bluuebunny/crossref_metadata_2025 huggingface dataset:
Estrogen receptor β induces autophagy of osteosarcoma through the mTOR signaling pathway
Authors: Yang Zhengming , Yu Wei , Liu Bing , Yang Minfei , Tao Huimin
Published: February 2020

Background

Estrogen receptor beta (ERβ) was considered as a tumor-inhibiting factor in estrogen-sensitive malignant tumors. In this study, we intended to investigate whether ERβ was involved in inducing autophagy in osteosarcoma.

Methods

This is an experimental study. The associations between ERβ and autophagy were detected in osteosarcoma U2-OS cells which were treated with E2, E2 + 2,3-Bis (4-hydroxyphenyl) propionitrile (DPN, ERβ agonists), E2 + DPN + water, E2 + DPN + 3-Methyladenine (3-MA, autophagy inhibitor), respectively. Cell viability and death were detected using cell counting kit 8 assay and flow cytometry, respectively. In addition, the expression of autophagy marker LC3II/I, sequestosome 1 (P62), mammalian target of rapamycin (mTOR), and phosphorylated-mTOR (p-mTOR) was determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting.

Results

Cell viability was significantly decreased with DPN treatment, while was reversed with 3-MA treatment. DPN treatment decreased living cells proportion and increased cell apoptosis proportion, while 3-MA treatment reversed those changes. However, there were significant differences between the E2 group and the E2 + DPN + 3-MA group for the living cell proportion and cell apoptosis proportion, suggesting apoptosis and autophagy all were induced. In addition, DPN treatment upregulated the LC3II/I expression level and downregulated P62 and mTOR (mRNA level) and p-mTOR (protein level) expression levels.

Conclusion

ERβ inhibited the cell viability and mediated cell death by inducing apoptosis and autophagy in osteosarcoma. ERβ-induced autophagy in osteosarcoma was associated with downregulating the P62 expression level and inhibiting mTOR activation.
The chloroplasts genomic analyses of Rosa laevigata, R. rugosa and R. canina
Authors: Yin Xianmei , Liao Baosheng , Guo Shuai , Liang Conglian , Pei Jin , Xu Jiang , Chen Shilin
Published: February 2020

Background

Many species of the genusRosahave been used as ornamental plants and traditional medicines. However, industrial development of roses is hampered due to highly divergent characteristics.

Methods

We analyzed the chloroplast (cp) genomes ofRosa laevigata, R. rugosaandR. canina, including the repeat sequences, inverted-repeat (IR) contractions and expansions, and mutation sites.

Results

The size of the cp genome ofR. laevigata, R. rugosaandR. caninawas between 156 333 bp and 156 533 bp, and contained 113 genes (30 tRNA genes, 4 rRNA genes and 79 protein-coding genes). The regions with a higher degree of variation were screened out (trnH-GUU,trnS-GCU,trnG-GCC,psbA-trnH,trnC-GCA,petN,trnT-GGU,psbD,petA,psbJ,ndhF,rpl32,psaCandndhE). Such higher-resolution loci lay the foundation of barcode-based identification of cp genomes inRosagenus. A phylogenetic tree of the genusRosawas reconstructed using the full sequences of the cp genome. These results were largely in accordance with the current taxonomic status ofRosa.

Conclusions

Our data: (i) reveal that cp genomes can be used for the identification and classification ofRosaspecies; (ii) can aid studies on molecular identification, genetic transformation, expression of secondary metabolic pathways and resistant proteins; (iii) can lay a theoretical foundation for the discovery of disease-resistance genes and cultivation ofRosaspecies.
Adverse event rates and economic burden associated with purine nucleoside analogs in patients with hairy cell leukemia: a US population-retrospective claims analysis
Authors: Epperla Narendranath , Pavilack Melissa , Olufade Temitope , Bashyal Richa , Li Jieni , Kabadi Shaum M. , Yuce Huseyin , Andritsos Leslie
Published: February 2020

Background

Purine nucleoside analogs (PNAs) are the recommended first-line treatment for patients with hairy cell leukemia (HCL), but they are associated with adverse events (AEs). Due to a lack of real-world evidence regarding AEs that are associated with PNAs, we used commercial data to assess AE rates, AE-related health care resource utilization (HCRU), and costs among PNA-treated patients with HCL. Adults aged ≥18 years with ≥2 claims for HCL ≥30 days apart from 1 January 2006 through 31 December 2015 were included. Included patients had ≥1 claim for HCL therapy (cladribine ± rituximab or pentostatin ± rituximab [index date: first claim date]) and continuous enrollment for a ≥ 6-month baseline and ≥ 12-month follow-up period. Patient sub-cohorts were based on the occurrence of myelosuppression and opportunistic infections (OIs). Generalized linear models were used to compare HCRU and costs.

