bluuebunny/crossref_metadata_2025 huggingface dataset:
CircPLEKHM3 acts as a tumor suppressor through regulation of the miR-9/BRCA1/DNAJB6/KLF4/AKT1 axis in ovarian cancer
Authors: Zhang Lei , Zhou Qing , Qiu Qiongzi , Hou Ling , Wu Mengting , Li Jia , Li Xufan , Lu Bingjian , Cheng Xiaodong , Liu Pengyuan , Lu Weiguo , Lu Yan
Published: October 2019

Background

Emerging evidence has shown that circular RNAs (circRNAs) play essential roles in cancer biology and are potential biomarkers and targets for cancer therapy. However, the expression and function of circRNAs in ovarian carcinogenesis and its progression remain elusive.

Methods

RNA sequencing was performed to reveal circRNA expression profiles in ovarian cancerous and normal tissues. Single-molecule RNA in-situ hybridization was used to quantify circPLEKHM3 expression in tumor tissues. Cell-based in-vitro and in-vivo assays were subsequently conducted to support the clinical findings.

Results

CircPLEKHM3 was identified as one of the most significantly down-regulated circRNAs in ovarian cancer tissues compared with normal tissues. Its expression was further decreased in peritoneal metastatic ovarian carcinomas compared to primary ovarian carcinomas. Patients with lower circPLEKHM3 tend to have a worse prognosis. Functionally, circPLEKHM3 overexpression inhibited cell growth, migration and epithelial–mesenchymal transition, whereas its knockdown exerted an opposite role. Further analyses showed that circPLEKHM3 sponged miR-9 to regulate the endogenous expression of BRCA1, DNAJB6 and KLF4, and consequently inactivate AKT1 signaling. In addition, AKT inhibitor MK-2206 could block the tumor-promoting effect of circPLEKHM3 depletion, and potentiate Taxol-induced growth inhibition of ovarian cancer cells.

Conclusions

Our findings demonstrated that circPLEKHM3 functions as a tumor suppressor in ovarian cancer cells by targeting the miR-9/BRCA1/DNAJB6/KLF4/AKT1 axis and may be used as a prognostic indicator and therapeutic target in ovarian cancer patients. The new strategy for treating ovarian cancer by a combination therapy of Taxol with MK-2206 is worth further investigation, especially in ovarian cancer patients with loss of circPLEKHM3 expression.
Prognostic significance of peripheral CD8+CD28+ and CD8+CD28− T cells in advanced non-small cell lung cancer patients treated with chemo(radio)therapy
Authors: Liu Chao , Jing Wang , An Ning , Li Aijie , Yan Weiwei , Zhu Hui , Yu Jinming
Published: October 2019

Background

Noninvasive prognostic biomarkers are needed for advanced non-small cell lung cancer (NSCLC) patients with different histological types to identify cases with poor survival. Here, we investigated the prognostic values of peripheral CD8+CD28+ T cells and CD8+CD28− T cells in advanced NSCLC patients treated with chemo(radio)therapy and the impact of histological type on them.

Methods

Of 232 registered advanced NSCLC patients, 101 treatment-naïve individuals were eligible and included in our study. Flow cytometry was used to evaluate CD8+CD28+ T cells, CD8+CD28− T cells, CD4+ CD25hi T cells, B cells, natural killer cells, γδT cells, and natural killer T cells in patients’ peripheral blood.

Results

The median follow-up time was 13.6 months. Fifty-nine (58.4%) patients died by the end of our study. Fifty-three of the 101 advanced NSCLC cases selected for our study were adenocarcinomas (ADs), and 48 were squamous cell carcinomas (SCCs). Multivariate analyses showed that increased levels of CD8+CD28+ T cells independently predicted favorable overall survival (OS) [hazard ratio (HR): 0.51, 95% confidence interval (CI) 0.30–0.89, P = 0.021] and progression-free survival (PFS) (HR: 0.66, 95% CI 0.37–0.93, P = 0.038) in ADs, but the prediction in SCCs was not statistically significant. In contrast, high levels of CD8+CD28− T cells independently predicted unfavorable OS (HR: 1.41, 95% CI 1.17–3.06, P = 0.035) and PFS (HR: 2.01, 95% CI 1.06–3.85, P = 0.029) in SCCs, but the prediction in ADs was not statistically significant. ADs had higher levels of CD4+CD25hi T cells and CD8+CD28− T cells and lower NK cells (all P < 0.05) than SCCs.

Conclusions

Our findings uncovered the prognostic values of peripheral CD8+CD28+ T cells and CD8+CD28− T cells in advanced NSCLC patients treated with chemo(radio)therapy, which could help to identify patients with poor outcomes and refine treatment strategies.
Dynamic response of microglia/macrophage polarization following demyelination in mice
Authors: Chu Tianci , Zhang Yi Ping , Tian Zhisen , Ye Chuyuan , Zhu Mingming , Shields Lisa B. E. , Kong Maiying , Barnes Gregory N. , Shields Christopher B. , Cai Jun
Published: October 2019

Background

The glial response in multiple sclerosis (MS), especially for recruitment and differentiation of oligodendrocyte progenitor cells (OPCs), predicts the success of remyelination of MS plaques and return of function. As a central player in neuroinflammation, activation and polarization of microglia/macrophages (M/M) that modulate the inflammatory niche and cytokine components in demyelination lesions may impact the OPC response and progression of demyelination and remyelination. However, the dynamic behaviors of M/M and OPCs during demyelination and spontaneous remyelination are poorly understood, and the complex role of neuroinflammation in the demyelination-remyelination process is not well known. In this study, we utilized two focal demyelination models with different dynamic patterns of M/M to investigate the correlation between M/M polarization and the demyelination-remyelination process.

