bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative Computed Tomographic Angiography Can Predict Need for Branch Pulmonary Artery Intervention in Patients With Ductal-Dependent Pulmonary Blood Flow
Authors: Graff Kirsten , Hlavacek Anthony M. , Aizcorbe Nicholas , Bradley Scott M. , Chowdhury Shahryar M. 
Published: March 2023

Background Neonates with ductal-dependent pulmonary blood flow (DD-PBF) are at risk for pulmonary artery (PA) stenosis. The objective of this study was to identify preoperative cardiovascular computed tomography angiography (CTA) measures that are associated with the need for branch PA intervention. Methods We identified neonates with DD-PBF who underwent preoperative CTA at our center and were followed for 24 months. The primary outcome was requiring intervention for branch PA stenosis at the initial or subsequent procedure. Patients were divided into three groups: 1) No PA intervention, 2) Initial PA intervention, and 3) Remote PA intervention. Measurements of the branch PAs and patent ductus arteriosus (PDA) were made prospectively. Results Forty patients were included, 7 (18%) did not receive a PA intervention, 23 (58%) were in the initial PA intervention group, and 10 (25%) were in the remote PA intervention group. The distance from PA bifurcation to the largest diameter of the PA that receives the PDA showed a difference between the no-intervention group versus the initial and remote intervention groups (0.8 mm [IQR 0.7, 2.0], 8.2 mm [IQR 1.9, 13.7], 8.5 mm [IQR 6.5, 11.1], respectively, P  =  .02). The receiver operating characteristic curve showed a distance >2.2 mm had a sensitivity  =  91% and specificity  =  86% in predicting the need for PA intervention. Conclusion The distance from the PA bifurcation to the largest diameter of the branch PA that accepts the PDA on preoperative CTA is highly predictive of the need for initial or remote PA intervention in this group. Preoperative CTA should be considered for risk stratification in neonates undergoing intervention for DD-PBF.
Operative vs Nonoperative Management of Achilles Tendon Rupture: A Cost Analysis
Authors: Murdock Christopher J. , Ochuba Arinze J. , Xu Amy L. , Snow Morgan , Bronheim Rachel , Vulcano Ettore , Aiyer Amiethab A. 
Published: March 2023

Background: Achilles tendon rupture (ATR) is a common injury with a growing incidence rate. Treatment is either operative or nonoperative. However, evidence is lacking on the cost comparison between these modalities. The objective of this study is to investigate the cost differences between operative and nonoperative treatment of ATR using a large national database. Methods: Patients who received treatment for an ATR were abstracted from the large national commercial insurance claims database, Marketscan Commercial Claims and Encounters Database (n = 100 825) and divided into nonoperative (n = 75 731) and operative (n = 25 094) cohorts. Demographics, location, and health care charges were compared using multivariable regression analysis. Subanalysis of costs for medical services including clinic visits, imaging studies, opioid usage, and physical therapy were conducted. Patients who underwent secondary repair were excluded. Results: Operative treatment was associated with increased net and total payments, coinsurance, copayment, deductible, coordination of benefits (COB) / savings, greater number of clinic visits, radiographs, magnetic resonance imaging (MRI) scans, and physical therapy (PT) sessions, and with higher net costs due to clinic visits, radiographs, MRIs, and PT ( P < .001). Operative repair at an ambulatory surgical center was associated with a lower net and total payment, and a significantly higher deductible compared to in-hospital settings ( P < .001). Both cohorts received similar numbers of opioid prescriptions during the study period. Yet, operative patients had a significantly shorter duration of opioid use. After controlling for confounders, operative repair was also independently associated with lower net costs due to opioid prescriptions. Conclusion: Compared with nonoperatively managed ATR, surgical repair is associated with greater costs partially because of greater utilization of clinic visits, imaging, and physical therapy sessions. However, surgical costs may be reduced when procedures are performed in ambulatory surgery centers vs hospital facilities. Nonoperative treatment is associated with higher prescription costs secondary to longer duration of opioid use. Level of Evidence: Level III, retrospective cohort study.
Clinically relevant combined effect of polygenic background, rare pathogenic germline variants, and family history on colorectal cancer incidence
Authors: Hassanin Emadeldin , Spier Isabel , Bobbili Dheeraj R. , Aldisi Rana , Klinkhammer Hannah , David Friederike , Dueñas Nuria , Hüneburg Robert , Perne Claudia , Brunet Joan , Capella Gabriel , Nöthen Markus M. , Forstner Andreas J. , Mayr Andreas , Krawitz Peter , May Patrick , Aretz Stefan , Maj Carlo 
Published: March 2023

Abstract
Background and aims
Summarised in polygenic risk scores (PRS), the effect of common, low penetrant genetic variants associated with colorectal cancer (CRC), can be used for risk stratification.

