bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigations on the mechanism of progesterone in inhibiting endometrial cancer cell cycle and viability via regulation of long noncoding RNA NEAT1/microRNA‐146b‐5p mediated Wnt/β‐catenin signaling
Authors: Huang Xiaohui , Zhong Rui , He Xiukui , Deng Qingshan , Peng Xiuhong , Li Jieming , Luo Xiping
Published: November 2018

Progesterone is often used to protect the endometrium and prevent endometrial cancer. An intensive study on its molecular mechanism in endometrial cancer would contribute to the development of more promising therapies. Relevant lncRNAs and mRNAs expression data in endometrial cancer cell line Ishikawa pretreated and post‐treated with progesterone were derived from Gene Expression Omnibus (accession no. GSE29435), and then we analyzed long noncoding RNAs and mRNAs with differential expressions in two different conditions. The Cytoscape software, TargetScan, miRanda, and Human microRNA Disease Database (HMDD) websites were employed. Gene set enrichment analysis (GSEA) was used to determine related Kyoto Encyclopedia of Genes and Genomes pathways alteration in Ishikawa cells treated with progesterone. In addition to bioinformatics analysis, Reverse Transcription‐Polymerase Chain Reaction (RT‐PCR), Western blot, and dual‐luciferase reporter assays were performed. The impact of progesterone on cell propagation and cell cycle was testified by colony formation and flow cytometry analysis. LncRNA nuclear enriched abundant transcript 1 (NEAT1) was the most significantly downregulated lncRNA in endometrial cancer cells treated with progesterone. Lymphoid enhancing factor 1 (LEF1) was positively associated with NEAT1, and eventually hsa_miR‐146b‐5p was validated to target both LEF1 and NEAT1. Wnt/β‐catenin signaling pathway was identified to involve in endometrial cancer. NEAT1 or LEF1 was overexpressed in endometrial cancer cells while downregulated following post‐treatment with progesterone. Conversely, miR‐146b‐5p was notably decreased in Ishikawa cells while upregulated after treatment with progesterone. Downstream gene c‐myc or MMP9 regulated by upstream gene LEF1 in Wnt/β‐catenin signaling pathway was remarkably increased in Ishikawa cells and positively related with NEAT1. Progesterone inhibited cell cycle and viability through regulating NEAT1/miR‐146b‐5p axis via Wnt/β‐catenin signaling pathway. Progesterone exerted suppressive influence on endometrial cancer progression via regulation of lncRNA NEAT1/miR‐146b‐5p‐mediated Wnt/β‐catenin signaling pathway, which might reveal new strategies for developing more effective therapeutics. © 2018 IUBMB Life, 71(1):223–234, 2019
Silencing of ADAM33 restrains proliferation and induces apoptosis of airway smooth muscle cells in ovalbumin‐induced asthma model
Authors: Zhou Jing , Bai Wei , Liu Qin , Cui Jian , Zhang Wei
Published: November 2018

A defibrinogen and metalloproteinase 33 (ADAM33) was reported to play an important role in asthma. Furthermore, ADAM33 may play a possible role in airway remodeling due to its high expression in myo‐/fibroblasts, epithelium, as well as the airway smooth muscle cells (ASMCs). Thus, the study is supposed to investigate the effect of the downregulation of ADAM33 on the proliferation and apoptosis of ASMCs in allergic asthma. An ovalbumin‐induced asthma model in rats was established for investigating the function of the silencing of ADAM33. ASMCs were cultured and divided into four groups after transfection. The messenger RNA and protein expressions of ADAM33 were measured by reverse transcription quantitative polymerase chain reaction and Western blot analysis. Cell proliferation was tested by cell counting kit‐8 and cell apoptosis by TdT‐mediated dUTP nick‐end labeling. The allergic asthma rats showed a large number of inflammatory cell infiltration, airway smooth muscle hypertrophy and hyperplasia, and increased WA
t, WA
m, and numbers of bronchial smooth muscle nucleus. Additionally, increased numbers of eosinophils and neutrophils, expressions of immunoglobulin E and interleukin‐4, content of airway air pressure, and NO, although decreased in expression of interferon‐γ, were exhibited in rats with allergic asthma. In our study, upregulated ADAM33 was found, and after the silencing of ADAM33, decreased proliferation and increased apoptosis of ASMCs were observed. The study evidences that silencing of ADAM33 can decrease the proliferation and increase the apoptosis of ASMCs in a rat model of allergic asthma, suggesting ADAM33 represents a potential investigative focus target aiding allergic asthma.
Key pathway and gene alterations in the gastric mucosa associated with obesity and obesity‐related diabetes
Authors: Wen Xin , Qian Chunhua , Zhang Yi , Wu Ruijin , Lu Liesheng , Zhu Cuiling , Cheng Xiaoyun , Cui Rai , You Hui , Mei Fangyun , Gao Jingyang , Li Feng , Bu Le , Qu Shen
Published: November 2018

Background and Objective

The stomach plays an important role in obesity and obesity‐related diabetes; yet, little is known about key pathways in the gastric mucosa associated with obesity and diabetes.

Methods

We performed gene microarray and real time‐polymerase chain reaction (RT‐PCR) on gut mucosa samples from control subjects (CON), patients with simple obesity (OB), and patients with obesity and comorbid diabetes (OD) (n = 3 per group). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to predict the functional significance of differentially expressed genes.

Results

In total, 262 genes were upregulated and 265 genes were downregulated in the OB group whereas 1756 genes were upregulated and 1053 genes were downregulated in the OD group compared with the CON group. Of these, 23 were co‐regulated in both comparisons. Seven differentially expressed genes were validated by RT‐PCR (NRIP3, L1CAM, TPO, P2RY1, OR8A1, ADAMTS19, and ASIC3). A functional analysis revealed that genes differentially expressed between the OB or OD and CON groups played crucial roles in metabolic, T cell, and G‐protein coupled receptor biological processes, and primarily participated in the PI3K‐Akt and AGE‐RAGE signaling pathways.

