bluuebunny/crossref_metadata_2025_split huggingface dataset:
Harnessing the bilingual descent down the mountain of life: Charting novel paths for Cognitive and Brain Reserves research
Authors: Rothman Jason 
Published: March 2024

Abstract
Evidence from various empirical study types have converged to show bilingualism's potential for serving as a cognitive and brain reserves contributor. In this article, I contextualize, frame the need for and offer some expanding questions in this endeavor, inclusive of empirical pathways to address them. While the set of variables and questions discussed herein are definitively incomplete, they embody a good starting point for shaping future directions in research that considers the role bilingual language engagement can have for the developing mind and brain, inclusive of how various, non-linear factors impact the descent bilinguals of various types take down the proverbial mountain of life.
Elevation Anomalies of the Volcanic Floor Unit and Their Relationships to the Multiple Lakes of Jezero Crater, Mars
Authors: Annex A. M. , Ehlmann B. L. 
Published: March 2024

AbstractWe reassessed several orbital topographic data sets for the Perseverance rover landing site at Jezero Crater, Mars to better understand its floor units. Tens‐of‐meters deep topographic anomalies occur in the volcanic floor of Jezero crater and are not a result of impact cratering. Eight km‐scale steep escarpment‐bounded depressions may be locations of paleotopographic highs that were embayed by the volcanic floor lava flows, forming inverted topography from either contemporaneous upward inflation of embaying lavas or later deep scour due to differential erosion over 107−9 years. Five multi km‐scale shallow‐sloped depressions linked by channel‐like forms may record locations of buried paleolakes and channels that predate the volcanic floor units or a drained magma system. These results indicate Jezero experienced multiple closed‐basin or dry phases, allowing erosion of the crater floor and creation of topography, which provides new geologic context for the samples gathered by Perseverance.
Density and Magnetic Field Asymmetric Kelvin‐Helmholtz Instability
Authors: Ma Xuanye , Delamere Peter , Nykyri Katariina , Otto Antonius , Eriksson Stefan , Chai Lihui , Burkholder Brandon , Dimmock Andrew , Liou Yu‐Lun , Kavosi Shiva 
Published: March 2024

AbstractThe Kelvin‐Helmholtz (KH) instability can transport mass, momentum, magnetic flux, and energy between the magnetosheath and magnetosphere, which plays an important role in the solar‐wind‐magnetosphere coupling process for different planets. Meanwhile, strong density and magnetic field asymmetry are often present between the magnetosheath (MSH) and magnetosphere (MSP), which could affect the transport processes driven by the KH instability. Our magnetohydrodynamics simulation shows that the KH growth rate is insensitive to the density ratio between the MSP and the MSH in the compressible regime, which is different than the prediction from linear incompressible theory. When the interplanetary magnetic field (IMF) is parallel to the planet's magnetic field, the nonlinear KH instability can drive a double mid‐latitude reconnection (DMLR) process. The total double reconnected flux depends on the KH wavelength and the strength of the lower magnetic field. When the IMF is anti‐parallel to the planet's magnetic field, the nonlinear interaction between magnetic reconnection and the KH instability leads to fast reconnection (i.e., close to Petschek reconnection even without including kinetic physics). However, the peak value of the reconnection rate still follows the asymmetric reconnection scaling laws. We also demonstrate that the DMLR process driven by the KH instability mixes the plasma from different regions and consequently generates different types of velocity distribution functions. We show that the counter‐streaming beams can be simply generated via the change of the flux tube connection and do not require parallel electric fields.
On Generalized Additive Models for Representation of Solar EUV Irradiance
Authors: Brandt Daniel A. , Vega Erick F. , Ridley Aaron J. 
Published: March 2024

AbstractIn the context of space weather forecasting, solar EUV irradiance specification is needed on multiple time scales, with associated uncertainty quantification for determining the accuracy of downstream parameters. Empirical models of irradiance often rely on parametric fits between irradiance in several bands and various solar indices. We build upon these empirical models by using Generalized Additive Models (GAMs) to represent solar irradiance. We apply the GAM approach in two steps: (a) A GAM is fitted between FISM2 irradiance and solar indices F10.7, Revised Sunspot Number, and the Lyman‐α solar index. (b) A second GAM is fit to model the residuals of the first GAM with respect to FISM2 irradiance. We evaluate the performance of this approach during Solar Cycle 24 using GAMs driven by known solar indices as well as those forecasted 3 days ahead with an autoregressive modeling approach. We demonstrate negligible dependence of performance on solar cycle and season, and we assess the efficacy of the GAM approach across different wavelengths.
Promising dawn in tumor microenvironment therapy: engineering oral bacteria
Authors: Wang Zifei , Sun Wansu , Hua Ruixue , Wang Yuanyin , Li Yang , Zhang Hengguo 
Published: March 2024

