bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preconditioning with selective autoretroperfusion: In vivo and in silico evidence of washout hypothesis
Authors: Choy Jenny S. , Hubbard Terry , Wang Haifeng , Awakeem Yousif , Khosravi Pouya , Khadivi Bahram , Navia Jose A. , Stone Gregg W. , Lee Lik Chuan , Kassab Ghassan S. 
Published: May 2024

IntroductionPrompt reperfusion of coronary artery after acute myocardial infarction (AMI) is crucial for minimizing heart injury. The myocardium, however, may experience additional injury due to the flow restoration itself (reperfusion injury, RI). The purpose of this study was to demonstrate that short preconditioning (10 min) with selective autoretroperfusion (SARP) ameliorates RI, based on a washout hypothesis.MethodsAMI was induced in 23 pigs (3 groups) by occluding the left anterior descending (LAD) artery. In SARP-b (SARP balloon inflated) and SARP-nb (SARP balloon deflated) groups, arterial blood was retroperfused for 10 min via the great cardiac vein before releasing the arterial occlusion. A mathematical model of coronary circulation was used to simulate the SARP process and evaluate the potential washout effect.ResultsSARP restored left ventricular function during LAD occlusion. Ejection fraction in the SARP-b group returned to baseline levels, compared to SARP-nb and control groups. Infarct area was significantly larger in the control group than in the SARP-b and SARP-nb groups. End-systolic wall thickness was preserved in the SARP-b compared to the SARP-nb and control groups. Analyte values (pH, lactate, glucose, and others), measured every 2 min during retroperfusion, suggest a “washout” effect as one important mechanism of action of SARP in reducing infarct size. With SARP, the values progressively approached baseline levels. The mathematical model also confirmed a possible washout effect of tracers.DiscussionRI can be ameliorated by delaying restoration of arterial flow for a brief period of time while pretreating the infarction with SARP to restore homeostasis via a washout mechanism.
Nf1 deficiency modulates the stromal environment in the pretumorigenic rat mammary gland
Authors: Arumugam Menusha , Tovar Elizabeth A. , Essenburg Curt J. , Dischinger Patrick S. , Beddows Ian , Wolfrum Emily , Madaj Zach B. , Turner Lisa , Feenstra Kristin , Gallik Kristin L. , Cohen Lorna , Nichols Madison , Sheridan Rachel T. C. , Esquibel Corinne R. , Mouneimne Ghassan , Graveel Carrie R. , Steensma Matthew R. 
Published: May 2024

Background:Neurofibromin, coded by the NF1 tumor suppressor gene, is the main negative regulator of the RAS pathway and is frequently mutated in various cancers. Women with Neurofibromatosis Type I (NF1)–a tumor predisposition syndrome caused by a germline NF1 mutation–have an increased risk of developing aggressive breast cancer with poorer prognosis. The mechanism by which NF1 mutations lead to breast cancer tumorigenesis is not well understood. Therefore, the objective of this work was to identify stromal alterations before tumor formation that result in the increased risk and poorer outcome seen among NF1 patients with breast cancer.Approach:To accurately model the germline monoallelic NF1 mutations in NF1 patients, we utilized an Nf1-deficient rat model with accelerated mammary development before presenting with highly penetrant breast cancer.Results:We identified increased collagen content in Nf1-deficient rat mammary glands before tumor formation that correlated with age of tumor onset. Additionally, gene expression analysis revealed that Nf1-deficient mature adipocytes in the rat mammary gland have increased collagen expression and shifted to a fibroblast and preadipocyte expression profile. This alteration in lineage commitment was also observed with in vitro differentiation, however, flow cytometry analysis did not show a change in mammary adipose-derived mesenchymal stem cell abundance.Conclusion:Collectively, this study uncovered the previously undescribed role of Nf1 in mammary collagen deposition and regulating adipocyte differentiation. In addition to unraveling the mechanism of tumor formation, further investigation of adipocytes and collagen modifications in preneoplastic mammary glands will create a foundation for developing early detection strategies of breast cancer among NF1 patients.
Clinicians in the Veterans Health Administration initiate gender-affirming hormone therapy in concordance with clinical guideline recommendations
Authors: Jasuja Guneet K. , Wolfe Hill L. , Reisman Joel I. , Vimalananda Varsha G. , Rao Sowmya R. , Blosnich John R. , Livingston Nicholas A. , Shipherd Jillian C. 
Published: May 2024

