bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human umbilical cord mesenchymal stem cell-derived exosomal miR-335-5p attenuates the inflammation and tubular epithelial–myofibroblast transdifferentiation of renal tubular epithelial cells by reducing ADAM19 protein levels
Authors: Qiu Zhenhua , Zhong Zhihui , Zhang Yuehan , Tan Haoling , Deng Bo , Meng Guohuang 
Published: July 2022

AbstractBackgroundRenal tubular epithelial–myofibroblast transdifferentiation (EMT) plays a key role in the regulation of renal fibrosis. Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) play a crucial role in alleviating renal fibrosis and injury. Additionally, hucMSC-derived exosomes contain numerous microRNAs (miRNAs). However, it is unclear whether mesenchymal stem cells can regulate the transforming growth factor (TGF)-β1-induced EMT of human renal tubular epithelial cells (RTECs) through exosomal miRNAs.MethodHK-2, a human RTEC line, was co-treated with TGF-β1 and hucMSC-derived exosomes. Additionally, TGF-β1-treated HK-2 cells were transfected with a miR-335-5p mimic and disintegrin and metalloproteinase domain-containing protein 19 (ADAM19)-overexpression plasmid. miR-335-5p expression and ADAM19 protein and inflammation levels were measured via quantitative reverse transcription polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assays, respectively.ResultsTGF-β1 treatment changed the shape of HK-2 cells from a cobblestone morphology to a long spindle shape, accompanied by an increase in interleukin (IL)-6, tumor necrosis factor-α, IL-1β, collagen I, collagen III, α-smooth muscle actin, vimentin, and N-cadherin protein levels, whereas E-cadherin protein levels were reduced in these HK-2 cells, suggesting that TGF-β1 treatment induced the inflammation and EMT of HK-2 cells. HucMSC-exosomes improved the inflammation and EMT phenotype of TGF-β1-induced HK-2 cells by transferring miR-335-5p. miR-335-5p was found to bind theADAM193′-untranslated region to reduce ADAM19 protein levels. Additionally, miR-335-5p improved the inflammation and EMT phenotype of HK-2 cells by reducing ADAM19 protein levels with TGF-β1 induction.ConclusionsHucMSC-derived exosomal miR-335-5p attenuates the inflammation and EMT of HK-2 cells by reducing ADAM19 protein levels upon TGF-β1 induction. This study provides a potential therapeutic strategy and identifies targets for clinically treating renal fibrosis.
RUNX1T1 function in cell fate
Authors: Hu Nan , Zou Linqing , Wang Cheng , Song Guoqi 
Published: July 2022

AbstractRUNX1T1 (Runt-related transcription factor 1, translocated to 1), a myeloid translocation gene (MTG) family member, is usually investigated as part of the fusion protein RUNX1-RUNX1T1 for its role in acute myeloid leukemia. In the main, by recruiting histone deacetylases, RUNX1T1 negatively influences transcription, enabling it to regulate the proliferation and differentiation of hematopoietic progenitors. Moreover, the formation of blood vessels, neuronal differentiation, microglial activation following injury, and intestinal development all relate closely to the expression of RUNX1T1. Furthermore, through alternative splicing ofRUNX1T1, short and long isoforms have been noted to mediate adipogenesis by balancing the differentiation and proliferation of adipocytes. In addition, RUNX1T1 plays wide-ranging and diverse roles in carcinoma as a biomarker, suppressor, or positive regulator of carcinogenesis, closely correlated to specific organs and dominant signaling pathways. The aim of this work was to investigate the structure of RUNX1T1, which contains four conserved nervy homolog domains, and to demonstrate crosstalk with the Notch signaling pathway. Moreover, we endeavored to illustrate the effects of RUNX1T1 on cell fate from multiple aspects, including its influence on hematopoiesis, neuronal differentiation, microglial activation, intestinal development, adipogenesis, angiogenesis, and carcinogenesis.
Exosome from indoleamine 2,3-dioxygenase-overexpressing bone marrow mesenchymal stem cells accelerates repair process of ischemia/reperfusion-induced acute kidney injury by regulating macrophages polarization
Authors: Xie Xiangcheng , Yang Xiu , Wu Junxia , Tang Shengjie , Yang LiLi , Fei Xiao , Wang Ming 
Published: July 2022

