bluuebunny/crossref_metadata_2025 huggingface dataset:
Late-onset Pompe disease (LOPD) in Belgium: clinical characteristics and outcome measures
Authors: Vanherpe P. , Fieuws S. , D’Hondt A. , Bleyenheuft C. , Demaerel P. , De Bleecker J. , Van den Bergh P. , Baets J. , Remiche G. , Verhoeven K. , Delstanche S. , Toussaint M. , Buyse B. , Van Damme P. , Depuydt C. E. , Claeys K. G.
Published: April 2020

Background

Late-onset Pompe disease (LOPD) is a rare, hereditary, progressive disorder that is usually characterized by limb-girdle muscle weakness and/or respiratory insufficiency. LOPD is caused by mutations in the acid alpha-glucosidase (GAA) gene and treated with enzyme replacement therapy (ERT).

Methods

We studied the clinical, brain imaging, and genetic features of the Belgian cohort of late-onset Pompe disease patients (N = 52), and explored the sensitivity of different outcome measures, during a longitudinal period of 7 years (2010–2017), including the activity limitations ActivLim score, 6 min walking distance (6MWD), 10 m walk test (10MWT), MRC sum score, and forced vital capacity (FVC) sitting/supine.

Results

In Belgium, we calculated an LOPD prevalence of 3.9 per million. Mean age at onset of 52 LOPD patients was 28.9 years (SD: 15.8 y), ranging from 7 months to 68 years. Seventy-five percent (N = 39) of the patients initially presented with limb-girdle weakness, whereas in 13% (N = 7) respiratory symptoms were the only initial symptom. Non-invasive ventilation (NIV) was started in 37% (N = 19), at a mean age of 49.5 years (SD: 11.9 y), with a mean duration of 15 years (SD: 10.2 y) after symptom onset. Brain imaging revealed abnormalities in 25% (N = 8) of the patients, with the presence of small cerebral aneurysm(s) in two patients and a vertebrobasilar dolichoectasia in another two. Mean diagnostic delay was 12.9 years. All patients were compound heterozygotes with the most prevalent mutation being c.-32-13 T > G in 96%. We identified two novel mutations in GAA: c.1610_1611delA and c.186dup11. For the 6MWD, MRC sum score, FVC sitting and FVC supine, we measured a significant decrease over time (p = 0.0002, p = 0.0001, p = 0.0077, p = 0.0151), which was not revealed with the ActivLim score and 10MWT (p > 0.05).

Conclusions

Awareness on LOPD should even be further increased because of the long diagnostic delay. The 6MWD, but not the ActivLim score, is a sensitive outcome measure to follow up LOPD patients.
Longitudinal natural history of type I spinal muscular atrophy: a critical review
Authors: Mercuri Eugenio , Lucibello Simona , Perulli Marco , Coratti Giorgia , de Sanctis Roberto , Pera Maria Carmela , Pane Marika , Montes Jacqueline , de Vivo Darryl C. , Darras Basil T. , Kolb Stephen J. , Finkel Richard S.
Published: April 2020

Background

The advent of new therapies in spinal muscular atrophy (SMA) has highlighted the need to have natural history data for comparison. Natural history studies using structured assessments in type I however are very limited. We identified and reviewed all the existing longitudinal history data in infants with type I SMA first assessed before the age of 7 months with the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND).

Main text

Three longitudinal natural history studies, two performed in the United States and one in Italy, were identified. The different study design of these three studies made it possible for the cumulative dataset to include the full spectrum of severity; from infants with neonatal onset to those with a milder phenotype that were not always included in the individual natural history studies. The cumulative analysis confirmed that, even in a larger cohort, there was never an improvement on the CHOP INTEND over time. This was true for all the infants, irrespective of their age or baseline CHOP INTEND scores. Infants with neonatal onset had low CHOP INTEND scores and a fast decline. The relatively large number of patients allowed us to calculate the rate of progression in subgroups identified according to SMN2 copy number and baseline CHOP INTEND scores.

Conclusion

A detailed understanding of the existing data is important, as it will be difficult to acquire new systematic longitudinal history data because of the availability of disease modifying therapies. The cumulative findings in this review help to better understand the variability of natural history data in untreated patients and will be of use for comparison to the real world patients treated with the recently approved therapies that have shown encouraging results in clinical trials.
Transcript, protein, metabolite and cellular studies in skin fibroblasts demonstrate variable pathogenic impacts of NPC1 mutations
Authors: Musalkova Dita , Majer Filip , Kuchar Ladislav , Luksan Ondrej , Asfaw Befekadu , Vlaskova Hana , Storkanova Gabriela , Reboun Martin , Poupetova Helena , Jahnova Helena , Hulkova Helena , Ledvinova Jana , Dvorakova Lenka , Sikora Jakub , Jirsa Milan , Vanier Marie T. , Hrebicek Martin
Published: April 2020

Background

Niemann-Pick type C (NP-C) is a rare neurovisceral genetic disorder caused by mutations in the NPC1 or the NPC2 gene. NPC1 is a multipass-transmembrane protein essential for egress of cholesterol from late endosomes/lysosomes. To evaluate impacts of NPC1 mutations, we examined fibroblast cultures from 26 NP-C1 patients with clinical phenotypes ranging from infantile to adult neurologic onset forms. The cells were tested with multiple assays including NPC1 mRNA expression levels and allele expression ratios, assessment of NPC1 promoter haplotypes, NPC1 protein levels, cellular cholesterol staining, localization of the mutant NPC1 proteins to lysosomes, and cholesterol/cholesteryl ester ratios. These results were correlated with phenotypes of the individual patients.

