bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multisystem Involvement Induced by Human Parvovirus B19 Infection in a Non-immunosuppressed Adult: A Case Report
Authors: Zou Qihang , Chen Peisong , Chen Jiaxin , Chen Dingbang , Xia Han , Chen Ling , Feng Huiyu , Feng Li 
Published: April 2022

BackgroundHuman parvovirus B19 (B19V) infection is usually symptomless and occurs in the childhood. While in immunocompromised adults, B19V infection also presents various clinical symptoms due to the host's immune status. The classic symptoms include erythema, anemia, arthropathy, and edema, but neurological involvement is rare.Case PresentationIn this report, we present a case of B19V infection caused multiple organ dysfunction in a non-immunosuppressed adult. Metagenomic next-generation sequencing (mNGS) was used and successfully detected the pathogen in multiple types of samples, including blood, cerebrospinal fluid (CSF), and bronchoalveolar lavage fluid (BALF). The diagnosis was subsequently confirmed by polymerase chain reaction (PCR). He was treated with intravenous gamma globulin, resulting in a significant resolution of symptoms after 1 month.ConclusionMultisystem involvement induced by B19V infection was found in this case report. mNGS performed great advantages in rapidly and accurately diagnosing B19V infection in multiple types of samples, which helps the timely adjustment of treatment and improves the prognosis.
Combination of Fat-Free Muscle Index and Total Spontaneous Portosystemic Shunt Area Identifies High-Risk Cirrhosis Patients
Authors: Faron Anton , Abu-Omar Jasmin , Chang Johannes , Böhling Nina , Sprinkart Alois Martin , Attenberger Ulrike , Rockstroh Jürgen K. , Luu Andreas Minh , Jansen Christian , Strassburg Christian P. , Trebicka Jonel , Luetkens Julian , Praktiknjo Michael 
Published: April 2022

BackgroundSarcopenia and spontaneous portosystemic shunts (SPSSs) are common complications of liver cirrhosis, and both are associated with higher rates of hepatic encephalopathy (HE) development in these patients. This study aimed to evaluate the simultaneous impact of skeletal muscle mass and spontaneous portosystemic shunting, measured from routine diagnostic CT on outcomes in patients with liver cirrhosis.MethodsRetrospective analysis of patients with cirrhosis. Skeletal muscle mass [including fat-free muscle index (FFMI) as a surrogate for sarcopenia] and total cross-sectional spontaneous portosystemic shunt area (TSA) were quantified from CT scans. The primary endpoint was the development of HE, while the secondary endpoint was 1-year mortality.ResultsOne hundred fifty-six patients with liver cirrhosis were included. Patients with low (L-) FFMI and large (L-)TSA showed higher rates of HE development. In multivariable analysis, L-FFMI and L-TSA were independent predictors of HE development (L-FFMI HR = 2.69, CI 1.22–5.93; L-TSA, HR = 2.50, CI = 1.24–4.72) and 1-year mortality (L-FFMI, HR = 7.68, CI 1.75–33.74; L-TSA, HR = 3.05, CI 1.32–7.04). The simultaneous presence of L-FFMI and L-TSA exponentially increased the risk of HE development (HR 12.79, CI 2.93–55.86) and 1-year mortality (HR 13.66, CI 1.75–106.50). An easy sequential algorithm including FFMI and TSA identified patients with good, intermediate, and poor prognoses.ConclusionThis study indicates synergy between low skeletal muscle mass and large TSA to predict exponentially increased risk of HE development and mortality in liver cirrhosis. Simultaneous screening for sarcopenia and TSA from routine diagnostic CT may help to improve the identification of high-risk patients using an easy-to-apply algorithm.Clinical Trial registration[ClinicalTrials.gov], identifier [NCT03584204].
Establishment and Verification of Prognostic Nomograms for Young Women With Breast Cancer Bone Metastasis
Authors: Wang Zhan , Shao Haiyu , Xu Qiang , Wang Yongguang , Ma Yaojing , Diaty Diarra Mohamed , Zhang Jiahao , Ye Zhaoming 
Published: April 2022

