bluuebunny/crossref_metadata_2025 huggingface dataset:
Children’s Throwing and Striking: A Longitudinal Study
Authors: Angell Rose M. , Butterfield Stephen A. , Tu Shihfen , Loovis E. Michael , Mason Craig A. , Nightingale Christopher J.
Published: April 2018

Object control skills (OCS) provide children the means to be physically active. However, gender equality in some OCS remains elusive. Particularly troublesome is the basic throwing pattern and, by extension, the striking pattern, both of which rely on forceful, rapid rotation of the pelvis, trunk, and shoulders. Some scholars argue that sex differences in throwing and striking are rooted in human evolution. The purpose of this study was to examine development of throwing and striking at the fundamental movement level. The design was multi-cohort sequential: 280 boys and girls grades K–8 (ages 4–15) were tested up to three times per year for 5 years on the Test of Gross Motor Development (TGMD-2). Hierarchical linear modeling (HLM) was applied to analyze individual growth curves. As anticipated, significant (p < .001) age-related gains were found for throwing and striking. In terms of sex (biology) or gender (sociocultural) differences, boys performed better longitudinally at throwing (p < .05) and striking (p < .05). These results reinforce theories that girls may be disadvantaged in achieving proficiency in throwing and striking. Interventions designed to enhance development of these skills should be in place long before grade 4, when most physical education curricula transitions to games and sports.
The nociceptin receptor inhibits axonal regeneration and recovery from spinal cord injury
Authors: Sekine Yuichi , Siegel Chad S. , Sekine-Konno Tomoko , Cafferty William B. J. , Strittmatter Stephen M.
Published: April 2018

Recovery from spinal cord injury is improved by blocking the receptors for Nogo and the opioid peptide nociceptin.
Protein Acetylation Mediated by YfiQ and CobB Is Involved in the Virulence and Stress Response of Yersinia pestis
Authors: Liu Wanbing , Tan Yafang , Cao Shiyang , Zhao Haihong , Fang Haihong , Yang Xiaoyan , Wang Tong , Zhou Yazhou , Yan Yanfeng , Han Yanping , Song Yajun , Bi Yujing , Wang Xiaoyi , Yang Ruifu , Du Zongmin
Published: April 2018

Recent studies revealed that acetylation is a widely used protein modification in prokaryotic organisms. The major protein acetylation acetyltransferase YfiQ and the sirtuin-like deacetylase CobB have been found to be involved in basic physiological processes, such as primary metabolism, chemotaxis, and stress responses, in
Escherichia coli
and
Salmonella
. However, little is known about protein acetylation modifications in
Yersinia pestis
, a lethal pathogen responsible for millions of human deaths in three worldwide pandemics. Here we found that
Yp_0659
and
Yp_1760
of
Y. pestis
encode the major protein acetylation acetyltransferase YfiQ and the sirtuin-like deacetylase CobB, respectively, which can acetylate and deacetylate PhoP enzymatically
in vitro
. Protein acetylation impairment in
cobB
and
yfiQ
mutants greatly decreased bacterial tolerance to cold, hot, high-salt, and acidic environments. Our comparative transcriptomic data revealed that the strongly decreased tolerance to stress stimuli was probably related to downregulation of the genes encoding the heat shock proteins (HtpG, HslV, HslR, and IbpA), cold shock proteins (CspC and CspA1), and acid resistance proteins (HdeB and AdiA). We found that the reversible acetylation mediated by CobB and YfiQ conferred attenuation of virulence, probably partially due to the decreased expression of the
psaABCDEF
operon, which encodes Psa fimbriae that play a key role in virulence of
Y. pestis
. This is the first report, to our knowledge, on the roles of protein acetylation modification in stress responses, biofilm formation, and virulence of
Y. pestis
.
Feline Herpesvirus 1 US3 Blocks the Type I Interferon Signal Pathway by Targeting Interferon Regulatory Factor 3 Dimerization in a Kinase-Independent Manner
Authors: Tian Jin , Liu Yongxiang , Liu Xiaoxiao , Sun Xue , Zhang Jikai , Qu Liandong
Published: April 2018

As a prevalent agent in cats, feline herpesvirus 1 (FHV-1) infection contributes to feline respiratory disease and acute and chronic conjunctivitis. FHV-1 can successfully evade the host innate immune response and persist for the lifetime of the cat. Several mechanisms of immune evasion by human herpesviruses have been elucidated, but the mechanism of immune evasion by FHV-1 remains unknown. In this study, we screened for FHV-1 open reading frames (ORFs) responsible for inhibiting the type I interferon (IFN) pathway with an IFN-β promoter reporter and analysis of IFN-β mRNA levels in HEK 293T cells and the Crandell-Reese feline kidney (CRFK) cell line, and we identified the Ser/Thr kinase US3 as the most powerful inhibitor. Furthermore, we found that the anti-IFN activity of US3 depended on its N terminus (amino acids 1 to 75) and was independent of its kinase activity. Mechanistically, the ectopic expression of US3 selectively inhibited IFN regulatory factor 3 (IRF3) promoter activation. Furthermore, US3 bound to the IRF association domain (IAD) of IRF3 and prevented IRF3 dimerization. Finally, US3-deleted recombinant FHV-1 and US3-repaired recombinant FHV-1 (rFHV-dUS3 and rFHV-rUS3, respectively) were constructed. Compared with wild-type FHV-1 and rFHV-rUS3, infection with rFHV-dUS3 induced large amounts of IFN-β
in vitro
and
in vivo
. More importantly, US3 deletion significantly attenuated virulence, reduced virus shedding, and blocked the invasion of trigeminal ganglia. These results indicate that FHV-1 US3 efficiently inhibits IFN induction by using a novel immune evasion mechanism and that FHV-1 US3 is a potential regulator of neurovirulence.

