bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Non-Invasive Nomogram for Preoperative Prediction of Microvascular Invasion Risk in Hepatocellular Carcinoma
Authors: Wang Huanhuan , Lu Ye , Liu Runkun , Wang Liang , Liu Qingguang , Han Shaoshan 
Published: December 2021

BackgroundMicrovascular invasion (MVI) is a significant predictive factor for early recurrence, metastasis, and poor prognosis of hepatocellular carcinoma. The aim of the present study is to identify preoperative factors for predicting MVI, in addition to develop and validate non-invasive nomogram for predicting MVI.MethodsA total of 381 patients with resected HCC were enrolled and divided into a training cohort (n = 267) and a validation cohort (n = 114). Serum VEGF-A level was examined by enzyme-linked immunosorbent assay (ELISA). Risk factors for MVI were assessed based on univariate and multivariate analyses in the training cohort. A nomogram incorporating independent risk predictors was established and validated.ResultThe serum VEGF-A levels in the MVI positive group (n = 198) and MVI negative group (n = 183) were 215.25 ± 105.68 pg/ml and 86.52 ± 62.45 pg/ml, respectively (P &lt;0.05). Serum VEGF-A concentration ≥138.30 pg/ml was an independent risk factor of MVI (OR: 33.088; 95%CI: 12.871–85.057; P &lt;0.001). Higher serum concentrations of AFP and VEGF-A, lower lymphocyte count, peritumoral enhancement, irregular tumor shape, and intratumoral artery were identified as significant predictors for MVI. The nomogram indicated excellent predictive performance with an AUROC of 0.948 (95% CI: 0.923–0.973) and 0.881 (95% CI: 0.820–0.942) in the training and validation cohorts, respectively. The nomogram showed a good model fit and calibration.ConclusionsHigher serum concentrations of AFP and VEGF-A, lower lymphocyte count, peritumoral enhancement, irregular tumor shape, and intratumoral artery are promising markers for MVI prediction in HCC. A reliable non-invasive nomogram which incorporated blood biomarkers and imaging risk factors was established and validated. The nomogram achieved desirable effectiveness in preoperatively predicting MVI in HCC patients.
First-Line Systemic Treatment Strategies for Unresectable Hepatocellular Carcinoma: A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials
Authors: Liu Wenfeng , Quan Bing , Lu Shenxin , Tang Bei , Li Miao , Chen Rongxin , Ren Zhenggang , Yin Xin 
Published: December 2021

ObjectiveSeveral new first-line treatments were recently approved for unresectable hepatocellular carcinoma (HCC). In this meta-analysis, we compare the efficacy and safety of first-line systemic treatments to provide information for clinical decision making in unresectable HCC.MethodsPubmed, Science Direct, Web of Science, Scopus, Ovid MEDLINE, Embase, Google Scholar, the Cochrane Library, EMbase, CNKI, CBM, VIP, and the Wanfang databases, as well as the Cochrane Central Register of Controlled Trails were searched for randomized clinical trials evaluating the efficacy of first-line chemotherapy, molecular targeted therapy, or immunotherapy for unresectable HCC. Hazard ratios with 95% confidence intervals (CIs) were calculated to explore the effects of various treatment options on overall survival (OS) and progression-free survival (PFS), whereas odd ratios with 95% CIs were used for adverse events (AEs) and serious adverse events (SAEs). A network meta-analysis was performed to synthesize data and for direct and indirect comparisons between treatments. The cumulative ranking curve (SUCRA) and P score were used to rank treatments. The risk of bias across studies was assessed graphically and numerically using the funnel plot and Egger’s regression test.ResultsFifteen studies including 9005 patients were analyzed. Sintilimab plus bevacizumab, atezolizumab plus bevacizumab, and donafenib had better OS outcomes than sorafenib. Sintilimab plus bevacizumab, atezolizumab plus bevacizumab, lenvatinib, and linifanib had better PFS outcomes than sorafenib. The results of network meta-analysis showed that sintilimab plus bevacizumab was associated with the best OS and PFS. Egger’s tests indicated that none of the included studies had obvious publication deviation.ConclusionSintilimab plus bevacizumab showed the best OS and PFS outcomes with no additional AEs or SAEs. Thus, sintilimab plus bevacizumab may be a better first line choice for the treatment of patients with unresectable HCC.Systematic Review RegistrationPROSPEROI [https://www.crd.york.ac.uk/PROSPERO/index.php], identifier CRD42021269734.
Case Report: Infusion-Related Reactions to Intravenous Infliximab and Subcutaneous Ustekinumab in Pediatric Crohn's Disease
Authors: Kakiuchi Toshihiko , Kimura Sakiko , Esaki Motohiro , Matsuo Muneaki 
Published: December 2021

