bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rehabilitation therapy for a severe case of coronavirus disease 2019: a case report
Authors: Takekawa Toru , Kashiwabara Kazumi , Yamada Naoki , Watanabe Shu , Hama Midori , Hashimoto Gentaro , Abo Masahiro , Shinfuku Kyota 
Published: September 2022

AbstractBackgroundPatients with severe coronavirus disease 2019 (COVID-19) infection require a long period of time to return to work and society due to significant physical weakness even after recovery. Here we report a patient with a history of nephrectomy who developed severe COVID-19 infection associated with muscle weakness but was able to return to society after rehabilitation therapy.Case presentationA Japanese man in his 40s was admitted to the hospital with PCR-based COVID-19 diagnosis. The respiratory condition worsened rapidly and was treated with extracorporeal membrane-assisted ventilation in the intensive case unit. On admission to the Rehabilitation Department on day T + 30 [T: day patient became febrile (38 °C)], he was unable to stand for a long time and used a walker. Rehabilitation therapy was postponed to prevent COVID-19 spread, but the patient was encouraged to exercise during isolation to improve trunk and lower extremity muscle strength. Physical therapy commenced on day T + 49 to improve gait and trunk and lower limb muscle strength. He was able to walk independently and later returned to work following discharge on day T + 53. A computed tomography scan showed an increase in psoas muscle volume from 276 before to 316 cm3after physical therapy, together with a decrease in whole-body extracellular water:total body weight ratio from 0.394 to 0.389.ConclusionsWe have described the beneficial effects of rehabilitation therapy in a patient with severe COVID-19 infection. In addition to exercise, we believe that nutrition is even more important in increasing skeletal muscle mass. Rehabilitation therapy is recommended to enhance the return of severely ill COVID-19 patients to routine daily activity.
Transcatheter arterial embolization for hemothorax caused by spinal fracture without arterial injury: a case report and review of the literature
Authors: Matsunaga Naoki , Okada Takuya , Ono Yuko , Matsushiro Keigo , Sasaki Koji , Gentsu Tomoyuki , Ueshima Eisuke , Sofue Keitaro , Yamaguchi Masato , Sugimoto Koji , Murakami Takamichi 
Published: September 2022

Abstract
Background
Spinal fractures rarely cause hemothorax, and no treatment consensus has been reached. Conservative treatment is generally selected in cases without arterial injury, but there have been some reports of uncontrolled bleeding. Here we report a case of hemothorax caused by spinal fracture without arterial injury treated with transcatheter arterial embolization.

Case presentation
An 88-year-old Japanese woman with back pain was diagnosed with hemothorax due to bleeding from an unstable fracture of the tenth thoracic vertebra. Contrast-enhanced computed tomography revealed no obvious arterial injury. We performed transcatheter arterial embolization of the bilateral tenth intercostal arteries to prevent rebleeding. The hemothorax did not worsen until surgical spinal fixation 9 days post-transcatheter arterial embolization, and she was discharged 30 days after admission.

Conclusion
Transcatheter arterial embolization for hemothorax caused by spinal fractures without obvious arterial injury may be a useful bridge to spinal fixation.
Knockdown of CDC20 promotes adipogenesis of bone marrow-derived stem cells by modulating β-catenin
Authors: Du Yangge , Liu Yunsong , Zhou Yongsheng , Zhang Ping 
Published: September 2022

Abstract
Background
Bone is a rigid organ that provides physical protection and support to vital organs of the body. Bone loss disorders are commonly associated with increased bone marrow adipose tissue. Bone marrow mesenchymal stromal/stem cells (BMSCs) are multipotent progenitors that can differentiate into osteoblasts, adipocytes, and chondrocytes. Cell division cycle 20 (CDC20) is a co-activator of anaphase promoting complex/cyclosome (APC/C), and is required for ubiquitin ligase activity. Our previous study showed that CDC20 promoted the osteogenic commitment of BMSCs and Cdc20 conditional knockout mice suggested a decline in bone mass. In this study, we found that knockdown of CDC20 promoted adipogenic differentiation of BMSCs by modulating β-catenin, which suggested a link between adipogenesis and osteogenesis.

Methods
Lentivirus containing a CDC20 shRNA was used for CDC20 knockdown in human BMSCs (hBMSCs). Primary mouse BMSCs (mBMSCs) were isolated from Cdc20f/f and Sp7-Cre;Cdc20f/f mice. Adipogenesis was examined using quantitative real-time reverse transcription PCR (qRT-PCR) and western blotting analysis of adipogenic regulators, Oil Red O staining, and transplantation into nude mice. CDC20 knockout efficiency was determined through immunochemistry, qRT-PCR, and western blotting of bone marrow. Accumulation of adiposity was measured through histology and staining of bone sections. Exploration of the molecular mechanism was determined through western blotting, Oil Red O staining, and qRT-PCR.

