bluuebunny/crossref_metadata_2025 huggingface dataset:
An international study on the use of peroral endoscopic myotomy (POEM) in the management of esophageal diverticula: the first multicenter D-POEM experience
Authors: Yang Juliana , Zeng Xianhui , Yuan Xianglei , Chang Kenneth , Sanaei Omid , Fayad Lea , Kumbhari Vivek , Singh Vikesh , Kalloo Anthony , Hu Bing , Khashab Mouen
Published: November 2018

Background The aim of this study is to report a novel, multicenter experience with the diverticular peroral endoscopic myotomy (D-POEM) technique in the management of esophageal diverticula.

Methods This is a multicenter, international, retrospective study involving three centers. D-POEM was performed using the principles of submucosal endoscopy.

Results A total of 11 patients with an esophageal diverticulum (Zenker’s 7, mid-esophagus 1, epiphrenic 3) were included. The mean size of the esophageal diverticula was 34.5 mm. The overall technical success rate of D-POEM was 90.9 %, with a mean procedure time of 63.2 minutes. There were no adverse events. Clinical success was achieved in 100 % (10 /10), with a decrease in mean dysphagia score from 2.7 to 0.1 (P < 0.001) during a median follow-up of 145 days (interquartile range 126 – 273).

Conclusion Endoscopic management of esophageal diverticula using the novel technique of D-POEM appears promising. This first case series on D-POEM suggests that the procedure is feasible, safe, and effective in the management of esophageal diverticula. D-POEM offers the distinct advantage of ensuring a complete septotomy. Larger studies are needed to confirm these intriguing results.
In vitro Anti-Trypanosomal Activities of Indanone-Based Chalcones
Authors: Beteck Richard M. , Legoabe Lesetje J. , Isaacs Michelle , Hoppe Heinrich C.
Published: November 2018

Human African trypanosomiasis is a neglected infectious disease that affects mostly people living in the rural areas of Africa. Current treatment options are limited to just four drugs that have been in use of four to nine decades. The life-threatening toxic side-effects associated with the use of these drugs are disconcerting. Poor efficacy, low oral bioavailability, and high cost are other shortcomings of current HAT treatments. Evaluating the potentials of known hits for other therapeutic areas may be a fast and convenient method to discover new hit compounds against alternative targets. A library of 34 known indanone based chalcones was screened against T.b. brucei and nine potent hits, having IC50 values between 0.5–8.9 µM, were found. The SAR studies of this series could provide useful information in guiding future exploration of this class of compounds in search of more potent, safe, and low cost anti-trypanosomal agents. Graphical Abstract
Electronic Collection of Multilingual Patient-Reported Outcomes across Europe
Authors: Soto-Rey I. , Rehr M. , Bruland P. , Zeidler C. , Riepe C. , Steinke S. , Ständer S. , Dugas M. , Storck M.
Published: November 2018

Background Patient-reported outcomes (PROs) are information provided directly by patients that helps in improving patient diagnosis and treatment. Validated translations of PROs can be used to treat international patients. Electronic systems and especially mobile devices provide a great opportunity for their collection; however, these systems are normally study-oriented and therefore single language, not scalable, and not interoperable.

Objectives This article reports the development of a multicenter, multilingual, and interoperable electronic PRO (ePRO) system and evaluates its user satisfaction in an international clinical study.

Methods The ePRO named “MoPat2” was developed using Java 8 and jQuery Mobile 1.4.5. The system was evaluated in the context of the European dermatology project “European Network on Assessment of Severity and Burden of Pruritus”(PruNet), which aimed to unify the assessment of itch in routine dermatological care in Europe. Twenty-six clinicians and 468 patients from 8 European clinical centers were asked to complete a user satisfaction questionnaire regarding the use of MoPat2 with a tablet personal computer. The results were then analyzed and correlated with the age, gender, and language of the respondents.

Results MoPat2 was enhanced with multilingual capabilities and is now able to conduct surveys in several languages, as well as store and display the results in the local language. The interviewed clinicians rated the system with an average score of 2.0 (“good”) in a 1 to 5 Likert scale. Note that 93.9% of the patients (439 of 468) reported having got on well using the system and 88.9% (416 of 456) would be willing to further use it. The age of the patients not willing to further use MoPat2 was, in average, considerably higher than the age of patients willing to use the system.

Conclusions This study represents the first use of an ePRO system for the collection of multilingual PROs in an international, multicenter setting. MoPat2 has been evaluated by both clinicians and patients in the context of a European dermatological study, resulting in a high user satisfaction. The system will be further developed to include new features such as patient follow-ups outside of the clinical setting.
A spatially smoothed device model for meso-structured perovskite solar cells
Authors: Xue Hansong , Birgersson Erik , Stangl Rolf
Published: November 2018

