bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated Analysis Reveals the Targets and Mechanisms in Immunosuppressive Effect of Mesalazine on Ulcerative Colitis
Authors: Li Rong , Huang Xue , Yang Lu , Liang Xiao , Huang Wenjun , Lai Keng Po , Zhou Liming 
Published: May 2022

BackgroundUlcerative colitis (UC) is an inflammatory bowel disease that causes inflammation and ulcers in the digestive tract. Approximately 3 million US adults suffer from this disease. Mesalazine, an anti-inflammatory agent, is commonly used for the treatment of UC. However, some studies have demonstrated side effects of mesalazine, such as acute pancreatitis and hypereosinophilia. Therefore, a better understanding of the anti-inflammatory mechanism of mesalazine in UC could help improve the effectiveness of the drug and reduce its side effects. In this study, we used a dextran sodium sulfate-induced UC mouse model, and applied network pharmacology and omics bioinformatics approaches to uncover the potential pharmaceutical targets and the anti-inflammatory mechanism of mesalazine.ResultsNetwork pharmacology analysis identified the core targets of mesalazine, biological processes, and cell signaling related to immunity and inflammatory responses mediated by mesalazine. Molecular docking analysis then indicated possible binding motifs on the core targets (including TNF-α, PTGS2, IL-1β, and EGFR). Metabolomics and 16S metagenomic analyses highlighted the correlation between gut microbiota and metabolite changes caused by mesalazine in the UC model.ConclusionsCollectively, the omics and bioinformatics approaches and the experimental data unveiled the detailed molecular mechanisms of mesalazine in UC treatment, functional regulation of the gut immune system, and reduction of intestinal inflammation. More importantly, the identified core targets could be targeted for the treatment of UC.
Nutritional Status and Other Clinical Variables Are Associated to the Resting Energy Expenditure in Patients With Chronic Kidney Disease: A Validity Study
Authors: Ramos-Acevedo Samuel , Rodríguez-Gómez Luis , López-Cisneros Sonia , González-Ortiz Ailema , Espinosa-Cuevas Ángeles 
Published: May 2022

BackgroundEstimating energy requirements (ER) is crucial for nutritional attention to chronic kidney disease (CKD) patients. Current guidelines recommend measuring ER with indirect calorimetry (IC) when possible. Due to clinical settings, the use of simple formulas is preferred. Few studies have modeled equations for estimating ER for CKD. Nevertheless, variables of interest such as nutritional status and strength have not been explored in these models. This study aimed to develop and validate a model for estimating REE in patients with CKD stages 3–5, who were not receiving renal replacement therapy (RTT), using clinical variables and comparing it with indirect calorimetry as the gold standard.MethodsIn this study 80 patients with CKD participated. Indirect calorimetry (IC) was performed in all patients. The calorimeter analyzed metabolic measurements every minute for 15 min after autocalibration with barometric pressure, temperature, and humidity. Bioelectrical Impedance Analysis (BIA) was performed. Fat-free mass (FFM) was registered among other bioelectrical components. Handgrip strength (HGS) was evaluated and an average of 3 repetitions was recorded. Nutritional status was assessed with the subjective global assessment (SGA). Patients categorized as B or C were then considered as having malnutrition.ResultsWe analyzed 71 patients and 3 models were generated. Model 1a included FFM; Model 2a included weight; Model 3c included handgrip strength (HGS). All other variables were stepwise, computer-selected with a p &lt; 0.01 significance level; Malnutrition was consistently associated with ER among other clinical variables in all models (p &lt; 0.05). The model that included BIA-FFM had R2adjusted = 0.46, while the model that included weight (Kg) had an adjusted R2adjusted = 0.44. The models had moderate concordance, LC = 0.60–0.65 with the gold standard, whereas other energy expenditure estimation equations had LC = 0.36 and 0.55 with indirect calorimetry. Using these previously validated equations as a reference, our models had concordance values ranging from 0.66 to 0.80 with them.ConclusionModels incorporating nutritional status and other clinical variables such as weight, FFM, comorbidities, gender, and age have a moderate agreement with REE. The agreement between our models and others previously validated for the CKD patient is good; however, the agreement between the latter and IC measurements is moderate. The KDOQI lowest recommendation (25 Kcals/kg body weight) considering the 22% difference with respect to the IC for total energy expenditure rather than for REE.
Prediction Breast Molecular Typing of Invasive Ductal Carcinoma Based on Dynamic Contrast Enhancement Magnetic Resonance Imaging Radiomics Characteristics: A Feasibility Study
Authors: Xu Aqiao , Chu Xiufeng , Zhang Shengjian , Zheng Jing , Shi Dabao , Lv Shasha , Li Feng , Weng Xiaobo 
Published: May 2022

