bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variability in grading of ductal carcinoma in situ among an international group of pathologists
Authors: van Seijen Maartje , Jóźwiak Katarzyna , Pinder Sarah E , Hall Allison , Krishnamurthy Savitri , Thomas Jeremy SJ , Collins Laura C , Bijron Jonathan , Bart Joost , Cohen Danielle , Ng Wen , Bouybayoune Ihssane , Stobart Hilary , Hudecek Jan , Schaapveld Michael , Thompson Alastair , Lips Esther H , Wesseling Jelle ,   The Grand Challenge PRECISION consortium.
Published: February 2021

AbstractThe prognostic value of cytonuclear grade in ductal carcinoma in situ (DCIS) is debated, partly due to high interobserver variability and the use of multiple guidelines. The aim of this study was to evaluate interobserver agreement in grading DCIS between Dutch, British, and American pathologists. Haematoxylin and eosin‐stained slides of 425 women with primary DCIS were independently reviewed by nine breast pathologists based in the Netherlands, the UK, and the USA. Chance‐corrected kappa (κma) for association between pathologists was calculated based on a generalised linear mixed model using the ordinal package in R. Overall κma for grade of DCIS (low, intermediate, or high) was estimated to be 0.50 (95% confidence interval [CI] 0.44–0.56), indicating a moderate association between pathologists. When the model was adjusted for national guidelines, the association for grade did not change (κma = 0.53; 95% CI 0.48–0.57); subgroup analysis for pathologists using the UK pathology guidelines only had significantly higher association (κma = 0.58; 95% CI 0.56–0.61). To assess if concordance of grading relates to the expression of the oestrogen receptor (ER) and HER2, archived immunohistochemistry was analysed on a subgroup (n = 106). This showed that non‐high grade according to the majority opinion was associated with ER positivity and HER2 negativity (100 and 89% of non‐high grade cases, respectively). In conclusion, DCIS grade showed only moderate association using whole slide images scored by nine breast pathologists. As therapeutic decisions and inclusion in ongoing clinical trials are guided by DCIS grade, there is a pressing need to reduce interobserver variability in grading. ER and HER2 might be supportive to prevent the accidental and unwanted inclusion of high‐grade DCIS in such trials.
Risk‐adapted starting age of breast cancer screening in women with a family history of ovarian or other cancers: A nationwide cohort study
Authors: Mukama Trasias , Kharazmi Elham , Sundquist Kristina , Sundquist Jan , Fallah Mahdi 
Published: February 2021

BACKGROUNDThere is a lack of evidence‐based recommendations for the age at which women with a family history of cancers other than breast cancer should start breast cancer screening.METHODSUsing Swedish family cancer data sets, the authors conducted a nationwide cohort study including 5,099,172 Swedish women born after 1931 (follow‐up, 1958‐2015). Accounting for calendar time, they calculated the relative risk of breast cancer for women with a family history of a discordant cancer in 1 first‐degree relative. Furthermore, the authors used 10‐year cumulative risk to determine the ages at which women with a family history of discordant cancer reached risk thresholds at which women in the general population were recommended to start breast cancer screening.RESULTSA family history of cancer at 15 sites was associated with an increased risk of breast cancer. Among women younger than 50 years, the highest risk of breast cancer was observed for those with a family history of ovarian cancer (standardized incidence ratio, 1.44; 95% confidence interval, 1.26‐1.64). In these women, the risk of breast cancer associated with a family history at other cancer sites ranged from 1.08‐fold for prostate cancer to 1.18‐fold for liver cancer. When breast cancer screening was recommended to be started at the age of 50 years for the general population, women with 1 first‐degree relative with ovarian cancer attained the threshold risk for screening at the age of 46 years. Women with a family history of other discordant cancers did not reach the risk thresholds for screening at younger ages.CONCLUSIONSMany cancers showed familial associations with breast cancer, but women with a family history of these cancers (except for ovarian cancer) did not reach risk thresholds for screening at younger ages.
Blind image quality assessment based on the multiscale and dual‐domains features fusion
Authors: Lu Yaxuan , Li Weijun , Ning Xin , Dong Xiaoli , Zhang Liping , Sun Linjun , Cheng Chuantong 
Published: February 2021

