bluuebunny/crossref_metadata_2025 huggingface dataset:
A Dual Inhibitor of DYRK1A and GSK3β for β‐Cell Proliferation: Aminopyrazine Derivative GNF4877
Authors: Liu Yahu A. , Jin Qihui , Ding Qiang , Hao Xueshi , Mo Tingting , Yan Shanshan , Zou Yefen , Huang Zhihong , Zhang Xiaoyue , Gao Wenqi , Wu Tom Y.‐H. , Li Chun , Bursalaya Badry , Di Donato Michael , Zhang You‐Qing , Deaton Lisa , Shen Weijun , Taylor Brandon , Kamireddy Anwesh , Harb George , Li Jing , Jia Yong , Schumacher Andrew M. , Laffitte Bryan , Glynne Richard , Pan Shifeng , McNamara Peter , Molteni Valentina , Loren Jon
Published: July 2020

Loss of β‐cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β‐cell mass are less developed. Promoting β‐cell proliferation with low‐molecular‐weight inhibitors of dual‐specificity tyrosine‐regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β‐cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β‐cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high‐throughput screening campaign measuring β‐cell proliferation.
An innovative derivatization‐free IC‐MS/MS method for the detection of bisphosphonates in horse plasma
Authors: Garcia Patrice , Pinètre Justine , Morel Sylvain , Jaubert Murielle , Deruy Xavier , Perot Isabelle , Delcourt Vivian , Loup Benoit , Popot Marie‐Agnès , Bailly‐Chouriberry Ludovic
Published: July 2020

Bisphosphonates are prohibited drugs according to Article 6 of the International Agreement on Breeding, Racing and Wagering of the International Federation of Horseracing Authorities (IFHA) and the International Equestrian Federation (FEI). These compounds are used for the treatment of lameness, navicular and bone diseases in horses and are divided into two groups: non‐nitrogen‐containing bisphosphonate drugs (e.g. clodronic acid) and nitrogen‐containing bisphosphonate drugs (e.g. zoledronic acid). Their hydrophilic properties and the high affinity for the bone matrix make the control of their use quite difficult. Current analytical strategies to detect such compounds often rely on a solid phase extraction (SPE) followed by detection by means of UHPLC–MS/MS after methylation with chemical reagents. To improve the analysis throughput and to eliminate the need for chemical derivatization, an innovative 96‐well SPE followed by ion chromatography‐mass spectrometry was developed. Analyses are conducted on an ICS‐6000 HPIC system coupled to a TSQ Altis™ (Thermo Scientific™). The use of a 96‐well SPE allowed 5‐fold sample increase and a 6‐fold throughput improvement. While preliminary results conducted on horse plasma exhibited similar performances to the method for the detection of non‐nitrogen‐containing bisphosphonates, the analytical performances of nitrogen‐containing bisphosphonates were greatly improved.
Movement patterns of large juvenile loggerhead turtles in the Mediterranean Sea: Ontogenetic space use in a small ocean basin
Authors: Chimienti Marianna , Blasi Monica F. , Hochscheid Sandra
Published: July 2020

Mechanisms that determine how, where, and when ontogenetic habitat shifts occur are mostly unknown in wild populations. Differences in size and environmental characteristics of ontogenetic habitats can lead to differences in movement patterns, behavior, habitat use, and spatial distributions across individuals of the same species. Knowledge of juvenile loggerhead turtles' dispersal, movements, and habitat use is largely unknown, especially in the Mediterranean Sea. Satellite relay data loggers were used to monitor movements, diving behavior, and water temperature of eleven large juvenile loggerhead turtles (Caretta caretta) deliberately caught in an oceanic habitat in the Mediterranean Sea. Hidden Markov models were used over 4,430 spatial locations to quantify the different activities performed by each individual: transit, low‐, and high‐intensity diving. Model results were then analyzed in relation to water temperature, bathymetry, and distance to the coast. The hidden Markov model differentiated between bouts of area‐restricted search as low‐ and high‐intensity diving, and transit movements. The turtles foraged in deep oceanic waters within 60 km from the coast as well as above 140 km from the coast. They used an average area of 194,802 km2, where most individuals used the deepest part of the Southern Tyrrhenian Sea with the highest seamounts, while only two switched to neritic foraging showing plasticity in foraging strategies among turtles of similar age classes. The foraging distribution of large juvenile loggerhead turtles, including some which were of the minimum size of adults, in the Tyrrhenian Sea is mainly concentrated in a relatively small oceanic area with predictable mesoscale oceanographic features, despite the proximity of suitable neritic foraging habitats. Our study highlights the importance of collecting high‐resolution data about species distribution and behavior across different spatio‐temporal scales and life stages for implementing conservation and dynamic ocean management actions.
Fluoroalkylation of Allylic Alcohols with Concomitant (Hetero)aryl Migration: Access to Fluoroalkylated Ketones and Evaluation of Antifungal Action against Magnaporthe grisea
Authors: Zhang Yanhu , Ren Ziyang , Liu Yun‐Lin , Wang Zhentao , Li Zhaodong
Published: July 2020

