bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic review and meta analysis of the valve of SHOX2 and RASSF1A gene methylation in bronchial elveslar lavage fluid in the diagnosis of lung cancer
Authors: Su Shanyang , Huang Yanling , Lu Xiang , Li Wenjia , Li Yongshun , Zhou Jihong 
Published: June 2022

AbstractIntroductionThe incidence of lung cancer worldwide has been increasing in recent years, and the latest cancer data published by the WHO International Agency for Research on Cancer in 2021 shows that lung cancer remains the cancer with the highest mortality rate. The sensitivity of early screening methods for lung cancer is not ideal. Because early lung cancer is mostly located in nodules with a diameter of 1 cm, it is difficult to obtain a definite pathological diagnosis from living tissue specimens. Therefore, it is necessary to find less invasive and effective tests to help detect lung cancer early. Therefore, the purpose of this systematic review (SR) and meta-analysis will be to analyze and explore the correlation between promoter methylation of SHOX2 and RASSF1A genes and lung cancer, and to provide a reference for early clinical diagnosis.Methods and AnalysisThe relevant literature will be comprehensively searched in 4 international electronic databases (PubMed, Cochrane Library, EMBASE and Web of Science) and 4 Chinese electronic databases (CNKI, VIP, Wanfang, Chinese Biomedicine). We only included studies from inception until publication in May 2022. The primary outcome measure was the methylation rate of the SHOX2 and RASSF1A gene promoters in lung cancer tissue and normal lung tissue in the control group in lung cancer patients. Secondary outcome measures included methylation rates of promoters of SHOX2 and RASSF1A genes in different tissue samples. Two reviewers will conduct independent research selection, data extraction, data synthesis and quality assessment. The assessment of bias risk and data synthesis will be conducted using Review Manager 5.3 software. The Cochrane Collaboration’s Bias Risk Assessment Tool (QUADAS) will be used to assess the quality of the individual studies included.DiscussionThis systematic review will help to clarify the correlation between PROMOTER methylation of the SHOX2 and RASSF1A genes with lung cancer, providing clinical evidence for early clinical diagnosis.Trial registration numberCRD42022330609 (PROSPERO)
Correlation of IL-6, Coping, &Depression in Adolescent and Adult Patients Receiving Hemodialysis: A Comparative Study
Authors: Kamal Sanaa A. , Khoweiled Aref A. , Gomaa Maged E. , Al-Dawy Sameh A. , Kamel Reham M. , Ayoub Doaa R. 
Published: June 2022

AbstractBackgroundThe research has long reported that depression and stress are highly prevalent among patients with end-stage kidney disease requiring dialysis. Growing studies suggest that the inflammatory gene IL-6, in particular, contributes to the etiology of depression & stress by affecting the function of serotonin; one of the other explanations is by causing hypercortisolemia with overstimulation of the HPA axis. This study aimed to assess the inflammatory gene IL-6 in adolescent & adult patients with end-stage kidney disease receiving hemodialysis. Furthermore, to assess the coping skills of those patients upon the emergence of depressive symptoms & stress levels.MethodOne hundred and twenty-one patients receiving hemodialysis were recruited in a cross-sectional study from King Fahd Unit at Kasr Al-Ainy Hospital, Cairo University, Egypt. They were assessed for depression using Beck’s II depression inventory, stress by the stress perceived scale, coping by the short COPE questionnaire & they had inflammatory gene IL-6 level measured.ResultsSeventy-six patients showed depressive symptoms; adults were more depressed than adolescent patients, yet adolescents were subjected to more stress. The mean level of Interleukin-6 was 148.0±50.5pg/ml, which is higher than average. Perceived Stress Scale mean scores showed a statistically significant difference between depressed adults and adolescents (p=0.050).ConclusionsInflammatory gene IL-6 shows a higher level in depressed adolescent and adult patients receiving hemodialysis. Adult patients are more depressed than adolescent patients with end-stage kidney disease yet coping strategies are far better in depressed adolescents than adults.
A genetic strategy to measure insulin signaling regulation and physiology in Drosophila
Authors: Tsao Deborah D. , Chang Kathleen R. , Kockel Lutz , Park Sangbin , Kim Seung K. 
Published: June 2022

