bluuebunny/crossref_metadata_2025 huggingface dataset:
Impairment of human terminal erythroid differentiation by histone deacetylase 5 deficiency
Authors: Wang Yaomei , Li Wei , Schulz Vincent P. , Zhao Huizhi , Qu Xiaoli , Qi Qian , Cheng Yong , Guo Xinhua , Zhang Shijie , Wei Xin , Liu Donghao , Yazdanbakhsh Karina , Hillyer Christopher D. , Mohandas Narla , Chen Lixiang , Gallagher Patrick G. , An Xiuli
Published: May 2021

Histone deacetylases (HDACs) are a group of enzymes that catalyze the removal of acetyl groups from histone and nonhistone proteins. HDACs have been shown to have diverse functions in a wide range of biological processes. However, their roles in mammalian erythropoiesis remain to be fully defined. This study showed that, of the 11 classic HDAC family members, 6 (HDAC1, -2, -3, and HDAC5, -6, -7) are expressed in human erythroid cells, with HDAC5 most significantly upregulated during terminal erythroid differentiation. Knockdown of HDAC5 by either short hairpin RNA or small interfering RNA in human CD34+ cells followed by erythroid cell culture led to increased apoptosis, decreased chromatin condensation, and impaired enucleation of erythroblasts. Biochemical analyses revealed that HDAC5 deficiency resulted in activation of p53 in association with increased acetylation of p53. Furthermore, although acetylation of histone 4 (H4) is decreased during normal terminal erythroid differentiation, HDAC5 deficiency led to increased acetylation of H4 (K12) in late-stage erythroblasts. This increased acetylation was accompanied by decreased chromatin condensation, implying a role for H4 (K12) deacetylation in chromatin condensation. ATAC-seq and RNA sequencing analyses revealed that HDAC5 knockdown leads to increased chromatin accessibility genome-wide and global changes in gene expression. Moreover, pharmacological inhibition of HDAC5 by the inhibitor LMK235 also led to increased H4 acetylation, impaired chromatin condensation, and enucleation. Taken together, our findings have uncovered previously unrecognized roles and molecular mechanisms of action for HDAC5 in human erythropoiesis. These results may provide insights into understanding the anemia associated with HDAC inhibitor treatment.
Primary vitreoretinal lymphoma: a diagnostic and management challenge
Authors: Soussain Carole , Malaise Denis , Cassoux Nathalie
Published: May 2021

Primary vitreoretinal lymphoma (PVRL) is a rare form of primary central nervous system (CNS) lymphoma (PCNSL) arising in the intraocular compartment without brain involvement. Despite its apparent indolent clinical course, PVRL can cause permanent vision loss and CNS relapse, the major cause of death in patients with PVRL. The pathophysiology of PVRL is unknown. As in PCNSL, the transformation of the tumor cells likely originates outside the CNS, before the cells migrate to the eye and proliferate within an immune-permissive microenvironment. PVRL exhibits a biased immunoglobulin repertoire, suggesting underlying antigen selection. The diagnosis remains challenging, requiring close coordination between ophthalmologists and cytologists. Because of their rarity and fragility in the vitreous, lymphoma cells cannot always be identified. Interleukin levels, molecular biology, and imaging are used in combination with clinical ophthalmological examination to support the diagnosis of PVRL. Multi-institutional prospective studies are urgently needed to validate the equivocal conclusions regarding treatments drawn from heterogeneous retrospective or small cohort studies. Intravitreal injection of methotrexate or rituximab or local radiotherapy is effective at clearing tumor cells within the eyes but does not prevent CNS relapse. Systemic treatment based on high-dose methotrexate chemotherapy, with or without local treatment, might reduce this risk. At relapse, intensive consolidation chemotherapy followed by stem cell transplantation can be considered. Single-agent ibrutinib, lenalidomide, and temozolomide treatments are effective in patients with relapsed PVRL and should be tested as first-line treatments. Therapeutic response assessment based on clinical examination is improved by measuring cytokine levels but still needs to be refined.
Invariant natural killer T-cell subsets have diverse graft-versus-host-disease–preventing and antitumor effects
Authors: Maas-Bauer Kristina , Lohmeyer Juliane K. , Hirai Toshihito , Ramos Teresa Lopes , Fazal Furqan M. , Litzenburger Ulrike M. , Yost Kathryn E. , Ribado Jessica V. , Kambham Neeraja , Wenokur Arielle S. , Lin Po-Yu , Alvarez Maite , Mavers Melissa , Baker Jeanette , Bhatt Ami S. , Chang Howard Y. , Simonetta Federico , Negrin Robert S.
Published: May 2021