IMPORTANCE
Despite widespread vaccination, the prevalence of FHV-1 remains high, suggesting that it can successfully evade the host innate immune response and infect cats. In this study, we screened viral proteins for inhibiting the IFN pathway and identified the Ser/Thr kinase US3 as the most powerful inhibitor. In contrast to other members of the alphaherpesviruses, FHV-1 US3 blocked the host type I IFN pathway in a kinase-independent manner and via binding to the IRF3 IAD and preventing IRF3 dimerization. More importantly, the depletion of US3 attenuated the anti-IFN activity of FHV-1 and prevented efficient viral replication
in vitro
and
in vivo
. Also, US3 deletion significantly attenuated virulence and blocked the invasion of trigeminal ganglia. We believe that these findings not only will help us to better understand the mechanism of how FHV-1 manipulates the host IFN response but also highlight the potential role of US3 in the establishment of latent infection
in vivo
.
Identification of the RNA Pseudoknot within the 3′ End of the Porcine Reproductive and Respiratory Syndrome Virus Genome as a Pathogen-Associated Molecular Pattern To Activate Antiviral Signaling via RIG-I and Toll-Like Receptor 3
Authors: Xie Sha , Chen Xin-xin , Qiao Songlin , Li Rui , Sun Yangang , Xia Shuangfei , Wang Lin-Jian , Luo Xuegang , Deng Ruiguang , Zhou En-Min , Zhang Gai-Ping
Published: April 2018

Once infected by viruses, cells can detect pathogen-associated molecular patterns (PAMPs) on viral nucleic acid by host pattern recognition receptors (PRRs) to initiate the antiviral response. Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of porcine reproductive and respiratory syndrome (PRRS), characterized by reproductive failure in sows and respiratory diseases in pigs of different ages. To date, the sensing mechanism of PRRSV has not been elucidated. Here, we reported that the pseudoknot region residing in the 3′ untranslated regions (UTR) of the PRRSV genome, which has been proposed to regulate RNA synthesis and virus replication, was sensed as nonself by retinoic acid-inducible gene I (RIG-I) and Toll-like receptor 3 (TLR3) and strongly induced type I interferons (IFNs) and interferon-stimulated genes (ISGs) in porcine alveolar macrophages (PAMs). The interaction between the two stem-loops inside the pseudoknot structure was sufficient for IFN induction, since disruption of the pseudoknot interaction powerfully dampened the IFN induction. Furthermore, transfection of the 3′ UTR pseudoknot transcripts in PAMs inhibited PRRSV replication
in vitro
. Importantly, the predicted similar structures of other arterivirus members, including equine arteritis virus (EAV), lactate dehydrogenase-elevating virus (LDV), and simian hemorrhagic fever virus (SHFV), also displayed strong IFN induction activities. Together, in this work we identified an innate recognition mechanism by which the PRRSV 3′ UTR pseudoknot region served as PAMPs of arteriviruses and activated innate immune signaling to produce IFNs that inhibit virus replication. All of these results provide novel insights into innate immune recognition during virus infection.

IMPORTANCE
PRRS is the most common viral disease in the pork industry. It is caused by PRRSV, a positive single-stranded RNA virus, whose infection often leads to persistent infection. To date, it is not yet clear how PRRSV is recognized by the host and what is the exact mechanism of IFN induction. Here, we investigated the nature of PAMPs on PRRSV and the associated PRRs. We found that the 3′ UTR pseudoknot region of PRRSV, which has been proposed to regulate viral RNA synthesis, could act as PAMPs recognized by RIG-I and TLR3 to induce type I IFN production to suppress PRRSV infection. This report is the first detailed description of pattern recognition for PRRSV, which is important in understanding the antiviral response of arteriviruses, especially PRRSV, and extends our knowledge on virus recognition.
Maternal effects better predict walleye recruitment in Escanaba Lake, Wisconsin, 1957–2015: implications for regulations
Authors: Shaw Stephanie L. , Sass Greg G. , VanDeHey Justin A.
Published: March 2018

Maternal influences on age-0 walleye (Sander vitreus (Mitchill, 1818)) recruit abundance and survival from egg to fall were observed in Escanaba Lake, Wisconsin, in 1957–2015. Annual egg production best explained variation in age-0 recruitment, compared with female relative abundance, and adult abundance (sexes combined). Age-0 recruitment was not significantly correlated with any temperature metric tested or our index of yellow perch (Perca flavescens (Mitchill, 1814)) abundance. Survival of walleye from egg to fall age-0 was positively correlated with the percent contribution of large females (>55.9 cm) to annual egg production. Mean size diversity of females by length class did not influence age-0 recruit abundance or survival over time. Evidence for maternal effects via size- and age-specific influences on fecundity and age-0 walleye survival suggest that exploitation may influence natural recruitment by altering adult female size structure. Given recent declines observed in walleye natural recruitment in the upper Midwestern USA, understanding the roles of maternal drivers and exploitation on recruitment is critical for sustainable walleye management.
A Novel Text Line Segmentation Method Based on Contour Curve Tracking for Tibetan Historical Documents
Authors: Zhou Fengming , Wang Weilan , Lin Qiang
Published: April 2018

