bluuebunny/crossref_metadata_2025 huggingface dataset:
Transient increase in VEGF‐A leads to cardiac tube anomalies and increased risk of congenital heart malformations
Authors: Rykiel Graham , Gray MacKenzie , Rongish Brenda , Rugonyi Sandra
Published: February 2021

Vascular endothelial growth factor (VEGF) plays a critical role during early heart development. Clinical evidence shows that conditions associated with changes in VEGF signaling in utero are correlated with an increased risk of congenital heart defects (CHD) in newborns. However, how malformations develop after abnormal VEGF exposure is unknown. During embryogenesis, a primitive heart, consisting of an endocardial tube enveloped by a myocardial mantle, is the first organ to function. This tubular heart ultimately transforms into a four‐chambered heart. To determine how a transient increase in VEGF prior to heart tube formation affects heart development leading to CHD, we applied exogenous VEGF or a control (vehicle) solution to quail embryos in ovo at Hamburger‐Hamilton (HH) stage 8 (28–30 hr of incubation), right before heart tube formation. Light microscopy analysis of embryos re‐incubated after treatment for 13 hrs (to approximately HH11/HH12) showed that increased VEGF leads to impaired heart tube elongation accompanied by diameter expansion. Micro‐CT analysis of embryos re‐incubated for 9 days (to approximately HH38), when the heart is fully formed, showed that VEGF treatment increased the rate of cardiac malformations in surviving embryos. Despite no sex differences in survival, female embryos were more likely to develop cardiac malformations. Our results further suggest that heart tube malformations after a transient increase in VEGF right before heart tube formation may be reversible, leading to normal hearts.
Current strategies with sensing technologies to eliminate stress cardiomyopathy
Authors: Sun Hao , Ji Yongjian , Li Shuang , Dong Hongwei
Published: February 2021

Stress cardiomyopathy refers weakening of heart muscle due to the continuous stress. Generally, the severe status of stress cardiomyopathy has been revealed after damaging the muscles and measured by the physical changes in the heart system. To overcome this issue, biosensor can be used, which could eliminate the late identification stress cardiomyopathy. With biosensors, different stress markers such as epinephrine, dopamine, catecholamine, α‐amylase, norepinephrine, serotonin and cortisol have been identified by a wide range of developments. These biosensors are available from laboratory to industry at the ranges of nano to macrodevices. To merge with the identification of stress cardiomyopathy, the above strategies might be utilized properly and can aid to reduce the stress‐related problems. This overview gleaned the currently available biosensing methods and the associated biomarkers at various stages of the developments and implementations of stress cardiomyopathy.
CCNI2 plays a promoting role in the progression of colorectal cancer
Authors: Lai Dong‐Ming , Bi Jiang‐Jiang , Chen Yong‐Hui , Wu Yu‐Di , Huang Qing‐Wen , Li Hai‐Jie , Zhang Sheng , Fu Zheng , Tong Yi‐Xin
Published: February 2021

Colorectal cancer (CRC) is one of the most common malignancies and most of the patients diagnosed with advanced CRC have unsatisfactory treatment effect and poor prognosis. The purpose of this study was to investigate the effect of CCNI2 on the development of CRC. In this sutdy, immunohistochemical staining was used to detect CCNI2 expression levels in clinical samples, meanwhile, the Kaplan‐Meier survival analysis was conducted. Celigo cell counting assay was used for screening shCCNI2s. QPCR and WB were performed to verify knockdown efficiency of CCNI2. Cell proliferation, colony formation, cell cycle, apoptosis, and mechanism investigation of CCNI2 knockdown were investigated by MTT assay, colony formation assay, fluorescence‐activated cell sorting, and human apoptosis antibody array, respectively. Otherwise, the mouse model of CCNI2 knockdown was also constructed. The results of immunohistochemical staining and qPCR indicated that CCNI2 had a high expression level in the CRC tissues and cell lines. Kaplan‐Meier survival analysis manifested that the high expression of CCNI2 suggested poor prognosis. The expression of CCNI2 was significantly reduced by CCNI2‐siRNAs, and the downregulated expression level of CCNI2 inhibited CRC cell proliferation and colony formation, arrested cell cycle in G2 phase, as well as promoted cell apoptosis. The various indexes of solid tumor in mice models indicated that CCNI2 knockdown could suppress the growth of CRC tumor. Based on the comprehensive analysis of the above results, CCNI2 was contributed to the progression of CRC and could serve as a prognostic marker for CRC.
Real world clinicopathologic observations of patients with metastatic solid tumors receiving immune checkpoint inhibitor therapy: Analysis from Kentucky Cancer Registry
Authors: Jacob Aasems , Wu Jianrong , Kolesar Jill , Durbin Eric , Mathew Aju , Arnold Susanne , Chauhan Aman
Published: February 2021

