bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-derived small extracellular vesicles facilitate omental metastasis of ovarian cancer by triggering activation of mesenchymal stem cells
Authors: Gong Lanqing , Li Guoqing , Yi Xiaoqing , Han Qing , Wu Qiulei , Ying Feiquan , Shen Lu , Cao Ying , Liu Xiaoli , Gao Lingling , Li Wenhan , Wang Zehua , Cai Jing 
Published: January 2024

Abstract
Background
Omental metastasis is the major cause of ovarian cancer recurrence and shortens patient survival, which can be largely attributed to the dynamic evolution of the fertile metastatic microenvironment driven by cancer cells. Previously, we found that adipose-derived mesenchymal stem cells (ADSCs) undergoing a phenotype shift toward cancer-associated fibroblasts (CAFs) participated in the orchestrated omental premetastatic niche for ovarian cancer. Here, we aim to elucidate the underlying mechanisms.

Methods
Small extracellular vesicles were isolated from ovarian cancer cell lines (ES-2 and its highly metastatic subline, ES-2-HM) and patient ascites using ultracentrifugation. Functional experiments, including Transwell and EdU assays, and molecular detection, including Western blot, immunofluorescence, and RT–qPCR, were performed to investigate the activation of ADSCs in vitro. High-throughput transcriptional sequencing and functional assays were employed to identify the crucial functional molecules inducing CAF-like activation of ADSCs and the downstream effector of miR-320a. The impact of extracellular vesicles and miR-320a-activated ADSCs on tumor growth and metastasis was assessed in subcutaneous and orthotopic ovarian cancer xenograft mouse models. The expression of miR-320a in human samples was evaluated using in situ hybridization staining.

Results
Primary human ADSCs cocultured with small extracellular vesicles, especially those derived from ES-2-HM, exhibited boosted migration, invasion, and proliferation capacities and elevated α-SMA and FAP levels. Tumor-derived small extracellular vesicles increased α-SMA-positive stromal cells, fostered omental metastasis, and shortened the survival of mice harboring orthotopic ovarian cancer xenografts. miR-320a was abundant in highly metastatic cell-derived extracellular vesicles, evoked dramatic CAF-like transition of ADSCs, targeted the 3′-untranslated region of integrin subunit alpha 7 and attenuated its expression. miR-320a overexpression in ovarian cancer was associated with omental metastasis and shorter survival. miR-320a-activated ADSCs facilitated tumor cell growth and omental metastasis. Depletion of integrin alpha 7 triggered CAF-like activation of ADSCs in vitro.

Conclusions
miR-320a in small extracellular vesicles secreted by tumor cells targets integrin subunit alpha 7 in ADSCs and drives CAF-like activation, which in turn facilitates omental metastasis of ovarian cancer.

Graphical Abstract
Hepatocyte GPCR signaling regulates IRF3 to control hepatic stellate cell transdifferentiation
Authors: Yu Jae-Hyun , Choi Myeung Gi , Lee Na Young , Kwon Ari , Lee Euijin , Koo Ja Hyun 
Published: January 2024

Abstract
Background
Interferon Regulatory Factor 3 (IRF3) is a transcription factor that plays a crucial role in the innate immune response by recognizing and responding to foreign antigens. Recently, its roles in sterile conditions are being studied, as in metabolic and fibrotic diseases. However, the search on the upstream regulator for efficient pharmacological targeting is yet to be fully explored. Here, we show that G protein-coupled receptors (GPCRs) can regulate IRF3 phosphorylation through of GPCR-Gα protein interaction.

Results
IRF3 and target genes were strongly associated with fibrosis markers in liver fibrosis patients and models. Conditioned media from MIHA hepatocytes overexpressing IRF3 induced fibrogenic activation of LX-2 hepatic stellate cells (HSCs). In an overexpression library screening using active mutant Gα subunits and Phos-tag immunoblotting, Gαs was found out to strongly phosphorylate IRF3. Stimulation of Gαs by glucagon or epinephrine or by Gαs-specific designed GPCR phosphorylated IRF3. Protein kinase A (PKA) signaling was primarily responsible for IRF3 phosphorylation and Interleukin 33 (IL-33) expression downstream of Gαs. PKA phosphorylated IRF3 on a previously unrecognized residue and did not require reported upstream kinases such as TANK-binding kinase 1 (TBK1). Activation of Gαs signaling by glucagon induced IL-33 production in hepatocytes. Conditioned media from the hepatocytes activated HSCs, as indicated by α-SMA and COL1A1 expression, and this was reversed by pre-treatment of the media with IL-33 neutralizing antibody.