Invariant natural killer T (iNKT) cells are a T-cell subset with potent immunomodulatory properties. Experimental evidence in mice and observational studies in humans indicate that iNKT cells have antitumor potential as well as the ability to suppress acute and chronic graft-versus-host-disease (GVHD). Murine iNKT cells differentiate during thymic development into iNKT1, iNKT2, and iNKT17 sublineages, which differ transcriptomically and epigenomically and have subset-specific developmental requirements. Whether distinct iNKT sublineages also differ in their antitumor effect and their ability to suppress GVHD is currently unknown. In this work, we generated highly purified murine iNKT sublineages, characterized their transcriptomic and epigenomic landscape, and assessed specific functions. We show that iNKT2 and iNKT17, but not iNKT1, cells efficiently suppress T-cell activation in vitro and mitigate murine acute GVHD in vivo. Conversely, we show that iNKT1 cells display the highest antitumor activity against murine B-cell lymphoma cells both in vitro and in vivo. Thus, we report for the first time that iNKT sublineages have distinct and different functions, with iNKT1 cells having the highest antitumor activity and iNKT2 and iNKT17 cells having immune-regulatory properties. These results have important implications for the translation of iNKT cell therapies to the clinic for cancer immunotherapy as well as for the prevention and treatment of GVHD.
Study on static lateral load–slip behavior of single-shear stapled connections in plywood for upholstered furniture frame construction
Authors: Hu Wengang , Zhang Jilei
Published: May 2021

The static lateral load–slip behavior of a single-shear plywood-to-plywood single-staple connection (SPSC) was investigated experimentally. A mechanics-based approach was used to develop mechanical models for deriving estimation equations for critical lateral loads of SPSCs based on failure modes of staple legs and connection member materials developed during static lateral loading process. Experimental results indicated that the static lateral load–slip behavior of SPSCs can be characterized with three major stages. This experiment provided the evidence that the ultimate lateral load capacity of SPSCs was partially governed by staple direct withdrawal load capacity in main members. The proposed mechanical models were verified experimentally as a valid means for deriving estimation equations for critical lateral loads of SPSCs evaluated in this study.
Tests of association based on genomic windows can lead to spurious associations when using genotype panels with heterogeneous SNP densities
Authors: Li Jinghui , Wang Zigui , Fernando Rohan , Cheng Hao
Published: May 2021

Dense single nucleotide polymorphism (SNP) panels are widely used for genome-wide association studies (GWAS). In these panels, SNPs within a genomic segment tend to be highly correlated. Thus, association studies based on testing the significance of single SNPs are not very effective, and genomic-window based tests have been proposed to address this problem. However, when the SNP density on the genotype panel is not homogeneous, genomic-window based tests can lead to the detection of spurious associations by declaring effects of genomic windows that explain a large proportion of genetic variance as significant. We propose two methods to solve this problem.
PTMViz: a tool for analyzing and visualizing histone post translational modification data
Authors: Chappell Kevin , Graw Stefan , Washam Charity L. , Storey Aaron J. , Bolden Chris , Peterson Eric C. , Byrum Stephanie D.
Published: May 2021

Background

Histone post-translational modifications (PTMs) play an important role in our system by regulating the structure of chromatin and therefore contribute to the regulation of gene and protein expression. Irregularities in histone PTMs can lead to a variety of different diseases including various forms of cancer. Histone modifications are analyzed using high resolution mass spectrometry, which generate large amounts of data that requires sophisticated bioinformatics tools for analysis and visualization. PTMViz is designed for downstream differential abundance analysis and visualization of both protein and/or histone modifications.

Results

PTMViz provides users with data tables and visualization plots of significantly differentiated proteins and histone PTMs between two sample groups. All the data is packaged into interactive data tables and graphs using the Shiny platform to help the user explore the results in a fast and efficient manner to assess if changes in the system are due to protein abundance changes or epigenetic changes. In the example data provided, we identified several proteins differentially regulated in the dopaminergic pathway between mice treated with methamphetamine compared to a saline control. We also identified histone post-translational modifications including histone H3K9me, H3K27me3, H4K16ac, and that were regulated due to drug exposure.

Conclusions

Histone modifications play an integral role in the regulation of gene expression. PTMViz provides an interactive platform for analyzing proteins and histone post-translational modifications from mass spectrometry data in order to quickly identify differentially expressed proteins and PTMs.
CpGmotifs: a tool to discover DNA motifs associated to CpG methylation events
Authors: Scala Giovanni , Federico Antonio , Greco Dario
Published: May 2021

Background

The investigation of molecular alterations associated with the conservation and variation of DNA methylation in eukaryotes is gaining interest in the biomedical research community. Among the different determinants of methylation stability, the DNA composition of the CpG surrounding regions has been shown to have a crucial role in the maintenance and establishment of methylation statuses. This aspect has been previously characterized in a quantitative manner by inspecting the nucleotidic composition in the region. Research in this field still lacks a qualitative perspective, linked to the identification of certain sequences (or DNA motifs) related to particular DNA methylation phenomena.

Results

Here we present a novel computational strategy based on short DNA motif discovery in order to characterize sequence patterns related to aberrant CpG methylation events. We provide our framework as a user-friendly, shiny-based application, CpGmotifs, to easily retrieve and characterize DNA patterns related to CpG methylation in the human genome. Our tool supports the functional interpretation of deregulated methylation events by predicting transcription factors binding sites (TFBS) encompassing the identified motifs.

Conclusions

CpGmotifs is an open source software. Its source code is available on GitHub https://github.com/Greco-Lab/CpGmotifs and a ready-to-use docker image is provided on DockerHub at https://hub.docker.com/r/grecolab/cpgmotifs.
Population transcriptomic sequencing reveals allopatric divergence and local adaptation in Pseudotaxus chienii (Taxaceae)
Authors: Liu Li , Wang Zhen , Su Yingjuan , Wang Ting
Published: May 2021

Background

Elucidating the effects of geography and selection on genetic variation is critical for understanding the relative importance of adaptation in driving differentiation and identifying the environmental factors underlying its occurrence. Adaptive genetic variation is common in tree species, especially widely distributed long-lived species. Pseudotaxus chienii can occupy diverse habitats with environmental heterogeneity and thus provides an ideal material for investigating the process of population adaptive evolution. Here, we characterize genetic and expression variation patterns and investigate adaptive genetic variation in P. chienii populations.

