bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world Safety Profile of Darunavir and its Boosted Agents: An Analysis of FDA Adverse Event Reporting System Database
Authors: Tian Xiaojiang , Yao Yao , He Guanglin , Jia Yuntao , Wang Kejing , Chen Lin 
Published: February 2021

Abstract
This current investigation was aimed to generate signals for adverse drug events of darunavir-containing agents by data mining using the US Food and Drug Administration Adverse Event Reporting System (FAERS). All adverse event (AE) reports for darunavir, darunavir/ritonavir, or darunavir/cobicistat between July 2006 and December 2019 were identified. The reporting Odds Ratio (ROR), proportional reporting ratio(PRR), Bayesian confidence propagation neural network(BCPNN) were used to detect the risk signals. A suspicious signal was generated only if the results of the three algorithms were all positive. A total of 10756 AE reports were identified commonly observed in cardiovascular, endocrine, musculoskeletal, gastrointestinal, hepatobiliary, metabolic, and nutrition system. 40 suspicious signals were generated, and therein 20 signals were not included in the label. Severe high signals (i.e. progressive extraocular muscle paralysis, acute pancreatitis, exfoliative dermatitis, acquired lipodystrophy and mitochondrial toxicity) were identified. In pregnant women, umbilical cord abnormality, fetal growth restriction, low birth weight, stillbirth, premature rupture of membranes, premature birth and spontaneous abortion showed positive signals. Darunavir and its boosted agents induced AEs in various organs/tissues, and were shown to be associated with multiple adverse pregnancy conditions. This study highlighted some novel and severe AEs of darunavir which need to be monitored prospectively.
Deep learning-based tumor segmentation on digital images of histopathology slides for microdosimetry applications
Authors: Weishaupt Luca L. , Torres Jose , Camilleri-Broët Sophie , Rayes Roni F. , Spicer Jonathan D. , Maldonado Sabrina Côté , Enger Shirin A. 
Published: February 2021

Abstract
The goal of this study was (i) to use artificial intelligence to automate the traditionally labor-intensive process of manual segmentation of tumor regions in pathology slides performed by a pathologist and (ii) to validate the use of a deep learning architecture. Automation will reduce the human error involved in the manual process, increase efficiency, and result in more accurate and reproducible segmentation. This advancement will alleviate the bottleneck in the workflow in clinical and research applications due to a lack of pathologist time. Our application is patient-specific microdosimetry and radiobiological modeling, which builds on the contoured pathology slides. A deep neural network named UNet was used to segment tumor regions in pathology core biopsies of lung tissue with adenocarcinoma stained using hematoxylin and eosin. A pathologist manually contoured the tumor regions in 56 images with binary masks for training. To overcome memory limitations overlapping and non-overlapping patch extraction with various patch sizes and image downsampling were investigated individually. Data augmentation was used to reduce overfitting and artificially create more data for training. Using this deep learning approach, the UNet achieved accuracy of 0.91±0.06, specificity of 0.90±0.08, sensitivity of 0.92±0.07, and precision of 0.8±0.1. The F1/DICE score was 0.85±0.07, with a segmentation time of 3.24±0.03 seconds per image, thus achieving a 370±3 times increased efficiency over manual segmentation, which took 20 minutes per image on average. In some cases, the neural network correctly delineated the tumor's stroma from its epithelial component in tumor regions that were classified as tumor by the pathologist. The UNet architecture can segment images with a level of efficiency and accuracy that makes it suitable for tumor segmentation of histopathological images in fields such as radiotherapy dosimetry, specifically in the subfields of microdosimetry.
Impacts of Antioxidant Vitamins, Curry Consumption and Heavy Metal Levels on The Metabolic Syndrome With Comorbidities: A National Cross-Sectional Study
Authors: Duc Hai Nguyen , Oh Hojin , Kim Min-Sun 
Published: February 2021

