bluuebunny/crossref_metadata_2025 huggingface dataset:
Reducing glucose variability with continuous subcutaneous insulin infusion is associated with reversal of axonal dysfunction in type 1 diabetes mellitus
Authors: Kamel Jordan , Loh Margaret , Cook Mark , MacIsaac Richard J. , Roberts Leslie J.
Published: October 2019

Introduction

We assess whether improvement in control of type 1 diabetes mellitus (T1DM) with continuous subcutaneous insulin infusion (CSII) can protect peripheral nerve function.

Methods

Twelve patients with T1DM treated with multiple daily insulin injections were assessed with nerve excitability testing prior to and 3 months after initiation of CSII.

Results

Although commencing treatment with CSII for 3 months improved mean glycosylated hemoglobin, it did not significantly alter nerve excitability or glycemic variability (GV). In four patients, some deterioration in GV was observed, while eight patients had improvement in SD and mean amplitude of glycemic excursions. For these eight patients, there was normalization of depolarizing and hyperpolarizing threshold electrotonus and recovery cycle superexcitablity.

Discussion

When CSII initiation is able to reduce glycemic variability in T1DM, reversal of axonal dysfunction is seen, likely due to normalization of sodium‐potassium pump function and restoration of transaxonal membrane potential.
Real‐time and fine‐grained network monitoring using in‐band network telemetry
Authors: Hyun Jonghwan , Van Tu Nguyen , Yoo Jae‐Hyoung , Hong James Won‐Ki
Published: October 2019

In the modern era of software‐defined networking (SDN), network monitoring is becoming more important for providing information about a network and helping SDN controllers to make decisions about the network. In‐band Network Telemetry (INT) is a new network monitoring framework that collects packet‐level network information to provide real‐time and fine‐grained network monitoring. In this paper, we present the design of the overall INT management architecture and its two main components: the INT management system and INTCollector. The INT management system controls heterogeneous INT‐capable devices through a common interface. INTCollector is a high‐performance collector for INT data, which uses eXpress Data Path and an event detection mechanism. The evaluation result shows that INTCollector processes telemetry reports 27 times faster than other packet‐level telemetry collectors. We made the implementation as open source, to make researchers who are interested in INT implement their own ideas on top of our work.
Palliative care utilization in hospitalized children with cancer
Authors: Cheng Brian T. , Wangmo Tenzin
Published: October 2019

Background

There is growing evidence that palliative care (PC) is associated with increased quality of life in children with cancer. Despite increasing recommendations in support of PC to improve pediatric oncology care, little is known about its patterns of use.

Methods

We analyzed the 2005‐2011 National Inpatient Sample, a representative, cross‐sectional sample of US hospital admissions. Our study cohort comprised 10 960 hospitalizations of children with cancer and high in‐hospital mortality risk. Survey‐weighted regression models were constructed to determine associations of person‐ and hospital‐level characteristics with PC involvement and healthcare costs.

Results

Overall, 4.4% of hospitalizations included PC involvement. In regression models invoking stepwise variable selection, a shorter length of stay (PC vs no PC; mean: 23.9 vs 32.6 days), solid cancer (solid vs hematologic vs brain cancer; PC use: 7.4% vs 2.8% vs 5.5%), and older age (PC vs no PC; mean: 10.2 vs 8.9 years) were associated with PC use. PC utilization was also associated with lower overall and daily hospital costs.

Conclusions

One in 20 pediatric inpatients with cancer and high mortality risk receives PC, with differential utilization by socio‐economic groups. These results have significant implications for public health resource allocation and the delivery of pediatric PC as high‐value care. Future research should focus on the development of new tools to help physicians assess when PC is appropriate for their patients.
Diversity in deafness: Assessing students who are deaf or hard of hearing
Authors: Smith Chad , Allman Tamby
Published: October 2019

The purpose of this article is to support members of a student's multidisciplinary team to identify complex factors involved in providing valid classroom‐based assessment data, including issues surrounding technology‐based assessment for students who are deaf or hard of hearing (DHH). The diversity of this population creates unique challenges in creating guidelines for assessment. An overview of the diversity of DHH students is used to provide a framework for examining current assessment practices, including both effective and ineffective practices. Cognitive and linguistic learning differences and diverse language learning experiences in the population are discussed as they relate to assessment protocols. Paralleling technology‐based learning experiences with comparable technology‐based assessment experiences is also presented. Recommendations for planning for accessible and meaningful assessment include the use of innovative technologies to align instruction and assessment.
Response assessment using [68Ga]Ga‐PSMA ligand PET in patients undergoing systemic therapy for metastatic castration‐resistant prostate cancer
Authors: Grubmüller Bernhard , Rasul Sazan , Baltzer Pascal , Fajkovic Harun , D'Andrea David , Berndl Florian , Maj‐Hes Agnes , Grubmüller Karl Hermann , Mitterhauser Markus , Wadsak Wolfgang , Pfaff Sarah , Shariat Shahrokh F. , Hacker Marcus , Kramer Gero , Hartenbach Markus
Published: October 2019

Background

To assess which parameters of [68Ga]Ga‐PSMA‐11 positron emission tomography (PSMA‐PET) predict response to systemic therapies in metastatic (m) castration‐resistant prostate cancer (CRPC). In addition, to investigate which of these factors are associated with overall survival (OS).

