus From Measles Cases With Known Vaccination Status in Shanghai, China
Authors: Cui Xiaoxian , Li Yunyi , Yang Yuying , Tang Wei , Li Zhi , Chen Hongyou , Li Yang , Cui Xinyi , Huang Zhuoying , Sun Xiaodong , Xu Songtao , Zhang Yan , Li Chongshan , Zhang Xi
Published: June 2022

Although the highly effective measles vaccine has dramatically reduced the incidence of measles, measles, and outbreaks continue to occur in individuals who received the measles vaccine because of immunization failure. In this study, patients who have definite records of immunization were enrolled based on measles surveillance in Shanghai, China, from 2009 to 2017, and genomic characteristics regarding viruses retrieved from these cases provided insights into immunization failure. A total of 147 complete genomes of measles virus (MV) were obtained from the laboratory-confirmed cases through Illumina MiSeq. Epidemiological, and genetic characteristics of the MV were focused on information about age, gender, immunization record, variation, and evolution of the whole genome. Furthermore, systematic genomics using phylogeny and selection pressure approaches were analyzed. Our analysis based on the whole genome of 147 isolates revealed 4 clusters: 2 for the genotype H1 (clusters named H1-A, including 73 isolates; H1-B, including 72 isolates) and the other 2 for D8 and B3, respectively. Estimated nucleotide substitution rates of genotype H1 MV derived using genome and individual genes are lower than other genotypes. Our study contributes to global measles epidemiology and proves that whole-genome sequencing was a useful tool for more refined genomic characterization. The conclusion indicates that vaccination may have an effect on virus evolution. However, no major impact was found on the antigenicity in Shanghai isolates.
Isolation and Characterization of Five Severe Acute Respiratory Syndrome Coronavirus 2 Strains of Different Clades and Lineages Circulating in Eastern India
Authors: Singh Bharati , Avula Kiran , Chatterjee Sanchari , Datey Ankita , Ghosh Arup , De Saikat , Keshry Supriya Suman , Ghosh Soumyajit , Suryawanshi Amol Ratnakar , Dash Rupesh , Senapati Shantibhusan , Beuria Tushar K. , Prasad Punit , Raghav Sunil , Swain Rajeeb , Parida Ajay , Hussain Syed Gulam , Chattopadhyay Soma
Published: June 2022

The emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as a serious pandemic has altered the global socioeconomic dynamics. The wide prevalence, high death counts, and rapid emergence of new variants urge for the establishment of research infrastructure to facilitate the rapid development of efficient therapeutic modalities and preventive measures. In agreement with this, SARS-CoV-2 strains were isolated from patient swab samples collected during the first COVID-19 wave in Odisha, India. The viral isolates were adapted to in vitro cultures and further characterized to identify strain-specific variations in viral growth characteristics. The neutralization susceptibility of viral isolates to vaccine-induced antibodies was determined using sera from individuals vaccinated in the Government-run vaccine drive in India. The major goal was to isolate and adapt SARS-CoV-2 viruses in cell culture with minimum modifications to facilitate research activities involved in the understanding of the molecular virology, host–virus interactions, drug discovery, and animal challenge models that eventually contribute toward the development of reliable therapeutics.
The Role of Ferroptosis in Acute Kidney Injury
Authors: Zhang Jinshi , Wang Binqi , Yuan Shizhu , He Qiang , Jin Juan
Published: June 2022

Ferroptosis is a novel cell death method discovered in recent years. It is usually accompanied by massive accumulations of iron and lipid peroxidation during cell death. Recent studies have shown that ferroptosis is closely associated with the pathophysiological processes of many diseases, such as tumors, neurological diseases, localized ischemia-reperfusion injury, kidney injury, and hematological diseases. How to intervene in the incidence and development of associated diseases by regulating the ferroptosis of cells has become a hot topic of research. This article provides a review of the role of ferroptosis in the pathogenesis and potential treatment of acute kidney injury.
Innate Immune Tolerance in Microglia Does Not Impact on Central Nervous System Prion Disease
Authors: Pal Reiss , Bradford Barry M. , Mabbott Neil A.
Published: June 2022

