bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRAF3 suppression encourages B cell recruitment and prolongs survival of microbiome-intact mice with ovarian cancer
Authors: Zorea Jonathan , Motro Yair , Mazor Roei D. , Carmi Yifat Koren , Shulman Ziv , Mahajna Jamal , Moran-Gilad Jacob , Elkabets Moshe 
Published: May 2023

Abstract
Background
Ovarian cancer (OC) is known for exhibiting low response rates to immune checkpoint inhibitors that activate T cells. However, immunotherapies that activate B cells have not yet been extensively explored and may be a potential target, as B cells that secrete immunoglobulins have been associated with better outcomes in OC. Although the secretion of immunoglobulins is often mediated by the microbiome, it is still unclear what role they play in limiting the progression of OC.

Methods
We conducted an in-vivo CRISPR screen of immunodeficient (NSG) and immune-intact wild type (WT) C57/BL6 mice to identify tumor-derived immune-escape mechanisms in a BRAC1- and TP53-deficient murine ID8 OC cell line (designated ITB1). To confirm gene expression and signaling pathway activation in ITB1 cells, we employed western blot, qPCR, immunofluorescent staining, and flow cytometry. Flow cytometry was also used to identify immune cell populations in the peritoneum of ITB1-bearing mice. To determine the presence of IgA-coated bacteria in the peritoneum of ITB1-bearing mice and the ascites of OC patients, we employed 16S sequencing. Testing for differences was done by using Deseq2 test and two-way ANOVA test. Sequence variants (ASVs) were produced in Qiime2 and analyzed by microeco and phyloseq R packages.

Results
We identified tumor necrosis factor receptor-associated factor 3 (TRAF3) as a tumor-derived immune suppressive mediator in ITB1 cells. Knockout of TRAF3 (TRAF3KO) activated the type-I interferon pathway and increased MHC-I expression. TRAF3KO tumors exhibited a growth delay in WT mice vs. NSG mice, which was correlated with increased B cell infiltration and activation compared to ITB1 tumors. B cells were found to be involved in the progression of TRAF3KO tumors, and B-cell surface-bound and secreted IgA levels were significantly higher in the ascites of TRAF3KO tumors compared to ITB1. The presence of commensal microbiota was necessary for B-cell activation and for delaying the progression of TRAF3KO tumors in WT mice. Lastly, we observed unique profiles of IgA-coated bacteria in the ascites of OC-bearing mice or the ascites of OC patients.

Conclusions
TRAF3 is a tumor-derived immune-suppressive modulator that influences B-cell infiltration and activation, making it a potential target for enhancing anti-tumor B-cell responses in OC.
The efficacy and safety of fluconazole in preventing invasive fungal infection in very low birth weight infants: a systematic review and meta-analysis
Authors: Xie Jinghong , Zeng Jiayue , Zheng Shouyan 
Published: April 2023

AbstractThis meta-analysis aimed to assess the efficacy and safety of fluconazole for the prevention of invasive fungal infections (IFI) in very low birth weight infants (VLBWI) and to provide a basis for the clinical use. A detailed search of Pubmed, Embase, Cochrane Library and other databases was performed to carefully screen eligible randomized controlled clinical studies to assess the safety and efficacy of fluconazole in very low birth weight infants in terms of the incidence of invasive fungal infections, fungal colonization rate, and mortality. Our research indicated that the application of fluconazole did not result in intolerable adverse reactions in patients. Fluconazole is effective in preventing invasive fungal infections in very low birth weight infants without serious adverse effects. The dose and frequency of fluconazole in very low birth weight infants still needs to be evaluated in consequent studies.
Evaluation of the efficacy of HEMO2life®, a marine OXYgen carrier for Organ Preservation (OxyOp2) in renal transplantation: study protocol for a multicenter randomized trial
Authors: Le Meur Yannick , Nowak Emmanuel , Barrou Benoit , Thierry Antoine , Badet Lionel , Buchler Matthias , Rerolle Jean-Philippe , Golbin Leonard , Duveau Agnès , Dantal Jacques , Merville Pierre , Kamar Nassim , Demini Leïla , Zal Franck 
Published: May 2023

Abstract
Background
Preventing ischemia‒reperfusion injury (IRI) is a major issue in kidney transplantation, particularly for transplant recipients receiving a kidney from extended criteria donors (ECD). The main consequence of IRI is delayed graft function (DGF). Hypoxia is one of the key factors in IRI, suggesting that the use of an oxygen carrier as an additive to preservation solution may be useful. In the OxyOp trial, we showed that the organs preserved using the oxygen carrier HEMO2life® displayed significantly less DGF. In the OxyOp2 trial, we aim to definitively test and quantify the efficacy of HEMO2life® for organ preservation in a large population of kidney grafts.

