bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD157 in bone marrow mesenchymal stem cells mediates mitochondrial production and transfer to improve neuronal apoptosis and functional recovery after spinal cord injury
Authors: Li Jing , Li Heyangzi , Cai Simin , Bai Shi , Cai Huabo , Zhang Xiaoming 
Published: May 2021

Abstract
Background
Recent studies demonstrated that autologous mitochondria derived from bone marrow mesenchymal stem cells (BMSCs) might be valuable in the treatment of spinal cord injury (SCI). However, the mechanisms of mitochondrial transfer from BMSCs to injured neurons are not fully understood.

Methods
We modified BMSCs by CD157, a cell surface molecule as a potential regulator mitochondria transfer, then transplanted to SCI rats and co-cultured with OGD injured VSC4.1 motor neuron. We detected extracellular mitochondrial particles derived from BMSCs by transmission electron microscope and measured the CD157/cyclic ADP-ribose signaling pathway-related protein expression by immunohistochemistry and Western blotting assay. The CD157 ADPR-cyclase activity and Fluo-4 AM was used to detect the Ca2+ signal. All data were expressed as mean ± SEM. Statistical analysis was analyzed by GraphPad Prism 6 software. Unpaired t-test was used for the analysis of two groups. Multiple comparisons were evaluated by one-way ANOVA or two-way ANOVA.

Results
CD157 on BMSCs was upregulated when co-cultured with injured VSC4.1 motor neurons. Upregulation of CD157 on BMSCs could raise the transfer extracellular mitochondria particles to VSC4.1 motor neurons, gradually regenerate the axon of VSC4.1 motor neuron and reduce the cell apoptosis. Transplantation of CD157-modified BMSCs at the injured sites could significantly improve the functional recovery, axon regeneration, and neuron apoptosis in SCI rats. The level of Ca2+ in CD157-modified BMSCs dramatically increased when objected to high concentration cADPR, ATP content, and MMP of BMSCs also increased.

Conclusion
The present results suggested that CD157 can regulate the production and transfer of BMSC-derived extracellular mitochondrial particles, enriching the mechanism of the extracellular mitochondrial transfer in BMSCs transplantation and providing a novel strategy to improve the stem cell treatment on SCI.
Heat shock preconditioning mesenchymal stem cells attenuate acute lung injury via reducing NLRP3 inflammasome activation in macrophages
Authors: Lv Haijin , Yuan Xiaofeng , Zhang Jiebin , Lu Tongyu , Yao Jia , Zheng Jun , Cai Jianye , Xiao Jiaqi , Chen Haitian , Xie Shujuan , Ruan Ying , An Yuling , Sui Xin , Yi Huimin 
Published: May 2021

Abstract
Objectives
Acute lung injury (ALI) remains a common cause of morbidity and mortality worldwide, and to date, there is no effective treatment for ALI. Previous studies have revealed that topical administration of mesenchymal stem cells (MSCs) can attenuate the pathological changes in experimental acute lung injury. Heat shock (HS) pretreatment has been identified as a method to enhance the survival and function of cells. The present study aimed to assess whether HS-pretreated MSCs could enhance immunomodulation and recovery from ALI.

Materials and methods
HS pretreatment was performed at 42 °C for 1 h, and changes in biological characteristics and secretion functions were detected. In an in vivo mouse model of ALI, we intranasally administered pretreated umbilical cord-derived MSCs (UC-MSCs), confirmed their therapeutic effects, and detected the phenotypes of the macrophages in bronchoalveolar lavage fluid (BALF). To elucidate the underlying mechanisms, we cocultured pretreated UC-MSCs with macrophages in vitro, and the expression levels of inflammasome-related proteins in the macrophages were assessed.

Results
The data showed that UC-MSCs did not exhibit significant changes in viability or biological characteristics after HS pretreatment. The administration of HS-pretreated UC-MSCs to the ALI model improved the pathological changes and lung damage-related indexes, reduced the proinflammatory cytokine levels, and modulated the M1/M2 macrophage balance. Mechanistically, both the in vivo and in vitro studies demonstrated that HS pretreatment enhanced the protein level of HSP70 in UC-MSCs, which negatively modulated NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in alveolar macrophages. These effects were partially reversed by knocking down HSP70 expression.

