bluuebunny/crossref_metadata_2025 huggingface dataset:
Continuous and high throughput production of alginate fibers using co‐flow in a millifluidic T‐junction
Authors: Pendyala G. , Bithi S. S. , Vanapalli S. A. , Fernandes G. E.
Published: October 2018

We present a new technique for continuous production of alginate fibers using off‐the‐shelf millifluidic components and syringe pumps. The components are quickly assembled to form a T‐junction to deliver co‐flowing streams of sodium alginate and calcium chloride allowing formation of hydrogel fibers in the exit channel. We vary the flow rates of the two streams, calcium chloride concentrations and length of exit channel and identify conditions where fibers of uniform and nonuniform thickness are produced. We find that uniform fibers can be produced at a maximum total flow rate of 10 mL min−1. As expected, for uniform fibers, we observe that the fiber diameter increases with increase in alginate solution flow rate, and we propose a simple model that predicts the fiber diameter as a function of flow rate ratio. We investigate the source of fiber nonuniformity and explain it using an empirical model that involves crosslinking time and gel strength. Our approach features easy device assembly and operation and enables continuous fiber production without clogging risks. Fiber production rates in the order of 10 m min−1 are achievable using our approach. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47120.
Fabrication of dual‐layer poly(styrene‐b‐4‐vinyl pyridine)–poly(vinylidene fluoride) membranes with tailored pore sizes under 10 nm via surface quaternization
Authors: Su Y. , Liu Y. , Liu T. , Wang X.
Published: October 2018

Block copolymer membranes can be applied to precise size‐based separation because of their highly ordered surface morphology and adjustable pore sizes. However, there is a lower limit of the scale of block copolymer self‐assembly; this makes it a challenge to tailor the pore size down to below 10 nm. In this study, poly(styrene‐b‐4‐vinyl pyridine) membranes were modified to quaternized selective layers with pores smaller than 10 nm and were supported by poly(vinylidene fluoride) hollow fibers as the substrate to provide a high mechanical strength. Two reactants, methyl iodide and 2‐chloroacetamide, were used in the quaternization. With this one‐step chemical modification, the molecular weight cutoff was reduced from 190 to 8 kDa, and the surface pore sizes were narrowed down from 20–30 to 3 nm; this bridged the gap of tailored pore sizes down to below 10 nm. Such membranes are promising candidates for low‐molecular‐weight separation with high resolution. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47137.
Improvement in mechanical and hygroscopic properties of modified SA fiber crosslinking with PEGDE
Authors: Meng Chihan , Li Huitao , Zhu Guofu , Cao Shiwen , Zhang Hong , Liu Yuanfa , Guo Jing
Published: October 2018

Modified sodium alginate (mSA) fiber is prepared through the wet spinning process using poly(ethylene glycol) diglycidyl ether (PEGDE, the molecular weight of PEGDE is 400) as the crosslinking agent to improve the mechanical and hygroscopic properties. Flowing property of the spinning solution and properties of the mSA fiber are characterized by DV‐C digital viscometer, single fiber electronic tensile strength tester and other instruments. Results show that viscosity of the spinning solution dropped firstly, then increased and decreased lastly with increasing PEGDE content in mSA fiber. The optimal value of the tensile strength of mSA fiber is 2.47 cN/dtex increasing by 64.67% compared to pure SA fiber. Both the crosslinking degree and crystallinity of mSA fiber rise first and then descended with the increase of PEGDE content. The hydroscopicity of mSA fiber increase from 30.5% to 70.9% at 20 wt % PEGDE in mSA fiber. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47155.
Multiple Sources for Sertoli Cells and Two Sertoli Phenotypes in the Adult Elasmobranch Testis: Insight from Two Species Belonging to Different Orders
Authors: McClusky Leon Mendel
Published: October 2018

Findings presented here for the chondrichthyans Prionace glauca and Isurus oxyrinchus show that the assembly of the spermatocyst and it's attached collecting duct are seamlessly connected developmental phenomena. The cyst's somatic cell component (i.e., Sertoli cells, SCs) and the duct's constituent cells derive both from a common precursor cell type (typically a large oblong cell) found among the A‐spermatogonia in the folliculogenic region. Novel findings show that the co‐developing collecting duct itself serves also as a source of either normal‐looking or basophilic atypical SCs (aSCs), depending on whether the duct–cyst transition remains mitotically active and open, or is sealed. The aSCs arise from accumulating slender basophilic cells at the duct–cyst interface after which the newly formed cyst is sealed. Quantitative analysis of the latter in P. glauca revealed a correlation between the appearance of this aSC in immature cysts and the degenerated testicular condition that displays a gradient of multinucleate cell (MNC) death among spermatogonial cysts. Findings seem to implicate these aSCs in the life–death balance in mature spermatogonial cohorts downstream in the spermatogenic sequence, rather than in newly formed cysts that exhibit low rates of apoptosis. Photomicrographs of developing spermatogonial cysts showing several aSCs interspersed among cytoplasmically linked spermatogonia that are proliferating or have died, seem to suggest that these small SCs may be involved in confining MNC death to a given cyst region under conditions of subthreshold levels of apoptosis such as to ensure cyst recovery in immature spermatogonial cysts. Anat Rec, 301:1944–1954, 2018. © 2018 Wiley Periodicals, Inc.
Co‐administration of nuciferine reduces the concentration of metformin in liver via differential inhibition of hepatic drug transporter OCT1 and MATE1
Authors: Li Liping , Lei Hongmei , Wang Wei , Du Weijuan , Yuan Jingqun , Tu Meijuan , Zhou Hui , Zeng Su , Jiang Huidi
Published: October 2018

