bluuebunny/crossref_metadata_2025_split huggingface dataset:
CDAnet: A Physics‐Informed Deep Neural Network for Downscaling Fluid Flows
Authors: Hammoud Mohamad Abed El Rahman , Titi Edriss S. , Hoteit Ibrahim , Knio Omar 
Published: November 2022

AbstractGenerating high‐resolution flow fields is of paramount importance for various applications in engineering and climate sciences. This is typically achieved by solving the governing dynamical equations on high‐resolution meshes, suitably nudged toward available coarse‐scale data. To alleviate the computational cost of such downscaling process, we develop a physics‐informed deep neural network (PI‐DNN) that mimics the mapping of coarse‐scale information into their fine‐scale counterparts of continuous data assimilation (CDA). Specifically, the PI‐DNN is trained within the theoretical framework described by Foias et al. (2014, https://doi.org/10.1070/rm2014v069n02abeh004891) to generate a surrogate of the theorized determining form map from the coarse‐resolution data to the fine‐resolution solution. We demonstrate the PI‐DNN methodology through application to 2D Rayleigh‐Bénard convection, and assess its performance by contrasting its predictions against those obtained by dynamical downscaling using CDA. The analysis suggests that the surrogate is constrained by similar conditions, in terms of spatio‐temporal resolution of the input, as the ones required by the theoretical determining form map. The numerical results also suggest that the surrogate's downscaled fields are of comparable accuracy to those obtained by dynamically downscaling using CDA. Consistent with the analysis of Farhat, Jolly, and Titi (2015, https://doi.org/10.48550/arxiv.1410.176), temperature observations are not needed for the PI‐DNN to predict the fine‐scale velocity, pressure and temperature fields.
Pim1 promotes IFN-β production by interacting with IRF3
Authors: Ko Ryeojin , Seo Jeongin , Park Hana , Lee Nawon , Lee Soo Young 
Published: November 2022

AbstractThe Pim (proviral integration site for Moloney murine leukemia virus) proteins compose a serine threonine kinase family whose members regulate cell proliferation, migration and cell survival. However, whether Pim kinases participate in innate immune responses is unclear. Here, we show for the first time that Pim1 plays an essential role in the production of interferon (IFN)-β by macrophages after their Toll-like receptor (TLR) pathway is activated by pathogen-associated molecular patterns (PAMPs). Specifically, Pim1 was quickly upregulated in an NF-κB-dependent manner after TLR stimulation with PAMPs. Pim1 deficiency reduced TLR3- or TLR4-stimulated IFN-β and IFN-stimulated gene (ISG) expression but not proinflammatory cytokine expression in macrophages. Mechanistically, Pim1 specifically upregulates IRF3 phosphorylation and nuclear translocation. However, this role is not dependent on Pim1 kinase activity. Rather, Pim1 appears to promote IRF3 phosphorylation by enhancing the formation of IFN-β signaling complexes composed of TRIF, TRAF3, TBK1, and IRF3. Poly (I:C)-treated Pim1−/− mice produced less serum IFN-β and were less likely to survive than wild-type mice. These findings show for the first time that Pim1 participates in TLR-mediated IFN-β production, thus revealing a novel target for controlling antiviral innate immune responses.
Psychopathic and autistic traits differentially influence the neural mechanisms of social cognition from communication signals
Authors: Skjegstad Christine L. , Trevor Caitlyn , Swanborough Huw , Roswandowitz Claudia , Mokros Andreas , Habermeyer Elmar , Frühholz Sascha 
Published: November 2022