Results

Overall we identified 5 variant promoter haplotypes. Three of them showed reporter activity decreased down to 70% of the control sequence. None of the haplotypes were consistently associated with more severe clinical presentation of NP-C. Levels of transcripts carrying null NPC1 alleles were profoundly lower than levels of the missense variants. Low levels of the mutant NPC1 protein were identified in most samples. The protein localised to lysosomes in cultures expressing medium to normal NPC1 levels. Fibroblasts from patients with severe infantile phenotypes had higher cholesterol levels and higher cholesterol/cholesteryl ester ratios. On the contrary, cell lines from patients with juvenile and adolescent/adult phenotypes showed values comparable to controls.

Conclusion

No single assay fully correlated with the disease severity. However, low residual levels of NPC1 protein and high cholesterol/cholesteryl ester ratios associated with severe disease. The results suggest not only low NPC1 expression due to non-sense mediated decay or low mutant protein stability, but also dysfunction of the stable mutant NPC1 as contributors to the intracellular lipid transport defect.
Circular RNA hsa_circ_0000326 acts as a miR-338-3p sponge to facilitate lung adenocarcinoma progression
Authors: Xu Yuzhu , Yu Jun , Huang Zhenli , Fu Bohua , Tao Yu , Qi Xuefei , Mou Yong , Hu Yinan , Wang Yi , Cao Yong , Jiang Dingsheng , Xie Jungang , Xu Yongjian , Zhao Jianping , Xiong Weining
Published: April 2020

Background

Circular RNAs (circRNAs) are a novel class of noncoding RNAs that regulate gene expression at the transcriptional or posttranscriptional level. According to recent studies, circRNAs are involved in the pathogenesis of cancer, but the roles of circRNAs in lung adenocarcinoma are largely unknown.

Methods

In this study, we identified a novel upregulated circRNA, hsa_circ_0000326, in human lung adenocarcinoma tissues using microarray analysis and qRT-PCR. We then explored the biological role of hsa_circ_0000326 using gain- and loss-of-function assays in adenocarcinoma cells. Bioinformatics databases were used to screen for potential target miRNAs and the luciferase reporter assays and RNA-FISH further validated the interaction. Downstream protein was detected by western blot. Finally, we established xenografts in nude mice to assess the function of hsa_circ_0000326 in vivo.

Results

We found that high expression of hsa_circ_0000326 was correlated with tumor size, regional lymph node status and differentiation in human lung adenocarcinoma. Additionally, we conducted gain- and loss-of-function assays and found that hsa_circ_0000326 acted as a positive regulator of cell proliferation and migration and a negative regulator of apoptosis. Mechanistic studies showed that hsa_circ_0000326 acted as a miR-338-3p sponge and altered the function of miR-338-3p, which in turn upregulated the expression of the downstream target RAB14 and affected the proliferation, migration and apoptosis of lung adenocarcinoma cells.

Conclusions

Collectively, our study results reveal crucial roles for hsa_circ_0000326 in the proliferation, migration and apoptosis of lung adenocarcinoma cells and suggest that hsa_circ_0000326 may represent a potential therapeutic target in patients with lung adenocarcinoma.
Long noncoding RNA HOST2, working as a competitive endogenous RNA, promotes STAT3-mediated cell proliferation and migration via decoying of let-7b in triple-negative breast cancer
Authors: Hua Kaiyao , Deng Xiaochong , Hu Jiashu , Ji Changle , Yu Yunhe , Li Jiayi , Wang Xuehui , Fang Lin
Published: April 2020

Background

Human ovarian cancer specific transcript 2 (HOST2) is a long non-coding RNA (lncRNA) reported to be specifically high expressed in human ovarian cancer. However, the mechanism that how HOST2 regulates triple negative breast cancer (TNBC) need to be explored.

Methods

In this study, expression of HOST2 was determined in 40 TNBC patients and matched non-cancerous tissues by qRT-PCR and in situ hybridization (ISH) assay. The biological functions of HOST2 was measured by losing features. The effect of HOST2 on viability, proliferation and migration was evaluated by MTT, colony formation assay, EDU analysis, transwell invasion assay and nude mouse xenograft model. Fluorescence in situ hybridization (FISH), Luciferase report assay, RNA immunoprecipitation (RIP) assay and Western blot were fulfilled to measure molecular mechanisms.

Results

The results showed that HOST2 was up-regulated in BC tissues and cell lines. Clinical outcome analysis demonstrated that high expression of HOST2 was associated with poor prognosis of TNBC patients. Functional experiments illustrated that knockdown of HOST2 significantly suppressed TNBC cell proliferation and migration. Western blot assays, qRT-PCR assays, RIP assays and luciferase reporter assays revealed that HOST2 regulated STAT3 via crosstalk with let-7b. Depression of HOST2 suppressed STAT3-mediated proliferation and migration in TNBC cells. HOST2 could function as a decoy of let-7b to depress expression of STAT3.

