bluuebunny/crossref_metadata_2025_split huggingface dataset:
TGF-β induces GBM mesenchymal transition through upregulation of CLDN4 and nuclear translocation to activate TNF-α/NF-κB signal pathway
Authors: Yan Tengfeng , Tan Yinqiu , Deng Gang , Sun Zhiqiang , Liu Baohui , Wang Yixuan , Yuan Fanen , Sun Qian , Hu Ping , Gao Lun , Tian Daofeng , Chen Qianxue 
Published: April 2022

AbstractGlioblastoma (GBM) is the most common and aggressive primary malignant brain tumor. The unregulated expression of Claudin-4 (CLDN4) plays an important role in tumor progression. However, the biological role of CLDN4 in GBM is still unknown. This study aimed to determine whether CLDN4 mediates glioma malignant progression, if so, it would further explore the molecular mechanisms of carcinogenesis. Our results revealed that CLDN4 was significantly upregulated in glioma specimens and cells. The inhibition of CLND4 expression could inhibit mesenchymal transformation, cell invasion, cell migration and tumor growth in vitro and in vivo. Moreover, combined with in vitro analysis, we found that CLDN4 can modulate tumor necrosis factor-α (TNF-α) signal pathway. Meanwhile, we also validated that the transforming growth factor-β (TGF-β) signal pathway can upregulate the expression of CLDN4, and promote the invasion ability of GBM cells. Conversely, TGF-β signal pathway inhibitor ITD-1 can downregulate the expression of CLDN4, and inhibit the invasion ability of GBM cells. Furthermore, we found that TGF-β can promote the nuclear translocation of CLDN4. In summary, our findings indicated that the TGF-β/CLDN4/TNF-α/NF-κB signal axis plays a key role in the biological progression of glioma. Disrupting the function of this signal axis may represent a new treatment strategy for patients with GBM.
IGFBP5 promotes diabetic kidney disease progression by enhancing PFKFB3-mediated endothelial glycolysis
Authors: Song Chengcheng , Wang Shuqiang , Fu Zhangning , Chi Kun , Geng Xiaodong , Liu Chao , Cai Guangyan , Chen Xiangmei , Wu Di , Hong Quan 
Published: April 2022

AbstractRenal inflammation is a critical pathophysiological characteristic of diabetic kidney disease (DKD). The mechanism of the inflammatory response is complicated, and there are few effective treatments for renal inflammation that can be used clinically. Insulin-like growth factor-binding protein 5 (IGFBP5) is an important secretory protein that is related to inflammation and fibrosis in several tissues. Studies have shown that the IGFBP5 level is significantly upregulated in DKD. However, the function of IGFBP5 and its mechanism in DKD remain unclear. Here, we showed that IGFBP5 levels were significantly increased in the kidneys of diabetic mice. Ablation of IGFBP5 alleviated kidney inflammation in DKD mice. Mechanistically, IGFBP5 increased glycolysis, which was characterized by increases in lactic acid and the extracellular acidification rate, by activating the transcription factor early growth response 1 (EGR1) and enhancing the expression of PFKFB3 in endothelial cells. Furthermore, a mutation in PFKFB3 attenuated renal inflammation in DKD mice. Taken together, we provided evidence that IGFBP5 enhanced kidney inflammation through metabolic reprogramming of glomerular endothelial cells. Our results provide new mechanistic insights into the effect of IGFBP5 on kidney and highlight potential therapeutic opportunities for IGFBP5 and the metabolic regulators involved in DKD.
Ultrastrong underwater adhesion on diverse substrates using non-canonical phenolic groups
Authors: Cheng Bohan , Yu Jinhong , Arisawa Toma , Hayashi Koki , Richardson Joseph J. , Shibuta Yasushi , Ejima Hirotaka 
Published: April 2022

AbstractRobust underwater adhesion is challenging because a hydration layer impedes the interaction between substrates and adhesives. Phenolic adhesives inspired by marine creatures such as mussels were extensively studied, but these adhesives have not reached the adhesion strength and substrate diversity of Man-made dry adhesives. Here, we report a class of ultrastrong underwater adhesives with molecular phenolic designs extending beyond what nature has produced. These non-canonical phenolic polymers show versatile adhesion on various materials, with adhesion strengths exceeding 10 MPa on metal. Incorporating even just a small amount (<10%) of non-canonical phenolic groups into a polymer is sufficient for dramatically enhancing underwater adhesion, suggesting that this new class of phenolic materials will be incorporated into various industrial polymer systems in the future.
Structural basis for the assembly and quinone transport mechanisms of the dimeric photosynthetic RC–LH1 supercomplex
Authors: Cao Peng , Bracun Laura , Yamagata Atsushi , Christianson Bern M. , Negami Tatsuki , Zou Baohua , Terada Tohru , Canniffe Daniel P. , Shirouzu Mikako , Li Mei , Liu Lu-Ning 
Published: April 2022