Results

We generated population transcriptome data and identified 13,545 single nucleotide polymorphisms (SNPs) in 5037 unigenes across 108 individuals from 10 populations. We observed lower nucleotide diversity (π = 0.000701) among the 10 populations than observed in other gymnosperms. Significant negative correlations between expression diversity and nucleotide diversity in eight populations suggest that when the species adapts to the surrounding environment, gene expression and nucleotide diversity have a reciprocal relationship. Genetic structure analyses indicated that each distribution region contains a distinct genetic group, with high genetic differentiation among them due to geographical isolation and local adaptation. We used FST outlier, redundancy analysis, and latent factor mixed model methods to detect molecular signatures of local adaptation. We identified 244 associations between 164 outlier SNPs and 17 environmental variables. The mean temperature of the coldest quarter, soil Fe and Cu contents, precipitation of the driest month, and altitude were identified as the most important determinants of adaptive genetic variation. Most candidate unigenes with outlier signatures were related to abiotic and biotic stress responses, and the monoterpenoid biosynthesis and ubiquitin-mediated proteolysis KEGG pathways were significantly enriched in certain populations and deserve further attention in other long-lived trees.

Conclusions

Despite the strong population structure in P. chienii, genomic data revealed signatures of divergent selection associated with environmental variables. Our research provides SNPs, candidate unigenes, and biological pathways related to environmental variables to facilitate elucidation of the genetic variation in P. chienii in relation to environmental adaptation. Our study provides a promising tool for population genomic analyses and insights into the molecular basis of local adaptation.
Growth inhibition of Spodoptera frugiperda larvae by camptothecin correlates with alteration of the structures and gene expression profiles of the midgut
Authors: Shu Benshui , Zou Yan , Yu Haikuo , Zhang Wanying , Li Xiangli , Cao Liang , Lin Jintian
Published: May 2021

Background

Spodoptera frugiperda is a serious pest that causes devastating losses to many major crops, including corn, rice, sugarcane, and peanut. Camptothecin (CPT) is a bioactive secondary metabolite of the woody plant Camptotheca acuminata, which has shown high toxicity to various pests. However, the effect of CPT against S. frugiperda remains unknown.

Results

In this study, bioassays have been conducted on the growth inhibition of CPT on S. frugiperda larvae. Histological and cytological changes were examined in the midgut of larvae fed on an artificial diet supplemented with 1.0 and 5.0 µg/g CPT. The potential molecular mechanism was explored by comparative transcriptomic analyses among midgut samples obtained from larvae under different treatments. A total of 915 and 3560 differentially expressed genes (DEGs) were identified from samples treated with 1.0 and 5.0 µg/g CPT, respectively. Among the identified genes were those encoding detoxification-related proteins and components of peritrophic membrane such as mucins and cuticle proteins. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that part of DEGs were involved in DNA replication, digestion, immunity, endocrine system, and metabolism.

Conclusions

Our results provide useful information on the molecular basis for the impact of CPT on S. frugiperda and for future studies on potential practical application.
Correlation of exhaled propofol with Narcotrend index and calculated propofol plasma levels in children undergoing surgery under total intravenous anesthesia - an observational study
Authors: Heiderich Sebastian , Ghasemi Tara , Dennhardt Nils , Sümpelmann Robert , Rigterink Vanessa , Nickel Katja , Keil Oliver , Böthig Dietmar , Beck Christiane E.
Published: May 2021

Background

Exhaled propofol concentrations correlate with propofol concentrations in adult human blood and the brain tissue of rats, as well as with electroencephalography (EEG) based indices of anesthetic depth. The pharmacokinetics of propofol are however different in children compared to adults. The value of exhaled propofol measurements in pediatric anesthesia has not yet been investigated. Breathing system filters and breathing circuits can also interfere with the measurements. In this study, we investigated correlations between exhaled propofol (exP) concentrations and the Narkotrend Index (NI) as well as calculated propofol plasma concentrations.

Methods

A multi-capillary-column (MCC) combined with ion mobility spectrometry (IMS) was used to determine exP. Optimal positioning of breathing system filters (near-patient or patient-distant) and sample line (proximal or distal to filter) were investigated. Measurements were taken during induction (I), maintenance (M) and emergence (E) of children under total intravenous anesthesia (TIVA). Correlations between ExP concentrations and NI and predicted plasma propofol concentrations (using pediatric pharmacokinetic models Kataria and Paedfusor) were assessed using Pearson correlation and regression analysis.

Results

Near-patient positioning of breathing system filters led to continuously rising exP values when exP was measured proximal to the filters, and lower concentrations when exP was measured distal to the filters. The breathing system filters were therefore subsequently attached between the breathing system tubes and the inspiratory and expiratory limbs of the anesthetic machine. ExP concentrations significantly correlated with NI and propofol concentrations predicted by pharmacokinetic models during induction and maintenance of anesthesia. During emergence, exP significantly correlated with predicted propofol concentrations, but not with NI.

