bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxia downregulated miR-4521 suppresses gastric carcinoma progression through regulation of IGF2 and FOXM1
Authors: Xing Shan , Tian Zhi , Zheng Wenying , Yang Wenjuan , Du Nan , Gu Yixue , Yin Jiang , Liu Hao , Jia Xiaoting , Huang Donglan , Liu Wanli , Deng Min
Published: January 2021

Background

MicroRNAs (miRNAs) show considerable promise as therapeutic agents to improve tumor treatment, as they have been revealed as crucial modulators in tumor progression. However, our understanding of their roles in gastric carcinoma (GC) metastasis is limited. Here, we aimed to identify novel miRNAs involved in GC metastasis and explored their regulatory mechanisms and therapeutic significance in GC.

Methods

The microRNA expression profiles of GC tumors at different stages and at different metastasis statuses were compared respectively using the stomach adenocarcinoma (STAD) miRNASeq dataset in TCGA. Using the above method, miR-4521 was picked out for further study. miR-4521 expression in GC tissues was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). Highly and lowly invasive cell sublines were established using a repetitive transwell assay. Gain-of-function and loss-of-function analyses were performed to investigate the functions of miR-4521 and its upstream and downstream regulatory mechanisms in vitro and in vivo. Moreover, we investigated the therapeutic role of miR-4521 in a mouse xenograft model.

Results

In this study, we found that miR-4521 expression was downregulated in GC tissues compared with adjacent normal tissues and that its downregulation was positively correlated with advanced clinical stage, metastasis status and poor patient prognosis. Functional experiments revealed that miR-4521 inhibited GC cell invasion and metastasis in vitro and in vivo. Further studies showed that hypoxia repressed miR-4521 expression via inducing ETS1 and miR-4521 mitigated hypoxia-mediated metastasis, while miR-4521 inactivated the AKT/GSK3β/Snai1 pathway by targeting IGF2 and FOXM1, thereby inhibiting the epithelial-mesenchymal transition (EMT) process and metastasis. In addition, we demonstrated that therapeutic delivery of synthetic miR-4521 suppressed gastric carcinoma progression in vivo.

Conclusions

Our results suggest an important role for miR-4521 in regulating GC metastasis and hypoxic response of tumor cells as well as the therapeutic significance of this miRNA in GC.
Association between lipoprotein cholesterol and future cardiovascular disease and mortality in older adults: a Korean nationwide longitudinal study
Authors: Kim Seung Hee , Son Ki Young
Published: January 2021

Background

Dyslipidemia is considered an independent health risk factor of cardiovascular disease (CVD), a leading cause of mortality in older adults. Despite its importance, there have been few reports on the association between lipoprotein cholesterol and future CVD and cardiovascular (CV) mortality among elderly Asians aged ≥ 65 years. This study investigated the association between lipoprotein cholesterol and future CVD and CV mortality in an elderly Korean population using a large nationwide sample.

Methods

From the cohort database of the Korean National Health Insurance Service, 62,604 adults aged ≥ 65 years (32,584 men and 30,020 women) were included. High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were categorized by quartiles. Cox proportional hazard models and linear regression analyses were used to assess the association between the quartiles of lipoprotein cholesterol and future CV events or mortality.

Results

The mean follow-up period was 3.3 years. The incidence rates of ischemic heart disease and ischemic brain disease were 0.97 and 0.61 per 1,000 person-years, respectively, and the mortality rates from these diseases were 0.22 and 0.34 per 1,000 person-years, respectively. In a completely adjusted model, high HDL-C and LDL-C levels were not associated with total CV events and CVD mortality. However, high LDL-C levels were significantly associated with a lower incidence of ischemic brain disease. Furthermore, diabetic patients with high LDL-C levels were more likely to have higher CV mortality, whereas non-smokers with high LDL-C levels were less likely to be at risk of CV events.

Conclusions

Neither high LDL-C nor HDL-C levels were significantly associated with future CV mortality in older adults aged ≥ 65 years. High LDL-C levels do not seem to be a risk factor for CVD in elderly individuals, and further studies are required.
Contribution of sarcomere gene mutations to left atrial function in patients with hypertrophic cardiomyopathy
Authors: Chung Hyemoon , Kim Yoonjung , Park Chul Hwan , Kim In-Soo , Kim Jong-Youn , Min Pil-Ki , Yoon Young Won , Kim Tae Hoon , Lee Byoung Kwon , Hong Bum-Kee , Rim Se-Joong , Kwon Hyuck Moon , Lee Kyung-A , Choi Eui-Young
Published: January 2021

Background

Left atrial (LA) enlargement and dysfunction are related to clinical course in patients with hypertrophic cardiomyopathy (HCM). We aimed to investigate genetic contribution to LA structural and functional remodeling.

Methods

Two hundred twelve patients were consecutively enrolled, and echocardiography and extensive genetic analysis were performed. Cardiac magnetic resonance (CMR) was performed in 135 patients. Echocardiography was also performed in controls (n = 30).

Results

Patients with HCM had lower late-diastolic mitral annular velocity (a’) and higher LA volume index (LAVI) than controls. Patients with pathogenic or likely pathogenic sarcomere gene mutations (PSM, n = 67, 32%) had higher LAVI and lower CMR-derived LA total emptying fraction (37.0 ± 18.5 vs. 44.2 ± 12.4%, p = 0.025). In patients without AF (n = 187), the PSM had lower a’ (6.9 ± 2.0 vs. 7.8 ± 1.9 cm/s, p = 0.004) than others. The PSM had higher prevalence and amount of late gadolinium enhancement (LGE) in the left ventricle (LV). In multivariate analysis, PSM was significantly related to lower a’ independent of E/e’, LV mass index, and LAVI. However, the relation significantly attenuated after adjustment for the extent of LGE in the LV, suggesting common myopathy in the LV and LA. In addition, PSM was significantly related to lower LA total emptying fraction independent of age, E/e’, s’, LV ejection fraction, LV myocardial global longitudinal strain and %LGE mass.

