bluuebunny/crossref_metadata_2025 huggingface dataset:
WeChat-based intervention to support breastfeeding for Chinese mothers: protocol of a randomised controlled trial
Authors: Tang Li , Lee Andy H. , Binns Colin W. , Duan Lian , Liu Yi , Li Chunrong
Published: November 2020

Background

Exclusive breastfeeding for the first 6 months of life is the optimal way to feed infants. However, recent studies suggest that exclusive breastfeeding rates in China remain low and are well below the recommended target. There has been evidence that a lack of awareness of, or exposure to, breastfeeding information is associated with poor breastfeeding practices. WeChat, the most widely used social networking platform in China, has shown some potential to promote health behaviours. We thus hypothesised that a breastfeeding intervention program delivered via WeChat would achieve at least a 10% increase in exclusive breastfeeding prevalence at 6 months compared to the control group.

Methods

A two-arm, parallel, multicentre randomised controlled trial of 1000 pregnant women will be conducted at four maternity hospitals of Chengdu, China. Eligible women who consent to participate in the trial will be recruited at 28–30 weeks of gestation, and randomly allocated to either the intervention group (participants receive breastfeeding-related information from WeChat) or the control group (participants receive non-breastfeeding information from WeChat) using a central randomisation system on a 1:1 ratio at each participating site. The primary outcomes are exclusive breastfeeding rate and full breastfeeding rate at 6 months postpartum. All randomised participants will be included in the outcome analyses with missing data being imputed based on the best-case and worst-case scenarios. Multilevel mixed regression models will be used in the primary analyses to assess the effectiveness of intervention program on the breastfeeding rates.

Discussion

This trial uses the most widely used social media program as a means of delivering messages to mothers to increase exclusive breastfeeding in China. Increasing exclusive breastfeeding will contribute to meeting the health and environmental goals of the Sustainable Development Guidelines.

Trial registration ClinicalTrials.gov, NCT04499404. Registered 5 August 2020—Retrospectively registered, https://clinicaltrials.gov/show/NCT04499404
Multi-targeted gene silencing strategies inhibit replication of Canine morbillivirus
Authors: de Carvalho Otávio Valério , Rebouças Santos Marcus , Lopes Rangel Fietto Juliana , Pires Moraes Mauro , de Almeida Márcia Rogéria , Costa Bressan Gustavo , José Pena Lindomar , Silva-Júnior Abelardo
Published: November 2020

Background

Canine morbilivirus (canine distemper virus, CDV) is a highly contagious pathogen associated with high morbidity and mortality in susceptible carnivores. Although there are CDV vaccines available, the disease poses a huge threat to dogs and wildlife hosts due to vaccine failures and lack of effective treatment. Thus, the development of therapeutics is an urgent need to achieve rapid outbreak control and reduce mortality in target species. Gene silencing by RNA interference has emerged as a promising therapeutic approach against different human and animal viruses. In this study, plasmid-based short hairpin RNAs (shRNAs) against three different regions in either CDV nucleoprotein (N), or large polymerase (L) genes and recombinant adenovirus-expressing N-specific multi-shRNAs were generated. Viral cytopathic effect, virus titration, plaque-forming unit reduction, and real-time quantitative RT-PCR analysis were used to check the efficiency of constructs against CDV.

Results

In CDV-infected VerodogSLAM cells, shRNA-expressing plasmids targeting the N gene markedly inhibited the CDV replication in a dose-dependent manner, with viral genomes and titers being decreased by over 99%. Transfection of plasmid-based shRNAs against the L gene displayed weaker inhibition of viral RNA level and virus yield as compared to CDV N shRNAs. A combination of shRNAs targeting three sites in the N gene considerably reduced CDV RNA and viral titers, but their effect was not synergistic. Recombinant adenovirus-expressing multiple shRNAs against CDV N gene achieved a highly efficient knockdown of CDV N mRNAs and successful inhibition of CDV replication.

Conclusions

We found that this strategy had strong silencing effects on CDV replication in vitro. Our findings indicate that the delivery of shRNAs using plasmid or adenovirus vectors potently inhibits CDV replication and provides a basis for the development of therapeutic strategies for clinical trials.
Sub-ohm vaping increases the levels of carbonyls, is cytotoxic, and alters gene expression in human bronchial epithelial cells exposed at the air–liquid interface
Authors: Noël Alexandra , Hossain Ekhtear , Perveen Zakia , Zaman Hasan , Penn Arthur L.
Published: November 2020

Background

Exposure to electronic-cigarette (e-cig) aerosols induces potentially fatal e-cig or vaping-associated lung injury (EVALI). The cellular and molecular mechanisms underlying these effects, however, are unknown. We used an air–liquid interface (ALI) in vitro model to determine the influence of two design characteristics of third-generation tank-style e-cig devices—resistance and voltage—on (1) e-cig aerosol composition and (2) cellular toxicity.

Methods

Human bronchial epithelial cells (H292) were exposed to either butter-flavored or cinnamon-flavored e-cig aerosols at the ALI in a Vitrocell exposure system connected to a third-generation e-cig device. Exposures were conducted following a standard vaping topography profile for 2 h per day, for 1 or 3 consecutive days. 24 h after ALI exposures cellular and molecular outcomes were assessed.

