bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recent Trends in the Incidence of Clear Cell Adenocarcinoma and Survival Outcomes: A SEER Analysis
Authors: Guo Yadong , Shrestha Anil , Maskey Niraj , Dong Xiaohui , Zheng Zongtai , Yang Fuhan , Wang Ruiliang , Ma Wenchao , Liu Ji , Li Cheng , Zhang Wentao , Mao Shiyu , Zhang Aihong , Liu Shenghua , Yao Xudong 
Published: February 2022

BackgroundClear cell adenocarcinoma (CCA) is considered a relatively rare tumor with a glycogen-rich phenotype. The prognosis of CCA patients is unclear. In this study, recent trends in the epidemiological and prognostic factors of CCA were comprehensively investigated.MethodsPatients with CCA from years 2000 to 2016 were identified from the Surveillance, Epidemiological, and End Results (SEER) database. Relevant population data were used to analyze the rates age-adjusted incidence, age-standardized 3-year and 5-year relative survivals, and overall survival (OS).ResultsThe age-adjusted incidence of CCA increased 2.7-fold from the year 2000 (3.3/100,000) to 2016 (8.8/100,000). This increase occurred across all ages, races, stages, and grades. Of all these subgroups, the increase was largest in the grade IV group. The age-standardized 3-year and 5-year relative survivals increased during this study period, rising by 9.1% and 9.5% from 2000 to 2011, respectively. Among all the stages and grades, the relative survival increase was greatest in the grade IV group. According to multivariate analysis of all CCA patients, predictors of OS were: age, gender, year of diagnosis, marital status, race, grade, stage, and primary tumor site (P &lt; 0.001). The OS of all CCA patients during the period 2008 to 2016 was significantly higher than that from 2000 to 2007 (P &lt; 0.001).ConclusionsThe incidence of CCA and survival of these patients improved over time. In particular, the highest increases were reported for grade IV CCA, which may be due to an earlier diagnosis and improved treatment.
Mesenchymal Stem Cells Exposed to Persistently High Glucocorticoid Levels Develop Insulin-Resistance and Altered Lipolysis: A Promising In Vitro Model to Study Cushing’s Syndrome
Authors: Di Vincenzo Mariangela , Martino Marianna , Lariccia Vincenzo , Giancola Giulia , Licini Caterina , Di Benedetto Giovanni , Arnaldi Giorgio , Orciani Monia 
Published: February 2022

BackgroundIn Cushing’s syndrome (CS), chronic glucocorticoid excess (GC) and disrupted circadian rhythm lead to insulin resistance (IR), diabetes mellitus, dyslipidaemia and cardiovascular comorbidities. As undifferentiated, self-renewing progenitors of adipocytes, mesenchymal stem cells (MSCs) may display the detrimental effects of excess GC, thus revealing a promising model to study the molecular mechanisms underlying the metabolic complications of CS.MethodsMSCs isolated from the abdominal skin of healthy subjects were treated thrice daily with GCs according to two different regimens: lower, circadian-decreasing (Lower, Decreasing Exposure, LDE) versus persistently higher doses (Higher, Constant Exposure, HCE), aimed at mimicking either the physiological condition or CS, respectively. Subsequently, MSCs were stimulated with insulin and glucose thrice daily, resembling food uptake and both glucose uptake/GLUT-4 translocation and the expression of LIPE, ATGL, IL-6 and TNF-α genes were analyzed at predefined timepoints over three days.ResultsLDE to GCs did not impair glucose uptake by MSCs, whereas HCE significantly decreased glucose uptake by MSCs only when prolonged. Persistent signs of IR occurred after 30 hours of HCE to GCs. Compared to LDE, MSCs experiencing HCE to GCs showed a downregulation of lipolysis-related genes in the acute period, followed by overexpression once IR was established.ConclusionsPreserving circadian GC rhythmicity is crucial to prevent the occurrence of metabolic alterations. Similar to mature adipocytes, MSCs suffer from IR and impaired lipolysis due to chronic GC excess: MSCs could represent a reliable model to track the mechanisms involved in GC-induced IR throughout cellular differentiation.
Characteristics of Intraoperative Hemodynamic Instability in Postoperatively Diagnosed Pheochromocytoma and Sympathetic Paraganglioma Patients
Authors: Kim Jung Hee , Lee Hyung-Chul , Kim Su-jin , Lee Kyu Eun , Jung Kyeong Cheon 
Published: February 2022