Fluoroalkyl(hetero)arylation of allylic alcohols with perfluoroalkyl iodide or difluoroacetic acid as fluoroalkyl source was developed herein, delivering functionalized ketones containing an α‐quaternary center. Formation of the fluoroalkyl radical was followed by its intermolecular addition to alkenes and the migration of a (hetero)aryl group with the concomitant generation of a ketone group to finish the domino sequence. Mechanistic studies indicated that the aryl migration proceeded through neophyl rearrangement in a radical pathway. Moreover, preliminary antifungal evaluation against Magnaporthe grisea is also described for the first time.
Insects as zoogeomorphic agents: an extended review
Authors: Bétard François
Published: July 2020

Insects are the largest and most diverse group of living organisms on Earth, playing a critical but underestimated role as agents of geomorphic change. Burrowing insects create micro‐scale landforms such as subterranean tunnels and surface mounds and, by this way, exert an influence on hydrology, soil erosion and sediment transfer at a wider landscape scale. However, social insects represented by ants and termites were the main taxa studied as geomorphic agents and ecosystem engineers. This article proposes an extended and critical literature review of insects as zoogeomorphic agents, with reference to various taxonomic orders and families of insects having a burrowing behaviour. It provides a large overview of their primary and secondary impacts on Earth surface systems, both supported by naturalistic evidence and available quantitative data. Some evolutionary insights are discussed based on fossil evidence of geomorphic work by insects and, at finer temporal scale, on recent advances in radiometric and luminescence dating of insect mounds. Finally, this article explores the fruitful links between geomorphology and entomology, and suggests several research perspectives in order to develop an integrated understanding of the importance of insects in Earth surface processes and landforms. © 2020 John Wiley & Sons, Ltd.
Using machine learning to quantify structural MRI neurodegeneration patterns of Alzheimer's disease into dementia score: Independent validation on 8,834 images from ADNI, AIBL, OASIS, and MIRIAD databases
Authors: Popuri Karteek , Ma Da , Wang Lei , Beg Mirza Faisal
Published: July 2020

Biomarkers for dementia of Alzheimer's type (DAT) are sought to facilitate accurate prediction of the disease onset, ideally predating the onset of cognitive deterioration. T1‐weighted magnetic resonance imaging (MRI) is a commonly used neuroimaging modality for measuring brain structure in vivo, potentially providing information enabling the design of biomarkers for DAT. We propose a novel biomarker using structural MRI volume‐based features to compute a similarity score for the individual's structural patterns relative to those observed in the DAT group. We employed ensemble‐learning framework that combines structural features in most discriminative ROIs to create an aggregate measure of neurodegeneration in the brain. This classifier is trained on 423 stable normal control (NC) and 330 DAT subjects, where clinical diagnosis is likely to have the highest certainty. Independent validation on 8,834 unseen images from ADNI, AIBL, OASIS, and MIRIAD Alzheimer's disease (AD) databases showed promising potential to predict the development of DAT depending on the time‐to‐conversion (TTC). Classification performance on stable versus progressive mild cognitive impairment (MCI) groups achieved an AUC of 0.81 for TTC of 6 months and 0.73 for TTC of up to 7 years, achieving state‐of‐the‐art results. The output score, indicating similarity to patterns seen in DAT, provides an intuitive measure of how closely the individual's brain features resemble the DAT group. This score can be used for assessing the presence of AD structural atrophy patterns in normal aging and MCI stages, as well as monitoring the progression of the individual's brain along with the disease course.
Observations from a systematic review of pharmacist‐led research in solid organ transplantation: An opinion paper of the American College of Clinical Pharmacy Immunology/Transplantation Practice and Research Network
Authors: Pilch Nicole A. , Park Jeong M. , Lichvar Alicia , Kane Clare , Bowman Lyndsey , Melaragno Jennifer I. , Sobhanian Minoosh , Perez Caroline , Trofe‐Clark Jennifer , Fleming James N.
Published: July 2020

Introduction

The contributions of transplant pharmacists to clinical and translational research in the United States are ill‐defined and have not been systematically reviewed.

Objectives

The American College of Clinical Pharmacy Immunology/Transplantation Practice and Research Network conducted a systematic review of available pharmacist‐led research publications involving solid organ transplantation with the intent to quantify and describe pharmacist‐led research endeavors and their changes over time.

Methods

An electronic search of Scopus was conducted to identify publications in the field of solid organ transplantation by pharmacist authors between January 1, 1975 and May 25, 2017. Articles were excluded if they were written in non‐English languages or originated from non‐US countries. Review articles, case reports, surveys, basic science research, pre‐clinical studies, and non‐transplant research were further excluded. Studies were categorized as one of four phases on the clinical and translational research spectrum, adapted from the Harvard Clinical and Translational Science Center description of a T1 to T4 classification system.

Results

A total of 10 354 publications were identified by the systematic search with 547 full‐text English‐language publications included in the analysis. Pharmacists served as the first author in 87% of the articles and as the senior author in 67% of the articles. A total of 71% of the articles included more than one pharmacist author. Transplant pharmacists published more studies that employed a retrospective or observational study design (55% and 78%, respectively). A total of 37% of studies were funded. On the spectrum of clinical and translation research, pharmacists were most involved in T3 (translation to practice) research (72%), followed by T2 (translation to patients) research (23%).

