bluuebunny/crossref_metadata_2025 huggingface dataset:
Organization of afferents to the orbitofrontal cortex in the rat
Authors: Murphy Monika J. M. , Deutch Ariel Y.
Published: March 2018

The prefrontal cortex (PFC) is usually defined as the frontal cortical area receiving a mediodorsal thalamic (MD) innervation. Certain areas in the medial wall of the rat frontal area receive a MD innervation. A second frontal area that is the target of MD projections is located dorsal to the rhinal sulcus and often referred to as the orbitofrontal cortex (OFC). Both the medial PFC and OFC are comprised of a large number of cytoarchitectonic regions. We assessed the afferent innervation of the different areas of the OFC, with a focus on projections arising from the mediodorsal thalamic nucleus, the basolateral nucleus of the amygdala, and the midbrain dopamine neurons. Although there are specific inputs to various OFC areas, a simplified organizational scheme could be defined, with the medial areas of the OFC receiving thalamic inputs, the lateral areas of the OFC being the recipient of amygdala afferents, and a central zone that was the target of midbrain dopamine neurons. Anterograde tracer data were consistent with this organization of afferents, and revealed that the OFC inputs from these three subcortical sites were largely spatially segregated. This spatial segregation suggests that the central portion of the OFC (pregenual agranular insular cortex) is the only OFC region that is a prefrontal cortical area, analogous to the prelimbic cortex in the medial prefrontal cortex. These findings highlight the heterogeneity of the OFC, and suggest possible functional attributes of the three different OFC areas.
Morphology of the utricular otolith organ in the toadfish, Opsanus tau
Authors: Boyle Richard , Ehsanian Reza , Mofrad Alireza , Popova Yekaterina , Varelas Joseph
Published: March 2018

The utricle provides the vestibular reflex pathways with the sensory codes of inertial acceleration of self‐motion and head orientation with respect to gravity to control balance and equilibrium. Here we present an anatomical description of this structure in the adult oyster toadfish and establish a morphological basis for interpretation of subsequent functional studies. Light, scanning, and transmission electron microscopy techniques were applied to visualize the sensory epithelium at varying levels of detail, its neural innervation and its synaptic organization. Scanning electron microscopy was used to visualize otolith mass and morphological polarization patterns of hair cells. Afferent nerve fibers were visualized following labeling with biocytin, and light microscope images were used to make three‐dimensional (3‐D) reconstructions of individual labeled afferents to identify dendritic morphology with respect to epithelial location. Transmission electron micrographs were compiled to create a serial 3‐D reconstruction of a labeled afferent over a segment of its dendritic field and to examine the cell‐afferent synaptic contacts. Major observations are: a well‐defined striola, medial and lateral extra‐striolar regions with a zonal organization of hair bundles; prominent lacinia projecting laterally; dependence of hair cell density on macular location; narrow afferent dendritic fields that follow the hair bundle polarization; synaptic specializations issued by afferents are typically directed towards a limited number of 7–13 hair cells, but larger dendritic fields in the medial extra‐striola can be associated with > 20 hair cells also; and hair cell synaptic bodies can be confined to only an individual afferent or can synapse upon several afferents.
Ni‐based Nanostructures as High‐performance Cathodes for Rechargeable Ni−Zn Battery
Authors: Zhang Haozhe , Wang Rui , Lin Dun , Zeng Yinxiang , Lu Xihong
Published: March 2018

Aqueous rechargeable Ni−Zn battery with high capacity, low cost, and reliable safety has stimulated extensive interests for their promising applications in electric vehicles and portable electronics. The electrochemical properties of electrodes mostly determine the performances of the whole batteries. Currently, the capacities of the most developed cathodes are still far away from that of commercial Zn anode (820 mAh g−1), which is the major barrier for further boosting the energy density of Ni−Zn battery. In recent years, various Ni based materials like α‐Ni(OH)2, β‐Ni(OH)2, NiO and NiCo2O4 have attracted considerable attention and been widely explored as cathode materials for Ni−Zn batteries. However, the poor conductivity and unsatisfactory cyclic stability of Ni‐based materials severely limit their implementation as robust cathodes for Ni−Zn batteries with high energy density and durability. To address these issues, substantial efforts have been made and great processes have been achieved. Herein, we highlight recent advances on rationally structural and componential design of Ni based electrodes for Ni−Zn batteries. The relationships between structures and performances as well as the mechanisms are also discussed. Finally, we present perspectives on the research of next‐generation electrodes with high electrochemical performances.
Risk factors associated with malignancy and with triage to surgery in thyroid nodules classified as Bethesda category IV (FN/SFN)
Authors: Kuru Bekir , Kefeli Mehmet
Published: March 2018

Background

Thyroid nodules diagnosed as Bethesda category IV [follicular neoplasm/suspicious for follicular neoplasm (FN/SFN)] are recommended for surgery. However, only 10%‐40% of these nodules turn out to be malignant on histopathological examination. Therefore, selection for surgery of nodules diagnosed as Bethesda category IV is important. We aimed to define predictive factors for malignancy and factors associated with triage to surgery.

Methods

The records of all patients with nodules who underwent fine needle aspiration biopsy (FNAB) and classified by Bethesda reporting system as FN/SFN between January 2011 and July 2017 at our institution were reviewed. Univariate and multivariate analysis were performed to select independent factors associated with thyroid cancer, and with triage to surgery. Using independent risk factors for malignancy predictive index categories were created.