Methods

We retrospectively assessed the following PSMA‐PET parameters in 43 patients before and after systemic therapies for mCRPC: PSMA total tumor volume (TTV), mean standardized uptake value (SUVmean), SUVmax, and SUVpeak. prostate‐specific antigen (PSA) levels and PSMA‐PET/CT(magnetic resonance imaging [MRI]) imaging were both performed within 8 weeks before and 6 weeks after systemic therapy. PSMA‐PET and CT (MRI) images were reviewed according to the modified PET Response Criteria in Solid Tumors (PERCIST) and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Results were compared to PSA response. Univariable survival analyses were performed.

Results

Overall, 43 patients undergoing 67 systemic therapies were included (9 patients radium‐223, 12 cabazitaxel, 22 docetaxel, 6 abiraterone, and 18 enzalutamide). Median serum PSA level before any therapy was 11.3 ng/mL (interquartile range [IQR] = 3.3, 30.1). Delta (d) PSA after systemic therapies was −41%, dTTV 10.5%, dSUVmean −7.5%, dSUVmax −13.3%, dSUVpeak −12%, and dRECIST −13.3%. Overall, 31 patients had dPSA response (46.3%), 12 stable disease (17.9%), and 24 progressive disease (35.8%). All observed PET parameters, as well as the RECIST evaluation, were significantly associated with PSA response (dTTV P = .003, dSUVmean P = .003, dSUVmax P = .011, dSUVpeak P < 0001, dRECIST P = .012), while RECIST assessment was applicable in 37 out of 67 patients (55.2%). Within a median follow‐up of 33 months (IQR = 26, 38), 10 patients (23.3%) died of PC. On univariable survival analyses, neither the investigated PET parameters nor PSA level or RECIST criteria were associated with OS.

Conclusion

PSMA‐PET provides reliable parameters for prediction of response to systemic therapies for mCRPC. These parameters, if confirmed, could enhance RECIST criteria, specifically concerning its limitations for sclerotic bone lesions.
Use of effective fragment potentials for simulation of excited states in an inhomogeneous environment
Authors: Dubinets Nikita O. , Freidzon Alexandra Y. , Bagaturyants Alexander A.
Published: October 2019

Singlet and triplet spectra of phosphorescent organic light‐emitting diode dopants such as bis(2‐methyldibenzo[f,h]quinoxaline)(acetylacetonate)iridium(III) in inhomogeneous amorphous hosts are simulated by time‐dependent density functional theory (TDDFT) using molecular dynamics and effective fragment potentials (EFPs). The EFPs of the host molecules N,N′‐di(1‐naphthyl)‐N,N′‐diphenyl‐(1,1′‐biphenyl)‐4,4′‐diamine and 4,4′‐bis(N‐carbazolyl)‐1,1′‐biphenyl are constructed from small fragments. The procedure for breaking large molecules into fragments and constructing an EFP is presented. It is demonstrated that polarizable inhomogeneous environment affects the position, intensity, and width of the spectral bands and, therefore, should be taken into account in accurate simulations of spectral bands.
Ultrasound markers for prediction of complex gastroschisis and adverse outcome: longitudinal prospective nationwide cohort study
Authors: Lap C. C. M. M. , Pistorius L. R. , Mulder E. J. H. , Aliasi M. , Kramer W. L. M. , Bilardo C. M. , Cohen‐Overbeek T. E. , Pajkrt E. , Tibboel D. , Wijnen R. M. H. , Visser G. H. A. , Manten G. T. R. ,   The FLAMINGO Study Working Group
Published: October 2019

Objectives

To identify antenatal ultrasound markers that can differentiate between simple and complex gastroschisis and assess their predictive value.

Methods

This was a prospective nationwide study of pregnancies with isolated fetal gastroschisis that underwent serial longitudinal ultrasound examination at regular specified intervals between 20 and 37 weeks' gestation. The primary outcome was simple or complex (i.e. involving bowel atresia, volvulus, perforation or necrosis) gastroschisis at birth. Fetal biometry (abdominal circumference and estimated fetal weight), the occurrence of polyhydramnios, intra‐ and extra‐abdominal bowel diameters and the pulsatility index (PI) of the superior mesenteric artery (SMA) were assessed. Linear mixed modeling was used to compare the individual trajectories of cases with simple and those with complex gastroschisis, and logistic regression analysis was used to estimate the strength of association between the ultrasound parameters and outcome.

Results

Of 104 pregnancies with isolated fetal gastroschisis included, four ended in intrauterine death. Eighty‐one (81%) liveborn infants with simple and 19 (19%) with complex gastroschisis were included in the analysis. We found no relationship between fetal biometric variables and complex gastroschisis. The SMA‐PI was significantly lower in fetuses with gastroschisis than in healthy controls, but did not differentiate between simple and complex gastroschisis. Both intra‐ and extra‐abdominal bowel diameters were larger in cases with complex, compared to those with simple, gastroschisis (P < 0.001 and P < 0.005, respectively). The presence of intra‐abdominal bowel diameter ≥ 97.7th percentile on at least three occasions, not necessarily on successive examinations, was associated with an increased risk of the fetus having complex gastroschisis (relative risk, 1.56 (95% CI, 1.02–2.10); P = 0.006; positive predictive value, 50.0%; negative predictive value, 81.4%).