Results
CDC20 expression in hBMSCs was significantly decreased during adipogenic differentiation. CDC20 knockdown enhanced hBMSC adipogenic differentiation in vitro. CDC20-knockdown hBMSCs showed more adipose tissue-like constructs upon hematoxylin and eosin (H&E) and Oil Red O staining. Sp7-Cre;Cdc20f/f mice presented increased adipocytes in their bone marrow compared with the control mice. mBMSCs from Sp7-Cre;Cdc20f/f mice showed upregulated adipogenic differentiation. Knockdown of CDC20 led to decreased β-catenin levels, and a β-catenin pathway activator (lithium chloride) abolished the role of CDC20 in BMSC adipogenic differentiation.

Conclusions
Our findings showed that CDC20 knockdown enhanced adipogenesis of hBMSC and mBMSCs adipogenesis in vitro and in vivo. CDC20 regulates both adipogenesis and osteogenesis of BMSCs, and might lead to the development of new therapeutic targets for “fatty bone” and osteoporosis.
The optimal transplantation strategy of umbilical cord mesenchymal stem cells in spinal cord injury: a systematic review and network meta-analysis based on animal studies
Authors: Lu Yubao , Zhang Wei , Tian Zhenming , Liang Qian , Liu Chenrui , Wu Yingjie , Zhang Liangming , Rong Limin 
Published: September 2022

Abstract
Objective
Umbilical cord mesenchymal stem cells (UCMSCs) have great potential in the treatment of spinal cord injury. However, the specific therapeutic effect and optimal transplantation strategy are still unclear. Therefore, exploring the optimal treatment strategy of UCMSCs in animal studies by systematic review can provide reference for the development of animal studies and clinical research in the future.

Methods
Databases of PubMed, Ovid-Embase, Web of Science, CNKI, WanFang, VIP, and CBM were searched for the literature in February 11, 2022. Two independent reviewers performed the literature search, identification, screening, quality assessment, and data extraction.

Results and Discussion
A total of 40 animal studies were included for combined analysis. In different subgroups, the results of traditional meta-analysis and network meta-analysis were consistent, that is, the therapeutic effect of high-dose (≥ 1 × 106) transplantation of UCMSCs was significantly better than that of low dose (< 1 × 106), the therapeutic effect of local transplantation of UCMSCs was significantly better than that of intravenous transplantation, and the therapeutic effect of subacute transplantation of UCMSCs was significantly better than that of acute and chronic transplantation. However, in view of the inherent risk of bias and limited internal and external validity of the current animal studies, more high-quality, direct comparison studies are needed to further explore the optimal transplantation strategy for UCMSCs in the future.
Characterizing the secretome of licensed hiPSC-derived MSCs
Authors: Ramos Yolande F. M. , Tertel Tobias , Shaw Georgina , Staubach Simon , de Almeida Rodrigo Coutinho , Suchiman Eka , Kuipers Thomas B. , Mei Hailiang , Barry Frank , Murphy Mary , Giebel Bernd , Meulenbelt Ingrid 
Published: September 2022

AbstractAlthough mesenchymal stromal cells (MSCs) from primary tissues have been successfully applied in the clinic, their expansion capabilities are limited and results are variable. MSCs derived from human-induced pluripotent stem cells (hiMSCs) are expected to overcome these limitations and serve as a reproducible and sustainable cell source. We have explored characteristics and therapeutic potential of hiMSCs in comparison to hBMSCs. RNA sequencing confirmed high resemblance, with average Pearson correlation of 0.88 and Jaccard similarity index of 0.99, and similar to hBMSCs the hiMSCs released extracellular vesicles with in vitro immunomodulatory properties. Potency assay with TNFα and IFNγ demonstrated an increase in well-known immunomodulatory genes such as IDO1, CXCL8/IL8, and HLA-DRA which was also highlighted by enhanced secretion in the media. Notably, expression of 125 genes increased more than 1000-fold. These genes were predicted to be regulated by NFΚB signaling, known to play a central role in immune response. Altogether, our data qualify hiMSCs as a promising source for cell therapy and/or cell-based therapeutic products. Additionally, the herewith generated database will add to our understanding of the mode of action of regenerative cell-based therapies and could be used to identify relevant potency markers.
Therapeutic potential of conditioned medium obtained from deferoxamine preconditioned umbilical cord mesenchymal stem cells on diabetic nephropathy model
Authors: Ozkan Serbay , Isildar Basak , Ercin Merve , Gezginci-Oktayoglu Selda , Konukoglu Dildar , Neşetoğlu Neşet , Oncul Mahmut , Koyuturk Meral 
Published: September 2022

Abstract
Background
The therapeutic potential of mesenchymal stem cells (MSCs)-derived conditioned media (CM) can be increased after preconditioning with various chemical agents. The aim of this study is comparative evaluation of effects of N-CM and DFS-CM which are collected from normal (N) and deferoxamine (DFS) preconditioned umbilical cord-derived MSCs on rat diabetic nephropathy (DN) model.