Results

We found that butter-flavored e-cig aerosol produced under ‘sub-ohm’ conditions (< 0.5 Ω) contains high levels of carbonyls (7–15 μg/puff), including formaldehyde, acetaldehyde and acrolein. E-cig aerosol produced under regular vaping conditions (resistance > 1 Ω and voltage > 4.5 V), contains lower carbonyl levels (< 2 μg/puff). We also found that the levels of carbonyls produced in the cinnamon-flavored e-cig aerosols were much lower than that of the butter-flavored aerosols. H292 cells exposed to butter-flavored or cinnamon-flavored e-cig aerosol at the ALI under ‘sub-ohm’ conditions for 1 or 3 days displayed significant cytotoxicity, decreased tight junction integrity, increased reactive oxygen species production, and dysregulated gene expression related to biotransformation, inflammation and oxidative stress (OS). Additionally, the cinnamon-flavored e-cig aerosol induced pro-oxidant effects as evidenced by increases in 8-hydroxy-2-deoxyguanosine protein levels. Moreover, we confirmed the involvement of OS as a toxicity process for cinnamon-flavored e-cig aerosol by pre-treating the cells with N-acetyl cysteine (NAC), an antioxidant that prevented the cells from the OS-mediated damage induced by the e-cig aerosol.

Conclusion

The production of high levels of carbonyls may be flavor specific. Overall, inhaling e-cig aerosols produced under ‘sub-ohm’ conditions is detrimental to lung epithelial cells, potentially via mechanisms associated with OS. This information could help policymakers take the necessary steps to prevent the manufacturing of sub-ohm atomizers for e-cig devices.
Molecular forms of Anopheles subpictus and Anopheles sundaicus in the Indian subcontinent
Authors: Sindhania Ankita , Das Manoj K. , Sharma Gunjan , Surendran Sinnathamby N. , Kaushal B. R. , Lohani Himanshu P. , Singh Om P.
Published: November 2020

Background

Anopheles subpictus and Anopheles sundaicus are closely related species, each comprising several sibling species. Ambiguities exist in the classification of these two nominal species and the specific status of members of these species complexes. Identifying fixed molecular forms and mapping their spatial distribution will help in resolving the taxonomic ambiguities and understanding their relative epidemiological significance.

Methods

DNA sequencing of Internal Transcribed Spacer-2 (ITS2), 28S-rDNA (D1-to-D3 domains) and cytochrome oxidase-II (COII) of morphologically identified specimens of two nominal species, An. subpictus sensu lato (s.l.) and An. sundaicus s.l., collected from the Indian subcontinent, was performed and subjected to genetic distance and molecular phylogenetic analyses.

Results

Molecular characterization of mosquitoes for rDNA revealed the presence of two molecular forms of An. sundaicus s.l. and three molecular forms of An. subpictus s.l. (provisionally designated as Form A, B and C) in the Indian subcontinent. Phylogenetic analyses revealed two distinct clades: (i) subpictus clade, with a single molecular form of An. subpictus (Form A) prevalent in mainland India and Sri Lanka, and (ii) sundaicus clade, comprising of members of Sundaicus Complex, two molecular forms of An. subpictus s.l. (Form B and C), prevalent in coastal areas or islands in Indian subcontinent, and molecular forms of An. subpictus s.l. reported from Thailand and Indonesia. Based on the number of float-ridges on eggs, all An. subpictus molecular Form B were classified as Species B whereas majority (80%) of the molecular Form A were classified as sibling species C. Fixed intragenomic sequence variation in ITS2 with the presence of two haplotypes was found in molecular Form A throughout its distribution.

Conclusion

A total of three molecular forms of An. subpictus s.l. and two molecular forms of An. sundaicus s.l. were recorded in the Indian subcontinent. Phylogenetically, two forms of An. subpictus s.l. (Form B and C) prevalent in coastal areas or islands in the Indian subcontinent and molecular forms reported from Southeast Asia are members of Sundaicus Complex. Molecular Form A of An. subpictus is distantly related to all other forms and deserve a distinct specific status.
Emerging insights into the relationship between hyperlipidemia and the risk of diabetic retinopathy
Authors: Chou Yuyu , Ma Jin , Su Xin , Zhong Yong
Published: November 2020

Hyperlipidemia is correlated with a series of health problems. Notably, aside from its established role in promoting cardiovascular morbidity and mortality, hyperlipidemia has also been considered for modulating the risk and the severity of multiple metabolic disorders. According to the results of epidemiologic investigations, several certain circulating lipoprotein species are correlated with the prevalence of diabetic retinopathy, suggesting that the physiological and pathological role of these lipoproteins is analogous to that observed in cardiovascular diseases. Furthermore, the lipid-lowering treatments, particularly using statin and fibrate, have been demonstrated to ameliorate diabetic retinopathy. Thereby, current focus is shifting towards implementing the protective strategies of diabetic retinopathy and elucidating the potential underlying mechanisms. However, it is worth noting that the relationship between major serum cholesterol species and the development of diabetic retinopathy, published by other studies, was inconsistent and overall modest, revealing the relationship is still not clarified. In this review, the current understanding of hyperlipidemia in pathogenesis of diabetic retinopathy was summarized and the novel insights into the potential mechanisms whereby hyperlipidemia modulates diabetic retinopathy were put forward.
The civil society monitoring of hepatitis C response related to the WHO 2030 elimination goals in 35 European countries
Authors: Maticic M. , Pirnat Z. , Leicht A. , Zimmermann R. , Windelinck T. , Jauffret-Roustide M. , Duffell E. , Tammi T. , Schatz E.
Published: November 2020

