bluuebunny/crossref_metadata_2025_split huggingface dataset:
A CRISPR interference strategy for gene expression silencing in multiple myeloma cell lines
Authors: Escrivá-Fernández Josep , Cueto-Ureña Cristina , Solana-Orts Amalia , Lledó Elisa , Ballester-Lurbe Begoña , Poch Enric 
Published: May 2023

Abstract
Background
Multiple myeloma (MM) is the second most common hematologic neoplasm which is characterized by proliferation and infiltration of plasmatic cells in the bone marrow. Currently, MM is considered incurable due to resistance to treatment. The CRISPR/Cas9 system has emerged as a powerful tool for understanding the role of different genetic alterations in the pathogenesis of hematologic malignancies in both cell lines and mouse models. Despite current advances of gene editing tools, the use of CRISPR/Cas9 technology for gene editing of MM have not so far been extended. In this work, we want to repress Rnd3 expression, an atypical Rho GTPase involved in several cellular processes, in MM cell lines using a CRISPR interference strategy.

Results
We have designed different guide RNAs and cloning them into a lentiviral plasmid, which contains all the machinery necessary for developing the CRISPR interference strategy. We co-transfected the HEK 293T cells with this lentiviral plasmid and 3rd generation lentiviral envelope and packaging plasmids to produce lentiviral particles. The lentiviral particles were used to transduce two different multiple myeloma cell lines, RPMI 8226 and JJN3, and downregulate Rnd3 expression. Additionally, the impact of Rnd3 expression absence was analyzed by a transcriptomic analysis consisting of 3’ UTR RNA sequencing. The Rnd3 knock-down cells showed a different transcriptomic profile in comparison to control cells.

Conclusions
We have developed a CRISPR interference strategy to generate stable Rnd3 knockdown MM cell lines by lentiviral transduction. We have evaluated this strategy in two MM cell lines, and we have demonstrated that Rnd3 silencing works both at transcriptional and protein level. Therefore, we propose CRISPR interference strategy as an alternative tool to silence gene expression in MM cell lines. Furthermore, Rnd3 silencing produces changes in the cellular transcriptomic profile.
Functional characterization of age-dependent p16 epimutation reveals biological drivers and therapeutic targets for colorectal cancer
Authors: Yang Li , Chen Xiaomin , Lee Christy , Shi Jiejun , Lawrence Emily B. , Zhang Lanjing , Li Yumei , Gao Nan , Jung Sung Yun , Creighton Chad J. , Li Jingyi Jessica , Cui Ya , Arimura Sumimasa , Lei Yunping , Li Wei , Shen Lanlan 
Published: May 2023

AbstractBackgroundMethylation of thep16promoter resulting in epigenetic gene silencing—known asp16epimutation—is frequently found in human colorectal cancer and is also common in normal-appearing colonic mucosa of aging individuals. Thus, to improve clinical care of colorectal cancer (CRC) patients, we explored the role of age-relatedp16epimutation in intestinal tumorigenesis.MethodsWe established a mouse model that replicates two common genetic and epigenetic events observed in human CRCs:Apcmutation andp16epimutation. We conducted long-term survival and histological analysis of tumor development and progression. Colonic epithelial cells and tumors were collected from mice and analyzed by RNA sequencing (RNA-seq), quantitative PCR, and flow cytometry. We performed single-cell RNA sequencing (scRNA-seq) to characterize tumor-infiltrating immune cells throughout tumor progression. We tested whether anti-PD-L1 immunotherapy affects overall survival of tumor-bearing mice and whether inhibition of both epigenetic regulation and immune checkpoint is more efficacious.ResultsMice carrying combinedApcmutation andp16epimutation had significantly shortened survival and increased tumor growth compared to those withApcmutation only. Intriguingly, colon tumors withp16epimutation exhibited an activated interferon pathway, increased expression of programmed death-ligand 1 (Pdl1), and enhanced infiltration of immune cells. scRNA-seq further revealed the presence ofFoxp3+Tregs and γδT17 cells, which contribute to an immunosuppressive tumor microenvironment (TME). Furthermore, we showed that a combined therapy using an inhibitor of DNA methylation and a PD-L1 immune checkpoint inhibitor is more effective for improving survival in tumor-bearing mice than blockade of either pathway alone.ConclusionsOur study demonstrated that age-dependentp16epimutation creates a permissive microenvironment for malignant transformation of polyps to colon cancer. Our findings provide a mechanistic rationale for future targeted therapy in patients withp16epimutation.
Quality of life in children undergoing tonsillectomy: a cross-sectional survey
Authors: Zhou Ying , Peng Mingqi , Zhou Jing 
Published: May 2023