AbstractInsulin regulation is a hallmark of health, and impaired insulin signaling promotes metabolic diseases like diabetes mellitus. However, current assays for measuring insulin signaling in all animals remain semi-quantitative and lack the sensitivity, tissue-specificity or temporal resolution needed to quantify in vivo physiological signaling dynamics. Insulin signal transduction is remarkably conserved across metazoans, including insulin-dependent phosphorylation and regulation of Akt/Protein kinase B. Here, we generated transgenic fruit flies permitting tissue-specific expression of an immunoepitope-labelled Akt (AktHF). We developed enzyme-linked immunosorption assays (ELISA) to quantify picomolar levels of phosphorylated (pAktHF) and total AktHF in single flies, revealing dynamic tissue-specific physiological regulation of pAktHF in response to fasting and re-feeding, exogenous insulin, or targeted genetic suppression of established insulin signaling regulators. Genetic screening revealed Pp1-87B as an unrecognized regulator of Akt and insulin signaling. Tools and concepts here provide opportunities to discover tissue-specific regulators of in vivo insulin signaling responses.Author SummaryInsulin is an essential hormone that controls metabolism in all animals, by regulating energy use and growth of target tissues. Impaired insulin signaling (“resistance”) in humans underlies development of type 2 diabetes, a pandemic disease causing significant morbidity and mortality. The genetic risk for insulin resistance is complex, and studies of diabetes are limited by a lack of tools to measure insulin resistance in a sensitive, quantitative, and tissue-specific way. Here, we describe a new technique to measure the strength of insulin signaling in fruit flies. By combining fruit fly genetics with antibody-based assays, we can quantify phosphorylated Akt, an evolutionarily conserved target of insulin signaling, in specific tissues of the adult fly. We show this technique can detect changes in insulin signaling after fasting and refeeding, addition of exogenous insulin, or genetic disruption of the insulin signaling pathway. We used this method to discover a new regulator of insulin signaling, a phosphatase enzyme encoded by Pp1-87B. This exciting new tool should advance our ability to study and discover additional regulators of insulin signaling and resistance.
Symptoms and signs of lung cancer prior to diagnosis: Comparative study using electronic health records
Authors: Prado Maria G. , Kessler Larry G. , Au Margaret A. , Burkhardt Hannah A. , Suchsland Monica Zigman , Kowalski Lesleigh , Stephens Kari A. , Yetisgen Meliha , Walter Fiona M. , Neal Richard D. , Lybarger Kevin , Thompson Caroline A. , Achkar Morhaf Al , Sarma Elizabeth A. , Turner Grace , Farjah Farhood , Thompson Matthew 
Published: June 2022

AbstractBackgroundLung cancer is the most common cause of cancer-related death in the United States (US), with most patients diagnosed at later stages (3 or 4). While most patients are diagnosed following symptomatic presentation, no studies have compared symptoms and physical examination signs at or prior to diagnosis from electronic health records (EHR) in the United States (US).ObjectiveTo identify symptoms and signs in patients prior to lung cancer diagnosis in EHR data.Study DesignCase-control study.MethodsWe studied 698 primary lung cancer cases in adults diagnosed between January 1, 2012 and December 31, 2019, and 6,841 controls matched by age, sex, smoking status, and type of clinic. Coded and free-text data from the EHR were extracted from 2 years prior to diagnosis date for cases and index date for controls. Univariate and multivariate conditional logistic regression were used to identify symptoms and signs associated with lung cancer. Analyses were repeated excluding symptom data from 1, 3, 6, and 12 months before the diagnosis/index dates.ResultsEleven symptoms and signs recorded during the study period were associated with a significantly higher chance of being a lung cancer case in multivariate analyses. Of these, seven were significantly associated with lung cancer six months prior to diagnosis: hemoptysis (OR 3.2, 95%CI 1.9-5.3), cough (OR 3.1, 95%CI 2.4-4.0), chest crackles or wheeze (OR 3.1, 95%CI 2.3-4.1), bone pain (OR 2.7, 95%CI 2.1-3.6), back pain (OR 2.5, 95%CI 1.9-3.2), weight loss (OR 2.1, 95%CI 1.5-2.8) and fatigue (OR 1.6, 95%CI 1.3-2.1).ConclusionsPatients diagnosed with lung cancer appear to have symptoms and signs recorded in the EHR that distinguish them from similar matched patients in ambulatory care, often six months or more before their diagnosis. These findings suggest opportunities to improve the diagnostic process for lung cancer in the US.
Artificial intelligence tool for the study of COVID-19 microdroplet spread across the human diameter and airborne space
Authors: Alsaadi Hesham H. , Aldwairi Monther , Yasin Faten , Cachinho Sandra C. P. , Hussein Abdullah 
Published: June 2022

