bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical characteristics and MRI-based phenotypes of perianal abscess formation in children with fistulizing Crohn's Disease
Authors: Tabari Azadeh , Kaplan Jess L. , Huh Susanna Y. , Moran Christopher J. , Gee Michael S. 
Published: November 2022

PurposeThe aim of this study was to explore potential correlation of the MR imaging features and clinical characteristics with formation of perianal abscess in children with Crohn's perianal fistulas (CPF).MethodsFrom 2010 to 2020, pediatric patients with CPF diagnosis on their first pelvic MRI were identified retrospectively. All patients were divided into two groups based on the presence or absence of perianal abscess. Baseline clinical and MRI characteristics were recorded for each patient. All the statistical calculations were performed using R (version 3.6.3).ResultsA total of 60 patients [F:M 17:43, median age 14 years (IQR 10-15), ranging 3–18 years] were included in this study. Forty-four abscesses were identified in 36/60 children (mean volume 3 ± 8.6 ml, median 0.3 ml). In 24/60 patients with perianal disease, no abscess was detected on the MRI. Ten patients (28%) showed perianal abscess on pelvic MRI at the initial diagnosis. The rate of active disease on colonoscopy (visible ulcerations/aphthous ulcers) was similar in both groups (95% vs. 94%). With regards to disease location, the majority of patients (40/60, 66.6%) in both groups had ileocolonic CD. All patients without abscess had a single perianal fistula (n = 24; 3 simple and 21 complex fistulae), however, patients with perianal abscess tended to have &gt;1 fistulous tracts (n = 50 fistulas; all complex, 27 single, 10 double and 1 triple). Intersphincteric fistula was the most common fistula type in both groups (79% and 66%, p = 0.1). The total length of fistula (3.8 ± 1.7 vs. 2.8 ± 0.8 cm, p = 0.006) and presence of multiple external openings (n = 25 vs. 7, p = 0.019) were significantly higher in patients with abscesses, and fistula length &gt;3.3 cm showed 80% specificity and 83% PPV for the presence of perianal abscess. Fistulas were symptomatic (pain, bleeding or drainage) at similar rates in both groups (68% and 70%, p = 0.1).ConclusionPediatric patients with CPF who develop perianal abscess have a distinct imaging phenotype defined by longer fistula length (&gt;3.3 cm), multiple skin openings and multiple fistulous tracts (≥2) on MRI. Patients who have these features but does not have an abscess on imaging may merit more aggressive treatment (and close monitoring) to prevent the development of an abscess.
Prediction and associated factors of non-steroidal anti-inflammatory drugs efficacy in migraine treatment
Authors: Lu Zhao-Xuan , Dong Bing-Qing , Wei Heng-Le , Chen Liang 
Published: November 2022

Background: The selection strategy of non-steroidal anti-inflammatory drugs (NSAIDs) for migraine is hard to judge whether it is effective, leading to unnecessary exposure to insufficient or lengthy treatment trials. The goal of the study was to investigate potential predictors of NSAIDs efficacy in migraine therapy and to explore their influence on efficacy.Methods: 610 migraine patients were recruited and assigned into responders and non-responders. Potential predictors among demographic and clinical characteristics for NSAIDs efficacy were extracted using multivariable logistic regression (LR) analysis, and were applied to construct prediction models via machine learning (ML) algorithms. Finally, Cochran-Mantel-Haenszel tests were used to examine the impact of each predictor on drug efficacy.Results: Multivariate LR analysis revealed migraine-related (disease duration, headache intensity and frequency) and psychiatric (anxiety, depression and sleep disorder) characteristics were predictive of NSAIDs efficacy. The accuracies of ML models using support vector machine, decision tree and multilayer perceptron were 0.712, 0.741, and 0.715, respectively. Cochran-Mantel-Haenszel test showed that, for variables with homogeneity of odds ratio, disease duration, frequency, anxiety, and depression and sleep disorder were associated with decreased likelihood of response to all NSAIDs. However, the variabilities in the efficacy of acetaminophen and celecoxib between patients with mild and severe headache intensity were not confirmed.Conclusion: Migraine-related and psychiatric parameters play a critical role in predicting the outcomes of acute migraine treatment. These models based on predictors could optimize drug selection and improve benefits from the start of treatment.
Ocular adverse events associated with anti-VEGF therapy: A pharmacovigilance study of the FDA adverse event reporting system (FAERS)
Authors: Ma Pan , Pan Xinmei , Liu Ruixiang , Qu Ya , Xie Linli , Xie Jiangchuan , Cao Liya , Chen Yongchuan 
Published: November 2022