Results

Among 6910 nodules that underwent FNAB, 180 (2.6%) were diagnosed as FN/SFN. Of the 180 patients, 139 (77%) underwent surgery with the associated malignancy rate of 37% (51/139) (upper boundary). Risk of malignancy among all FN/SFN nodules was 28% (lower boundary). Solid structure, size ≥ 4 cm, microcalcification, hypoechogenicity, and increased vascularization were found to be significant and independent risk factors associated for malignancy. None of the clinical and ultrasound factors were associated with triage to surgery.

Conclusions

Our findings showed that using predictive factors for malignancy in the Bethesda IV category as risk indices, 17% of patients who had nodules without any risk factors could be spared surgery. Predictive indices could be considered for the malignancy risk and for selection of patients for surgery.
Serum calcitonin negative mixed medullary‐follicular carcinoma initially diagnosed as medullary thyroid carcinoma by fine‐needle aspiration cytology: A case report and review of the literatures
Authors: Liu Yonghua , Yuan Lin , Yang Daohua , Jin Yubiao
Published: March 2018

Medullary thyroid carcinoma (MTC) is potentially lethal. A prompt and accurate diagnosis is the prerequisite for the treatment of MTC. Fine‐needle aspiration (FNA) is a reliable diagnostic tool in the assessment of thyroid nodules. However, cytologic assessment of MTC based on FNA has several drawbacks due to morphological variants. We present a case of MTC diagnosed through FNA cytology, which was eventually histologically confirmed as a mixed medullary‐follicular carcinoma with negative serum calcitonin expression. Hence, diagnosis of MTC based on FNA should be applied with caution. Ultrasound characteristics of suspicious thyroid nodules are recommended to be evaluated by FNA. However, calcitonin levels should be measured in both the FNA washout fluid and serum when features of MTC are presented or cytology result is inconclusive. If adequate FNA sample is available, a supplementary immunocytochemical staining of markers such as calcitonin, chromogranin, carcinoembryonic antigen, and thyroglobulin is helpful for a correct diagnosis of MTC.
Drug‐facilitated sexual assault (DFSA) involving 4‐methylethcathinone (4‐MEC), 3,4‐Methylenedioxypyrovalerone (MDPV), and doxylamine highlighted by hair analysis
Authors: Larabi Islam Amine , Martin Marie , Etting Isabelle , Penot Pauline , Fabresse Nicolas , Alvarez Jean Claude
Published: March 2018

Recently, the emergence of new psychoactive substances (NPS) has led to their wide use among clubbers and men who have sex with men (MSM) for their stimulant effects. However, their use in drug‐facilitated sexual assault (DFSA) has rarely been described. Herein we report a case of a 44‐year‐old man who was assaulted after a party. Due to late reporting of the offense, only hair (black) was sampled 15 days later and a segmental analysis was achieved to look for most DFSA agents and NPS. Twenty mg of each segment (A: 0–1 cm, B: 1–3 cm, and C: 3–5 cm) were incubated in phosphate buffer pH 5.0. After alkaline liquid extraction and chromatographic separation on 1.9 μm Hypersil GOLD PFP column, compounds were detected by a TSQ Vantage mass spectrometer with electrospray ionization in positive mode with multiple reaction monitoring (MRM) acquisition. 4‐methylethcathinone (4‐MEC), methylenedioxypyrovalerone (MDPV) and doxylamine were found in proximal segment at very low concentrations (3, 5, and 9 pg/mg, respectively) which is in agreement with a single exposure in the previous month corresponding to the alleged facts. These substances were not detected in segments B and C showing a lack of repetitive exposure before the alleged event. Thus, the results do not contradict the patient's claim of being assaulted. Doxylamine has already been encountered in such cases but no publications referring to 4‐MEC or MDPV use have ever been documented. Our case reports the unusual administration of cathinones to achieve a sexual assault and stresses the interest of looking for designer drugs when dealing with DFSA cases.
Development and validation of a liquid chromatography–tandem mass spectrometry method for the determination of nicotine and its metabolites in placenta and umbilical cord
Authors: Paniagua‐González Lucía , Jiménez‐Morigosa Cristian , Lendoiro Elena , Concheiro Marta , Cruz Angelines , López‐Rivadulla Manuel , de Castro Ana
Published: March 2018

Tobacco exposure during pregnancy is associated with obstetric and fetal complications. We developed and validated a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method to determine nicotine, cotinine, and hydroxycotinine (OH‐cotinine) in placenta (PL) and umbilical cord (UC). Specimens were homogenized in water, followed by solid‐phase extraction. Chromatographic separation was performed using an Atlantis® HILIC Silica column. Detection was accomplished in electrospray in positive mode. Method validation included: linearity (5 to 1000 ng/g), accuracy (86.9 to 105.2% of target concentration in PL, and 89.1 to 105.0% in UC), imprecision (6.8 to 11.8% in PL, and 7.6 to 12.2% in UC), limits of detection (2 ng/g for cotinine and OH‐cotinine, and 5 ng/g for nicotine) and quantification (5 ng/g), selectivity (no endogenous or exogenous interferences), matrix effect (−34.1 to −84.5% in PL, %CV = 9.1–24.0%; −18.9 to −84.7% in UC, %CV = 10.2–23.9%), extraction efficiency (60.7 to 131.5% in PL, and 64.1 to 134.2% in UC), and stability 72 h in the autosampler (<11.5% loss in PL, and < 13% loss in UC). The method was applied to 14 PL and UC specimens from tobacco users during pregnancy. Cotinine (6.8–312.2 ng/g in PL; 6.7–342.3 ng/g in UC) was the predominant analyte, followed by OH‐cotinine (<LOQ‐80.2 ng/g in PL; <LOQ‐80.5 ng/g in UC) and nicotine (5.7–63.7 ng/g in PL; 5.1–63.3 ng/g in UC). This method will be applied to more than 150 specimens collected from a wide clinical study to evaluate the usefulness of maternal hair, meconium, placenta and umbilical cord compared to the maternal interview to detect in utero drug exposure.
Comparative transcriptional profiling analysis of the effect of heat waves during embryo incubation on the hatchlings of the Chinese soft‐shelled turtle (Pelodiscus sinensis)
Authors: Dang Wei , Lu Hongliang , Wu Qiong , Gao Yuan , Qi Qinqin , Fan Handong
Published: March 2018