BackgroundDespite an improved understanding of pheochromocytoma and extra-adrenal sympathetic parganglioma (PPGL), including diagnosis and management, some PPGLs are postoperatively diagnosed. Clinical characteristics and intraoperative haemodynamic instability (HI) in postoperatively diagnosed PPGL patients have been poorly defined. Thus, we investigated the clinical characteristics and HI in patients with postoperatively diagnosed PPGLs compared to patients with preoperatively diagnosed PPGLs.MethodsWe obtained clinical and haemodynamic data from the electronic medical records of 256 patients with pathologically confirmed PPGLs at our institution from January 2005 to December 2019. We assessed the intraoperative HI (systolic blood pressure [SBP]&gt;160 mmHg (min) or mean blood pressure [MBP]&lt;60 mmHg (min)) over time.ResultsTwenty-nine patients (11.3%) were diagnosed with PPGLs postoperatively. Hypertension (34.5% vs. 63.0%, P=0.006) and pheochromocytoma (17.2% vs. 81.1%, P&lt;0.001) case rates were lower in postoperatively diagnosed patients than in preoperatively diagnosed patients. Preoperative SBP in the ward was similar between groups, but the use of α-blockers and β-blockers was more frequent in preoperatively diagnosed patients (89.0% vs. 3.4%, P&lt;0.001; 36.3% vs. 6.9%, P=0.003). Considering intraoperative HI, postoperatively diagnosed patients demonstrated a similar percentage of time with SBP&gt;160 mmHg (median [IQR]; 7.9% [2.5; 11.9] % vs. 4.6% [0.0; 11.9], P=0.088) but a significantly lower percentage of time with MBP&lt;60 mmHg (0.0% [0.0; 3.0] vs. 5.6% [0.0, 12.6], P=0.002) compared with preoperatively diagnosed patients.ConclusionsPatients diagnosed with PPGLs postoperatively may have no further higher risk of intraoperative hypertension than those diagnosed preoperatively despite insufficient preoperative management for PPGLs. Further study will be needed to ascertain intrinsic tumour characteristics, and need for universal preoperative use of α- and β-blockers in PPGL patients postoperatively diagnosed or without typical symptoms related PPGLs.
Exploration of Potential Roles of m5C-Related Regulators in Colon Adenocarcinoma Prognosis
Authors: Huang Yuancheng , Huang Chaoyuan , Jiang Xiaotao , Yan Yanhua , Zhuang Kunhai , Liu Fengbin , Li Peiwu , Wen Yi 
Published: February 2022

Objectives: The purpose of this study was to investigate the role of 13 m5C-related regulators in colon adenocarcinoma (COAD) and determine their prognostic value.Methods: Gene expression and clinicopathological data were obtained from The Cancer Genome Atlas (TCGA) datasets. The expression of m5C-related regulators was analyzed with clinicopathological characteristics and alterations within m5C-related regulators. Subsequently, different subtypes of patients with COAD were identified. Then, the prognostic value of m5C-related regulators in COAD was confirmed via univariate Cox regression and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. The prognostic value of risk scores was evaluated using the Kaplan-Meier method, receiver operating characteristic (ROC) curve. The correlation between the two m5C-related regulators, risk score, and clinicopathological characteristics were explored. Additionally, Gene Set Enrichment Analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and Gene Ontology (GO) analysis were performed for biological functional analysis. Finally, the expression level of two m5C-related regulators in clinical samples and cell lines was detected by quantitative reverse transcription-polymerase chain reaction and through the Human Protein Atlas database.Results: m5C-related regulators were found to be differentially expressed in COAD with different clinicopathological features. We observed a high alteration frequency in these genes, which were significantly correlated with their mRNA expression levels. Two clusters with different prognostic features were identified. Based on two independent prognostic m5C-related regulators (NSUN6 and ALYREF), a risk signature with good predictive significance was constructed. Univariate and multivariate Cox regression analyses suggested that the risk score was an independent prognostic factor. Furthermore, this risk signature could serve as a prognostic indicator for overall survival in subgroups of patients with different clinical characteristics. Biological processes and pathways associated with cancer, immune response, and RNA processing were identified.Conclusion: We revealed the genetic signatures and prognostic values of m5C-related regulators in COAD. Together, this has improved our understanding of m5C RNA modification and provided novel insights to identify predictive biomarkers and develop molecular targeted therapy for COAD.
Sex-Specific Cell Types and Molecular Pathways Indicate Fibro-Calcific Aortic Valve Stenosis
Authors: Myasoedova Veronika A. , Massaiu Ilaria , Moschetta Donato , Chiesa Mattia , Songia Paola , Valerio Vincenza , Alfieri Valentina , Capoulade Romain , Trabattoni Daniela , Andreini Daniele , Mass Elvira , Parisi Valentina , Poggio Paolo 
Published: February 2022

