bluuebunny/crossref_metadata_2025 huggingface dataset:
Teacher Feedback, Student ADHD Behavior, and the Teacher–Student Relationship: Are These Related?
Authors: Staff Anouck I. , Oosterlaan Jaap , van der Oord Saskia , de Swart Fanny , Imeraj Lindita , van den Hoofdakker Barbara J. , Luman Marjolein
Published: November 2022

This cross-sectional study aimed to compare positive and corrective teacher feedback toward children with attention-deficit/hyperactivity disorder (ADHD) and typically developing children, and to examine whether the quality of the teacher–student relationship moderated associations between child behavior and teacher feedback. We observed and coded classroom ADHD behaviors of 55 children with ADHD and 34 typically developing children (TDC; 6–12 years), as well as the levels of positive and corrective teacher feedback they received. Teachers rated closeness and conflict using the Student–Teacher Relationship Scale in the ADHD group. Multilevel analyses revealed that teachers provided significantly more corrective feedback to children in the ADHD compared to the TDC group. Children in the ADHD group received more corrective than positive feedback, but this pattern was reversed for the TDC group. Multiple regression analyses in the ADHD group indicated that lower levels of positive feedback were related to higher levels of motor hyperactivity. Higher levels of corrective feedback were associated with higher levels of verbal hyperactivity. Closeness moderated this association: Corrective feedback was related to levels of verbal hyperactivity only if teachers experienced less closeness in the relationship with the child. None of the other moderation effects were significant. Teachers provided more corrective feedback to children with ADHD than to typically developing children, and teacher feedback toward children with ADHD was associated with levels of hyperactivity. A close teacher–student relationship may serve as protective factor for the receipt of corrective feedback in this group, but experimental studies are needed to confirm this hypothesis.
Melatonin controls cell proliferation and modulates mitochondrial physiology in pancreatic stellate cells
Authors: Estaras Matias , Ortiz-Placin Candido , Castillejo-Rufo Alba , Fernandez-Bermejo Miguel , Blanco Gerardo , Mateos Jose M. , Vara Daniel , Gonzalez-Cordero Pedro L. , Chamizo Sandra , Lopez Diego , Rojas Adela , Jaen Isabel , de Armas Noelia , Salido Gines M. , Iovanna Juan L. , Santofimia-Castaño Patricia , Gonzalez Antonio
Published: November 2022

We have investigated the effects of melatonin on major pathways related with cellular proliferation and energetic metabolism in pancreatic stellate cells. In the presence of melatonin (1 mM, 100 µM, 10 µM, or 1 µM), decreases in the phosphorylation of c-Jun N-terminal kinase and of p44/42 and an increase in the phosphorylation of p38 were observed. Cell viability dropped in the presence of melatonin. A rise in the phosphorylation of AMP-activated protein kinase was detected in the presence of 1 mM and 100 µM melatonin. Treatment with 1 mM melatonin decreased the phosphorylation of protein kinase B, whereas 100 µM and 10 µM melatonin increased its phosphorylation. An increase in the generation of mitochondrial reactive oxygen species and a decrease of mitochondrial membrane potential were noted following melatonin treatment. Basal and maximal respiration, ATP production by oxidative phosphorylation, spare capacity, and proton leak dropped in the presence of melatonin. The expression of complex I of the mitochondrial respiratory chain was augmented in the presence of melatonin. Conversely, in the presence of 1 mM melatonin, decreases in the expression of mitofusins 1 and 2 were detected. The glycolysis and the glycolytic capacity were diminished in cells treated with 1 mM or 100 µM melatonin. Increases in the expression of phosphofructokinase-1 and lactate dehydrogenase were noted in cells incubated with 100 µM, 10 µM, or 1 µM melatonin. The expression of glucose transporter 1 was increased in cells incubated with 10 µM or 1 µM melatonin. Conversely, 1 mM melatonin decreased the expression of all three proteins. Our results suggest that melatonin, at pharmacological concentrations, might modulate mitochondrial physiology and energy metabolism in addition to major pathways involved in pancreatic stellate cell proliferation.
Detection of brook trout in spatiotemporally separate locations using validated eDNA technology
Authors: Nolan Kathleen P. , Loeza-Quintana Tzitziki , Little Hannah A. , McLeod Joschka , Ranger Benjamin , Borque Danielle A. , Hanner Robert H.
Published: November 2022

Brook trout are a species of conservation concern in Southwestern Ontario, Canada, and effective monitoring of their populations is crucial for making informed management decisions. Electrofishing is a traditional, yet invasive, method that allows for fish abundance estimation. Environmental DNA (eDNA) is an emerging molecular tool that presents a non-invasive alternative to electrofishing. This study was a collaborative effort between researchers in academia, industry, and an NGO, with the following objectives: 1) compare eDNA detections with electrofishing when monitoring brook trout populations in a site of known occupancy, 2) compare existing eDNA collection methods, and 3) extend eDNA surveys to regions of unknown occupancy that could be of conservation concern (Hanlon Creek and Twelve Mile Creek, Ontario). First, eDNA sampling methods were validated with standard electrofishing. Water samples were filtered in tandem at each site using two commercially available eDNA samplers. The results suggest a significant difference in total eDNA capture and incidence of PCR inhibitors between the two autosamplers. Brook trout eDNA was detected at all locations in Hanlon Creek in September and November, as well as 5/6 sampling locations in Twelve Mile Creek. Brook trout signal in Hanlon Creek was stronger in November compared to September 2019, suggesting possible spawning activity. Brook trout eDNA was also detected in Twelve Mile Creek where brook trout were previously unreported. This study provides a technical validation for the use of eDNA in brook trout monitoring and illustrates the opportunity to use eDNA surveys in regulated settings to complement and improve conventional biomonitoring methods for the management of elusive species.
Characteristics and outcomes of acute hepatitis of unknown etiology in Egypt: first report of adult adenovirus-associated hepatitis
Authors: Ramadan Haidi Karam-Allah , Sayed Ibrahim M. , Elkhawaga Amal A. , Meghezel El-Zahraa M. , Askar Ashraf A. , Moussa Abdelmajeed M. , Osman Asmaa O. B. S. , Elfadl Azza Abo , Khalifa Walaa A. , Ashmawy Ahmed M. , El-Mokhtar Mohamed A.
Published: November 2022

