bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of toll‐like receptors 2 and 4 in the neuroprotective effects of bone marrow–derived mesenchymal stem cells in an experimental model of ischemic stroke
Authors: Nejati Majid , Tameh Abolfazl Azami , Atlasi Mohammad Ali
Published: November 2018

Objective

Ischemic stroke is a major cause of death and prolonged disability worldwide. Inflammation plays an important role in post‐ischemic injury. Mesenchymal stem cells (MSCs) have protective effects in stroke treatment due to their anti‐inflammatory properties. Toll‐like receptors (TLRs) 2 and 4 are two innate immune receptors that trigger inflammatory processes. Here, we investigated the association of these receptors with the protective effect of MSCs after middle cerebral artery occlusion (MCAO) in rats.

Methods

MSCs were isolated from the bone marrow of young rats and expanded in vitro. A model of ischemic stroke was performed by transient MCAO with 24 or 72 hours of reperfusion. Two hours after ischemia/reperfusion (I/R), the rats received MSCs or saline via tail vein and the sham group underwent surgery without MCAO. The relative gene expressions of TLR2, TLR4, and MyD88 were evaluated in the ischemic penumbra by the real‐time PCR technique. Active astrocyte and microglia and TLR‐expressing cells were detected by immunohistochemistry (IHC).

Results

MSCs significantly decreased the genes expression of TLR2 (P = 0.006
), TLR4 (P = 0.038
), and MyD88 (P = 0.009
) after their upregulation by I/R. Moreover, the IHC results indicated that glial fibrillary acidic protein (GFAP) and ionized calcium‐binding adapter molecule 1 (Iba‐1) positive cells were significantly increased by I/R (
P < 0.001), and MSCs significantly decreased the number of GFAP (
P = 0.003), Iba‐1 (
P = 0.001), TLR2 (
P = 0.004), and TLR4 (
P = 0.007) positive cells 72 hours after I/R.

Conclusion

The neuroprotective effect of MSCs in brain ischemic injury is associated with its anti‐inflammatory effects and modulation of the activity of immune cells. Inhibition of TLR2 and TLR4 expression is one of the possible mechanisms of this protective effect.
Long noncoding RNA LINC00339 promotes laryngeal squamous cell carcinoma cell proliferation and invasion via sponging miR‐145
Authors: Liu Shouzhou , Duan Wenchao
Published: November 2018

Laryngeal squamous cell carcinoma (LSCC) is a very common neoplasm of the head and neck in the world. Long noncoding RNAs play key roles in cell infiltration, fate, apoptosis, and invasion. However, the functional role and expression of LINC00339 remains unclear in LSCC. In this study, we showed that the expression level of LINC00339 was upregulated in LSCC tissues and cell lines. LINC00339 silencing suppressed the proliferation, invasion, and epithelial‐mesenchymal transition (EMT) progression of LSCC cells. In addition, we showed that LINC00339 acted as a sponge of miR‐145, and LINC00339 silencing promoted the expression of miR‐145 in Hep2 cell. Furthermore, the expression of miR‐145 was lower in LSCC tissues than in their paired normal samples and the miR‐145 expression level was negatively correlated with LINC00339 expression in LSCC tissues. The knockdown of miR‐145 promoted the proliferation, invasion, and EMT progression of LSCC cells. Finally, we indicated that LINC00339 silencing inhibited the proliferation, invasion, and EMT progression of LSCC cells by suppressing the miR‐145 expression. These data suggested that LINC00339 acted as an oncogene in the development of LSCC, partly by regulating the miR‐145 expression.
Association study of copy number variation in BMP8A gene with the risk of ankylosing spondylitis in Iranian population
Authors: Shahba Sara , Jafari Shakib Reza , Jamshidi Ahmadreza , Vojdanian Mahdi , Akhtari Maryam , Aslani Saeed , Poursani Shiva , Nikokar Iraj , Mahmoudi Mahdi
Published: November 2018

Background

Copy number variation (CNV) of DNA segments has been considered as an important component of genetic variation, affecting the quality and quantity of gene expression. Bone morphogenic protein 8A (BMP8A) has been reported to function in bone formation. With respect to the bone and joint complications in ankylosing spondylitis (AS), this investigation aimed to study the role of BMP8A gene CNV in impressing the gene expression as well as the disease risk.

Methods

A total of 900 individuals, including 450 patients with AS and 450 healthy controls were enrolled. The copy numbers of BMP8A gene were detected by TaqMan real‐time polymerase chain reaction (PCR) method. BMP8A messenger RNA (mRNA) transcript level in peripheral blood mononuclear cells (PBMCs) was also measured by SYBR Green real‐time gene expression PCR method.

Results

No significant association of BMP8A copy number was detected with the risk of AS. BMP8A mRNA expression level was significantly downregulated in patients compared with controls. mRNA expression level of BMP8A in both AS patients with and without syndesmophyte was significantly lower than the healthy control group. There was no correlation between the mRNA expression level of BMP8A and both demographic and clinical data of the patients.

