bluuebunny/crossref_metadata_2025 huggingface dataset:
Asymmetric Sequential Cu‐Catalyzed 1,6/1,4‐Conjugate Additions of Hard Nucleophiles to Cyclic Dienones: Determination of Absolute Configurations and Origins of Enantioselectivity
Authors: Blons Charlie , Morin Marie S. T. , Schmid Thibault E. , Vives Thomas , Colombel‐Rouen Sophie , Baslé Olivier , Reynaldo Thibault , Covington Cody L. , Halbert Stéphanie , Cuskelly Sean N. , Bernhardt Paul V. , Williams Craig M. , Crassous Jeanne , Polavarapu Prasad L. , Crévisy Christophe , Gérard Hélène , Mauduit Marc
Published: April 2017

The first stereocontrolled Cu‐catalyzed sequential 1,6/1,4‐asymmetric conjugate addition (ACA) of C‐metalated hard nucleophiles to cyclic dienones is reported. The use of DiPPAM (diphenylphosphinoazomethinylate) followed by a phosphoramidite as the stereoinducing ligands facilitated both high ee values for the 1,6‐ACA and high de values for the 1,4‐ACA reaction components, which thus gave enantioenriched 1,3‐dialkylated moieties. The absolute configurations were determined by using vibrational circular dichroism (VCD) and optical rotatory dispersion (ORD) spectroscopy, in combination with DFT calculations and X‐ray analysis. Interestingly, DFT calculations for the mechanism of enantioselective 1,6‐addition by using an unprecedented Cu–Zn bimetallic catalytic system confirmed this attribution. Lastly, exploring intramolecular cyclization avenues for enantioenriched 1,3‐dialkylated products provided access to the challenging drimane skeleton.
A comprehensive comparative analysis of treatment modalities for sinonasal malignancies
Authors: Robin Tyler P. , Jones Bernard L. , Gordon Oren M. , Phan Andy , Abbott Diana , McDermott Jessica D. , Goddard Julie A. , Raben David , Lanning Ryan M. , Karam Sana D.
Published: April 2017

BACKGROUND

Sinonasal malignancies are a rare and heterogeneous group of tumors for which there is a paucity of robust data with which to guide management decisions. The authors used the National Cancer Data Base to better understand the presenting characteristics of these tumors and to compare outcomes by treatment modality.

METHODS

The National Cancer Data Base was queried for sinonasal malignancies diagnosed between 2004 and 2012. Overall survival was assessed using multivariate analyses and propensity score matching.

RESULTS

A total of 11,160 patients were identified for the initial analysis. The majority were male, aged 40 to 69 years, with tumors of the nasal cavity or maxillary sinus. Squamous cell histology was most common. The majority of patients presented with advanced tumor stage but without locoregional lymph node or distant metastases. Treatment modalities were compared for squamous cell carcinomas. In multivariate analysis, compared with surgery alone, patients who received adjuvant radiotherapy (hazard ratio [HR], 0.658 [P<.001]), adjuvant chemoradiotherapy (HR, 0.696 [P = .002]), or neoadjuvant therapy (HR, 0.656 [P = .007]) had improved overall survival. Patients who received radiotherapy alone (HR, 1.294 [P = .001]) or chemotherapy alone (HR, 1.834 [P<.001]) had worse outcomes. These findings were validated in propensity score matching. It is important to note that neoadjuvant chemoradiotherapy was associated with achieving a negative surgical margin (odds ratio, 2.641 [P = .045]).

CONCLUSIONS

Surgery is the mainstay of therapy for patients with sinonasal malignancies, but multimodality therapy is associated with improved overall survival. Cancer 2017;123:3040–49. © 2017 American Cancer Society.
Quantum Mechanics Approach to Hydration Energies and Structures of Alanine and Dialanine
Authors: Lanza Giuseppe , Chiacchio Maria A.
Published: April 2017

A systematic approach to the phenomena related to hydration of biomolecules is reported at the state of the art of electronic‐structure methods. Large‐scale CCSD(T), MP4‐SDQ, MP2, and DFT(M06‐2X) calculations for some hydrated complexes of alanine and dialanine (Ala⋅13 H2O, Ala2H+⋅18 H2O, and Ala2⋅18 H2O) are compared with experimental data and other elaborate modeling to assess the reliability of a simple bottom‐up approach. The inclusion of a minimal number of water molecules for microhydration of the polar groups together with the polarizable continuum model is sufficient to reproduce the relative bulk thermodynamic functions of the considered biomolecules. These quantities depend on the adopted electronic‐structure method, which should be chosen with great care. Nevertheless, the computationally feasible MP2 and M06‐2X functionals with the aug‐cc‐pVTZ basis set satisfactorily reproduce values derived by high‐level CCSD(T) and MP4‐SDQ methods, and thus they are suitable for future developments of more elaborate and hence more biochemically significant peptides.
Measurement of Tumor Necrosis Factor and Lymphotoxins
Authors: Hogan M. Michele , Vogel Stefanie N.
Published: April 2017

The tumor necrosis factor (TNF) superfamily of cytokines plays critical roles in all aspects of the immune response. TNF and the lymphotoxins (LT), LTα and LTβ, are particularly important as major effector cytokines and mediators or lymphoid organ development. One of the classical methods for the measurement of TNF and LTα activity is by demonstrating their ability to lyse certain target cells. A detailed protocol for the measurement of this activity using a highly sensitive indicator cell line is presented. More recently, ELISA assays have been developed to measure the protein concentration of these cytokines in any type of biologic fluid. © 2017 by John Wiley & Sons, Inc.
Analysis of the advantages of cis reporters in optimized FACS‐Gal
Authors: Sánchez‐Luengo Miguel Ángel , Rovira Miguel , Serrano Manuel , Fernandez‐Marcos Pablo Jose , Martinez Lola
Published: April 2017

