bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silencing of SmgGDS, a Novel mTORC1 Inducer That Binds to RHEBs, Inhibits Malignant Mesothelioma Cell Proliferation
Authors: Sato Tatsuhiro , Mukai Satomi , Ikeda Haruna , Mishiro-Sato Emi , Akao Ken , Kobayashi Toshiyuki , Hino Okio , Shimono Wataru , Shibagaki Yoshio , Hattori Seisuke , Sekido Yoshitaka 
Published: February 2021

Abstract

Malignant mesothelioma (MM) is an aggressive tumor that typically develops after a long latency following asbestos exposure. Although mechanistic target of rapamycin complex 1 (mTORC1) activation enhances MM cell growth, the mTORC1 inhibitor everolimus has shown limited efficacy in clinical trials of MM patients. We explored the mechanism underlying mTORC1 activation in MM cells and its effects on cell proliferation and progression. Analysis of the expression profiles of 87 MMs from The Cancer Genome Atlas revealed that 40 samples (46%) displayed altered expression of RPTOR (mTORC1 component) and genes immediately upstream that activate mTORC1. Among them, we focused on RHEB and RHEBL1, which encode direct activators of mTORC1. Exogenous RHEBL1 expression enhanced MM cell growth, indicating that RHEB–mTORC1 signaling acts as a pro-oncogenic cascade. We investigated molecules that directly activate RHEBs, identifying SmgGDS as a novel RHEB-binding protein. SmgGDS knockdown reduced mTORC1 activation and inhibited the proliferation of MM cells with mTORC1 activation. Interestingly, SmgGDS displayed high binding affinity with inactive GDP-bound RHEBL1, and its knockdown reduced cytosolic RHEBL1 without affecting its activation. These findings suggest that SmgGDS retains GDP-bound RHEBs in the cytosol, whereas GTP-bound RHEBs are localized on intracellular membranes to promote mTORC1 activation. We revealed a novel role for SmgGDS in the RHEB–mTORC1 pathway and its potential as a therapeutic target in MM with aberrant mTORC1 activation.

Implications:
Our data showing that SmgGDS regulates RHEB localization to activate mTORC1 indicate that SmgGDS can be used as a new therapeutic target for MM exhibiting mTORC1 activation.
Novel Lesional Transcriptional Signature Separates Atherosclerosis With and Without Diabetes in Yorkshire Swine and Humans
Authors: Haemmig Stefan , Hashemi Gheinani Ali , Zaromytidou Marina , Siasos Gerasimos , Coskun Ahmet Umit , Cormier Michelle A. , Gross David A. , Wara A.K.M. Khyrul , Antoniadis Antonios P. , Sun Xinghui , Sukhova Galina K. , Welt Fred G.P. , Andreou Ioannis , Whatling Carl , Gan Li-Ming , Wikström Johannes , Edelman Elazer R. , Libby Peter , Stone Peter H. , Feinberg Mark W. 
Published: February 2021

Objective:
Accelerated atherosclerosis in diabetes constitutes an ongoing challenge despite optimal medical therapies. This study aimed to identify evolutionarily conserved lesion-based regulatory signaling networks in diabetic versus nondiabetic conditions during the development of atherosclerosis in an initial translational effort to provide insights for targets.

Approach and Results:
Serial 3-mm coronary artery segments of hypercholesterolemic Yorkshire swine and diabetic-hypercholesterolemic swine were characterized as mild, moderate, or severe phenotypic manifestations of coronary atherosclerosis based on histopathologic examination. Lesional RNA sequencing was performed (n=3–8 lesions per group) corresponding to increasing phenotypic severity. Differentially expressed genes, transcription factors, upstream regulators, and hubs were validated using the NanoString technology and a human atherosclerotic specimen cohort.

Despite similar stage histopathologic characterization of lesions, genome-wide transcriptomics revealed gene sets and nodal signaling pathways uniquely expressed in diabetic lesions including signaling pathways for Th17, IL (interleukin)-17F, TWEAK (TNF [tumor necrosis factor]-related weak inducer of apoptosis), CD27, and PI3K/Akt. In contrast, pathways of nondiabetic lesions involved TREM-1 and Th1 and Th2 responses during the initiation stage, whereas networks for mitochondrial dysfunction, oxidative phosphorylation, and lipid metabolism emerged with progression. RNA sequencing data were validated in a human atherosclerosis specimen cohort using machine learning algorithms.
F8
,
MAPKAPK3
, and
ITGB1
emerged as powerful genes for clustering diabetic versus nondiabetic lesions and for separating different degrees of atherosclerosis progression.