Conclusions

Although BMP8A gene expression was downregulated in patients with AS, its copy number could not affect the transcript level of BMP8A gene in PBMCs and was not associated with susceptibility to AS in Iranian population. BMP8a may take into account as an indicator of bone formation process in AS, but it seems that mechanisms other than CNV may regulate this protein.
Effects of miR‐181a targeting XIAP gene on apoptosis of cardiomyocytes induced by hypoxia/reoxygenation and its mechanism
Authors: Hao Peiyuan , Cao Xueming , Zhu Zhongyu , Gao Chuanyu , Chen Yan , Qi Datun
Published: November 2018

To investigate the effect of miR‐181a targeting XIAP gene on the apoptosis of cardiomyocytes induced by hypoxia/reoxygenation (H/R) and its mechanism. The primary cultured cardiomyocytes were treated with hypoxia for 3 hours and reoxygenation for 4 hours to construct H/R cell model. The expression of miR‐181a and XIAP messenger RNA in cardiomyocytes was detected by reverse‐transcription polymerase chain reaction, and the expression of XIAP protein in cardiomyocytes was detected by Western blot analysis. H/R cardiomyocytes with low expression of miR‐181a and overexpression of XIAP were constructed, and the effects of low expression of miR‐181a and upregulation of XIAP on cardiomyocyte apoptosis were detected by flow cytometry. A dual luciferase reporter assay was used to detect the target relationship between miR‐181a and XIAP. Further, H/R myocardial cells with low XIAP expression were constructed to observe the effect of downregulation of XIAP expression on apoptosis of myocardial cells with low expression of microarray‐181a. The expression of apoptosis‐related proteins Bax and Bcl‐2 in myocardial cells was detected by Western blot analysis. After H/R treatment, the expression of microRNAs‐181a was high but that of XIAP was low. The apoptosis of cardiomyocytes could be inhibited by both the low expression of miR‐181a and the upregulation of XIAP. The results of dual luciferase reporter gene showed that XIAP was a potential target gene for miR‐181a. The inhibitory effect of low expression of miR‐181a on myocardial apoptosis could be reversed and the inhibitory effect of low expression of miR‐181a on Bax protein expression and the promotion of Bcl‐2 protein expression could be reversed by the downregulation of XIAP. MiR‐181a can inhibit the apoptosis of hypoxic‐reoxygenated cardiomyocytes by targeting XIAP to downregulate Bax and upregulate Bcl expression.
Mechanism of miR‐137 regulating migration and invasion of melanoma cells by targeting PIK3R3 gene
Authors: Qi Jia , Wang Wei‐wei , Chen Wei , Lu Wen‐ying , Shang An‐quan
Published: November 2018

Objective

To investigate the effect of microRNA‐137 (miR‐137) on the migration and invasion of melanoma cells and its mechanism.

Methods

Quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to detect the expression of miR‐137 in melanoma tissues and cells. miR‐137 mimics, phosphoinositide‐3‐kinase regulatory subunit 3 (PIK3R3) small interfering RNA and corresponding controls were transfected into A375 and WM451 cells by lipofection. The expression of PIK3R3 was examined by qRT‐PCR and Western blot analysis. The Trans‐well assay was conducted to measure cell migration and invasion. Dual luciferase reporter assay was used to detect the interaction between miR‐137 and PIK3R3.

Results

Compared with normal pigmented nevus tissue, miR‐137 expression was significantly reduced in melanoma tissues. Compared with keratinous HaCaT cells, the level of miR‐137 was significantly decreased in melanoma SK‐MEL‐1, A375, and WM451 cells. Knockdown of miR‐137 significantly reduced the migrated and invasive abilities of melanoma A375 and WM451 cells. Moreover, inhibition of PIK3R3 obviously suppressed the migration and invasion abilities of melanoma A375 and WM451 cells. Luciferase activity assay showed that PIK3R3 was a direct target of miR‐137. In addition, overexpression of miR‐137‐inhibited PIK3R3 expression, while knockdown of miR‐137‐enhanced PIK3R3 abundance. Restoration of PIK3R3 reversed the regulatory effect of miR‐137 on cell migration and invasive in melanoma A375 and WM451 cells.

Conclusion

miR‐137 inhibited melanoma cell migration and invasion by targeting PIK3R3 gene.
Expression of DEC2 enhances chemosensitivity by inhibiting STAT5A in gastric cancer
Authors: Li Hongyu , Ma Xiaoli , Xiao Dongjie , Jia Yanfei , Wang Yunshan
Published: November 2018

Gastric cancer (GC) is one of the most common cancers. Resistance to 5‐fluorouracil (5‐Fu)‐based chemotherapy is a major cause of treatment failure followed by the poor prognosis of patients. In GC, it was reported that human differentiated embryonic chondrocyte‐expressed gene 2 (DEC2), suppressed tumor proliferation and metastasis, but the effect of DEC2 on chemosensitivity of GC cells was unknown. In our study, we found that DEC2 can obviously increase the sensibility of GC cells to 5‐Fu by promoting 5‐Fu‐induced apoptosis. DEC2 overexpression is significantly associated with decreased phosphorylation of STAT5A (P‐STAT5A). More importantly, negative correlations between DEC2 with P‐STAT5A expression were observed in tissue sections from GC patients. GC patients with low expression levels of DEC2 and high expression levels of P‐STAT5A showed a poor prognosis. Furthermore, enhanced chemosensitivity mediated by DEC2 can be reversed by STAT5A which confer GC cells resistance to apoptosis induced by 5‐Fu. Together, our results suggest that through inhibiting activation of STAT5A, DEC2 enhances 5‐Fu‐induced apoptosis and suppression of proliferation in GC cells. These findings will provide new insight for identifying potential targets that can be used to sensitize GC cells to chemotherapy.
Transcellular traversal of the blood‐brain barrier by the pathogenic Propionibacterium acnes
Authors: Lu Xuetao , Qi Xianlong , Yi Xiuli , Jian Zhe , Gao Tianwen
Published: November 2018

Background

Propionibacterium acnes (P. acnes) is an anaerobe commonly stay in the body as part of the commensal microbiota, and a dominant bacterium of the human skin and hair follicles. It has been found that this bacterium could participate in brain inflammation that causes Alzheimer's disease (AD) and Parkinson's disease (PD). But how P. acnes invade the brain remains elusive.

