bluuebunny/crossref_metadata_2025 huggingface dataset:
Future direction of searching for root economics spectrum: focusing on the fibrous roots “absorptive unit”
Authors: Shao Xinliang , Wang Lijun , Zhang Qin , Liu Yuhui , Yang Xitian
Published: May 2019

As one of the trait‐based approaches, leaf economics spectrum (LES) has led to significant advances in plant ecology; however, hypothetical root economics spectrum (RES) which is even more important than the LES aboveground is still less well understood. By analogy with the LES, hypothetical RES may emerge from the coordinated functional traits of fine roots. However, lots of previous studies revealed inconsistent evidence of an RES across the woody species which dominate the terrestrial ecosystem. By discussing the sampling problems in previous studies, we realize that the main reason of failing to search the RES across woody species might be the lack of a standardized sampling protocol. Using inconsistent and inaccurate basic samples of absorptive roots in previous studies impeded the search for an RES. Mycorrhizal interactions and soil matrix constraints do have influences on fine‐root traits; however, there is no adequate evidence to support that these factors can offset or impede selection for an RES. In order to make sure the comparability across species and between studies, we come up with a concept absorptive unit of fibrous roots. The absorptive unit, which integrates all the absorptive fibrous root orders interconnected in a distal nonwoody cluster as a whole, is a parallel to a leaf. Excluding all the pioneer roots and treating absorptive unit as a basic sample can make sure the comparability across species and between studies. We believe it will offer a promising way to find consistent evidence that support the RES.
Influence of lipids on stable isotope ratios in mammal hair: highlighting the importance of validation
Authors: Rioux Ève , Pelletier Fanie , St‐Laurent Martin‐Hugues
Published: May 2019

Carbon (δ13C) and nitrogen (δ15N) stable isotope ratios are increasingly used in ecological studies to evaluate diet composition and trophic relationships. However, lipids may influence stable isotope ratios due to the depletion of 13C in adipose tissues relative to proteins and carbohydrates. δ13C values can be corrected by lipid extraction or normalization models. The aims of our study were to evaluate the effects of lipid extraction on stable isotope ratios in a terrestrial mammal, the caribou (Rangifer tarandus caribou), and to propose relevant lipid normalization models that are method‐ and tissue‐specific for δ13C values. We also evaluated whether four δ13C lipid normalization and correction models proposed in the literature were applicable to our study species. Stable isotope ratios were obtained for hair, plasma, and red blood cell samples of 44 caribou in the Gaspésie National Park (Québec, Canada). The effects of lipid extraction on stable isotope ratios were tested using a paired t‐test. A simple linear model was used to correct for the effects of lipid extraction and to assess its performance compared to that of published equations. Lipid content significantly influenced δ13C values in caribou hair. The four lipid normalization equations commonly used in the literature did not accurately predict δ13Clipid‐free values of caribou hair. Based on our results, we recommend controlling systematically for lipids in terrestrial systems and analyzing δ13C (lipid‐free) and δ15N (bulk) from two separate aliquots to reach a greater precision. We also recommend controlling for lipids in hair tissue. If not possible, we recommend using a lipid normalization model that is tissue‐, method‐, and species‐specific or applying a model that has been previously validated for the tissue and species of interest.
Photoinduced Sulfonylation Reactions through the Insertion of Sulfur Dioxide
Authors: Ye Shengqing , Li Xiaofang , Xie Wenlin , Wu Jie
Published: May 2019

Recent advances in the photoinduced sulfonylation reactions through the insertion of sulfur dioxide are summarized. Among the approaches developed in the sulfonylation reactions, the insertion of sulfur dioxide via radical process can be accomplished with the assistance of photoredox catalysis in the presence of visible light or under ultraviolet irradiation, depending the substrates used in the reactions. Under ultraviolet irradiation, the conversion can be completed under metal‐ and additive‐free conditions. It is noteworthy that alkyl halides possessing eliminable β‐hydrogen atom are effective as alkyl radical precursors with the insertion of sulfur dioxide. Two parts, according to the photoinduced reaction pathways, are introduced: (a) photo‐initiated formation of radical with the subsequent capture of sulfur dioxide; (b) photo‐assisted single electron transfer (SET) after insertion of sulfur dioxide. During the transformation, an oxidative or reductive single electron transfer would occur under visible light photoredox catalysis.
Synthesis and Properties of Acridone Oligomers
Authors: Liu Renfei , Zhu Guanxing , Ji Yongxin , Zhang Gang
Published: May 2019

Length‐defined 2,7‐acridone oligomers were synthesized via a sequence of bromination, borylation and Suzuki–Miyaura cross‐coupling reaction. Both the single crystal structure analysis and the theoretical calculations demonstrate that the anti conformation is favored in the oligomer. The relationship of the properties and the number of acridone units in the oligomer was investigated. The UV/Vis absorption and fluorescence spectroscopy reveal that the absorption and emission of oligomers are red‐shifted and energy gaps narrow with the increase of acridone moieties, as well as a decline in the radiative decay rate. Cyclic voltammetry measurements and theoretical calculations elucidate that the quantity of acridone in the oligomer plays a greater effect on the HOMO energy levels than on the LUMO ones.
Measurement and estimation of densities of different biodiesel–diesel–alcohol ternary blends
Authors: Gülüm Mert , Onay Funda Kutlu , Bilgin Atilla
Published: May 2019