Flow cytometry is a powerful multiparametric technology, widely used for the identification, quantification, and isolation of defined populations of cells based on the expression of target proteins. It also allows for the use of surrogate reporters, either enzymatic or fluorescent, to indirectly monitor the expression of these target proteins. In this work, we optimised the dissociation protocol for the detection of the enzymatic reporter LacZ using the FACS‐Gal detection system with the fluorogenic substrate FDG to compare cis‐ versus trans‐positioned reporters efficiency. Particularly, for the FACS‐Gal optimization, we studied lung and haematopoietic tissues, focusing on cell recovery, viability, FDG loading conditions and distribution of cellular populations. Reporter genes such as LacZ can be placed together with the gene of interest in the same polycistronic mRNA (in cis), or in independent alleles (in trans), which can strongly affect the correlation with the reporter readout. To address this issue, we generated a mouse model containing both types of reporters for the same gene, and compared them. Our results clearly indicate that trans‐positioned reporters can be misleading, and that using a reporter gene in cis rather than trans is a much more specific method to sort for cells undergoing Cre‐mediated recombination. © 2017 International Society for Advancement of Cytometry
Recognizing facial expressions of emotion in infancy: A replication and extension
Authors: Safar Kristina , Moulson Margaret C.
Published: April 2017

Infants may recognize facial expressions of emotion more readily when familiar faces express the emotions. Studies 1 and 2 investigated whether familiarity influences two metrics of emotion processing: Categorization and spontaneous preference. In Study 1 (n = 32), we replicated previous findings showing an asymmetrical pattern of categorization of happy and fearful faces in 6.5‐month‐old infants, and extended these findings by demonstrating that infants’ categorization did not differ when emotions were expressed by familiar (i.e., caregiver) faces. In Study 2 (n = 34), we replicated the spontaneous preference for fearful over happy expressions in 6.5‐month‐old infants, and extended these findings by demonstrating that the spontaneous preference for fear was also present for familiar faces. Thus, infants’ performance on two metrics of emotion processing did not differ depending on face familiarity.
Climatically driven changes in population composition and offspring sex‐morph ratio in a polymorphic species
Authors: Tuttle E. M. , Grunst A. S. , Grunst M. L. , Korody M. L. , Betuel A. M. , Barcelo‐Serra M. , Bierly G. , Gonser R. A.
Published: April 2017

Females from polymorphic species could theoretically benefit by adjusting offspring morph composition, since morphs often differ in ecological and behavioral traits, and may be differentially susceptible to environmental conditions. Although offspring sex ratio adjustments have been increasingly supported, whether, and in which contexts, genetically determined morph ratios are adjusted has not been established. We used a long‐term dataset to examine whether broad‐scale climatic patterns characterized by teleconnection indices, population composition, and other environmental factors affect offspring sex‐morph ratios in the white‐throated sparrow (Zonotrichia albicollis), a species with chromosomal morph determination. We predicted that females might overproduce the underrepresented sex or morph, since pairing is disassortative by morph, and might also produce more white morph male offspring given favorable climatic conditions, because white males (WMs) are large, promiscuous, and expensive to produce. The proportion of WM‐by‐tan female breeding pairs and recruitment of WMs declined following winters with high Pacific North American teleconnection indices, and females of both morphs produced more WM offspring after these relatively cold winters. These winters and the following springs were also associated with low Southern Oscillation indices, indicating El Niño. Females of both morphs also produced fewer males late in asynchronously hatching broods. Adjustment of brood composition in response to climatically mediated changes in population composition could stabilize the white‐throated sparrow's disassortative breeding system and genetic polymorphism.
Broad shifts in the resource use of a commercially harvested fish following the invasion of dreissenid mussels
Authors: Fera Shannon A. , Rennie Michael D. , Dunlop Erin S.
Published: April 2017

Dreissenid mussels, including the zebra (Dreissena polymorpha) and quagga (Dreissena rostiformus bugensis) mussel, are invasive species known for their capacity to act as ecosystem engineers. They have caused significant changes in the many freshwater systems they have invaded by increasing water clarity, reducing primary productivity, and altering zooplankton and benthic invertebrate assemblages. What is less clear is how their ecosystem engineering effects manifest up the food web to impact higher trophic levels, including fish. Here, we use a biological tracer (stable isotopes of carbon and nitrogen) to analyze long‐term and broad‐scale trends in the resource use of benthivorous lake whitefish (Coregonus clupeaformis) in the Laurentian Great Lakes, where dreissenid mussels have become established in each lake except Lake Superior. We measured stable isotope ratios from archived material (fish scale samples) collected over several decades by multiple agencies and from 14 locations around the Great Lakes. In the majority of locations, the δ13C of lake whitefish increased following the establishment of dreissenid mussels. Trends in δ15N were less clear, but significant breakpoints in the time series occurred within 5 yr of dreissenid establishment in several locations, followed by declines in δ15N. In contrast, isotopic signatures in Lake Superior locations did not show these trends. Our results provide evidence that lake whitefish shifted toward greater reliance on nearshore benthic production, supporting the theory that fundamental energy pathways are changed when dreissenid mussels become established. Importantly, these effects were noted across multiple, large, and complex ecosystems spanning a broad geographic area. Our study underscores the potential for aquatic invasive species to alter key ecosystem services as demonstrated here through their impacts on energy pathways supporting a commercially harvested fish species.
NKG2D stimulation of CD8+ T cells during priming promotes their capacity to produce cytokines in response to viral infection in mice
Authors: Kavazović Inga , Lenartić Maja , Jelenčić Vedrana , Jurković Slaven , Lemmermann Niels A.W. , Jonjić Stipan , Polić Bojan , Wensveen Felix M.
Published: April 2017