BackgroundAortic stenosis (AS) is the most common valve disorder characterized by fibro-calcific remodeling of leaflets. Recent evidence indicated that there is a sex-related difference in AS development and progression. Fibrotic remodeling is peculiar in women’s aortic valves, while men’s leaflets are more calcified. Our study aimed to assess aortic valve fibrosis (AVF) in a severe AS cohort using non-invasive diagnostic tools and determine whether sex-specific pathological pathways and cell types are associated with severe AS.Materials and MethodsWe have included 28 men and 28 women matched for age with severe AS who underwent echocardiography and cardiac contrast-enhanced computed tomography (CT) before intervention. The calcium and fibrosis volumes were assessed and quantified using the ImageJ thresholding method, indexed calcium and fibrosis volume were calculated by dividing the volume by the aortic annular area. For a deeper understanding of molecular mechanisms characterizing AS disorder, differentially expressed genes and functional inferences between women and men’s aortic valves were carried out on a publicly available microarray-based gene expression dataset (GSE102249). Cell types enrichment analysis in stenotic aortic valve tissues was used to reconstruct the sex-specific cellular composition of stenotic aortic valves.ResultsIn agreement with the literature, our CT quantifications showed that women had significantly lower aortic valve calcium content compared to men, while fibrotic tissue composition was significantly higher in women than men. The expression profiles of human stenotic aortic valves confirm sex-dependent processes. Pro-fibrotic processes were prevalent in women, while pro-inflammatory ones, linked to the immune response system, were enhanced in men. Cell-type enrichment analysis showed that mesenchymal cells were over-represented in AS valves of women, whereas signatures for monocytes, macrophages, T and B cells were enriched men ones.ConclusionsOur data provide the basis that the fibro-calcific process of the aortic valve is sex-specific, both at gene expression and cell type level. The quantification of aortic valve fibrosis by CT could make it possible to perform population-based studies and non-invasive assessment of novel therapies to reduce or halt sex-related calcific aortic valve stenosis (CAVS) progression, acting in an optimal window of opportunity early in the course of the disease.
Cross-Neutralizing Breadth and Longevity Against SARS-CoV-2 Variants After Infections
Authors: Kurahashi Yukiya , Sutandhio Silvia , Furukawa Koichi , Tjan Lidya Handayani , Iwata Sachiyo , Sano Shigeru , Tohma Yoshiki , Ohkita Hiroyuki , Nakamura Sachiko , Nishimura Mitsuhiro , Arii Jun , Kiriu Tatsunori , Yamamoto Masatsugu , Nagano Tatsuya , Nishimura Yoshihiro , Mori Yasuko 
Published: February 2022

BackgroundSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus responsible for the Coronavirus Disease 2019 (COVID-19) pandemic. The emergence of variants of concern (VOCs) has become one of the most pressing issues in public health. To control VOCs, it is important to know which COVID-19 convalescent sera have cross-neutralizing activity against VOCs and how long the sera maintain this protective activity.MethodsSera of patients infected with SARS-CoV-2 from March 2020 to January 2021 and admitted to Hyogo Prefectural Kakogawa Medical Center were selected. Blood was drawn from patients at 1-3, 3-6, and 6-8 months post onset. Then, a virus neutralization assay against SARS-CoV-2 variants (D614G mutation as conventional strain; B.1.1.7, P.1, and B.1.351 as VOCs) was performed using authentic viruses.ResultsWe assessed 97 sera from 42 patients. Sera from 28 patients showed neutralizing activity that was sustained for 3-8 months post onset. The neutralizing antibody titer against D614G significantly decreased in sera of 6-8 months post onset compared to those of 1-3 months post onset. However, the neutralizing antibody titers against the three VOCs were not significantly different among 1-3, 3-6, and 6-8 months post onset.DiscussionOur results indicate that neutralizing antibodies that recognize the common epitope for several variants may be maintained for a long time, while neutralizing antibodies having specific epitopes for a variant, produced in large quantities immediately after infection, may decrease quite rapidly.
Low-Dose 5-Aza and DZnep Alleviate Acute Graft-Versus-Host Disease With Less Side Effects Through Altering T-Cell Differentiation
Authors: Wang Qing Ya , Liu Hui Hui , Dong Yu Jun , Liang Ze Yin , Yin Yue , Liu Wei , Wang Qing Yun , Wang Qian , Sun Yu Hua , Xu Wei Lin , Han Na , Li Yuan , Ren Han Yun 
Published: February 2022