Density is one of the most important fuel properties influencing the injection, spray, and combustion characteristics. Since a number of articles have recently been performed investigating the effects of biodiesel–diesel–alcohol ternary blends on combustion characteristics and exhaust emissions, the reliable density data and regression models for the ternary blends become more important in developing accurate spray, combustion and emission models. However, there is lack of studies which focus on (a) the measurement of densities of ternary blends including higher alcohols over wide alcohol blending ratio at different temperatures, (b) development of one‐dimensional regression models to predict densities of ternary blends, and (c) comparison of predictive capabilities of models with artificial neural networks (ANNs). Therefore, in this article, to eliminate the lack of such studies in the existing literature, waste cooking oil biodiesel was produced, and it was mixed with diesel fuel and several alcohols to prepare ternary blends. The density measurements of ternary blends were performed under various temperatures (278.15 K−368.15 K). The exponential equation which can be used in spray or combustion model was derived by fitting the density data. The predictive capability of the exponential model was compared with the linear model and ANN using different density data of ternary blends to determine the best‐fit correlation. According to results, ANN is the most suitable one to estimate density; however, the exponential model is also thought to be an alternative to ANN.
The association between specific neuropsychiatric disturbances in people with Alzheimer's disease and dementia with Lewy bodies and carer distress
Authors: Terum Toril Marie , Testad Ingelin , Rongve Arvid , Aarsland Dag , Svendsboe Ellen , Andersen John Roger
Published: May 2019

Objective

Neuropsychiatric symptoms (NPSs) are identified as important care‐recipient variables in terms of the impact on carer distress. The aim of this study was to determine whether specific neuropsychiatric disturbances in people with Alzheimer disease (AD) and dementia with Lewy bodies (DLB) differentially impact carer distress.

Methods

This was a cross‐sectional study of people diagnosed with AD and DLB and their primary carers. The Relatives' Stress Scale (RSS) was used to assess the level of reported distress in carers, and the Neuropsychiatric Inventory (NPI) was used to assess NPSs. The effect of NPSs on carer distress was analyzed using correlation analysis and partial least squares regression.

Results

This study included 159 participants diagnosed with AD (n = 97) and DLB (n = 62) and their primary carers (spouses and adult children). The majority of people diagnosed with dementia were women (64.2%), with a mean age of 75.9 years (SD, 7.4) and a mean Mini‐Mental State Examination (MMSE) score of 23.5 (SD, 2.9). The main analysis identified apathy as the most important NPS contributing to carer distress. Compared with AD, the explained variance in the DLB group was higher (r2 = 37.3 vs r2 = 53.7). In addition, more NPSs were considered clinically important in the DLB group.

Conclusion

The findings of this study identify apathy as the most important NPS contributing to carer distress among carers of people with AD and DLB. These findings help us identify the support needs of families dealing with dementia.
Cognitive screening instruments to identify vascular cognitive impairment: A systematic review
Authors: Ghafar Mohd Zaquan Arif Abd , Miptah Hayatul Nawwar , O'Caoimh Rónán
Published: May 2019

Introduction

Vascular cognitive impairment (VCI) is common and important to detect as controlling risk factors, particularly hypertension, may slow onset and progression. There is no consensus as to which cognitive screening instrument (CSI) is most suitable for VCI. We systematically reviewed the psychometric properties of brief CSIs for vascular mild cognitive impairment (VMCI) and vascular dementia (VaD).

Methods

Literature searches were performed using scholarly databases from inception until 31 May 2018. Studies were eligible if participants were aged 18 or older, interviewed face‐to‐face, and standard diagnostic criteria for VCI were applied, excluding those specifically identifying post‐stroke dementia. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool.

Results

Fifteen studies were identified including eight types of CSIs (27 subtests/variants) and 4575 participants (1015 with VCI), mean age range: 51.6 to 75.5 years. Most studies compared more than one instrument. Five papers examined clock‐drawing; four, the Montreal Cognitive Assessment (MoCA) and Mini‐Mental State Examination (MMSE); and three used the Brief Memory and Executive Test (BMET). The MoCA (AUC > 0.90) and MMSE (AUC: 0.86‐0.99) had excellent accuracy in differentiating VaD from controls; the MoCA had good internal consistency (Cronbach's α: .83‐.88). The MoCA (AUC: 0.87‐0.93) and BMET (AUC: 0.94) had the greatest accuracy in separating VMCI from controls. Most studies had low to moderate risk of bias in all domains of the QUIPS. Data were heterogeneous, precluding a meta‐analysis.

Conclusions

Although few studies were available and further research is required, data suggests that the MoCA is accurate and reliable for differentiating VaD and VMCI from controls.
Metal Doping/Alloying of Cesium Lead Halide Perovskite Nanocrystals and their Applications in Light‐Emitting Diodes with Enhanced Efficiency and Stability
Authors: Kumawat Naresh Kumar , Yuan Zhongcheng , Bai Sai , Gao Feng
Published: May 2019

Metal halide perovskite nanocrystals (NCs) have demonstrated great advances for light‐emitting diodes (LEDs) applications, owing to their excellent optical, electrical properties and cost‐effective solution‐processing potentials. Tremendous progress has been made in perovskite NCs‐based LEDs during the past several years, with the external quantum efficiency (EQE) boosted to over 20 %. Recently, metal doping/alloying strategy has been explored to finely tune the optoelectronic properties and enhance material stability of perovskite NCs, leading to further improved device efficiency and stability of the obtained perovskite NCs‐based LEDs. In this review, we summarize recent progress on the metal doping/alloying of perovskite NCs and their applications in LEDs. We focus on the effects of different metal doping strategies on the structural and optoelectronic properties of the perovskite NCs. In addition, several works on high‐performance LEDs based on metal doped/alloyed perovskite NCs with different light emission colours are highlighted. Finally, we present an outlook on employing metal doping/alloying strategies to further improve the device efficiency and stability of LEDs based on perovskite NCs.
A systematic review and meta‐analysis of dihydroartemisinin‐piperaquine versus sulphadoxine‐pyrimethamine for malaria prevention in pregnancy
Authors: Olaleye Atinuke , Okusanya Babasola O. , Oduwole Olabisi , Esu Ekpereonne , Meremikwu Martin
Published: May 2019

Background

Intermittent preventive treatment (IPT) with sulphadoxine‐pyrimethamine (SP) is recommended for preventing maternal and fetal effects of malaria in pregnancy. Increasing parasite resistance to SP has necessitated the search for an alternative medication.