Natural killer group 2 member D (NKG2D) is an activating receptor that is expressed on most cytotoxic cells of the immune system, including NK cells, γδ, and CD8+ T cells. It is still a matter of debate whether and how NKG2D mediates priming of CD8+ T cells in vivo, due to a lack of studies where NKG2D is eliminated exclusively in these cells. Here, we studied the impact of NKG2D on effector CD8+ T‐cell formation. NKG2D deficiency that is restricted to murine CD8+ T cells did not impair antigen‐specific T‐cell expansion following mouse CMV and lymphocytic choriomeningitis virus infection, but reduced their capacity to produce cytokines. Upon infection, conventional dendritic cells induce NKG2D ligands, which drive cytokine production on CD8+ T cells via the Dap10 signaling pathway. T‐cell development, homing, and proliferation were not affected by NKG2D deficiency and cytotoxicity was only impaired when strong T‐cell receptor (TCR) stimuli were used. Transfer of antigen‐specific CD8+ T cells demonstrated that NKG2D deficiency attenuated their capacity to reduce viral loads. The inability of NKG2D‐deficient cells to produce cytokines could be overcome with injection of IL‐15 superagonist during priming. In summary, our data show that NKG2D has a nonredundant role in priming of CD8+ T cells to produce antiviral cytokines.
Synthesis and Structural Studies of Three‐Dimensional Supramolecular Motifs Derived from Neutral and Cationic Zinc Alkanesulfonates
Authors: Shankar Ravi , Singh Rohit , Mendiratta Swati , Jassal Amanpreet Kaur , Kociok‐Köhn Gabriele , Molloy Kieran C.
Published: April 2017

Invited for the cover of this issue is the group of Ravi Shankar from the Indian Institute of Technology Delhi, India, in collaboration with the group of Kieran C. Molloy from the University of Bath, UK. The cover image shows the potential of zincate anions bearing weakly coordinating alkanesulfonate groups as synthons for three‐dimensional supramolecular assemblies.
Unique Strategies for Controlling Enantioselective Stereochemistry of Cyclizations via Radical Intermediates
Authors: Miyabe Hideto
Published: April 2017

Enantioselective stereocontrol in cyclization reactions continues to attract much interest. This review article highlights the recent progress in the conceptually and mechanistically unique enantioselective cyclization approaches involving radical intermediates, which cannot be strictly classified according to the typical enantioselective radical cyclizations. This review summarizes the chiral memory effect or transfer of axial chirality in radical cyclizations, [2+2] photocycloaddition controlled by chiral Lewis acids or by chiral hydrogen‐bonding organocatalysts, CoII‐based metalloradical catalysis, and radical‐polar/polar‐radical crossover reactions controlled by chiral imidazolidinone organocatalysts or chiral copper catalysts.
Miniaturized Biamperometric Detectors for Electrochemical Detection in Flowing Streams
Authors: Komendová Martina , Metelka Radovan , Urban Jiří
Published: April 2017

Capillary electrochemical detectors with various configurations of electrodes were developed by inserting platinum multielectrodes (tetrodes) or platinum and carbon microelectrodes into the ending of capillaries. The biamperometric mode of detection, without the need of classical reference electrode, was employed in flow injection analysis of dopamine and norepinephrine selected as model samples. The influences of geometric shape of tetrodes, arrangement of electrodes and internal diameter of the capillary were studied thoroughly with respect to intensity of recorded currents. A novel pulse biamperometric technique was employed with the aim to enhance further the recorded currents of dopamine oxidation and to minimize the passivation of electrodes in mixed aqueous‐organic carrier solution, which improved considerably the repeatability of measurements. Proposed low‐cost microelectrode devices showed good prospects as detectors in simple and miniaturized flow systems, such as flow injection analysis and capillary high‐performance liquid chromatography with monolithic columns.
A New and Cost Effective Approach for Simultaneous Voltammetric Analysis of two Related Benzimidazole Drugs and their Determination in Biological Fluids
Authors: Khashaba Pakinaz Y. , Ali Hassan Refat H. , El‐Wekil Mohamed M.
Published: April 2017

A polymerized film of eriochrome black T (EBT) was prepared on the surface of pencil graphite electrode in alkaline solution by cyclic voltammetry. The redox response of the poly (EBT) film at the electrode appeared in a couple of redox peak in 0.1 M sodium hydroxide. The poly (EBT) film‐coated electrode exhibited excellent electrocatalytic activity towards the oxidation of rabeprazole sodium (RAB sodium) and domperidone (DOM) in Britton‐Robinson buffer (pH 4.0). The polymer film modified electrode conspicuously enhanced the redox currents of the cited mixture and could sensitively and separately determine them. Both cyclic voltammetry (CV) and square wave adsorptive stripping voltammetric (SWAdSV) methods were utilized to determine this mixture. The linearity of CV ranged from 4.1‐120 μM and 5.2‐90 μM for RAB sodium and DOM, respectively while SWAdSV was 7.5‐80×10−7M and 5–70×10−7M for RAB sodium and DOM, respectively. With good selectivity and sensitivity, the present method provides a simple method for selective detection of RAB sodium and DOM binary mixture in synthetic mixtures and biological fluids.
Seismic strengthening of existing RC beam‐column joints by wing walls
Authors: Li Yuebing , Sanada Yasushi
Published: April 2017