Abstract
The burden of metabolic syndrome (MetS) is increasing worldwide especially in the coronavirus disease 2019 (COVID-19). This phenomenon can be related to environmental, dietary, and lifestyle risk factors. We aimed to determine the association between the levels of serum heavy metals, vitamins, and curry intake, subsequently predict the risks for MetS by margin effects. Daily intake of vitamins was measured by 24-h recall was calculated using a food frequency questionnaire. Heavy metals were quantified by graphite furnace atomic absorption spectrometry, and mercury analyzer. The risk of MetS was significantly lower in the high curry consumption than in the low curry consumption, risks of Mets were reduced by 7%, 13%, 1%, and 1%, when the levels of vitamin B1, B2, B3, and C intake increased by one mg, respectively. However, risks of Mets were increased by 9%, 3%, 5%, when the levels of serum Pb, Hg, and CRP increased by one unit. The potential health benefits resulting from vitamin and curry supplementation could guard the public against the dual burden of communicable and non-communicable diseases. Further works are required to thwart risk factors related to heavy metals and determine the mechanistic dual effects of vitamins and curry in MetS.
Effects&nbsp;of different treatment of faecal microbiota transplantation techniques on ulcerative colitis in rats
Authors: Zhu Fangyuan , Ke Yifan , Luo Yiting , Wu Jiaqian , Wu Pei , Ma Fangxiao , Liu Yingchao 
Published: February 2021

Abstract
Background: Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease with abdominal pain, mucus, pus, and blood in the stool as the main clinical manifestations. The pathogenesis of UC is still not completely clear, and multiple factors such as genetic susceptibility, immune response, intestinal microecological changes, and environmental factors together lead to the onset of UC. In recent years, the role of intestinal flora disturbance on the pathogenesis of UC has received widespread attention. Therefore, fecal microbiota transplantation(FMT), which changes the intestinal microecological environment of UC patients by transplantation of normal fecal bacteria, has attracted increasing attention from researchers. However, there are no guidelines at home and abroad to recommend fresh FMT or frozen FMT in the treatment of UC, and there are a few studies on this. Therefore the purpose of this experiment was to explore the effects of fresh and frozen fecal microbiota transplantation methods on the treatment of experimental ulcerative colitis models in rats.Results: Compared with the model control group, all faecal microbiota transplantation groups achieved better efficacy, mainly manifested as weight gain by the rats, improvements in faecal characteristics and blood stools, reduced inflammatory factors, and normal bacterial flora. The efficacy of the frozen faecal microbiota transplantation group was better than that of the fresh faecal microbiota transplantation group in terms of behaviour and colon length .Conclusions: FMT is a feasible method for treating UC. The mechanism of action may be via competitive inhibition of pathogenic microorganisms, improved immune metabolism, and reduced inflammatory response to mitigate the damage to the intestinal barrier and cause UC remission. Compared with fresh FMT, the therapeutic effect of frozen FMT may be greater.
Nomograms individually predict the overall survival and cancer-specific survival of adult patients with hemispheres lower-grade gliomas: A SEER-Based Study
Authors: Che Wenqiang , Li Chengzhuo , Lyu Jun , Wang Xiangyu 
Published: February 2021

Abstract
(1) Background: The 2016 WHO classification of Tumors of the Central Nervous System brought an escalating research interest in lower-grade gliomas (LGGs). This study aims to establish individualized prognostic nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with LGGs;(2) Methods: We searched the Surveillance, Epidemiology, and End Results (SEER) database for adult patients diagnosed with LGGs from 1998 to 2016. The patient data set selected from SEER was randomly divided into training and validation data sets at a ratio of 7:3. The significant prognostic factors were identified by using multivariate regression models in the training dataset. Then OS and CSS nomograms were developed and internally validated;(3) Results: After the inclusion and exclusion criteria set, a total of 12,630 patients were enrolled in our research. The prognosticators for OS contained age, sex, race, marital status, surgery, radiotherapy, chemotherapy, tumor size/site, laterality, WHO grade, while only chemotherapy among the 11 indicators mentioned above was not related to CSS. The c-indexes of OS and CSS of the validation cohort were 0.749 and 0.761, respectively. The calibration curve plots showed that the predicted probability of 3-, 5-, and 8-years survival rates corresponded well with the actual observed OS and CSS rates;(4) Conclusion: The present study using the SEER database constructed and internally validated prognostic nomograms to predict the OS and CSS of patients with LGGs. The nomograms showed perfect predictive abilities and may be useful clinical tools for decision aids and better supporting patient counselling.
Comparison of Methods to Improve Fracture Risk Assessment in Chinese Diabetic Postmenopausal Women: A Case-Control Study
Authors: Wen Zhangxin , Na Ding , Rong Chen , Liu Shuyin , Wang Qinyi , Zhifeng Sheng , Sheng Zhifeng , Hong Liu 
Published: February 2021