Objective

To compare dihydroartemisinin‐piperaquine (DP) and sulphadoxine‐pyrimethamine in preventing malaria during pregnancy.

Search strategy

Databases including CENTRAL, MEDLINE, and ICTRP were searched until August 2018.

Selection criteria

Randomized and quasi‐randomized controlled trials that compared DP with SP given to pregnant women to prevent adverse maternal or fetal effects of malaria were included.

Data collection and analysis

Quality of evidence was determined with GRADE criteria. Effectiveness measures were calculated using odds ratios at 95% confidence intervals.

Results

Three randomized controlled trials were included. Compared with IPT‐SP, moderate certainty evidence indicated that women who received IPT‐DP had significantly lower risks of clinical malaria during pregnancy. High certainty evidence showed intermittent screening and treatment with DP did not reduce placental malaria or maternal parasitemia at delivery. Effect of DP on low birth weight and adverse birth outcomes was minimal.

Conclusions

Moderate certainty evidence suggests that IPT‐DP may reduce maternal and placental malaria compared with IPT‐SP, and monthly DP is more effective than SP in reducing placental malaria.

PROSPERO ID: CRD42018084651.
Optical and photoacoustic radiofrequency spectroscopic analysis for detecting red blood cell death
Authors: Fadhel Muhannad N. , Hysi Eno , Strohm Eric M. , Kolios Michael C.
Published: May 2019

Under stress, red blood cells (RBCs) undergo programmed cell death (eryptosis). One of the signaling molecules for eryptosis, sphingomyelinase (SMase), plays an important role in monitoring the efficacy of vascular targeted cancer therapy. The high optical absorption of erythrocytes coupled with the changes of eryptotic RBCs makes RBCs ideal targets for the photoacoustic (PA) detection and characterization of vascular treatments. In this work, experiments characterizing eryptosis were performed: PA detection of high frequencies (>100 MHz) that enabled analysis at the single‐cell level and of low frequencies (21 MHz) that enabled analysis at the RBC ensemble level. Ultrasound spectral analysis was performed on control and SMase‐treated RBCs. Spectral unmixing was applied to quantify methemoglobin production as a by‐product of RBC death. Validation was performed using a blood gas analyzer and optical spectrometry. Our results indicate that PA radiofrequency spectra could be used to differentiate the biochemically induced morphological changes as RBCs lose their native biconcave shape, and release hemoglobin into the surroundings. Spectral unmixing revealed a 7% increase in methemoglobin content for SMase‐treated samples due to the oxidative stress on the RBCs. These findings suggest that PA spectral analysis of RBC death can potentially serve as a biomarker of the efficacy of vascular targeted cancer therapies.
Long noncoding RNA RMRP promotes proliferation and invasion via targeting miR‐1‐3p in non–small‐cell lung cancer
Authors: Wang Yi , Luo Xigang , Liu Yang , Han Guanying , Sun Dapeng
Published: May 2019

The long noncoding RNA component of mitochondrial RNA‐processing endoribonuclease (lncRNA RMRP) plays an important role in tumor development. In the present study, we determined the regulatory function of RMRP in non–small‐cell lung cancer (NSCLC). The NSCLC tissues and the adjacent nontumor tissues were collected for the study. The RMRP expression was detected by quantitative real time‐PCR in NSCLC and lung cancer cell lines. The functional validation experiments were performed to determine the role of RMRP on NSCLC progression. In addition, we identified the downstream target miRNAs for RMRP. The results showed that RMRP was elevated in NSCLC tissues and cell lines. High RMRP expression was closely associated with advanced stage for the clinical features and low overall survival in NSCLC patients. Functional assay showed that loss of RMRP markedly inhibited cell proliferation, migration, and invasion. Flow cytometry assay demonstrated that the inhibition of RMRP dramatically induced cell cycle arrest in the G0/G1 phase. Moreover, we found that the role of RMRP on NSCLC cell progression was modulated by the inhibition of miR‐1‐3p. Collectively, our results demonstrated that the “RMRP‐miR‐1‐3p” axis might promote NSCLC progression. Hence, these investigations will provide a therapeutic target and strategy for the treatment of NSCLC progression.
Ab initio structure and vibration‐rotation dynamics of germylene, GeH2
Authors: Koput Jacek
Published: May 2019

