bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: Herpes Simplex Virus Type 2 Acute Retinal Necrosis With Viral Encephalitis in Children
Authors: He Luyao , Duan Jialiang , Shang Qingli 
Published: March 2022

BackgroundFew cases concerning acute retinal necrosis with viral encephalitis in children have been reported, especially cases where the fundus cannot be identified due to severe vitreous opacity in the early stage that makes diagnosis difficult.MethodsWe conducted a retrospective review of an unusual case of herpes simplex virus-2 (HSV-2) acute retinal necrosis with viral encephalitis in an immunocompetent child, along with a review of relevant literature published up to September 2021.ResultAn 11-year-old girl presented with an approximate 20-day history of ocular redness and decreased visual acuity in the left eye. Examination revealed anterior uveitis and vitreous opacity in the left eye. An anterior chamber tap was performed because the fundus could not be observed clearly, and the aqueous humor was positive for HSV-2 DNA. Cerebrospinal fluid also tested positive for HSV-2. She was diagnosed with acute retinal necrosis syndrome and viral encephalitis. The condition was controlled with timely antiviral and steroid therapy. She was also treated with prophylactic laser therapy to prevent retinal detachment during subsequent follow-up. The pathogenesis, diagnosis, and treatment of HSV-2 acute retinal necrosis in children and the association between acute retinal necrosis and viral encephalitis are further discussed, based on published literature.ConclusionHSV-2-related pediatric acute retinal necrosis may be due to the acquisition of subclinical infection with HSV-2 during parturition, followed by reactivation of the virus latent in the body on account of certain factors. Moreover, it may be complicated with viral encephalitis. For suspected cases with invisible fundus, early intraocular fluid examination is especially helpful for differential diagnosis. Early diagnosis, early treatment, and timely prophylactic laser treatment to prevent retinal detachment are key to a better prognosis. Physicians need to pay attention to such suspected cases during diagnosis and treatment.
Transfusional Approach in Multi-Ethnic Sickle Cell Patients: Real-World Practice Data From a Multicenter Survey in Italy
Authors: Graziadei Giovanna , De Franceschi Lucia , Sainati Laura , Venturelli Donatella , Masera Nicoletta , Bonomo Piero , Vassanelli Aurora , Casale Maddalena , Lodi Gianluca , Voi Vincenzo , Rigano Paolo , Pinto Valeria Maria , Quota Alessandra , Notarangelo Lucia D. , Russo Giovanna , Allò Massimo , Rosso Rosamaria , D'Ascola Domenico , Facchini Elena , Macchi Silvia , Arcioni Francesco , Bonetti Federico , Rossi Enza , Sau Antonella , Campisi Saveria , Colarusso Gloria , Giona Fiorina , Lisi Roberto , Giordano Paola , Boscarol Gianluca , Filosa Aldo , Marktel Sarah , Maroni Paola , Murgia Mauro , Origa Raffaella , Longo Filomena , Bortolotti Marta , Colombatti Raffaella , Di Maggio Rosario , Mariani Raffaella , Piperno Alberto , Corti Paola , Fidone Carmelo , Palazzi Giovanni , Badalamenti Luca , Gianesin Barbara , Piel Frédéric B. , Forni Gian Luca 
Published: March 2022

Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder characterized by recurrent acute vaso-occlusive crises (VOCs and anemia). Gold standard treatments are hydroxycarbamide (HC) and/or different red blood cell (RBC) transfusion regimens to limit disease progression. Here, we report a retrospective study on 1,579 SCD patients (median age 23 years; 802 males/777 females), referring to 34 comprehensive Italian centers for hemoglobinopathies. Although we observed a similar proportion of Caucasian (47.9%) and African (48.7%) patients, Italian SCD patients clustered into two distinct overall groups: children of African descent and adults of Caucasian descent. We found a subset of SCD patients requiring more intensive therapy with a combination of HC plus chronic transfusion regimen, due to partial failure of HC treatment alone in preventing or reducing sickle cell-related acute manifestations. Notably, we observed a higher use of acute transfusion approaches for SCD patients of African descent when compared to Caucasian subjects. This might be related to (i) age of starting HC treatment; (ii) patients' low social status; (iii) patients' limited access to family practitioners; or (iv) discrimination. In our cohort, alloimmunization was documented in 135 patients (8.5%) and was more common in Caucasians (10.3%) than in Africans (6.6%). Alloimmunization was similar in male and female and more frequent in adults than in children. Our study reinforces the importance of donor-recipient exact matching for ABO, Rhesus, and Kell antigen systems for RBC compatibility as a winning strategy to avoid or limit alloimmunization events that negatively impact the clinical management of SCD-related severe complications.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT03397017.
Exploring the Change of Host and Microorganism in Chronic Obstructive Pulmonary Disease Patients Based on Metagenomic and Metatranscriptomic Sequencing
Authors: Yang Jing , Zhang Qiang , Zhang Jun , Ouyang Yan , Sun Zepeng , Liu Xinlong , Qaio Feng , Xu Li-Qun , Niu Yunfei , Li Jian 
Published: March 2022