Temperature is one of most the important environmental factors that affect the ontogenesis of organisms. In this study, we incubated Chinese soft‐shelled turtle eggs at 28°C (control temperature, C treatment), a temperature with a 16°C cold shock and a 36°C heat shock twice per week (S treatment) or a ramp‐programmed temperature of 29 ± 9°C (with 12 hr (+) and 12 hr (−) every day) (F treatment). The incubation period, hatching success, hatchling weight, and locomotor performance were significantly different between the controls and the different heat treatment groups. The pathogen challenge results illustrated that hatchlings from the S treatment group were more resistant to bacterial infection, whereas hatchlings from the F treatment group were more vulnerable. We used RNA‐seq quantification analysis to identify differentially expressed genes (DEGs) of hatchlings in the S treatment group. Based on the functional annotation results for the DEGs, 9 genes were chosen to verify the RNA‐seq results. The background expression of DEGs was also analyzed for the three treatments, as was the regulation of the pathogen challenge. The results showed that 8 DEGs were related to the immune response after pathogen challenge and that temperature was an important factor in differential regulation of the immunity pathways.
Integrated analysis of flow, form, and function for river management and design testing
Authors: Lane Belize A. , Pasternack Gregory B. , Sandoval Solis Samuel
Published: March 2018

The extent and timing of many river ecosystem functions is controlled by the interplay of streamflow dynamics with the river corridor shape and structure. However, most river management studies evaluate the role of either flow or form without regard to their dynamic interactions. This study develops an integrated modelling approach to assess changes in ecosystem functions resulting from different river flow and form configurations. Moreover, it investigates the role of temporal variability in such flow–form–function trade‐offs. The use of synthetic, archetypal channel forms in lieu of high‐resolution topographic data reduces time and financial requirements, overcomes site‐specific topographic features, and allows for evaluation of any morphological structure of interest. In an application to California's Mediterranean‐montane streams, the interacting roles of channel form, water year type, and hydrologic impairment were evaluated across a suite of ecosystem functions related to hydrogeomorphic processes and aquatic habitat. Channel form acted as the dominant control on hydrogeomorphic processes, whereas water year type controlled salmonid habitat functions. Streamflow alteration for hydropower increased redd dewatering risk and altered aquatic habitat availability. Study results highlight critical trade‐offs in ecosystem function performance and emphasize the significance of spatio‐temporal diversity of flow and form at multiple scales for maintaining river ecosystem integrity. The proposed approach is broadly applicable and extensible to other systems and ecosystem functions, where findings can be used to inform river management and design testing.
Pulmonary artery hypertension following coronary artery bypass grafting: a case report
Authors: Robinson Renana , Weinstein Jean Marc , Cafri Carlos , Avriel Avital
Published: March 2018

Post‐operative pulmonary complications in coronary artery bypass grafting (CABG) surgery are mostly reversible. We report a patient who developed pulmonary arterial hypertension (PAH) post‐CABG and did not have pulmonary hypertension prior to surgery. PAH Group 1 was diagnosed after right and left heart catheterization. To the best of our knowledge, this is the only reported case of a patient developing PAH post‐CABG surgery. This could be explained by immunological and/or haemostatic changes triggered by cardiopulmonary bypass. We hope that as more knowledge is gained regarding the pathophysiology of PAH, cases like these could be better understood.
NCR+ ILC3 maintain larger STAT4 reservoir via T‐BET to regulate type 1 features upon IL‐23 stimulation in mice
Authors: Mikami Yohei , Scarno Gianluca , Zitti Beatrice , Shih Han‐Yu , Kanno Yuka , Santoni Angela , O'Shea John J , Sciumè Giuseppe
Published: March 2018

Innate lymphoid cells (ILCs) producing IL‐22 and/or IL‐17, designated as ILC3, comprise a heterogeneous subset of cells involved in regulation of gut barrier homeostasis and inflammation. Exogenous environmental cues in conjunction with regulated expression of endogenous factors are key determinants of plasticity of ILC3 toward the type 1 fate. Herein, by using mouse models and transcriptomic approaches, we defined at the molecular level, initial events driving ILC3 expressing natural cytotoxicity receptors (NCR+ ILC3) to acquire type 1 features. We observed that NCR+ ILC3 exhibited high basal expression of the signal‐dependent transcription factor STAT4 due to T‐BET, leading to predisposed potential for the type 1 response. We found that the prototypical inducer of type 3 response, IL‐23, played a predominant role over IL‐12 by accessing STAT4 and preferentially inducing its phosphorylation in ILC3 expressing T‐BET. The early effector program driven by IL‐23 was characterized by the expression of IL‐22, followed by a production of IFN‐γ, which relies on STAT4, T‐BET and required chromatin remodeling of the Ifng locus. Altogether, our findings shed light on a feed‐forward mechanism involving STAT4 and T‐BET that modulates the outcome of IL‐23 signaling in ILC3.
Immobilization of an Aminobisphosphine–PdII Complex over Graphene Oxide: An Efficient and Reusable Catalyst for Suzuki–Miyaura, Ullmann Coupling and Cyanation Reactions
Authors: Sengupta Debasish , Pandey Madhusudan K. , Mondal Dipanjan , Radhakrishna Latchupatula , Balakrishna Maravanji S.
Published: March 2018