AbstractThe 2019 novel coronavirus (SARS-COV2 / COVID-19), with a point of origin in Wuhan, China, has spread rapidly all over the world. It turned into a raging pandemic wrecking havoc on health care facilities, world economy and affecting everyone’s life to date. With every new variant, rate of transmission, spread of infections and the number of cases continues to rise at an international level and scale. There are limited reliable researches that study microdroplets spread and transmissions from human sneeze or cough in the airborne space. In this paper, we propose an intelligent technique to visualize, detect, measure the distance of the spread in a real-world settings of microdroplet transmissions in airborne space, called ”COVNET45”. In this paper, we investigate the microdroplet transmission and validate the measurements accuracy compared to published researches, by examining several microscopic and visual images taken to investigate the novel coronavirus (SARS-COV2 / COVID-19). The ultimate contribution is to calculate the spread of the microdroplets measurements precisely with graphical presentation.
Antiviral immune responses, cellular metabolism and adhesion are differentially modulated by SARS-CoV-2 ORF7a or ORF7b
Authors: García-García Tránsito , Fernández-Rodríguez Raúl , Redondo Natalia , de Lucas-Rius Ana , Zaldívar-López Sara , Dies López-Ayllón Blanca , Suárez-Cárdenas José M. , Jiménez-Marín Ángeles , Montoya María , Garrido Juan J. 
Published: June 2022

AbstractSARS-CoV-2, the causative agent of the present COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome, and some have been implicated in facilitating infection and pathogenesis through their interaction with cellular components. Among these proteins, accessory protein ORF7a and ORF7b functions are poorly understood. In this study, A549 cells were transduced to express ORF7a and ORF7b, respectively, to explore more in depth the role of each accessory protein in the pathological manifestation leading to COVID-19. Bioinformatic analysis and integration of transcriptome results identified defined canonical pathways and functional groupings revealing that after expression of ORF7a or ORF7b, the lung cells are potentially altered to create conditions more favorable for SARS-CoV-2, by inhibiting the IFN-I response, increasing proinflammatory cytokines release, and altering cell metabolic activity and adhesion. Based on these results, it is reasonable to suggest that ORF7a and ORF7b could be targeted by new therapies or used as future biomarkers during this pandemic.
Early Stages of Misfolding of PAP248-286 at two different pH values: An Insight from Molecular Dynamics Simulations
Authors: Agrawal Nikhil , Parisini Emilio 
Published: June 2022

AbstractPAP248-286 peptides, which are highly abundant in human semen, aggregate and form amyloid fibrils that enhance HIV infection. Previous experimental studies have shown that the infection-promoting activity of PAP248-286 begins to increase well before amyloid formation takes place and that pH plays a key role in the enhancement of PAP248-286-related infection. Hence, understanding the early stages of misfolding of the PAP2482-86 peptide is crucial. To this end, we have performed 60 independent MD simulations for a total of 24 μs at two different pH values (4.2 and 7.2). Our data shows that misfolding of the PAP248-286 peptide is a multistage process and that the first step of the process is a transition from an “I-shaped” structure to a “U-shaped” structure. We further observed that the structure of PAP248-286 at the two different pH values shows significantly different features. At pH 4.2, the peptide has less intra-molecular H-bonds and a reduced α-helical content than at pH 7.2. Moreover, differences in intra-peptide residues contacts are also observed at the two pH values. Finally, free energy landscape analysis shows that there are more local minima in the energy surface of the peptide at pH 7.2 than at pH 4.2. Overall, the present study elucidates the early stages of misfolding of the PAP248-286 peptide at the atomic level, thus possibly opening new avenues in structure-based drug discovery against HIV infection.
Glycoproteomics Identifies Plexin-B3 as Targetable Cell Surface Protein Required for Growth and Invasion of Triple Negative Breast Cancer Cells
Authors: Kuhlmann Laura , Govindarajan Meinusha , Mejia-Guerrero Salvador , Ignatchenko Vladimir , Liu Lydia Y. , Grünwald Barbara T. , Cruickshank Jennifer , Berman Hal , Khokha Rama , Kislinger Thomas 
Published: June 2022