BackgroundChronic obstructive pulmonary disease (COPD) is a universal respiratory disease resulting from the complex interactions between genes and environmental conditions. The process of COPD is deteriorated by repeated episodes of exacerbations, which are the primary reason for COPD-related morbidity and mortality. Bacterial pathogens are commonly identified in patients’ respiratory tracts both in the stable state and during acute exacerbations, with significant changes in the prevalence of airway bacteria occurring during acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Therefore, the changes in microbial composition and host inflammatory responses will be necessary to investigate the mechanistic link between the airway microbiome and chronic pulmonary inflammation in COPD patients.MethodsWe performed metatranscriptomic and metagenomic sequencing on sputum samples for twelve AECOPD patients before treatment and for four of them stable COPD (stabilization of AECOPD patients after treatment). Sequencing reads were classified by Kraken2, and the host gene expression was analyzed by Hisat2 and HTseq. The correlation between genes was obtained by the Spearman correlation coefficient. Mann–Whitney U-test was applied to identify microbes that exhibit significantly different distribution in two groups.ResultsAt the phyla level, the top 5 dominant phyla were Firmicutes, Actinobacteria, Proteobacteria, Bacteroidetes, and Fusobacteria. The proportion of dominant gates in metagenomic data was similar in metatranscriptomic data. There were significant differences in the abundance of specific microorganisms at the class level between the two methods. No significant difference between AECOPD and stable COPD was found. However, the different expression levels of 5 host genes were significantly increased in stable COPD and were involved in immune response and inflammatory pathways, which were associated with macrophages.ConclusionOur study may provide a clue to investigate the mechanism of COPD and potential biomarkers in clinical diagnosis and treatment.
Effects of Keemun and Dianhong Black Tea in Alleviating Excess Lipid Accumulation in the Liver of Obese Mice: A Comparative Study
Authors: Liao Wenjing , Liu Suyu , Chen Yunxi , Kong Yashuai , Wang Dongxu , Wang Yijun , Ling Tiejun , Xie Zhongwen , Khalilova Irada , Huang Jinbao 
Published: March 2022

Graphical AbstractSchematic diagram of the effects of two black teas in alleviating excess hepatic lipid accumulation.
High Stromal SFRP2 Expression in Urothelial Carcinoma Confers an Unfavorable Prognosis
Authors: Lai Hong-Yue , Chiu Chia-Chun , Kuo Yu-Hsuan , Tsai Hsin-Hwa , Wu Li-Ching , Tseng Wen-Hsin , Liu Chien-Liang , Hsing Chung-Hsi , Huang Steven K. , Li Chien-Feng 
Published: March 2022

BackgroundUrothelial carcinoma (UC) patients often bear clinical and genetic heterogeneity, which may differ in management and prognosis. Especially, patients with advanced/metastatic UC generally have a poor prognosis and survive for only few months. The Wnt/β-catenin signaling is found to be highly activated in several cancers, including UC. However, accumulated evidence has shown discordance between the Wnt/β-catenin signaling and UC carcinogenesis. Accordingly, we aim to get a better understanding of the molecular characterization of UC, focusing on the Wnt signaling, which may add value to guiding management more precisely.Patients and MethodsClinical data and pathological features were retrospectively surveyed. The correlations of secreted Frizzled-related protein 2 (SFRP2) immunoexpression with clinicopathological features were analyzed by Pearson’s chi-square test. The Kaplan–Meier method with a log-rank test was employed to plot survival curves. All significant features from the univariate analysis were incorporated into the Cox regression model for multivariate analysis.ResultsFollowing data mining on a transcriptome dataset (GSE31684), we identified that 8 transcripts in relation to the Wnt signaling pathway (GO: 0016055) were significantly upregulated in advanced/metastatic bladder tumors. Among these transcripts, the SFRP2 level showed the most significant upregulation. Additionally, as SFRP2 is a putative Wnt inhibitor and may be expressed by stroma, we were interested in examining the immunoexpression and clinical relevance of stromal and tumoral SFRP2 in our urothelial carcinoma cohorts containing 295 urinary bladder UC (UBUC) and 340 upper urinary tract UC (UTUC) patients. We observed that high SFRP2 expression in stroma but not in tumors is significantly linked to aggressive UC features, including high tumor stage and histological grade, positive nodal metastasis, the presence of vascular and perineural invasion, and high mitotic activity in UBUC and UTUC. Moreover, high stromal SFRP2 expression significantly and independently predicted worse clinical outcomes in UBUC and UTUC. Utilizing bioinformatic analysis, we further noticed that stromal SFRP2 may link epithelial–mesenchymal transition (EMT) to UC progression.ConclusionCollectively, these results imply that stromal SFRP2 may exert oncogenic function beyond its Wnt antagonistic ability, and stromal SFRP2 expression can provide prognostic and therapeutic implications for UC patients.
Cardiotocography and Clinical Risk Factors in Early Term Labor: A Retrospective Cohort Study Using Computerized Analysis With Oxford System
Authors: Lovers Aimée A. K. , Ugwumadu Austin , Georgieva Antoniya 
Published: March 2022