AbstractImage quality assessment is to simulate subjective human visual perception and realize image quality inference automatically. Although deep neural networks have achieved great success, the majority of them do not fully consider perception characteristics. Therefore, according to the human visual scale characteristics, we proposed an image quality assessment algorithm based on multiscale and dual domains fusion. Firstly, the original image and its phase congruency respectively input into two branches, feature pyramid and channel attention mechanism are adopted to extract multiscale features. After that, bilinear pool is used to aggregate the spatial and frequency domain characteristics of the corresponding scales, and allows arbitrary scale input to ensure that the features are extracted from the inherent quality images. Finally, the single quality score is obtained through learned weights of each scale. Comparative experiments between our approach and state‐of‐the‐art are conducted on five public databases, the results demonstrate that the proposed algorithm is not only robust to different types and across database, but also sensitive to scale.
Aromaticity of ortho and meta 8‐Cycloparaphenylene and Their Dications: Induced Magnetic Field Analysis with Localized and Delocalized Orbitals in Strained Nanohoops
Authors: Lingas Rafael , Charistos Nickolas D. , Muñoz‐Castro Alvaro 
Published: February 2021

AbstractDications of cycloparaphenyles ([n]CPPs) are known to exhibit in‐plane global aromaticity, contained in a nanobelt structure. Recently synthesized ortho and meta isomers of [n]CPPs break the radial symmetry of π structure incorporating perpendicular oriented π orbitals. Herein we set to explore the aromaticity of neutral and dicationic ortho and meta isomers of [8]CPP by dissecting the induced magnetic field to contributions of the twofold radial/perpendicular π system using delocalized canonical molecular orbitals (CMO), and introducing the natural localized molecular orbitals (NLMO) analysis with DFT methods. The dications sustain a reduced global aromatic character of the radial π system under a perpendicular orientation of the external field which declines from ortho to meta isomer and reinforces local aromaticity of ortho ring while it destroys aromaticity of meta ring. Aromaticity variations are determined by symmetry governed rotational excitations of frontier π orbitals. The parallel orientation reveals a substantial reduction of local aromaticity verified with NICSπ analysis and electron delocalization indices.
Vulnerable narcissism as beneficial factor for the therapeutic alliance in borderline personality disorder
Authors: Busmann Mareike , Meyer Andrea H. , Wrege Johannes , Lang Undine E. , Gaab Jens , Walter Marc , Euler Sebastian 
Published: February 2021

AbstractEvidence suggests that narcissism and borderline personality disorder are associated with each other. This naturalistic study investigated the predictive value of grandiose and vulnerable narcissism on the development of the therapeutic alliance in short‐term psychodynamic treatment across 12 weeks. The sample consisted of 99 patients with borderline personality disorder. Narcissism was assessed with the Pathological Narcissism Inventory at treatment onset. The therapeutic alliance was rated with the Scale to Assess Therapeutic Relationships by both patient and therapist at four time points during treatment. Results showed a significant predictive value of vulnerable narcissism on the therapeutic alliance, revealing a more beneficial progression for patients with higher vulnerable narcissism. Grandiose narcissism had no predictive value on the therapeutic alliance. The study strengthens the clinical utility of the concept of vulnerable narcissism towards the evaluation of treatment processes in borderline personality disorder.
Photophysical Characteristics of Polarity‐Sensitive and Lipid Droplet‐Specific Phenylbenzothiadiazoles
Authors: Colas Kilian , Doloczki Susanne , Kesidou Aikaterina , Sainero‐Alcolado Lourdes , Rodriguez‐Garcia Aida , Arsenian‐Henriksson Marie , Dyrager Christine 
Published: February 2021