Conclusion

In this study, we demonstrated that exP correlates with calculated propofol concentrations and NI during induction and maintenance in pediatric patients. However, the correlations are highly variable and there are substantial obstacles: Without patient proximal placement of filters, the breathing circuit tubing must be changed after each patient, and furthermore, during ventilation, a considerable additional loss of heat and moisture can occur. Adhesion of propofol to plastic parts (endotracheal tube, breathing circle) may especially be problematic during emergence.

Trial Registration

The study was registered in the German registry of clinical studies (DRKS-ID: DRKS00015795).
Anaesthesia and orphan disease: management of a case of Nicolaides-Baraitser syndrome undergoing cleft palate surgery
Authors: Goehring Marie , Choorapoikayil Suma , Zacharowski Kai , Messroghli Leila
Published: May 2021

Background

Nicolaides-Baraitser syndrome (NCBRS) is a rare disease caused by mutations in the SMRCA2 gene, which affects chromatin remodelling and leads to a wide range of symptoms including microcephaly, distinct facial features, recurrent seizures, and severe mental retardation. Until now, less than 100 cases have been reported.

Case presentation

A 22-month old male infant with NCBRS underwent elective cleft palate surgery. The anaesthetists were challenged by the physiological condition of the patient: narrow face, very small mouth, mild tachypnea, slight sternal retractions, physical signs of partial monosomy 9p, and plagiocephalus, midface hypoplasia, V-shaped cleft palate, enhanced muscular hypotension, dysplastic kidneys (bilateral, estimated GFR: approx. 40 ml/m2), nocturnal oxygen demand, and combined apnea. In addition, little information was available about interaction of the NCBRS displayed by the patient and anaesthesia medications.

Conclusions

The cleft palate was successfully closed using the bridge flap technique. Overall, we recommend to perform a trial video assisted laryngoscopy in the setting of spontaneous breathing with deep inhalative anaesthesia before administration of muscle relaxation to detect any airway difficulties while remaining spontaneoues breathing and protective reflexes.
Current trends in optimal medical therapy after PCI and its influence on clinical outcomes in China
Authors: Zhang Jian , Hao Jing-Yan , Jing Rui , Liu Jing-Jing , Di Cheng-Ye , Lu Yu-Jie , Gao Peng , Wang Ya-Jie , Yang Rui-Fei , Lin Wen-Hua
Published: May 2021

Background

Limited data were available on the current trends in optimal medical therapy (OMT) after PCI and its influence on clinical outcomes in China. We aimed to evaluate the utilization and impact of OMT on the main adverse cardiovascular and cerebrovascular events (MACCEs) in post-PCI patients and analyzed the factors predictive of OMT after discharge.

Methods

We collected data from 3812 individuals from 2016.10 to 2017.09 at TEDA International Cardiovascular Hospital. They were classified into an OMT group and a non-OMT group according to their OMT status, which was defined as the combination of dual antiplatelet therapy, statins, β-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers after PCI. Multivariable Cox regression models were developed to assess the association between OMT and MACCEs, defined as all-cause mortality, nonfatal myocardial infarction, stroke, and target vessel revascularization. A logistic regression model was established to analyze the factors predictive of OMT.

Results

Our results revealed that the proportion of patients receiving OMT and its component drugs decreased over time. A total of 36.0% of patients were still adherent to OMT at the end of follow-up. Binary logistic regression analysis revealed that baseline OMT (P < 0.001,OR = 52.868) was the strongest predictor of OMT after PCI. The Cox hazard model suggested that smoking after PCI was associated with the 1-year risk of MACCE (P = 0.001,HR = 2.060, 95% CI 1.346–3.151), while OMT (P = 0.001,HR = 0.486, 95% CI 0.312–0.756) was an independent protective factor against postoperative MACCEs.

Conclusions

There was still a gap between OMT utilization after PCI and the recommendations in the evidence-based guidelines. Sociodemographic and clinical factors influence the application of OMT. The management of OMT and smoking cessation after PCI should be emphasized.
Socioeconomic differentials in trends in the prevalence of hypertension and pre-hypertension and hypertension awareness, treatment, and control in rural Southwestern China
Authors: Fan Lu-Ming , Wang Fang , Zhao Min , Cui Wen-Long , Cai Le
Published: May 2021

Background

This study examines the socioeconomic differentials in trends in the prevalence of hypertension and pre-hypertension and hypertension awareness, treatment, and control in rural Southwestern China.

Methods

Two cross-sectional interviews and health examination surveys were administered in rural Yunnan Province, including 6,350 consenting participants in 2009 and 6,359 consenting participants in 2016 (aged ≥ 35 years). Participant demographics, socioeconomic status (SES), and ethnicity, along with information about hypertension awareness, treatment, and control, were collected using similar questionnaires in the two surveys. The participants’ blood pressure levels were also measured.