ObjectiveThe role of cardiotocography (CTG) in fetal risk assessment around the beginning of term labor is controversial. We used routinely collected clinical data in a large tertiary hospital to investigate whether infants with “severe compromise” at birth exhibited fetal heart rate abnormalities in their first-hour CTGs and/or other clinical risks, recorded as per routine care.Materials and MethodsRetrospective data from 27,927 parturitions (single UK tertiary site, 2001–2010) were analyzed. Cases were included if the pregnancy was singleton, ≥36 weeks' gestation, cephalic presentation, and if they had routine intrapartum CTG as per clinical care. Cases with congenital abnormalities, planned cesarean section (CS), or CS for reasons other than “presumed fetal compromise” were excluded. We analyzed first-hour intrapartum CTG recordings, using intrapartum Oxford System (OxSys) computer-based algorithms. To reflect the effect of routine clinical care, the data was stratified into three exclusive groups: infants delivered by CS for “presumed fetal compromise” within 2 h of starting the CTG (Emergency CS, n = 113); between 2 and 5 h of starting the CTG (Urgent CS, n = 203); and the rest of deliveries (Others, n = 27,611). First-hour CTG and clinical characteristics were compared between the groups, sub-divided to those with and without severe compromise: a composite outcome of stillbirth, neonatal death, neonatal seizures, encephalopathy, resuscitation followed by ≥48 h in neonatal intensive care unit. Two-sample t-test, X2 test, and Fisher's exact test were used for analysis.ResultsCompared to babies without severe compromise, those with compromise had significantly higher proportion of cases with baseline fetal heart rate ≥150 bpm; non-reactive trace; reduced long-term and short-term variability; decelerative capacity; and no accelerations in the first-hour CTG across all groups. Prolonged decelerations(≥3 min) were also more common. Thick meconium and small for gestational age were consistently more common in compromised infants across all groups. There was more often thick meconium, maternal fever ≥38 C, sentinel events, and other clinical risk factors in the Emergency CS and Urgent CS compared to the Others group.ConclusionA proportion of infants born with severe compromise had significantly different first-hour CTG features and clinical risk factors.
Baicalein Ameliorates Myocardial Ischemia Through Reduction of Oxidative Stress, Inflammation and Apoptosis via TLR4/MyD88/MAPKS/NF-κB Pathway and Regulation of Ca2+ Homeostasis by L-type Ca2+ Channels
Authors: Li Jinghan , Yang Yakun , Wang Hua , Ma Donglai , Wang Hongfang , Chu Li , Zhang Yuanyuan , Gao Yonggang 
Published: March 2022