Results

In total, 647 PNA-treated patients were identified (mean age: 57.1 years). Myelosuppression and OI incidence were 461 and 42 per 1000 patient-years, respectively. Adjusted results indicated that those with myelosuppression had higher rates of hospitalization (47.4% vs 12.4%; P < .0001) and incurred higher mean inpatient costs ($23,517 vs $12,729; P = .011) and total costs ($57,325 vs $34,733; P = .001) as compared with those without myelosuppression. Similarly, patients with OIs had higher rates of hospitalization (53.8% vs 30.8%; P = .025) and incurred higher mean inpatient costs ($21,494 vs $11,229; P < .0001) as compared with those without OIs.

Conclusions

PNA therapy is highly effective but associated with significant toxicities that increase costs; these findings indicate a need for therapies with improved toxicity profiles and better risk stratification of patients at risk of developing myelosuppression and OIs.
Cervical cancer prevention among long-term screening non-attendees by vaginal self-collected samples for hr-HPV mRNA detection
Authors: Ernstson Avalon , Urdell Annika , Forslund Ola , Borgfeldt Christer
Published: February 2020

Background

The efficacy of cervical cancer screening programs is dependent on the participation rate. To increase participation among women not attending cervical cancer screening, self-collected samples for detection of high-risk human papillomavirus (hr-HPV) may be an option.

The aims of this study were: to investigate the response rate to sending a self-collected vaginal sample for hr-HPV mRNA detection to long-term non-attendees; the compliance with follow-up among women positive for HPV in the self-sample; the prevalence of cervical dysplasia (high grade squamous intraepithelial lesion (HSIL), atypical squamous cells that cannot exclude HSIL (ASC-H) or adenocarcinoma in situ (AIS)) or cancer among the responders; as well as to explore reasons for not returning a self-sample.

Methods

A vaginal self-sampling kit was sent to 6023 women aged 30–70 years who had not provided a cervical screening sample for ≥7 years in the Region of Skåne, Sweden in November and December 2017. The self-sample was analyzed by Aptima HPV mRNA assay (Hologic). All vaginal self-samples returned no later than May 31, 2018 were included in the study. Follow-up of the results was registered until January 31, 2019 with a follow-up time varying between eight to 14 months. Women positive for hr-HPV mRNA were invited for a follow-up examination. This examination consisted of a cervical sample for cytological analysis and renewed Aptima HPV mRNA testing. Two hundred thirty-five women who had not returned the self-sample were randomly selected for telephone interviews, in order to explore their reasons.

Results

The response rate for the self-collected vaginal hr-HPV sample was 13.2% [(797/6023), 95% CI 12.4–14.1%] and 9.9% [(79/796), 95% CI 7.9–12.2%] were positive for hr-HPV mRNA. The prevalence of severe dysplasia or cancer in the whole group of responders was 1.3% [(10/796), 95% CI 0.6–2.3%], with a cervical cancer prevalence of 0.4% [(3/796), 95% CI 0.1–1.1%]. Only 27 women participated in the telephone interviews, no particular reason for not returning self-samples was observed.

Conclusions

Self-collected vaginal hr-HPV samples increased participation in the cervical cancer screening among long-term non-attendees. The prevalence of cervical cancer was almost seven times higher for long-term non-attendees than in the organized screening population.
Challenges and lessons learned in re-filming the WHO mhGAP training videos for Sri Lankan context - a qualitative study
Authors: Doherty Shannon , Dass Giselle , Edward Anne , Manolova Gergana , Solomon Madonna
Published: February 2020

Background

Understanding and addressing the unmet mental health needs burden in the Northern Province of Sri Lanka is the subject of the COMGAP-S two-phase study. Phase Two involves the implementation of the World Health Organization’s mental health Gap Action Programme (mhGAP) in primary healthcare settings. As part of the contextual adaptation of mhGAP, eleven of the videos provided in the mhGAP training package have been re-filmed by a local team. We investigated the challenges, barriers and good practices of this adaptation effort from the point of view of team participants.

Methods

Twelve persons from the adaptation team, including students of medicine and drama, doctors, drama lecturers and professionals, consented to in-depth individual interviews following an open-ended topic guide with a member of the COMGAP-S study team. Interviews were recorded, transcribed, translated as necessary, and subjected to thematic analysis.

Results

The majority of participants perceived the process positively and had pride in their involvement. Expectations, opportunities, and exposure were discussed as stemming from the video production. The main challenges derived from the analysis were lack of discussion around budgeting, logistical difficulties, struggles with team cooperation, and creative differences. Issues around exact translation into the local Tamil dialect and modelling around mental health were emphasised by the majority of participants. Potential uses for the videos were identified beyond the current study and recommendations included setting out clear guidance around available funding and role allocation, and increasing the flexibility in adapting the material.

Conclusions

This study illustrated details of the adaptation of existing video materials to facilitate locally-based training for non-specialists on mhGAP curricula. With this, we have added to the knowledge base on conducting cultural and language adaptations and our findings indicate participants felt adapting the mhGAP films to local context was vital to ensuring training materials were culturally appropriate and valid.