Conclusions

Transplant pharmacists are increasingly represented in the US literature and frequently published across domains. Further demonstrating the relevance of pharmacist‐delivered interventions and outcomes is a critical area of practice focus.
Use of continuous glucose monitoring to improve glycemic management: A clinician's guide
Authors: Schumacher Christie A. , Isaacs Diana , Collier Izabela , Klinkebiel Drew
Published: July 2020

Adoption of continuous glucose monitoring (CGM) technology in clinical practice has increased over the past few years with numerous studies demonstrating its benefit in persons with diabetes. In addition, the use of CGM systems is now recommended in multiple guidelines for diabetes care. Implementation of personal‐ and professional‐use CGM technology can facilitate patient‐centered discussions in clinical decision making and empower behavioral change. Pharmacists can incorporate CGM into diabetes management practices to help optimize therapy and overcome therapeutic inertia. This “how to” guide is written for pharmacists who are interested in integrating CGM into their clinical practice to improve care for those living with diabetes. It provides an overview of the different CGM systems available and describes the differences between personal‐ and professional‐use CGM to facilitate decision making for use in clinical practice. It also discusses considerations for use, candidates for coverage, billing for CGM services, data interpretation, and documentation. Lessons learned and advice for implementing into clinical practice are also provided.
Tree ring width‐based January–March mean minimum temperature reconstruction from Larix gmelinii in the Greater Khingan Mountains, China since AD 1765
Authors: Jiang Yangao , Liu Chuan , Zhang Junhui , Han Shijie , Coombs Cassius E. O. , Wang Xiaoguang , Wang Junwei , Hao Lin , Dong Shengzhong
Published: July 2020

A ring‐width chronology of Larix gmelinii (LG) was developed in the northern Greater Khingan Mountains region of China. The response function analyses revealed that the local mean minimum temperature of January–March (T1–3) was the most limiting factor affecting the radial growth of LG trees. Based on correlation analysis, a reconstructed T1–3 series from 1765 to 2013 was produced using standard ring‐width chronology. The reconstruction explained 41.2% of the total variance in recorded monthly mean minimum temperatures from 1960 to 2013. The reconstructed T1–3 series had similar variability when compared with the May–September mean temperature reconstruction in Inner Mongolia (IM) and the February–March mean minimum temperature reconstruction in Yichun (YC). This reconstructed T1–3 series also captured the severe snow disaster and cold wave events recorded from historical documents in Heilongjiang and Inner Mongolia. Spatial correlations between reconstructed series and gridded temperature data also provided a high level of confidence. In addition, significant relationships between the reconstructed T1–3 series and the Pacific Decadal Oscillation (PDO), El Niño–Southern Oscillation (ENSO), North Atlantic Oscillation (NAO), solar activity, indicated that the T1–3 variation might be influenced by large‐scale ocean–atmosphere interactions.
Application of near‐infrared handheld spectrometers to predict semolina quality
Authors: Cecchini Cristina , Antonucci Francesca , Costa Corrado , Marti Alessandra , Menesatti Paolo
Published: July 2020

BACKGROUND

Durum wheat semolina is the best raw material for pasta production and its protein content and gluten strength are essential for cooking quality. The need to develop rapid methods to speed up quality control makes near‐infrared spectroscopy (NIR) a useful method that is widely accepted in the cereal sector. In this study, two non‐destructive and rapid technologies, a low‐cost sensor providing a short wavelength NIR range (swNIR: 700–1100 nm) and a handheld NIR spectrometer (NIR: 1600–2400 nm), were employed to evaluate semolina quality.

The spectra data were correlated with chemical (protein content) and rheological parameters (i.e., Gluten Index, Alveograph®, Sedimentation test, GlutoPeak®). A partial least squares (PLS) model was used to compare the efficacy of swNIR and NIR.

RESULTS

The protein content was the reference parameter that correlated best with the spectra data and provided the best regression model (r model = 0.9788 for NIR and 0.9561 for swNIR). GlutoPeak indices also correlated well with spectral data, particularly with swNIR spectra. A provisional multivariate model was applied to classify semolina samples in quality classes by using their spectra. Better modeling efficiency was obtained for swNIR.

CONCLUSION

The results highlighted the advantages of a pocket‐sized low cost sensor (swNIR), which is easier to use directly at the sample source than laboratory instruments or more expensive portable devices. © 2020 Society of Chemical Industry
Opportunistic muscle measurements on staging chest CT for extremity and truncal soft tissue sarcoma are associated with survival
Authors: Phan Eileen N. , Thorpe Steven W. , Wong Felix S. , Saiz Augustine M. , Taylor Sandra L. , Canter Robert J. , Lenchik Leon , Randall R. Lor , Boutin Robert D.
Published: July 2020

Background and Objectives

Computed tomography (CT) measurements of sarcopenia have been proposed as biomarkers associated with outcomes in various cancers and have typically been evaluated at the L3 vertebral level. However, staging imaging for patients with extremity and truncal soft tissue sarcoma (STS) often only includes chest CT imaging which precludes evaluation at L3. Therefore, we sought to evaluate muscle metrics at T12 on standard staging chest CT scans and evaluate for correlation with overall and event‐free survival in patients with STS.

Methods

CT chest imaging for 89 patients with intermediate and high‐grade STS (53 male, 36 female; 58.5 ± 19.0 years old, follow‐up 37.4 ± 27.1 months) was reviewed on PACS at T12 for skeletal muscle density (SMD) and skeletal muscle index (SMI).