Conclusions

HOST2 could function as a oncogene and promoted STAT3-mediated proliferation and migration through acting as a competing endogenous RNA, which might act as a potential biomarker for TNBC patients.
The EMPOWER-SUSTAIN e-Health Intervention to improve patient activation and self-management behaviours among individuals with Metabolic Syndrome in primary care: study protocol for a pilot randomised controlled trial
Authors: Daud Maryam Hannah , Ramli Anis Safura , Abdul-Razak Suraya , Isa Mohamad Rodi , Yusoff Fakhrul Hazman , Baharudin Noorhida , Mohamed-Yassin Mohamed Syarif , Badlishah-Sham Siti Fatimah , Nikmat Azlina Wati , Jamil Nursuriati , Mohd-Nawawi Hapizah
Published: April 2020

Background

Epidemiological studies conducted in various parts of the world have clearly demonstrated that metabolic syndrome (MetS) is an increasing global health problem, not only in Western societies but also in Asian populations. Web-based and mobile phone-based self-management applications have been proven to be effective in improving self-management behaviour of patients with MetS components (i.e., diabetes or hypertension). However, evidence is lacking in terms of their effectiveness specifically for patients with MetS. The aim of this pilot study is to evaluate the feasibility and potential effectiveness of the EMPOWER-SUSTAIN Self-Management e-Health Intervention in improving activation and self-management behaviours among patients with MetS. This paper presents the study protocol.

Methods

A pilot randomised controlled trial will be conducted in a university primary care clinic. A total of 232 patients aged 18–60 years with MetS will be recruited; 116 will be randomised to receive the EMPOWER-SUSTAIN intervention for 6 months, and another 116 patients will continue with usual care. The EMPOWER-SUSTAIN intervention is a multifaceted chronic disease management strategy based on the Chronic Care Model and persuasive technology theory. It consists of training primary care physicians, nurses and patients to use the EMPOWER-SUSTAIN web-based self-management mobile app, strengthening the patient–physician relationship and reinforcing the use of relevant clinical practice guidelines to guide management and prescribing. The primary outcome is the mean change in patient activation score using the Patient Activation Measure short form Malay version (PAM-13-M) questionnaire. The secondary outcomes include the changes in waist circumference, body mass index, blood pressure, patient physical activity level, eating behaviour, perception of chronic illness care, satisfaction with patient–physician interaction, and perceived absolute 10-year cardiovascular disease risk. Feasibility of implementing the intervention will be evaluated. This includes acceptability of the intervention, estimating the likely rate of participant recruitment and retention, appropriateness of the outcome measures, calculation of sample size, and the intervention’s potential effectiveness.

Conclusion

To our knowledge, this is the first study in Malaysia that aims to determine the feasibility of a multifaceted e-health intervention, as well as to indicate more useful aspects of this intervention for further exploration in a larger trial.

Trial registration

ClinicalTrials.gov, NCT04120779. Registered on 9 October 2019, protocol version 1.
Effectiveness of TOcilizumab in comparison to Prednisone In Rheumatoid Arthritis patients with insufficient response to disease-modifying antirheumatic drugs (TOPIRA): study protocol for a pragmatic trial
Authors: van der Leeuw Matthijs S. , Welsing Paco M. J. , de Hair Maria J. H. , Jacobs Johannes W. G. , Marijnissen Anne C. A. , Linn-Rasker Suzanne P. , Fodili Faouzia , Bos Reinhard , Tekstra Janneke , van Laar Jacob M.
Published: April 2020

Background

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, predominantly affecting joints, which is initially treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). In RA patients with insufficient response to csDMARDs, the addition of prednisone or tocilizumab, a biological DMARD (bDMARD), to the medication has been shown to be effective in reducing RA symptoms. However, which of these two treatment strategies has superior effectiveness and safety is unknown.

Methods

In this multicenter, investigator-initiated, open-label, randomized, pragmatic trial, we aim to recruit 120 RA patients meeting the 2010 ACR/EULAR classification criteria for RA, with active disease defined as a Clinical Disease Activity Index (CDAI) > 10 and at least one swollen joint of the 28 assessed. Patients must be on stable treatment with csDMARDs for ≥ 8 weeks prior to screening and must have been treated with ≥ 2 DMARDs, of which a maximum of one tumor necrosis factor inhibitor (a class of bDMARDs) is allowed. Previous use of other bDMARDs or targeted synthetic DMARDs is not allowed. Patients will be randomized in a 1:1 ratio to receive either tocilizumab (subcutaneously at 162 mg/week) or prednisone (orally at 10 mg/day) as an addition to their current csDMARD therapy. Study visits will be performed at screening; baseline; and months 1, 2, 3, 6, 9, and 12. Study medication will be tapered in case of clinical remission (CDAI ≤ 2.8 and ≤ 1 swollen joint at two consecutive 3-monthly visits) with careful monitoring of disease activity. In case of persistent high disease activity at or after month 3 (CDAI > 22 at any visit or > 10 at two consecutive visits), patients will switch to the other strategy arm. Primary outcome is a change in CDAI from baseline to 12 months. Secondary outcomes are additional clinical response and quality of life measures, drug retention rate, radiographically detectable progression of joint damage, functional ability, and cost utility. Safety outcomes include tocilizumab-associated adverse events (AEs), glucocorticoid-associated AEs, and serious AEs.

Discussion

This will be the first randomized clinical trial comparing addition of oral prednisone or of tocilizumab head to head in RA patients with insufficient response to csDMARD therapy. It will yield important information for clinical rheumatology practice.