Conclusions

Obesity and obesity‐related diabetes are associated with important gene expression and pathway alterations in the stomach.
Long noncoding RNA STXBP5‐AS1 inhibits cell proliferation, migration, and invasion via preventing the PI3K/AKT against STXBP5 expression in non–small‐cell lung carcinoma
Authors: Huang Jingyu , Xie Nianlin , Huang Hu , Yao Jie , Hu Weidong
Published: November 2018

Long noncoding RNAs participate in carcinogenesis and tumor progression in non–small‐cell lung carcinoma (NSCLC), but the mechanisms underlying NSCLC tumorigenesis remain to be fully elucidated. Here, we reported the functional role and potential mechanism of long noncoding RNA syntaxin‐binding protein 5‐antisense RNA 1 (STXBP5‐AS1) in NSCLC. First, our data revealed that the expression levels of STXBP5‐AS1 in 31 NSCLC tissues were lower than in adjacent tissues using quantitative polymerase chain reaction (qPCR) and its expression was significantly associated with tumor metastasis of NSCLC patients. Moreover, CCK‐8, scratch wound healing and transwell assay suggested that upregulation of STXBP5‐AS1 repressed the proliferation, migration, and invasion in A549, NCI‐H292, and NCI‐H460 cells. To explore the potential mechanism of STXBP5‐AS1 in NSCLC, we first investigated the relationship among STXBP5‐AS1, STXBP5, and AKT1 in A549 cells. Results indicated that STXBP5‐AS1 was negatively related with STXBP5 and AKT1 at messenger RNA expression level using qPCR. In addition, we observed that STXBP5‐AS1 had reverse effects on the protein levels of STXBP5 and phosphorylated AKT1 (p‐AKT1) in A549 cells via Western blot assay, despite no significant effects on AKT1. Subsequently, LY294002, as the phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) pathway inhibitor, was used to further confirm the regulatory mechanism of STXBP5‐AS1, which showed that knockdown of STXBP5‐AS1 could rescue the expression of STXBP5 and p‐AKT1 protein expression levels in A549 cells. Taken together, our results suggested that STXBP5‐AS1, as a tumor suppressor, inhibits cell proliferation, migration, and invasion by preventing the PI3K/AKT against STXBP5 expression in NSCLC.
LncRNA CASC2 inhibits proliferation and migration of adenocarcinoma cells via miR‐4735‐3p and mTOR
Authors: Luo Meng , Kong Demiao , Pei Dengke , Jin Xing , Liu Di
Published: November 2018

Lung adenocarcinoma is a major form of non–small‐cell lung cancer that frequently strikes nonsmokers. The disease is often diagnosed at a late stage and the 5‐year survival rate is very low. Although previous studies found many somatic alterations associated with lung adenocarcinoma, the molecular basis of the development and progression of the disease is not well understood. We found that long noncoding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2), a putative tumor suppressor, was downregulated in both patient adenocarcinoma tissues and cultured lung cancer cells. Its tumor suppression function seemed to be dependent on its binding to miR‐4735‐5p. Changing the levels of CASC2 and miR‐4735‐3p in the cultured adenocarcinoma cells could affect the malignant phenotypes as well as growth of tumors derived from the cells injected into nude mice. Furthermore, the lncRNA and miR‐4735‐3p interplay likely the suppressed tumor growth through the downstream mammalian target of rapamycin signaling pathway. The results have revealed molecular details that may be critical for the development of lung adenocarcinoma, opening opportunities for the development of novel, and therapeutic tools.
IL‐28β gene polymorphism determines virological response to PEGylated interferon therapy in hepatitis C virus genotype 4 Egyptian patients
Authors: El‐Khazragy Nashwa , El Sayed Naglaa , Salem Ahmed M. , Hassan Nahla S. , Abdelmoeaz Amal Tohamy , Maher Amany M. , Mansy Azza El‐Sayed
Published: November 2018

Background

PEGylated interferon (PEG‐IFN) in combination with ribavirin is the gold standard for chronic hepatitis C virus (HCV). The majority of patients received PEG‐IFN/ribavirin achieve a sustained viral response (SVR), but few cases failed to respond. It was evident that host genetic factors determine the treatment‐induced viral clearance as well as spontaneous response. In the current study, the rs12979860 polymorphism of IL28β gene was analyzed and its association with the virological response to PEG‐IFN treatment was determined.

Methods

One hundred and fifty Egyptian patients with HCV genotype 4 treated with PEG‐IFN/ribavirin were assessed at 12 and 24 weeks of therapy, the rs12979860 genotype was determined using TaqMan‐based quantitative polymerase chain reaction.

Results

Although the CC genotype was the most frequent (58%), the higher SVR was achieved for patients with favorable CC genotype (93%) in contrast to CT and TT genotypes.