The state of Kentucky has the highest cancer incidence and mortality in the United States. High‐risk populations such as this are often underrepresented in clinical trials. The study aims to do a comprehensive analysis of molecular landscape of metastatic cancers among these patients with detailed evaluation of factors affecting response and outcomes to immune checkpoint inhibitor (ICI) therapy. We performed a retrospective analysis of metastatic solid tumor patients who received ICI and underwent molecular profiling at our institution.

Sixty nine patients with metastatic solid tumors who received ICI were included in the study. Prevalence of smoking and secondhand tobacco exposure was 78.3% and 14.5%, respectively. TP53 (62.3%), CDKN1B/2A (40.5%), NOTCH and PIK3 (33.3%) were the most common alterations in tumors. 67.4% were PDL1 positive and 59.4% had intermediate‐high tumor mutational burden (TMB). Median TMB (12.6) was twofold to fourfold compared to clinical trials. The prevalence of mutations associated with smoking, homologous recombinant repair and PIK3/AKT/mTOR pathway mutations was higher compared to historic cohorts.

PDL1 expression had no significant effect on radiologic response, but PFS improvement in patients with tumors expressing PDL1 trended toward statistical significance (median 18 vs. 40 weeks. HR = 1.43. 95%CI 0.93, 4.46). Median PFS was higher in the high‐TMB cohort compared to low‐intermediate TMB (median not reached vs. 26 weeks; HR = 0.37. 95%CI 0.13, 1.05). A statistically significant improvement in PFS was observed in the PIK3 mutated cohort (median 123 vs. 23 weeks. HR = 2.51. 95%CI 1.23, 5.14). This was independent of tumor mutational burden (TMB) status or PDL1 expression status. PIK3 mutants had a higher overall response rate than the wild type (69.6% vs. 43.5%, OR 0.34; p = 0.045). The results should prompt further evaluation of these potential biomarkers and more widespread real‐world data publications which might help determine biomarkers that could benefit specific populations.
Anti N‐Methyl‐D‐Aspartate (NMDA) receptor encephalitis: from psychosis to cognitive impairment
Authors: Vahabi Zahra , Etesam Farnaz , Zandifar Atefeh , Alizadeh Fatemeh , Badrfam Rahim
Published: February 2021

In this study, while presenting a clinical case with early psychiatric manifestations, we emphasized the need to pay attention to neurological diagnoses such as Anti N‐Methyl‐D‐Aspartate Receptor (NMDAR) encephalitis at the time of manifestation of these common symptoms.
Catalyst Deactivation by Carbon Deposition: The Remarkable Case of Nickel Confined by Atomic Layer Deposition
Authors: Afzal Shaik , Prakash Anuj , Littlewood Patrick , Choudhury Hanif , Khan Ghouri Zafar , Mansour Said , Wang Dingdi , Marks Tobin , Weitz Eric , Stair Peter , Elbashir Nimir
Published: February 2021

In hydrocarbon reforming processes, coke formation on the catalyst usually reduces reaction rates. We show that when subjected to thermal treatment, a commercial nickel catalyst, overcoated with alumina, ALD exhibited both higher activity per g Ni and higher carbon formation rates than an uncoated catalyst. During the temperature‐programmed reaction in a CH4+CO2 atmosphere, the uncoated catalyst deactivated rapidly from carbon buildup, but the overcoated catalyst displayed an increase in catalytic activity per g Ni, despite generating two times the surface carbon. The unexpected phenomenon was investigated via TEM/EDS, TGA/DSC, SEM, XRD and Raman spectroscopy. We hypothesize that this may be due to (a) formation of a thicker than expected ‘quasi‐ALD’ overcoat of amorphous alumina, (b) crystallization of ALD overcoat into nanofibers that act as secondary supports for migrating Ni, and (c) the ability of ALD overcoat to isolate carbon as carbon nano‐onions (CNOs).
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

The 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.
Malignant mesothelioma: Advances in immune checkpoint inhibitor and mesothelin‐targeted therapies
Authors: Hu Zishuo I. , Ghafoor Azam , Sengupta Manjistha , Hassan Raffit
Published: February 2021

Malignant mesothelioma is an aggressive cancer with a poor prognosis and limited treatment options. For many years, the only US Food and Drug Administration‐approved first‐line treatment for unresectable mesothelioma was pemetrexed plus cisplatin. However, the recent approval of nivolumab plus ipilimumab as frontline treatment for patients with pleural mesothelioma marks a significant milestone for the treatment of this disease. In this review, the authors describe recent advances in therapeutic strategies for the treatment of patients with advanced, unresectable mesothelioma, highlighting the emerging use of immunotherapy and mesothelin‐targeted therapies for the management of malignant mesothelioma.
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

BACKGROUND

There 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.

