bluuebunny/crossref_metadata_2025 huggingface dataset:
The cross-sectional average length of healthy life (HCAL): a measure that summarizes the history of cohort health and mortality
Authors: Sauerberg Markus , Guillot Michel , Luy Marc
Published: August 2020

Background

Healthy life years have superseded life expectancy (LE) as the most important indicator for population health. The most common approach to separate the total number of life years into those spent in good and poor health is the Sullivan method which incorporates the health dimension to the classic period life table, thus transforming the LE indicator into the health expectancy (HE) indicator. However, life years derived from a period life table and health prevalence derived from survey data are based on different conceptual frameworks.

Method

We modify the Sullivan method by combining the health prevalence data with the conceptually better fitting cross-sectional average length of life (CAL). We refer to this alternative HE indicator as the “cross-sectional average length of healthy life” (HCAL). We compare results from this alternative indicator with the conventional Sullivan approach for nine European countries. The analyses are based on EU-SILC data in three empirical applications, including the absolute and relative level of healthy life years, changes between 2008 and 2014, and the extent of the gender gap.

Results

HCAL and conventional HE differ in each of these empirical applications. In general, HCAL provides larger gains in healthy life years in recent years, but at the same time greater declines in the proportion of healthy life years. Regarding the gender gap, HCAL provides a more favourable picture for women compared to conventional HE. Nonetheless, the extent of these differences between the indicators is only of minor extent.

Conclusions

Albeit the differences between HE and HCAL are small, we found some empirical examples in which the two indicators led to different conclusions. It is important to note, however, that the measurement of health and the data quality are much more important for the healthy life years indicator than the choice of the variant of the Sullivan method. Nonetheless, we suggest to use HCAL in addition to HE whenever possible because it widens the spectrum of empirical analyses and serves for verification of results based on the highly sensitive HE indicator.
The crosstalk: exosomes and lipid metabolism
Authors: Wang Wei , Zhu Neng , Yan Tao , Shi Ya-Ning , Chen Jing , Zhang Chan-Juan , Xie Xue-Jiao , Liao Duan-Fang , Qin Li
Published: August 2020

Exosomes have been considered as novel and potent vehicles of intercellular communication, instead of “cell dust”. Exosomes are consistent with anucleate cells, and organelles with lipid bilayer consisting of the proteins and abundant lipid, enhancing their “rigidity” and “flexibility”. Neighboring cells or distant cells are capable of exchanging genetic or metabolic information via exosomes binding to recipient cell and releasing bioactive molecules, such as lipids, proteins, and nucleic acids. Of note, exosomes exert the remarkable effects on lipid metabolism, including the synthesis, transportation and degradation of the lipid. The disorder of lipid metabolism mediated by exosomes leads to the occurrence and progression of diseases, such as atherosclerosis, cancer, non-alcoholic fatty liver disease (NAFLD), obesity and Alzheimer’s diseases and so on. More importantly, lipid metabolism can also affect the production and secretion of exosomes, as well as interactions with the recipient cells. Therefore, exosomes may be applied as effective targets for diagnosis and treatment of diseases.
AKT/FOXO1 axis links cross-talking of endothelial cell and pericyte in TIE2-mutated venous malformations
Authors: Si Yameng , Huang Jiadong , Li Xiang , Fu Yu , Xu Rongyao , Du Yifei , Cheng Jie , Jiang Hongbing
Published: August 2020

Background

Venous malformations (VMs), most of which associated with activating mutations in the endothelial cells (ECs) tyrosine kinase receptor TIE2, are characterized by dilated and immature veins with scarce smooth muscle cells (SMCs) coverage. However, the underlying mechanism of interaction between ECs and SMCs responsible for VMs has not been fully understood.

Methods

Here, we screened 5 patients with TIE2-L914F mutation who were diagnosed with VMs by SNP sequencing, and we compared the expression of platelet-derived growth factor beta (PDGFB) and α-SMA in TIE2 mutant veins and normal veins by immunohistochemistry. In vitro, we generated TIE2-L914F-expressing human umbilical vein endothelial cells (HUVECs) and performed BrdU, CCK-8, transwell and tube formation experiments on none-transfected and transfected ECs. Then we investigated the effects of rapamycin (RAPA) on cellular characteristics. Next we established a co-culture system and investigated the role of AKT/FOXO1/PDGFB in regulating cross-talking of mutant ECs and SMCs.

Results

VMs with TIE2-L914F mutation showed lower expression of PDGFB and α-SMA than normal veins. TIE2 mutant ECs revealed enhanced cell viability and motility, and decreased tube formation, whereas these phenotypes could be reversed by rapamycin. Mechanically, RAPA ameliorated the physiological function of mutant ECs by inhibiting AKT-mTOR pathway, but also facilitated the nuclear location of FOXO1 and the expression of PDGFB in mutant ECs, and then improved paracrine interactions between ECs and SMCs. Moreover, TIE2 mutant ECs strongly accelerated the transition of SMCs from contractile phenotype to synthetic phenotype, whereas RAPA could prevent the phenotype transition of SMCs.

Conclusions

Our data demonstrate a previously unknown mechanistic linkage of AKT-mTOR/FOXO1 pathway between mutant ECs and SMCs in modulating venous dysmorphogenesis, and AKT/FOXO1 axis might be a potential therapeutic target for the recovery of TIE2-mutation causing VMs.