Conclusion
HS pretreatment can enhance the beneficial effects of UC-MSCs in inhibiting NLRP3 inflammasome activation in macrophages during ALI. The mechanism may be related to the upregulated expression of HSP70.

Graphical abstract
The role of Serpina3n in the reversal effect of ATRA on dexamethasone-inhibited osteogenic differentiation in mesenchymal stem cells
Authors: Jiang Hai-Tao , Deng Rui , Deng Yan , Nie Mao , Deng Yi-Xuan , Luo Hong-Hong , Yang Yuan-Yuan , Ni Na , Ran Cheng-Cheng , Deng Zhong-Liang 
Published: May 2021

Abstract
Background
Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis. Patients with GIOP are susceptible to fractures and the subsequent delayed bone union or nonunion. Thus, effective drugs and targets need to be explored. In this regard, the present study aims to reveal the possible mechanism of the anti-GIOP effect of all-trans retinoic acid (ATRA).

Methods
Bone morphogenetic protein 9 (BMP9)-transfected mesenchymal stem cells (MSCs) were used as an in vitro osteogenic model to deduce the relationship between ATRA and dexamethasone (DEX). The osteogenic markers runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), and osteopontin were detected using real-time quantitative polymerase chain reaction, Western blot, and immunofluorescent staining assay. ALP activities and matrix mineralization were evaluated using ALP staining and Alizarin Red S staining assay, respectively. The novel genes associated with ATRA and DEX were detected using RNA sequencing (RNA-seq). The binding of the protein–DNA complex was validated using chromatin immunoprecipitation (ChIP) assay. Rat GIOP models were constructed using intraperitoneal injection of dexamethasone at a dose of 1 mg/kg, while ATRA intragastric administration was applied to prevent and treat GIOP. These effects were evaluated based on the serum detection of the osteogenic markers osteocalcin and tartrate-resistant acid phosphatase 5b, histological staining, and micro-computed tomography analysis.

Results
ATRA enhanced BMP9-induced ALP, RUNX2 expressions, ALP activities, and matrix mineralization in mouse embryonic fibroblasts as well as C3H10T1/2 and C2C12 cells, while a high concentration of DEX attenuated these markers. When DEX was combined with ATRA, the latter reversed DEX-inhibited ALP activities and osteogenic markers. In vivo analysis showed that ATRA reversed DEX-inhibited bone volume, bone trabecular number, and thickness. During the reversal process of ATRA, the expression of retinoic acid receptor beta (RARβ) was elevated. RARβ inhibitor Le135 partly blocked the reversal effect of ATRA. Meanwhile, RNA-seq demonstrated that serine protease inhibitor, clade A, member 3N (Serpina3n) was remarkably upregulated by DEX but downregulated when combined with ATRA. Overexpression of Serpina3n attenuated ATRA-promoted osteogenic differentiation, whereas knockdown of Serpina3n blocked DEX-inhibited osteogenic differentiation. Furthermore, ChIP assay revealed that RARβ can regulate the expression of Serpina3n.

Conclusion
ATRA can reverse DEX-inhibited osteogenic differentiation both in vitro and in vivo, which may be closely related to the downregulation of DEX-promoted Serpina3n. Hence, ATRA may be viewed as a novel therapeutic agent, and Serpina3n may act as a new target for GIOP.
Sex differences in vancomycin-resistant enterococci bloodstream infections—a systematic review and meta-analysis
Authors: Correa-Martínez Carlos L. , Schuler Franziska , Kampmeier Stefanie 
Published: May 2021

Abstract
Background
Vancomycin-resistant enterococci (VRE) have emerged in the healthcare setting worldwide. Infections with these pathogens, i.e., bloodstream infections (BSI), are accompanied with an impaired patient outcome. Diverse factors comprising patient characteristics, therapeutic strategies, and infection control measures are positively or negatively associated with VRE BSI occurrence. However, whether sex-specific differences influence the frequency of VRE BSI is yet unknown.
The aim of this systematic review was to comprehensively summarize and analyze sex prevalence in VRE BSI patients.