AbstractDespite decades of research, cancer continues to be a major global health concern. The human mouth appears to be a multiplicity of local environments communicating with other organs and causing diseases via microbes. Nowadays, the role of oral microbes in the development and progression of cancer has received increasing scrutiny. At the same time, bioengineering technology and nanotechnology is growing rapidly, in which the physiological activities of natural bacteria are modified to improve the therapeutic efficiency of cancers. These engineered bacteria were transformed to achieve directed genetic reprogramming, selective functional reorganization and precise control. In contrast to endotoxins produced by typical genetically modified bacteria, oral flora exhibits favorable biosafety characteristics. To outline the current cognitions upon oral microbes, engineered microbes and human cancers, related literatures were searched and reviewed based on the PubMed database. We focused on a number of oral microbes and related mechanisms associated with the tumor microenvironment, which involve in cancer occurrence and development. Whether engineering oral bacteria can be a possible application of cancer therapy is worth consideration. A deeper understanding of the relationship between engineered oral bacteria and cancer therapy may enhance our knowledge of tumor pathogenesis thus providing new insights and strategies for cancer prevention and treatment.
Can flow proneness be protective against mental and cardiovascular health problems? A genetically informed prospective cohort study
Authors: Gaston Emma , Ullén Fredrik , Wesseldijk Laura W. , Mosing Miriam A. 
Published: March 2024

AbstractFlow is a phenomenon where one experiences optimal challenge, marked by an intense, effortless, and rewarding concentration on a task. Past research shows that flow proneness is associated with good mental and cardiovascular health. However, this research has been primarily cross-sectional, based on self-report data, and has not controlled for potential confounding effects of neuroticism. In a large, longitudinal twin sample (N = 9361), we used nationwide patient registry data to test whether flow proneness predicted registry-based diagnoses of depression, anxiety, schizophrenia, bipolar disorder, stress-related disorders, or cardiovascular diseases. We used survival analyses taking time to diagnosis into account to test if (a) there is a relationship between flow proneness and health diagnoses over time, (b) neuroticism confounds this relationship, and (c) the relationship remains present within discordant monozygotic twin pairs (N = 952), thereby controlling for genetic and shared environmental confounding. Individuals with higher flow proneness had a decreased risk of receiving diagnoses for depression (16%; CI [14%, 18%]), anxiety (16%; CI [13%, 18%]), schizophrenia (15%; CI [4%, 25%]), bipolar (12%; CI [6%, 18%]), stress-related (9%; CI [9%, 12%]), and cardiovascular disorders (4%; CI [1%, 8%]). When controlling for neuroticism, higher flow proneness still decreased the risk of depression (6%; CI [3%, 9%]) and anxiety diagnoses (5%; CI [1%, 8%]). Monozygotic twins who experienced more flow than their co-twin had a lower risk for depression (16%; CI [5%, 26%]) and anxiety (13%; CI [1%, 24%]), though only the association with depression remained significant when also controlling for neuroticism (13%; CI [1%, 24%]). Findings are in line with a causal protective role of flow experiences on depression and potentially anxiety and highlight that neuroticism and familial factors are notable confounding factors in observed associations between flow proneness and health outcomes.
The MITF/mir-579-3p regulatory axis dictates BRAF-mutated melanoma cell fate in response to MAPK inhibitors
Authors: Liguoro Domenico , Frigerio Rachele , Ortolano Arianna , Sacconi Andrea , Acunzo Mario , Romano Giulia , Nigita Giovanni , Bellei Barbara , Madonna Gabriele , Capone Mariaelena , Ascierto Paolo Antonio , Mancini Rita , Ciliberto Gennaro , Fattore Luigi 
Published: March 2024