The grafting of an aminobis(phosphine)–PdII complex (PNP–PdII) [PdCl2{(Ph2P)2N(CH2)3Si(OMe)3}] (2) on graphene oxide (GO) has been carried out by a condensation reaction between methoxysilane groups of 2 and hydroxyl groups of GO. The composite material was characterized by FTIR spectroscopy , solid‐state 31P NMR spectroscopy, SEM, TEM, XPS and ICP‐AES techniques. All these tools support the clean immobilization of compound 2 on GO. The composite material showed high catalytic activity in Suzuki–Miyaura, Ullmann coupling and cyanation reactions. The heterogeneity of the composite was confirmed by a hot filtration test. The immobilized PNP–PdII shows comparable activity to its homogeneous analogue 2. The recycling ability of the catalyst was examined for five consecutive runs, which showed little or no reduction in its catalytic efficiency.
Lewis Base Promoted Reduction of CO2 with BH3NH3 into Boryl Formates: CO2 as a Carbon Source in Organic Synthesis Under Mild Conditions
Authors: Zhang Bo , Du Gaixia , Hang Wei , Wang Sheng , Xi Chanjuan
Published: March 2018

Lewis base promoted selective reduction of CO2 into boryl formates by using BH3NH3 as a reductant under mild conditions has been reported. The boryl formates, generated in situ, were shown to be reactive and versatile sources of formyl compounds to create new C–N, C–O, and C–C bonds. The reactivity of the boryl formates to yield formic acid, formamides, formates, secondary alcohols, and benzoheterocyclic rings was investigated.
Recent remote sensing applications for hydro and morphodynamic monitoring and modelling
Authors: Entwistle Neil , Heritage George , Milan David
Published: March 2018

It is not new to recognize that data from remote sensing platforms is transforming the way we characterize and analyse our environment. The ability to collect continuous data spanning spatial scales now allows geomorphological research in a data rich environment and this special issue [coming just eight years after the 2010 special issue of Earth Surface Processes and Landforms (ESPL) associated with the remote sensing of rivers] highlights the considerable research effort being made to exploit this information, for studies of geomorphic form and process. The 2010 special issue on the remote sensing of rivers noted that fluvial remote sensing articles made up some 14% of the total river related articles in ESPL. A similar review of articles up to 2017 reveals that this figure has increased to around 25% with a recent proliferation of articles utilizing satellite‐based data and structure from motion photogrammetry derived data. It is interesting to note, however that many studies published to date are proof of concept, concentrating on confirming the accuracy of the remotely sensed data at the expense of generating new insights and ideas on fluvial form and function. Data is becoming ever more precise and researchers should now be concentrating on analysing these early data sets to develop increased geomorphic insight, to challenge existing paradigms and to advance geomorphic science. The prospect of this occurring is increased by the fact that many of the new remote sensed platforms allow accurate spatial data to be collected cheaply and efficiently, reducing the need for substantial research funding to advance river science. Fluvial geomorphologists have never before been in such a liberated position. As techniques and analytical skills continue to improve it is inevitable that the prediction that remotely sensed data will revolutionize our understanding of geomorphological form and process will prove true, altering our ideas on the very nature of system functioning in the process. © 2018 The Authors. Earth Surface Processes and Landforms published by John Wiley & Sons Ltd.
Toward improving photosynthesis in cassava: Characterizing photosynthetic limitations in four current African cultivars
Authors: De Souza Amanda P. , Long Stephen P.
Published: March 2018

Despite the vast importance of cassava (Manihot esculenta Crantz) for smallholder farmers in Africa, yields per unit land area have not increased over the past 55 years. Genetic engineering or breeding for increased photosynthetic efficiency may represent a new approach. This requires the understanding of limitations to photosynthesis within existing germplasm. Here, leaf photosynthetic gas exchange, leaf carbon and nitrogen content, and nonstructural carbohydrates content and growth were analyzed in four high‐yielding and farm‐preferred African cultivars: two landraces (TME 7, TME 419) and two improved lines (TMS 98/0581 and TMS 30572). Surprisingly, the two landraces had, on average, 18% higher light‐saturating leaf CO2 uptake (Asat) than the improved lines due to higher maximum apparent carboxylation rates of Rubisco carboxylation (Vcmax) and regeneration of ribulose‐1,5‐biphosphate expressed as electron transport rate (Jmax). TME 419 also showed a greater intrinsic water use efficiency. Except for the cultivar TMS 30572, photosynthesis in cassava showed a triose phosphate utilization (TPU) limitation at high intercellular [CO2]. The capacity for TPU in the leaf would not limit photosynthesis rates under current conditions, but without modification would be a barrier to increasing photosynthetic efficiency to levels predicted possible in this crop. The lower capacity of the lines improved through breeding, may perhaps reflect the predominant need, until now, in cassava breeding for improved disease and pest resistance. However, the availability today of equipment for high‐throughput screening of photosynthetic capacity provides a means to select for maintenance or improvement of photosynthetic capacity while also selecting for pest and disease resistance.
Guava leaf extract suppresses osteoarthritis progression in a rat anterior cruciate ligament transection model
Authors: Kawasaki Keiko , Fushimi Takashi , Nakamura Junji , Ota Noriyasu
Published: March 2018

