bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceived utility and feasibility of pathogen genomics for public health practice: a survey among public health professionals working in the field of infectious diseases, Belgium, 2019
Authors: Van Goethem N. , Struelens M. J. , De Keersmaecker S. C. J. , Roosens N. H. C. , Robert A. , Quoilin S. , Van Oyen H. , Devleesschauwer B.
Published: August 2020

Background

Pathogen genomics is increasingly being translated from the research setting into the activities of public health professionals operating at different levels. This survey aims to appraise the literacy level and gather the opinions of public health experts and allied professionals working in the field of infectious diseases in Belgium concerning the implementation of next-generation sequencing (NGS) in public health practice.

Methods

In May 2019, Belgian public health and healthcare professionals were invited to complete an online survey containing eight main topics including background questions, general attitude towards pathogen genomics for public health practice and main concerns, genomic literacy, current and planned NGS activities, place of NGS in diagnostic microbiology pathways, data sharing obstacles, end-user requirements, and key drivers for the implementation of NGS. Descriptive statistics were used to report on the frequency distribution of multiple choice responses whereas thematic analysis was used to analyze free text responses. A multivariable logistic regression model was constructed to identify important predictors for a positive attitude towards the implementation of pathogen genomics in public health practice.

Results

146 out of the 753 invited public health professionals completed the survey. 63% of respondents indicated that public health agencies should be using genomics to understand and control infectious diseases. Having a high level of expertise in the field of pathogen genomics was the strongest predictor of a positive attitude (OR = 4.04, 95% CI = 1.11 – 17.23). A significantly higher proportion of data providers indicated to have followed training in the field of pathogen genomics compared to data end-users (p < 0.001). Overall, 79% of participants expressed interest in receiving further training. Main concerns were related to the cost of sequencing technologies, data sharing, data integration, interdisciplinary working, and bioinformatics expertise.

Conclusions

Belgian health professionals expressed favorable views about implementation of pathogen genomics in their work activities related to infectious disease surveillance and control. They expressed the need for suitable training initiatives to strengthen their competences in the field. Their perception of the utility and feasibility of pathogen genomics for public health purposes will be a key driver for its further implementation.
Chest roentgenography is complementary to interferon-gamma release assay in latent tuberculosis infection screening of rheumatic patients
Authors: Wang Ping-Huai , Lin Chou-Han , Chang Ting-Hui , Wu Chien-Sheng
Published: August 2020

Background

A study of latent tuberculosis infection (LTBI) burden by chest roentgenography (CXR) with reference to interferon-gamma release assay (IGRA) is still lacking in rheumatic patients of an intermediate tuberculosis burden area.

Methods

We retrospectively reviewed clinical data of patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA) receiving LTBI screening for biologics from Jan 2013 to April 2014.

Results

A total of 238 rheumatic patients who underwent LTBI screening were included in this study, of whom 46 (19.3%) had positive IGRA tests, 178 (74.8%) had negative results, and 14 (5.9%) had indeterminate results. Radiological findings suggesting healed tuberculosis (CXR-old-TB) were found in 18.1% of all patients, 23.9% in the IGRA -positive patients vs 16.9% in the IGRA-negative patients (OR 1.55 95% CI: 0.71–3.39, p = 0.27). Forty (40/46, 87.0%) IGRA-positive patients received isoniazid prophylaxis and 77.5% of them finished treatment. Six patients developed adverse effects of isoniazid treatment, resulting in an overall number needed to harm (NNH) of 6.7 (40/6). IGRA-non-positive patients with old TB-suggestive CXR comprised 13.4% (32/238) of all our rheumatic patients, and one of them developed pulmonary tuberculosis within one year after screening.

Conclusions

LTBI disease burden in rheumatic patients is substantial according to the estimation of CXR and IGRA screening. Correlation between CXR and IGRA is not significant in rheumatic patients, which implies their complementary roles. IGRA-non-positive patients with old TB-suggestive CXR comprise a significant portion in rheumatic patients and merit cautious follow-up by rheumatologists, tuberculosis specialists, and pulmonologists.
Correction to: Bilobalide protects against ischemia/reperfusion-induced oxidative stress and inflammatory responses via the MAPK/NF-κB pathways in rats
Authors: Li Ying , Jiang Jiliang , Tong Liangcheng , Gao Tingting , Bai Lei , Xue Qing , Xing Jianxin , Wang Qin , Lyu Haoran , Cai Min , Sun Zhongyang
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
Repository corticotropin injection attenuates collagen-induced arthritic joint structural damage and has enhanced effects in combination with etanercept
Authors: Decker Dima A. , Higgins Paul , Hayes Kyle , Bollinger Chris , Becker Patrice , Wright Dale
Published: August 2020

Background

Melanocortin receptor (MCR) agonists have anti-inflammatory and immunomodulatory properties mediated by receptors expressed on cells relevant to arthritis. Repository corticotropin injection (RCI; Acthar® Gel), an MCR agonist preparation, is approved as adjunctive therapy for rheumatoid arthritis (RA), but its mechanism of action in RA is unclear. This study explored the efficacy of RCI as monotherapy or adjunctive therapy with etanercept (ETN) in an established animal model of collagen-induced arthritis (CIA).