Meso-structured perovskite solar cells (PSC), utilizing a mesoporous absorber layer consisting of mesoporous metal oxide and the perovskite material inside, are still delivering the highest solar cell efficiency for perovskite-based solar cells up to date. Their outstanding performance critically depends on the nanoscopic morphology formed inside the mesoporous absorber layer. This, however, is not accounted for in most of the perovskite device models, as they are based on an effective-medium formulation for the mesoporous absorber layer, and the details of its underlying morphology are ignored. The mesoporous absorber layer is treated as a two-phase model that describes intrinsic solar cell physics such as free charge carrier generation, carrier transport, and recombination within the two phases, as well as at the interface between the two phases. We derive a spatially smoothed device model for meso-structured PSCs based on volume-averaging of electric potential and electron and hole concentrations of the two-phase model, and this spatially smoothed formulation captures two essential morphological descriptors that are not found in existing effective-medium formulations for meso-structured PSCs, namely, surface-to-volume ratio and porosity inside the mesoporous layer. Furthermore, we determine the explicit functional forms of the effective parameters in the spatially smoothed model for the case of an ideal “Spaghetti” blend morphology.
Damping-like spin-orbit-torque-induced magnetization dynamics in ferrimagnets based on Landau-Lifshitz-Bloch equation
Authors: Zhu Zhifeng , Fong Xuanyao , Liang Gengchiau
Published: November 2018

A theoretical model based on the Landau-Lifshitz-Bloch equation is developed to study the effect of damping-like spin-orbit torque in ferrimagnets, which can capture many experimental findings. For example, the sample changes from Gd to FeCo dominate by increasing temperature, the damping-like spin-orbit torque has a peak at the magnetization compensation temperature, and angular-momentum compensation temperature increases as a function of Gd concentration. In contrast to the ferromagnet system, the switching trajectory in ferrimagnets is found to be precession free. The two sublattices are not always collinear, which produce a large exchange field affecting the magnetization dynamics. The study of material composition shows the existence of an oscillation region at intermediate current density, induced by the nondeterministic switching. Compared to the Landau-Lifshitz-Gilbert model, our developed model based on the Landau-Lifshitz-Bloch equation enables the systematic study of the spin-torque effect and the evaluation of ferrimagnet-based devices.
Atomic layer deposition of titanium nitride for quantum circuits
Authors: Shearrow Abigail , Koolstra Gerwin , Whiteley Samuel J. , Earnest Nathan , Barry Peter S. , Heremans F. Joseph , Awschalom David D. , Shirokoff Erik , Schuster David I.
Published: November 2018

Superconducting thin films with high intrinsic kinetic inductance are of great importance for photon detectors, achieving strong coupling in hybrid systems, and protected qubits. We report on the performance of titanium nitride resonators, patterned on thin films (9–110 nm) grown by atomic layer deposition, with sheet inductances of up to 234 pH/□. For films thicker than 14 nm, quality factors measured in the quantum regime range from 0.2 to 1.0 × 106 and are likely limited by dielectric two-level systems. Additionally, we show characteristic impedances up to 28 kΩ, with no significant degradation of the internal quality factor as the impedance increases. These high impedances correspond to an increased single photon coupling strength of 24 times compared to a 50 Ω resonator, transformative for hybrid quantum systems and quantum sensing.
Phase-dependent structural and electrochemical properties of single crystalline MnS thin films deposited by DC reactive sputtering
Authors: Tiwari Pranjala , Malik Gaurav , Chandra Ramesh
Published: November 2018

Single crystalline α- and γ-MnS thin films have been deposited on Si and ITO substrates by reactive DC sputtering (Ar:H2S 2:1) of a manganese target for electrochemical energy storage application. We found that working pressure was one of the major parameters while optimizing the crystallinity of thin films, whereas the phase tuning (γ to α) was primarily controlled by temperature variations. The temperature was varied from RT to 450 °C, keeping the gas pressure constant at 10 mTorr optimized value, resulting in a transition between two different polymorphs of MnS as confirmed by XRD results. AFM and contact angle measurements were also performed to study the surface roughness, wetting properties, and surface energy calculations of prepared thin films. α-MnS films prepared at 400 °C were found to have a maximum contact angle of 118° and a minimum free surface energy (γSV) of 8.38 mN/m. Moreover, we have also studied the phase dependent electrochemical properties and found that γ-MnS thin films prepared at ambient substrate temperature displayed the highest specific capacitance of 178.3 F/g at a scan rate of 5 mV/s with superior charge-discharge rates in neutral electrolytes. As the substrate temperature was increased to 300 °C, we observed a continuous decrease in the respective specific capacitance values, and α-MnS electrodes were found to have a minimum specific capacitance of 120 F/g. The enhanced electrochemical performance of γ-MnS thin films can be attributed to the superior water interacting properties (θw = 90.4°) and its wurtzite structure, which enables easy penetration of electrolytes into the active materials.
Nonlinear vibrations of circular single-layer black phosphorus resonators
Authors: Liu Rumeng , Wang Lifeng , Zhao Junhua
Published: November 2018

A strong nonlinear relationship between the displacement and the load in single-layer black phosphorus sheets (SLBPs) was observed under the large deflection by nanoindentation experiments. However, the nonlinear effect is rarely considered in the Nano-Electro-Mechanical-System (NEMS) resonators based on the SLBPs. In this letter, nonlinear static and dynamics behaviors of circular SLBPs (CSLBPs) are investigated using molecular dynamics (MD) simulations and a nonlinear orthotropic plate model (NOPM), respectively, where the geometrical nonlinearity is systematically considered in the NOPM. Our results show that the response-frequency curves of forced vibrations in CSLBPs meet clear hardening-type nonlinearity. The damping ratios of CSLBPs are proportional to the square of the vibration amplitude. In particular, the NOPM together with the law of energy equipartition is further utilized to study the nonlinear thermal vibrations of the CSLBPs. Checking against present MD calculations shows that the solution of the present NOPM has high accuracy. The present study should be of great help for designing NEMS resonators based on two-dimensional (2D) orthotropic materials.
Non-intrusive probing of fluid mixing with double diffusion layers brings insight into its origin and evolution
Authors: DeJarnette Drew
Published: November 2018