Purpose

Several outbreaks of acute hepatitis of unknown etiology (AHUE) in children were reported in 2022 in many countries, with adenovirus identified as the etiological agent in most of them. We aimed to evaluate the characteristics and outcomes of AHUE cases in Egypt.

Methodology

Hospitalized patients with acute hepatitis were included in the study. Drug-induced, alcoholic hepatitis, autoimmune hepatitis, and Wilson’s disease were identified either by medical history or by routine laboratory diagnosis. Molecular and serological approaches were used to investigate common viral causes of hepatitis, such as hepatitis A–E viruses, cytomegalovirus, Epstein–Barr virus, herpes simplex viruses (HSV1/2), adenovirus, parvovirus B19, and coxsackie virus.

Results

A total of 42 patients were recruited and divided into two groups: 24 cases of unknown hepatitis after excluding the common causes and 18 cases of known hepatitis. About two-thirds of the patients were male (61.9%), and the mean age was 34.55 ± 16.27 years. Jaundice, dark urine, abdominal pain and diarrhea were recorded at a higher incidence in group 1, while jaundice and fever were frequent in group 2. Fulminant hepatitis occurred in 28.6% of the cases, but the two groups did not differ significantly in terms of patient outcome, duration of hospitalization, ascites, and development of fulminant hepatitis. Adenovirus was detected in five cases (20.8%) in group 1, and one case co-infecting with hepatitis E virus in group 2. Herpes simplex virus 1/2, coxsackie virus, and parvovirus B19 were not detected in any case, while etiologies of 75% of the cases were still not confirmed. One out of the six adenovirus-infected patients died. The outcome significantly correlated with the severity of the liver disease.

Conclusion

This is the first report describing etiologies and characteristics of AHUE cases in Egypt, and interestingly, adenovirus was detected in adults. Further studies are required to determine the prevalence of this newly emerging viral hepatitis pathogens.
Field-driven merging of polarizations and enhanced electrocaloric effect in BaTiO3-based lead-free ceramics
Authors: Niu Xiang , Jian Xiaodong , Gong Weiping , Liang Wei , Gong Xuetian , Zhang Guangzu , Jiang Shenglin , Yu Kun , Zhao Xiaobo , Yao Yingbang , Tao Tao , Liang Bo , Lu Sheng-Guo
Published: November 2022

Solid-state cooling technology based on electrocaloric effect (ECE) has been advanced as an alternative to replace the vapour-compression approach to overcome the releasing of the global warming gases. However, the development in high ECE materials is still a challenge. In this work, polarization merging strategy was proposed to achieve a large ECE in xBa(Sn0.07Ti0.93)O3-(1−x)Ba(Hf0.1Ti0.9)O3 ferroelectric ceramics, where x = 0, 0.2, 0.4, 0.6, 0.8, and 1. Ba(Sn0.07Ti0.93)O3 with an orthorhombic phase and Ba(Hf0.1Ti0.9)O3 with a rhombohedral phase at room temperature were prepared beforehand as precursors, and phase-coexisted xBSnT-(1−x)BHfT ceramics were formed via a solid-state reaction approach. Phase coexisting structures were confirmed using the X-ray diffraction. The merged polarization was confirmed by the dielectric and ferroelectric properties. Optimal ECEs were obtained for 0.2BSnT-0.8BHfT ceramics, i.e., adiabatic temperature change ΔT = 2.16±0.08 K at 80 °C and 5 MV/m, and ΔT = 3.35±0.09 K at 80 °C and 7 MV/m.
Novel germline variants of CDKN1B and CDKN2C identified during screening for familial primary hyperparathyroidism
Authors: Mazarico-Altisent I. , Capel I. , Baena N. , Bella-Cueto M. R. , Barcons S. , Guirao X. , Albert L. , Cano A. , Pareja R. , Caixàs A. , Rigla M.
Published: November 2022

Purpose

CDKN1B mutations were established as a cause of multiple endocrine neoplasia 4 (MEN4) syndrome in patients with MEN1 phenotype without a mutation in the MEN1 gene. In addition, variants in other cyclin-dependent kinase inhibitors (CDKIs) were found in some MEN1-like cases without the MEN1 mutation. We aimed to describe novel germline mutations of these genes in patients with primary hyperparathyroidism (PHPT).

Methods

During genetic screening for familial hyperparathyroidism, three novel CDKIs germline mutations in three unrelated cases between January 2019 and November 2021 were identified. In this report, we describe clinical features, DNA sequence analysis, and familial segregation studies based on these patients and their relatives. Genome-wide DNA study of loss of heterozygosity (LOH), copy number variation (CNV), and p27/kip immunohistochemistry was performed on tumour samples.