SummaryDriven by the lack of targeted therapies, triple negative breast cancers (TNBC) have the worst overall survival of all breast cancer subtypes. Considering cell surface proteins are favorable drug targets and are predominantly glycosylated, glycoproteome profiling has significant potential to facilitate the identification of much-needed drug targets for TNBC. Here, we performed N-glycoproteomics on six TNBC and five normal control (NC) cell lines using hydrazide-based enrichment. Quantitative proteomics and integrative data mining led to the discovery of Plexin-B3 (PLXNB3), a previously undescribed TNBC-enriched cell surface protein. Furthermore, siRNA knock-down and CRISPR-Cas9 editing of in vitro and in vivo models show that PLXNB3 is required for TNBC cell line growth, invasion, and migration. Altogether, we provide insight into N-glycoproteome remodeling associated with TNBC and functional evaluation of an extracted target, which indicate the surface protein PLXNB3 as a potential therapeutic target for TNBC.HighlightsIn-depth N-glycoproteomic profiles of six TNBC and five NC cell line modelsIdentification of PLXNB3 as a novel TNBC-enriched cell surface proteinPLXNB3 affects growth, invasion, and migration in TNBC modelsPLXNB3 inhibition represents a targeted treatment option for TNBC
Spatiotemporal dynamics of zygotic genome activation in basal chordates revealed by interspecific hybrids
Authors: Wei Jiankai , Zhang Wei , Leng Liang , Jiang An , Li Yuting , Ge Yonghang , Zhang Quanyong , Zhang Liya , Yu Haiyan , Chen Kai , Dong Bo 
Published: June 2022

AbstractZygotic genome activation (ZGA), a universal process in early embryogenesis that occurs during the maternal-to-zygotic transition, involves reprogramming in the zygotic nucleus that initiates global transcription. In recent decades, knowledge of this process has been acquired from research on various model organisms; however, a consensus explanation of the mechanism underlying the process, especially in relation to housekeeping gene reactivation, is lacking. Here, we used hybrids derived from two ascidian species (Ciona robusta and C. savignyi), which diverged >120 Mya with significant divergence among most orthologous genes, to symmetrically document the unique dynamics of ZGA in urochordates. We found two co-ordinated waves of ZGA, representing early developmental and housekeeping gene reactivation, during the 8-cell to 110-cell stage. Comparative analysis revealed the regulatory connection between maternal and zygotic genes as well as allelic-specific expression in a species-rather than parental-related manner, which was attributed to the divergence of cis-regulatory elements. Single-cell RNA sequencing revealed that spatial differential reactivation of paternal housekeeping genes was significantly correlated with the mechanical property of each cell type. These findings potentially provide a new system for understanding the evolution and adaptation of strategies regulating ZGA in basal chordates.
Cortical areas involved in grasping and reaching actions with and without visual information: an ALE meta-analysis of neuroimaging studies
Authors: Sartin Samantha , Ranzini Mariagrazia , Scarpazza Cristina , Monaco Simona 
Published: June 2022

AbstractThe functional specialization of the ventral stream in Perception and the dorsal stream in Action is the cornerstone of the leading model proposed by Goodale and Milner in 1982. This model is based on neuropsychological evidence and has been a matter of debate for almost three decades, during which the dual-visual stream hypothesis has received much attention, including support and criticisms. The advent of functional magnetic resonance imaging (fMRI) has allowed investigating the brain areas involved in Perception and Action and provided useful data on the functional specialization of the two streams. Research on this topic has been quite prolific, yet very little attempt has been made so far to identify consistent neuroimaging results across the available literature. In particular, no meta-analysis has explored the spatial convergence in the involvement of the two streams in Action. The present meta-analysis (N=53) was designed to reveal the specific neural activations associated with Action (i.e., grasping and reaching movements), and the extent to which visual information affects the involvement of the two streams during motor control. Our results provide a comprehensive view of the consistent and spatially convergent neural correlates of Action based on neuroimaging studies conducted over the past two decades. We discuss our results in light of the well-established dual-visual stream model and frame these findings in the context of recent discoveries obtained with advanced fMRI methods, such as multivoxel pattern analysis.
Rapid and Live-cell Detection of Senescence in Mesenchymal Stem Cells by Micro Magnetic Resonance Relaxometry
Authors: Thamarath Smitha Surendran , Tee Ching Ann , Neo Shu Hui , Yang Dahou , Othman Rashidah , Boyer Laurie A. , Han Jongyoon 
Published: June 2022