Methods

The temporal and spatial features of M/M activation/polarization and OPC response in two focal demyelination models induced by lysolecithin (LPC) and lipopolysaccharide (LPS) were examined in mice. Detailed discrimination of morphology, sensorimotor function, diffusion tensor imaging (DTI), inflammation-relevant cytokines, and glial responses between these two models were analyzed at different phases.

Results

The results show that LPC and LPS induced distinctive temporal and spatial lesion patterns. LPS produced diffuse demyelination lesions, with a delayed peak of demyelination and functional decline compared to LPC. Oligodendrocytes, astrocytes, and M/M were scattered throughout the LPS-induced demyelination lesions but were distributed in a layer-like pattern throughout the LPC-induced lesion. The specific M/M polarization was tightly correlated to the lesion pattern associated with balance beam function.

Conclusions

This study elaborated on the spatial and temporal features of neuroinflammation mediators and glial response during the demyelination-remyelination processes in two focal demyelination models. Specific M/M polarization is highly correlated to the demyelination-remyelination process probably via modulations of the inflammatory niche, cytokine components, and OPC response. These findings not only provide a basis for understanding the complex and dynamic glial phenotypes and behaviors but also reveal potential targets to promote/inhibit certain M/M phenotypes at the appropriate time for efficient remyelination.
Persistence of multiple patterns and intraspecific polymorphism in multi-species Müllerian communities of net-winged beetles
Authors: Bocek Matej , Kusy Dominik , Motyka Michal , Bocak Ladislav
Published: October 2019

Background

In contrast to traditional models of purifying selection and a single aposematic signal in Müllerian complexes, some communities of unprofitable prey contain members with multiple aposematic patterns. Processes responsible for diversity in aposematic signaling are poorly understood and large multi-species communities are seldom considered.

Results

We analyzed the phylogeny and aposematic patterns of closely related Eniclases net-winged beetles in New Guinea using mtDNA and nextRAD data. We suggest three clades of closely related and incompletely reproductively isolated lineages, detail the extent of polymorphism among Eniclases, and categorize their low-contrast aposematic patterns. The warning signal of Eniclases consists of body shape and color, with ambiguous color perception under some circumstances, i.e., when resting on the undersides of leaves. Field observations suggest that perception of the aposematic signal is affected by beetle behavior and environmental conditions. Local communities containing Eniclases consisted of 7–85 metriorrhynchine species assigned to 3–10 colour patterns.

Conclusion

As a result, we suggest that under certain light conditions the aposematic colour signal is less apparent than the body shape in net-winged beetle communities. We document variable environmental factors in our study area and highly diverse multi-species communities of other net-winged beetles. Which implies dynamically changing community structure in space and time. Variable environmental conditions and diverse community composition are suggested to be favorable for the persistence of multiple aposematic patterns, imperfect mimics, and intraspecific polymorphism. Further research should identify the relative effect of these factors on purifying selection and the alleles which are responsible for phenotypic differences.
Evaluation of white sweet potato tube-feeding formula in elderly diabetic patients: a randomized controlled trial
Authors: Chen Chiao-Ming , Shih Chun-Kuang , Su Yi-Jing , Cheang Kuan-Un , Lo Shu-Fang , Li Sing-Chung
Published: October 2019

Background

Elderly people with type 2 diabetes mellitus (T2DM) have an increased risk of diabetes-related microvascular and macrovascular complications, thus diabetic patients with a functioning gastrointestinal tract but without sufficient oral intake require enteral nutrition (EN) formulas to control blood glucose. White sweet potato (WSP) was a kind of sweet potato could provide a healthy carbohydrate source to EN formula. The aim of this study was to examine at risk of malnutrition T2DM patients whether a WSP-EN would attenuate glucose response and elevate nutritional index compared to a standard polymeric formulas.

Methods

In this randomized, parallel, placebo-controlled, pilot clinical trial to investigate the effects of EN with WSP on aged residents with T2DM in long-term care institutions. In total, 54 eligible participants were randomly assigned to either the non-WSP-EN or WSP-EN group. For 60 days, the WSP-EN group received a WSP formula through nasogastric tube via a stoma with a large-bore syringe. The participants received EN of standard polymeric formulas without WSP in the non-WSP-EN group.

Results

The body weight, body mass index, Mini Nutritional Assessment score, and Geriatric Nutritional Risk Index were significantly higher in the WSP-EN group (p < 0.05). Moreover, the WSP-EN intervention reduced glycated hemoglobin levels (6.73% ± 1.47% vs. 6.40% ± 1.16%), but increased transferrin (223.06 ± 38.85 vs. 245.85 ± 46.08 mg/dL), high-density lipoprotein cholesterol (42.13 ± 10.56 vs. 44.25 ± 8.43 mg/dL), and vitamin A (2.45 ± 0.77 vs 2.74 ± 0.93 μM) levels (p < 0.05). In addition, there was no important side effects including gastrointestinal intolerance with prescribed doses in our WSP-EN treated patients when compared with control ones.

Conclusions

The results suggest WSP incorporated into enteral formulas can improve nutrition status and glycemic control in elderly diabetic patients.