A setup combining interferometry and particle image velocimetry observes compositional and flow dynamics of double diffusive layers, elucidating the stability and evolution of the these fields’ gradients.
Genotype × environment interaction and genetic association of grain iron and zinc content with other agronomic traits in RIL population of pearl millet
Authors: Singhal Tripti , Satyavathi C. Tara , Kumar Aruna , Sankar S. Mukesh , Singh S. P. , Bharadwaj C. , Aravind J. , Anuradha N. , Meena M. C. , Singh Nirupama
Published: November 2018

Biofortification of lines of pearl millet (Pennisetum glaucum (L.) R.Br.) with increased iron (Fe) and zinc (Zn) will have great impact because pearl millet is an indispensable component of food and nutritional security of inhabitants of arid and semi-arid regions. The aim of the present study was to assess the stability of Fe and Zn content in recombinant inbred lines (RILs) developed for grain Fe and Zn content, and to use these lines in developing micronutrient-rich pearl millet hybrids. A mapping population consisting of 210 RILs along, with parents and checks, was assessed in three consecutive years (2014–16) under rainfed conditions at the same experimental location in an alpha design with two repetitions. Significant differences were observed in genotype, environment and genotype × environment interaction mean squares for all variables, particularly grain micronutrients. The first two principal components of an interaction principal component analysis cumulatively explained 100% of the total variation; respective contributions of the first and second components were 64.0% and 36.0% for Fe, and 58.1% and 41.9% for Zn. A positive and moderately high correlation (0.696**) between Fe and Zn contents suggests good prospects of simultaneous improvement for both micronutrients. Among the 210 RILs, RIL 69, RIL 186, RIL 191, RIL 149 and RIL 45 were found to be more stable with higher mean micronutrient content, additive main effects and multiplicative interaction stability value (ASV) and genotype selection index (GSI) under rainfed condition. These RILs are promising and can be tested further for their combining ability for yield as well as grain micronutrient content for developing superior biofortified, heterotic pearl millet hybrids.
Association of steroid 17-alpha-hydroxylase/17,20 lyase (CYP17) single nucleotide polymorphism (SNP) 628 and dopamine receptor D2 (DRD2) SNP939 genotypes with sheep reproductive performance
Authors: Qiu Xiaoyan , Xiao Xiong , Li Nan , Ling Wenhui , Wang Mingyu , Li Yuemin
Published: November 2018

In a previous study we investigated the association between two single nucleotide polymorphism (SNP) genotypes, namely steroid 17-alpha-hydroxylase/17,20 lyase (CYP17) SNP628 and dopamine receptor D2 (DRD2) SNP939, with two temperaments (calm and nervous) in Australian Merino sheep and concluded that the DRD2 SNP939 T/T genotype combined with the CYP17 SNP628 G/G genotype is associated with a calm temperament and could be used as a potential marker for calm sheep, whereas the DRD2 SNP939C allele combined with the CYP17 SNP628 A/A genotype is associated with a nervous temperament and could be used as a potential marker for nervous sheep. In sheep, the association between temperament and reproductive performance has been determined, but the association of these two SNP genotypes with sheep reproduction has not been investigated. Therefore, using Chinese Sinkiang Merino sheep, the present study investigated the association of the two CYP17 SNP628 and DRD2 SNP939 genotypes with sheep reproductive performance. Sheep with the DRD2 SNP939 T/T genotype combined with the CYP17 SNP628 G/G genotype had a higher ovulation rate, multiple gestation rate, better maternal behaviour and lower lamb mortality. Thus, the results of this study contribute to our knowledge of the association between genotypes and reproduction in sheep, which is beneficial for sheep genetics and breeding.
Testing the retroelement invasion hypothesis for the emergence of the ancestral eukaryotic cell
Authors: Lee Gloria , Sherer Nicholas A. , Kim Neil H. , Rajic Ema , Kaur Davneet , Urriola Niko , Martini K. Michael , Xue Chi , Goldenfeld Nigel , Kuhlman Thomas E.
Published: November 2018

Significance

Phylogenetic evidence suggests that a factor in the emergence of the ancestral eukaryotic cell may have been selection pressure resulting from invasion and proliferation of retroelements. Here we experimentally determine the effects of a retroelement invasion on genetically simple host organisms, and we demonstrate theoretically that the observed effects are sufficient to explain their observed rarity in bacteria. We also show that nonhomologous end-joining (NHEJ), a mechanism of DNA repair found in all extant eukaryotes, but only some bacteria, significantly enhances the efficiency of retrotransposition and the effects of retroelements on the host. We hypothesize that the interplay of NHEJ and retroelements may have played a previously unappreciated role in the evolution of advanced life.
Structural analysis of transient reaction intermediate in formic acid dehydrogenation catalysis using two-dimensional IR spectroscopy
Authors: Zhang Yufan , Chen Xin , Zheng Bin , Guo Xunmin , Pan Yupeng , Chen Hailong , Li Huaifeng , Min Shixiong , Guan Chao , Huang Kuo-Wei , Zheng Junrong
Published: November 2018