Methods

We established the in vitro blood‐brain barrier (BBB) model by culturing the HBMEC/D3 cell line on collagen‐coated PFTE membrane. The BBB model was verified by the transepithelial electrical resistance (TEER) and horseradish peroxidase (HRP) permeability rate, and observed by the scanning electron microscope (SEM), transmission electron microscope (TEM), as well as confocal microscope. The P. acnes was then cocultured with the in vitro BBB model and the permeability of P. acnes was measured by counting the bacteria clones collected from the lower chamber of the model.

Results

High local concentration of P. acnes invaded the in vitro BBB model through the transcellular traversal pathway. The permeability for P. acnes was increased by the treatment of lipopolysaccharide (LPS), but not mannitol. P. acnes invasion elevated the expression of cell adhesion molecules E‐selectin, ICAM‐1, and VCAM‐1 in HBMEC cells.

Conclusion

P. acnes has the ability to penetrate the brain though transcellular invasion of the blood‐brain barrier.
Study of p16 promoter methylation in Egyptian colorectal cancer patients
Authors: Karam Rehab A. , Zidan Haidy E. , Abd Elrahman Tamer M. , Badr Samir A. , Amer Samar A.
Published: November 2018

Many tumor‐suppressor genes contain CpG islands in their promoter regions which raised the necessity of investigating the role of methylation in silencing these genes. We examined p16 methylation as a potential biomarker in the peripheral blood of colorectal cancer (CRC) patients. Using methylation‐specific polymerase chain reaction method, the methylation status of p16 was investigated in the tumor tissue and blood of 65 CRC patients and blood samples from 70 healthy control individuals. Also, the relationship between p16 methylation level and the clinical‐pathological findings in CRC was evaluated. The frequency of blood p16 methylation in CRC cases was significantly higher than in control (P = 0.0001). The sensitivity and specificity of p16 methylation in diagnosing CRC was 55.38% and 98.5%, respectively, with 77.7% diagnostic accuracy. There was significant association between p16 methylation and age, sex, Dukes staging, lymph node involvement, and carcinoembryonic antigen levels. Our study revealed that p16 promoter methylation could be considered as both potential diagnostic and prognostic biomarker of CRC.
Fractionated radiotherapy might induce epithelial‐mesenchymal transition and radioresistance in a cellular context manner
Authors: Tahmasebi‐Birgani Mohammad‐Javad , Teimoori Ali , Ghadiri Ata , Mansoury‐Asl Halime , Danyaei Amir , Khanbabaei Hashem
Published: November 2018

Despite the fact that radiotherapy is a main therapeutic modality in cancer treatment, recent evidence suggests that fractionated radiotherapy (FR) might confer radioresistance through epithelial‐mesenchymal transition (EMT). Nevertheless, the effects of FR on EMT phenotype and the potential link between EMT induction and radioresistance development yet to be clarified. The aim of this study was to assess whether FR could promote EMT, and to elucidate if induction of EMT contributes to the acquisition of radioresistance. To this end, two human cancer cell lines (A549 and HT‐29) were irradiated (2 Gy/day) and analyzed using wound healing, transwell migration and invasion assays, real‐time polymerase chain reaction (for E‐cadherin, N‐cadherin, Vimentin, CD44, CD133, Snail, and Twist), clonogenic assay, Annexin V/PI, and 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide (MTT) assay. Irradiation of A549 (for 5 or 10 consecutive days) resulted in morphological changes including elongation of cytoplasm and nuclei and pleomorphic nuclei. Also, irradiation‐enhanced migratory and invasive potential of A549. These phenotypic changes were in agreement with decreased expression of the epithelial marker (E‐cadherin), enhanced expression of mesenchymal markers (N‐cadherin, Vimentin, Snail, and Twist) and increased stemness factors (CD44 and CD133). Moreover, induction of EMT phenotype was accompanied with enhanced radioresistance and proliferation of irradiated A549. However, FR (for 5 consecutive days) did not increase HT‐29 motility. Furthermore, molecular alterations did not resemble EMT phenotype (downregulation of E‐cadherin, Vimentin, ALDH, CD44, CD133, and Snail). Eventually, FR led to enhanced radiosensitivity and decreased proliferation of HT‐29. Altogether, our findings suggest that FR might induce EMT and confer radioresistance in a cell context‐dependent manner.
Predictors of change in cognitive processing therapy for veterans in a residential PTSD treatment program
Authors: Hale Andrew C. , Rodriguez Jessica L. , Wright Theodore P. , Driesenga Scott A. , Spates C. Richard
Published: November 2018

Objective

Cognitive processing therapy is an evidence‐based treatment for posttraumatic stress disorder (PTSD); however, questions remain regarding variability in treatment response.

Method

A total of 123 veterans participated in group‐based cognitive processing therapy (CPT) in residential PTSD treatment. Change over time in PTSD symptoms was modeled as a function of selected demographic and clinical variables.

Results

PTSD checklist (PCL) scores decreased by an average of 1 point per session (standard deviation [SD] = 0.1). Initial PCL scores were predicted by the Beck Depression Inventory‐II (γ01 = 0.25; standard error [SE] = 0.08), Insomnia Severity Index (γ02 = 0.53; SE = 0.15), and Infrequency (F) scale of the Minnesota Multiphasic Personality Inventory‐2 (γ03 = 0.09; SE = 0.04). Rate of change was predicted by the Somatic Complaints (RC1) scale (γ11 = −0.03; SE = 0.01) and the Antisocial Behavior (RC4) scale (γ12 = 0.02; SE = 0.01).

