bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical features of SMARCA2 duplication overlap with Coffin–Siris syndrome
Authors: Miyake Noriko , Abdel‐Salam Ghada , Yamagata Takanori , Eid Maha M. , Osaka Hitoshi , Okamoto Nobuhiko , Mohamed Amal M. , Ikeda Takahiro , Afifi Hanan H. , Piard Juliette , van Maldergem Lionel , Mizuguchi Takeshi , Miyatake Satoko , Tsurusaki Yoshinori , Matsumoto Naomichi
Published: June 2016

Coffin–Siris syndrome is a rare congenital malformation and intellectual disability syndrome. Mutations in at least seven genes have been identified. Here, we performed copy number analysis in 37 patients with features of CSS in whom no causative mutations were identified by exome sequencing. We identified a patient with a 9p24.3–p22.2 duplication and another patient with the chromosome der(6)t(6;9)(p25;p21)mat. Both patients share a duplicated 15.8‐Mb region containing 46 protein coding genes, including SMARCA2. Dominant negative effects of SMARCA2 mutations may contribute to Nicolaides–Baraitser syndrome. We conclude that their features better resemble Coffin–Siris syndrome, rather than Nicolaides–Baraitser syndrome and that these features likely arise from SMARCA2 over‐dosage. Pure 9p duplications (not caused by unbalanced translocations) are rare. Copy number analysis in patients with features that overlap with Coffin–Siris syndrome is recommended to further determine their genetic aspects. © 2016 Wiley Periodicals, Inc.
Association of IgG4‐Related Disease With History of Malignancy
Authors: Wallace Zachary S. , Wallace Carly J. , Lu Na , Choi Hyon K. , Stone John H.
Published: June 2016

Objective

IgG4‐related disease (IgG4‐RD) is a fibroinflammatory disease of unclear etiology. Some studies suggest that IgG4‐RD predisposes patients to malignancy or is a forme fruste of cancer, but we have frequently observed IgG4‐RD patients who have a history of malignancy preceding the clinical onset of IgG4‐RD. This study was undertaken to characterize IgG4‐RD in the setting of previous malignancy diagnosis.

Methods

We identified IgG4‐RD patients with a history of invasive malignancy from a well‐defined cohort of 125 patients and compared their malignancy history to those of 2 reference groups. First, we calculated a standardized prevalence ratio against general US population estimates from the Surveillance, Epidemiology, and End Results (SEER) database. Second, we identified up to 5 age‐ and sex‐matched controls for each case and calculated the odds of malignancy among those with IgG4‐RD compared to controls, using conditional logistic regression.

Results

The mean ± SD age at IgG4‐RD onset was 50.3 ± 14.9 years, and 61% of the patients were male. Twenty (16%) had been diagnosed as having malignancies (total 21 malignancies) before the diagnosis of IgG4‐RD. The observed prevalence of malignancy in this cohort was 2.5 times higher (95% confidence interval [95% CI] 1.1–3.6) than expected compared to the SEER database. Compared to matched controls, the frequency of history of malignancy was >3‐fold higher in IgG4‐RD patients (95% CI 1.6–6.2).

Conclusion

Our findings suggest that, in a subset of patients with IgG4‐RD, malignancy may be associated with subsequent IgG4‐RD development. Potential explanations include shared risk factors for both IgG4‐RD and cancer, the triggering by cancer of autoantigen expression leading to IgG4‐RD, and an increased risk of IgG4‐RD resulting from cancer treatment.
Brief Report: Management of Chronic Post‐Chikungunya Rheumatic Disease: The Martinican Experience
Authors: Blettery Marie , Brunier Lauren , Polomat Kathleen , Moinet Florence , Deligny Christophe , Arfi Serge , Jean‐Baptiste Georges , De Bandt Michel
Published: June 2016

Objective

To describe chronic chikungunya manifestations seen during the outbreak in the Caribbean from December 2013 to January 2015.

Methods

Patients were seen at our center, the only rheumatology department in Martinique Island, and were examined by a senior rheumatologist using a standard care report form. Chikungunya was diagnosed collectively based on consensus among all clinicians. The median time from onset of acute chikungunya to the first rheumatology consultation was calculated, severity was evaluated based on clinical scales and the degree of joint destruction, and each patient's treatment was recorded.

Results

For the 147 patients analyzed, the median time between onset of acute chikungunya and the first rheumatology consultation was 8 months. After review of each patient's medical record, 19 (12.9%) were diagnosed as having epidemic‐influenced chikungunya. Four distinct rheumatologic patterns were observed in the remaining patients (those with compatible history and positive serologic findings): 47 patients (32%) had reactivation of painful chronic mechanical manifestations, 9 patients (6.1%) had fibromyalgia, 45 patients (30.6%) met criteria for spondyloarthritis (as evaluated before the chikungunya virus infection in all patients) and experienced a flare, and 27 patients (18.4%), with no history of joint disease, developed de novo bilateral symmetric chronic inflammatory joint disease in response to chikungunya virus infection. For inflammatory arthritis, most patients were treated with methotrexate (up to 25 mg/week), with good response and tolerance. Thirteen patients were treated with conventional doses of anti–tumor necrosis factor agents, with good tolerance and efficacy as expected.