AbstractPsychopathy is associated with severe deviations in social behavior and cognition. While previous research described such cognitive and neural alterations in the processing of rather specific social information from human expressions, some open questions remain concerning central and differential neurocognitive deficits underlying psychopathic behavior. Here we investigated three rather unexplored factors to explain these deficits, first, by assessing psychopathy subtypes in social cognition, second, by investigating the discrimination of social communication sounds (speech, non-speech) from other non-social sounds, and third, by determining the neural overlap in social cognition impairments with autistic traits, given potential common deficits in the processing of communicative voice signals. The study was exploratory with a focus on how psychopathic and autistic traits differentially influence the function of social cognitive and affective brain networks in response to social voice stimuli. We used a parametric data analysis approach from a sample of 113 participants (47 male, 66 female) with ages ranging between 18 and 40 years (mean 25.59, SD 4.79). Our data revealed four important findings. First, we found a phenotypical overlap between secondary but not primary psychopathy with autistic traits. Second, primary psychopathy showed various neural deficits in neural voice processing nodes (speech, non-speech voices) and in brain systems for social cognition (mirroring, mentalizing, empathy, emotional contagion). Primary psychopathy also showed deficits in the basal ganglia (BG) system that seems specific to the social decoding of communicative voice signals. Third, neural deviations in secondary psychopathy were restricted to social mirroring and mentalizing impairments, but with additional and so far undescribed deficits at the level of auditory sensory processing, potentially concerning deficits in ventral auditory stream mechanisms (auditory object identification). Fourth, high autistic traits also revealed neural deviations in sensory cortices, but rather in the dorsal auditory processing streams (communicative context encoding). Taken together, social cognition of voice signals shows considerable deviations in psychopathy, with differential and newly described deficits in the BG system in primary psychopathy and at the neural level of sensory processing in secondary psychopathy. These deficits seem especially triggered during the social cognition from vocal communication signals.
Chronic lymphocytic leukemia treatment algorithm 2022
Authors: Hampel Paul J. , Parikh Sameer A. 
Published: November 2022

AbstractThe treatment landscape for patients with chronic lymphocytic leukemia (CLL) has changed considerably with the introduction of very effective oral targeted therapies (such as Bruton tyrosine kinase inhibitors and venetoclax) and next-generation anti-CD20 monoclonal antibodies (such as obinutuzumab). These agents lead to improved outcomes in patients with CLL, even among those with high-risk features, such as del17p13 or TP53 mutation and unmutated immunoglobulin heavy chain (IGHV) genes. Selecting the right treatment for the right patient requires consideration of disease characteristics and prior treatment sequence, as well as patient preferences and comorbidities. The CLL-International Prognostic Index (CLL-IPI) remains the best-validated tool in predicting the time to first therapy among previously untreated patients, which guides selection for early intervention efforts. This review summarizes our current approach to the management of CLL, right from the time of diagnosis through relapsed disease.
MiR-148a deletion protects from bone loss in physiological and estrogen-deficient mice by targeting NRP1
Authors: Pan Bin , Zheng Lin , Liu Shijie , Fang Jiawei , Lou Chao , Hu Xingyu , Ye Lin , Lai Hehuan , Gao Jiawei , Zhang Yejin , Ni Kainan , He Dengwei 
Published: November 2022

AbstractBone metabolic homeostasis is largely dependent on the dynamic balance between osteoblasts and osteoclasts. MicroRNAs (miRNAs) play critical roles in regulating bone metabolism. In this study, we explored the role of a new miRNA (miR-148a) in osteoporosis. We compared the bone phenotype between miR-148a knockout (KO) mice and the wild-type (WT) littermates. We found miR-148a KO mice exhibited an increased bone mass phenotype and decreased osteoclastogenesis compared to the WT group. In vitro, miR-148a overexpression promoted osteoclastogenesis and bone resorption function. Mechanistically, NRP1 was identified as a novel direct target of miR-148a, and NRP1 silencing reversed the effect of miR-148a knockout. In OVX and calvarial osteolysis models, miR-148a KO protects mice against excessive bone resorption, while miR-148a agomiR/AAV-shNRP1 accelerates pathologic bone loss. Finally, the miR-148a level was found to be positively correlated with β-CTX in postmenopausal osteoporosis (PMOP) serum specimens. In summary, our findings revealed that miR-148a genetic deletion ameliorates bone loss under physiological and pathological conditions by targeting NRP1. In osteoclast-related bone metabolic diseases such as PMOP, miR-148a may be an attractive therapeutic target in the future.
Estimation of stillbirths attributable to ambient fine particles in 137 countries
Authors: Xue Tao , Tong Mingkun , Li Jiajianghui , Wang Ruohan , Guan Tianjia , Li Jiwei , Li Pengfei , Liu Hengyi , Lu Hong , Li Yanshun , Zhu Tong 
Published: November 2022