Trial registration

NCT02711839, registered 27 May 2015.
Inhaled gold nanoparticles cause cerebral edema and upregulate endothelial aquaporin 1 expression, involving caveolin 1 dependent repression of extracellular regulated protein kinase activity
Authors: Chen Ching-Yi , Liao Po-Lin , Tsai Chi-Hao , Chan Yen-Ju , Cheng Yu-Wen , Hwang Ling-Ling , Lin Kuan-Hung , Yen Ting-Ling , Li Ching-Hao
Published: October 2019

Background

Gold nanoparticles (Au-NPs) have extensive applications in electronics and biomedicine, resulting in increased exposure and prompting safety concerns for human health. After absorption, nanoparticles enter circulation and effect endothelial cells. We previously showed that exposure to Au-NPs (40–50 nm) collapsed endothelial tight junctions and increased their paracellular permeability. Inhaled nanoparticles have gained significant attention due to their biodistribution in the brain; however, little is known regarding their role in cerebral edema. The present study investigated the expression of aquaporin 1 (AQP1) in the cerebral endothelial cell line, bEnd.3, stimulated by Au-NPs.

Results

We found that treatment with Au-NPs induced AQP1 expression and increased endothelial permeability to water. Au-NP exposure rapidly boosted the phosphorylation levels of focal adhesion kinase (FAK) and AKT, increased the accumulation of caveolin 1 (Cav1), and reduced the activity of extracellular regulated protein kinases (ERK). The inhibition of AKT (GDC-0068) or FAK (PF-573228) not only rescued ERK activity but also prevented AQP1 induction, whereas Au-NP-mediated Cav1 accumulation remained unaltered. Neither these signaling molecules nor AQP1 expression responded to Au-NPs while Cav1 was silenced. Inhibition of ERK activity (U0126) remarkably enhanced Cav1 and AQP1 expression in bEnd.3 cells. These data demonstrate that Au-NP-mediated AQP1 induction is Cav1 dependent, but requires the repression on ERK activity. Mice receiving intranasally administered Au-NPs displayed cerebral edema, significantly augmented AQP1 protein levels; furthermore, mild focal lesions were observed in the cerebral parenchyma.

Conclusions

These data suggest that the subacute exposure of nanoparticles might induce cerebral edema, involving the Cav1 dependent accumulation on endothelial AQP1.
Correlation of tilt of the anterior pelvic plane angle with anatomical pelvic tilt and morphological configuration of the acetabulum in patients with developmental dysplasia of the hip: a cross-sectional study
Authors: Imai Norio , Suzuki Hayato , Nozaki Asami , Hirano Yuki , Endo Naoto
Published: October 2019

Background

It was previously reported that pelvises with developmental dysplasia of the hip are tilted anteriorly, which increases bony coverage of the femoral head. This study aimed to investigate the correlation between anatomical parameters of the pelvis such as pelvic incidence and anatomical pelvic tilt and functional parameters of the spine and pelvis such as tilt of the anterior pelvic plane.

Methods

We examined 84 female patients with bilateral developmental dysplasia of the hip who had undergone curved periacetabular osteotomy at author’s institution. Radiographs of the thoracic to lumbar spines and the pelvis were obtained in the standing position to measure spino-pelvic parameters before surgery. Morphological parameters of the acetabulum such as the anterior center-edge (CE) angle, posterior CE angle, lateral CE angle, and acetabular anteversion were measured using a preoperative three-dimensional pelvic model reconstructed from computed tomography images. Pearson’s correlation analysis was conducted to evaluate the relationship of these parameters.

Results

With regard to correlations between pelvic incidence (PI) and other parameters, the sacral slope (SS) value (r = 0.666) was the highest among functional parameters and the anatomical-SS value (r = 0.789) was the highest among morphological parameters. There were moderate correlations of the anterior pelvic plane angle (APPA) with pelvic tilt (PT) (r = − 0.594) and anatomical-PT (r = 0.646). With regard to correlations between spino-pelvic parameters and bony morphological parameters of the acetabulum, there was a moderate correlation between anatomical-PT and acetabular anteversion (AA) (r = 0.424). There were moderate correlations of APPA with the anterior CE angle (r = − 0.478), posterior CE angle (r = 0.432), and AA (r = 0.565). APPA had a stronger correlation with anatomical-PT (r = 0.646) than with AA.

Conclusions

The tilt of the pelvis may be more dependent on anatomical-PT, a morphological parameter of the pelvis, than the lateral CE angle, anterior CE angle, posterior CE angle, and acetabular anteversion on bony coverage of the acetabulum. This study is the first to investigate the correlation between functional parameters of the pelvis and spine and morphological parameters of the pelvis and acetabulum besides PI.
De Novo Isolation & Affinity Maturation of yeast-displayed Virion-binding human fibronectin domains by flow cytometric screening against Virions
Authors: Heinzelman Pete , Low Alyssa , Simeon Rudo , Wright Gus A. , Chen Zhilei
Published: October 2019

Background

The promise of biopharmaceuticals comprising one or more binding domains motivates the development of novel methods for de novo isolation and affinity maturation of virion-binding domains. Identifying avenues for overcoming the challenges associated with using virions as screening reagents is paramount given the difficulties associated with obtaining high-purity virus-associated proteins that retain the conformation exhibited on the virion surface.

Results

Fluorescence activated cell sorting (FACS) of 1.5 × 107clones taken from a naïve yeast surface-displayed human fibronectin domain (Fn3) against whole virions yielded two unique binders to Zika virions. Construction and FACS of site-directed binding loop mutant libraries based on one of these binders yielded multiple progeny clones with enhanced Zika-binding affinities. These affinity-matured clones bound Zika virions with low double- or single-digit nanomolar affinity in ELISA assays, and expressed well as soluble proteins inE. colishake flask culture, with post-purification yields exceeding 10 mg/L.