Results

Overall survival increased with increased SMD on univariate (hazard ratio [HR] = 0.61 [0.43, 0.86]) and age‐adjusted analysis (HR = 0.65 [0.42, 0.89]. Event‐free survival also increased with increased SMD in univariate analyses (HR = 0.68 [0.49, 0.95]) but did not maintain significance after adjusting for age (HR = 0.68 [0.43, 1.07]). SMI was not a predictor of overall or event‐free survival.

Conclusions

Higher SMD measured on routinely obtained staging chest CTs in STS patients is associated with improved survival.
Detection of sentinel lymph node in laparoscopic surgery for uterine cervical cancer using carbon nanoparticles
Authors: Wang Yating , Dan Zhao , Yuan Guangwen , Zhang Gongyi , Liu Shuanghuan , Zhang Yanan , Li Bin
Published: July 2020

Background and Objectives

Carbon nanoparticles (CNPs) has been widely confirmed the efficiency in sentinel lymph node (SLN) mapping for various solid tumors. This study aims to explore the feasibility and effectiveness of CNPs during laparoscopic surgery for cervical cancer.

Methods

We analyzed 45 women with stage IB1‐IIA1 cervical cancer who underwent SLN mapping using CNPs during laparoscopic surgery. The effectiveness of CNPs was evaluated by the detection rate and accuracy parameters. Factors associated with SLN laterality and SLNs localizations were analyzed.

Results

The overall and bilateral detection rate was 93.3% (42/45) and 60.0% (27/45), respectively. Elevated body mass index was associated with decreased bilateral detection rate (P = .015). A total of 225 SLNs were harvested, with a mean number of 5.0 ± 3.6. A total of 81.3% of SLNs were in expected localizations including external iliac (39.1%), internal iliac (25.8%), and obturator (16.4%) regions, while 18.7% in unusual localizations including common iliac (10.7%), parametrial (7.6%), and presarcal (0.4%) regions. None positive lymph node was found in non‐SLNs with a false‐negative rate of 0%.

Conclusion

Laparoscopic SLN mapping with CNPs appears to be simple and efficient for patients with early‐stage cervical cancer.
Global academic response to COVID‐19: Cross‐sectional study
Authors: Helliwell Jack A. , Bolton William S. , Burke Joshua R. , Tiernan Jim P. , Jayne David G. , Chapman Stephen J.
Published: July 2020

This study explores the response to COVID‐19 from investigators, editors, and publishers and seeks to define challenges during the early stages of the pandemic. A cross‐sectional bibliometric review of COVID‐19 literature was undertaken between 1 November 2019 and 24 March 2020, along with a comparative review of Middle East respiratory syndrome (MERS) literature. Investigator responsiveness was assessed by measuring the volume and type of research published. Editorial responsiveness was assessed by measuring the submission‐to‐acceptance time and availability of original data. Publisher‐responsiveness was assessed by measuring the acceptance‐to‐publication time and the provision of open access. Three hundred and ninety‐eight of 2,835 COVID‐19 and 55 of 1,513 MERS search results were eligible. Most COVID‐19 studies were clinical reports (n = 242; 60.8%). The submission‐to‐acceptance [median: 5 days (IQR: 3–11) versus 71.5 days (38–106); P < .001] and acceptance‐to‐publication [median: 5 days (IQR: 2–8) versus 22.5 days (4–48·5‐; P < .001] times were strikingly shorter for COVID‐19. Almost all COVID‐19 (n = 396; 99.5%) and MERS (n = 55; 100%) studies were open‐access. Data sharing was infrequent, with original data available for 104 (26.1%) COVID‐19 and 10 (18.2%) MERS studies (P = .203). The early academic response was characterized by investigators aiming to define the disease. Studies were made rapidly and openly available. Only one‐in‐four were published alongside original data, which is a key target for improvement.

Key points

COVID‐19 publications show rapid response from investigators, specifically aiming to define the disease.

Median time between submission and acceptance of COVID‐19 articles is 5 days demonstrating rapid decision‐making compared with the median of 71.5 days for MERS articles.

Median time from acceptance to publication of COVID‐19 articles is 5 days, confirming the ability to introduce rapid increases at times of crisis, such as during the SARS outbreak.

The majority of both COVID‐19 and MERS articles are available open‐access.
MicroRNAs 155‐5p, 122‐5p, and 181a‐5p Identify Patients With Graft Dysfunction Due to T Cell–Mediated Rejection After Liver Transplantation
Authors: Ruiz Pablo , Millán Olga , Ríos Jose , Díaz Alba , Sastre Lydia , Colmenero Jordi , Crespo Gonzalo , Brunet Mercè , Navasa Miquel
Published: July 2020