Background

People who inject drugs (PWID) account for the majority of new cases of hepatitis C virus (HCV) infection in Europe; however, HCV testing, and treatment for PWID remain suboptimal. With the advent of direct acting antivirals (DAAs) the World Health Organization (WHO) adopted a strategy to eliminate HCV as public health threat by 2030. To achieve this, key policies for PWID must be implemented and HCV continuum of care needs to be monitored. This study presents results of the first monitoring led by civil society that provide harm reduction services for PWID.

Methods

In 2019, harm reduction civil society organizations representing focal points of Correlation-European Harm Reduction Network in 36 European countries were invited to complete a 27-item online survey on four strategic fields: use/impact of guidelines on HCV testing and treatment for PWID, availability/functioning of continuum of care, changes compared to the previous year and, the role of harm reduction services and non-governmental organizations (NGOs) of PWID. A descriptive analysis of the responses was undertaken.

Results

The response rate was 97.2%. Six countries reported having no guidelines on HCV treatment (17.1%). Twenty-three (65.7%) reported having treatment guidelines with specific measures for PWID; guidelines that impact on accessibility to HCV testing/treatment and improve access to harm reduction services in 95.6% and 86.3% of them, respectively. DAAs were available in 97.1% of countries; in 26.4% of them they were contraindicated for active drug users. HCV screening/confirmatory tests performed at harm reduction services/community centers, prisons and drug dependence clinics were reported from 80.0%/25.7%, 60.0%/48.6%, and 62.9%/34.3% of countries, respectively. Provision of DAAs at drug dependence clinics and prisons was reported from 34.3 to 42.9% of countries, respectively. Compared to the previous year, HCV awareness campaigns, testing and treatment on service providers’ own locations were reported to increase in 42.9%, 51.4% and 42.9% of countries, respectively. NGOs of PWID conducted awareness campaigns on HCV interventions in 68.9% of countries, and 25.7% of countries had no such support.

Conclusion

Further improvements in continuum-of-care interventions for PWID are needed, which could be achieved by including harm reduction and PWID organizations in strategic planning of testing and treatment and in efforts to monitor progress toward WHO 2030 elimination goal.
Status of racial disparities between black and white women undergoing assisted reproductive technology in the US
Authors: Seifer David B. , Simsek Burcin , Wantman Ethan , Kotlyar Alexander M.
Published: November 2020

Background

Numerous studies have demonstrated substantial differences in assisted reproductive technology outcomes between black non-Hispanic and white non-Hispanic women. We sought to determine if disparities in assisted reproductive technology outcomes between cycles from black non-Hispanic and white non-Hispanic women have changed and to identify factors that may have influenced change and determine racial differences in cumulative live birth rates.

Methods

This is a retrospective cohort study of the SARTCORS database outcomes for 2014–2016 compared with those previously reported in 2004–2006 and 1999/2000. Patient demographics, etiology of infertility, and cycle outcomes were compared between black non-hispanic and white non-hispanic patients. Categorical values were compared using Chi-squared testing. Continuous variables were compared using t-test. Multiple logistic regression was used to assess confounders.

Results

We analyzed 122,721 autologous, fresh, non-donor embryo cycles from 2014 to 2016 of which 13,717 cycles from black and 109,004 cycles from white women. The proportion of cycles from black women increased from 6.5 to 8.4%. Cycles from black women were almost 3 times more likely to have tubal and/or uterine factor and body mass index ≥30 kg/m2. Multivariate logistic regression demonstrated that black women had a lower live birth rate (OR 0.71;P < 0.001) and a lower cumulative live birth rate for their initial cycle (OR 0.64; P < 0.001) independent of age, parity, body mass index, etiology of infertility, ovarian reserve, cycle cancellation, past spontaneous abortions, use of intra-cytoplasmic sperm injection or number of embryos transferred. A lower proportion of cycles in black women were represented among non-mandated states (P < 0.001) and cycles in black women were associated with higher clinical live birth rates in mandated states (P = 0.006).

Conclusions

Disparities in assisted reproductive technology outcomes in the US have persisted for black women over the last 15 years. Limited access to state mandated insurance may be contributory. Race has continued to be an independent prognostic factor for live birth and cumulative live birth rate from assisted reproductive technology in the US.
Oral P. gingivalis impairs gut permeability and mediates immune responses associated with neurodegeneration in LRRK2 R1441G mice
Authors: Feng Yu-Kun , Wu Qiong-Li , Peng Yan-Wen , Liang Feng-Yin , You Hua-Jing , Feng Yi-Wei , Li Ge , Li Xue-Jiao , Liu Shu-Hua , Li Yong-Chao , Zhang Yu , Pei Zhong
Published: November 2020

Background

The R1441G mutation in the leucine-rich repeat kinase 2 (LRRK2) gene results in late-onset Parkinson’s disease (PD). Peripheral inflammation and gut microbiota are closely associated with the pathogenesis of PD. Chronic periodontitis is a common type of peripheral inflammation, which is associated with PD. Porphyromonas gingivalis (Pg), the most common bacterium causing chronic periodontitis, can cause alteration of gut microbiota. It is not known whether Pg-induced dysbiosis plays a role in the pathophysiology of PD.