Background: The purpose of this study is to identify and characterize ocular adverse events (AEs) that are significantly associated with anti-VEGF drugs for treatment of neovascular age-related macular degeneration and compare the differences between each drug, and provide clinical reference.Methods: Ocular AEs submitted to the US Food and Drug Administration were analyzed to map the safety profile of anti-VEGF drugs. The Pharmacovigilance tools used for the quantitative detection of signals were reporting odds ratio and bayesian confidence propagation neural network.Results: A total of 10,608,503 AE reports were retrieved from FAERS, with 20,836 for ranibizumab, 19,107 for aflibercept, and 2,442 for brolucizumab between the reporting period of Q1, 2004 and Q3, 2021. We found and analyzed the different AEs with the strongest signal in each drug—ranibizumab-macular ischaemia (ROR = 205.27, IC-2SD = 3.70), retinal pigment epithelial tear (ROR = 836.54, IC-2SD = 7.19); aflibercept-intraocular pressure increased (ROR = 31.09, IC-2SD = 4.61), endophthalmitis (ROR = 178.27, IC-2SD = 6.70); brolucizumab-retinal vasculitis (ROR = 2930.41, IC-2SD = 7.47) and/or retinal artery occlusion (ROR = 391.11, IC-2SD = 6.10), dry eye (ROR = 12.48, IC-2SD = 2.88).Conclusion: The presence of AEs should bring clinical attention. The use of anti-VEGF drugs should be based on the patient’s underlying or present medical condition to reduce any adverse event associated with the treatment.
Identification of highly effective inhibitors against SARS-CoV-2 main protease: From virtual screening to in vitro study
Authors: Wang Hu , Wen Jun , Yang Yang , Liu Hailin , Wang Song , Ding Xiaoli , Zhou Chunqiao , Zhang Xuelin 
Published: November 2022

Background and Objective: The public’s safety has been significantly jeopardized by the pandemic of COVID-19, which is brought on by the highly virulent and contagious SARS-CoV-2 virus. Finding novel antiviral drugs is currently of utmost importance for the treatment of patients with COVID-19. Main protease (3CLpro) of SARS-CoV-2 is involved in replication of virus, so it is considered as a promising target. Using small molecules to inhibit SARS-CoV-2-3CLpro activity may be an effective way to prevent viral replication to fight COVID-19. Despite the fact that some SARS-CoV-2-3CLpro inhibitors have been described, only few of them have high levels of inhibition at nanomolar concentrations. In this study, we aimed to screen out effective SARS-CoV-2-3CLpro inhibitors.Methods: To identify highly effective SARS-CoV-2-3CLpro inhibitors, a pharmacophore mapping and multiple-conformation docking were efficiently applied to find novel hit compounds from a database. Then, the stability of the 3CLpro-hit complexes was validated by using molecular dynamics simulation. Finally, biological assay was used to assess the inhibition effects of hit compounds on SARS-CoV-2-3CLpro.Results: Four hit compounds were identified by using computer-assisted strategy. Molecular dynamics simulation suggested that these hits bound stably to the 3CLpro-active pocket. Bioassay showed that all the hits had potent inhibition against SARS-CoV-2-3CLpro with IC50 values in the range of 0.017–0.83 μM. Particularly, hit one was the best 3CLpro inhibitor and its inhibition effect of SARS-CoV-2-3CLpro (IC50 = 0.017 ± 0.003 µM) was about 236 times stronger than that of ML300 (IC50 = 4.01 ± 0.66 µM).Conclusion: These data indicate that hit one could be regarded as an anti-SARS-CoV-2 candidate worth exploring further for the treatment of COVID-19.
Combined metabolomics and network pharmacology to elucidate the mechanisms of Dracorhodin Perchlorate in treating diabetic foot ulcer rats
Authors: Deng Pin , Liang Huan , Wang Shulong , Hao Ruinan , Han Jinglu , Sun Xiaojie , Pan Xuyue , Li Dongxiao , Wu Yinwen , Huang Zhichao , Xue Jiajia , Chen Zhaojun 
Published: November 2022