Conclusion

we conclude that IL28B polymorphism is highly associated with SVR to therapy in the Egyptian population infected with HCV genotype 4 and patients who carry CC genotype have a higher chance of SVR.
Sestrin2 regulates monocyte activation through AMPK‐mTOR nexus under high‐glucose and dyslipidemic conditions
Authors: Sundararajan Saravanakumar , Jayachandran Isaivani , Balasubramanyam Muthuswamy , Mohan Viswanathan , Venkatesan Balachandar , Manickam Nagaraj
Published: November 2018

The vicious cycle between hyperinsulinemia and insulin resistance results in the progression of atherosclerosis in the vessel wall. The complex interaction between hyperglycemia and lipoprotein abnormalities promotes the development of atherogenesis. In the early phase of atherosclerosis, macrophage‐derived foam cells play an important role in vascular remodeling. Mechanistic target of rapamycin (mTOR) signaling pathway has been identified to play an essential role in the initiation, progression, and complication of atherosclerosis. Recently sestrin2, an antioxidant, was shown to modulate TOR activity and thereby regulating glucose and lipid metabolism. But the role of sestrin2 in monocyte activation is still not clearly understood. Hence, this study is focussed on investigating the role of sestrin2 in monocyte activation under hyperglycemic and dyslipidemic conditions. High‐glucose and oxidized low‐density lipoprotein (LDL) treatments mediated proinflammatory cytokine production (M1) with a concomitant decrease in the anti‐inflammatory cytokine (M2) levels in human monocytic THP1 cells. Both glucose and oxidized LDL (OxLDL) in a dose and time‐dependent manner increased the mTOR activation with a marked reduction in the levels of pAMPK and sestrin2 expression. Both high‐glucose and OxLDL treatment increased foam cell formation and adhesion of THP1 cells to endothelial cells. Experiments employing activator or inhibitor of adenosine monophosphate kinase (AMPK) as well as overexpression or silencing of sestrin2 indicated that high‐glucose mediated monocyte polarization and adhesion of monocytes to the endothelial cells were appeared to be programmed via sestrin2‐AMPK‐mTOR nexus. Our results evidently suggest that sestrin2 plays a major role in regulating monocyte activation via the AMPK–mTOR‐pathway under diabetic and dyslipidemic conditions and also AMPK regulates sestrin2 in a feedback mechanism.
Accelerated long‐range corrected exchange functional using a two‐gaussian operator combined with one‐parameter progressive correlation functional [LC‐BOP(2Gau)]
Authors: Song Jong‐Won , Hirao Kimihiko
Published: November 2018

Recently, we proposed a simple yet efficient method for the computation of a long‐range corrected (LC) hybrid scheme [LC‐DFT(2Gau)], which uses a modified two‐Gaussian attenuating operator instead of the error function for the long‐range HF exchange integral. This method dramatically reduced the computational time while maintaining the improved features of the LC density functional theory (DFT). Here, we combined an LC hybrid scheme using a two‐Gaussian attenuating operator with one‐parameter progressive correlation functional and Becke88 exchange functional with varying range‐separation parameter values [LC‐BOP(2Gau) with various μ values of 0.16, 0.2, 0.25, 0.3, 0.35, 0.4, and 0.42] and demonstrated that LC‐BOP(2Gau) reproduces well the thermochemical and frontier orbital energies of LC‐BOP. Additionally, we revised the scaling factors of the Gaussian multipole screening scheme for LC‐DFT(2Gau) to correspond to the angular momentum of orbitals, which decreased the energy deviations from the energy with the no‐screening scheme. © 2018 Wiley Periodicals, Inc.
Glutamate triggers intracellular Ca2+ oscillations and nitric oxide release by inducing NAADP‐ and InsP3‐dependent Ca2+ release in mouse brain endothelial cells
Authors: Zuccolo Estella , Kheder Dlzar A. , Lim Dmitry , Perna Angelica , Nezza Francesca Di , Botta Laura , Scarpellino Giorgia , Negri Sharon , Martinotti Simona , Soda Teresa , Forcaia Greta , Riboni Laura , Ranzato Elia , Sancini Giulio , Ambrosone Luigi , D’Angelo Egidio , Guerra Germano , Moccia Francesco
Published: November 2018

The neurotransmitter glutamate increases cerebral blood flow by activating postsynaptic neurons and presynaptic glial cells within the neurovascular unit. Glutamate does so by causing an increase in intracellular Ca2+ concentration ([Ca2+]i) in the target cells, which activates the Ca2+/Calmodulin‐dependent nitric oxide (NO) synthase to release NO. It is unclear whether brain endothelial cells also sense glutamate through an elevation in [Ca2+]i and NO production. The current study assessed whether and how glutamate drives Ca2+‐dependent NO release in bEND5 cells, an established model of brain endothelial cells. We found that glutamate induced a dose‐dependent oscillatory increase in [Ca2+]i, which was maximally activated at 200 μM and inhibited by α‐methyl‐4‐carboxyphenylglycine, a selective blocker of Group 1 metabotropic glutamate receptors. Glutamate‐induced intracellular Ca2+ oscillations were triggered by rhythmic endogenous Ca2+ mobilization and maintained over time by extracellular Ca2+ entry. Pharmacological manipulation revealed that glutamate‐induced endogenous Ca2+ release was mediated by InsP3‐sensitive receptors and nicotinic acid adenine dinucleotide phosphate (NAADP) gated two‐pore channel 1. Constitutive store‐operated Ca2+ entry mediated Ca2+ entry during ongoing Ca2+ oscillations. Finally, glutamate evoked a robust, although delayed increase in NO levels, which was blocked by pharmacologically inhibition of the accompanying intracellular Ca2+ signals. Of note, glutamate induced Ca2+‐dependent NO release also in hCMEC/D3 cells, an established model of human brain microvascular endothelial cells. This investigation demonstrates for the first time that metabotropic glutamate‐induced intracellular Ca2+ oscillations and NO release have the potential to impact on neurovascular coupling in the brain.
Analyses of Adverse Drug Reactions–Nationwide Active Surveillance Network: Canadian Pharmacogenomics Network for Drug Safety Database
Authors: Tanoshima Reo , Khan Amna , Biala Agnieszka K. , Trueman Jessica N. , Drögemöller Britt I. , Wright Galen E. B. , Hasbullah Jafar S. , Groeneweg Gabriella S. S. , Ross Colin J. D. , Carleton Bruce C. ,   on behalf of the Canadian Pharmacogenomics Network for Drug Safety Consortium
Published: November 2018

