bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does Reorganization of Clinicopathological Information Improve Prognostic Stratification and Prediction of Chemoradiosensitivity in Sinonasal Carcinomas? A Retrospective Study on 145 Patients
Authors: Ferrari Marco , Mattavelli Davide , Schreiber Alberto , Gualtieri Tommaso , Rampinelli Vittorio , Tomasoni Michele , Taboni Stefano , Ardighieri Laura , Battocchio Simonetta , Bozzola Anna , Ravanelli Marco , Maroldi Roberto , Piazza Cesare , Bossi Paolo , Deganello Alberto , Nicolai Piero 
Published: June 2022

BackgroundThe classification of sinonasal carcinomas (SNCs) is a conundrum. Consequently, prognosis and prediction of response to non-surgical treatment are often unreliable. The availability of prognostic and predictive measures is an unmet need, and the first logical source of information to be investigated is represented by the clinicopathological features of the disease. The hypothesis of the study was that clinicopathological information on SNC could be exploited to better predict prognosis and chemoradiosensitivity.MethodsAll patients affected by SNC who received curative treatment, including surgery, at the Unit of Otorhinolaryngology—Head and Neck Surgery of the University of Brescia between October 1998 and February 2019 were included in the analysis. The institutional series was reviewed and a survival analysis was performed. Machine learning and multivariable statistical methods were employed to develop, analyze, and test 3 experimental classifications (classification #1, based on cytomorphological, histomorphological, and differentiation information; classification #2, based on differentiation information; and classification #3, based on locoregional extension) of SNC, based on the inherent clinicopathological information. The association of experimental classifications with prognosis and chemoradiosensitivity was tested.ResultsThe study included 145 patients. From a prognostic standpoint, the machine learning-generated classification of SNC provided better prediction than the current World Health Organization classification. However, the prediction of the chemoradiosensitivity of SNC was not achievable.ConclusionsReorganization of clinicopathological information, with special reference to those related to tumor differentiation, can improve the reliability of prognosis of SNC. Prediction of chemoradiosensitivity remains an unmet need and further research is required.
Differential Diagnosis of Type 1 and Type 2 Papillary Renal Cell Carcinoma Based on Enhanced CT Radiomics Nomogram
Authors: Gao Yankun , Wang Xingwei , Wang Shihui , Miao Yingying , Zhu Chao , Li Cuiping , Huang Guoquan , Jiang Yan , Li Jianying , Zhao Xiaoying , Wu Xingwang 
Published: June 2022

ObjectivesTo construct a contrast-enhanced CT-based radiomics nomogram that combines clinical factors and a radiomics signature to distinguish papillary renal cell carcinoma (pRCC) type 1 from pRCC type 2 tumours.MethodsA total of 131 patients with 60 in pRCC type 1 and 71 in pRCC type 2 were enrolled and divided into training set (n=91) and testing set (n=40). Patient demographics and enhanced CT imaging characteristics were evaluated to set up a clinical factors model. A radiomics signature was constructed and radiomics score (Rad-score) was calculated by extracting radiomics features from contrast-enhanced CT images in corticomedullary phase (CMP) and nephrographic phase (NP). A radiomics nomogram was then built by incorporating the Rad-score and significant clinical factors according to multivariate logistic regression analysis. The diagnostic performance of the clinical factors model, radiomics signature and radiomics nomogram was evaluated on both the training and testing sets.ResultsThree validated features were extracted from the CT images and used to construct the radiomics signature. Boundary blurring as an independent risk factor for tumours was used to build clinical factors model. The AUC value of the radiomics nomogram, which was based on the selected clinical factors and Rad-score, were 0.855 and 0.831 in the training and testing sets, respectively. The decision curves of the radiomics nomogram and radiomics signature in the training set indicated an overall net benefit over the clinical factors model.ConclusionRadiomics nomogram combining clinical factors and radiomics signature is a non-invasive prediction method with a good prediction for pRCC type 1 tumours and type 2 tumours preoperatively and has some significance in guiding clinicians selecting subsequent treatment plans.
A Phase 1 Proof of Concept Study Evaluating the Addition of an LSD1 Inhibitor to Nab-Paclitaxel in Advanced or Metastatic Breast Cancer (EPI-PRIMED)
Authors: Prasanna Thiru , Malik Laeeq , McCuaig Robert D. , Tu Wen Juan , Wu Fan , Lim Pek Siew , Tan Abel H. Y. , Dahlstrom Jane E. , Clingan Philip , Moylan Eugene , Chrisp Jeremy , Fuller David , Rao Sudha , Yip Desmond 
Published: June 2022