AbstractIn this study, we present a series of solvatochromic phenylbenzothiadiazoles that display dual emission from the locally excited (LE) and intramolecular charge transfer (ICT) excited states. The donor‐acceptor derivatives are highly sensitive to polarity changes, which can be monitored by differences in emission efficiency, spectroscopic shifts and variations of the LE/ICT ratio. One of the compounds in the series, containing a thiomethyl substituent, emerged as an excellent blue emitting stain for intracellular lipid droplets, a biomarker for various types of cancer. In addition, a non‐emissive nitro derivative becomes fluorescent upon bioreduction in hypoxic cancer cells and accumulates in lipid droplets with a high signal‐to‐background ratio.
Single‐Cell RNA Sequencing Analysis of the Drosophila Larval Ventral Cord
Authors: Nguyen Tho Huu , Vicidomini Rosario , Choudhury Saumitra Dey , Coon Steven L. , Iben James , Brody Thomas , Serpe Mihaela 
Published: February 2021

AbstractDrosophila provides a powerful genetic system and an excellent model to study the development and function of the nervous system. The fly's small brain and complex behavior has been instrumental in mapping neuronal circuits and elucidating the neural basis of behavior. The fast pace of fly development and the wealth of genetic tools has enabled systematic studies on cell differentiation and fate specification, and has uncovered strategies for axon guidance and targeting. The accessibility of neuronal structures and the ability to edit and manipulate gene expression in selective cells and/or synaptic compartments has revealed mechanisms for synapse assembly and neuronal connectivity. Recent advances in single‐cell RNA sequencing (scRNA‐seq) have further enhanced our appreciation and understanding of neuronal diversity in a fly brain. However, due to the small size of the fly brain and its constituent cells, scRNA‐seq methodologies require a few adaptations. Here, we describe a set of protocols optimized for scRNA‐seq analysis of the Drosophila larval ventral nerve cord, starting from tissue dissection and cell dissociation to cDNA library preparation, sequencing, and data analysis. We apply this workflow to three separate samples and detail the technical challenges associated with successful application of scRNA‐seq to studies on neuronal diversity. An accompanying article (Vicidomini, Nguyen, Choudhury, Brody, & Serpe, 2021) presents a custom multistage analysis pipeline that integrates modules contained in different R packages to ensure high‐flexibility, high‐quality RNA‐seq data analysis. These protocols are developed for Drosophila larval ventral nerve cord, but could easily be adapted to other tissues and model organisms. © 2021 U.S. Government.This article was corrected on 19 July 2022. See the end of the full text for details.Basic Protocol 1: Dissection of larval ventral nerve cords and preparation of single‐cell suspensionsBasic Protocol 2: Preparation and sequencing of single‐cell transcriptome librariesBasic Protocol 3: Alignment of raw sequencing data to indexed genome and generation of count matrices.
Electrical model formulation for multicolor light‐emitting diode modules and its application to design dimmable driver
Authors: Gupta Bakshi Biswadeep , Roy Biswanath 
Published: February 2021

SummaryA multicolor light‐emitting diode (LED) module comprises LED chips of more than one type or color and is frequently used for spectrally tunable lighting applications. In this paper, electrical models of such multicolor LED modules are formulated taking two basic circuit configurations into account, namely, (i) conventional, where a parallel string is made of one particular LED type, and (ii) nonconventional, where a parallel string is composed of different LED types. For deriving the model equations, the basic exponential model of a single LED chip has been applied, which is experimentally found to be the suitable option out of the four existing models, namely, linear, parabolic, exponential, and modified Shockley models. The formulated models are experimentally validated, results of which show maximum deviations of 4.71% and 4.19% from the measured data in the nonlinear and the linear operating regions, respectively. The formulated models are utilized to design dimmable, isolated LED drivers for red‐green‐blue (R‐G‐B) LED module. Performance evaluation of the drivers is conducted in Matlab‐Simulink. The results reveal the satisfactory operation of the LED modules in terms of current and power regulation, branch current matching, and fast response and thus establish the effectiveness of the proposed algorithm.
Palaeoecological features of Lower Asselian (Lower Permian) carbonate skeletal mounds in the Pisanyi Kamen’ section (Un’ya River, Northern Urals)
Authors: Ponomarenko Evgeniy S. 
Published: February 2021