AbstractTherapy of melanoma has improved dramatically over the last years thanks to the development of targeted therapies (MAPKi) and immunotherapies. However, drug resistance continues to limit the efficacy of these therapies. Our research group has provided robust evidence as to the involvement of a set of microRNAs in the development of resistance to target therapy in BRAF-mutated melanomas. Among them, a pivotal role is played by the oncosuppressor miR-579-3p. Here we show that miR-579-3p and the microphthalmia-associated transcription factor (MITF) influence reciprocally their expression through positive feedback regulatory loops. In particular we show that miR-579-3p is specifically deregulated in BRAF-mutant melanomas and that its expression levels mirror those of MITF. Luciferase and ChIP studies show that MITF is a positive regulator of miR-579-3p, which is located in the intron 11 of the human gene ZFR (Zink-finger recombinase) and is co-transcribed with its host gene. Moreover, miR-579-3p, by targeting BRAF, is able to stabilize MITF protein thus inducing its own transcription. From biological points of view, early exposure to MAPKi or, alternatively miR-579-3p transfection, induce block of proliferation and trigger senescence programs in BRAF-mutant melanoma cells. Finally, the long-term development of resistance to MAPKi is able to select cells characterized by the loss of both miR-579-3p and MITF and the same down-regulation is also present in patients relapsing after treatments. Altogether these findings suggest that miR-579-3p/MITF interplay potentially governs the balance between proliferation, senescence and resistance to therapies in BRAF-mutant melanomas.
Hypoxia induced exosomal Circ-ZNF609 promotes pre-metastatic niche formation and cancer progression via miR-150-5p/VEGFA and HuR/ZO-1 axes in esophageal squamous cell carcinoma
Authors: Mao Yu , Wang Jiahao , Wang Yimin , Fu Zhanzhao , Dong Lixin , Liu Jia 
Published: March 2024

AbstractExosomes derived from cancer are regarded as significant mediators of cancer-host crosstalk. Hypoxia, on the other hand, is one of the essential characteristics of solid tumors. This research set out to discover how circulating exosomes from hypoxic esophageal squamous cell carcinoma (ESCC) contribute to the formation of metastatic niches and distant metastasis. First, we noticed that human umbilical vein endothelial cells (HUVECs) had their tight connections disrupted and the expression of proteins involved in angiogenesis boosted by ESCC hypoxic exosomes. Hypoxia significantly induced Circ-ZNF609 expression in exosomes from ESCC, which was then internalized by HUVECs, as determined by circular RNA screening. High Circ-ZNF609 expression in HUVECs facilitated angiogenesis and vascular permeability, thereby promoting pre-metastatic niche formation, and enhancing distant metastasis in vitro and in vivo. Exosomal Circ-ZNF609 activated vascular endothelial growth factor A (VEGFA) mechanistically by sponging miR-150-5p. Exosomal Circ-ZNF609 also interacted with HuR and inhibited HuR binding to ZO-1, Claudin-1, and Occludin mRNAs, thereby reducing their translation. Collectively, our findings identified an essential function for exosomal Circ-ZNF609 from ESCC cells, suggesting the potential therapeutic value of exosomes for ESCC patients.
Arnicolide D induces endoplasmic reticulum stress-mediated oncosis via ATF4 and CHOP in hepatocellular carcinoma cells
Authors: Lin Yu-Shan , Sun Zhiwei , Shen Li-Sha , Gong Rui-Hong , Chen Jia-Wen , Xu Yanfeng , Yu Haiyang , Chen Sibao , Chen Guo-Qing 
Published: March 2024

AbstractEndoplasmic reticulum (ER) stress can trigger various cell death mechanisms beyond apoptosis, providing promise in cancer treatment. Oncosis, characterized by cellular swelling and increased membrane permeability, represents a non-apoptotic form of cell death. In our study, we discovered that Arnicolide D (AD), a natural sesquiterpene lactone compound, induces ER stress-mediated oncosis in hepatocellular carcinoma (HCC) cells, and this process is reactive oxygen species (ROS)-dependent. Furthermore, we identified the activation of the PERK-eIF2α-ATF4-CHOP pathway during ER stress as a pivotal factor in AD-induced oncosis. Notably, the protein synthesis inhibitor cycloheximide (CHX) was found to effectively reverse AD-induced oncosis, suggesting ATF4 and CHOP may hold crucial roles in the induction of oncosis by AD. These proteins play a vital part in promoting protein synthesis during ER stress, ultimately leading to cell death. Subsequent studies, in where we individually or simultaneously knocked down ATF4 and CHOP in HCC cells, provided further confirmation of their indispensable roles in AD-induced oncosis. Moreover, additional animal experiments not only substantiated AD’s ability to inhibit HCC tumor growth but also solidified the essential role of ER stress-mediated and ROS-dependent oncosis in AD’s therapeutic potential. In summary, our research findings strongly indicate that AD holds promise as a therapeutic agent for HCC by its ability to induce oncosis.
Controlled formation of three-dimensional cavities during lateral epitaxial growth
Authors: Zhang Yiwen , Wang Baoming , Miao Changxu , Chai Haozhi , Hong Wei , Ross Frances M. , Wen Rui-Tao 
Published: March 2024