Methods
To assess the combined impact of the PRS and other main factors on CRC risk, 163,516 individuals from the UK Biobank were stratified as follows: 1. carriers status for germline pathogenic variants (PV) in CRC susceptibility genes (APC, MLH1, MSH2, MSH6, PMS2), 2. low (< 20%), intermediate (20–80%), or high PRS (> 80%), and 3. family history (FH) of CRC. Multivariable logistic regression and Cox proportional hazards models were applied to compare odds ratios and to compute the lifetime incidence, respectively.

Results
Depending on the PRS, the CRC lifetime incidence for non-carriers ranges between 6 and 22%, compared to 40% and 74% for carriers. A suspicious FH is associated with a further increase of the cumulative incidence reaching 26% for non-carriers and 98% for carriers. In non-carriers without FH, but high PRS, the CRC risk is doubled, whereas a low PRS even in the context of a FH results in a decreased risk. The full model including PRS, carrier status, and FH improved the area under the curve in risk prediction (0.704).

Conclusion
The findings demonstrate that CRC risks are strongly influenced by the PRS for both a sporadic and monogenic background. FH, PV, and common variants complementary contribute to CRC risk. The implementation of PRS in routine care will likely improve personalized risk stratification, which will in turn guide tailored preventive surveillance strategies in high, intermediate, and low risk groups.
Classical monocyte-derived macrophages as therapeutic targets of umbilical cord mesenchymal stem cells: comparison of intratracheal and intravenous administration in a mouse model of pulmonary fibrosis
Authors: Choi Sun Mi , Mo Yosep , Bang Ji-Young , Ko Young Gyun , Ahn Yoon Hae , Kim Hye Young , Koh Jaemoon , Yim Jae-Joon , Kang Hye-Ryun 
Published: March 2023

Abstract
Background
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that has no cure. Although mesenchymal stem cells (MSCs) have been reported to ameliorate lung inflammation and fibrosis in mouse models, their mechanisms of action remain unknown. Therefore, we aimed to determine the changes in various immune cells, especially macrophages and monocytes, involved in the effects of MSC treatment on pulmonary fibrosis.

Methods
We collected and analyzed explanted lung tissues and blood from patients with IPF who underwent lung transplantation. After establishing a pulmonary fibrosis model via the intratracheal administration of bleomycin (BLM) to 8-week-old mice, MSCs derived from human umbilical cords were administered intravenously or intratracheally on day 10 and the lungs were immunologically analyzed on days 14 and 21. Flow cytometry was performed to analyze the immune cell characteristics, and gene expression levels were examined using quantitative reverse transcription-polymerase chain reaction.

Results
In the histological analysis of explanted human lung tissues, the terminally fibrotic areas contained a larger number of macrophages and monocytes than the early fibrotic areas of the lungs. When human monocyte-derived macrophages (MoMs) were stimulated with interleukin-13 in vitro, the expression of type 2 macrophage (M2) markers was more prominent in MoMs from the classical monocyte subset than in those from intermediate or non-classical monocyte subsets, and MSCs suppressed M2 marker expression independent of MoM subsets. In the mouse model, the increased number of inflammatory cells in the bronchoalveolar lavage fluid and the degree of lung fibrosis observed in BLM-treated mice were significantly reduced by MSC treatment, which tended to be more prominent with intravenous administration than intratracheal administration. Both M1 and M2 MoMs were upregulated in BLM-treated mice. The M2c subset of M2 MoMs was significantly reduced by MSC treatment. Among M2 MoMs, M2 MoMs derived from Ly6C+ monocytes were most effectively regulated by the intravenous administration, not intratracheal administration, of MSCs.