Methods

In this study, live Pg were orally administrated to animals, three times a week for 1 month. Pg-derived lipopolysaccharide (LPS) was used to stimulate mononuclear cells in vitro. The effects of oral Pg administration on the gut and brain were evaluated through behaviors, morphology, and cytokine expression.

Results

Dopaminergic neurons in the substantia nigra were reduced, and activated microglial cells were increased in R1441G mice given oral Pg. In addition, an increase in mRNA expression of tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β) as well as protein level of α-synuclein together with a decrease in zonula occludens-1 (Zo-1) was detected in the colon in Pg-treated R1441G mice. Furthermore, serum interleukin-17A (IL-17A) and brain IL-17 receptor A (IL-17RA) were increased in Pg-treated R1441G mice.

Conclusions

These findings suggest that oral Pg-induced inflammation may play an important role in the pathophysiology of LRRK2-associated PD.
Comparative analysis of human microglial models for studies of HIV replication and pathogenesis
Authors: Rai Mohammad A. , Hammonds Jason , Pujato Mario , Mayhew Christopher , Roskin Krishna , Spearman Paul
Published: November 2020

Background

HIV associated neurocognitive disorders cause significant morbidity and mortality despite the advent of highly active antiretroviral therapy. A deeper understanding of fundamental mechanisms underlying HIV infection and pathogenesis in the central nervous system is warranted. Microglia are resident myeloid cells of the brain that are readily infected by HIV and may constitute a CNS reservoir. We evaluated two microglial model cell lines (C20, HMC3) and two sources of primary cell-derived microglia (monocyte-derived microglia [MMG] and induced pluripotent stem cell-derived microglia [iPSC-MG]) as potential model systems for studying HIV-microglia interactions.

Results

All four microglial model cells expressed typical myeloid markers with the exception of low or absent CD45 and CD11b expression by C20 and HMC3, and all four expressed the microglia-specific markers P2RY12 and TMEM119. Marked differences were observed upon gene expression profiling, however, indicating that MMG and iPSC-MG cluster closely together with primary human microglial cells, while C20 and HMC3 were similar to each other but very different from primary microglia. Expression of HIV-relevant genes also revealed important differences, with iPSC-MG and MMG expressing relevant genes at levels more closely resembling primary microglia. iPSC-MG and MMG were readily infected with R5-tropic HIV, while C20 and HMC3 lack CD4 and require pseudotyping for infection. Despite many similarities, HIV replication dynamics and HIV-1 particle capture by Siglec-1 differed markedly between the MMG and iPSC-MG.

Conclusions

MMG and iPSC-MG appear to be viable microglial models that are susceptible to HIV infection and bear more similarities to authentic microglia than two transformed microglia cell lines. The observed differences in HIV replication and particle capture between MMG and iPSC-MG warrant further study.
Pathogen burden and leukocyte telomere length in the United States
Authors: Noppert Grace A. , Feinstein Lydia , Dowd Jennifer B. , Stebbins Rebecca C. , Zang Emma , Needham Belinda L. , Meier Helen C. S. , Simanek Amanda , Aiello Allison E.
Published: November 2020

Background

Prior studies in humans have suggested that telomere shortening may be accelerated by infection, but research on multiple pathogens and use of large population-based study samples has been limited. We estimated cross-sectional associations between seropositivity to five persistent pathogens (Herpes Simplex Virus Type-1 (HSV-1), Herpes Simplex Virus Type-2 (HSV-2), cytomegalovirus (CMV), Helicobacter pylori (H.pylori), and Hepatitis B) as well as total pathogen burden and leukocyte telomere length. Data were derived from the National Health and Nutrition Examination Survey (1999–2000) for individuals 20–49 years of age, N = 1708. We analyzed the influence of each pathogen separately, a pathogen count score and a latent class model of pathogen burden on log telomere length using linear regression models, adjusted for covariates.

Results

Individuals in a latent pathogen burden class characterized by high probabilities of infection with HSV-1, CMV, and H. pylori, had significantly decreased log telomere length (− 0.30 [95% CI: − 0.36, − 0.24]) compared to those in a latent class characterized by low probabilities of all five infections. There were limited significant associations using other pathogen measures.

Conclusions

These results suggest that infection with specific combinations of pathogens may be one mechanism contributing to accelerated cellular senescence with possible origins early in the life course.
A novel use of inertial sensors to measure the craniocervical flexion range of motion associated to the craniocervical flexion test: an observational study
Authors: Pérez-Fernández Tomás , Armijo-Olivo Susan , Liébana Sonia , de la Torre Ortíz Pablo José , Fernández-Carnero Josué , Raya Rafael , Martín-Pintado-Zugasti Aitor
Published: November 2020

Background

The craniocervical flexion test (CCFT) is recommended when examining patients with neck pain related conditions and as a deep cervical retraining exercise option. During the execution of the CCFT the examiner should visually assess that the amount of craniocervical flexion range of motion (ROM) progressively increases. However, this task is very subjective. The use of inertial wearable sensors may be a user-friendly option to measure and objectively monitor the ROM. The objectives of our study were (1) to measure craniocervical flexion range of motion (ROM) associated with each stage of the CCFT using a wearable inertial sensor and to determine the reliability of the measurements and (2) to determine craniocervical flexion ROM targets associated with each stage of the CCFT to standardize their use for assessment and training of the deep cervical flexor (DCF) muscles.

