bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cloud Responses to Abrupt Solar and CO2 Forcing: 1. Temperature Mediated Cloud Feedbacks
Authors: Aerenson T. , Marchand R. 
Published: June 2024

AbstractThere are many uncertainties in future climate, including how the Earth may react to different types of radiative forcing, such as CO2, aerosols, and even geoengineered changes in the amount of sunlight absorbed by Earth's surface. Here, we analyze model simulations where the climate system is subjected to an abrupt change of the solar constant by ±4%, and where the atmospheric CO2 concentration is abruptly changed to quadruple and half its preindustrial value. Using these experiments, we examine how clouds respond to changes in solar forcing, compared to CO2, and feedback on global surface temperature. The total cloud response can be decomposed into those responses driven by changes in global surface temperature, called the temperature mediated cloud feedbacks, and responses driven directly by the forcing that are independent of the global surface temperature. In this paper, we study the temperature mediated cloud changes to answer two primary questions: (a) How do temperature mediated cloud feedbacks differ in response to abrupt changes in CO2 and solar forcing? And (b) Are there symmetrical (equal and opposite) temperature mediated cloud feedbacks during global warming and global cooling? We find that temperature mediated cloud feedbacks are similar in response to increasing solar and increasing CO2 forcing, and we provide a short review of recent literature regarding the physical mechanisms responsible for these feedbacks. We also find that cloud responses to warming and cooling are not symmetric, due largely to non‐linearity introduced by phase changes in mid‐to‐high latitude low clouds and sea ice loss/formation.
How Atmospheric Forcing Frequency, Horizontal and Vertical Grid Resolutions Impact Mesoscale Eddy Evolution in a Numerical Model
Authors: Barboni Alexandre , Stegner Alexandre , Dumas Franck , Carton Xavier 
Published: June 2024

AbstractSeasonal evolution of both surface signature and subsurface structure of a Mediterranean mesoscale anticyclones is assessed using the Coastal and Regional Ocean Community high‐resolution numerical model with realistic background stratification and fluxes. In good agreement with remote‐sensing and in‐situ observations, our numerical simulations capture the seasonal cycle of the anomalies induced by the anticyclone, both in the sea surface temperature (SST) and in the mixed layer depth (MLD). The eddy signature on the SST shifts from warm‐core in winter to cold‐core in summer, while the MLD deepens significantly in the core of the anticyclone in late winter. Our sensitivity analysis shows that the eddy SST anomaly can be accurately reproduced only if the vertical resolution is high enough (∼4 m in near surface) and if the atmospheric forcing contains high‐frequency. In summer with this configuration, the vertical mixing parameterized by the k − ϵ closure scheme is three times higher inside the eddy than outside the eddy, and leads to an anticyclonic cold core SST anomaly. This differential mixing is explained by near‐inertial waves, triggered by the high‐frequency atmospheric forcing. Near‐inertial waves propagate more energy inside the eddy because of the lower effective Coriolis parameter in the anticyclone core. On the other hand, eddy MLD anomaly appears more sensitive to horizontal resolution, and requires SST retroaction on air‐sea fluxes. These results detail the need of high frequency forcing, high vertical and horizontal resolutions to accurately reproduce the evolution of a mesoscale eddy.
Bayesian Approach to Estimate Proglacial Lake Volume (BE‐GLAV)
Authors: Gantayat Prateek , Sattar Ashim , Haritashya Umesh K. , Watson C. Scott , Kargel Jeffrey S. 
Published: June 2024

AbstractWe present a new model called Bayesian Estimated Glacial Lake Volume (BE‐GLAV) to estimate the volume of proglacial lakes. Presuming the lake cross‐section as trapezoidal, BE‐GLAV uses a Bayesian calibration approach to adjust the cross‐sectional geometry to match modeled and observed lake surface widths. We validated our model using bathymetric measurements from lakes spread across High Mountain Asia (specifically, the Himalaya and Tien‐Shan), with aerial extents ranging from 0.01 to 5.5 km2. The modeled lake volumes agreed with the measured lake volume with a root‐mean‐square absolute uncertainty of ∼14%. With minimum and maximum errors of ∼0.3% and ∼61.2%, BE‐GLAV performed well compared to 10 other models in a model inter‐comparison experiment. Using the measured set of volumes, our model can constrain both the root mean square (RMS) error and the maximum percentage error in modeled lake volume, unlike other models, some of which can compute just the RMS uncertainty.
Uptake and Transfer of Heat Within the Firn Layer of Greenland Ice Sheet's Percolation Zone
Authors: Saito Jun , Harper Joel , Humphrey Neil 
Published: June 2024