Conclusion

The term “chronic chikungunya syndrome” covers multiple etiologies. Compliance with the French Society of Rheumatology recommendations, careful recording of patient histories, and serologic verification help prevent errors inherent to the epidemic context and ensure early therapeutic intervention for these patients. To avoid late initiation of treatment, patients should receive rheumatologic consultation as early as possible.
Interactive anatomical and surgical live stream lectures improve students' academic performance in applied clinical anatomy
Authors: Shiozawa Thomas , Butz Benjamin , Herlan Stephan , Kramer Andreas , Hirt Bernhard
Published: June 2016

Tuebingen's Sectio Chirurgica (TSC) is an innovative, interactive, multimedia, and transdisciplinary teaching method designed to complement dissection courses. The Tuebingen's Sectio Chirurgica (TSC) allows clinical anatomy to be taught via interactive live stream surgeries moderated by an anatomist. This method aims to provide an application‐oriented approach to teaching anatomy that offers students a deeper learning experience. A cohort study was devised to determine whether students who participated in the TSC were better able to solve clinical application questions than students who did not participate. A total of 365 students participated in the dissection course during the winter term of the 2012/2013 academic year. The final examination contained 40 standard multiple‐choice (S‐MC) and 20 clinically‐applied multiple‐choice (CA‐MC) items. The CA‐MC items referred to clinical cases but could be answered solely using anatomical knowledge. Students who regularly participated in the TSC answered the CA‐MC questions significantly better than the control group (75% and 65%, respectively; P < 0.05, Mann‐Whitney U test). The groups exhibited no differences on the S‐MC questions (85% and 82.5%, respectively; P > 0.05). The CA‐MC questions had a slightly higher level of difficulty than the S‐MC questions (0.725 and 0.801, respectively; P = 0.083). The discriminatory power of the items was comparable (S‐MC median Pearson correlations: 0.321; CA‐MC: 0.283). The TSC successfully teaches the clinical application of anatomical knowledge. Students who attended the TSC in addition to the dissection course were able to answer CA‐MC questions significantly better than students who did not attend the TSC. Thus, attending the TSC in addition to the dissection course supported students' clinical learning goals. Anat Sci Educ 10: 46–52. © 2016 American Association of Anatomists.
Looking for “normal”: Sense making in the context of health disruption
Authors: Genuis Shelagh K. , Bronstein Jenny
Published: June 2016

This investigation examines perceptions of normality emerging from two distinct studies of information behavior associated with life disrupting health symptoms and theorizes the search for normality in the context of sense making theory. Study I explored the experiences of women striving to make sense of symptoms associated with menopause; Study II examined posts from two online discussion groups for people with symptoms of obsessive compulsive disorder. Joint data analysis demonstrates that normality was initially perceived as the absence of illness. A breakdown in perceived normality because of disruptive symptoms created gaps and discontinuities in understanding. As participants interacted with information about the experiences of health‐challenged peers, socially constructed notions of normality emerged. This was internalized as a “new normal.” Findings demonstrate normality as an element of sense making that changes and develops over time, and experiential information and social contexts as central to health‐related sense making. Re‐establishing perceptions of normality, as experienced by health‐challenged peers, was an important element of sense making. This investigation provides nuanced insight into notions of normality, extends understanding of social processes involved in sense making, and represents the first theorizing of and model development for normality within the information science and sense making literature.
Effects of extremely low frequency magnetic field on production of mannatide by α‐hemolytic Streptococcus
Authors: Zhang Jialan , Xu Cui , Wan Yunlei , Gao Mengxiang
Published: June 2016

The effect of the extremely low frequency magnetic field (ELF‐MF) on biomass and mannatide production by α‐hemolytic Streptococcus in liquid‐state fermentation culture medium was studied during shake flask culture. Magnetic field (MF) inductions, exposure times, and exposure periods varied in a range of 0–1.5 mT, 0–16 h, and six periods of incubation time, respectively. Results showed both biomass and mannatide production increased significantly at MF induction 0.4, 0.6, and 0.9 mT and decreased at both 1.2 and 1.5 mT. Biomass increased by exposure for initial and middle stages of fermentation. Mannatide production increased significantly at 4–8, 8–12, and 17–21 h. Peak yield of biomass and mannatide production increased by 10.7% and 14.0% at 25 and 27 h of incubation at 0.6 mT MF induction and exposure to 8–12 h of incubation time, compared with the control experiment, respectively. ELF‐MF could also enhance the growth rate and mannatide production rate of α‐hemolytic Streptococcus. However, ELF‐MF did not alter α‐hemolytic Streptococcus cell growth and mannatide metabolizing regulation or fermentation pattern. Mannatide production was not associated with cellular growth but rather only partially associated. Bioelectromagnetics. 37:331–337, 2016. © 2016 Wiley Periodicals, Inc.
Defining heterogeneity within bacterial populations via single cell approaches
Authors: Davis Kimberly M. , Isberg Ralph R.
Published: June 2016

Bacterial populations are heterogeneous, which in many cases can provide a selective advantage during changes in environmental conditions. In some instances, heterogeneity exists at the genetic level, in which significant allelic variation occurs within a population seeded by a single cell. In other cases, heterogeneity exists due to phenotypic differences within a clonal, genetically identical population. A variety of mechanisms can drive this latter strategy. Stochastic fluctuations can drive differential gene expression, but heterogeneity in gene expression can also be driven by environmental changes sensed by individual cells residing in distinct locales. Utilizing multiple single cell approaches, workers have started to uncover the extent of heterogeneity within bacterial populations. This review will first describe several examples of phenotypic and genetic heterogeneity, and then discuss many single cell approaches that have recently been applied to define heterogeneity within bacterial populations.
Correlated versus uncorrelated frailty Cox models: A comparison of different estimation procedures
Authors: Elghafghuf Adel , Stryhn Henrik
Published: June 2016