Conclusions

This large prospective longitudinal study found that intra‐abdominal bowel dilatation when present repeatedly during fetal development can differentiate between simple and complex gastroschisis; however, the positive predictive value is low, and therefore the clinical usefulness of this marker is limited. © 2019 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Glossary of Methodological Approaches
Authors: Bruch Julia , de la Garza-Gil Karina , Ewert Ulf Christian , Hitz Benjamin , Kypta Ulla , Kypta Martin , Müller Ulrich , Petersen Niels , Pindl Kathrin , Skambraks Tanja , Steinbach Sebastian
Published: October 2019

This glossary provides a concise overview of all the methods and approaches employed in the reviewed sample studies (see Chaps. 6, 7 and 8). We use the term method in a very broad sense: It comprises all the possible ways of dealing with the sources. The glossary thus gives an impression of how a tool kit for doing premodern economic history could look like. We aim to give you an impression of how the method works, which should help you decide whether this approach may help you deal with your sources and answer the questions that you are studying. Every entry summarises the basic idea underlying this approach. It sketches how the method is applied and which sources and data you need if you want to get meaningful results. The choice of a method for doing a study in premodern economic history depends heavily on the sources that have survived and are available. Every entry thus points out the scope and the limitations of the respective method.
Apathy as a behavioural marker of cognitive impairment in Parkinson’s disease: a longitudinal analysis
Authors: Martin Glen P. , McDonald Kathryn R. , Allsop David , Diggle Peter J. , Leroi Iracema
Published: October 2019

Background

Understanding the longitudinal course of non-motor symptoms, and finding markers to predict cognitive decline in Parkinson’s disease (PD), are priorities. Previous work has demonstrated that apathy is one of the only behavioural symptoms that differentiates people with PD and intact cognition from those with mild cognitive impairment (MCI-PD). Other psychiatric symptoms emerge as dementia in PD develops.

Objective

We explored statistical models of longitudinal change to detect apathy as a behavioural predictor of cognitive decline in PD.

Methods

We followed 104 people with PD intermittently over 2 years, undertaking a variety of motor, behavioural and cognitive measures. We applied a linear mixed effects model to explore behavioural factors associated with cognitive change over time. Our approach goes beyond conventional modelling based on a random-intercept and slope approach, and can be used to examine the variability in measures within individuals over time.

Results

Global cognitive scores worsened during the two-year follow-up, whereas the longitudinal evolution of self-rated apathy scores and other behavioural measures was negligible. Level of apathy was negatively (− 0.598) correlated with level of cognitive impairment and participants with higher than average apathy scores at baseline also had poorer cognition. The model indicated that departure from the mean apathy score at any point in time was mirrored by a corresponding departure from average global cognitive score.

Conclusion

High levels of apathy are predictive of negative cognitive and behavioural outcomes over time, suggesting that apathy may be a behavioural indicator of early cognitive decline. This has clinical and prognostic implications.
Large deviations of bivariate Gaussian extrema
Authors: van der Hofstad Remco , Honnappa Harsha
Published: October 2019

We establish sharp tail asymptotics for componentwise extreme values of bivariate Gaussian random vectors with arbitrary correlation between the components. We consider two scaling regimes for the tail event in which we demonstrate the existence of a restricted large deviations principle and identify the unique rate function associated with these asymptotics. Our results identify when the maxima of both coordinates are typically attained by two different versus the same index, and how this depends on the correlation between the coordinates of the bivariate Gaussian random vectors. Our results complement a growing body of work on the extremes of Gaussian processes. The results are also relevant for steady-state performance and simulation analysis of networks of infinite server queues.
MPS-FEM Coupled Method for Study of Wave-Structure Interaction
Authors: Zhang Guanyu , Chen Xiang , Wan Decheng
Published: October 2019

Nowadays, an increasing number of ships and marine structures are manufactured and inevitably operated in rough sea. As a result, some phenomena related to the violent fluid-elastic structure interactions (e.g., hydrodynamic slamming on marine vessels, tsunami impact on onshore structures, and sloshing in liquid containers) have aroused huge challenges to ocean engineering fields. In this paper, the moving particle semi-implicit (MPS) method and finite element method (FEM) coupled method is proposed for use in numerical investigations of the interaction between a regular wave and a horizontal suspended structure. The fluid domain calculated by the MPS method is dispersed into fluid particles, and the structure domain solved by the FEM method is dispersed into beam elements. The generation of the 2D regular wave is firstly conducted, and convergence verification is performed to determine appropriate particle spacing for the simulation. Next, the regular wave interacting with a rigid structure is initially performed and verified through the comparison with the laboratory experiments. By verification, the MPS-FEM coupled method can be applied to fluid-structure interaction (FSI) problems with waves. On this basis, taking the flexibility of structure into consideration, the elastic dynamic response of the structure subjected to the wave slamming is investigated, including the evolutions of the free surface, the variation of the wave impact pressures, the velocity distribution, and the structural deformation response. By comparison with the rigid case, the effects of the structural flexibility on wave-elastic structure interaction can be obtained.
Application of geostatistics in facies modeling of Reservoir-E, “Hatch Field” offshore Niger Delta Basin, Nigeria
Authors: Jika H. T. , Onuoha K. M. , Dim C. I. P.
Published: October 2019