Results

From 2009 to 2016, the prevalence of hypertension substantially increased from 28.4% to 39.5% (P < 0.01), and awareness and control rose from 42.2 and 25.8% to 53.1 (P < 0.01) and 30.6% (P < 0.05), respectively. Although people with a higher education level also had higher awareness and control rates than the lower education level ones, there were no conspicuous differences in the improvement of awareness and control between publics with different education levels over the 7 years studied. Increases were observed in both rates of awareness and control in people with a high level of income (P < 0.01). However, only the awareness rate increased in participants with a low level of income. Furthermore, the prevalence (P < 0.01) and treatment (P < 0.05) of hypertension were higher in the Han people than in ethnic minorities.

Conclusions

Individual SES has clear associations with trends in the prevalence, awareness, and control of hypertension. Future interventions to improve hypertension prevention and control should be tailored to address individual SES.
Patient perspectives on tablet-based technology to collect risk factor information in primary care
Authors: Kosowan Leanne , Katz Alan , Halas Gayle , Singer Alexander
Published: May 2021

Background

Primary care provides an opportunity to introduce prevention strategies and identify risk behaviours. Algorithmic information technology such as the Risk Factor Identification Tool (RFIT) can support primary care counseling. This study explores the integration of the tablet-based RFIT in primary care clinics to support exploration of patient risk factor information.

Methods

Qualitative study to explore patients’ perspectives of RFIT. RFIT was implemented in two primary care clinics in Manitoba, Canada. There were 207 patients who completed RFIT, offered to them by eight family physicians. We conducted one-on-one patient interviews with 86 patients to capture the patient’s perspective. Responses were coded and categorized into five common themes.

Results

RFIT had a completion rate of 86%. Clinic staff reported that very few patients declined the use of RFIT or required assistance to use the tablet. Patients reported that the tablet-based RFIT provided a user-friendly interface that enabled self-reflection while in the waiting room. Patients discussed the impact of RFIT on the patient-provider interaction, utility for the clinician, their concerns and suggested improvements for RFIT. Among the patients who used RFIT 12.1% smoked, 21.2% felt their diet could be improved, 9.3% reported high alcohol consumption, 56.4% reported less than 150 min of PA a week, and 8.2% lived in poverty.

Conclusion

RFIT is a user-friendly tool for the collection of patient risk behaviour information. RFIT is particularly useful for patients lacking continuity in the care they receive. Information technology can promote self-reflection while providing useful information to the primary care clinician. When combined with practical tools and resources RFIT can assist in the reduction of risk behaviours.
Mobile application for monitoring patients under home oxygen therapy: a protocol for a randomized controlled trial
Authors: Naranjo-Rojas Anisbed , Perula-de-Torres Luis Ángel , Cruz-Mosquera Freiser Eceomo , Molina-Recio Guillermo
Published: May 2021

Background

Mobile technologies have become capable of changing the paradigm of healthcare services. A clear example is that, nowadays, these technologies are an important instrument for data collection processes, epidemiologic surveillance, health promotion and disease prevention. Therefore, technological tools should be exploited to optimize the monitoring of patients with chronic diseases, including patients who require home oxygen therapy. Purpose: The purpose of this study is to determine the efficacy of a mobile application in the clinical monitoring of patients under home oxygen therapy.

Methods

This is a randomized controlled trial includes subjects of 18 years or older diagnosed with Chronic Obstructive Pulmonary Disease (COPD) who are under home oxygen therapy. Subjects will be divided into two arms: the intervention group will include patients who will be monitored with a mobile application, and the control group will include patients monitored by conventional follow-up methods (periodic visits of a respiratory therapist). The following outcome variables will be considered to measure the effect of the intervention: identification of dyspnea self-management, number of acute exacerbations associated with oxygen therapy, and the occurrence of oxygen supply underuse.

Discussion

This study is expected to assess the efficacy of a mobile application in the follow up of patients under home oxygen therapy. It will also determine whether the monitoring of a six-month intervention by a team comprising a physician, a nurse and respiratory therapists can decrease acute exacerbations, determine the most appropriate oxygen dose, and identify the underuse of oxygen systems and supplies.

Trial registration

The study has been registered at ClinicalTrials.gov (NCT04820790; date of registration: March 29, 2021)
Impacts of the SOAT1 genetic variants and protein expression on HBV-related hepatocellular carcinoma
Authors: Chen Yulong , Yang Xunjun , Chen Yao , Chen Guorong , Winkler Cheryl A. , An Ping , Lyu Jianxin
Published: May 2021

Background

Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains a major public health problem and its pathogenesis remains unresolved. A recent proteomics study discovered a lipid enzyme Sterol O-acyltransferase (SOAT1) involvement in the progression of HCC. We aimed to explore the association between SOAT1 genetic variation and HCC.

Methods

We genotyped three exonic SOAT1 variants (rs10753191, V323V; rs3753526, L475L; rs13306731, Q526R) tagging most variations in the gene, in 221 HCC patients and 229 healthy individuals, to assess the impact of SOAT1 gene variation on risk of HCC occurrence. We further conducted immunohistochemistry to compare SOAT1 protein expression levels in 42 paired tumor and adjacent non-tumor tissues.

Results

We found that rs10753191 (Odds ratio (OR) = 0.58, P = 0.04) and a haplotype TGA (OR = 0.40, P = 0.01) were associated with reduced HCC risk after adjusting for lipid levels. In the immunohistochemistry experiment, we found that the protein expression of SOAT1 was significantly increased in the tumor compared with adjacent tissue (P < 0.001).