Conclusions
Inflammatory classical monocytes may play a role in lung fibrosis in human IPF and BLM-induced pulmonary fibrosis. Intravenous rather than intratracheal administration of MSCs may ameliorate pulmonary fibrosis by inhibiting monocyte differentiation into M2 macrophages.
Nomogram prediction for the risk of venous thromboembolism in patients with lung cancer
Authors: Lei Haike , Tao Dan , Zhang Ningning , Sun Mao , Sun Lisi , Yang Dingyi , Jiang Yong , Zhou Wei , Xie Yue , Wang Ying 
Published: March 2023

Abstract
Objective
The aim of this study was to establish a nomogram graph model to accurately predict the venous thromboembolism (VTE) risk probability in the general population with lung cancer.

Methods
Based on data from patients with lung cancer in Chongqing University Cancer Hospital of China, the independent risk factors of VTE were identified by the logistic univariable and multivariable analysis and were integrated to construct a nomogram, which was validated internally. The predictive effectiveness of the nomogram was evaluated by the receiver operating characteristic curve (ROC) and calibration curve.

Results
A total of 3398 lung cancer patients were included for analysis. The nomogram incorporated eleven independent VTE risk factors including karnofsky performance scale (KPS), stage of cancer, varicosity, chronic obstructive pulmonary disease (COPD), central venous catheter (CVC), albumin, prothrombin time (PT), leukocyte counts, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), dexamethasone, and bevacizumab. The C-index of the nomogram model was 0.843 and 0.791 in the training and validation cohort, respectively, demonstrating good discriminative power. The calibration plots of the nomogram revealed excellent agreement between the predicted and actual probabilities.

Conclusions
We established and validated a novel nomogram for predicting the risk of VTE in patients with lung cancer. The nomogram model could precisely estimate the VTE risk of individual lung cancer patients and identify high-risk patients who are in need of a specific anticoagulation treatment strategy.
CircDNAJC11 interacts with TAF15 to promote breast cancer progression via enhancing MAPK6 expression and activating the MAPK signaling pathway
Authors: Wang Bin , Chen Hang , Deng Yumei , Chen Hong , Xing Lei , Guo Yuping , Wang Min , Chen Junxia 
Published: March 2023

Abstract
Background
Breast cancer (BC) is a common malignant tumor in women worldwide. Circular RNA (circRNA) has been proven to play a critical role in BC progression. However, the exact biological functions and underlying mechanisms of circRNAs in BC remain largely unknown.

Methods
Here, we first screened for differentially expressed circRNAs in 4 pairs of BC tissues and adjacent non-tumor tissues using a circRNA microarray. Functionally, gain- and loss-of-function experiments in vitro and in vivo showed that circDNAJC11 promoted BC cell proliferation, migration, invasion, and tumor growth. Mechanistically, RNA pull-down, mass spectrum, RNA immunoprecipitation, fluorescence in situ hybridization assays, and rescue experiments were executed.

Results
We found that circDNAJC11 was significantly upregulated in triple-negative breast cancer tissues and cells. Clinical data revealed that the high expression of circDNAJC11 was closely correlated with a poor prognosis of BC patients and could be an independent risk factor for BC prognosis. Functionally, gain- and loss-of-function experiments in vitro and in vivo showed that circDNAJC11 promoted BC cell proliferation, migration, invasion, and tumor growth. Mechanistically, RNA pull-down, mass spectrum, RNA immunoprecipitation, fluorescence in situ hybridization assays, and rescue experiments were executed. We demonstrated that circDNAJC11 combined with TAF15 to promote BC progression via stabilizing MAPK6 mRNA and activating the MAPK signaling pathway.