AbstractEpitaxial growth is a fundamental step required to create devices for the semiconductor industry, enabling different materials to be combined in layers with precise control of strain and defect structure. Patterning the growth substrate with a mask before performing epitaxial growth offers additional degrees of freedom to engineer the structure and hence function of the semiconductor device. Here, we demonstrate that conditions exist where such epitaxial lateral overgrowth can produce complex, three-dimensional structures that incorporate cavities of deterministic size. We grow germanium on silicon substrates patterned with a dielectric mask and show that fully-enclosed cavities can be created through an unexpected self-assembly process that is controlled by surface diffusion and surface energy minimization. The result is confined cavities enclosed by single crystalline Ge, with size and position tunable through the initial mask pattern. We present a model to account for the observed cavity symmetry, pinch-off and subsequent evolution, reflecting the dominant role of surface energy. Since dielectric mask patterning and epitaxial growth are compatible with conventional device processing steps, we suggest that this mechanism provides a strategy for developing electronic and photonic functionalities.
Reconfigurable spin current transmission and magnon–magnon coupling in hybrid ferrimagnetic insulators
Authors: Li Yan , Zhang Zhitao , Liu Chen , Zheng Dongxing , Fang Bin , Zhang Chenhui , Chen Aitian , Ma Yinchang , Wang Chunmei , Liu Haoliang , Shen Ka , Manchon Aurélien , Xiao John Q. , Qiu Ziqiang , Hu Can-Ming , Zhang Xixiang 
Published: March 2024

AbstractCoherent spin waves possess immense potential in wave-based information computation, storage, and transmission with high fidelity and ultra-low energy consumption. However, despite their seminal importance for magnonic devices, there is a paucity of both structural prototypes and theoretical frameworks that regulate the spin current transmission and magnon hybridization mediated by coherent spin waves. Here, we demonstrate reconfigurable coherent spin current transmission, as well as magnon–magnon coupling, in a hybrid ferrimagnetic heterostructure comprising epitaxial Gd3Fe5O12 and Y3Fe5O12 insulators. By adjusting the compensated moment in Gd3Fe5O12, magnon–magnon coupling was achieved and engineered with pronounced anticrossings between two Kittel modes, accompanied by divergent dissipative coupling approaching the magnetic compensation temperature of Gd3Fe5O12 (TM,GdIG), which were modeled by coherent spin pumping. Remarkably, we further identified, both experimentally and theoretically, a drastic variation in the coherent spin wave-mediated spin current across TM,GdIG, which manifested as a strong dependence on the relative alignment of magnetic moments. Our findings provide significant fundamental insight into the reconfiguration of coherent spin waves and offer a new route towards constructing artificial magnonic architectures.
Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications
Authors: Chelban Viorica , Aksnes Henriette , Maroofian Reza , LaMonica Lauren C. , Seabra Luis , Siggervåg Anette , Devic Perrine , Shamseldin Hanan E. , Vandrovcova Jana , Murphy David , Richard Anne-Claire , Quenez Olivier , Bonnevalle Antoine , Zanetti M. Natalia , Kaiyrzhanov Rauan , Salpietro Vincenzo , Efthymiou Stephanie , Schottlaender Lucia V. , Morsy Heba , Scardamaglia Annarita , Tariq Ambreen , Pagnamenta Alistair T. , Pennavaria Ajia , Krogstad Liv S. , Bekkelund Åse K. , Caiella Alessia , Glomnes Nina , Brønstad Kirsten M. , Tury Sandrine , Moreno De Luca Andrés , Boland-Auge Anne , Olaso Robert , Deleuze Jean-François , Anheim Mathieu , Cretin Benjamin , Vona Barbara , Alajlan Fahad , Abdulwahab Firdous , Battini Jean-Luc , İpek Rojan , Bauer Peter , Zifarelli Giovanni , Gungor Serdal , Kurul Semra Hiz , Lochmuller Hanns , Da’as Sahar I. , Fakhro Khalid A. , Gómez-Pascual Alicia , Botía Juan A. , Wood Nicholas W. , Horvath Rita , Ernst Andreas M. , Rothman James E. , McEntagart Meriel , Crow Yanick J. , Alkuraya Fowzan S. , Nicolas Gaël ,   SYNaPS Study Group, Houlden Henry , Alkuraya Fowzan S. , Arnesen Thomas , Houlden Henry 
Published: March 2024