Accurate structure and potential energy surface of germylene, GeH2, in its ground electronic state
1A1 were determined from ab initio calculations using the coupled‐cluster approach in conjunction with the correlation‐consistent basis sets up to sextuple‐zeta quality. The Born‐Oppenheimer equilibrium structural parameters for the
1A1 state are estimated to be re(GeH) = 1.5793 Å and ∠e(HGeH) = 91.19∘. The term value Te for the lowest excited electronic state ã3B1 of GeH2 is predicted to be 9140 cm–1. The vibration‐rotation energy levels for the
1A1 state of the 74GeH2, 74GeD2, 72GeH2, and 70GeH2 isotopologues were determined using a variational approach and compared with the experimental data. The role of the core‐electron correlation, higher‐order valence‐electron correlation, scalar relativistic, spin‐orbit, and adiabatic effects for prediction of the structure and vibration‐rotation dynamics of the GeH2 molecule is discussed. © 2019 Wiley Periodicals, Inc.
Genome‐wide microRNA screening reveals miR‐582‐5p as a mesenchymal stem cell‐specific microRNA in subchondral bone of the human knee joint
Authors: Wang Pinger , Dong Rui , Wang Baoli , Lou Zhaohuan , Ying Jun , Xia Chenjie , Hu Songfeng , Wang Weidong , Sun Qi , Zhang Peng , Ge Qinwen , Xiao Luwei , Chen Di , Tong Peijian , Li Ju , Jin Hongting
Published: May 2019

Emerging evidence suggests that microRNAs (miRNAs) may be pathologically involved in osteoarthritis (OA). Subchondral bone (SCB) sclerosis is accounted for the knee osteoarthritis (KOA) development and progression. In this study, we aimed to screen the miRNA biomarkers of KOA and investigated whether these miRNAs regulate the differentiation potential of mesenchymal stem cells (MSCs) and thus contributing to SCB. We identified 48 miRNAs in the blood samples in KOA patients (n = 5) through microarray expression profiling detection. After validation with larger sample number, we confirmed hsa‐miR‐582‐5p and hsa‐miR‐424‐5p were associated with the pathology of SCB sclerosis. Target genes prediction and pathway analysis were implemented with online databases, indicating these two candidate miRNAs were closely related to the pathways of pluripotency of stem cells and pathology of OA. Surprisingly, mmu‐miR‐582‐5p (homology of hsa‐miR‐582‐5p) was downregulated in osteogenic differentiation and upregulated in adipogenic differentiation of mesenchymal progenitor C3H10T1/2 cells, whereas mmu‐mir‐322‐5p (homology of hsa‐miR‐424‐5p) showed no change through the in vitro study. Supplementing mmu‐miR‐582‐5p mimics blocked osteogenic and induced adipogenic differentiation of C3H10T1/2 cells, whereas silencing of the endogenous mmu‐miR‐582‐5p enhanced osteogenic and repressed adipogenic differentiation. Further mechanism studies showed that mmu‐miR‐582‐5p was directly targeted to Runx2. Mutation of putative mmu‐miR‐582‐5p binding sites in Runx2 3′ untranslated region (3′UTR) could abolish the response of the 3′UTR‐luciferase construct to mmu‐miR‐582‐5p supplementation. Generally speaking, our data suggest that miR‐582‐5p is an important biomarker of KOA and is able to regulate osteogenic and adipogenic differentiation of MSCs via targeting Runx2. The study also suggests that miR‐582‐5p may play a crucial role in SCB sclerosis of human KOA.
LncRNA LINC01857 promotes growth, migration, and invasion of glioma by modulating miR‐1281/TRIM65 axis
Authors: Hu Guozhang , Liu Naijie , Wang Han , Wang Yue , Guo Zhigang
Published: May 2019

The great importance of long noncoding RNAs (lncRNAs) has been acknowledged in tumorigenesis gradually. LncRNA LINC01857 is a novel lncRNA and has been reported to promote breast cancer progression. However, the biological roles of LINC01857 in glioma are not explored. In the present research, LINC01857 levels were found to be upregulated in glioma. In addition, LINC01857 expression is negatively correlated with survival rate in glioma patients. Functional investigation revealed that LINC01857 downregulation impaired glioma proliferation and invasiveness. Furthermore, LINC01857 knockdown led to repressed growth of glioma in vivo. We found that LINC01857 could be a sponge for miR‐1281 and inhibits its level to upregulate TRIM65 expression. What's more, we showed that miR‐1281 mimics also attenuated tumor cell proliferation, migration, and invasion. And rescue assays demonstrated that LINC01857 promotes glioma progression through modulating miR‐1281/TRIM65 pathway. Collectively, this study first demonstrated that a novel LINC01857/miR‐1281/TRIM65 signaling regulates glioma progression.
Design and construction of a recombinant lentiviral vector with specific tropism to human epidermal growth factor‐overexpressed cancer cells: Developing a new retargeting system for lentivirus vectors
Authors: Ebrahimabadi Sima , Shahbazi Majid , Akbari Mona , Golalipour Masoud , Farazmandfar Touraj
Published: May 2019

Background

Targeting of specific tissues and cells by viruses is one of the challenges faced by researchers. Lentiviral vectors (LVs) are one of the most promising gene delivery systems in cancer gene therapy. Therefore, we aimed to design a novel lentiviral delivery system that expresses anti‐ human epidermal growth factor 2 (HER2) designed anykrin repeat protein (DARPin) on the vector envelope to create a pseudotyped lentivirus for targeting HER2‐positive cancer cells.

Methods

A helper plasmid producing the viral vector envelope containing anti‐HER2 DARPin‐G3 was constructed. LV was produced by transfer vector containing green fluorescent protein (GFP) gene and helper plasmids in human embryonic kidney 293 cells. The human breast cancer cell lines SKBR3 (normal and with inhibited endocytosis) (HER2‐positive) and MDA‐MB‐231 (HER2‐negative) were transduced by the recombinant viral vector. The GFP‐based transduction rate was determined by flow cytometry and fluorescence microscopy.