Abstract
PurposeThis study compared the performance of three proposed Fracture Risk Assessment Tool (FRAX) alternatives to the current standard Chinese FRAX in predicting bone fracture risk in type 2 diabetic (T2DM) postmenopausal women, and to explore the optimal strategy to better predicted fracture risk in postmenopausal women with diabetes in China.MethodsWe recruited 434 patients from community-medical centers, 217 with T2DM and 217 without T2DM (non-T2DM). All participants completed self-reported questionnaires detailing their characteristics and risk factors. Bone mineral density (BMD) and spinal radiographs were evaluated. The China FRAX model calculated all scores. The area under the receiver operator characteristic curve (ROC-AUC) evaluated the sensitivity, specificity, and accuracy for predicting 10-year risk for major (MOF) and hip (OHF) osteoporotic fractures in T2DM patients. ResultsT2DM patients had higher BMD but lower average FRAX values than non-T2DM patients. The unadjusted FRAX ROC-AUC was 0.774, significantly smaller than that for 0.5-unit femoral neck T-score-adjusted FRAX (0.800; p = 0.004). Rheumatoid arthritis (RA; AUC = 0.810, p = 0.033) and T-score (AUC = 0.816, p = 0.002) adjustments significantly improved fracture prediction in T2DM patients. Conclusions: Femoral neck T-score adjustment might be the preferred method for predicting MOF and OHF in Chinese diabetic postmenopausal women, while RA adjustment only effectively predicted HF risk.Conclusions﻿Femoral neck T-score adjustment might be the preferred method for predicting MOF and OHF in Chinese diabetic postmenopausal women, while RA adjustment only effectively predicted HF risk.
Preoperative Detection of the TERT Promoter Mutations in Papillary Thyroid Carcinomas
Authors: Nakao Tomoe , Matsuse Michiko , Saenko Vladimir , Rogounovitch Tatiana , Tanaka Aya , Suzuki Keiji , Higuchi Miyoko , Sasai Hisanori , Sano Tsutomu , Hirokawa Mitsuyoshi , Miyauchi Akira , Kawakami Atsushi , Mitsutake Norisato 
Published: February 2021

Abstract
Telomerase reverse transcriptase promoter (TERT-p) mutations are strongly associated with tumor aggressiveness and worse prognosis in papillary thyroid carcinomas (PTCs). Since the TERT-p promoter mutations have been reported to be subclonal, it is unclear how accurately they can be detected by preoperative fine needle aspiration (FNA). The objective of this study was to analyze the concordance rate of the TERT-p mutations between preoperative FNA and corresponding postoperative surgical specimens. The mutational status of the TERT-p in FNA samples detected by our ddPCR assay was highly concordant with that in postoperative FFPE specimens. The TERT-p mutation was significantly associated with age, tumor size, extrathyroidal extension, and the Ki-67 labeling index in multivariate analysis in both FNA and FFPE samples. The detection of the TERT-p mutations using FNA samples has a good ability to predict disease aggressiveness and, therefore, could be clinically useful in the determination of PTC management.
Effect of High Blood Cortisol Concentration on the Spectroscopically Determined Secondary Structure of Proteins and Lipid Balance on the Example of Elite Women Volleyball Players
Authors: Depciuch Joanna , Czarny Wojciech , Szuszkiewicz Wojciech , Reich Adam , Klebowski Bartosz , Bajorek Wojciech , Płonka Artur , Łuszczewska-Sierakowska Iwona , Cebulski Jozef , Król Paweł 
Published: February 2021

Abstract
Cortisol is a stress hormone plays a crucial role in the balance between phospholipids and lipids level. In consequence, it affects the secondary structure of proteins. Currently cortisol concentration in plasma is determined by biochemical analysis. A new, optical method to estimate stress level is proposed in this work. Infrared and Raman spectroscopies were used to determine quantitative and qualitative changes in the lipids and proteins fraction in function of cortisol concentration in 49 samples of plasma collected from volleyball players at various stages of preparation for the competition. With the cortisol level increase, a decrease of structures related to PO2- phospholipids groups and amides III, II and I bonds was noticed in the transmission spectra. Changes in the secondary structure of protein were indicated as a frequency shift of α-helix and β-sheet vibrations observed in Raman spectra and second derivative of transmission spectra. Pearson correlation test presented positive correlations between phospholipids and proteins level and between cortisol concentration and phospholipids in transmittance spectra. Negative correlations between cortisol concentration and proteins and phospholipids level was observed in the Raman spectra. Both optical techniques are considered to become effective tools for estimating the concentration of cortisol in the plasma.
Management of Liver Hydatid Cysts: A Cross-Sectional Retrospective Analysis of 293 Cases From Southern Iran
Authors: Erfani Amirhossein , shahriarirad Reza , Eskandarisani Mehrdad , Rastegarian Mohammad , Sarkari Bahador 
Published: February 2021