Abstract
Background
Ischemia–reperfusion injury (IRI)-induced acute kidney injury (AKI) can repair itself completely. However, most moderate and severe patients undergoing IRI-AKI progress to chronic kidney disease due to incomplete repair. The present study is aimed to investigate the role of bone marrow mesenchymal stem cell-derived exosomes (MSC-Exo) with indoleamine 2,3-dioxygenase (IDO) overexpression on incomplete repair in mice after IRI.

Methods
IRI mice was established by clamping the unilateral renal pedicles and challenged with MSC-Exo. Blood biochemical indexes and inflammation factors contents were measured by ELISA assay. Histopathological examinations were monitored by HE, Masson, Immunohistochemical and TUNEL staining. Immunofluorescence, flow cytometry and immunoblotting were used to detect the polarization of macrophages, respectively.

Results
As compared to sham operation mice, IRI mice showed high contents of serum BUN and Scr, and more severe damaged kidney tissues on days 1 and 3, which all gradually declined over time, showing the lowest level on day 7 after injury. Once treated with MSCs-Exo that could directly transfer to kidney tubular cells, the restoration of kidney functions significantly accelerated by contrast to IRI mice, and the promotive effects were more obvious in IDO-overexpressed MSCs-Exo (MSCs-Exo-IDO)-treated IRI mice. Furthermore, MSCs-Exo-IDO administration also accelerated renal tubular cells proliferation, restrained tubular cells apoptosis, fibrosis and inflammation factor secretions during self-repair process compared to IRI mice, whose effects were higher than MSCs-Exo-NC-challenged IRI mice and IDO overexpressing plasmid-injected IRI mice. Mechanistically, MSCs-Exo-NC and MSCs-Exo-IDO exposure promoted the polarization from M1 macrophage to M2 macrophage, leading to more anti-inflammatory factors production, and subsequently altered the inflammatory microenvironment of renal tubular cells, which facilitated the self-repair process in mice after IRI.

Conclusion
MSCs-derived exosome accelerated renal self-repair in IRI mice by activating M2 macrophages polarization, which effects were amplified by IDO overexpression in MSCs. Potentially, genetically modified MSCs-Exo is an effective approach to improve renal self-repair in IRI-AKI mice.
Dysregulation of Tweak and Fn14 in skeletal muscle of spinal muscular atrophy mice
Authors: Meijboom Katharina E. , Sutton Emma R. , McCallion Eve , McFall Emily , Anthony Daniel , Edwards Benjamin , Kubinski Sabrina , Tapken Ines , Bünermann Ines , Hazell Gareth , Ahlskog Nina , Claus Peter , Davies Kay E. , Kothary Rashmi , Wood Matthew J. A. , Bowerman Melissa 
Published: July 2022

Abstract
Background
Spinal muscular atrophy (SMA) is a childhood neuromuscular disorder caused by depletion of the survival motor neuron (SMN) protein. SMA is characterized by the selective death of spinal cord motor neurons, leading to progressive muscle wasting. Loss of skeletal muscle in SMA is a combination of denervation-induced muscle atrophy and intrinsic muscle pathologies. Elucidation of the pathways involved is essential to identify the key molecules that contribute to and sustain muscle pathology. The tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/TNF receptor superfamily member fibroblast growth factor-inducible 14 (Fn14) pathway has been shown to play a critical role in the regulation of denervation-induced muscle atrophy as well as muscle proliferation, differentiation, and metabolism in adults. However, it is not clear whether this pathway would be important in highly dynamic and developing muscle.