Conclusions

FACS of a yeast-displayed binding domain library is an efficient method for de novo isolation of virion-binding domains. Affinities of isolated virion-binding clones are readily enhanced via FACS screening of mutant progeny libraries. Given that most binding domains are compatible with yeast display, the approach taken in this work may be broadly utilized for generating virion-binding domains against many different viruses for use in passive immunotherapy and the prevention of viral infection.
Assessment of histological liver alterations in dogs naturally infected with Leishmania infantum
Authors: Lima Isadora S. , Solcá Manuela S. , Tafuri Wagner L. , de Freitas Luiz A. R. , dos-Santos Washington L. C.
Published: October 2019

Background

The liver plays a central role in the development of canine visceral leishmaniasis. Studies of natural infection in animals and humans indicate a direct relationship between resolution of infection and the formation and maturation of granulomas in the liver. However, in contrast to other reports in the literature, the present study found no differences in the characteristics of hepatic granulomas that could be related to resistance or susceptibility to Leishmania. Here, we describe the hepatic alterations observed in dogs with differing clinical manifestations of visceral leishmaniasis in an endemic area in the state of Bahia, Brazil.

Methods

We examined 148 animals in an endemic area. The animals were clinically examined, and the infection was determined by ELISA, spleen aspirate culture and quantitative PCR. The animals were grouped into asymptomatic or symptomatic based on the number of signs of LV. The histological liver evaluation was performed in a blinded way.

Results

Our results indicated no association between the characteristics of granulomas and clinical presentation. We found an association between the intensity of this inflammatory response and parasite load in the animals’ spleens. It is important to note that while hepatic alterations, such as portal and perivascular inflammation and the presence of larger amounts of granulomas, were linked with higher parasite loads, we found the inverse to be true with respect to intrasinusoidal lymphocytosis, the formation of intrasinusoidal inflammatory cell aggregates and Kupffer cell hypertrophy.

Conclusions

Our findings suggest that the presence of mononuclear inflammatory cells inside the sinusoids is more important than that of organized granulomas in terms of the containment of parasitism by the host. We suggest that the presence of granulomas indicates the failure of a first line of defense mechanism in the control of parasite infection, which could be related to the presence of inflammatory cells and Kupffer cell hypertrophy inside the sinusoids. We further demonstrated that dogs with active Leishmania spp. infection present a higher frequency of inflammatory changes in the liver. In addition to being correlated with the severity of clinical manifestation, these hepatic alterations were also associated with changes in hematological and biochemical parameters.
Striking differences in virulence, transmission and sporocyst growth dynamics between two schistosome populations
Authors: Le Clecʼh Winka , Diaz Robbie , Chevalier Frédéric D. , McDew-White Marina , Anderson Timothy J. C.
Published: October 2019

Background

Parasite traits associated with transmission success, such as the number of infective stages released from the host, are expected to be optimized by natural selection. However, in the trematode parasite Schistosoma mansoni, a key transmission trait, i.e. the number of cercariae larvae shed from infected Biomphalaria spp. snails, varies significantly within and between different parasite populations and selection experiments demonstrate that this variation has a strong genetic basis. In this study, we compared the transmission strategies of two laboratory schistosome population and their consequences for their snail host.

Methods

We infected inbred Biomphalaria glabrata snails using two S. mansoni parasite populations (SmBRE and SmLE), both isolated from Brazil and maintained in the laboratory for decades. We compared life history traits of these two parasite populations by quantifying sporocyst growth within infected snails (assayed using qPCR), output of cercaria larvae and impact on snail host physiological response (i.e. hemoglobin rate, laccase-like activity) and survival.

Results

We identified striking differences in virulence and transmission between the two studied parasite populations. SmBRE (low shedder (LS) parasite population) sheds very low numbers of cercariae and causes minimal impact on the snail physiological response (i.e. laccase-like activity, hemoglobin rate and snail survival). In contrast, SmLE (high shedder (HS) parasite population) sheds 8-fold more cercariae (mean ± SE cercariae per shedding: 284 ± 19 vs 2352 ± 113), causes high snail mortality and has strong impact on snail physiology. We found that HS sporocysts grow more rapidly inside the snail host, comprising up to 60% of cells within infected snails, compared to LS sporocysts, which comprised up to 31%. Cercarial production is strongly correlated to the number of S. mansoni sporocyst cells present within the snail host tissue, although the proportion of sporocyst cells alone does not explain the low cercarial shedding of SmBRE.

Conclusions

We demonstrated the existence of alternative transmission strategies in the S. mansoni parasite consistent with trade-offs between parasite transmission and host survival: a “boom-bust” strategy characterized by high virulence, high transmission and short duration infections and a “slow and steady” strategy with low virulence, low transmission but long duration of snail host infections.
University students’ alcohol use behaviour and self-efficacy to abstain from alcohol use: data from Ghana
Authors: Glozah Franklin N. , Komesuor Joyce
Published: October 2019

Objectives

The university students’ alcohol use behaviour and alcohol use self-efficacy data were collected among Ghanaian university students. This survey had two main objectives: (a) to examine the factorial validity, structure, and reliability of the 20-item alcohol abstinence self-efficacy scale among undergraduate students and (b) to examine the role of alcohol abstinence self-efficacy in the pros and cons of alcohol use. These two objectives have been published as separate research articles without the data (including data management) that were used for analyses. As the data are not already available as part of these published papers, this data note provides a composite and integrated data grounded on these published research articles with detailed information on the instruments used to collect data, raw data in statistical software, managed/coded data in statistical software, and generated correlation matrix used to perform complex analysis.