Significance

We demonstrate that the transient intermediate structure, which is too fast for traditional techniques, e.g. NMR or X-ray diffraction, to resolve in a thermally driven reaction can be determined in situ with the vibrational cross-angle method. The principle of the method illustrated in the work is general for other organic reactions and the method is expected to bring profound impacts for the studies of chemical reactions. The reaction mechanism of a well-defined catalytic system with performance to generate H
2
from formic acid is elucidated.
On a Discretization of Confocal Quadrics. A Geometric Approach to General Parametrizations
Authors: Bobenko Alexander I , Schief Wolfgang K , Suris Yuri B , Techter Jan
Published: November 2018

We propose a discretization of classical confocal coordinates. It is based on a novel characterization thereof as factorizable orthogonal coordinate systems. Our geometric discretization leads to factorizable discrete nets with a novel discrete analog of the orthogonality property. A discrete confocal coordinate system may be constructed geometrically via polarity with respect to a sequence of classical confocal quadrics. Various sequences correspond to various discrete parametrizations. The coordinate functions of discrete confocal quadrics are computed explicitly. The theory is illustrated with a variety of examples in two and three dimensions. These include confocal coordinate systems parametrized in terms of Jacobi elliptic functions. Connections with incircular nets and a generalized Euler–Poisson–Darboux system are established.
Neutron transfer reactions in accreting neutron stars
Authors: Chugunov A I
Published: November 2018

I suggest a novel type of nuclear reactions in accreting neutron stars – neutron transfer, which is quantum tunnelling of weakly bounded neutron from one nucleus to another. I estimate the rate of this process for fixed nuclei separation and then average the result over realistic distribution of nuclei to get the rate value for astrophysical conditions. The neutron transfer can modify reaction chains in accreting neutron stars, thus affecting their heating and cooling. In particular, it can suppress cooling by URCA pairs of nuclei, which is supposed to be crucial for the hottest neutron stars.
Combined Transpetrosal Approach With Preservation of Superior Petrosal Vein Drainage for a Cerebellopontine Angle Epidermoid Cyst Extending Into Meckel's Cave: 3-Dimensional Operative Video
Authors: Matsushima Ken , Kohno Michihiro , Nakajima Nobuyuki , Ichimasu Norio
Published: November 2018

The combined transpetrosal approach enables wide exposure around the petroclival region by cutting the tentorium and superior petrosal sinus. We often choose this approach for removal of tumors ventral to the facial and vestibulocochlear nerves, such as petroclival meningioma and epidermoid cyst, because complete removal of the tumor under direct visualization is required to prevent its later recurrence, especially in young patients. Recent reports revealed anatomical variations of the drainage of the superior petrosal sinus, and dural incision considering preservation of the superior petrosal vein was proposed.
1-3
This 3-dimensional video shows a patient with an epidermoid cyst, which was surgically treated using the combined transpetrosal approach, with consideration of the variation of the superior petrosal sinus and preservation of the drainage route of the superior petrosal vein. The video was reproduced after informed consent of the patient. The patient is a 31-yr-old woman who presented with a left cerebellopontine angle epidermoid cyst extending into Meckel's cave. The superior petrosal sinus was of the lateral type, draining only laterally into the transverse–sigmoid junction without medial connection with the cavernous sinus.
1
The combined transpetrosal approach was performed with cutting of the superior petrosal sinus medial to the entry point of the superior petrosal vein, in order to preserve its drainage into the transverse–sigmoid junction. Meckel’ cave was opened along its lateral margin, and tumor removal was accomplished, leaving only a minute part of the capsule strongly adhering to the neurovascular structures. The patient had no new permanent neurological deficits during follow-up.

The figures in the video were modified from Matsushima et al
1
by permission of the Congress of Neurological Surgeons.
Multiple Introductions Without Admixture of Colletotrichum truncatum Associated with Soybean Anthracnose in Brazil
Authors: Rogério Flávia , Gladieux Pierre , Massola Nelson Sidnei , Ciampi-Guillardi Maisa
Published: November 2018

Knowledge of the population structure, genetic diversity, and reproductive mode of plant pathogens can help to implement effective disease management strategies. Anthracnose is one of the most prominent diseases in soybean and is mainly associated with the species Colletotrichum truncatum. However, the genetic structure of C. truncatum populations associated with soybean remains unknown. We collected C. truncatum isolates from 10 sites representing two Brazilian states (Mato Grosso and Goiás) and used 13 highly polymorphic microsatellite markers to investigate the population genetic structure of the pathogen. Analyses revealed high gene and haplotypic diversity within populations, as well low genetic differentiation and sharing of multilocus haplotypes among populations and regions. Bayesian and multivariate analysis revealed the presence of three distinct genetic clusters with at least two coexisting in all locations, and all of them coexisting in eight locations. We found limited evidence for admixture between clusters, with only two isolates showing nonzero membership with a second cluster. Analyses of linkage disequilibrium rejected the hypothesis of random mating in all clusters, but values of the index of association were low and not consistent with long-term lack of sexual reproduction. Our findings suggest that Brazilian C. truncatum populations resulted from at least three founder events that led to three genetic clusters that spread throughout the country, raising questions with respect to the factors allowing their maintenance in syntopy without evidence of admixture between them.
Necrotrophic Exploitation and Subversion of Plant Defense: A Lifestyle or Just a Phase, and Implications in Breeding Resistance
Authors: Lorang Jennifer
Published: November 2018