BackgroundGender-affirming hormone therapy (GAHT) is a common medical intervention sought by transgender and gender diverse (TGD) individuals. Initiating GAHT in accordance with clinical guideline recommendations ensures delivery of high-quality care. However, no prior studies have examined how current GAHT initiation compares to recommended GAHT initiation.ObjectiveThis study assessed guideline concordance around feminizing and masculinizing GAHT initiation in the Veterans Health Administration (VHA).MethodsThe sample included 4,676 veterans with a gender identity disorder diagnosis who initiated feminizing (n=3,547) and masculinizing (n=1,129) GAHT between 2007 and 2018 in VHA. Demographics and health conditions on veterans receiving feminizing and masculinizing GAHT were assessed. Proportion of guideline concordant veterans on six VHA guidelines on feminizing and masculinizing GAHT initiation were determined.ResultsCompared to veterans receiving masculinizing GAHT, a higher proportion of veterans receiving feminizing GAHT were older (≥60 years: 23.7% vs. 6.3%), White non-Hispanic (83.5% vs. 57.6%), and had a higher number of comorbidities (≥7: 14.0% vs. 10.6%). A higher proportion of veterans receiving masculinizing GAHT were Black non-Hispanic (21.5% vs. 3.5%), had posttraumatic stress disorder (43.0% vs. 33.9%) and positive military sexual trauma (33.5% vs.16.8%; all p-values&lt;0.001) than veterans receiving feminizing GAHT. Among veterans who started feminizing GAHT with estrogen, 98.6% were guideline concordant due to no documentation of venous thromboembolism, or breast cancer. Among veterans who started spironolactone as part of feminizing GAHT, 98.1% were guideline concordant as they had no documentation of contraindication, including hyperkalemia or acute renal failure. Among veterans starting masculinizing GAHT, 90.1% were guideline concordant due to no documentation of contraindications, such as breast or prostate cancer. Hematocrit had been measured in 91.8% of veterans before initiating masculinizing GAHT, with 96.5% not having an elevated hematocrit (&gt;50%) prior to starting masculinizing GAHT. Among veterans initiating feminizing and masculinizing GAHT, 91.2% had documentation of a gender identity disorder diagnosis prior to GAHT initiation.ConclusionWe observed high concordance between current GAHT initiation practices in VHA and guidelines, particularly for feminizing GAHT. Findings suggest that VHA clinicians are initiating feminizing GAHT in concordance with clinical guidelines. Future work should assess guideline concordance on monitoring and management of GAHT in VHA.
Association between maternal and fetal inflammatory biomarkers and offspring weight and BMI during the first year of life in pregnancies with GDM: MySweetheart study
Authors: Antoniou Maria-Christina , Quansah Dan Yedu , Gilbert Leah , Arhab Amar , Schenk Sybille , Lacroix Alain , Stuijfzand Bobby , Horsch Antje , Puder Jardena Jacqueline 
Published: May 2024

BackgroundGestational Diabetes Mellitus (GDM) is frequently associated with chronic, low-grade inflammation. Whether this environment affects offspring anthropometry during early childhood remains to be elucidated. The aim of this study was to investigate the associations between maternal and fetal (cord blood-umbilical artery) inflammatory biomarkers and offspring weight and BMI up to 1 year in pregnancies with GDM.MethodsIn this prospective secondary analysis of the MySweetheart study, we included 193 women with GDM and their offspring. Maternal and fetal (N=39) predictors included serum levels of inflammatory biomarkers including CRP, IL-6, and TNF-α at 24-32 weeks of gestational age (GA) and in the cord blood. Offspring outcomes were small and large for gestational age (SGA, LGA), sex- and age-adjusted weight, and BMI at birth and at 1 year. Univariate and multivariate regression models were performed. Associations were adjusted for maternal pre-pregnancy BMI, age, and ethnicity.ResultsMean maternal age was 33.6 ± 4.8 years, and pre-pregnancy BMI 25.9 ± 5.6 kg/m2. Their mean gestational age at the 1st GDM visit was 29 ± 2.4 weeks. Gestational age at delivery was 39.7 ± 1.1 weeks, with a mean birthweight of 3.4 ± 0.46 kg; 11.8% of offspring were LGA and 10.8% were SGA. At 1 year of age, mean offspring weight was 9.8 ± 1.2 kg and BMI z-score 0.23 ± 1.1 kg/m2. In the models including only maternal predictors, TNF-α at 24-32 weeks of GA was positively associated with SGA and inversely with offspring weight and BMI at birth and at 1 year (p ≤0.034). In the models including only fetal predictors and the combined model, CRP was inversely associated with BMI at 1 year (p ≤0.020).ConclusionsIn women with GDM, maternal and fetal inflammatory biomarkers distinctively influenced offspring anthropometry during the first year of life, independent of maternal age, prepregnancy BMI and ethnicity. These results suggest that low-grade inflammation during pregnancy may affect the developing offspring by leading to a decrease in weight and BMI and may have implications for future personalized follow-up of women with GDM and their offspring.
The relationship between health literacy and blood sugar control in rural areas among diabetes patients
Authors: Chen Jingfeng , Wen Lina , Fu Guifen , Bai Chaoqun , Lei Xiaoxue , Zhang Yanping 
Published: May 2024