Main text
A systematic search for relevant articles was conducted in PubMed and Web of Science. After screening for eligibility, data extraction from included articles and risk of bias assessment were processed. The prevalence of male/female sex in VRE BSI patients and 95% CI were calculated for each study and summarized as pooled estimated effect.
In total, nine articles met the inclusion criteria. Risk of bias assessment resulted in low (six studies) to moderate bias (three studies). The pooled prevalence of male patients suffering from VRE BSI was 59% resulting in a 1.4 male/female prevalence ratio.

Conclusions
Current literature suggests sex differences with male preference (59%) in the distribution of VRE BSI cases. Further primary studies should address the question of male-specific factors favoring the enhanced frequency of VRE BSI.
Learning adaptive representations for entity recognition in the biomedical domain
Authors: Lauriola Ivano , Aiolli Fabio , Lavelli Alberto , Rinaldi Fabio 
Published: May 2021

AbstractBackgroundNamed Entity Recognition is a common task in Natural Language Processing applications, whose purpose is to recognize named entities in textual documents. Several systems exist to solve this task in the biomedical domain, based on Natural Language Processing techniques and Machine Learning algorithms. A crucial step of these applications is the choice of the representation which describes data. Several representations have been proposed in the literature, some of which are based on a strong knowledge of the domain, and they consist of features manually defined by domain experts. Usually, these representations describe the problem well, but they require a lot of human effort and annotated data. On the other hand, general-purpose representations like word-embeddings do not require human domain knowledge, but they could be too general for a specific task.ResultsThis paper investigates methods to learn the best representation from data directly, by combining several knowledge-based representations and word embeddings. Two mechanisms have been considered to perform the combination, which are neural networks and Multiple Kernel Learning. To this end, we use a hybrid architecture for biomedical entity recognition which integrates dictionary look-up (also known as gazetteers) with machine learning techniques. Results on the CRAFT corpus clearly show the benefits of the proposed algorithm in terms ofF1score.ConclusionsOur experiments show that the principled combination of general, domain specific, word-, and character-level representations improves the performance of entity recognition. We also discussed the contribution of each representation in the final solution.
Single cell RNA-seq analysis of the flexor digitorum brevis mouse myofibers
Authors: Verma Rohan X. , Kannan Suraj , Lin Brian L. , Fomchenko Katherine M. , Nieuwenhuis Tim O. , Patil Arun H. , Lukban Clarisse , Yang Xiaoping , Fox-Talbot Karen , McCall Matthew N. , Kwon Chulan , Kass David A. , Rosenberg Avi Z. , Halushka Marc K. 
Published: May 2021

Abstract
Background
Skeletal muscle myofibers can be separated into functionally distinct cell types that differ in gene and protein expression. Current single cell expression data is generally based upon single nucleus RNA, rather than whole myofiber material. We examined if a whole-cell flow sorting approach could be applied to perform single cell RNA-seq (scRNA-seq) in a single muscle type.

Methods
We performed deep, whole cell, scRNA-seq on intact and fragmented skeletal myofibers from the mouse fast-twitch flexor digitorum brevis muscle utilizing a flow-gated method of large cell isolation. We performed deep sequencing of 763 intact and fragmented myofibers.

Results
Quality control metrics across the different gates indicated only 171 of these cells were optimal, with a median read count of 239,252 and an average of 12,098 transcripts per cell. scRNA-seq identified three clusters of myofibers (a slow/fast 2A cluster and two fast 2X clusters). Comparison to a public skeletal nuclear RNA-seq dataset demonstrated a diversity in transcript abundance by method. RISH validated multiple genes across fast and slow twitch skeletal muscle types.

Conclusion
This study introduces and validates a method to isolate intact skeletal muscle myofibers to generate deep expression patterns and expands the known repertoire of fiber-type-specific genes.
Bone marrow mesenchymal stem cells promote prostate cancer cell stemness via cell–cell contact to activate the Jagged1/Notch1 pathway
Authors: Cheng Ji-wen , Duan Li-xia , Yu Yang , Wang Pu , Feng Jia-le , Feng Guan-zheng , Liu Yan 
Published: May 2021

Abstract
Background
Mesenchymal stem cells (MSCs) play a crucial role in cancer development and tumor resistance to therapy in prostate cancer, but the influence of MSCs on the stemness potential of PCa cells by cell–cell contact remains unclear. In this study, we investigated the effect of direct contact of PCa cells with MSCs on the stemness of PCa and its mechanisms.