Methods
OxyOp2 is a prospective, multicenter, randomized, comparative, single-blinded, parallel-group study versus standard of care in renal transplantation. After the selection of a suitable donor according to the inclusion/exclusion criteria, both kidneys will be used in the study. Depending on the characteristics of the donor, both kidneys will be preserved either in static cold storage (standard donors) or on machine perfusion (for ECD and deceased-after-cardiac-death donors (DCD)). The kidneys resulting from one donor will be randomized: one to the standard-of-care arm (organ preserved in preservation solution routinely used according to the local practice) and the other to the active treatment arm (HEMO2life® on top of routinely used preservation solution). HEMO2life® will be used for ex vivo graft preservation at a dose of 1 g/l preservation solution. The primary outcome is the occurrence of DGF, defined as the need for renal replacement therapy during the first week after transplantation.

Discussion
The use of HEMO2life® in preservation solutions is a novel approach allowing, for the first time, the delivery of oxygen to organs. Improving graft survival by limiting ischemic lesions is a major public-health goal in the field of organ transplantation.

Trial registration
ClinicalTrials.gov, ID: NCT04181710. registered on November 29, 2019.
Exploring implementation outcomes in the clinical trial context: a qualitative study of physician trial stakeholders
Authors: Stensland Kristian D. , Sales Anne E. , Vedapudi Varsha K. , Damschroder Laura J. , Skolarus Ted A. 
Published: April 2023

Abstract
Introduction
Cancer clinical trials can be considered evidence-based interventions with substantial benefits, but suffer from poor implementation leading to low enrollment and frequent failure. Applying implementation science approaches such as outcomes frameworks to the trial context could aid in contextualizing and evaluating trial improvement strategies. However, the acceptability and appropriateness of these adapted outcomes to trial stakeholders are unclear. For these reasons, we interviewed cancer clinical trial physician stakeholders to explore how they perceive and address clinical trial implementation outcomes.

Methods
We purposively selected 15 cancer clinical trial physician stakeholders from our institution representing different specialties, trial roles, and trial sponsor types. We performed semi-structured interviews to explore a previous adaptation of Proctor’s Implementation Outcomes Framework to the clinical trial context. Emergent themes from each outcome were developed.

Results
The implementation outcomes were well understood and applicable (i.e., appropriate and acceptable) to clinical trial stakeholders. We describe cancer clinical trial physician stakeholder understanding of these outcomes and current application of these concepts. Trial feasibility and implementation cost were felt to be most critical to trial design and implementation. Trial penetration was most difficult to measure, primarily due to eligible patient identification. In general, we found that formal methods for trial improvement and trial implementation evaluation were poorly developed. Cancer clinical trial physician stakeholders referred to some design and implementation techniques used to improve trials, but these were infrequently formally evaluated or theory-based.

Conclusion
Implementation outcomes adapted to the trial context were acceptable and appropriate to cancer clinical trial physician stakeholders. Use of these outcomes could facilitate the evaluation and design of clinical trial improvement interventions. Additionally, these outcomes highlight potential areas for the development of new tools, for example informatics solutions, to improve the evaluation and implementation of clinical trials.
Epigenetic modifier alpha-ketoglutarate modulates aberrant gene body methylation and hydroxymethylation marks in diabetic heart
Authors: Dhat Rohini , Mongad Dattatray , Raji Sivarupa , Arkat Silpa , Mahapatra Nitish R. , Singhal Nishant , Sitasawad Sandhya L. 
Published: April 2023

Abstract
Background
Diabetic cardiomyopathy (DCM) is a leading cause of death in diabetic patients. Hyperglycemic myocardial microenvironment significantly alters chromatin architecture and the transcriptome, resulting in aberrant activation of signaling pathways in a diabetic heart. Epigenetic marks play vital roles in transcriptional reprogramming during the development of DCM. The current study is aimed to profile genome-wide DNA (hydroxy)methylation patterns in the hearts of control and streptozotocin (STZ)-induced diabetic rats and decipher the effect of modulation of DNA methylation by alpha-ketoglutarate (AKG), a TET enzyme cofactor, on the progression of DCM.