ObjectiveTo investigate the feasibility of radiomics in predicting molecular subtype of breast invasive ductal carcinoma (IDC) based on dynamic contrast enhancement magnetic resonance imaging (DCE-MRI).MethodsA total of 303 cases with pathologically confirmed IDC from January 2018 to March 2021 were enrolled in this study, including 223 cases from Fudan University Shanghai Cancer Center (training/test set) and 80 cases from Shaoxing Central Hospital (validation set). All the cases were classified as HR+/Luminal, HER2-enriched, and TNBC according to immunohistochemistry. DCE-MRI original images were treated by semi-automated segmentation to initially extract original and wavelet-transformed radiomic features. The extended logistic regression with least absolute shrinkage and selection operator (LASSO) penalty was applied to identify the optimal radiomic features, which were then used to establish predictive models combined with significant clinical risk factors. Receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis were adopted to evaluate the effectiveness and clinical benefit of the models established.ResultsOf the 223 cases from Fudan University Shanghai Cancer Center, HR+/Luminal cancers were diagnosed in 116 cases (52.02%), HER2-enriched in 71 cases (31.84%), and TNBC in 36 cases (16.14%). Based on the training set, 788 radiomic features were extracted in total and 8 optimal features were further identified, including 2 first-order features, 1 gray-level run length matrix (GLRLM), 4 gray-level co-occurrence matrices (GLCM), and 1 3D shape feature. Three multi-class classification models were constructed by extended logistic regression: clinical model (age, menopause, tumor location, Ki-67, histological grade, and lymph node metastasis), radiomic model, and combined model. The macro-average areas under the ROC curve (macro-AUC) for the three models were 0.71, 0.81, and 0.84 in the training set, 0.73, 0.81, and 0.84 in the test set, and 0.76, 0.82, and 0.83 in the validation set, respectively.ConclusionThe DCE-MRI-based radiomic features are significant biomarkers for distinguishing molecular subtypes of breast cancer noninvasively. Notably, the classification performance could be improved with the fusion analysis of multi-modal features.
A Radiomics Model Based on Gd-EOB-DTPA-Enhanced MRI for the Prediction of Microvascular Invasion in Solitary Hepatocellular Carcinoma ≤ 5 cm
Authors: Qu Chengming , Wang Qiang , Li Changfeng , Xie Qiao , Cai Ping , Yan Xiaochu , Sparrelid Ernesto , Zhang Leida , Ma Kuansheng , Brismar Torkel B. 
Published: May 2022

AimThe aim of this study is to establish and validate a radiomics-based model using preoperative Gd-EOB-DTPA-enhanced MRI to predict microvascular invasion (MVI) in patients with hepatocellular carcinoma ≤ 5 cm.MethodsClinicopathologic and MRI data of 178 patients with solitary hepatocellular carcinoma (HCC) (≤5 cm) were retrospectively collected from a single medical center between May 2017 and November 2020. Patients were randomly assigned into training and test subsets by a ratio of 7:3. Imaging features were extracted from the segmented tumor volume of interest with 1-cm expansion on arterial phase (AP) and hepatobiliary phase (HBP) images. Different models based on the significant clinical risk factors and/or selected imaging features were established and the predictive performance of the models was evaluated.ResultsThree radiomics models, the AP_model, the HBP_model, and the AP+HBP_model, were constructed for MVI prediction. Among them, the AP+HBP_model outperformed the other two. When it was combined with a clinical model, consisting of tumor size and alpha-fetoprotein (AFP), the combined model (AP+HBP+Clin_model) showed an area under the curve of 0.90 and 0.70 in the training and test subsets, respectively. Its sensitivity and specificity were 0.91 and 0.76 in the training subset and 0.60 and 0.79 in the test subset, respectively. The calibration curve illustrated that the combined model possessed a good agreement between the predicted and the actual probabilities.ConclusionsThe radiomics-based model combining imaging features from the arterial and hepatobiliary phases of Gd-EOB-DTPA-enhanced MRI and clinical risk factors provides an effective and reliable tool for the preoperative prediction of MVI in patients with HCC ≤ 5 cm.
Real-World Therapy Management and Outcomes of First-Line Axitinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma in the United States
Authors: Zakharia Yousef , Thomaidou Despina , Li Benjamin , Siu Gordon , Levin Rebecca , Vlahiotis Anna , Rao Dharanija , Zanotti Giovanni 
Published: May 2022