Numerous non‐ductile reinforced concrete (RC) buildings with little or no shear reinforcement in beam‐column joints can be found in regions of moderate seismicity. To strengthen such substandard beam‐column joints, this study proposes a method in which RC wing walls are installed beside existing columns, which overcomes the lack of realistic strengthening methods for congested connections in RC buildings. The proposed strengthening mechanism improves the joint moment capacity by utilizing tension and compression acting on the beam–wing wall boundaries; thus, brittle joint hinging failure is prevented. Three 3/4‐scale RC exterior beam‐column joint specimens without shear reinforcement, two of which were strengthened by installing wing walls with different strengthening elements, were fabricated and tested. The test results verified the effectiveness of the proposed strengthening method and the applicability of this method to seismically substandard beam‐column joints. © 2017 The Authors. Earthquake Engineering & Structural Dynamics Published by John Wiley & Sons Ltd.
Simplified estimation of the expected annual loss of reinforced concrete buildings
Authors: Cardone Donatello , Sullivan Timothy , Gesualdi Giuseppe , Perrone Giuseppe
Published: April 2017

Performance‐based earthquake engineering procedures have now developed to the point that it is possible to evaluate a range of possible decision variables, including the expected annual monetary loss (EAL). Quantification of the EAL is considered to be particularly useful because it could assist with the identification of effective design and retrofit measures that consider seismic performance over a range of intensity levels. Recognizing, however, that existing procedures for the evaluation of EAL tends to be quite time consuming, this paper builds on a recent proposal to use simplified limit state loss versus intensity relationships to compute EAL via a closed‐form equation, without the need to compile an inventory of damageable components and with freedom in the choice of structural analysis method. Various developments to the simplified approach are made in this paper to allow consideration of loss thresholds, non‐uniform damage distributions and the impact of differences in seismic performance in orthogonal directions. In addition, means of accounting for uncertainties in the simplified EAL assessment are described. The work has focused on the assessment of EAL for reinforced concrete frame buildings with details representative of construction practice adopted in Italy in the 1950s through to the early 1970s. By comparing loss assessment results obtained using a refined methodology with those obtained using the new guidelines developed here for two case study buildings, it is concluded that the simplified approach works well. Future research should therefore aim to further validate the approach and extend it to other building typologies and construction eras. Copyright © 2017 John Wiley & Sons, Ltd.
Multidimensional quantification of uncertainty and application to a turbulent mixing model
Authors: Barmparousis Christos , Drikakis Dimitris
Published: April 2017

This paper concerns the implementation of the generalized polynomial chaos (gPC) approach for parametric studies, including the quantification of uncertainty (UQ), of turbulence modelling. The method is applied to Richtmyer‐Meshkov turbulent mixing. The K−L turbulence model has been chosen as a prototypical example, and parametric studies have been performed to examine the effects of closure coefficients and initial conditions on the flow results. It is shown that the proposed method can be used to obtain a relation between the uncertain inputs and the monitored flow quantities, thus efficiently performing parametric studies. It allows the simultaneous calibration and quantification of uncertainty in an efficient numerical framework.
Special segments at the cross passages in the Filder Tunnel – Interpretation of the data from monitoring segments
Authors: Atzl Georg , Soranzo Enrico , Mihaylov Vladislav , Hochgatterer Bernhard
Published: April 2017

The 9,468 m long twin‐bored Fildertunnel is the longest railway tunnel of the Stuttgart 21 project. The maximum overburden is approximately 220 m, the tunnel tubes lie up to 60 m below the water table and the distance between the cross‐passages is approximately 500 m. The precast concrete segments for the mechanised excavation of the Fildertunnel are equipped with measuring devices in proximity of the cross‐passages to assess the lining strains prior to the construction of the cross‐passages and to serve as a basis for the further design. The lining stresses are derived by applying an appropriate calculation method, which transforms the measured strains into material stresses, hence achieving the active load configuration. The strains measured on the outside and inside of the lining with embedded vibrating wire strain gauges are converted into stresses and internal forces, enabling a direct assessment of the internal forces along the entire circumference of the segmental lining. In this article the measurement results in the area of the cross passages 6a and 7a of the Fildertunnel are described and interpreted. The significant internal forces in the segments after their installation and their time development are described, their dependence on influence factors such as self‐weight, thrust forces, grout pressure, rock mass and water pressure is discussed and the results are compared to the design calculation.
Demyelination induced by oxidative stress is regulated by sphingosine 1‐phosphate receptors
Authors: O'Sullivan Sinead A. , Velasco‐Estevez Maria , Dev Kumlesh K.
Published: April 2017

Oxidative stress is a pathological condition defined as an imbalance between production and removal of reactive oxygen species. This process causes structural cell damage, disrupts DNA repair and induces mitochondrial dysfunction. Many in vitro studies have used direct bolus application of H2O2 to investigate the role of oxidative stress in cell culture. In this study, using mouse organotypic cerebellar slice cultures, the effects of H2O2‐induced oxidative stress on myelination state were examined, using bolus concentrations of H2O2 (0.1–1 mM) and low‐continuous H2O2 (∼20 μM) generated from glucose oxidase and catalase (GOX‐CAT). Using these models, the potential therapeutic effects of pFTY720, an oral therapy used in multiple sclerosis, was also examined. We found bolus treatment of H2O2 (0.5 mM) and, for the first time, low‐continuous H2O2 (GOX‐CAT) to induce demyelination in organotypic slices. Both bolus H2O2 and GOX‐CAT treatments significantly decreased vimentin expression in these slice cultures as well as increased cell death in isolated astrocyte cultures. Importantly, pre‐treatment with pFTY720 significantly attenuated both bolus H2O2 and GOX‐CAT‐induced demyelination and the GOX‐CAT‐induced decrease in vimentin in cerebellar slices, without altering levels of the proinflammatory cytokines such as IL‐6 and CX3CL1. We also observed increased SMI‐32 immunoreactivity in the white matter tract induced by GOX‐CAT indicating axonal damage, which was remarkably attenuated by pFTY720. Taken together, this data establishes a novel GOX‐CAT model of demyelination and demonstrates that pFTY720 can act independently of inflammatory cytokines to attenuate decreases in vimentin, as well as axonal damage and demyelination induced by oxidative stress.
The occurrence and persistence of thoughts of suicide, self‐harm and death in family caregivers of people with dementia: a longitudinal data analysis over 2 years
Authors: Joling Karlijn J. , O'Dwyer Siobhan T. , Hertogh Cees M.P.M. , van Hout Hein P.J.
Published: April 2017