AbstractAmong the many Upper Carboniferous and Lower Permian reef structures that are known worldwide, a Lower Permian 360 m long succession of reefal rocks in the Urals, interpreted as representing skeletal mounds, stands out for its complexity. The abundance of lime mud material, both in the skeletal mounds and in the adjacent sediments, indicates that they grew below fair‐weather wave base. An important feature of these Lower Permian organic buildups in the Urals is the widespread development of synsedimentary biologically induced cements, which often prevail in the rock volume. One of the most representative (and unique) skeletal mounds sequences in the Northern Urals is the Pisanyi Kamen’ section located on the Un'ya River. This paper aims to identify changes in the character of the palaeocommunity in the Pisanyi Kamen’ section. In the skeletal mounds development in the Lower Asselian interval of the Pisanyi Kamen’ section, seven events are distinguished. These are: (a) stabilisation of a soft sea floor by bryozoans and heterotrophic microbes; (b) colonisation of a hard sea floor by bryozoans and the appearance of abundant bioinduced cements; (c) displacement of bryozoans by a phylloid algae community; (d) appearance of a higher diversity community; (e) the mound top reaching the fair‐weather wave base; (f) collapse of the ecosystem; and (g) recurrent colonisation of a hard sea floor by phylloid algae. This work summarises the current state of knowledge regarding the Lower Permian skeletal mounds structure of the Northern Urals. The description of the ecological succession offers a new tool for the analysis of similar structures.
STRADA‐mutant human cortical organoids model megalencephaly and exhibit delayed neuronal differentiation
Authors: Dang Louis T. , Vaid Shivanshi , Lin Grace , Swaminathan Preethi , Safran Jordan , Loughman Anna , Lee Monica , Glenn Trevor , Majolo Fernanda , Crino Peter B. , Parent Jack M. 
Published: February 2021

AbstractGenetic diseases involving overactivation of the mechanistic target of rapamycin (mTOR) pathway, so‐called “mTORopathies,” often manifest with malformations of cortical development (MCDs), epilepsy, and cognitive impairment. How mTOR pathway hyperactivation results in abnormal human cortical development is poorly understood. To study the effect of mTOR hyperactivity on early stages of cortical development, we focused on Pretzel Syndrome (polyhydramnios, megalencephaly, symptomatic epilepsy; PMSE syndrome), a rare mTORopathy caused by homozygous germline mutations in the STRADA gene. We developed a human cortical organoid (hCO) model of PMSE and examined morphology and size for the first 2 weeks of organoid growth, and cell type composition at weeks 2, 8, and 12 of differentiation. In the second week, PMSE hCOs enlarged more rapidly than controls and displayed an abnormal Wnt pathway‐dependent increase in neural rosette structures. PMSE hCOs also exhibited delayed neurogenesis, decreased subventricular zone progenitors, increased proliferation and cell death, and an abnormal architecture of primary cilia. At week 8, PMSE hCOs had fewer deep layer neurons. By week 12, neurogenesis recovered in PMSE organoids, but they displayed increased outer radial glia, a cell type thought to contribute to the expansion of the human cerebral cortex. Together, these findings suggest that megalencephaly in PMSE arises from the expansion of neural stem cells in early corticogenesis and potentially also from increased outer radial glial at later gestational stages. The delayed neuronal differentiation in PMSE organoids demonstrates the important role the mTOR pathway plays in the maintenance and expansion of the stem cell pool.
Climate and habitat configuration limit range expansion and patterns of dispersal in a non‐native lizard
Authors: Williams Robert J. , Dunn Alison M. , Mendes da Costa Lily , Hassall Christopher 
Published: February 2021