BackgroundCombination axitinib plus pembrolizumab is a standard of care in the first-line treatment of patients with advanced clear cell renal cell carcinoma (RCC). This analysis describes the clinical characteristics, treatment management and outcomes of patients receiving first-line (1L) axitinib plus pembrolizumab in a real-world US setting.MethodsElectronic health record (EHR)-derived data from the Flatiron Health Database, which includes ~280 cancer clinics across 800 sites in the US, were used. Patients had confirmed Stage IV or metastatic RCC and initiated 1L axitinib plus pembrolizumab on or after 1/1/2018 to 3/31/2021. Outcomes were best overall response rate; real-world progression-free survival (rwPFS) and overall survival (OS) at landmark time periods (3, 6, 9, and 12 months). Therapy management (TM) included dose hold, dose change and discontinuation. Data are reported as medians (IQR) unless otherwise noted.Results355 patients received 1L axitinib plus pembrolizumab, with median follow-up of 9.7 (0.1–24.3) months. IMDC Risk Score was favorable, intermediate, and poor in 27 (7.6%), 126 (35.5%), and 76 (21.4%) patients, respectively (23.4% intermediate/poor, 12.1% unknown). 270 patients (76.1%) received only 1L axitinib plus pembrolizumab and 85 patients (24.3%) received ≥1 subsequent line of treatment; cabozantinib was the most frequent subsequent line of treatment (47.9%). rwPFS at 3 months and 1 year was 77.2% and 39.3%, respectively. OS ranged from 90.8% at 3 months to 73.5% at 1 year. Best overall response rate was 47.9%. Toxicity was the most common reason for first TM events of dose hold, change and discontinuation at, 58.6%, 58.5%, and 45.8%, respectively. Over 80% of patients with TM were able to continue with 1L axitinib plus pembrolizumab.ConclusionsIn a real-world setting, axitinib plus pembrolizumab was effective as a 1L treatment for patients with advanced RCC. Dose holds, changes and discontinuation were driven by treatment-related toxicity. Dose holds may represent an effective TM strategy to toxicity.
Management of Children With Food-Induced Anaphylaxis: A Cross-Sectional Survey of Parental Knowledge, Attitude, and Practices
Authors: Polloni Laura , Baldi Ileana , Amadi Margherita , Tonazzo Valentina , Bonaguro Roberta , Lazzarotto Francesca , Toniolo Alice , Gregori Dario , Muraro Antonella 
Published: May 2022

BackgroundAnaphylaxis is a life-threatening event, but it is frequently undertreated in pediatric patients with food allergies. Previous studies showed that auto-injectable adrenaline (AAI) is underused by patients and parents. This is especially troubling since fatal anaphylaxis has been associated with delayed adrenaline administration.ObjectivesThis study aimed to investigate parental practice and knowledge in anaphylaxis management, and perceived barriers and facilitators in using AAI.ResultsA retrospective survey was completed by 75 parents (41 mothers, 34 fathers) of children with food allergy and AAI prescription attending the Food Allergy Referral Center of Veneto, Italy. Results showed poor parental preparedness and reluctance to use AAI despite a high/moderate self-rated knowledge (median total score of 23–min. 3, max. 30). Most parents (77%) declared they were carrying AAI but only 20% used it in case of a severe reaction. Most reported Fear/Fear of making mistakes (46 parents) and Concern about possible side effects as barriers (35), while Poor knowledge of the correct AAI use (1) and Lack of knowledge/ incorrect assessment of symptoms (2) were reported less frequently. Theoretical-practical courses for parents on AAI use (65), Psycho-education/Psychological support (3) for better dealing with the emotional aspects of anaphylaxis and Written instructions (1) have been suggested as main facilitators.ConclusionUnderstanding parents' experience and perspective on managing anaphylaxis is crucial to implement effective educational programs. A multidisciplinary approach should be considered.
Treatment of Refractory/High-Risk Pregnancies With Antiphospholipid Syndrome: A Systematic Review of the Literature
Authors: Hoxha Ariela , Tormene Daniela , Campello Elena , Simioni Paolo 
Published: May 2022