AbstractBackgroundThe quality of life in children undergoing tonsillectomy remains unclear. We aimed to analyze the current status and influencing factors of quality of life in children undergoing tonsillectomy, to provide useful insights to clinical postoperative care for children.MethodsChildren who underwent tonsillectomy in our hospital from June 1, 2021 to October 31, 2022 were selected. The characteristics of children were collected and Paediatric Quality of Life Inventory Version 4.0 (PedsQL™ 4.0) was used for evaluating the quality of life in children. Pearson correlation, univariate and logistic regression analyses were condcuted to evaluate the influencing factors of quality of life in children undergoing tonsillectomy.ResultsA total of 118 children undergoing tonsillectomy were included. The total score of PedsQL™ 4.0 in children undergoing tonsillectomy was (70.28 ± 13.15). Pearson correlation analyses indicated that age(r = 0.586), courses of tonsillitis(r = 0.595), parental education level(r = 0.612) and monthly family income(r = 0.608) were associated with the PedsQL™ 4.0 total score in children undergoing tonsillectomy (all P < 0.05). Logistic regression analyses indicated that age ≤ 5y (OR = 2.009,95%CI: 1.826 ~ 2.401), courses of tonsillitis ≥ 3years (OR = 2.167,95%CI: 1.688 ~ 2.547), high school of parental education level (OR = 1.807,95%CI: 1.224 ~ 2.181) and monthly family income ≤ 5000 RMB(OR = 2.624,95%CI:2.092 ~ 3.077) were the independent influencing factors of quality of life in children with undergoing tonsillectomy (all P < 0.05).ConclusionsThe quality of life of children after tonsillectomy is not high, and the quality of life of children is affected by many factors. Medical staff should take early targeted nursing countermeasures tageted on those influencing factors to improve the quality of life of children.
Utility of eConsults for COVID-19 vaccine-related concerns in Ontario: a cross-sectional analysis
Authors: Walter Graham , Jeimy Samira , Liddy Clare , Guglani Sheena , Ellis Anne K. , Blair Amy , Kobayaa Hazar , Chad Zave , Keely Erin 
Published: May 2023

Abstract
Background
The Champlain BASE™ and Ontario eConsult services are virtual platforms that serve to facilitate contact between primary care providers and specialists across Ontario, relaying patient-specific questions to relevant specialists via a secure web-based platform. Despite ample evidence regarding the general effectiveness of these platforms, their utility as it pertains to clinical concerns regarding COVID-19 vaccines has not yet been explored.

Methods
We performed a cross-sectional descriptive analysis of COVID-19 vaccine related eConsults on Ontario patients completed by five allergy specialists between February and October of 2021. 4318 COVID-19 vaccine-related eConsults were completed in total during this time; with 1857 completed by the five allergists participating in this analysis. Question types/content were categorized using a taxonomy developed through consensus on a weighted monthly sample of 499 total cases. Data regarding whether external resources were required to answer each eConsult, impact on primary care provider referral decisions, and allergy consultant response times were collected. A 2-question survey was completed by primary care providers following eConsultation and results were collected.

Results
41.08% of eConsults received involved safety concerns regarding COVID-19 vaccine administration in the setting of prior allergic disease and another 36.1% involved a potential reaction the first dose of a COVID-19 vaccine. 72.1% of eConsults were answered by specialist without needing external resources, and only 9.8% of all eConsults received resulted in a recommendation for formal in-person referral to Clinical Immunology & Allergy specialist or another subspecialty. Average time to complete eConsult was 16.4 min, and 79.7% of PCP eConsult queries which would have traditionally resulted in formal consultation were resolved based on advice provided in the eConsult without need for in-person assessment.