PurposeThe prognosis of patients with metastatic breast cancer usually varies greatly among individuals. At present, the application of nomogram is very popular in metastatic tumors. The present study was conducted to identify independent survival predictors and construct nomograms among young women with breast cancer bone metastasis (BCBM).Patients and MethodsWe searched the Surveillance, Epidemiology, and End Results (SEER) database to identify young women diagnosed with BCBM between 2010 and 2016. We first analyzed the potential risk factors of overall survival (OS) and cancer-specific survival (CSS) by applying univariate Cox regression analysis. Then we conducted multivariate Cox analysis to identify independent survival predictors. Based on significant independent predictors, we developed and validated novel prognostic nomograms by using the R version 4.1.0 software.ResultsWe finally identified 715 eligible young women with BCBM for survival analysis, of which 358 patients were in the training set, and 357 patients in the validation set. Approximately four-fifths of patients are between 31 and 40 years old. The 5-year OS and CSS rates of this research population were 41.9 and 43.3%, respectively. Multivariate analysis revealed seven independent predictors of both OS and CSS, including race, tumor subtype, tumor size, surgical treatment, brain metastasis, liver metastasis, and lung metastasis. Based on these predictors, we developed and validated OS and CSS nomograms. The C-index of the OS nomogram reached 0.728 and 0.73 in the training and validation sets, respectively. The C-index of the CSS nomogram reached 0.743 and 0.695 in the training and validation sets, respectively. Meanwhile, high quality calibration plots were revealed in both OS and CSS nomograms.ConclusionThe current novel nomograms can provide an individualized survival evaluation of young women with BCBM and instruct clinicians to treat them appropriately.
Senescence-Associated Molecules and Tumor-Immune-Interactions as Prognostic Biomarkers in Colorectal Cancer
Authors: Kellers Franziska , Fernandez Aurélie , Konukiewitz Björn , Schindeldecker Mario , Tagscherer Katrin E. , Heintz Achim , Jesinghaus Moritz , Roth Wilfried , Foersch Sebastian 
Published: April 2022

Background and AimsThe initiation of cellular senescence in response to protumorigenic stimuli counteracts malignant progression in (pre)malignant cells. Besides arresting proliferation, cells entering this terminal differentiation state adopt a characteristic senescence-associated secretory phenotype (SASP) which initiates alterations to their microenvironment and effects immunosurveillance of tumorous lesions. However, some effects mediated by senescent cells contribute to disease progression. Currently, the exploration of senescent cells' impact on the tumor microenvironment and the evaluation of senescence as possible target in colorectal cancer (CRC) therapy demand reliable detection of cellular senescence in vivo. Therefore, specific immunohistochemical biomarkers are required. Our aim is to analyze the clinical implications of senescence detection in colorectal carcinoma and to investigate the interactions of senescent tumor cells and their immune microenvironment in vitro and in vivo.MethodsSenescence was induced in CRC cell lines by low-dose-etoposide treatment and confirmed by Senescence-associated β-galactosidase (SA-β-GAL) staining and fluorescence activated cell sorting (FACS) analysis. Co-cultures of senescent cells and immune cells were established. Multiple cell viability assays, electron microscopy and live cell imaging were conducted. Immunohistochemical (IHC) markers of senescence and immune cell subtypes were studied in a cohort of CRC patients by analyzing a tissue micro array (TMA) and performing digital image analysis. Results were compared to disease-specific survival (DSS) and progression-free survival (PFS).ResultsVarying expression of senescence markers in tumor cells was associated with in- or decreased survival of CRC patients. Proximity analysis of p21-positive senescent tumor cells and cytotoxic T cells revealed a significantly better prognosis for patients in which these cell types have the possibility to directly interact. In vitro, NK-92 cells (mimicking natural killer T cells) or TALL-104 cells (mimicking both cytotoxic T cells and natural killer T cells) led to dose-dependent specific cytotoxicity in &gt;75 % of the senescent CRC cells but &lt;20 % of the proliferating control CRC cells. This immune cell-mediated senolysis seems to be facilitated via direct cell-cell contact inducing apoptosis and granule exocytosis.ConclusionCounteracting tumorigenesis, cellular senescence is of significant relevance in CRC. We show the dual role of senescence bearing both beneficial and malignancy-promoting potential in vivo. Absence as well as exceeding expression of senescence markers are associated with bad prognosis in CRC. The antitumorigenic potential of senescence induction is determined by tumor micromilieu and immune cell-mediated elimination of senescent cells.
Long-Term Prognosis of Patients With Anti-N-Methyl-D-Aspartate Receptor Encephalitis Who Underwent Teratoma Removal: An Observational Study
Authors: Zhang Hesheng , Xiong Weixi , Liu Xu , Liu Wenyu , Zhou Dong , Wu Xintong 
Published: April 2022