In this paper, we proposed a novel method for text line segmentation of Tibetan historical document image with uchen script based on contour tracking. Our method is mainly to segment the text lines from the image documents using the contour curve of the text lines, which consists of three parts: First, we calculate the barycentre coordinates of the connected components for the text regions, and then the barycentre of each text line is connected in order, so that the main part of each text line is connected and a new connected component is formed; then the contour curve of the connected component is obtained using the contour tracing algorithm; Second, the contour curve and the barycentre gravity are used to assign key elements (such as the syllable point, the upper vowel, the lower vowel, and the broken strokes and so on) of the text lines, and next the candidate text lines are obtained based on these connected components; Finally, the contour tracking algorithm is used to calculate the contour curve of the candidate text lines and segment the text lines. We evaluated our text line segmentation method on the 200 document image data sets. Experimental results show that the proposed method based on contour curve tracing can accurately segment the text lines of image documents and achieve the encouraging results.
Beam dynamics design for a compact accelerator-driven neutron source
Authors: Li Haipeng , Gan Pingping , Fu Qi , Tan Qiuyun , Lu Yuanrong , Wang Zhi , Zhu Kun , Easton Matt
Published: April 2018

A compact accelerator-driven neutron source (CANS) has been proposed and designed by the Peking University (PKU) RFQ group. The source is based on a compact deuteron RF accelerator that delivers an average current of a few mA of deuterons at 11[Formula: see text]MeV to the target. The accelerator consists of a short radio frequency quadrupole (RFQ) followed by efficient interdigital H-mode drift tube linac (IH-DTL) structure. The total length of the whole accelerator structure is 4.96[Formula: see text]m, including 1.76[Formula: see text]m for the 4-vane RFQ and 2.70[Formula: see text]m for the IH-DTL. The dynamic simulation results show that the beam has excellent quality, with transmission efficiency higher than 99%. The transverse and longitudinal normalized rms emittance at the DTL exit is 0.29[Formula: see text]mm⋅mrad and 0.12 MeV⋅deg, respectively. Details of the beam dynamics of the RFQ and IH-DTL are presented in this paper.
PLASMA PRETREATMENT ON TASAR SILK FABRICS COATED WITH ZnO NANOPARTICLES AGAINST ANTIBACTERIAL ACTIVITY
Authors: RANI K. VINISHA , SARMA BORNALI , SARMA ARUN
Published: April 2018

Plasma pretreatment is an eco-friendly process employed to modify the surface properties and improve the adhesion properties of tasar silk fabrics. The plasma pretreatment has been carried out in DC glow discharge plasma at constant power and for different treatment durations (5, 10 and 30[Formula: see text]min). ZnO nanoparticles (ZnO NPs) play a significant role in antibacterial, cleaning and UV protection. ZnO NPs have been synthesized by the wet chemical method and the average crystallite size of the same is found to be 49[Formula: see text]nm using X-ray diffraction (XRD). Plasma treated silk fabrics are coated with ZnO NPs using vacuum thermal evaporation technique. Structural and chemical change of raw, untreated and plasma treated silk fabrics coated with ZnO NPs are analyzed by XRD and attenuated total reflection Fourier transform infrared (ATR-FTIR) studies. The surface morphologies of all the fabrics are analyzed by using scanning electron microscope (SEM), which confirms the adherence of ZnO NPs on the surface of the fabrics. Elemental analysis is carried out using energy dispersive spectroscopy, which confirms the presence of ZnO NPs on the surface of the fabrics. The improved surface property in terms of hydrophobicity is analyzed by using a contact angle test. It is found that the plasma pretreated silk fabrics coated with ZnO NPs have better antibacterial activities against Escherichia Coli bacteria.
Finite Deformations of an Elastic Cylinder During Indentation
Authors: Astapov Yuri , Khristich Dmitrii
Published: April 2018

The problem about the indentation of the rigid spherical stamp into the cylindrical specimen was considered. The material of the specimen was assumed to be weakly compressible. The formulation of the problem was performed for the case of finite deformations. The method of construction of the constitutive relations in terms of logarithmic strain tensor for elastic media and the variant of the algorithm to take into account the variation of the contact zone were proposed. The expansion of Hencky tensor and its time derivative into the series in powers of Cauchy strain tensor were used to calculate correctly the components of these tensors. Within the indentation problem, we used the model of nonlinear elastic material which provides the best agreement between numerical solution and experimental data among other used types of constitutive relations including various elastic and hypoelastic models.
Static Pull-in Analysis of Electrostatically Actuated Functionally Graded Micro-Beams Based on the Modified Strain Gradient Theory
Authors: Taati Ehsan , Sina Nima
Published: April 2018