Methods
First, the flow cytometry, colony formation, and sphere formation were performed to determine the stemness of PCaMSCs, and the expression of stemness-related molecules (Sox2, Oct4, and Nanog) was investigated by western blot analysis. Then, we used western blot and qPCR to determine the activity levels of two candidate pathways and their downstream stemness-associated pathway. Finally, we verified the role of the significantly changed pathway by assessing the key factors in this pathway via in vitro and in vivo experiments.

Results
We established that MSCs promoted the stemness of PCa cells by cell–cell contact. We here established that the enhanced stemness of PCaMSCs was independent of the CCL5/CCR5 pathway. We also found that PCaMSCs up-regulated the expression of Notch signaling-related genes, and inhibition of Jagged1-Notch1 signaling in PCaMSCs cells significantly inhibited MSCs-induced stemness and tumorigenesis in vitro and in vivo.

Conclusions
Our results reveal a novel interaction between MSCs and PCa cells in promoting tumorigenesis through activation of the Jagged1/Notch1 pathway, providing a new therapeutic target for the treatment of PCa.
Synonymous point mutation of gtfB gene caused by therapeutic X-rays exposure reduced the biofilm formation and cariogenic abilities of Streptococcus mutans
Authors: Wang Zheng , Zhou Yujie , Han Qi , Ye Xingchen , Chen Yanyan , Sun Yan , Liu Yaqi , Zou Jing , Qi Guohai , Zhou Xuedong , Cheng Lei , Ren Biao 
Published: May 2021

Abstract
Background
The shift of oral microbiota is a critical factor of radiation caries in head and neck cancer patients after the radiotherapy. However, the direct effects of irradiation on the genome and virulence of cariogenic bacteria are poorly described. Here we investigated the genomic mutations and virulence change of Streptococcus mutans (S. mutans), the major cariogenic bacteria, exposed to the therapeutic doses of X-rays.

Results
X-ray reduced the survival fraction of S. mutans and impacted its biofilm formation. We isolated a biofilm formation-deficient mutant #858 whose genome only possessed three synonymous mutations (c.2043 T > C, c.2100C > T, c.2109A > G) in gtfB gene. The “silent mutation” of c.2043 T > C in gtfB gene can cause the down-regulation of all of the gtfs genes’ expression and decrease the GtfB enzyme secretion without the effect on the growth due to the codon bias. #858 and synonymous point mutation strain gtfB2043 T>C, similar to the gtfB gene null mutant Δ gtfB, can significantly decrease the extracellular polysaccharide production, biofilm formation and cariogenic capabilities both in vitro and in vivo compared with wild type.

Conclusion
The direct exposure of X-ray radiation can affect the genome and virulence of oral bacteria even at therapeutic doses. The synonymous mutations of genome are negligent factors for gene expression and related protein translation due to the codon usage frequency.
Fluid-induced harm in the hospital: look beyond volume and start considering sodium. From physiology towards recommendations for daily practice in hospitalized adults
Authors: Van Regenmortel Niels , Moers Lynn , Langer Thomas , Roelant Ella , De Weerdt Tim , Caironi Pietro , Malbrain Manu L. N. G. , Elbers Paul , Van den Wyngaert Tim , Jorens Philippe G. 
Published: May 2021

AbstractPurposeIatrogenic fluid overload is a potential side effect of intravenous fluid therapy in the hospital. Little attention has been paid to sodium administration as a separate cause of harm. With this narrative review, we aim to substantiate the hypothesis that a considerable amount of fluid-induced harm is caused not only by fluid volume, but also by the sodium that is administered to hospitalized patients.MethodsWe show how a regular dietary sodium intake is easily surpassed by the substantial amounts of sodium that are administered during typical hospital stays. The most significant sodium burdens are caused by isotonic maintenance fluid therapy and by fluid creep, defined as the large volume unintentionally administered to patients in the form of dissolved medication. In a section on physiology, we elaborate on the limited renal handling of an acute sodium load. We demonstrate how the subsequent retention of water is an energy-demanding, catabolic process and how free water is needed to excrete large burdens of sodium. We quantify the effect size of sodium-induced fluid retention and discuss its potential clinical impact. Finally, we propose preventive measures, discuss the benefits and risks of low-sodium maintenance fluid therapy, and explore options for reducing the amount of sodium caused by fluid creep.ConclusionThe sodium burdens caused by isotonic maintenance fluids and fluid creep are responsible for an additional and avoidable derailment of fluid balance, with presumed clinical consequences. Moreover, the handling of sodium overload is characterized by increased catabolism. Easy and effective measures for reducing sodium load and fluid retention include choosing a hypotonic rather than isotonic maintenance fluid strategy (or avoiding these fluids when enough free water is provided through other sources) and dissolving as many medications as possible in glucose 5%.
Resuscitative endovascular balloon occlusion of the aorta vs epinephrine in the treatment of non-traumatic cardiac arrest in swine
Authors: Hutin Alice , Levy Yaël , Lidouren Fanny , Kohlhauer Matthias , Carli Pierre , Ghaleh Bijan , Lamhaut Lionel , Tissier Renaud 
Published: May 2021