ObjectivePrevious studies showed that hypomethylating agents (HMAs) could alleviate acute graft-versus-host disease (aGvHD), but affect engraftment after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The combination of two different HMAs in lower doses might overcome this problem. This study aimed to evaluate the treatment effect of the combination of two HMAs—azacitidine (5-Aza) and histone H3K27 methyltransferase inhibitor 3-deazaneplanocin (DZNep)—for the prophylaxis of aGvHD after allo-HSCT and to explore the possible mechanisms.MethodsWe first optimized the concentrations of individual and combinational 5-Aza and DZNep treatments to ensure no obvious toxicities on activated T cells by evaluating T-cell proliferation, viability, and differentiation. A mouse model of aGvHD was then established to assess the prophylactic efficacy of 5-Aza, DZNep, and their combination on aGvHD. The immunomodulatory effect on T cells and the hematopoietic reconstruction were assessed. Additionally, RNA sequencing (RNA-seq) was performed to identify the underlying molecular mechanisms.ResultsCompared with single treatments, the in vitro application of 5-Aza with DZNep could more powerfully reduce the production of T helper type 1 (Th1)/T cytotoxic type 1 (Tc1) cells and increase the production of regulatory T cells (Tregs). In an allo-HSCT mouse model, in vivo administration of 5-Aza with DZNep could enhance the prophylactic effect for aGvHD compared with single agents. The mechanism study demonstrated that the combination of 5-Aza and DZNep in vivo had an enhanced effect to inhibit the production of Th1/Tc1, increase the proportions of Th2/Tc2, and induce the differentiation of Tregs as in vitro. RNA-seq analysis revealed the cytokine and chemokine pathways as one mechanism for the alleviation of aGvHD with the combination of 5-Aza and DZNep.ConclusionThe combination of 5-Aza and DZNep could enhance the prophylactic effect for aGvHD by influencing donor T-cell differentiation through affecting cytokine and chemokine pathways. This study shed light on the effectively prophylactic measure for aGvHD using different epigenetic agent combinations.
An Unsupervised Machine Learning Clustering and Prediction of Differential Clinical Phenotypes of COVID-19 Patients Based on Blood Tests—A Hong Kong Population Study
Authors: Lau Kitty Yu-Yeung , Ng Kei-Shing , Kwok Ka-Wai , Tsia Kevin Kin-Man , Sin Chun-Fung , Lam Ching-Wan , Vardhanabhuti Varut 
Published: February 2022

BackgroundTo better understand the different clinical phenotypes across the disease spectrum in patients with COVID-19 using an unsupervised machine learning clustering approach.Materials and MethodsA population-based retrospective study was conducted utilizing demographics, clinical characteristics, comorbidities, and clinical outcomes of 7,606 COVID-19–positive patients on admission to public hospitals in Hong Kong in the year 2020. An unsupervised machine learning clustering was used to explore this large cohort.ResultsFour clusters of differing clinical phenotypes based on data at initial admission was derived in which 86.6% of the deceased cases were aggregated in one of the clusters without prior knowledge of their clinical outcomes. Other distinctive clinical characteristics of this cluster were old age and high concurrent comorbidities as well as laboratory characteristics of lower hemoglobin/hematocrit levels, higher neutrophil, C-reactive protein, lactate dehydrogenase, and creatinine levels. The clinical patterns captured by the cluster analysis was validated on other temporally distinct cohorts in 2021. The phenotypes aligned with existing literature.ConclusionThe study demonstrated the usefulness of unsupervised machine learning techniques with the potential to uncover latent clinical phenotypes. It could serve as a more robust classification for patient triaging and patient-tailored treatment strategies.
High-Flow vs. Low-Flow Nasal Cannula in Reducing Hypoxemic Events During Bronchoscopic Procedures: A Systematic Review and Meta-Analysis
Authors: Sampsonas Fotios , Karamouzos Vasileios , Karampitsakos Theodoros , Papaioannou Ourania , Katsaras Matthaios , Lagadinou Maria , Zarkadi Eirini , Malakounidou Elli , Velissaris Dimitrios , Stratakos Grigorios , Tzouvelekis Argyrios 
Published: February 2022