Graphical abstract
Identification and validation of stemness-related lncRNA prognostic signature for breast cancer
Authors: Li Xiaoying , Li Yang , Yu Xinmiao , Jin Feng
Published: August 2020

Background

Long noncoding RNAs (lncRNAs) are emerging as crucial contributors to the development of breast cancer and are involved in the stemness regulation of breast cancer stem cells (BCSCs). LncRNAs are closely associated with the prognosis of breast cancer patients. It is critical to identify BCSC-related lncRNAs with prognostic value in breast cancer.

Methods

A co-expression network of BCSC-related mRNAs-lncRNAs from The Cancer Genome Atlas (TCGA) was constructed. Univariate and multivariate Cox proportional hazards analyses were used to identify a stemness risk model with prognostic value. Kaplan–Meier analysis, univariate and multivariate Cox regression analyses and receiver operating characteristic (ROC) curve analysis were performed to validate the risk model. Principal component analysis (PCA) and Gene Set Enrichment Analysis (GSEA) functional annotation were conducted to analyze the risk model.

Results

In this study, BCSC-related lncRNAs in breast cancer were identified. We evaluated the prognostic value of these BCSC-related lncRNAs and eventually obtained a prognostic risk model consisting of 12 BCSC-related lncRNAs (Z68871.1, LINC00578, AC097639.1, AP003119.3, AP001207.3, LINC00668, AL122010.1, AC245297.3, LINC01871, AP000851.2, AC022509.2 and SEMA3B-AS1). The risk model was further verified as a novel independent prognostic factor for breast cancer patients based on the calculated risk score. Moreover, based on the risk model, the low- risk and high-risk groups displayed different stemness statuses.

Conclusions

These findings suggested that the 12 BCSC-related lncRNA signature might be a promising prognostic factor for breast cancer and can promote the management of BCSC-related therapy in clinical practice.
Genomic landscape of the immune microenvironments of brain metastases in breast cancer
Authors: Lu Wei-cheng , Xie Hui , Yuan Ce , Li Jin-jiang , Li Zhao-yang , Wu An-hua
Published: August 2020

Background

This study was intended to investigate the genomic landscape of the immune microenvironments of brain metastases in breast cancer.

Methods

Three gene expression profile datasets (GSE76714, GSE125989 and GSE43837) of breast cancer with brain metastases were downloaded from Gene Expression Omnibus (GEO) database. After differential expression analysis, the tumor immune microenvironment and immune cell infiltration were analyzed. Then immune-related genes were identified, followed by function analysis, transcription factor (TF)-miRNA–mRNA co-regulatory network analysis, and survival analysis of metastatic recurrence.

Results

The present results showed that the tumor immune microenvironment in brain metastases was immunosuppressed compared with primary caner. Compared with primary cancer samples, the infiltration ratio of plasma cells in brain metastases samples was significantly higher, while the infiltration ratio of macrophages M2 cells in brain metastases samples was significantly lower. Total 42 immune-related genes were identified, such asTHY1andNEU2.CD1B,THY1andDOCK2were found to be implicated in the metastatic recurrence of breast cancer.

Conclusions

Targeting macrophages or plasma cells may be new strategies for immunotherapy of breast cancer with brain metastases.THY1andNEU2may be potential therapeutic targets for breast cancer with brain metastases, andTHY1,CD1BandDOCK2may serve as potential prognostic markers for improvement of brain metastases survival.
Emerging of a SARS-CoV-2 viral strain with a deletion in nsp1
Authors: Benedetti Francesca , Snyder Greg A. , Giovanetti Marta , Angeletti Silvia , Gallo Robert C. , Ciccozzi Massimo , Zella Davide
Published: August 2020

Background

The new Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first detected in Wuhan (China) in December of 2019 is responsible for the current global pandemic. Phylogenetic analysis revealed that it is similar to other betacoronaviruses, such as SARS-CoV and Middle-Eastern Respiratory Syndrome, MERS-CoV. Its genome is ∼ 30 kb in length and contains two large overlapping polyproteins, ORF1a and ORF1ab that encode for several structural and non-structural proteins. The non-structural protein 1 (nsp1) is arguably the most important pathogenic determinant, and previous studies on SARS-CoV indicate that it is both involved in viral replication and hampering the innate immune system response. Detailed experiments of site-specific mutagenesis and in vitro reconstitution studies determined that the mechanisms of action are mediated by (a) the presence of specific amino acid residues of nsp1 and (b) the interaction between the protein and the host’s small ribosomal unit. In fact, substitution of certain amino acids resulted in reduction of its negative effects.

Methods

A total of 17,928 genome sequences were obtained from the GISAID database (December 2019 to July 2020) from patients infected by SARS-CoV-2 from different areas around the world. Genomes alignment was performed using MAFFT (REFF) and the nsp1 genomic regions were identified using BioEdit and verified using BLAST. Nsp1 protein of SARS-CoV-2 with and without deletion have been subsequently modelled using I-TASSER.

Results

We identified SARS-CoV-2 genome sequences, from several Countries, carrying a previously unknown deletion of 9 nucleotides in position 686-694, corresponding to the AA position 241-243 (KSF). This deletion was found in different geographical areas. Structural prediction modelling suggests an effect on the C-terminal tail structure.