Lithofacies are very influential in the transmission of fluids within the reservoir. The objective of this study is to use geostatistical techniques of sequential indicator simulation (SISIM) a variogram-based algorithm (VBA), single normal equation simulation (SNESIM) and filter-based simulation (FILTERSIM) of multiple-point geostatistics (MPG) in developing realistic facies model. A reservoir sand package “Reservoir-E” was correlated across five wells in the field. Synthetic seismogram of well HT-1 was generated, and Horizon E picked on seismic section to produce time and depth surfaces of the reservoir. The conditional if statement to generate lithofacies was applied on the extracted volume of shale data within “Reservoir-E,” and the data were inputted in Stanford Geostatistics Modeling Software for facies modeling. The first realization from SISIM was converted to a training image used for MPG. Visually, the MPG algorithm of SNESIM and FILTERSIM produced realization that is substantially better and more realistic than the VBA of SISIM. The magnitude of correlation coefficients of algorithms was carried out using the mean and variance of realizations, the results revealed mean and variance magnitude of correlation coefficients between SISIM and SNESIM with 0.8933 and 0.9637, SISIM and FILTERSIM with 0.8639 and 0.5097 and SNESIM and FILTERSIM with 0.9717 and 0.8603. The results revealed a very good mean and variance magnitude of correlation coefficients between SISIM and SNESIM; good between SISIM and FILTERSIM; and very good mean and variance correlation coefficient between SNESIM and FILTERSIM. The qualitative interpretation of the model built with SNESIM and FILTERSIM clearly detects lithofacies in the field which makes them a better algorithm in facies modeling.
Post-transplant recurrence of steroid resistant nephrotic syndrome in children: the Italian experience
Authors: Morello William , Puvinathan Sairaj , Puccio Giuseppe , Ghiggeri Gian Marco , Dello Strologo Luca , Peruzzi Licia , Murer Luisa , Cioni Michela , Guzzo Isabella , Cocchi Enrico , Benetti Elisa , Testa Sara , Ghio Luciana , Caridi Gianluca , Cardillo Massimo , Torelli Rosanna , Montini Giovanni
Published: October 2019

Background

Steroid resistant nephrotic syndrome (SRNS) is a frequent cause of end stage renal disease in children and post-transplant disease recurrence is a major cause of graft loss.

Methods

We identified all children with SRNS who underwent renal transplantation in Italy, between 2005 and 2017. Data were retrospectively collected for the presence of a causative gene mutation, sex, histology, duration of pre-transplant dialysis, age at onset and transplant, HLA matching, recurrence, therapy for recurrence, and graft survival.

Results

101 patients underwent a first and 22 a second renal transplant. After a median follow-up of 58.5 months, the disease recurred on the first renal transplant in 53.3% of patients with a non-genetic and none with a genetic SRNS. Age at transplant > 9 years and the presence of at least one HLA-AB match were independent risk factors for recurrence. Duration of dialysis was longer in children with relapse, but did not reach statistical significance. Overall, 24% of patients lost the first graft, with recurrence representing the commonest cause. Among 22 patients who underwent a second transplant, 5 suffered of SRNS recurrence. SRNS relapsed in 5/9 (55%) patients with disease recurrence in their first transplant and 2 of them lost the second graft.

Conclusions

Absence of a causative mutation represents the major risk factor for post-transplant recurrence in children with SRNS, while transplant can be curative in genetic SRNS. A prolonged time spent on dialysis before transplantation has no protective effect on the risk of relapse and should not be encouraged. Retransplantation represents a second chance after graft loss for recurrence.
High-dose intravenous methotrexate in the management of breast cancer with leptomeningeal disease
Authors: Kapke Jonathan T. , Schneidewend Robert J. , Jawa Zeeshan A. , Huang Chiang-Ching , Connelly Jennifer M. , Chitambar Christopher R.
Published: October 2019

Leptomeningeal metastasis (LM) in breast cancer is associated with significant morbidity and mortality. While there is currently no standard therapy, treatment options include craniospinal radiotherapy, intrathecal chemotherapy and systemic chemotherapy. Craniospinal radiotherapy has not demonstrated improved survival and intrathecal chemotherapy is often poorly tolerated due to associated neurotoxicity. The use of systemic chemotherapy can be limited by inadequate central nervous system penetration. High-dose systemic methotrexate administered intravenously (HD-MTX), has been reported to improve quality of life and provide durable remissions for LM in breast cancer. We present three cases of metastatic breast cancer and LM with prolonged survival after administration of HD-MTX. Based on our observations and review of the literature, HD-MTX seems to be a viable treatment option for patients with LM in breast cancer, and in select cases, the use of HD-MTX, as part of a multimodality treatment plan, may be associated with prolonged survival.
Should We Worry About Sponsorship-Induced Bias in Online Political Science Surveys?
Authors: Leeper Thomas J. , Thorson Emily A.
Published: October 2019

Political scientists rely heavily on survey research to gain insights into public attitudes and behaviors. Over the past decade, survey data collection has moved away from personal face-to-face and telephone interviewing towards a model of computer-assisted self-interviewing. A hallmark of many online surveys is the prominent display of the survey’s sponsor, most often an academic institution, in the initial consent form and/or on the survey website itself. It is an open question whether these displays of academic survey sponsorship could increase total survey error. We measure the extent to which sponsorship (by a university or marketing firm) affects data quality, including satisficing behavior, demand characteristics, and socially desirable responding. In addition, we examine whether sponsor effects vary depending on the participant’s experience with online surveys. Overall, we find no evidence that response quality is affected by survey sponsor or by past survey experience.
The Effects of Certain and Uncertain Incentives on Effort and Knowledge Accuracy
Authors: Jamieson Thomas , Weller Nicholas
Published: October 2019