AbstractThe thermal field within the firn layer on the Greenland Ice Sheet (GrIS) governs meltwater retention processes, firn densification with surface elevation change, and heat transfer from the surface boundary to deep ice. However, there are few observational data to constrain these processes with only sparse in situ temperature time series that do not extend through the full firn depth. Here, we quantify the thermal structure of Western Greenland’s firn column using instrumentation installed in an elevation transect of boreholes extending to 30 and 96 m depths. During the high‐melt summer of 2019, heat gain in the firn layer showed strong elevation dependency, with greater uptake and deeper penetration of heat at lower elevations. The bulk thermal conductivity increased by 15% per 100 m elevation loss due to higher density related to ice layers. Nevertheless, the conductive heat gain remained relatively constant along the transect due to stronger temperature gradients in the near surface firn at higher elevations. The primary driver of heat gain during this high melt summer was latent heat transfer, which increased up to ten‐fold over the transect, growing by 34 MJ m−2 per 100 m elevation loss. The deep‐firn temperature gradient beneath the seasonally active layer doubled over a 270‐m elevation drop across the study transect, increasing heat flux from the firn layer into deep ice at lower elevations. Our in situ firn temperature time series offers observational constraints for modeling studies and insights into the future evolution of the percolation zone in a warmer climate.
Neoadjuvant camrelizumab (an anti-PD-1 antibody) plus chemotherapy or apatinib (a VEGFR-2 inhibitor) for initially unresectable stage II–III non-small-cell lung cancer: a multicentre, two-arm, phase 2 exploratory study
Authors: Xia Haoran , Zhang Han , Ruan Zheng , Zhang Huibiao , Sun Liangdong , Chen Hezhong , Zhou Yongxin , Zhang Lele , Bian Dongliang , Zhu Xinsheng , Zhang Jing , Sun Fenghuan , Yu Huansha , Song Nan , Liu Xiaogang , Zhu Yuming , Zhang Haiping , He Wenxin , Chen Jian , Yang Jie , Chen Guohan , Xie Shiliang , Tang Dongfang , Zhang Xiaomiao , Duan Liang , Zhao Deping , Li Qinchuan , Zhang Peng , Jiang Gening 
Published: June 2024

AbstractThis multicentre, two-arm, phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II–III non-small-cell lung cancer (NSCLC). Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks (arm A) or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily (arm B), for 2–4 cycles, followed by surgery. The primary endpoint was major pathological response (MPR) rate. Thirty patients in arm A and 21 in arm B were enrolled. Surgery rates were 50.0% (15/30) in arm A and 42.9% (9/21) in arm B, with all patients achieving R0 resections. Of these patients, the MPR and pathological complete response rates were both 20.0% (95% CI 4.3–48.1) in arm A and were 55.6% (95% CI 21.2–86.3) and 11.1% (95% CI 0.3–48.2) in arm B, respectively. The corresponding objective response rates were 33.3% (95% CI 11.8–61.6) and 55.6% (95% CI 21.2–86.3). With a median follow-up of 22.4 months (95% CI 19.0–26.0), the median event-free survival was not reached (NR; 95% CI 13.6-NR) in arm A and 16.8 months (95% CI 8.6-NR) in arm B. Grade 3 or above treatment-related adverse events occurred in eight (26.7%) patients in arm A and three (14.3%) in arm B. Biomarker analysis showed baseline TYROBP expression was predictive of treatment response in arm B. Neoadjuvant camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II–III NSCLC.
Antipsychotics possess anti-glioblastoma activity by disrupting lysosomal function and inhibiting oncogenic signaling by stabilizing PTEN
Authors: Jacob John Ryan , Palanichamy Kamalakannan , Chakravarti Arnab 
Published: June 2024