Prion diseases such as Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy in cattle, and scrapie in sheep, are infectious and chronic neurodegenerative diseases to which there are no cures. Infection with prions in the central nervous system (CNS) ultimately causes extensive neurodegeneration, and this is accompanied by prominent microglial and astrocytic activation in affected regions. The microglia are the CNS macrophages and help maintain neuronal homeostasis, clear dead or dying cells and provide defense against pathogens. The microglia also provide neuroprotection during CNS prion disease, but their pro-inflammatory activation may exacerbate the development of the neuropathology. Innate immune tolerance induced by consecutive systemic bacterial lipopolysaccharide (LPS) treatment can induce long-term epigenetic changes in the microglia in the brain that several months later can dampen their responsiveness to subsequent LPS treatment and impede the development of neuritic damage in a transgenic mouse model of Alzheimer’s disease-like pathology. We therefore reasoned that innate immune tolerance in microglia might similarly impede the subsequent development of CNS prion disease. To test this hypothesis groups of mice were first infected with prions by intracerebral injection, and 35 days later given four consecutive systemic injections with LPS to induce innate immune tolerance. Our data show that consecutive systemic LPS treatment did not affect the subsequent development of CNS prion disease. Our data suggests innate immune tolerance in microglia does not influence the subsequent onset of prion disease-induced neuropathology in mice, despite previously published evidence of this effect in an Alzheimer’s disease mouse model.
Reduction of Interhemispheric Homotopic Connectivity in Cognitive and Visual Information Processing Pathways in Patients With Thyroid-Associated Ophthalmopathy
Authors: Qi Chen-Xing , Wen Zhi , Huang Xin
Published: June 2022

Purpose

Thyroid-associated ophthalmopathy (TAO) is a vision threatening autoimmune and inflammatory orbital disease, and has been reported to be associated with a wide range of structural and functional abnormalities of bilateral hemispheres. However, whether the interhemisphere functional connectivity (FC) of TAO patients is altered still remain unclear. A new technique called voxel-mirrored homotopic connectivity (VMHC) combined with support vector machine (SVM) method was used in the present study to explore interhemispheric homotopic functional connectivity alterations in patients with TAO.

Methods

A total of 21 TAO patients (14 males and 7 females) and 21 wellmatched healthy controls (HCs, 14 males and 7 females), respectively, underwent functional magnetic resonance imaging (fMRI) scanning in the resting state. We evaluated alterations in the resting state functional connectivity between hemispheres by applying VMHC method and then selected these abnormal brain regions as seed areas for subsequent study using FC method. Furthermore, the observed changes of regions in the VMHC analysis were chosen as classification features to differentiate patients with TAO from HCs through support vector machine (SVM) method.

Results

The results showed that compared with HCs, TAO patients showed significantly lower VMHC values in the bilateral postcentral gyrus, lingual gyrus, calcarine, middle temporal gyrus, middle occipital gyrus and angular. Moreover, significantly decreased FC values were found between the right postcentral gyrus/lingual gyrus/calcarine and left lingual gyrus/cuneus/superior occipital gyrus, left postcentral gyrus/lingual gyrus/calcarine and right lingual gyrus/ middle temporal gyrus, right middle temporal gyrus and left cerebellum-8/lingual gyrus/middle occipital gyrus/supplementary motor area, left middle temporal gyrus and right middle occipital gyrus, right middle occipital gyrus/angular and left middle temporal pole (voxel-level p < 0.01, Gaussian random field correction, cluster-level p < 0.05). The SVM classification model achieved good performance in differentiating TAO patients from HCs (total accuracy: 73.81%; area under the curve: 0.79).