Results

The anti‐HER2 DARPin concentration in DARPin‐LVs was significantly higher than the envelope G glycoprotein of the vesicular stomatitis virus‐LVs (non‐anti‐HER2 control) (p < 0.0001). In flow cytometry assays, the percentage of transduction by recombinant LV was significantly higher in SKBR3 cells than in SKBR3 cells with inhibited endocytosis (p = 0.0074) and MDA‐MB‐231 cells (p = 0.0037). In fluorescence microscopy assays, the percentage of transduction by new LV was significantly higher in SKBR3 cells than in SKBR3 cells with inhibited endocytosis (p = 0.0026) and MDA‐MB‐231 cells (p = 0.0014).

Conclusions

We constructed a new recombinant LV with a defect in cell entry directly, containing an anti‐HER2 DARPin on the vector envelope with specific tropism to HER2 receptor on HER2‐positive cancer cells. We assumed that this viral vector transduces cells via an endocytosis‐dependent process.
Recognition and interaction of CphA from Aeromonas hydrophila with imipenem and biapenem by spectroscopic analysis in combination with molecular docking
Authors: Zhang Yeli , Bian Liujiao
Published: May 2019

The molecular recognition and interaction of CphA from Aeromonas hydrophila with imipenem (Imip) and biapenem (Biap) were studied by means of the combined use of fluorescence spectra and molecular docking. The results showed that both the fluorescence quenching of CphA by Imip and Biap were caused through the combined dynamic and static quenching, and the latter was dominating in the process; the microenvironment and conformational of CphA were altered upon the addition of Imip and Biap from synchronous and three‐dimensional fluorescence. The binding of CphA with Imip or Biap caused a conformational change in the loop of CphA, and through the conformational change, the loop opened the binding pocket of CphA to allow for an induced fit of the newly introduced ligand. In the binding of CphA with Imip, the whole molecule entered into the active pocket of CphA. The binding was driven by enthalpy change, and the binding force between them was mainly hydrogen bonding and Van der Waals force; whereas in the binding of CphA with Biap, only the beta‐lactam ring of Biap entered into the binding pocket of CphA while the side chain was located outside the active pocket. The binding was driven by the enthalpy change and entropy change together, and the binding force between them was mainly electrostatic interaction. This study provided an insight into the recognition and binding of CphA with antibiotics, which may be helpful for designing new substrate for beta‐lactamase and developing new antibiotics resistant to superbugs.
Deep learning enables automatic detection and segmentation of brain metastases on multisequence MRI
Authors: Grøvik Endre , Yi Darvin , Iv Michael , Tong Elizabeth , Rubin Daniel , Zaharchuk Greg
Published: May 2019

Background

Detecting and segmenting brain metastases is a tedious and time‐consuming task for many radiologists, particularly with the growing use of multisequence 3D imaging.

Purpose

To demonstrate automated detection and segmentation of brain metastases on multisequence MRI using a deep‐learning approach based on a fully convolution neural network (CNN).

Study Type

Retrospective.

Population

In all, 156 patients with brain metastases from several primary cancers were included.

Field Strength

1.5T and 3T. [Correction added on May 24, 2019, after first online publication: In the preceding sentence, the first field strength listed was corrected.]

Sequence

Pretherapy MR images included pre‐ and postgadolinium T1‐weighted 3D fast spin echo (CUBE), postgadolinium T1‐weighted 3D axial IR‐prepped FSPGR (BRAVO), and 3D CUBE fluid attenuated inversion recovery (FLAIR).

Assessment

The ground truth was established by manual delineation by two experienced neuroradiologists. CNN training/development was performed using 100 and 5 patients, respectively, with a 2.5D network based on a GoogLeNet architecture. The results were evaluated in 51 patients, equally separated into those with few (1–3), multiple (4–10), and many (>10) lesions.

Statistical Tests

Network performance was evaluated using precision, recall, Dice/F1 score, and receiver operating characteristic (ROC) curve statistics. For an optimal probability threshold, detection and segmentation performance was assessed on a per‐metastasis basis. The Wilcoxon rank sum test was used to test the differences between patient subgroups.

Results

The area under the ROC curve (AUC), averaged across all patients, was 0.98 ± 0.04. The AUC in the subgroups was 0.99 ± 0.01, 0.97 ± 0.05, and 0.97 ± 0.03 for patients having 1–3, 4–10, and >10 metastases, respectively. Using an average optimal probability threshold determined by the development set, precision, recall, and Dice score were 0.79 ± 0.20, 0.53 ± 0.22, and 0.79 ± 0.12, respectively. At the same probability threshold, the network showed an average false‐positive rate of 8.3/patient (no lesion‐size limit) and 3.4/patient (10 mm3 lesion size limit).

Data Conclusion

A deep‐learning approach using multisequence MRI can automatically detect and segment brain metastases with high accuracy.