Objective

Family caregivers of people with dementia often report high levels of stress and depression, but little is known about those who contemplate suicide or self‐harm. This study explores thoughts of suicide, self‐harm and death in dementia caregivers and investigates the characteristics that distinguish them from those without such thoughts.

Methods

Data were collected every 3 months, for 24 months, from 192 family caregivers of people with dementia living in the Netherlands. Caregivers did not have a clinical depression or anxiety disorder at baseline. Suicide‐related thoughts were measured with an item from the Mini International Neuropsychiatric Interview, a diagnostic instrument for DSM‐IV mental disorders. Fisher exact, analysis of variance or Kruskal–Wallis tests compared the characteristics of caregivers who had contemplated suicide with two comparison groups.

Results

Within 24 months, 76 caregivers reported symptoms of a potential depression and were further assessed for suicidal thoughts. Nine carers (11.8%, 4.7% of the total sample) reported suicidal thoughts with three of those at multiple points. Caregivers with suicidal thoughts had more severe depressive and anxious symptoms, had a lower sense of competence and mastery, felt less happy and experienced more health problems, less family support and more feelings of loneliness than caregivers who had not.

Conclusion

Suicidal thoughts are present in dementia caregivers and can persist across the care trajectory. Various psychological and social characteristics significantly distinguish caregivers with suicidal thoughts from those without. More research is needed to enable the identification of high‐risk caregivers and provide an evidence base for the development of preventive strategies and interventions. © 2017 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.
Assessing cerebrovascular reactivity by the pattern of response to progressive hypercapnia
Authors: Fisher Joseph A. , Sobczyk Olivia , Crawley Adrian , Poublanc Julien , Dufort Paul , Venkatraghavan Lashmi , Sam Kevin , Mikulis David , Duffin James
Published: April 2017

Cerebral blood flow responds to a carbon dioxide challenge, and is often assessed as cerebrovascular reactivity, assuming a linear response over a limited stimulus range or a sigmoidal response over a wider range. However, these assumed response patterns may not necessarily apply to regions with pathophysiology. Deviations from sigmoidal responses are hypothesised to result from upstream flow limitations causing competition for blood flow between downstream regions, particularly with vasodilatory stimulation; flow is preferentially distributed to regions with more reactive vessels. Under these conditions, linear or sigmoidal fitting may not fairly describe the relationship between stimulus and flow. To assess the range of response patterns and their prevalence a survey of healthy control subjects and patients with cerebrovascular disease was conducted. We used a ramp carbon dioxide challenge from hypo‐ to hypercapnia as the stimulus, and magnetic resonance imaging to measure the flow responses. We categorized BOLD response patterns into four types based on the signs of their linear slopes in the hypo‐ and hypercapnic ranges, color coded and mapped them onto their respective anatomical scans. We suggest that these type maps complement maps of linear cerebrovascular reactivity by providing a better indication of the actual response patterns. Hum Brain Mapp 38:3415–3427, 2017. © 2017 Wiley Periodicals, Inc.
Ultra–low‐dose radiotherapy for definitive management of ocular adnexal B‐cell lymphoma
Authors: Pinnix Chelsea C. , Dabaja Bouthaina S. , Milgrom Sarah A. , Smith Grace L. , Abou Zeinab , Nastoupil Loretta , Romaguera Jorge , Turturro Francesco , Fowler Nathan , Fayad Luis , Westin Jason , Neelapu Sattva , Fanale Michelle A. , Rodriguez Maria A. , Hagemeister Frederick , Lee Hun Ju , Oki Yasuhiro , Wang Michael , Samaniego Felipe , Chi Linda , Esmaeli Bita
Published: April 2017

Background

The purpose of this study was to report the response to and toxicity of ultra–low‐dose radiotherapy (RT) for B‐cell ocular adnexal lymphoma (OAL).

Methods

We conducted a retrospective review of patients with indolent B‐cell and mantle cell OAL treated with 4 Gy to the orbit(s) in two 2‐Gy fractions. Disease response was assessed clinically and/or radiographically at 2 to 4‐month intervals after RT. Data collected included rates of overall response, complete response (CR), partial response (PR), and treatment‐related toxic effects.

Results

Twenty‐two patients (median age, 65 years) had the following histologic subtypes: mucosa‐associated lymphoid tissue (MALT; 14 patients; 64%); follicular lymphoma (5 patients; 23%); mantle cell lymphoma (MCL; 2 patients; 9%); and unclassifiable (1 patient, 4%). The overall response rate was 100%; 19 patients (86%) had a CR and 3 patients (14%) had a PR. The only acute toxic effect was grade 1 dry eye syndrome in 1 patient.