Trial registration

This trial was prospectively registered in the Netherlands Trial Register on October 7, 2019 (NL8070). The Netherlands Trial Register contains all items from the World Health Organization Trial Registration Data Set.
Insights about the structure of farnesyl diphosphate synthase (FPPS) and the activity of bisphosphonates on the proliferation and ultrastructure of Leishmania and Giardia
Authors: Gadelha Ana Paula R. , Brigagao Claudia Maia , da Silva Martha Barros , Rodrigues Aline Beatriz Mello , Guimarães Ana Carolina Ramos , Paiva Fernando , de Souza Wanderley , Henriques Cristina
Published: April 2020

Background

The enzyme farnesyl diphosphate synthase (FPPS) is positioned in the intersection of different sterol biosynthesis pathways such as those producing isoprenoids, dolichols and ergosterol. FPPS is ubiquitous in eukaryotes and is inhibited by nitrogen-containing bisphosphonates (N-BP). N-BP activity and the mechanisms of cell death as well as damage to the ultrastructure due to N-BP has not yet been investigated in Leishmania infantum and Giardia. Thus, we evaluated the effect of N-BP on cell viability and ultrastructure and then performed structural modelling and phylogenetic analysis on the FPPS enzymes of Leishmania and Giardia.

Methods

We performed multiple sequence alignment with MAFFT, phylogenetic analysis with MEGA7, and 3D structural modelling for FPPS with Modeller 9.18 and on I-Tasser server. We performed concentration curves with N-BP in Leishmania promastigotes and Giardia trophozoites to estimate the IC50via the MTS/PMS viability method. The ultrastructure was evaluated by transmission electron microscopy, and the mechanism of cell death by flow cytometry.

Results

The nitrogen-containing bisphosphonate risedronate had stronger anti-proliferative activity in Leishmania compared to other N-BPs with an IC50 of 13.8 µM, followed by ibandronate and alendronate with IC50 values of 85.1 µM and 112.2 µM, respectively. The effect of N-BPs was much lower on trophozoites of Giardia than Leishmania (IC50 of 311 µM for risedronate). Giardia treated with N-BP displayed concentric membranes around the nucleus and nuclear pyknosis. Leishmania had mitochondrial swelling, myelin figures, double membranes, and plasma membrane blebbing. The same population labelled with annexin-V and 7-AAD had a loss of membrane potential (TMRE), indicative of apoptosis. Multiple sequence alignments and structural alignments of FPPS proteins showed that Giardia and Leishmania FPPS display low amino acid identity but possess the conserved aspartate-rich motifs.

Conclusions

Giardia and Leishmania FPPS enzymes are phylogenetically distant but display conserved protein signatures. The N-BPs effect on FPPS was more pronounced in Leishmania than Giardia. This might be due to general differences in metabolism and differences in the FPPS catalytic site.
Timing and original features of flagellum assembly in trypanosomes during development in the tsetse fly
Authors: Lemos Moara , Mallet Adeline , Bertiaux Eloïse , Imbert Albane , Rotureau Brice , Bastin Philippe
Published: April 2020

Background

Trypanosoma bruceiexhibits a complex life-cycle alternating between tsetse flies and mammalian hosts. When parasites infect the fly, cells differentiate to adapt to life in various tissues, which is accompanied by drastic morphological and biochemical modifications especially in the proventriculus. This key step represents a bottleneck for salivary gland infection.

Methods

Here, we monitored flagellum assembly in trypanosomes during differentiation from the trypomastigote to the epimastigote stage, i.e. when the nucleus migrates to the posterior end of the cell, by using three-dimensional electron microscopy (focused ion beam scanning electron microscopy, FIB-SEM) and immunofluorescence assays.

Results

The combination of light and electron microscopy approaches provided structural and molecular evidence that the new flagellum is assembled while the nucleus migrates towards the posterior region of the body. Two major differences with well-known procyclic cells are reported. First, growth of the new flagellum begins when the associated basal body is found in a posterior position relative to the mature flagellum. Secondly, the new flagellum acquires its own flagellar pocket before rotating on the left side of the anterior-posterior axis. FIB-SEM revealed the presence of a structure connecting the new and mature flagellum and serial sectioning confirmed morphological similarities with the flagella connector of procyclic cells. We discuss the potential function of the flagella connector in trypanosomes from the proventriculus.

Conclusions

These findings show thatT. bruceifinely modulates its cytoskeletal components to generate highly variable morphologies.
Development of the Japanese version of the Other As Shamer Scale using item response theory
Authors: Hiramatsu Yoichi , Asano Kenichi , Kotera Yasuhiro , Sensui Toshihiko , Endo Ayumu , Shimizu Eiji , Basran Jaskaran , Goss Ken
Published: April 2020

Objective

External shame reflects a person’s anxiety that he or she might be rejected by others. The Other as Shamer Scale (OAS) is a scale for assessing external shame. The Japanese version of the OAS was developed, and its reliability and validity were examined using Item Response Theory (IRT).

Results

A survey was conducted with university students (N = 199). Exploratory factor analysis of the results indicated a significantly high factor loading on the first factor, which was identical to the original version of the scale as well as high internal consistency. Moreover, the results confirmed that each item had adequate discrimination and information levels, suggesting that external shame could be discriminated against with high accuracy for a wide range of relatively low and relatively high external shame groups. These results suggest that the OAS could be used to screen external shame as a stress factor and to assess intervention effects.
DNA methylation age calculators reveal association with diabetic neuropathy in type 1 diabetes
Authors:   DCCT/EDIC Research Group, Roshandel Delnaz , Chen Zhuo , Canty Angelo J. , Bull Shelley B. , Natarajan Rama , Paterson Andrew D.
Published: April 2020

Background

Many CpGs become hyper or hypo-methylated with age. Multiple methods have been developed by Horvath et al. to estimate DNA methylation (DNAm) age including Pan-tissue, Skin & Blood, PhenoAge, and GrimAge. Pan-tissue and Skin & Blood try to estimate chronological age in the normal population whereas PhenoAge and GrimAge use surrogate markers associated with mortality to estimate biological age and its departure from chronological age. Here, we applied Horvath’s four methods to calculate and compare DNAm age in 499 subjects with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study using DNAm data measured by Illumina EPIC array in the whole blood. Association of the four DNAm ages with development of diabetic complications including cardiovascular diseases (CVD), nephropathy, retinopathy, and neuropathy, and their risk factors were investigated.