Methods

After induction of CIA, rats (n = 10 per group) were randomized to receive subcutaneous RCI (40, 160, or 400 U/kg twice daily) alone or in combination with ETN (10 mg/kg 3 times daily), ETN alone, or vehicle (on days 13 through 19). Inflammation was assessed via changes in paw edema. Bone damage was determined by microfocal computed tomography histopathology, and immunohistochemistry. Statistical analyses were performed using a 2-way analysis of variance (ANOVA) followed by the Newman-Keuls, Dunn’s, or Dunnett’s multiple comparisons test or a 1-way ANOVA followed by the Dunnett’s or Holm-Sidak multiple comparisons test.

Results

RCI administration resulted in dose-dependent decreases in ankle edema and histopathologic measures of inflammation, pannus formation, cartilage damage, bone resorption, and periosteal bone formation. RCI and ETN showed combined benefits on all parameters measured. Radiographic evidence of bone damage was significantly reduced in rats that received RCI alone or in combination with ETN. This reduction in bone density loss correlated with decreases in the number of CD68-positive macrophages and cathepsin K–positive osteoclasts within the lesions.

Conclusions

As monotherapy or adjunctive therapy with ETN, RCI attenuated CIA-induced joint structural damage in rats. These data support the clinical efficacy of RCI as adjunctive therapy for patients with RA.
Comprehensive study of altered proteomic landscape in proximal renal tubular epithelial cells in response to calcium oxalate monohydrate crystals
Authors: Wang Zhu , Li Ming-xing , Xu Chang-zhi , Zhang Ying , Deng Qiong , Sun Rui , Hu Qi-yi , Zhang Sheng-ping , Zhang Jian-wen , Liang Hui
Published: August 2020

Background

Calcium oxalate monohydrate (COM), the major crystalline composition of most kidney stones, induces inflammatory infiltration and injures in renal tubular cells. However, the mechanism of COM-induced toxic effects in renal tubular cells remain ambiguous. The present study aimed to investigate the potential changes in proteomic landscape of proximal renal tubular cells in response to the stimulation of COM crystals.

Methods

Clinical kidney stone samples were collected and characterized by a stone component analyzer. Three COM-enriched samples were applied to treat human proximal tubular epithelial cells HK-2. The proteomic landscape of COM-crystal treated HK-2 cells was screened by TMT-labeled quantitative proteomics analysis. The differentially expressed proteins (DEPs) were identified by pair-wise analysis. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEPs were performed. Protein interaction networks were identified by STRING database.

Results

The data of TMT-labeled quantitative proteomic analysis showed that a total of 1141 proteins were differentially expressed in HK-2 cells, of which 699 were up-regulated and 442 were down-regulated. Functional characterization by KEGG, along with GO enrichments, suggests that the DEPs are mainly involved in cellular components and cellular processes, including regulation of actin cytoskeleton, tight junction and focal adhesion. 3 high-degree hub nodes, CFL1, ACTN and MYH9 were identified by STRING analysis.

Conclusion

These results suggested that calcium oxalate crystal has a significant effect on protein expression profile in human proximal renal tubular epithelial cells.
Seed germination prediction of Salvia limbata under ecological stresses in protected areas: an artificial intelligence modeling approach
Authors: Saffariha Maryam , Jahani Ali , Potter Daniel
Published: August 2020

Background

Salvia is a large, diverse, and polymorphous genus of the family Lamiaceae, comprising about 900 ornamentals, medicinal species with almost cosmopolitan distribution in the world. The success of Salvia limbata seed germination depends on a numerous ecological factors and stresses. We aimed to analyze Salvia limbata seed germination under four ecological stresses of salinity, drought, temperature and pH, with application of artificial intelligence modeling techniques such as MLR (Multiple Linear Regression), and MLP (Multi-Layer Perceptron). The S.limbata seeds germination was tested in different combinations of abiotic conditions. Five different temperatures of 10, 15, 20, 25 and 30 °C, seven drought treatments of 0, −2, −4, −6, −8, −10 and −12 bars, eight treatments of salinity containing 0, 50, 100.150, 200, 250, 300 and 350 mM of NaCl, and six pH treatments of 4, 5, 6, 7, 8 and 9 were tested. Indeed 228 combinations were tested to determine the percentage of germination for model development.

Results

Comparing to the MLR, the MLP model represents the significant value of R2 in training (0.95), validation (0.92) and test data sets (0.93). According to the results of sensitivity analysis, the values of drought, salinity, pH and temperature are respectively known as the most significant variables influencing S. limbata seed germination. Areas with high moisture content and low salinity in the soil have a high potential to seed germination of S. limbata. Also, the temperature of 18.3 °C and pH of 7.7 are proposed for achieving the maximum number of germinated S. limbata seeds.

Conclusions

Multilayer perceptron model helps managers to determine the success of S.limbata seed planting in agricultural or natural ecosystems. The designed graphical user interface is an environmental decision support system tool for agriculture or rangeland managers to predict the success of S.limbata seed germination (percentage) in different ecological constraints of lands.
Medical student perceptions of curricular influences on their wellbeing: a qualitative study
Authors: Byrnes Christine , Ganapathy Vaishnavi Anu , Lam Melinda , Mogensen Lise , Hu Wendy
Published: August 2020

Background

Medical student mental health and wellbeing is highly topical and the subject of much research. While theoretically informed definitions of wellbeing abound, how do medical students themselves understand and perceive wellbeing? What aspects of the curriculum do they regard as affecting their wellbeing and mental health? This study explored these questions, and aimed to identify factors associated with student acceptability of wellbeing programs and interventions.