Conclusions

Modelling analysis of a newly identified deletion of 3 amino acids (KSF) of SARS-CoV-2 nsp1 suggests that this deletion could affect the structure of the C-terminal region of the protein, important for regulation of viral replication and negative effect on host’s gene expression. In addition, substitution of the two amino acids (KS) from nsp1 of SARS-CoV was previously reported to revert loss of interferon-alpha expression. The deletion that we describe indicates that SARS-CoV-2 is undergoing profound genomic changes. It is important to: (i) confirm the spreading of this particular viral strain, and potentially of strains with other deletions in the nsp1 protein, both in the population of asymptomatic and pauci-symptomatic subjects, and (ii) correlate these changes in nsp1 with potential decreased viral pathogenicity.
“They haven’t asked me. I haven’t told them either”: fertility plan discussions between women living with HIV and healthcare providers in western Ethiopia
Authors: Feyissa Tesfaye Regassa , Harris Melissa L. , Loxton Deborah
Published: August 2020

Background

Despite the importance of women living with HIV (WLHIV) engaging in fertility plan discussions with their healthcare providers (HCPs), little research exists. This study explored perceptions surrounding fertility plan discussions between WLHIV and their HCPs in western Ethiopia, from the perspectives of both women and providers.

Methods

Thirty-one interviews (27 with WLHIV and 4 with HCPs) were conducted at four healthcare facilities in western Ethiopia in 2018. Data were transcribed verbatim and translated into English. Codes and themes were identified using inductive thematic analysis.

Results

There was a discordance between HCPs and WLHIV’s perception regarding the delivery of fertility plan discussions. Only nine of the 27 WLHIV reported they had discussed their personal fertility plans with their HCPs. When discussions did occur, safer conception and contraceptive use were the primary focus. Referrals to mother support groups, adherence counsellors as well as family planning clinics (where they can access reproductive counselling) facilitated fertility discussions. However, lack of initiating discussions by either HCPs or women, high client load and insufficient staffing, and a poor referral system were barriers to discussing fertility plans. Where discussions did occur, barriers to good quality interactions were: (a) lack of recognizing women’s fertility needs; (b) a lack of time and being overworked; (c) mismatched fertility desire among couples; (d) non-disclosure of HIV-positive status to a partner; (e) poor partner involvement; (f) fear of repercussions of disclosing fertility desires to a HCP; and (g) HCPs fear of seroconversion.

Conclusions

Our findings highlight the need for policies and guidelines to support fertility plan discussions. Training of HCPs, provision of non-judgmental and client-centered fertility counselling, improving integration of services along with increased human resources are crucial to counselling provision. Enhancing partner involvement, and supporting and training mother support groups and adherence counsellors in providing fertility plan discussions are crucial to improving safer conception and effective contraceptive use, which helps in having healthy babies and reducing HIV transmission.
Characterization of integrated prophages within diverse species of clinical nontuberculous mycobacteria
Authors: Glickman Cody , Kammlade Sara M. , Hasan Nabeeh A. , Epperson L. Elaine , Davidson Rebecca M. , Strong Michael
Published: August 2020

Background

Nontuberculous mycobacterial (NTM) infections are increasing in prevalence, with current estimates suggesting that over 100,000 people in the United States are affected each year. It is unclear how certain species of mycobacteria transition from environmental bacteria to clinical pathogens, or what genetic elements influence the differences in virulence among strains of the same species. A potential mechanism of genetic evolution and diversity within mycobacteria is the presence of integrated viruses called prophages in the host genome. Prophages may act as carriers of bacterial genes, with the potential of altering bacterial fitness through horizontal gene transfer. In this study, we quantify the frequency and composition of prophages within mycobacteria isolated from clinical samples and compare them against the composition of PhagesDB, an environmental mycobacteriophage database.

Methods

Prophages were predicted by agreement between two discovery tools, VirSorter and Phaster, and the frequencies of integrated prophages were compared by growth rate. Prophages were assigned to PhagesDB lettered clusters. Bacterial virulence gene frequency was calculated using a combination of the Virulence Factor Database (VFDB) and the Pathosystems Resource Integration Center virulence database (Patric-VF) within the gene annotation software Prokka. CRISPR elements were discovered using CRT. ARAGORN was used to quantify tRNAs.

Results

Rapidly growing mycobacteria (RGM) were more likely to contain prophage than slowly growing mycobacteria (SGM). CRISPR elements were not associated with prophage abundance in mycobacteria. The abundance of tRNAs was enriched in SGM compared to RGM.

We compared the abundance of bacterial virulence genes within prophage genomes from clinical isolates to mycobacteriophages from PhagesDB. Our data suggests that prophages from clinical mycobacteria are enriched for bacterial virulence genes relative to environmental mycobacteriophage from PhagesDB.

Conclusion

Prophages are present in clinical NTM isolates. Prophages are more likely to be present in RGM compared to SGM genomes. The mechanism and selective advantage of this enrichment by growth rate remain unclear. In addition, the frequency of bacterial virulence genes in prophages from clinical NTM is enriched relative to the PhagesDB environmental proxy. This suggests prophages may act as a reservoir of genetic elements bacteria could use to thrive within a clinical environment.
High intensity exercise downregulates FTO mRNA expression during the early stages of recovery in young males and females
Authors: Danaher Jessica , Stathis Christos G. , Wilson Robin A. , Moreno-Asso Alba , Wellard R. Mark , Cooke Matthew B.
Published: August 2020

Background

Physical exercise and activity status may modify the effect of the fat mass- and obesity-associated (FTO) genotype on body weight and obesity risk. To understand the interaction between FTO’s effect and physical activity, the present study investigated the effects of high and low intensity exercise on FTO mRNA and protein expression, and potential modifiers of exercise-induced changes in FTO in healthy-weighted individuals.