Conclusions
The circDNAJC11/TAF15/MAPK6 axis played a crucial role in the progression and development of BC, suggesting that circDNAJC11 might be a novel biomarker and therapeutical target for BC.
IFNAR signaling of neuroectodermal cells is essential for the survival of C57BL/6 mice infected with Theiler’s murine encephalomyelitis virus
Authors: Bühler Melanie , Li Dandan , Li Lin , Runft Sandra , Waltl Inken , Pavlou Andreas , Kalinke Ulrich , Ciurkiewicz Malgorzata , Huehn Jochen , Floess Stefan , Beineke Andreas , Baumgärtner Wolfgang , Gerhauser Ingo 
Published: March 2023

Abstract
Background
Theiler’s murine encephalomyelitis virus (TMEV) is a single-stranded RNA virus that causes encephalitis followed by chronic demyelination in SJL mice and spontaneous seizures in C57BL/6 mice. Since earlier studies indicated a critical role of type I interferon (IFN-I) signaling in the control of viral replication in the central nervous system (CNS), mouse strain-specific differences in pathways induced by the IFN-I receptor (IFNAR) might determine the outcome of TMEV infection.

Methods
Data of RNA-seq analysis and immunohistochemistry were used to compare the gene and protein expression of IFN-I signaling pathway members between mock- and TMEV-infected SJL and C57BL/6 mice at 4, 7 and 14 days post-infection (dpi). To address the impact of IFNAR signaling in selected brain-resident cell types, conditional knockout mice with an IFNAR deficiency in cells of the neuroectodermal lineage (NesCre±IFNARfl/fl), neurons (Syn1Cre±IFNARfl/fl), astrocytes (GFAPCre±IFNARfl/fl), and microglia (Sall1CreER±IFNARfl/fl) on a C57BL/6 background were tested. PCR and an immunoassay were used to quantify TMEV RNA and cytokine and chemokine expression in their brain at 4 dpi.

Results
RNA-seq analysis revealed upregulation of most ISGs in SJL and C57BL/6 mice, but Ifi202b mRNA transcripts were only increased in SJL and Trim12a only in C57BL/6 mice. Immunohistochemistry showed minor differences in ISG expression (ISG15, OAS, PKR) between both mouse strains. While all immunocompetent Cre-negative control mice and the majority of mice with IFNAR deficiency in neurons or microglia survived until 14 dpi, lack of IFNAR expression in all cells (IFNAR−/−), neuroectodermal cells, or astrocytes induced lethal disease in most of the analyzed mice, which was associated with unrestricted viral replication. NesCre±IFNARfl/fl mice showed more Ifnb1, Tnfa, Il6, Il10, Il12b and Ifng mRNA transcripts than Cre−/−IFNARfl/fl mice. IFNAR−/− mice also demonstrated increased IFN-α, IFN-β, IL1-β, IL-6, and CXCL-1 protein levels, which highly correlated with viral load.

Conclusions
Ifi202b and Trim12a expression levels likely contribute to mouse strain-specific susceptibility to TMEV-induced CNS lesions. Restriction of viral replication is strongly dependent on IFNAR signaling of neuroectodermal cells, which also controls the expression of key pro- and anti-inflammatory cytokines during viral brain infection.
A full genome tiling array enhanced the inspection and quarantine of SARS-CoV-2
Authors: Qi Runzi , Wang Gang , Wang Xu , Li Cheng , Huang Lei , Xiao Weixi , Shao Bing , Zhou Chunya , Ding Xun , Li Feng , Zhou Wei 
Published: March 2023

AbstractAs the worldwide spreading epidemic of SARS-CoV-2, quick inspection and quarantine of passengers for SARS-CoV-2 infection are essential for controlling the spread of SARS-CoV-2, especially the cross-border transmission. This study reports a SARS-CoV-2 genome sequencing method based on a re-sequencing tiling array successfully used in border inspection and quarantine. The tiling array chip has four cores, with one core of 240,000 probes dedicated to the whole genome sequencing of the SAR-CoV-2 genome. The assay protocol has been improved to reduce the detection time to within one day and can detect 96 samples in parallel. The detection accuracy has been validated. This fast and simple procedure is also of low cost and high accuracy, and it is particularly suitable for the rapid tracking of viral genetic variants in custom inspection applications. Combining these properties means this method has significant application potential in the clinical investigation and quarantine of SARS-CoV-2. We used this SARS-CoV-2 genome re-sequencing tiling array to inspect and quarantine China's entry and exit ports in the Zhejiang Province. From November 2020 to January 2022, we observed the gradual shift of SARS-CoV-2 variants from the D614G type to the Delta Variant, and then to the dominance of the Omicron variant recently, consistently with the global emergency pattern of the new SARS-CoV-2 variant.
Lung versus gut exposure to air pollution particles differentially affect metabolic health in mice
Authors: Bosch Angela J. T. , Rohm Theresa V. , AlAsfoor Shefaa , Low Andy J. Y. , Keller Lena , Baumann Zora , Parayil Neena , Stawiski Marc , Rachid Leila , Dervos Thomas , Mitrovic Sandra , Meier Daniel T. , Cavelti-Weder Claudia 
Published: March 2023