Breeding disease-resistant plants is a critical, environmentally friendly component of any strategy to sustainably feed and clothe the 9.8 billion people expected to live on Earth by 2050. Here, I review current literature detailing plant defense responses as they relate to diverse biological outcomes; disease resistance, susceptibility, and establishment of mutualistic plant–microbial relationships. Of particular interest is the degree to which these outcomes are a function of plant-associated microorganisms’ lifestyles; biotrophic, hemibiotrophic, necrotrophic, or mutualistic. For the sake of brevity, necrotrophic pathogens and the necrotrophic phase of pathogenicity are emphasized in this review, with special attention given to the host-specific pathogens that exploit defense. Defense responses related to generalist necrotrophs and mutualists are discussed in the context of excellent reviews by others. In addition, host evolutionary trade-offs of disease resistance with other desirable traits are considered in the context of breeding for durable disease resistance.
The Impact of Endoscopic Retrograde Cholangiopancreatography on Islet Cell Yield During Total Pancreatectomy With Islet Autotransplantation
Authors: LaBarre Nicolas T. , Morgan Katherine A. , Adams David B. , Waljee Akbar K. , Coté Gregory A. , Elmunzer B. Joseph
Published: November 2018

Objectives

Many patients with recurrent acute and chronic pancreatitis who are candidates for total pancreatectomy and islet cell autotransplantation (TPIAT) undergo endoscopic retrograde cholangiopancreatography (ERCP). However, little is known on the impact of ERCP on TPIAT outcomes. We aimed to explore the effect of antecedent ERCP on islet yield and postoperative insulin requirement after TPIAT.

Methods

Through a prospectively maintained database, we identified patients who underwent TPIAT at our institution between 2009 and 2016. After adjusting for confounders, islet cell yield and postoperative insulin requirement were compared between subjects who did and did not undergo ERCP within 2 years prior to TPIAT.

Results

Data were available on 167 TPIAT patients during the study period; 105 (62.9%) had undergone ERCP within 2 years prior. Prior ERCP was not associated with a reduction in islet equivalents per patient kilogram (odds ratio, 1.37; 95% confidence interval, 0.75–2.5; P = 0.31). Antecedent ERCP was not associated with increased postoperative insulin requirement among patients with no diabetes undergoing TPIAT (odds ratio, 0.85; 95% confidence interval, 0.39–1.83; P = 0.67).

Conclusions

Antecedent ERCP does not appear to have a deleterious impact on islet cell yield during TPIAT. Additional multicenter data are needed to more clearly determine the impact of ERCP in this context.
Perineural Invasion is a Strong Prognostic Moderator in Ampulla of Vater Carcinoma
Authors: Luchini Claudio , Veronese Nicola , Nottegar Alessia , Riva Giulio , Pilati Camilla , Mafficini Andrea , Stubbs Brendon , Simbolo Michele , Mombello Aldo , Corbo Vincenzo , Cheng Liang , Yachida Shinichi , Wood Laura D. , Lawlor Rita T. , Salvia Roberto , Scarpa Aldo
Published: November 2018

Objective

Ampulla of Vater carcinoma (AVC) has a broad spectrum of different prognoses. As such, new moderators of survival are urgently needed. We aimed at clarifying the prognostic role of perineural invasion in AVC.

Methods

Using PubMed and SCOPUS databases, we conducted the first systematic review and meta-analysis on this topic.

Results

Analyzing 29 articles for a total of 2379 patients, we found that the presence of perineural invasion increased the risk of all-cause mortality more than 2 times (relative risk [RR], 2.07; 95% confidence interval [CI], 1.78–2.42 [P < 0.0001]; hazard ratio [HR], 2.72; 95% CI, 1.86–3.97 [P < 0.0001]), of cancer-specific mortality more than 6 times (RR, 6.12; 95% CI, 3.25–11.54 [P < 0.0001]; HR, 6.59; 95% CI, 2.29–3.49 [P < 0.0001]), and of recurrence more than 2 times (RR, 2.63; 95% CI, 1.89–3.67 [P < 0.0001]; HR, 2.54; 95% CI, 1.24–5.21 [P = 0.01]).

Conclusions

Perineural invasion is strongly associated with a poorer prognosis in AVC, influencing both survival and risk of recurrence. It should be reported in the final pathology report and should be taken into account by future oncologic staging systems, identifying a group of AVC with a more malignant biological behavior.
Expression of Epithelial-Mesenchymal Transition Proteins in Pancreatic Anaplastic (Undifferentiated) Carcinoma
Authors: Ishida Kazuyuki , Yamashita Rina , Osakabe Mitsumasa , Uesugi Noriyuki , Yamada Noriyuki , Nitta Hiroyuki , Fujishima Fumiyoshi , Motoi Fuyuhiko , Suzuki Hiroyoshi , Shimamura Hiromune , Noda Yutaka , Sawai Takashi , Unno Michiaki , Sasano Hironobu , Sasaki Akira , Sugai Tamotsu
Published: November 2018

Objectives

The aim of this study was to identify an association of pancreatic anaplastic carcinoma (APC) with the epithelial-mesenchymal transition (EMT).