Conclusions
Gαs-coupled GPCR signaling increases IRF3 phosphorylation through cAMP-mediated activation of PKA. This leads to an increase of IL-33 expression, which further contributes to HSC activation. Our findings that hepatocyte GPCR signaling regulates IRF3 to control hepatic stellate cell transdifferentiation provides an insight for understanding the complex intercellular communication during liver fibrosis progression and suggests therapeutic opportunities for the disease.
Cryopreservation of Abies alba × A. numidica and Pinus nigra embryogenic tissues by stepwise dehydration method
Authors: Hazubska-Przybył Teresa , Wawrzyniak Mikołaj Krzysztof , Obarska Agata , Salaj Terezia 
Published: January 2024

Abstract
Background
Cryopreservation makes it possible to preserve plant biodiversity for thousands of years in ex situ storage. The stepwise dehydration method is a simple and versatile cryopreservation technique based on the vitrification phenomenon. However, the commonly used dimethyl sulfoxide (DMSO) in this cryopreservation technique is considered harmful for plant material, thus alternative methods are needed to be applied.

Results
In this study, the possibility of cryopreservation of embryogenic tissues (ETs) of Abies alba x A. numidica and Pinus nigra was investigated. Before freezing, ETs were partially dehydrated in the presence of increasing concentrations of sucrose (from 0.25 to 1.0 M) for 7 days, followed by desiccation of the tissues over silica gel for 2 and 2.5 h, respectively. After these pretreatments, the plant material was frozen in liquid nitrogen (LN; –196 °C). For both coniferous trees the ET survival rate was high and reached 84.4% for A. alba x A. numidica (28 days) and 86.7% for P. nigra (35 days) after recovery of the tissues from liquid nitrogen (LN). The regenerated tissue of A. alba x A. numidica was characterized by more intense growth after storage in LN compared to tissue that had not been cryopreserved (control). The tissue of this tree also undertook relatively rapid growth after thawing from LN. In turn, the ET growth of P. nigra was significantly lower after thawing compared to the other treatment.

Conclusions
The present study demonstrated, that the stepwise dehydration method could be successfully applied to the cryostorage of ETs of both studied trees. To the best of our knowledge, this is the first report on ET cryopreservation based on this method for Abies and Pinus genus representatives, which may be the alternative way for efficient, long-term preservation of germplasm in LN.
The hidden scabies: a rare case of atypical Norwegian scabies, case report and literature review
Authors: Mauro Angela , Colonna Cristiana , Taranto Silvia , Garella Vittoria , Castelletti Francesca , Giordano Laura , Monzani Nicola Adriano , Bernardo Luca 
Published: January 2024

Abstract
Background
Norwegian scabies is a rare dermatological manifestation that usually affects the most fragile populations, such as elderly and immunocompromised patients, and its diagnosis is quite complex, due to its low prevalence in the general population and because of a broad spectrum manifestation.

Case Presentation
Here we describe a rare case of Norwegian scabies that was previously misdiagnosed in a sixteen year old patient affected by Down syndrome and we conducted a non-systematic literature review about this topic. Lesions were atypical, pruritic and associated with periodic desquamation of the palms and soles and after a series of specialist evaluations, she finally underwent topical treatment with complete remission.

Conclusion
It is therefore crucial to take in consideration the relation between Down syndrome and community acquired crusted scabies, to enable preventative measures, early detection, and proper treatment.
Lung clearance index short-term variability in cystic fibrosis: a pre-post pulmonary exacerbation study
Authors: De Marchis Matteo , Montemitro Enza , Boni Alessandra , Federici Alessandra , Di Giovanni Daniele , Cristiani Luca , Cutrera Renato , Fiocchi Alessandro G. 
Published: January 2024

Abstract
Background
Multiple Breath washout (MBW) represents an important tool to detect early a possible pulmonary exacerbation especially in Cystic Fibrosis (CF) disease. Lung clearance index (LCI) is the most commonly reported multiple breath washout (MBW) index and in the last years was used as management measure for evaluation. Our aim was to analyze clinical utility of LCI index variability in pulmonary exacerbation in CF after intravenous (IV) antibiotic therapy.