Methods

All students at an Australian undergraduate medical school (n = 619) were invited to complete a qualitative online questionnaire between 2017 and 2018 following the introduction of several wellbeing initiatives, including “Wellbeing Days” (WBD). WBD allow students to take single absence days for self-care. Open-ended questions were asked about perceptions and experience of mental health and wellbeing, and views on interventions to improve wellbeing such as WBD. Thematic analysis was conducted across all responses. Three authors developed preliminary themes, which were then refined and confirmed by all researchers. Thematic saturation was achieved within data from the 68 respondents, which included participants from all cohorts.

Results

Participants described wellbeing as positively experienced work/life balance, impacted by four factors; contact hours, peer relationships, staff relationships, and trust in how wellbeing initiatives were used. Long contact hours were deemed incompatible with self-care activities, maintaining employment, and seeking professional medical/psychological help. Peers could promote wellbeing by offering social and academic support, but also undermine wellbeing by being competitors. Degree of trust, engagement and communication with staff influenced acceptability of interventions. Participants viewed initiatives such as WBD favourably, but distrust of peers, and of staff, led to perceptions that WBD could be prone to misuse, or used for surveillance rather than support.

Conclusion

Our findings suggest that wellbeing days which allow self-care, reduction in contact hours, and peer support may promote student wellbeing, but the acceptability of any interventions is influenced by relationships between staff and students, and in particular, trust in these relationships. We suggest strategies to strengthen trust and further research to investigate the relationship between trust and perceptions of wellbeing in self and peers.
Ethical practice in my work: community health workers’ perspectives using photovoice in Wakiso district, Uganda
Authors: Musoke David , Ssemugabo Charles , Ndejjo Rawlance , Molyneux Sassy , Ekirapa-Kiracho Elizabeth
Published: August 2020

Background

Health service delivery should ensure ethical principles are observed at all levels of healthcare. Working towards this goal requires understanding the ethics-related priorities and concerns in the day-to-day activities among different health practitioners. These practitioners include community health workers (CHWs) who are involved in healthcare delivery in communities in many low-and middle-income countries such as Uganda. In this study, we used photovoice, an innovative community based participatory research method that uses photography, to examine CHWs' perspectives on ethical concerns in their work.

Methods

We explored perspectives of 10 CHWs (5 females and 5 males) on ethical dimensions of their work for 5 months using photovoice in a rural community in Wakiso district, Uganda. As part of the study, we: 1. Oriented CHWs on photovoice research and ethics; 2. Asked CHWs to take photographs of key ethical dimensions of their work; 3. Held monthly meetings to discuss and reflect on the photos; and 4. Disseminated the findings. The discussions from the monthly meetings were audio recorded, transcribed, and emerging data analysed using conventional content analysis with the help of Atlas ti version 6.0.15.

Results

CHWs were aware of and highly concerned about the need to observe ethical principles while carrying out their roles. The ethical principles CHWs were aware of and endeavoured to observe during their work were: maintaining professional integrity and abiding by ethical principles of practice; ethical responsibility in patient care; maintaining confidentiality while handling clients; respect for persons and communities; and enhancing their knowledge and skills for better practice. However, CHWs also identified challenges concerning their observance of ethical principles including: low commitment to their work due to other obligations; availability of some reference materials and guidelines in English yet majority could only read in the local language; and minimal avenues for knowledge enhancement such as trainings.

Conclusions

CHWs were aware of and keen to discuss ethical issues in their work. However, there is need to address the challenges they face so as to facilitate observing ethical principles during the course of their work in communities.
Exploring psychological safety in healthcare teams to inform the development of interventions: combining observational, survey and interview data
Authors: O’Donovan Róisín , McAuliffe Eilish
Published: August 2020

Background

Psychological safety allows healthcare professionals to take the interpersonal risks needed to engage in effective teamwork and to maintain patient safety. In order to improve psychological safety in healthcare teams, an in-depth understanding of the complex and nuanced nature of psychological safety is needed. Psychological safety concepts, including voice, silence, learning behaviour, support and familiarity, informed the current study’s investigation of psychological safety. This study aims to use a mixed-methods approach to develop an in-depth understanding of psychological safety within healthcare teams and to build on this understanding to inform the development of future interventions to improve it.

Methods

Survey, observational and interview data are triangulated in order to develop an in- depth understanding of psychological safety within four healthcare teams, working within one case study hospital. The teams taking part included one multidisciplinary and three unidisciplinary teams. Observational and survey data were collected during and immediately following team meetings. Individual interviews were conducted with 31 individuals across the four teams. Thematic analysis was used to analyse these interviews.

Results

Survey results indicated a high level of psychological safety. However, observations and interviews captured examples of silence and situations where participants felt less psychologically safe. Findings from across all three data sources are discussed in relation to voice and silence, learning, familiarity and support.