Conclusion

This study revealed for the first time SOAT1 genetic variation that associates with host susceptibility to HCC occurrence. Our results suggest a role of SOAT1 in the HCC development, which warrants further elucidation.
Identification of significant genes as prognostic markers and potential tumor suppressors in lung adenocarcinoma via bioinformatical analysis
Authors: Lu Mingze , Fan Xiaowen , Liao Weilin , Li Yijiao , Ma Lijie , Yuan Mu , Gu Rui , Wei Zhengdao , Wang Chao , Zhang Hua
Published: May 2021

Background

Lung adenocarcinoma (LAC) is the predominant histologic subtype of lung cancer and has a complicated pathogenesis with high mortality. The purpose of this study was to identify differentially expressed genes (DEGs) with prognostic value and determine their underlying mechanisms.

Methods

Gene expression data of GSE27262 and GSE118370 were acquired from the Gene Expression Omnibus database, enrolling 31 LAC and 31 normal tissues. Common DEGs between LAC and normal tissues were identified using the GEO2R tool and Venn diagram software. Next, the Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to analyze the Gene Ontology and Kyoto Encyclopedia of Gene and Genome (KEGG) pathways. Then, protein-protein interaction (PPI) network of DEGs was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes and central genes were identified via Molecular Complex Detection. Furthermore, the expression and prognostic information of central genes were validated via Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan-Meier analysis, respectively. Finally, DAVID, real-time PCR and immunohistochemistry were applied to re-analyze the identified genes, which were also further validated in two additional datasets from ArrayExpress database.

Results

First, 189 common DEGs were identified among the two datasets, including 162 downregulated and 27 upregulated genes. Next, Gene Ontology and KEGG pathway analysis of the DEGs were conducted through DAVID. Then, PPI network of DEGs was constructed and 17 downregulated central genes were identified. Furthermore, the 17 downregulated central genes were validated via GEPIA and datasets from ArrayExpress, and 12 of them showed a significantly better prognosis. Finally, six genes were identified significantly enriched in neuroactive ligand-receptor interactions (EDNRB, RXFP1, P2RY1, CALCRL) and Rap1 signaling pathway (TEK, P2RY1, ANGPT1) via DAVID, which were further validated to be weakly expressed in LAC tissues via RNA quantification and immunohistochemistry analysis.

Conclusions

The low expression pattern and relation to prognosis indicated that the six genes were potential tumor suppressor genes in LAC. In conclusion, we identified six significantly downregulated DEGs as prognostic markers and potential tumor suppressor genes in LAC based on integrated bioinformatics methods, which could act as potential molecular markers and therapeutic targets for LAC patients.
Safety and efficacy profile of mogamulizumab (Poteligeo) in the treatment of cancers: an update evidence from 14 studies
Authors: Zhang Ting , Sun Jing , Li Jinying , Zhao Yunuo , Zhang Tao , Yang Ruoning , Ma Xuelei
Published: May 2021

Background

CC chemokine receptor 4 (CCR4), the receptor for CCL22 and CCL17, is expressed on the surface of effector Tregs that have the highest suppressive effects on antitumor immune response. CCR4 is also widely expressed on the surface of tumor cells from patients with adult T-cell leukemia/lymphoma (ATL), peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL). Mogamulizumab is a humanized, IgG1 kappa monoclonal antibody that is directed against CCR4. By reducing the number of CCR4-positive Tregs and tumor cells, the mogamulizumab can reduce tumor burden and boost antitumor immunity to achieve antitumor effects.

Methods

We examined the PubMed and ClinicalTrials.gov until 1 February 2020. Considering variability in different studies, we selected the adverse events (AEs), overall survival (OS), progression-free survival (PFS), objective responses rate (ORR) and Hazard Ratio (HR) for PFS to evaluate the safety and efficacy profile of mogamulizumab.

Results

When patients were treated with mogamulizumab monotherapy, the most common all-grade AEs were lymphopenia, infusion reaction, fever, rash and chills while the most common grade ≥ 3 AEs were lymphopenia, neutropenia and rash. When patients were treated with combined therapy of mogamulizumab and other drugs, the most common all-grade AEs were neutropenia, anaemia, lymphopenia and gastrointestinal disorder, while the most common grade ≥ 3 AEs was lymphopenia. For patients treated with mogamulizumab monotherapy, the pooled ORR and mean PFS were 0.430 (95% CI: 0.393–0.469) and 1.060 months (95% CI: 1.043–1.077), respectively. For patients treated with combined therapy of mogamulizumab and other drugs, the pooled ORR was 0.203 (95% CI: 0.022–0.746) while the pooled PFS and OS were 2.093 months (95% CI: 1.602–2.584) and 6.591 months (95% CI: 6.014–7.167), respectively.