Conclusions:
This study identifies evolutionarily conserved gene signatures and signaling pathways in a stage-specific manner that successfully distinguishes diabetes- and non–diabetes-associated atherosclerosis. These findings establish new molecular insights and therapeutic opportunities to address accelerated atherosclerotic lesion formation in diabetes.
Mast Cells Are the Trigger of Small Vessel Disease and Diastolic Dysfunction in Diabetic Obese Mice
Authors: Guimbal Sarah , Cornuault Lauriane , Rouault Paul , Hollier Pierre-Louis , Chapouly Candice , Bats Marie-Lise , Imbault Julien , Gadeau Alain-Pierre , Couffinhal Thierry , Renault Marie-Ange 
Published: February 2021

Objective:
Heart failure with preserved ejection fraction is a major health care issue which has been difficult to manage to date, due to its complex and not well understood pathophysiology. Specifically, if a wealth of literature focuses on heart failure with preserved ejection fraction cardiac component, very little information can be found on its vascular component. Our goal is to unravel the critical role of cardiac small vessel disease in the pathophysiology of diastolic dysfunction.

Approach and Results:

To do so, we used leptin receptor deficient (Lepr
db/db
) female mice, a recognized model of diastolic dysfunction. In these mice, the increased end-diastolic pressure signing diastolic dysfunction is associated with vascular leakage, endothelial cell activation, and leucocyte infiltration. Strikingly, a RNA sequencing analysis of the cardiac vascular fraction of both Lepr
db/db
and control mice confirmed endothelial dysfunction and systemic inflammation, but above all, revealed a strong increase in several mast cell markers (notably FceR1a [high affinity immunoglobulin epsilon receptor subunit α], tryptase, and chymase). We then confirmed this accumulation of activated mast cells in the heart of Lepr
db/db
mice via histology. Importantly, we found that both mast cell degranulation inhibition and specific histamine blockade reduced vascular leakage, leucocyte infiltration, and subsequently end-diastolic pressure in Lepr
db/db
mice. This demonstrated, for the first time, that mast cells, via histamine release, participate in the development of cardiac small vessel disease leading to diastolic dysfunction.

Conclusions:
Cardiac small vessel disease is a key mechanism of heart failure with preserved ejection fraction pathophysiology that can be targeted to prevent the occurrence of diastolic dysfunction, by using both mast cell stabilizers and antihistaminic drugs.
Aβ (Amyloid Beta) and Tau Tangle Pathology Modifies the Association Between Small Vessel Disease and Cortical Microinfarcts
Authors: Kapasi A. , Leurgans S.E. , Arvanitakis Z. , Barnes L.L. , Bennett D.A. , Schneider J.A. 
Published: February 2021

Background and Purpose:
There is increasing recognition of the importance of cortical microinfarcts to overall brain health, cognition, and Alzheimer dementia. Cerebral small vessel pathologies are associated with microinfarcts and frequently coexist with Alzheimer disease; however, the extent to which Aβ (amyloid beta) and tau pathology modulates microvascular pathogenesis is not fully understood. Study objective was to examine the relationship of small vessel pathologies, arteriolosclerosis, and cerebral amyloid angiopathy, with cortical microinfarcts in people with differing levels of Aβ or tau tangle burden.

Methods:
Participants were 1489 autopsied older people (mean age at death, 89 years; 67% women) from 1 of 3 ongoing clinical-pathological cohort studies of aging. Neuropathological evaluation identified cortical Aβ and tau tangle burden using immunohistochemistry in 8 brain regions, provided semiquantitative grading of cerebral vessel pathologies, and identified the presence of cortical microinfarcts. Logistic regression models adjusted for demographics and atherosclerosis and examined whether Aβ or tau tangle burden modified relations between small vessel pathologies and cortical microinfarcts.