Conclusions

These results provide insight into characteristics that may influence degree of benefit received from group‐based CPT.
Partitioning a graph into monochromatic connected subgraphs
Authors: Girão António , Letzter Shoham , Sahasrabudhe Julian
Published: November 2018

We show that every ‐edge‐colored graph on vertices with minimum degree at least can be partitioned into two monochromatic connected subgraphs, provided is sufficiently large. This minimum degree condition is tight and the result proves a conjecture of Bal and DeBiasio. We also make progress on another conjecture of Bal and DeBiasio on covering graphs with large minimum degree with monochromatic components of distinct colors.
Functionalization of Quinazolin‐4‐ones Part 3: Synthesis, Structures Elucidation, DNA‐PK, PI3K, and Cytotoxicity of Novel 8‐Aryl‐2‐morpholino‐quinazolin‐4‐ones
Authors: Heppell Jacob T. , Islam Md. Amirul , McAlpine Shelli R. , Al‐Rawi Jasim M. A.
Published: November 2018

A series of novel 8‐aryl‐2‐morpholino quinazolines (11a–n, 12a–d, 14a–f, and 15) were synthesized from the precursor 2‐thioxo quinazolin‐4‐ones 8. The 8‐aryl‐2‐morpholino quinazolines compounds were assayed for DNA‐PK and PI3K. All compounds showed low DNA‐PK % inhibition activity at 10 μM compound concertation, and the most active was 8‐(dibenzo[b,d]thiophen‐4‐yl) 12d with 38% inhibition. Similar pattern of PI3K α, β, γ, and δ isoforms inhibition activity at 10 μM were observed. The most active isoform was PI3K δ of 41% inhibition for 8‐(dibenzo[b,d]furan‐4‐yl) compound 11. Most compounds were less active than expected in spite of the strong structural resemblance to known inhibitors (NU7441, 3, 4, and 6). Loss of activity could be attributed to the tautomerization to the aromatic enol (4‐OH), which could specify that the important functional group for the activity is the 4‐carbonyl (C=O) group. Alternatively, the aromatization of the pyrimidine heterocyclic ring could alter the conformation, and thus binding site, of the 2‐morpholine ring, which could reduce the compound‐receptor hydrogen bonding to the morpholine 4‐oxygen. Selected compounds displayed appreciable cytotoxicity with 6‐chloro‐8‐(dibenzo[b,d]thiophen‐4‐yl)‐2‐morpholinoquinazolin‐4(1H)‐one 11j exhibiting the greatest activity with an IC50 of 9.95 μM. Therefore, the mechanism of the cytotoxicity of compound 11j were not through DNA‐PK or PI3K inhibition activity.
The importance of local epidemic conditions in monitoring progress towards HIV epidemic control in Kenya: a modelling study
Authors: Anderson Sarah‐Jane , Garnett Geoffrey P , Enstone Joanne , Hallett Timothy B
Published: November 2018

Introduction

Setting and monitoring progress towards targets for HIV control is critical in ensuring responsive programmes. Here, we explore how to apply targets for reduction in HIV incidence to local settings and which indicators give the strongest signal of a change in incidence in the population and are therefore most important to monitor.

Methods

We use location‐specific HIV transmission models, tailored to the epidemics in the counties and major cities in Kenya, to project a wide range of plausible future epidemic trajectories through varying behaviours, treatment coverage and prevention interventions. We look at the change in incidence across modelled scenarios in each location between 2015 and 2030 to inform local target setting. We also simulate the measurement of a library of potential indicators and assess which are most strongly associated with a change in incidence.

Results

Considerable variation was observed in the trajectory of the local epidemics under the plausible scenarios defined (only 10 of 48 locations saw a median reduction in incidence of greater than or equal to an 80% target by 2030). Indicators that provide strong signals in certain epidemic types may not perform consistently well in settings with different epidemiological features. Predicting changes in incidence is more challenging in advanced generalized epidemics compared to concentrated epidemics where changes in high‐risk sub‐populations track more closely to the population as a whole. Many indicators demonstrate only limited association with incidence (such as “condom use” or “pre‐exposure prophylaxis coverage”). This is because many other factors (low effectiveness, impact of other interventions, countervailing changes in risk behaviours, etc.) can confound the relationship between interventions and their ultimate long‐term impact, especially for an intervention with low expected coverage. The population prevalence of viral suppression shows the most consistent associations with long‐term changes in incidence even in the largest generalized epidemics.