Nuciferine (NF), one of the main and effective components in Nelumbo nucifera Gaertn. leaf extracts, is a promising drug candidate for the treatment of obesity‐related diseases, while metformin is a first line therapeutic drug for type 2 diabetes mellitus. Since nuciferine and metformin are likely to be co‐administered, the aim of the present study was to evaluate whether co‐administration of nuciferine would influence the liver (target tissue) distribution and the anti‐diabetic effect of metformin by inhibiting hepatic organic cation transporter 1 (OCT1) and multidrug and toxin extrusion 1 (MATE1). The data demonstrated that nuciferine significantly reduced metformin accumulation in MDCK cells stably expressing human OCT1 (MDCK‐hOCT1) or hMATE1 (MDCK‐hMATE1), and primary cultured mouse hepatocytes. Furthermore, the presence of nuciferine in the basal compartment caused a concentration‐dependent reduction of intracellular metformin accumulation in MDCK‐hOCT1/hMATE1 cell monolayers. Compared with the metformin treatment‐alone group, co‐administration of nuciferine (40 mg/kg) markedly reduced the metformin concentration in mouse livers at 30 and 60 min after a single oral dose of metformin (200 mg/kg), and subsequently impaired the glucose‐lowering effect of metformin (200 mg/kg), but the glucose‐lowering effect became no different at 90 and 120 min. Therefore, nuciferine influenced the liver concentration and glucose‐lowering effect of metformin only for a period of time after dose, administration of nuciferine and metformin with an interval might prevent the drug–drug interaction mediated by OCT1 and MATE1.
High‐throughput screening of antibody‐expressing CHO clones using an automated shaken deep‐well system
Authors: Wang Benjamin , Albanetti Thomas , Miro‐Quesada Guillermo , Flack Layla , Li Lina , Klover Judith , Burson Kerri , Evans Krista , Ivory William , Bowen Michael , Schoner Ronald , Hawley‐Nelson Pamela
Published: October 2018

Biopharmaceutical protein manufacturing requires the highest producing cell lines to satisfy current multiple grams per liter requirements. Screening more clones increases the probability of identifying the high producers within the pool of available transfectant candidate cell lines. For the predominant industry mammalian host cell line, Chinese hamster ovary (CHO), traditional static‐batch culture screening does not correlate with the suspension fed‐batch culture used in manufacturing, and thus has little predictive utility. Small scale fed‐batch screens in suspension culture correlate better with bioreactor processes but a limited number of clones can be screened manually. Scaled‐down systems, such as shaken deep well plates, combined with automated liquid handling, offer a way for a limited number of scientists to screen many clones. A statistical analysis determined that 384 is the optimal number of clones to screen, with a 99% probability that six clones in the 95th percentile for productivity are included in the screen. To screen 384 clones efficiently by the predictive method of suspension fed‐batch, the authors developed a shaken deep‐well plate culturing platform, with an automated liquid handling system integrating cell counting and protein titering instruments. Critical factors allowing deep‐well suspension culture to correlate with shake flask culture were agitation speed and culture volume. Using our automated system, one scientist can screen five times more clones than by manual fed‐batch shake‐flask or shaken culture tube screens and can identify cell lines for some therapeutic protein projects with production levels greater than 6 g/L. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1460–1471, 2018
Bioprosthetic aortic valve leaflet disruption with high energy electrocautery to prevent coronary artery obstruction during valve‐in‐valve transcatheter aortic valve replacement
Authors: Nelson Bradley C. , Chadderdon Scott , Song Howard , Zahr Firas E.
Published: October 2018

Transcatheter aortic valve replacement (TAVR) is well‐established for the treatment of bioprosthetic aortic valve stenosis (AS) in high surgical risk patients. Coronary artery obstruction from displacement of the bioprosthetic valve leaflets during valve‐in‐valve (VIV) TAVR is a rare, but potentially fatal, complication. Recently, the bioprosthetic aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction (BASILICA) procedure was developed as a method for disrupting bioprosthetic leaflets in patients undergoing VIV TAVR at high risk for coronary obstruction. This case describes a successful VIV TAVR utilizing a simplified concept of the BASILICA technique in a patient where the full procedure could not be completed.
Splenic mass in a case of CALR‐mutated essential thrombocythemia
Authors: Imashuku Shinsaku , Kotani Shinichi , Hinami Junsuke , Nishimura Keisuke
Published: October 2018

Key Clinical Message

We report here an intrasplenic large mass in an elderly case of essential thrombocythemia (ET)‐myelofibrosis. Laparoscopic splenectomy revealed extramedullary hematopoiesis (EMH) and a type 1 CALR gene mutation (CALR‐c.1092_1143del52) in the splenic mass. It remains to be determined if CALR‐mutated ET has an increased tendency to develop mass‐forming EMH.
Poly(4‐styrene sulfonic acid) to Disperse Graphene for Applications in Lithium‐Sulfur Batteries
Authors: Cheng Wei‐Ju , Chang Shinn‐Jen , Cho Chuan‐Sheng , Li Chia‐Chen
Published: October 2018