Conclusion

The present study revealed that the altered interhemisphere interaction and integration of information involved in cognitive and visual information processing pathways including the postcentral gyrus, cuneus, cerebellum, angular, widespread visual cortex and temporal cortex in patients with TAO relative to HC group. VMHC variability had potential value for accurately and specifically distinguishing patients with TAO from HCs. The new findings may provide novel insights into the neurological mechanisms underlying visual and cognitive disorders in patients with TAO.
A Dichotomous Role for FABP7 in Sleep and Alzheimer’s Disease Pathogenesis: A Hypothesis
Authors: Needham Hope , Torpey Grace , Flores Carlos C. , Davis Christopher J. , Vanderheyden William M. , Gerstner Jason R.
Published: June 2022

Fatty acid binding proteins (FABPs) are a family of intracellular lipid chaperone proteins known to play critical roles in the regulation of fatty acid uptake and transport as well as gene expression. Brain-type fatty acid binding protein (FABP7) is enriched in astrocytes and has been implicated in sleep/wake regulation and neurodegenerative diseases; however, the precise mechanisms underlying the role of FABP7 in these biological processes remain unclear. FABP7 binds to both arachidonic acid (AA) and docosahexaenoic acid (DHA), resulting in discrete physiological responses. Here, we propose a dichotomous role for FABP7 in which ligand type determines the subcellular translocation of fatty acids, either promoting wakefulness aligned with Alzheimer’s pathogenesis or promoting sleep with concomitant activation of anti-inflammatory pathways and neuroprotection. We hypothesize that FABP7-mediated translocation of AA to the endoplasmic reticulum of astrocytes increases astrogliosis, impedes glutamatergic uptake, and enhances wakefulness and inflammatory pathways via COX-2 dependent generation of pro-inflammatory prostaglandins. Conversely, we propose that FABP7-mediated translocation of DHA to the nucleus stabilizes astrocyte-neuron lactate shuttle dynamics, preserves glutamatergic uptake, and promotes sleep by activating anti-inflammatory pathways through the peroxisome proliferator-activated receptor-γ transcriptional cascade. Importantly, this model generates several testable hypotheses applicable to other neurodegenerative diseases, including amyotrophic lateral sclerosis and Parkinson’s disease.
Causality Analysis to the Abnormal Subcortical–Cortical Connections in Idiopathic-Generalized Epilepsy
Authors: Qin Yun , Li Sipei , Yao Dezhong , Luo Cheng
Published: June 2022

Idiopathic generalized epilepsy (IGE) was characterized by 3–6 Hz generalized spike-wave discharges (GSWDs), and extensive altered interactions in subcortical-cortical circuit. However, the dynamics and the causal relationship among these interactions were less studied. Using resting-state functional magnetic resonance imaging (fMRI) data, the abnormal connections in the subcortical-cortical pathway in IGE were examined. Then, we proposed a novel method of granger causal analysis based on the dynamic functional connectivity, and the predictive effects among these abnormal connections were calculated. The results showed that the thalamus, and precuneus were key regions representing abnormal functional network connectivity (FNC) in the subcortical-cortical circuit. Moreover, the connectivity between precuneus and adjacent regions had a causal effect on the widespread dysfunction of the thalamocortical circuit. In addition, the connection between the striatum and thalamus indicated the modulation role on the cortical connection in epilepsy. These results described the causality of the widespread abnormality of the subcortical-cortical circuit in IGE in terms of the dynamics of functional connections, which provided additional evidence for understanding the potential modulation pattern of the abnormal epileptic pathway.
Function of Transient Receptor Potential-Like Channel in Insect Egg Laying
Authors: Zhang Yan , Zhang Yi-Jie , Guo Di , Wang Li-Xiang , Niu Chun-Dong , Wu Shun-Fan , Zhang Yali V. , Gao Cong-Fen
Published: June 2022