Different treatment protocols have been employed to manage heparin/low-dose aspirin refractory or high-risk pregnancies in antiphospholipid antibody syndrome (APS) pregnancies. A systematic review of the literature on additional treatments used in refractory and/or high-risk APS pregnancies was conducted. Records from February 2006 to October 2021 were retrieved from PubMed, Web of Science, Cochrane, and the www.clinicaltrials.gov platform. Twenty-one studies met our eligibility criteria. Live birth rate is this study’s primary endpoint, while pregnancy complications and adverse events are secondary endpoints. A total of 434 pregnancies, 162 (37.3%) refractory and 272 (62.7%) high-risk/refractory pregnancies, were included. Both IVIG &lt;2 gr/kg/monthly/HCQ/LDS and PEX/IA ± LDS led to 100% viable infants in refractory APS. Furthermore, HCQ 200–400 mg showed a higher live birth rate than HCQ + LDS (88.6% vs. 82.7%). Following treatment protocol with HCQ 200–400 mg and IVIG &lt;2 gr/kg/monthly/HCQ/LDS, pregnancy complications rates of 16.7 and 83.3% were registered, respectively. Pravastatin 20 mg, IA weekly + IVIG 2 gr/monthly, and PEX weekly + IVIg 2 gr/kg/monthly showed higher live birth rates in high-risk APS pregnancies of 100, 100 and 92%, respectively, whereas the lower severe pregnancy complications were reported in pregnancies treated with PEX weekly + IVIg 2 gr/kg/monthly (11.1%). One (0.6%) case of dermatitis during treatment with HCQ was observed. The results of this study showed that HCQ 200–400 mg and PEX weekly + IVIG 2 gr/kg/monthly achieved a higher live birth rate in refractory APS and high-risk/refractory APS, respectively. The results presented provide clinicians with up-to-date knowledge in the management of APS pregnancies according to risk stratification.
Pharmacist-Urologist Collaborative Management Improves Clinical Outcomes in Patients With Castration-Resistant Prostate Cancer Receiving Enzalutamide
Authors: Hirabatake Masaki , Ikesue Hiroaki , Iwama Yuna , Irie Kei , Yoshino Shintaro , Yamasaki Toshinari , Hashida Tohru , Kawakita Mutsushi , Muroi Nobuyuki 
Published: May 2022

Background: Enzalutamide is useful for the treatment of castration-resistant prostate cancer (CRPC). Despite its usefulness, adverse events (AEs) sometimes force patients to discontinue treatment. To maximize patient care, we developed an ambulatory care pharmacy practice that allows collaboration between a pharmacist and urologist to manage patients with CRPC receiving enzalutamide. In this study, we investigated the efficacy of this collaborative management.Methods: A retrospective chart review of 103 patients with CRPC receiving enzalutamide in our hospital between May 2014 and December 2020 was performed. Our collaborative management was implemented in October 2016. Before being examined by urologists, patients visited the oncology pharmacy consultation room for a face-to-face consultation, wherein the oncology pharmacists assessed factors such as adherence to enzalutamide, any AEs and their grades, and provided their suggestions to the urologists. The time to enzalutamide discontinuation and prostate-specific antigen progression were compared between patients who started enzalutamide before (n = 41) and after (n = 62) the implementation of the collaborative management. A multivariate Cox regression analysis was performed to analyze the factors associated with enzalutamide discontinuation.Results: After implementing collaborative management, the pharmacists had 881 patient consultations. Among the 476 suggestions from pharmacists, 345 were accepted by urologists. The most frequent suggestion was supportive care in enzalutamide treatment (224 suggestions). Multivariate analysis showed that collaborative management [hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.31–0.89, p = 0.017] and higher prostate-specific antigen (PSA; HR 2.41, 95% CI 1.36–4.28, p = 0.003) were significantly associated with enzalutamide discontinuation. The median time to discontinuation (18.9 vs. 7.6 months, p = 0.012), time to discontinuation due to AEs (not reached in both groups, p = 0.001), and time to PSA progression (13.3 vs. 5.8 months, p = 0.002) were all significantly longer in the after group.Conclusions: We implemented a pharmacist-urologist collaborative management program for outpatients with CRPC receiving enzalutamide. The results revealed that collaborative management was useful for prolonging the time to enzalutamide discontinuation.
Development of a Novel Retina−Based Diagnostic Score for Early Detection of Major Depressive Disorder: An Interdisciplinary View
Authors: Liu Xiao , Lai Shunkai , Ma Shisi , Yang Hong , Liu Lian , Yu Guocheng , Zhong Shuming , Jia Yanbin , Zhong Jingxiang 
Published: May 2022