METHODS

Using 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.

RESULTS

A 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.

CONCLUSIONS

Many 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

Image 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

Dications 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

Evidence 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

In 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

Drosophila 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 suspensions

Basic Protocol 2: Preparation and sequencing of single‐cell transcriptome libraries

Basic 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

A 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.
Amplify your efforts in higher education to create long‐lasting social change
Authors: Sutton Halley
Published: February 2021

Julie Coonrod, Ph.D., Dean of Graduate Studies at the University of New Mexico, was born and raised in Albuquerque. “I absolutely love everything about this place,” Coonrod said, adding that she's spent 25 years at the institution.
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

Among 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

Genetic 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

Invasive 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

The 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

Aims

To 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 methods

We 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.

Results

We 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).

Conclusions

We 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.
Creation and implementation of an electronic health record note for quality improvement in pediatric epilepsy: Practical considerations and lessons learned
Authors: Buchhalter Jeffrey R. , Scantlebury Morris H. , D’Alfonso Sabrina , Appendino Juan Pablo , Bello Espinosa Luis , Brooks Brian L. , Claassen Curtis , Corbeil Jane , Czank David , Dean Stafford , Ho Alice W. , Jacobs Julia , Mackay Maarit , McMahon Joka , Mineyko Aleksandra , Rho Jong M. , Roberts Trina , Rothenmund Sonia , Ruta Gary , Sawchuk Tyson , Simms Brett A. , Smyth Kim , Still Tammy , Thornton Nancy
Published: February 2021

Objective

To describe the development of the Pediatric Epilepsy Outcome‐Informatics Project (PEOIP) at Alberta Children's Hospital (ACH), which was created to provide standardized, point‐of‐care data entry; near‐time data analysis; and availability of outcome dashboards as a baseline on which to pursue quality improvement.

Methods

Stakeholders involved in the PEOIP met weekly to determine the most important outcomes for patients diagnosed with epilepsy, create a standardized electronic note with defined fields (patient demographics, seizure and syndrome type and frequency and specific outcomes‐ seizure type and frequency, adverse effects, emergency department visits, hospitalization, and care pathways for clinical decision support. These were embedded in the electronic health record from which the fields were extracted into a data display platform that provided patient‐ and population‐level dashboards updated every 36 hours. Provider satisfaction and family experience surveys were performed to assess the impact of the standardized electronic note.

Results

In the last 5 years, 3,245 unique patients involving 13, 831 encounters had prospective, longitudinal, standardized epilepsy data accrued via point‐of‐care data entry into an electronic note as part of routine clinical care. A provider satisfaction survey of the small number of users involved indicated that the vast majority believed that the note makes documentation more efficient. A family experience survey indicated that being provided with the note was considered “valuable” or “really valuable” by 86% of respondents and facilitated communication with family members, school, and advocacy organizations.

Significance

The PEOIP serves as a proof of principle that information obtained as part of routine clinical care can be collected in a prospective, standardized, efficient manner and be used to construct filterable process/outcome dashboards, updated in near time (36 hours). This information will provide the necessary baseline data on which multiple of QI projects to improve meaningful outcomes for children with epilepsy will be based.
Middlebox selection optimization via an intelligent framework in software‐defined networking
Authors: Zadkhosh Ehsan , Bahramgiri Hossein , Sabaei Masoud
Published: February 2021