BackgroundAlthough the relationship between health literacy and glycemic control has been explored in patients with diabetes, little is known about the relationship between different categories of diabetes health literacy and glycemic control in rural areas. Therefore, this study focused on the relationship between different categories of health literacy and glycemic control among diabetic patients in rural areas of Guangxi, ChinaObjectiveTo explore the potential profiles of health literacy among rural diabetes patients in Guangxi and investigate their relationship with blood sugar control.MethodsA health literacy questionnaire was administered to 2280 rural diabetes patients in five cities in the Guangxi Zhuang Autonomous Region. Latent profile analysis was conducted to identify potential health literacy profiles.ResultsHealth literacy among rural diabetes patients in Guangxi could be categorized into high literacy-high functionality and low literacy-low criticality groups. The latent categories of health literacy were associated with blood sugar control, with diabetes patients in the high literacy-high functionality group demonstrating better blood sugar control than those in the low literacy-low criticality group (P &lt; 0.05).ConclusionHealth literacy among rural diabetes patients in Guangxi exhibits heterogeneity. Healthcare professionals should pay attention to patients with low literacy and low criticality in rural areas and develop interventions to enhance their health literacy, thereby improving their blood sugar control.
Increased interleukin-26 in the peripheral joints of patients with axial spondyloarthritis and psoriatic arthritis, co-localizing with CD68-positive synoviocytes
Authors: Hammitzsch Ariane , Ossadnik Andreas , Bachmann Quirin , Merwald-Fraenk Helga , Lorenz Georg , Witt Matthias , Wiesent Franziska , Mühlhofer Heinrich , Simone Davide , Bowness Paul , Heemann Uwe , Arbogast Martin , Moog Philipp , Schmaderer Christoph 
Published: May 2024

ObjectivesIL26 levels are elevated in the blood and synovial fluid of patients with inflammatory arthritis. IL26 can be produced by Th17 cells and locally within joints by tissue-resident cells. IL26 induces osteoblast mineralization in vitro. As osteoproliferation and Th17 cells are important factors in the pathogenesis of axial spondyloarthritis (axSpA), we aimed to clarify the cellular sources of IL26 in spondyloarthritis.MethodsSerum, peripheral blood mononuclear cells (n = 15–35) and synovial tissue (n = 3–9) of adult patients with axSpA, psoriatic arthritis (PsA) and rheumatoid arthritis (RA) and healthy controls (HCs, n = 5) were evaluated by ELISA, flow cytometry including PrimeFlow assay, immunohistochemistry and immunofluorescence and quantitative PCR.ResultsSynovial tissue of axSpA patients shows significantly more IL26-positive cells than that of HCs (p &lt; 0.01), but numbers are also elevated in PsA and RA patients. Immunofluorescence shows co-localization of IL26 with CD68, but not with CD3, SMA, CD163, cadherin-11, or CD90. IL26 is elevated in the serum of RA and PsA (but not axSpA) patients compared with HCs (p &lt; 0.001 and p &lt; 0.01). However, peripheral blood CD4+ T cells from axSpA and PsA patients show higher positivity for IL26 in the PrimeFlow assay compared with HCs. CD4+ memory T cells from axSpA patients produce more IL26 under Th17-favoring conditions (IL-1β and IL-23) than cells from PsA and RA patients or HCs.ConclusionIL26 production is increased in the synovial tissue of SpA and can be localized to CD68+ macrophage-like synoviocytes, whereas circulating IL26+ Th17 cells are only modestly enriched. Considering the osteoproliferative properties of IL26, this offers new therapeutic options independent of Th17 pathways.
Tumor-associated CD8+T cell tolerance induced by erythroid progenitor cells
Authors: Fan Xue , Peng Han , Wang Xuesong , Sun Yixin , Dong Yan , Zhou Jie , Chen Jianfang , Huang Shuo 
Published: May 2024