Results:

Cortical microinfarcts were present in 17% of older people, moderate-to-severe cerebral amyloid angiopathy pathology in 36%, and arteriolosclerosis in 34%. In logistic regression models, we found interactions with Aβ and tau tangles, reflecting that the association between arteriolosclerosis and cortical microinfarcts was stronger in the context of greater Aβ (estimate, 0.15; SE=0.07;
P
=0.02) and tau tangle burden (estimate, 0.13; SE=0.06;
P
=0.02). Interactions also emerged for cerebral amyloid angiopathy, suggesting that the association between cerebral amyloid angiopathy and cortical microinfarcts is more robust in the presence of higher Aβ (estimate, 0.27; SE=0.07;
P
<0.001) and tangle burden (estimate, 0.16; SE=0.06;
P
=0.005).

Conclusions:
These findings suggest that in the presence of elevated Aβ or tangle pathology, small vessel pathologies are associated with greater microvascular tissue injury, highlighting a potential link between neurodegenerative and vascular mechanisms.
Did Gainful Employment Regulations Result in College and Program Closures?
Authors: Kelchen Robert , Liu Zhuoyao 
Published: February 2021

AbstractFor decades, the federal government has expected vocationally focused programs in higher education, especially among for-profit colleges, to lead to gainful employment in a profession. In the mid-2010s, the U.S. Department of Education developed gainful employment (GE) regulations that sought to tie a program's federal financial aid eligibility to graduates’ debt-to-earnings ratios. We use a regression discontinuity design to examine whether for-profit programs’ performance on GE was associated with the likelihood of closing the program or college. Although the regulations were repealed before any program lost federal funding, we find that passing GE regulations was associated with a lower likelihood of program and college closures.
Motor Inhibition to Dangerous Objects: Electrophysiological Evidence for Task-dependent Aversive Affordances
Authors: Mustile Magda , Giocondo Flora , Caligiore Daniele , Borghi Anna M. , Kourtis Dimitrios 
Published: February 2021

Abstract
Previous work suggests that perception of an object automatically facilitates actions related to object grasping and manipulation. Recently, the notion of automaticity has been challenged by behavioral studies suggesting that dangerous objects elicit aversive affordances that interfere with encoding of an object's motor properties; however, related EEG studies have provided little support for these claims. We sought EEG evidence that would support the operation of an inhibitory mechanism that interferes with the motor encoding of dangerous objects, and we investigated whether such mechanism would be modulated by the perceived distance of an object and the goal of a given task. EEGs were recorded by 24 participants who passively perceived dangerous and neutral objects in their peripersonal, boundary, or extrapersonal space and performed either a reachability judgment task or a categorization task. Our results showed that greater attention, reflected in the visual P1 potential, was drawn by dangerous and reachable objects. Crucially, a frontal N2 potential, associated with motor inhibition, was larger for dangerous objects only when participants performed a reachability judgment task. Furthermore, a larger parietal P3b potential for dangerous objects indicated the greater difficulty in linking a dangerous object to the appropriate response, especially when it was located in the participants' extrapersonal space. Taken together, our results show that perception of dangerous objects elicits aversive affordances in a task-dependent way and provides evidence for the operation of a neural mechanism that does not code affordances of dangerous objects automatically, but rather on the basis of contextual information.
Dimensions of Humility in Early Confucian Thought
Authors: Shun Kwong-loi 
Published: February 2021

Abstract
Through an examination of the problematic forms of pride highlighted in early texts and the traits to which they are opposed, the paper identifies three main dimensions of humility in early Confucian thought. These include a deflated self-conception, caution and fearfulness, as well as seriousness and awe. It then shows that the term jing 敬 is closely related to all three dimensions, and hence that this is the term in early Confucian thought closest to encompassing all the different aspects of humility understood in a broad sense.
The Sequence of Heavy Precipitation and Flash Flooding of 12 and 13 September 2019 in Eastern Spain. Part I: Mesoscale Diagnostic and Sensitivity Analysis of Precipitation
Authors: Hermoso Alejandro , Homar Victor , Amengual Arnau 
Published: February 2021

