bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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.
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

AbstractAdverse 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

AbstractAlthough 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

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

AbstractBackground: 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

ObjectivesAdequate 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).MethodsThree 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.ResultsPatients 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.DiscussionGiven 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.ConclusionIntegrating 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 Evidence4 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/HypothesisTo develop an experimental model in rabbits for assessment of tracheal epithelium regeneration through application of either natural or artificial polymer scaffolds.Study DesignFirst, 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).ResultsThe 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.ConclusionWe 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 EvidenceNALaryngoscope, 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

AbstractUnderstanding 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

AbstractProf. 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.
Recent clinical trends in Toll‐like receptor targeting therapeutics
Authors: Anwar Muhammad Ayaz , Shah Masaud , Kim Jason , Choi Sangdun 
Published: November 2018

AbstractToll‐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.
Novel D SRR‐based dual band antenna for WiMAX/C applications
Authors: Ambika A. , Tharini C. , Ali M. T. 
Published: November 2018

AbstractA 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.