Background: Baicalein (Bai) is the principal ingredient of Scutellaria baicalensis Georgi. Reports concerning the therapeutic advantages in treating cardiovascular diseases have been published. However, its protective mechanism towards myocardial ischemia (MI) is undefined.Objective: The aim of this study was to investigate the protective mechanisms of Bai on mouse and rat models of MI.Methods: Mice were pre-treated with Bai (30 and 60 mg/kg/day) for 7 days followed by subcutaneous injections of isoproterenol (ISO, 85 mg/kg/day) for 2 days to establish the MI model. Electrocardiograms were recorded and serum was used to detect creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA). Cardiac tissues were used to detect Ca2+ concentration, morphological pathologies, reactive oxygen species (ROS), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In addition, the expression levels of Bcl-2-associated X (Bax), B cell lymphoma-2 (Bcl-2), Caspase-3, Toll-like receptor-4 (TLR4), myeloid differentiation protein 88 (MyD88), nuclear factor-kappa B (NF-κB), p-p38, p-extracellular signal-regulated kinase1/2 (p-ERK1/2) and c-Jun N-terminal kinase (p-JNK) were assessed by western blots in myocardial tissues. The effects of Bai on L-type Ca2+ currents (ICa-L), contractility and Ca2+ transients in rat isolated cardiomyocytes were monitored by using patch clamp technique and IonOptix system. Moreover, ISO-induced H9c2 myocardial injury was used to detect levels of inflammation and apoptosis.Results: Bai caused an improvement in heart rate, ST-segment and heart coefficients. Moreover, Bai led to a reduction in CK, LDH and Ca2+ concentrations and improved morphological pathologies. Bai inhibited ROS generation and reinstated SOD, CAT and GSH activities in addition to inhibition of replenishing MDA content. Also, expressions of IL-6 and TNF-α in addition to Bax and Caspase-3 were suppressed, while Bcl-2 expression was upregulated. Bai inhibited protein expressions of TLR4/MyD88/MAPKS/NF-κB and significantly inhibited ICa-L, myocyte contraction and Ca2+ transients. Furthermore, Bai caused a reduction in inflammation and apoptosis in H9c2 cells.Conclusions: Bai demonstrated ameliorative actions towards MI, which might have been related to attenuation of oxidative stress, inflammation and apoptosis via suppression of TLR4/MyD88/MAPKS/NF-κB pathway and adjustment of Ca2+ homeostasis via L-type Ca2+ channels.
PKPD Modeling of the Inoculum Effect of Acinetobacter baumannii on Polymyxin B in vivo
Authors: Chauzy Alexia , Akrong Grace , Aranzana-Climent Vincent , Moreau Jérémy , Prouvensier Laure , Mirfendereski Hélène , Buyck Julien M , Couet William , Marchand Sandrine 
Published: March 2022

The reduction in antimicrobial activity at high bacterial counts is a microbiological phenomenon known as the inoculum effect (IE). In a previous in vitro study, a significant IE was observed for polymyxin B (PMB) against a clinical isolate of Acinetobacter baumannii, and well described by a new pharmacokinetic-pharmacodynamic model. Few in vivo studies have investigated the impact of inoculum size on survival or antibiotic efficacy. Therefore, our objective was to confirm the influence of inoculum size of this A. baumannii clinical isolate on PMB in vivo effect over time. Pharmacokinetics and pharmacodynamics of PMB after a single subcutaneous administration (1, 15 and 40 mg/kg) were studied in a neutropenic murine thigh infection model. The impact of A. baumannii inoculum size (105, 106 and 107 CFU/thigh) on PMB efficacy was also evaluated. In vivo PMB PK was well described by a two-compartment model including saturable absorption from the subcutaneous injection site and linear elimination. The previous in vitro PD model was modified to adequately describe the decrease of PMB efficacy with increased inoculum size in infected mice. The IE was modeled as a decrease of 32% in the in vivo PMB bactericidal effect when the starting inoculum increases from 105 to 107 CFU/thigh. Although not as important as previously characterized in vitro an IE was confirmed in vivo.
Liquorice Extract and 18β-Glycyrrhetinic Acid Protect Against Experimental Pyrrolizidine Alkaloid-Induced Hepatotoxicity in Rats Through Inhibiting Cytochrome P450-Mediated Metabolic Activation
Authors: Wang Zhangting , Ma Jiang , Yao Sheng , He Yisheng , Miu Kai-Kei , Xia Qingsu , Fu Peter P. , Ye Yang , Lin Ge 
Published: March 2022