Adverse drug reactions (ADRs) are a major problem in modern medicine, representing up to the fourth‐highest cause of mortality. Pharmacogenomic tests are 1 of the most promising methods to tackle the challenge of ADRs. The objective of this study was to analyze the clinical and demographic information of the pan‐Canadian active surveillance network, Canadian Pharmacogenomics Network for Drug Safety (CPNDS). Information entered into the database by trained active surveillors between May 15, 2005 and May 9, 2017 was collected and analyzed. Specific data included for analysis were number of ADR reports, reports of drug use without ADRs, date of onset of ADR, suspected drugs, concomitant drugs, and fatal ADR cases. The CPNDS database consisted of 93,974 reports of medication use, including 10,475 reports of ADRs, of which 72.6% occurred in pediatric patients (≤21 years old). Self‐reported ancestries were predominantly Europe (38.2%), Canada (9.6%), and East Asia (4.9%). The 5 most frequent ADRs were cutaneous ADRs, peripheral neuropathy, cardiotoxicity, central nervous system toxicity, and ototoxicity. The 5 drugs most commonly suspected to cause ADRs were methotrexate, vincristine, doxorubicin, cisplatin, and L‐asparaginase. The CPNDS database is a valuable resource to identify clinical and genomic predictors of ADRs. The database also highlights our candidate ADRs for pharmacogenomic discovery research to identify additional ADR biomarkers. Additionally, the database provides information that can be used for developing strategies to prevent ADRs and raises awareness of ADRs among Canadian healthcare professionals.
Dosing Recommendations for Quetiapine When Coadministered With HIV Protease Inhibitors
Authors: Sampson Mario R. , Cao Kelly Y. , Gish Paula L. , Hyon Kyong , Mishra Poonam , Tauber William , Zhao Ping , Zhou Esther H. , Younis Islam R.
Published: November 2018

Although current quetiapine labeling recommends that its dosage should be lowered 6‐fold when coadministered with strong cytochrome P450 (CYP)3A inhibitors, a reported case of coma in a patient receiving quetiapine with lopinavir and ritonavir prompted the reevaluation of labeling recommendations for the dosing of quetiapine when coadministered with human immunodeficiency virus (HIV) protease inhibitors. Literature and database (FDA Adverse Event Reporting System and United States Symphony Health Solutions’ Integrated Dataverse Database) searches allowed us to identify cases of coma and related adverse events involving the coadministration of quetiapine and HIV protease inhibitors and to estimate the frequency of concomitant use. Literature review and physiologically based pharmacokinetic modeling allowed us to estimate the potential for CYP3A inhibition to contribute to adverse events related to HIV protease inhibitor–quetiapine coadministration. We identified excess sedation following coadministration of quetiapine and an HIV protease inhibitor in 3 reports without obvious confounders. In prescription claims data, 0.4% of quetiapine patients were dispensed a concurrent ritonavir prescription. The quetiapine dose was not reduced on ritonavir initiation in 90% of therapy episodes. Available data indicate to us that all HIV protease inhibitors combined with ritonavir are likely to be strong CYP3A inhibitors. We predicted that ritonavir would increase quetiapine exposure comparable to the strong CYP3A inhibitor ketoconazole. The current dosing recommendations for use of quetiapine with strong CYP3A inhibitors (ie, 6‐fold lower quetiapine dose) are appropriate and should be followed when quetiapine is coadministered with HIV protease inhibitors.
Effects of Nutrition Supplementation on Osmolality of Expressed Human Milk
Authors: Lamport Lyssa , Hartman Chelsea , Codipilly Champa , Weinberger Barry , Schanler Richard
Published: November 2018

Background

Provision of human milk to premature infants optimizes outcomes, but it must be supplemented to meet their nutrient and caloric requirements for growth. Our objective was to quantify the osmolality of human milk mixed with commercially available human milk fortifiers (HMF) and powdered infant formula, as currently fed to premature infants, simulating standard neonatal intensive care unit feeding practices for mixing and refrigerator storage.

Methods

Expressed human milk (EHM) samples obtained from mothers of premature infants (≤32 weeks gestation) were mixed with standard commercial products, and osmolalities were quantified.

Results

HMF significantly increased the micronutrient content and osmolality of EHM. Osmolalities were 291 ± 6 mOsm/kg (mean ± SD) for unsupplemented milk, and 505 ± 5 and 315 ± 19 mOsm/kg after supplementation to 24 kcal/oz using 2 current U.S. Liquid EHM fortifiers. When using powdered infant formulas to further increase the caloric content of fortified EHM >24 kcal/oz, osmolalities increased by 10.5–23.0 mOsm/kg for each additional kcal/oz. The use of powdered formulas alone (without HMF) increased osmolality without comparable increases in nutrient content. Refrigeration for 24 hours did not affect osmolalites.

Conclusion

Our finding that several common feeding formulations exceed 450 mOsm/kg, and the lack of evidence of adverse effect, raise the question of whether current maximum osmolality guidelines should be reevaluated to enable optimal nutrition for infants in neonatal intensive care.
Prevalence, Characteristics, and Outcome of Cow's Milk Protein Allergy in Chinese Infants: A Population‐Based Survey
Authors: Yang Min , Tan Meizhen , Wu Jieling , Chen Zhuojie , Long Xiaoling , Zeng Yongmei , Cai Huabo , Zhang Yong , Geng Lanlan , Xiao Yulian , Ke Haijin , Liu Ying , Rong Linhui , Fu Simao , Wang Hong , Wang Yuan , Li Xiaoxiu , Chen Peiyu , Li Kelvin , Xie Jing , Chen Huan , Li Huiwen , Wang Hongli , Li Ding‐You , Gong Sitang
Published: November 2018