ObjectiveLysine-Specific Demethylase-1 (LSD1) is overexpressed in breast cancer cells and facilitate mesenchymal properties which may contribute to therapeutic resistance and cancer progression. The purpose of this study was to investigate the safety of combination, nab-paclitaxel and phenelzine, an irreversible LSD1 inhibitor in patients with metastatic breast cancer (mBC).MethodsEligible patients with mBC were treated with nab-paclitaxel (100mg/m2) weekly for 3 weeks with one week break in a 28-day cycle. Dose escalation of phenelzine followed the Cumulative Cohort Design and phenelzine treatment commenced from day 2 of first cycle. Eleven patients were screened, and eligible patients were enrolled in cohorts with the dose of phenelzine ranging from 45mg to 90mg.ResultsThe Optimum Biological Dose was established at 60mg of phenelzine daily in combination with nab-paclitaxel and considered as the recommended phase 2 dose. Most (95%) of adverse events were grade 1 or 2 with two grade 3 events being diarrhea and neutropenia at 45mg and 60mg phenelzine respectively, with no unexpected toxicity/deaths. Commonly reported toxicities were fatigue (n=4,50%), dizziness (n=6,75%), neutropenia (n=3,37.5%), peripheral neuropathy (n=3,37.5%), diarrhea (n=2,25%), and hallucination (n=2,25%). After a median follow up of 113 weeks, all patients showed disease progression on trial with 4 patients being alive at the time of data cut off, including one patient with triple negative breast cancer. Median progression-free survival was 34 weeks. Significant inhibition of LSD1 and suppression of mesenchymal markers in circulating tumor cells were noted.ConclusionPhenelzine in combination with nab-paclitaxel was well tolerated, without any unexpected toxicities in patients with mBC and demonstrated evidence of antitumor activity. For the first time, this proof-of-concept study showedin-vivoinhibition of LSD1 suppressed mesenchymal markers, which are known to facilitate generation of cancer stem cells with metastatic potential.Clinical Trial Registration:ClinicalTrials.GovNCT03505528, UTN of U1111-1197-5518.
Application of Imaging Indicators Based on 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Colorectal Peritoneal Carcinomatosis
Authors: Sun Chun-Feng , Zhang Ding , Gao Yan , Mao Xiao-Ying , Tan Zhong-Hua , Bao Shan-Lei , Shen Chen 
Published: June 2022

ObjectiveThe imaging features of peritoneal carcinomatosis (PC) with different locations and pathological types of colorectal cancer (CRC) on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) were analyzed and discussed.MethodsThe PET/CT data of 132 patients with colorectal peritoneal carcinomatosis (CRPC) who met the inclusion and exclusion criteria between May 30, 2016, and December 31, 2019, were collected and analyzed. Observations included the location and pathological type of CRC, the peritoneal cancer index (PCI), standardized uptake maximum value (SUVmax), and retention index (RI) of the CRPC. Statistical analysis was performed using SPSS 20.0 software, and P &lt; 0.05 was considered statistically significant.Results(1) The range of the PCI in the 132 patients studied was 2–30, with a mean value of 7.40 ± 8.14. The maximum long diameter of the CRPC lesions ranged from 0.6 to 12.1 cm, with an average of 3.23 ± 1.94 cm. The SUVmax ranged from 1.2 to 31.0, with a mean value of 9.65 ± 6.01. The SUVmax and size correlation coefficient for maximal CRPC lesions was r = 0.47 (P &lt; 0.001). The RI range of the 72 patients who underwent time-lapse scanning was -10.0–112.2%, with RI quartiles of 13.5–48.9%; RI was ≥5% in 65 cases and &lt;5% in seven cases. (2) The patients were grouped by the location of their CRC: the right-sided colon cancer (RCC, n = 37), left-sided colon cancer (LCC, n = 44), and rectal cancer groups (RC, n = 51). There were significant differences in the CRC pathological types (P = 0.009) and PCI scores (P = 0.02) between the RCC and RC groups and the RI between the RCC group and the other two groups (P &lt; 0.001). (3) There were 88 patients organized into three groups by the pathology of their CRC: the moderately well-differentiated adenocarcinoma (group A, n = 57), poorly differentiated adenocarcinoma (group B, n = 16), and mucinous adenocarcinoma groups (group C, n = 15 cases, including one case of signet-ring cell carcinoma). There were significant differences in the CRC position (P = 0.003) and SUVmax (P = 0.03) between groups A and C.ConclusionThe PCI, SUVmax, and RI of peritoneal metastatic carcinoma caused by CRC in different locations and pathological types vary. Mucinous adenocarcinoma and poorly differentiated adenocarcinoma are relatively common in the right colon, and the PCI of peritoneal metastatic carcinoma is fairly high, but the SUVmax and RI are somewhat low.
The Percentage of Signet Ring Cells Is Inversely Related to Aggressive Behavior and Poor Prognosis in Mixed-Type Gastric Cancer
Authors: Marano Luigi , Ambrosio Maria Raffaella , Resca Luca , Carbone Ludovico , Carpineto Samorani Osvaldo , Petrioli Roberto , Savelli Vinno , Costantini Maurizio , Malaspina Lara , Polom Karol , Biviano Ivano , Marrelli Daniele , Roviello Franco 
Published: June 2022