Results

Pan-tissue and GrimAge were higher whereas Skin & Blood and PhenoAge were lower than chronological age (p < 0.0001). DNAm age was not associated with the risk of CVD or retinopathy over 18–20 years after DNAm measurement. However, higher PhenoAge (β = 0.023, p = 0.007) and GrimAge (β = 0.029, p = 0.002) were associated with higher albumin excretion rate (AER), an indicator of diabetic renal disease, measured over time. GrimAge was also associated with development of both diabetic peripheral neuropathy (OR = 1.07, p = 9.24E−3) and cardiovascular autonomic neuropathy (OR = 1.06, p = 0.011). Both HbA1c (β = 0.38, p = 0.026) and T1D duration (β = 0.01, p = 0.043) were associated with higher PhenoAge. Employment (β = − 1.99, p = 0.045) and leisure time (β = − 0.81, p = 0.022) physical activity were associated with lower Pan-tissue and Skin & Blood, respectively. BMI (β = 0.09, p = 0.048) and current smoking (β = 7.13, p = 9.03E−50) were positively associated with Skin & Blood and GrimAge, respectively. Blood pressure, lipid levels, pulse rate, and alcohol consumption were not associated with DNAm age regardless of the method used.

Conclusions

Various methods of measuring DNAm age are sub-optimal in detecting people at higher risk of developing diabetic complications although some work better than the others.
MSX2 suppression through inhibition of TGFβ signaling enhances hematopoietic differentiation of human embryonic stem cells
Authors: Wang Hongtao , Wang Mengge , Wang Yu , Wen Yuqi , Chen Xiaoyuan , Wu Dan , Su Pei , Zhou Wen , Shi Lihong , Zhou Jiaxi
Published: April 2020

Background

Strategies of generating functional blood cells from human pluripotent stem cells (hPSCs) remain largely unsuccessful due to the lack of a comprehensive understanding of hematopoietic development. Endothelial-to-hematopoietic transition (EHT) serves as the pivotal mechanism for the onset of hematopoiesis and is negatively regulated by TGF-β signaling. However, little is known about the underlying details of TGF-β signaling during EHT.

Methods

In this study, by applying genome-wide gene profiling, we identified muscle segment homeobox2 (MSX2) as a potential mediator of TGF-β signaling during EHT. We generated MSX2-deleted human embryonic stem cell (hESC) lines using the CRISPR/Cas9 technology and induced them to undergo hematopoietic differentiation. The role of MSX2 in hematopoiesis and functional regulation of TGFβ signaling in EHT was studied.

Results

We identified MSX2 as a novel regulator of human hematopoiesis. MSX2 deletion promotes the production of hematopoietic cells from hESCs. Functional and bioinformatics studies further demonstrated that MSX2 deletion augments hematopoietic differentiation of hESCs by facilitating EHT. Mechanistically, MSX2 acts as a downstream target of TGFβ signaling to mediate its function during EHT.

Conclusions

Our results not only improve the understanding of EHT, but may also provide novel insight into the efficient production of functional blood cells from hPSCs for regenerative medicine.
HIF1α overexpression enhances diabetic wound closure in high glucose and low oxygen conditions by promoting adipose-derived stem cell paracrine function and survival
Authors: Xu Jin , Liu Xiaoyu , Zhao Feng , Zhang Ying , Wang Zhe
Published: April 2020

Background

Adipose-derived stem cell (ADSC) transplantation is a promising strategy to promote wound healing because of the paracrine function of stem cells. However, glucose-associated effects on stem cell paracrine function and survival contribute to impaired wound closure in patients with diabetes, limiting the efficacy of ADSC transplantation. Hypoxia-inducible factor (HIF)1α plays important roles in wound healing, and in this study, we investigated the effects of HIF1α overexpression on ADSCs in high glucose and low oxygen conditions.

Methods

Adipose samples were obtained from BALB/C mice, and ADSCs were cultured in vitro by digestion. Control and HIF1α-overexpressing ADSCs were induced by transduction. The mRNA and protein levels of angiogenic growth factors in control and HIF1α-overexpressing ADSCs under high glucose and low oxygen conditions were analyzed by quantitative reverse transcription-polymerase chain reaction and western blotting. The effects of ADSC HIF1α overexpression on the proliferation and migration of mouse aortic endothelial cells (MAECs) under high glucose were evaluated using an in vitro coculture model. Intracellular reactive oxygen species (ROS) and 8-hydroxydeoxyguanosine (8-OHdG) levels in ADSCs were observed using 2,7-dichlorodihydrofluorescein diacetate staining and enzyme-linked immunosorbent assays, respectively. Apoptosis and cell cycle analysis assays were performed by flow cytometry. An in vivo full-thickness skin defect mouse model was used to evaluate the effects of transplanted ADSCs on diabetic wound closure.