Level of Evidence: 3

Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:175–182.
Persistent easterly winds leading to precipitation in the Atlantic Coast of Patagonia
Authors: Agosta Eduardo A. , Martin Paula B. , Serio Leonardo A.
Published: May 2019

The relationship between daily precipitation and unusually persistent easterly wind recorded at station level along the coast of Eastern Patagonia is examined. Easterly wind events that persist for more than 20 h (E) are infrequent in Comodoro Rivadavia (CMR); but in about 80% of the times they do occur daily precipitation exceeds 1 mm. Although 2‐day persistent easterlies (2E) occur only about 1% of the time in CMR they are associated with 20% of the >75% percentile rain events. The occurrence of precipitation days (P ≥ 1 mm) during 2E events (P1&2E) is far from randomness for most stations. For daily P1&2E events in CMR, the convergence of westward moisture flux from the Atlantic is the key. Its daily frequency shifts towards Niño (44%), followed by Neutral 35 (32%), and Niña (25%) conditions. The probability of null precipitation days with westerlies was higher than 95% on average among the stations. The tropospheric circulation anomalous conditions associated with P1&2E events are characterized by a blocking‐like flow along 80–90°W, with anticyclonic anomalies near 60°–70°S and cyclonic anomalies in the mid‐latitudes. The strength of the anomalies is given by the meridional gradient of tropospheric circulation anomalies, stronger during the Niño phase. A P1&2E event at CMR is linked to active slow‐moving weather systems linked to tropospheric Rossby waves triggered by upper‐level tropospheric mass divergence anomalies in low latitudes. The source and trajectory these Rossby waves are different through ENSO phases. We have found that heavy precipitation over subtropical eastern Argentina during Niño precede CMR P1&2E events by 10 to 8 days. Daily P1&2E events contribute substantially to the mean precipitation total from April to June. The differential influence of the ENSO phases through the seasons of year is evident in such a contribution.
Synergistic effects triggered by simultaneous Toll‐like receptor‐2 and ‐3 activation in human periodontal ligament stem cells
Authors: Blufstein Alice , Behm Christian , Gahn Johannes , Uitz Oksana , Naumovska Ivana , Moritz Andreas , Rausch‐Fan Xiaohui , Andrukhov Oleh
Published: May 2019

Background

Although periodontitis is associated with disruption of the host‐microbial homeostasis, viruses are currently discussed to influence disease progression. Viral pathogens are recognized by Toll‐like receptor (TLR)‐3, which engages a different signaling pathway than other TLRs. This study aimed to investigate the effect of TLR‐3 agonist polyinosinic:polycytidylic acid (Poly I:C) on the expression of inflammatory markers and bone metabolism proteins by human periodontal ligament stem cells (hPDLSCs) compared with TLR‐2 agonist Pam3CSK4, which mimics the effect of bacterial lipoproteins. To assess potential combined effects of bacterial and viral infections, hPDLSCs response to simultaneous TLR‐2 and TLR‐3 activation was investigated.

Methods

HPDLSCs were stimulated with Poly I:C (0.0001‐1 µg/mL), Pam3CSK4 (1 µg/mL), and their combinations for 24 hours. Gene expression and protein levels of interleukin (IL)‐6, IL‐8, monocyte chemoattractant protein (MCP)‐1, and osteoprotegerin (OPG) were measured with qPCR and ELISA.

Results

Production of IL‐6, IL‐8, MCP‐1, and OPG was significantly increased by Poly I:C or Pam3CSK4 to a similar extent. The levels of all inflammatory mediators induced by simultaneous stimulation with Poly I:C and Pam3CSK4 were significantly higher compared with single stimuli as well as to their summed response. Gene expression and protein levels of OPG were enhanced by Poly I:C, but by lesser extent than by Pam3CSK4. OPG levels upon simultaneous stimulation with Pam3CSK4 and Poly I:C were significantly lower compared with Pam3CSK4 stimulation alone.

Conclusions

Simultaneous TLR‐2 and TLR‐3 activation synergistically triggers IL‐6, IL‐8, and MCP‐1 production, which was not observed for OPG. These findings suggest that TLR‐3 activation by viral infections might promote periodontitis progression.
Trend of surgery for orbital cellulitis: An analysis of state inpatient databases
Authors: Jiramongkolchai Pawina , Lander Daniel P. , Kallogjeri Dorina , Olsen Margaret A. , Keller Matthew , Schneider John S. , Lee Jake J. , Jiramongkolchai Kim , Piccirillo Jay F.
Published: May 2019

Objectives/Hypothesis

To evaluate the trend and factors associated with surgical management of orbital cellulitis.

Study Design

Retrospective database study.

Methods

Study using the State Inpatient Databases (SIDs) from 2008 to 2015. Patients with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM) diagnosis code for orbital cellulitis were identified in the SIDs for the following states: Arkansas, Florida, Iowa, Maryland, Nebraska, New York, and Wisconsin. Surgery was defined as an ICD‐9‐CM procedure code for orbitotomy and/or functional endoscopic sinus surgery. The trend of surgery over time was evaluated using the Cochran‐Armitage test. Multivariable logistic regression models were used to identify patient‐ and hospital‐level factors associated with surgery.

Results

From 2008 to 2013, the number of hospitalizations for orbital cellulitis ranged from 1,349 to 1,574, but declined to 865 in 2014. From 2008 to 2015, the number of surgeries ranged from 103 to 154. For children (n = 3,041), age, ophthalmologic comorbidity, and conjunctival edema were significantly associated with surgery, whereas for adults (n = 7,961), male gender, private insurance, optic neuritis, and cranial nerves III/VI/VI palsy were associated with surgery.

Conclusions

Although the number of inpatient hospitalizations for orbital cellulitis has markedly declined, the number of surgeries for orbital cellulitis has remained fairly stable, leading to an observed higher proportion of hospitalized patients undergoing surgery. Future directions include extending the time frame to the present day to assess current rates of hospitalization and surgery. Knowledge of surgical trends and patient‐ and hospital‐level characteristics associated with surgery may help improve management guidelines for and understanding of this vision‐threatening disease.