AbstractThe repurposing of medications developed for central nervous system (CNS) disorders, possessing favorable safety profiles and blood-brain barrier permeability, represents a promising strategy for identifying new therapies to combat glioblastoma (GBM). In this study, we investigated the anti-GBM activity of specific antipsychotics and antidepressants in vitro and in vivo. Our results demonstrate that these compounds share a common mechanism of action in GBM, disrupting lysosomal function and subsequently inducing lysosomal membrane rupture and cell death. Notably, PTEN intact GBMs possess an increased sensitivity to these compounds. The inhibition of lysosomal function synergized with inhibitors targeting the EGFR-PI3K-Akt pathway, leading to an energetic and antioxidant collapse. These findings provide a foundation for the potential clinical application of CNS drugs in GBM treatment. Additionally, this work offers critical insights into the mechanisms and determinants of cytotoxicity for drugs currently undergoing clinical trials as repurposing agents for various cancers, including Fluoxetine, Sertraline, Thioridazine, Chlorpromazine, and Fluphenazine.
An analytic theory for the degree of Arctic Amplification
Authors: Zhou Wenyu , Leung L. Ruby , Xie Shang-Ping , Lu Jian 
Published: June 2024

AbstractArctic Amplification (AA), the amplified surface warming in the Arctic relative to the globe, is a salient feature of climate change. While the basic physical picture of AA has been depicted, how its degree is determined has not been clearly understood. Here, by deciphering atmospheric heat transport (AHT), we build a two-box energy-balance model of AA and derive that the degree of AA is a simple nonlinear function of the Arctic and global feedbacks, the meridional heterogeneity in radiative forcing, and the partial sensitivities of AHT to global mean and meridional gradient of warming. The formula captures the varying AA in climate models and attributes the spread to models’ feedback parameters and AHT physics. The formula clearly illustrates how essential physics mutually determine the degree of AA and limits its range within 1.5-3.5. Our results articulate AHT as both forcing and feedback to AA, highlight its fundamental role in forming a baseline AA that exists even with uniform feedbacks, and underscore its partial sensitivities instead of its total change as key parameters of AA. The lapse-rate feedback has been widely recognized as a major contributor to AA but its effect is fully offset by the water-vapor feedback.
Dissecting tumor microenvironment from spatially resolved transcriptomics data by heterogeneous graph learning
Authors: Zuo Chunman , Xia Junjie , Chen Luonan 
Published: June 2024

AbstractSpatially resolved transcriptomics (SRT) has enabled precise dissection of tumor-microenvironment (TME) by analyzing its intracellular molecular networks and intercellular cell-cell communication (CCC). However, lacking computational exploration of complicated relations between cells, genes, and histological regions, severely limits the ability to interpret the complex structure of TME. Here, we introduce stKeep, a heterogeneous graph (HG) learning method that integrates multimodality and gene-gene interactions, in unraveling TME from SRT data. stKeep leverages HG to learn both cell-modules and gene-modules by incorporating features of diverse nodes including genes, cells, and histological regions, allows for identifying finer cell-states within TME and cell-state-specific gene-gene relations, respectively. Furthermore, stKeep employs HG to infer CCC for each cell, while ensuring that learned CCC patterns are comparable across different cell-states through contrastive learning. In various cancer samples, stKeep outperforms other tools in dissecting TME such as detecting bi-potent basal populations, neoplastic myoepithelial cells, and metastatic cells distributed within the tumor or leading-edge regions. Notably, stKeep identifies key transcription factors, ligands, and receptors relevant to disease progression, which are further validated by the functional and survival analysis of independent clinical data, thereby highlighting its clinical prognostic and immunotherapy applications.
Altered chromatin topologies caused by balanced chromosomal translocation lead to central iris hypoplasia
Authors: Sun Wenmin , Xiong Dan , Ouyang Jiamin , Xiao Xueshan , Jiang Yi , Wang Yingwei , Li Shiqiang , Xie Ziying , Wang Junwen , Tang Zhonghui , Zhang Qingjiong 
Published: June 2024