Results

DNA screening was performed for atypical parathyroid adenomas in cases 1 and 2 and for cystic parathyroid adenoma and young age at diagnosis of PHPT in case 3. Genetic analysis identified likely pathogenic variants of CDKN1B in cases 1 and 2 and a variant of the uncertain significance of CDKN2C, with uniparental disomy in the tumour sample, in case 3. Neoplasm screening of probands showed other non-endocrine tumours in case 1 (colon adenoma with dysplasia and atypical lipomas) and case 2 (aberrant T-cell population) and a non-functional pituitary adenoma in case 3.

Conclusion

Germline mutations in CDKIs should be included in gene panels for genetic testing of primary hyperparathyroidism. New germline variants here described can be added to the current knowledge.
An investigation of edge F-index on fuzzy graphs and application in molecular chemistry
Authors: Islam Sk Rabiul , Pal Madhumangal
Published: November 2022

The molecular descriptors are a useful tool in the spectral graph, molecular chemistry and several fields of chemistry and mathematics. The edge F-index is proposed for fuzzy graphs (FGs) here. Bounds of this index are calculated for FGs. The FG has been investigated for a given set of vertices as having maximum edge F-index. Some relations of this index with the second Zagreb index and hyper-Zagreb index are established. For an isomorphic FGs, it is shown that the value of this index is the same. Bounds of this index for some FG operations are determined. Also, an application of the index in mathematical chemistry is studied. For this, 18 octane isomers and 67 alkanes are considered and analyzed the correlation between this index with some properties of the octane isomers and alkanes. From the correlation coefficient value, we have obtained this index is highly correlated with enthalpy of vaporization, standard enthalpy of vaporization, entropy, acentric factor and heat of vaporization and less correlated with heat capacity for octane isomers. Also, this index is correlated with critical pressure, critical temperature, molar refraction, molar volume and boiling point and is less correlated with surface tension and heat of vaporization for alkanes. But, this index is inadequate to determine the melting point of alkanes.
Automation Is Coming! Exploring Future(s)-Oriented Methods in Education
Authors: Cerratto Pargman Teresa , Lindberg Ylva , Buch Anders
Published: November 2022

Emerging automated-decision making (ADM) technologies invite scholars to engage with future points in time and contexts that have not yet arisen. This particular state of not knowing yet implies the methodological challenge of examining images of the future and how such images will materialize in practice. In this respect, we ask the following: what are appropriate research methods for studying emerging ADM technologies in education? How do researchers explore sociotechnical practices that are in the making? Guided by these questions, we investigate the increasing adoption of ADM in teachers’ assessment practices. This constitutes a case in point for reflecting on the research methods applied to address the future of assessment in education. In this context, we distinguish between representational methods oriented to recounting past experiences and future(s) methods oriented to making futures. Studying the literature on speculative methods in digital education, we illustrate four categories of future(s)-oriented methods and reflect on their characteristics through a backcasting workshop conducted with teachers. We conclude by discussing the need to reconsider the methodological choices made for studying emerging technologies in critical assessment practices and generate new knowledge on methods able to contribute to alternative imaginaries of automation in education.
Introduction to Experimental Particle Physics
Authors: Fernow Richard Clinton
Published: November 2022

This book brings together the most important topics in experimental particle physics in the late twentieth century to give a brief but balanced overview of the subject. The author begins by reviewing particle physics and discussing electromagnetic and nuclear interactions. He then goes on to discuss three nearly universal aspects of particle physics experiments: beams, targets, and fast electronics. The second part of the book treats in detail the properties of various types of particle detector, such as scintillation counters, Cerenkov counters, proportional chambers, drift chambers, sampling calorimeters, and specialized detectors. Wherever possible the author attempts to enumerate the advantages and disadvantages of performance. Finally, he discusses aspects of specific experiments, such as properties of triggers, types of measurement, spectrometers, and the integration of detectors into coherent systems. First published in 1986, this title has been reissued as an Open Access publication on Cambridge Core.
Epigenetic mechanisms of Strip2 in differentiation of pluripotent stem cells
Authors: Srinivasan Sureshkumar Perumal , Nemade Harshal , Cherianidou Anna , Peng Luying , Cruz-Molina Sara , Rada-Iglesias Alvaro , Sachinidis Agapios
Published: November 2022

Significant evidence points to Strip2 being a key regulator of the differentiation processes of pluripotent embryonic stem cells. However, Strip2 mediated epigenetic regulation of embryonic differentiation and development is quite unknown. Here, we identified several interaction partners of Strip2, importantly the co-repressor molecular protein complex nucleosome remodeling deacetylase/Tripartite motif-containing 28/Histone deacetylases/Histone-lysine N-methyltransferase SETDB1 (NuRD/TRIM28/HDACs/SETDB1) histone methyltransferase, which is primarily involved in regulation of the pluripotency of embryonic stem cells and its differentiation. The complex is normally activated by binding of Krueppel-associated box zinc-finger proteins (KRAB-ZFPs) to specific DNA motifs, causing methylation of H3 to Lysin-9 residues (H3K9). Our data showed that Strip2 binds to a DNA motif (20 base pairs), like the KRAB-ZFPs. We establish that Strip2 is an epigenetic regulator of pluripotency and differentiation by modulating DNA KRAB-ZFPs as well as the NuRD/TRIM28/HDACs/SETDB1 histone methyltransferase complex.
UM171 cooperates with PIM1 inhibitors to restrict HSC expansion markers and suppress leukemia progression
Authors: Hu Anling , Gao Jian , Varier Krishnapriya M. , Gajendran Babu , Jiang Fei , Liu Wuling , Wang Chunlin , Xiao Xiao , Li Yanmei , Zacksenhaus Eldad , Ali Sajjad , Ben-David Yaacov
Published: November 2022