Guava leaf extract and ellagic acid, one of its polyphenolic components, inhibit the activity of a disintegrin and metalloproteinase with thrombospondin type 5 (ADAMTS‐5), which is associated with aggrecan degeneration during the early stage of osteoarthritis (OA). To investigate the efficacy of guava leaf extract for preventing OA, we examined the effect of its dietary intake on cartilage destruction in anterior cruciate ligament‐transected (ACLT) rats. Rats were randomly assigned to four groups: ACLT control rats fed with control diet, ACLT rats fed with diet containing 0.2% guava leaf extract, ACLT rats fed with diet containing 0.5% guava leaf extract, and sham‐operated rats fed with control diet. Mankin's scores, an index of cartilage damage, were higher in rats that underwent ACLT. Guava leaf extract treatment dose‐dependently led to lower Mankin's scores and higher concentrations of ellagic acid in the serum and synovial membrane. Ellagic acid levels in the synovial membrane negatively correlated with cartilage destruction scores. These results suggest that dietary guava leaf extract suppresses OA progression in ACLT rats through ellagic acid‐mediated inhibition of early joint destruction.
Information properties of morphologically complex words modulate brain activity during word reading
Authors: Hakala Tero , Hultén Annika , Lehtonen Minna , Lagus Krista , Salmelin Riitta
Published: March 2018

Neuroimaging studies of the reading process point to functionally distinct stages in word recognition. Yet, current understanding of the operations linked to those various stages is mainly descriptive in nature. Approaches developed in the field of computational linguistics may offer a more quantitative approach for understanding brain dynamics. Our aim was to evaluate whether a statistical model of morphology, with well‐defined computational principles, can capture the neural dynamics of reading, using the concept of surprisal from information theory as the common measure. The Morfessor model, created for unsupervised discovery of morphemes, is based on the minimum description length principle and attempts to find optimal units of representation for complex words. In a word recognition task, we correlated brain responses to word surprisal values derived from Morfessor and from other psycholinguistic variables that have been linked with various levels of linguistic abstraction. The magnetoencephalography data analysis focused on spatially, temporally and functionally distinct components of cortical activation observed in reading tasks. The early occipital and occipito‐temporal responses were correlated with parameters relating to visual complexity and orthographic properties, whereas the later bilateral superior temporal activation was correlated with whole‐word based and morphological models. The results show that the word processing costs estimated by the statistical Morfessor model are relevant for brain dynamics of reading during late processing stages.
Age‐related changes in the ease of dynamical transitions in human brain activity
Authors: Ezaki Takahiro , Sakaki Michiko , Watanabe Takamitsu , Masuda Naoki
Published: March 2018

Executive functions, a set of cognitive processes that enable flexible behavioral control, are known to decay with aging. Because such complex mental functions are considered to rely on the dynamic coordination of functionally different neural systems, the age‐related decline in executive functions should be underpinned by alteration of large‐scale neural dynamics. However, the effects of age on brain dynamics have not been firmly formulated. Here, we investigate such age‐related changes in brain dynamics by applying “energy landscape analysis” to publicly available functional magnetic resonance imaging data from healthy younger and older human adults. We quantified the ease of dynamical transitions between different major patterns of brain activity, and estimated it for the default mode network (DMN) and the cingulo‐opercular network (CON) separately. We found that the two age groups shared qualitatively the same trajectories of brain dynamics in both the DMN and CON. However, in both of networks, the ease of transitions was significantly smaller in the older than the younger group. Moreover, the ease of transitions was associated with the performance in executive function tasks in a doubly dissociated manner: for the younger adults, the ability of executive functions was mainly correlated with the ease of transitions in the CON, whereas that for the older adults was specifically associated with the ease of transitions in the DMN. These results provide direct biological evidence for age‐related changes in macroscopic brain dynamics and suggest that such neural dynamics play key roles when individuals carry out cognitively demanding tasks.
Major prognostic factors for recurrence and survival independent of the American Joint Committee on Cancer eighth edition staging system in patients with cutaneous squamous cell carcinoma treated with multimodality therapy
Authors: Xu Melody J. , Lazar Ann A. , Garsa Adam A. , Arron Sarah T. , Ryan William R. , El‐Sayed Ivan H. , George Jonathan R. , Algazi Alain P. , Heaton Chase M. , Ha Patrick K. , Yom Sue S.
Published: March 2018

Background

The purpose of this study was to assess changes resulting from the American Joint Committee on Cancer (AJCC) eighth edition for cutaneous squamous cell carcinoma (SCC) and evaluate pertinent excluded factors.

Methods

In 101 patients receiving surgery and postoperative radiation, recurrence and survival were estimated by cumulative incidence and Kaplan‐Meier method. Time‐to‐event analysis was performed using Cox proportional hazards and Fine‐Gray competing risks regression models.

Results

The 2‐year locoregional recurrence, overall survival (OS), and cause‐specific mortality rates were 25%, 72%, and 13%, respectively. The AJCC eighth edition upstaged T classification in 50% of patients and overall stage in 39%. In multivariate analysis, immunosuppression and in‐transit metastasis were associated with locoregional recurrence. Older age and in‐transit metastasis were associated with worse OS. In univariate analysis (limited by number of events), cause‐specific mortality was associated with positive margin, in‐transit metastasis, and the seventh edition dichotomized T classification and overall stage.