Trial registration

This project was nested within the larger COMGAP-S clinical trial. Ethics approval was granted from the Ethics Review Committee, Faculty of Medicine, University of Jaffna (J/ERC/17/81/NDR/0170) and the Faculty Research Ethics Panel, Faculty of Medical Science, Anglia Ruskin University (SC/jc/FMSFREP/16/17076). The project is registered with the Sri Lankan Clinical Trial Registry (SLCTR/2018/008) and listed on the ISRCTN registry (trial ID ISRCTN62598070).
Determining the optimal time for liberation from renal replacement therapy in critically ill patients: a systematic review and meta-analysis (DOnE RRT)
Authors: Katulka Riley Jeremy , Al Saadon Abdalrhman , Sebastianski Meghan , Featherstone Robin , Vandermeer Ben , Silver Samuel A. , Gibney R. T. Noel , Bagshaw Sean M. , Rewa Oleksa G.
Published: February 2020

Introduction

Renal replacement therapy (RRT) is associated with high mortality and costs; however, no clinical guidelines currently provide specific recommendations for clinicians on when and how to stop RRT in recovering patients. Our objective was to systematically review the current evidence for clinical and biochemical parameters that can be used to predict successful discontinuation of RRT.

Methods

A systematic review and meta-analysis were performed with a peer-reviewed search strategy combining the themes of renal replacement therapy (IHD, CRRT, SLED), predictors of successful discontinuation or weaning (defined as an extended period of time free from further RRT), and patient outcomes. Major databases were searched and citations were screened using predefined criteria. Studied parameters were reported and, where possible, data was analyzed in the pooled analysis.

Results

Our search yielded 23 studies describing 16 variables for predicting the successful discontinuation of RRT. All studies were observational in nature. None were externally validated. Fourteen studies described conventional biochemical criteria used as surrogates of glomerular filtration rate (serum urea, serum creatinine, creatinine clearance, urine urea excretion, urine creatinine excretion). Thirteen studies described physiologic parameters such as urine output before and after cessation of RRT, and 13 studies reported on newer kidney biomarkers, such as serum cystatin C and serum neutrophil gelatinase-associated lipocalin (NGAL). Six studies reported sensitivity and specificity characteristics of multivariate models. Urine output prior to discontinuation of RRT was the most-studied variable, with nine studies reporting. Pooled analysis found a sensitivity of 66.2% (95% CI, 53.6–76.9%) and specificity of 73.6% (95% CI, 67.5–79.0%) for urine output to predict successful RRT discontinuation. Due to heterogeneity in the thresholds of urine output used across the studies, an optimal threshold value could not be determined.

Conclusions

Numerous variables have been described to predict successful discontinuation of RRT; however, available studies are limited by study design, variable heterogeneity, and lack of prospective validation. Urine output prior to discontinuation of RRT was the most commonly described and robust predictor. Further research should focus on the determination and validation of urine output thresholds, and the evaluation of additional clinical and biochemical parameters in multivariate models to enhance predictive accuracy.
Predictability of drug-induced liver injury by machine learning
Authors: Chierici Marco , Francescatto Margherita , Bussola Nicole , Jurman Giuseppe , Furlanello Cesare
Published: February 2020

Background

Drug-induced liver injury (DILI) is a major concern in drug development, as hepatotoxicity may not be apparent at early stages but can lead to life threatening consequences. The ability to predict DILI from in vitro data would be a crucial advantage. In 2018, the Critical Assessment Massive Data Analysis group proposed the CMap Drug Safety challenge focusing on DILI prediction.

Methods and results

The challenge data included Affymetrix GeneChip expression profiles for the two cancer cell lines MCF7 and PC3 treated with 276 drug compounds and empty vehicles. Binary DILI labeling and a recommended train/test split for the development of predictive classification approaches were also provided. We devised three deep learning architectures for DILI prediction on the challenge data and compared them to random forest and multi-layer perceptron classifiers. On a subset of the data and for some of the models we additionally tested several strategies for balancing the two DILI classes and to identify alternative informative train/test splits. All the models were trained with the MAQC data analysis protocol (DAP), i.e., 10x5 cross-validation over the training set. In all the experiments, the classification performance in both cross-validation and external validation gave Matthews correlation coefficient (MCC) values below 0.2. We observed minimal differences between the two cell lines. Notably, deep learning approaches did not give an advantage on the classification performance.

Discussion

We extensively tested multiple machine learning approaches for the DILI classification task obtaining poor to mediocre performance. The results suggest that the CMap expression data on the two cell lines MCF7 and PC3 are not sufficient for accurate DILI label prediction.

Reviewers

This article was reviewed by Maciej Kandula and Paweł P. Labaj.
Effect of an educational booklet for prevention and treatment of foot musculoskeletal dysfunctions in people with diabetic neuropathy: the FOotCAre (FOCA) trial II, a study protocol of a randomized controlled trial
Authors: Silva E. Q. , Suda E. Y. , Santos D. P. , Veríssimo J. L. , Ferreira J. S. S. P. , Cruvinel Júnior R. H. , Monteiro R. L. , Sartor C. D. , Sacco I. C. N.
Published: February 2020

Background

This study is a part of a series of two clinical trials. We consider diabetic polyneuropathy (DPN), a common chronic and progressive complication of diabetes mellitus that has several impacts on individuals’ foot health and quality of life. Based on the current trends of self-monitoring and self-care, providing a tool with foot-related exercises and educational care may help patients to avoid or reduce the musculoskeletal complications resulting from DPN, improving autonomous performance in daily living tasks. The aim of this trial is to evaluate the effects of an educational booklet for foot care and foot muscle strengthening on DPN symptoms and severity, clinical outcomes, and gait biomechanics in patients with DPN.