Data description

The data includes information on two major dimensions: (a) alcohol abstinence self-efficacy—negative affect, social interactions and positive states, physical pain/illness, and alcohol craving (thoughts about using) and (b) decisional balance—measuring the benefits (pros) of alcohol use and the costs (cons) of alcohol use. In addition, data were collected on socio-demographic characteristics of students including their age, sex, level/year in school, stream of study, place of residence and religious affiliation. The data collected is more representative of students in private universities.
Optimized fixation of actin filaments for improved indirect immunofluorescence staining of rickettsiae
Authors: Danchenko Monika , Csaderova Lucia , Fournier Pierre Edouard , Sekeyova Zuzana
Published: October 2019

Objective

The objective was to investigate fixative solutions: 3.7% formaldehyde, 4% paraformaldehyde, 4% paraformaldehyde in the cytoskeletal buffer and 4% paraformaldehyde in PHEM buffer (containing PIPES, HEPES, EGTA and MgCl2), applicable for immunofluorescence assay.

Results

Herein we optimized this serological technique, testing four fixative solutions, for the sensitive detection of rickettsial antigens, and preservation of intracellular structures of the host cells, particularly filamentous actin. Rickettsial antigens were presented equally well both with formaldehyde and all paraformaldehyde-based fixations, but only protocol with 4% paraformaldehyde in PHEM buffer allowed accurate imaging of actin filaments, and simultaneously allows monitoring of rickettsiae using actin-based motility during infection inside the host cells.
Oral vitamin C supplementation to patients with myeloid cancer on azacitidine treatment: Normalization of plasma vitamin C induces epigenetic changes
Authors: Gillberg Linn , Ørskov Andreas D. , Nasif Ammar , Ohtani Hitoshi , Madaj Zachary , Hansen Jakob W. , Rapin Nicolas , Mogensen Johanne B. , Liu Minmin , Dufva Inge H. , Lykkesfeldt Jens , Hajkova Petra , Jones Peter A. , Grønbæk Kirsten
Published: October 2019

Background

Patients with haematological malignancies are often vitamin C deficient, and vitamin C is essential for the TET-induced conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), the first step in active DNA demethylation. Here, we investigate whether oral vitamin C supplementation can correct vitamin C deficiency and affect the 5hmC/5mC ratio in patients with myeloid cancers treated with DNA methyltransferase inhibitors (DNMTis).

Results

We conducted a randomized, double-blinded, placebo-controlled pilot trial (NCT02877277) in Danish patients with myeloid cancers performed during 3 cycles of DNMTi-treatment (5-azacytidine, 100 mg/m2/d for 5 days in 28-day cycles) supplemented by oral dose of 500 mg vitamin C (n = 10) or placebo (n = 10) daily during the last 2 cycles. Fourteen patients (70%) were deficient in plasma vitamin C (< 23 μM) and four of the remaining six patients were taking vitamin supplements at inclusion. Global DNA methylation was significantly higher in patients with severe vitamin C deficiency (< 11.4 μM; 4.997 vs 4.656% 5mC relative to deoxyguanosine, 95% CI [0.126, 0.556], P = 0.004). Oral supplementation restored plasma vitamin C levels to the normal range in all patients in the vitamin C arm (mean increase 34.85 ± 7.94 μM, P = 0.0004). We show for the first time that global 5hmC/5mC levels were significantly increased in mononuclear myeloid cells from patients receiving oral vitamin C compared to placebo (0.037% vs − 0.029%, 95% CI [− 0.129, − 0.003], P = 0.041).

Conclusions

Normalization of plasma vitamin C by oral supplementation leads to an increase in the 5hmC/5mC ratio compared to placebo-treated patients and may enhance the biological effects of DNMTis. The clinical efficacy of oral vitamin C supplementation to DNMTis should be investigated in a large randomized, placebo-controlled clinical trial.

Trial registration

ClinicalTrials.gov, NCT02877277. Registered on 9 August 2016, retrospectively registered.
KIF5B modulates central spindle organization in late-stage cytokinesis in chondrocytes
Authors: Gan Huiyan , Xue Wenqian , Gao Ya , Zhu Guixia , Chan Danny , Cheah Kathryn S. E. , Huang Jiandong
Published: October 2019

Background

The growth plate is a special region of the cartilage that drives longitudinal growth of long bones. Proliferating chondrocytes in the growth plate, arranged in columns, divide perpendicular to the long axis of the growth plate then intercalate to re-align with parental columns. Which molecular partners maintain growth plate columnar structures and chondrocyte cytokinesis has not been fully revealed. It is reported that kinesin family member 3A (KIF3A), a subunit of kinesin-2, plays an important role in maintaining columnar organization in growth plates via controlling primary cilia formation and cell proliferation.

Result

Here we identify kinesin family member 5B (KIF5B), the heavy chain of kinesin-1, a ubiquitously expressed motor protein for anterograde intracellular transport along the microtubule network, as a key modulator of cytokinesis in chondrocytes via maintenance of central spindle organization. We show that KIF5B is concentrated in the central spindle during cytokinesis in both primary chondrocytes and chondrogenic ATDC5 cells.