Abstract
Background
Air pollution has emerged as an unexpected risk factor for diabetes. However, the mechanism behind remains ill-defined. So far, the lung has been considered as the main target organ of air pollution. In contrast, the gut has received little scientific attention. Since air pollution particles can reach the gut after mucociliary clearance from the lungs and through contaminated food, our aim was to assess whether exposure deposition of air pollution particles in the lung or the gut drive metabolic dysfunction in mice.

Methods
To study the effects of gut versus lung exposure, we exposed mice on standard diet to diesel exhaust particles (DEP; NIST 1650b), particulate matter (PM; NIST 1649b) or phosphate-buffered saline by either intratracheal instillation (30 µg 2 days/week) or gavage (12 µg 5 days/week) over at least 3 months (total dose of 60 µg/week for both administration routes, equivalent to a daily inhalation exposure in humans of 160 µg/m3 PM2.5) and monitored metabolic parameters and tissue changes. Additionally, we tested the impact of the exposure route in a “prestressed” condition (high-fat diet (HFD) and streptozotocin (STZ)).

Results
Mice on standard diet exposed to particulate air pollutants by intratracheal instillation developed lung inflammation. While both lung and gut exposure resulted in increased liver lipids, glucose intolerance and impaired insulin secretion was only observed in mice exposed to particles by gavage. Gavage with DEP created an inflammatory milieu in the gut as shown by up-regulated gene expression of pro-inflammatory cytokines and monocyte/macrophage markers. In contrast, liver and adipose inflammation markers were not increased. Beta-cell secretory capacity was impaired on a functional level, most likely induced by the inflammatory milieu in the gut, and not due to beta-cell loss. The differential metabolic effects of lung and gut exposures were confirmed in a “prestressed” HFD/STZ model.

Conclusions
We conclude that separate lung and gut exposures to air pollution particles lead to distinct metabolic outcomes in mice. Both exposure routes elevate liver lipids, while gut exposure to particulate air pollutants specifically impairs beta-cell secretory capacity, potentially instigated by an inflammatory milieu in the gut.
TGM2 accelerates migration and differentiation of BMSCs by activating Wnt/β-catenin signaling
Authors: Liu Feng , Wu Mingzheng , Wu Xixia , Chen Dan , Xie Ming , Pan Hao 
Published: March 2023

Abstract
Background
Transglutaminase 2 (TGM2) is a gene previously reported to be associated with the differentiation of bone marrow mesenchymal stem cells (BMSCs). The study was developed to reveal the impact of TGM2 on the migration and differentiation of BMSCs.

Methods
Cells were isolated from bone marrow of mice and then the surface antigens were identified by flow cytometry. Wound healing assays were conducted to assess the migratory ability of BMSCs. The mRNA levels of TGM2 and osteoblast-associated genes (ALP, OCN, and RUNX2) were subjected to RT-qPCR analysis, and protein levels of these genes as well as β-catenin were quantitated by western blotting. Alizarin red staining was conducted for detection of osteogenic ability. The activation of Wnt signaling was assessed by TOP/FOP flash assays.

Results
Surface antigens were positively identified in MSCs, indicating good multidirectional differentiation ability of cells. TGM2 silencing suppressed BMSC migration while weakening mRNA and protein levels of osteoblast-associated genes. While TGM2 overexpression exerts the opposite impact on cell migration and expression levels of osteoblast-associated genes. Additionally, overexpressed TGM2 promotes the mineralization of BMSCs according to results of Alizarin red staining. Moreover, TGM2 activated the Wnt/β-catenin signaling, and DKK1 (an inhibitor of Wnt signaling) reversed the promoting influence of TGM2 on cell migration and differentiation.

Conclusion
TGM2 promotes the migration and differentiation of BMSCs via activation of the Wnt/β-catenin signaling.