Methods/design

The FOotCAre (FOCA) trial II study has been designed as a single-blind, two-parallel-arm randomized controlled trial. It will include 48 patients with DPN who will be randomly allocated to a control (recommended foot care by international consensus with no foot exercises) group or an intervention (foot-related exercises using an educational booklet three times/week at home for 8 weeks) group. Participants from both groups will be assessed at baseline, after 8 weeks, and at 16 weeks for follow-up. The primary outcomes are the DPN symptoms and severity, and the secondary outcomes are foot–ankle kinematics, gait kinetics, plantar pressure distribution during gait, tactile and vibratory sensitivities, foot strength, functional balance, and foot health and functionality.

Discussion

The booklet is a management tool that allows users to be autonomous in their treatment by choosing how and where to perform the exercises. This allows the patients to perform the exercises regularly as a continuous habit for foot care and health, which is an important element in the management of the diabetic foot. As the booklet focuses on specific foot–ankle exercises, we expect that it will improve the clinical aspects of DPN and produce beneficial biomechanical changes during gait, becoming a powerful self-management tool that can be easily implemented to improve the performance of daily living tasks.

Trial registration

ClinicalTrials.gov,NCT04008745. Registered on 2 July 2019.
Molecular phylogenetics and mitogenomics of three avian dicrocoeliids (Digenea: Dicrocoeliidae) and comparison with mammalian dicrocoeliids
Authors: Suleman  , Khan Mian Sayed , Tkach Vasyl V. , Muhammad Nehaz , Zhang Dong , Zhu Xing-Quan , Ma Jun
Published: February 2020

Background

The Dicrocoeliidae are digenetic trematodes mostly parasitic in the bile ducts and gall bladder of various avian and mammalian hosts. Until recently their systematics was based on morphological data only. Due to the high morphological uniformity across multiple dicrocoeliid taxa and insufficient knowledge of relative systematic value of traditionally used morphological characters, their taxonomy has always been unstable. Therefore, DNA sequence data provide a critical independent source of characters for phylogenetic inference and improvement of the system.

Methods

We examined the phylogenetic affinities of three avian dicrocoeliids representing the genera Brachylecithum, Brachydistomum and Lyperosomum, using partial sequences of the nuclear large ribosomal subunit (28S) RNA gene. We also sequenced the complete or nearly complete mitogenomes of these three isolates and conducted a comparative mitogenomic analysis with the previously available mitogenomes from three mammalian dicrocoeliids (from 2 different genera) and examined the phylogenetic position of the family Dicrocoeliidae within the order Plagiorchiida based on concatenated nucleotide sequences of all mitochondrial genes (except trnG and trnE).

Results

Combined nucleotide diversity, Kimura-2-parameter distance, non-synonymous/synonymous substitutions ratio and average sequence identity analyses consistently demonstrated that cox1, cytb, nad1 and two rRNAs were the most conserved and atp6, nad5, nad3 and nad2 were the most variable genes across dicrocoeliid mitogenomes. Phylogenetic analyses based on mtDNA sequences did not support the close relatedness of the Paragonimidae and Dicrocoeliidae and suggested non-monophyly of the Gorgoderoidea as currently recognized.

Conclusions

Our results show that fast-evolving mitochondrial genes atp6, nad5 and nad3 would be better markers than slow-evolving genes cox1 and nad1 for species discrimination and population level studies in the Dicrocoeliidae. Furthermore, the Dicrocoeliidae being outside of the clade containing other xiphidiatan trematodes suggests a need for the re-evaluation of the taxonomic content of the Xiphidiata.
Pig-hunting dogs are an at-risk population for canine heartworm (Dirofilaria immitis) infection in eastern Australia
Authors: Orr Bronwyn , Ma Gemma , Koh Wei Ling , Malik Richard , Norris Jacqui M. , Westman Mark E. , Wigney Denise , Brown Graeme , Ward Michael P. , Šlapeta Jan
Published: February 2020

Background

Canine heartworm disease, caused byDirofilaria immitis, has global veterinary importance. In Australia, the prevalence of canine heartworm infection decreased markedly following the introduction of over-the-counter macrocyclic lactones. We aimed to estimate the prevalence of canine heartworm infection in at-risk populations of dogs in eastern Australia and analyse published prevalence data from Australia.

Methods

In total, 566 dogs from eastern Australia were tested for the presence ofD. immitisantigen. Four cohorts were studied: pig-hunting dogs from Queensland (Cohort 1,n = 104), dogs from remote New South Wales (NSW) (Cohort 2,n = 332), urban pets from rural NSW (Cohort 3,n = 45) and ex-racing Greyhounds from Sydney, NSW (Cohort 4,n = 85). Serum samples were screened forD. immitisantigen using a reference laboratory microwell-based assay (DiroChek®) or a point-of-care immunochromatography test kit (Anigen Rapid®). Risk factors associated with the odds ofD. immitisantigen seropositivity were identified using binary logistic regression models. Seropositive blood samples were tested for the presence and quantity ofD. immitisDNA using a species specific real-time (q)PCR assay. A metanalysis of the Australian canine heartworm literature was conducted.