Methods

Resected APCs (n = 24) were examined to assess components of APCs, including carcinomatous, transitional, and sarcomatous regions. Analysis was performed based on the immunoreactivity of E-cadherin and 3 EMT-related proteins: Slug (zinc finger protein SNAI2), Twist (Twist-related protein 1), and Zeb1 (zinc finger E-box–binding homeobox 1). Expression score was determined based on staining intensity and stained area of the target cells. Finally, we performed a hierarchical clustering based on the expression pattern of E-cadherin and EMT-related proteins of the sarcomatous component.

Results

The expression score of E-cadherin decreased in the order of sarcomatous > transitional > carcinomatous components (P < 0.01). Although there were significant differences in the immunohistochemical scores of Slug, Twist, and Zeb1 between carcinomatous and transitional components (P < 0.01), the significant difference in immunohistochemical score of Zeb1 between transitional and sarcomatous components was found (P < 0.05). Furthermore, APCs were divided into 2 subgroups based on the expression patterns of E-cadherin and EMT-related proteins (hierarchical clustering analysis). Consequently, these subgroups were distinguished by Twist expression.

Conclusions

Epithelial-mesenchymal transition plays an essential role in the pathogenesis of APC.
Transient Expression of Interleukin-21 in the Second Hit of Acute Pancreatitis May Potentiate Immune Paresis in Severe Acute Pancreatitis
Authors: Thomson John-Edwin , Nweke Ekene E. , Brand Martin , Nel Marietha , Candy Geoffrey P. , Fonteh Pascaline N.
Published: November 2018

Objectives

Interleukin-21 (IL-21) is a cytokine associated with tissue inflammation, autoimmune and infectious diseases. Organ dysfunction and death can occur in patients with acute pancreatitis (AP) in two distinct clinical phases. Initially, a systemic inflammatory response syndrome may be followed by systemic sepsis from infected pancreatic necrosis, known as the “second hit.” The expression and possible role of IL-21 in AP has not been established.

Methods

Thirty-six patients with mild, moderate, and severe AP (SAP) were enrolled. Peripheral blood samples of patients were drawn on days 7, 9, 11, and 13. Reverse transcription–polymerase chain reaction and enzyme-linked immunosorbent assay were performed to determine the expression and concentration of IL-21.

Results

Interleukin-21 mRNA levels increased significantly at day 9 in severe (P = 0.002) pancreatitis compared with both the mild and control patient groups. At the protein level, IL-21 was elevated in SAP patients compared with those with mild pancreatitis, although this was not significant. Furthermore, day 9 IL-21 was elevated in septic SAP patients and patients with pancreatic necrosis.

Conclusions

Interleukin-21 is transiently elevated in SAP compared with the mild/moderate group, and hence IL-21 may contribute to the immune imbalance that occurs in AP.
Performance of a Multidisciplinary Pancreatic Cancer Conference in Predicting and Managing Resectable Pancreatic Cancer
Authors: Rao Bharat , Syed Aslam , Singh Shailendra , Gulati Abhishek , Moussiade Ghita , Garg Mrinal , Sharma Manav , Morrissey Suzanne , Williams Harry , Atkinson Donald , Schiffman Suzanne , Monga Dulabh , Lupetin Anthony , Kirichenko Alexander , Mitre Marcia , Tang Amy , Dhawan Manish , Kulkarni Abhijit , Thakkar Shyam
Published: November 2018

Objectives

Surgery is the curative treatment for pancreatic ductal adenocarcinoma (PDA). Guidelines recommend utilizing a multidisciplinary pancreatic cancer conference (MDPC) in treatment; however, data are limited. The objective of this study was to assess the accuracy of an MDPC.

Methods

Patients with PDA presented at an MDPC were prospectively collected from April 2013 to August 2016. Patients were included if the MDPC predicted them to have resectable PDA and underwent upfront surgery. Secondary aims were to compare differences in tumor characteristics, time to surgery, and resection rates with patients prior to MDPC implementation (pre-MDPC).

Results

A total of 278 patients were presented at the MDPC. After excluding borderline and nonresectable cases, 91 patients were predicted as resectable on evaluation, and 70 were fit for surgery. The MDPC predicted resection in 91.4%. The MDPC had larger tumor size (32.6 vs 24.0 mm), greater proportion of stage II tumor, and a shorter time from diagnosis to resection (27.3 vs 35.5 days) compared with the pre-MDPC. Microscopically negative resections were similar between MDPC and pre-MDPC (85.9% vs 88.0%) despite advanced tumor size and stage.

Conclusions

The MDPC demonstrates a high resection rate. Compared with a pre-MDPC, MDPC provides shorter time to surgery and selects for advanced tumors.
Using insect natural history collections to study global change impacts: challenges and opportunities
Authors: Kharouba Heather M. , Lewthwaite Jayme M. M. , Guralnick Rob , Kerr Jeremy T. , Vellend Mark
Published: November 2018

Over the past two decades, natural history collections (NHCs) have played an increasingly prominent role in global change research, but they have still greater potential, especially for the most diverse group of animals on Earth: insects. Here, we review the role of NHCs in advancing our understanding of the ecological and evolutionary responses of insects to recent global changes. Insect NHCs have helped document changes in insects' geographical distributions, phenology, phenotypic and genotypic traits over time periods up to a century. Recent work demonstrates the enormous potential of NHCs data for examining insect responses at multiple temporal, spatial and phylogenetic scales. Moving forward, insect NHCs offer unique opportunities to examine the morphological, chemical and genomic information in each specimen, thus advancing our understanding of the processes underlying species’ ecological and evolutionary responses to rapid, widespread global changes.