Methods
Diabetes was induced in male adult Wistar rats with an intraperitoneal injection of STZ. Diabetic and vehicle control animals were randomly divided into groups with/without AKG treatment. Cardiac function was monitored by performing cardiac catheterization. Global methylation (5mC) and hydroxymethylation (5hmC) patterns were mapped in the Left ventricular tissue of control and diabetic rats with the help of an enrichment-based (h)MEDIP-sequencing technique by using antibodies specific for 5mC and 5hmC. Sequencing data were validated by performing (h)MEDIP-qPCR analysis at the gene-specific level, and gene expression was analyzed by qPCR. The mRNA and protein expression of enzymes involved in the DNA methylation and demethylation cycle were analyzed by qPCR and western blotting. Global 5mC and 5hmC levels were also assessed in high glucose-treated DNMT3B knockdown H9c2 cells.

Results
We found the increased expression of DNMT3B, MBD2, and MeCP2 with a concomitant accumulation of 5mC and 5hmC, specifically in gene body regions of diabetic rat hearts compared to the control. Calcium signaling was the most significantly affected pathway by cytosine modifications in the diabetic heart. Additionally, hypermethylated gene body regions were associated with Rap1, apelin, and phosphatidyl inositol signaling, while metabolic pathways were most affected by hyperhydroxymethylation. AKG supplementation in diabetic rats reversed aberrant methylation patterns and restored cardiac function. Hyperglycemia also increased 5mC and 5hmC levels in H9c2 cells, which was normalized by DNMT3B knockdown or AKG supplementation.

Conclusion
This study demonstrates that reverting hyperglycemic damage to cardiac tissue might be possible by erasing adverse epigenetic signatures by supplementing epigenetic modulators such as AKG along with an existing antidiabetic treatment regimen.
COVID-19 cases reported in Colorado following screening at selected US airports, January – July 2020
Authors: Shaum Anna , Harlow Tye , Gulati Reena K. , Berro Andre , House Jennifer 
Published: April 2023

Abstract
Objective
We sought to estimate the proportion of air travelers who may have been infected with SARS-CoV-2 upon arrival to Colorado by comparing data on Colorado residents screened upon entering the US to COVID-19 cases reported in the state. Data on Colorado’s screened passengers arriving into the US between January 17 and July 30, 2020 were compared to Colorado’s Electronic Disease Reporting System. We conducted a descriptive analysis of true matches, including age, gender, case status, symptom status, time from arrival to symptom onset (days), and time from arrival to specimen collection date (days).

Results
Fourteen confirmed COVID-19 cases in travelers who were diagnosed within 14 days after arriving in Colorado were matched to the 8,272 travelers who underwent screening at 15 designated airports with a recorded destination of Colorado, or 0.2%. Most (N = 13/14 or 93%) of these infected travelers arrived in Colorado in March 2020; 12 (86%) of them were symptomatic. Entry screening for COVID-19 and the sharing of traveler information with the Colorado Department of Public Health and Environment appeared to identify few cases early in the pandemic. Symptom-based entry screening and sharing of traveler information was minimally effective at decreasing travel-associated COVID-19 transmission.
Bilateral pneumothorax in a patient with angiosarcoma of the scalp: a case report
Authors: Vaqar Maham , Sharif Ayesha , Iqbal Nousheen , Irfan Muhammad 
Published: May 2023

Abstract
Background
Angiosarcoma is a rare, vascular malignancy that arises from endothelial cells of blood vessels. This case report aims to create the awareness of its existence in the region and its mode of presentation.

Case presentation
A 63-year-old Pakistani man presented to the emergency department with sudden bilateral chest pain and shortness of breath for 2 days. On examination, a scalp lesion was seen which had been increasing in size over the last 6 weeks. The lesion was 8 × 10 cm in size with an irregular border, non-tender, violet and dome-shaped in elevation on the right occipito-parietal lobe of the skull. Chest computed tomography (CT) showed multiple cystic lesions on both lungs, patchy areas of ground-glass opacities, nodules of variable sizes and bilateral pneumothorax. Bilateral tube thoracostomy was performed which provided symptomatic relief for shortness of breath. His bronchoalveolar lavage (BAL) was negative for infection. He underwent biopsy of scalp lesion which was positive for aggressive angiosarcoma.