Background and ObjectivesOnly recently the percentage of signet ring cells (SRCs) in gastric cancer (GC) has been proposed as an independent predictor of survival. High amounts of SRCs have been related to lower recurrence and mortality rates, better prognosis, and favorable clinicopathological features in a poorly cohesive histotype. It is not known what the effect of SRC percentage in mixed-type GC is. We investigate the role of SRCs as a prognostic marker in mixed-histotype GC.MethodsA retrospective analysis was performed through a prospectively maintained database of patients with diagnosed “mixed-type” gastric carcinoma, defined according to 2019 WHO classification. These patients underwent surgery between 1995 and 2016, and their tissue samples were stored in a tissue bank. All slides were analyzed, and patients were divided into three groups according to the percentage of SRCs: “Group 1” (displaying ≤10% of SRCs), “Group 2” (displaying &lt;90% but &gt;10% of SRCs), and “Group 3” (displaying ≥90% of SRCs). We compared clinical and pathological features as well as prognostic factors between the different groups.ResultsAmong 164 enrolled patients, 68.9% were male and 31.1% were female (p = 0.612). The mean (±SD) age at diagnosis was 71.4 ± 9.6 years. Ninety-eight (59.7%) patients were classified as “Group 1”, 66 (40.3%) as “Group 2”, and none as “Group 3”. Five-year overall survival was remarkably higher in Group 2 (73.8%) in comparison to Group 1 (35.4%), p &lt; 0.001. Mortality risk was three times higher in patients with ≤10% SRC pattern compared to those with &gt;10% [HR 2.70 (95% CI 1.72–4.24)]. After adjusting according to potential confounding factors, SRC percentage was still an independent predictor of survival.ConclusionsThe proportion of SRCs is inversely related to aggressive behavior and poor prognosis in mixed-type GCs, highlighting the role of SRC amount as an independent predictor of survival.
Biallelic Heterozygous Mutations in Crumbs Homolog-1 Gene Associated With Macular Retinoschisis and Angle-Closure Glaucoma: A Case Report and Literature Review
Authors: Sun Jia-Xing , Yan Hong-Xiang , Hu Dan , Zhou Jian , Wang Yu-Sheng , Wu Jing , Song Xiao-Jin , Hou Xu 
Published: June 2022

BackgroundMutations in the Crumbs homolog-1 (CRB1) gene are associated with a variety of retinal degenerations including Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). It is also important to highlight atypical features to make proper diagnosis and treatment.Case PresentationWe present the case of a 7-year-old girl with biallelic heterozygous CRB1 mutations. The clinical features include macular retinoschisis, Coats-like vasculopathy, short axial length, and angle-closure glaucoma (ACG). We also briefly review the current opinion on CRB1 mutation-related diseases.ConclusionCRB1 mutations could result in a combined manifestation in anterior and posterior segments. This case emphasizes the importance of genetic diagnosis for those young patients with complicated rare clinical features to call for a specific treatment and follow-up plan. It also highlights the crucial role of CRB1 in eyeball development.
Applicability of the Guide for Monitoring Child Development as a Telehealth Delivered Intervention During the Pandemic
Authors: Ozalp Akin Ezgi , Akbas Aysen , Atasoy Sidika Canan , Kanatli Merve Cicek , Ince Acici Selin , Mustafayev Revan , Karaaslan Bedriye Tugba , Ertem Hilmi Deniz , Bingoler Pekcici Bahar , Ertem Ilgi 
Published: June 2022