Conclusion

In‐transit metastasis was significantly associated with locoregional recurrence, OS, and cause‐specific mortality. Efforts should be made to define in‐transit metastasis in the staging system.
Loss of FFAR2 promotes colon cancer by epigenetic dysregulation of inflammation suppressors
Authors: Pan Pan , Oshima Kiyoko , Huang Yi‐Wen , Agle Kimberle A. , Drobyski William R. , Chen Xiao , Zhang Jianying , Yearsley Martha M. , Yu Jianhua , Wang Li‐Shu
Published: March 2018

Free fatty acid receptor 2 (FFAR2, also named GPR43), is activated by short‐chain fatty acids (SCFAs), such as butyrate, that are produced when gut bacteria ferment dietary fiber. FFAR2 has been suggested to regulate colonic inflammation, which is a major risk factor for the development of colon cancer and is also linked to epigenetic dysregulation in colon carcinogenesis. The current study assessed whether FFAR2, acting as an epigenetic regulator, protects against colon carcinogenesis. To mimic the mild inflammation that promotes human colon cancer, we treated mice with dextran sodium sulfate (DSS) overnight, which avoids excessive inflammation but induces mild inflammation that promotes colon carcinogenesis in the ApcMin/+ and the azoxymethane (AOM)‐treated mice. Our results showed that FFAR2 deficiency promotes the development of colon adenoma in the ApcMin/+/DSS mice and the progression of adenoma to adenocarcinoma in the AOM/DSS mice. FFAR2's downstream cAMP–PKA–CREB pathway was enhanced, leading to overexpression of histone deacetylases (HDACs) in the FFAR2‐deficient mice. ChIP‐qPCR analysis revealed differential binding of H3K27me3 and H3K4me3 histone marks onto the promoter regions of inflammation suppressors (e.g., sfrp1, dkk3, socs1), resulting in decreased expression of these genes in the FFAR2‐deficient mice. Also, more neutrophils infiltrated into tumors and colon lamina propria of the FFAR2‐deficient mice. Depletion of neutrophils blocked the progression of colon tumors. In addition, FFAR2 is required for butyrate to suppress HDAC expression and hypermethylation of inflammation suppressors. Therefore, our results suggest that FFAR2 is an epigenetic tumor suppressor that acts at multiple stages of colon carcinogenesis.
Lifetime and baseline alcohol intakes and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition study
Authors: Naudin Sabine , Li Kuanrong , Jaouen Tristan , Assi Nada , Kyrø Cecilie , Tjønneland Anne , Overvad Kim , Boutron‐Ruault Marie‐Christine , Rebours Vinciane , Védié Anne‐Laure , Boeing Heiner , Kaaks Rudolf , Katzke Verena , Bamia Christina , Naska Androniki , Trichopoulou Antonia , Berrino Franco , Tagliabue Giovanna , Palli Domenico , Panico Salvatore , Tumino Rosario , Sacerdote Carlotta , Peeters Petra H. , Bueno‐de‐Mesquita H. B(as) , Weiderpass Elisabete , Gram Inger Torhild , Skeie Guri , Chirlaque Maria‐Dolores , Rodríguez‐Barranco Miguel , Barricarte Aurelio , Quirós Jose Ramón , Dorronsoro Miren , Johansson Ingegerd , Sund Malin , Sternby Hanna , Bradbury Kathryn E. , Wareham Nick , Riboli Elio , Gunter Marc , Brennan Paul , Duell Eric J. , Ferrari Pietro
Published: March 2018

Recent evidence suggested a weak relationship between alcohol consumption and pancreatic cancer (PC) risk. In our study, the association between lifetime and baseline alcohol intakes and the risk of PC was evaluated, including the type of alcoholic beverages and potential interaction with smoking. Within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1,283 incident PC (57% women) were diagnosed from 476,106 cancer‐free participants, followed up for 14 years. Amounts of lifetime and baseline alcohol were estimated through lifestyle and dietary questionnaires, respectively. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and their 95% confidence interval (CI). Alcohol intake was positively associated with PC risk in men. Associations were mainly driven by extreme alcohol levels, with HRs comparing heavy drinkers (>60 g/day) to the reference category (0.1–4.9 g/day) equal to 1.77 (95% CI: 1.06, 2.95) and 1.63 (95% CI: 1.16, 2.29) for lifetime and baseline alcohol, respectively. Baseline alcohol intakes from beer (>40 g/day) and spirits/liquors (>10 g/day) showed HRs equal to 1.58 (95% CI: 1.07, 2.34) and 1.41 (95% CI: 1.03, 1.94), respectively, compared to the reference category (0.1–2.9 g/day). In women, HR estimates did not reach statistically significance. The alcohol and PC risk association was not modified by smoking status. Findings from a large prospective study suggest that baseline and lifetime alcohol intakes were positively associated with PC risk, with more apparent risk estimates for beer and spirits/liquors than wine intake.
MRI background parenchymal enhancement, breast density and serum hormones in postmenopausal women
Authors: Brooks Jennifer D. , Sung Janice S. , Pike Malcolm C. , Orlow Irene , Stanczyk Frank Z. , Bernstein Jonine L. , Morris Elizabeth A.
Published: March 2018