Background: Cow's milk protein allergy (CMPA) is commonly seen in children. There have been no reports of the true prevalence of CMPA in Chinese infants. The aim of this population‐based study is to determine the prevalence, clinical characteristics, and outcome of CMPA in Chinese infants. Methods: We carried out a prospective survey in 7 participating hospitals throughout southern China. We included infants ≤12 months of age during the survey. For those suspected of CMPA, oral food challenge with cow's milk protein (CMP) was performed. A follow‐up telephone interview was conducted at 12 months after the diagnosis to assess the clinical outcome of CMPA. Results: A total of 9910 questionnaire surveys were distributed and 7364 (74.3%) were returned. The eligible survey number of surveys was 6768 (91.9%). A total of 182 infants was confirmed with CMPA, including 13 with anaphylactic reactions, 28 with clinical symptoms and serum immunoglobulin E (sIgE) >3.5 IU/mL, and 141 with positive CMP challenge test. The prevalence of CMPA was 2.69%. Infants with confirmed CMPA had significantly stronger family history of either 1 or both parents with food allergy, higher Cesarean section rate, and lower rate of breastfeeding, compared with those without CMPA. At 12‐month telephone follow‐up of 176 CMPA infants, 136 infants (77.3%) had become tolerant to CMP. Conclusions: The prevalence of CMPA was 2.69%. CMPA infants had a strong family history of food allergy and atopy. Both Cesarean delivery and formula feeding were risk factors for CMPA. At 12‐month follow‐up, the majority of CMPA infants had become tolerant to CMP.
Mucocele formation following laryngeal cleft injection
Authors: Burton Wood C. , Rieber Alexis K. , Penn Edward B.
Published: November 2018

A 12‐month‐old male underwent injection laryngoplasty for dysphagia associated with a deep interarytenoid notch. He subsequently developed a large postcricoid mucocele requiring revision surgery and marsupialization of the cyst just 2 weeks following the initial surgery.

Laryngoscope, 129:1696–1698, 2019
Osteoradionecrosis of the sternoclavicular joint after laryngopharyngeal radiation
Authors: Irizarry Rachel , Shatzkes Deborah R. , Teng Stephanie , Kohli Nikita , Har‐El Gady
Published: November 2018

Objectives

Adequate treatment of laryngopharyngeal malignancy often incorporates radiation therapy. Structures surrounding laryngopharynx exposed to traditional radiation doses are susceptible to posttreatment toxicity. Among poorly understood sequelae is the rare manifestation of sternoclavicular joint (SCJ) osteoradionecrosis (ORN).

Methods

Three institutional encounters prompted a comprehensive literature search, generating three published case reports. Systematic extraction and analysis (n = 6) of demographics, cancer history, comorbidities, ORN presentation, imaging, and management established the largest series to investigate this pathology.

Results

Patients were males (6), 54 to 70 years old, smokers (4), with Hypertension/dyslipidemia, myocardial infarction/coronary artery disease, second primary (2), diabetes mellitus (1), and myelofibrosis(1). Four underwent total laryngectomy, one primary, three as salvage. Five patients had concurrent chemoradiation (≥70 Gy). All patients presented with swollen, tender neck wounds concerning for persistent/recurrent malignancy. Computed tomography (CT) demonstrated bone erosion (5 of 5) and increased bone scan uptake (2 of 2). All responded to surgical exploration with drainage alone (1), sequestrectomy (2), or bone resection with synovectomy (3). Complete healing took 2 months to 3 years. One unrelated patient death occurred before control of ORN was achieved.

Discussion

Given varied patient characteristics, synergistic risk factors exist that alter bone radiation threshold, resulting in irreversible ischemic damage and osteoradionecrosis. Vascular susceptibility and inability to repair may regulate that threshold. Understanding this relationship will facilitate early detection and intervention.

Conclusion

Integrating cases of sternoclavicular joint ORN promotes awareness of atypical laryngopharyngeal radiation complications, elucidates contributing factors, educates physicians on presentation and management, and provides a platform for prospective investigation.

Level of Evidence

4 Laryngoscope, 129:865–870, 2019
Experimental animal model for assessment of tracheal epithelium regeneration
Authors: Safronova Elizaveta I. , Dydykin Sergey S. , Grigorevskiy Evgeny D. , Tverye Ekaterina A. , Kolchenko Stepan I. , Piskunova Natalia N. , Denisova Anna V. , Titova Galina P. , Parshin Vladimir D. , Romanova Olga A. , Panteleyev Andrey A.
Published: November 2018

Objectives/Hypothesis

To develop an experimental model in rabbits for assessment of tracheal epithelium regeneration through application of either natural or artificial polymer scaffolds.

Study Design

First, we identified the size of full‐thickness mucosal defect, which does not allow self‐healing (a “critical defect”), thus representing an adequate experimental model for regenerative therapy of tracheal epithelium damage. Then, two methods of polymer scaffold fixation at the site of the epithelium defect were compared: suturing and fixation with a stent. This was done through: 1) formation of a full‐thickness anterolateral mucosal defect by tracheal mucosa excision; and 2) fixation of the scaffold at the site of the tracheal epithelium defect using sutures (through a tracheal wall “window”) or a vascular stent (through a small tracheal incision).

Results

The dimension of a critical anterolateral mucosal defect of the trachea for rabbits was found to be 1.5 cm in length and more than 50% of the tracheal circumference. Fixation of the scaffold with a stent proved to be more efficient due to a uniform distribution of the pressure over the entire surface of the scaffold, whereas the suturing of the scaffold provided unsatisfactory results. In addition, fixation of the scaffold by suturing required formation of a large “window” in the tracheal wall. Thus, using the stent appeared to be technically less complicated and much less traumatic as compared to suturing.