Misuse of pyrrolizidine alkaloid (PA)-containing plants or consumption of PA-contaminated foodstuffs causes numerous poisoning cases in humans yearly, while effective therapeutic strategies are still limited. PA-induced liver injury was initiated by cytochrome P450 (CYP)-mediated metabolic activation and subsequent formation of adducts with cellular proteins. Liquorice, a hepato-protective herbal medicine, is commonly used concurrently with PA-containing herbs in many compound traditional Chinese medicine formulas, and no PA-poisoning cases have been reported with this combination. The present study aimed to investigate hepato-protective effects of liquorice aqueous extract (EX) and 18β-glycyrrhetinic acid (GA, the primary bioactive constituent of liquorice) against PA-induced hepatotoxicity and the underlying mechanism. Histopathological and biochemical analysis demonstrated that both single- and multiple-treatment of EX (500 mg/kg) or GA (50 mg/kg) significantly attenuated liver damage caused by retrorsine (RTS, a representative hepatotoxic PA). The formation of pyrrole-protein adducts was significantly reduced by single- (30.3% reduction in liver; 50.8% reduction in plasma) and multiple- (32.5% reduction in liver; 56.5% reduction in plasma) treatment of GA in rats. Single- and multiple-treatment of EX also decreased the formation of pyrrole-protein adducts, with 30.2 and 31.1% reduction in rat liver and 51.8 and 53.1% reduction in rat plasma, respectively. In addition, in vitro metabolism assay with rat liver microsomes demonstrated that GA reduced the formation of metabolic activation-derived pyrrole-glutathione conjugate in a dose-dependent manner with the estimated IC50 value of 5.07 µM. Further mechanism study showed that GA inhibited activities of CYPs, especially CYP3A1, the major CYP isoform responsible for the metabolic activation of RTS in rats. Enzymatic kinetic study revealed a competitive inhibition of rat CYP3A1 by GA. In conclusion, our findings demonstrated that both EX and GA exhibited significant hepato-protective effects against RTS-induced hepatotoxicity, mainly through the competitive inhibition of CYP-mediated metabolic activation of RTS.
Social Support and Fear of Cancer Recurrence Among Chinese Breast Cancer Survivors: The Mediation Role of Illness Uncertainty
Authors: Yu Zhichao , Sun Di , Sun Jia 
Published: March 2022

ObjectiveTo examine the relations between social support, illness uncertainty (IU), and fear of cancer recurrence (FCR).MethodsUsing data from a convenience sample of 231 breast cancer survivors in China to perform structural equation modeling with bootstrapping estimation. Participants were recruited from a general hospital in Shenyang, China. Participants completed the Perceived Social Support Scale, Mishel Uncertainty in Illness Scale, and Fear of Cancer Recurrence Inventory- Shorter Form.ResultsThe majority of breast cancer survivors have FCR (67.5%). FCR was significantly negatively associated with social support, and was significantly positively associated with IU (both P &lt; 0.01). Moreover, IU was found to mediate the relationship between social support and FCR (standardized indirect effect = –0.18; bias-corrected 95% confidence interval: –0.255, –0.123).ConclusionThe findings support the final model. Good social support can directly mitigate FCR, while illness uncertainty can play a mediation role between social support and FCR. Further studies should be conducted to explore effective interventions for social support and IU to ultimately mitigate FCR in cancer survivors.
Pre-treatment Pain Symptoms Influence Antidepressant Response to Ketamine in Depressive Patients
Authors: Lan Xiaofeng , Zhou Yanling , Wang Chengyu , Li Weicheng , Zhang Fan , Liu Haiyan , Fu Ling , Wu Kai , McIntyre Roger S. , Ning Yuping 
Published: March 2022

BackgroundPain strongly coexists with depression. Ketamine has great analgesic and antidepressant effects, acting as a promising role in treating depression with pain. Few studies have evaluated impact of pain symptoms on antidepressant effect of ketamine infusions. Thus, present study investigated whether pain symptoms in individuals with depression moderate response to ketamine.MethodsOne hundred and four individuals with major depressive disorder and bipolar depression received six intravenous infusions of ketamine. The Montgomery–Åsberg Depression Rating Scale (MADRS) was administered at baseline, the next morning after each infusion and 2 weeks (Day 26) after the last infusion. Pain symptoms were collected at baseline using the short-form McGill Pain Questionnaire (SF-MPQ).ResultsThe prevalence of pain in patients with depression was 48.8%. Mix model analyses showed that pre-treatment pain symptoms assessed by each domain of SF-MPQ significantly moderated antidepressant response to six infusions of ketamine from baseline to day 26 (all p &lt; 0.05). Then follow-up simple slopes analyses suggested that all patients across groups showed a significant symptomatic improvement after ketamine infusions (all p &lt; 0.05), and patients with severe pain (across all domains of SF-MPQ) had greater improvement in depressive symptoms than those with mild pain or non-pain (all p &lt; 0.05).ConclusionA significant and rapid improvement in depressive symptoms was observed in patients with depression and pain after ketamine treatment. Ketamine may be a novel and promising antidepressant preferentially for the therapy of depression with severe pain.