Results

The prevalence of dirofilariasis in pig-hunting dogs from Queensland (Cohort 1) was 12.5% (95% CI: 6.5–18.9%), with a subpopulation of dogs from Central Queensland having a prevalence of 21% (95% CI: 12.3–33.4%). Age was significantly associated withD. immitisantigen seropositivity (increased risk with increased age). The odds of being > 5 yearsversus≤ 5 years was 3.7-times (95% CI: 1.1–12.5) greater in antigen positive versus antigen negative dogs. NoD. immitisantigen positive dogs were detected in dogs from NSW (Cohorts 2–4). The Australian canine heartworm disease literature includes 98 peer-reviewed publications (1901–2019) with 30 studies reporting onD. immitisprevalence in dogs. Throughout the publication peak period (1980s), the primary antemortem diagnostic test was detection of microfilariae.

Conclusions

Canine heartworm infection in dogs used for pig hunting is a previously unexplored topic in Australia. Pig-hunting dogs are infected with canine heartworm in Queensland, Australia, placing pet dogs and cats at increased risk of infection.
Human Herpesvirus 8 infection may contribute to oxidative stress in diabetes type 2 patients
Authors: Incani Alessandra , Marras Luisa , Serreli Gabriele , Ingianni Angela , Pompei Raffaello , Deiana Monica , Angius Fabrizio
Published: February 2020

Objective

To investigate the link between Human Herpesvirus 8 (HHV8) infection and plasma oxidative stress in patients with diabetes mellitus type 2 (DM2).

Results

Blood samples collected from DM2 and control subjects were screened for the presence of antibodies against HHV8 and for biomarkers of oxidative stress. We determined the products of radical damage on the plasma lipid fraction, such as malondialdehyde (MDA), fatty acid hydroperoxides (HP) and 7-ketocholesterol (7-keto), the oxidation products of unsaturated fatty acids (UFA) and cholesterol, respectively. The level of plasma antioxidant α-tocopherol (α-toc) was also assessed. Relevant differences were observed in the redox status in DM2 and either HHV8-positive or -negative control subjects. The level of α-toc significantly decreased in both DM2 and HHV8-positive subjects. Levels of MDA, HP and 7-keto were much higher in HHV8-positive and DM2 subjects, indicating that plasma oxidative stress is a common feature in both DM2 and HHV8-infection. In addition, 7-keto was further increased in HHV8-positive DM2 patients. We hypothesized that the HHV8-infection may contribute to the production of ROS, and hence to the oxidative stress closely related to the pathogenesis and development of DM2.
Imaging spectrum of abnormal subcutaneous and visceral fat distribution
Authors: Yamamoto Asako , Kikuchi Yoshinao , Kusakabe Toru , Takano Hideyuki , Sakurai Keita , Furui Shigeru , Oba Hiroshi
Published: February 2020

Adipose tissue plays multiple and complex roles not only in mechanical cushioning and energy storage but also as an important secretory organ that regulates energy balance and homeostasis multilaterally. Fat tissue is categorized into subcutaneous fat tissue (SCAT) or visceral fat tissue (VSA) depending on its distribution, with the two having different metabolic functions. Near-total lack of fat in congenital/acquired generalized lipodystrophy, cachexia, or any other severe malnutrition condition induces severe multi-organ dysfunction due to lack of production of leptin and other adipokines. Increased visceral fat tissue secondary to obesity, hypercortisolism, or multiple symmetric lipomatosis raises the risk of insulin resistance, cardiac complications, and airway or spinal canal stenosis, although the fat distribution pattern differs in each condition. Partial abnormal fat distribution conditions such as HIV/HAART therapy-associated lipodystrophy, familial partial lipodystrophies, and acquired partial lipodystrophy frequently show a mixture of lipoatrophy and lipohypertrophy with metabolic dysfunction. Characteristic imaging features in conditions with local abnormal fat distribution can provide information about a patient’s co-existent/unrecognized disease(s), past medical history, or lifestyle. Knowledge of characteristic abnormal fat distribution patterns can contribute to proper and timely therapeutic decision-making and patient education.
Exosomal miR-135a derived from human amnion mesenchymal stem cells promotes cutaneous wound healing in rats and fibroblast migration by directly inhibiting LATS2 expression
Authors: Gao Shaoying , Chen Tao , Hao Yi , Zhang Feifei , Tang Xiujun , Wang Dali , Wei Zairong , Qi Jianping
Published: February 2020

Background

Wound healing is a complex pathophysiological process that involves a variety of cells and cytokines. In this study, we found that local injection of human amnion mesenchymal stem cells into wounds in rats could promote wound healing. Therefore, we hypothesized that the exosomes of human amnion mesenchymal stem cells contain substances that regulate the migration of epidermal cells. It has been reported that miR-135a is involved in cell migration and transformation. However, there have been no reports of its function in skin wound healing.