Results

In vitro, HIF1α overexpression in ADSCs significantly increased the expression of vascular endothelial growth factor A, fibroblast growth factor 2, and C-X-C motif chemokine ligand 12, which were inhibited by high glucose. HIF1α overexpression in ADSCs alleviated high glucose-induced defects in MAEC proliferation and migration and significantly suppressed ADSC ROS and 8-OHdG levels, thereby decreasing apoptosis and enhancing survival. In vivo, HIF1α overexpression in ADSCs prior to transplantation significantly enhanced angiogenic growth factor expression, promoting wound closure in diabetic mice.

Conclusions

HIF1α overexpression in ADSCs efficiently alleviates high glucose-induced paracrine dysfunction, decreases oxidative stress and subsequent DNA damage, improves viability, and enhances the therapeutic effects of ADSCs on diabetic wound healing.
Dedifferentiated soft tissue leiomyosarcoma with heterologous osteosarcoma component: case report and review of the literature
Authors: Gaeta Raffaele , Matera Davide , Muratori Francesco , Roselli Giuliana , Baldi Giacomo , Campanacci Domenico Andrea , Franchi Alessandro
Published: April 2020

Background

Soft tissue dedifferentiated leiomyosarcoma with heterologous osteosarcomatous component is an extremely rare entity described in only few cases in the literature.

Case presentation

We report the case of a 65-year-old male patient who, after initial inadequate surgery of a tumor of the left forearm, developed local recurrence that was treated with neoadjuvant chemotherapy, surgery and postoperative radiation therapy. Histologically the tumor showed an abrupt separation of two different patterns. One component consisted of interlacing fascicles of spindle cells with cigar-shaped nuclei strongly positive for smooth muscle actin, desmin and H-caldesmon. The other component consisted of a high-grade pleomorphic sarcoma with osteoid and chondroid matrix production, which positive for SATB2. Thus, a final diagnosis of dedifferentiated leiomyosarcoma was rendered. Fifteen months after treatment, the patient presented further local and distant relapse with pulmonary metastases and died 23 months after the first presentation.

Discussion and conclusions

Dedifferentiated leiomyosarcoma is a highly malignant neoplasm with a poor outcome. Extensive sampling of soft tissue leiomyosarcomas is recommended to detect possible dedifferentiated areas as they represent a crucial prognostic parameter.
DFT-based low-complexity optimal cell ID estimation in NB-IoT
Authors: Savaux Vincent
Published: April 2020

This paper deals with cell identifier (ID) estimation for narrowband-Internet of things (NB-IoT) system. It is suggested to transform the usual maximum likelihood (ML) estimator expression in order to highlight a discrete Fourier transform (DFT), which can be computed with fast algorithms. Therefore, the proposed method is a DFT-based low-complexity cell ID estimator that can be qualified as optimal in the ML sense. The principle is extended to the practical case where the channel is unknown and must be estimated. In this scenario, the concentrated likelihood function needs to be maximized, in which the ML channel estimate is a function of the unknown cell ID parameter. This operation only involves a few additional multiplications. Simulation results reveal that the performance of the proposed method actually matches the optimal one of the ML cell ID estimator. Furthermore, the technique is robust to residual frequency offset up to several hundreds of Hertz. We also show that the mean square error of channel estimation reaches its Cramér-Rao bound (CRB).
Seamless clustering multi-hop routing protocol based on improved artificial bee colony algorithm
Authors: Zhang Tianyi , Chen Geng , Zeng Qingtian , Song Ge , Li Chao , Duan Hua
Published: April 2020

An important issue in the mobile sink wireless sensor networks (MSWSNs) is sensor energy optimization. In order to alleviate the problem of unbalanced network load and high energy consumption in MSWSNs, we proposed a new data collection protocol in this paper: seamless clustering multi-hop routing protocol based on improved artificial bee colony algorithm (IABCP). Because of limited by the communication sensing range and intelligence of ordinary nodes, routing paths can only be constructed by crude methods. And the movement of the sink node will generate a large amount of energy consumption for locating the sink node. In order to solve this problem, we assign the task of routing table generation to the sink node, which will generate the routing table through the improved artificial bee colony algorithm. In addition, we adopt a new method to select cluster head (CH) nodes; node uses the average energy of the surrounding nodes and its own residual energy to calculate the claimed cluster head time. Moreover, we added a sub cluster head CH-β node. When the CH node reaches the number of replacement rounds, the CH-β node becomes CH directly. The simulation results show that our routing protocol is more robust compared with three other protocols.
Discrete Hopfield neural network based indoor Wi-Fi localization using CSI
Authors: Dang Xiaochao , Tang Xuhao , Hao Zhanjun , Ren Jiaju
Published: April 2020

The fingerprint indoor localization method based on channel state information (CSI) has gained widespread attention. However, this method fails to provide a better localization effect and higher localization accuracy due to poor fingerprint accuracy, unsatisfactory classification and matching effect, and vulnerability to environmental impacts. In order to solve the problem, this paper proposes a CSI fingerprint indoor localization method based on the Discrete Hopfield Neural Network (DHNN). The method mainly consists of off-line and on-line phases. At the off-line phase, a low-pass filter is applied to conduct a preliminary processing on the fingerprint information of each reference point, and then, phase difference is adopted to correct the fingerprint data of all reference points. In this way, the quality of fingerprint data is improved, hence avoiding problems such as indoor environmental changes and multipath effect of signals, etc. in which impact the fingerprint data. Finally, the characteristic fingerprint database is established after acquiring relatively accurate fingerprint data. At the on-line phase, to maintain the consistency of data, the data of each reference point in the fingerprint database is set as an attractor. Meanwhile, the localization information of the test point is processed to make convergence judgment through DHNN. Eventually, the localization result is obtained. The experimental results show that the localization accuracy with a median error of 1.6 m can be achieved through the proposed method in the experimental environment. Compared with similar methods, it has a higher stability which can significantly reduce the cost of manpower and time.
Error reduction through post processing for wireless capsule endoscope video
Authors: Floor Pål Anders , Farup Ivar , Pedersen Marius , Hovde Øistein
Published: April 2020