AbstractDespite the advent of genomic sequencing, molecular diagnosis remains unsolved in approximately half of patients with Mendelian disorders, largely due to unclarified functions of noncoding regions and the difficulty in identifying complex structural variations. In this study, we map a unique form of central iris hypoplasia in a large family to 6q15-q23.3 and 18p11.31-q12.1 using a genome-wide linkage scan. Long-read sequencing reveals a balanced translocation t(6;18)(q22.31;p11.22) with intergenic breakpoints. By performing Hi-C on induced pluripotent stem cells from a patient, we identify two chromatin topologically associating domains spanning across the breakpoints. These alterations lead the ectopic chromatin interactions between APCDD1 on chromosome 18 and enhancers on chromosome 6, resulting in upregulation of APCDD1. Notably, APCDD1 is specifically localized in the iris of human eyes. Our findings demonstrate that noncoding structural variations can lead to Mendelian diseases by disrupting the 3D genome structure and resulting in altered gene expression.
Nanoscale optical nonreciprocity with nonlinear metasurfaces
Authors: Tripathi Aditya , Ugwu Chibuzor Fabian , Asadchy Viktar S. , Faniayeu Ihar , Kravchenko Ivan , Fan Shanhui , Kivshar Yuri , Valentine Jason , Kruk Sergey S. 
Published: June 2024

AbstractOptical nonreciprocity is manifested as a difference in the transmission of light for the opposite directions of excitation. Nonreciprocal optics is traditionally realized with relatively bulky components such as optical isolators based on the Faraday rotation, hindering the miniaturization and integration of optical systems. Here we demonstrate free-space nonreciprocal transmission through a metasurface comprised of a two-dimensional array of nanoresonators made of silicon hybridized with vanadium dioxide (VO2). This effect arises from the magneto-electric coupling between Mie modes supported by the resonator. Nonreciprocal response of the nanoresonators occurs without the need for external bias; instead, reciprocity is broken by the incident light triggering the VO2 phase transition for only one direction of incidence. Nonreciprocal transmission is broadband covering over 100 nm in the telecommunication range in the vicinity of λ = 1.5 µm. Each nanoresonator unit cell occupies only ~0.1 λ3 in volume, with the metasurface thickness measuring about half-a-micron. Our self-biased nanoresonators exhibit nonreciprocity down to very low levels of intensity on the order of 150 W/cm2 or a µW per nanoresonator. We estimate picosecond-scale transmission fall times and sub-microsecond scale transmission rise. Our demonstration brings low-power, broadband and bias-free optical nonreciprocity to the nanoscale.
MRI-based microthrombi detection in stroke with polydopamine iron oxide
Authors: Jacqmarcq Charlène , Picot Audrey , Flon Jules , Lebrun Florent , Martinez de Lizarrondo Sara , Naveau Mikaël , Bernay Benoît , Goux Didier , Rubio Marina , Malzert-Fréon Aurélie , Michel Anita , Proamer Fabienne , Mangin Pierre , Gauberti Maxime , Vivien Denis , Bonnard Thomas 
Published: June 2024

AbstractIn acute ischemic stroke, even when successful recanalization is obtained, downstream microcirculation may still be obstructed by microvascular thrombosis, which is associated with compromised brain reperfusion and cognitive decline. Identifying these microthrombi through non-invasive methods remains challenging. We developed the PHySIOMIC (Polydopamine Hybridized Self-assembled Iron Oxide Mussel Inspired Clusters), a MRI-based contrast agent that unmasks these microthrombi. In a mouse model of thromboembolic ischemic stroke, our findings demonstrate that the PHySIOMIC generate a distinct hypointense signal on T2*-weighted MRI in the presence of microthrombi, that correlates with the lesion areas observed 24 hours post-stroke. Our microfluidic studies reveal the role of fibrinogen in the protein corona for the thrombosis targeting properties. Finally, we observe the biodegradation and biocompatibility of these particles. This work demonstrates that the PHySIOMIC particles offer an innovative and valuable tool for non-invasive in vivo diagnosis and monitoring of microthrombi, using MRI during ischemic stroke.
Canalization reduces the nonlinearity of regulation in biological networks
Authors: Kadelka Claus , Murrugarra David 
Published: June 2024