Background: Diabetic foot ulcer (DFU) is a severe chronic complication of diabetes, that can result in disability or death. Dracorhodin Perchlorate (DP) is effective for treating DFU, but the potential mechanisms need to be investigated. We aimed to explore the mechanisms underlying the acceleration of wound healing in DFU by the topical application of DP through the combination of metabolomics and network pharmacology.Methods: A DFU rat model was established, and the rate of ulcer wound healing was assessed. Different metabolites were found in the skin tissues of each group, and MetaboAnalyst was performed to analyse metabolic pathways. The candidate targets of DP in the treatment of DFU were screened using network pharmacology. Cytoscape was applied to construct an integrated network of metabolomics and network pharmacology. Moreover, the obtained hub targets were validated using molecular docking. After the topical application of DP, blood glucose, the rate of wound healing and pro-inflammatory cytokine levels were assessed.Results: The levels of IL-1, hs-CRP and TNF-α of the Adm group were significantly downregulated. A total of 114 metabolites were identified. These could be important to the therapeutic effects of DP in the treatment of DFU. Based on the network pharmacology, seven hub genes were found, which were partially consistent with the metabolomics results. We focused on four hub targets by further integrated analysis, namely, PAH, GSTM1, DHFR and CAT, and the crucial metabolites and pathways. Molecular docking results demonstrated that DP was well combined with the hub targets.Conclusion: Our research based on metabolomics and network pharmacology demonstrated that DP improves wound healing in DFU through multiple targets and pathways, and it can potentially be used for DFU treatment.
Integrated analysis of comprehensive metabolomics and network pharmacology to reveal the mechanisms of abelmoschus manihot (L.) medik. in the treatment of cisplatin-induced chronic kidney disease
Authors: Liao Jian-Cheng , Li Chang-Yin , Teng Feng-Meng , Jian-Chen  , Yu Jiang-Yi , Ju Wen-Zheng , Zou Jian-Dong 
Published: November 2022

Background: Abelmoschus manihot (L.) Medik (“Huangkui” in Chinese, HK) has been widely used for the treatment of kidney diseases. Nephrotoxicity is the side effect of cisplatin (CDDP), which greatly limits its clinical application. Therefore, CDDP could be used to establish the chronic kidney disease (CKD) model. However, the protective effects of HK on CDDP-induced CKD have not been investigated.Purpose: To explore the protective effect and underlying mechanisms of HK on multiple low-dose CDDP-induced CKD in rats by the integrated analysis of serum, kidney, and urine metabolomics and network pharmacology.Methods: The CKD model was induced by multiple low-dose CDDP. Body weight, organ index, serum biochemical, and kidney histology were examined to evaluate the effect of HK. Serum, kidney, and urine were collected and profiled by HILIC/RPLC-Q-TOF/MS-based metabolomics. Potential biomarkers (PBs) were screened according to the criteria of VIP &gt;1, p &lt; 0.01, and FC &gt; 2, and then identified or assigned. The pathway analysis and PBs enrichment were conducted by MetaboAnalyst and ChemRICH. Furthermore, network pharmacology was adopted to dig out the active components and targets. Finally, the results from metabolomics and network pharmacology were integrated to confirm each other.Results: HK could recover the CDDP-induced abnormal pharmacological and metabolic profile changes. A total of 187 PBs were screened and identified from the serum, kidney, and urine metabolomics. Pathway analysis showed that multiple metabolic pathways, mainly related to amino acid and lipid metabolisms, were involved in the nephroprotective effect of HK, and especially, HK could significantly alleviate the disorder of tryptophan metabolism pathway in serum, kidney, and urine. Meanwhile, network pharmacology analysis revealed that 5 components in HK and 4 key genes could be responsible for the nephroprotection of HK, which also indicated that the metabolism of tryptophan played an important role in HK against CKD.Conclusion: HK has a nephroprotection on CDDP-induced CKD, mainly by restoring the dysregulation of tryptophan metabolism. Integrated analysis of serum, kidney, and urine metabolomics and network pharmacology was a powerful method for exploring pharmacological mechanisms and screening active components and targets of traditional Chinese medicine.
Priming exercise accelerates oxygen uptake kinetics during high-intensity cycle exercise in middle-aged individuals with type 2 diabetes
Authors: Rocha Joel , Gildea Norita , O’Shea Donal , Green Simon , Egaña Mikel 
Published: November 2022