Methods
After incubation of the MSCs in serum-free medium with/without 150 µM DFS for 48 h, the contents of N-CM and DFS-CM were analyzed by enzyme-linked immunosorbent assay. Diabetes (D) was induced by single dose of 55 mg/kg streptozotocin. Therapeutic effects of CMs were evaluated by biochemical, physical, histopathological and immunohistochemical analysis.

Results
The concentrations of vascular endothelial growth factor alpha, nerve growth factor and glial-derived neurotrophic factor in DFS-CM increased, while one of brain-derived neurotrophic factor decreased in comparison with N-CM. The creatinine clearance rate increased significantly in both treatment groups, while the improvement in albumin/creatinine ratio and renal mass index values were only significant for D + DFS-CM group. Light and electron microscopic deteriorations and loss of podocytes-specific nephrin and Wilms tumor-1 (WT-1) expressions were significantly restored in both treatment groups. Tubular beclin-1 expression was significantly increased for DN group, but it decreased in both treatment groups. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cell death increased in the tubules of D group, while it was only significantly decreased for D + DFS-CM group.

Conclusions
DFS-CM can be more effective in the treatment of DN by reducing podocyte damage and tubular apoptotic cell death and regulating autophagic activity with its more concentrated secretome content than N-CM.

Graphical Abstract
Stable expression of a truncated TLX variant drives differentiation of induced pluripotent stem cells into self-renewing neural stem cells for production of extracellular vesicles
Authors: Xu Mingzhi , Chen Gang , Dong Yanan , Xiang Shensi , Xue Miaomiao , Liu Yongxue , Song Haijing , Song Haifeng , Wang Yi 
Published: September 2022

AbstractBackgroundNeural stem cells (NSCs)-derived extracellular vesicles (EVs) possess great potential in treating severe neurological and cerebrovascular diseases, as they carry the modulatory and regenerative ingredients of NSCs. Induced pluripotent stem cells (iPSCs)-derived NSCs culture represents a sustainable source of therapeutic EVs. However, there exist two major challenges in obtaining a scalable culture of NSCs for high-efficiency EVs production: (1) the heterogeneity of iPSC-derived NSCs culture impairs the production of high-quality EVs and (2) the intrinsic propensity of neuronal or astroglial differentiation of NSCs during prolonged culturing reduces the number of NSCs for preparing EVs. A NSCs strain that is amenable to stable self-renewal and proliferation is thus greatly needed for scalable and long-term culture.MethodsVarious constructs of the genes encoding the orphan nuclear receptor NR2E1 (TLX) were stably transfected in iPSCs, which were subsequently cultured in a variety of differentiation media for generation of iNSCsTLX. Transcriptomic and biomarker profile of iNSCsTLXwere investigated. In particular, the positivity ratios of Sox2/Nestin and Musashi/Vimentin were used to gauge the homogeneity of the iNSCsTLXculture. The iNSCs expressing a truncated version of TLX (TLX-TP) was expanded for up to 45 passages, after which its neuronal differentiation potential and EV activity were evaluated.ResultsStable expression of TLX-TP could confer the iPSCs with rapid and self-driven differentiation into NSCs through stable passaging up to 225 days. The long-term culture of NSCs maintained the highly homogenous expression of NSC-specific biomarkers and potential of neuronal differentiation. EVs harvested from the TLX-expressing NSCs cultures exhibited anti-inflammatory and neuroprotective activities.ConclusionsiPSC-derived NSCs stably expressing TLX-TP is a promising cell line for scalable production of EVs, which should be further exploited for therapeutic development in neurological treatment.
Generation of corrected hiPSC clones from a Cornelia de Lange Syndrome (CdLS) patient through CRISPR-Cas-based technology
Authors: Umbach Alessandro , Maule Giulia , Kheir Eyemen , Cutarelli Alessandro , Foglia Marika , Guarrera Luca , Fava Luca L. , Conti Luciano , Garattini Enrico , Terao Mineko , Cereseto Anna 
Published: September 2022

Abstract
Background
Cornelia de Lange syndrome (CdLS) is a rare multisystem genetic disorder which is caused by genetic defects involving the Nipped-B-like protein (NIPBL) gene in the majority of clinical cases (60–70%). Currently, there are no specific cures available for CdLS and clinical management is needed for life. Disease models are highly needed to find a cure. Among therapeutic possibilities are genome editing strategies based on CRISPR-Cas technology.