Conclusion

The results of this study provide a detailed description and in-depth understanding of psychological safety within four healthcare teams. Based on this, recommendations are made for future research and the development of interventions to improve psychological safety.
Analysis of hospitalization expenses of 610 HIV/AIDS patients in Nantong, China
Authors: Zhuang Xun , Chen Yujia , Wu Zunyou , Scott Sarah Robbins , Lu Renfei , Xu Zhengcheng , Yu Yuhui , Wang Wei , Cao Luyao , Liang Yuanyuan , Qin Gang , Zou Meiyin
Published: August 2020

Background

The goal of this study was to describe the expenses related to human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) management and care in Nantong Infectious Disease Hospital from October 2013 through June 2017.

Methods

The information of 610 HIV/AIDS inpatients were collected from the Electronic Medical Record System of the hospital. Univariate and path analysis were employed to evaluate the association between hospitalization expense and its related factors.

Results

The average hospitalization expenses per person was 5454 RMB (Renminbi, the currency of China, about $808 USD) and 23,555 RMB (about $3489 USD), respectively for HIV/AIDS patients. The average length of hospital stay was 10.0 ± 5.5 days for HIV patients and 21.7 ± 12.4 days for AIDS patients. For HIV patients, laboratory test fees constituted 37.46% of total expenses; while drug fees accounted for the largest proportion for AIDS patients. Path analysis indicated that the length of hospital stay was the most important factor affecting total expenses (total path coefficient = 0.563 for HIV patients and 0.649 for AIDS patients). Total expenses for HIV-infected females was higher than that of males (total path coefficient = 0.217), and the more complications led to higher expenses for AIDS patients.

Conclusions

Though antiretroviral therapy (ART) is provided for free in China, associated medical care, particularly hospitalizations and fees, continue to drive up the medical costs of patients living with HIV and AIDS. Understanding the factors influencing these costs are crucial for determining policies and strategies that can reduce the economic burden of HIV/AIDS patients in China.
Association of the functional ovarian reserve with serum metabolomic profiling by nuclear magnetic resonance spectroscopy: a cross-sectional study of ~ 400 women
Authors: Al Rashid Karema , Taylor Amy , Lumsden Mary Ann , Goulding Neil , Lawlor Deborah A. , Nelson Scott M.
Published: August 2020

Background

Women with diminished ovarian reserve are known to have increased cardiovascular risk, whether there is a continuous association between the ovarian reserve biomarkers; anti-Müllerian hormone (AMH), antral follicle count (AFC) and cardio-metabolic risk factors are unknown.

Methods

A cross-sectional study of 398 women intending to undergo IVF with pre-treatment early follicular AMH and AFC measurements. Serum lipids, lipoprotein subclasses and low-molecular-weight metabolites were quantified by NMR spectroscopy (155 metabolic measures). Associations were analysed using multivariable regression.

Results

Participants were mean 35.5 (SD 4.43) years old and had a median AMH of 16 pmol/l (IQR 8.8, 28.0 pmol/l) and a median AFC of 12 (IQR 7.16). AMH showed positive associations with HDL, omega-6 and polyunsaturated fatty acids and the amino acids isoleucine, leucine and tyrosine, with effects ranging from 0.11 (95%CI 0.004 to 0.21) for total lipids in small HDL to 0.16 (0.06 to 0.26) for isoleucine, for a mean difference of one SD of metabolite per one SD increment in AMH, and negatively with acetate: − 0.31(− 0.22, − 0.004) SD per 1 SD AMH. AFC was positively associated with alanine, glutamine and glycine. Results were consistent, though less precisely estimated, when restricted to those women who were preparing for treatment because of their partner’s infertility.

Conclusions

In women intending to have IVF, AMH and AFC were not associated with traditional lipid measured but were associated with a number of novel cardiovascular risk factors. Prospective studies will be required for replication, determination of causality and confirmation that ovarian reserve is impacting on metabolism rather than variation in metabolism is influencing ovarian reserve.
Intentional Carbofuran poisoning in 7 dogs
Authors: Pivariu Dalma , Oros Adrian-Nechita , Tabaran Flaviu , Gal Adrian , Martonos Cristian , Nagy Andras-Laszlo
Published: August 2020

Background

Carbofuran is a widely used broad-spectrum pesticide that, despite strict regulation and being banned for more than a decade, is still encountered in cases of intentional poisoning in dogs and wildlife. The objective of the study was to provide a complete and detailed description of the pathological, histological and toxicological findings of 7 cases of intentional carbofuran poisoning in dogs.

Results

In this retrospective study, 7 cases of carbofuran intoxication recorded from July 2015 to June 2017 were analyzed. Following complete history recording, all cases were examined by complete necropsy and histopathology. Carbofuran intoxication was confirmed in all cases by gas chromatography. The postmortem examination revealed extensive hemorrhaging and congestion located mainly within the respiratory, nervous and cardiovascular systems, accompanied by degeneration and necrosis within the lungs, heart, and kidneys.

Conclusions

Although carbamates have been banned in the European Union, carbamate poisoning is still frequently encountered, especially in wild animals. This paper will contribute to a better understanding of the occurrence and pathogenesis of acute carbofuran exposure in dogs and contribute some peculiar pathological features of this type of poisoning to the current literature.
Integrative genomics analysis of various omics data and networks identify risk genes and variants vulnerable to childhood-onset asthma
Authors: Ma Xiuqing , Wang Peilan , Xu Guobing , Yu Fang , Ma Yunlong
Published: August 2020

Background

Childhood-onset asthma is highly affected by genetic components. In recent years, many genome-wide association studies (GWAS) have reported a large group of genetic variants and susceptible genes associated with asthma-related phenotypes including childhood-onset asthma. However, the regulatory mechanisms of these genetic variants for childhood-onset asthma susceptibility remain largely unknown.