Methods
A single-center study was conducted at CF Unit of Bambino Gesù Children’s Hospital among hospitalized > 3 years patients for pulmonary exacerbations and treated with antibiotic IV treatment for 14 days. MBW and spirometry were evaluated within 72 h of admission to hospital and at the end of hospitalization. Descriptive analysis was conducted and correlations between quantitative variables were investigated.

Results
Fifty-seven patients (M22/F35) with an average age 18.56 (± 8.54) years were enrolled. LCI2.5 was significantly reduced at the end of antibiotic treatment in both pediatric and adult populations with an average reduction of -6,99%; 37/57 patients denoted an improvement, 20/57 are stable or worsened in LCI2.5 values and 4/57 (7.02%) had a significant deterioration (> 15%) at end of treatment. On the contrary a significative elevation of FEV1 and FVC were found, respectively of + 7,30% and of + 5,46%. A positive good correlection among LCI 2.5 and Scond (rho = + 0,615, p = 0.000) and LCI 2.5 and Sacin (rho = + 0,649, p = 0.000) and a negative strong correlation between FEV1 and LCI 2.5 were found in post treatment period. A similar modification of LCI 2.5 and FEV1 was noticed in both adult and pediatric population.

Conclusions
LCI may have a role in the routine clinical care of both adult and pediatric CF patients as a good tool to assess response to IV antibiotic end-therapy in the same way as FEV1.
Investigation of early literacy skills of preschool children with hearing loss
Authors: Akmese Pelin Pistav , Kucuk Destina Sezgin , Kirazli Gulce 
Published: January 2024

Abstract
Background
Early literacy development is critical for children with hearing loss to develop literacy skills in the years to come. The aim of this study is to compare the early literacy skills of 60–72 months’ children with hearing loss to the results of children with normal hearing.

Methods
A total of 40 children (20 children with hearing aid (HA) and 20 children with normal hearing (NH) were evaluated in the study. Receptive and expressive language was assessed by Test of Early Language Development (TELD-3) and Early Literacy Test (EROT) was applied to assess the early literacy skills of all children in the study.

Results
The receptive and expressive language results of the hearing-impaired group were significantly lower than those of normal hearing. Moreover, in EROT when a general analysis is made with main test titles such as, the vocabulary knowledge, letter knowledge, the listening comprehension, results showed that there was a significant difference between the HA and NH groups.

Conclusions
This study highlights the importance of supporting early literacy skills, which are prerequisite skills for reading and writing skills, in children who receive both mainstreaming education and special education in the risk group and/or continue their education in kindergarten.
Protein profiling in systemic sclerosis patients with different pulmonary complications using proteomic antibody microarray
Authors: Huang Jing , Zhu Honglin , Liu Sijia , Li Mengtao , Li Yisha , Luo Hui , Zuo Xiaoxia 
Published: January 2024

Abstract
Background
Pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) are leading causes of systemic sclerosis (SSc)-related death. In this study, we aimed to identify biomarkers for detecting SSc pulmonary complications that are mild and in the early stages to improve the prognosis.

Methods
We screened for serum biomarkers using a proteomic antibody microarray that simultaneously assessed 1000 proteins. Differentially expressed proteins were further verified using ELISA. Finally, we performed a correlation analysis using clinical data.

Results
We identified 125 differentially expressed proteins, of which calcitonin, sclerostin (SOST), CD40, and fibronectin were selected for further verification. Serum calcitonin and SOST levels were significantly elevated in all SSc pulmonary complication subgroups, whereas serum calcitonin levels were higher in the SSc with PAH subgroup than in the SSc without PAH and ILD subgroup. Serum SOST levels were possibly associated with the presence of ILD and positively related to the presence of cardiac and gastrointestinal involvement. Serum CD40 and calcitonin levels appeared to be positively related to the presence of renal involvement, and serum calcitonin was also positively related to the presence of gastrointestinal involvement.