Methods
A comparative analysis was performed to test the most recent CRISPR-Cas technologies comprising base- and prime-editors which introduce modifications without DNA cleavages and compared with sequence substitution approaches through homology directed repair (HDR) induced by Cas9 nuclease activity. The HDR method that was found more efficient was applied to repair a CdLS-causing mutation in the NIPBL gene. Human-induced pluripotent stem cells (hiPSCs) derived from a CdLS patient carrying the c.5483G > A mutation in the NIPBL were modified through HDR to generate isogenic corrected clones.

Results
This study reports an efficient method to repair the NIPBL gene through HDR mediated by CRISPR-Cas and induced with a compound (NU7441) inhibiting non-homologous end joining (NHEJ) repair. This sequence repair method allowed the generation of isogenic wild-type hiPSCs clones with regular karyotype and preserved pluripotency.

Conclusions
CdLS cellular models were generated which will facilitate the investigation of the disease molecular determinants and the identification of therapeutic targets. In particular, the hiPSC-based cellular models offer the paramount advantage to study the tissue differentiation stages which are altered in the CdLS clinical development. Importantly, the hiPSCs that were generated are isogenic thus providing the most controlled experimental set up between wild-type and mutated conditions.
Multi-omics analysis of an in vitro photoaging model and protective effect of umbilical cord mesenchymal stem cell-conditioned medium
Authors: Zou Xiaocang , Zou Dayang , Li Linhao , Yu Renfeng , Li XianHuang , Du Xingyue , Guo JinPeng , Wang KeHui , Liu Wei 
Published: September 2022

Abstract
Background
Skin ageing caused by long-term ultraviolet (UV) irradiation is a complex biological process that involves multiple signalling pathways. Stem cell-conditioned media is believed to have anti-ageing effects on the skin. The purpose of this study was to explore the biological effects of UVB irradiation and anti-photoaging effects of human umbilical cord mesenchymal stem cell-conditioned medium (hUC-MSC-CM) on HaCaT cells using multi-omics analysis with a novel cellular photoaging model.

Methods
A cellular model of photoaging was constructed by irradiating serum-starved HaCaT cells with 20 mJ/cm2 UVB. Transcriptomics and proteomics analyses were used to explore the biological effects of UVB irradiation on photoaged HaCaT cells. Changes in cell proliferation, apoptosis, and migration, the cell cycle, and expression of senescence genes and proteins were measured to assess the protective effects of hUC-MSC-CM in the cellular photoaging model.

Results
The results of the multi-omics analysis revealed that UVB irradiation affected various biological functions of cells, including cell proliferation and the cell cycle, and induced a senescence-associated secretory phenotype. hUC-MSC-CM treatment reduced cell apoptosis, inhibited G1 phase arrest in the cell cycle, reduced the production of reactive oxygen species, and promoted cell motility. The qRT-PCR results indicated that MYC, IL-8, FGF-1, and EREG were key genes involved in the anti-photoaging effects of hUC-MSC-CM. The western blotting results demonstrated that C-FOS, C-JUN, TGFβ, p53, FGF-1, and cyclin A2 were key proteins involved in the anti-photoaging effects of hUC-MSC-CM.

Conclusion
Serum-starved HaCaT cells irradiated with 20 mJ/cm2 UVB were used to generate an innovative cellular photoaging model, and hUC-MSC-CM demonstrates potential as an anti-photoaging treatment for skin.
Time-regulated transcripts with the potential to modulate human pluripotent stem cell-derived cardiomyocyte differentiation
Authors: Muñoz Juan J. A. M. , Dariolli Rafael , da Silva Caio Mateus , Neri Elida A. , Valadão Iuri C. , Turaça Lauro Thiago , Lima Vanessa M. , de Carvalho Mariana Lombardi Peres , Velho Mariliza R. , Sobie Eric A. , Krieger Jose E. 
Published: September 2022

Abstract
Background
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising disease model, even though hiPSC-CMs cultured for extended periods display an undifferentiated transcriptional landscape. MiRNA–target gene interactions contribute to fine-tuning the genetic program governing cardiac maturation and may uncover critical pathways to be targeted.