The transient receptor potential-like channel (TRPL) is a member of the transient receptor potential (TRP) channel family involved in regulating many fundamental senses, such as vision, pain, taste, and touch, in both invertebrates and vertebrates. Yet, the function of TRPL in other important biological processes remains unclear. We discover that TRPL regulates egg laying in two insect species, the brown planthopper, Nilaparvata lugens, and the fruit fly, Drosophila melanogaster. In both insects, trpl is expressed in the female reproductive organ. Loss of trpl leads to significantly defects in egg laying. In addition, TRPL is functionally interchangeable between the brown planthoppers and flies in egg laying. Altogether, our work uncovers a novel role played by TRPL in regulating egg laying and indicates TRPL as a potential pesticide target in brown planthoppers.
Improving Antioxidative and Antiproliferative Properties Through the Release of Bioactive Compounds From Eucommia ulmoides Oliver Bark by Steam Explosion
Authors: Kong Feng , Zeng Qinghua , Li Yue , Ding Yishuai , Xue Di , Guo Xingfeng
Published: June 2022

Eucommia ulmoides Oliver bark is a potential medicinal plant-based feedstock for bioactive products and possesses the effective functions of antioxidant and antitumor. Network pharmacology was employed to reveal the oxidative and free radical damage and cancer-related potential compounds of Eucommia ulmoides Oliver in this study. The result showed that quercetin might be the key compound to resist these two types of diseases. Then, the effect of steam explosion on the release of bioactive compounds and the antioxidative and antiproliferative properties of the extract from Eucommia ulmoides Oliver bark were investigated. Results showed that steam explosion at 0.7 MPa for 30 min significantly enhanced the total phenolic, total flavonoids, and quercetin content of Eucommia ulmoides Oliver bark. Reducing power and 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging activity of the steam-exploded extracting solution were 1.72 and 2.76 times of native. The antiproliferative activity to CT26 and HepG2 of the extract from steam-exploded Eucommia ulmoides Oliver bark (SEU) was higher than those of native-exploded Eucommia ulmoides Oliver bark (NEU). All these results suggested that steam explosion could be applied to release the bioactive compounds, thus enhanced the antioxidative and antiproliferative activities of medicinal and edible plant-based sources.
Incremental Value of Radiomics in 5-Year Overall Survival Prediction for Stage II–III Rectal Cancer
Authors: Nie Ke , Hu Peng , Zheng Jianjun , Zhang Yang , Yang Pengfei , Jabbour Salma K. , Yue Ning , Dong Xue , Xu Shufeng , Shen Bo , Niu Tianye , Hu Xiaotong , Cai Xiujun , Sun Jihong
Published: June 2022

Although rectal cancer comprises up to one-third of colorectal cancer cases and several prognosis nomograms have been established for colon cancer, statistical tools for predicting long-term survival in rectal cancer are lacking. In addition, previous prognostic studies did not include much imaging findings, qualitatively or quantitatively. Therefore, we include multiparametric MRI information from both radiologists’ readings and quantitative radiomics signatures to construct a prognostic model that allows 5-year overall survival (OS) prediction for advance-staged rectal cancer patients. The result suggested that the model combined with quantitative imaging findings might outperform that of conventional TNM staging or other clinical prognostic factors. It was noteworthy that the identified radiomics signature consisted of three from dynamic contrast-enhanced (DCE)-MRI, four from anatomical MRI, and one from functional diffusion-weighted imaging (DWI). This highlighted the importance of multiparametric MRI to address the issue of long-term survival estimation in rectal cancer. Additionally, the constructed radiomics signature demonstrated value to the conventional prognostic factors in predicting 5-year OS for stage II–III rectal cancer. The presented nomogram also provides a practical example of individualized prognosis estimation and may potentially impact treatment strategies.
Association Between Internal Organ/Liver Tumor and External Surface Motion From Cine MR Images on an MRI-Linac
Authors: Mao Weihua , Kim Joshua , Chetty Indrin J.
Published: June 2022

Purposes/Objectives

Historically, motion correlation between internal tumor and external surrogates have been based on limited sets of X-ray or magnetic resonance (MR) images. With the recent clinical implementation of MR-guided linear accelerators, a vast quantity of continuous planar real-time MR imaging data is acquired. In this study, information was extracted from MR cine imaging during liver cancer treatments to establish associations between internal tumor/diaphragm and external surface/skin movement.