Conclusions

PSM was related to LA dysfunction independent of LV filling pressure and LAVI, suggesting its contribution to atrial myopathy in HCM.
Hyaluronic acid modified covalent organic polymers for efficient targeted and oxygen-evolved phototherapy
Authors: Shu Fangpeng , Yang Taowei , Zhang Xuefeng , Chen Wenbin , Wu Kaihui , Luo Junqi , Zhou Xumin , Liu Guochang , Lu Jianming , Mao Xiangming
Published: January 2021

The integration of multiple functions with organic polymers-based nanoagent holds great potential to potentiate its therapeutic efficacy, but still remains challenges. In the present study, we design and prepare an organic nanoagent with oxygen-evolved and targeted ability for improved phototherapeutic efficacy. The iron ions doped poly diaminopyridine (FeD) is prepared by oxidize polymerization and modified with hyaluronic acid (HA). The obtained FeDH appears uniform morphology and size. Its excellent colloidal stability and biocompatibility are demonstrated. Specifically, the FeDH exhibits catalase-like activity in the presence of hydrogen peroxide. After loading of photosensitizer indocyanine green (ICG), the ICG@FeDH not only demonstrates favorable photothermal effect, but also shows improved generation ability of reactive oxygen species (ROS) under near-infrared laser irradiation. Moreover, the targeted uptake of ICG@FeDH in tumor cells is directly observed. As consequence, the superior phototherapeutic efficacy of the targeted ICG@FeDH over non-targeted counterparts is also confirmed in vitro and in vivo. Hence, the results demonstrate that the developed nanoagent rationally integrates the targeted ability, oxygen-evolved capacity and combined therapy in one system, offering a new paradigm of polymer-based nanomedicine for tumor therapy.
Hydrophobic insertion-based engineering of tumor cell-derived exosomes for SPECT/NIRF imaging of colon cancer
Authors: Jing Boping , Gai Yongkang , Qian Ruijie , Liu Zhen , Zhu Ziyang , Gao Yu , Lan Xiaoli , An Rui
Published: January 2021

Background

Tumor cell-derived exosomes (TEx) have emerged as promising nanocarriers for drug delivery. Noninvasive multimodality imaging for tracing the in vivo trafficking of TEx may accelerate their clinical translation. In this study, we developed a TEx-based nanoprobe via hydrophobic insertion mechanism and evaluated its performance in dual single-photon emission computed tomography (SPECT) and near-infrared fluorescence (NIRF) imaging of colon cancer.

Results

TEx were successfully isolated from HCT116 supernatants, and their membrane vesicle structure was confirmed by TEM. The average hydrodynamic diameter and zeta potential of TEx were 110.87 ± 4.61 nm and –9.20 ± 0.41 mV, respectively. Confocal microscopy and flow cytometry findings confirmed the high tumor binding ability of TEx. The uptake rate of 99mTc-TEx-Cy7 by HCT116 cells increased over time, reaching 14.07 ± 1.31% at 6 h of co-incubation. NIRF and SPECT imaging indicated that the most appropriate imaging time was 18 h after the injection of 99mTc-TEx-Cy7 when the tumor uptake (1.46% ± 0.06% ID/g) and tumor-to-muscle ratio (8.22 ± 0.65) peaked. Compared with radiolabeled adipose stem cell derived exosomes (99mTc-AEx-Cy7), 99mTc-TEx-Cy7 exhibited a significantly higher tumor accumulation in tumor-bearing mice.

Conclusion

Hydrophobic insertion-based engineering of TEx may represent a promising approach to develop and label exosomes for use as nanoprobes in dual SPECT/NIRF imaging. Our findings confirmed that TEx has a higher tumor-targeting ability than AEx and highlight the potential usefulness of exosomes in biomedical applications.
Density of surface charge is a more predictive factor of the toxicity of cationic carbon nanoparticles than zeta potential
Authors: Weiss Maud , Fan Jiahui , Claudel Mickaël , Sonntag Thomas , Didier Pascal , Ronzani Carole , Lebeau Luc , Pons Françoise
Published: January 2021

Background

A positive surface charge has been largely associated with nanoparticle (NP) toxicity. However, by screening a carbon NP library in macrophages, we found that a cationic charge does not systematically translate into toxicity. To get deeper insight into this, we carried out a comprehensive study on 5 cationic carbon NPs (NP2 to NP6) exhibiting a similar zeta (ζ) potential value (from + 20.6 to + 26.9 mV) but displaying an increasing surface charge density (electrokinetic charge, Qek from 0.23 to 4.39 µmol/g). An anionic and non-cytotoxic NP (NP1, ζ-potential = − 38.5 mV) was used as control.

Results

The 5 cationic NPs induced high (NP6 and NP5, Qek of 2.95 and 4.39 µmol/g, respectively), little (NP3 and NP4, Qek of 0.78 and 1.35 µmol/g, respectively) or no (NP2, Qek of 0.23 µmol/g) viability loss in THP-1-derived macrophages exposed for 24 h to escalating NP dose (3 to 200 µg/mL). A similar toxicity trend was observed in airway epithelial cells (A549 and Calu-3), with less viability loss than in THP-1 cells. NP3, NP5 and NP6 were taken up by THP-1 cells at 4 h, whereas NP1, NP2 and NP4 were not. Among the 6 NPs, only NP5 and NP6 with the highest surface charge density induced significant oxidative stress, IL-8 release, mitochondrial dysfunction and loss in lysosomal integrity in THP-1 cells. As well, in mice, NP5 and NP6 only induced airway inflammation. NP5 also increased allergen-induced immune response, airway inflammation and mucus production.