Conclusions

Based on present evidence, we believed that mogamulizumab had clinically meaningful antitumor activity with acceptable toxicity which is a novel therapy in treating patients with cancers.
Body-mass index, blood pressure, diabetes and cardiovascular mortality in Cuba: prospective study of 146,556 participants
Authors: Armas Rojas Nurys B , Lacey Ben , Soni Monica , Charles Shaquille , Carter Jennifer , Varona-Pérez Patricia , Burrett Julie Ann , Martínez Marcy Calderón , Lorenzo-Vázquez Elba , Constantén Sonia Bess , Taylor Hannah , Sherliker Paul , Rigau José Manuel Morales , Ross Stephanie , Massa M. Sofia , López Osvaldo Jesús Hernández , Islam Nazrul , Morales Miguel Ángel Martínez , Alomá Ismell Alonso , Estupiñan Fernando Achiong , González Mayda Díaz , Muñoz Noel Rosquete , Asencio Marelis Cendra , Díaz-Diaz Oscar , Iglesias-Marichal Ileydis , Emberson Jonathan , Peto Richard , Lewington Sarah
Published: May 2021

Background

Cardiovascular disease accounts for about one-third of all premature deaths (ie, age < 70) in Cuba. Yet, the relevance of major risk factors, including systolic blood pressure (SBP), diabetes, and body-mass index (BMI), to cardiovascular mortality in this population remains unclear.

Methods

In 1996–2002, 146,556 adults were recruited from the general population in five areas of Cuba. Participants were interviewed, measured (height, weight and blood pressure) and followed up by electronic linkage to national death registries until Jan 1, 2017; in 2006–08, 24,345 participants were resurveyed. After excluding all with missing data, cardiovascular disease at recruitment, and those who died in the first 5 years, Cox regression (adjusted for age, sex, education, smoking, alcohol and, where appropriate, BMI) was used to relate cardiovascular mortality rate ratios (RRs) at ages 35–79 years to SBP, diabetes and BMI; RR were corrected for regression dilution to give associations with long-term average (ie, ‘usual’) levels of SBP and BMI.

Results

After exclusions, there were 125,939 participants (mean age 53 [SD12]; 55% women). Mean SBP was 124 mmHg (SD15), 5% had diabetes, and mean BMI was 24.2 kg/m2 (SD3.6); mean SBP and diabetes prevalence at recruitment were both strongly related to BMI. During follow-up, there were 4112 cardiovascular deaths (2032 ischaemic heart disease, 832 stroke, and 1248 other). Cardiovascular mortality was positively associated with SBP (>=120 mmHg), diabetes, and BMI (>=22.5 kg/m2): 20 mmHg higher usual SBP about doubled cardiovascular mortality (RR 2.02, 95%CI 1.88–2.18]), as did diabetes (2.15, 1.95–2.37), and 10 kg/m2 higher usual BMI (1.92, 1.64–2.25). RR were similar in men and in women. The association with BMI and cardiovascular mortality was almost completely attenuated following adjustment for the mediating effect of SBP. Elevated SBP (>=120 mmHg), diabetes and raised BMI (>=22.5 kg/m2) accounted for 27%, 14%, and 16% of cardiovascular deaths, respectively.

Conclusions

This large prospective study provides direct evidence for the effects of these major risk factors on cardiovascular mortality in Cuba. Despite comparatively low levels of these risk factors by international standards, the strength of their association with cardiovascular death means they nevertheless exert a substantial impact on premature mortality in Cuba.
Application of the health action process approach model for reducing excessive internet use behaviors among rural adolescents in China: a school-based intervention pilot study
Authors: Tang Chengmeng , Raat Hein , Yan Mingxia , Zhang Qiang , Li Kehan , Jiang Min , Tang Wanjie , Chen Jiayi , Zhao Ying , Liu Qiaolan
Published: May 2021

Objective

There are few studies regarding Internet use behaviors of Chinese rural adolescents based on behavioral theory. The aim of this study is to examine the applicability and effectiveness of the health action process approach model (HAPA) in the intervention of excessive Internet use behaviors among rural adolescents in China.

Methods

Three hundred twenty-seven participants who met the excessive Internet use criteria were involved in this study. Four interventions based on the HAPA model were conducted during 2015–2017. The structural equation model (SEM) was applied to fit the HAPA model.

Results

The rate of average daily time spent online on weekends more than 4 h dropped from 57.2 to 39.1% (P < 0.001). The rate of daily game time more than 2 h decreased from 51.1 to 35.2% (P < 0.001). The result of SEM showed that both the applicability and effectiveness of the HAPA model were well in the intervention of excessive Internet use behaviors with good fitted indicators (χ2/df = 2.066, GFI = 0.889, CFI = 0.938, TLI = 0.928, IFI = 0.938, RMSEA = 0.057). The direct and indirect effects of the main pathways in the HAPA model were statistically significant (P < 0.05). The comparison analysis of HAPA model variables identified that outcome expectancy, intention, maintenance self-efficacy had been improved significantly after interventions.

Conclusion

The intervention measures based on the HAPA model can effectively reduce excessive Internet use behaviors of Chinese rural adolescents, mainly through strengthen outcome expectancy, intention, and maintenance self-efficacy.
Risk of stress/depression and functional impairment in Denmark immediately following a COVID-19 shutdown
Authors: Andersen Lars H. , Fallesen Peter , Bruckner Tim A.
Published: May 2021

Background

Existing estimates of the impact of the COVID-19 burden on mental wellbeing come from countries with high mortality rates. This study therefore aimed to investigate the impact of the first COVID-19 lockdown (March–April 2020) on risk for stress/depression and functional impairment in a representative sample of adult individuals in Denmark, which had lower infection rates, and whether the impact of lockdown was heterogeneous across living situation.