Conclusions
This study indicated that serum calcitonin and SOST levels may be promising biomarkers for SSc-related PAH and ILD, respectively. Further research is needed to verify this result and understand the underlying mechanisms.
MRSamePopTest: introducing a simple falsification test for the two-sample mendelian randomisation ‘same population’ assumption
Authors: Woolf Benjamin , Mason Amy , Zagkos Loukas , Sallis Hannah , Munafò Marcus R. , Gill Dipender 
Published: January 2024

AbstractTwo-sample MR is an increasingly popular method for strengthening causal inference in epidemiological studies. For the effect estimates to be meaningful, variant-exposure and variant-outcome associations must come from comparable populations. A recent systematic review of two-sample MR studies found that, if assessed at all, MR studies evaluated this assumption by checking that the genetic association studies had similar demographics. However, it is unclear if this is sufficient because less easily accessible factors may also be important. Here we propose an easy-to-implement falsification test. Since recent theoretical developments in causal inference suggest that a causal effect estimate can generalise from one study to another if there is exchangeability of effect modifiers, we suggest testing the homogeneity of variant-phenotype associations for a phenotype which has been measured in both genetic association studies as a method of exploring the ‘same-population’ test. This test could be used to facilitate designing MR studies with diverse populations. We developed a simple R package to facilitate the implementation of our proposed test. We hope that this research note will result in increased attention to the same-population assumption, and the development of better sensitivity analyses.
Sampling approaches and geographic coverage in Mayi Kuwayu: the national study of Aboriginal and Torres Strait Islander wellbeing
Authors: Thandrayen Joanne , Walker Jennie , Chapman Janet , Lovett Raymond , Thurber Katherine A 
Published: January 2024

Abstract
Objective
The objective of this paper is to investigate the geographic distribution of participants in Mayi Kuwayu, the National Study of Aboriginal and Torres Strait Islander Wellbeing. The Mayi Kuwayu Study is the largest national longitudinal study of the health and wellbeing of Aboriginal and Torres Strait Islander adults (aged 16 years and over) in Australia. It is an Aboriginal-led and governed Study with embedded community engagement. The Study collects data through self-report questionnaires, using multiple sampling approaches: (1) a large-scale mail-out based on stratified random sampling; (2) convenience sampling; (3) snowball sampling; (4) voluntary sampling. A comparison of the geographic distribution of Mayi Kuwayu Study participants to that of the total Aboriginal and Torres Strait Islander population was also conducted.

Results
A total of 9,843 people participated in the Mayi Kuwayu Study baseline survey from 2018 to 2022. Participants resided in all Australian States and Territories. The geographic distribution of participants broadly matched the total population distribution, with participants generally located on the east and south-east coast of Australia. Apparent differences in the geographic distribution were identified by sex and age group.
Emergency department CT examinations demonstrate no evidence of early viral circulation at the start of the COVID-19 pandemic—a multicentre epidemiological study
Authors: Crombé Amandine , Dupont Claire , Casalonga François , Seux Mylène , Favard Nicolas , Coulon Agnès , Jurkovic Thomas , Nivet Hubert , Gorincour Guillaume 
Published: January 2024

Abstract
Background
Biological studies suggested that the COVID-19 outbreak in France occurred before the first official diagnosis on January 24, 2020. We investigated this controversial topic using a large collection of chest CTs performed throughout French emergency departments within 6 months before the 1st lockdown.

Results
Overall, 49,311 consecutive patients (median age: 60 years, 23,636/49,311 [47.9%] women) with available chest CT images and reports from 61 emergency departments between September 1, 2020, and March 16, 2020 (day before the 1st French lockdown), were retrospectively included in this multicentre study. In the macroscopic analysis of reports automatically (labelled for presence of ground glass opacities [GGOs], reticulations, and bilateral and subpleural abnormalities), we found a significant breakpoint on February 17, 2020, for the weekly time series with 1, 2 and ≥ 3 of these 4 radiological features, with 146/49,311 (0.3%) patients showing bilateral abnormalities and ground glass opacities (GGOs) from that day. According to radiologists, 22/146 (15.1%) CT images showed typical characteristics of COVID-19, including 4/146 (2.7%) before February 2020. According to hospital records, one patient remained without microbial diagnosis, two patients had proven influenza A and one patient had concomitant influenza A and mycoplasma infection.

Conclusion
These results suggest that SARS-CoV-2 was not circulating in the areas covered by the 61 emergency departments involved in our study before the official beginning of the COVID-19 outbreak in France. In emergency patients, the strong resemblance among mycoplasma, influenza A and SARS-CoV-2 lung infections on chest CT and the nonspecificity of CT patterns in low prevalence periods is stressed.

Critical relevance statement
We proposed here an innovative approach to revisit a controversial ‘real’ start of the COVID-19 pandemic in France based on (1) a population-level approach combining text mining, time series analysis and an epidemiological dataset and (2) a patient-level approach with careful retrospective reading of chest CT scans complemented by analysis of samples performed contemporarily to the chest CT. We showed no evidence that SARS-CoV-2 was actively circulating in France before February 2020.