AbstractBiological networks, such as gene regulatory networks, possess desirable properties. They are more robust and controllable than random networks. This motivates the search for structural and dynamical features that evolution has incorporated into biological networks. A recent meta-analysis of published, expert-curated Boolean biological network models has revealed several such features, often referred to as design principles. Among others, the biological networks are enriched for certain recurring network motifs, the dynamic update rules are more redundant, more biased, and more canalizing than expected, and the dynamics of biological networks are better approximable by linear and lower-order approximations than those of comparable random networks. Since most of these features are interrelated, it is paramount to disentangle cause and effect, that is, to understand which features evolution actively selects for, and thus truly constitute evolutionary design principles. Here, we compare published Boolean biological network models with different ensembles of null models and show that the abundance of canalization in biological networks can almost completely explain their recently postulated high approximability. Moreover, an analysis of random N–K Kauffman models reveals a strong dependence of approximability on the dynamical robustness of a network.
Biomedical Data Repository Concepts and Management Principles
Authors: Lin Dawei , McAuliffe Matthew , Pruitt Kim D. , Gururaj Anupama , Melchior Christine , Schmitt Charles , Wright Susan N. 
Published: June 2024

AbstractThe demand for open data and open science is on the rise, fueled by expectations from the scientific community, calls to increase transparency and reproducibility in research findings, and developments such as the Final Data Management and Sharing Policy from the U.S. National Institutes of Health and a memorandum on increasing public access to federally funded research, issued by the U.S. Office of Science and Technology Policy. This paper explores the pivotal role of data repositories in biomedical research and open science, emphasizing their importance in managing, preserving, and sharing research data. Our objective is to familiarize readers with the functions of data repositories, set expectations for their services, and provide an overview of methods to evaluate their capabilities. The paper serves to introduce fundamental concepts and community-based guiding principles and aims to equip researchers, repository operators, funders, and policymakers with the knowledge to select appropriate repositories for their data management and sharing needs and foster a foundation for the open sharing and preservation of research data.
Capturing the antimicrobial profile of Paeonia officinalis, Jasminum officinale and Rosa damascene against methicillin resistant Staphylococcus aureus with metabolomics analysis and network pharmacology
Authors: Shady Nourhan Hisham , Mokhtar Fatma Alzahraa , Mahmoud Basma Khalaf , Yahia Ramadan , Ibrahim Ayman M. , Sayed Nada Ahmed , Samy Mamdouh Nabil , Alzubaidi Mubarak A. , Abdelmohsen Usama Ramadan 
Published: June 2024

AbstractIn the current study, we evaluated the in vitro antibacterial efficacy of the roots’ extracts of Jasminum officinale, Rosa damascene and Paeonia officinalis against MRSA (methicillin-resistant Staphylococcus aureus) by well diffusion technique. The root extract of P. officinalis exerted a potent anti-MRSA with MIC 0.4673 µg/ml, while both J. officinale and R. damascene exhibited very weak activity. Therefore, chemical profiling of the crude extract P. officinalis roots assisted by LC-HR-ESI-MS was performed and led to the dereplication of twenty metabolites of different classes, in which terpenes are the most abundant compounds. On a molecular level, network pharmacology was used to determine the targets of active metabolites to bacterial infections, particularly MRSA. Online databases PubChem, UniProt, STRING, and Swiss Target Prediction were used. In addition to using CYTOSCAPE software to display and analyze the findings, ShinyGO and FunRich tools were used to identify the gene enrichment analysis to the set of recognized genes. The results detected the identified metabolites were annotated by 254 targets. ALB, ACHE, TYMS, PRKCD, PLG, MMP9, MMP2, ERN1, EDNRA, BRD4 were found to be associated with MRSA infection. The top KEGG pathway was the vascular smooth muscle contraction pathway according to enrichment FDR. The present study suggested a possible implication of P. officinalis roots as a potent candidate having a powerful antibacterial activity against MRSA.