Methods

Adults from a university community able to successfully perform the CCFT participated in this study. Two independent examiners evaluated the CCFT in two separate sessions. During the CCFT, a small wireless inertial sensor was adhered to the centre of the forehead to provide real-time monitoring and to record craniocervical flexion ROM. The intra- and inter-rater reliability of the assessment of craniocervical ROM was calculated. This study was approved by the Research Ethics Committee of CEU San Pablo University (236/17/08).

Results

Fifty-six participants (18 males, 23 females; mean [SD] age, 21.8 [3.45] years) were included in the study and successfully completed the study protocol. All interclass correlation coefficient (ICC) values indicated good or excellent reliability of the assessment of craniocervical ROM using a wearable inertial sensor. There was high variability between subjects on the amount of craniocervical ROM necessary to achieve each stage of the CCFT.

Conclusions

The use of inertial sensors is a reliable method to measure the craniocervical flexion ROM associated with the CCFT. The great variability in the ROM limits the possibility to standardize a set of targets of craniocervical flexion ROM equivalent to each of the pressure targets of the pressure biofeedback unit.
Admission deep venous thrombosis of lower extremity after intertrochanteric fracture in the elderly: a retrospective cohort study
Authors: Zuo Jinzeng , Hu Yongcheng
Published: November 2020

Objective

The purpose of this study was to investigate the incidence, location, and related factors of deep venous thrombosis (DVT) of the bilateral lower extremities after intertrochanteric fractures in the elderly.

Methods

Retrospective analysis was performed on the elderly patients with intertrochanteric fracture who were admitted from January 2017 to December 2019. At admission, patients receive routine ultrasound Doppler scanning of bilateral lower extremities to detect DVT; those with DVT were assigned to the case group and those without DVT to the control group. Patient data on demographics, comorbidities, injury-related data, and laboratory test results at admission were extracted. Logistic regression analyses were conducted to identify the independent risk factors associated with DVT.

Results

Five hundred seventy-eight patients were included, among whom 116 (20.1%) had DVT. Among those with DV, 70.7% (82/116) had DVT of the distal type, 24 (29.6%) had DVT of the proximal type, and 10 (10.4%) had mixed DVT. In 76.7% (89/116) of patients, DVT occurred in the fractured extremity, 9.5% (11/116) in the bilateral and 13.8% (16/116) in the non-fractured extremity. Multivariate analyses identified obesity, delay to admission, increased D-dimer level (> 1.44 mg/L) and reduced albumin (< 31.7 g/L) as independent factors.

Conclusions

Admission incidence of DVT was high in elderly patients with intertrochanteric fractures, especially the proximal DVT. Identification of associated risk factors is useful for individualized assessment risk of DVT and early targeted interventions.
The promising role of noncoding RNAs in cancer-associated fibroblasts: an overview of current status and future perspectives
Authors: Fang Zengli , Xu Jin , Zhang Bo , Wang Wei , Liu Jiang , Liang Chen , Hua Jie , Meng Qingcai , Yu Xianjun , Shi Si
Published: November 2020

As the most important component of the stromal cell population in the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) are crucial players in tumor initiation and progression. The interaction between CAFs and tumor cells, as well as the resulting effect, is much greater than initially expected. Numerous studies have shown that noncoding RNAs (ncRNAs) play an irreplaceable role in this interplay, and related evidence continues to emerge and advance. Under the action of ncRNAs, normal fibroblasts are directly or indirectly activated into CAFs, and their metabolic characteristics are changed; thus, CAFs can more effectively promote tumor progression. Moreover, via ncRNAs, activated CAFs can affect the gene expression and secretory characteristics of cells, alter the TME and enhance malignant biological processes in tumor cells to contribute to tumor promotion. Previously, ncRNA dysregulation was considered the main mechanism by which ncRNAs participate in the crosstalk between CAFs and tumor cells. Recently, however, exosomes containing ncRNAs have been identified as another vital mode of interaction between these two types of cells, with a more direct and clear function. Gaining an in-depth understanding of ncRNAs in CAFs and the complex regulatory network connecting CAFs with tumor cells might help us to establish more effective and safer approaches for cancer therapies targeting ncRNAs and CAFs and offer new hope for cancer patients.
Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer
Authors: Zhao Senlin , Mi Yushuai , Guan Bingjie , Zheng Binbin , Wei Ping , Gu Yanzi , Zhang Zhengxiang , Cai Sanjun , Xu Ye , Li Xinxiang , He Xuefeng , Zhong Xinyang , Li Guichao , Chen Zhiyu , Li Dawei
Published: November 2020

Background

Mounting evidence has demonstrated the vital importance of tumor-associated macrophages (TAMs) and exosomes in the formation of the premetastatic niche. However, the molecular mechanisms by which tumor-derived exosomal miRNAs interact with TAMs underlying premetastatic niche formation and colorectal cancer liver metastasis (CRLM) remain largely unknown.