Level of Evidence

NA

Laryngoscope, 130:567–574, 2020
Halophyte residue decomposition and microbial community structure in coastal soil
Authors: Chaudhary Doongar R. , Rathore Aditya P. , Jha Bhavanath
Published: May 2019

Saltmarshes are known for higher primary productivity and play a crucial role in carbon‐sequestration, nutrient‐cycling, and ecological services; however, scarce information are available on halophyte residue mineralization and microbial community structure during decomposition. Soil microcosms with residues (1% w/w) of three dominant halophytes (Aeluropus lagopoides, Arthrocnemum indicum, and Suaeda nudiflora) and one control were incubated under laboratory conditions and sampled at 1, 5, 10, 20, 40, and 90 days to link the microbial community structure and residues decomposition in degraded coastal soil. Samples were subjected to identification of active microbial groups and residue mineralization using fatty acid methyl ester (FAME) and CO2 evolution methods, respectively. Biochemical composition of residues was also analyzed. Cumulative CO2 evolution was elevated in residue‐amended soils compared with control, and it was highest in Arthrocnemum followed by Suaeda, Aeluropus, and control soil. The Aeluropus residue decomposed slower than others due to its high C/N ratio and low protein content. The contents of total FAME and biomarker FAMEs of microbial groups (bacterial, fungal, and actinomycetes) responded positively to the residue amendments compared with control, which indicate the improvement in soil microbial biomass. Soils amended with Suaeda had the highest amount of total (76.8 nmol/g) and fungal FAMEs (6.7 nmol/g), and bacterial (28.6 nmol/g) and actinomycete (3.0 nmol/g) FAMEs were elevated in Arthrocnemum amended soil. At the same time, soils amended with Suaeda (6.2%), Arthrocnemum (28.4%), and control (15.4%) had the greatest abundance of fungal, Gram‐negative and Gram‐positive FAME biomarkers, respectively. The present study suggests that residue of halophyte species affected the abundance of fungal and bacterial biomarkers, and the microbial community structure.
An intuitionistic formula hierarchy based on high‐school identities
Authors: Brock‐Nannestad Taus , Ilik Danko
Published: May 2019

We revisit the notion of intuitionistic equivalence and formal proof representations by adopting the view of formulas as exponential polynomials. After observing that most of the invertible proof rules of intuitionistic (minimal) propositional sequent calculi are formula (i.e., sequent) isomorphisms corresponding to the high‐school identities, we show that one can obtain a more compact variant of a proof system, consisting of non‐invertible proof rules only, and where the invertible proof rules have been replaced by a formula normalization procedure. Moreover, for certain proof systems such as the G4ip sequent calculus of Vorob'ev, Hudelmaier, and Dyckhoff, it is even possible to see all of the non‐invertible proof rules as strict inequalities between exponential polynomials; a careful combinatorial treatment is given in order to establish this fact. Finally, we extend the exponential polynomial analogy to the first‐order quantifiers, showing that it gives rise to an intuitionistic hierarchy of formulas, resembling the classical arithmetical hierarchy, and the first one that classifies formulas while preserving isomorphism.
Bifurcation analysis of a multidelayed HIV model in presence of immune response and understanding of in‐host viral dynamics
Authors: Adak Debadatta , Bairagi Nandadulal
Published: May 2019

In this paper, we proposed a multidelayed in‐host HIV model to represent the interaction between human immunodeficiency virus and immune response. One delay was considered to incorporate the time required by the virus for various intracellular events to make a host cell productively infective, and the second delay was introduced to take into account the time required for adaptive immune system to respond against infection. We extensively analyzed this multidelayed model analytically and numerically. We show that delay may have both destabilizing and stabilizing effects even when the system contains a single immune response delay. It happens when there exists two sequences of critical values of this delay. If the system starts with stable state in absence of delay, then the smallest value of these critical delays causes instability and the next higher value causes stability. The system may also show stability switching for different values of the virus replication factor. These results demonstrate the possible reasons of intrapatients and interpatients variability of CD4+ T cells and virus counts in HIV‐infected patients.
Local and blowing‐up solutions for a space‐time fractional evolution system with nonlinearities of exponential growth
Authors: Alsaedi Ahmed , Ahmad Bashir , Kirane Mokhtar , Rebiai Belgacem
Published: May 2019

Local and blowing‐up solutions for the Cauchy problem for a system of space and time fractional evolution equations with time‐nonlocal nonlinearities of exponential growth are considered. The existence and uniqueness of the local mild solution is assured by the Banach fixed point principle. Then, we establish a blow‐up result by Pokhozhaev capacity method. Finally, under some suitable conditions, an estimate of the life span of blowing‐up solutions is established.
Physical Activity Improves Lipid and Weight‐Loss Outcomes After Metabolic Bariatric Surgery in Adolescents with Severe Obesity
Authors: Price Paula Holland , Kaizer Alexander M. , Daniels Stephen R. , Jenkins Todd M. , Inge Thomas H. , Eckel Robert H.
Published: May 2019

Objective

This study tested the hypothesis that physical activity improves cardiovascular disease–related lipids beyond that associated with weight loss in adolescents with severe obesity after metabolic/bariatric surgery (MBS).

Methods

Objective activity monitor data from 108 participants of the Teen Longitudinal Assessment of Bariatric Surgery (Teen‐LABS) study from baseline to 3 years post MBS were used. Primary outcomes included absolute change in LDL cholesterol (LDL‐C) and non‐HDL cholesterol (non‐HDL‐C) from baseline. Baseline measurement, visit, surgical procedure, and percent change in iliac waist circumference or BMI from baseline in linear regression models were adjusted for use of generalized estimating equations. PROC TRAJ in SAS generated optimal activity trajectories based on individual step count.