Background: The primary phase time constant of pulmonary oxygen uptake kinetics (V·O2τp) during submaximal efforts is longer in middle-aged people with type 2 diabetes (T2D), partly due to limitations in oxygen supply to active muscles. This study examined if a high-intensity “priming” exercise (PE) would speed V·O2τp during a subsequent high-intensity cycling exercise in T2D due to enhanced oxygen delivery.Methods: Eleven (4 women) middle-aged individuals with type 2 diabetes and 11 (4 women) non-diabetic controls completed four separate cycling bouts each starting at an ‘unloaded’ baseline of 10 W and transitioning to a high-intensity constant-load. Two of the four cycling bouts were preceded by priming exercise. The dynamics of pulmonary V·O2 and muscle deoxygenation (i.e. deoxygenated haemoglobin and myoglobin concentration [HHb + Mb]), were calculated from breath-by-breath and near-infrared spectroscopy data at the vastus lateralis, respectively.Results: At baseline V·O2τp, was slower (p &lt; 0.001) in the type 2 diabetes group (48 ± 6 s) compared to the control group (34 ± 2 s) but priming exercise significantly reduced V·O2τp (p &lt; 0.001) in type 2 diabetes (32 ± 6 s) so that post priming exercise it was not different compared with controls (34 ± 3 s). Priming exercise reduced the amplitude of the V·O2 slow component (As) in both groups (type 2 diabetes: 0.26 ± 0.11 to 0.16 ± 0.07 L/min; control: 0.33 ± 0.13 to 0.25 ± 0.14 L/min, p &lt; 0.001), while [HHb + Mb] kinetics remained unchanged.Conclusion: These results suggest that in middle-aged men and women with T2D, PE speeds V·O2τp likely by a better matching of O2 delivery to utilisation and reduces the V·O2 As during a subsequent high-intensity exercise.
Cognitive flexibility in younger and older children who stutter
Authors: Paphiti Maria , Eggers Kurt 
Published: November 2022

PurposeRecent research findings suggest possible weaknesses in cognitive flexibility (CF) in children who stutter (CWS) when compared to children who do not stutter (CWNS). Studies so far, have been conducted with either younger (3–6 years old) or older children (6–12 years old) with a variety of measures. The purpose of the present study was to investigate CF with the use of a single behavioral measure across a broader age range (4–10 years old).MethodsParticipants were 37 CWS (mean age = 6.90 years) and 37 age-and gender-matched CWNS (mean age = 6.88 years), divided in a younger (below 7 years) and older (above 7 years) age group. All participants undertook a computerized visual set-shifting task consisting of three blocks. CF was evaluated through across-and within-block comparisons of the actual response speed and accuracy values. In addition, mixing-and set-shifting-costs were evaluated based on the mean response speed and accuracy.ResultsAll participants showed expected mixing-and set-shifting-costs. Only the within-block analyses yielded significant between (sub)group differences. Investigation of the block × classification group × age group interactions showed that older CWS had larger set-shifting-costs (slowed down more and made more errors) compared to older CWNS.ConclusionWhile all participants required more time during set-shifting trials, only the older CWS (7–10 years old), and not younger CWS, were slower and made more errors. This finding corroborates previous findings in CWS of a similar age and could possibly point to a role of CF in stuttering persistence.
Influence of different playing styles among the top three teams on action zones in the World Cup in 2018 using a Markov state transition matrix
Authors: Liu Tianbiao , Zhou Chenye , Shuai Xumei , Zhang Li , Zhou Jingjing , Yang Lang 
Published: November 2022