Conclusions

Thus, this study clearly reveals that the surface charge density of a cationic carbon NP rather than the absolute value of its ζ-potential is a relevant descriptor of its in vitro and in vivo toxicity.
Peer-assisted injection as a harm reduction measure in a supervised consumption service: a qualitative study of client experiences
Authors: Pijl Em , Oosterbroek Tracy , Motz Takara , Mason Erin , Hamilton Keltie
Published: January 2021

Background

Peer assistance is an emerging area of study in injection drug use. When Canada’s first supervised consumption site (SCS) opened in 2003 in Vancouver, Canada, clients were prohibited from injecting their peers; only recently has this practise been introduced as a harm reduction measure at these sites. In 2018, Health Canada granted federal exemption to allow peer-assisted injection at certain SCS sites, under the Controlled Drugs and Substances Act. Literature pertaining to peer-assisted injection addresses several topics: interpersonal relationships between the injection provider and recipient; the role of pragmatism; trust and expertise; and gender relations.

Methods

In this qualitative study, participants (n = 16) were recruited to be interviewed about their experiences in a peer-assisted injection program (PAIP) at one SCS regulated by Health Canada. Interview data were transcribed and thematically analyzed. Quantitative administrative data were used to provide context and to describe the study population, comprised of people in the PAIP (n = 248).

Results

PAIP clients made up 17.4% of all SCS clients. PAIP clients were more likely to be female and Indigenous. Injection providers expressed being moved by compassion to help others inject. While their desire to assist was pragmatic, they felt a significant burden of responsibility for the outcomes. Other prominent factors related to the injection provider-recipient relationship were social connection, trust, safety, social capital, and reciprocity. Participants also made suggestions for improving the PAIP which included adding more inhalation rooms so that if someone was unable to inject they could smoke in a safe place instead. Additionally, being required by law to divide drugs outside of the SCS, prior to preparing and using in the site, created unsafe conditions for clients.

Conclusions

Regular use of the SCS, and access to its resources, enabled participants to lower their risk through smoking and to practice lower-risk injections. At the federal level, there is considerable room to advocate for allowing clients to divide drugs safely within the SCS, and to increase capacity for safer alternatives such as inhalation.
Collaborative research and knowledge translation on road crashes in Burkina Faso: the police perspective 18 months on
Authors: Dagenais Christian , Proulx Michelle , Mc Sween-Cadieux Esther , Nikiema Aude , Bonnet Emmanuel , Ridde Valéry , Somé Paul-André
Published: January 2021

In this commentary, we present a follow-up of two articles published in 2017 and 2018 about road traffic crashes, which is an important public health issue in Africa and Burkina Faso. The first article reported on a research project, conducted in partnership with local actors involved in road safety, carried out in Ouagadougou in 2015. Its aim was to test the effectiveness, acceptability, and capacity of a surveillance system to assess the number of road traffic crashes and their consequences on the health of crash victims. Several knowledge translation activities were carried out to maximize its impact and were reported in the 2018 article published in HRPS: monthly reports presenting the research data, large-format printed maps distributed to the city’s police stations, and a deliberative workshop held at the end of the research project. The present commentary presents our efforts to deepen our understanding of the impacts of the knowledge translation strategy, based on follow-up interviews, 18 months after the workshop, with the heads of the road traffic crash units in Ouagadougou police stations (n = 5). Several benefits were reported by respondents. Their involvement in the process prompted them to broaden their knowledge of other ways of dealing with the issue of road crashes. This led them, sometimes with their colleagues, to intervene differently: more rapid response at collision sites, increased surveillance of dangerous intersections, user awareness-raising on the importance of the highway code, etc. However, sustaining these actions over the longer term has proven difficult. Several lessons were derived from this experience, regarding the importance of producing useful and locally applicable research data, of ensuring the acceptability of the technologies used for data collection, of using collaborative approaches in research and knowledge translation, of ensuring the visibility of actions undertaken by actors in the field, and of involving decision-makers in the research process to maximize its impacts.
Connecting the αα-hubs: same fold, disordered ligands, new functions
Authors: Staby Lasse , Bugge Katrine , Falbe-Hansen Rasmus Greve , Salladini Edoardo , Skriver Karen , Kragelund Birthe B.
Published: January 2021

Background

Signal fidelity depends on protein–protein interaction–‘hubs’ integrating cues from large interactomes. Recently, and based on a common secondary structure motif, the αα-hubs were defined, which are small α-helical domains of large, modular proteins binding intrinsically disordered transcriptional regulators.

Methods

Comparative structural biology.

Results

We assign the harmonin-homology-domain (HHD, also named the harmonin N-terminal domain, NTD) present in large proteins such as harmonin, whirlin, cerebral cavernous malformation 2, and regulator of telomere elongation 1 to the αα-hubs. The new member of the αα-hubs expands functionality to include scaffolding of supra-modular complexes mediating sensory perception, neurovascular integrity and telomere regulation, and reveal novel features of the αα-hubs. As a common trait, the αα-hubs bind intrinsically disordered ligands of similar properties integrating similar cellular cues, but without cross-talk.