Methods and Materials

This retrospective study used 305,644 MR image frames acquired over 118 treatment/imaging sessions of the first 23 liver cancer patients treated on an MRI-linac. 9 features were automatically determined on each MR image frame: Lung_Area, the posterior (Dia_Post), dome (Dia_Dome), and anterior (Dia_Ant) points of a diaphragmatic curve and the diaphragm curve point (Dia_Max), the chest (Chest) and the belly (Belly) skin points experiencing the maximum motion ranges; the superior-interior (SI) and posterior-anterior (PA) positions of a target. For every session, correlation analyses were performed twice among the 9 features: 1) over a breath-hold (BH) set and 2) on a pseudo free-breathing (PFB) generated by removing breath-holding frames.

Results

303,123 frames of images were successfully analyzed. For BH set analysis, correlation coefficients were as follows: 0.94 ± 0.07 between any two features among Dia_Post, Dia_Dome, Dia_Max, and Lung_Area; 0.95 ± 0.06 between SI and any feature among Dia_Post, Dia_Dome, Dia_Max, or Lung_Area; 0.76 ± 0.29 between SI and Belly (with 50% of correlations ≥ 0.87). The PFB set had 142,862 frames of images. For this set, correlation coefficients were 0.96 ± 0.06 between any two features among Dia_Post, Dia_Dome, Dia_Max, and Lung_Area; 0.95 ± 0.06 between SI and any feature among Dia_Post, Dia_Dome, Dia_Max, or Lung_Area; 0.80 ± 0.26 between SI and Belly (with 50% of correlations ≥ 0.91).

Conclusion

Diaphragmatic motion as assessed by cine MR imaging is highly correlated with liver tumor motion. Belly vertical motion is highly correlated with liver tumor longitudinal motion in approximately half of the cases. More detailed analyses of those cases displaying weak correlations are in progress.
Prediction of Gastric Cancer-Related Genes Based on the Graph Transformer Network
Authors: Chen Yan , Sun Xuan , Yang Jiaxing
Published: June 2022

Gastric cancer is a complex multifactorial and multistage process that involves a large number of tumor-related gene structural changes and abnormal expression. Therefore, knowing the related genes of gastric cancer can further understand the pathogenesis of gastric cancer and provide guidance for the development of targeted drugs. Traditional methods to discover gastric cancer-related genes based on biological experiments are time-consuming and expensive. In recent years, a large number of computational methods have been developed to identify gastric cancer-related genes. In addition, a large number of experiments show that establishing a biological network to identify disease-related genes has higher accuracy than ordinary methods. However, most of the current computing methods focus on the processing of homogeneous networks, and do not have the ability to encode heterogeneous networks. In this paper, we built a heterogeneous network using a disease similarity network and a gene interaction network. We implemented the graph transformer network (GTN) to encode this heterogeneous network. Meanwhile, the deep belief network (DBN) was applied to reduce the dimension of features. We call this method “DBN-GTN”, and it performed best among four traditional methods and five similar methods.
The Molecular Role of HIF1α Is Elucidated in Chronic Myeloid Leukemia
Authors: Singh Vivek , Singh Ranjana , Kushwaha Rashmi , Verma Shailendra Prasad , Tripathi Anil Kumar , Mahdi Abbas Ali
Published: June 2022