Conclusion

The failure of cytokinesis in KIF5B null chondrocytes leads to incomplete cell rotation, disrupting proliferation and differentiation, and results in a disorganized growth plate.
Hadamard k-fractional inequalities of Fejér type for GA-s-convex mappings and applications
Authors: Lei Hui , Hu Gou , Cao Zhi-Jie , Du Ting-Song
Published: October 2019

The main aim of this paper is to establish some Fejér-type inequalities involving hypergeometric functions in terms of GA-s-convexity. For this purpose, we construct a Hadamard k-fractional identity related to geometrically symmetric mappings. Moreover, we give the upper and lower bounds for the weighted inequalities via products of two different mappings. Some applications of the presented results to special means are also provided.
Least energy sign-changing solutions for Kirchhoff–Poisson systems
Authors: Chai Guoqing , Liu Weiming
Published: October 2019

The paper deals with the following Kirchhoff–Poisson systems:
$$ \textstyle\begin{cases} - ( {1+b\int _{{\mathbb{R}}^{3}} { \vert \nabla u \vert ^{2}\,dx} } ) \Delta u+u+k(x)\phi u+\lambda \vert u \vert ^{p-2}u=h(x) \vert u \vert ^{q-2}u, & x\in {\mathbb{R}}^{3}, \\ -\Delta \phi =k(x)u^{2}, & x\in {\mathbb{R}}^{3}, \end{cases} $$

{

−
(
1
+
b

∫

R
3

|
∇
u

|
2

d
x
)
Δ
u
+
u
+
k
(
x
)
ϕ
u
+
λ
|
u

|

p
−
2

u
=
h
(
x
)
|
u

|

q
−
2

u
,

x
∈

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3

,

−
Δ
ϕ
=
k
(
x
)

u
2

,

x
∈

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3

,

where the functions k and h are nonnegative, $0\le \lambda , b$
0
≤
λ
,
b
; $2\le p\le 4< q<6$
2
≤
p
≤
4
<
q
<
6
. Via a constraint variational method combined with a quantitative lemma, some existence results on one least energy sign-changing solution with two nodal domains to the above systems are obtained. Moreover, the convergence property of $u_{b}$

u
b

as $b \searrow 0$
b
↘
0
is established.
A segmented Adomian algorithm for the boundary value problem of a second-order partial differential equation on a plane triangle area
Authors: Yun Yin-shan , Wen Ying , Chaolu Temuer , Rach Randolph
Published: October 2019

For the boundary value problem (BVP) of a second-order partial differential equation on a plane triangle area, we propose a new algorithm based on the Adomian decomposition method (ADM) combined with a segmented technique. In addition, we present a new theorem that ensures the convergence of the algorithm. By this algorithm, the model for the effect of regional recharge on the plane triangle groundwater flow region is solved, from which we obtain the segmented exact solution of the problem, which satisfies the governing equation and all of the specified boundary conditions. Then, by the algorithm combined with Taylor’s formula, the heterogeneous aquifer model on the plane triangle groundwater flow region is considered, from which we obtain the segmented high-precision approximate solution of the problem.
Solitons for the modified $(2 + 1)$-dimensional Konopelchenko–Dubrovsky equations
Authors: Lyu Xiumei , Gu Wei
Published: October 2019

In the paper, we consider the modified $(2 + 1)$
(
2
+
1
)
-dimensional Konopelchenko–Dubrovsky equations which possess high order nonlinear terms. Under the aid of Maple, we derive the exact traveling wave solutions of the mKDs by the auxiliary equation approach. Under some special conditions, Jacobi elliptic function solutions, degenerated triangular function solutions, and solitons for the mKD equations are constructed.
Some symmetries, similarity solutions and various conservation laws of a type of dispersive water waves
Authors: Zhang Yufeng , Bai Na , Guan Hongyang
Published: October 2019

We investigate the point symmetries, Lie–Bäcklund symmetries for a type of dispersive water waves. We obtain some Lie transformation groups, various group-invariant solutions, and some similarity solutions. Besides, we produce different formats of conservation laws of the dispersive water waves by using different schemes. Finally, we consider some special solutions of the stationary dispersive water-wave equations.
Effect of a pedometer-based walking challenge on increasing physical activity levels amongst hospital workers
Authors: Al-Mohannadi Abdulla S. , Sayegh Suzan , Ibrahim Izzeldin , Salman Ahmad , Farooq Abdulaziz
Published: October 2019

Background

More than 50% of Qatari adults are physically inactive. The workplace is an excellent environment to implement cost-effective, efficient behavioural physical activity (PA) interventions to increase PA. This study evaluated whether a pedometer-based walking challenge would increase PA levels amongst hospital workers.

Methods

A pedometer-based workplace walking intervention was implemented in April–August 2017. Amongst 800 recruited full-time hospital workers, a cross-sectional sample of 212 workers completed the online questionnaires Quality of Life Questionnaire, International Physical Activity Questionnaire (IPAQ), and Workforce Sitting Questionnaire. A sub-sample of participants (n = 54) wore a pedometer for 3 months. They recorded their daily step count through an online web platform linked to the pedometer. Another cross-sectional sample (n = 194) in the same target population completed online questionnaires at post intervention.

Results

The IPAQ assessed physical activity at post-intervention was higher compared to pre-intervention. In a sub-sample (n = 54) that provided pedometer data, workers’ step count during intervention was significantly higher (9270) from pre-intervention (7890) (p = 0.048).

