bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractThe 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

Abstract
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.
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

AbstractSignificant 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

AbstractThe 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

AbstractDual-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

AbstractThe 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

AbstractAdopting 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

AbstractExsolution 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

AbstractHigh-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

AbstractMagnonic 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

AbstractLymphocystis 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

AbstractStudies 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

AbstractRecurrence 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

AbstractThis 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.