Methods
We thus investigated the potential role of the TWEAK/Fn14 pathway in SMA muscle pathology, using the severe Taiwanese Smn−/−; SMN2 and the less severe Smn2B/− SMA mice, which undergo a progressive neuromuscular decline in the first three post-natal weeks. We also used experimental models of denervation and muscle injury in pre-weaned wild-type (WT) animals and siRNA-mediated knockdown in C2C12 muscle cells to conduct additional mechanistic investigations.

Results
Here, we report significantly dysregulated expression of Tweak, Fn14, and previously proposed downstream effectors during disease progression in skeletal muscle of the two SMA mouse models. In addition, siRNA-mediated Smn knockdown in C2C12 myoblasts suggests a genetic interaction between Smn and the TWEAK/Fn14 pathway. Further analyses of SMA, Tweak−/−, and Fn14−/− mice revealed dysregulated myopathy, myogenesis, and glucose metabolism pathways as a common skeletal muscle feature, providing further evidence in support of a relationship between the TWEAK/Fn14 pathway and Smn. Finally, administration of the TWEAK/Fn14 agonist Fc-TWEAK improved disease phenotypes in the two SMA mouse models.

Conclusions
Our study provides mechanistic insights into potential molecular players that contribute to muscle pathology in SMA and into likely differential responses of the TWEAK/Fn14 pathway in developing muscle.
Arcuate AgRP, but not POMC neurons, modulate paraventricular CRF synthesis and release in response to fasting
Authors: Fernandes Alan Carlos Alves , de Oliveira Franciane Pereira , Fernandez Gimena , da Guia Vieira Luane , Rosa Cristiane Gugelmin , do Nascimento Taís , de Castro França Suzelei , Donato Jose , Vella Kristen R. , Antunes-Rodrigues Jose , Mecawi André Souza , Perello Mario , Elias Lucila Leico Kagohara , Rorato Rodrigo 
Published: July 2022

Abstract
Background
The activation of the hypothalamic–pituitary–adrenal (HPA) axis is essential for metabolic adaptation in response to fasting. However, the neurocircuitry connecting changes in the peripheral energy stores to the activity of hypothalamic paraventricular corticotrophin-releasing factor (CRFPVN) neurons, the master controller of the HPA axis activity, is not completely understood. Our main goal was to determine if hypothalamic arcuate nucleus (ARC) POMC and AgRP neurons can communicate fasting-induced changes in peripheral energy stores, associated to a fall in plasma leptin levels, to CRFPVN neurons to modulate the HPA axis activity in mice.

Results
We observed increased plasma corticosterone levels associate with increased CRFPVN mRNA expression and increased CRFPVN neuronal activity in 36 h fasted mice. These responses were associated with a fall in plasma leptin levels and changes in the mRNA expression of Agrp and Pomc in the ARC. Fasting-induced decrease in plasma leptin partially modulated these responses through a change in the activity of ARC neurons. The chemogenetic activation of POMCARC by DREADDs did not affect fasting-induced activation of the HPA axis. DREADDs inhibition of AgRPARC neurons reduced the content of CRFPVN and increased its accumulation in the median eminence but had no effect on corticosterone secretion induced by fasting.

Conclusion
Our data indicate that AgRPARC neurons are part of the neurocircuitry involved in the coupling of PVNCRF activity to changes in peripheral energy stores induced by prolonged fasting.
Sharp subcritical and critical $L^{p}$ Hardy inequalities on the sphere
Authors: Abdelhakim Ahmed A. 
Published: July 2022

AbstractWe obtain sharp inequalities of Hardy type for functions in the Sobolev space $W^{1,p}$