Methods

In the current investigation, we conducted a two-stage designed Sherlock-based integrative genomics analysis to explore the cis- and/or trans-regulatory effects of genome-wide SNPs on gene expression as well as childhood-onset asthma risk through incorporating a large-scale GWAS data (N = 314,633) and two independent expression quantitative trait loci (eQTL) datasets (N = 1890). Furthermore, we applied various bioinformatics analyses, including MAGMA gene-based analysis, pathway enrichment analysis, drug/disease-based enrichment analysis, computer-based permutation analysis, PPI network analysis, gene co-expression analysis and differential gene expression analysis, to prioritize susceptible genes associated with childhood-onset asthma.

Results

Based on comprehensive genomics analyses, we found 31 genes with multiple eSNPs to be convincing candidates for childhood-onset asthma risk; such as,PSMB9(cis-rs4148882 and cis-rs2071534) andTAP2(cis-rs9267798, cis-rs4148882, cis-rs241456, and trans-10,447,456). These 31 genes were functionally interacted with each other in our PPI network analysis. Our pathway enrichment analysis showed that numerous KEGG pathways including antigen processing and presentation, type I diabetes mellitus, and asthma were significantly enriched to involve in childhood-onset asthma risk. The co-expression patterns among 31 genes were remarkably altered according to asthma status, and 25 of 31 genes (25/31 = 80.65%) showed significantly or suggestively differential expression between asthma group and control group.

Conclusions

We provide strong evidence to highlight 31 candidate genes for childhood-onset asthma risk, and offer a new insight into the genetic pathogenesis of childhood-onset asthma.
Co-presence of human papillomaviruses and Epstein–Barr virus is linked with advanced tumor stage: a tissue microarray study in head and neck cancer patients
Authors: Al-Thawadi Hamda , Gupta Ishita , Jabeen Ayesha , Skenderi Faruk , Aboulkassim Tahar , Yasmeen Amber , Malki Mohammed I. , Batist Gerald , Vranic Semir , Al Moustafa Ala-Eddin
Published: August 2020

Background

Human papillomaviruses (HPVs) and Epstein–Barr virus (EBV), known oncoviruses, can be co-present and cooperate in the initiation and/or progression of human carcinomas, including head and neck. Based on this fact, we recently reported the prevalence of both HPVs and EBV in cervical and breast cancers.

Methods

We herein explore for the first time the co-prevalence of high-risk HPVs and EBV in 98 head and neck (HN) squamous cell carcinoma (SCC) tissues from Bosnian patients using polymerase chain reaction (PCR) and immunohistochemistry (IHC) analysis, as well as tissue microarray methodology.

Results

The majority of these cancer tissue cases were from the oral cavity (68%). We found that high-risk HPVs and EBV are co-present in 34.7% of the SCC samples; with a significant correlation between the various HPV types and EBV co-incidence (p = 0.03). Our data showed that 30.8% of oral SCCs are positive for E6 oncoprotein of high-risk HPVs and 44.6% are positive for LMP1 of EBV. The most commonly expressed HPVs in our HNSCC samples include HPV types 16, 18, 45 and 58. Additionally, 37.5% of oral SCCs are positive for both HPVs and EBV, with statistically significant association between high-risk HPV types and EBV (p < 0.05). More importantly, our data revealed that the co-presence of HPV and EBV is strongly correlated with advanced tumor stage (p = 0.035).

Conclusion

In this study we show that HPV and EBV oncoviruses are co-present in HNSCC, particularly in oral cancer, where they can cooperate in the initiation and/or progression of this cancer. Thus, further studies are necessary to elucidate the mechanism of this cooperation.
NONO promotes hepatocellular carcinoma progression by enhancing fatty acids biosynthesis through interacting with ACLY mRNA
Authors: Ding Hongda , Liu Junpeng , Wang Caibin , Su Yang
Published: August 2020

Background

Dysregulation of fatty acid (FA) metabolism is involved in hepatocellular carcinoma (HCC) development. Non-POU domain-containing octamer binding protein (NONO), known as the component of nuclear paraspeckles, has recently been found to promote HCC progression. In this study, we investigated the functions of NONO in regulating de novo FA synthesis and its underling mechanism during HCC development.

Methods

The roles of NONO in HCC development by applying gene function loss analysis in HCC cells were detected by quantitative real-time polymerase chain reaction, cell proliferation, and cell invasion assays. The underlying mechanism of NONO in HCC development was examined by western blotting, subcellular fractionation, RNA-binding protein immunoprecipitation-sequencing, chromatin immunoprecipitation, co-immunoprecipitation and mass spectrometry. The effect of NONO on tumorigenesis in vivo was performed with a subcutaneous xenograft mouse model of HCC.

Results

NONO promotes HCC progression by interacting with and increasing ATP-citrate lyase (ACLY) mRNA to enhance FA biosynthesis. Furthermore, NONO promotes ACLY expression through enhancing nuclear ACLY mRNA stability in Diethylnitrosamine-stimulated HCC cells, not related to nuclear paraspeckles. Moreover, we find that NONO/SFPQ (Splicing factor proline and glutamine rich) heterodimer is essential for NONO interacting with ACLY mRNA in DEN stimulated HCC cells. In addition, NONO, Insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) and ACLY expressions contribute HCC development in mice and are related to poor survival.