This article is part of the theme issue ‘Biological collections for understanding biodiversity in the anthropocene’.
Systems Biology Theory Clarification of a Controversy in Pancreatic Beta Cell Regeneration
Authors: Cai Haoran , Cheng Runtan , Yuan Ruoshi , Zhu Xiaomei , Ao Ping
Published: November 2018

Whether new pancreatic beta-cells arise via pre-existing beta-cells or from differentiation of precursor cells − a question of fundamental importance for diabetic therapy − has long been debated. Recent experiments suggest that multipotent precursors from adult mouse pancreas, that give rise to beta-cells, do exist. However, such a finding is at odds with prior evidence that beta-cell expansions occurs exclusively through self-replication. Here we show that these two observations can be partially compatible. We use a systems biology approach to analyze the dynamics of the endogenous molecular-cellular network in the pancreas. Our results show that self-replicating ‘beta-cells’ can themselves be multipotent precursors. In addition, our model predicts heterogeneity in beta-cell regeneration and suggests various differentiation paths of precursors. This work therefore provides a means of reconciling an apparent contradiction in the field, but also sheds light on possible paths of beta-cell regeneration from a systems biology perspective.
Concurrent Multisensory Integration and Segregation with Complementary Congruent and Opposite Neurons
Authors: Zhang Wen-Hao , Wang He , Chen Aihua , Gu Yong , Lee Tai Sing , Wong K. Y. Michael , Wu Si
Published: November 2018

Our brain perceives the world by exploiting multiple sensory modalities to extract information about various aspects of external stimuli. If these sensory cues are from the same stimulus of interest, they should be integrated to improve perception; otherwise, they should be segregated to distinguish different stimuli. In reality, however, the brain faces the challenge of recognizing stimuli without knowing in advance whether sensory cues come from the same or different stimuli. To address this challenge and to recognize stimuli rapidly, we argue that the brain should carry out multisensory integration and segregation concurrently with complementary neuron groups. Studying an example of inferring heading-direction via visual and vestibular cues, we develop a concurrent multisensory processing neural model which consists of two reciprocally connected modules, the dorsal medial superior temporal area (MSTd) and the ventral intraparietal area (VIP), and that at each module, there exists two distinguishing groups of neurons, congruent and opposite neurons. Specifically, congruent neurons implement cue integration, while opposite neurons compute the cue disparity, both optimally as described by Bayesian inference. The two groups of neurons provide complementary information which enables the neural system to assess the validity of cue integration and, if necessary, to recover the lost information associated with individual cues without re-gathering new inputs. Through this process, the brain achieves rapid stimulus perception if the cues come from the same stimulus of interest, and differentiates and recognizes stimuli based on individual cues with little time delay if the cues come from different stimuli of interest. Our study unveils the indispensable role of opposite neurons in multisensory processing and sheds light on our understanding of how the brain achieves multisensory processing efficiently and rapidly.

Significance Statement

Our brain perceives the world by exploiting multiple sensory cues. These cues need to be integrated to improve perception if they come from the same stimulus and otherwise be segregated. To address the challenge of recognizing whether sensory cues come from the same or different stimuli that are unknown in advance, we propose that the brain should carry out multisensory integration and segregation concurrently with two different neuron groups. Specifically, congruent neurons implement cue integration, while opposite neurons compute the cue disparity, and the interplay between them achieves rapid stimulus recognition without information loss. We apply our model to the example of inferring heading-direction based on visual and vestibular cues and reproduce the experimental data successfully.
Allelic polymorphism at foxo contributes to local adaptation in Drosophila melanogaster
Authors: Betancourt Nicolas J. , Rajpurohit Subhash , Durmaz Esra , Fabian Daniel K. , Kapun Martin , Flatt Thomas , Schmidt Paul
Published: November 2018

The insulin insulin-like growth factor signaling pathway has been hypothesized as a major determinant of life history profiles that vary adaptively in natural populations. InDrosophila melanogaster, multiple components of this pathway vary predictably with latitude; this includesfoxo, a conserved gene that regulates insulin signaling and has pleiotropic effects on a variety of fitness-associated traits. We hypothesized that allelic variation atfoxounderlies genetic variance for traits that vary with latitude and reflect local adaptation. To evaluate this, we generated recombinant outbred populations in which the focalfoxoallele was homozygous and fixed for either the allele common at high latitude or low latitude and the genomic background was randomized across 20 inbred lines. After eight generations of recombination, experimental populations were phenotyped for a series of traits related to gene function. Our results demonstrate that natural allelic variation atfoxohas major and predictable effects on body size and starvation tolerance, but not on development time. These patterns mirror those observed in natural populations collected across the latitudinal gradient in the eastern U.S.: clines were observed for starvation tolerance and body size, but development time exhibited no association with latitude. Furthermore, differences in size betweenfoxogenotypes were equivalent to those observed between populations sampled from the latitudinal extremes, although contribution to the genetic variance for starvation tolerance was less pronounced. These results suggest that allelic variation atfoxois a major contributor to adaptive patterns of life history variation in natural populations of this genetic model.
A study on the protective effects of CpG ODN-induced mucosal immunity against lung injury in a mouse ARDS model
Authors: Wang Guan , Liu Zong-Jian , Liu Xuan , Liu Feng-Ge , Li Yan , Weng Yi-Bing , Zhou Jian-Xin
Published: November 2018