In many situations, incentives exist to acquire knowledge and make correct political decisions. We conduct an experiment that contributes to a small but growing literature on incentives and political knowledge, testing the effect of certain and uncertain incentives on knowledge. Our experiment builds on the basic theoretical point that acquiring and using information is costly, and incentives for accurate answers will lead respondents to expend greater effort on the task and be more likely to answer knowledge questions correctly. We test the effect of certain and uncertain incentives and find that both increase effort and accuracy relative to the control condition of no incentives for accuracy. Holding constant the expected benefit of knowledge, we do not observe behavioral differences associated with the probability of earning an incentive for knowledge accuracy. These results suggest that measures of subject performance in knowledge tasks are contingent on the incentives they face. Therefore, to ensure the validity of experimental tasks and the related behavioral measures, we need to ensure a correspondence between the context we are trying to learn about and our experimental design.
Isolating the Factors That Govern Fracture Development in Rocks Throughout Dynamic In Situ X‐Ray Tomography Experiments
Authors: McBeck Jessica , Kandula Neelima , Aiken John M. , Cordonnier Benoît , Renard François
Published: October 2019

Centuries of work have highlighted the importance of several characteristics on fracture propagation. However, the relative importance of each characteristic on the likelihood of propagation remains elusive. We rank this importance by performing dynamic X‐ray microtomography experiments that provide unique access to characteristics of evolving fracture networks as rocks are triaxially compressed toward failure. We employed a machine learning technique based on logistic regression analysis to predict whether or not a fracture grows from 14 fracture geometry and network characteristics identified throughout four experiments on crystalline rocks in which thousands of fractures propagated. The characteristics that best predict fracture growth are the length, thickness, volume, and orientation of fractures with respect to the external stress field and the distance to the closest neighboring fracture. Growing fractures tend to be more clustered, shorter, thinner, volumetrically smaller, and dipping closer to 30–60° from the maximum compression direction than closing fractures.
Climatology Explains Intermodel Spread in Tropical Upper Tropospheric Cloud and Relative Humidity Response to Greenhouse Warming
Authors: Po‐Chedley Stephen , Zelinka Mark D. , Jeevanjee Nadir , Thorsen Tyler J. , Santer Benjamin D.
Published: October 2019

The response of upper tropospheric clouds and relative humidity (RH) to warming is important to the overall sensitivity of the Earth to increasing greenhouse gas concentrations. Previous research has shown that changes in hydrologic fields should closely track rising isotherms in a warming climate. Here we show that the distribution of tropical clouds and RH in general circulation models is approximately constant under greenhouse warming when using temperature as a vertical coordinate. By assuming that these fields are an invariant function of atmospheric temperature and that temperature change follows a dilute moist adiabat, we are able to accurately predict cloud fraction and RH changes in the tropical upper troposphere (150–400 hPa) in 27 general circulation models. Our results indicate that intermodel spread in changes of tropical upper tropospheric clouds and RH is closely related to differences in model climatology and could be substantially reduced if model ensembles reliably reproduced observed climatologies.
Machine Learning Analysis of Jupiter's Far‐Ultraviolet Auroral Morphology
Authors: Nichols J. D. , Kamran A. , Milan S. E.
Published: October 2019

We present the first principal component analysis of Jupiter's far‐ultraviolet auroras, in order to identify the most repeatable sources of variation in the auroral morphology. We show that the most recurrent source of variance is emission just poleward of the statistical oval on the dawnside. Further significant repeatable sources of variance are localized expansions of the main emission on the dawnside or duskside and poleward emission near noon and along the duskside. We go on to show using a density‐based spatial clustering of applications with noise clustering analysis that the most significant auroral components form six repeatable auroral morphological classes. One class, exhibiting bright main and poleward dusk emissions, occurs solely during solar wind compressions. This presents an important new tool for diagnosing magnetospheric compressions at Jupiter.
Saturn's North Polar Vortex Structure Extracted From Cloud Images by the Optical Flow Method
Authors: Liu Tianshu , Sayanagi Kunio M. , Brueshaber Shawn R. , Blalock John J. , Ingersoll Andrew P. , Dyudina Ulyana A. , Ewald Shawn P.
Published: October 2019

The paper presents velocity fields with ~3‐km spatial resolution of Saturn's north polar vortex (NPV) retrieved using the optical flow method from a sequence of polar‐projected cloud images captured by the Imaging Science Subsystem camera on board NASA's Cassini spacecraft. The fields of the velocity magnitude, velocity variation, relative vorticity, divergence, and second invariant are determined to characterize the flow structures of the inner core of the NPV. The mean zonal and mean meridional velocity profiles of the NPV are compared with previous measurements. We also describe the relevant details of application of the optical flow method to planetary cloud‐tracking wind measurements. The mean zonal velocity profile is consistent with the previous measurements using correlation image velocimetry methods. The small but significant meridional velocity corresponds to outwardly spiraling streams observed in the region near the north pole (NP). The concentrated vorticity and second invariant within 1° planetographic latitude of the NP indicate strong rotational motion of the fluid. An analysis is presented to explore a possible physical origin of the observed spiraling node at the NP.
Specific NOTCH1 antibody targets DLL4-induced proliferation, migration, and angiogenesis in NOTCH1-mutated CLL cells
Authors: López-Guerra Mónica , Xargay-Torrent Sílvia , Fuentes Patricia , Roldán Jocabed , González-Farré Blanca , Rosich Laia , Silkenstedt Elisabeth , García-León María J. , Lee-Vergés Eriong , Giménez Neus , Giró Ariadna , Aymerich Marta , Villamor Neus , Delgado Julio , López-Guillermo Armando , Puente Xose S. , Campo Elias , Toribio María L. , Colomer Dolors
Published: October 2019