Conclusion

We present an experimental in vivo animal model of tracheal epithelium injury and recovery. It can be effectively used with certain further modifications as a basis for routine testing of bioengineered constructs.

Level of Evidence

NA

Laryngoscope, 129:E213–E219, 2019
Exploring nonlinear functional responses of zooplankton grazers in dilution experiments via optimization techniques
Authors: Sandhu S. K. , Morozov A. Yu. , Mitra A. , Flynn K.
Published: November 2018

Understanding complex dynamics of planktonic ecosystems requires good knowledge of predator functional responses, especially for microzooplankton grazers. Although natural microzooplankton communities are highly diverse, we often need to quantify microzooplankton grazing at the macrolevel, considering them as a single “box.” Here, we consider community microzooplankton predation rates as a function of their prey abundance. Estimating the functional response of microzooplankton as a function of bulk prey often exploits the dilution approach: joint incubation experiments of grazers and their prey where samples are subjected to a range of dilution factors. However, the classic methodology appears reliable only for a simple linear functional response of grazers and it requires appropriate adjustments for nonlinearity and saturation of food consumption at high prey abundance. We explore how recently suggested methods applying nonlinear functional responses of bulk microzooplankton grazing can be enhanced to provide more robust results. We argue that different formulations of the functional response should be fitted to the data and that an appropriate choice of dilution factors in experiments can substantially improve the accuracy of feeding rate estimation. Pragmatically, our work shows that for oligotrophic ecosystems, it is best to run incubations where the majority of dilution factors are close to
D = 1 (undiluted), whereas, for eutrophic waters, dilution factors should be run close to
D = 0 as well as
D = 1. Furthermore, running equidistant dilution factors represents a waste of effort; it is more important to run at fewer values of D with greater replication.
From Dendrimers to Macrocycles: 80 Years George R. Newkome—Milestones of a Gentleman Scientist
Authors: Zechel Stefan , Hager Martin D. , Schubert Stephanie , Manners Ian , Schubert Ulrich S.
Published: November 2018

Prof. George R. Newkome will become 80 years old in November 2018 and his extraordinary research results of the last 50 years are highlighted in this essay. He was one of the pioneers of dendrimers and invented the new field of metallodendrimers, which feature the high benefit of a selective synthesis. This building principle was later utilized for the preparation of 2D and 3D molecules. For this purpose, simple molecular units were assembled to complex architectures by simple complexation of terpyridines with metals.
Inequalities for eigenvalues of the buckling problem of arbitrary order on bounded domains of
Authors: Wang Qiaoling , Xia Changyu
Published: November 2018

We prove universal inequalities for eigenvalues of the buckling problem of arbitrary order on bounded domains in which are independent of the domains.
Recent clinical trends in Toll‐like receptor targeting therapeutics
Authors: Anwar Muhammad Ayaz , Shah Masaud , Kim Jason , Choi Sangdun
Published: November 2018

Toll‐like receptors (TLRs) are germline‐encoded receptors that are central to innate and adaptive immune responses. Owing to their vital role in inflammation, TLRs are rational targets in clinics; thus, many ligands and biologics have been reported to overcome the progression of various inflammatory and malignant conditions and support the immune system. For each TLR, at least one, and often many, drug formulations are being evaluated. Ligands reported as stand‐alone drugs may also be reported based on their use in combinatorial therapeutics as adjuvants. Despite their profound efficacy in TLR‐modulation in preclinical studies, multiple drugs have been terminated at different stages of clinical trials. Here, TLR modulating drugs that have been evaluated in clinical trials are discussed, along with their mode of action, suggestive failure reasons, and ways to improve the clinical outcomes. This review presents recent advances in TLR‐targeting drugs and provides directions for more successful immune system manipulation.
SAMHSA announces four‐year strategic plan
Authors: Canady Valerie A.
Published: November 2018

The Substance Abuse and Mental Health Services Administration (SAMHSA) announced the release of its strategic plan for FY2019–FY2023, which officials say provides a roadmap to carry out SAMHSA's vision and mission.
Novel D SRR‐based dual band antenna for WiMAX/C applications
Authors: Ambika A. , Tharini C. , Ali M. T.
Published: November 2018

A novel miniaturized D shape split ring resonator (SRR) antenna is proposed for dual band (3.6 GHz and 4.7 GHz) applications. This proposed antenna structure has dimensions of 18 × 20 × 0.8 mm3 which is built on FR4 dielectric constant (
ε
r=4.4). This antenna consists of top and bottom side dual SRR creating dual band resonant frequency which is excited from microstrip line as monopole and slotted partial ground plane for better impedance matching. The microstrip line (monopole) is creating a resonance frequency at 4.7 GHz and the SRR is responsible for creating resonance frequency at the frequency of 3.6 GHz. The parametric study of microstrip line and the position of SRR has been analyzed. The D shape SRR in the monopole is generating another resonating frequency at 3.6 GHz. The metamaterial property of proposed D shape SRR is also verified to validate the resonance frequency. The antenna radiation measurement is carried out in Antenna Research Centre (ARC) FKE, Universiti Teknologi MARA, Malaysia. Both simulated and measured results agreed well. Measured gain achieved with this dual band antenna is around 2‐3 dB.
Cerebrospinal fluid–suppressed T2‐weighted MR imaging at 7 T for human brain
Authors: Pan Jullie W. , Moon Chan Hong , Hetherington Hoby P.
Published: November 2018

Purpose

T2‐weighted lesional imaging is most commonly performed using inversion recovery turbo spin echoes. At 7 T, however, this acquisition is limited for specific absorption rate and resolution. This work describes and implements a method to generate CSF‐suppressed T2‐weighted imaging.