Results

Despite low step counts and slow cadence, differences by activity trajectory were found. Greater absolute decreases in LDL‐C and non‐HDL‐C (−15 mg/dL [95% CI: −28 to −2], P  = 0.026; and −15 mg/dL [95% CI: −28 to −1], P  = 0.035), respectively, were associated with more activity. More activity was associated with greater resolution of triglycerides, LDL‐C, and non‐HDL‐C dyslipidemia and with greater weight loss 3 years post MBS.

Conclusions

More activity in adolescents was associated with improvements in cardiovascular disease–related lipid measures and weight loss after MBS.
A multiobjective optimization approach to filter tuning applied to coupled hyperbolic PDEs describing gas flow dynamics
Authors: Uilhoorn Ferdinand Evert
Published: May 2019

In this work, we introduce a multiobjective optimization approach that seeks the optimal process noise statistics in the extended Kalman filter (EKF). The bi‐objective Mesh Adaptive Direct Search (BiMADS) algorithm was used to minimize a performance index based on state estimate errors. The EKF estimated the gas flow dynamics in a pipeline system. Simulations were conducted with outflow boundary conditions for the flow model that contain gradual changes and discontinuities. To ensure shock‐capturing properties, the model was approximated with a semidiscrete finite volume scheme using Roe's SUPERBEE limiter. The knee point in the Pareto front was based on normal boundary intersection approach and selected to compute the flow estimates. Numerical experiments demonstrated that BiMADS is suitable for tuning the EKF and, compared to the normalized weighted sum method and nondominated sorting genetic algorithm, it showed to be superior in terms of computation time and most effective in finding Pareto optimal solutions.
Engaging stakeholders in pharmacoepidemiology research: Current state and recommendations
Authors: Camelo Castillo Wendy , Heath Nicholas , Kim John , Yang Kimberly , Ritchey Mary E. , dosReis Susan , Santanello Nancy , West Suzanne L.
Published: May 2019

Purpose

Given current efforts to enhance patient‐centered care and shared decision‐making, the International Society of Pharmacoepidemiology Workgroup on Patient Engagement assessed patient and other stakeholder engagement in pharmacoepidemiology research and provides recommendations for the field.

Methods

A systematic review used MEDLINE and EMBASE to identify published literature from 2005 to 2016 addressing how stakeholders—patients, caregivers, and others—assisted researchers conducting pharmacoepidemiologic research. Three pairs of Workgroup members screened titles and abstracts to select articles for full‐text review and analysis. Two Workgroup members abstracted the following data: research focus, characterization and role of stakeholders, and type(s) of engagement strategy employed. Data were summarized descriptively.

Results

We identified 5717 references for abstract screening. Of these, 69 met the criteria for full‐text screening, and 11 were selected for data abstraction. Of these 11 studies, seven focused on the development of a research agenda and eight had stakeholders react or advise on an aspect of the study. Although patients were the most commonly identified stakeholders, advocacy groups and health care professionals were also frequently identified. Some studies reported the engagement of other stakeholders, including local government or policy experts. Engagement strategies varied, with five studies using more than one strategy. Studies often did not indicate the involvement of stakeholders in developing the study design or with implementation.

Conclusions

Currently, few pharmacoepidemiology publications mention patient or other stakeholder engagement in the design, analysis, or reporting of research. This suggests that there are opportunities to expand stakeholder engagement and/or increase the transparency of reporting stakeholder engagement.
Lack of meaning, purpose and direction in life in personality disorder: A comparative quantitative approach using Livesley's General Assessment of Personality Disorder
Authors: Steen A. , Berghuis H. , Braam A.W.
Published: May 2019

Meaning in life is a motivational force and an existential theme for many people. The concept of meaning comprises purpose, comprehension and mattering. According to the Section III model of personality disorder (DSM‐5), lack of meaning, purpose and direction in life is part of personality dysfunction. The present study aimed to determine the association between personality disorder (PD), personality dysfunction and ‘lack of meaning, purpose and direction’ as a distinct facet of personality dysfunction, using Livesley's self‐report questionnaire—the General Assessment of Personality Disorder. This comparative quantitative study showed significant differences in lack of meaning, purpose and direction between a group of patients with PD (n = 126, PD with depression n = 51 and PD without depression n = 75), a group of non‐PD patients (n = 76, with depression n = 27 and without depression n = 49) and a control group (n = 444). The PD groups had similar scores as the non‐PD patients with depression. Lack of meaning was significantly associated with ‘difficulty setting and attaining goals’ in all groups, with ‘lack of affiliative relationships’ in the PD groups and ‘sense of inner emptiness’ in the PD group without depression and in controls. © 2019 John Wiley & Sons, Ltd.
Identification and Quantification of Proteoforms by Mass Spectrometry
Authors: Schaffer Leah V. , Millikin Robert J. , Miller Rachel M. , Anderson Lissa C. , Fellers Ryan T. , Ge Ying , Kelleher Neil L. , LeDuc Richard D. , Liu Xiaowen , Payne Samuel H. , Sun Liangliang , Thomas Paul M. , Tucholski Trisha , Wang Zhe , Wu Si , Wu Zhijie , Yu Dahang , Shortreed Michael R. , Smith Lloyd M.
Published: May 2019

A proteoform is a defined form of a protein derived from a given gene with a specific amino acid sequence and localized post‐translational modifications. In top‐down proteomic analyses, proteoforms are identified and quantified through mass spectrometric analysis of intact proteins. Recent technological developments have enabled comprehensive proteoform analyses in complex samples, and an increasing number of laboratories are adopting top‐down proteomic workflows. In this review, some recent advances are outlined and current challenges and future directions for the field are discussed.