ObjectiveThis study aimed to evaluate the clinical characteristics and long-term surgical outcomes of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis with teratoma.MethodsPatients who were admitted to West China Hospital from June 2012 to June 2019 and diagnosed with anti-NMDAR encephalitis were enrolled in the study. Medical records were reviewed prospectively to gather clinical characteristic data. Patients were followed up at long-term every 3 months.ResultsThis study included 192 patients, among whom 21 (10.9%) were detected with having a teratoma. Patients included 20 women, with a mean age of 24.62 ± 7.61 years. Seizure and psychiatric symptoms were the most dominant symptoms in both groups, followed by memory deficits. Central hypoventilation (52.4 vs. 17%, p &lt; 0.001) and decreased consciousness (71.4 vs. 31.3%, p = 0.002) were significantly more frequent in patients with teratoma than in those without. Moreover, the anti-NMDAR antibody titer was higher (p = 0.021) and the baseline modified Rankin scale score was lower (p = 0.004) in patients with teratoma than in those without. First-line immunotherapy was performed in 21 (100%) patients with teratoma and 167 (97.7%) patients without teratoma. All patients with teratoma had the tumor removed. During follow-up, two (9.5%) patients with teratoma and 11 (6.4%) patients without teratoma died, whereas 1 (4.8%) patient with teratoma and 37 (21.6%) patients without teratoma had relapses. Overall, 19 (90.5%) patients with teratoma and 151 (88.3%) patients without teratoma achieved favorable clinical outcomes at the final follow-up.ConclusionsWith early detection and removal of teratoma, most patients with anti-NMDAR encephalitis and teratoma achieved a favorable long-term prognosis.
Prepubertal Children With Metabolically Healthy Obesity or Overweight Are More Active Than Their Metabolically Unhealthy Peers Irrespective of Weight Status: GENOBOX Study
Authors: Llorente-Cantarero Francisco Jesús , Leis Rosaura , Rupérez Azahara I. , Anguita-Ruiz Augusto , Vázquez-Cobela Rocío , Flores-Rojas Katherine , González-Gil Esther M. , Aguilera Concepción M. , Moreno Luis A. , Gil-Campos Mercedes , Bueno Gloria 
Published: April 2022

Background and AimThe association of a metabolically healthy status with the practice of physical activity (PA) remains unclear. Sedentarism and low PA have been linked to increased cardiometabolic risk. The aim of this study was to evaluate the PA levels in metabolically healthy (MH) or unhealthy (MU) prepubertal children with or without overweight/obesity.MethodsA total 275 children (144 boys) with 9 ± 2 years old were selected for the GENOBOX study. PA times and intensities were evaluated by accelerometry, and anthropometry, blood pressure, and blood biochemical markers were analyzed. Children were considered to have normal weight or obesity, and further classified as MH or MU upon fulfillment of the considered metabolic criteria.ResultsClassification resulted in 119 MH children (21% with overweight/obesity, referred to as MHO) and 156 MU children (47% with overweight/obesity, referred to as MUO). Regarding metabolic profile, MHO showed lower blood pressure levels, both systolic and diastolic and biochemical markers levels, such as glucose, Homeostatic Model Assessment of Insulin Resistance, triglycerides and higher HDL-c levels than MUO (P &lt; 0.001). In addition, MHO children spent more time in PA of moderate intensity compared with MUO children. In relation to vigorous PA, MH normal weight (MHN) children showed higher levels than MUO children. Considering sex, boys spent more time engaged in moderate, vigorous, and moderate–vigorous (MV) PA than girls, and the number of boys in the MH group was also higher.ConclusionPrepubertal MHO children are less sedentary, more active, and have better metabolic profiles than their MUO peers. However, all children, especially girls, should increase their PA engagement, both in terms of time and intensity because PA appears to be beneficial for metabolic health status itself.
Fructose Induces Insulin Resistance of Gestational Diabetes Mellitus in Mice via the NLRP3 Inflammasome Pathway
Authors: Liu Yao , Wei Yuanhuan , Wu Lanlan , Lin Xiaoping , Sun Ruifang , Chen Hengying , Shen Siwen , Deng Guifang 
Published: April 2022