Conclusion

The inclusion of the HHD in the αα-hubs has uncovered new features, exemplifying the utility of identifying groups of hub domains, whereby discoveries in one member may cross-fertilize discoveries in others. These features make the αα-hubs unique models for decomposing signal specificity and fidelity. Using these as models, together with other suitable hub domain, we may advance the functional understanding of hub proteins and their role in cellular communication and signaling, as well as the role of intrinsically disordered proteins in signaling networks.
Qualitative and quantitative comparison of cell-free DNA and cell-free fetal DNA isolation by four (semi-)automated extraction methods: impact in two clinical applications: chimerism quantification and noninvasive prenatal diagnosis
Authors: Pedini Pascal , Graiet Hajer , Laget Laurine , Filosa Lugdivine , Chatron Jade , Cherouat Nicem , Chiaroni Jacques , Hubert Lucas , Frassati Coralie , Picard Christophe
Published: January 2021

Background

Non-invasive molecular analysis of cell-free DNA (cfDNA) became a sensitive biomarker for monitoring organ transplantation or for detection of fetal DNA (cffDNA) in noninvasive prenatal test. In this study, we compared the efficiencies of four (semi)-automated cfDNA isolation instruments using their respective isolation kit: MagNA Pure 24 (Roche®), IDEAL (IDSolution®), LABTurbo 24 (Taigen®) and Chemagic 360 (Perkin Elmer®). The cfDNA was isolated from 5 plasma samples and the Rhesus D (RhD)-cffDNA from 5 maternal plasmas. The cfDNA were quantified by digital droplet PCR (ddPCR), BIABooster system and QUBIT fluorometer. The cfDNA fragment size profiles were assessed by BIABooster system. Chimerism were quantified by home-made ddPCR and Devyser NGS kit. RhD-cffDNA in maternal plasma were detected between weeks 14 and 24 of amenorrhea using free DNA Fetal RHD Kit® (Biorad®).

Results

Statistical tests have shown differences in DNA yield depending on the isolation procedure and quantification method used. Magna Pure isolates smaller cfDNA fragment size than other extraction methods (90% ± 9% vs. 74% ± 8%; p = 0.009). Chimerism was only reliable from LABTurbo 24 extractions using the NGS but not with ddPCR whatever extraction methods. RhD-cffDNA were detected by all isolation methods, although IDEAL and LABTurbo 24 systems seemed more efficient.

Conclusions

This comparative study showed a dependency of cfDNA yield depending on isolation procedure and quantification method used. In total, these results suggest that the choice of pre-analytical isolation systems needs to be carefully validated in routine clinical practice.
A novel long intergenic non-coding RNA, Nostrill, regulates iNOS gene transcription and neurotoxicity in microglia
Authors: Mathy Nicholas W. , Burleigh Olivia , Kochvar Andrew , Whiteford Erin R. , Behrens Matthew , Marta Patrick , Tian Cong , Gong Ai-Yu , Drescher Kristen M. , Steyger Peter S. , Chen Xian-Ming , Shibata Annemarie
Published: January 2021

Background

Microglia are resident immunocompetent and phagocytic cells in the CNS. Pro-inflammatory microglia, stimulated by microbial signals such as bacterial lipopolysaccharide (LPS), viral RNAs, or inflammatory cytokines, are neurotoxic and associated with pathogenesis of several neurodegenerative diseases. Long non-coding RNAs (lncRNA) are emerging as important tissue-specific regulatory molecules directing cell differentiation and functional states and may help direct proinflammatory responses of microglia. Characterization of lncRNAs upregulated in proinflammatory microglia, such as NR_126553 or 2500002B13Rik, now termed Nostrill (iNOS Transcriptional Regulatory Intergenic LncRNA Locus) increases our understanding of molecular mechanisms in CNS innate immunity.

Methods

Microglial gene expression array analyses and qRT-PCR were used to identify a novel long intergenic non-coding RNA, Nostrill, upregulated in LPS-stimulated microglial cell lines, LPS-stimulated primary microglia, and LPS-injected mouse cortical tissue. Silencing and overexpression studies, RNA immunoprecipitation, chromatin immunoprecipitation, chromatin isolation by RNA purification assays, and qRT-PCR were used to study the function of this long non-coding RNA in microglia. In vitro assays were used to examine the effects of silencing the novel long non-coding RNA in LPS-stimulated microglia on neurotoxicity.

Results

We report here characterization of intergenic lncRNA, NR_126553, or 2500002B13Rik now termed Nostrill (iNOS Transcriptional Regulatory Intergenic LncRNA Locus). Nostrill is induced by LPS stimulation in BV2 cells, primary murine microglia, and in cortical tissue of LPS-injected mice. Induction of Nostrill is NF-κB dependent and silencing of Nostrill decreased inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in BV2 and primary microglial cells. Overexpression of Nostrill increased iNOS expression and NO production. RNA immunoprecipitation assays demonstrated that Nostrill is physically associated with NF-κB subunit p65 following LPS stimulation. Silencing of Nostrill significantly reduced NF-κB p65 and RNA polymerase II recruitment to the iNOS promoter and decreased H3K4me3 activating histone modifications at iNOS gene loci. In vitro studies demonstrated that silencing of Nostrill in microglia reduced LPS-stimulated microglial neurotoxicity.

Conclusions

Our data indicate a new regulatory role of the NF-κB-induced Nostrill and suggest that Nostrill acts as a co-activator of transcription of iNOS resulting in the production of nitric oxide by microglia through modulation of epigenetic chromatin remodeling. Nostrill may be a target for reducing the neurotoxicity associated with iNOS-mediated inflammatory processes in microglia during neurodegeneration.
Clinical evaluation of neuroinflammation in child-onset focal epilepsy: a translocator protein PET study
Authors: Kagitani-Shimono Kuriko , Kato Hiroki , Kuwayama Ryoko , Tominaga Koji , Nabatame Shin , Kishima Haruhiko , Hatazawa Jun , Taniike Masako
Published: January 2021

Background

Neuroinflammation is associated with various chronic neurological diseases, including epilepsy; however, neuroimaging approaches for visualizing neuroinflammation have not been used in the clinical routine yet. In this study, we used the translocator protein positron emission tomography (PET) with [11C] DPA713 to investigate neuroinflammation in the epileptogenic zone in patients with child-onset focal epilepsy.