Methods
We analyzed a hiPSC-CM public dataset to identify time-regulated miRNA–target gene interactions based on three logical steps of filtering. We validated this process in silico using 14 human and mouse public datasets, and further confirmed the findings by sampling seven time points over a 30-day protocol with a hiPSC-CM clone developed in our laboratory. We then added miRNA mimics from the top eight miRNAs candidates in three cell clones in two different moments of cardiac specification and maturation to assess their impact on differentiation characteristics including proliferation, sarcomere structure, contractility, and calcium handling.

Results
We uncovered 324 interactions among 29 differentially expressed genes and 51 miRNAs from 20,543 transcripts through 120 days of hiPSC-CM differentiation and selected 16 genes and 25 miRNAs based on the inverse pattern of expression (Pearson R-values < − 0.5) and consistency in different datasets. We validated 16 inverse interactions among eight genes and 12 miRNAs (Person R-values < − 0.5) during hiPSC-CMs differentiation and used miRNAs mimics to verify proliferation, structural and functional features related to maturation. We also demonstrated that miR-124 affects Ca2+ handling altering features associated with hiPSC-CMs maturation.

Conclusion
We uncovered time-regulated transcripts influencing pathways affecting cardiac differentiation/maturation axis and showed that the top-scoring miRNAs indeed affect primarily structural features highlighting their role in the hiPSC-CM maturation.
From theory to experiment: transformer-based generation enables rapid discovery of novel reactions
Authors: Wang Xinqiao , Yao Chuansheng , Zhang Yun , Yu Jiahui , Qiao Haoran , Zhang Chengyun , Wu Yejian , Bai Renren , Duan Hongliang 
Published: September 2022

AbstractDeep learning methods, such as reaction prediction and retrosynthesis analysis, have demonstrated their significance in the chemical field. However, the de novo generation of novel reactions using artificial intelligence technology requires further exploration. Inspired by molecular generation, we proposed a novel task of reaction generation. Herein, Heck reactions were applied to train the transformer model, a state-of-art natural language process model, to generate 4717 reactions after sampling and processing. Then, 2253 novel Heck reactions were confirmed by organizing chemists to judge the generated reactions. More importantly, further organic synthesis experiments were performed to verify the accuracy and feasibility of representative reactions. The total process, from Heck reaction generation to experimental verification, required only 15 days, demonstrating that our model has well-learned reaction rules in-depth and can contribute to novel reaction discovery and chemical space exploration.
Multiple-site decontamination regimen decreases acquired infection incidence in mechanically ventilated COVID-19 patients
Authors: Massart Nicolas , Reizine Florian , Fillatre Pierre , Seguin Philippe , La Combe Béatrice , Frerou Aurélien , Egreteau Pierre-Yves , Hourmant Baptiste , Kergoat Pierre , Lorber Julien , Souchard Jerome , Canet Emmanuel , Rieul Guillaume , Fedun Yannick , Delbove Agathe , Camus Christophe 
Published: September 2022

Abstract
Background
Among strategies that aimed to prevent acquired infections (AIs), selective decontamination regimens have been poorly studied in the COVID-19 setting. We assessed the impact of a multiple-site decontamination (MSD) regimen on the incidence of bloodstream infections (BSI) and ventilator-associated pneumonia (VAP) in COVID-19 patients receiving mechanical ventilation.

Methods
We performed an ancillary analysis of a multicenter retrospective observational study in 15 ICUs in western France. In addition to standard-care (SC), 3 ICUs used MSD, a variant of selective digestive decontamination, which consists of the administration of topical antibiotics four times daily in the oropharynx and the gastric tube, chlorhexidine body wash and a 5-day nasal mupirocin course. AIs were compared between the 3 ICUs using MSD (MSD group) and the 12 ICUs using SC.

Results
During study period, 614 of 1158 COVID-19 patients admitted in our ICU were intubated for at least 48 h. Due to missing data in 153 patients, 461 patients were finally included of whom 89 received MSD. There were 34 AIs in the MSD group (2117 patient-days), as compared with 274 AIs in the SC group (8957 patient-days) (p < 0.001). MSD was independently associated with a lower risk of AI (IRR = 0.56 [0.38–0.83]; p = 0.004) (Table 2). When the same model was used for each site of infection, MSD remained independently associated with a lower risk of VAP (IRR = 0.52 [0.33–0.89]; p = 0.005) but not of BSI (IRR = 0.58, [0.25–1.34], p = 0.21). Hospital mortality was lower in the MSD group (16.9% vs 30.1%, p = 0.017).

Conclusions
In ventilated COVID-19 patients, MSD was independently associated with lower AI incidence.