The use of poly(4‐styrene sulfonic acid) (PSSA) to effectively disperse graphene in an aqueous sulfur (S) cathode slurry is proposed, and the cell performance of the resulting Li−S battery is investigated and compared to that of the battery prepared by adding as‐received graphene. The addition of PSSA improves not only the dispersion of the as‐received graphene, but also the homogeneity of the constituents in the S cathode slurry; accordingly, better electronic and ionic conductivities are obtained. The electrical impedance of the cell constructed using the S cathode with the as‐received graphene is greatly reduced from 142.0 to 14.6 Ω when PSSA is added during the preparation of the cathode. Moreover, the addition of the PSSA‐dispersed graphene to the S cathode significantly improves the capacity, cycle life, and coulombic efficiency during the charge‐discharge process, since PSSA increases the contact between the dispersed graphene and the insulated S powder.
Normal diffusivity of the domestic feline brain
Authors: Barry Erica F. , Cerda‐Gonzalez Sofia , Luh Wen‐Ming , Daws Richard E. , Raj Ashish , Johnson Philippa J.
Published: October 2018

Diffusion magnetic resonance imaging (MRI) provides useful information about neuroanatomy and improves detection of neuropathology. As yet, a comprehensive evaluation of the diffusivity parameters within the feline brain has not been documented. In this study, we anesthetized and performed in vivo MRI on the brain of eight neurologically normal felines. A T1‐weighted structural sequence with a resolution of 0.5 mm3 and a parallel diffusion weighted sequence with 61 directions and a resolution of 1.5 mm3 was obtained. After correction and processing the diffusion brain data were parcellated into 151 regions of interest using previously published priors. These regions were grouped according to their lobar location within the brain (frontal, occipital, temporal, parietal, thalamus, midbrain, cerebellum, and white matter). The mean and standard deviation of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for these 151 individual regions and lobar groups were calculated and averaged across participants, creating a comprehensive distribution range of diffusion tensor values. When regions were statistically evaluated, white matter had significantly higher FA and RD and lower AD and MD diffusivity parameters when compared to other regions. Additionally, thalamic regions had significantly higher FA values than parietal and occipital regions. This information will not only help inform feline neuroanatomy but also will serve as a reference standard for future feline neuroimaging studies.
Unique hues and principal hues
Authors: Fairchild Mark D.
Published: October 2018

This note examines the different concepts of encoding hue perception based on four unique hues (like NCS) or five principal hues (like Munsell). Various sources of psychophysical and neurophysiological information on hue perception are reviewed in this context and the essential conclusion that is reached suggests there are two types of hue perceptions being quantified. Hue discrimination is best quantified on scales based on five, equally spaced, principal hues while hue appearance is best quantified using a system based on four unique hues as cardinal axes. Much more remains to be learned.
Interband Electron Pairing for Superconductivity from the Breakdown of the Born‐Oppenheimer Approximation
Authors: Whangbo Myung‐Hwan , Deng Shuiquan , Köhler Jürgen , Simon Arndt
Published: October 2018

The origin of interband electron pairing, responsible for enhancing superconductivity, and the factors controlling its strength were examined. We show that interband electron pairing is a natural consequence of breaking down the Born‐Oppenheimer approximation during electron‐phonon interactions. Its strength is determined by the pair‐state excitations around the Fermi surfaces that take place to form a superconducting state. Fermi surfaces favorable for the pairing were found, and the implications of this observation are discussed.
Electrostatic cnoidal waves and soliton structures in multi‐ions plasmas
Authors: Ur‐Rehman Hafeez , Mahmood S.
Published: October 2018

Using a reductive perturbation technique (RPT), the Korteweg‐de Vries (KdV) equation for nonlinear electrostatic waves in multi‐ion plasmas is derived with appropriate boundary conditions. Furthermore, compressive and rarefactive cnoidal wave and soliton solutions are discussed. In our model, the multi‐ion plasma consists of light dynamic warm ions, heavy cold ions, and inertialess electrons, which follows the Maxwell‐Boltzmann distribution. It is observed that in such an unmagnetized multi‐ion plasma, two characteristic electrostatic waves i.e., slow ion‐acoustic (SIA) waves and fast ion‐acoustic (FIA) waves, can propagate. The results are discussed by considering two types of multi‐ion plasmas i.e., H+–O+–e plasma and H−–O+–e plasma that exist in space plasmas. It is found that for H+–O+–e plasma, the SIA cnoidal wave and soliton form both positive (compressive) and negative (rarefactive) potential pulses, which depend on the temperature and density of the light and warm ions. However, only electrostatic positive potential structures are obtained for FIA cnoidal wave and soliton in H+–O+–e plasma. In the case of H−–O+–e plasma, the SIA cnoidal wave and soliton form only compressive structures, while the FIA cnoidal wave and soliton compose rarefactive structures. The effects of light ions' density and temperature on nonlinear potential structures are investigated in detail. The parametric results are also demonstrated, which are applicable to space and laboratory multi‐ion plasma situations.
Using Moral Foundations Theory to Enhance Multicultural Competency
Authors: Romig Charles A. , Holeman Virginia T. , Sauerheber Jill Duba
Published: October 2018

Multicultural competency requires awareness of one's own values and possession of the knowledge and skills necessary to work ethically with clients who hold worldviews and values that may differ from the counselor. Recent cross‐cultural research on moral psychology provides a useful framework for categorizing values and understanding how clients prioritize competing values when making decisions. Six foundations of moral foundations theory are presented and matched to 6 ethical principles that are foundational to the ACA Code of Ethics (American Counseling Association, ). A case study illustrates how moral foundations theory can be applied in a culturally sensitive way.
Effectiveness and safety of rivaroxaban vs. warfarin in patients with non‐valvular atrial fibrillation and heart failure
Authors: Martinez Brandon K. , Bunz Thomas J. , Eriksson Daniel , Meinecke Anna‐Katharina , Sood Nitesh A. , Coleman Craig I.
Published: October 2018

Aims

Heart failure (HF) is a common co‐morbidity in non‐valvular atrial fibrillation (NVAF) patients and a potent risk factor for stroke, bleeding, and a decreased time‐in‐therapeutic range with warfarin. We assessed the real‐world effectiveness and safety of rivaroxaban and warfarin in NVAF patients with co‐morbid HF.