IntroductionHigh-flow nasal cannula (HFNC) oxygenation method has been proven to be successful in oxygenation of patients with respiratory failure and has exhibited clinical superiority compared to low-flow nasal cannula (LFNC).MethodsWe performed a systematic review and meta-analysis to evaluate the potential favorable impact of HFNC oxygenation during bronchoscopy and related procedures like endobronchial ultrasound-transbronchial needle aspiration. Only randomized control trials (RCTs) were included in the meta-analysis.ResultsSix randomized control trials with 1,170 patients were included in this meta-analysis. Patients who underwent bronchoscopy with the use of high-flow nasal cannula experienced less hypoxemic events/desaturations, less procedural interruptions and pneumothoraxes compared to patients under low-flow nasal cannula treatment. This beneficial effect of HFNC in hypoxemic events was persistent 10 min after the end of procedure.ConclusionThe high-flow nasal cannula (HFNC) oxygenation method could reduce hypoxemic events and related peri- and post-bronchoscopic complications.
Demodex folliculorum Infestation in Meibomian Gland Dysfunction Related Dry Eye Patients
Authors: Hao Yiran , Zhang Xiaoyu , Bao Jiayu , Tian Lei , Jie Ying 
Published: February 2022

ObjectiveTo report the influence of Demodex folliculorum (D. folliculorum) infestation in patients with meibomian gland dysfunction (MGD) related dry eye and the associations of the infestation with MGD related dry eye.MethodsEyelashes (three from the upper eyelid and three from the lower eyelid) from 119 eyes of 119 patients diagnosed with MGD related dry eye were examined under a light microscope. There were 68 eyes of 68 patients with MGD related dry eye and D. folliculorum infestation (Demodex positive group) and 51 eyes of 51 patients without infestation (Demodex negative group). All patients completed an Ocular Surface Disease Index (OSDI) questionnaire and underwent tests for dry eye and MGD. The tests included fluorescein tear breakup time (TBUT), corneal fluorescein staining, Schirmer I test (SIT), lid margin abnormalities, meibum expression assessment, and meibomian gland dropout.ResultsThe scores for OSDI, corneal fluorescein staining, lid margin abnormalities, meibum expression, and meibomian gland dropout were significantly higher (all P &lt; 0.05), while TBUT was significantly shorter in the Demodex positive group compared to the Demodex negative group (P = 0.020). The SIT values did not significantly differ between groups. Chalazion was significantly more prevalent in the Demodex positive group. The number of D. folliculorum was positively correlated with all three MGD parameters (P ≤ 0.035), OSDI; corneal fluorescein scores, and it was inversely correlated with BUT. The correlation for SIT was R2 = 0.075 (P = 0.064).ConclusionDemodex folliculorum infestation is possibly one of the key contributors in the pathogenesis of MGD related dry eye, and a higher prevalence of chalazion was found in D. folliculorum infected patients. The possible causal role of D. folliculorum infestation needs to be further studied.
A Subset of Nucleus Accumbens Neurons Receiving Dense and Functional Prelimbic Cortical Input Are Required for Cocaine Seeking
Authors: Siemsen Benjamin M. , Barry Sarah M. , Vollmer Kelsey M. , Green Lisa M. , Brock Ashley G. , Westphal Annaka M. , King Raven A. , DeVries Derek M. , Otis James M. , Cowan Christopher W. , Scofield Michael D. 
Published: February 2022

BackgroundPrelimbic cortical projections to the nucleus accumbens core are critical for cue-induced cocaine seeking, but the identity of the accumbens neuron(s) targeted by this projection, and the transient neuroadaptations contributing to relapse within these cells, remain unknown.MethodsMale Sprague-Dawley rats underwent cocaine or sucrose self-administration, extinction, and cue-induced reinstatement. Pathway-specific chemogenetics, patch-clamp electrophysiology, in vivo electrochemistry, and high-resolution confocal microscopy were used to identify and characterize a small population of nucleus accumbens core neurons that receive dense prelimbic cortical input to determine their role in regulating cue-induced cocaine and natural reward seeking.ResultsChemogenetic inhibition of prelimbic cortical projections to the nucleus accumbens core suppressed cue-induced cocaine relapse and normalized real-time cue-evoked increases in accumbens glutamate release to that of sucrose seeking animals. Furthermore, chemogenetic inhibition of the population of nucleus accumbens core neurons receiving the densest prelimbic cortical input suppressed cocaine, but not sucrose seeking. These neurons also underwent morphological plasticity during the peak of cocaine seeking in the form of dendritic spine expansion and increased ensheathment by astroglial processes at large spines.ConclusionWe identified and characterized a unique subpopulation of nucleus accumbens neurons that receive dense prelimbic cortical input. The functional specificity of this subpopulation is underscored by their ability to mediate cue-induced cocaine relapse, but not sucrose seeking. This subset of cells represents a novel target for addiction therapeutics revealed by anterograde targeting to interrogate functional circuits imbedded within a known network.