Software‐defined networking (SDN) has a vital role in network resource utilization. However, it does not provide a comprehensive view of middleboxes (MBs). In this article, we proposed an intelligent dynamic routing framework for performance optimization based on a SDN architecture with a comprehensive view of all network properties. This routing framework also uses the genetic algorithm (GA) for performance improvement. It extracts the CPU, memory, and bandwidth utilization of MBs as dynamic routing parameters. The implemented GA calculates the impact factor (IF) of these parameters to declare the impact of each parameter in network performance. The obtained results show that considering MBs status in flow forwarding improves the tested network's resource utilization by 13, 10, and 7 times compared with hop‐based shortest path first, random path selection, and Round Robin methods, respectively. The results also showed that considering IFs (IFCPU, IFRAM, and IFBW) in routing procedure would improve the network's performance. Therefore, we used the GA to calculate optimal IFs for fairness load balancing and performance optimization. The GA calculates 0.4 and 0.6, for IFCPU and IFBW, respectively. It calculates these IFs only after five iterations. It also showed that we could ignore the RAM utilization parameter in our dynamic routing as our MBs are not memory‐bounded. The simulation results declared that routing with optimal IFs not only improves the network' throughput but also improves load distribution fairness by about 25% compared with routing without the IFs.
Visual investigation of CO2 dissolution and convection in heterogeneous porous media at reservoir temperature and pressure conditions
Authors: Amarasinghe Widuramina Sameendranath , Fjelde Ingebret , Flaata Anna Maija Nørstebø
Published: February 2021

CO2 convective mixing in saline aquifers has been widely studied numerically and experimentally. Reservoir heterogeneity is significant for CO2 convective mixing and experimental studies are still limited. In this study, we have conducted a visualization of CO2 convective mixing experiments in heterogeneous porous media at reservoir conditions using CO2 and water. We have used a two‐dimension Hele–Shaw cell, different glass beads of different permeability at porous media, and water solution with pH indicator. Glass beads were packed in a different way (horizontally and vertically) to generate the heterogeneity inside the test cell. We have studied transport velocity deviation due to the heterogeneity and effects of permeability transition zone together with the effects of boundary conditions. It was found out that having a low permeable layer below a high permeable layer restructure the flow of CO2 fingers and dampens the CO2 transport velocity. With the vertical permeability zones, having a high permeability zone accelerates CO2 gravity transport through that zone which is a good representation for a fracture or a fault in the reservoir. CO2 convection onset is governed by the vertical high‐permeable layer. Boundary conditions have been dominant with the presence of high permeable zones. It also found out that the experimental results presented in this study match with the simulation studies that are available in the literature. © 2021 The Authors. Greenhouse Gases: Science and Technology published by Society of Chemical Industry and John Wiley & Sons Ltd.
Activated microglia drive demyelination via CSF1R signaling
Authors: Marzan Dave E. , Brügger‐Verdon Valérie , West Brian L. , Liddelow Shane , Samanta Jayshree , Salzer James L.
Published: February 2021

Microgliosis is a prominent pathological feature in many neurological diseases including multiple sclerosis (MS), a progressive auto‐immune demyelinating disorder. The precise role of microglia, parenchymal central nervous system (CNS) macrophages, during demyelination, and the relative contributions of peripheral macrophages are incompletely understood. Classical markers used to identify microglia do not reliably discriminate between microglia and peripheral macrophages, confounding analyses. Here, we use a genetic fate mapping strategy to identify microglia as predominant responders and key effectors of demyelination in the cuprizone (CUP) model. Colony‐stimulating factor 1 (CSF1), also known as macrophage colony‐stimulating factor (M‐CSF) ‐ a secreted cytokine that regulates microglia development and survival—is upregulated in demyelinated white matter lesions. Depletion of microglia with the CSF1R inhibitor PLX3397 greatly abrogates the demyelination, loss of oligodendrocytes, and reactive astrocytosis that results from CUP treatment. Electron microscopy (EM) and serial block face imaging show myelin sheaths remain intact in CUP treated mice depleted of microglia. However, these CUP‐damaged myelin sheaths are lost and robustly phagocytosed upon‐repopulation of microglia. Direct injection of CSF1 into CNS white matter induces focal microgliosis and demyelination indicating active CSF1 signaling can promote demyelination. Finally, mice defective in adopting a toxic astrocyte phenotype that is driven by microglia nevertheless demyelinate normally upon CUP treatment implicating microglia rather than astrocytes as the primary drivers of CUP‐mediated demyelination. Together, these studies indicate activated microglia are required for and can drive demyelination directly and implicate CSF1 signaling in these events.
Effects of pipe outlet blocking on hydrological functioning in a degraded blanket peatland
Authors: Regensburg Taco H. , Chapman Pippa J. , Pilkington Michael G. , Chandler David M. , Evans Martin G. , Holden Joseph
Published: February 2021