Abstract
Background: The current study aimed to evaluate the therapeutic features and complications of liver hydatid cyst in patients who underwent surgery for CE in Fars province, southern Iran.Methods: A total of 293 patients who underwent surgery for liver hydatid cyst from 2004 to 2018 in Fars Province, southern Iran, were retrospectively evaluated. The clinical records of patients were reviewed and the demographic and clinical characteristics of each patient were assessed.Results: Of the total of 293 cases, 178 (60.9%) were females and 115 (39.1%) were males. The mean age of the subjects was 37.22 (±20.55) years. The mean size of the liver hydatid cyst was 9.18 (± 4.365). Of the 293 patients studied, 227 (77.4%) had hydatid cysts only in the liver, while 55 (9.4%) had both liver and lung cysts. More than half of the liver cysts (65.9%) were located in the right portion of the liver (segment 5 to 8). Of the 293 cases, 52 (17.7%) underwent radical surgery while 241 (82.3%) underwent conservative surgery. Recurrence of hydatid cyst was recorded in 46 (15%) of cases. Patients who were treated with radical surgery in comparison with those who had conservative surgery had a lower recurrence rate but a longer duration of hospital stay (p<0.05). Conclusion: Recurrence remains as one of the major challenges in the management of hydatid cyst. Radical surgery reduces the chance of recurrence, although this procedure increases the length of hospital stay.This study was registered at Clinicaltrials.gov with registration ID of NCT04363151. https://clinicaltrials.gov/ct2/show/NCT04363151?cntry=IR&city=Shiraz&draw=2&rank=1
GC-TOF/MS-Based Metabolomics Analysis to Investigate the Antimicrobial Activity of N-Acetylcysteine in the Plant-Pathogen Xanthomonas Citri Subsp. Citri
Authors: Picchi Simone Cristina , Silva Mariana Souza e , Saldanha Luiz Leonardo , Ferreira Henrique , Takita Marco Aurélio , Caldana Camila , Souza Alessandra Alves 
Published: February 2021

Abstract
N-Acetylcysteine (NAC) is an antioxidant, anti-adhesive, and antimicrobial compound. Even though there is much information regarding the role of NAC as an antioxidant and anti-adhesive agent, little is known about its antimicrobial activity. In order to assess its mode of action in bacterial cells, we investigated the metabolic responses triggered by NAC at neutral pH. As a model organism, we chose the Gram-negative plant pathogen Xanthomonas citri subsp. citri (X. citri), the causal agent of citrus canker disease, due to the potential use of NAC as a sustainable molecule against phytopathogens dissemination in citrus cultivated areas. In presence of NAC, cell proliferation was affected after 4 hours, but damages to the cell membrane were observed only after 24 hours. Targeted metabolite profiling analysis using GC-MS/TOF unravelled that NAC seems to be metabolized by the cells affecting cysteine metabolism. Intriguingly, glutamine, a marker for nitrogen status, was not detected among the cells treated with NAC. The absence of glutamine was followed by a decrease in the levels of the majority of the proteinogenic amino acids, suggesting that the reduced availability of amino acids affect protein synthesis and consequently cell proliferation.
Chromosome Karyotype and Stability Identification of New Synthetic Hexaploid Wheat
Authors: Wang Yajuan , Wang Siwen , Jia Xiujuan , Tian Zengrong , Wang Yongfu , Wang Changyou , Zhang Hong , Liu Xinlun , Zhao Jixin , Deng Pingchuan , Wanquan Ji 
Published: February 2021