Methods

To test this hypothesis, we injected exosomes overexpressing miR-135a directly into the wound margin. In addition, we tested the migration of BJ cells with overexpression or knockdown of miR-135a in vitro. Additionally, Western blot analysis was used to detect the expression of fibroblast migration-associated proteins after treatment with miR-135a overexpression or knockdown.

Results

MiR-135a significantly promoted wound healing compared to the control treatment. Western blot analysis showed a significant downregulation of LATS2 after overexpression of miR-135a. In addition, knockdown of miR-135a effectively attenuated the promoting effect of exosomes on cell migration.

Conclusions

Our results indicated that miR-135a promotes wound healing, which may be mediated by downregulating LATS2 levels to increase cell migration. This study provides a rationale for the therapeutic effect on wound healing of miR-135a in exosomes derived from human amnion mesenchymal stem cells.
Targeted silencing of miRNA-132-3p expression rescues disuse osteopenia by promoting mesenchymal stem cell osteogenic differentiation and osteogenesis in mice
Authors: Hu Zebing , Zhang Lijun , Wang Han , Wang Yixuan , Tan Yingjun , Dang Lei , Wang Ke , Sun Zhongyang , Li Gaozhi , Cao Xinsheng , Zhang Shu , Shi Fei , Zhang Ge
Published: February 2020

Background

Skeletal unloading can induce severe disuse osteopenia that often occurs in spaceflight astronauts or in patients subjected to prolonged bed-rest or immobility. Previously, we revealed a mechano-sensitive factor, miRNA-132-3p, that is closely related to the osteoblast function. The aim of this study was to investigate whether miRNA-132-3p could be an effective target for treating disuse osteopenia.

Methods

The 2D-clinostat device and the hindlimb-unloaded (HU) model were used to copy the mechanical unloading condition at the cellular and animal levels, respectively. Mimics or inhibitors of miRNA-132-3p were used to interfere with the expression of miRNA-132-3p in bone marrow-derived mesenchymal stem cells (BMSCs) in vitro for analyzing the effects on osteogenic differentiation. The special in vivo antagonists of miRNA-132-3p was delivered to the bone formation regions of HU mice for treating disuse osteopenia by a bone-targeted (AspSerSer)6-cationic liposome system. The bone mass, microstructure, and strength of the hindlimb bone tissue were analyzed for evaluating the therapeutic effect in vivo.

Results

miRNA-132-3p expression was declined under normal conditions and increased under gravitational mechanical unloading conditions during osteogenic differentiation of BMSCs in vitro. The upregulation of miRNA-132-3p expression resulted in the inhibition of osteogenic differentiation, whereas the downregulation of miRNA-132-3p expression enhanced osteogenic differentiation. The inhibition of miRNA-132-3p expression was able to attenuate the negative effects of mechanical unloading on BMSC osteogenic differentiation. Most importantly, the targeted silencing of miRNA-132-3p expression in the bone tissues could effectively preserve bone mass, microstructure, and strength by promoting osteogenic differentiation and osteogenesis in HU mice.

Conclusion

The overexpression of miRNA-132-3p induced by mechanical unloading is disadvantageous for BMSC osteogenic differentiation and osteogenesis. Targeted silencing of miRNA-132-3p expression presents a potential therapeutic target for the prevention and treatment of disuse osteoporosis.
Feasibility, reproducibility and diagnostic usefulness of right ventricular strain by 2-dimensional speckle-tracking echocardiography in ARDS patients: the ARD strain study
Authors: Lemarié Jérémie , Maigrat Charles-Henri , Kimmoun Antoine , Dumont Nathalie , Bollaert Pierre-Edouard , Selton-Suty Christine , Gibot Sébastien , Huttin Olivier
Published: February 2020

Background

Right ventricular (RV) function evaluation by echocardiography is key in the management of ICU patients with acute respiratory distress syndrome (ARDS), however, it remains challenging. Quantification of RV deformation by speckle-tracking echocardiography (STE) is a recently available and reproducible technique that provides an integrated analysis of the RV. However, data are scarce regarding its use in critically ill patients. The aim of this study was to assess its feasibility and clinical usefulness in moderate–severe ARDS patients.

Results

Forty-eight ARDS patients under invasive mechanical ventilation (MV) were consecutively enrolled in a prospective observational study. A full transthoracic echocardiography was performed within 36 h of MV initiation. STE-derived and conventional parameters were recorded. Strain imaging of the RV lateral, inferior and septal walls was highly feasible (47/48 (98%) patients). Interobserver reproducibility of RV strain values displayed good reliability (intraclass correlation coefficients (ICC) > 0.75 for all STE-derived parameters) in ARDS patients. ROC curve analysis showed that lateral, inferior, global (average of the 3 RV walls) longitudinal systolic strain (LSS) and global strain rate demonstrated significant diagnostic values when compared to several conventional indices (TAPSE, S′, RV FAC). A RV global LSS value > − 13.7% differentiated patients with a TAPSE < vs > 12 mm with a sensitivity of 88% and a specificity of 83%. Regarding clinical outcomes, mortality and cumulative incidence of weaning from MV at day 28 were not different in patients with normal versus abnormal STE-derived parameters.