W

1
,
p

on the unit sphere $\mathbb{S}^{n-1}$

S

n
−
1

in $\mathbb{R}^{n}$

R
n

. We achieve this in both the subcritical and critical cases. The method we use to show optimality takes into account all the constants involved in our inequalities. We apply our results to obtain lower bounds for the the first eigenvalue of the p-Laplacian on the sphere.
BVFLEMR: an integrated federated learning and blockchain technology for cloud-based medical records recommendation system
Authors: Hai Tao , Zhou Jincheng , Srividhya S. R. , Jain Sanjiv Kumar , Young Praise , Agrawal Shweta 
Published: July 2022

AbstractBlockchain is the latest boon in the world which handles mainly banking and finance. The blockchain is also used in the healthcare management system for effective maintenance of electronic health and medical records. The technology ensures security, privacy, and immutability. Federated Learning is a revolutionary learning technique in deep learning, which supports learning from the distributed environment. This work proposes a framework by integrating the blockchain and Federated Deep Learning in order to provide a tailored recommendation system. The work focuses on two modules of blockchain-based storage for electronic health records, where the blockchain uses a Hyperledger fabric and is capable of continuously monitoring and tracking the updates in the Electronic Health Records in the cloud server. In the second module, LightGBM and N-Gram models are used in the collaborative learning module to recommend a tailored treatment for the patient’s cloud-based database after analyzing the EHR. The work shows good accuracy. Several metrics like precision, recall, and F1 scores are measured showing its effective utilization in the cloud database security.
Olfactory swab sampling optimization for α-synuclein aggregate detection in patients with Parkinson’s disease
Authors: Bongianni Matilde , Catalan Mauro , Perra Daniela , Fontana Elena , Janes Francesco , Bertolotti Claudio , Sacchetto Luca , Capaldi Stefano , Tagliapietra Matteo , Polverino Paola , Tommasini Valentina , Bellavita Giulia , Kachoie Elham Ataie , Baruca Roberto , Bernardini Andrea , Valente Mariarosaria , Fiorini Michele , Bronzato Erika , Tamburin Stefano , Bertolasi Laura , Brozzetti Lorenzo , Cecchini Maria Paola , Gigli Gianluigi , Monaco Salvatore , Manganotti Paolo , Zanusso Gianluigi 
Published: July 2022

Abstract
Background
In patients with Parkinson’s disease (PD), real-time quaking-induced conversion (RT-QuIC) detection of pathological α-synuclein (α-syn) in olfactory mucosa (OM) is not as accurate as in other α-synucleinopathies. It is unknown whether these variable results might be related to a different distribution of pathological α-syn in OM. Thus, we investigated whether nasal swab (NS) performed in areas with a different coverage by olfactory neuroepithelium, such as agger nasi (AN) and middle turbinate (MT), might affect the detection of pathological α-syn.

Methods
NS was performed in 66 patients with PD and 29 non-PD between September 2018 and April 2021. In 43 patients, cerebrospinal fluid (CSF) was also obtained and all samples were analyzed by RT-QuIC for α-syn.

Results
In the first round, 72 OM samples were collected by NS, from AN (NSAN) or from MT (NSMT), and 35 resulted positive for α-syn RT-QuIC, including 27/32 (84%) from AN, 5/11 (45%) from MT, and 3/29 (10%) belonging to the non-PD patients. Furthermore, 23 additional PD patients underwent NS at both AN and MT, and RT-QuIC revealed α-syn positive in 18/23 (78%) NSAN samples and in 10/23 (44%) NSMT samples. Immunocytochemistry of NS preparations showed a higher representation of olfactory neural cells in NSAN compared to NSMT. We also observed α-syn and phospho-α-syn deposits in NS from PD patients but not in controls. Finally, RT-QuIC was positive in 22/24 CSF samples from PD patients (92%) and in 1/19 non-PD.