SummaryDetection of cellular senescence is important quality analytics for cell therapy products, including mesenchymal stromal cells (MSCs). However, their detection is critically limited by the lack of specific markers and the destructive assays used to read out these markers. Here, we establish a rapid, live-cell assay for detecting senescent cells using heterogeneous mesenchymal stromal cell (MSC) cultures. We report that the T2 relaxation time measured by microscale Magnetic Resonance Relaxometry (µMRR), which is related to intracellular iron accumulation, correlates strongly with senescent markers in MSC cultures under diverse conditions including different passages and donors, size-sorted MSCs by inertial spiral microfluidic device, and drug-induced senescence. In addition, the live-cell and non-destructive method presented here has general applicability to other cells and tissues, and can critically advance our understanding of cellular senescence.
Diacylglycerol at the inner nuclear membrane fuels nuclear envelope expansion in closed mitosis
Authors: Foo Sherman , Cazenave-Gassiot Amaury , Wenk Markus R. , Oliferenko Snezhana 
Published: June 2022

AbstractNuclear envelope (NE) expansion must be controlled to maintain nuclear shape and function. The nuclear membrane expands massively during ‘closed’ mitosis, enabling chromosome segregation within an intact NE. Phosphatidic acid (PA) and diacylglycerol (DG) can both serve as biosynthetic precursors for membrane lipid synthesis. How they are regulated in time and space and what are the implications of changes in their flux for mitotic fidelity is largely unknown. Using genetically encoded PA and DG probes, we show that DG is depleted from the inner nuclear membrane during mitosis in the fission yeastSchizosaccharomyces pombe, but PA does not accumulate, indicating that it is rerouted to membrane synthesis. We demonstrate that DG-to-PA conversion catalysed by the diacylglycerol kinase Dgk1 and direct glycerophospholipid synthesis from DG by diacylglycerol cholinephosphotransferase / ethanolaminephosphotransferase Ept1 reinforce NE expansion. We conclude that DG consumption through bothde novoand the Kennedy pathways fuels a spike in glycerophospholipid biosynthesis, controlling NE expansion, and ultimately, mitotic fidelity.
Hydrophobic mismatch drives self-organization of designer proteins into synthetic membranes
Authors: Peruzzi Justin A. , Steinkühler Jan , Vu Timothy Q. , Gunnels Taylor F. , Lu Peilong , Baker David , Kamat Neha P. 
Published: June 2022

AbstractThe extent to which membrane biophysical properties, such as hydrophobic thickness, can drive membrane protein organization remains unknown. Inspired by this question, we usedde novoprotein design, molecular dynamic simulations, and cell-free systems to elucidate how membrane-protein hydrophobic mismatch affects protein integration and organization in synthetic lipid membranes. We found that membranes must deform to accommodate membrane-protein hydrophobic mismatch, which reduces the expression and co-translational insertion of membrane proteins into synthetic membranes. We used this principle to sort proteins both between and within membranes, thereby achieving one-pot assembly of vesicles with distinct functions and controlled split-protein assembly, respectively. Our results shed light on protein organization in biological membranes and provide a framework to self-organizing membrane-based materials with new functions.
Targeted protein degradation using degradFP in Trypanosoma brucei
Authors: Ishii Midori , Akiyoshi Bungo 
Published: June 2022

AbstractTargeted protein degradation is an invaluable tool in studying the function of proteins. Such a tool was not available in Trypanosoma brucei, an evolutionarily divergent eukaryote that causes human African trypanosomiasis. Here, we have adapted degradFP (degrade Green Fluorescent Protein), a protein degradation system based on the SCF E3 ubiquitin ligase complex and anti-GFP nanobody, in T. brucei. As a proof of principle, we targeted a kinetoplastid kinetochore protein (KKT3) that constitutively localizes at kinetochores in the nucleus. Induction of degradFP in a cell line that had both alleles of KKT3 tagged with YFP caused more severe growth defect than RNAi in procyclic (insect form) cells. degradFP also worked on a cytoplasmic protein (COPII subunit, SEC31). Given the easiness in making GFP fusion cell lines in T. brucei, degradFP can serve as a powerful tool to rapidly deplete proteins of interest, especially those with low turnover rates.