The pyrimido-indole derivative UM171 promotes human Hematopoietic Stem Cells Expansion (HSCE), but its impact on leukemia is not known. Herein, we show in a mouse model of erythroleukemia that UM171 strongly suppresses leukemia progression. UM171 inhibits cell cycle progression and apoptosis of leukemic cells in culture. The effect of UM171 on leukemia differentiation was accompanied by increased expression of HSCE markers. RNAseq analysis combined with Q-RT-PCR and western blotting revealed that the PIM1 protein kinase is highly elevated in response to UM171 treatment. Moreover, docking analysis combined with immunoprecipitation assays revealed high binding affinity of UM171 to PIM1. Interestingly, pan-PIM kinase inhibitors counteracted the effect of UM171 on HSCE marker expression and PIM1 transcription, but not its suppression of leukemic cell growth. Moreover, combination treatment with UM171 and a pan-PIM inhibitor further suppressed leukemic cell proliferation compared to each drug alone. To uncover the mechanism of growth inhibition, we showed strong upregulation of the cyclin-dependent kinase inhibitor P21CIP1 and the transcription factor KLF2 by UM171. In accordance, KLF2 knockdown attenuated growth inhibition by UM171. KLF2 upregulation by UM171 is also responsible for the activation of P21CIP1 in leukemic cells leading to a G1/S arrest and suppression of leukemogenesis. Thus, suppression of leukemic growth by UM171 through KLF2 and P21CIP1 is thwarted by PIM-mediated expansion of leukemic stemness, uncovering a novel therapeutic modality involving combined UM171 plus PIM inhibitors.
Dusp6 deficiency attenuates neutrophil-mediated cardiac damage in the acute inflammatory phase of myocardial infarction
Authors: Zhou Xiaohai , Zhang Chenyang , Wu Xueying , Hu Xinli , Zhang Yan , Wang Xuelian , Zheng Lixia , Gao Peng , Du Jianyong , Zheng Wen , Shang Haibao , Hu Keping , Jiang Zhengfan , Nie Yu , Hu Shengshou , Xiao Rui-Ping , Zhu Xiaojun , Xiong Jing-Wei
Published: November 2022

Dual-specificity phosphatase 6 (DUSP6) serves a specific and conserved function on the dephosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). We previously identified Dusp6 as a regenerative repressor during zebrafish heart regeneration, therefore we propose to investigate the role of this repressor in mammalian cardiac repair. Utilizing a rat strain harboringDusp6nonsense mutation, rat neutrophil-cardiomyocyte co-culture, bone marrow transplanted rats and neutrophil-specificDusp6knockout mice, we find thatDusp6deficiency improves cardiac outcomes by predominantly attenuating neutrophil-mediated myocardial damage in acute inflammatory phase after myocardial infarction. Mechanistically,Dusp6is transcriptionally activated by p38-C/EBPβ signaling and acts as an effector for maintaining p-p38 activity by down-regulating pERK and p38-targeting phosphatases DUSP1/DUSP16. Our findings provide robust animal models and novel insights for neutrophil-mediated cardiac damage and demonstrate the potential of DUSP6 as a therapeutic target for post-MI cardiac remodeling and other relevant inflammatory diseases.
Short hydrogen-bond network confined on COF surfaces enables ultrahigh proton conductivity
Authors: Shi Benbing , Pang Xiao , Li Shunning , Wu Hong , Shen Jianliang , Wang Xiaoyao , Fan Chunyang , Cao Li , Zhu Tianhao , Qiu Ming , Yin Zhuoyu , Kong Yan , Liu Yiqin , Zhang Mingzheng , Liu Yawei , Pan Feng , Jiang Zhongyi
Published: November 2022

The idea of spatial confinement has gained widespread interest in myriad applications. Especially, the confined short hydrogen-bond (SHB) network could afford an attractive opportunity to enable proton transfer in a nearly barrierless manner, but its practical implementation has been challenging. Herein, we report a SHB network confined on the surface of ionic covalent organic framework (COF) membranes decorated by densely and uniformly distributed hydrophilic ligands. Combined experimental and theoretical evidences have pointed to the confinement of water molecules allocated to each ligand, achieving the local enrichment of hydronium ions and the concomitant formation of SHBs in water-hydronium domains. These overlapped water-hydronium domains create an interconnected SHB network, which yields an unprecedented ultrahigh proton conductivity of 1389 mS cm−1 at 90 °C, 100% relative humidity.
Economy-wide evaluation of CO2 and air quality impacts of electrification in the United States
Authors: Bistline John E. T. , Blanford Geoffrey , Grant John , Knipping Eladio , McCollum David L. , Nopmongcol Uarporn , Scarth Heidi , Shah Tejas , Yarwood Greg
Published: November 2022

Adopting electric end-use technologies instead of fossil-fueled alternatives, known as electrification, is an important economy-wide decarbonization strategy that also reduces criteria pollutant emissions and improves air quality. In this study, we evaluate CO2 and air quality co-benefits of electrification scenarios by linking a detailed energy systems model and a full-form photochemical air quality model in the United States. We find that electrification can substantially lower CO2 and improve air quality and that decarbonization policy can amplify these trends, which yield immediate and localized benefits. In particular, transport electrification can improve ozone and fine particulate matter (PM2.5), though the magnitude of changes varies regionally. However, growing activity from non-energy-related PM2.5 sources—such as fugitive dust and agricultural emissions—can offset electrification benefits, suggesting that additional measures beyond CO2 policy and electrification are needed to meet air quality goals. We illustrate how commonly used marginal emissions approaches systematically underestimate reductions from electrification.
Anti-phase boundary accelerated exsolution of nanoparticles in non-stoichiometric perovskite thin films
Authors: Han Hyeon , Xing Yaolong , Park Bumsu , Bazhanov Dmitry I. , Jin Yeongrok , Irvine John T. S. , Lee Jaekwang , Oh Sang Ho
Published: November 2022