Graphical Abstract
CT energy spectral parameters of creeping fat in Crohn’s disease and correlation with inflammatory activity
Authors: Li Xianchu , Wu Wei , Yuan Yan , Zhu Zhiming , Liu Xiaowei , Xiao Desheng , Long Xueying 
Published: January 2024

Abstract
Objectives
Creeping fat is a kind of unique abnormal mesenteric tissue at the sites of diseased bowel of Crohn’s disease. By using dual-energy CT enterography, this study aimed to evaluate the feasibility of spectral parameters in the quantitative analysis of mesenteric adipose tissue or creeping fat.

Methods
In this study, patients with known or suspected Crohn’s disease who underwent dual-energy CT enterography from March 1, 2019, to March 31, 2021, were enrolled. Among them, 40 patients with surgery and pathology-proven creeping fat were selected as the creeping fat Crohn’s disease group, and 40 normal patients were selected as the control group. The quantitative spectral parameters including the slope of the Hounsfield unit curve, normalised fat–water concentration, normalised fat-iodine concentration, and normalised fat volume fraction at the enteric phases were obtained. Mann–Whitney U test, Kruskal–Wallis H test, and receiver operating characteristic curve analysis were applied to compare quantitative parameters among various groups.

Results
A significant difference was observed in the slope of the Hounsfield unit curve, normalised fat–water concentration, normalised fat-iodine concentration, and normalised fat volume fraction between mesenteric adipose tissue and creeping fat with Crohn’s disease at the enteric phase (all p < 0.001). The slope of the Hounsfield unit curve of creeping fat at the enteric phase had a better capability to distinguish inactive and active Crohn’s disease (AUC = 0.93, p < 0.001).

Conclusion
Dual-energy CT enterography with quantitative spectral parameters is a potentially novel noninvasive tool for evaluating creeping fat in Crohn’s disease.

Critical relevance statement
Energy spectral parameters of creeping fat in Crohn’s disease are significantly different from normal mesenteric adipose tissues and are correlated with inflammatory activity.

Key points
• Dual-energy CT enterography allows quantitatively assessing creeping fat with spectral parameters.
• The creeping fat has distinct spectral parameters to normal mesenteric adipose.
• The spectral parameters accurately differentiate active and inactive Crohn’s disease.

Graphical Abstract
Comparison of the ability of exosomes and ectosomes derived from adipose-derived stromal cells to promote cartilage regeneration in a rat osteochondral defect model
Authors: Xu Tengjing , Yu Xinning , Xu Kaiwang , Lin Yunting , Wang Jiajie , Pan Zongyou , Fang Jinghua , Wang Siheng , Zhou Zhuxing , Song Hongyun , Zhu Sunan , Dai Xuesong 
Published: January 2024

Abstract
Background
Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) offer promising prospects for stimulating cartilage regeneration. The different formation mechanisms suggest that exosomes and ectosomes possess different biological functions. However, little attention has been paid to the differential effects of EV subsets on cartilage regeneration.

Methods
Our study compared the effects of the two EVs isolated from adipose-derived MSCs (ASCs) on chondrocytes and bone marrow–derived MSCs (BMSCs) in vitro. Additionally, we loaded the two EVs into type I collagen hydrogels to optimize their application for the treatment of osteochondral defects in vivo.

Results
In vitro experiments demonstrate that ASC-derived exosomes (ASC-Exos) significantly promoted the proliferation and migration of both cells more effectively than ASC-derived ectosomes (ASC-Ectos). Furthermore, ASC-Exos facilitated a stronger differentiation of BMSCs into chondrogenic cells than ASC-Ectos, but both inhibited chondrocyte apoptosis to a similar extent. In the osteochondral defect model of rats, ASC-Exos promoted cartilage regeneration in situ better than ASC-Ectos. At 8 weeks, the hydrogel containing exosomes group (Gel + Exo group) had higher macroscopic and histological scores, a higher value of trabecular bone volume fraction (BV/TV), a lower value of trabecular thickness (Tb.Sp), and a better remodeling of extracellular matrix than the hydrogel containing ectosomes group (Gel + Ecto group). At 4 and 8 weeks, the expression of CD206 and Arginase-1 in the Gel + Exo group was significantly higher than that in the Gel + Ecto group.

Conclusion
Our findings indicate that administering ASC-Exos may be a more effective EV strategy for cartilage regeneration than the administration of ASC-Ectos.