AbstractThe Mediterranean region is frequently affected by heavy precipitation episodes and subsequent flash flooding. An exemplary case is the heavy precipitation episode that occurred in the regions of València, Murcia, and Almería (eastern Spain) on 12 and 13 September 2019. Observed rainfall amounts were close to 500 mm in 48 h, causing seven fatalities and estimated economical losses above EUR 425 million. This case exemplifies the challenging aspects of convective-scale forecasting in the Mediterranean region, with kilometer-resolution meteorological fields required over long forecast spans. Understanding the key mesoscale factors acting on the triggering, location, and intensity of the convective systems responsible for extreme accumulations is essential to gain insight into these episodes and contribute toward their accurate hydrometeorological forecasting. Mesoscale diagnosis suggests that local and distant orography, together with air–sea fluxes, were instrumental in developing convection and intensifying precipitation rate. Sensitivity experiments confirm the role of orography in organizing the cyclonic flow over the southeast part of the western Mediterranean, and also acting as a convection-triggering mechanism. Furthermore, results highlight the role of latent heat flux from the Mediterranean Sea in enhancing convective instability at lower levels and moistening the environment. These moist feeding flows substantially contribute to increasing precipitation rates. Such high sensitivity to environmental moisture distribution naturally propagates to the sea surface temperature, which, by means of sensible and latent heat flux exchanges, dominated the evolution of convective activity for the 12–13 September 2019 episode.
Filgrastim-induced rhabdomyolysis in a healthy stem cells donor
Authors: Reyna-de la Garza Roberto A. , Jiménez-Castillo Raúl A. 
Published: February 2021

Introduction Mobilization of peripheral blood progenitor cells with the use of granulocyte-colony stimulating factors is a mainstay in every protocol for allogenic stem cell transplants. Despite being considered safe, there are multiple adverse effects for this procedure some of which can be severe and bring serious complications to otherwise healthy donors. Case report An otherwise healthy 17-year-old patient who underwent progenitor cell mobilization with filgrastim and developed rhabdomyolysis and acute kidney injury. Management and outcome: The urine analysis and kidney ultrasound failed to reveal abnormalities in the kidneys or collector system. We began reanimation with crystalloid solutions for 5 days with normalization of liver and muscle enzymes as well as a complete resolution of the acute kidney injury. Discussion We present the case of a potentially serious adverse drug reaction during mobilization of peripheral blood progenitor cells with filgrastim. Physicians need to be aware of every possible complication associated with the use of these agents in order to establish a good prognosis via an accurate diagnosis and a timely treatment.
Palisaded neutrophilic and granulomatous dermatitis following a long-standing monoclonal gammopathy: A case report
Authors: Zabihi-pour Dorsa , Bahrani Bahar , Assaad Dalal , Yeung Jensen 
Published: February 2021

Background: Palisaded neutrophilic granulomatous dermatitis is a rare inflammatory dermatosis with possible underlying systemic conditions including rheumatoid arthritis, autoimmune connective tissue disease, and malignancies. Case Summary: We report a case of an 84-year-old man presenting with a 3-week eruption of asymptomatic annular plaques on his neck, which progressed to involve his back and legs. Skin biopsies confirmed a diagnosis of palisaded neutrophilic granulomatous dermatitis, and he was treated with prednisone. Full workup related to potential underlying causes of palisaded neutrophilic granulomatous dermatitis was completed. Conclusion: Palisaded neutrophilic granulomatous dermatitis may precede the onset of underlying systemic conditions or occur concomitantly. Following the diagnosis, clinicians should perform a comprehensive focused history, physical examination, and laboratory investigation related to the associated underlying diseases.
Peer-led exercise program for ageing adults to improve physical functions - a randomized trial
Authors: Bouchard D. R. , Olthuis J. V. , Bouffard-Levasseur V. , Shannon C. , McDonald T. , Sénéchal M. 
Published: February 2021

Abstract
Background
A peer-led exercise program is one way to empower people sharing similar characteristics to encourage others to be active, but there is a lack of evidence that these programs have physical function and other benefits when delivered to ageing adults.

Methods
This randomized controlled trial lasting 12 weeks proposed an exercise peer-led program offered to 31 adults aged 50 and above, twice a week, by a trained leader of the same age from March to May 2019. The program was offered for free with limited space and equipment. Valid tests of physical function (e.g., 30-s chair stand, 6-min walk test) were used to assess the functional benefits. Psychosocial outcomes were assessed using self-reported questionnaires and metabolic outcomes via a fasted blood draw.