The wireless capsule endoscope (WCE) is a pill-sized device taking images, which are transmitting to an on-body receiver, while traveling through the digestive system. Since image data is transmitted through the human body, which is a harsh medium for electromagnetic wave propagation, noise may at times heavily corrupt the reconstructed image frames. A common way to combat noise is to use error-correcting codes. In addition one may also utilize inter- and intra frame correlation to reduce the impact of noise at the receiver side, placing no extra demand on the WCE. However, it is then of great importance that the chosen post processing methods do not alter the content of the image as this can lead to miss-detection by gastroenterologists. In this paper we will investigate the possibility for additional noise suppression and error concealment at the receiver side in a high intensity error regime. Due to the high correlation generally inherent in WCE video, satisfactory results are obtained, as concluded from both subjective tests with gastroenterologists as well as the structural similarity (SSIM) metric. More surprisingly, the subjective tests indicate that the inpainted frames in many cases can be used for clinical assessment. These results indicate that one can apply error reduction through post processing together with error-correcting codes to obtain a more noise-robust system without any further demand on the WCE.
Mathematical evaluation of the role of cross immunity and nonlinear incidence rate on the transmission dynamics of two dengue serotypes
Authors: Janreung Sutawas , Chinviriyasit Wirawan , Chinviriyasit Settapat
Published: April 2020

Dengue fever is a common disease which can cause shock, internal bleeding, and death in patients if a second infection is involved. In this paper, a multi-serotype dengue model with nonlinear incidence rate is formulated to study the transmission of two dengue serotypes. The dynamical behaviors of the proposed model depend on the threshold value $R_{{0}}^{{n}}$R0n known as the reproductive number which depends on the associated reproductive numbers with serotype-1 and serotype-2. The value of $R_{{0}}^{{n}}$R0n is used to reflect whether the disease dies out or becomes endemic. It is found that the proposed model has a globally stable disease-free equilibrium if $R_{{0}}^{{n}}\leq 1$R0n≤1, which indicates that if public health measures that make (and keep) the threshold to a value less than unity are carried out, the strategy in disease control is effective in the sense that the number of infected human and mosquito populations in the community will be brought to zero irrespective of the initial sizes of sub-populations. When $R_{{0}}^{{n}}>1$R0n>1, the endemic equilibria called the co-existence primary and secondary infection equilibria are locally asymptotically stable. The effects of cross immunity and nonlinear incidence rate are explored using data from Thailand to determine the effective strategy in controlling and preventing dengue transmission and reinfection.
Energy-efficient sensory data gathering based on compressed sensing in IoT networks
Authors: Du Xinxin , Zhou Zhangbing , Zhang Yuqing , Rahman Taj
Published: April 2020

The Internet of Things (IoT) networks have become the infrastructure to enable the detection and reaction of anomalies in various domains, where an efficient sensory data gathering mechanism is fundamental since IoT nodes are typically constrained in their energy and computational capacities. Besides, anomalies may occur occasionally in most applications, while the majority of time durations may reflect a healthy situation. In this setting, the range, rather than an accurate value of sensory data, should be more interesting to domain applications, and the range is represented in terms of the category of sensory data. To decrease the energy consumption of IoT networks, this paper proposes an energy-efficient sensory data gathering mechanism, where the category of sensory data is processed by adopting the compressed sensing algorithm. The sensory data are forecasted through a data prediction model in the cloud, and sensory data of an IoT node is necessary to be routed to the cloud for the synchronization purpose, only when the category provided by this IoT node is different from the category of the forecasted one in the cloud. Experiments are conducted and evaluation results demonstrate that our approach performs better than state-of-the-art techniques, in terms of the network traffic and energy consumption.
Effect of Lamellar Inorganic Fillers on the Properties of Epoxy Emulsion Cement Mortar
Authors: Li Huabing , Zuo Jiandong , Dong Biqin , Xing Feng
Published: April 2020

Lamellar inorganic fillers have been used to improve the performance of polymer composites. In this paper, five kinds of lamellar inorganic fillers, including montmorillonite (MMT), mica, talc, glass flake (GF) and lamellar double hydroxide (LDH), were selected to modify epoxy emulsion cement mortar (EECM). The research evaluated the effects of the structure characteristics of lamellar fillers on the mechanical properties, water absorption and chloride ion permeability resistance of EECM, with comparison to granular ground calcium carbonate (GCC). Results indicated that lamellar fillers had no obvious superiority than GCC in the mechanical strength of EECM, even MMT caused the decline of the mechanical strength. However, lamellar fillers had improved the chloride ion permeability resistance of EECM compared with GCC, and they had the similar effect on reducing of water absorption except MMT. Although the low aspect ratio (AR) of the lamellar fillers benefited the increase of the strength and water resistance of EECM, the lamellar fillers with higher AR could improve the chloride ion permeability resistance of EECM more efficiently.
Ground golf-induced changes in the blood pressure of healthy elderly people
Authors: Ebine Naoyuki , Itoh Masahiro , Horiuchi Masahiro , Hojo Tatsuya , Yoshimura Miho , Fukuoka Yoshiyuki
Published: April 2020

Background

Ground golf is a popular sport among the elderly in Japan. Several types of exercise can reduce the body's mean arterial pressure (MAP), but little is known about how ground golf affects the MAP. We investigated the effects of ground golf on the MAP and the oxygen uptake ($$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$V̇O2) in a healthy elderly population.