Conclusion
Bilateral spontaneous pneumothorax can be the initial manifestation of aggressive cutaneous angiosarcoma and frequently leads to respiratory failure. Early recognition is essential to prevent delay in diagnosis and management.
Spinocerebellar ataxia type 14 (SCA14) in an Argentinian family: a case report
Authors: Duggirala Niharika , Ngo Kathie J. , Pagnoni Sabrina M. , Rosa Alberto L. , Fogel Brent L. 
Published: April 2023

Abstract
Background
Hereditary spinocerebellar ataxias are a group of genetic neurological disorders that result in degeneration of the cerebellum and brainstem, leading to difficulty in controlling balance and muscle coordination.

Case presentation
A family affected by spinocerebellar ataxia was identified in Argentina and investigated using whole exome sequencing to determine the genetic etiology. The proband, a female white Hispanic aged 48, was noted to have slowly progressive gait ataxia, dysarthria, nystagmus, and moderate cerebellar atrophy. Whole exome sequencing was performed on three affected and two unaffected family members and revealed a dominant pathogenic variant, p.Gln127Arg (19:54392986 A>G), in the protein kinase C gamma gene, and the family was diagnosed with spinocerebellar ataxia type 14.

Conclusions
To our knowledge, no previous cases of spinocerebellar ataxia type 14 have been reported in Argentina, expanding the global presence of this neurological disorder. This diagnosis supports whole exome sequencing as a high-yield method for identifying coding variants causing cerebellar ataxias and emphasizes the importance of broadening the clinical availability of whole exome sequencing for undiagnosed patients and families.
The pluripotent factor OCT4A enhances the self-renewal of human dental pulp stem cells by targeting lncRNA FTX in an LPS-induced inflammatory microenvironment
Authors: Hong Hong , Zeng Kai , Zhou Can , Chen Xiaochuan , Xu Zhezhen , Li Mengjie , Liu Lu , Zeng Qian , Tao Qian , Wei Xi 
Published: April 2023

Abstract
Background
Regulating the pluripotency of human dental pulp stem cells (hDPSCs) is key for the self-repair of injured dental pulp. We previously found that OCT4A promotes the proliferation and odontogenic differentiation of human dental pulp cells (hDPCs). Recent studies have shown the interaction between OCT4A and lncRNAs in pluripotency maintenance of various stem cells. The aim of this study was to explore the underlying roles and mechanisms of OCT4A and its related lncRNAs in the proliferation and multidirectional differentiation of hDPSCs in an inflammatory microenvironment.

Methods
Human lncRNA microarrays were applied to screen out the differentially expressed lncRNAs in hDPSCs between the OCT4A-overexpressing and vector groups. Lipopolysaccharide (LPS) was used to simulate the inflammatory microenvironment. The effects of OCT4A and the lncRNA FTX on the proliferation and multidifferentiation of hDPSCs were observed by the CCK-8 assay, EdU staining, real-time PCR, western blotting, and Alizarin red and oil red O staining. Bioinformatics analysis and chromatin immunoprecipitation (ChIP) assays were performed to clarify the targeted mechanism of OCT4A on FTX. The regulation by FTX of the expression of OCT4A and its downstream pluripotent transcription factors SOX2 and c-MYC was further detected by real-time PCR and western blotting.

Results
The microarray results showed that 978 lncRNAs (250 of which were upregulated and 728 downregulated) were potentially differentially expressed genes (fold change ≥ 2, P < 0.05). LPS stimulation attenuated the self-renewal of hDPSCs. OCT4A enhanced the cell proliferation and multidifferentiation capacities of hDPSCs in an inflammatory microenvironment, while FTX exhibited the opposite effects. OCT4A negatively regulated FTX function by binding to specific regions on the FTX promoter, thereby inhibiting the transcription of FTX. Moreover, overexpression of FTX downregulated the expression of OCT4A, SOX2 and c-MYC, whereas knockdown of FTX facilitated their expression.