Methods and results

Using US Truven MarketScan Commercial and Medicare supplemental database claims data from 11/2011 to 12/2016, we identified oral anticoagulant (OAC)‐naïve NVAF patients with HF (International Classification of Diseases, 10th Revision codes of I50 or I09.81) and ≥12 months of insurance coverage prior to the qualifying OAC dispensing. Rivaroxaban users (20 or 15 mg once daily) were 1:1 propensity score matched to warfarin users, with residual absolute standardized differences <0.1 being achieved for all covariates after matching. Patients were followed up until an event, OAC discontinuation/switch, insurance disenrolment, or end of follow‐up. Rates [events per 100 person‐years (PYs) of follow‐up] for stroke or systemic embolism and major bleeding (using the Cunningham algorithm) were compared between the matched cohorts using Cox proportion hazard regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). We matched 3418 rivaroxaban (32% receiving the reduced dose) and 3418 warfarin users with NVAF and HF with a median (interquartile range) available follow‐up of 1.4 (0.6, 2.5) years. Median age was 74 (63, 82) years, and median CHA2DS2‐VASc and HASBLED scores were 4 (3, 5) and 2 (2, 3). Common HF medications included beta‐blockers (64%), angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers (62%), loop diuretics (46%), digoxin (11%), and aldosterone receptor antagonists (10%). The hazard of developing stroke or systemic embolism (0.98 events/100PY vs. 1.28 events/100PY; HR = 0.82, 95% CI = 0.47–1.44), ischaemic stroke (0.70 events/100PY vs. 1.02 events/100PY; HR = 0.77, 95% CI = 0.41–1.46), or major bleeding (3.86 events/100PY vs. 4.23 events/100PY; HR = 0.98, 95% CI = 0.73–1.31) was not found to be different between rivaroxaban and warfarin users. Intracranial haemorrhage was infrequent in both cohorts and numerically less with rivaroxaban (0.27 events/100PY vs. 0.36 events/100PY; HR = 0.73, 95% CI = 0.25–2.08).

Conclusions

Effectiveness and safety of rivaroxaban vs. warfarin are sustained in NVAF patients with co‐morbid HF treated in routine practice. The general consistency between this real‐world study and those from phase III randomized trial data of rivaroxaban should provide additional reassurance to clinicians regarding the use of rivaroxaban in NVAF patients with HF.
Regioselective Oxidative Chlorination of Arenols Using NaCl and Oxone
Authors: Uyanik Muhammet , Sahara Naoto , Ishihara Kazuaki
Published: October 2018

We developed a practical and environmentally benign method for the chlorinative dearomatization of arenols using transient electrophilic chlorinating species generated in situ from inexpensive sodium chloride and Oxone as a Cl source and oxidant, respectively, under mild conditions. Moreover, the regioselective chlorination or chlorinative dearomatization of 1‐naphthols was also achieved by changing the reaction conditions.
Fluvial dynamics and 14C‐10Be disequilibrium on the Bolivian Altiplano
Authors: Hippe Kristina , Gordijn Tiemen , Picotti Vincenzo , Hajdas Irka , Jansen John D. , Christl Marcus , Vockenhuber Christof , Maden Colin , Akçar Naki , Ivy‐Ochs Susan
Published: October 2018

Determining sediment transfer times is key to understanding source‐to‐sink dynamics and the transmission of environmental signals through the fluvial system. Previous work on the Bolivian Altiplano applied the in situ cosmogenic 14C‐10Be‐chronometer to river sands and proposed sediment storage times of ~10–20 kyr in four catchments southeast of Lake Titicaca. However, the fidelity of those results hinges upon isotopic steady‐state within sediment supplied from the source area. With the aim of independently quantifying sediment storage times and testing the 14C‐10Be steady‐state assumption, we dated sediment storage units within one of the previously investigated catchments using radiocarbon dating, cosmogenic 10Be‐26Al isochron burial dating, and 10Be‐26Al depth‐profile dating. Palaeosurfaces appear to preserve remnants of a former fluvial system, which has undergone drainage reversal, reduction in catchment area, and local isostatic uplift since ~2.8 Ma. From alluvium mantling the palaeosurfaces we gained a deposition age of ~580 ka, while lower down fluvial terraces yielded ≤34 ka, and floodplains ~3–1 ka. Owing to restricted channel connectivity with the terraces and palaeosurfaces, the main source of channel sediment is via reworking of the late Holocene floodplain. Yet modelling a set of feasible scenarios reveals that floodplain storage and burial depth are incompatible with the 14C‐10Be disequilibrium measured in the channel. Instead we propose that the 14C‐10Be offset results from: (i) non‐uniform erosion whereby deep gullies supply hillslope‐derived debris; and/or (ii) holocene landscape transience associated with climate or human impact. The reliability of the 14C‐10Be chronometer vitally depends upon careful evaluation of sources of isotopic disequilibrium in a wide range of depositional and erosional landforms in the landscape. © 2018 John Wiley & Sons, Ltd.
Critical review: Grand challenges in assessing the adverse effects of contaminants of emerging concern on aquatic food webs
Authors: Nilsen Elena , Smalling Kelly L. , Ahrens Lutz , Gros Meritxell , Miglioranza Karina S.B. , Picó Yolanda , Schoenfuss Heiko L.
Published: October 2018