Background: Although the biological agent ustekinumab (UST) is reported to be effective for Crohn's disease (CD) in pediatric as well as adult patients, data on the efficacy and safety of UST in pediatric patients with CD are limited. Here, we describe the case of a pediatric patient who showed an allergic reaction to UST after subcutaneous (SC) maintenance injections but not immediately after initial intravenous (IV) injection.Case Presentation: A 9-year-old boy presented to our hospital with diarrhea lasting 2 years and weight loss, leading to the diagnosis of CD. After prednisolone (PSL) was tapered and discontinued, he promptly relapsed. According to our institution's protocol, we introduced the biological agent infliximab (IFX) with premedication. Coughing and vomiting was observed after the second dose of IFX and it was changed to adalimumab (ADA). However, the effect of ADA gradually disappeared after 18 months; therefore, it was discontinued and he was treated using UST. The first IV UST dose was given after administering hydrocortisone (HDC), an antiallergic and antipyretic analgesic, as premedication, and no obvious adverse reaction was observed. After 8 weeks, UST was subcutaneously injected without premedication. The patient then complained of nausea, dizziness, and headache within 15 min of UST administration. Therefore, for the third dose of UST, HDC was administered again as premedication. However, nausea, dizziness, and headache presented 10 min after UST administration, resulting in discontinuation of further UST treatment.Conclusion: Careful distinction between “true” infusion-related reactions (IRRs) and anaphylaxis or allergic reactions is necessary to determine whether biological agents can be continued after the development of “so-called” IRRs. For true IRRs, it may be possible to continue using the biological agent with appropriate premedication; however, in cases of anaphylaxis, the biological agent itself should be changed.
Potential Benefits of Antiviral African Medicinal Plants in the Management of Viral Infections: Systematic Review
Authors: Beressa Tamirat Bekele , Deyno Serawit , Mtewa Andrew G. , Aidah Namuli , Tuyiringire Naasson , Lukubye Ben , Weisheit Anke , Tolo Casim Umba , Ogwang Patrick Engeu 
Published: December 2021

Background: Viruses cause various human diseases, some of which become pandemic outbreaks. This study synthesized evidence on antiviral medicinal plants in Africa which could potentially be further studied for viral infections including Coronavirus disease 2019 (COVID-19) treatment.Methods: PUBMED, CINAHIL, Scopus, Google Scholar, and Google databases were searched through keywords; antiviral, plant, herb, and Africa were combined using “AND” and “OR”. In-vitro studies, in-vivo studies, or clinical trials on botanical medicine used for the treatment of viruses in Africa were included.Results: Thirty-six studies were included in the evidence synthesis. Three hundred and twenty-eight plants were screened for antiviral activities of which 127 showed noteworthy activities against 25 viral species. These, were Poliovirus (42 plants), HSV (34 plants), Coxsackievirus (16 plants), Rhinovirus (14plants), Influenza (12 plants), Astrovirus (11 plants), SARS-CoV-2 (10 plants), HIV (10 plants), Echovirus (8 plants), Parvovirus (6 plants), Semiliki forest virus (5 plants), Measles virus (5 plants), Hepatitis virus (3 plants), Canine distemper virus (3 plants), Zika virus (2 plants), Vesicular stomatitis virus T2 (2 plants). Feline herpesvirus (FHV-1), Enterovirus, Dengue virus, Ebola virus, Chikungunya virus, Yellow fever virus, Respiratory syncytial virus, Rift Valley fever virus, Human cytomegalovirus each showed sensitivities to one plant.Conclusion: The current study provided a list of African medicinal plants which demonstrated antiviral activities and could potentially be candidates for COVID-19 treatment. However, all studies were preliminary and in vitro screening. Further in vivo studies are required for plant-based management of viral diseases.
Comparative Cardio-Renal Outcomes of Type 2 Diabetes Patients Administered Glucagon-Like Peptide-1 Receptor Agonists: A Network Meta-Analysis
Authors: Zhuo Chuanjun , Lin Chongguang , Zhou Chunhua , Gao Xiangyang , Shao Hailin , Fang Tao , Tian Hongjun , Ding Li , Liu Ming 
Published: December 2021