Conclusions

Target setting should be appropriate for the local epidemic and what can feasibly be achieved. There is no one universally reliable indicator to predict future HIV incidence across settings. Thus, the signature of epidemic control must contain indications of success across a wide range of interventions and outcomes.
Terahertz ultrasensitive biosensing metamaterial and metasurface based on spoof surface plasmon polaritons
Authors: Cheng Dong , Zhang Bao , Liu Guo , Wang Jianxun , Luo Yong
Published: November 2018

As a promising candidate for rapid and ultrasensitive sensing of biomolecules, terahertz time‐domain spectroscopy (THz‐TDS) can be considered with superior performance in label‐free, noncontact, noninvasive, and nondestructive detection. In particular, almost significant conformational information can be captured with THz‐TDS. Meanwhile, terahertz (THz) metamaterial or metasurface biosensing chips based on THz‐TDS were proposed to promote the detection sensitivity within strong local field‐matter enhancement. In this paper, the ultrasensitive THz biosensing metamaterial and metasurface for DNA/RNA detecting based on spoof surface plasmon polaritons (SSPPs) is probed. The simulated results show that the maximum frequency sensitivity of the proposed metamaterial and metasurface for DNA/RNA biosensing can respectively approach to 2.52 THz/refractive index unit (RIU) and 2.23 THz/RIU. In addition, the film thickness sensitivities of metamaterial and metasurface biosensors are respectively higher than 71.1 GHz/μm and 79.2 GHz/μm when the thickness of biomaterial is thinner than 4 μm. All these ascendant performances achieved in the proposed metamaterial and metasurface biosensors can be realized and exploited for ultrasensitive biomolecules detection, health monitoring, medical film sensing, and safety inspection in THz regime.
Bacteriophages: an overview of the control strategies against multiple bacterial infections in different fields
Authors: Jamal Muhsin , Bukhari Sayed M. A. U. S. , Andleeb Saadia , Ali Muhammad , Raza Sana , Nawaz Muhammad A. , Hussain Tahir , Rahman Sadeeq u. , Shah Syed S. A.
Published: November 2018

Bacteriophages (phages/viruses) need host bacteria to replicate and propagate. Primarily, a bacteriophage contains a head/capsid to encapsidate the genetic material. Some phages contain tails. Phages encode endolysins to hydrolyze bacterial cell wall. The two main classes of phages are lytic or virulent and lysogenic or temperate. In comparison with antibiotics, to deal with bacterial infections, phage therapy is thought to be more effective. In 1921, the use of phages against bacterial infections was first demonstrated. Later on, in humans, phage therapy was used to treat skin infections caused by Pseudomonas species. Furthermore, phages were successfully employed against infections in animals – calves, lambs, and pigs infected with Escherichia coli. In agriculture, for instance, phages have successfully been used e.g., Apple blossom infection, caused by Erwinia amylovora, was effectively catered with the use of bacteriophages. Bacteriophages were also used to control E. coli, Salmonella, Listeria, and Campylobacter contamination in food. Comparatively, phage display is a recently discovered technology, whereby, bacteriophages play a significant role. This review is an effort to collect almost recent and relevant information regarding applications and complications associated with the use of bacteriophages.
SDHx gene detection and clinical Phenotypic analysis of multiple paraganglioma in the head and neck
Authors: Ding Yiming , Feng Yaru , Wells Michael , Huang Zhigang , Chen Xiaohong
Published: November 2018

Objectives

The goal of this study was to detect and explore the mechanisms of the succinate dehydrogenase (SDH) complex subunit‐related gene mutations in cases of multiple paraganglioma (PGL) in the head and neck.

Methods

In Beijing Tongren Hospital (Capital Medical University, Beijing, People's Republic of China) between January 2013 and February 2017, 23 cases of head and neck multiple PGL were evaluated by genetic sequencing. From these cases, four hereditary families and 10 cases with sporadic occurrences were found. Gene mutations, including SDHD, SDHB, SDHC, SDHAF2, VHL and RET in germ cells and somatic cells, were detected by gene capture and high throughput sequencing.

Results

In family 1, 12 instances of SDHD gene mutation were detected, eight of which manifested as bilateral carotid body tumor (CBT) with one bilateral malignant CBT. In family 2, three cases of SDHD mutation were found with one case of bilateral CBT and two cases of unilateral CBT. In family 3, two cases of SDHD gene mutation were found, both characterized by vagus PGL and pheochromocytoma. Of the 10 patients with sporadic manifestations, five cases of SDHD gene mutation and one case of RET gene mutation were detected. Two novel gene mutations, c.387_393del7 mutation of SDHD gene and c.3247A>G mutation of RET gene, were also detected.

Conclusion

In patients with multiple PGL in the head and neck, these are accompanied by a genetic mutation of the germ cell. In this case study, this mutation was most commonly a mutation of the SDHD gene.

Level of Evidence

4 Laryngoscope, 129:E67–E71, 2019
Impact of coblation versus electrocautery on acute post‐operative outcomes in pediatric tonsillectomy
Authors: Lin Chen , Thung Arlyne K. , Jatana Kris R. , Cooper Jennifer N. , Barron L. Christine , Elmaraghy Charles A.
Published: November 2018

Objective

Based on previous studies in the pediatric population, it remains unclear whether there is a difference in postoperative pain between two widely used tonsillectomy techniques: coblation and bovie electrocautery. This large prospective study investigates whether postoperative pain scores differ between these two surgical techniques for tonsillectomy.

Methods

Prospective, non‐randomized study of children aged 2–8 enrolled in a randomized controlled trial of single‐dose intravenous acetaminophen for pain associated with adenotonsillectomy. Included procedures occurred between October 2012 and June 2015 at a tertiary referral center. Only patients whose operations exclusively used coblation or electrocautery and who required postoperative admission for extended observation were included. Follow‐up period was the length of inpatient stay. Patients and nurses who recorded the pain scores were blinded to the tonsillectomy technique.

Results

A total of 183 patients were included: 117 coblation cases and 66 electrocautery cases. Pain scores in the surgical recovery unit and pain scores after admission to the floor unit were not significantly different between coblation and electrocautery, either before or after adjustment for patient age, body mass index, intravenous acetaminophen use, and surgeon. There was also no difference in length of stay, readmission rate, or post‐tonsillectomy hemorrhage.