Methods

Patients with intractable focal epilepsy were recruited at the Epilepsy Center of Osaka University; those who were taking any immunosuppressants or steroids were excluded. PET images were acquired for 60 min after intravenous administration of [11C] DPA713. The PET image of [11C] DPA713 was co-registered to individual’s magnetic resonance imaging (MRI), and the standardized uptake value ratio (SUVr) in regions of interest, which were created in non-lesions and lesions, was calculated using the cerebellum as a pseudo-reference region. In the case of epilepsy surgery, the correlation between SUVr in lesions and pathological findings was analyzed.

Results

Twenty-seven patients (mean age: 11.3 ± 6.2 years, male/female: 17/10) were included in this study. Of these, 85.1% showed increased uptake of [11C] DPA713 in the focal epileptic lesion. Three patients showed epileptic spasms, suggesting partial seizure onset, and all 18 patients with abnormal lesions on MRI were similarly highlighted by significant uptake of [11C] DPA713. DPA713-positive patients had a broad range of etiologies, including focal cortical dysplasia, tumors, infarction, and hippocampal sclerosis. Five out of nine MRI-negative patients showed abnormal [11C] DPA713 uptake. The SUVr of [11C] DPA713 in lesions was significantly higher than that in non-lesions. In seven patients who underwent epilepsy surgery, increased [11C] DPA713 uptake was associated with microglial activation.

Conclusions

This study indicates that [11C] DPA713 uptake has valuable sensitivity in the identification of epileptic foci in child-onset focal epilepsy, and inflammation is implicated in the pathophysiology in the epileptic foci caused by various etiologies. Further research is required to establish diagnostic tools for identifying focal epileptogenic zones.
Metagenomic analyses and genetic diversity of Tomato leaf curl Arusha virus affecting tomato plants in Kenya
Authors: Avedi Edith Khamonya , Adediji Adedapo Olutola , Kilalo Dora Chao , Olubayo Florence Mmogi , Macharia Isaac , Ateka Elijah Miinda , Machuka Eunice Magoma , Mutuku Josiah Musembi
Published: January 2021

Background

Tomato production is threatened worldwide by the occurrence of begomoviruses which are associated with tomato leaf curl diseases. There is little information on the molecular properties of tomato begomoviruses in Kenya, hence we investigated the population and genetic diversity of begomoviruses associated with tomato leaf curl in Kenya.

Methods

Tomato leaf samples with virus-like symptoms were obtained from farmers’ field across the country in 2018 and Illumina sequencing undertaken to determine the genetic diversity of associated begomoviruses. Additionally, the occurrence of selection pressure and recombinant isolates within the population were also evaluated.

Results

Twelve complete begomovirus genomes were obtained from our samples with an average coverage of 99.9%. The sequences showed 95.7–99.7% identity among each other and 95.9–98.9% similarities with aTomato leaf curl virus Arusha virus(ToLCArV) isolate from Tanzania. Analysis of amino acid sequences showed the highest identities in the regions coding for the coat protein gene (98.5–100%) within the isolates, and 97.1–100% identity with the C4 gene of ToLCArV. Phylogenetic algorithms clustered all Kenyan isolates in the same clades with ToLCArV, thus confirming the isolates to be a variant of the virus. There was no evidence of recombination within our isolates. Estimation of selection pressure within the virus population revealed the occurrence of negative or purifying selection in five out of the six coding regions of the sequences.

Conclusions

The begomovirus associated with tomato leaf curl diseases of tomato in Kenya is a variant of ToLCArV, possibly originating from Tanzania. There is low genetic diversity within the virus population and this information is useful in the development of appropriate management strategies for the disease in the country.
Ever-increasing viral diversity associated with the red imported fire ant Solenopsis invicta (Formicidae: Hymenoptera)
Authors: Xavier César Augusto Diniz , Allen Margaret Louise , Whitfield Anna Elizabeth
Published: January 2021

Background

Advances in sequencing and analysis tools have facilitated discovery of many new viruses from invertebrates, including ants. Solenopsis invicta is an invasive ant that has quickly spread worldwide causing significant ecological and economic impacts. Its virome has begun to be characterized pertaining to potential use of viruses as natural enemies. Although the S. invicta virome is the best characterized among ants, most studies have been performed in its native range, with less information from invaded areas.

Methods

Using a metatranscriptome approach, we further identified and molecularly characterized virus sequences associated with S. invicta, in two introduced areas, U.S and Taiwan. The data set used here was obtained from different stages (larvae, pupa, and adults) of S. invicta life cycle. Publicly available RNA sequences from GenBank’s Sequence Read Archive were downloaded and de novo assembled using CLC Genomics Workbench 20.0.1. Contigs were compared against the non-redundant protein sequences and those showing similarity to viral sequences were further analyzed.