AbstractGestational exposure to ambient fine particles (PM2.5) increases the risk of stillbirth, but the related disease burden is unknown, particularly in low- and middle-income countries (LMICs). We combine state-of-the-art estimates on stillbirths, and multiple exposure–response functions obtained from previous meta-analyses or derived by a self-matched case-control study in 54 LMICs. 13,870 stillbirths and 32,449 livebirths are extracted from 113 geocoded surveys from the Demographic and Health Surveys. Each stillbirth is compared to livebirth(s) of the same mother using a conditional logit regression. We find that 10-µg/m3 increase of PM2.5 is associated with an 11.0% (95% confidence interval [CI] 6.4, 15.7) increase in the risk of stillbirth, and the association is significantly enhanced by maternal age. Based on age-specific nonlinear PM2.5–stillbirth curves, we evaluate the PM2.5-related stillbirths in 137 countries. In 2015, of 2.09 (95% CI: 1.98, 2.20) million stillbirths, 0.83 (0.54, 1.08) million or 39.7% (26.1, 50.8) are attributable to PM2.5 exposure exceeding the reference level of 10 μg/m3. In LMICs, preventing pregnant women from being exposed to PM2.5 can improve maternal health.
A population-based serological study of post-COVID syndrome prevalence and risk factors in children and adolescents
Authors: Dumont Roxane , Richard Viviane , Lorthe Elsa , Loizeau Andrea , Pennacchio Francesco , Zaballa María-Eugenia , Baysson Hélène , Nehme Mayssam , Perrin Anne , L’Huillier Arnaud G. , Kaiser Laurent , Barbe Rémy P. , Posfay-Barbe Klara M. , Stringhini Silvia ,   SEROCoV-KIDS study group, Amrein Deborah , Azman Andrew S. , Bal Antoine , Balavoine Michael , Berthelot Julie , Bleich Patrick , Boehm Livia , Bryand Gaëlle , Bucolli Viola , Collombet Prune , Cudet Alain , Davidovic Vladimir , de Mestral Vargas Carlos , D’Ippolito Paola , Dubos Richard , Eckerle Isabella , Favier Marion , El Merjani Nacira , Francioli Natalie , Graindorge Clément , Harnal Séverine , Hurst Samia , Kherad Omar , Lamour Julien , Lescuyer Pierre , Martinez Chantal , Mermet Stéphanie , Noël Natacha , Perez-Saez Javier , Pittet Didier , Portier Jane , Poulain Géraldine , Pugin Caroline , Pullen Nick , Rinaldi Frederic , Rizzo Jessica , Rochat Deborah , Sahyoun Cyril , Sakvarelidze Irine , Samir Khadija , Ramirez Hugo Alejandro Santa , Schrempft Stephanie , Semaani Claire , Testini Stéphanie , Tisserand Yvain , Rivas Deborah Urrutia , Verolet Charlotte , Villers Jennifer , Violot Guillemette , Vuilleumier Nicolas , Yerly Sabine , Zavlanou Christina , Guessous Idris 
Published: November 2022

AbstractPost-COVID syndrome remains poorly studied in children and adolescents. Here, we aimed to investigate the prevalence and risk factors of pediatric post-COVID in a population-based sample, stratifying by serological status. Children from the SEROCoV-KIDS cohort study (State of Geneva, Switzerland), aged 6 months to 17 years, were tested for anti-SARS-CoV-2 N antibodies (December 2021-February 2022) and parents filled in a questionnaire on persistent symptoms in their children (lasting over 12 weeks) compatible with post-COVID. Of 1034 children tested, 570 (55.1%) were seropositive. The sex- and age-adjusted prevalence of persistent symptoms among seropositive children was 9.1% (95%CI: 6.7;11.8) and 5.0% (95%CI: 3.0;7.1) among seronegatives, with an adjusted prevalence difference (ΔaPrev) of 4.1% (95%CI: 1.1;7.3). Stratifying per age group, only adolescents displayed a substantial risk of having post-COVID symptoms (ΔaPrev = 8.3%, 95%CI: 3.5;13.5). Identified risk factors for post-COVID syndrome were older age, having a lower socioeconomic status and suffering from chronic health conditions, especially asthma. Our findings show that a significant proportion of seropositive children, particularly adolescents, experienced persistent COVID symptoms. While there is a need for further investigations, growing evidence of pediatric post-COVID urges early screening and primary care management.
Shedding light on the base-pair opening dynamics of nucleic acids in living human cells
Authors: Yamaoki Yudai , Nagata Takashi , Kondo Keiko , Sakamoto Tomoki , Takami Shohei , Katahira Masato 
Published: November 2022