Conclusions

Coblation and electrocautery tonsillectomy are associated with similar post‐operative pain scores in the recovery and inpatient units in the pediatric population. As coblation is costlier, the results of this study may affect which tool is used by otolaryngologists from a cost–benefit perspective.

Level of evidence

III
Distribution of label‐retaining cells and their properties in the vocal fold mucosa
Authors: Sato Kiminobu , Kurita Takashi , Chitose Shun‐ichi , Sato Kiminori , Umeno Hirohito , Yano Hirohisa
Published: November 2018

Objective

The latest research suggests cells in the maculae flavae (MFe) are putative stem cells of the vocal fold mucosa and the MFe are a candidate for a stem cell niche. Distribution and properties of label‐retaining cells (LRCs) in the vocal fold mucosa were investigated.

Study Design

Histologic analysis of the rat vocal folds.

Methods

Oral administration of bromodeoxyuridine (BrdU) was given to rats and the LRCs in the vocal fold mucosa were observed by immunohistochemistry. Immunoreactivity to antibodies directed to BrdU, Ki67, cytokeratin, vimentin, glial fibrillary acidic protein, desmin, Sox17, CD34, CD45, Type I collagen, and CD44 was studied. Extracellular matrices around LRCs were observed by Alcian blue staining and hyaluronidase digestion study.

Results

LRCs were present in the MFe and were resting cells (G0‐phase). They expressed epithelium, muscle, neural, and mesenchymal cell–associated intermediate filament proteins, and an endodermal marker, indicating cells in the MFe are undifferentiated and express proteins of all three germ layers. They expressed hematopoietic markers (CD34, CD45) and Type I collagen, which are the major markers of bone marrow derived circulating fibrocytes. The hyaluronan concentration in the MFe was high and the cells in the MFe expressed the surface hyaluronan receptor CD44, indicating that the MFe were a hyaluronan‐rich matrix.

Conclusion

LRCs reside in the MFe and MFe had a hyaluronan‐rich matrix. The results of this study are consistent with the hypothesis that the cells in the MFe are putative stem cells and the MFe are a candidate for a stem cell niche.

Level of Evidence

N/A
Symptoms in cervical vertigo
Authors: Thompson‐Harvey Adam , Hain Timothy C.
Published: November 2018

Objective

To use a unique, 41‐question survey to identify patient features distinguishing cervical vertigo from vestibular causes of vertigo and vestibular migraine.

Methods

In this study, a unique, 41‐question survey was administered to 48 patients diagnosed with cervical vertigo (n = 16), migraine (n = 16), and vestibular vertigo (eg, unilateral vestibular paresis, Meniere's disease) (n = 16) to test the hypothesis that a set of distinct symptoms can characterize cervical vertigo. Responses between the three diagnostic groups were compared to identify questions which differentiated patients based on their symptoms.

Results

Eight questions were successful in differentiating vestibular vertigo from migraine and cervical vertigo. Symptoms endorsed by subjects with cervical vertigo overlapped substantially with subjects with well‐established vestibular disturbances as well as symptoms of subjects with migraine. Twenty‐seven percent of cervical vertigo subjects reported having true vertigo, 50% having headache, and 94% having neck pain.

Conclusion

Lacking knowledge of neck disturbance, the symptoms we elicited in our questionnaire suggest that cervical vertigo subjects may resemble migraine subjects who also have evidence of neck injury. Whether or not subjects with “cervical vertigo” also overlap with other diagnoses defined by a combination of symptoms and exclusion of objective findings such as chronic subjective dizziness and other variants of psychogenic dizziness remain to be established.

Level of Evidence

IV
Determination of the Phosphatidylcholine/Lysophosphatidylcholine Ratio in Intact Serum by Matrix‐Assisted Laser Desorption/Ionization Mass Spectrometry with Prior Enzymatic Albumin Digestion
Authors: Ditz Timo , Fuchs Beate
Published: November 2018

Lysophosphatidylcholine (lysoPtdCho) is a well‐known biomarker in body fluids for inflammation and oxidative stress and provides a possible clinical screening marker for certain diseases where inflammation is involved. It was shown in our previous article that the measurement of intact serum using matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐TOF MS) provides the phosphatidylcholine (PtdCho)/lysoPtdCho ratios faster than the measurements after organic extraction, while the standard deviations of those “intact” measurements are even smaller. Surprisingly, the PtdCho/lysoPtdCho ratio is about two times higher in the intact serum MALDI‐TOF MS measurement than in the MALDI‐TOF MS analysis of the organic extracts. Albumin binding of lysoPtdCho seems to be a very likely reason for increased PtdCho/lysoPtdCho ratios in the intact serum measurements. In this article, this hypothesis is tested on horse serum as a biological sample. Albumin (equine and bovine) addition to serum shows an increase in the PtdCho/lysoPtdCho ratio detected by MALDI‐TOF MS. Further experiments with a comparable lipid model suspension verify that pepsin and trypsin are able to liberate the bound lipids. Under different conditions, the effects of both enzymes on the lipid model suspension are compared. Finally, an improved MALDI‐TOF MS measurement of the PtdCho/lysoPtdCho ratio in intact serum after a prior pepsin digestion step was established. As is known that lysoPtdCho is cytotoxic and albumin is capable of decreasing this cytotoxicity by binding lysoPtdCho, this study proposes to consider both PtdCho/lysoPtdCho ratios—with and without albumin‐bound lysoPtdCho—that could be superior diagnostic markers for inflammation and oxidative stress.
Effect of ammonium bisulphite and chloride on the pitting and stress corrosion cracking resistance of super duplex stainless steel pipes under combined internal pressure and axial tension
Authors: Lasebikan Daley , Akisanya Alfred , Deans Bill
Published: November 2018