Conclusion
In PD patients, RT-QuIC sensitivity is significantly increased (from 45% to 84%) when NS is performed at AN, indicating that α-syn aggregates are preferentially detected in olfactory areas with higher concentration of olfactory neurons. Although RT-QuIC analysis of CSF showed a higher diagnostic accuracy compared to NS, due to the non-invasiveness, NS might be considered as an ancillary procedure for PD diagnosis.
Improved Meta-learning Neural Network for the Prediction of the Historical Reinforced Concrete Bond–Slip Model Using Few Test Specimens
Authors: Zhang Chengwen , Chun Qing , Sun Ao , Lin Yijie , Wang HaoYu 
Published: July 2022

AbstractThe bond–slip model plays an important role in the structural analysis of reinforced concrete structures. However, many factors affect the bond–slip behavior, which means that a large number of tests are required to establish an accurate bond–slip model. This paper aims to establish a data-driven method for the prediction of the bond–slip model of historical reinforced concrete with few test specimens and many features. Therefore, a new Mahalanobis-Meta-learning Net algorithm was proposed, which can be used to solve the implicit regression problem in few-shot learning. Compared with the existing algorithms, the Mahalanobis-Meta-learning Net achieves fast convergence, accurate prediction and good generalization without performing a large number of tests. The algorithm was applied to the prediction task of the bond–slip model of square rebar-reinforced concrete. First, the first large pretraining database for the bond–slip model, BondSlipNet, was established containing 558 samples from the existing literature. The BondSlipNet database can be used to provide a priori knowledge for learning. Then, another database, named SRRC-Net, was obtained by 16 groups of pull-out tests with square rebar. The SRRC-Net database can be used to provide the posteriori knowledge. Finally, based on the databases, the algorithm not only successfully predicted the bond–slip model of square rebar-reinforced concrete, but also that of the other 23 types of reinforced concrete. The research results can provide a scientific basis for the conservation of square rebar-reinforced concrete structures and can contribute to the bond–slip model prediction of the other types of reinforced concrete structures.
Age–period–cohort analysis of pulmonary tuberculosis reported incidence, China, 2006–2020
Authors: Dong Zhe , Wang Qi-Qi , Yu Shi-Cheng , Huang Fei , Liu Jian-Jun , Yao Hong-Yan , Zhao Yan-Lin 
Published: July 2022

Abstract
Background
Tuberculosis (TB) poses a severe public health challenge in China and worldwide. This study evaluated the effects of age, period, and birth cohort on reported incidence trends of TB based on population and refined the characteristics of high-risk groups.

Methods
Aggregate data that reported pulmonary tuberculosis (PTB) cases from China Tuberculosis Management Information System (TBIMS) from 2006 to 2020 were used to analyze effect coefficients through the age–period–cohort (APC) model based on intrinsic estimator (IE) method, and converted them into relative risk (RR) to estimate trends.

Results
A total of 14.82 million cases of PTB were reported in China from 2006 to 2020, showing a continuous downward trend. The reporting rate increased with age by age group, with 70–74 years old being 2–3 times higher than that in 20–24 years old. APC analysis model showed that age effects were bimodal in 20–24 years old [RR = 2.29, 95% confidence interval (CI): 1.73–3.03] and 70–74 years old (RR = 1.95, 95% CI: 1.67–2.27), and lower than the overall average in the groups under 15 years old. Stratified results showed that the risk was higher for women under age 40 than men and higher for men over 40. The risk was higher in urban than in rural areas under 30 years old and slightly higher in rural than in urban between 30 and 64 years old. The risk for 15–34 years old was significantly higher in the east than in other regions. The period effects showed a decreasing trend, and the risk was higher in rural in recent years. Except for cohorts born in 1961–1965 and 2001–2005, where the RR increased, the later the cohort was born, the lower the risk. The cohort 1926–1930 in eastern had the highest risk (RR = 3.49, 95% CI: 2.44–4.98).

Conclusions
The reported incidence of PTB continued to decline in China from 2006 to 2020. The young (20–24 years old) and the elderly (70–74 years old) were equally at high risk. There were differences in the age, period and cohort effects on PTB incidence among gender, urban–rural and regions. Our findings better reflected the characteristics of high-risk populations, thus contributing to the development of timely and effective intervention strategies, and providing clues for etiological research.