Conclusions
Our study demonstrates the utility of the eConsult service as it pertains to COVID-19 vaccine-related concerns. The eConsult platform proved an effective tool in diverting the need for in-person assessment by an Allergist or other medical specialty. This is significant given the large volume of eConsults completed by Allergists, and demonstrates the impact of an effective electronic delivery of care model during a time of strained resources and public health efforts directed at mass vaccination.
COVID-19 risk perception and vaccine acceptance in individuals with self-reported chronic respiratory or autoimmune conditions
Authors: Smith Brianna A. , Ricotta Emily E. , Kwan Jennifer L. , Evans Nicholas G. 
Published: May 2023

Abstract
Background
COVID-19 disproportionately affects those with preexisting conditions, but little research has determined whether those with chronic diseases view the pandemic itself differently - and whether there are differences between chronic diseases. We theorized that while individuals with respiratory disease or autoimmune disorders would perceive greater threat from COVID-19 and be more supportive of non-pharmaceutical interventions (NPIs), those with autoimmune disorders would be less likely to support vaccination-based interventions.

Methods
We conducted a two-wave online survey conducted in February and November 2021 asking respondents their beliefs about COVID-19 risk perception, adoption and support of interventions, willingness to be vaccinated against COVID-19, and reasons for vaccination. Regression analysis was conducted to assess the relationship of respondents reporting a chronic disease and COVID-19 behaviors and attitudes, compared to healthy respondents adjusting for demographic and political factors.

Results
In the initial survey, individuals reporting a chronic disease had both stronger feelings of risk from COVID-19 as well as preferences for NPIs than healthy controls. The only NPI that was still practiced significantly more compared to healthy controls in the resample was limiting trips outside of the home. Support for community-level NPIs was higher among individuals reporting a chronic disease than healthy controls and remained high among those with respiratory diseases in sample 2. Vaccine acceptance produced more divergent results: those reporting chronic respiratory diseases were 6% more willing to be vaccinated than healthy controls, while we found no significant difference between individuals with autoimmune diseases and healthy controls. Respondents with chronic respiratory disease and those with autoimmune diseases were more likely to want to be vaccinated to protect themselves from COVID-19, and those with an autoimmune disease were more likely to report fear of a bad vaccine reaction as the reason for vaccine hesitancy. In the resample, neither those with respiratory diseases nor autoimmune diseases reported being more willing to receive a booster vaccine than healthy controls.

Conclusions
It is not enough to recognize the importance of health in determining attitudes: nuanced differences between conditions must also be recognized.
CheckList for EvaluAtion of Radiomics research (CLEAR): a step-by-step reporting guideline for authors and reviewers endorsed by ESR and EuSoMII
Authors: Kocak Burak , Baessler Bettina , Bakas Spyridon , Cuocolo Renato , Fedorov Andrey , Maier-Hein Lena , Mercaldo Nathaniel , Müller Henning , Orlhac Fanny , Pinto dos Santos Daniel , Stanzione Arnaldo , Ugga Lorenzo , Zwanenburg Alex 
Published: May 2023

AbstractEven though radiomics can hold great potential for supporting clinical decision-making, its current use is mostly limited to academic research, without applications in routine clinical practice. The workflow of radiomics is complex due to several methodological steps and nuances, which often leads to inadequate reporting and evaluation, and poor reproducibility. Available reporting guidelines and checklists for artificial intelligence and predictive modeling include relevant good practices, but they are not tailored to radiomic research. There is a clear need for a complete radiomics checklist for study planning, manuscript writing, and evaluation during the review process to facilitate the repeatability and reproducibility of studies. We here present a documentation standard for radiomic research that can guide authors and reviewers. Our motivation is to improve the quality and reliability and, in turn, the reproducibility of radiomic research. We name the checklist CLEAR (CheckList for EvaluAtion of Radiomics research), to convey the idea of being more transparent. With its 58 items, the CLEAR checklist should be considered a standardization tool providing the minimum requirements for presenting clinical radiomics research. In addition to a dynamic online version of the checklist, a public repository has also been set up to allow the radiomics community to comment on the checklist items and adapt the checklist for future versions. Prepared and revised by an international group of experts using a modified Delphi method, we hope the CLEAR checklist will serve well as a single and complete scientific documentation tool for authors and reviewers to improve the radiomics literature.
Automatic differentiation of ruptured and unruptured intracranial aneurysms on computed tomography angiography based on deep learning and radiomics
Authors: Feng Junbang , Zeng Rong , Geng Yayuan , Chen Qiang , Zheng Qingqing , Yu Fei , Deng Tie , Lv Lei , Li Chang , Xue Bo , Li Chuanming 
Published: May 2023

Abstract
Objectives
Rupture of intracranial aneurysm is very dangerous, often leading to death and disability. In this study, deep learning and radiomics techniques were used to automatically detect and differentiate ruptured and unruptured intracranial aneurysms.