Methods

The strategy uses a driven equilibrium spin‐echo preparation within an inversion recovery with multiple 3D gradient‐echo imaging blocks. Images are combined using the self‐normalization approach, which achieves CSF suppression through optimized timing of individual blocks and minimizes sources of variation due to coil receptivity, T2*, and proton density. Simulations of the magnetization‐prepared fluid‐attenuated inversion recovery gradient‐echo (MPFLAGRE) method over T1 and T2 relaxation values are performed, and in vivo demonstrations using an 8 2 transceiver array in healthy controls are shown.

Results

The specific absorption rate of the calculated MPFLAGRE sequence is 11.1 ± 0.5 W (n = 5 volunteers), which is 74 ± 2% of the US Food and Drug Administration guidelines. This method acquires both contrasts for CSF suppression with detection of long T2 components and T2‐weighted imaging in a single acquisition. In healthy controls, the former contrast generates increased signal in the cortical rim and ependyma. A comparison is shown with a conventional 3D SPACE fluid‐attenuated inversion recovery acquisition, and sensitivity to pathology is demonstrated in an epilepsy patient.

Conclusion

As applied with the 8 2 transceiver, the MPFLAGRE sequence generates both whole‐brain contrast suitable for lesional and T2‐weighted imaging at 7 T in fewer than 10 minutes within the US Food and Drug Administration's specific absorption rate guidelines.
GLAD to study genetic links in anxiety and depression
Authors: Ogden Joy
Published: November 2018

A major new study aims to recruit 40 000 people, who will sign up online to take part in trailblazing research into the genetic links to anxiety and depression.
Rapidly progressive dementia with psychosis caused by CJD
Authors: Mousailidis Georgios , Lazzari Carlo , Bhan‐Kotwal Shafalica , Shoka Ahmed
Published: November 2018

Rapidly progressive dementias are conditions that typically cause dementia over weeks or months. They are a particular challenge for psychiatrists and neurologists as the differential diagnosis is often different from the more typical, slowly progressive dementias. Early and accurate diagnosis is essential, as many of the aetiologies are treatable. CreutzfeldtJakob Disease (CJD) is a very rare, progressive and lethal illness caused by prions. Here, the authors present a case of CJD that manifested itself as rapidly progressive dementia, with psychosis, without any neurological signs and symptoms initially.
Beta‐amyloid PET imaging for Alzheimer's dementia diagnosis
Authors: Byrne Andrew , Prichard James
Published: November 2018

Alzheimer's dementia is the most commonly diagnosed dementia. Despite this, diagnosis can be especially complex in certain circumstances. Any additional, novel diagnostic aids can positively add to the diagnostic process, overall accuracy and ultimately to patient care and treatment. Beta‐amyloid (Aβ) positron emission tomography (PET) imaging is utilised as an important diagnostic tool in NHS dementia research in the UK and worldwide. Aβ PET imaging is now licensed for clinical use in the UK. This review explores the potential for the use of Aβ PET imaging in clinical practice highlighting recent evidence base followed by a discussion of potential benefits in the context of important clinical and practical considerations.
Prevalence and heritability of benign prostatic hyperplasia and LUTS in men aged 40 years or older in Zhengzhou rural areas
Authors: Yue Limin , Wang Tao , Ge Yongchao , Ge Mengying , Zhang Chengda , Hou Quanliang , Wang Wenhua , Tian Huizi , Ren Bingnan , Du Binghui , Zhang Weidong
Published: November 2018

Background

Benign prostate hyperplasia (BPH) is the most common disease among aging males, but no reports have addressed the prevalence of BPH in Zhengzhou. Therefore, we aimed to understand the prevalence of BPH in men aged 40 years or older in Zhengzhou's rural areas through a cross‐sectional study and analyzed the correlation with epidemiologic factors and the heritability of the disease.

Materials and Methods

A multistage sampling method was used to randomly select male respondents in Zhengzhou's rural areas. Men who were 40 years of age or older and their first‐degree relatives were subjected to the International Prostate Symptom Score (IPSS) and related examinations. Heritability was calculated according to the prevalence of the first‐degree relatives in the case and control groups.

Results

The prevalence of BPH was 10.04%. Its prevalence increased with age, from 2.17% in men aged 40‐44 years to 31.11% in men aged 80 years or older. The average volume of the prostate was 17.16 ± 7.96 mL, and the average IPSS was 5.89 ± 5.91. The analysis of the correlation between the associated risk factors and BPH revealed that prostatitis and a history of prostatic hyperplasia were significant factors. Obesity, smoking, drinking, diabetes, and hypertension were not correlated with BPH. Of the 94 first‐degree relatives of the cases, 53 had BPH (56.38%); of the 106 first‐degree relatives of the controls, five had BPH (4.72%). Heritability appeared to account for 40.48% of BPH cases. The heritability of incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia was 43.28, 71.37, 9.67, 5.67, 2.70, 53.36, and 19.12%, respectively.

Conclusion

The total prevalence of BPH in men aged 40 years or older in Zhengzhou's rural areas was 10.04%, and the heritability of prostatic hyperplasia was 40.48%.
Dual benefit of supplementary oral 5‐aminolevulinic acid to pelvic radiotherapy in a syngenic prostate cancer model
Authors: Miyake Makito , Tanaka Nobumichi , Hori Shunta , Ohnishi Sayuri , Takahashi Hiroo , Fujii Tomomi , Owari Takuya , Ohnishi Kenta , Iida Kota , Morizawa Yosuke , Gotoh Daisuke , Itami Yoshitaka , Nakai Yasushi , Inoue Takeshi , Anai Satoshi , Torimoto Kazumasa , Aoki Katsuya , Fujimoto Kiyohide
Published: November 2018

Background

Normal tissue damage caused by radiotherapy remains the largest dose‐limiting factor in radiotherapy for cancer. Therefore, the aim of this study was to investigate the supplementary oral 5‐aminolevulinic acid (ALA) to standard radiation therapy as a novel radioprotective approach that would not compromise the antitumor effect of radiation in normal rectal and bladder mucosa in a syngenic prostate cancer (PCa) model.