Conclusion

Ultra–low‐dose RT in patients with OAL is associated with high response rates and minimal toxic effects, and is much shorter in duration and cost. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1095–1100, 2017
Reviewing the genetic alterations in high‐risk cutaneous squamous cell carcinoma: A search for prognostic markers and therapeutic targets
Authors: Ashford Bruce G. , Clark Jonathan , Gupta Ruta , Iyer N. Gopalakrishna , Yu Bing , Ranson Marie
Published: April 2017

Cutaneous squamous cell carcinoma (SCC) is second only in incidence to basal cell carcinoma (BCC), effecting up to 500 000 people in the United States annually. Metastasis to regional lymph nodes occurs in approximately 5% of cases and imparts significant morbidity. Standard treatment in this group involves a combination of surgery and adjuvant radiation. Currently, there are no clinically useful biomarkers of metastatic potential in primary cutaneous SCC and histological predictors can be unreliable. The high level of mutational burden in normal UV‐exposed skin has hampered the search for novel drivers of invasive disease, and indeed metastatic potential. This review outlines the clinical problems in high‐risk and metastatic cutaneous SCCs, reviews the known genetic events and molecular mechanisms in high‐risk primary cutaneous SCC and metastasis, and identifies avenues for further investigation and potential therapy.
Minimally invasive wire‐guided balloon catheter puncture for voice prosthesis insertion
Authors: Tobed Secall Marc , Bores Toni , Sambola Ignacio , Lop Joan , García Rica Eduardo , Lluansi Jordi
Published: April 2017

Background

Tracheoesophageal puncture is an effective and reliable method for voice restoration after total laryngectomy that may be performed as a primary or secondary procedure.

Methods

We describe our technique for secondary tracheoesophageal puncture using a wire‐guided balloon catheter in an office setting. A 72‐year‐old patient with a total laryngectomy performed 2 years ago was selected for wire‐guided balloon catheter puncture and voice prosthesis insertion.

Results

Successful tracheoesophageal puncture placement was achieved without complications and the patient tolerated the procedure well. The voice result was satisfactory and immediate.

Conclusion

We conclude that balloon catheter tracheoesophageal puncture can be a simple and safe option for secondary voice prosthesis insertion in total laryngectomy for selected patients. It can be performed in an office setting using only local anesthetic for secondary puncture.
Hepatic FXR/SHP axis modulates systemic glucose and fatty acid homeostasis in aged mice
Authors: Kim Kang Ho , Choi Sungwoo , Zhou Ying , Kim Eun Young , Lee Jae Man , Saha Pradip K. , Anakk Sayeepriyadarshini , Moore David D.
Published: April 2017

The nuclear receptors farnesoid X receptor (FXR; NR1H4) and small heterodimer partner (SHP; NR0B2) play crucial roles in bile acid homeostasis. Global double knockout of FXR and SHP signaling (DKO) causes severe cholestasis and liver injury at early ages. Here, we report an unexpected beneficial impact on glucose and fatty acid metabolism in aged DKO mice, which show suppressed body weight gain and adiposity when maintained on normal chow. This phenotype was not observed in single Fxr or Shp knockouts. Liver‐specific Fxr/Shp double knockout mice fully phenocopied the DKO mice, with lower hepatic triglyceride accumulation, improved glucose/insulin tolerance, and accelerated fatty acid use. In both DKO and liver‐specific Fxr/Shp double knockout livers, these metabolic phenotypes were associated with altered expression of fatty acid metabolism and autophagy‐machinery genes. Loss of the hepatic FXR/SHP axis reprogrammed white and brown adipose tissue gene expression to boost fatty acid usage. Conclusion: Combined deletion of the hepatic FXR/SHP axis improves glucose/fatty acid homeostasis in aged mice, reversing the aging phenotype of body weight gain, increased adiposity, and glucose/insulin tolerance, suggesting a central role of this axis in whole‐body energy homeostasis. (Hepatology 2017;66:498–509).
Follicular lymphoma: State‐of‐the‐art ICML workshop in Lugano 2015
Authors: Gascoyne Randy D. , Nadel Bertrand , Pasqualucci Laura , Fitzgibbon Jude , Payton Jacqueline E. , Melnick Ari , Weigert Oliver , Tarte Karin , Gribben John G. , Friedberg Jonathan W. , Seymour John F. , Cavalli Franco , Zucca Emanuele
Published: April 2017

The 13th International Conference on Malignant Lymphoma held in Lugano in June 2015 was preceded by a closed workshop (organized in collaboration with the American Association for Cancer Research and the European School of Oncology) with the aim of developing an up‐to‐date understanding of the biology of follicular lymphoma and the clinical implications of new findings in the field. Discussed topics included the mutational spectrum at diagnosis, the clinical correlates of genetic and epigenetic alterations, the mechanisms of clonal evolution and histological transformation, the cross talk between tumor cells and microenvironment, and the development of novel treatments. This report represents a summary of the workshop.
Review of clinical indicators, including serum anti‐Müllerian hormone levels, for identification of women who should consider egg freezing
Authors: Martyn Fiona , O'Brien Yvonne M. , Wingfield Mary
Published: April 2017

Objective

To identify women, on the basis of clinical history and serum anti‐Müllerian hormone (AMH) levels, who are at risk of premature ovarian insufficiency and thereby guide appropriate early referral for egg freezing.

Methods

In a retrospective study, data were reviewed from women attending two fertility clinics in Dublin, Ireland, between August 2011 and December 2012. Case histories of women aged 35 years or younger were assessed to identify risk factors for reduced ovarian reserve, including endometriosis, ovarian surgery, and family history of premature ovarian failure (POF).