Materials and methods
363 ruptured aneurysms and 535 unruptured aneurysms from Hospital 1 were included in the training set. 63 ruptured aneurysms and 190 unruptured aneurysms from Hospital 2 were used for independent external testing. Aneurysm detection, segmentation and morphological features extraction were automatically performed with a 3-dimensional convolutional neural network (CNN). Radiomic features were additionally computed via pyradiomics package. After dimensionality reduction, three classification models including support vector machines (SVM), random forests (RF), and multi-layer perceptron (MLP) were established and evaluated via area under the curve (AUC) of receiver operating characteristics. Delong tests were used for the comparison of different models.

Results
The 3-dimensional CNN automatically detected, segmented aneurysms and calculated 21 morphological features for each aneurysm. The pyradiomics provided 14 radiomics features. After dimensionality reduction, 13 features were found associated with aneurysm rupture. The AUCs of SVM, RF and MLP on the training dataset and external testing dataset were 0.86, 0.85, 0.90 and 0.85, 0.88, 0.86, respectively, for the discrimination of ruptured and unruptured intracranial aneurysms. Delong tests showed that there was no significant difference among the three models.

Conclusions
In this study, three classification models were established to distinguish ruptured and unruptured aneurysms accurately. The aneurysms segmentation and morphological measurements were performed automatically, which greatly improved the clinical efficiency.

Clinical relevance statement
Our fully automatic models could rapidly process the CTA data and evaluate the status of aneurysms in one minute.

Graphical Abstract
Mesenchymal stromal cell-derived secretome-based therapy for neurodegenerative diseases: overview of clinical trials
Authors: Ghasemi Maryam , Roshandel Elham , Mohammadian Mozhdeh , Farhadihosseinabadi Behrouz , Akbarzadehlaleh Parvin , Shamsasenjan Karim 
Published: May 2023

AbstractBackgroundOver the past few years, mesenchymal stromal cells (MSCs) have attracted a great deal of scientific attention owing to their promising results in the treatment of incurable diseases. However, there are several concerns about their possible side effects after direct cell transplantation, including host immune response, time-consuming cell culture procedures, and the dependence of cell quality on the donor, which limit the application of MSCs in clinical trials. On the other hand, it is well accepted that the beneficial effects of MSCs are mediated by secretome rather than cell replacement. MSC secretome refers to a variety of bioactive molecules involved in different biological processes, specifically neuro-regeneration.Main bodyDue to the limited ability of the central nervous system to compensate for neuronal loss and relieve disease progress, mesenchymal stem cell products may be used as a potential cure for central nervous system disorders. In the present study, the therapeutic effects of MSC secretome were reviewed and discussed the possible mechanisms in the three most prevalent central nervous system disorders, namely Alzheimer's disease, multiple sclerosis, and Parkinson's disease. The current work aimed to help discover new medicine for the mentioned complications.ConclusionThe use of MSC-derived secretomes in the treatment of the mentioned diseases has encouraging results, so it can be considered as a treatment option for which no treatment has been introduced so far.
Efficacy and safety of human umbilical cord-derived mesenchymal stem cells for COVID-19 pneumonia: a meta-analysis of randomized controlled trials
Authors: Liu Qinxue , Ma Fengjie , Zhong Yizhi , Wang Gaojian , Hu Li , Zhang Yaping , Xie Junran 
Published: May 2023