In this paper, the static pull-in behavior of electrostatically actuated functionally graded (FG) micro-beams resting on an elastic medium is studied using the modified strain gradient (MSG) theory. To this end, the equilibrium equation along with classical and non-classical boundary conditions is obtained by considering the fringing field and elastic foundations effects within the principle of minimum total potential energy. Also, the elastic medium is composed of a shear layer (Pasternak foundation) and a linear normal layer (Winkler foundation). The governing differential equation is solved for cantilever and doubly fixed FG beams using an iterative numerical method. This method is a combination of the reduced-order technique, the fourth-order Runge–Kutta and shooting methods. The pull-in voltages of silicon beams obtained from the present model are compared with the experimental and theoretical results reported in the literature. It is seen that the MSG theory is able to reduce significantly the difference between pull-in voltages predicted by theoretical approaches based on the classical continuum theory and the experimental observations. Finally, a parametric study is carried out to analyze in detail the influences of power index, length scale parameters, coefficients of elastic foundations and boundary conditions on the pull-in behavior of FG micro-beams. Findings indicate that the size effect on the pull-in instability of FG micro-beams with both boundary conditions is significant; however, it is seen that the variation with the normalized length scale parameter of static pull-in voltages for doubly fixed beams is larger than cantilever beams. Also, it is shown that the increase of ceramic volume fraction can improve the pull-in resistance of beams. However, this influence becomes smaller with rise of power index for both cases.
Statistical Analysis of Nonlinear Response of Rectangular Cracked Plate Subjected to Chaotic Interrogation
Authors: Jalili Sina , Daneshmehr A. R.
Published: April 2018

The presence of part-through cracks with limited length is one of the prevalent defects in plate structures. The vibrational response of plates can be used to investigate the effect of crack presence. In this paper the modified line spring method (MLSM) is used to develop a nonlinear multi degree of freedom model of part-through cracked rectangular plate. After a convergence study in time series domain, tuning of the chaotic signal is conducted in two steps: (i) crossing of the Lyapunov exponents’ spectrums for the nonlinear model of the plate and the chaotic signal which assures the effectiveness of the model filter on the Lyapunov dimension of chaotic signal and (ii) varying the tuning parameter of chaotic signal to find a span in which tangible sensitivity in statistical parameters can be observed. Standard deviation, skewness and kurtosis are proposed as features to analyze the time series response of cracked plate. Damage characteristics such as: length, angle, location and depth of crack are considered as parameters to be varied in order to scrutinize the response of plates. Results show that by implementation of a tuned chaotic interrogator signal, tangible sensitivity and also near to monotonic behavior of statistical parameters versus damage characteristics are achievable.
Similarity and variation in the insulin-like growth factor 2 - H19 locus in primates
Authors: Rotwein Peter
Published: March 2018

Insulin-like growth factor 2 (IGF2), a small, secreted protein, is critical for fetal and prenatal growth in humans and other mammals. The IGF2 gene and its mouse homolog comprise part of a conserved linkage group that is regulated by parental imprinting, with IGF2/ Igf2 being expressed from the paternal chromosome, and the adjacent H19 gene from the maternal chromosome. By using information extracted from public genomic and gene expression databases, I have now analyzed this locus in nine nonhuman primate species representing over 60 million years of evolutionary divergence from a common progenitor. Both IGF2 and H19 genes and the entire locus have been conserved among these primates. Each primate IGF2 gene except for gibbon and marmoset is composed of 10 exons and contains five potential promoters, each with distinctive 5′-untranslated exons. Similarly, except for marmoset and mouse lemur, H19 consists of six exons and has two promoters. DNA sequence conservation is high, not only in orthologous exons and promoters, but also in a putative imprinting control region located 5′ to H19 and in multiple potential distal enhancer elements found 3′ to H19. Collectively, these results support the hypothesis that common regulatory processes shaped the IGF2 - H19 locus before the onset of primate speciation more than 85 million years ago. This study also leads to the conclusion that inaccuracies in data presentation in genetic repositories could limit our ability to develop novel insights about roles of individual genes and multigene loci in mammalian physiology and disease.
Endovascular Repair of Aortobronchial Fistula after Bentall Procedure
Authors: Gruenebaum Dane D. , Graf Ray , Alexander Thomas , Tavares Sergio , Surani Salim
Published: April 2018

Aortobronchial fistula (ABF) is a rare complication of aortic repair seen with both surgical and endovascular manipulation. The available literature largely refers to the need for surgical repair. We are not aware of any reports of endovascular repair after the Bentall procedure. This report describes a patient who after the Bentall procedure presented with massive hemoptysis from ABF, a multidisciplinary team decided on endovascular repair due to patient frailty to avoid redo sternotomy. We believe this is the first case report of endovascular repair and represents the success of multidisciplinary collaboration.
Postoperative Respiratory Impairment Is a Real Risk for Our Patients: The Intensivist’s Perspective
Authors: Rao Vidya K. , Khanna Ashish K.
Published: April 2018

Postoperative respiratory impairment occurs as a result of a combination of patient, surgical, and management factors and contributes to both surgical and anesthetic risk. This complication is challenging to predict and has been associated with an increase in mortality and hospital length of stay. There is mounting evidence to suggest that patients remain vulnerable to respiratory impairment well into the postoperative period, with the vast majority of adverse events occurring during the first 24 hours following discharge from anesthesia care. At present, preoperative risk stratification scores may be able to identify patients who are particularly prone to respiratory complications but cannot consistently and globally predict risk in an ongoing fashion as they do not incorporate the impact of intra- and postoperative events. Current postoperative monitoring strategies are not always continuous or comprehensive and do not dependably identify all cases of respiratory impairment or mitigate their sequelae, which may be severe and require the use of increasingly limited intensive care unit resources. As a result, postoperative respiratory impairment has the potential to cause significant downstream effects that can increase cost and adversely impact the care of other patients.
A GTCC-Based Underwater HMM Target Classifier with Fading Channel Compensation
Authors: Mohammed Shameer K. , Hariharan Supriya M. , Kamal Suraj
Published: April 2018