MicroRNAs (miRNAs) are small noncoding RNAs that can be detected in plasma and whose expression is associated with pathological processes. The role of miRNAs in the noninvasive diagnosis of T cell–mediated rejection (TCMR) after liver transplantation (LT) is unclear. Thus, we aimed to assess the effectiveness of a panel of 4 miRNAs (155‐5p, 122‐5p, 181a‐5p, and 148‐3p) in diagnosing TCMR in LT recipients with graft dysfunction (GD), and we compared its accuracy with previously published tests for diagnosing TCMR based on routine laboratory parameters. From a prospective cohort of 145 patients followed during the first year after transplant, 49 developed GD and underwent a liver biopsy and plasma collection for miRNA analysis using quantitative real‐time polymerase chain reaction. Patients with GD due to TCMR (n = 21) exhibited significantly higher (P < 0.001) expression of miRNA 155‐5p (2.05 versus 0.07), 122‐5p (19.36 versus 1.66), and 181a‐5p (1.33 versus 0.37) compared with those with GD from other causes (n = 28). The area under the receiver operating characteristic curve of miRNAs 155‐5p, 122‐5p, and 181a‐5p for the diagnosis of TCMR was 0.87, 0.91, and 0.89, respectively, significantly higher than those of the other noninvasive tests (P < 0.001). Furthermore, miRNA 155‐5p identified all patients who presented TCMR during the first 2 weeks after transplant. miRNA plasmatic expression differentiates TCMR from other causes of GD in patients who have undergone LT and may be a useful tool in clinical practice.
The expression and regulation of HOX genes and membrane proteins among different cytogenetic groups of acute myeloid leukemia
Authors: Wang Huili , Lin Sheng‐Yan , Hu Fei‐Fei , Guo An‐Yuan , Hu Hui
Published: July 2020

Background

The cytogenetic aberrations were considered as markers for diagnosis and prognosis in acute myeloid leukemia (AML), while the expression and regulation under different cytogenetic groups remain to be fully elucidated.

Methods

In this paper, for favorable, poor, and cytogenetically normal groups of AML patients, we performed comprehensive bioinformatics analyses including identifying differentially expressed genes (DEGs) and microRNAs (miRNAs) among them, functional enrichment and regulatory networks.

Results

We found that DEGs were enriched in membrane‐related processes. Eleven genes and two miRNAs were significantly differentially expressed among these three AML groups. In survival analysis, membrane‐related genes and several miRNAs were significant on prognostic outcome. Notably, six HOXA and three HOXB genes were significantly in low expression and high methylation in AML with favorable cytogenetics. Meanwhile, the miRNA‐HOX gene co‐regulatory networks revealed that HOXA5 was a hub node and regulated an AML oncogene SPARC.

Conclusion

Our work may provide novel insights to the molecular characteristics and classification between AML with different cytogenetics.
Long Term Exposure to a Grape Seed Proanthocyanidin Extract Enhances L‐Cell Differentiation in Intestinal Organoids
Authors: Casanova‐Martí Àngela , González‐Abuín Noemi , Serrano Joan , Blay Maria Teresa , Terra Ximena , Frost Gary , Pinent Montserrat , Ardévol Anna
Published: July 2020

Scope

A grape‐seed proanthocyanidin extract (GSPE) interacts at the intestinal level, enhancing glucagon‐like peptide‐1 (GLP‐1) and peptide YY (PYY) release, which modulate appetite and glucose homeostasis. Thus, enhancing L‐cell numbers could be a strategy to promote hormone production, providing a potential strategy for obesity and type‐2 diabetes mellitus (T2DM) treatment.

Methods and results

Mice ileum organoids are used to evaluate the long‐term effects of GSPE and two of its main components, epicatechin (EC) and gallic acid (GA), on intestinal differentiation. Hormone levels are determined using RIA and ELISA kits, and gene expression of transcription factors involved in intestinal cell differentiation, as well as markers of different cell types, are assessed by real‐time qPCR. GSPE upregulates enterohormone gene expression and content, as well as the pan‐endocrine marker chromogranin A. GSPE also modulates the temporal gene expression profile of early and late transcription factors involved in L‐cell differentiation. Furthermore, GSPE upregulates goblet cell (Muc2) and enterocyte (sucraseisomaltase) markers, while downregulating stem cell markers (Lgr5+). Although EC and GA modified enterohormone release, they do not reproduce GSPE effects on transcription factor's profile.

Conclusions

This study shows the potential role of GSPE in promoting enteroendocrine differentiation, effect that is not mediated by EC or GA.
Self‐supervised learning of physics‐guided reconstruction neural networks without fully sampled reference data
Authors: Yaman Burhaneddin , Hosseini Seyed Amir Hossein , Moeller Steen , Ellermann Jutta , Uğurbil Kâmil , Akçakaya Mehmet
Published: July 2020

Purpose

To develop a strategy for training a physics‐guided MRI reconstruction neural network without a database of fully sampled data sets.

Methods

Self‐supervised learning via data undersampling (SSDU) for physics‐guided deep learning reconstruction partitions available measurements into two disjoint sets, one of which is used in the data consistency (DC) units in the unrolled network and the other is used to define the loss for training. The proposed training without fully sampled data is compared with fully supervised training with ground‐truth data, as well as conventional compressed‐sensing and parallel imaging methods using the publicly available fastMRI knee database. The same physics‐guided neural network is used for both proposed SSDU and supervised training. The SSDU training is also applied to prospectively two‐fold accelerated high‐resolution brain data sets at different acceleration rates, and compared with parallel imaging.

Results

Results on five different knee sequences at an acceleration rate of 4 shows that the proposed self‐supervised approach performs closely with supervised learning, while significantly outperforming conventional compressed‐sensing and parallel imaging, as characterized by quantitative metrics and a clinical reader study. The results on prospectively subsampled brain data sets, in which supervised learning cannot be used due to lack of ground‐truth reference, show that the proposed self‐supervised approach successfully performs reconstruction at high acceleration rates (4, 6, and 8). Image readings indicate improved visual reconstruction quality with the proposed approach compared with parallel imaging at acquisition acceleration.