Methods

Twenty-eight untrained males and females (25.4 ± 1.1 years; 73.1 ± 2.0 kg; 178.8 ± 1.4 cm; 39.0 ± 1.2 ml.kg.min− 1 VO2peak) were genotyped for the FTO rs9939609 (T > A) polymorphism and performed isocaloric (400 kcal) cycle ergometer exercise on two separate occasions at different intensities: 80% (High Intensity (HI)) and 40% (Low Intensity (LO)) VO2peak. Skeletal muscle biopsies (vastus lateralis) and blood samples were taken pre-exercise and following 10 and 90 mins passive recovery.

Results

FTO mRNA expression was significantly decreased after HI intensity exercise (p = 0.003). No differences in basal and post-exercise FTO protein expression were evident between FTO genotypes. Phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and Akt substrate of 160 kDa (AS160) were significantly increased following HI intensity exercise (p < 0.05). Multivariate models of metabolomic data (orthogonal two partial least squares discriminant analysis (O2PLS-DA)) were unable to detect any significant metabolic differences between genotypes with either exercise trial (p > 0.05). However, skeletal muscle glucose accumulation at 10 mins following HI (p = 0.021) and LO (p = 0.033) intensity exercise was greater in AA genotypes compared to TT genotypes.

Conclusion

Our novel data provides preliminary evidence regarding the effects of exercise on FTO expression in skeletal muscle. Specifically, high intensity exercise downregulates expression of FTO mRNA and suggests that in addition to nutritional regulation, FTO could also be regulated by exercise.

Trial registration

ACTRN12612001230842. Registered 21 November 2012 – Prospectively registered, https://www.anzctr.org.au/
An overview of the commercial determinants of health
Authors: Mialon Melissa
Published: August 2020

Background

Different terms are described in the literature that refer to commercial determinants as drivers of ill-health. The aim of the present review was to provide an overview of the commercial determinants of health, through a review of the literature on this subject. The review was conducted in December 2019 and updated in February 2020. Searches were conducted from peer-reviewed scientific articles, commentaries, books, and books chapters, with no restriction in their publication dates and languages.

Main body

The commercial determinants of health cover three areas. First, they relate to unhealthy commodities that are contributing to ill-health. Secondly, they include business, market and political practices that are harmful to health and used to sell these commodities and secure a favourable policy environment. Finally, they include the global drivers of ill-health, such as market-driven economies and globalisation, that have facilitated the use of such harmful practices.

Short conclusion

The discussion on the commercial determinants of health offers a unique opportunity to shift the dominant paradigm in public health, where individual behaviours are considered to be driven by inadequate environments. Ill-health, damages to the environment, and health and social inequalities, might be better understood through a commercial determinant lens.
An ethnoveterinary study on medicinal plants used by the Buyi people in Southwest Guizhou, China
Authors: Xiong Yong , Long Chunlin
Published: August 2020

Background

The Buyi (Bouyei) people in Qianxinan Buyi and Miao Autonomous Prefecture, Southwest Guizhou, China, have used medicinal plants and traditional remedies for ethnoveterinary practices, such as treating domestic animals during livestock breeding, since ancient times. However, the unique ethnoveterinary practices of the Buyi have rarely been recorded. This study aimed to identify the plants used in their traditional ethnoveterinary practices, and to propose suggestions for future conservation and sustainable use of this knowledge.

Methods

Ethnobotanical fieldwork was conducted in 19 villages/townships in Qianxinan Prefecture between 2017 and 2018. Data were collected from the local Buyi people through semi-structured interviews and participatory observations. The informant consensus factor (FIC) and use reports (URs) were utilized to evaluate the consent of the current ethnoveterinary practices among the local communities, and 83 informants were interviewed during the field investigations. Plant samples and voucher specimens were collected for taxonomic identification.

Results

A total of 122 plant species, belonging to 60 families and 114 genera, were recorded as being used in ethnoveterinary practices by the Buyi people. The most used ethnoveterinary medicinal plant (EMP) parts included the roots, whole plant, and bulb, and the most common preparation methods included decoction, crushing, and boiling. Some EMPs, such as Quisqualis indica and Paris polyphylla, have special preparation methods. The informant consensus factor (FIC) and use reports (URs) of the EMP species were analyzed. Twenty EMP species with the highest URs were noted as having particular importance in the daily lives of Buyi people in Qianxinan Prefecture.

Conclusion

In this study, we identified traditional ethnoveterinary knowledge of the medicinal plants among the Buyi communities in Qianxinan Prefecture. This knowledge has previously been limited to local vets, herders, and aged community members. Plants with important medicinal uses need to be validated phytochemically and pharmacologically in the future, to develop new alternative drugs for veterinary purposes.
Reconstruction method and optimum range of camera-shooting angle for 3D plant modeling using a multi-camera photography system
Authors: Lu Xingtong , Ono Eiichi , Lu Shan , Zhang Yu , Teng Poching , Aono Mitsuko , Shimizu Yo , Hosoi Fumiki , Omasa Kenji
Published: August 2020

Background

Measurement of plant structure is useful in monitoring plant conditions and understanding the responses of plants to environmental changes. 3D imaging technologies, especially the passive-SfM (Structure from Motion) algorithm combined with a multi-camera photography (MCP) system has been studied to measure plant structure due to its low-cost, close-range, and rapid image capturing ability. However, reconstruction of 3D plant models with complex structure is a time-consuming process and some systems have failed to reconstruct 3D models properly. Therefore, an MCP based SfM system was developed and an appropriate reconstruction method and optimal range of camera-shooting angles were investigated.