Much progress has been made in the past few decades in understanding the sources, transport, fate, and biological effects of contaminants of emerging concern (CECs) in aquatic ecosystems. Despite these advancements, significant obstacles still prevent comprehensive assessments of the environmental risks associated with the presence of CECs. Many of these obstacles center around the extrapolation of effects of single chemicals observed in the laboratory or effects found in individual organisms or species in the field to impacts of multiple stressors on aquatic food webs. In the present review, we identify 5 challenges that must be addressed to promote studies of CECs from singular exposure events to multispecies aquatic food web interactions. There needs to be: 1) more detailed information on the complexity of mixtures of CECs in the aquatic environment, 2) a greater understanding of the sublethal effects of CECs on a wide range of aquatic organisms, 3) an ascertaining of the biological consequences of variable duration CEC exposures within and across generations in aquatic species, 4) a linkage of multiple stressors with CEC exposure in aquatic systems, and 5) a documenting of the trophic consequences of CEC exposure across aquatic food webs. We examine the current literature to show how these challenges can be addressed to fill knowledge gaps. Environ Toxicol Chem 2019;38:46–60. © 2018 SETAC
MiR‐409‐3p and MiR‐1896 co‐operatively participate in IL‐17‐induced inflammatory cytokine production in astrocytes and pathogenesis of EAE mice via targeting SOCS3/STAT3 signaling
Authors: Liu Xiaomei , Zhou Feng , Yang Ying , Wang Weixiao , Niu Liping , Zuo Dongjiao , Li Xiangyang , Hua Hui , Zhang Bo , Kou Yanbo , Guo Jingjing , Kong Fanyun , Pan Wei , Gao Dianshuai , Meves Jessica M. , Sun Hong , Xue Min , Zhang Qingxiu , Wang Yingwei , Tang Renxian
Published: October 2018

Th17 cells and interleukin‐17 (IL‐17) have been found to play an important role in the pathology of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Response to IL‐17, reactive astrocytes accompany with immune cells infiltration and axonal damage in MS/EAE. However, the role and the regulatory mechanism of IL‐17‐activated astrocytes in inflammation and in the EAE process still remain largely unknown. Here, we elucidated that miR‐409‐3p and miR‐1896, as co‐upregulated microRNAs in activated astrocytes and in EAE mice, targeted suppressor of cytokine signaling proteins 3 (SOCS3). Overexpression of miR‐409‐3p or miR‐1896 significantly reduced SOCS3 expression and increased phosphorylation of STAT3 as well as induced the inflammatory cytokines production (IL‐1β, IL‐6, IP‐10, MCP‐1, and KC), CD4+T cells migration and demyelination, in turn aggravating EAE development. Importantly, the effects of co‐overexpression of miR‐409‐3p and miR‐1896 in vitro or in vivo are strongly co‐operative. In contrast, simultaneously silenced miR‐409‐3p and miR‐1896 co‐operatively ameliorates inflammation and demyelination in the central nervous system of EAE mice. Collectively, our findings highlight that miR‐409‐3p and miR‐1896 co‐ordinately promote the production of inflammatory cytokines in reactive astrocytes through the SOCS3/STAT3 pathway and enhance reactive astrocyte‐directed chemotaxis of CD4+T cells, leading to aggravate pathogenesis in EAE mice. Co‐inhibition of miR‐409‐3p and miR‐1896 may be a therapeutic target for treating MS and neuroinflammation.
Prognostic role of baseline 18F‐FDG PET/CT parameters in MALT lymphoma
Authors: Albano Domenico , Bosio Giovanni , Camoni Luca , Farina Mirko , Re Alessandro , Tucci Alessandra , Giubbini Raffaele , Bertagna Francesco
Published: October 2018

Mucosa‐associated lymphoid tissue (MALT) lymphoma is an indolent lymphoma with good prognosis and variable fluorine‐18 fluorodeoxyglucose (18F‐FDG) avidity. Many possible prognostic factors have been investigated with controversial results, but the possible prognostic role of 18F‐FDG positron emission tomography/computed tomography (PET/CT) remains unclear. Our aim was to evaluate the prognostic impact of qualitative and semiquantitative baseline PET/CT parameters on outcome of MALT lymphoma. We retrospectively enrolled 161 patients with histologically confirmed MALT lymphoma who underwent 18F‐FDG PET/CT before any treatment. PET images were qualitatively and semiquantitatively analyzed by measuring the maximum standardized uptake value body weight (SUVbw), lean body mass (SUVlbm), body surface area (SUVbsa), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The Kaplan‐Meier method was used to estimate the progression‐free survival (PFS) and overall survival (OS) times. Cox regression models were performed to determine the relation between PET/CT features and OS and PFS. Ninety‐eight patients had positive 18F‐FDG PET/CT showing 18F‐FDG uptake (mean SUVbw, 10.1; SUVlbm, 7.2; SUVbsa, 2.7; MTV, 88.8; and TLG, 526); the remaining 63 were not 18F‐FDG avid. 18F‐FDG avidity was significantly correlated with tumor size and Ki‐67 score. Relapse/progression of disease occurred in 47 patients with an average time of 40.2 months; death occurred in 12 patients with an average of 59 months. At a median follow‐up of 62 months, median PFS and OS were 52 and 62 months, respectively. Advanced tumor stage and extragastric site were demonstrated to be independent prognostic factors for PFS, while only tumor stage for OS. Instead, PET/CT parameters were not related to survival, despite positive correlation at univariate analysis between MTV and TLG with PFS and positive PET/CT with PFS and OS. In conclusion, a 61% rate of PET avidity in biopsy‐confirmed MALT lymphoma was found, and it was correlated with tumor size and Ki‐67 score. Only tumor stage and localization were independently correlated with PFS and OS.
Understanding Practitioner‐Driven Assessment and Evaluation Efforts for Social Justice
Authors: Zerquera Desiree , Reyes Kimberly A. , Pender Jason T. , Abbady Ramy
Published: October 2018