Participants and methods

Thirteen elderly Japanese people (3 males and 10 females, mean age of 66 years) participated. All participants played 8 holes of ground golf 6 times, as game (G)1 to G6. The MAP, heart rate (HR), and$$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$V̇O2were measured at rest and every 5 min during each game.

Results

A linear trend analysis revealed that participants’ MAP values progressively decreased as each game proceeded with marginal differences (p= 0.054). There were no significant differences in HR between at rest and any of the games. The$$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$V̇O2during the games (except for G6) were significantly higher than that at-rest (p< 0.05). The resting MAP values were negatively associated with the ground golf-induced changes in MAP (r= 0.786,p= 0.001). The participants with greater changes in$$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$V̇O2during the games showed significantly greater reductions in MAP (r= 0.276,p= 0.043).

Conclusions

Playing ground golf reduced the participants’ MAP and increased their$$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$V̇O2. Participants with higher resting MAP experienced greater reductions in MAP by playing ground golf, which suggests that ground golf can be a useful recreational sport for the elderly.
Annexin A2–STAT3–Oncostatin M receptor axis drives phenotypic and mesenchymal changes in glioblastoma
Authors: Matsumoto Yuji , Ichikawa Tomotsugu , Kurozumi Kazuhiko , Otani Yoshihiro , Fujimura Atsushi , Fujii Kentaro , Tomita Yusuke , Hattori Yasuhiko , Uneda Atsuhito , Tsuboi Nobushige , Kaneda Keisuke , Makino Keigo , Date Isao
Published: April 2020

Glioblastoma (GBM) is characterized by extensive tumor cell invasion, angiogenesis, and proliferation. We previously established subclones of GBM cells with distinct invasive phenotypes and identified annexin A2 (ANXA2) as an activator of angiogenesis and perivascular invasion. Here, we further explored the role of ANXA2 in regulating phenotypic transition in GBM. We identified oncostatin M receptor (OSMR) as a key ANXA2 target gene in GBM utilizing microarray analysis and hierarchical clustering analysis of the Ivy Glioblastoma Atlas Project and The Cancer Genome Atlas datasets. Overexpression of ANXA2 in GBM cells increased the expression of OSMR and phosphorylated signal transducer and activator of transcription 3 (STAT3) and enhanced cell invasion, angiogenesis, proliferation, and mesenchymal transition. Silencing of OSMR reversed the ANXA2-induced phenotype, and STAT3 knockdown reduced OSMR protein expression. Exposure of GBM cells to hypoxic conditions activated the ANXA2–STAT3–OSMR signaling axis. Mice bearing ANXA2-overexpressing GBM exhibited shorter survival times compared with control tumor-bearing mice, whereas OSMR knockdown increased the survival time and diminished ANXA2-mediated tumor invasion, angiogenesis, and growth. Further, we uncovered a significant relationship between ANXA2 and OSMR expression in clinical GBM specimens, and demonstrated their correlation with tumor histopathology and patient prognosis. Our results indicate that the ANXA2–STAT3–OSMR axis regulates malignant phenotypic changes and mesenchymal transition in GBM, suggesting that this axis is a promising therapeutic target to treat GBM aggressiveness.
Association between craniofacial morphological patterns and tooth agenesis-related genes
Authors: Rodrigues Amanda Silva , Teixeira Ellen Cardoso , Antunes Leonardo Santos , Nelson-Filho Paulo , Cunha Arthur Silva , Levy Simone Carvalho , de Souza Araújo Mônica Tirre , de Carvalho Ramos Alice Gomes , Cruz Giuseppe Valduga , Omori Marjorie Ayumi , Matsumoto Mírian Aiko Nakane , Vieira Alexandre Rezende , Küchler Erika Calvano , Marañón-Vásquez Guido Artemio , Antunes Lívia Azeredo Alves
Published: April 2020

Background

The aim of the present study was to assess if genetic polymorphisms in tooth agenesis (TA)-related genes are associated with craniofacial morphological patterns.

Methods

This cross-sectional, multi-center, genetic study evaluated 594 orthodontic Brazilians patients. The presence or absence of TA was determined by analysis of panoramic radiography. The patients were classified according to their skeletal malocclusion and facial growth pattern by means of digital cephalometric analysis. Genomic DNA was extracted from squamous epithelial cells of buccal mucosa and genetic polymorphisms inMSX1(rs1042484),PAX9(rs8004560),TGF-α(rs2902345),FGF3(rs1893047),FGF10(rs900379), andFGF13(rs12838463, rs5931572, and rs5974804) were genotyped by polymerase chain reaction using TaqMan chemistry and end-point analysis.

Results

Genotypes (p= 0.038) and allele (p= 0.037) distributions for theFGF3rs1893047 were significantly different according to the skeletal malocclusion. Carrying at least one G allele increased in more than two times the chance of presenting skeletal class III malocclusion (OR = 2.21, CI 95% = 1.14–4.32;p= 0.017). There was no association between another skeletal craniofacial pattern and some polymorphism assessed in the present study.

Conclusion

Our results suggest that the genetic polymorphism rs1893047 inFGF3might contribute to variations in the craniofacial sagittal pattern.