Abstract
Synthetic hexaploid wheats offer breeder ready access to potentially novel genetic variations in wild ancestral species. In present study, we used MY3478 (2n = 4x = 28, AABB) as female crossing with SY41 (2n = 2x = 14, DD) of stripe rust resistant as male through natural chromosome doubling to constructed the new hexaploid wheat line NA0928. Agronomic traits and cytological analysis were characterized in NA0928 of S8-S9 generations. The major study and results were described as follows, agronomic character variation coefficient in NA0928 of S8 generation showed that the effective tiller number (55.3%) > spike length (15.3%) > number of spikelets (13.9%) > plant height (8.7). It is suggested that the effective tiller number and spike length have great utilization value in breeding. Cytological observation and fluorescence in situ hybridization (FISH) results showed that the chromosome number and configuration have rich variations in S9 of NA0928. Chromosome number variation range of 36–44. Numerous chromosome karyotype variations were almost detected in A and B subgenomes. In addition, more diverse types of chromosomal structure variations were observed in the stripe rust resistant strains with more excellent performance than susceptible strains in agronomic traits. Especially, the tillering number of the resistant strains were much higher. Here, Meiosis stage of pollen mother cells and multicolor-GISH (Mc-GISH) results showed that two new synthetic hexaploid wheat lines were obtained, which showed genetic stability, one line was resistance to stripe rust, and the other one line was susceptible stripe rust, at the same time, there had two excellent characteristics with high 1000-grain weight and multiple tillers. They will be valuable germplasm materials in wheat breeding utilization.
Anlotinib in the treatment of advanced hepatocellular carcinoma: an open label phase II study (ALTER-0802 study)
Authors: Sun Yongkun , Zhou Aiping , Zhang Wen , Jiang Zhichao , Chen Bo , Zhao Jianjun , Li Zhiyu , Wang Liming , Bi Xinyu , Zhao Hong , Liu Kan 
Published: February 2021

Abstract
Purpose: This study aimed to assess efficacy and safety of anlotinib as a first- or second-line treatment for advanced or metastatic hepatocellular carcinoma (aHCC) and to identify the predictive plasma cytokines on efficacy of anlotinib.Methods: It was a phase II clinical study. Patients with aHCC were recruited from October 2016 to April 2019 and divided into two cohorts according to previous tyrosine kinase inhibitors (TKIs) therapy. Those without or with prior TKIs were in Cohort 1 or 2, respectively. All patients took anlotinib (12mg/day, Day1–14, three weeks per cycle). The primary endpoint was 12-week progression free survival (PFS) rate. Relationship between series plasma cytokine level and efficacy of anlotinib was analyzed.Results: Enrolled 26 patients in Cohort 1 and 24 in Cohort 2. In Cohort 1, the 12-week PFS rate was 80.8% (95% confidence interval [CI]; 59.8%–91.5%) and median time to progression (TTP) was 5.9 months (95% CI; 4.8–6.9). In Cohort 2, the 12-week PFS rate and median TTP was 72.5% (95% CI; 48.7%–86.6%) and 4.6 months (95% CI; 2.7–10.0), respectively. The median TTP on patients with baseline plasma level of CXCL1 (C-X-C motif chemokine ligand 1) less than 7.6 ng/μl was significant longer in both cohorts. The most common grade 3–5 adverse events were hypertension (8%), diarrhea (8%) and hand-foot syndrome (6%). Conclusion: Anlotinib showed promising efficacy and safety as a first- or second-line treatment with a continuous TKIs treatment strategy in aHCC. The plasma CXCL1 might be a predictor for efficacy of anlotinib.
Morphological Changes of Anak Krakatau after the 22 December 2018 Flank Collapsed
Authors: Darmawan Herlan , Worosuprojo Suratman , Wahyudi Wahyudi , Harijoko Agung , Wibowo Haryo Edi , Mutaqin Bachtiar W. , Haerani Nia , Syarifuddin Syarifuddin , Albab Milya Aflah Ulul , Jati Raditya , Asriningrum Wikanti 
Published: February 2021

Abstract
After the 22 December 2018 flank collapse, series of hydrothermal, phreatomagmatic, and effusive eruptions occurred and changed the morphology of Anak Krakatau. The ejected volcanic materials enlarge and increase the elevation of the west flank, which may indicate a reconstruction phase of the Anak Krakatau edifice. Here, we investigated the morphological changes of Anak Krakatau between 2019 and 2020 by using drone SfM photogrammetry, Sentinel and Pleiades satellite imageries, and fieldworks photograph data. The result shows volcaniclastic deposit due to the hydrothermal and/or phreatomagmatic eruptions that covered 0.08 km2 around an active crater lake at Anak Krakatau between February and January 2020. The large phreatomagmatic and effusive eruptions on 10 April 2020 produced tephra and lava flow deposits that significantly changed the morphology of Anak Krakatau. The deposit of tephra covered 0.815 km2 at the north – northwest flanks of Anak Krakatau, while the lava flow emplaced 0.2 km2 and elongated around 742 m from the pre-existing crater lake to the west shoreline of Anak Krakatau. The lava flow has a blocky surface and highly fractured that possibly formed due to compression – extension stresses during lava flow emplacement. The emplacement of the massive lava flow at the pre-existing crater lake may change the future eruption style at Anak Krakatau, which was previously dominated by hydrovolcanism activities, such as hydrothermal and phreatomagmatic events.