Results

An MCP system which utilized 10 cameras and a rotary table for plant was developed. The 3D mesh model of a single leaf reconstruction using a set of images taken at each viewing zenith angle (VZA) from 12° (C2 camera) to 60° (C6 camera) by the MCP based SfM system had less undetected or unstable regions in comparison with other VZAs. The 3D mesh model of a whole plant, which merged 3D dense point cloud models built from a set of images taken at each appropriate VZA (Method 1), had high accuracy. The Method 1 error percentages for leaf area, leaf length, leaf width, stem height, and stem width are in the range of 2.6–4.4%, 0.2–2.2%, 1.0–4.9%, 1.9–2.8%, and 2.6–5.7% respectively. Also, the error of the leaf inclination angle was less than 5°. Conversely, the 3D mesh model of a whole plant built directly from a set of images taken at all appropriate VZAs (Method 2) had lower accuracy than that of Method 1. For Method 2, the error percentages of leaf area, leaf length, and leaf width are in the range of 3.1–13.3%, 0.4–3.3%, and 1.6–8.6%, respectively. It was difficult to obtain the error percentages of stem height and stem width because some information was missing in this model. In addition, the calculation time for Method 2 was 1.97 times longer computational time in comparison to Method 1.

Conclusions

In this study, we determined the optimal shooting angles on the MCP based SfM system developed. We found that it is better in terms of computational time and accuracy to merge partial 3D models from images taken at each appropriate VZA, then construct complete 3D model (Method 1), rather than to construct 3D model by using images taken at all appropriate VZAs (Method 2). This is because utilization of incorporation of incomplete images to match feature points could result in reduced accuracy in 3D models and the increase in computational time for 3D model reconstruction.
Recent changes in trends of opioid overdose deaths in North America
Authors: Imtiaz Sameer , Shield Kevin D. , Fischer Benedikt , Elton-Marshall Tara , Sornpaisarn Bundit , Probst Charlotte , Rehm Jürgen
Published: August 2020

Background

As several regulatory and environmental changes have occurred in North America, trends in overdose deaths were examined in the United States (US), Ontario and British Columbia (BC), including changes in consumption levels of prescription opioids (PO) and overdose deaths, changes in correlations between consumption levels of PO and overdose deaths and modeled differences between observed and predicted overdose deaths if no changes had occurred.

Methods

Consumption levels of PO included defined daily doses for statistical purposes per million inhabitants per day for the US and Canada (2001–2015). Overdose deaths included opioid overdose deaths for the US (2001–2017) and Ontario (2003–2017) and illicit drug overdose deaths for BC (2001–2017). The analytic techniques included structural break point analyses, Pearson product-moment correlations and multivariate Gaussian state space modeling.

Results

Consumption levels of PO changed in the US in 2010 and in Canada in 2012. Overdose deaths changed in the US in 2014 and in Ontario and BC in 2015. Prior to the observed changes in consumption levels of PO, there were positive correlations between consumption levels of PO and overdose deaths in the US (r = 0.99, p < 0.001) and Ontario (r = 0.92, p = 0.003). After the observed changes in consumption levels of PO, there was a negative correlation between consumption levels of PO and overdose deaths in the US (r = − 0.99, p = 0.002). Observed overdose deaths exceeded predicted overdose deaths by 5.7 (95% Confidence Interval [CI]: 4.8–6.6), 3.5 (95% CI: 3.2–3.8) and 21.8 (95% CI: 18.6–24.9) deaths per 100,000 people in the US, Ontario and BC, respectively in 2017. These excess deaths corresponded to 37.7% (95% CI: 31.9–43.6), 39.2% (95% CI: 36.3–42.1) and 72.2% (95% CI: 61.8–82.6) of observed overdose deaths in the US, Ontario and BC, respectively in 2017.

Conclusions

The opioid crisis has evolved in North America, as a sizeable proportion of overdose deaths are now attributable to the several regulatory and environmental changes. These findings necessitate substance use policies to be conceptualized more broadly as well as the continued expansion of harm reduction services and types of pharmacotherapy interventions.
Grade III blunt splenic injury without contrast extravasation - World Society of Emergency Surgery Nijmegen consensus practice
Authors: Amico Francesco , Anning Rebecca , Bendinelli Cino , Balogh Zsolt J. ,   Participants of the 2019 World Society of Emergency Surgery (WSES) Nijmegen splenic injury collaboration group., Leppäniemi Ari , Aparicio-Sánchez Daniel , Hermans Erik , Coccolini Federico , Abu-Zidan Fikri M. , Chiarugi Massimo , Arvieux Catherine , Pirozzolo Giovanni , Khokha Vladimir , Tolonen Matti , Edward Tan , Sugrue Michael , Ceresoli Marco , Muhrbeck Måns , Mohan Rajashekar , Piscioneri Frank , Ietto Giuseppe , Chiara Osvaldo , Catena Fausto
Published: August 2020

Background

Recent trauma guidelines recommend non-operative management for grade III splenic injury without contrast extravasation on computed tomography. Nevertheless, such recommendations rely on low-quality evidence, and practice variation characterizes clinical management for this type of injury. We aimed to identify the role of eleven selected clinical factors influencing the management of grade III splenic injury without contrast extravasation by expert consensus and a modified Delphi approach.