Chronic myeloid leukemia (CML) is potentially fatal blood cancer, but there is an unmet need to discover novel molecular biomarkers. The hypothesis of this study aimed to elucidate the relationship of HIF1α with the redox system, Krebs cycles, notch1, and other regulatory proteins to better understand the pathophysiology and clinical relevance in chronic myeloid leukemia (CML) patients, as the molecular mechanism of this axis is still not clear. This study included CML patient samples (n = 60; 60: blood; 10: bone marrow tissues) and compared them with healthy controls (n = 20; blood). Clinical diagnosis confirmed on bone marrow aspiration, marrow trephine biopsy, and BCR/ABL1 translocation. Cases were subclassified into chronic, accelerated, and blast crises as per WHO guidelines. Molecular experiments included redox parameters, DNA fragmentation, Krebs cycle metabolites, and gene expression by RT-PCR/Western blot/LC-MS, PPI (STRING), Pearson correlation, and ROC curve analysis. Here, our findings show that p210/p190BCR/ABL1 translocation is common in all blast crisis phases of CML. Redox factor/Krebs oncometabolite concentrations were high, leading to upregulation and stabilization of HIF1α. HIF1α leads to the pathogenesis in CML cells by upregulating their downstream genes (Notch 2/4/Ikaros/SIRT1/Foxo-3a/p53, etc.). Whereas, downregulated ubiquitin proteasomal and apoptotic factors in CML pateints, can trigger degradation of HIF1α through proline hydroxylation. However, HIF1α showed a negative corelation with the notch1 pathway. Notch1 plays a tumor-suppressive role in CML and might have the potential to be used as a diagnostic marker along with other factors in CML patients. The outcome also revealed that oxidant treatment could not be effective in augmentation with conventional therapy because CML cells can enhance the levels of antioxidants for their survival. HIF1α might be a novel therapeutic target other than BCR/ABL1 translocation.
Depression and Self-Efficacy Among Iranian Children During the Prevalence of COVID-19 Disease
Authors: Zakeri Mohammad Ali , Dakkalirad Abdollah , Saedi Fahimeh , Shahnavazi Allahyar , Kordi Mehri , Ahmadipour Maryam , Dehghan Mahlagha
Published: June 2022

The coronavirus disease 2019 (COVID-19) outbreak has quickly endangered the physical and mental health of people in the community, particularly vulnerable people such as children. This study was carried out to investigate the depression and self-efficacy of Iranian children during the COVID-19 outbreak. This cross-sectional research was conducted on 321 students aged 8 to 17 in southeast Iran. A social media-based online questionnaire was used to collect data. The information was gathered using demographic and COVID-related items, the Children's Depression Inventory (CDI), and the Self-Efficacy Questionnaire for Children (SEQ-C). No significant correlation was observed between depression and self-efficacy of children (P = 0.23). However, in subscale of CDI, negative mood, ineffectiveness and negative self-esteem had a significant correlation with self-efficacy (<0.001). Depression had a significant correlation with family income (p = 0.017), being at risk of coronavirus infection (p = 0.036), effectiveness of preventive measures (p = 0.015) and how information about the coronavirus disease was obtained (p = 0.018). According to the results, the mean score of depression was higher than the midpoint of the questionnaire in Iranian children, therefore, it is needed to take the necessary measures and treatment plans to reduce the rate of depression in children. Further research is needed to assess and prevent childhood depression.
The Neglected Price of Pediatric Acute Kidney Injury: Non-renal Implications
Authors: Pande Chetna K. , Smith Mallory B. , Soranno Danielle E. , Gist Katja M. , Fuhrman Dana Y. , Dolan Kristin , Conroy Andrea L. , Akcan-Arikan Ayse
Published: June 2022

Preclinical models and emerging translational data suggest that acute kidney injury (AKI) has far reaching effects on all other major organ systems in the body. Common in critically ill children and adults, AKI is independently associated with worse short and long term morbidity, as well as mortality, in these vulnerable populations. Evidence exists in adult populations regarding the impact AKI has on life course. Recently, non-renal organ effects of AKI have been highlighted in pediatric AKI survivors. Given the unique pediatric considerations related to somatic growth and neurodevelopmental consequences, pediatric AKI has the potential to fundamentally alter life course outcomes. In this article, we highlight the challenging and complex interplay between AKI and the brain, heart, lungs, immune system, growth, functional status, and longitudinal outcomes. Specifically, we discuss the biologic basis for how AKI may contribute to neurologic injury and neurodevelopment, cardiac dysfunction, acute lung injury, immunoparalysis and increased risk of infections, diminished somatic growth, worsened functional status and health related quality of life, and finally the impact on young adult health and life course outcomes.
Reference Values for Point-of-Care Echocardiographic Measurements of Preterm Infants in China
Authors: Lu Dan-Fang , Tong Xiao-Mei , Liu Yun-Feng , Zhang Hua
Published: June 2022