Targeting Notch signaling has emerged as a promising therapeutic strategy for chronic lymphocytic leukemia (CLL), particularly inNOTCH1-mutated patients. We provide first evidence that the Notch ligand DLL4 is a potent stimulator of Notch signaling inNOTCH1-mutated CLL cells while increases cell proliferation. Importantly, DLL4 is expressed in histiocytes from the lymph node, both inNOTCH1-mutated and -unmutated cases. We also show that the DLL4-induced activation of the Notch signaling pathway can be efficiently blocked with the specific anti-Notch1 antibody OMP-52M51. Accordingly, OMP-52M51 also reverses Notch-inducedMYC, CCND1, andNPM1gene expression as well as cell proliferation inNOTCH1-mutated CLL cells. In addition, DLL4 stimulation triggers the expression of protumor target genes, such asCXCR4,NRARP, andVEGFA, together with an increase in cell migration and angiogenesis. All these events can be antagonized by OMP-52M51. Collectively, our results emphasize the role of DLL4 stimulation inNOTCH1-mutated CLL and confirm the specific therapeutic targeting of Notch1 as a promising approach for this group of poor prognosis CLL patients.
LncRNA HOXA-AS3 confers cisplatin resistance by interacting with HOXA3 in non-small-cell lung carcinoma cells
Authors: Lin Shuang , Zhang Rui , An Xiaoxia , Li Zhoubin , Fang Cheng , Pan Bo , Chen Wei , Xu Guodong , Han Weili
Published: October 2019

Many studies have indicated that the aberrant expression of long noncoding RNAs (lncRNAs) is responsible for drug resistance, which represents a substantial obstacle for cancer therapy. In the present study, we aimed to investigate the role of the lncRNA HOXA-AS3 in drug resistance and elucidate its underlying mechanisms in non-small-cell lung carcinoma (NSCLC) cells. The role of HOXA-AS3 in drug resistance was demonstrated by the cell counting kit-8 assay (CCK-8), ethynyldeoxyuridine (EDU) assay, and flow cytometry analysis. Tumor xenografts in nude mice were established to evaluate the antitumor effects of HOXA-AS3 knockdown in vivo. Western blotting and quantitative real-time PCR were used to evaluate protein and RNA expression. RNA pull-down assays, mass spectrometry, and RNA immunoprecipitation were performed to confirm the molecular mechanism of HOXA-AS3 in the cisplatin resistance of NSCLC cells. We found that HOXA-AS3 levels increased with cisplatin treatment and knockdown of HOXA-AS3 enhance the efficacy of cisplatin in vitro and in vivo. Mechanistic investigations showed that HOXA-AS3 conferred cisplatin resistance by down-regulating homeobox A3 (HOXA3) expression. Moreover, HOXA-AS3 was demonstrated to interact with both the mRNA and protein forms of HOXA3. In addition, HOXA3 knockdown increased cisplatin resistance and induced epithelial-mesenchymal transition (EMT). Taken together, our findings suggested that additional research into HOXA-AS3 might provide a better understanding of the mechanisms of drug resistance and promote the development of a novel and efficient strategy to treat NSCLC.
The TLR7/8 agonist R848 remodels tumor and host responses to promote survival in pancreatic cancer
Authors: Michaelis Katherine A. , Norgard Mason A. , Zhu Xinxia , Levasseur Peter R. , Sivagnanam Shamilene , Liudahl Shannon M. , Burfeind Kevin G. , Olson Brennan , Pelz Katherine R. , Angeles Ramos Diana M. , Maurer H. Carlo , Olive Kenneth P. , Coussens Lisa M. , Morgan Terry K. , Marks Daniel L.
Published: October 2019

A priority in cancer research is to innovate therapies that are not only effective against tumor progression but also address comorbidities such as cachexia that limit quality and quantity of life. We demonstrate that TLR7/8 agonist R848 induces anti-tumor responses and attenuates cachexia in murine models of pancreatic ductal adenocarcinoma (PDAC). In vivo, tumors from two of three cell lines were R848-sensitive, resulting in smaller tumor mass, increased immune complexity, increased CD8+ T-cell infiltration and activity, and decreased Treg frequency. R848-treated mice demonstrated improvements in behavioral and molecular cachexia manifestations, resulting in a near-doubling of survival duration. Knockout mouse studies revealed that stromal, not neoplastic, TLR7 is requisite for R848-mediated responses. In patient samples, we found Tlr7 is ubiquitously expressed in stroma across all stages of pancreatic neoplasia, but epithelial Tlr7 expression is relatively uncommon. These studies indicate immune-enhancing approaches including R848 may be useful in PDAC and cancer-associated cachexia.
Ba-induced phase segregation and band gap reduction in mixed-halide inorganic perovskite solar cells
Authors: Xiang Wanchun , Wang Zaiwei , Kubicki Dominik J. , Wang Xueting , Tress Wolfgang , Luo Jingshan , Zhang Jiahuan , Hofstetter Albert , Zhang Lijun , Emsley Lyndon , Grätzel Michael , Hagfeldt Anders
Published: October 2019