Underwater acoustic target classifiers are found to have many applications in military and security areas where a higher degree of prediction accuracy is needed that makes classifier efficiency and reliability an interesting subject. Classifiers are often trained with known acoustic target specimens with their characteristic feature set and tested with measurements obtained from the sonar that is deployed in the surveillance or observation zone. The selection of source-specific deterministic features in automatic target recognition (ATR) system is very significant, since it determines the reliability, efficiency, and success rate of the classifier. The robustness of the gammatone cepstral coefficients (GTCC) in combination with the statistical Euclidean distance, artificial neural network (ANN), and hidden Markov model (HMM) classifiers has been investigated, and its performance is compared with that of other feature extraction schemes. The classifier performance has been analyzed in Rayleigh fading conditions, based on which the performance is enhanced by incorporating an autoregressive (AR) Rayleigh fading channel compensation. The performance of the classifier in different operating conditions is investigated, with underwater target signals consisting of the real field data collected during expedition, and the results are presented in this paper.
Clinical and Pathological Characteristics of KEAP1- and NFE2L2-Mutated Non–Small Cell Lung Carcinoma (NSCLC)
Authors: Frank Rieke , Scheffler Matthias , Merkelbach-Bruse Sabine , Ihle Michaela A. , Kron Anna , Rauer Michael , Ueckeroth Frank , König Katharina , Michels Sebastian , Fischer Rieke , Eisert Anna , Fassunke Jana , Heydt Carina , Serke Monika , Ko Yon-Dschun , Gerigk Ulrich , Geist Thomas , Kaminsky Britta , Heukamp Lukas C. , Clement-Ziza Mathieu , Büttner Reinhard , Wolf Jürgen
Published: April 2018

Purpose: KEAP1 and NFE2L2 mutations are associated with impaired prognosis in a variety of cancers and with squamous cell carcinoma formation in non–small cell lung cancer (NSCLC). However, little is known about frequency, histology dependence, molecular and clinical presentation as well as response to systemic treatment in NSCLC.

Experimental Design: Tumor tissue of 1,391 patients with NSCLC was analyzed using next-generation sequencing (NGS). Clinical and pathologic characteristics, survival, and treatment outcome of patients with KEAP1 or NFE2L2 mutations were assessed.

Results: KEAP1 mutations occurred with a frequency of 11.3% (n = 157) and NFE2L2 mutations with a frequency of 3.5% (n = 49) in NSCLC patients. In the vast majority of patients, both mutations did not occur simultaneously. KEAP1 mutations were found mainly in adenocarcinoma (AD; 72%), while NFE2L2 mutations were more common in squamous cell carcinoma (LSCC; 59%). KEAP1 mutations were spread over the whole protein, whereas NFE2L2 mutations were clustered in specific hotspot regions. In over 80% of the patients both mutations co-occurred with other cancer-related mutations, among them also targetable aberrations like activating EGFR mutations or MET amplification. Both patient groups showed different patterns of metastases, stage distribution and performance state. No patient with KEAP1 mutation had a response on systemic treatment in first-, second-, or third-line setting. Of NFE2L2-mutated patients, none responded to second- or third-line therapy.

Conclusions: KEAP1- and NFE2L2-mutated NSCLC patients represent a highly heterogeneous patient cohort. Both are associated with different histologies and usually are found together with other cancer-related, partly targetable, genetic aberrations. In addition, both markers seem to be predictive for chemotherapy resistance. Clin Cancer Res; 24(13); 3087–96. ©2018 AACR.
Genetic Analysis of 779 Advanced Differentiated and Anaplastic Thyroid Cancers
Authors: Pozdeyev Nikita , Gay Laurie M. , Sokol Ethan S. , Hartmaier Ryan , Deaver Kelsi E. , Davis Stephanie , French Jena D. , Borre Pierre Vanden , LaBarbera Daniel V. , Tan Aik-Choon , Schweppe Rebecca E. , Fishbein Lauren , Ross Jeffrey S. , Haugen Bryan R. , Bowles Daniel W.
Published: April 2018

Purpose: To define the genetic landscape of advanced differentiated and anaplastic thyroid cancer (ATC) and identify genetic alterations of potential diagnostic, prognostic, and therapeutic significance.

Experimental Design: The genetic profiles of 583 advanced differentiated and 196 ATCs generated with targeted next-generation sequencing cancer-associated gene panels MSK-IMPACT and FoundationOne were analyzed.

Results: ATC had more genetic alterations per tumor, and pediatric papillary thyroid cancer had fewer genetic alterations per tumor when compared with other thyroid cancer types. DNA mismatch repair deficit and activity of APOBEC cytidine deaminases were identified as mechanisms associated with high mutational burden in a subset of differentiated thyroid cancers and ATCs. Copy number losses and mutations of CDKN2A and CDKN2B, amplification of CCNE1, amplification of receptor tyrosine kinase genes KDR, KIT, and PDGFRA, amplification of immune evasion genes CD274, PDCD1LG2, and JAK2, and activating point mutations in small GTPase RAC1 were associated with ATC. An association of KDR, KIT, and PDGFRA amplification with the sensitivity of thyroid cancer cells to lenvatinib was shown in vitro. Three genetically distinct types of ATCs are proposed.