In many studies in medicine, including clinical trials and epidemiological investigations, data are clustered into groups such as health centers or herds in veterinary medicine. Such data are usually analyzed by hierarchical regression models to account for possible variation between groups. When such variation is large, it is of potential interest to explore whether additionally the effect of a within‐group predictor varies between groups. In survival analysis, this may be investigated by including two frailty terms at group level in a Cox proportional hazards model. Several estimation methods have been proposed to estimate this type of frailty Cox models. We review four of these methods, apply them to real data from veterinary medicine, and compare them using a simulation study.
Collagen‐like antimicrobial peptides
Authors: Masuda Ryo , Kudo Masakazu , Dazai Yui , Mima Takehiko , Koide Takaki
Published: June 2016

Combinatorial library composed of rigid rod‐like peptides with a triple‐helical scaffold was constructed. The component peptides were designed to have various combinations of basic and neutral (or hydrophobic) amino acid residues based on collagen‐like (Gly‐Pro‐Yaa)‐repeating sequences, inspired from the basic and amphiphilic nature of naturally occurring antimicrobial peptides. Screening of the peptide pools resulted in identification of antimicrobial peptides. A structure‐activity relationship study revealed that the position of Arg‐cluster at N‐terminus and cystine knots at C‐terminus in the triple helix significantly contributed to the antimicrobial activity. The most potent peptide RO‐A showed activity against Gram‐negative Escherichia coli and Gram‐positive Bacillus subtilis. In addition, Escherichia coli exposed to RO‐A resulted in abnormal elongation of the cells. RO‐A was also shown to have remarkable stability in human serum and low cytotoxicity to mammalian cells. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 453–459, 2016.
Specific affinity‐labeling of the nociceptin ORL1 receptor using a thiol‐activated Cys(Npys)‐containing peptide ligand
Authors: Matsushima Ayami , Nishimura Hirokazu , Matsuyama Yutaka , Liu Xiaohui , Costa Tommaso , Shimohigashi Yasuyuki
Published: June 2016

We previously showed that an antagonist‐based peptide ligand, H‐Cys(Npys)‐Arg‐Tyr‐Tyr‐Arg‐ Ile‐Lys‐NH2, captures the free thiol groups in the ligand‐binding site of the nociceptin receptor ORL1. However, the exact receptor sites of this thiol‐disulfide exchange reaction have not been uncovered, although such identification would help to clarify the ligand recognition site. Since the Cys→Ala substitution prevents the reaction, we performed the so‐called Ala scanning for all the Cys residues in the transmembrane (TM) domains of the ORL1 receptor. Seven different mutant receptors were soundly expressed in the COS‐7 cells and examined for their specific affinity labeling by a competitive binding assay using nociceptin and [3H]nociceptin. The results of in vitro Ala scanning analyses revealed that the labeled residues were Cys59 in TM1, Cys215 and Cys231 in TM5, and Cys310 in TM7. The present study has provided a novel method of Cys(Npys)‐affinity labeling for identification of the ligand‐binding sites in the ORL1 receptor. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 460–469, 2016.
Controlling the time evolution of mAb N‐linked glycosylation ‐ Part II: Model‐based predictions
Authors: Villiger Thomas K. , Scibona Ernesto , Stettler Matthieu , Broly Hervé , Morbidelli Massimo , Soos Miroslav
Published: June 2016

N‐linked glycosylation is known to be a crucial factor for the therapeutic efficacy and safety of monoclonal antibodies (mAbs) and many other glycoproteins. The nontemplate process of glycosylation is influenced by external factors which have to be tightly controlled during the manufacturing process. In order to describe and predict mAb N‐linked glycosylation patterns in a CHO‐S cell fed‐batch process, an existing dynamic mathematical model has been refined and coupled to an unstructured metabolic model. High‐throughput cell culture experiments carried out in miniaturized bioreactors in combination with intracellular measurements of nucleotide sugars were used to tune the parameter configuration of the coupled models as a function of extracellular pH, manganese and galactose addition. The proposed modeling framework is able to predict the time evolution of N‐linked glycosylation patterns during a fed‐batch process as a function of time as well as the manipulated variables. A constant and varying mAb N‐linked glycosylation pattern throughout the culture were chosen to demonstrate the predictive capability of the modeling framework, which is able to quantify the interconnected influence of media components and cell culture conditions. Such a model‐based evaluation of feeding regimes using high‐throughput tools and mathematical models gives rise to a more rational way to control and design cell culture processes with defined glycosylation patterns. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1135–1148, 2016
Prevalence of hypercalcemia among cancer patients in the United States
Authors: Gastanaga Victor M. , Schwartzberg Lee S. , Jain Rajul K. , Pirolli Melissa , Quach David , Quigley Jane M. , Mu George , Scott Stryker W. , Liede Alexander
Published: June 2016