IntroductionCD8+T cell tolerance plays an important role in tumor escape. Recent studies have shown that CD45+ erythroid progenitor cells (CD45+EPCs) generated through splenic extramedullary erythropoiesis suppress tumor immunity. However, the mechanism underlying how CD45+EPCs mediate CD8+T cell tolerance remains incompletely understood and requires further research.MethodsIn this study, the antigen-processing abilities of CD45+EPCs was verified through both in vitro and in vivo experiments. We have used the method of co-culture in vitro and adoptive transfer experiments in vivo to explore the effects of CD45+EPCs on CD8+T cell tolerance. RNA-sequencing analysis and blocking experiments were used to evaluate the role of ROS in the CD45+EPC mediated tolerance of CD8+T cells. Finally, we incorporated uric acid into the adoptive transfer experiments to rescue the CD45+EPC mediated tumor-promoting effect.Results and discussionWe found that CD45+EPCs take up soluble proteins, present antigenic epitopes on their surface, and induce antigen-specific CD8+T cell anergy. In addition, we found that CD45+EPC directly nitrates tyrosine within the TCR/CD8 complex via the production of reactive oxygen species and peroxynitrite, preventing CD8+ T cells from responding to their specific peptide antigens. Furthermore, uric acid treatment effectively abolished the immunosuppressive effects of CD45+EPCs during CD8+T cell adoptive transfer, thereby enhancing the anti-tumor efficacy. These results demonstrated that CD8+T cell tolerance in tumor-bearing mice is induced by CD45+EPCs. The results of this study have direct implications for tumor immunotherapy.
Lysosome-related genes predict acute myeloid leukemia prognosis and response to immunotherapy
Authors: Wan Peng , Zhong Liang , Yu Lihua , Shen Chenlan , Shao Xin , Chen Shuyu , Zhou Ziwei , Wang Meng , Zhang Hongyan , Liu Beizhong 
Published: May 2024

BackgroundAcute myeloid leukemia (AML) is a highly aggressive and pathogenic hematologic malignancy with consistently high mortality. Lysosomes are organelles involved in cell growth and metabolism that fuse to form specialized Auer rods in AML, and their role in AML has not been elucidated. This study aimed to identify AML subtypes centered on lysosome-related genes and to construct a prognostic model to guide individualized treatment of AML.MethodsGene expression data and clinical data from AML patients were downloaded from two high-throughput sequencing platforms. The 191 lysosomal signature genes were obtained from the database MsigDB. Lysosomal clusters were identified by unsupervised consensus clustering. The differences in molecular expression, biological processes, and the immune microenvironment among lysosomal clusters were subsequently analyzed. Based on the molecular expression differences between lysosomal clusters, lysosomal-related genes affecting AML prognosis were screened by univariate cox regression and multivariate cox regression analyses. Algorithms for LASSO regression analyses were employed to construct prognostic models. The risk factor distribution, KM survival curve, was applied to evaluate the survival distribution of the model. Time-dependent ROC curves, nomograms and calibration curves were used to evaluate the predictive performance of the prognostic models. TIDE scores and drug sensitivity analyses were used to explore the implication of the model for AML treatment.ResultsOur study identified two lysosomal clusters, cluster1 has longer survival time and stronger immune infiltration compared to cluster2. The differences in biological processes between the two lysosomal clusters are mainly manifested in the lysosomes, vesicles, immune cell function, and apoptosis. The prognostic model consisting of six prognosis-related genes was constructed. The prognostic model showed good predictive performance in all three data sets. Patients in the low-risk group survived significantly longer than those in the high-risk group and had higher immune infiltration and stronger response to immunotherapy. Patients in the high-risk group showed greater sensitivity to cytarabine, imatinib, and bortezomib, but lower sensitivity to ATRA compared to low -risk patients.ConclusionOur prognostic model based on lysosome-related genes can effectively predict the prognosis of AML patients and provide reference evidence for individualized immunotherapy and pharmacological chemotherapy for AML.
The association between the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio and systemic sclerosis and its complications: a systematic review and meta-analysis
Authors: Zinellu Angelo , Mangoni Arduino A. 
Published: May 2024