Conclusions: This large-scale analysis describes genetic alterations in a cohort of thyroid cancers enriched in advanced cases. Many novel genetic events previously not seen in thyroid cancer were found. Genetic alterations associated with anaplastic transformation were identified. An updated schematic of thyroid cancer genetic evolution is proposed. Clin Cancer Res; 24(13); 3059–68. ©2018 AACR.
Diagnosis and Management of Asthma – The Swiss Guidelines
Authors: Rothe Thomas , Spagnolo Paolo , Bridevaux Pierre-Olivier , Clarenbach Christian , Eich-Wanger Christine , Meyer Franca , Miedinger David , Möller Alexander , Nicod Laurent P. , Nicolet-Chatelain Geneviève , Sauty Alain , Steurer-Stey Claudia , Leuppi Joerg D.
Published: April 2018

The Global Initiative for Asthma (GINA) is a network of individuals, organizations, and public health officials that was established to disseminate information about the care of patients with asthma and to improve asthma care. The GINA (“Global Strategy for Asthma Management and Prevention”) report has been updated annually since 2002. Due to new knowledge and therapeutic development in the field, the Swiss Respiratory Society felt the need to provide a new document that is based on both the available literature and the recommendations of the 2016 GINA report. Key new features of the 2016 GINA report include a “new” definition of asthma, underscoring its heterogeneous nature, and the core elements of variable symptoms and variable expiratory airflow limitation; the importance of confirming the diagnosis of asthma in order to minimize both under- and overtreatment; practical tools for the assessment of symptom control and risk factors for adverse outcomes; a comprehensive approach to asthma management that acknowledges the foundational role of inhaled corticosteroid therapy, but also provides a framework for individualizing patient care; an emphasis on maximizing the benefit of available medications by addressing common problems such as incorrect inhaler technique and poor adherence; a continuum of care for worsening asthma, starting with early self-management and progressing to primary care or acute care management; and diagnosis of the asthma/chronic obstructive pulmonary disease overlap syndrome. This document is meant to advice the key stakeholders on the diagnosis and management of asthma and highlights the need to individualize the care of each and every asthmatic patient.
Prevention Effect of Antiplatelets on Aneurysm Rupture in a Mouse Intracranial Aneurysm Model
Authors: Suzuki Tomo , Kamio Yoshinobu , Makino Hiroshi , Hokamura Kazuya , Kimura Tetsuro , Yamasaki Tomohiro , Hiramatsu Hisaya , Umemura Kazuo , Namba Hiroki
Published: April 2018

Background and Purpose: Subarachnoid hemorrhage (SAH) from intracranial aneurysm rupture results in significant morbidity and mortality. In the present study, we examined the effect of most widely used antiplatelet drugs, aspirin and cilostazol, on aneurysm rupture prevention using a mouse intracranial aneurysm model. Materials and Methods: Intracranial aneurysms were induced by a combination of deoxycorticosterone acetate-salt and a single injection of elastase into the cerebrospinal fluid in mice. Treatment with aspirin or cilostazol was started 1 day after aneurysm induction. Aneurysm rupture was detected by neurological symptoms and the presence of intracranial aneurysm with SAH was confirmed by post-mortem examination. Results: Aspirin (10 mg/kg) significantly reduced aneurysm rupture (control:aspirin = 80%:31%, p < 0.05) without affecting the overall incidence of aneurysm formation (60%:62%). Cilostazol (3 mg/kg, 30 mg/kg) did not reduce both rupture rate (control:3 mg/kg:30 mg/kg = 81%:67%:77%) and the overall incidence of aneurysm formation (control:3 mg/kg:30 mg/kg = 72%:71%:76%). Tail vein bleeding time prolonged significantly in both aspirin and cilostazol groups (p < 0.01). Conclusion: Aspirin prevented aneurysm rupture in a mouse intracranial aneurysm model, while cilostazol did not. Aspirin, the most frequently used drug for patients with ischemic myocardial and cerebral diseases, is also effective in preventing cerebral aneurysmal rupture.
Propofol Disrupts Aerobic Glycolysis in Colorectal Cancer Cells via Inactivation of the NMDAR-CAMKII-ERK Pathway
Authors: Chen Xiangyuan , Wu Qichao , Sun Pengfei , Zhao Yanjun , Zhu Minmin , Miao Changhong
Published: April 2018

Background/Aims: To investigate the effect of propofol on glucose metabolism in colorectal cancer cells and in an in vivo xenograft model. Methods: Glucose metabolism was assessed by measuring the extracellular acidification rate in HT29 and SW480 colorectal cancer cells. Quantitative real-time PCR and western blot analyses were used to detect mRNA and protein levels, respectively. Intracellular calcium was assessed by using a Fluo-3 AM fluorescence kit. Micro-positron emission tomography/computed tomography (microPET/CT) imaging was used to analyze glucose metabolism in the tumors of the xenograft model. Results: Propofol exposure induced a dose-dependent decrease of aerobic glycolysis in HT29 and SW480 colorectal cancer cells. MicroPET/CT indicated that propofol also inhibited 18F-FDG uptake in the xenograft model. In addition, hypoxia-inducible factor 1α (HIF1α) was also reduced by propofol dose-dependently. Propofol repressed the NMDAR-CAMKII-ERK pathway to inactivate HIF1α and therefore reduced glycolysis. Conclusion: Propofol inhibited aerobic glycolysis in colorectal cancer cells through the inactivation of the NMDAR-CAMKII-ERK pathway, which may facilitate a better understanding of the use of propofol in the clinical setting.
TTR (Transthyretin) Stabilizers Are Associated With Improved Survival in Patients With TTR Cardiac Amyloidosis
Authors: Rosenblum Hannah , Castano Adam , Alvarez Julissa , Goldsmith Jeff , Helmke Stephen , Maurer Mathew S.
Published: April 2018

Background:

TTR (transthyretin) cardiac amyloidosis is caused by dissociation of TTR into monomers, which misassemble into amyloid fibrils. TTR stabilizers act at the dimer–dimer interface to prevent dissociation. We investigated differences in survival among patients with TTR cardiac amyloidosis on stabilizer medications compared with those not on stabilizers.