Methods

To evaluate the radiosensitizing effect of ALA in vitro, clonogenic survival assays were performed in DU145, PC3, and MyC‐CaP cell lines. To evaluate the effect of ALA in vivo a single dose (25 Gy) of radiation with or without ALA was given to healthy mice. Next, a syngenic PCa model of MyC‐CaP cells in FVB mice was created, and multiple doses (12 Gy total) of radiation were administered to the mouse pelvic area with or without ALA administration. Resected tumors, recta, and urinary bladders were immunostained with antibodies against Ki‐67, γ‐H2AX, CD204, and uroplakin‐III. Total RNA levels in recta and urinary bladders were analyzed via RT2 Profiler polymerase chain reaction (PCR) arrays related to “Stress & Toxicity PathwayFinder,” “Mitochondria,” and “Inflammasomes.”

Results

The addition of in vitro single or in vivo repeated administration of exogenous ALA acted as a radiosensitizer for PCa cells. Rectal toxicity was characterized by histological changes including loss of surface epithelium, fibrosis, severe DNA damage, and the aggregation of M2 macrophages. Urinary bladder toxicity was characterized by bladder wall thickening and urothelium denuding. The higher dose (300 mg/kg/day) of ALA exerted a better radioprotective profile than the lower dose (30 mg/kg/day) in normal recta and urinary bladders. Out of the 252 genes tested, 35 (13.4%) were detected as relevant genes which may be involved in the radioprotective role of ALA administration. These included interleukin‐1a (IL‐1a), IL‐1b, IL‐12, chemokine (C‐X‐C motif) ligand 1 (CXCL1), CXCL3, and NLRP3.

Conclusions

Our study provides novel and comprehensive insights into the dual benefits including radiosensitizing PCa tumor tissues and radioprotection of normal pelvic organs from radiation therapy. Knowledge of the underlying mechanism will facilitate the search for optimal treatment parameters for supplemental oral ALA during radiotherapy for PCa.
Finite frequency H∞ control of singularly perturbed Euler‐Lagrange systems: An artificial delay approach
Authors: Xu Jing , Niu Yugang , Fridman Emilia , Fridman Leonid
Published: November 2018

In this paper, we show that small artificial delays in the feedback loops operating in different time scales may stabilize singularly perturbed systems (SPSs). An artificial delay approach is proposed for the robust stabilization and L2‐gain analysis of SPSs in the finite frequency domain. A two‐time‐scale delayed static output feedback controller is designed, in which the controller gains are formulated via a linear matrix inequality (LMI) algorithm. A distinctive feature of the proposed algorithm is setting controller parameters as free variables, which increases the degrees of freedom in controller design and leads to more flexibility in solving LMIs. Moreover, the proposed method is further extended to analyze the finite frequency system specifications of SPSs. The L2‐gain performance analysis is conducted for parameter‐independent subsystems in their dominant frequency ranges, and the disturbance attenuation level of the original high‐order system is then estimated. Finally, the efficiency of the proposed design method is verified in an active suspension system subject to multiple finite frequency disturbance.
Interaction of Indole Derivative with Human Serum Albumin: A Combined Spectroscopic and Molecular Dynamics Study
Authors: Pawar Suma K. , Kalalbandi Veerendra Kumar A. , Jaldappagari Seetharamappa
Published: November 2018

In the present work, we have studied the interaction of synthesized indole derivative (ID) with a model protein, human serum albumin (HSA). Various spectroscopic and molecular dynamic simulation methods were employed to characterize the binding between ID and HSA. ID showed strong binding affinity towards HSA (1.86x106 M−1) and quenched the fluorescence intensity of HSA by dynamic quenching mechanism. The existence of dynamic quenching mechanism in ID‐HSA interaction was further confirmed by lifetime measurement study. ID‐HSA interaction was favored by hydrophobic forces. The binding site for ID on HSA was examined by site probe competitive experiments and molecular docking studies. The results revealed that ID was bound to HSA primarily at site I of subdomain IIA. Absorption, 3D fluorescence and circular dichroism (CD) studies provided information on the conformational and microenvironmental changes in HSA upon binding to ID.
Semiconductor α‐Fe2O3 Hematite Fabricated Electrode for Sensitive Detection of Phenolic Pollutants
Authors: Rahman Mohammed M. , Fabregat Francisco , Guerrero Antonio , Asiri Abdullah M. , Bisquert Juan
Published: November 2018

Hematite (α‐Fe2O3) semiconductor is an abundant and non‐toxic catalyst for different (photo)electrochemical reactions. In this work, a selective p‐nitrophenol sensor was developed by fabricating a thin‐layer of a glassy carbon electrode (GCE) with 5% nafion coating binders onto α‐Fe2O3 thin film synthesized by a simple and inexpensive process. High sensitivity including linear dynamic range, long‐term stability, and enhanced electrochemical performance towards p‐nitrophenol were achieved by a reliable current‐voltage method. A linear calibration curve was observed over a wide range of p‐nitrophenol concentrations. Very low detection limit (0.6±0.02 nM), good limit of quantification (2.0 nM) and high sensor sensitivity (K=74.1 μA⋅cm−2) are calculated based on noise to signal ratio of ∼3 N/S. Very importantly, the detection range covers over 7 orders of magnitude concentrations, from nM to mM. Figures of merits are comparable with best reported results whilst using a very simple device configuration. We show that hematite is an excellent material for the development of chemical sensors to detect hazardous compounds for environmental safety in a broad scale of concentrations.