Results

Among 490 women aged 35 years or younger, 195 (39.7%) had an AMH level below 10 pmol/L, 94 (19.2%) had an AMH below 5 pmol/L, and 21 (4.3%) had an AMH below 1 pmol/L. Among 104 women aged 30 years or younger, the respective numbers were 28 (26.9%), 15 (14.4%), and 9 (8.7%). Among the 490 women, significantly lower AMH levels were observed for those with endometriosis (P=0.017) and a family history of POF (P=0.006). However, 53 (56.4%) of 94 women aged 35 years or younger with low AMH levels had no clinical risk factors.

Conclusion

Universal AMH screening should be considered for all women in their 30s who are not ready to try to conceive; clinical risk factors will only identify approximately 50% of women at risk of low ovarian reserve.
College Women's Gender Identity and Their Drinking Choices
Authors: Likis‐Werle Elizabeth , Borders L. DiAnne
Published: April 2017

Because college women's drinking rates now rival men's rates, the authors interviewed college women to ascertain how gender identity affected their drinking choices. Interpretative phenomenological analysis indicated that high‐risk drinkers viewed their gender identity differently than did low‐risk drinkers. Counseling implications are discussed.
Graphene as multifunctional delivery platform in cancer therapy
Authors: Nejabat Mojgan , Charbgoo Fahimeh , Ramezani Mohammad
Published: April 2017

The biomedical applications of graphene‐based nanomaterials including drug and gene delivery have grown rapidly in the past few years. This is due to its high surface area that results in high cargo loading capacity. It is demonstrated that graphene can improve drug efficacy without increasing the dose of the chemotherapeutic agent in cancer treatment. Considering these valuable benefits of graphene, this review focused on the newest advancements in drug and gene delivery systems using graphene and unveiling advantages and disadvantages of different graphene‐based materials in introducing an effective cargo delivery system for cancer therapy. Different approaches for reducing cytotoxic impacts of graphene oxide and production of biocompatible delivery platform were also reviewed. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2355–2367, 2017.
The Long Non‐Coding RNA TP73‐AS1 Interacted With miR‐142 to Modulate Brain Glioma Growth Through HMGB1/RAGE Pathway
Authors: Zhang Rong , Jin Hekun , Lou Fan
Published: April 2017

P73 antisense RNA 1T (non‐protein coding), also known as TP73‐AS1 or PDAM, is a long non‐coding RNA which may regulate apoptosis via regulation of p53‐dependent anti‐apoptotic genes. An abnormal change of TP73‐AS1 expression was noticed in cancers. The effects of TP73‐AS1 in brain glioma growth and the underlying mechanism remain unclear so far. In the present study, TP73‐AS1 was specifically upregulated in brain glioma tissues and cell lines, and was associated with poorer prognosis in patients with glioma. TP73‐AS1 knocking down suppressed human brain glioma cell proliferation and invasion in vitro, as well as HMGB1 protein. MiR‐142 has been reported to play a pivotal role in cancers; here we observed that TP73‐AS1 and miR‐142 could negatively regulate each other. Results from luciferase assays suggested that TP73‐AS1 might compete with HMGB1 for miR‐142 binding. Further, HMGB1/RAGE was involved in TP73‐AS1/miR‐142 regulation of glioma cell proliferation and invasion. In glioma tissues, TP73‐AS1 and HMGB1 expression was up‐regulated, whereas miR‐142 expression was down‐regulated. Data from the present study revealed that TP73‐AS1 promoted the brain glioma growth and invasion through acting as a competing endogenous RNA (ceRNA) to promote HMGB1 expression by sponging miR‐142. In conclusion, we regarded TP73‐AS1 as an oncogenic lncRNA promoting brain glioma proliferation and invasion, and a potential target for human brain glioma treatment. J. Cell. Biochem. 119: 3007–3016, 2018. © 2017 Wiley Periodicals, Inc.
Increased von Willebrand factor over decreased ADAMTS‐13 activity is associated with poor prognosis in patients with advanced non‐small‐cell lung cancer
Authors: Guo Renyong , Yang Jiezuan , Liu Xia , Wu Jianping , Chen Yu
Published: April 2017

Background

Hypercoagulability induced by the imbalance between von Willebrand factor (VWF) secretion and its cleaving protease (ADAMTS‐13) has been correlated with cancer metastasis. The aim of this study was to explore the prognostic significance of the VWF/ADAMTS‐13 ratio in advanced non‐small‐cell lung cancer (NSCLC).

Methods

Pre‐treatment sera/plasma levels of VWF, ADAMTS‐13, VWF/ADAMTS‐13 ratio, factor (F) VIII, and other clinical/laboratory parameters were measured in 119 patients with advanced NSCLC and 102 healthy controls. All patients were followed up to determine the predictive value of these parameters for prognosis of advanced NSCLC.

Results

Elevated VWF, VWF/ADAMTS‐13 ratio, and reduced ADAMTS‐13 were significantly correlated with the stage and grade of advanced NSCLC and the final status of disease (P<.05). VWF levels and the VWF/ADAMTS‐13 ratio were also associated with response to chemotherapy (P<.05). Multivariate analysis identified the VWF/ADAMTS‐13 ratio and D‐dimer as significant independent predictors of patient mortality. The area under the curve showed that the VWF/ADAMTS‐13 ratio was more useful than VWF, ADAMTS‐13, and D‐dimer to predict mortality. Kaplan‐Meier analysis showed that a low VWF/ADAMTS‐13 ratio was significantly predictive of improved survival (P=.004).