Methods AND RESULTS:

A retrospective study of patients with TTR cardiac amyloidosis presenting to a single center was conducted. Baseline characteristics were compared between those treated with stabilizers and those not treated with stabilizers. Cox proportional hazards modeling assessed for univariate predictors of the composite outcome of death or orthotopic heart transplant (OHT). Multivariable Cox proportional hazards assessed whether stabilizer treatment was independently associated with improved death or OHT after controlling for significant univariate predictors. One hundred twenty patients (mean age, 75±8, 88% male) were included: 29 patients who received stabilizers and 91 patients who did not. Stabilizer use was associated with a lower risk of the combined end point of death or OHT (hazard ratio, 0.32; 95% confidence interval, 0.18–0.58;
P
<0.0001). Subjects treated with stabilizers were more likely to be of White race (93% versus 55%;
P
<0.001), classified as New York Heart Association classes I and II (79% versus 38%;
P
=0.002), less likely to have a mutation (10% versus 36%;
P
=0.010), have lower troponin I (median 0.06 versus 0.12 ng/mL;
P
=0.002), and higher left ventricular ejection fraction (49% versus 40%;
P
=0.011), suggesting earlier stage of disease. In multivariable Cox analysis, the association between stabilizer and death or OHT persisted when adjusted for all noncollinear univariate predictors with
P
<0.05 (hazard ratio, 0.37; 95% confidence interval, 0.19–0.75;
P
=0.003).

Conclusions:

TTR stabilizers are associated with decreased death and OHT in TTR cardiac amyloidosis. These results need to be confirmed by ongoing randomized clinical trials.
Rashbam’s Approach to Targum Onqelos in His Commentary to the Torah
Authors: Jacobs Jonathan
Published: April 2018

The Targum of Onqelos was the principal pentateuchal targum on which medieval Jews in northern France relied. When Rashbam referenced Onqelos, he used a consistent format composed of four elements. His use of the targum is varied: in most instances, his purpose was lexical. In about one-third of cases, his purpose was exegetical. In three cases, Rashbam cited the targum in order to consider its precise intention (while finding fault with the conclusion reached by Rashi in that regard), an indication of the great importance that Rashbam ascribed to the targum. Nevertheless, despite the high esteem in which he held the targum, Rashbam occasionally allowed himself to disagree with it in his quest to uncover the simplest sense of Scripture. Targum Onqelos is the work most often quoted in Rashbam’s commentary to the Torah, and his use of it demonstrates extensive knowledge of this targum to the Torah.
Erasmus on Dogs and Baths and Other Odious Comparisons
Authors: Eden Kathy
Published: March 2018

Fully aware of an antipathy to comparisons that looks back not only to ancient philosophy and law but to the early modern schoolroom, Erasmus nevertheless puts his full prestige behind the strategy so foundational to the rhetorical theory of Plato, Cicero, Quintilian and Aphthonius. This essay examines the key role of comparison in the form of similitudo, parabola or collatio, and imago in Erasmus’ educational reform as represented by his De copia, De ratione studii, and De conscribendis epistolis, as well as in his own literary production, especially his Adages.
Two new species of Craterellus (Cantharellaceae) from tropical India
Authors: BIJEESH C. , KUMAR A. MANOJ , VRINDA K.B. , PRADEEP C.K.
Published: April 2018

Two unusual species of Craterellus have been collected numerous times from the evergreen tropical forests in Kerala State, India. The species Craterellus albostrigosus and Craterellus inusitatus are described as new based on morphological and phylogenetic analyses of nrLSU-rDNA gene region. Complete morphological descriptions, photographs and comparisons with similar species are provided as well as a key to the known species of Craterellus from India.
Discovery of a new species of Dryocosmus Giraud, 1859 (Hymenoptera: Cynipidae: Cynipini) on Castanopsis tibetana from China
Authors: PANG YIN , SU CHENG-YUAN , ZHU DAO-HONG
Published: April 2018

A new gall wasp species, Dryocosmus liui Pang, Su et Zhu n. sp., is described from Hunan Province, China. The new species forms integral galls on branches of Castanopsis tibetana Hance. The results of morphological comparison, pair-wise genetic distance of mtDNA COI, and phylogenetic analysis based on COI gene sequences did not support treating Chilaspis and Dryocosmus as separate genera. Our results also provided new evidence supporting the notion that the Nearctic Dryocosmus species may represent a lineage distinct from the Old World species of the genus.
Sea-Effect Precipitation over the Shandong Peninsula, Northern China
Authors: Bao Baoleerqimuge , Ren Guoyu
Published: April 2018