Conclusion

NONO promotes HCC progression by enhancing FA biosynthesis through interacting with ACLY mRNA and provide a novel potential target for HCC therapy.
Genetic analysis of the orthologous crt and mdr1 genes in Plasmodium malariae from Thailand and Myanmar
Authors: Pimpat Yupawadee , Saralamba Naowarat , Boonyuen Usa , Pukrittayakamee Sasithon , Nosten Francois , Smithuis Frank , Day Nicholas P. J. , Dondorp Arjen M. , Imwong Mallika
Published: August 2020

Background

Plasmodium malariae is a widely spread but neglected human malaria parasite, which causes chronic infections. Studies on genetic polymorphisms of anti-malarial drug target genes in P. malariae are limited. Previous reports have shown polymorphisms in the P. malariae dihydrofolate reductase gene associated with pyrimethamine resistance and linked to pyrimethamine drug pressure. This study investigated polymorphisms of the P. malariae homologous genes, chloroquine resistant transporter and multidrug resistant 1, associated with chloroquine and mefloquine resistance in Plasmodium falciparum.

Methods

The orthologous P. malariae crt and mdr1 genes were studied in 95 patients with P. malariae infection between 2002 and 2016 from Thailand (N = 51) and Myanmar (N = 44). Gene sequences were analysed using BioEdit, MEGA7, and DnaSP programs. Mutations and gene amplifications were compared with P. falciparum and Plasmodium vivax orthologous genes. Protein topology models derived from the observed pmcrt and pmmdr1 haplotypes were constructed and analysed using Phyre2, SWISS MODEL and Discovery Studio Visualization V 17.2.

Results

Two non-synonymous mutations were observed in exon 2 (H53P, 40%) and exon 8 (E278D, 44%) of pmcrt. The topology model indicated that H53P and E278D were located outside of the transmembrane domain and were unlikely to affect protein function. Pmmdr1 was more diverse than pmcrt, with 10 non-synonymous and 3 synonymous mutations observed. Non-synonymous mutations were located in the parasite cytoplasmic site, transmembrane 11 and nucleotide binding domains 1 and 2. Polymorphisms conferring amino acid changes in the transmembrane and nucleotide binding domains were predicted to have some effect on PmMDR1 conformation, but were unlikely to affect protein function. All P. malariae parasites in this study contained a single copy of the mdr1 gene.

Conclusions

The observed polymorphisms in pmcrt and pmmdr1 genes are unlikely to affect protein function and unlikely related to chloroquine drug pressure. Similarly, the absence of pmmdr1 copy number variation suggests limited mefloquine drug pressure on the P. malariae parasite population, despite its long time use in Thailand for the treatment of falciparum malaria.
TBL2 methylation is associated with hyper-low-density lipoprotein cholesterolemia: a case-control study
Authors: Li Yang , Liu Shuai , Wang Yong-Tao , Min Han , Adi Dilare , Li Xiao-Mei , Yang Yi-Ning , Fu Zhen yan , Ma Yi-Tong
Published: August 2020

Background

HMGCR, SCAP, SREBF1, SREBF2 and TBL2 are well-known genes that are involved in the process of lipid metabolism. However, it is not known whether epigenetic changes of these genes are associated with lipid metabolism. In this study, the methylation levels of the HMGCR, SCAP, SREBF1, SREBF2 and TBL2 genes were analyzed between samples from a hyper-low-density lipoprotein cholesterolemia (hyper-LDL) group and a control group to examine the association between the methylation levels of these genes and the risk of hyper-LDL.

Methods

In this study, a case-control approach was used to explore the association between DNA methylation and hyper-LDL. The DNA methylation levels of HMGCR, SCAP, SREBF1, SREBF2 and TBL2 genes and 231 CpG sites in the promoter regions of these genes were measured in 98 hyper-LDL participants and 89 participants without hypo-LDL.

Results

Compared with participants without hyper-LDL, patients with hyper-LDL TBL2 gene had lower methylation levels (11.93 vs. 12.02, P = 0.004). The methylation haplotypes with significant abundance in the TBL2 gene are tcttttttttt (P = 0.034), ctttttttcct (P = 0.025), ctctttctttt (P = 0.040), ccttttttttt (P = 0.028), and tctttttttttttttt.

Conclusion

The study demonstrates that participants with hyper-LDL have lower methylation of TBL2. The results suggest that DNA methylation of TBL2 can decrease the risk for hyper-LDL in humans.
Brain region–specific lipid alterations in the PLB4 hBACE1 knock-in mouse model of Alzheimer’s disease
Authors: Dey Madhurima , Gunn-Moore Frank J. , Platt Bettina , Smith Terry K.
Published: August 2020

Background

Lipid dysregulation is associated with several key characteristics of Alzheimer’s disease (AD), including amyloid-β and tau neuropathology, neurodegeneration, glucose hypometabolism, as well as synaptic and mitochondrial dysfunction. The β-site amyloid precursor protein cleavage enzyme 1 (BACE1) is associated with increased amyloidogenesis, and has been affiliated with diabetes via its role in metabolic regulation.