Exsolution of excess transition metal cations from a non-stoichiometric perovskite oxide has sparked interest as a facile route for the formation of stable nanoparticles on the oxide surface. However, the atomic-scale mechanism of this nanoparticle formation remains largely unknown. The present in situ scanning transmission electron microscopy combined with density functional theory calculation revealed that the anti-phase boundaries (APBs) characterized by the a/2 < 011> type lattice displacement accommodate the excess B-site cation (Ni) through the edge-sharing of BO6 octahedra in a non-stoichiometric ABO3 perovskite oxide (La0.2Sr0.7Ni0.1Ti0.9O3-δ) and provide the fast diffusion pathways for nanoparticle formation by exsolution. Moreover, the APBs further promote the outward diffusion of the excess Ni toward the surface as the segregation energy of Ni is lower at the APB/surface intersection. The formation of nanoparticles occurs through the two-step crystallization mechanism, i.e., the nucleation of an amorphous phase followed by crystallization, and via reactive wetting on the oxide support, which facilitates the formation of a stable triple junction and coherent interface, leading to the distinct socketing of nanoparticles to the oxide support. The atomic-scale mechanism unveiled in this study can provide insights into the design of highly stable nanostructures.
Quantum capacities of transducers
Authors: Wang Chiao-Hsuan , Li Fangxin , Jiang Liang
Published: November 2022

High-performance quantum transducers, which faithfully convert quantum information between disparate physical carriers, are essential in quantum science and technology. Different figures of merit, including efficiency, bandwidth, and added noise, are typically used to characterize the transducers’ ability to transfer quantum information. Here we utilize quantum capacity, the highest achievable qubit communication rate through a channel, to define a single metric that unifies various criteria of a desirable transducer. Using the continuous-time quantum capacities of bosonic pure-loss channels as benchmarks, we investigate the optimal designs of generic quantum transduction schemes implemented by transmitting external signals through a coupled bosonic chain. With physical constraints on the maximal coupling rate $${g}_{\max }$$

g

max

, the highest continuous-time quantum capacity $${Q}^{\max }\approx 31.4{g}_{\max }$$

Q

max

≈
31.4

g

max

is achieved by transducers with a maximally flat conversion frequency response, analogous to Butterworth electric filters. We further investigate the effect of thermal noise on the performance of transducers.
Giant stress response of terahertz magnons in a spin-orbit Mott insulator
Authors: Kim Hun-Ho , Ueda Kentaro , Nakata Suguru , Wochner Peter , Mackenzie Andrew , Hicks Clifford , Khaliullin Giniyat , Liu Huimei , Keimer Bernhard , Minola Matteo
Published: November 2022

Magnonic devices operating at terahertz frequencies offer intriguing prospects for high-speed electronics with minimal energy dissipation However, guiding and manipulating terahertz magnons via external parameters present formidable challenges. Here we report the results of magnetic Raman scattering experiments on the antiferromagnetic spin-orbit Mott insulator Sr2IrO4 under uniaxial stress. We find that the energies of zone-center magnons are extremely stress sensitive: lattice strain of 0.1% increases the magnon energy by 40%. The magnon response is symmetric with respect to the sign of the applied stress (tensile or compressive), but depends strongly on its direction in the IrO2 planes. A theory based on coupling of the spin-orbit-entangled iridium magnetic moments to lattice distortions provides a quantitative explanation of the Raman data and a comprehensive framework for the description of magnon-lattice interactions in magnets with strong spin-orbit coupling. The possibility to efficiently manipulate the propagation of terahertz magnons via external stress opens up multifold design options for reconfigurable magnonic devices.
Interaction of a viral insulin-like peptide with the IGF-1 receptor produces a natural antagonist
Authors: Moreau Francois , Kirk Nicholas S. , Zhang Fa , Gelfanov Vasily , List Edward O. , Chrudinová Martina , Venugopal Hari , Lawrence Michael C. , Jimenez Veronica , Bosch Fatima , Kopchick John J. , DiMarchi Richard D. , Altindis Emrah , Kahn C. Ronald
Published: November 2022

Lymphocystis disease virus-1 (LCDV-1) and several other Iridoviridae encode viral insulin/IGF-1 like peptides (VILPs) with high homology to human insulin and IGFs. Here we show that while single-chain (sc) and double-chain (dc) LCDV1-VILPs have very low affinity for the insulin receptor, scLCDV1-VILP has high affinity for IGF1R where it can antagonize human IGF-1 signaling, without altering insulin signaling. Consequently, scLCDV1-VILP inhibits IGF-1 induced cell proliferation and growth hormone/IGF-1 induced growth of mice in vivo. Cryo-electron microscopy reveals that scLCDV1-VILP engages IGF1R in a unique manner, inducing changes in IGF1R conformation that led to separation, rather than juxtaposition, of the transmembrane segments and hence inactivation of the receptor. Thus, scLCDV1-VILP is a natural peptide with specific antagonist properties on IGF1R signaling and may provide a new tool to guide development of hormonal analogues to treat cancers or metabolic disorders sensitive to IGF-1 without affecting glucose metabolism.
Amino acid variability, tradeoffs and optimality in human diet
Authors: Dai Ziwei , Zheng Weiyan , Locasale Jason W.
Published: November 2022