BackgroundEarly intervention delivered through telehealth is critically needed during crises, particularly for children in low and middle-income countries (LMICs). We aimed to determine the applicability of the international Guide for Monitoring Child Development (GMCD) intervention delivered through telehealth during the COVID-19 lockdown in Turkey.MethodsUsing a mixed-methods longitudinal design, we recruited children with developmental difficulties aged 0–42 months with an appointment during the first lockdown at Ankara University Developmental Pediatrics Division and seen face-to-face only once before. Developmental pediatricians applied the GMCD intervention during a single telephone call. As a novel intervention component, caregivers were asked to record and send back videos of the child's development when there were doubts about the child's functioning. Caregivers were called 1 year later by blinded independent researchers and a semi-structured interview on applicability was conducted. Applicability of the caregiver recorded video component of the intervention was assessed by a blinded observer using the GMCD Video Observation Tool.ResultsOf 122 children that received the telehealth delivered GMCD intervention, 114 (93.4%) were included in the 1-year outcome study. Most were boys (51.8%); median age was 16.5 (IQR: 10.0–29.0) months, 51.0% had chronic health conditions, and 66.7% had developmental delay. All caregivers that received the intervention were mothers; 75.4% had at least high school education. The intervention was reported as applicable by 80.7% with high levels of satisfaction. On multivariate regression analysis, absence of chronic health related conditions was significantly associated with applicability (OR = 2.87, 95% CI = 1.02–8.09). Of 31 caregivers that were asked for videos, 19 sent back 93 videos that were technically observable. One or more developmental domains were observed in all videos; in 52.6%, caregivers provided early learning opportunities.ConclusionsThe findings of this study imply that the telehealth delivered GMCD intervention for children with developmental difficulties is applicable during the pandemic. The intervention content and frequency needs to be augmented for children with chronic health conditions. Further research is required to examine applicability and effectiveness of the GMCD intervention in other settings, particularly in LMICs.
Weaker Response to XueBiJing Treatment in Severe Community-Acquired Pneumonia Patients With Higher Body Mass Index or Hyperglycemia: A Post Hoc Analysis of a Randomized Controlled Trial
Authors: Song Yansha , Wang Xiaocen , Chen Cuicui , Wei Tingting , Lang Ke , Yang Dong , Song Yuanlin 
Published: June 2022

Background: Overweight and hyperglycemia might result in poor prognosis in patients with severe community-acquired pneumonia (SCAP). XueBiJing treatment could significantly improve the outcomes of patients with SCAP. We investigated the efficacy of XueBiJing injection in patients with SCAP stratified by body mass index (BMI) and fasting blood glucose (FBG).Methods: This is a post hoc analysis of XueBiJing trial, a large prospective, randomized, controlled study conducted in 33 hospitals in China. We compared data from non-overweight (BMI &lt;24 kg/m2, n = 425) vs. overweight (BMI ≥24 kg/m2, n = 250) patients as well as non-hyperglycemia (FBG &lt;7 mmol/L, n = 315) vs. hyperglycemia (FBG ≥7 mmol/L, n = 360) patients with XueBiJing, 100 ml, q12 h, or a visually indistinguishable placebo treatment for 5–7 days.Results: Among patients with BMI &lt;24 kg/m2 (n = 425), 33 (15.3%), XueBiJing recipients and 52 (24.9%) placebo recipients (p = 0.0186) died within 28 days. Among patients with BMI ≥24 kg/m2 (n = 250), XueBiJing recipients still had lower mortality (XueBiJing 16.9% vs. placebo 24.2%; p = 0.2068) but without significantly statistical difference. For the FBG group, patients with FBG &lt;7 mmol/L (n = 315), 18 (11.2%) XueBiJing recipients and 32 (20.8%) placebo recipients (p = 0.030) died within 28 days. Among patients with FBG ≥7 mmol/L (n = 360), XueBiJing recipients still had lower mortality (XueBiJing 20.2% vs. placebo 27.8%; p = 0.120) but without significantly statistical difference. The total duration of the ICU stay and the duration of mechanical ventilation were similar in both groups (p &gt; 0.05).Conclusion: Overweight or hyperglycemia might weaken the efficacy of XueBiJing injection in the treatment of SCAP as indicated by the significant elevated risk of 28-day mortality. Additional studies are needed to validate our findings and to further understand the underlying mechanisms.
Tilianin Reduces Apoptosis via the ERK/EGR1/BCL2L1 Pathway in Ischemia/Reperfusion-Induced Acute Kidney Injury Mice
Authors: Liu Zengying , Guan Chen , Li Chenyu , Zhang Ningxin , Yang Chengyu , Xu Lingyu , Zhou Bin , Zhao Long , Luan Hong , Man Xiaofei , Xu Yan 
Published: June 2022