Conclusions
OCT4A was found to be a crucial factor maintaining the self-renewal of hDPSCs by transcriptionally targeting FTX in an inflammatory microenvironment. Moreover, we proposed a novel function of FTX in negatively regulating the pluripotency and multilineage differentiation capacity of hDPSCs. The hierarchical organization between OCT4A and FTX expanded the understanding of the network between transcription factors and lncRNAs in fine-tuning the pluripotency/differentiation balance of adult stem cells, and provided prospective targets for optimizing dental-derived stem cell sources for regenerative endodontics.
Semi-automated optimized method to isolate CRISPR/Cas9 edited human pluripotent stem cell clones
Authors: Frank Elie , Cailleret Michel , Nelep Constantin , Fragner Pascal , Polentes Jérome , Herardot Elise , El Kassar Lina , Giraud-Triboult Karine , Monville Christelle , Ben M’Barek Karim 
Published: April 2023

Abstract
Background
CRISPR/Cas9 editing systems are currently used to generate mutations in a particular gene to mimic a genetic disorder in vitro. Such “disease in a dish” models based on human pluripotent stem cells (hPSCs) offer the opportunity to have access to virtually all cell types of the human body. However, the generation of mutated hPSCs remains fastidious. Current CRISPR/Cas9 editing approaches lead to a mixed cell population containing simultaneously non-edited and a variety of edited cells. These edited hPSCs need therefore to be isolated through manual dilution cloning, which is time-consuming, labor intensive and tedious.

Methods
Following CRISPR/Cas9 edition, we obtained a mixed cell population with various edited cells. We then used a semi-automated robotic platform to isolate single cell-derived clones.

Results
We optimized CRISPR/Cas9 editing to knock out a representative gene and developed a semi-automated method for the clonal isolation of edited hPSCs. This method is faster and more reliable than current manual approaches.

Conclusions
This novel method of hPSC clonal isolation will greatly improve and upscale the generation of edited hPSCs required for downstream applications including disease modeling and drug screening.

Graphical Abstract
Immunomodulatory amnion-derived mesenchymal stromal cells preserve muscle function in a mouse model of Duchenne muscular dystrophy
Authors: Nitahara-Kasahara Yuko , Nakayama Soya , Kimura Koichi , Yamaguchi Sho , Kakiuchi Yuko , Nito Chikako , Hayashi Masahiro , Nakaishi Tomoyuki , Ueda Yasuyoshi , Okada Takashi 
Published: April 2023

AbstractBackgroundDuchenne muscular dystrophy (DMD) is an incurable genetic disease characterized by degeneration and necrosis of myofibers, chronic inflammation, and progressive muscle weakness resulting in premature mortality. Immunosuppressive multipotent mesenchymal stromal cell (MSC) therapy could be an option for DMD patients. We focused on amnion-derived mesenchymal stromal cells (AMSCs), a clinically viable cell source owing to their unique characteristics, such as non-invasive isolation, mitotic stability, ethical acceptability, and minimal risk of immune reaction and cancer. We aimed to identify novel immunomodulatory effects of AMSCs on macrophage polarization and their transplantation strategies for the functional recovery of skeletal and cardiac muscles.MethodsWe used flow cytometry to analyze the expression of anti-inflammatory M2 macrophage markers on peripheral blood mononuclear cells (PBMCs) co-cultured with human AMSCs (hAMSCs). hAMSCs were intravenously injected into DMD model mice (mdxmice) to assess the safety and efficacy of therapeutic interventions. hAMSC-treated and untreatedmdxmice were monitored using blood tests, histological examinations, spontaneous wheel-running activities, grip strength, and echocardiography.ResultshAMSCs induced M2 macrophage polarization in PBMCs via prostaglandin E2production. After repeated systemic hAMSC injections,mdxmice exhibited a transient downregulation of serum creatin kinase. Limited mononuclear cell infiltration and a decreased number of centrally nucleated fibers were indicative of regenerated myofibers following degeneration, suggesting an improved histological appearance of the skeletal muscle of hAMSC-treatedmdxmice. Upregulated M2 macrophages and altered cytokine/chemokine expressions were observed in the muscles of hAMSC-treatedmdxmice. During long-term experiments, a significant decrease in the grip strength in controlmdxmice significantly improved in the hAMSC-treatedmdxmice. hAMSC-treatedmdxmice maintained running activity and enhanced daily running distance. Notably, the treated mice could run longer distances per minute, indicating high running endurance. Left ventricular function in DMD mice improved in hAMSC-treatedmdxmice.ConclusionsEarly systemic hAMSC administration inmdxmice ameliorated progressive phenotypes, including pathological inflammation and motor dysfunction, resulting in the long-term improvement of skeletal and cardiac muscle function. The therapeutic effects might be associated with the immunosuppressive properties of hAMSCs via M2 macrophage polarization. This treatment strategy could provide therapeutic benefits to DMD patients.