Results
A significant difference was found between pre-and post-values in most physical function tests in the intervention group (all p < 0.05). When adjusted for potential confounders, the intervention group was significantly associated with a more significant improvement on the chair stand test (ß = .26; p < 0.001; r2 = 0.26), the arm curl (ß = .29; p < 0.001; r2 = 0.49), as well as the 6-min walk test (ß = -.14; p < 0.001; r2 = 0.62) compared with the control group. Using repetitive measures generalized linear model, the interaction between the changes and the group was significant for all three tests. Benefits were also observed for participants’ stress level and perceived health in the intervention group compared to the control. Finally, no significant difference was observed between groups for metabolic health.

Conclusions
The current work suggests that a 12-week peer-led exercise program can improve physical function for adults age 50 and above.

Trial registration
NCT03799952(ClinicalTrials.gov) 12/20/2018.
Enhancer RNAs: transcriptional regulators and workmates of NamiRNAs in myogenesis
Authors: Odame Emmanuel , Chen Yuan , Zheng Shuailong , Dai Dinghui , Kyei Bismark , Zhan Siyuan , Cao Jiaxue , Guo Jiazhong , Zhong Tao , Wang Linjie , Li Li , Zhang Hongping 
Published: February 2021

AbstractmiRNAs are well known to be gene repressors. A newly identified class of miRNAs termed nuclear activating miRNAs (NamiRNAs), transcribed from miRNA loci that exhibit enhancer features, promote gene expression via binding to the promoter and enhancer marker regions of the target genes. Meanwhile, activated enhancers produce endogenous non-coding RNAs (named enhancer RNAs, eRNAs) to activate gene expression. During chromatin looping, transcribed eRNAs interact with NamiRNAs through enhancer-promoter interaction to perform similar functions. Here, we review the functional differences and similarities between eRNAs and NamiRNAs in myogenesis and disease. We also propose models demonstrating their mutual mechanism and function. We conclude that eRNAs are active molecules, transcriptional regulators, and partners of NamiRNAs, rather than mere RNAs produced during enhancer activation.
A Biaxial Strain Sensor Using a Single MoS2 Grating
Authors: Xiang Junxiang , Wang Wenhui , Feng Lantian , Feng Chao , Huang Meng , Liu Ping , Ren XiFeng , Xiang Bin 
Published: February 2021

AbstractIn this paper, we report a new type of MoS2-based grating sensor for in-plane biaxial strain gauges with a precision limit of ~ 1‰. The MoS2grating is numerically simulated with different biaxial strains up to 5%. Our first-principles calculations reveal that the strain sensitivity of the MoS2reflectance spectrum can be considered an additional strain sensor integrated with the grating structure, enabling the mapping of in-plane biaxial strains. Our experimental studies on a prototype MoS2-grating sensor further confirm that a strain component perpendicular to the grating period can cause intensity peak shifts in the grating’s first-order diffraction patterns. This work opens a new path towards the sensing of in-plane biaxial strain within a single-grating device. Our new approach is applicable for other materials that have predictable reflectance response under biaxial strains and the capacity to form a two-dimensional single-crystal layer.
Analysis of perovskite oxide etching using argon inductively coupled plasmas for photonics applications
Authors: Chen Guanyu , Cheung Eric Jun Hao , Cao Yu , Pan Jisheng , Danner Aaron J. 
Published: February 2021

AbstractWe analyzed the dry etching of perovskite oxides using argon-based inductively coupled plasmas (ICP) for photonics applications. Various chamber conditions and their effects on etching rates have been demonstrated based on Z-cut lithium niobate (LN). The measured results are predictable and repeatable and can be applied to other perovskite oxides, such as X-cut LN and barium titanium oxide (BTO). The surface roughness is better for both etched LN and BTO compared with their as-deposited counterparts as confirmed by atomic force microscopy (AFM). Both the energy-dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS) methods have been used for surface chemical component comparisons, qualitative and quantitative, and no obvious surface state changes are observed according to the measured results. An optical waveguide fabricated with the optimized argon-based ICP etching was measured to have -3.7 dB/cm loss near 1550 nm wavelength for Z-cut LN, which validates this kind of method for perovskite oxides etching in photonics applications.