Hypercalcemia of malignancy (HCM) is a serious metabolic complication whose population‐based prevalence has not been quantified. Rates of HCM differ by tumor type, with highest rates reported in multiple myeloma and lowest among colorectal and prostate cancer patients. This analysis estimates HCM prevalence in the US. This retrospective study used the Oncology Services Comprehensive Electronic Records (OSCER) warehouse of electronic health records (EHR) including laboratory values from 569000 patients treated at 565 oncology outpatient sites. OSCER data were projected to the national level by linking EHR to claims data. Cancer patients included were ≥18 years, and had serum calcium (Ca) and albumin (for corrected serum Ca [CSC]) records. Period prevalence was estimated by HCM CTCAE grade, tumor type, and year (2009–2013). Estimates were adjusted to capture patients diagnosed with HCM outside oncology practices based on a subset of patients linkable to office and hospital data. The analysis included 68023 (2009) to 121482 (2013) cancer patients. In 2013, patients with HCM had a median of six Ca tests, 69.7% had chemotherapy, and 34% received bone modifying agents. HCM rates were highest for multiple myeloma patients (7.5% [2012]–10.2% [2010]), lowest for prostate cancer (1.4% [2012]–2.1% [2011]).The estimated adjusted annual prevalence of HCM from 2009 to 2013 was 95441, 96281, 89797, 70158, and 71744, respectively. HCM affected 2.0–2.8% of all cancer patients. EHR data from oncology clinics were critical for this study because these data contain results from laboratory studies (i.e., serum calcium values) that are routinely ordered in that setting. We estimated that the prevalence of HCM in the US in 2013 is 71744, affecting approximately 2% of cancer patients overall. This percentage differs by tumor type and appears to have decreased over the five‐year study period.
The impact of marital status at diagnosis on cancer survival in patients with differentiated thyroid cancer
Authors: Shi Rong‐liang , Qu Ning , Lu Zhong‐wu , Liao Tian , Gao Yi , Ji Qing‐hai
Published: June 2016

Previous studies have revealed that marital status influences the prognosis of patients with various types of cancer. We evaluated the influence of marriage on the survival outcomes in differentiated thyroid cancer (DTC). The Surveillance, Epidemiology and End Results (SEER) database between 2002 and 2012 was used to compare cancer‐specific mortality in different marital status, and in each sex, age, and stage stratification by multivariate Cox regression model. In total, 61,077 eligible patients were identified. The widowed group had the highest proportion of women, elderly patients (≥45 years), and advanced stage III/IV tumor (P = 0.001), but the total thyroidectomy (TT) performed and radioisotopes therapy rates were lower than those in the married group. Married patients had a better cancer‐specific survival (CSS) than the unmarried (P < 0.05). Further analysis showed that widowed patients always presented the lowest CSS compared with other groups. Widowed patients had a significant increased risk for CSS compared with married patients in males [hazard ratio (HR) 2.72, 95% confidence interval (CI): 1.59–4.65, P = 0.001], females (HR 2.02, 95% CI: 2.24–4.06, P = 0.001), young patients (<45, HR 28.12, 95% CI: 3.48–227.25, P = 0.002), elderly patients (≥45, HR 28.12, 95% CI: 2.97, 95% CI: 2.30–3.83, P = 0.001), stage I (HR 8.44, 95% CI: 4.05–17.59, P = 0.001), stage II (HR 3.64, 95% CI: 1.30–10.20, P = 0.014), stage III (HR 2.27, 95% CI: 1.08–4.78, P = 0.031), and stage IV (HR 2.63, 95% CI: 1.94–3.57, P = 0.001). These results showed that unmarried status, especially for widowhood, increased the risk of cancer mortality in DTC patients.
Genetic alterations of differentiated thyroid carcinoma in iodine‐rich and iodine‐deficient countries
Authors: Vuong Huy Gia , Kondo Tetsuo , Oishi Naoki , Nakazawa Tadao , Mochizuki Kunio , Inoue Tomohiro , Tahara Ippei , Kasai Kazunari , Hirokawa Mitsuyoshi , Tran Thong Minh , Katoh Ryohei
Published: June 2016

BRAF V600E mutation, RET rearrangements, and RAS mutations are the common genetic alterations in differentiated thyroid carcinomas derived from follicular thyroid cells. However, the relationship between these alterations and iodine intake is still controversial. To clarify the influence of iodine intake on the occurrence of differentiated thyroid carcinomas, we performed molecular analyses for two differentiated carcinomas, papillary thyroid carcinomas (PTCs) and follicular thyroid carcinomas (FTCs), from an iodine‐rich country (Japan) and an iodine‐deficient country (Vietnam). We examined 120 PTCs (67 Japanese and 53 Vietnamese) and 74 FTCs (51 Japanese and 23 Vietnamese). We carried out allele‐specific polymerase chain reaction (AS‐PCR) for BRAF V600E, PCR and direct sequencing for RAS mutations (codon 12, 13, and 61 in NRAS, HRAS, and KRAS), and RT‐PCR for RET/PTC1 and RET/PTC3. BRAF V600E was present in 55/67 (82.1%) Japanese PTCs and 44/53 (83%) Vietnamese PTCs. RET/PTC1 was identified in only one PTC from each country, and no samples had RET/PTC3. NRAS mutation was found in 17/51 (33.3%) Japanese FTCs and 4/23 (17.4%) Vietnamese FTCs. NRAS mutation was cited in codon 61 (20 cases) and codon 12 (one case). None of FTCs had KRAS or HRAS mutations. There were no significant differences in the prevalence of BRAF V600E, RET/PTC, or RAS mutations between the two countries. Our study showed no differences in genetic alterations of thyroid cancers from iodine‐rich and iodine‐deficient countries, possibly suggesting that iodine intake might not affect the genetic alterations of differentiated thyroid cancer.
Tracking Protein S‐Fatty Acylation with Proteomics
Authors: Birner‐Gruenberger Ruth , Breinbauer Rolf
Published: June 2016