This chapter presents findings from a national survey that sought to capture the ways practitioners work to integrate both assessment and social justice into their work as central concepts and practices that guide their efforts in student affairs. In so doing, these practitioners are working to reclaim assessment from the traditional, dominant framing of assessment work through neoliberal lenses and advance social justice in higher education.
Are DNA damage response kinases a target for the differentiation treatment of acute myeloid leukemia?
Authors: Pennisi Rosa , Albanesi Jacopo , Ascenzi Paolo , Nervi Clara , di Masi Alessandra
Published: October 2018

Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy characterized by the expansion of hematopoietic stem/progenitor cells (HPCs) blocked at different stages of maturation/differentiation. The poor outcome of AMLs necessitates therapeutic improvement. In AML, genes encoding for myeloid transcription factors, signaling receptors regulating cell proliferation, and epigenetic modifiers can be mutated by somatically acquired genetic mutations or altered by chromosomal translocations. These mutations modify chromatin organization at genes sites regulating HPCs proliferation, terminal differentiation, and DNA repair, contributing to the development and progression of the disease. The reversibility of the epigenetic modifications by drug treatment makes epigenetic changes attractive targets for AML therapeutic intervention. Recent findings underline increased DNA damage and abnormalities in the DNA damage response (DDR) as a critical feature of AML blasts. The DDR preserves cell integrity and must be tightly coordinated with DNA methylation and chromatin remodeling to ensure the accessibility to the DNA of transcription factors and repair enzymes. A crucial role in these events is played by the ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3‐related protein (ATR) kinases, which are hyperactive in AML. Based on these findings, we hypothesize the inhibition of DNA damage kinases as an alternative or complementary strategy for the differentiation treatment of AML as it leads to a reduced ability to repair the DNA damage, and to the inhibition of specific epigenetic modifiers whose function is altered in leukemic cells. © 2018 IUBMB Life, 70(11):1057–1066, 2018
Implementation and evaluation of a pharmacy‐driven transitions of care program for patients discharged from the emergency department
Authors: Lacy Mary C. , Bryant Ginelle A. , Herring Morgan S. , Koenigsfeld Carrie F. , Lehman Nicholas P. , Smith Hayden L.
Published: October 2018

Purpose

To evaluate a pharmacy‐driven post‐emergency department (ED) transitions of care program.

Methods

Patients admitted to the ED who receive primary care at a network clinic were eligible for inclusion. Pharmacy team members contacted patients within 7 days of ED discharge to perform medication reconciliation and assess for appropriate follow‐up. Following the calling period, rates of repeat ED visits, urgent care visits, hospitalizations, and clinic visits within 30 days of ED discharge were evaluated.

Results

Seventy percent of eligible patients were successfully contacted via phone. At least one new medication was prescribed in the ED to 61% of contacted patients, 22% of which were not picked up at the time of the call. Medication reconciliation was successfully completed during 87% of the phone calls, with 64% resulting in at least one identified medication discrepancy. A total of 230 pharmacist interventions were completed. Contacted patients had an adjusted 44% (95% confidence interval [CI]: 9–65) lower risk of subsequent ED visits compared with patients unable to be reached. Four percent of patients successfully contacted were admitted to the hospital within 30 days of ED discharge compared with 8% of patients unable to be reached (adjusted relative risk [RR]: 0.39; 95% CI: 0.18–0.84).

Conclusion

Patients who received post‐ED transitions of care calls were less likely to be seen again in the ED or be admitted to the hospital within 30 days. Follow‐up phone calls provided by pharmacy team members may be an effective tool to improve transitions of care following ED visits.
Rapid identification of gram‐negative bacteremia and impact on antipseudomonal antibiotic consumption with antimicrobial stewardship at a community hospital system
Authors: Box Maggie J. , Lee Jennifer M. , Ortiz Courtney D. , Ortwine Kristine N. , Richardson Caitlin A. , Sullivan Eva L. , Wong Samantha S.
Published: October 2018

Background

Rapid identification of gram‐negative bacteremia can improve time to effective antibiotic therapy and antibiotic de‐escalation; however, there are little data that quantify the change in antibiotic utilization. This study evaluates the impact of the Verigene gram‐negative blood culture test (BC‐GN) in combination with an antimicrobial stewardship team (AST) intervention on antipseudomonal (AP) antibiotic utilization in a community hospital system among infections where AP antibiotics are not necessary.

Methods

This multicenter, pre‐post, quasi‐experimental pilot study was conducted at Scripps Health in San Diego, California. Internal antibiogram data was reviewed, and among the 4 targets of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Proteus species (that lacked resistance genes) detected by the BC‐GN test, antimicrobial sensitivities did not warrant therapy with AP antibiotics. The BC‐GN test was performed at each site where clinical pharmacists notified physicians of results and assisted with antibiotic modifications. The primary end point was AP vs non‐AP antibiotic consumption within the first 5 days of admission. This was measured by days of therapy per patient day (DOT/PD). Secondary end points included hospital and intensive care unit (ICU) length of stay (LOS) and mortality.