All-inorganic metal halide perovskites are showing promising development towards efficient long-term stable materials and solar cells. Element doping, especially on the lead site, has been proved to be a useful strategy to obtain the desired film quality and material phase for high efficient and stable inorganic perovskite solar cells. Here we demonstrate a function by adding barium in CsPbI2Br. We find that barium is not incorporated into the perovskite lattice but induces phase segregation, resulting in a change in the iodide/bromide ratio compared with the precursor stoichiometry and consequently a reduction in the band gap energy of the perovskite phase. The device with 20 mol% barium shows a high power conversion efficiency of 14.0% and a great suppression of non-radiative recombination within the inorganic perovskite, yielding a high open-circuit voltage of 1.33 V and an external quantum efficiency of electroluminescence of 10−4.
Statistical learning goes beyond the d-band model providing the thermochemistry of adsorbates on transition metals
Authors: García-Muelas Rodrigo , López Núria
Published: October 2019

The rational design of heterogeneous catalysts relies on the efficient survey of mechanisms by density functional theory (DFT). However, massive reaction networks cannot be sampled effectively as they grow exponentially with the size of reactants. Here we present a statistical principal component analysis and regression applied to the DFT thermochemical data of 71 C$${}_{1}$$

1

–C$${}_{2}$$

2

species on 12 close-packed metal surfaces. Adsorption is controlled by covalent ($$d$$
d
-band center) and ionic terms (reduction potential), modulated by conjugation and conformational contributions. All formation energies can be reproduced from only three key intermediates (predictors) calculated with DFT. The results agree with accurate experimental measurements having error bars comparable to those of DFT. The procedure can be extended to single-atom and near-surface alloys reducing the number of explicit DFT calculation needed by a factor of 20, thus paving the way for a rapid and accurate survey of whole reaction networks on multimetallic surfaces.
Analog Coupled Oscillator Based Weighted Ising Machine
Authors: Chou Jeffrey , Bramhavar Suraj , Ghosh Siddhartha , Herzog William
Published: October 2019

We report on an analog computing system with coupled non-linear oscillators which is capable of solving complex combinatorial optimization problems using the weighted Ising model. The circuit is composed of a fully-connected 4-node LC oscillator network with low-cost electronic components and compatible with traditional integrated circuit technologies. We present the theoretical modeling, experimental characterization, and statistical analysis our system, demonstrating single-run ground state accuracies of 98% on randomized MAX-CUT problem sets with binary weights and 84% with 5-bit weight resolutions. Solutions are obtained within 5 oscillator cycles, and the time-to-solution has been demonstrated to scale directly with oscillator frequency. We present scaling analysis which suggests that large coupled oscillator networks may be used to solve computationally intensive problems faster and more efficiently than conventional algorithms. The proof-of-concept system presented here provides the foundation for realizing such larger scale systems using existing hardware technologies and could pave the way towards an entirely novel computing paradigm.
Low Dose Carbon Monoxide Exposure in Idiopathic Pulmonary Fibrosis Produces a CO Signature Comprised of Oxidative Phosphorylation Genes
Authors: Casanova Nancy , Zhou Tong , Gonzalez-Garay Manuel L. , Rosas Ivan O. , Goldberg Hilary J. , Ryter Stefan W. , Collard Harold R. , El-Chemaly Souheil , Flaherty Kevin R. , Hunninghake Gary M. , Lasky Joseph A. , Lederer David J. , Machado Roberto F. , Martinez Fernando J. , Noth Imre , Raghu Ganesh , Choi Augustine M. K. , Garcia Joe G. N.
Published: October 2019

Compelling preclinical studies indicate that low-dose carbon monoxide (CO) abrogates experimental lung fibrosis. We recently reported the results of a multicenter, double-blinded, clinical trial of inhaled CO in patients with idiopathic pulmonary fibrosis (IPF). Identifying no significantly changes in metalloproteinase-7 (MMP7) serum concentration, or secondary endpoints of physiologic measurements, hospitalization, death, or patient-reported outcomes. In the present study, we evaluated the effect of low dose CO exposure (100–200 ppm) for 12 weeks on genome-wide gene expression in peripheral blood mononuclear cells (PBMC) derived from these IPF study subjects. We conducted transcriptome profiling on 38 IPF subjects with time points available at 0, 12, and 24 weeks. Total RNA isolated from PBMCs was hybridized onto the Affymetrix Human Gene 2.0 ST Array. We identified 621 genes significantly upregulated in the 24-week CO exposed group compared with the 12-week. Pathway analysis demonstrated association with Oxidative Phosphorylation (adjusted P < 0.05). We identified a clear CO signature dominated with 23 oxidative phosphorylation-related genes (FDR <10%). We confirmed the expression of nine selected gene products using Nanostring’s nCounter analysis system. These findings suggest this signature may serve as a potential genomic biomarker for CO exposure and for potential titration of dosage to allow precision testing of therapies in future low dose CO therapeutic studies in IPF.
Rich Magnetic Quantization Phenomena in AA Bilayer Silicene
Authors: Shih Po-Hsin , Do Thi-Nga , Gumbs Godfrey , Huang Danhong , Pham Hai Duong , Lin Ming-Fa
Published: October 2019