BackgroundInsulin resistance (IR), which is affected by dietary factors, is the main pathology underlying of gestational diabetes mellitus (GDM). Fructose (Fru), a sugar found in fruits, honey, and food sweeteners, has been reported to induce IR and inflammation. This study explored the effects and mechanisms of Fru on IR of GDM in pregnant and postpartum mice and their offspring.MethodsThe 6-week-old female C57BL/6J mice were randomly divided into control (Chow) and fructose (Fru) groups, with the latter receiving 20% (w/v) Fru in drinking water from 2 weeks before pregnancy to the end of pregnancy. The effects of Fru on IR and inflammation were determined using serum parameters, glucose metabolism tests, immunohistochemistry, and western blotting.ResultsCompared with the Chow group mice, pregnant mice treated with Fru exhibited greater gestational weight gain, higher fasting blood glucose and insulin concentrations, and a higher homeostasis model of assessment (HOMA) for IR index, but a lower HOMA for insulin sensitivity index. Treatment with Fru also increased the concentrations of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-17, and C-reactive protein in sera and the expression of IL-6, TNF-α, IL-17, and IL-1β mRNA in liver tissues of pregnant mice. Both CD68 and IL-1β positive cell were increased in Fru-treated mice compared with in Chow mice. Fru treatment also promoted IR and inflammation in mice at 4 weeks after delivery and in offspring mice. Mechanistically, Fru promoted the nuclear translocation of nuclear factor-kappa B (NF-κB) p65 to activate the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome.ConclusionsExposure to Fru before and during pregnancy induced IR in pregnant mice, which continued at 4 weeks postpartum and affected the offspring. The effects of Fru may be associated with activation of the NF-κB–NLRP3 pathway.
EVOO Promotes a Less Atherogenic Profile Than Sunflower Oil in Smooth Muscle Cells Through the Extracellular Vesicles Secreted by Endothelial Cells
Authors: Santiago-Fernandez Concepción , Rodríguez-Díaz Cristina , Ho-Plagaro Ailec , Gutierrez-Repiso Carolina , Oliva-Olivera Wilfredo , Martin-Reyes Flores , Mela Virginia , Bautista Rocío , Tome Mónicas , Gómez-Maldonado Josefa , Tinahones Francisco J. , Garcia-Fuentes Eduardo , Garrido-Sánchez Lourdes 
Published: April 2022

BackgroundLittle is known about the effect of extra virgin olive (EVOO) and sunflower oil (SO) on the composition of extracellular vesicles (EVs) secreted by endothelial cells and the effects of these EVs on smooth muscle cells (SMCs). These cells play an important role in the development of atherosclerosis.MethodsWe evaluated the effects of endothelial cells-derived EVs incubated with triglyceride-rich lipoproteins obtained after a high-fat meal with EVOO (EVOO-EVs) and SO (SO-EVs), on the transcriptomic profile of SMCs.ResultsWe found 41 upregulated and 19 downregulated differentially expressed (DE)-miRNAs in EVOO-EVs. Afterwards, SMCs were incubated with EVOO-EVs and SO-EVs. SMCs incubated with SO-EVs showed a greater number of DE-mRNA involved in pathways related to cancer, focal adhesion, regulation of actin cytoskeleton, and MAPK, toll-like receptor, chemokine and Wnt signaling pathways than in SMCs incubated with EVOO-EVs. These DE-mRNAs were involved in biological processes related to the response to endogenous stimulus, cell motility, regulation of intracellular signal transduction and cell population proliferation.ConclusionEVOO and SO can differently modify the miRNA composition of HUVEC-derived EVs. These EVs can regulate the SMCs transcriptomic profile, with SO-EVs promoting a profile more closely linked to the development of atherosclerosis than EVOO-EVs.
Quantifying Societal Burden of Radiation-Induced Cardiovascular Events in Breast Cancer Survivors
Authors: Kimpe Eva , Werbrouck Amber , De Ridder Mark , Putman Koen 
Published: April 2022

Background and PurposeRadiation-induced cardiotoxicity is an important health concern for clinicians during treatment of breast cancer (BC) patients. Underlying mechanisms are well-documented, whereas little is known about the societal impact of this long-term effect. This study aimed to quantify the additional burden of radiation-induced cardiovascular (CV) diseases in BC survivors.Materials and MethodsConventional health economic modelling techniques were applied to estimate attributed CV-related costs and disutility in a hypothetical cohort of BC survivors. A situation in which radiotherapy caused an additional CV risk was compared with a situation in which this risk was not taken into account. Uncertainty was assessedviadeterministic and probabilistic sensitivity analyses. Analyses were performed from a broad societal perspective up until 20 years after BC treatment.ResultsRadiation-induced cardiotoxicity evokes a mean incremental cost of €275.10 per woman over a time horizon of 20 years after BC treatment. An additional decrement of 0.017 QALYs (per woman) might be expected when taking the radiation-induced cardiotoxic risk into account in BC survivors. Incremental costs and disutility increased with age. A scenario analysis showed that these results were more profound in women with more advanced staging.ConclusionOur analyses suggest that with current radiation techniques, rather minor costs and disutility are to be expected from radiation-induced cardiotoxicity in BC survivors. The cost of past investments in order to achieve current mean heart dose (MHD) seems justified when considering the gains from cost and disutility reduction resulting from radiation-induced cardiovascular events. The question we might consider is whether future opportunity costs associated with investments on further technological advancements offset the expected marginal benefit from further reducing the MHD.
Single-Cell RNA Sequencing of Metastatic Testicular Seminoma Reveals the Cellular and Molecular Characteristics of Metastatic Cell Lineage
Authors: Mo Linjian , Yu Zhenyuan , Lv Yufang , Cheng Jiwen , Yan Haibiao , Lu Wenhao , Su Cheng , Ling Qiang , Mo Zengnan 
Published: April 2022