Results

A total of 1051 patients were included; 512 in the pre‐intervention group, and 539 in the intervention group. Compared with the pre‐intervention group, AP antibiotic consumption significantly decreased (0.4 vs 0.2 DOT/PD, P < .0001) and non‐AP antibiotic consumption significantly increased (0.6 vs 0.8 DOT/PD, P < .0001) in the intervention group. Overall median LOS was 5 days vs 5 days (P = .85) and median ICU LOS was 3 days vs 2 days (P = .12), in the pre‐intervention and intervention groups, respectively. Mortality was similar between groups (7.0% vs 5.2% in the pre‐intervention and intervention groups, P = .21).

Conclusion

Rapid identification of gram‐negative bacteremia with AST intervention decreased AP antibiotic consumption among infections caused by pathogens where AP coverage is not needed.
Systematic evaluation of the methodological quality of clinical practice guidelines intended for pharmacists
Authors: Beckett Robert D. , Linn Dustin D. , Tellor Katie B. , Sheehan Amy H. , Montagano Kaitlin J. , Vonada Brooke
Published: October 2018

Introduction

The Appraisal of Guidelines, Research, and Evaluation version II (AGREE II) tool is a validated instrument designed to assess the methodological rigor and transparency of clinical practice guidelines.

Objective

The primary objective of this study was to determine the quality of clinical practice guidelines of which pharmacists are indexed as an intended user using AGREE II.

Methods

AGREE II was used to assess for methodological rigor and transparency in a systematic evaluation. The National Guideline Clearinghouse was used to identify guidelines published from 2010 to 2016, focused on treatment, and indexed to pharmacists as potential intended users. Each guideline was reviewed according to AGREE II by 3 independent reviewers: 1 clinical specialist pharmacist, 1 drug information pharmacist, and 1 student pharmacist, with domain and item scores calculated according to the AGREE II User Manual.

Results

Of 140 identified guidelines, mean AGREE II domain scores ranged from 54.8 ± 20.1% (Domain 5, Applicability) to 86.5 ± 9.0% (Domain 4, Clarity of Presentation). Mean AGREE II item scores ranged from 38.2 ± 34.4% (Item 5, “The views and preferences of the target population have been sought”) to 91.4 ± 11.2% (Item 17, “Key recommendations are easily identifiable”). For Item 24 (“Rate the overall quality of this guideline”), the mean score was 71.5 ± 17.8% (median: 75.0%). For Item 25 (“I would recommend this guideline for use”), the most common responses were “yes, with modifications” (n= 66, 47.1%) and “yes” (n= 57, 40.7%).

Conclusion

Guidelines intended for pharmacists were generally high quality, with opportunity for improvement in areas related to applicability.
Metal‐catalyzed alkyne oxidation/CH functionalization: Effects of oxidant, temperature, and metal catalyst on chemoselectivity
Authors: Wang Yong‐Heng , Wu An‐An , Tan Kai , Lu Xin
Published: October 2018

Gold‐catalyzed intermolecular alkyne oxidation has attracted much synthetic attention, but mostly suffering undesired over‐oxidation. Recent experiments demonstrated that over‐oxidation could be dramatically suppressed in zinc(II)‐catalyzed intermolecular alkyne oxidation/CH functionalization. By means of first‐principle density functional theory calculations, we explored the mechanism of the M‐catalyzed intermolecular alkyne oxidations (M = Zn(OTf)2 and Au+PR3) as well as the effects of oxidants, temperature, and metal catalysts on chemoselectivity, in an effort to disclose the origin of the extraordinary chemoselectivity pertaining to zinc catalysis. Our calculations indicate that the Zn‐catalyzed intermolecular alkyne oxidation/CH functionalization proceeds by a Friedel–Crafts alkylation mechanism rather than metal carbene insertion mechanism. The chemoselectivity of CH functionalization against over‐oxidation in Zn catalysis, in comparison with gold catalysis, can be jointly controlled by four factors: (1) the use of less nucleophilic N‐oxide, (2) the enhanced electrophilicity and carbocationic nature of the carbenic site in the α‐oxo metal carbenoid intermediate, (3) enhanced steric repulsion to incoming oxidant exerted by bulky ancillary ligand in the close nearby of the carbenic site to disfavor intermolecular over‐oxidation and (4) the large negative value of activation entropy in the intermolecular over‐oxidation pathway, that jointly give rise to lower activation free energy for the intramolecular cyclization/CH functionalization pathway than for the intermolecular over‐oxidation pathway. © 2018 Wiley Periodicals, Inc.
Effect of marital relationship on women's quality of life: Testing the mediating role of subjective well‐being
Authors: Wang Hua , Xu Congde , Fan Xiaoyan
Published: October 2018

Because of a large number of Chinese women and the widespread concern about women's living conditions, this study aimed to examine how subjective well‐being mediates the association between marital relationship and women's quality of life in Chinese context. The data used in this study were collected by conducting a multi‐stage cluster random sampling method of 756 women in Huai'an city of Mainland China. Data included women's basic demographics, women's quality of life and marital quality, and women's subjective well‐being. Structural equation modeling was adopted to analyze the data. The results of structural equation modeling analysis suggested a good fit for the sample. Overall findings showed that marital relationship has a significantly direct effect on women's quality of life, and subjective well‐being can partially mediate the impact of marital relationship on women's quality of life. The implications on theory and social policy were also discussed.
Evaluation of cell proliferation in cystic lesions associated with impacted third molars
Authors: Embaló Bubacar , Parize Hian Nivaldo , Rivero Elena Riet Correa
Published: October 2018