Background: Acute kidney injury (AKI) is a common syndrome impacting about 13.3 million patients per year. Tilianin has been reported to alleviate myocardial ischemia/reperfusion (I/R) injury, while its effect on AKI is unknown; thus, this study aimed to explore if tilianin protects I/R-induced AKI and the underlying mechanisms.Methods: The microarray dataset GSE52004 was downloaded from GEO DataSets (Gene Expression Omnibus). Differential expression analysis and gene-set enrichment analysis (GSEA) were performed by R software to identify apoptosis pathway-related genes. Then, RcisTarget was applied to identify the transcription factor (TF) related to apoptosis. The STRING database was used to construct a protein–protein interaction (PPI) network. Cytoscape software visualized PPI networks, and hub TFs were selected via cytoHubba. AutoDock was used for molecular docking of tilianin and hub gene-encoded proteins. The expression levels of hub genes were assayed and visualized by quantitative real-time PCR, Western blotting, and immunohistochemistry by establishing I/R-induced AKI mouse models.Results: Bioinformatics analysis showed that 34 genes, including FOS, ATF4, and Gadd45g, were involved in the apoptosis pathway. In total, seven hub TFs might play important roles in tilianin-regulating apoptosis pathways. In in vivo, tilianin improved kidney function and reduced the number of TUNEL-positive renal tubular epithelial cells (RTECs) after I/R-induced AKI. Tilianin reduced the activation of the ERK pathway and then downregulated the expression of EGR1. This further ameliorated the expression of anti-apoptotic genes such as BCL2L1 and BCL2, reduced pro-apoptotic genes such as BAD, BAX, and caspase-3, and reduced the release of cytochrome c.Conclusion: Tilianin reduced apoptosis after I/R-induced AKI by the ERK/EGR1/BCL2L1 pathway. Our findings provided novel insights for the first time into the protective effect and underlying molecular mechanisms of tilianin on I/R-induced AKI.
Modulation of Gut Microbiota and Metabolites by Berberine in Treating Mice With Disturbances in Glucose and Lipid Metabolism
Authors: Fang Xinyi , Wu Haoran , Wang Xinmiao , Lian Fengmei , Li Min , Miao Runyu , Wei Jiahua , Tian Jiaxing 
Published: June 2022

Introduction: Glucose and lipid metabolism disturbances has become the third major disease after cancer and cardio-cerebrovascular diseases. Emerging evidence shows that berberine can effectively intervene glucose and lipid metabolism disturbances, but the underlying mechanisms of this remain unclear. To investigate this issue, we performed metagenomic and metabolomic analysis in a group of normal mice (the NC group), mice with disturbances in glucose and lipid metabolism (the MC group) and mice with disturbances in glucose and lipid metabolism after berberine intervention (the BER group).Result: Firstly, analysis of the clinical indicators revealed that berberine significantly improved the blood glucose and blood lipid of the host. The fasting blood glucose level decreased by approximately 30% in the BER group after 8 weeks and the oral glucose tolerance test showed that the blood glucose level of the BER group was lower than that of the MC group at any time. Besides, berberine significantly reduced body weight, total plasma cholesterol and triglyceride. Secondly, compared to the NC group, we found dramatically decreased microbial richness and diversity in the MC group and BER group. Thirdly, LDA effect size suggested that berberine significantly altered the overall gut microbiota structure and enriched many bacteria, including Akkermansia (p &lt; 0.01), Eubacterium (p &lt; 0.01) and Ruminococcus (p &lt; 0.01). Fourthly, the metabolomic analysis suggested that there were significant differences in the metabolomics signature of each group. For example, isoleucine (p &lt; 0.01), phenylalanine (p &lt; 0.05), and arbutin (p &lt; 0.05) significantly increased in the MC group, and berberine intervention significantly reduced them. The arbutin content in the BER group was even lower than that in the NC group. Fifthly, by combined analysis of metagenomics and metabolomics, we observed that there were significantly negative correlations between the reduced faecal metabolites (e.g., arbutin) in the BER group and the enriched gut microbiota (e.g., Eubacterium and Ruminococcus) (p &lt; 0.05). Finally, the correlation analysis between gut microbiota and clinical indices indicated that the bacteria (e.g., Eubacterium) enriched in the BER group were negatively associated with the above-mentioned clinical indices (p &lt; 0.05).Conclusion: Overall, our results describe that the changes of gut microbiota and metabolites are associated with berberine improving glucose and lipid metabolism disturbances.