AbstractThe reaction center (RC) and light-harvesting complex 1 (LH1) form a RC–LH1 core supercomplex that is vital for the primary reactions of photosynthesis in purple phototrophic bacteria. Some species possess the dimeric RC–LH1 complex with a transmembrane polypeptide PufX, representing the largest photosynthetic complex in anoxygenic phototrophs. However, the details of the architecture and assembly mechanism of the RC–LH1 dimer are unclear. Here we report seven cryo-electron microscopy (cryo-EM) structures of RC–LH1 supercomplexes fromRhodobacter sphaeroides. Our structures reveal that two PufX polypeptides are positioned in the center of the S-shaped RC–LH1 dimer, interlocking association between the components and mediating RC–LH1 dimerization. Moreover, we identify another transmembrane peptide, designated PufY, which is located between the RC and LH1 subunits near the LH1 opening. PufY binds a quinone molecule and prevents LH1 subunits from completely encircling the RC, creating a channel for quinone/quinol exchange. Genetic mutagenesis, cryo-EM structures, and computational simulations provide a mechanistic understanding of the assembly and electron transport pathways of the RC–LH1 dimer and elucidate the roles of individual components in ensuring the structural and functional integrity of the photosynthetic supercomplex.
Nuclear translocation of p85β promotes tumorigenesis of PIK3CA helical domain mutant cancer
Authors: Hao Yujun , He Baoyu , Wu Liping , Li Yamu , Wang Chao , Wang Ting , Sun Longci , Zhang Yanhua , Zhan Yangyang , Zhao Yiqing , Markowitz Sanford , Veigl Martina , Conlon Ronald A. , Wang Zhenghe 
Published: April 2022

AbstractPI3Ks consist of p110 catalytic subunits and p85 regulatory subunits. PIK3CA, encoding p110α, is frequently mutated in human cancers. Most PIK3CA mutations are clustered in the helical domain or the kinase domain. Here, we report that p85β disassociates from p110α helical domain mutant protein and translocates into the nucleus through a nuclear localization sequence (NLS). Nuclear p85β recruits deubiquitinase USP7 to stabilize EZH1 and EZH2 and enhances H3K27 trimethylation. Knockout of p85β or p85β NLS mutant reduces the growth of tumors harboring a PIK3CA helical domain mutation. Our studies illuminate a novel mechanism by which PIK3CA helical domain mutations exert their oncogenic function. Finally, a combination of Alpelisib, a p110α-specific inhibitor, and an EZH inhibitor, Tazemetostat, induces regression of xenograft tumors harboring a PIK3CA helical domain mutation, but not tumors with either a WT PIK3CA or a PIK3CA kinase domain mutation, suggesting that the drug combination could be an effective therapeutic approach for PIK3CA helical domain mutant tumors.
CHD7 regulates bone-fat balance by suppressing PPAR-γ signaling
Authors: Liu Caojie , Xiong Qiuchan , Li Qiwen , Lin Weimin , Jiang Shuang , Zhang Danting , Wang Yuan , Duan Xiaobo , Gong Ping , Kang Ning 
Published: April 2022

AbstractChromodomain helicase DNA-binding protein 7 (CHD7), an ATP-dependent eukaryotic chromatin remodeling enzyme, is essential for the development of organs. The mutation of CHD7 is the main cause of CHARGE syndrome, but its function and mechanism in skeletal system remain unclear. Here, we show conditional knockout of Chd7 in bone marrow mesenchymal stem cells (MSCs) and preosteoblasts leads to a pathological phenotype manifested as low bone mass and severely high marrow adiposity. Mechanistically, we identify enhancement of the peroxisome proliferator-activated receptor (PPAR) signaling in Chd7-deficient MSCs. Loss of Chd7 reduces the restriction of PPAR-γ and then PPAR-γ associates with trimethylated histone H3 at lysine 4 (H3K4me3), which subsequently activates the transcription of downstream adipogenic genes and disrupts the balance between osteogenic and adipogenic differentiation. Our data illustrate the pathological manifestations of Chd7 mutation in MSCs and reveal an epigenetic mechanism in skeletal health and diseases.
Nasal symbiont Staphylococcus epidermidis restricts the cellular entry of influenza virus into the nasal epithelium
Authors: Jo Ara , Won Jina , Gil Chan Hee , Kim Su Keun , Lee Kang-Mu , Yoon Sang Sun , Kim Hyun Jik 
Published: April 2022