Conclusion

The proposed SSDU approach allows training of physics‐guided deep learning MRI reconstruction without fully sampled data, while achieving comparable results with supervised deep learning MRI trained on fully sampled data.
Digital spatial cracking behaviors of fine‐grained sandstone with precracks under uniaxial compression
Authors: Zhou Xiao‐Ping , Zhao Zhi , Liu Yang
Published: July 2020

X‐ray computed tomography (CT) imaging and digital image correlation techniques are applied to study spatial cracking behaviors of sandstone under uniaxial compression, in which the angle between precracks is 45°, 90°, and 135° and the crack depth is 7.5 mm and 10 mm, respectively. Layered anisotropy damages and spatial cracking evolution are quantitatively analyzed by the defined digital layered anisotropy index and digital damage ratio, respectively. Three cases with different array of precracks evidence the depth effects of precracks on spatial crack propagation. Results show that the failure process of samples is first controlled by the coalescence of surface cracks in 2D space and then the samples are failed by the propagation of coalesced cracks (shear cracks with different shapes). The crack types for samples with precrack depth of 7.5 mm are all shear cracks for Cases 1‑3. Nevertheless, the crack types for samples with precrack depth of 10 mm are, respectively, the half X‐shape crack for Case 1, X‐shape crack for Case 2, and double shell crack for Case 3. The precrack has a significant promotion effect on the failure process when the angle between the two precracks is β = 90°, and the precrack has little to no effect on the failure process when the angle between the two precracks is β = 135°. As the depth of precrack increases to 10 mm, the crack types are changed in this study. The peak strength of sample subjected to uniaxial compression decreases with increasing depth of precracks, implying the decrease of the rock strength by the discontinuity.
3D variable‐density SPARKLING trajectories for high‐resolution T2*‐weighted magnetic resonance imaging
Authors: Lazarus Carole , Weiss Pierre , El Gueddari Loubna , Mauconduit Franck , Massire Aurélien , Ripart Mathilde , Vignaud Alexandre , Ciuciu Philippe
Published: July 2020

We have recently proposed a new optimization algorithm called SPARKLING (Spreading Projection Algorithm for Rapid K‐space sampLING) to design efficient compressive sampling patterns for magnetic resonance imaging (MRI). This method has a few advantages over conventional non‐Cartesian trajectories such as radial lines or spirals: i) it allows to sample the k‐space along any arbitrary density while the other two are restricted to radial densities and ii) it optimizes the gradient waveforms for a given readout time. Here, we introduce an extension of the SPARKLING method for 3D imaging by considering both stacks‐of‐SPARKLING and fully 3D SPARKLING trajectories. Our method allowed to achieve an isotropic resolution of 600 μm in just 45 seconds for T2∗‐weighted ex vivo brain imaging at 7 Tesla over a field‐of‐view of 200 × 200 × 140 mm3. Preliminary in vivo human brain data shows that a stack‐of‐SPARKLING is less subject to off‐resonance artifacts than a stack‐of‐spirals.
What do we know about nonprofit collaboration? A systematic review of the literature
Authors: Gazley Beth , Guo Chao
Published: July 2020

This systematic literature review reports on the content of past empirical studies of nonprofit collaboration within and across the sectors, published between 1972 and 2015 (n = 657). An analysis of these articles reveals four major themes: diverse but “siloed” data; imbalance in research coverage; the dominance of “big four” organization theories; and limited improvement in research sophistication. It further identifies five specific research gaps: the insufficient attention to the forms and intensity of nonprofit collaboration; the divergences and contradictions in theoretical reasoning and empirical evidence; the lack of attention to the moderators and/or mediators of collaboration; the lack of understanding of collaborative failure; and the lack of comparative studies. These findings help to inform collaboration research and practice by observing the value in using a broader scope of literature and methods to build knowledge in this area.
Hurthle cell carcinoma in childhood: A retrospective analysis of five cases and review of pediatric literature
Authors: Zirilli Giuseppina , Valenzise Mariella , Dionigi Gianlorenzo , Tuccari Giovanni , Romeo Carmelo , Campennì Alfredo , Corrias Andrea , Tuli Gerdi , Ieni Antonio , Pajno Giovanni Battista , Wasniewska Malgorzata
Published: July 2020

Background

the available studies on Hurthle cell carcinoma (HCC) in pediatric age are scarce and based on isolated case reports. Aims of the present study were to review the available pediatric literature on HCC (2000‐2019), to describe the cohort of children with this cancer histotype, and to estimate its relative prevalence in pediatric age.

Procedure

We retrospectively reconstructed an HCC course in five patients < 19 years who were identified in our departments during the period 2000‐2019, and we reviewed the available pediatric studies on this differentiated thyroid cancer (DTC) variant.

Results

HCC occurred with a relative prevalence of 5.8% at a median chronological age of 12.5 years. None of HCC patients exhibited, at diagnosis, thyroid dysfunction, extensive lateral neck disease, or distant metastases, and all showed a persistent remission over time. Three patients showed, at diagnosis, antecedents of other diseases (Hashimoto's thyroiditis, neurofibromatosis type 1, and osteosarcoma).