AbstractBase-pair opening is a fundamental property of nucleic acids that plays important roles in biological functions. However, studying the base-pair opening dynamics inside living cells has remained challenging. Here, to determine the base-pair opening kinetics inside living human cells, the exchange rate constant ($${k}_{{{{{{\rm{ex}}}}}}}$$

k

ex

) of the imino proton with the proton of solvent water involved in hairpin and G-quadruplex (GQ) structures is determined by the in-cell NMR technique. It is deduced on determination of $${k}_{{{{{{\rm{ex}}}}}}}$$

k

ex

values that at least some G-C base pairs of the hairpin structure and all G-G base-pairs of the GQ structure open more frequently in living human cells than in vitro. It is suggested that interactions with endogenous proteins could be responsible for the increase in frequency of base-pair opening. Our studies demonstrate a difference in dynamics of nucleic acids between in-cell and in vitro conditions.
Genetically personalised organ-specific metabolic models in health and disease
Authors: Foguet Carles , Xu Yu , Ritchie Scott C. , Lambert Samuel A. , Persyn Elodie , Nath Artika P. , Davenport Emma E. , Roberts David J. , Paul Dirk S. , Di Angelantonio Emanuele , Danesh John , Butterworth Adam S. , Yau Christopher , Inouye Michael 
Published: November 2022

AbstractUnderstanding how genetic variants influence disease risk and complex traits (variant-to-function) is one of the major challenges in human genetics. Here we present a model-driven framework to leverage human genome-scale metabolic networks to define how genetic variants affect biochemical reaction fluxes across major human tissues, including skeletal muscle, adipose, liver, brain and heart. As proof of concept, we build personalised organ-specific metabolic flux models for 524,615 individuals of the INTERVAL and UK Biobank cohorts and perform a fluxome-wide association study (FWAS) to identify 4312 associations between personalised flux values and the concentration of metabolites in blood. Furthermore, we apply FWAS to identify 92 metabolic fluxes associated with the risk of developing coronary artery disease, many of which are linked to processes previously described to play in role in the disease. Our work demonstrates that genetically personalised metabolic models can elucidate the downstream effects of genetic variants on biochemical reactions involved in common human diseases.
EZH2-H3K27me3 mediated KRT14 upregulation promotes TNBC peritoneal metastasis
Authors: Verma Ayushi , Singh Akhilesh , Singh Manish Pratap , Nengroo Mushtaq Ahmad , Saini Krishan Kumar , Satrusal Saumya Ranjan , Khan Muqtada Ali , Chaturvedi Priyank , Sinha Abhipsa , Meena Sanjeev , Singh Anup Kumar , Datta Dipak 
Published: November 2022

AbstractTriple-Negative Breast Cancer (TNBC) has a poor prognosis and adverse clinical outcomes among all breast cancer subtypes as there is no available targeted therapy. Overexpression of Enhancer of zeste homolog 2 (EZH2) has been shown to correlate with TNBC’s poor prognosis, but the contribution of EZH2 catalytic (H3K27me3) versus non-catalytic EZH2 (NC-EZH2) function in TNBC progression remains elusive. We reveal that selective hyper-activation of functional EZH2 (H3K27me3) over NC-EZH2 alters TNBC metastatic landscape and fosters its peritoneal metastasis, particularly splenic. Instead of H3K27me3-mediated repression of gene expression; here, it promotes KRT14 transcription by attenuating binding of repressor SP1 to its promoter. Further, KRT14 loss significantly reduces TNBC migration, invasion, and peritoneal metastasis. Consistently, human TNBC metastasis displays positive correlation between H3K27me3 and KRT14 levels. Finally, EZH2 knockdown or H3K27me3 inhibition by EPZ6438 reduces TNBC peritoneal metastasis. Altogether, our preclinical findings suggest a rationale for targeting TNBC with EZH2 inhibitors.
Lamellar carbon nitride membrane for enhanced ion sieving and water desalination
Authors: Wang Yang , Lian Tingting , Tarakina Nadezda V. , Yuan Jiayin , Antonietti Markus 
Published: November 2022

AbstractMembrane-based water treatment processes offer possibility to alleviate the water scarcity dilemma in energy-efficient and sustainable ways, this has been exemplified in filtration membranes assembled from two-dimensional (2D) materials for water desalination purposes. Most representatives however tend to swell or disintegrate in a hydrated state, making precise ionic or molecular sieving a tough challenge. Here we report that the chemically robust 2D carbon nitride can be activated using aluminum polycations as pillars to modulate the interlayer spacing of the conjugated framework, the noncovalent interaction concomitantly affords a well-interlinked lamellar structure, to be carefully distinguished from random stacking patterns in conventional carbon nitride membranes. The conformally packed membrane is characterized by adaptive subnanochannel and structure integrity to allow excellent swelling resistance, and breaks permeability-selectivity trade-off limit in forward osmosis due to progressively regulated transport passage, achieving high salt rejection (>99.5%) and water flux (6 L m−2 h−1), along with tunable permeation behavior that enables water gating in acidic and alkaline environments. These findings position carbon nitride a rising building block to functionally expand the 2D membrane library for applications in water desalination and purification scenarios.
HSP90-CDC37-PP5 forms a structural platform for kinase dephosphorylation
Authors: Oberoi Jasmeen , Guiu Xavi Aran , Outwin Emily A. , Schellenberger Pascale , Roumeliotis Theodoros I. , Choudhary Jyoti S. , Pearl Laurence H. 
Published: November 2022