BackgroundClinically effective markers for the diagnosis of major depressive disorder (MDD) are lacking. Alterations in retinal features are closely related to the pathophysiological progression of MDD. However, the reliable retina-related diagnostic model for MDD remains to be developed. Thus, our study aimed to quantitatively evaluate retinal vascular and structural changes in MDD patients and to develop a reliable diagnostic model of MDD based on retinal parameters.MethodsSeventy-eight patients with MDD and 47 healthy controls (HCs) underwent retinal vessel density and structure examination using optical coherence tomography angiography and visual field examination using perimetry. Independent-sample t test was used to assess the differences in retinal parameters between the groups. Meanwhile, we constructed the corresponding retina-based diagnostic model by LASSO logistic regression. Finally, the diagnostic ability of the model was evaluated by area under the curve (AUC) of receiver operating characteristic curves and calibration plot of nomogram.ResultsMDD patients showed lower retinal vessel density (including radial peripapillary capillary vessel density, superficial and deep capillary plexus vessel density), thinner subfoveal choroidal thickness, and poorer visual fields compared to HCs (all p &lt; 0.05). Furthermore, a retina-based diagnostic model was constructed and shows a strong diagnostic capability for MDD (AUC = 0.9015, p &lt; 0.001).ConclusionPatients with MDD showed distinct retinal features compared to HCs. The retina-based diagnostic model is expected to be a necessary complement to the diagnosis of MDD.
Economic Burden and Quality of Life of Hepatocellular Carcinoma in Greater China: A Systematic Review
Authors: Zou Huimin , Li Meng , Lei Qing , Luo Zejun , Xue Yan , Yao Dongning , Lai Yunfeng , Ung Carolina Oi Lam , Hu Hao 
Published: May 2022

BackgroundHepatocellular carcinoma (HCC) accounts for more than 85%-90% of primary liver cancer globally, and approximately 45% of deaths from HCC occur in greater China. This disease poses a significant economic burden for patients, payers and society and significantly affects patients' quality of life (QoL). However, such impact of HCC in greater China has not been well characterized. This review was conducted to analyze the current evidence about the economic and humanistic impact of HCC in greater China for informing national disease management and identifying clinical gaps yet to be resolved.MethodsA systematic search literature using seven databases (Web of Science, PubMed, Medline, Cochrane Central, China National Knowledge Infrastructure, Wanfang, and Weipu) was performed to identify interventional and observational studies that reported the impact of HCC on cost or QoL and published before April 6, 2021. The focus population included adult patients with HCC in greater China. This review excluded any studies that focused on any specific treatment. Study quality was assessed using the Effective Public Health Practice Project tool.ResultsOf 39,930 studies retrieved, 27 were deemed eligible for inclusion. The methodologies, perspectives and data sources used in studies were heterogeneous. In greater China, while few studies reported the health expenditures of HCC patients and investigations about economic burden at national level was lacking, the significant economic impact of HCC on patients and their families had been reported. Health-related costs increased as the disease deteriorated. Additionally, HCC also has a negative impact on the QoL of patients, mostly in terms of physical, cognitive, social functioning and severe symptoms.ConclusionsHCC has brought significant economic and QoL burden to patients in greater China. Both physical and psychological factors predicted QoL in patients with HCC in greater China. Future studies should explore the disease-related economic effects on Chinese patients and their families, the effects of physical and psychological factors on QoL and the relationships of physical and psychological factors in the region.Systematic Review Registration:www.crd.york.ac.uk/prospero/display_record.php?RecordID=278421, PROSPERO: CRD42021278421