Peatland restoration practitioners are keen to understand the role of drainage via natural soil pipes, especially where erosion has released large quantities of fluvial carbon in stream waters. However, little is known about pipe‐to‐stream connectivity and whether blocking methods used to impede flow in open ditch networks and gullies also work on pipe networks. Two streams in a heavily degraded blanket bog (southern Pennines, UK) were used to assess whether impeding drainage from pipe networks alters the streamflow responses to storm events, and how such intervention affects the hydrological functioning of the pipe network and the surrounding peat. Pipeflow was impeded in half of the pipe outlets in one stream, either by inserting a plug‐like structure in the pipe‐end or by the insertion of a vertical screen at the pipe outlet perpendicular to the direction of the predicted pipe course. Statistical response variable η2 showed the overall effects of pipe outlet blocking on stream responses were small with η2 = 0.022 for total storm runoff, η2 = 0.097 for peak discharge, η2 = 0.014 for peak lag, and η2 = 0.207 for response index. Both trialled blocking methods either led to new pipe outlets appearing or seepage occurring around blocks within 90 days of blocking. Discharge from four individual pipe outlets was monitored for 17 months before blocking and contributed 11.3% of streamflow. Pipe outlets on streambanks with headward retreat produced significantly larger peak flows and storm contributions to streamflow compared to pipe outlets that issued onto straight streambank sections. We found a distinctive distance‐decay effect of the water table around pipe outlets, with deeper water tables around pipe outlets that issued onto straight streambanks sections. We suggest that impeding pipeflow at pipe outlets would exacerbate pipe development in the gully edge zone, and propose that future pipe blocking efforts in peatlands prioritize increasing the residence time of pipe water by forming surface storage higher up the pipe network.
Prevalence and risk factors for malignancy in hysteroscopy‐resected endometrial polyps
Authors: Wong Cheong Lung Henry , So Po Lam
Published: February 2021

Introduction

To determine the prevalence of malignant lesions in endometrial polyps by hysteroscopic polypectomy, and risk factors for malignant transformation. The secondary aim was to evaluate background endometrium of atypical hyperplasia in endometrial polyps, and the risk of coexisting endometrial carcinoma after hysterectomy.

Methods

This retrospective study included women who underwent hysteroscopic polypectomy between January 2015 and December 2019. Demographic characteristics, hysteroscopic findings, and histopathology results of the polyp and the uterus, in the case of a hysterectomy, were collected.

Results

In all, 946 women were included in the study. Endometrial carcinoma in a polyp was found in 10 women (1.06%), and atypical hyperplasia was found in 11 women (1.16%). At the multivariate logistic regression model of risk factors, old age (P = 0.022) and obesity (P = 0.011) were significantly associated with (pre‐)malignant polyp. Five of the ten women (50%) with atypical hyperplasia confined to a polyp had coexisting endometrial carcinoma in the hysterectomy specimen.

Conclusion

Women with risk factors should be offered hysteroscopic polypectomy to allow a reliable histologic evaluation. Furthermore, hysterectomy is recommended in women with atypical hyperplasia in endometrial polyps even after complete resection.
Clinical and CT features of ovarian torsion in infants, children and adolescents
Authors: Li Dumin , Zhang Jingwen , Kiryu Shigeru , Zhang Xiaoming , Wang Fang
Published: February 2021

Objective

To investigate the clinical features and computed tomography (CT) findings of pediatric ovarian torsion.

Methods

A retrospective analysis of the clinical and CT data of 61 newborns, infants, children, and adolescents with ovarian torsion confirmed by histopathology was performed.

Results

Clinical features included abdominal mass, abdominal pain, nausea and vomiting, and fever. The tumor marker α‐fetoprotein was increased in five cases. Ovarian enlargement was found in 26 cases, and follicles were detected in the peripheral region of the ovary in 21 cases. Twenty‐one cases presented as solid mixed‐density masses on CT images. A total of 30 cases of ovarian torsion were associated with a benign ovarian mass. Among 27 cases of cystic or predominantly cystic masses, the mass had a thickened wall in 26 cases and showed an uneven density in 23 cases. Among all 61 patients, a torsed pedicle was detected in 47 cases. A torsed ovary or mass exhibited mild contrast enhancement in seven cases. Uterine deviation toward the involved side, blurred fat space around lesions, and pelvic free fluid were also found.

Conclusion

Pediatric ovarian torsion presents a relatively characteristic CT appearance. Correct diagnosis can be established based on clinical and imaging features.