PurposeIn football, attacking has seen evolving for decades and attacking pattern detection is an important topic in this sport. The purpose of this study was to identify the general and threatening attacking patterns of different playing styles in world top football matches, which represented the latest evolvement of soccer attacking.MethodsAttacking sequence data of the top three teams from 21 matches in the 2018 World Cup were collected. The three teams were classified into two playing styles according to a previous study, France was a direct-play team, and Croatia and Belgium were possession-play teams. The football field was divided into 12 zones and Markov transition matrix-based zone models were applied to assess the attacking pattern in the 21 matches. Both descriptive analysis and simulative analysis were conducted using this model.ResultsThe results revealed that (1) flanker attacks were frequently taken among all three teams, and possession playing teams (Croatia and Belgium) played more often than direct playing teams (France) in their center of the midfield zone and (2) forward passes across/through zones toward the middle of attacking quarter (A1/4) have a positive impact of creating a chance of a goal.ConclusionUsing Markov transition matrix, general and threatening attacking patterns were found. The combination of possession play and counterattack was a new trend that emerged in the 2018 World Cup. These findings can help coaches to develop corresponding strategies when facing opponents of different playing styles.
Vaccination with SARS-CoV-2 inactivated vaccines reduced the risk of anxiety and depression in a population majored by health care workers during the recent omicron variant outbreak
Authors: Zhao Hong , Yu Xia , Ye Wenyi , Wang Runzhu , Sheng Jifang , Shi Yu 
Published: November 2022

BackgroundThe mental health status of the population majored by health care workers in China during the omicron variant outbreak remains unknown. Furthermore, the effect of COVID-19-inactivated vaccines on mental health is yet to be investigated.MethodsA cross-sectional, online survey study was conducted from 12–20 April, 2022. The prevalence of symptoms of depression and anxiety were evaluated using the Hospital Anxiety and Depression Scale.ResultsResponses from a total of 1,387 participants were analyzed, 39.7% of which reported symptoms of mental health illness. The incidence of anxiety (30.4% vs. 48.4%, p &lt; 0.001) and depression (27.1% vs. 46.3%, p &lt; 0.001) decreased with COVID-19 inactivated vaccination. From multivariate analysis, living in Shanghai (anxiety: Odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.14–2.19, p = 0.006; depression: OR: 1.61, 95% CI: 1.16–2.25, p = 0.005), with a mental illness (anxiety: OR: 8.97, 95% CI: 1.01–79.56, p = 0.049; depression: OR: 9.32, 95% CI: 1.06–82.30, p = 0.045) increased the incidence of anxiety and depression. Elderly participants (anxiety: OR: 0.986, 95% CI: 0.975–0.997, p = 0.012; depression: OR: 0.976, 95% CI: 0.965–0.987, p &lt; 0.001) who had been vaccinated against COVID-19 (anxiety: OR: 0.49, 95% CI: 0.32–0.75, p = 0.001; depression: OR: 0.45, 95% CI: 0.29–0.69, p &lt; 0.001) had decreased incidences of anxiety and depression.ConclusionOur findings increase the awareness of the high incidence of mental health illness symptoms during the omicron variant outbreak despite previous experiences with the COVID-19 pandemic, and vaccination is suggested to reduce the risk of anxiety and depression.
Hepatic dysfunctions in COVID-19 patients infected by the omicron variant of SARS-CoV-2
Authors: Zhang Jianguo , Zhao Daguo , Hu Jianhui , Huang Xing , Gu Qingqing , Tao Zhimin 
Published: November 2022

BackgroundPresently, the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dominates amid the coronavirus disease 2019 (COVID-19) pandemic, but its clinical characteristics with intrinsic severity and organ tropism remain understudied.MethodsWe reported 1,001 mild COVID-19 patients that were infected with the omicron variant of SARS-CoV-2 and hospitalized in China from February to June 2022, including their demographic information, medical/immunization history, clinical symptom, and hematological profile. Patients with one-, two- and three-dose vaccination were compared to assess the vaccine effectiveness. Importantly, liver damage caused by the omicron variant infection was evaluated, in comparison to that caused by the wild-type or the delta variant SARS-CoV-2 infection.ResultsFor the reported COVID-19 patients infected by the omicron variant of SARS-CoV-2, their median age was 36.0 [interquartile range (IQR): 26.0-50.0] and 49.7% were female. Hypertension, diabetes, and bronchitis were the leading comorbidities, and asymptomatic patients took up a major portion (61.2%). While most hematological parameters revealed the alleviated pathogenicity, full vaccination or booster shot showed effective protection against clinical severity. Furthermore, liver damages caused by viral infection of the omicron variant were largely attenuated when compared to those by infection of the wild-type or the delta variant SARS-CoV-2.ConclusionsOur results supported that the viremic effect of the omicron variant tended to be modest, while the liver damage caused by this strain became milder than the previous circulating variants.