Methods

A questionnaire was developed with the endorsement of the World Society of Emergency Surgery (WSES). This was delivered and answered live by acute care surgeons attending the 6th WSES congress in Nijmegen in 2019. A dedicated mobile phone application was utilized to collect the answers. All answers were evaluated for areas of discrepancy with an 80% threshold for consensus between respondents.

Results

Three factors generated discrepancy in opinion for managing this pattern of injury: the patients’ injury severity, the presence of a bleeding diathesis, and an associated intra-abdominal injury. Agreement was obtained for the other eight factors.

Conclusion

Researchers should focus their efforts on the identified area of discrepancy. Clinicians should use additional care in the presence of the three factors for which discordant opinions were found.
Training to identify red flags in the acute care of trauma: who are the patients at risk for early death despite a relatively good prognosis? An analysis from the TraumaRegister DGU®
Authors: Nolte Philip-C. , Häske David , Lefering Rolf , Bernhard Michael , Casu Sebastian , Frankenhauser Susanne , Gather Andreas , Grützner Paul A. , Münzberg Matthias ,   the TraumaRegister DGU
Published: August 2020

Background

In the acute care of trauma, some patients with a low estimated risk of death die suddenly and unexpectedly. In this study, we aim to identify predictors for early death within 24 h following hospital admission in low-risk patients.

Methods

The TraumaRegister DGU® was used to collect records of patients who were primarily treated in a participating hospital between 2004 and 2013 with a RISC II score below 10%.

Results

During the study period, 64,379 patients met the inclusion criteria. The mean RISC II score was 2.0%, and the mean ISS was 16 ± 9. The overall hospital mortality rate was 2.1%, and 0.5% of patients (n = 301) died within the first 24 h. A SPB of ≤ 90 mmHg was associated with an increased risk of death (p < 0.001). An AIS abdomen score of ≥ 3 was associated with increased risk of death within the first 24 h (p < 0.001). A high risk of early death was also seen in patients with an AIS score (thorax) ≥ 3; 51% of those who died died within the first 24 h (p < 0.005). Death in patients over 60 years was more common after 24 h (p < 0.001). Patients with an ASA score of ≥ 3 were more likely to die after the first 24 h (p < 0.001).

Conclusions

Indicators predicting a high risk of early death in patients with a low RISC II score include a SPB ≤ 90 mmHg and severe chest and abdominal trauma. Emergency teams involved in the acute care of trauma patients should be aware of these “red flags” and treat their patients accordingly.
How the clinical dosage of bone cement biomechanically affects adjacent vertebrae
Authors: Chen Xu-shi , Jiang Jian-ming , Sun Pei-dong , Zhang Zhao-fei , Ren Hai-long
Published: August 2020

Objective

This study evaluated the biomechanical changes in the adjacent vertebrae under a physiological load (500 N) when the clinically relevant amount of bone cement was injected into fractured cadaver vertebral bodies.

Methods

The embalmed cadaver thoracolumbar specimens in which each vertebral body (T12–L2) had a BMD of < 0.75 g/cm2 were used for the experiment. For establishing a fracture model, the upper one third of the L1 vertebra was performed wedge osteotomy and the superior endplate was kept complete. Stiffness of specimens was measured in different states. Strain of the adjacent vertebral body and intervertebral disc were measured in pre-fracture, post-fracture, and after augmentation by non-contact optical strain measurement system.

Results

The average amount of bone cement was 4.4 ml (3.8–5.0 ml). The stiffness of after augmentation was significantly higher than the stiffness of post-fracture (p < 0.05), but still lower than pre-fracture stiffness (p < 0.05). After augmentation, the adjacent upper vertebral strain showed no significant difference (p > 0.05) with pre-fracture, while the strain of adjacent lower vertebral body was significantly higher than that before fracture (p < 0.05). In flexion, T12/L1 intervertebral disc strain was significantly greater after augmentation than after the fracture (p < 0.05), but there was no significant difference from that before the fracture (p > 0.05); L1/2 vertebral strain after augmentation was significantly less than that after the fracture (p < 0.05), but there was no significant difference from that before the fracture (p > 0.05).

Conclusions

PVP may therefore have partially reversed the abnormal strain state of adjacent vertebral bodies which was caused by fracture.
Clinical profiles and risk factors of 7-day and 30-day mortality among 160 pediatric patients with hemophagocytic lymphohistiocytosis
Authors: Li Xun , Yan Haipeng , Zhang Xinping , Huang Jiaotian , Xiang Shi-Ting , Yao Zhenya , Zang Ping , Zhu Desheng , Xiao Zhenghui , Lu Xiulan
Published: August 2020

Background

Hemophagocytic lymphohistiocytosis (HLH) is a relatively rare and life-threatening disorder. Early mortality remains significantly high among patients with HLH. Our aim was to investigate clinical features and risk factors associated with 7-day and 30-day mortality among pediatric HLH patients. We retrospectively collected medical records of patients with discharge diagnosis of HLH between August 2014 and October 2018 from a tertiary children’s hospital in China. The main outcome measures were the 7-day and 30-day outcome after hospital admission. The associations between symptoms, concomitant diagnoses, laboratory test results, and the risk of 7-day and 30-day mortality were examined.

Results

Among 160 pediatric HLH patients, 18 (11.3%) patients were deceased within 7 days after admission, and 46 (28.8%) patients were deceased within 30 days. The identified strong risk factors (OR > 10 and p < 0.05) for 30-day mortality were myocardial damage, severe pneumonia, respiratory failure, coagulopathy, gastrointestinal disorder, and multiple organ dysfunction syndrome (MODS). Factors strongly associated with 7-day mortality were sepsis, myocardial damage, shock, and respiratory failure. All patients deceased within 7 days developed hepatic dysfunction, coagulopathy, and MODS.