AbstractOur recent study presented that human nasal commensal Staphylococcus epidermidis could potentiate antiviral immunity in the nasal mucosa through interferon-related innate responses. Here, we found that human nasal commensal S. epidermidis promoted protease–protease inhibitor balance in favor of the host and prevented influenza A virus (IAV) replication in the nasal mucosa and lungs. A relatively higher induction of Serpine1 exhibited in S. epidermidis-inoculated nasal epithelium and S. epidermidis-induced Serpine1 significantly decreased the expression of serine proteases. Furthermore, the transcription of urokinase plasminogen activator (uPA) and Serpine1 was biologically relevant in S. epidermidis-inoculated nasal epithelium, and the induction of uPA might be related to the sequential increase of Serpine1 in human nasal epithelium. Our findings reveal that human nasal commensal S. epidermidis manipulates the cellular environment lacking serine proteases in the nasal epithelium through Serpine1 induction and disturbs IAV spread to the lungs at the level of the nasal mucosa.
The upregulation of circFNDC3B aggravates the recurrence after endoscopic submucosal dissection (ESD) in early gastric cancer (EGC) patients
Authors: Zhang Jing , Bai Jun , Zhu Hongbing , Li Wei , An Qunxing , Wang Dongxu 
Published: April 2022

AbstractIt has been reported that the expression of CD44 variant 9 could be utilized as a predictive marker for the recurrence in early gastric cancer (EGC) after endoscopic submucosal dissection (ESD). And circFNDC3B was proved to increase the migration and invasion of gastric cancer (GC) cells. In this study, we recruited 96 EGC patients after ESD treatment and grouped them into High circFNDC3B expression group (High expression group) and Low circFNDC3B expression group (Low expression group). Accordingly, we found that the recurrence-free rate in the High expression group was lower than that in the Low expression group. In the High expression group, the relative expression of miR-942 and miR-510 was both suppressed while the relative expression of CDH1 mRNA and CD44 mRNA/protein was increased compared with those in the Low expression group. CircFNDC3B was found to target miR-942 and miR-510 and suppress their expressions respectively. Moreover, miR-942 was found to target CD44 mRNA while miR-510 was found to target CDH1 mRNA. The overexpression of circFNDC3B led to the down-regulation of miR-942 and miR-510, which accordingly resulted in the up-regulation of CD44 and CDH1 in MKN28 cells. Moreover, we found H. pylori infection could promote the expression of circFNDC3B, which also resulted in up-regulated CD44 and CDH1 mRNA level in rTip-α cultivated MKN28 cells. In summary, our study demonstrated that a higher level of circFNDC3B could lead to the increased expression of CD44 and CDH1 via modulating the signaling pathways of miR-942/CD44 and miR-510/CDH1 in EGC patients. And the up-regulation of CD44 and CDH1 would accordingly result in a higher recurrence rate of EGC patients treated by ESD.
Evaluating efficacy of indoor non-pharmaceutical interventions against COVID-19 outbreaks with a coupled spatial-SIR agent-based simulation framework
Authors: Gunaratne Chathika , Reyes Rene , Hemberg Erik , O’Reilly Una-May 
Published: April 2022

AbstractContagious respiratory diseases, such as COVID-19, depend on sufficiently prolonged exposures for the successful transmission of the underlying pathogen. It is important that organizations evaluate the efficacy of non-pharmaceutical interventions aimed at mitigating viral transmission among their personnel. We have developed a operational risk assessment simulation framework that couples a spatial agent-based model of movement with an agent-based SIR model to assess the relative risks of different intervention strategies. By applying our model on MIT’s Stata center, we assess the impacts of three possible dimensions of intervention: one-way vs unrestricted movement, population size allowed onsite, and frequency of leaving designated work location for breaks. We find that there is no significant impact made by one-way movement restrictions over unrestricted movement. Instead, we find that reducing the frequency at which individuals leave their workstations combined with lowering the number of individuals admitted below the current recommendations lowers the likelihood of highly connected individuals within the contact networks that emerge, which in turn lowers the overall risk of infection. We discover three classes of possible interventions based on their epidemiological effects. By assuming a direct relationship between data on secondary attack rates and transmissibility in the agent-based SIR model, we compare relative infection risk of four respiratory illnesses, MERS, SARS, COVID-19, and Measles, within the simulated area, and recommend appropriate intervention guidelines.
Impact of temperature, inoculum flow pattern, inoculum type, and their ratio on dry anaerobic digestion for biogas production
Authors: Hossain Md Shahadat , Karim Tahmid ul , Onik Mahade Hassan , Kumar Deepak , Rahman Md Anisur , Yousuf Abu , Uddin Mohammad Rakib 
Published: April 2022