Graphical abstract
Circ_0000144 acts as a miR-1178-3p decoy to promote cell malignancy and angiogenesis by increasing YWHAH expression in papillary thyroid cancer
Authors: Ma Yinli , Yang Dan , Guo Pingan 
Published: July 2022

Papillary thyroid cancer (PTC) is the most common subtype of thyroid cancer. Circular RNA hsa_circ_0000144 (circ_0000144) is related to the progression of thyroid cancer. However, the mechanism by which circ_0000144 accelerates PTC progression is still unclear. Circ_0000144 and YWHAH were upregulated in PTC tissues and cells, while miR-1178-3p had an opposite result. Circ_0000144 silencing constrained PTC cell growth in vitro and in vivo and induced apoptosis and repressed migration, invasion, and angiogenesis of PTC cells in vitro. Circ_0000144 acted as a molecular sponge for miR-1178-3p, which targeted YWHAH. MiR-1178-3p inhibitor reversed circ_0000144 silencing-mediated influence on PTC cell malignancy and angiogenesis. Furthermore, YWHAH overexpression overturned miR-1178-3p mimic-mediated influence on malignant behaviors and angiogenesis of PTC cells. Notably, circ_0000144 regulated YWHAH expression by adsorbing miR-1178-3p. Circ_0000144 promoted cell malignancy and angiogenesis by regulating the miR-1178-3p/YWHAH axis in PTC, offering a novel mechanism for the malignancy and angiogenesis of PTC cells. Graphical Abstract
Probing a southern hemisphere VLBI Intensive baseline configuration for UT1 determination
Authors: Böhm Sigrid , Böhm Johannes , Gruber Jakob , Kern Lisa , McCallum Jamie , McCallum Lucia , McCarthy Tiege , Quick Jonathan , Schartner Matthias 
Published: July 2022

AbstractThe deviation of Universal Time from atomic time, expressed as UT1−UTC, reflects the irregularities of the Earth rotation speed and is key to precise geodetic applications which depend on the transformation between celestial and terrestrial reference frames. A rapidly varying quantity such as UT1−UTC demands observation scenarios enabling fast delivery of good results. These criteria are currently met only by the Very Long Baseline Interferometry (VLBI) Intensive sessions. Due to stringent requirements of a fast UT1−UTC turnaround, the observations are limited to a few baselines and a duration of one hour. Hence, the estimation of UT1−UTC from Intensives is liable to constraints and prone to errors introduced by inaccurate a priori information. One aspect in this context is that the regularly operated Intensive VLBI sessions organised by the International VLBI Service for Geodesy and Astrometry solely use stations in the northern hemisphere. Any potential systematic errors due to this northern hemisphere dominated geometry are so far unknown. Besides the general need for stimulating global geodetic measurements with southern observatories, this served as a powerful motivation to launch the SI (Southern Intensive) program in 2020. The SI sessions are observed using three VLBI antennas in the southern hemisphere: Ht (South Africa), Hb (Tasmania) and Yg (Western Australia). On the basis of UT1−UTC results from 53 sessions observed throughout 2020 and 2021, we demonstrate the competitiveness of the SI with routinely operated Intensive sessions in terms of operations and UT1−UTC accuracy. The UT1−UTC values of the SI reach an average agreement of 32 µs in terms of weighted standard deviation when compared with the conventional Intensives results of five independent analysis centers and of 27 µs compared with the 14C04 series. The mean scatter of all solutions of the considered northern hemisphere Intensives with respect to C04 is at a comparable level of 29 µs. The quality of the results is only slightly degraded if just the baseline HtHb is evaluated. In combination with the e-transfer capabilities from Ht to Hb, this facilitates continuation of the SI by ensuring rapid service UT1−UTC provision.
Graphical Abstract