Recently, Hang and co‐workers developed “acyl‐PEG exchange” (APE), which allows the investigation of protein S‐fatty acylation with mass‐tag labelling and gel electrophoresis, methods that are accessible to any biochemistry laboratory.
Synthesis of Vinyl Carboxylic Acids using Carbon Dioxide as a Carbon Source by Iron‐Catalyzed Hydromagnesiation
Authors: Santhoshkumar Rajagopal , Hong Ya‐Chun , Luo Ching‐Zong , Wu Yun‐Ching , Hung Chen‐Hsun , Hwang Kuen‐Yuan , Tu An‐Pang , Cheng Chien‐Hong
Published: June 2016

An iron‐catalyzed synthesis of α,β‐unsaturated carboxylic acids from alkynes and carbon dioxide was developed. This reaction proceeds through hydromagnesiation of alkynes followed by carbon dioxide insertion under atmospheric pressure and ambient temperature in the presence of iron and a Grignard reagent as a catalyst and hydride source, respectively. Several symmetrical and unsymmetrical alkynes were transformed into the corresponding acids in good to excellent yields. The methodology provides an efficient route to the synthesis of vinyl carboxylic acids.
On the Availability of Active Sites for the Hydrogen Peroxide and Oxygen Reduction Reactions on Highly Dispersed Platinum Nanoparticles
Authors: Timperman Laure , Luo Yun , Alonso‐Vante Nicolas
Published: June 2016

Carbon‐supported platinum nanoparticles (Pt/C) were synthesized by the carbonyl chemical route. The obtained Pt/C catalysts with different Pt mass loadings, varying from 5 to 50 wt %, showed constant morphology with particle sizes of about 2 nm and a dispersion of around 50 %. The electrochemical surface area, determined from CO stripping and hydrogen underpotential deposition, increased with the Pt mass loading, which confirmed that agglomeration was negligible. The oxygen reduction reaction (ORR) half‐wave potential was positively shifted with an increase in the Pt mass loading, and the ORR kinetic current was (40±10) μA cm−2Pt. The data collected on a rotating ring‐disk electrode for the ORR pathway revealed a two‐electron serial mechanism (hydrogen peroxide), instead of the four‐electron transfer (water). The determined turnover frequency factor indicated good selectivity of the Pt active sites for the ORR with 1 or 2 mm H2O2 in the electrolyte for samples with mass loadings ranging from 15 to 40 wt %. The ORR was markedly affected by the mass loading (5–10 wt % Pt/C) in the presence of 2 mm H2O2.
Designed Formation of MnO2@NiO/NiMoO4 Nanowires@Nanosheets Hierarchical Structures with Enhanced Pseudocapacitive Properties
Authors: Chu Yanting , Xiong Shenglin , Li Baosong , Qian Yitai , Xi Baojuan
Published: June 2016

Although the preparation of hierarchical structures of transition‐metal oxides (TMOs) has been intensively studied in recent years, it is still a great challenge to synthesize hierarchical multicomponent TMOs. Herein, we report a versatile method to fabricate three‐component TMOs, namely MnO2@NiO/NiMoO4 nanowires@nanosheets hierarchical porous composite structures (HPCSs). Through a combination of a chemical‐solution‐based route and subsequent calcination, the as‐prepared MnOOH@NiMo precursor is topotactically transformed to MnO2@NiO/NiMoO4 HPCSs without notable structural variation. Ultrathin NiO/NiMoO4 nanosheets become interconnected into a honeycomb analogue with plentiful mesopores. Comparative results demonstrate the vital role of hexamethylenetetramine (HMT), and the solvent system in the formation of the MnOOH@NiMo precursor. When examined as electrode materials for electrochemical capacitors, MnO2@NiO/NiMoO4 HPCSs, with an areal mass loading as high as 5 mg cm−2, deliver a specific capacitance of 918 F g−1 at a current density of 1.0 A g−1 and maintain good cycling stability, which displays better electrochemical performance than electrodes composed of a single component. Note that a high‐voltage asymmetric supercapacitor is configured with MnO2@NiO/NiMoO4 HPCSs (still as high as 2 mg cm−2) against activated carbon, and exhibits outstanding cycling stability with a high energy density of 26.5 Wh kg−1 and a power density of 401 W kg−1. These analytical and experimental results clearly confirm the advantages of distinctive 3D multicomponent hierarchical architectures for engineering high‐performance electrochemical capacitors.
Electrochemically Prepared Poly(3,4‐ethylenedioxy‐ thiophene)/Polypyrrole Films with Hollow Micro‐/Nanohorn Arrays as High‐Efficiency Counter Electrodes for Dye‐Sensitized Solar Cells
Authors: Bai Yang , Xu Youlong , Wang Jie , Gao Mingqi , Zhu Jianbo , Rehman Wasif ur
Published: June 2016

A two‐step approach is employed for quick and controllable electropolymerization of poly(3,4‐ethylenedioxythiophene) (PEDOT)/polypyrrole (PPy) hollow micro‐/nanohorns on fluorinated tin oxide (FTO) glass substrates as counter electrodes (CEs) for Pt‐free dye‐sensitized solar cells (DSCs). PPy films with hollow micro‐/nanohorn arrays are grown on FTO glasses by a modified pulse potentiostatic method in the first step. Then PEDOT is potentiostatically polymerized onto them as the CEs. Owing to the relatively high catalytic activity of PEDOT and the high specific surface area of hollow micro‐/nanohorn PPy (hPPy), the compound film shows electrocatalytic activity for I3− reduction similar to that of Pt. Therefore, DSCs assembled with this CE exhibit comparable power conversion efficiency (7.08 %) to DSCs with Pt CEs (6.88 %). The PEDOT/PPy film with hollow micro‐/nanohorn arrays can be considered to be a promising alternative CE material for Pt‐free DSCs.
Coadministration of ticagrelor and ritonavir: Toward prospective dose adjustment to maintain an optimal platelet inhibition using the PBPK approach
Authors: Marsousi N , Samer CF , Fontana P , Reny JL , Rudaz S , Desmeules JA , Daali Y
Published: June 2016