AbstractPrimary familial brain calcification (PFBC) is characterized by calcium deposition in the brain, causing progressive movement disorders, psychiatric symptoms, and cognitive decline. PFBC is a heterogeneous disorder currently linked to variants in six different genes, but most patients remain genetically undiagnosed. Here, we identify biallelic NAA60 variants in ten individuals from seven families with autosomal recessive PFBC. The NAA60 variants lead to loss-of-function with lack of protein N-terminal (Nt)-acetylation activity. We show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro. In cells, loss of NAA60 caused reduced surface levels of SLC20A2 and a reduction in extracellular phosphate uptake. This study establishes NAA60 as a causal gene for PFBC, provides a possible biochemical explanation of its disease-causing mechanisms and underscores NAA60-mediated Nt-acetylation of transmembrane proteins as a fundamental process for healthy neurobiological functioning.
Precise atom-to-atom mapping for organic reactions via human-in-the-loop machine learning
Authors: Chen Shuan , An Sunggi , Babazade Ramil , Jung Yousung 
Published: March 2024

AbstractAtom-to-atom mapping (AAM) is a task of identifying the position of each atom in the molecules before and after a chemical reaction, which is important for understanding the reaction mechanism. As more machine learning (ML) models were developed for retrosynthesis and reaction outcome prediction recently, the quality of these models is highly dependent on the quality of the AAM in reaction datasets. Although there are algorithms using graph theory or unsupervised learning to label the AAM for reaction datasets, existing methods map the atoms based on substructure alignments instead of chemistry knowledge. Here, we present LocalMapper, an ML model that learns correct AAM from chemist-labeled reactions via human-in-the-loop machine learning. We show that LocalMapper can predict the AAM for 50 K reactions with 98.5% calibrated accuracy by learning from only 2% of the human-labeled reactions from the entire dataset. More importantly, the confident predictions given by LocalMapper, which cover 97% of 50 K reactions, show 100% accuracy for 3,000 randomly sampled reactions. In an out-of-distribution experiment, LocalMapper shows favorable performance over other existing methods. We expect LocalMapper can be used to generate more precise reaction AAM and improve the quality of future ML-based reaction prediction models.
High-resolution cryo-EM of the human CDK-activating kinase for structure-based drug design
Authors: Cushing Victoria I. , Koh Adrian F. , Feng Junjie , Jurgaityte Kaste , Bondke Alexander , Kroll Sebastian H. B. , Barbazanges Marion , Scheiper Bodo , Bahl Ash K. , Barrett Anthony G. M. , Ali Simak , Kotecha Abhay , Greber Basil J. 
Published: March 2024

AbstractRational design of next-generation therapeutics can be facilitated by high-resolution structures of drug targets bound to small-molecule inhibitors. However, application of structure-based methods to macromolecules refractory to crystallization has been hampered by the often-limiting resolution and throughput of cryogenic electron microscopy (cryo-EM). Here, we use high-resolution cryo-EM to determine structures of the CDK-activating kinase, a master regulator of cell growth and division, in its free and nucleotide-bound states and in complex with 15 inhibitors at up to 1.8 Å resolution. Our structures provide detailed insight into inhibitor interactions and networks of water molecules in the active site of cyclin-dependent kinase 7 and provide insights into the mechanisms contributing to inhibitor selectivity, thereby providing the basis for rational design of next-generation therapeutics. These results establish a methodological framework for the use of high-resolution cryo-EM in structure-based drug design.