Methods

Using a representative, randomly drawn sample from the complete Danish adult population interviewed in March 2 to April 13, 2020 (n = 2836) and again in July 2020 (n = 1526, 54% retention rate), we study how the imposed lockdown announced March 11 following the onset of the first Danish wave of COVID-19 infections affected mental wellbeing. We use the World Health Organization Five Well-being Index (WHO-5) and the Work and Social Adjustment Scale (WSAS) to capture risk for stress/depression (WHO-5 < 50) and functional impairment (WSAS > 10). Using covariate adjusted ordinary least squares linear probability models and exploiting variation in the timing of responses occurring just before and just after the introduction of lockdown, we compare respondents before lockdown to respondents that answered during lockdown, as well as to answers in re-interviews in July.

Results

In our fully controlled models, we find reduced depressive symptoms among adults immediately after the shutdown, concentrated in adults with children living at home (−.089,p < .01 (from pre lockdown baseline .273)). Measures of functional impairment also declined immediately after the March shutdown among adults with children living at home (−.066,p < .05 (from pre lockdown baseline .150)). Impairment intensified for the entire sample between March and July (+.199,p < .001 (from pre lockdown baseline .248)), but depressive symptoms remained at lower rate in July (−.033,p < .05 (from pre lockdown baseline .332).

Conclusions

Findings in Denmark indicate that living with children at home may have, in the short term, buffered the potential mental health sequelae of the COVID-19 shutdown.
Re-conceptualizing sustainable urban sanitation in Uganda: why the roots of ‘Slumification’ must be dealt with
Authors: Kwiringira Japheth Nkiriyehe , Kabumbuli Robert , Zakumumpa Henry , Mugisha James , Akugizibwe Mathias , Ariho Paulino , Rujumba Joseph
Published: May 2021

Background

Country-wide urbanization in Uganda has continued amidst institutional challenges. Previous interventions in the water and sanitation sector have not addressed the underlying issues of a poorly managed urbanization processes. Poor urbanisation is linked to low productivity, urban poverty, unemployment, limited capacity to plan and offer basic services as well as a failure to enforce urban standards.

Methods

This ethnographic study was carried out in three urban centres of Gulu, Mbarara and Kampala. We explored relationships between urban livelihoods and sustainable urban sanitation, using theeconomic sociology of urban sanitation framework.This framework locates the urbanization narrative within a complex system entailing demand, supply, access, use and sustainability of slum sanitation. We used both inductive and deductive thematic analysis.

Results

More than any other city in Uganda, Kampala was plagued with poor sanitation services characterized by a mismatch between demand and the available capacity for service provision. Poor slum sanitation was driven by; the need to escape rural poverty through urban migration, urban governance deficits, corruption and the survival imperative, poor service delivery and lack of capacity, pervasive (urban) informality, lack of standards:‘to whom it may concern’attitudes and the normalization of risk as a way of life. Amidst a general lack of affordability, there was a critical lack ofpublic goodconscience. Most urbanites were trapped in poverty, whereby economic survival trumped for the need for meeting desirable sanitation standards.

Conclusions

Providing sustainable urban livelihoods and meeting sanitation demands is nested within sustainable livelihoods. Previous interventions have labored to fix the sanitation problem in slums without considering the drivers of this problem. Sustainable urban livelihoods are critical in reducing slums, improving slum living and curtailing the onset ofslumification. Urban authorities need to make urban centres economically vibrant as an integral strategy for attaining better sanitation standards.
Effect of pre-operative internal obturator muscle mass index in MRI on biochemical recurrence of prostate cancer patients after radical prostatectomy: a multi-center study
Authors: Kim Won Tae , Kang Ho Won , Seo Sung Pil , Kim Yong-June , Lee Sang Cheol , Kim Wun-Jae , Cho Bum Sang , Ha Yun Sok , Kwon Tae Gyun , Park Jinsung , Park Seung Chol , Jeong Young Beom , Kang Taek Won , Park Sung-Woo , Yun Seok Joong
Published: May 2021

Background

Recent reports show that the pre-operative or post-operative skeletal mass index (sarcopenia) affects survival rates for various cancers; however, the link between prostate cancer survival and sarcopenia is unclear. Therefore, this study examined the effect of the pre-operative internal obturator muscle (IOM) mass index on biochemical recurrence (BCR) of prostate cancer (PCa) patients who underwent radical prostatectomy.

Methods

In total, 222 patients, who underwent open, laparoscopic, or robot-assisted radical prostatectomy at seven centers in 2011 and were followed up for 5 years, were enrolled. BCR was examined in the context of pre-operative IOM mass index and BMI.

Results

The mean age of the patients was 67.82 ± 6.23 years, and the mean pre-operative prostate-specific antigen (PSA) level was 11.61 ± 13.22 ng/ml. There was no significant difference in baseline characteristics between the low and high IOM mass index groups (p > 0.05). Age, pre-op PSA level, ECE, and T-stage were associated with BCR (p = 0.049, p < 0.001, p = 0.001, p = 0.004, respectively). BMI, prostate volume, Gleason score, resection margin, N-stage, M-stage and IOM mass index was not associated with BCR (p > 0.05).

Conclusions

Pre-operative IOM mass index was not associated with BCR; however, long-term follow-up is necessary to evaluate cancer-specific and overall survival of PCa patients.