Conclusions

The identified risk factors could help to stratify patients with high risk of early death, and need to be considered in the development of treatment protocols. As early mortality of HLH remains high, studies are needed to investigate how to initiate adequate HLH-directed treatment strategies for patients at higher risk of early death.
The human microbiome and its link in prostate cancer risk and pathogenesis
Authors: Katongole Paul , Sande Obondo J. , Joloba Moses , Reynolds Steven J. , Niyonzima Nixon
Published: August 2020

There is growing evidence of the microbiome’s role in human health and disease since the human microbiome project. The microbiome plays a vital role in influencing cancer risk and pathogenesis. Several studies indicate microbial pathogens to account for over 15–20% of all cancers. Furthermore, the interaction of the microbiota, especially the gut microbiota in influencing response to chemotherapy, immunotherapy, and radiotherapy remains an area of active research. Certain microbial species have been linked to the improved clinical outcome when on different cancer therapies. The recent discovery of the urinary microbiome has enabled the study to understand its connection to genitourinary malignancies, especially prostate cancer. Prostate cancer is the second most common cancer in males worldwide. Therefore research into understanding the factors and mechanisms associated with prostate cancer etiology, pathogenesis, and disease progression is of utmost importance. In this review, we explore the current literature concerning the link between the gut and urinary microbiome and prostate cancer risk and pathogenesis.
Intact gastro-intestinal tract removal from pig carcasses in a novel Meat Factory Cell approach
Authors: Alvseike Ole , Prieto Miguel , Bjørnstad Per Håkon , Mason Alex
Published: August 2020

Conventional automated slaughter lines for pigs are organised as disassembly lines with many specialised machines. High costs and capacities make them relevant only for large scale meat production. The ambition with the novel Meat Factory Cell (MFC) concept is to provide the meat industry with a robust and flexible automation platform that is also relevant for smaller scale production. The MFC process deviates radically from conventional processing of pig carcasses after singeing. In MFC, the limbs are removed first. Then the dorsal muscles along the spinal axis from tail to head are removed with the column and rind in one meat cut, followed by removal of the viscera. Finally, the cut ribs and belly are removed. Such approaches to automation in pig abattoirs and cutting plants are highly needed in smaller scale production, and they should produce meat and offal as hygienically as conventional factories. This case study reports the evisceration of 37 pigs in 9 trials performed in 2019. Several approaches were tested with a prototype carcass holding unit. Evisceration could be undertaken without the need to cut through the gastrointestinal tract from tongue to rectum, reducing the probability of accidental faecal contamination of pork carcasses from the gut content. The Meat Factory Cell procedure is an advance towards automated evisceration of pig carcasses which is both simple and hygienic. The traditional separation of internal organs into a pluck set and a set of stomach and bowels was more prone to leakages.
Conditional knockout of leptin receptor in neural stem cells leads to obesity in mice and affects neuronal differentiation in the hypothalamus early after birth
Authors: Ren Zhonggan , Liu Yitong , Hong Wentong , Pan Xinjie , Gong Pifang , Liu Qiong , Zhou Guomin , Qin Song
Published: August 2020

Leptin, secreted by peripheral adipocytes, binds the leptin receptor (Lepr) in the hypothalamus, thereby contributing to the regulation of satiety and body weight. Lepr is expressed in the embryonic brain as early as embryonic day 12.5. However, the function of Lepr in neural precursor cells in the brain has not been resolved. To address this issue, we crossed the Leprflox/flox mice with each of Shh-Cre mice (Shh, sonic hedgehog) and Nestin (Nes)-Cre mice. We found that deletion of Lepr specifically in nestin-expressing cells led to extreme obesity, but the conditional null of Lepr in Shh-expressing cells had no obvious phenotype. Moreover, the level of leptin-activated pSTAT3 decreased in the anterior and central subregions of the arcuate hypothalamus of Shh-Cre; Leprflox/flox mice compared with the controls. By contrast, in Nes-Cre; Leprflox/flox mice, the level of leptin-activated pSTAT3 decreased in all subregions including the anterior, central, and posterior arcuate hypothalamus as well as the dorsomedial, ventromedial, and median eminence of the hypothalamus, revealing that the extensive lack of Lepr in the differentiated neurons of the hypothalamus in the conditional null mice. Notably, conditional deletion of Lepr in nestin-expressing cells enhanced the differentiation of neural precursor cells into neurons and oligodendroglia but inhibited differentiation into astrocytes early in postnatal development of hypothalamus. Our results suggest that Lepr expression in neural precursor cells is essential for maintaining normal body weight as well as the differentiation of neural precursor cells to the neural/glial fate in the hypothalamus shortly after birth.
Dendritic cell biology and its role in tumor immunotherapy
Authors: Wang Yingying , Xiang Ying , Xin Victoria W. , Wang Xian-Wang , Peng Xiao-Chun , Liu Xiao-Qin , Wang Dong , Li Na , Cheng Jun-Ting , Lyv Yan-Ning , Cui Shu-Zhong , Ma Zhaowu , Zhang Qing , Xin Hong-Wu
Published: August 2020