IntroductionThe identification of new, easily measurable biomarkers might assist clinicians in diagnosing and managing systemic sclerosis (SSc). Although the full blood count is routinely assessed in the evaluation of SSc, the diagnostic utility of specific cell-derived inflammatory indices, i.e., neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), has not been critically appraised in this patient group.MethodsWe conducted a systematic review and meta-analysis of studies investigating the NLR, PLR, and MLR, in SSc patients and healthy controls and in SSc patients with and without relevant complications. PubMed, Scopus, and Web of Science were searched from inception to 23 February 2024. Risk of bias and certainty of evidence were assessed using validated tools.ResultsIn 10 eligible studies, compared to controls, patients with SSc had significantly higher NLR (standard mean difference, SMD=0.68, 95% CI 0.46 to 0.91, p&lt;0.001; I2 = 74.5%, p&lt;0.001), and PLR values (SMD=0.52, 95% CI 0.21 to 0.83, p=0.001; I2 = 77.0%, p=0.005), and a trend towards higher MLR values (SMD=0.60, 95% CI -0.04 to 1.23, p=0.066; I2 = 94.1%, p&lt;0.001). When compared to SSc patients without complications, the NLR was significantly higher in SSc with interstitial lung disease (ILD, SMD=0.31, 95% CI 0.15 to 0.46, p&lt;0.001; I2 = 43.9%, p=0.11), pulmonary arterial hypertension (PAH, SMD=1.59, 95% CI 0.04 to 3.1, p=0.045; I2 = 87.6%, p&lt;0.001), and digital ulcers (DU, SMD=0.43, 95% CI 0.13 to 0.74, p=0.006; I2 = 0.0%, p=0.49). The PLR was significantly higher in SSc patients with ILD (SMD=0.42, 95% CI 0.25 to 0.59, p&lt;0.001; I2 = 24.8%, p=0.26). The MLR was significantly higher in SSc patients with PAH (SMD=0.63, 95% CI 0.17 to 1.08, p=0.007; I2 = 66.0%, p=0.086), and there was a trend towards a higher MLR in SSc patients with ILD (SMD=0.60, 95% CI -0.04 to 1.23, p=0.066; I2 = 94.1%, p&lt;0.001).DiscussionPending the results of appropriately designed prospective studies, the results of this systematic review and meta-analysis suggest that blood cell-derived indices of inflammation, particularly the NLR and PLR, may be useful in the diagnosis of SSc and specific complications.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024520040.
The real life experience goes on: update after 4 years on the first cohort treated with lanadelumab at our center
Authors: Buttgereit Thomas , Vera Ayala Carolina , Aykanat Seda , Weller Karsten , Gutsche Annika , Maurer Marcus , Magerl Markus 
Published: May 2024

IntroductionLanadelumab is a first-line long-term prophylaxis (LTP) in hereditary angioedema (HAE). Real-life data on its long-term efficacy and safety are limited. It is unknown whether patients using lanadelumab need short-term prophylaxis (STP).ObjectivesTo provide 4-year follow-up data for our first 34 patients treating with lanadelumab.MethodsPatients were assessed for their current injection interval, attacks, treatment satisfaction, disease control (AECT), quality of life impairment (AE-QoL), events that can induce attacks, and the use of STP since the start of their treatment with lanadelumab.ResultsOf 34 patients who started lanadelumab treatment, 32 were still using it after 4 years, with a median injection interval of 33 (range 14-90) days. HAE patients (n=28) reported longer intervals, i.e. 35 (14-90) days, than patients with angioedema due to acquired C1 inhibitor deficiency (n=4, 23 (14-31) days). With their current injection intervals, used for a mean duration of 29 ± 17 months, patients reported a yearly attack rate of 0.3 ± 0.1. More than 70% of patients were attack-free since starting their current injection interval. All patients reported well-controlled disease, i.e. ≥10 points in the AECT; 21 patients had complete control (16 points). AE-QoL scores improved further compared to our initial report, most prominently in the fears/shame domain (-6 points). Treatment satisfaction was very high. No angioedema occurred after 146 of 147 potentially attack-inducing medical procedures without STP.ConclusionsOur results demonstrate the long-term efficacy and safety of lanadelumab in real-life and question the need for STP in patients who use effective LTP.