Background

Few studies have examined the reference value of the left ventricular structure and function in preterm infants. This study was designed to establish a point-of-care echocardiographic reference range of left ventricular structure and function based on different gestational age, weight, and body surface area (BSA) for preterm infants within 7 days after birth.

Methods

We retrospectively studied 489 patients with traditional echocardiographic data of left ventricular (LV) M-mode: LV end diastolic dimensions (LVED), LV end systolic dimension (LVES), end-diastolic interventricular septal thickness (IVSd), end diastolic LV posterior wall thickness (LVPWd), left atrial (LA) and aortic root (AO) diameters, and index of LA/AO, LV ejection fraction (LVEF), LV fractional shortening (LVFS), and pulsed wave Doppler: aortic valve flow rate (AV), peak mitral valve flow rate E(MV-E), peak mitral valve flow rate A(MV-A), and MV-E/A. The LV dimensions and the maximum blood flow velocities of the aortic valves and mitral valves according to gestational age, birth weight, and body surface area (BSA) are presented in percentiles tables. Percentile curves of aforesaid four cardiac measurements (LVED, LA diameter (LAD), MV-E, MV-E/A) using the R language Generalized Additive Models for Location, Scale and Shape (GAMLSS) method were developed according to different gestational ages and weights.

Results

Measurements of all cardiac dimensions and Doppler maximum velocities of AV, MV-E, and MV-E/A showed a correlation with gestational age, weight, and BSA. LVED, LAD, MV-E, and MV-E/A showed a trend of increasing values with gestational age and weight on the percentile curves.

Conclusion

The percentile tables and graphs of these point-of-care echocardiographic data can provide reliable reference data for Chinese neonates. Normative values are recommended as a source of reference data for the identification of potentially abnormal echocardiography.
Intralobar Pulmonary Sequestration Presenting as Hemothorax Secondary to Spontaneous Pneumothorax: Case Report and Literature Review
Authors: Chen Tian , Yu Jie , Zhang Na , Chen Chenghao , Fu Libing , Zeng Qi
Published: June 2022

Introduction

Patients with pulmonary sequestration (PS), a rare congenital lung malformation, are mostly asymptomatic. Recurrent localized infection is a major complication, while sudden hemothorax is extremely rare. We present a case of intralobar PS presenting as hemothorax secondary to spontaneous pneumothorax and comprehensively review the relevant literature.

Case Report

A 16-year-old male presented with chest pain after strenuous exercise. Chest X-ray showed a moderate pneumothorax. After admission and conservative treatment, he developed dizziness, amaurosis, and urinary incontinence. Bedside chest X-ray suggested a massive pleural effusion, and hemothorax was further identified via catheter drainage. Contrast-enhanced computed tomography was performed, and no abnormal blood vessels or leakage of contrast agent were observed. As the hemoglobin level continued to drop, exploratory thoracoscopic surgery was performed immediately. The abnormal systemic artery supplying the lung tissue was found to be ruptured; therefore, ligation of the abnormal artery with resection of the diseased lung tissue was performed. Pathological examination revealed non-specific manifestations of PS. He was followed up for 1 year without related complications.

Conclusion

Our case suggests that the abnormal supply vessels of PS are unstable, which may cause sudden hemothorax. Therefore, patients with PS should undergo surgery promptly after diagnosis. In patients with hemothorax, we should consider the diagnosis of PS; however, contrast-enhanced computed tomography or angiography cannot confirm the diagnosis in all cases. Surgical intervention is recommended in emergency settings.