Conclusion

These results suggest that the imbalance between VWF secretion and ADAMTS‐13 may play a critical role in the hypercoagulability state in advanced NSCLC. Moreover, elevation of the plasma VWF/ADAMTS‐13 ratio may serve as an independent predictive factor for mortality in patients with advanced NSCLC.
Determinant roles of gender and age on SII, PLR, NLR, LMR and MLR and their reference intervals defining in Henan, China: A posteriori and big‐data‐based
Authors: Meng Xianchun , Chang Qian , Liu Yuying , Chen Ling , Wei Gaohui , Yang Jingjing , Zheng Peiguo , He Fucheng , Wang Wanhai , Ming Liang
Published: April 2017

Objectives

By now, there are few data of the reference intervals (RIs) of SII, PLR, NLR, LMR and MLR. We aimed to establish RIs of SII, PLR, NLR, LMR and MLR for healthy persons.

Methods

A retrospective analysis on a cohort of ostensibly healthy, aged no <18 years old physical examinees who took health examination from January to December in 2013 was conducted to explore influences of age and gender on SII, PLR, NLR, LMR and MLR and to establish their RIs. And another cohort of 450 persons in our hospital from January to July in 2016 is included for validations of RIs.

Results

NLR, LMR and MLR were significantly different between gender groups (P=.010; P<.001; P<.001, separately), while SII and PLR were not (P=.137; P=.267, separately). While SII was not changed much between age groups (P=.842), PLR, NLR, LMR and MLR were significantly different (all with P<.001). RIs of SII, PLR, NLR, LMR and MLR were: SII: [161,701]; PLR: 18‐65 year‐old: [61,179]/>65 year‐old: [55,179]; NLR: 18‐65 year‐old male: [0.90,2.94]/18‐65 year‐old female: [0.85,3.06]/>65 year‐old male: [0.95,3.57]/aged >65 year‐old female: [0.83,3.30]; LMR: 18‐65 year‐old male: [2.50,7.50]/18‐65 year‐old female: [2.75,8.50]/>65 year‐old male: [2.16,7.41]/>65 year‐old female: [2.40,8.33]; MLR: 18‐65 year‐old male: [0.12,0.35]/18‐65 year‐old female: [0.10,0.32]/>65 year‐old male: [0.12,0.41]/>65 year‐old male: [0.11,0.33].

Conclusions

RIs of SII, PLR, NLR, LMR and MLR of people in central China were established and validated. It will benefit experimental design of the related studies and lead to better standardizations of SII, PLR, NLR, LMR and MLR for their clinical applications.
Nuclear spatial and spectral features based evolutionary method for meningioma subtypes classification in histopathology
Authors: Fatima Kiran , Majeed Hammad , Irshad Humayun
Published: April 2017

Meningioma subtypes classification is a real‐world multiclass problem from the realm of neuropathology. The major challenge in solving this problem is the inherent complexity due to high intra‐class variability and low inter‐class variation in tissue samples. The development of computational methods to assist pathologists in characterization of these tissue samples would have great diagnostic and prognostic value. In this article, we proposed an optimized evolutionary framework for the classification of benign meningioma into four subtypes. This framework investigates the imperative role of RGB color channels for discrimination of tumor subtypes and compute structural, statistical and spectral phenotypes. An evolutionary technique, Genetic Algorithm, in combination with Support Vector Machine is applied to tune classifier parameters and to select the best possible combination of extracted phenotypes that improved the classification accuracy (94.88%) on meningioma histology dataset, provided by the Institute of Neuropathology, Bielefeld. These statistics show that computational framework can robustly discriminate four subtypes of benign meningioma and may aid pathologists in the diagnosis and classification of these lesions.
Travel medicine: Part 2—Special situations
Authors: Kamata Kazuhiro , Birrer Richard B , Tokuda Yasuharu
Published: April 2017

Travel should be educational, fun, and safe if the appropriate care is rendered by counseling physicians and travelers take an active role in their health. In the second paper of the 2‐part special articles, we provide a practical summary of up‐to‐date travel medicine about special situations for primary care physicians. We focus on in‐flight emergencies, pregnancy, and specific precautions for injury and infectious disease as special situations. Physicians are frequently called upon to examine patients with in‐flight emergencies, and thus, they should have knowledge and skills for effectively caring patients. Common health problems over the flights include syncope, chest pain, dyspnea, and gastrointestinal symptoms. Cautious and prudent behaviors should be recommended for travelers to prevent injury and infectious disease. Follow‐up after the return home optimizes a positive outcome.
Quantum‐chemical perspective of nanoscale Raman spectroscopy with the three‐dimensional phonon confinement model
Authors: Korepanov Vitaly I. , Hamaguchi Hiro‐o
Published: April 2017

Raman spectroscopy of crystalline/molecular systems is well grounded with quantum‐chemical calculations and group theory, making it a unique tool for material characterization. For the ‘intermediate’ case of nanometer‐scale systems, however, the application of Raman spectroscopy is limited by the lack of such theoretical bases. Here, we couple a scaled quantum‐chemical calculation with the phonon confinement model to construct a universal and physically consistent basis for nanoscale Raman spectroscopy. Unlike the commonly assumed one‐dimensional approximation of phonon dispersion, we take into account the confinement along all the three dimensions of the k‐space. We apply it to diamond nanoparticles of sub‐50‐nm size, a system with pronounced anisotropy of dispersion for which consideration of three‐dimensional dispersion is a requisite. The model excellently reproduces size‐sensitive Raman spectral features, including the peak position, bandwidth, and asymmetry of the sp3 C–C stretch Raman line. This fundamental approach can be easily generalized to contribute the future development of quantitative nanoscale Raman spectroscopy. Copyright © 2017 John Wiley & Sons, Ltd.