Ticagrelor is a potent antiplatelet drug metabolized by cytochrome (CYP)3A. It is contraindicated in patients with human immunodeficiency virus (HIV) because of the expected CYP3A inhibition by most protease inhibitors, such as ritonavir and an increased bleeding risk. In this study, a physiologically based pharmacokinetic (PBPK) model was created for ticagrelor and its active metabolite (AM). Based on the simulated interaction between ticagrelor 180 mg and ritonavir 100 mg, a lower dose of ticagrelor was calculated to obtain, when coadministered with ritonavir, the same pharmacokinetic (PK) and platelet inhibition as ticagrelor administered alone. A clinical study was thereafter conducted in healthy volunteers. Observed PK profiles of ticagrelor and its AM were successfully predicted with the model. Platelet inhibition was nearly complete in both sessions despite administration of a fourfold lower dose of ticagrelor in the second session. This PBPK model could be prospectively used to broaden the usage of ticagrelor in patients with ritonavir‐treated HIV regardless of the CYP3A inhibition.
The Nature and Impact of Side Reactions in Glyme‐based Sodium–Oxygen Batteries
Authors: Black Robert , Shyamsunder Abhinandan , Adeli Parvin , Kundu Dipan , Murphy Graham K. , Nazar Linda F.
Published: June 2016

Although Na–O2 batteries have a low overpotential and good capacity retention, degradation reactions of glyme‐based electrolytes are the primary reason for inefficiency in cell performance. The discharge capacity is accounted for through analysis of the side‐products. Although sodium superoxide is the primary product (90 % theoretical), quantitative and qualitative evaluation of the side‐products (using 1H NMR, iodometric titration, and on‐line mass spectrometry) shows the presence of sodium acetate (∼3.5 %), and three‐fold less sodium formate, methoxy (oxo)acetic anhydride, and sodium carbonate. Our reaction mechanism proposes two paths for their formation. Because the side‐products are not fully removed during oxidation, they accumulate on the cathode upon cycling. Resting the cell at open circuit potential during discharge results in consumption of the superoxide through the reaction with diglyme, which greatly increases the fraction of side products, as also confirmed by ex situ reaction studies. These findings have implications in the search for more stable electrolytes.
Modeling of Sustainable Base Production by Microbial Electrolysis Cell
Authors: Blatter Maxime , Sugnaux Marc , Comninellis Christos , Nealson Kenneth , Fischer Fabian
Published: June 2016

A predictive model for the microbial/electrochemical base formation from wastewater was established and compared to experimental conditions within a microbial electrolysis cell. A Na2SO4/K2SO4 anolyte showed that model prediction matched experimental results. Using Shewanella oneidensis MR‐1, a strong base (pH≈13) was generated using applied voltages between 0.3 and 1.1 V. Due to the use of bicarbonate, the pH value in the anolyte remained unchanged, which is required to maintain microbial activity.
Optimized automated data analysis for the cytokinesis‐block micronucleus assay using imaging flow cytometry for high throughput radiation biodosimetry
Authors: Rodrigues M. A. , Probst C. E. , Beaton‐Green L. A. , Wilkins R. C.
Published: June 2016

The cytokinesis‐block micronucleus (CBMN) assay is a well‐established technique that can be employed in triage radiation biodosimetry to estimate whole body doses of radiation to potentially exposed individuals through quantitation of the frequency of micronuclei (MN) in binucleated lymphocyte cells (BNCs). The assay has been partially automated using traditional microscope‐based methods and most recently has been modified for application on the ImageStreamX (ISX) imaging flow cytometer. This modification has allowed for a similar number of BNCs to be automatically scored as compared to traditional microscopy in a much shorter time period. However, the MN frequency measured was much lower than both manual and automated slide‐based methods of performing the assay. This work describes the optimized analysis template which implements newly developed functions in the IDEAS® data analysis software for the ISX that enhances specificity for BNCs and increases the frequency of scored MN. A new dose response calibration curve is presented in which the average rate of MN per BNC is of similar magnitude to those presented in the literature using automated CBMN slide scoring methods. In addition, dose estimates were generated for nine irradiated, blinded samples and were found to be within ±0.5 Gy of the delivered dose. Results demonstrate that the improved identification accuracy for MN and BNCs in the ISX‐based version of the CBMN assay will translate to increased accuracy when estimating unknown radiation doses received by exposed individuals following large‐scale radiological or nuclear emergencies. © 2016 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of ISAC
Multiple squamous cells in thyroid fine needle aspiration: Friends or foes?
Authors: Gage Heather , Hubbard Elizabeth , Nodit Laurentia
Published: June 2016

Background

Abundant squamous cells are rarely encountered in thyroid FNA with only few case reports noted in the literature. Their presence and cytologic features may pose a diagnostic dilemma and challenges for proper classification and follow‐up. We intend to gain more insight into the frequency of this finding and its clinical significance.