This study aims to determine the feasibility of using oligodeoxynucleotides with unmethylated cytosine-guanine dinucleotide sequences (CpG ODN) as an immunity protection strategy for a mouse model of acute respiratory distress syndrome (ARDS). This is a prospective laboratory animal investigation. 20-week old BALB/c mice in Animal research laboratory were randomized into groups. An ARDS model was induced in mice using lipopolysaccharides. CpG ODN was intranasally and transrectally immunized before or after the 3rdand 7thday of establishing the ARDS model. Mice were euthanized on day seven after the 2ndimmunization. Then, retroorbital bleeding was carried, out and the chest was rapidly opened to collect the trachea and tissues from both lungs for testing. CpG ODN significantly improved the pathologic impairment in mice lung, especially after the intranasal administration of 50 ug. This resulted in the least severe lung tissue injury. Furthermore, IL-6 and IL-8 concentrations were lower, which was second to mice treated with the rectal administration of 20 μg CpG ODN. In contrast, the nasal and rectal administration of CpG ODN in BALB/c mice before LPS immunization did not appear to exhibit any significant protective effects. In conclusion, the intranasal administration of CpG ODN may be is a potential treatment approach to ARDS. More studies are needed to further determine the protective mechanism of CpG ODN.
Genome-wide co-localization of RNA-DNA interactions and fusion RNA pairs
Authors: Yan Zhangming , Huang Norman , Wu Weixin , Chen Weizhong , Jiang Yiqun , Chen Jingyao , Huang Xuerui , Wen Xingzhao , Xu Jie , Jin Qiushi , Zhang Kang , Chen Zhen , Chien Shu , Zhong Sheng
Published: November 2018

Fusion transcripts are used as biomarkers in companion diagnoses. Although more than 15,000 fusion RNAs have been identified from diverse cancer types, few common features have been reported. Here, we compared 16,410 fusion transcripts detected in cancer (from a published cohort of 9,966 tumor samples of 33 cancer types) with genome-wide RNA-DNA interactions mapped in two normal, non-cancerous cell types (using iMARGI, an enhanced version of the MARGI [Mapping RNA-Genome Interactions assay]). Among the top 10 most significant RNA-DNA interactions in normal cells, 5 co-localized with the gene pairs that formed fusion RNAs in cancer. Furthermore, throughout the genome, the frequency of a gene pair to exhibit RNA-DNA interactions is positively correlated with the probability of this gene pair to present documented fusion transcripts in cancer. To test whether RNA-DNA interactions in normal cells are predictive of fusion RNAs, we analyzed these in a validation cohort of 96 lung cancer samples using RNA-seq. 37 out of 42 fusion transcripts in the validation cohort were found to exhibit RNA-DNA interactions in normal cells. Finally, by combining RNA-seq, single-molecule RNA FISH, and DNA FISH, we detected a cancer sample with EML4-ALK fusion RNA without forming the EML4-ALK fusion gene. Collectively, these data suggest a novel RNA-poise model, where spatial proximity of RNA and DNA could poise for the creation of fusion transcripts.
Protective immunity against severe malaria is associated with antibodies to a conserved repertoire of PfEMP1 variants
Authors: Tessema Sofonias K. , Nakajima Rie , Jasinskas Algis , Monk Stephanie L. , Lekieffre Lea , Lin Enmoore , Kiniboro Benson , Proietti Carla , Siba Peter , Felgner Philip L. , Doolan Denise L. , Mueller Ivo , Barry Alyssa E.
Published: November 2018

Extreme diversity of the major surface antigen and virulence determinant of the malaria parasite Plasmodium falciparum, Erythrocyte Membrane Protein-1 (PfEMP1), poses a major barrier to identifying targets of protective immunity. To overcome this problem, we developed a PfEMP1 protein microarray containing 456 DBLα domains, which was used to characterize the immunome of a cohort of semi-immune children and to identify variants associated with protective immune responses. Children with high mean antibody levels to DBLα group 2 had a 26-36% reduced risk of uncomplicated (clinical) malaria, however only 8 diverse DBLα variants were weakly associated with protection from clinical malaria and had low predictive accuracy. On the other hand, children with high mean antibodies to DBLα groups 1 and 2 (which are markers for pathogenic “Type A” PfEMP1) and elevated antibodies to 85 (18.6%) of individual DBLα variants had a 70 −100% reduced risk of severe malaria. Of the top 20 predictive variants for severe disease protection, 17 were strongly associated with protection (86 - 100% reduction in risk of severe malaria) and had high predictive accuracy for severe disease risk. Many variants were conserved and had highly correlated antibody responses, including the three highest-ranking variants, which were linked to EPCR-binding CIDR domains. The results suggest that while immunity to uncomplicated malaria is characterised by antibodies to a diverse repertoire of PfEMP1, immunity to severe malaria requires antibodies to a limited subset of antigenically conserved variants. These findings provide new insights into antimalarial immunity and potential biomarkers for tracking disease risk.