AbstractActivation of client protein kinases by the HSP90 molecular chaperone system is affected by phosphorylation at multiple sites on HSP90, the kinase-specific co-chaperone CDC37, and the kinase client itself. Removal of regulatory phosphorylation from client kinases and their release from the HSP90-CDC37 system depends on the Ser/Thr phosphatase PP5, which associates with HSP90 via its N-terminal TPR domain. Here, we present the cryoEM structure of the oncogenic protein kinase client BRAFV600E bound to HSP90-CDC37, showing how the V600E mutation favours BRAF association with HSP90-CDC37. Structures of HSP90-CDC37-BRAFV600E complexes with PP5 in autoinhibited and activated conformations, together with proteomic analysis of its phosphatase activity on BRAFV600E and CRAF, reveal how PP5 is activated by recruitment to HSP90 complexes. PP5 comprehensively dephosphorylates client proteins, removing interaction sites for regulatory partners such as 14-3-3 proteins and thus performing a ‘factory reset’ of the kinase prior to release.
IL6 supports long-term expansion of hepatocytes in vitro
Authors: Guo Ren , Jiang Mengmeng , Wang Gang , Li Bing , Jia Xiaohui , Ai Yan , Chen Shanshan , Tang Peilan , Liu Aijie , Yuan Qianting , Xie Xin 
Published: November 2022

AbstractHepatocytes are very difficult to expand in vitro. A few studies have demonstrated that chemical cocktails with growth factors or Wnt ligands can support long-term expansion of hepatocytes via dedifferentiation. However, the culture conditions are complex, and clonal expansion of hepatic progenitors with full differentiation capacity are rarely reported. Here, we discover IL6, combined with EGF and HGF, promotes long-term expansion (>30 passages in ~150 days with theoretical expansion of ~1035 times) of primary mouse hepatocytes in vitro in simple 2D culture, by converting hepatocytes into induced hepatic progenitor cells (iHPCs), which maintain the capacity of differentiation into hepatocytes. IL6 also supports the establishment of single hepatocyte-derived iHPC clones. The summation of the downstream STAT3, ERK and AKT pathways induces a number of transcription factors which support rapid growth. This physiological and simple way may provide ideas for culturing previously difficult-to-culture cell types and support their future applications.
Ultrastrong MXene films via the synergy of intercalating small flakes and interfacial bridging
Authors: Wan Sijie , Li Xiang , Chen Ying , Liu Nana , Wang Shijun , Du Yi , Xu Zhiping , Deng Xuliang , Dou Shixue , Jiang Lei , Cheng Qunfeng 
Published: November 2022

AbstractTitanium carbide MXene combines high mechanical and electrical properties and low infrared emissivity, making it of interest for flexible electromagnetic interference (EMI) shielding and thermal camouflage film materials. Conventional wisdom holds that large MXene is the preferable building block to assemble high-performance films. However, the voids in the films comprising large MXene degrade their properties. Although traditional crosslinking strategies can diminish the voids, the electron transport between MXene flakes is usually disrupted by the insulating polymer bonding agents, reducing the electrical conductivity. Here we demonstrate a sequential densification strategy to synergistically remove the voids between MXene flakes while strengthening the interlayer electron transport. Small MXene flakes were first intercalated to fill the voids between multilayer large flakes, followed by interfacial bridging of calcium ions and borate ions to eliminate the remaining voids, including those between monolayer flakes. The obtained MXene films are compact and exhibit high tensile strength (739 MPa), Young’s modulus (72.4 GPa), electrical conductivity (10,336 S cm−1), and EMI shielding capacity (71,801 dB cm2 g−1), as well as excellent oxidation resistance and thermal camouflage performance. The presented strategy provides an avenue for the high-performance assembly of other two-dimensional flakes.