As crucial antigen presenting cells, dendritic cells (DCs) play a vital role in tumor immunotherapy. Taking into account the many recent advances in DC biology, we discuss how DCs (1) recognize pathogenic antigens with pattern recognition receptors through specific phagocytosis and through non-specific micropinocytosis, (2) process antigens into small peptides with proper sizes and sequences, and (3) present MHC-peptides to CD4+ and CD8+ T cells to initiate immune responses against invading microbes and aberrant host cells. During anti-tumor immune responses, DC-derived exosomes were discovered to participate in antigen presentation. T cell microvillar dynamics and TCR conformational changes were demonstrated upon DC antigen presentation. Caspase-11-driven hyperactive DCs were recently reported to convert effectors into memory T cells. DCs were also reported to crosstalk with NK cells. Additionally, DCs are the most important sentinel cells for immune surveillance in the tumor microenvironment. Alongside DC biology, we review the latest developments for DC-based tumor immunotherapy in preclinical studies and clinical trials. Personalized DC vaccine-induced T cell immunity, which targets tumor-specific antigens, has been demonstrated to be a promising form of tumor immunotherapy in patients with melanoma. Importantly, allogeneic-IgG-loaded and HLA-restricted neoantigen DC vaccines were discovered to have robust anti-tumor effects in mice. Our comprehensive review of DC biology and its role in tumor immunotherapy aids in the understanding of DCs as the mentors of T cells and as novel tumor immunotherapy cells with immense potential.
Circular RNA circ-CPA4/ let-7 miRNA/PD-L1 axis regulates cell growth, stemness, drug resistance and immune evasion in non-small cell lung cancer (NSCLC)
Authors: Hong Weijun , Xue Min , Jiang Jun , Zhang Yajuan , Gao Xiwen
Published: August 2020

Background

Non-small cell lung cancer (NSCLC) cells derived intracellular and extracellular programmed cell death ligand 1 (PD-L1) promoted cancer progression and drug resistance, and facilitated tumor immune evasion. However, the detailed molecular mechanisms are still largely unknown. In the present study, we aimed to explore the role of circular RNA circ-CPA4/let-7 miRNA/PD-L1 axis in the regulation of NSCLC progression, drug resistance and tumor immune microenvironment.

Methods

Real-Time qPCR and Western Blot analysis were conducted to examine gene expressions at transcriptional and translated levels, respectively. The regulatory mechanisms of circ-CPA4, let-7 miRNA and PD-L1 were validated by dual-luciferase reporter gene system and RNA pull-down assay. Cell growth and apoptosis were determined by CCK-8 assay, colony formation assay and Annexin V-FITC/PI double staining assay. Cell mobility was evaluated by transwell assay.

Results

Circ-CPA4 and PD-L1 were high-expressed, while let-7 miRNA was low-expressed in NSCLC cells and cancer tissues compared to the human bronchial epithelial (HBE) cells and their paired clinical normal adjacent tissues, respectively. Besides, knock-down of circ-CPA4 inhibited cell growth, mobility and epithelial-mesenchymal transition (EMT), and promoted cell death in NSCLC cells by downregulating PD-L1 through serving as a RNA sponge for let-7 miRNA. In addition, the NSCLC cells derived PD-L1-containing exosomes promoted cell stemness and increased resistance of NSCLC cells to cisplatin. Notably, by co-culturing the NSCLC cells with CD8+ T cells isolated from human peripheral blood mononuclear cells (hPBMCs) in a transwell co-culturing system, we found that NSCLC cells inactivated CD8+ T cells in a secreted PD-L1-dependent manner. Further results suggested that circ-CPA4 also positively regulated exosomal PD-L1, and the NSCLC cells with circ-CPA4 ablation re-activated CD8+ T cells in the co-culturing system.

Conclusion

Taken together, circ-CPA4 regulated cell growth, mobility, stemness and drug resistance in NSCLC cells and inactivated CD8+ T cells in the tumor immune microenvironment through let-7 miRNA/PD-L1 axis.
COL4A1 promotes the growth and metastasis of hepatocellular carcinoma cells by activating FAK-Src signaling
Authors: Wang Ting , Jin Haojie , Hu Jingying , Li Xi , Ruan Haoyu , Xu Huili , Wei Lin , Dong Weihua , Teng Fei , Gu Jianren , Qin Wenxin , Luo Xiaoying , Hao Yujun
Published: August 2020

Background

Collagens are the most abundant proteins in extra cellular matrix and important components of tumor microenvironment. Recent studies have showed that aberrant expression of collagens can influence tumor cell behaviors. However, their roles in hepatocellular carcinoma (HCC) are poorly understood.

Methods

In this study, we screened all 44 collagen members in HCC using whole transcriptome sequencing data from the public datasets, and collagen type IV alpha1 chain (COL4A1) was identified as most significantly differential expressed gene. Expression of COL4A1 was detected in HCC samples by quantitative real-time polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry (IHC). Finally, functions and potential mechanisms of COL4A1 were explored in HCC progression.

Results

COL4A1 is the most significantly overexpressed collagen gene in HCC. Upregulation of COL4A1 facilitates the proliferation, migration and invasion of HCC cells through FAK-Src signaling. Expression of COL4A1 is upregulated by RUNX1 in HCC. HCC cells with high COL4A1 expression are sensitive to the treatment with FAK or Src inhibitor.

Conclusion

COL4A1 facilitates growth and metastasis in HCC via activation of FAK-Src signaling. High level of COL4A1 may be a potential biomarker for diagnosis and treatment with FAK or Src inhibitor for HCC.