Conclusions

Global STE assessment of the RV was highly achievable and reproducible in moderate–severe ARDS patients under MV and additionally correlated with several conventional parameters of RV function. In our cohort, STE-derived parameters did not provide any incremental value in terms of survival or weaning from MV prediction. Further investigations are needed to evaluate their theranostic usefulness.

Trial registration NCT02638844: NCT
Inter-domain resource optimization method of software-defined multi-domain optical network
Authors: Li Zikang , Yang Changming , Zhang Zhenrong , Hu Sifeng
Published: February 2020

In practical application scenarios, the division of different operators or the same operator in different regions constitutes a natural network region, forming a multi-domain optical network. At the beginning, this paper introduces the hierarchical architecture of software-defined optical network (SDON) and the functional model of control plane. Then, it describes a control system of software-defined multi-domain optical network based on hierarchical control mode and briefly analyzes their basic functional model. In the end, around the problems of resource allocation between scenarios in multi-domain optical network, this paper respectively analyzes the optimization of routing resources in inter-domain and the mechanism of spectrum defragmentation. At the same time, it separately simulates the resource optimization algorithms of single control architecture and hierarchical control architecture to verify the superiority of hierarchical control system.
Prehabilitation programs for cancer patients: a systematic review of randomized controlled trials (protocol)
Authors: Meneses-Echávez Jose F. , Loaiza-Betancur Andrés F. , Díaz-López Víctor , Echavarría-Rodríguez Andrés M.
Published: February 2020

Background

Around twenty million new cases and ten million of deaths were attributed to cancer in 2018. Physical exercise, as main component of prehabilitation programs, has been associated with clinical improvements in aerobic capacity, muscular strength, gait speed, and fewer postoperative complications. This systematic review aims to determine the benefits and harms of prehabilitation programs, mainly composed of physical exercise, compared with standard care for cancer patients.

Methods/design

A librarian will systematically search for randomized controlled trials in the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), and EMBASE. Two independent reviewers will independently screen the retrieved references, appraise the methodological quality of the included studies, and extract data. If possible, we will pool the data. We will evaluate the completeness of reporting of prehabilitation programs by using the CERT checklist, and the GRADE approach will be used to evaluate the quality of the evidence.

Discussion

This systematic review will determine the benefits and harms of prehabilitation programs for cancer patients. We will provide a complete appraisal of the quality of the evidence, our confidence in the results, and completeness of reporting of the exercise interventions evaluated in the prehabilitation programs. Findings from this review will assist health care providers, patients, decision-makers, and international organizations to make informed decisions in this field.

Systematic review registration

PROSPERO CRD42019125658
Nonlinear ordered variational inclusion problem involving XOR operation with fuzzy mappings
Authors: Ahmad Iqbal , Irfan Syed Shakaib , Farid Mohammad , Shukla Preeti
Published: February 2020

In the setting of real ordered positive Hilbert spaces, a nonlinear fuzzy ordered variational inclusion problem with its corresponding nonlinear fuzzy ordered resolvent equation problem involving XOR operation has been recommended and solved by employing an iterative algorithm. We establish the equivalence between nonlinear fuzzy ordered variational inclusion problem and nonlinear fuzzy ordered resolvent equation problem. The existence and convergence analysis of the solution of nonlinear fuzzy ordered variational inclusion problem involving XOR operation has been substantiated by applying a new resolvent operator method with XOR operation technique. The iterative algorithm and results demonstrated in this article have witnessed a significant improvement in many previously known results of this domain.
Impact of international labor migration on regional economic growth in Thailand
Authors: Tipayalai Katikar
Published: February 2020

The movement of labor in the Southeast Asia and particularly Thailand, which is home to more than half of all ASEAN migrant workers, is an issue of growing interest and increasing importance. As Thailand is now confronted with the new challenge of the so-called “middle-income trap”, the Thai government has recently implemented the long-run economic development plan called “Thailand 4.0”, focusing on high productivity and innovative creation from skilled foreign workers. To put Thailand 4.0 in action, the Eastern Economic Corridor (EEC), which is an example of region-based development, serves as a pilot project. However, while demand for high-skilled workers from developed countries increases, the majority of immigrants in Thailand is considered to comprise low-skilled workers from neighboring countries within ASEAN. This article, therefore, examines the impact of international labor migration on regional economic growth in Thailand from 2003 to 2015 through an econometric estimation of the production function by considering the economic consequences of immigration through production and productivity separately for skill-classified migrant workers. The findings empirically indicate that immigrants, and particularly high-skilled ones, have a statistically significant and positive impact on the growth of the regional economy as well as labor productivity in Thailand, thereby suggesting more attention should be paid to the role of regional area-based development policies as well as the ability of the host country to absorb high-skilled migrant workers.
Adding country resolution to EXIOBASE: impacts on land use embodied in trade
Authors: Bjelle Eivind Lekve , Többen Johannes , Stadler Konstantin , Kastner Thomas , Theurl Michaela C. , Erb Karl-Heinz , Olsen Kjartan-Steen , Wiebe Kirsten S. , Wood Richard
Published: February 2020