Conclusions

(1) In childhood, the relative prevalence of HCC among different thyroid cancer histotypes is 5.8%, that is close to the one previously reported both in the general population and in other less numerous children's cohorts; (2) HCC may develop even early, at the age of 7; (3) in childhood, HCC does not seem to have a more aggressive behavior when compared with other DTC histotypes; (4) antecedents of other diseases are not infrequent in the history of children with HCC.
Excessive positive response of model‐simulated land net primary production to climate changes over circumboreal forests
Authors: Tei Shunsuke , Sugimoto Atsuko
Published: July 2020

Land carbon cycle components in an Earth system model (ESM) play a crucial role in the projections of forest ecosystem responses to climate/environmental changes. Evaluating models from the viewpoint of observations is essential for an improved understanding of model performance and for identifying uncertainties in their outputs. Herein, we evaluated the land net primary production (NPP) for circumboreal forests simulated with 10 ESMs in Phase 5 of the Coupled Model Intercomparison Project by comparisons with observation‐based indexes for forest productivity, namely, the composite version 3G of the normalized difference vegetation index (NDVI3g) and tree‐ring width index (RWI). These indexes show similar patterns in response to past climate change over the forests, i.e., a one‐year time lag response and smaller positive responses to past climate changes in comparison with the land NPP simulated by the ESMs. The latter showed overly positive responses to past temperature and/or precipitation changes in comparison with the NDVI3g and RWI. These results indicate that ESMs may overestimate the future forest NPP of circumboreal forests (particularly for inland dry regions, such as inner Alaska and Canada, and eastern Siberia, and for hotter, southern regions, such as central Europe) under the expected increases in both average global temperature and precipitation, which are common to all current ESMs.
Targeted Mass Spectrometry of a Clinically Relevant PSA Variant from Post‐DRE Urines for Quantitation and Genotype Determination
Authors: Otto Joseph J. , Correll Vanessa L. , Engstroem Hampus A. , Hitefield Naomi L. , Main Brian P. , Albracht Brenna , Johnson‐Pais Teresa , Yang Li Fang , Liss Michael , Boutros Paul C. , Kislinger Thomas , Leach Robin J. , Semmes Oliver J. , Nyalwidhe Julius O.
Published: July 2020

Purpose

The rs17632542 single nucleotide polymorphism (SNP) results in lower serum prostate specific antigen (PSA) levels which may further mitigate against its clinical utility as a prostate cancer biomarker. Post‐digital rectal exam (post‐DRE) urine is a minimally invasive fluid that is currently utilized in prostate cancer diagnosis. To detect and quantitate the variant protein in urine.

Experimental design

Fifty‐three post‐DRE urines from rs17632542 genotyped individuals processed and analyzed by liquid chromatography/mass spectrometry (LC‐MS) in a double‐blinded randomized study. The ability to distinguish between homozygous wild‐type, heterozygous, or homozygous variant is examined before unblinding.

Results

Stable‐isotope labeled peptides are used in the detection and quantitation of three peptides of interest in each sample using parallel reaction monitoring (PRM). Using these data, groupings are predicted using hierarchical clustering in R. Accuracy of the predictions show 100% concordance across the 53 samples, including individuals homozygous and heterozygous for the SNP.

Conclusions and clinical relevance

The study demonstrates that MS based peptide variant quantitation in urine could be useful in determining patient genotype expression. This assay provides a tool to evaluate the utility of PSA variant (rs17632542) in parallel with current and forthcoming urine biomarker panels.
The endothelin receptor antagonist macitentan for the treatment of pulmonary arterial hypertension: A cross‐species comparison of its cytochrome P450 induction pattern
Authors: Treiber Alexander , Delahaye Stephane , Seeland Swen , Gnerre Carmela
Published: July 2020

The dual endothelin receptor antagonist macitentan was approved in 2013 for the treatment of pulmonary arterial hypertension. Macitentan is an inducer of cytochrome P450 expression in vivo in animal species but not in man. In rat and dog, changes in P450 expression manifest as autoinduction upon repeat dosing. The induction pattern, however, significantly differed between both species, and between male and female rats. While macitentan exposure steadily declined with dose in the dog, P450 induction was saturable in the rat reaching levels of 40%‐60% and 60%‐80% at steady‐state in male and female animals, respectively. The nature and number of P450 enzymes involved in macitentan clearance were identified as a major reason for the observed species differences. In the dog, macitentan was metabolized by a single P450 enzyme, that is, Cyp3a12, whereas several members of the Cyp2c and Cyp3a families were involved in the rat. Macitentan selectively upregulated Cyp3a expression in rat, whereas the expression of the Cyp2c enzymes involved in macitentan metabolism remained mostly unchanged, eventually leading to a higher contribution of Cyp3a upon induction. Macitentan also induced CYP3A4 expression in human hepatocytes via initial activation of the human pregnane X receptor. No such induction was evident in humans at the therapeutic macitentan dose of 10 mg as shown in a clinical drug‐drug interaction study with the CYP3A4 substrate sildenafil.
Young adults' return migration from large cities in Sweden: The role of siblings and parents
Authors: Mulder Clara H. , Lundholm Emma , Malmberg Gunnar
Published: July 2020