The oil and gas industry, like many others is constantly looking at ways to keep costs of well completion down based on cost effective solutions that do not compromise safety. This combined with the desire to develop new oil and gas fields that are very challenging in terms of operating pressures, temperatures, and corrosivity of the environment may result in the need to utilize materials closer to their mechanical loading limit in a corrosive environment. Modern alloys of high strength and corrosion resistance are often more susceptible to cracking. With a move toward higher production pressures, and temperature, production tubing for downhole use may become a limiting factor for exploration of future oil and gas wells. Typically, materials and corrosion test samples are usually set up to examine material behavior under single mode loading (e.g., tensile sample) and not combined loads experienced by a production tubing in a well completion. A novel test set‐up was developed to simulate stresses in a production tubing string with the potential to define combined load conditions in a corrosive environment once mechanical load limit is determined. In small scale tests cold worked super duplex stainless steel mini pipes were subjected to combined load, that is, axial stress simulating weight of the tubing string and internal pressure (from the reservoir). The mechanical load limit (failure envelope) was determined in the absence of a corrosive environment thereafter the mini pipes were subjected to load conditions below mechanical limit in a corrosive environment to determine load and environment conditions that would not lead to crack initiation. The potential pipe load limit when in the corrosive environment is below the corrosion test load condition to avoid crack initiation and failure.
Variable Hardy–Lorentz spaces
Authors: Jiao Yong , Zuo Yahui , Zhou Dejian , Wu Lian
Published: November 2018

Let be a measurable function on with . We introduce the variable Hardy–Lorentz space for via the radial grand maximal function. Under the assumption that satisfies the log‐Hölder condition, we establish a version of Fefferman–Stein vector‐valued inequality in variable Lorentz space by interpolation. We also construct atomic decompositions for , and develop a theory of real interpolation and formulate the dual space of the variable Hardy–Lorentz space with and . As a byproduct, we obtain a new John–Nirenberg theorem. Furthermore, we get equivalent characterizations of the variable Hardy–Lorentz space by means of the Lusin area function, the Littlewood–Paley g‐function and the Littlewood–Paley ‐function. Finally, we investigate the boundedness of singular operators on for and .
Design of firm‐specific training in an agency relationship: Who should take the initiative?
Authors: Marino Anthony M.
Published: November 2018

This paper considers the twofold problem of compensation contracting and the design of a human capital investment scheme. Before contracting, the principal and the agent can engage in a joint stochastic production process of exerting effort to raise the agent's productivity in the firm. The principal can employ synchronous effort exertion, or either actor can assume a leadership role. We determine which organizational design is best for the principal at the endogenously optimal compensation contract, depending on how the efforts interact.
Design of Hedgehog pathway inhibitors for cancer treatment
Authors: Bariwal Jitender , Kumar Virender , Dong Yuxiang , Mahato Ram I.
Published: November 2018

Hedgehog (Hh) signaling is involved in the initiation and progression of various cancers and is essential for embryonic and postnatal development. This pathway remains in the quiescent state in adult tissues but gets activated upon inflammation and injuries. Inhibition of Hh signaling pathway using natural and synthetic compounds has provided an attractive approach for treating cancer and inflammatory diseases. While the majority of Hh pathway inhibitors target the transmembrane protein Smoothened (SMO), some small molecules that target the signaling cascade downstream of SMO are of particular interest. Substantial efforts are being made to develop new molecules targeting various components of the Hh signaling pathway. Here, we have discussed the discovery of small molecules as Hh inhibitors from the diverse chemical background. Also, some of the recently identified natural products have been included as a separate section. Extensive structure‐activity relationship (SAR) of each chemical class is the focus of this review. Also, clinically advanced molecules are discussed from the last 5 to 7 years. Nanomedicine‐based delivery approaches for Hh pathway inhibitors are also discussed concisely.
A Survey of Multi‐task Learning Methods in Chemoinformatics
Authors: Sosnin Sergey , Vashurina Mariia , Withnall Michael , Karpov Pavel , Fedorov Maxim , Tetko Igor V.
Published: November 2018

Despite the increasing volume of available data, the proportion of experimentally measured data remains small compared to the virtual chemical space of possible chemical structures. Therefore, there is a strong interest in simultaneously predicting different ADMET and biological properties of molecules, which are frequently strongly correlated with one another. Such joint data analyses can increase the accuracy of models by exploiting their common representation and identifying common features between individual properties. In this work we review the recent developments in multi‐learning approaches as well as cover the freely available tools and packages that can be used to perform such studies.
Analytical and approximate solutions of fractional‐order susceptible‐infected‐recovered epidemic model of childhood disease
Authors: Srivastava H. M. , Günerhan Hatira
Published: November 2018

In this work, we make use of the conformable fractional differential transform method (CFDTM) in order to compute an approximate solution of the fractional‐order susceptible‐infected‐recovered (SIR) epidemic model of childhood disease. The method provides the solution in the form of a rapidly convergent series. Two explanatory and illustrative examples are given to represent the efficacy of the obtained results.
Influence of the microstructural properties of biocemented sand on its mechanical behavior
Authors: Dadda Abdelali , Geindreau Christian , Emeriault Fabrice , Esnault Filet Annette , Garandet Aurélie
Published: November 2018