Studies at the molecular level demonstrate that dietary amino acid intake produces substantial effects on health and disease by modulating metabolism. However, how these effects may manifest in human food consumption and dietary patterns is unknown. Here, we develop a series of algorithms to map, characterize and model the landscape of amino acid content in human food, dietary patterns, and individual consumption including relations to health status, covering over 2,000 foods, ten dietary patterns, and over 30,000 dietary profiles. We find that the type of amino acids contained in foods and human consumption is highly dynamic with variability far exceeding that of fat and carbohydrate. Some amino acids positively associate with conditions such as obesity while others contained in the same food negatively link to disease. Using linear programming and machine learning, we show that these health trade-offs can be accounted for to satisfy biochemical constraints in food and human eating patterns to construct a Pareto front in dietary practice, a means of achieving optimality in the face of trade-offs that are commonly considered in economic and evolutionary theories. Thus this study may enable the design of human protein quality intake guidelines based on a quantitative framework.
Epigenetic Alterations of Repeated Relapses in Patient-matched Childhood Ependymomas
Authors: Zhao Sibo , Li Jia , Zhang Huiyuan , Qi Lin , Du Yuchen , Kogiso Mari , Braun Frank K. , Xiao Sophie , Huang Yulun , Li Jianfang , Teo Wan-Yee , Lindsay Holly , Baxter Patricia , Su Jack M. F. , Adesina Adekunle , Laczik Miklós , Genevini Paola , Veillard Anne-Clemence , Schvartzman Sol , Berguet Geoffrey , Ding Shi-Rong , Du Liping , Stephan Clifford , Yang Jianhua , Davies Peter J. A. , Lu Xinyan , Chintagumpala Murali , Parsons Donald William , Perlaky Laszlo , Xia Yun-Fei , Man Tsz-Kwong , Huang Yun , Sun Deqiang , Li Xiao-Nan
Published: November 2022

Recurrence is frequent in pediatric ependymoma (EPN). Our longitudinal integrated analysis of 30 patient-matched repeated relapses (3.67 ± 1.76 times) over 13 years (5.8 ± 3.8) reveals stable molecular subtypes (RELA and PFA) and convergent DNA methylation reprogramming during serial relapses accompanied by increased orthotopic patient derived xenograft (PDX) (13/27) formation in the late recurrences. A set of differentially methylated CpGs (DMCs) and DNA methylation regions (DMRs) are found to persist in primary and relapse tumors (potential driver DMCs) and are acquired exclusively in the relapses (potential booster DMCs). Integrating with RNAseq reveals differentially expressed genes regulated by potential driver DMRs (CACNA1H, SLC12A7, RARA in RELA and HSPB8, GMPR, ITGB4 in PFA) and potential booster DMRs (PLEKHG1 in RELA and NOTCH, EPHA2, SUFU, FOXJ1 in PFA tumors). DMCs predicators of relapse are also identified in the primary tumors. This study provides a high-resolution epigenetic roadmap of serial EPN relapses and 13 orthotopic PDX models to facilitate biological and preclinical studies.
Abemaciclib in combination with pembrolizumab for HR+, HER2− metastatic breast cancer: Phase 1b study
Authors: Rugo Hope S. , Kabos Peter , Beck J. Thad , Jerusalem Guy , Wildiers Hans , Sevillano Elena , Paz-Ares Luis , Chisamore Michael J. , Chapman Sonya C. , Hossain Anwar M. , Chen Yanyun , Tolaney Sara M.
Published: November 2022

This nonrandomized, open-label, multi-cohort Phase 1b study (NCT02779751) investigated the safety and efficacy of abemaciclib plus pembrolizumab with/without anastrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC) without prior CDK4 and 6 inhibitor exposure. Patients were divided into two cohorts: treatment naïve (cohort 1) and pretreated (cohort 2). Patients received abemaciclib plus pembrolizumab with (cohort 1) or without (cohort 2) anastrozole over 21-day cycles. The primary objective was safety, and secondary objectives included efficacy and pharmacokinetics (PK). Cohort 1/2 enrolled 26/28 patients, respectively. Neutropenia (30.8/28.6%), AST increase (34.6/17.9%), ALT increase (42.3/10.7%), and diarrhea (3.8/10.7%) were the most frequent grade ≥3 adverse events in cohort 1/2, respectively. A total of two deaths occurred, which investigators attributed to treatment-related adverse events (AEs), both in cohort 1. Higher rates of all grade and grade ≥3 interstitial lung disease (ILD)/pneumonitis were observed compared to previously reported with abemaciclib and pembrolizumab monotherapy. The PK profiles were consistent between cohorts and with previous monotherapy studies. In cohorts 1/2, the overall response rate and disease control rate were 23.1/28.6% and 84.6/82.1%, respectively. Median progression-free survival and overall survivals were 8.9 (95% CI: 3.9–11.1) and 26.3 months (95% CI: 20.0–31.0) for cohort 2; cohort 1 data are immature. Abemaciclib plus pembrolizumab demonstrated antitumor activity, but high rates of ILD/pneumonitis and severe transaminase elevations occurred with/without anastrozole compared to the previous reporting. Benefit/risk analysis does not support further evaluation of this combination in the treatment of HR+, HER2− MBC.
Association of apolipoprotein M and sphingosine-1-phosphate with brown adipose tissue after cold exposure in humans
Authors: Borup Anna , Donkin Ida , Boon Mariëtte R. , Frydland Martin , Martinez-Tellez Borja , Loft Annika , Keller Sune H. , Kjaer Andreas , Kjaergaard Jesper , Hassager Christian , Barrès Romain , Rensen Patrick C. N. , Christoffersen Christina
Published: November 2022