BackgroundTesticular cancer is the most common solid malignancy in young men. Given the many histological classifications of testicular tumors, seminoma is one of the most treatable cancers. The survival rate in early-stage disease was more than 90%. Thus, seminoma at the cellular and molecular levels, especially at the single-cell level, is worth studying.MethodsWe performed a single-cell RNA sequencing (scRNA-seq) study on a patient who was diagnosed with testicular seminoma with lymph node metastasis. This study presented tumor tissue, PBMC, pelvic and renal hilus lymph node in a total of 18,206 high-quality single-cell transcriptome information. The characteristics of metastatic cell lineage were revealed by the comparison between different tumor cell subtypes at the scRNA level.ResultsA single-cell map of testicular seminoma with lymph node metastasis was constructed by scRNA-seq. We discovered the gene expression characteristics of the tumor cells in testicular seminoma, especially metastatic tumor cells. KRT8 and KRT18 were commonly expressed in the three tumor cell subtypes. However, TCF7L1, SCG3 and SV2C were the specifically expressed genes of tumor cell subtypes in primary tumor sites. Some molecular markers specifically expressed by the metastatic cell lineage, such as POU5F1, were identified.ConclusionsWe revealed the molecular characteristics of testicular seminoma at the single-cell level, especially the metastatic tumor cells. This study could provide new insights into the diagnosis and treatment of testicular seminoma.
Epidemiology and Clinical Characteristics of Human Coronaviruses-Associated Infections in Children: A Multi-Center Study
Authors: Jo Kyo Jin , Choi Soo-Han , Oh Chi Eun , Kim HyeonA , Choi Bong Seok , Jo Dae Sun , Park Su Eun 
Published: April 2022

BackgroundHuman coronaviruses (HCoVs) are associated with upper respiratory tract infections. Although studies have analyzed the clinical and epidemiological characteristics of HCoV-associated infections, no multi-center studies have been conducted in Korean children. We aimed to describe the epidemiology and clinical characteristics of HCoV-associated infection in children.MethodsWe retrospectively reviewed medical records of children in whom HCoVs were detected using multiplex reverse transcriptase-polymerase chain reaction amplification in five centers from January 2015 to December 2019.ResultsOverall, 1,096 patients were enrolled. Among them, 654 (59.7%) patients were male. The median age was 1 year [interquartile range (IQR), 0–2 years]. HCoVs were identified mainly in winter (55.9%). HCoV-229E, HCoV-OC43, and HCoOV-NL63 were detected mainly in winter (70.9, 55.8, and 57.4%, respectively), but HCoV-HKU1 was mainly identified in spring (69.7%). HCoV-OC43 (66.0%) was detected most frequently, followed by HCoV-NL63 (33.3%), and HCoV-229E (7.7%). Two different types of HCoVs were co-detected in 18 samples, namely. Alphacoronavirus-betacoronavirus co-infection (n = 13) and, alphacoronavirus-alphacoronavirus co-infection (n = 5). No betacoronavirus-betacoronavirus co-infection was detected. Patients were diagnosed with upper respiratory tract infection (41.4%), pneumonia (16.6%), acute bronchiolitis (15.5%), non-specific febrile illness (13.1%), croup (7.3%), and acute gastroenteritis (5.1%). There were 832 (75.9%) hospitalized patients with a median duration of hospitalization of 4 days (IQR, 3–5 days); 108 (9.9%) patients needed supplemental oxygen with 37 (3.4%) needing high-flow nasal cannula or mechanical ventilation. There were no deaths.ConclusionHCoV-associated infections exhibit marked seasonality with peaks in winter. Patients with lower respiratory tract infection, a history of prematurity, or underlying chronic diseases may progress to a severe course and may need oxygen therapy.