Methods

Transmission electron microscopy and differential ultracentrifugation were used to verify the existence of exosomes. In vivo and in vitro assays were used to identify roles of exosomal miR-934. RNA pull-down assay, dual-luciferase reporter assay, etc. were applied to clarify the mechanism of exosomal miR-934 regulated the crosstalk between CRC cells and M2 macrophages.

Results

In the present study, we first demonstrated the aberrant overexpression of miR-934 in colorectal cancer (CRC), especially in CRLM, and its correlation with the poor prognosis of CRC patients. Then, we verified that CRC cell-derived exosomal miR-934 induced M2 macrophage polarization by downregulating PTEN expression and activating the PI3K/AKT signaling pathway. Moreover, we revealed that hnRNPA2B1 mediated miR-934 packaging into exosomes of CRC cells and then transferred exosomal miR-934 into macrophages. Interestingly, polarized M2 macrophages could induce premetastatic niche formation and promote CRLM by secreting CXCL13, which activated a CXCL13/CXCR5/NFκB/p65/miR-934 positive feedback loop in CRC cells.

Conclusions

These findings indicate that tumor-derived exosomal miR-934 can promote CRLM by regulating the crosstalk between CRC cells and TAMs. These findings reveal a tumor and TAM interaction in the metastatic microenvironment mediated by tumor-derived exosomes that affects CRLM. The present study also provides a theoretical basis for secondary liver cancer.
Quadruple-negative breast cancer: novel implications for a new disease
Authors: Bhattarai Shristi , Saini Geetanjali , Gogineni Keerthi , Aneja Ritu
Published: November 2020

Based on the androgen receptor (AR) expression, triple-negative breast cancer (TNBC) can be subdivided into AR-positive TNBC and AR-negative TNBC, also known as quadruple-negative breast cancer (QNBC). QNBC characterization and treatment is fraught with many challenges. In QNBC, there is a greater paucity of prognostic biomarkers and therapeutic targets than AR-positive TNBC. Although the prognostic role of AR in TNBC remains controversial, many studies revealed that a lack of AR expression confers a more aggressive disease course. Literature characterizing QNBC tumor biology and uncovering novel biomarkers for improved management of the disease remains scarce. In this comprehensive review, we summarize the current QNBC landscape and propose avenues for future research, suggesting potential biomarkers and therapeutic strategies that warrant investigation.
Human adipose-derived stem cells enriched with VEGF-modified mRNA promote angiogenesis and long-term graft survival in a fat graft transplantation model
Authors: Yu Fei , Witman Nevin , Yan Dan , Zhang Siyi , Zhou Meng , Yan Yan , Yao Qinke , Ding Feixue , Yan Bingqian , Wang Huijing , Fu Wei , Lu Yang , Fu Yao
Published: November 2020

Background

Fat grafting, as a standard treatment for numerous soft tissue defects, remains unpredictable and technique-dependent. Human adipose-derived stem cells (hADSCs) are promising candidates for cell-assisted therapy to improve graft survival. As free-living fat requires nutritional and respiratory sources to thrive, insufficient and unstable vascularization still impedes hADSC-assisted therapy. Recently, cytotherapy combined with modified mRNA (modRNA) encoding vascular endothelial growth factor (VEGF) has been applied for the treatment of ischemia-related diseases. Herein, we hypothesized that VEGF modRNA (modVEGF)-engineered hADSCs could robustly enhance fat survival in a fat graft transplantation model.

Methods

hADSCs were acquired from lipoaspiration and transfected with modRNAs. Transfection efficiency and expression kinetics of modRNAs in hADSCs were first evaluated in vitro. Next, we applied an in vivo Matrigel plug assay to assess the viability and angiogenic potential of modVEGF-engineered hADSCs at 1 week post-implantation. Finally, modVEGF-engineered hADSCs were co-transplanted with human fat in a murine model to analyze the survival rate, re-vascularization, proliferation, fibrosis, apoptosis, and necrosis of fat grafts over long-term follow-up.

Results

Transfections of modVEGF in hADSCs were highly tolerable as the modVEGF-engineered hADSCs facilitated burst-like protein production of VEGF in both our in vitro and in vivo models. modVEGF-engineered hADSCs induced increased levels of cellular proliferation and proangiogenesis when compared to untreated hADSCs in both ex vivo and in vivo assays. In a fat graft transplantation model, we provided evidence that modVEGF-engineered hADSCs promote the optimal potency to preserve adipocytes, especially in the long-term post-transplantation phase. Detailed histological analysis of fat grafts harvested at 15, 30, and 90 days following in vivo grafting suggested the release of VEGF protein from modVEGF-engineered hADSCs significantly improved neo-angiogenesis, vascular maturity, and cell proliferation. The modVEGF-engineered hADSCs also significantly mitigated the presence of fibrosis, apoptosis, and necrosis of grafts when compared to the control groups. Moreover, modVEGF-engineered hADSCs promoted graft survival and cell differentiation abilities, which also induced an increase in vessel formation and the number of surviving adipocytes after transplantation.