Multiregional input–output (MRIO) databases are used to analyze the impact of resource use and environmental impacts along global supply chains. To accurately account for pressures and impacts that are highly concentrated in specific sectors or regions of the world, such as agricultural and land-use-related impacts, MRIO databases are being fueled by increasingly more detailed data. To date no MRIO database exists which couples a high level of harmonized sector detail with high country resolution. Currently available databases either aggregate minor countries into rest-of-the-world (WIOD and EXIOBASE 3), or the high country resolution is achieved at the cost of non-harmonized or lower sectoral detail (Eora, OECD-ICIO or the GTAP-MRIO). This aggregation can cause potentially significant differences in environmental and socioeconomic impact calculations. In this paper, we describe the development of an EXIOBASE 3 variant that expands regional coverage from 49 regions to 214 countries, while keeping the high and harmonized sectoral detail. We show the relevance of disaggregation for land-use accounting. Previous rest-of-the-world regions supply one-third of global land, which is used to produce a large range of different products under very different levels of productivity. We find that the aggregation of regions leads to a difference in the balance of land embodied in trade of up to 6% and a difference of land embodied in imports of up to 68% for individual countries and up to 600% for land-use-relevant sectors. Whilst the database can still be considered experimental, it is expected to increase the accuracy of estimates for environmental footprint studies of the original EXIOBASE countries, and provides the first estimates for the countries in the previous rest-of-the world.
Evaluating sectoral effects of agricultural nitrogen pollution reduction policy in Croatia within a CGE framework
Authors: Nadoveza Jelić Ozana , Šimurina Jurica
Published: February 2020

Environmental policies are becoming an important part of agricultural policy portfolio in the EU, which is binding on Croatia. This paper seeks to evaluate potential sectoral effects of several nitrogen pollution reduction policy measures within CGE model for Croatia. Finding appropriate agri-environmental policy design represents a typical optimization problem. Thus, the paper attempts to find potential agri-environmental measures which comply with supranational directives without jeopardizing other economic policy goals. Results show that polluter-pays principle-based measures, if not accompanied by the provider-gets principle measures, could have relatively large negative economy-wide effects in Croatia. However, these effects can be reduced by the appropriate policy mix.
Emigrant citizenship, privileged local belonging and the option to return: Germans on the Turkish coast
Authors: Fauser Margit
Published: February 2020

The current migratory dynamics in the Mediterranean are characterized by large numbers of displaced people, refugees, and other vulnerable groups. In addition, the Mediterranean attracts more privileged individuals who are migrating for lifestyle reasons to find a better life abroad. But, while political and economic crises are at the roots of many movements across the Mediterranean, the question is whether these are also leading to the “displacement” of the privileged. In addressing this question, the article links privileged lifestyle migration to a perspective on mobile citizenship, focusing on German retirees who have found a new home on the Turkish coast. It builds on various stages of field research, including a recent field trip in May 2018. The article shows how lifestyle migrants engage and entangle emigrant and other sites of citizenship when navigating residential security and when expressing their way of local belonging in times of turmoil, and how their decision to stay in Turkey is paradoxically enabled by their option to return. The article’s focus on privileged migration thus also reveals the role of return as a neglected aspect in the study of (emigrant) citizenship.
How causal information affects decisions
Authors: Zheng Min , Marsh Jessecae K. , Nickerson Jeffrey V. , Kleinberg Samantha
Published: February 2020

Background

Causality is inherently linked to decision-making, as causes let us better predict the future and intervene to change it by showing which variables have the capacity to affect others. Recent advances in machine learning have made it possible to learn causal models from observational data. While these models have the potential to aid human decisions, it is not yet known whether the output of these algorithms improves decision-making. That is, causal inference methods have been evaluated on their accuracy at uncovering ground truth, but not the utility of such output for human consumption. Simply presenting more information to people may not have the intended effects, particularly when they must combine this information with their existing knowledge and beliefs. While psychological studies have shown that causal models can be used to choose interventions and predict outcomes, that work has not tested structures of the complexity found in machine learning, or how such information is interpreted in the context of existing knowledge.

Results

Through experiments on Amazon Mechanical Turk, we study how people use causal information to make everyday decisions about diet, health, and personal finance. Our first experiment, using decisions about maintaining bodyweight, shows that causal information can actually lead to worse decisions than no information at all. In Experiment 2, we test decisions about diabetes management, where some participants have personal domain experience and others do not. We find that individuals without such experience are aided by causal information, while individuals with experience do worse. Finally, our last two experiments probe how prior experience interacts with causal information. We find that while causal information reduces confidence in individuals with prior experience, it has the opposite effect on those without experience. In Experiment 4 we show that our results are not due to an inability to use causal models, and that they may be due to familiarity with a domain rather than actual knowledge.

Conclusion

While causal inference can potentially lead to more informed decisions, we find that more work is needed to make causal models useful for the types of decisions found in daily life.