Abstract
Background
The administration of epinephrine in the management of non-traumatic cardiac arrest remains recommended despite controversial effects on neurologic outcome. The use of resuscitative endovascular balloon occlusion of the aorta (REBOA) could be an interesting alternative. The aim of this study was to compare the effects of these 2 strategies on return of spontaneous circulation (ROSC) and cerebral hemodynamics during cardiopulmonary resuscitation (CPR) in a swine model of non-traumatic cardiac arrest.

Results
Anesthetized pigs were instrumented and submitted to ventricular fibrillation. After 4 min of no-flow and 18 min of basic life support (BLS) using a mechanical CPR device, animals were randomly submitted to either REBOA or epinephrine administration before defibrillation attempts. Six animals were included in each experimental group (Epinephrine or REBOA). Hemodynamic parameters were similar in both groups during BLS, i.e., before randomization. After epinephrine administration or REBOA, mean arterial pressure, coronary and cerebral perfusion pressures similarly increased in both groups. However, carotid blood flow (CBF) and cerebral regional oxygenation saturation were significantly higher with REBOA as compared to epinephrine administration (+ 125% and + 40%, respectively). ROSC was obtained in 5 animals in both groups. After resuscitation, CBF remained lower in the epinephrine group as compared to REBOA, but it did not achieve statistical significance.

Conclusions
During CPR, REBOA is as efficient as epinephrine to facilitate ROSC. Unlike epinephrine, REBOA transitorily increases cerebral blood flow and could avoid its cerebral detrimental effects during CPR. These experimental findings suggest that the use of REBOA could be beneficial in the treatment of non-traumatic cardiac arrest.
RANSAC algorithm for instantaneous frequency estimation and reconstruction of frequency-modulated undersampled signals
Authors: Djurović Igor 
Published: May 2021

AbstractFrequency modulated (FM) signals sampled below the Nyquist rate or with missing samples (nowadays part of wider compressive sensing (CS) framework) are considered. Recently proposed matching pursuit and greedy techniques are inefficient for signals with several phase parameters since they require a search over multidimensional space. An alternative is proposed here based on the random samples consensus algorithm (RANSAC) applied to the instantaneous frequency (IF) estimates obtained from the time-frequency (TF) representation of recordings (undersampled or signal with missing samples). The O’Shea refinement strategy is employed to refine results. The proposed technique is tested against third- and fifth-order polynomial phase signals (PPS) and also for signals corrupted by noise.
Single base station positioning based on multipath parameter clustering in NLOS environment
Authors: Wang Yong , Wu Qihong , Zhou Mu , Yang Xiaolong , Nie Wei , Xie Liangbo 
Published: May 2021

AbstractThis paper proposes a scattering area model for processing multipath parameters achieve single base station positioning. First of all, we construct a scattering area model based on the spatial layout of obstacles near the base station and then collect the multipath signals needed for positioning and extract parameters. Second, we use the joint clustering algorithm improved by k-means clustering and mean shift clustering algorithm to process the parameters and extract useful information. Third, the processed information is combined with the spatial layout information of the scattering area model to construct equations, and then the solving problem of equations is converted into a least-squares optimization problem. Finally, the Levenberg-Marquardt (LM) algorithm is used to solve the optimal solution and estimate the mobile target position. The simulation results show that the positioning algorithm in this paper can be used by a single base station to locate the target in an outdoor non-line-of-sight (NLOS) environment, and the accuracy is improved compared with the traditional positioning algorithm.