The purpose of this study was to evaluate the metabolism and epithelial cell proliferation of odontogenic keratocyst (OKC), dentigerous cyst (DC), and unicystic ameloblastoma (UA) by quantifying the nucleolar organizing regions (AgNORs) and Ki‐67 protein immunoexpression. Forty‐eight cases (16 OKC, 16 DC, and 16 UA) were evaluated retrospectively. The metabolism and epithelial cell proliferation was measured by the Ki‐67 positive cell percentage index and by the mean AgNOR count in each group. The Ki‐67 and AgNOR counts were significantly higher in OKC comparing to the DC and UA (p < .001). Ki‐67 positive cells were observed higher in suprabasal cell layers of OKC with uniform distribution, a few of them were predominantly observed in basal cell layer in DC and UA. The AgNOR count was significantly higher in the OKC basal cell layers and observed throughout the lining epithelium of DC and UA. Ki‐67 and AgNOR reinforced the aggressive character of OKC, presenting high metabolism and cellular proliferation compared to DC and UA, possibly due to its more aggressive clinical behavior and high recurrence rate.

Research Highlights

We evidence higher metabolism and epithelial cell proliferation in OKC when compared to UA and DC, supporting its aggressive aspect and its high rate of recurrence.

OKC had intense and predominant labeling of Ki‐67 on the suprabasal layer unlike UA and DC.
Morphological evaluation of liposomal iron carriers
Authors: Battistelli Michela , Salucci Sara , Falcieri Elisabetta
Published: October 2018

Iron is one of the most important elements for human, because it plays an essential role in many metabolic processes. However, it is also recognized to be dangerous for its detrimental effect inside human cells, where, in the absence of homeostatic balance, it can induce free radicals formation. Moreover, an excessive accumulation of iron in tissues can produce iron overload, a condition incompatible with life. The use of liposomes as carriers can represent an interesting iron therapy to improve iron bioavailability and reduce its negative effects, in particular during pregnancy. In this study, a morphological analysis has been performed on commercial liposome vesicles at various drying times, both in saline solution and in distilled water. Furthermore, to highlight their possible interaction or internalization in cells, liposomes have been administered to human hemopoietic U937 cells. Ultrastructural analyses confirm that vesicle morphology and size are comparable with classical liposomal structures. Products are stable during specimen preparation and drying. Additionally, they have a good ability to penetrate into cells, interacting with cytoplasmic organelles, without inducing, at least apparently, any ultrastructural damage.
Histomorphometry of ectopic mineralization using undecalcified frozen bone sections
Authors: Fujihara Ryuji , Chiba Yoichi , Nakagawa Toshitaka , Murakami Ryuta , Matsumoto Koichi , Kawauchi Machi , Fujii Takayuki , Shimono Ryuichi , Yamamoto Tetsuji , Ueno Masaki
Published: October 2018

To investigate the correlation between mineral formation and enhanced expressions of some proteins using undecalcified frozen bone sections. Histological studies have revealed that some proteins, such as BMP2, BMPR1A, and Connexin 43, are expressed in and around sites of ectopic ossification. However, the relationship between the expressed proteins considered to be associated with the ossification and mineral formation in vivo is not clear. Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1)‐mutant spinal hyperostotic TWY mice and ICR mice as controls were euthanized after calcein labeling, and undecalcified frozen sections were obtained from the middle thoracic spine. Intervertebral disc areas were examined histologically and by measuring calcein‐labeled areas and areas showing immunoreactivity for BMP2, BMPR1A, and Connexin 43. Calcein‐labeled areas, indicating mineralization in the ectopic mineralization sites, were significantly larger in the mutant mice than in controls. The expression of Connexin 43 was elevated in the annulus fibrosus. Increases in the calcein‐labeled areas was not correlated with increases in the areas showing immunoreactivity for Connexin 43 in the annulus fibrosus. There was no statistical correlation between enhanced immunohistochemical expression and elevated calcein‐labeled areas. By applying the morphometrical analysis method using undecalcified frozen sections to ENPP1‐mutant mice, quantitative evaluation of the mineralization and proteins expressed in the surrounding area in the same animal became possible.
JAG2 signaling induces differentiation of CD14+ monocytes into Langerhans cell histiocytosis-like cells
Authors: Schwentner Raphaela , Jug Gunhild , Kauer Maximilian O , Schnöller Thomas , Waidhofer-Söllner Petra , Holter Wolfgang , Hutter Caroline
Published: October 2018

Langerhans cell histiocytosis (LCH) is a MAPK pathway-driven disease characterized by the accumulation of CD1a+langerin+ cells of unknown origin. We have previously reported that the Notch signaling pathway is active in LCH lesions and that the Notch ligand Jagged2 (JAG2) induces CD1a and langerin expression in monocytes in vitro. Here we show that Notch signaling induces monocytes to acquire an LCH gene signature and that Notch inhibition suppresses the LCH phenotype. In contrast, while also CD1c+ dendritic cells or IL-4-stimulated CD14+ monocytes acquire CD1a and langerin positivity in culture, their gene expression profiles and surface phenotypes are more different from primary LCH cells. We propose a model where CD14+ monocytes serve as LCH cell precursor and JAG2-mediated activation of the Notch signaling pathway initiates a differentiation of monocytes toward LCH cells in selected niches and thereby contributes to LCH pathogenesis.

This study aims to identify the cell of origin of Langerhans Cell Histiocytosis and the molecular mechanisms of its pathogenesis.