The HDL-associated apolipoprotein M (apoM) and its ligand sphingosine-1-phosphate (S1P) may control energy metabolism. ApoM deficiency in mice is associated with increased vascular permeability, brown adipose tissue (BAT) mass and activity, and protection against obesity. In the current study, we explored the connection between plasma apoM/S1P levels and parameters of BAT as measured via 18F-FDG PET/CT after cold exposure in humans. Fixed (n = 15) vs personalized (n = 20) short-term cooling protocols decreased and increased apoM (− 8.4%, P = 0.032 vs 15.7%, P < 0.0005) and S1P (− 41.0%, P < 0.0005 vs 19.1%, P < 0.005) plasma levels, respectively. Long-term cooling (n = 44) did not affect plasma apoM or S1P levels. Plasma apoM and S1P did not correlate significantly to BAT volume and activity in the individual studies. However, short-term studies combined, showed that increased changes in plasma apoM correlated with BAT metabolic activity (β: 0.44, 95% CI [0.06–0.81], P = 0.024) after adjusting for study design but not BAT volume (β: 0.39, 95% CI [− 0.01–0.78], P = 0.054). In conclusion, plasma apoM and S1P levels are altered in response to cold exposure and may be linked to changes in BAT metabolic activity but not BAT volume in humans. This contrasts partly with observations in animals and highlights the need for further studies to understand the biological role of apoM/S1P complex in human adipose tissue and lipid metabolism.
Predicting overall survival in diffuse glioma from the presurgical connectome
Authors: Kesler Shelli R. , Harrison Rebecca A. , Rao Vikram , Dyson Hannah , Petersen Melissa , Prinsloo Sarah
Published: November 2022

Diffuse gliomas are incurable brain tumors, yet there is significant heterogeneity in patient survival. Advanced computational techniques such as radiomics show potential for presurgical prediction of survival and other outcomes from neuroimaging. However, these techniques ignore non-lesioned brain features that could be essential for improving prediction accuracy. Gray matter covariance network (connectome) features were retrospectively identified from the T1-weighted MRIs of 305 adult patients diagnosed with diffuse glioma. These features were entered into a Cox proportional hazards model to predict overall survival with 10-folds cross-validation. The mean time-dependent area under the curve (AUC) of the connectome model was compared with the mean AUCs of clinical and radiomic models using a pairwise t-test with Bonferroni correction. One clinical model included only features that are known presurgery (clinical) and another included an advantaged set of features that are not typically known presurgery (clinical +). The median survival time for all patients was 134.2 months. The connectome model (AUC 0.88 ± 0.01) demonstrated superior performance (P < 0.001, corrected) compared to the clinical (AUC 0.61 ± 0.02), clinical + (AUC 0.79 ± 0.01) and radiomic models (AUC 0.75 ± 0.02). These findings indicate that the connectome is a feasible and reliable early biomarker for predicting survival in patients with diffuse glioma. Connectome and other whole-brain models could be valuable tools for precision medicine by informing patient risk stratification and treatment decision-making.
Energy-efficient distributed heterogeneous re-entrant hybrid flow shop scheduling problem with sequence dependent setup times considering factory eligibility constraints
Authors: Geng Kaifeng , Liu Li , Wu Zhanyong
Published: November 2022

In the face of energy crisis, manufacturers pay more and more attention to energy-saving scheduling. In the paper, we consider the distributed heterogeneous re-entrant hybrid flow shop scheduling problem (DHRHFSP) with sequence dependent setup times (DHRHFSP-SDST) considering factory eligibility constraints under time of use (TOU) price, which means that each job can only be assigned to its available set of factories and all factories have different number of machines and processing capacity, and so on. To deal with DHRHFSP-SDST, a multi-objective Artificial Bee Colony Algorithm (MOABC) is proposed to optimize both the makespan and total energy consumption. For the MOABC, firstly, a hybrid initialization method is presented to initialize the population; then, due to the electricity price shows significant differences vary from periods under TOU price, the energy saving operator based on right-shift strategy is proposed to avoid processing jobs with the high electricity price without affecting the productivity; thirdly, based on the full consideration of distributed heterogeneous and factory eligibility, crossover and mutation operators, three neighborhood search operators and new food sources generation strategy are designed; lastly, extensive experiments demonstrate the effectiveness of the proposed algorithm on solving the DHRHFSP-SDST.
Acute poisoning in children in Ethiopia: a cross-sectional study
Authors: Molla Yalew Melkamu , Belachew Kassahun Denekew , Ayehu Gashaw Walle , Teshome Assefa Agegnehu
Published: November 2022

Acute poisoning is a global pediatric emergency problem. However, a wide variation in patterns of acute poisoning and associated factors across different geographical regions was stated. As a result, our research focused on the investigation of acute poisoning in children. An Institutional-based Retrospective study design was conducted at the University of Gondar comprehensive specialized hospital from October 2016 to October 2020. The analysis of the data was performed via SPSS Version 25. Furthermore, multiple logistic regression analysis was recruited. A P-value ≤ 0.05 was declared as statistically significant. Our study's prevalence of acute poisoning was 82/5489 (1.5%). 53 (64.6%) of patients were males. Of the total patients who had the diagnosis of poisoning, 54 (65.9%) came from rural areas. Venom was the most frequent offending agent (26.8%) and oral ingestion was the most common route of exposure (70.7%). Of the total patients who had the diagnosis of poisoning, 54 (65.9%) came from rural areas. Venom was the most frequent offending agent (26.8%), followed by insecticides (organophosphates) (21.5%). Accidental poisoning was the most common mode of poisoning more often than intentional (75.6–24.4%). The digestive tract (oral ingestion) (69.5%) was the commonest route of poisoning, followed by the cutaneous (skin bite) (24.4%). Death was three times more likely in the rural population than in urban residents [AOR 2.9 (1.21–13.7); P value 0.046]. Appropriate emergency care is the mainstay of the supportive management protocol for childhood poisoning.
Closed-loop vagus nerve stimulation for heart rate control evaluated in the Langendorff-perfused rabbit heart
Authors: Haberbusch Max , Kronsteiner Bettina , Kramer Anne-Margarethe , Kiss Attila , Podesser Bruno K. , Moscato Francesco
Published: November 2022