Results

We characterized five putative new viruses associated with S. invicta transcriptomes. Sequence comparisons revealed extensive divergence across ORFs and genomic regions with most of them sharing less than 40% amino acid identity with those closest homologous sequences previously characterized. The first negative-sense single-stranded RNA virus genomic sequences included in the orders Bunyavirales and Mononegavirales are reported. In addition, two positive single-strand virus genome sequences and one single strand DNA virus genome sequence were also identified. While the presence of a putative tenuivirus associated with S. invicta was previously suggested to be a contamination, here we characterized and present strong evidence that Solenopsis invicta virus 14 (SINV-14) is a tenui-like virus that has a long-term association with the ant. Furthermore, based on virus sequence abundance compared to housekeeping genes, phylogenetic relationships, and completeness of viral coding sequences, our results suggest that four of five virus sequences reported, those being SINV-14, SINV-15, SINV-16 and SINV-17, may be associated to viruses actively replicating in the ant S. invicta.

Conclusions

The present study expands our knowledge about viral diversity associated with S. invicta in introduced areas with potential to be used as biological control agents, which will require further biological characterization.
HEV prevalence and potential risk factors in a large multi-ethnic youth cohort in China
Authors: Li Huixia , Zhang Yinxia , Ma Zhongren , Liu Zewen , Ikram Aqsa , Liu Lijiang , Zhao Guoqin , Pan Qiuwei , Baloch Zulqarnain
Published: January 2021

Background

This cohort study was designed to investigate the prevalence of and potential risk factors of HEV infection in a large multi-ethnic youth cohort in China.

Methods

Blood samples were collected from participants (n = 6269) and serum was isolated. All serum samples were tested for anti-HEV IgG, anti-HEV IgM antibodies using commercial enzyme immunoassay kits (Wantai Biological Pharmacy Enterprise, Beijing, China).

Results

The overall rate of anti-HEV IgG and anti-HEV IgM prevalence was 4.78% and 0.14%, 0.03% were positive for both anti-HEV IgG and anti-HEV IgM antibodies. Anti-HEV IgG positivity is significantly higher in females (5.27%) compared to males (4.14%) (P = 0.028). Anti-HEV IgG prevalence is significantly (P = 0.0001) higher in Dong (17.57%), Miao (12.23%), Yi (11.04%), Gelao (9.76%), and Bai (10.00%) compared to other ethnic groups. It is significantly higher in Guizhou (11.4%), Sichuan (10.1%), Yunnan (9.3%), and Guangxi (6.9%) than that other province. We found that ethnicity and provincial background are significantly associated with HEV infection in this cohort.

Conclusion

This study provides comprehensive information on HEV prevalence in multi-ethnic populations in China. However, our study only focused on a youth population from different provinces of China. Future studies are recommended to investigate HEV prevalence in other age groups of the ethnic populations.
Sialylated human milk oligosaccharides prevent intestinal inflammation by inhibiting toll like receptor 4/NLRP3 inflammasome pathway in necrotizing enterocolitis rats
Authors: Zhang Wenting , He-Yang Jingqiu , Tu Wenjuan , Zhou Xiaoying
Published: January 2021

Background

Necrotizing enterocolitis (NEC) remains a fatal gastrointestinal disorder in neonates and has very limited therapeutic options. Sialylated human milk oligosaccharides (SHMOs) improve pathological changes in experimental NEC models. The objectives of this study were to investigate the involvement of NLRP3 inflammasome in NEC pathology and to explore the effects of SHMOs on toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB)/NLRP3 inflammatory pathway in experimental NEC.

Methods

The intestinal-tissue segments were collected from NEC infants, NLRP3 and caspase-1 positive cell were examined by immunohistochemistry. Newborn rats were hand-fed with formula containing or non-containing SHMOs (1500 mg/L) and exposed to hypoxia/cold stress to induce experimental NEC. The NEC pathological scores were evaluated; ileum protein expression of membrane TLR4 (mTLR4), inhibitor κB-α (IκB-α), NF-κB p65 subunit and phospho-NF-κB p65, as well as NLRP3 and caspase-1 were analyzed; ileum concentrations of interleukin-1β, interleukin-6, tumor necrosis factor-α (TNF-α) were also measured. Human colon epithelial Caco-2 cells were pre-treated with or without SHMOs and stimulated with TLR4 activator, lipopolysaccharide. Cell viabilities, mitochondrial membrane potential and supernatant matrix metalloprotease 2 (MMP-2) activities were analyzed.

Results

Increased frequencies of NLRP3 and caspase-1 positive cells were found in the lamina propria of damaged intestinal area of NEC neonates. SHMOs supplementation reduced NEC incidence and pathological damage scores of rats challenged with hypoxia/cold stress. Accumulation of interleukin-1β, interleukin-6 and TNF-α in NEC group were attenuated in SHMOs + NEC group. Protein expression of mTLR4, NLRP3 and caspase-1 were elevated, cytoplasmic IκB-α were reduced, nuclear phospho-NF-κB p65 were increased in the ileum of NEC rats. SHMOs supplementation ameliorated the elevation of mTLR4, NLRP3 and caspase-1, restored IκB-α in the cytoplasmic fraction and reduced phospho-NF-κB p65 in the nuclear fraction in the ileum of NEC rats. SHMOs pre-treatment improved Caco-2 cell viability, mitigated loss of mitochondrial membrane potential and modulated MMP-2 activities in the presence of lipopolysaccharide in-vitro.

Conclusions

This study provided clinical evidence of involvement of NLRP3 inflammasome in NEC pathology, and demonstrated the protective actions of SHMOs might be owing to the suppression of TLR4/NF-κB/NLRP3-mediated inflammation in NEC.
Association between breastfeeding and new mothers’ sleep: a unique Australian time use study
Authors: Smith Julie P. , Forrester Robert I.
Published: January 2021

Background

Infant sleep is of great interest to new parents. There is ongoing debate about whether infants fed with breastmilk substitutes sleep longer than those exclusively or partially breastfed, but what does this mean for the mother? What expectations are realistic for mothers desiring to exclusively breastfeed as recommended by health authorities?