Background parenchymal enhancement (BPE) is the degree to which normal breast tissue enhances on contrast‐enhanced magnetic resonance imaging (MRI). MRI‐density is a volumetric measure of breast density that is highly correlated with mammographic density, an established breast cancer risk factor. Endogenous estrogen concentrations are positively associated with postmenopausal breast cancer risk and BPE has been shown to be sensitive to hormonal exposures. The objective of our study was to examine the relationship between BPE and MRI‐density and serum hormone concentrations in postmenopausal women. This was a study of cancer‐free postmenopausal women undergoing contrast‐enhanced breast MRI (N = 118). At the time of MRI all women completed a self‐administered questionnaire and blood samples were collected for hormone analyses. Serum concentrations of estrone (E1), estradiol (E2) and bioavailable E2 were examined by category of BPE and MRI‐density. Compared to women with “minimal” BPE, those who had “marked” BPE had significantly higher serum concentrations of E1, E2 and bioavailable E2 (90% increase,ptrendacross all categories = 0.001; 150% increase,ptrend = 0.001; and 158% increase,ptrend = 0.001, respectively). These associations were only affected to a minor extent by adjustment for BMI and other variables. After adjustment for BMI, no significant associations between MRI‐density and serum E1, E2 and bioavailable E2 were observed. Serum estrogen concentrations were significantly positively associated with BPE. Our study provides further evidence of the hormone‐sensitive nature of BPE, indicating a potential role for BPE as an imaging marker of endogenous and exogenous hormonal exposures in the breast.
Indications for and outcomes of therapeutic plasma exchange after cardiac transplantation: A single center retrospective study
Authors: Onwuemene Oluwatoyosi A. , Grambow Steven C. , Patel Chetan B. , Mentz Robert J. , Milano Carmelo A. , Rogers Joseph G. , Metjian Ara D. , Arepally Gowthami M. , Ortel Thomas L.
Published: March 2018

Introduction

Limited data are available describing indications for and outcomes of therapeutic plasma exchange (TPE) in cardiac transplantation.

Methods

In a retrospective study of patients who underwent cardiac transplantation at Duke University Medical Center from 2010 to 2014, we reviewed 3 TPE treatment patterns: a Single TPE procedure within 24 h of transplant; Multiple TPE procedures initiated within 24 h of transplant; and 1 or more TPE procedures beginning >24 h post‐transplant. Primary and secondary outcomes were overall survival (OS) and TPE survival (TS), respectively.

Results

Of 313 patients meeting study criteria, 109 (35%) underwent TPE. TPE was initiated in 82 patients within 24 h, 40 (37%) receiving a single procedure (Single TPE), and 42 (38%) multiple procedures (Multiple TPE). Twenty‐seven (25%) began TPE >24 h after transplant (Delayed TPE). The most common TPE indication was elevated/positive panel reactive or human leukocyte antigen antibodies (32%). With a median follow‐up of 49 months, the non‐TPE treated and Single TPE cohorts had similar OS (HR 1.08 [CI, 0.54, 2.14], P = .84), while the Multiple and Delayed TPE cohorts had worse OS (HR 2.62 [CI, 1.53, 4.49] and HR 1.98 [CI, 1.02, 3.83], respectively). The Multiple and Delayed TPE cohorts also had worse TS (HR 2.59 [CI, 1.31, 5.14] and HR 3.18 [CI, 1.56, 6.50], respectively). Infection rates did not differ between groups but was independently associated with OS (HR 2.31 [CI, 1.50, 3.54]).

Conclusions

TPE is an important therapeutic modality in cardiac transplant patients. Prospective studies are needed to better define TPE's different roles in this patient population.
Oxidation‐assisted structural elucidation of compounds containing a tertiary amine side chain using liquid chromatography mass spectrometry
Authors: Shamai Yamin Tamar , Prihed Hagit , Shifrovitch Avital , Dagan Shai , Weissberg Avi
Published: March 2018

A novel analytical technique for the structural elucidation of compounds bearing a tertiary amine side chain via “in vial” instantaneous oxidation and liquid chromatography mass spectrometry (LC‐MS) was developed. A series of lidocaine homologs and benzimidazole derivatives with a major/single amine representative base peak in both their EI‐MS and ESI‐MS/MS spectra were subjected to oxidation by a 0.1% solution of hydrogen peroxide (including several 16O/18O exchange experiments), followed by LC‐ESI‐MS/MS analysis. The N‐oxide counterparts promoted extensive fragmentation with complete coverage of all parts of the molecule, enabling detailed structural elucidation and unambiguous identification of the unoxidized analytes at low nanogram per milliliter levels.
MALDI‐MS argininyl bufadienolide esters fingerprint from parotoid gland secretions of Rhinella arenarum: Age, gender, and seasonal variation
Authors: Petroselli Gabriela , Raices Marilina , Jungblut Lucas D. , Pozzi Andrea G. , Erra‐Balsells Rosa
Published: March 2018

In many amphibians, the granular glands can be grouped in special regions forming macroglands. This is the case of toads, characterized by the presence of a pair of parotoid macroglands, strategically located to give protection by poison release in case of attacks. The product secreted consists of a wide variety of chemical compounds including proteins, peptides, biogenic amines, toxic steroidal bufadienolides, and various alkaloids, depending on the species. In this work, using Rhinella arenarum, we have performed, for the first time, the matrix assisted‐ultraviolet laser desorption/ionization mass spectrometry and tandem mass spectrometry characterization of the components of the secretion used as crude material, just suspended in MeOH (or MeCN). The crude sample as a whole (whole suspension) was spotted on the matrix assisted‐ultraviolet laser desorption plate for analysis. Electrospray ionization‐Orbitrap was used for cross‐checking experiments. The pattern of signals obtained at m/z ranges 600 to 800 and 1200 to 1600 could be assigned as the argininyl bufadienolide esters fingerprint characteristic of female and male. Variation patterns for gender (female, male), age (non‐reproductive, reproductive), and season (non‐reproductive, reproductive) are described.
Evaluation of ionic liquids supported on silica as a sorbent for fully automated online solid‐phase extraction with LC–MS determination of sulfonamides in bovine milk samples
Authors: da Silva Meire Ribeiro , Mauro Lanças Fernando
Published: March 2018