Living in cities affects young adults' access to education and work. With the use of register data for 2000–2013, we examined the role of having siblings and parents living close by and having siblings and parents living in the area of origin, in young adults' return migration from the four largest cities in Sweden. We found that young adults were less likely to return, and also less likely to migrate elsewhere, if they had siblings or parents living in the city of residence than if this was not the case. If the parents no longer lived in the region of origin, the young adults were very unlikely to return. Young adults were more likely to return if they had siblings living in that region than if they had no siblings or the siblings lived elsewhere. Adverse circumstances such as dropping out of tertiary education, low income, and unemployment were associated with a greater likelihood of return migration.
Single Ion Implantation of Bismuth
Authors: Cassidy Nathan , Blenkinsopp Paul , Brown Ian , Curry Richard J. , Murdin B. N. , Webb Roger , Cox David
Published: July 2020

Herein, the results from a focused ion beam instrument, designed to implant single ions with a view to the fabrication of qubits for quantum technologies, are presented. The difficulty of single ion implantation is accurately counting the ion impacts. This is achieved here through the detection of secondary electrons generated upon each ion impact. The implantation of single bismuth ions with different charge states into Si, Ge, Cu, and Au substrates is reported, and the counting detection efficiency for single ion implants and the factors that affect such detection efficiencies are determined. It is found that for 50 keV implants of Bi++ ions into silicon an 89% detection efficiency can be achieved, which is the first quantitative detection efficiency measurement for single ion implants into silicon without implanting through a thick SiO2 film. This level of counting accuracy provides implantation of single impurity ions with a success rate significantly exceeding that achievable by random (Poissonian) implantation.
The Splitting of Electron States in Ge/Si Heterostructure with Germanium Quantum Dots
Authors: Pokutnyi Sergey I.
Published: July 2020

It is shown that electron tunneling through a potential barrier that separates two quantum dots (QDs) of germanium leads to the splitting of electron states localized over spherical interfaces (QD–silicon matrix). The dependence of the splitting values of the electron levels on the parameters of the nanosystem (the radius a of germanium QDs, as well as the distance D between the surfaces of the QDs) is obtained. It is shown that, the splitting of electron levels in the QD chain of germanium causes the appearance of a zone of localized electron states, which is located in the bandgap of silicon matrix. It is found that the motion of a charge‐transport exciton along a chain of QDs of germanium causes an increase in photoconductivity in the nanosystem.
Second SVC stent treatment for tumour ingrowth
Authors: Takahara Yutaka , Ishige Yoko , Shionoya Ikuyo , Fujimoto Yuki , Oikawa Taku , Mizuno Shiro
Published: July 2020

Key message

We herein report a case of lung cancer with recurrent superior vena cava (SVC) syndrome, which was treated with additional stent placement. Our report suggests the possibility that additional SVC stent placement is an option for treatment of tumour ingrowth, even in patients with poor performance status.
Using heat to kill SARS‐CoV‐2
Authors: Abraham John P. , Plourde Brian D. , Cheng Lijing
Published: July 2020

The current coronavirus pandemic has reached global proportions and requires unparalleled collective and individual efforts to slow its spread. One critically important issue is the proper sterilization of physical objects that have been contaminated by the virus. Here, we review the currently existing literature on thermal inactivation of coronavirus (SARS‐CoV‐2) and present preliminary guideless on temperatures and exposure durations required to sterilize. We also compare these temperatures/exposure durations with potential household appliances that may be thought capable of performing sterilization.
Risks of producing and using indicators of sustainable development goals
Authors: Lyytimäki Jari , Salo Hanna , Lepenies Robert , Büttner Leonie , Mustajoki Jyri
Published: July 2020

The Sustainable Development Goals (SDG) aim to provide humanity with a global roadmap to sustainability. Official SDG indicators have been intensively developed, and they have a prominent and pronounced role as a key monitoring and policy instrument. Furthermore, various complementary or alternative indicator sets have been introduced at the global, regional and national levels. This article focuses on the risks related to the national indicators. The analysis is based on experiences from the preparation processes of sustainable development indicators in Finland and insights from indicator professionals and stakeholders in Finland and Germany. The risks related to overuse, nonuse and misuse of indicators are analyzed from the perspectives of indicator contents, processes of production and communication and external context factors. Opportunities for avoiding different risks and improving the desired societal impacts and influences of indicator usage are discussed. The concept of risk is helpful in terms of empirical diagnosis and for formulating mitigation recommendations.
Green Preparation of Few‐Layer Graphene Sheet Materials Using Naturally Occurring Calcium Carbonate and Plant Leaves
Authors: Xing Baoyan , Zhao Jianguo , Pan Qiliang , Yang Hui , Wang Lihua , Qu Wenshan , Gu Ling , Wang Haiqing , Han Peide , Ma Guibin
Published: July 2020

Graphene sheets were prepared by calcination of calcium carbonate with plant leaves under the protection of an argon gas atmosphere. This is an environmentally friendly approach to produce graphene. Calcium carbonate decomposes with the evolution of carbon dioxide at high temperature, which is reduced into graphene by the magnesium from plant leaves. The formation mechanism of graphene is discussed in detail. The synthesized graphene sheets were characterized by scanning electron microscopy (SEM), X‐ray diffraction (XRD), and Raman spectroscopy. Calcium carbonate and plant leaves are readily available and inexpensive natural resources, and this new methodology can be applied for large‐scale graphene production in industry.