There are both biological and social influences on infant and maternal sleep. More accurate information on average maternal sleep hours for diverse feeding practices may help guide realistic expectations and better outcomes for mothers, infants and families.

Methods

Using a unique time use dataset purposefully designed to study the time use of new mothers, this study investigated whether the weekly duration of maternal sleep, sleep disturbance, unpaid housework, and free time activities differed by detailed feeding method. The study collected 24/7 time use data from 156 mothers of infants aged 3, 6 and/or 9 months between April 2005 and April 2006, recruited via mother’s groups, infant health clinics, and childcare services throughout Australia. Sociodemographic and feeding status data were collected by questionnaire. Statistical analysis used linear mixed modelling and residual maximum likelihood analysis to compare effects of different infant feeding practices on maternal time use.

Results

There were no significant differences in time spent asleep between lactating and non lactating mothers, though lactating mothers had more time awake at night. Lactating mothers spent more time (8.5 h weekly) in childcaring activity (p = 0.007), and in employment (2.7 vs. 1.2 h, p < 0.01), but there were no significant differences in free time. Those not breastfeeding spent more time in unpaid domestic work.

Exclusive breastfeeding was associated with reduced maternal sleep hours (average 7.08 h daily). Again, free time did not differ significantly between feeding groups. Exclusively breastfeeding mothers experienced reduced sleep hours, but maintained comparable leisure time to other mothers by allocating their time differently. Domestic work hours differed, interacting in complex ways with infant age and feeding practice.

Conclusions

Optimal breastfeeding may require realistic maternal sleep expectations and equitable sharing of paid and unpaid work burdens with other household members in the months after the birth of an infant.
Comparing breastfeeding experiences between mothers spending the traditional Chinese confinement period in a confinement centre and those staying at home: a cohort study
Authors: Foong Siew Cheng , Tan May Loong , Foong Wai Cheng , Ho Jacqueline J. , Rahim Fairuz Fadzilah
Published: January 2021

Background

Ethnic Chinese mothers in Malaysia adhere to 30 days of traditional postpartum practices (the “confinement period”) aimed at recuperation after delivery. Recently there has been an emergence of confinement centres (CCs) where mothers stay and receive traditional confinement care. Ethnic Chinese mothers have low breastfeeding rates. There are concerns that practices in CCs could contribute to this but no data exists. We described mothers’ breastfeeding experiences at CCs and identified areas for potential improvement in breastfeeding support.

Methods

Ethnic Chinese mothers intending to breastfeed their healthy infants were recruited post-delivery between August and October 2017 then, at 1 and 6 months, they were telephone interviewed about their experience. For every participant going to a CC after the birth, another mother going home (“home”) for her confinement was recruited. Chi-square test was used to compare groups and multiple logistic regression was used to assess the effect of confinement place on exclusive breastfeeding.

Results

Of 187 mothers, 88 (47%) went to CCs. Significantly more were primipara and fewer had previous breastfeeding experience. Response rates for the 1- and 6- month interviews were 88% (CC) versus 97% (home); and 77% (CC) versus 87% (home) respectively.

Exclusive breastfeeding rates were similar between the groups: 62% (CC) versus 56% (home) at 1 month (p = 0.4); and 37% (CC) versus 42% (home) at 6 months (p = 0.5). Multiple logistic regression did not show that CCs were a factor affecting exclusive breastfeeding rates at 1 month, (adjusted odds ratio [aOR] 1.7, 95% confidence interval [CI] 0.9, 3.3), or 6 months (aOR 0.9, 95% CI 0.4, 1.7). However, significantly more CC participants only fed expressed breast milk. Despite 66% of CC participants reporting that their centre supported breastfeeding, only 6 (8%) CC participants compared to 66 (69%) of home participants roomed-in with their baby (p < 0.001). The proportion encountering breastfeeding difficulties were similar between groups. CC participants sought help for breastfeeding problems mainly from CC staff and support groups while home participants obtained help from friends and healthcare professionals.

Conclusions

Breastfeeding rates appeared to be similar at CCs and at home during the confinement period, but there were gaps in how CCs supported breastfeeding. Targeted training to CC staff to support breastfeeding may result in better outcomes for mothers staying in CCs.
Cytoreductive radiotherapy combined with abiraterone in metastatic castration-resistance prostate cancer: a single center experience
Authors: Liu Yang , Long Wen , Zhang Zitong , Mai Lixin , Huang Sijuan , Liu Boji , Cao Wufei , Wu Jianhua , Zhou Fangjian , Li Yonghong , He Liru
Published: January 2021

Background

To investigate the potential benefit of cytoreductive radiotherapy (cRT) in metastatic castration-resistant prostate cancer (mCRPC) patients receiving abiraterone.

Methods

From February 2014 to February 2019, 149 mCRPC patients treated with abiraterone were identified. Patients receiving cRT before abiraterone failure (AbiRT group) were matched by one-to-two propensity score to patients without cRT before abiraterone failure (non-AbiRT group).

Results

The median follow-up was 23.5 months. Thirty patients (20.1%) were in the AbiRT group, whereas 119 patients (79.9%) were in the non-AbiRT group. The 2-year OS of patients managed by AbiRT and non-AbiRT were 89.5% and 73.5%, respectively (P = 0.0003). On multivariate analysis, only AbiRT (HR 0.17; 95% CI 0.05–0.58; P = 0.004) and prognostic index (HR 2.71; 95% CI 1.37–5.35; P = 0.004) were significant factors. After matching, AbiRT continued to be associated with improved OS (median OS not reached vs. 44.0 months, P = 0.009). Subgroup analysis revealed that patients aged ≤ 65 years (HR 0.09; 95% CI 0.01–0.65; P = 0.018), PSA ≤ 20 ng/mL (HR 0.29; 95% CI 0.09–0.99; P = 0.048), chemotherapy-naïve upon abiraterone treatment (HR 0.20; 95% CI 0.06–0.66; P = 0.008) and in intermediate prognosis groups by COU-AA-301 prognostic index (HR 0.13; 95% CI 0.03–0.57; P = 0.007) had improved OS with AbiRT.