AbstractBackgroundElevated levels of inflammatory factors are associated with poor prognosis in coronavirus disease-19 (COVID-19). However, mesenchymal stem cells (MSCs) have immunomodulatory functions. Accordingly, this meta-analysis aimed to determine the efficacy and safety of MSC-based therapy in patients with COVID-19 pneumonia.MethodsOnline global databases were used to find relevant studies. Two independent researchers then selected and evaluated the studies for suitability while the Cochrane risk of bias tool determined the quality of all articles and Cochran's Q test and I2index assessed the degree of heterogeneity in the principal studies. Statistical analysis was performed using Review Manager software, and the effect of each study on the overall estimate was evaluated by sensitivity analysis.ResultsSeven studies were included in the meta-analysis, and all MSCs used in the trials were acquired from the umbilical cord. The results of these studies (n = 328) indicated that patients with COVID-19 pneumonia who received MSCs had a 0.58 risk of death compared with controls (95% CI = 0.38, 0.87; P = 0.53; I2 = 0%). In terms of inflammatory biomarkers, MSCs reduced the levels of C-reactive protein (n = 88; MD =  − 32.49; 95% CI =  − 48.43, − 16.56; P = 0.46; I2 = 0%) and interferon-gamma (n = 44; SMD =  − 1.23; 95% CI =  − 1.89, − 0.57; P = 0.37; I2 = 0%) in severe COVID-19 patients but had no significant effect on interleukin-6 (n = 185; MD =  − 0.75; 95% CI =  − 7.76, 6.27; P = 0.57; I2 = 0%). A summary of the data revealed no significant differences in adverse events (n = 287) or serious adverse events (n = 229) between the MSC and control groups.ConclusionsInfusion of umbilical cord-derived MSCs is an effective strategy for treating patients with COVID-19 pneumonia, with no noticeable adverse effects.
Comparison of therapeutic effects of mesenchymal stem cells derived from superficial and deep subcutaneous adipose tissues
Authors: Ishiuchi Naoki , Nakashima Ayumu , Maeda Satoshi , Miura Yoshie , Miyasako Kisho , Sasaki Kensuke , Uchiki Toshio , Sasaki Ayano , Nagamatsu Shogo , Nakao Naoki , Nagao Masataka , Masaki Takao 
Published: May 2023

Abstract
Background
Fibrosis is a common histological feature in the process from chronic organ injury to organ failure. Chronic tissue injury causes inflammatory cell infiltration into the injured tissue. The persistence of this inflammatory cell infiltration leads to fibrosis and organ failure. Adipose-derived mesenchymal stem cells (ASCs) have received much attention as a regenerative therapeutic tool to prevent progression from organ injury to failure. Subcutaneous abdominal adipose tissue is divided into superficial and deep layers by a superficial fascia. Adipose tissue easily collected by liposuction is usually obtained from a deep layer, so ASCs derived from a deep layer are generally used for regenerative medicine. However, no research has been conducted to investigate differences in the therapeutic effects of ASCs from the superficial and deep layers (Sup-ASCs and Deep-ASCs, respectively). Therefore, we compared the therapeutic potencies of Sup-ASCs and Deep-ASCs.

Methods
ASCs were isolated from superficial and deep subcutaneous abdominal adipose tissues collected from patients who underwent breast reconstruction. We first compared cell characteristics, such as morphology, cell proliferation, cell surface markers, adipogenic and osteogenic differentiation, cell senescence markers, and expression of coagulation and anticoagulant factors between Sup-ASCs and Deep-ASCs. Furthermore, we compared their ability to promote polarization of M2 macrophages and to inhibit transforming growth factor (TGF)-β/Smad signaling using THP-1 cells and TGF-β1 stimulated HK-2 cells incubated with conditioned media from Sup-ASCs or Deep-ASCs. In in vivo experiments, after renal ischemia–reperfusion injury (IRI) procedure, Sup-ASCs or Deep-ASCs were injected through the abdominal aorta. At 21 days post-injection, the rats were sacrificed and their left kidneys were collected to evaluate fibrosis. Finally, we performed RNA-sequencing analysis of Sup-ASCs and Deep-ASCs.

Results
Sup-ASCs had greater proliferation and adipogenic differentiation compared with Deep-ASCs, whereas both ASC types had similar morphology, cell surface markers, senescence markers, and expression of coagulation and anticoagulant factors. Conditioned media from Sup-ASCs and Deep-ASCs equally promoted polarization of M2 macrophages and suppressed TGF-β/Smad signaling. Moreover, administration of Sup-ASCs and Deep-ASCs equally ameliorated renal fibrosis induced by IRI in rats. RNA-sequencing analysis revealed no significant difference in the expression of genes involved in anti-inflammatory and anti-fibrotic effects between Sup-ASCs and Deep-ASCs.

Conclusions
These results indicate that both Sup-ASCs and Deep-ASCs can be used effectively and safely as an intravascular ASC therapy for organ injury.