Conclusions

Although self-reported PA was higher post-intervention, the subsample showed objectively assessed physical activity did not exceed the threshold recommended for optimal health. Therefore, encouraging participation and maintaining motivation amongst workers in a work-based PA programme is challenging.
Improvement of fiber optic based localized surface plasmon resonance sensor by optical fiber surface etching and Au capping
Authors: Bae Se-Woong , Kim Hyeong-Min , Park Jae-Hyoung , Lee Seung-Ki
Published: October 2019

Fiber optic based localized surface plasmon resonance (FO-LSPR) sensor is one of the biosensors that detects specific biomolecules and can detect the onset of disease. In this paper, we propose two methods to improve the signal to noise ratio (SNR) of the sensor, which is one of the main characteristics of the FO-LSPR sensor. The first method is to increase the intensity of the sensor by increasing the size of gold nanoparticle (Au NP) formed on the optical fiber surface by Au capping method. The second method is to form a structure that reduces the reflection by increasing the roughness of the surface by etching the surface of the optical fiber using the Au NP formed on the surface of the optical fiber as a mask. Increasing the roughness of the optical fiber surface can reduce the background signal of the sensor. The two methods mentioned above can increase the SNR of the sensor. When the SNR of the sensor is increased, the efficiency of the sensor is improved.
Casing failure identification of long-abandoned geothermal wells in Field Dieng, Indonesia
Authors: Marbun B. T. H. , Ridwan R. H. , Sinaga S. Z. , Pande B. , Purbantanu B. A.
Published: October 2019

Integrity issues create challenges for maintaining the production of mature geothermal wells. Such problems are likely to occur in wells designed according to oil and gas standards, without considering the extreme geothermal environment. PT Geo Dipa Energi as the operator of the Dieng geothermal field, one of the longest operated in Indonesia, has experienced this difficulty since acquiring the field. Almost half of the production wells have been abandoned because of casing issues. To increase production, the operator plans to reactivate wells that have been previously abandoned. An initial study was performed to assess the technical feasibility of reactivating wells at Dieng; it included the development of a well assessment methodology including casing design, comprising historical data analysis, identification of well problems, and investigation of well integrity. The study focused on the identification and characterization of two abandoned wells, HCE9B and HCE28B, current casing conditions, limitations, and challenges to perform a well intervention and workover which is realistic, measurable, economic, and technically feasible. The result of this study will be applicable for casing design for future wells.
Improving the performance of support-vector machine by selecting the best features by Gray Wolf algorithm to increase the accuracy of diagnosis of breast cancer
Authors: Kamel Seyed Reza , YaghoubZadeh Reyhaneh , Kheirabadi Maryam
Published: October 2019

One of the most common diseases among women is breast cancer, the early diagnosis of which is of paramount importance. Given the time-consuming nature of the diagnosis process of the disease, using new methods such as computer science is extremely important for early detection of the condition. Today, the main emphasis is on the science of data mining as one of the computer methods in the field of diagnosis. In the present study, we used data mining as a combination of feature selection method by Gray Wolf Optimization (GWO) and support vector machine (SVM), which is a new technique with high accuracy compared to other methods in this classification, to increase the accuracy of breast cancer diagnosis. The UCI dataset and functional parameters and various statistical criteria were applied to evaluate the proposed method and assess the validity of the results in MATLAB, respectively. Application of the proposed method increased the improvement of the evaluated criteria, which increased the accuracy of diagnosis by 27.68%, compared to former works in the field. As such, it could be concluded that the proposed method had a higher ability to diagnose breast cancer, compared to previous techniques.
Emotion analysis of Arabic tweets using deep learning approach
Authors: Baali Massa , Ghneim Nada
Published: October 2019

Nowadays, sharing moments on social networks have become something widespread. Sharing ideas, thoughts, and good memories to express our emotions through text without using a lot of words. Twitter, for instance, is a rich source of data that is a target for organizations for which they can use to analyze people’s opinions, sentiments and emotions. Emotion analysis normally gives a more profound overview of the feelings of an author. In Arabic Social Media analysis, nearly all projects have focused on analyzing the expressions as positive, negative or neutral. In this paper we intend to categorize the expressions on the basis of emotions, namely happiness, anger, fear, and sadness. Different approaches have been carried out in the area of automatic textual emotion recognition in the case of other languages, but only a limited number were based on deep learning. Thus, we present our approach used to classify emotions in Arabic tweets. Our model implements a deep Convolutional Neural Networks (CNN) trained on top of trained word vectors specifically on our dataset for sentence classification tasks. We compared the results of this approach with three other machine learning algorithms which are SVM, NB and MLP. The architecture of our deep learning approach is an end-to-end network with word, sentence, and document vectorization steps. The deep learning proposed approach was evaluated on the Arabic tweets dataset provided by SemiEval for the EI-oc task, and the results-compared to the traditional machine learning approaches-were excellent.
The decreased SIRT1 level may account for the lipid profile in chronic kidney disease
Authors: Chen Gang , Li Xuemei
Published: October 2019

Dysregulated lipid profile with hypertriglyceridemia and increased low-density lipoprotein (LDL) is common in chronic kidney disease (CKD) whereas the reason is unclear. A similar phenomenon is found in the elder population. Silent information regulator-1 (SIRT1) associates with many modulators regulating lipid metabolism and results in increased expression of sterol regulatory element-binding proteins (SREBPs), which functions as a key modulator in lipid synthesis. Since CKD is being viewed as a premature aging model and SIRT1 is known to decrease during the process of aging, we hypothesize that SIRT1 level is reduced in the liver when CKD develops and eventually result in dysregulated lipid profile.
Rayleigh wave propagation in transversely isotropic magneto-thermoelastic medium with three-phase-lag heat transfer and diffusion
Authors: Kaur Iqbal , Lata Parveen
Published: October 2019