Conclusions

cRT before resistance to abiraterone may improve survival in selected mCRPC patients: age ≤ 65 years old, chemotherapy-naïve, with a relatively low PSA level at the diagnosis of mCRPC and intermediate prognosis.
Intra-articular opening osteotomy combined with lateral ligament reconstruction for varus ankle arthritis
Authors: Xu Yang , Li Xing-chen , Guo Chang-jun , Xu Xiang-yang
Published: January 2021

Background

Takakura 3B ankle arthritis is featured as obliteration of ankle space with subchondral bone contact. Among these patients, some have medial distal tibial platform erosion. It is hard to treat this kind of patients. The purpose of this study was to evaluate the therapeutic outcomes of intra-articular opening osteotomy combined with lateral ligament reconstruction for Takakura 3B ankle arthritis with medial distal tibial platform erosion.

Methods

From September 2009 to May 2016, 17 patients with Takakura 3B ankle arthritis were reviewed, including 3 male and 14 female patients. All underwent the operation of intra-articular opening osteotomy combined with lateral ligament reconstruction. All patients were available for analysis. The main outcome measurements included TT angle, AOFAS score, VAS score, SF-36 scale, and AOS scale.

Results

All patients were followed for a mean follow-up of 87.2 months (range, 49 to 129 months). The VAS scale improved from 5.5 ± 1.6 to 2.3 ± 1.9. The mean AOFAS score improved from 47.7 ± 15.7 to 75.8 ± 12.0. The SF-36 scale improved from 41.6 ± 14.0 to 67.7 ± 14.6. The AOS improved from 60.9 ± 13.9 to 28.2 ± 17.7. The TT angle improved from 14.3 ± 5.0° to 5.3 ± 4.0°. The TAS and TLS changed from 83.4 ± 2.6° and 77.5 ± 2.3° to 90.7 ± 2.3° and 78.6 ± 2.2°. However, the LTAS was not corrected significantly.

Conclusion

Intra-articular opening osteotomy combined with lateral ligament reconstruction is an effective method to treat varus ankle arthritis with medial distal tibial platform erosion.
From pathogenesis to treatment, a systemic review of cardiac lipoma
Authors: Shu Shenglei , Wang Jing , Zheng Chuangsheng
Published: January 2021

Cardiac lipoma is an uncommon primary cardiac tumor. With the advancement of diagnostic methods and treatment techniques, more cases of cardiac lipomas have been reported and suggest that the entity previously widely thought to display classic features may also show atypical findings. A systemic review of the rare cardiac tumor was done by searching the literature of cardiac lipoma. We endeavor to summarize the clinical features of the rare disease from pathogenesis to treatment. Literature of cardiac lipoma was retrospectively searched through PubMed and 255 cases of cardiac lipoma were included into this analysis. Cardiac lipomas can occur anywhere within the heart, 53.1% were located within the cardiac chambers, 32.5% in the pericardium, 10,7% within the myocardium and 3.7% involved multiple structures. More than half of the reported cardiac lipomas (66%) may be clinically symptomatic, presenting with symptoms ranging from chest discomfort to syncope depending on their size and location as well as extent of myocardial involvement. Noninvasive cardiac imaging has replaced the role of autopsy and cardiothoracic surgery in detection and diagnosis of cardiac lipomas. Most symptomatic patients (83.7%) were treated by resection of cardiac lipomas and 68.3% of asymptomatic patients also underwentprophylactic resection. Overgrowth and myocardial infiltration of lipomas may result in unsuccessful resection. Recurrence of cardiac lipomas was rare but reported in a few cases. The early detection and accurate diagnosis of cardiac lipoma is of great significance in clinical management, to avoid an unfavourable outcome due to overgrowth.
Risk assessment of acute kidney injury following cardiopulmonary bypass
Authors: Wittlinger Thomas , Maus Martin , Kutschka Ingo , Baraki Hassina , Friedrich Martin G.
Published: January 2021

Background

Acute kidney injury (AKI) is a frequent and serious complication of cardiac surgery, associated with a high incidence of morbidity and mortality. Although the RIFLE criteria serve as a prominent tool to identify patients at high risk of AKI, an optimized diagnosis model in clinical practice is desired.

Methods

Based on the SOP-criteria, 365 patients (10%) developed AKI following surgery and were subjected to RRT. In contrast, the incidence of AKI, defined according to the RIFLE criteria, was only 7% (n = 251 patients). Prominent risk factors identified by SOP were patients’ sex, valve and combined valve and bypass surgery, deep hypothermia, use of intra-aortic balloon pump (IABP) and previous coronary interventions. Ischemia, reperfusion, blood loss and surgery time also served as significant risk factors for patient evaluated by SOP.

Results

Risk assessment by RIFLE differed in as much as most patients with normothermia and those receiving only cardiovascular bypass developed AKI. However, patients’ sex and valve surgery did not serve as a risk factor.

Conclusion

Evaluation of patients by the RIFLE versus SOP criteria yielded different results with more AKI patients detected by SOP. Based on the present data, it is concluded that patients may not prone to AKI when surgery and ischemia time will be kept short, when blood loss is mitigated to a minimum and when surgery is performed under non-hypothermic conditions.