Methods

The research presented herein investigates the role of hBACE1 in lipid metabolism and whether specific brain regions show increased vulnerability to lipid dysregulation. By utilising advanced mass spectrometry techniques, a comprehensive, quantitative lipidomics analysis was performed to investigate the phospholipid, sterol, and fatty acid profiles of the brain from the well-known PLB4 hBACE1 knock-in mouse model of AD, which also shows a diabetic phenotype, to provide insight into regional alterations in lipid metabolism.

Results

Results show extensive region – specific lipid alterations in the PLB4 brain compared to the wild-type, with decreases in the phosphatidylethanolamine content of the cortex and triacylglycerol content of the hippocampus and hypothalamus, but increases in the phosphatidylcholine, phosphatidylinositol, and diacylglycerol content of the hippocampus. Several sterol and fatty acids were also specifically decreased in the PLB4 hippocampus.

Conclusion

Collectively, the lipid alterations observed in the PLB4 hBACE1 knock-in AD mouse model highlights the regional vulnerability of the brain, in particular the hippocampus and hypothalamus, to lipid dysregulation, hence supports the premise that metabolic abnormalities have a central role in both AD and diabetes.
Social network support and harm reduction activities in a peer researcher-led pilot study, British Columbia, Canada
Authors: Elkhalifa Sulaf , Jozaghi Ehsan , Marsh Samona , Thomson Erica , Gregg Delilah , Buxton Jane , Jolly Ann
Published: August 2020

Background

People who smoke drugs (PWSD) are at high risk of both infectious disease and overdose. Harm reduction activities organized by their peers in the community can reduce risk by providing education, safer smoking supplies, and facilitate access to other services. Peers also provide a network of people who provide social support to PWSD which may reinforce harm reducing behaviors. We evaluated the numbers of supportive network members and the relationships between received support and participants’ harm-reducing activities.

Methods

Initial peer-researchers with past or current lived drug use experience were employed from communities in Abbotsford and Vancouver to interview ten friends from their social networks who use illegal drugs mainly through smoking. Contacts completed a questionnaire about people in their own harm reduction networks and their relationships with each other. We categorized social support into informational, emotional, and tangible aspects, and harm reduction into being trained in the use of, or carrying naloxone, assisting peers with overdoses, using brass screens to smoke, obtaining pipes from service organizations and being trained in CPR.

Results

Fifteen initial peer researchers interviewed 149 participants who provided information on up to 10 people who were friends or contacts and the relationships between them. People who smoked drugs in public were 1.46 (95% CI, 1.13-1.78) more likely to assist others with possible overdoses if they received tangible support; women who received tangible support were 1.24 (95% CI; 1.02-1.45) more likely to carry and be trained in the use of naloxone. There was no relationship between number of supportive network members and harm reduction behaviors.

Conclusions

In this pilot study, PWSD who received tangible support were more likely to assist peers in possible overdoses and be trained in the use of and/or carry naloxone, than those who did not receive tangible support. Future work on the social relationships of PWSD may prove valuable in the search for credible and effective interventions.
ANDC: an early warning score to predict mortality risk for patients with Coronavirus Disease 2019
Authors: Weng Zhihong , Chen Qiaosen , Li Sumeng , Li Huadong , Zhang Qian , Lu Sihong , Wu Li , Xiong Leiqun , Mi Bobin , Liu Di , Lu Mengji , Yang Dongliang , Jiang Hongbo , Zheng Shaoping , Zheng Xin
Published: August 2020

Background

Patients with severe Coronavirus Disease 2019 (COVID-19) will progress rapidly to acute respiratory failure or death. We aimed to develop a quantitative tool for early predicting mortality risk of patients with COVID-19.

Methods

301 patients with confirmed COVID-19 admitted to Main District and Tumor Center of the Union Hospital of Huazhong University of Science and Technology (Wuhan, China) between January 1, 2020 to February 15, 2020 were enrolled in this retrospective two-centers study. Data on patient demographic characteristics, laboratory findings and clinical outcomes was analyzed. A nomogram was constructed to predict the death probability of COVID-19 patients.

Results

Age, neutrophil-to-lymphocyte ratio, d-dimer and C-reactive protein obtained on admission were identified as predictors of mortality for COVID-19 patients by LASSO. The nomogram demonstrated good calibration and discrimination with the area under the curve (AUC) of 0.921 and 0.975 for the derivation and validation cohort, respectively. An integrated score (named ANDC) with its corresponding death probability was derived. Using ANDC cut-off values of 59 and 101, COVID-19 patients were classified into three subgroups. The death probability of low risk group (ANDC < 59) was less than 5%, moderate risk group (59 ≤ ANDC ≤ 101) was 5% to 50%, and high risk group (ANDC > 101) was more than 50%, respectively.

Conclusion

The prognostic nomogram exhibited good discrimination power in early identification of COVID-19 patients with high mortality risk, and ANDC score may help physicians to optimize patient stratification management.
Localized cytokine responses to total knee arthroplasty and total knee revision complications
Authors: Prince Nicole , Penatzer Julia A. , Dietz Matthew J. , Boyd Jonathan W.
Published: August 2020

Background

The study of localized immune-related factors has proven beneficial for a variety of conditions, and one area of interest in the field of orthopaedics is the impact of implants and localized infections on immune response. Several cytokines have shown increased systemic concentrations (in serum/plasma) in response to implants and infection, but tissue-level cytokines have not been investigated as thoroughly.