The rich magneto-electronic properties of AA-bottom-top (bt) bilayer silicene are investigated using a generalized tight-binding model. The electronic structure exhibits two pairs of oscillatory energy bands for which the lowest conduction and highest valence states of the low-lying pair are shifted away from the K point. The quantized Landau levels (LLs) are classified into various separated groups by the localization behaviors of their spatial distributions. The LLs in the vicinity of the Fermi energy do not present simple wave function modes. This behavior is quite different from other two-dimensional systems. The geometry symmetry, intralayer and interlayer atomic interactions, and the effect of a perpendicular magnetic field are responsible for the peculiar LL energy spectra in AA-bt bilayer silicene. This work provides a better understanding of the diverse magnetic quantization phenomena in 2D condensed-matter materials.
Anatomic Factors Predicting Postoperative Strabismus in Orbital Wall Fracture Repair
Authors: Hsu Chih-Kang , Hsieh Meng-Wei , Chang Hsu-Chieh , Tai Ming-Cheng , Chien Ke-Hung
Published: October 2019

This study is aimed to determine the relationship between orbital fracture sites in each CT scan view and postoperative diplopia. Data for 141 patients of orbital wall fracture were analyzed retrospectively. One group of examiners reviewed sagittal, coronal and axial CT scans. Descriptive statistical analysis was used to assess each fracture area and its potential relationship with the occurrence of postoperative diplopia. Among the three anatomical views, sagittal sections were significantly associated with post-operative diplopia (PD) (p = 0.044). For orbital wall fractures in a single location, C1 (p = 0.015), A1 (p = 0.004) and S3 (p = 0.006) fractures were significantly related to PD. Orbital wall fractures found in more than one location resulted in a higher probability of PD in all sections:, C1 + C2 group (p = 0.010), C1 + C2 + C3 group (p = 0.005), A1 + A2 group (p = 0.034), A3 + A1 group (p = 0.005), S1 + S2 group (p < 0.001), S2 + S3 group (p = 0.006) and S1 + S2 + S3 group (p < 0.001). For combinations of two or three sections, we found that only fractures involving both coronal and sagittal sections led to a significantly increased risk of PD (p = 0.031). PD is the main posttreatment complication of orbital bone fracture reduction. In addition to the known myogenic cause (failure to relieve entrapment) of diplopia, both trauma and surgical manipulation can compromise ocular motor nerve function and possibly result in the development of neurogenic causes of diplopia. Careful assessment of patient symptoms (whether preoperative diplopia is present), and the location of orbital fractures (and the influence of related musculature, fat, and nerves) on CT scans are strongly related to surgical success.
Subjective estimates of uncertainty during gambling and impulsivity after subthalamic deep brain stimulation for Parkinson’s disease
Authors: Paliwal Saee , Mosley Philip E. , Breakspear Michael , Coyne Terry , Silburn Peter , Aponte Eduardo , Mathys Christoph , Stephan Klaas E.
Published: October 2019

Subthalamic deep brain stimulation (DBS) for Parkinson’s disease (PD) may modulate chronometric and instrumental aspects of choice behaviour, including motor inhibition, decisional slowing, and value sensitivity. However, it is not well known whether subthalamic DBS affects more complex aspects of decision-making, such as the influence of subjective estimates of uncertainty on choices. In this study, 38 participants with PD played a virtual casino prior to subthalamic DBS (whilst ‘on’ medication) and again, 3-months postoperatively (whilst ‘on’ stimulation). At the group level, there was a small but statistically significant decrease in impulsivity postoperatively, as quantified by the Barratt Impulsiveness Scale (BIS). The gambling behaviour of participants (bet increases, slot machine switches and double or nothing gambles) was associated with this self-reported measure of impulsivity. However, there was a large variance in outcome amongst participants, and we were interested in whether individual differences in subjective estimates of uncertainty (specifically, volatility) were related to differences in pre- and postoperative impulsivity. To examine these individual differences, we fit a computational model (the Hierarchical Gaussian Filter, HGF), to choices made during slot machine game play as well as a simpler reinforcement learning model based on the Rescorla-Wagner formalism. The HGF was superior in accounting for the behaviour of our participants, suggesting that participants incorporated beliefs about environmental uncertainty when updating their beliefs about gambling outcome and translating these beliefs into action. A specific aspect of subjective uncertainty, the participant’s estimate of the tendency of the slot machine’s winning probability to change (volatility), increased subsequent to DBS. Additionally, the decision temperature of the response model decreased post-operatively, implying greater stochasticity in the belief-to-choice mapping of participants. Model parameter estimates were significantly associated with impulsivity; specifically, increased uncertainty was related to increased postoperative impulsivity. Moreover, changes in these parameter estimates were significantly associated with the maximum post-operative change in impulsivity over a six month follow up period. Our findings suggest that impulsivity in PD patients may be influenced by subjective estimates of uncertainty (environmental volatility) and implicate a role for the subthalamic nucleus in the modulation of outcome certainty. Furthermore, our work outlines a possible approach to characterising those persons who become more impulsive after subthalamic DBS, an intervention in which non-motor outcomes can be highly variable.