Sea-effect precipitation (SEP) over the Shandong Peninsula is a unique climatological phenomenon in mainland China, and it exerts a considerable impact on the southern shore of the Bohai Sea. From observed data from 123 stations for the period 1962–2012, the characteristics of cold-season (November–February) SEP in this area were analyzed. Results showed that SEP occurred throughout the late autumn and winter. In all, 1173 SEP days were identified during the 51 years, of which snow days accounted for 73.7% and rain and snow–rain days accounted for 16.1% and 10.1%, respectively. December had the largest number of SEP snow days, followed by January and November. November was the most productive month in terms of SEP rain and snow–rain days. Intense SEP snowfall mainly affected the inland hill area of the peninsula, whereas light SEP snowfall reached farther inland. SEP rainfall shared a similar pattern with snowfall. The SEP frequency showed a significant interannual variability and a nonsignificant upward trend over the period analyzed. SEP was most likely to occur when the temperature difference between sea surface and 850 hPa over the Bohai Sea was above 10°C, indicating a dominant influence of low-level cold-air advection over the sea on the generation and development of the weather phenomenon. A significant negative correlation was also found between the area of sea ice in the Bohai Sea and intense SEP snowfall, indicating that sea ice extent had an important effect on SEP variability over the peninsula. In the case of extremely intense SEP events, a deeper East Asian trough at the 500-hPa level developed over the southwest of the study area and temperature and geopotential height contours were orthogonal to each other, indicating strong geostrophic cold-air advection over the Bohai Sea and the Shandong Peninsula. The extremely intense SEP events were also characterized by anomalous low temperature and high relative humidity in the lower troposphere, which contributed to greater gravitational instability in the study area.
Political Participation of Women in Local Governance: A Case Study of Selected Local Government Bodies in Eastern Sri Lanka
Authors: Rameez Aboobacker
Published: April 2018

Although Sri Lanka has 51% women, their participation in local governance as well as in the national parliament is 5% in total. The strong social development indicator of women in areas such as health and education has not translated into their increased political participation. As such, this study focuses on the level of women’s participation in local governance and explores why there is a low level of political participation of women in local governance. Both quantitative and qualitative methods comprising of questionnaire survey, interviews and focus group discussions were employed in this study. The findings show organized collective involvement of women was effective only in social welfare, livelihood and social security than political participation. The study also reveals that the low level of political participation by women is attributable to biological, economic, psychological, religious and political factors. Overall, it was found that although women are interested in participating in local governance, they have a lack of space for political participation.
The Evidence Base for the Maternal, Infant, and Early Childhood Home Visiting Program Constructs
Authors: Campos Sofia , Kapp Julie M. , Simoes Eduardo J.
Published: April 2018

Objectives:

The federal Maternal, Infant, and Early Childhood Home Visiting (MIECHV) program requires grantees to demonstrate program improvement as a condition of funding. The MIECHV program monitors grantee progress in federally mandated conceptual areas (ie, benchmarks) that are further subcategorized into related sub-areas or constructs (eg, breastfeeding). Each construct has an associated performance measure that helps MIECHV collect data on program implementation and performance. In 2016, MIECHV modified the constructs and associated performance measures required of grantees. Our objective was to identify whether the constructs were supported by the home visiting literature.

Methods:

We conducted an evaluation of one of the MIECHV program’s benchmarks (Benchmark 1: Maternal and Newborn Health) for alignment of the Benchmark 1 constructs (preterm birth, breastfeeding, depression screening, well-child visit, postpartum care, and tobacco cessation referrals) with home visiting evidence. In March 2016, we searched the Home Visiting Evidence of Effectiveness database for all publicly available articles on studies conducted in the United States to determine how well the study findings aligned with the MIECHV program constructs.

Results:

Of 59 articles reviewed, only 3 of the 6 MIECHV constructs—preterm birth, breastfeeding, and well-child visits—were supported by home visiting evidence.

Conclusions:

This evaluation highlights a limited evidence base for the MIECHV Benchmark 1 constructs and a need to clarify other criteria, beyond evidence, used to choose constructs and associated performance measures. One implication of not having evidence-based performance measures is a lack of confidence that the program will drive positive outcomes. If performance measures are not evidence based, it is difficult to attribute positive outcomes to the home visiting services.
Identifying Barriers to Collaboration Between Primary Care and Public Health: Experiences at the Local Level
Authors: Pratt Rebekah , Gyllstrom Beth , Gearin Kim , Lange Carol , Hahn David , Baldwin Laura-Mae , VanRaemdonck Lisa , Nease Don , Zahner Susan
Published: April 2018

Objectives:

Interest is increasing in collaborations between public health and primary care to address the health of a community. Although the understanding of how these collaborations work is growing, little is known about the barriers facing these partners at the local level. The objective of this study was to identify barriers to collaboration between primary care and public health at the local level in 4 states.

Methods:

The study team, which comprised 12 representatives of Practice-Based Research Networks (networks of practitioners interested in conducting research in practice-based settings), identified 40 key informants from the public health and primary care fields in Colorado, Minnesota, Washington State, and Wisconsin. The key informants participated in standardized, semistructured telephone interviews with 8 study team members in 2014 and 2015. Interviews were audio recorded and transcribed verbatim. We analyzed key themes and subthemes by drawing on grounded theory.

Results:

Primary care and public health participants identified similar barriers to collaboration. Barriers at the institutional level included the challenges of the primary care environment, in which providers feel overwhelmed and resources are tight; the need for systems change; a lack of partnership; and geographic challenges. Barriers to collaboration included mutual awareness, communication, data sharing, capacity, lack of resources, and prioritization of resources.

Conclusions:

Some barriers to collaboration (eg, changes to health care billing, demands on provider time) require systems change to overcome, whereas others (eg, a lack of shared priorities and mutual awareness) could be addressed through educational approaches, without adding resources or making a systemic change. Overcoming these common barriers may lead to more effective collaboration.