AbstractInvasive species are one of the main causes of biodiversity loss worldwide. As introduced, populations increase in abundance and geographical range, so does the potential for negative impacts on native communities. As such, there is a need to better understand the processes driving range expansion as species become established in recipient landscapes. Through an investigation into capacity for population growth and range expansion of introduced populations of a non‐native lizard (Podarcis muralis), we aimed to demonstrate how multi‐scale factors influence spatial spread, population growth, and invasion potential in introduced species. We collated location records of P. muralis presence in England, UK through data collected from field surveys and a citizen science campaign. We used these data as input for presence‐background models to predict areas of climate suitability at a national‐scale (5 km resolution), and fine‐scale habitat suitability at the local scale (2 m resolution). We then integrated local models into an individual‐based modeling platform to simulate population dynamics and forecast range expansion for 10 populations in heterogeneous landscapes. National‐scale models indicated climate suitability has restricted the species to the southern parts of the UK, primarily by a latitudinal cline in overwintering conditions. Patterns of population growth and range expansion were related to differences in local landscape configuration and heterogeneity. Growth curves suggest populations could be in the early stages of exponential growth. However, annual rates of range expansion are predicted to be low (5–16 m). We conclude that extensive nationwide range expansion through secondary introduction is likely to be restricted by currently unsuitable climate beyond southern regions of the UK. However, exponential growth of local populations in habitats providing transport pathways is likely to increase opportunities for regional expansion. The broad habitat niche of P. muralis, coupled with configuration of habitat patches in the landscape, allows populations to increase locally with minimal dispersal.
Boreal conifer seedling responses to experimental competition removal during summer drought
Authors: Shovon Tanvir Ahmed , Gagnon Daniel , Vanderwel Mark C. 
Published: February 2021

AbstractThe southern range limit of white spruce (Picea glauca) in western Canada is believed to arise from effects of moisture limitation on seedling recruitment. Within stands near white spruce’s range limit, the adverse effects of water limitation on seedling growth and survival may be compounded by competition from neighboring understory plants and trees. To test this hypothesis, we conducted a competition removal experiment on white spruce seedlings in the Cypress Hills, an isolated forest landscape within the Canadian Prairies. We measured the height and diameter at root collar of 371 natural seedlings, and then we manually cleared all vegetation within a 75‐cm radius of 83 seedlings to remove local competition from neighboring plants. In addition to removal of neighboring plants, we excavated a 75‐cm radius trench around another 46 of these seedlings to remove competition for belowground resources. We took hemispherical photographs above each seedling to calculate canopy openness (a proxy for light availability) and re‐measured height and diameter over two years to calculate pre‐ and post‐treatment growth. There was a pronounced difference in precipitation between the two years of our experiment, with spring–summer precipitation 58% higher than average in the pre‐treatment year and 62% lower than average in the post‐treatment year. The diameter growth and survival of seedlings growing without competition showed smaller decreases in the dry post‐treatment year than control seedlings. Removing competition by trenching increased the height growth of seedlings located under an open canopy, but not of those growing under heavy shade. These interactions suggest that white spruce regeneration in water‐limited areas is sensitive to both light availability and local competition. Competition exacerbated drought effects on seedlings, which suggests that frequent droughts could have greater negative impacts on boreal tree seedlings that are growing under a closed canopy.
The mechanism by which imeglimin inhibits gluconeogenesis in rat liver cells
Authors: Vial Guillaume , Lamarche Frédéric , Cottet‐Rousselle Cécile , Hallakou‐Bozec Sophie , Borel Anne‐Laure , Fontaine Eric 
Published: February 2021

AbstractAimsTo understand the mechanism by which imeglimin (a new oral hypoglycemic agent whose phase 3 development program in Japan has now been completed) decreases hepatic glucose production.Materials and methodsWe compared the effect of imeglimin and metformin on glucose production, ATP/ADP ratio, oxygen consumption rate, mitochondrial redox potential and membrane potential in primary rat hepatocytes.ResultsWe found that both imeglimin and metformin dose‐dependently decreased glucose production and the ATP/ADP ratio. Moreover, they both increased mitochondrial redox potential (assessed by mitochondrial NAD(P)H fluorescence) and decreased membrane potential (assessed by TMRM fluorescence). However, contrary to metformin, which inhibits mitochondrial Complex I, imeglimin did not decrease the oxygen consumption rate in intact cells. By measuring the oxygen consumption of in situ respiratory chain as a function of the concentration of NADH, we observed that imeglimin decreased the affinity of NADH for the respiratory chain but did not affect its Vmax (ie competitive inhibition) whereas metformin decreased both the Vmax and the affinity (ie uncompetitive inhibition).ConclusionsWe conclude that imeglimin induces a kinetic constraint on the respiratory chain that does not affect its maximal activity. This kinetic constraint is offset by a decrease in the mitochondrial membrane potential, which induces a thermodynamic constraint on the ATPase responsible for a decrease in the ATP/ADP ratio.