AbstractThis study is aimed to apply dry anaerobic digestion (DAD) for methane (CH4) enriched biogas production from unsorted organic municipal solid waste (MSW). Cumulative biogas production was monitored for 35 days of operation in batch digesters at fixed feedstock to inoculum (F/I) ratio 2. Anaerobic sludge (AS) and cow manure (CM) were used as inoculum in single and mixed modes. Several process parameters such as inoculum flow pattern (single layer, multilayer, and spiral), digestion temperature (25 to 40 °C), inoculation modes (single and mixed mode), and inoculation proportion (AS:CM = 1:1, 1:2, 1:3, and 2:1) were investigated to determine the optimum DAD conditions to maximize the CH4 laden biogas yield. The study of inoculum flow pattern showed that digester with multilayer inoculum configuration generated the maximum 555 mL cumulative biogas with the production rate of 195 mL/day (at 25 °C). Biogas production rate and cumulative biogas production were found to increase with a rise in temperature and the maximum values of 380 mL/day and 1515 mL respectively were observed at 37 °C. The mixed mode of inoculation containing AS and CM augmented the biogas yield at previously optimized conditions. Final results showed that digester with multilayer inoculum flow pattern at 37 °C produced 1850 mL cumulative biogas with 1256.58 mL CH4/kg volatile solid (VS) when the mixed inoculum was used at the AS:CM—1:2 ratio. Biogas production with this significant amount of CH4 justifies the use of the DAD process for energy (biogas) generation from widely available biomass feedstock (MSW), offering various advantages to the environment.
The relationship between stability of interpersonal coordination and inter-brain EEG synchronization during anti-phase tapping
Authors: Kurihara Yuto , Takahashi Toru , Osu Rieko 
Published: April 2022

AbstractInter-brain synchronization is enhanced when individuals perform rhythmic interpersonal coordination tasks, such as playing instruments in music ensembles. Experimentally, synchronization has been shown to correlate with the performance of joint tapping tasks. However, it is unclear whether inter-brain synchronization is related to the stability of interpersonal coordination represented as the standard deviation of relative phase (SDRP). In this study, we simultaneously recorded electroencephalograms of two paired individuals during anti-phase tapping in three interactive tapping conditions: slow (reference inter-tap interval [ITI]: 0.5 s), fast (reference ITI: 0.25 s), and free (preferred ITI), and pseudo tapping where each participant tapped according to the metronome sounds without interaction. We calculated the inter-brain synchronization between pairs of six regions of interest (ROI): frontal, central, left/right temporal, parietal, and occipital regions. During the fast tapping, the inter-brain synchronization significantly increased in multiple ROI pairs including temporoparietal junction in comparison to pseudo tapping. Synchronization between the central and left-temporal regions was positively correlated with SDRP in the theta in the fast condition. These results demonstrate that inter-brain synchronization occurs when task requirements are high and increases with the instability of the coordination.
Deep learning of chest X-rays can predict mechanical ventilation outcome in ICU-admitted COVID-19 patients
Authors: Gourdeau Daniel , Potvin Olivier , Biem Jason Henry , Cloutier Florence , Abrougui Lyna , Archambault Patrick , Chartrand-Lefebvre Carl , Dieumegarde Louis , Gagné Christian , Gagnon Louis , Giguère Raphaelle , Hains Alexandre , Le Huy , Lemieux Simon , Lévesque Marie-Hélène , Nepveu Simon , Rosenbloom Lorne , Tang An , Yang Issac , Duchesne Nathalie , Duchesne Simon 
Published: April 2022