Persistent sinus tachycardia substantially increases the risk of cardiac death. Vagus nerve stimulation (VNS) is known to reduce the heart rate, and hence may be a non-pharmacological alternative for the management of persistent sinus tachycardia. To precisely regulate the heart rate using VNS, closed-loop control strategies are needed. Therefore, in this work, we developed two closed-loop VNS strategies using an in-silico model of the cardiovascular system. Both strategies employ a proportional-integral controller that operates on the current amplitude. While one control strategy continuously delivers stimulation pulses to the vagus nerve, the other applies bursts of stimuli in synchronization with the cardiac cycle. Both were evaluated in Langendorff-perfused rabbit hearts (n = 6) with intact vagal innervation. The controller performance was quantified by rise time (Tr), steady-state error (SSE), and percentual overshoot amplitude (%OS). In the ex-vivo setting, the cardiac-synchronized variant resulted in Tr = 10.7 ± 4.5 s, SSE = 12.7 ± 9.9 bpm and %OS = 5.1 ± 3.6% while continuous stimulation led to Tr = 10.2 ± 5.6 s, SSE = 10 ± 6.7 bpm and %OS = 3.2 ± 1.9%. Overall, both strategies produced a satisfying and reproducible performance, highlighting their potential use in persistent sinus tachycardia.
Kidney segmentation from DCE-MRI converging level set methods, fuzzy clustering and Markov random field modeling
Authors: El-Melegy Moumen , Kamel Rasha , El-Ghar Mohamed Abou , Shehata Mohamed , Khalifa Fahmi , El-Baz Ayman
Published: November 2022

Early diagnosis of transplanted kidney function requires precise Kidney segmentation from Dynamic Contrast-Enhanced Magnetic Resonance Imaging images as a preliminary step. In this regard, this paper aims to propose an automated and accurate DCE-MRI kidney segmentation method integrating fuzzy c-means (FCM) clustering and Markov random field modeling into a level set formulation. The fuzzy memberships, kidney’s shape prior model, and spatial interactions modeled using a second-order MRF guide the LS contour evolution towards the target kidney. Several experiments on real medical data of 45 subjects have shown that the proposed method can achieve high and consistent segmentation accuracy regardless of where the LS contour was initialized. It achieves an accuracy of 0.956 ± 0.019 in Dice similarity coefficient (DSC) and 1.15 ± 1.46 in 95% percentile of Hausdorff distance (HD95). Our quantitative comparisons confirm the superiority of the proposed method over several LS methods with an average improvement of more than 0.63 in terms of HD95. It also offers HD95 improvements of 9.62 and 3.94 over two deep neural networks based on the U-Net model. The accuracy improvements are experimentally found to be more profound on low-contrast images as well as DCE-MRI images with high noise levels.
Dispersive silicon–nitride optical phased array incorporating arrayed waveguide delay lines for passive line beam scanning
Authors: Bhandari Bishal , Wang Chenxi , Gwon Ji-Yeong , Heo Jin-Moo , Ko Sung-Yong , Oh Min-Cheol , Lee Sang-Shin
Published: November 2022

As optical phased arrays (OPAs), used as solid-state beam scanning elements, swiftly stride towards higher efficiency and faster scanning speed, the line beam scanner is emerging as a viable substitute for its counterpart relying on point-beam-incorporated raster scanning. However, line-beam scanners require active phase shifters for beam scanning; thus, they consume more power and have complex device designs. This study proposes and demonstrates a dispersive silicon–nitride OPA that allows for passive wavelength-tuned steering of a line beam with an elongated vertical beamwidth. To steer the line beam passively covering the two-dimensional field of view, we deployed an array of delay lines with progressive delay lengths across adjacent channels. Furthermore, adiabatic tapers that allow precise effective array aperture adjustment are used as emitter elements to flexibly realize different vertical beamwidths. Combinations of different delay-length differences and taper tip-widths resulted in beam coverage (lateral × vertical) ranging from 6.3° × 19° to 23.8° × 40° by tuning the wavelength from 1530 to 1600 nm. The main lobe emission throughput was as small as − 2.8 dB. To the best of our knowledge, the embodied OPA is the first demonstration of a passive line beam scanner facilitating an adjustable beam coverage with quick operation and enhanced efficiency.
Humans modulate arm stiffness to facilitate motor communication during overground physical human-robot interaction
Authors: Regmi Sambad , Burns Devin , Song Yun Seong
Published: November 2022

Humans can physically interact with other humans adeptly. Some overground interaction tasks, such as guiding a partner across a room, occur without visual and verbal communication, which suggests that the information exchanges occur through sensing movements and forces. To understand the process of motor communication during overground physical interaction, we hypothesized that humans modulate the mechanical properties of their arms for increased awareness and sensitivity to ongoing interaction. For this, we used an overground interactive robot to guide a human partner across one of three randomly chosen paths while occasionally providing force perturbations to measure the arm stiffness. We observed that the arm stiffness was lower at instants when the robot’s upcoming trajectory was unknown compared to instants when it was predicable - the first evidence of arm stiffness modulation for better motor communication during overground physical interaction.