Sulfonamides are antibiotics widely used in the treatment of diseases in dairy cattle. However, their indiscriminate use for disease control may lead to their presence in tissues and milk and their determination requires a sample preparation step as part of an analytical approach. Among the several sample preparation techniques available, those based upon the use of sorptive materials have been widely employed. Recently, the application of ionic liquids immobilized on silica surfaces or polymeric materials has been evaluated for such an application. This manuscript addresses the evaluation of silica‐based ionic liquid obtained by a sol–gel synthesis process by basic catalysis as sorbent for online solid‐phase extraction with liquid chromatography and electrospray ionization time‐of‐flight mass spectrometry for sulfonamides determination. Infrared vibrational spectroscopy confirmed the presence of the ionic liquid on the silica surface, suggesting that the ionic liquid was anchored on to the silica surface. Other sorbents varying the ionic liquid alkyl chain were also synthesized and evaluated by off‐line solid‐phase extraction in the sulfonamide extraction. As the length of the alkyl chain increased, the amount of extracted sulfonamides decreased, possibly due to a decrease in the electrostatic interaction caused by the reduction in the polarity, as well as the presence of a hexafluorophosphate anion that increases the hydrophobic character of the material. The use of 1‐butyl‐3‐methylimidazolium hexafluorophosphate as a selective ionic liquid sorbent enabled the isolation and sulfonamide preconcentration in bovine milk by online solid‐phase extraction with liquid chromatography and electrospray ionization time‐of‐flight mass spectrometry. The limit of quantification for the method developed was 5–7, 5 μg/mL, with extraction recoveries ranging between 74 and 93% and intra‐ and interassay between 1.5–12.5 and 2.3–13.1, respectively.
CAAT/enhancer binding protein–homologous protein deficiency attenuates liver ischemia/reperfusion injury in mice
Authors: Wada Seidai , Hatano Etsuro , Yoh Tomoaki , Nakamura Naohiko , Okuda Yukihiro , Okuno Masayuki , Kasai Yosuke , Iwaisako Keiko , Seo Satoru , Taura Kojiro , Uemoto Shinji
Published: March 2018

Ischemia/reperfusion injury (IRI) is one of the main causes of liver dysfunction after liver surgery. Involvement of endoplasmic reticulum (ER) stress in various diseases has been demonstrated, and CAAT/enhancer binding protein–homologous protein (CHOP) is a transcriptional regulator that is induced by ER stress. It is also a key regulator of ER stress‐mediated apoptosis. The aim of this study was to investigate the role of CHOP in liver IRI. Wild type (WT) and CAAT/enhancer binding protein–homologous protein knockout (CHOP–/–) mice were subjected to 70% liver warm ischemia/reperfusion for 60 minutes. At different times after reperfusion, liver tissues and blood samples were collected for evaluation. Induction of ER stress including CHOP expression was ascertained. Liver damage was evaluated based on serum liver enzymes, liver histology, and neutrophil infiltration. Hepatocyte death including apoptosis was assessed. Liver warm IRI induced ER stress in both WT and CHOP–/– mice. In addition, CHOP expression was up‐regulated in WT mice. At 6 hours after reperfusion, liver damage was attenuated in CHOP–/– mice. On the basis of terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick‐end labeling staining, apoptotic and necrotic cells were significantly reduced in CHOP–/– mice. CHOP deficiency also reduced the cleavage of caspase 3 and expression of the proapoptotic protein B cell lymphoma 2–associated X protein. Liver IRI induces CHOP expression, and CHOP deficiency attenuates liver IRI by inhibiting apoptosis. Elucidation of the function of CHOP in liver IRI may contribute to further investigation for a therapy against liver IRI associated with the ER stress pathway. Liver Transplantation 24 645–654 2018 AASLD.
Comparison of MEMS switches and PIN diodes for switched dual tuned RF coils
Authors: Maunder Adam , Rao Madhwesha , Robb Fraser , Wild Jim M.
Published: March 2018

Purpose

To evaluate the performance of micro‐electromechanical systems (MEMS) switches against PIN diodes for switching a dual‐tuned RF coil between 19F and 1H resonant frequencies for multi‐nuclear lung imaging.

Methods

A four‐element fixed‐phase and amplitude transmit–receive RF coil was constructed to provide homogeneous excitation across the lungs, and to serve as a test system for various switching methods. The MR imaging and RF performance of the coil when switched between the 19F and 1H frequencies using MEMS switches, PIN diodes and hardwired configurations were compared.

Results

The performance of the coil with MEMS or PIN diode switching was comparable in terms of RF measurements, transmit efficiency and image SNR on both 19F and 1H nuclei. When the coil was not switched to the resonance frequency of the respective nucleus being imaged, reductions in the transmit efficiency were observed of 32% at the 19F frequency and 12% at the 1H frequency. The coil provides transmit field homogeneity of ±12.9% at the 1H frequency and ±14.4% at the 19F frequency in phantoms representing the thorax with the air space of the lungs filled with perfluoropropane gas.

Conclusion

MEMS and PIN diodes were found to provide comparable performance in on‐state configuration, while MEMS were more robust in off‐state high‐powered operation (>1 kW), providing higher isolation and requiring a lower DC switching voltage than is needed for reverse biasing of PIN diodes. In addition, clear benefits of switching between the 19F and 1H resonances were demonstrated, despite the proximity of their Larmor frequencies.