AbstractThe COVID-19 pandemic repeatedly overwhelms healthcare systems capacity and forced the development and implementation of triage guidelines in ICU for scarce resources (e.g. mechanical ventilation). These guidelines were often based on known risk factors for COVID-19. It is proposed that image data, specifically bedside computed X-ray (CXR), provide additional predictive information on mortality following mechanical ventilation that can be incorporated in the guidelines. Deep transfer learning was used to extract convolutional features from a systematically collected, multi-institutional dataset of COVID-19 ICU patients. A model predicting outcome of mechanical ventilation (remission or mortality) was trained on the extracted features and compared to a model based on known, aggregated risk factors. The model reached a 0.702 area under the curve (95% CI 0.707-0.694) at predicting mechanical ventilation outcome from pre-intubation CXRs, higher than the risk factor model. Combining imaging data and risk factors increased model performance to 0.743 AUC (95% CI 0.746-0.732). Additionally, a post-hoc analysis showed an increase performance on high-quality than low-quality CXRs, suggesting that using only high-quality images would result in an even stronger model.
Uncovering the hydride ion diffusion pathway in barium hydride via neutron spectroscopy
Authors: Novak Eric , Daemen Luke , Ramirez-Cuesta Anibal Javier , Cheng Yongqiang , Smith Robert , Egami Takeshi , Jalarvo Niina 
Published: April 2022

AbstractSolid state materials possessing the ability for fast ionic diffusion of hydrogen have immense appeal for a wide range of energy-related applications. Ionic hydrogen transport research is dominated by proton conductors, but recently a few examples of hydride ion conductors have been observed as well. Barium hydride, BaH2, undergoes a structural phase transition around 775 K that leads to an order of magnitude increase in the ionic conductivity. This material provides a prototypical system to understand hydride ion diffusion and how the altered structure produced by the phase transition can have an enormous impact on the diffusion. We employ quasielastic and inelastic neutron scattering to probe the atomic scale diffusion mechanism and vibrational dynamics of hydride ions in both the low- and high-temperature phases. Jump lengths, residence times, diffusion coefficients, and activation energies are extracted and compared to the crystal structure to uncover the diffusion pathways. We find that the hydrogen jump distances, residence times, and energy barriers become reduced following the phase transition, allowing for the efficient conduction of hydride ions through a series of hydrogen jumps of length L = 3.1 Å.
The association between institutional delivery and neonatal mortality based on the quality of maternal and newborn health system in India
Authors: Lee Hwa-Young , Leslie Hannah H. , Oh Juhwan , Kim Rockli , Kumar Alok , Subramanian S. V. , Kruk Margaret E. 
Published: April 2022

AbstractOver 600,000 newborns in India died in their first month of life in 2017 despite large increases in access to maternal health services. We assess whether maternal and newborn health system quality in India is adequate for institutional delivery to reduce neonatal mortality. We identified recent births from the cross-sectional 2015–2016 National Family Health Survey and used reported content of antenatal care and immediate postpartum care averaged at the district level to characterize health system quality for maternity and newborn services. We used random effect logistic models to assess the relationship between institutional delivery and neonatal (death within the first 28 days of life) and early neonatal (death within 7 days of live births) mortality by quintile of district maternal and newborn health system quality. Three quarters of 191,963 births were in health facilities; 2% of newborns died within 28 days. District-level quality scores ranged from 40 to 90% of expected interventions. Institutional delivery was not protective against newborn mortality in the districts with poorest health system quality, but was associated with decreased mortality in districts with higher quality. Predicted neonatal mortality in the highest quintile of quality would be 0.018 (95% CI 0.010, 0.026) for home delivery and 0.010 (0.007, 0.013) for institutional delivery. Measurement of quality is limited by lack of data on quality of acute and referral care. Institutional delivery is associated with meaningful survival gains where quality of maternity services is higher. Addressing health system quality is an essential element of achieving the promise of increased access to maternal health services.
The appropriate and sequential value of standard radiograph, computed tomography and magnetic resonance imaging to characterize a bone tumor
Authors: Gaume M. , Chevret S. , Campagna R. , Larousserie F. , Biau D. 
Published: April 2022

AbstractRadiographs (XR), computed tomography (CT) or magnetic resonance imaging (MRI) are regularly analyzed to determine whether a bone lesion is benign or malignant. An online quiz was created providing 15 cases with a clinical summary, MRI, CT, and XR. After each image, participants were asked to rate the probability (0–100%) the bone tumor was malignant. Order and difficulty of the images were randomly determined. Probability statements regarding the diagnosis were actualized along the sequence of exam, to quantify how the degree of belief changed to account for evidence from those exams. 64 physicians participated and provided 154 assessments from 1 (n = 18) to 3 (n = 44) different cases. After the first image, participants favored the correct malignancy status at 70%; 80% after the second and 80% after the third one. Participants were more likely to favor the correct malignancy status when the lesion was malignant and when first confronted with XR or CT, rather than MRI, though the most predictive factor of correct diagnosis was the difficulty of the case. In conclusion, the additional information provided by successive imaging studies was moderate. XR or CT seemed more appropriate than MRI as first imaging study. Bypassing XR should be discouraged.