Conclusion

This current study demonstrates the employment of modVEGF-engineered hADSCs as an advanced alternative to the clinical treatment involving soft-tissue reconstruction and rejuvenation.
Norm inequalities for submultiplicative functions involving contraction sector $2 \times 2$ block matrices
Authors: Zhou Xiaoying
Published: November 2020

In this article, we show unitarily invariant norm inequalities for sector $2\times 2$
2
×
2
block matrices which extend and refine some recent results of Bourahli, Hirzallah, and Kittaneh (Positivity, 2020, 10.1007/s11117-020-00770-w).
Modified differential transform method for solving linear and nonlinear pantograph type of differential and Volterra integro-differential equations with proportional delays
Authors: Moosavi Noori Seyyedeh Roodabeh , Taghizadeh Nasir
Published: November 2020

In this study, a hybrid technique for improving the differential transform method (DTM), namely the modified differential transform method (MDTM) expressed as a combination of the differential transform method, Laplace transforms, and the Padé approximant (LPDTM) is employed for the first time to ascertain exact solutions of linear and nonlinear pantograph type of differential and Volterra integro-differential equations (DEs and VIDEs) with proportional delays. The advantage of this method is its simple and trusty procedure, it solves the equations straightforward and directly without requiring large computational work, perturbations or linearization, and enlarges the domain of convergence, and leads to the exact solution. Also, to validate the reliability and efficiency of the method, some examples and numerical results are provided.
Improving agreement of ASA physical status class between pre-anesthesia screening and day of surgery by adding institutional-specific and ASA-approved examples: a quality improvement project
Authors: Abouleish Amr E. , Vinta Sandhya R. , Shabot Sarah M. , Patel Nikul V. , Hurwitz Erin E. , Krishnamurthy Partha , Simon Michelle
Published: November 2020

Background

A successful anesthesia pre-assessment clinic needs to identify patients who need further testing, evaluation, and optimization prior to the day of surgery to avoid delays and cancelations. Although the ASA Physical Status Classification system (ASA PS) has been used widely for over 50 years, it has poor interrater agreement when only using the definitions. In 2014, ASA-approved examples for each ASA physical status class (ASA PS). In this quality improvement study, we developed and evaluated the effectiveness of institutional-specific examples on interrater reliability between anesthesia pre-anesthesia clinic (APAC) and the day of surgery evaluation (DOS).

Methods

A multi-step, multi-year quality improvement project was performed. Step 1, pre-intervention, was a retrospective review to determine the percentage agreement of ASA PS assignment between APAC and DOS for adult and pediatric patients. Step 2 was a retrospective review of the step 1 cases where the ASA PS assignment differed to determine which medical conditions were valued differently and then develop institutional-specific examples for medical conditions not addressed by ASA-approved examples. Step 3 was to educate clinicians about the newly implemented examples and how they should be used as a guide. Step 4, post-intervention, was a retrospective review to determine if the examples improved agreement between APAC and DOS ASA PS assignments. Weighted Kappa coefficient was used to measure of interrater agreement excluding chance agreement.

Results

Having only ASA PS definitions available, APAC and DOS agreement was only 74% for adults (n = 737) and 63% for pediatric patients (n = 216). For adults, 20 medical co-morbidity categories and, for pediatric patients, 9 medical co-morbidity categories accounted for > 90% the differences in ASA PS. After development and implementation of institutional-specific examples with ASA-approved examples, the percentage agreement increased for adult patients (n = 795) to 91% and for pediatric patients (n = 239) to 84%. Weighted Kappa coefficients increased significantly for all patients (from 0.62 to 0.85, p < .0001), adult patients (from 0.62 to 0.86, p < .0001), and pediatric patients (from 0.48 to 0.78, p < .0001).

Conclusions

ASA-approved examples do not address all medical conditions that account for differences in the assignment of ASA PS between pre-anesthesia screening and day of anesthesia evaluation at our institution. The process of developing institutional-specific examples addressed the medical conditions that caused differences in assignment at one institution. The implementation of ASA PS examples improved consistency of assignment, and therefore communication of medical conditions of patients presenting for anesthesia care.
Characteristics of adolescent boys who have displayed harmful sexual behaviour (HSB) against children of younger or equal age
Authors: Jensen Monica , Smid Sanne C. , Bøe Tormod
Published: November 2020

Background

Adolescents who have displayed harmful sexual behaviour (HSB) are often described as a heterogeneous population, but different offender-, offense-, or victim-based typologies have been proposed. Two common typologies are based on the victim’s age and/or on offender–victim age discrepancies.

Methods

Using data from a Norwegian clinical sample, we aimed to investigate the characteristics of two subgroups of adolescents: those with younger/child victims (HSB-C) and peer victims (HSB-P). The sample was collected from a public child and adolescent psychiatry outpatient clinic.N = 54 boys, mean age 14.1 (younger age: HSB-C,n = 30, equal age: HSB-P,n = 24). Based on patient records, all patient registries within the sample were reviewed retrospectively. The data were analysed in R with different statistical tests (e.g. N − 1 chi-square test, Fisher’s exact test).