The mechanical efficiency of the biocementation process is directly related to the microstructural properties of the biocemented sand, such as the volume fraction of calcite, its distribution within the pore space, coordination number, contact surface area, and types of contact. In the present work, some of these microscopic properties are computed, from 3D images obtained by X‐ray tomography of biocemented sand. These properties are then used as an input in current analytical models to estimate the elastic properties (Young and shear moduli) and the strength properties (Coulomb cohesion). For the elastic properties, the analytical estimates (contact cement theory model) are compared with classical bounds, self‐consistent estimate and numerical results obtained by direct computation (FEM computation) on the same 3D images. Concerning the cohesion, an analytical model initially developed to estimate the cohesion due to suction in unsaturated soils is modified to evaluate the macroscopic cohesion of biocemented sands. Such analytical model is calibrated on experimental data obtained from triaxial tests performed on the same biocemented sand. In overall, the presented results point out the important role of some microstructural parameters, notably those related to the contact, on such effective parameters.
SBA15–Fluconazole as a Protective Approach Against Mild Steel Corrosion: Synthesis, Characterization, and Computational Studies
Authors: Bustos‐Terrones Victoria , Serratos Iris N. , Vargas Rubicelia , Landeros‐Rivera Bruno C. , Bustos‐Terrones Yaneth A. , Soto Estrada Ana M. , Vicente Escobar Jonathan O. , Romero Romo Mario A. , Uruchurtu Jorge , Menchaca Carmina , Esparza Schulz Juan M. , Domínguez Armando
Published: November 2018

A SBA15–Fluconazole composite (SBA15‐Flu) was prepared to formulate a self‐healing coating for mild steel. The composite was obtained by dispersing SBA15 in a methanolic solution containing Fluconazole (Flu). The materials were characterized by using different techniques. Electrochemical impedance spectroscopy (EIS) was used for protective behavior evaluation of the coatings on mild steel substrates in an electrolytic solution prepared from sodium chloride and ammonium sulfate. The EIS results indicate that the inhibitor trapped in the SiO2matrix is released when it comes into contact the aggressive solution, thus protecting the metal. To understand the inhibitor release mechanism, docking studies were used to model the SBA15‐Flu complex, which allowed us to further determine polar and non‐polar contributions to the binding free energy. An analysis of the electron density within the quantum theory of atoms in molecules and the non‐covalent interaction index frameworks were also carried out for the most favorable models of SBA15‐Flu. The results indicate that the liberation rate of the Flu molecules is mainly determined by the formation of strong O−H⋅⋅⋅O, O−H⋅⋅⋅N, and O−H⋅⋅⋅F hydrogen bonds.
Ketogenic diet treatment in recurrent diffuse intrinsic pontine glioma in children: A safety and feasibility study
Authors: van der Louw Elles J.T.M. , Reddingius Roel E. , Olieman Joanne F. , Neuteboom Rinze F. , Catsman‐Berrevoets Coriene E.
Published: November 2018

Background

The mean overall survival rate of children with diffuse intrinsic pontine glioma (DIPG) is 9–11 months, with current standard treatment with fractionated radiotherapy and adjuvant chemotherapy. So far, novel therapeutic strategies have not yet resulted in significantly better survival. The main source of energy for glioblastoma cells is glucose. Therefore, metabolic alterations induced by the use of the extremely carbohydrate‐restricted ketogenic diet (KD) as adjuvant therapy are subject of interest in cancer research.

Procedure

This study explores the safety and feasibility of the KD in children with recurrent DIPG and no remaining treatment options. Safety was defined as the number of adverse effects. Feasibility was defined as the number of patients who were able to use the KD for three months. Coping of patients and parents was measured with questionnaires.

Results

Three of 14 children referred to our hospital between 2010 and 2015 were included. Two patients completed the study, and one died before the end of the study. Hospitalizations were needed for placing a nasogastric tube (n = 1) and epileptic seizures (n = 1). Adverse effects related to the diet were mild and transient. Parents were highly motivated during the study.

Conclusion

Use of KD is safe and feasible, but the effect on survival has to be proven in a larger cohort of children who start the KD earlier after diagnosis, preferably as adjuvant therapy to fractionated radiotherapy.
Experiences and health care preferences of women with ovarian cancer during the diagnosis phase
Authors: Jelicic Lebecca , Brooker Joanne , Shand Lyndel , Knight Tess , Ricciardelli Lina , Denham Geoff , Burney Sue
Published: November 2018

Objective

An ovarian cancer diagnosis presents physical and psychological challenges. Usually identified at an advanced stage, the disease involves invasive treatment and has a high mortality rate. The diagnosis phase is generally a time of heightened distress. Accordingly, the aim of this qualitative study was to explore the health care experiences and preferences of women with ovarian cancer during this phase, and identify opportunities to enhance women's experiences and outcomes.

Methods

Thirty‐four women diagnosed with ovarian cancer were recruited from across Australia (median age = 60.5 years, range = 31‐74 years). Semistructured interviews explored participants' experience of health care services and preferences during the diagnosis phase. Thematic analysis of interview transcripts followed.

Results

Five themes were identified including “navigating uncertainty” which summarized women's general experiences throughout the diagnosis phase and provided a context for concomitant health care preferences. Four other themes highlighted significant areas where health care may be better aligned with women's preferences. These included “responsiveness in health care,” “relational communication,” “person‐centered information,” and “preparation for living beyond cancer treatment.”

Conclusions

Responsive and prompt health care services that employ relational communication, provide patient‐centered information, and prepare women for survivorship could improve the health care experiences of women diagnosed with ovarian cancer.