Design

Our electronic records were searched over 16 years to reveal 15 thyroid FNAs with abundant squamous cells. The available cytology and surgical resection slides were reviewed and radiologic records and clinical follow‐up was documented.

Results

Only 15 out of 8811 thyroid FNAs from our department contained predominantly squamous cells (0.17%) of which two were interpreted as nondiagnostic, four as atypical, eight as benign, and one malignant. Surgical follow‐up was available in eight cases only with benign lesions representing the majority of the cases (squamous metaplasia in Hashimoto thyroiditis, benign epidermoid/branchial cleft or thyroglossal duct cysts, and one case squamous cell carcinoma). The cases without surgical resection were stable on subsequent ultrasound studies.

Conclusion

Thyroid aspirates with predominance of squamous cells cannot be classified in the current Bethesda categories. Even when interpreted as atypical or equivocal, the squamous cells present in our small case series were mostly benign. The only malignant case was easily identified cytologically because of its higher degree of differentiation. The most common pitfall for atypical squamous cells in these aspirates was squamous metaplasia in the setting of Hashimoto thyroiditis and degenerative changes. Diagn. Cytopathol. 2016;44:676–681. © 2016 Wiley Periodicals, Inc.
Gap junctional signaling in pattern regulation: Physiological network connectivity instructs growth and form
Authors: Mathews Juanita , Levin Michael
Published: June 2016

Gap junctions (GJs) are aqueous channels that allow cells to communicate via physiological signals directly. The role of gap junctional connectivity in determining single‐cell functions has long been recognized. However, GJs have another important role: the regulation of large‐scale anatomical pattern. GJs are not only versatile computational elements that allow cells to control which small molecule signals they receive and emit, but also establish connectivity patterns within large groups of cells. By dynamically regulating the topology of bioelectric networks in vivo, GJs underlie the ability of many tissues to implement complex morphogenesis. Here, a review of recent data on patterning roles of GJs in growth of the zebrafish fin, the establishment of left‐right patterning, the developmental dysregulation known as cancer, and the control of large‐scale head‐tail polarity, and head shape in planarian regeneration has been reported. A perspective in which GJs are not only molecular features functioning in single cells, but also enable global neural‐like dynamics in non‐neural somatic tissues has been proposed. This view suggests a rich program of future work which capitalizes on the rapid advances in the biophysics of GJs to exploit GJ‐mediated global dynamics for applications in birth defects, regenerative medicine, and morphogenetic bioengineering. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 643–673, 2017
BMP signaling regulates the fate of chondro‐osteoprogenitor cells in facial mesenchyme in a stage‐specific manner
Authors: Celá Petra , Buchtová Marcela , Veselá Iva , Fu Kathy , Bogardi Jean‐Philippe , Song Yiping , Barlow Amanda , Buxton Paul , Medalová Jirina , Francis‐West Philippa , Richman Joy M.
Published: June 2016

Background: Lineage tracing has shown that most of the facial skeleton is derived from cranial neural crest cells. However, the local signals that influence postmigratory, neural crest‐derived mesenchyme also play a major role in patterning the skeleton. Here, we study the role of BMP signaling in regulating the fate of chondro‐osteoprogenitor cells in the face. Results: A single Noggin‐soaked bead inserted into stage 15 chicken embryos induced an ectopic cartilage resembling the interorbital septum within the palate and other midline structures. In contrast, the same treatment in stage 20 embryos caused a loss of bones. The molecular basis for the stage‐specific response to Noggin lay in the simultaneous up‐regulation of SOX9 and downregulation of RUNX2 in the maxillary mesenchyme, increased cell adhesiveness as shown by N‐cadherin induction around the beads and increased RA pathway gene expression. None of these changes were observed in stage 20 embryos. Conclusions: These experiments demonstrate how slight changes in expression of growth factors such as BMPs could lead to gain or loss of cartilage in the upper jaw during vertebrate evolution. In addition, BMPs have at least two roles: one in patterning the skull and another in regulating the skeletogenic fates of neural crest‐derived mesenchyme. Developmental Dynamics 245:947–962, 2016. © 2016 Wiley Periodicals, Inc.
A stochastic model for landscape patterns of biodiversity
Authors: Prevedello Jayme A. , Gotelli Nicholas J. , Metzger Jean Paul
Published: June 2016

Many factors have been proposed to affect biodiversity patterns across landscapes, including patch area, patch isolation, edge distances, and matrix quality, but existing models emphasize only one or two of these factors at a time. Here we introduce a synthetic but simple individual‐based model that generates realistic patterns of species richness and density as a function of landscape structure. In this model, we simulated the stochastic placement of home ranges in landscapes, thus combining features of existing random placement and mid‐domain effect models. As such, the model allows investigation of whether and how geometric constraints on home range placement of individuals scale up to affect species abundance and richness in landscapes. The model encompassed a gradient of possible landscapes, from a strictly homogeneous landscape to an archipelago of discrete patches. The model incorporated only variation in home range size of individuals of different species, with a simple suitability index that controlled home range spread into areas of habitat and areas of inter‐habitat matrix. Demographic details of birth, death, and migration, as well as effects of species interactions were not included. Nevertheless, this simple model generated realistic patterns of biodiversity, including species–area curves and increases in diversity and abundance with decreasing isolation and increasing distance from patch edges. Species–area slopes (z values) generated by the model fell within the range observed in empirical studies on both true islands and habitat patches. Isolation and edge effects were stronger when the matrix was unsuitable, and became progressively weaker as matrix suitability increased, again in accordance with many empirical studies. When applied to a real data set on the abundance of 20 small mammal species sampled in forest patches in the Atlantic Forest of Brazil, the model predicted increases in abundance and richness with increasing patch size, consistent with the general pattern observed with field data. The ability of this simple model to reproduce realistic qualitative patterns of biodiversity suggests that such patterns may be driven, at least in part, by geometric constraints acting on the placement of individual ranges, which ultimately affect biodiversity patterns at the landscape level.
Spatial patterns and controls on burned area for two contrasting fire regimes in Southern California
Authors: Faivre N. R. , Jin Y. , Goulden M. L. , Randerson J. T.
Published: June 2016