Results

After adjusting thepvalues for multiple comparisons, none of the test statistics showed significant results. Based on the magnitude of the effect-size estimates, the following tendencies and potential meaningful differences emerged: more adolescents in the HSB-C group had experienced their own trauma early (V = 0.42), had more than one victim (V = 0.32), and had displayed repeated HSB (V = 0.27), and their caregivers required extensive interventions (V = 0.20). More adolescents in the HSB-P group had cognitive abilities in the normal/high range (V = 0.32), and their caregivers more often had difficulties acknowledging the need for support and treatment (V = 0.20).

Conclusions

The nonsignificant differences between the subgroups, despite some strong and moderate effects, bring about a discussion on the utility of using “victim age” in combination with the “offender–victim age differences” as the sole classification criterion for adolescents who have displayed HSB. The heterogeneity of the adolescent HSB population and lack of reliable information on more homogenous subgroups dynamics will remain challenges for clinicians and other practitioners needing a broad assessment and intervention focus.
New approaches to housing complexity: designing dwellings in the age of cognitive economy
Authors: Spanedda Francesco , Fusaro Matteo Carmine
Published: November 2020

Space is produced by a society in accordance with its habits, and habits, mostly in the Western society, have been heavily influenced by forms of production. Indeed, it is widely acknowledged that the Industrial Revolution definitely changed the space of modern landscapes, cities and dwellings life at all scales, and the way in which we perceive them. Cognitive capitalism is no exception. Since it fully established itself as one of the prevailing economic forces in the 21st century and in the Western world, it produced deep changes in the way in which people work, connect, and live. Starting from the assumption that changes in means of production generate new social relationships, this paper investigates how these changes might result in new ways of building architectural space. Without indulging in a deterministic attitude, it focuses on housing as one of the fundamental artefacts where a society expresses its approach to space. The house is a basic element of complex urban systems and is, therefore, the one calling for a more radical conceptual rethinking, marking an effective distance with the forms inherited from the previous centuries. Finally, the paper aims at understanding the repercussions of the digital paradigm on the space of dwelling, reasoning on some crucial questions to understand how housing might evolve, unfolding through its spatial configuration the new ways of life of the digital society.
Size effect characteristics of structural surfaces by improved projective covering method
Authors: Chen S. J. , Chang J. P. , Liu X. G. , Li Z. H.
Published: November 2020

Accurate characteristic of structural surfaces roughness at the relevant scale is very important to understand mechanical properties of rock mass discontinuities. So, a systematic investigation has been carried out to understand the effect of scale on the structural surface roughness by fractal dimension method. Firstly, considering the shortcoming of the projective covering method (PCM), we improved this method based on stochastic approach. Secondly, to investigate the size effect of the structural surface roughness, we selected six sampling windows, respectively, from the central and four corners part of structural planes (2 m × 2 m). The sampling windows range from 62.5 mm × 62.5 mm to 2000 mm × 2000 mm. And then, we calculated fractal parameters of the different size surfaces using improved projective covering method (IPCM) at the same resolution. Thirdly, we discussed a new method of determining reasonable size of structural surfaces by the parameter $$\Delta D_{\max }^{SD}$$

Δ

D

max

SD

. This parameter is difference of the maximum fractal dimension of the same size structural surface in different regions. The results show that: (1) The size effect of structure surfaces is different with different morphological surface. Generally, as the size increases, the roughness of structure surfaces increases and then decreases. There is positive size effect in small scale and negative size effect in large scale. (2) For a given structural surface, when the same size surfaces are selected from different locations of the structural planes, and the size effect characteristics are also different. (3) As the size of structure surfaces increases, the parameter $$\Delta D_{\max }^{SD}$$

Δ

D

max

SD

gradually decreases and tends to almost constant. The result of this study is a useful supplement to the comprehensive understanding of the size effect of structural surfaces roughness.
Food habits in pregnancy and its association with gestational diabetes mellitus: results from a prospective cohort study in public hospitals of urban India
Authors: Deepa R. , Lewis Melissa Glenda , Van Schayck Onno C. P. , Babu Giridhara R.
Published: November 2020

Background

Few studies have explored the relationship between food habits and the risk of gestational diabetes mellitus (GDM) in women from India. We aimed to investigate the associations of food habits and the risk of GDM.

Methods

As part of the MAASTHI prospective cohort study in urban Bengaluru, India, pregnant women between 18 and 45 years, less than 36 weeks of gestation were included. During baseline, the participant’s age, education, physical activity levels, and food habits were recorded. Screening of GDM was done by the World Health Organization diagnostic criteria using a 2-h 75-g oral glucose tolerance test between the 24th–36th weeks of gestation.

Results

We included 1777 pregnant women in the study. We show that 17.6% of the women had GDM, of which 76.7% consume red meat. Red meat consumption was associated with an increased risk of GDM (aRR = 2.1, 95% CI 1.5, 2.9) after adjusting for age, family history of diabetes and socioeconomic status.

Conclusion

The high intake of red meat consumption in pregnancy needs further examination. Also, future evaluations should consider evaluating the risk of red meat consumption against the combined effect of inadequate consumption of vegetables, fruits, and dairy products in pregnant women. Interventions to educate women in lower socioeconomic status on inexpensive, seasonal, and healthy food might be helpful.