Methods

This exploratory study investigated tissue-level cytokines in a cohort of patients (N = 17) in response to total knee arthroplasty and total knee revision to better understand the immune response to implants and localized infection (e.g., prosthetic joint infection). The overall goal of this study was to provide insight into the localized cytokine response of tissues and identify tissue-level markers specific to inflammation caused by implants vs. inflammation caused by infection. Tissues were collected across several anatomical locations and assayed with a panel of 20 human inflammatory cytokines to understand spatial differences in cytokine levels.

Results

In this study, six cytokines were elevated in implanted joints, as compared to native joints: IL-10, IL-12p70, IL-13, IL-17A, IL-4, and TNF-α (p < 0.05). Seven cytokines showed infection-dependent increases in localized tissues: IL-1α, IL-1β, IL-6, IL-8, MCP-1, MIP-1α, and MIP-1β (p < 0.05).

Conclusions

This study demonstrated that differences exist in tissue-level cytokines in response to presence of implant, and some cytokines were specifically elevated for infection; these responses may be informative of overall tissue health. These results highlight the utility of investigating localized cytokine concentrations to offer novel insights for total knee arthroplasty and total knee revision procedures, as well as their complications. Ultimately, this information could provide additional, quantitative measurements of tissue to aid clinical decision making and patient treatment options.
Correction to: Role of hepatitis B virus X protein in regulating LIM and SH3 protein 1 (LASP-1) expression to mediate proliferation and migration of hepatoma cells
Authors: Tang Renxian , Kong Fanyun , Hu Lina , You Hongjuan , Zhang Peng , Du Weidong , Zheng Kuiyang
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
Low-arginine and low-protein diets induce hepatic lipid accumulation through different mechanisms in growing rats
Authors: Otani Lila , Nishi Hiroki , Koyama Ayaka , Akasaka Yuta , Taguchi Yusuke , Toyoshima Yuka , Yamanaka Daisuke , Hakuno Fumihiko , Jia Huijuan , Takahashi Shin-Ichiro , Kato Hisanori
Published: August 2020

Background

Dietary protein deficiency and amino acid imbalance cause hepatic fat accumulation. We previously demonstrated that only arginine deficiency or total amino acid deficiency in a diet caused significant hepatic triglyceride (TG) accumulation in young Wistar rats. In this study, we explored the mechanisms of fatty liver formation in these models.

Methods

We fed 6-week-old male Wistar rats a control diet (containing an amino acid mixture equivalent to 15% protein), a low-total-amino acid diet (equivalent to 5% protein; 5PAA), and a low-arginine diet (only the arginine content is as low as that of the 5PAA diet) for 2 weeks.

Results

Much greater hepatic TG accumulation was observed in the low-arginine group than in the low-total-amino acid group. The lipid consumption rate and fatty acid uptake in the liver did not significantly differ between the groups. In contrast, the low-total-amino acid diet potentiated insulin sensitivity and related signaling in the liver and enhanced de novo lipogenesis. The low-arginine diet also inhibited hepatic very-low-density lipoprotein secretion without affecting hepatic insulin signaling and lipogenesis.

Conclusions

Although the arginine content of the low-arginine diet was as low as that of the low-total-amino acid diet, the two diets caused fatty liver via completely different mechanisms. Enhanced lipogenesis was the primary cause of a low-protein diet-induced fatty liver, whereas lower very-low-density lipoprotein secretion caused low-arginine diet-induced fatty liver.
Aquaporin 7 involved in GINSENOSIDE-RB1-mediated anti-obesity via peroxisome proliferator-activated receptor gamma pathway
Authors: Guo Rong , Wang Lei , Zeng Xianqin , Liu Minghao , Zhou Peng , Lu Huixia , Lin Huili , Dong Mei
Published: August 2020

Background

Obesity, characterized by the excessive accumulation of triglycerides in adipocytes and their decreased excretion from adipocytes, is closely related to various health problems. Ginsenoside Rb1 (Rb1), the most active component of the traditional Chinese medicine ginseng, has been reported to have positive effects on lipid metabolism. The aim of the present study was to determine the protective effects of Rb1 on glycolipid metabolism under obesity conditions and its mechanisms and to reveal the signaling pathways involved.

Methods

In our study, male C57BL/6 mice with obesity induced by a high-fat diet (HFD) and mature 3 T3-L1 adipocytes were used to investigate the role of Rb1 in lipid accumulation and explore its possible molecular mechanism in vivo and in vitro, respectively.

Results

Rb1 reduced the body weight, fat mass, adipocytes size and serum free fatty acid (FFA) concentration of obese mice. In differentiated 3 T3-L1 adipocytes, Rb1 reduced the accumulation of lipid droplets and stimulated output of triglycerides. Additionally, the expression of peroxisome proliferator-activated receptor gamma (PPARγ), phosphorylated PPARγ (Ser112) and aquaporin 7 (AQP7) was upregulated in adipocytes and adipose tissues upon Rb1 treatment. However, intervention of GW9662, PPARγ antagonist, attenuated Rb1-mediated effects on glycolipid metabolism and AQP7 levels.

Conclusions

These data indicated that Rb1 reduced body weight and improved glycolipid metabolism by upregulating PPARγ and AQP7 protein levels. Our study indicated a potential role for Rb1 in the prevention and treatment of obesity.