An improved understanding of the mechanisms that regulate wildfire risk at local to regional scales is needed for the design of effective fire and ecosystem management. We investigated the spatial distribution of burned area in Southern California during 1960–2009 using five different data‐driven methods: multiple linear regression, generalized additive models (GAMs),GAMs with spatial autocorrelation, non‐linear multiplicative models, and random forest models. We used each method to separately develop burned area risk maps for Southern California's two distinct wildfire regimes: Santa Ana (SAfires), which occur during high wind events mostly in autumn, and non‐Santa Ana fires (non‐SAfires), which occur mostly during the hot and dry Mediterranean‐climate summer. The different methods explained 38–63% of the spatial variance in burned area forSAfires and 21–48% for non‐SAfires. The two fire regimes had contrasting drivers, with Fosberg fire weather index, relative humidity, minimum temperature, and distance to housing most important forSAfires, and shrub cover, road density, and distance to minor and major roads most important for non‐SAfires. Our modeling framework carries implications for the strategic placement of fire suppression resources, and for prevention planning in areas facing increasing human and climate pressures.
The role of local and regional processes on population synchrony along the gradients of habitat specialization
Authors: Pandit Shubha N. , Cottenie Karl , Enders Eva C. , Kolasa Jurek
Published: June 2016

Metacommunity perspective highlights the role of space as a factor contributing to local community structure and dynamics. Often tests of metacommunity models rely on snapshot patterns of species distribution and abundance. Such patterns may introduce biases because they overlook differences in responses of constituent species to changing environmental conditions, particularly when such responses override patterns predicted from dispersal and biotic interactions alone. This applies, for example, to habitat generalists, whose responses to environmental variations differ from those of habitat specialists, resulting in different snapshot patterns at different times. Synchronized (i.e., correlated among sites) environmental variation is perhaps the most obvious case of environmental variation that could generate regular differences among species of different specialization. We hypothesized that synchronized environmental variation synchronizes local populations of habitat specialists to a greater degree than it does for habitat generalists as experiments have shown that habitat generalists are less sensitive to changing environmental conditions. To test this in an empirical system, we used time series data (nine annual surveys) on an invertebrate metacommunity of 49 rock pools on the coast of Jamaica. We found that population synchrony of a significant portion of 24 species sharing these rock pools increased with habitat specialization in response to environmental synchrony (represented by synchrony of environment). However, distance among rock pools, which may affect dispersal or shared perturbations, was negatively correlated with population synchrony of individual species, irrespective of their specialization. As only habitat specialists showed increasing synchrony with environmental synchrony, and both generalist and specialist synchrony were negatively correlated with distance, we infer that habitat generalists must be synchronized more by space‐related processes while habitat specialists by a combination of environmental forcing and dispersal. Overall, the study suggests that species of different habitat specialization show consistent differences with respect to local processes involving environmental variations but show fewer differences with respect to regional processes involving distance, at least when long‐term dynamics are concerned. Furthermore, the study identifies a rarely recognized link between variation in space and its consequences for variation in time—a link much more expressed among spatially restricted species such as habitat specialists.
Partitioning scleractinian coral diversity across reef sites and regions in the Western Indian Ocean
Authors: Ateweberhan Mebrahtu , McClanahan Timothy R.
Published: June 2016

Understanding how diversity is organized is essential for inference about appropriate scales for natural resource research and management. In this study, we investigated variation in scleractinian coral taxonomic richness and community diversity in the Western Indian Ocean (WIO) at different spatial scales. We sampled corals in 331 sites across nine countries. Sites were pooled into 11 distinct subregions based on previous investigations on coral community structure and between closures and reefs open to fishing for five regions with sufficient closure replication. We analyzed similarities in coral communities and compared differences in mean richness and Shannon diversity. Significant differences in alpha and beta components of diversity were tested at multiple spatial scales and between management types against a random distribution null model. Rarefaction was used to investigate significant difference in total taxonomic richness among regions. Coral communities were mainly structured along Acropora and massive Porites dominance lines. Highest dissimilarity among coral communities was found at the regional level and within‐ and between‐subregion variations accounted for most of the coral diversity. Beta components were responsible for higher proportions of taxonomic richness of which a large part was explained by the site‐region interaction. Alpha diversity contributed most to Shannon diversity and site level richness and Shannon diversity had similar relationships with latitude, peaking at about 10°S. Alpha diversity also showed significant relationship with water temperature variability, peaking at a sea surface temperature standard deviation of about 1.4 °C, corresponding to the same 10°S latitude. Relatively higher alpha and beta components contributed to high richness and Shannon diversity in three regions: southern Kenya–northern Tanzania, southern Tanzania–northern Mozambique and northwestern Madagascar–Mayotte. Consequently, the findings support the proposal for delineating these locations as a regional priority for biodiversity conservation.