The present research deals with the propagation of Rayleigh wave in transversely isotropic magneto-thermoelastic homogeneous medium in the presence of mass diffusion and three-phase-lag heat transfer. The wave characteristics such as phase velocity, attenuation coefficients, specific loss, and penetration depths are computed numerically and depicted graphically. The normal stress, tangential stress components, temperature change, and mass concentration are computed and drawn graphically. The effects of three-phase-lag heat transfer, GN type-III, and LS theory of heat transfer are depicted on the various quantities. Some particular cases are also deduced from the present investigation.
Phase II study of R–CVP followed by rituximab maintenance therapy for patients with advanced marginal zone lymphoma: consortium for improving survival of lymphoma (CISL) study
Authors: Oh Sung Yong , Kim Won Seog , Kim Jin Seok , Kim Seok Jin , Yoon Dok Hyun , Yang Deok‐Hwan , Lee Won Sik , Kim Hyo Jung , Yhim Ho‐Young , Jeong Seong Hyun , Won Jong Ho , Lee Suee , Kong Jee Hyun , Lim Sung‐Nam , Ji Jun Ho , Kwon Kyung A. , Lee Gyeong‐Won , Lee Jae Hoon , Lee Ho Sup , Shin Ho‐Jin , Suh Cheolwon
Published: October 2019

Background

The response rate and survival improvement for rituximab, a CD20‐targeting monoclonal antibody, have been demonstrated in marginal zone lymphoma (MZL) as monotherapy and in combination with chemotherapeutic regimens, yet relapses still occur despite treatment completion. Thus, extending the period of remission in MZL patients remains an essential goal. This multicenter, single‐arm, open‐label phase II study evaluated the survival efficacy of 2 years of rituximab‐maintenance therapy in patients with stage III–IV CD20‐positive MZL who had responded to first‐line R–CVP (rituximab, cyclophosphamide, vincristine, and prednisolone). The objective of this study was to determine whether rituximab maintenance following R–CVP warrants further investigation.

Methods

Prior to rituximab‐maintenance therapy, patients received 6–8 cycles of first‐line R–CVP therapy for stage III–IV MZL. Rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), and vincristine (1.4 mg/m2; maximum 2 mg) were administered via an intravenous infusion on day 1 of each 3‐week cycle, while oral prednisolone (100 mg) was given on days 1–5 of each 3‐week cycle. The patients who achieved complete response (CR), partial response (PR), or stable disease (SD) to R–CVP treatment, were prescribed rituximab‐maintenance therapy which was administered intravenously at a dose of 375 mg/m2 every 8 weeks for up to 12 cycles. The primary endpoint was progression‐free survival (PFS). Secondary endpoints were overall survival (OS) and treatment safety.

Results

47 patients were enrolled, of whom, 45 (96%) received rituximab‐maintenance treatment. Fifteen (33%) patients had nodal MZL. Following R–CVP first‐line therapy, 20 (44%), 22 (49%), and 3 (7%) patients achieved CR, PR, and SD, respectively. After a median follow‐up of 38.2 months, their observed 3‐year PFS rate was 81%. During the rituximab‐maintenance, 6 PR and 1 SD patients achieved CR following the administration of R–CVP. Elevated LDH and the presence of B symptoms were found to be significant prognostic factors for PFS (P= 0.003) and demonstrated a 3‐year OS rate of 90%. Rituximab‐maintenance therapy was well tolerated, and the common treatment‐emergent adverse events were sensory neuropathy (18%), myalgia (13%), fatigue (9%), and neutropenia (9%).

Conclusion

Rituximab‐maintenance therapy following first‐line R–CVP demonstrated good PFS in patients with stage III–IV MZL, in addition to a favorable toxicity profile.

Trial registration clinicaltrials.gov: NCT01213095
Application of botulinum toxin in maxillofacial field: Part II. Wrinkle, intraoral ulcer, and cranio-maxillofacial pain
Authors: Kwon Kyung-Hwan , Shin Kyung Su , Yeon Sung Hee , Kwon Dae Gun
Published: October 2019

Botulinum toxin (BTX) is used in various ways such as temporarily resolving muscular problems in musculoskeletal temporomandibular disorders, inducing a decrease in bruxism through a change in muscular patterns in a patient’s bruxism, and solving problems in patients with tension headache. And also, BTX is widely used in cosmetic applications for the treatment of facial wrinkles after local injection, but conditions such as temporomandibular joint disorders, headache, and neuropathic facial pain could be treated with this drug. In this report, we will discuss the clinical use of BTX for facial wrinkle, intraoral ulcer, and cranio-maxillofacial pain with previous studies and share our case.
Extra-pleural solitary fibrous tumors: a review
Authors: Almeida Costa Nuno , Fonseca Diogo , Santos João
Published: October 2019

Solitary fibrous tumor (SFT) is a rare mesenchymal ubiquitous tumor reported in the pleura and a wide variety of extrapleural locations, most frequently in the orbits and extremities.

Approximately 78–88% of SFTs are benign and 12–22% are malignant.

Although tumor characteristics are highly dependent on the location there are unifying features in MR imaging suggesting SFT: well-circumscribed, often lobulated nodular lesion, delayed contrast enhancement and the presence of fibrous contents which are hypointense on T1 and T2-weighted MRI imaging.

There are many SFT differential diagnosis, highly dependent to the tumor location. Due to its rarity the diagnosis of extrapleural SFTs may be challenging. Histopathologic analysis is always required to confirm the diagnosis and to allow the distinction between the benign and malignant forms.

We review pleural and extrapleural SFTs, presenting diagnostic clues, differential diagnosis and prognostic factors.