Background: Cardio-renal profiles are available from cardiovascular outcome trials of glucagon-like peptide-1 receptor agonists (GLP-1 RAs).Methods: A comprehensive systematic review of Embase, Medline, Web of Knowledge, and CENTRAL databases was conducted. Randomized controlled cardiovascular outcome trials of type 2 diabetes mellitus (T2DM) patients administered GLP-1 RAs were included. The following primary outcomes were examined: cardiovascular death, major adverse cardiovascular events (MACE), myocardial infarction, stroke, mortality, heart failure, hypoglycemia, pancreatitis, and thyroid carcinoma. Secondary outcomes included: composite kidney outcome, worsening kidney function, macroalbuminuria, and retinopathy.Results: Seven trials involving 56,004 patients and eight interventions were identified. Albiglutide was associated with fewer MACE and myocardial infarction events compared with lixisenatide. Lixisenatide was related to a greater number of stroke events and cardiovascular deaths compared to once-weekly semaglutide and oral semaglutide, respectively. Improved mortality was associated with oral semaglutide compared with once-weekly semaglutide, albiglutide, dulaglutide, exenatide, or lixisenatide. Risks of heart failure, thyroid carcinoma, and pancreatitis were similar among all the treatments. Weighting of the nine primary outcomes identified oral semaglutide as first among the eight treatments examined. Among three of the secondary outcomes, once-weekly semaglutide ranked first. Better composite kidney outcome was observed with once-weekly semaglutide than with dulaglutide or exenatide; once-weekly semaglutide improved macroalbuminuria compared with exenatide or lixisenatide; and albiglutide, exenatide, and placebo was associated with fewer cases of retinopathy compared with once-weekly semaglutide. Meanwhile, kidney function was less likely to worsen with dulaglutide than with lixisenatide or placebo.Conclusion: Semaglutide should be considered when GLP-1 RAs are indicated for T2DM patients.
Nanoparticles use for Delivering Ursolic Acid in Cancer Therapy: A Scoping Review
Authors: Miatmoko Andang , Mianing Ester Adelia , Sari Retno , Hendradi Esti 
Published: December 2021

Ursolic acid is a natural pentacyclic triterpenoid that exerts a potent anticancer effect. Furthermore, it is classified as a BCS class IV compound possessing low permeability and water solubility, consequently demonstrating limited bioavailability in addition to low therapeutic effectiveness. Nanoparticles are developed to modify the physical characteristics of drug and can often be produced in the range of 30–200 nm, providing highly effective cancer therapy due to the Enhanced Permeation and Retention (EPR) Effect. This study aims to provide a review of the efficacy and safety of various types of Ursolic Acid-loading nanoparticles within the setting of preclinical and clinical anticancer studies. This literature study used scoping review method, where the extracted data must comply with the journal inclusion criteria of within years of 2010–2020. The identification stage produced 237 suitable articles. Duplicate screening was then conducted followed by the initial selection of 18 articles that had been reviewed and extracted for data analysis. Based on this review, the use of nanoparticles can be seen to increase the anticancer efficacy of Ursolic Acid in terms of several parameters including pharmacokinetic data, survival rates and inhibition rates, as well as the absence of serious toxicity in preclinical and clinical trials in terms of several parameters including body weight, blood clinical chemistry, and organ histipathology. Based on this review, the use of nanoparticles has been able to increase the anticancer efficacy of Ursolic Acid, as well as show the absence of serious toxicity in preclinical and clinical trials. Evenmore, the liposome carrier provides development data that has reached the clinical trial phase I. The use of nanoparticle provides high potential for Ursolic Acid delivery in cancer therapy.
Antioxidant Activity of Fluoxetine and Vortioxetine in a Non-Transgenic Animal Model of Alzheimer’s Disease
Authors: Caruso Giuseppe , Grasso Margherita , Fidilio Annamaria , Torrisi Sebastiano Alfio , Musso Nicolò , Geraci Federica , Tropea Maria Rosaria , Privitera Anna , Tascedda Fabio , Puzzo Daniela , Salomone Salvatore , Drago Filippo , Leggio Gian Marco , Caraci Filippo 
Published: December 2021

Depression is a risk factor for the development of Alzheimer’s disease (AD). A neurobiological and clinical continuum exists between AD and depression, with neuroinflammation and oxidative stress being involved in both diseases. Second-generation antidepressants, in particular selective serotonin reuptake inhibitors (SSRIs), are currently investigated as neuroprotective drugs in AD. By employing a non-transgenic AD model, obtained by intracerebroventricular (i.c.v.) injection of amyloid-β (Aβ) oligomers in 2-month-old C57BL/6 mice, we recently demonstrated that the SSRI fluoxetine (FLX) and the multimodal antidepressant vortioxetine (VTX) reversed the depressive-like phenotype and memory deficits induced by Aβ oligomers rescuing the levels of transforming growth factor-β1 (TGF-β1). Aim of our study was to test FLX and VTX for their ability to prevent oxidative stress in the hippocampus of Aβ-injected mice, a brain area strongly affected in both depression and AD. The long-term intraperitoneal (i.p.) administration of FLX (10 mg/kg) or VTX (5 and 10 mg/kg) for 24 days, starting 7 days before Aβ injection, was able to prevent the over-expression of inducible nitric oxide synthase (iNOS) and NADPH oxidase 2 (Nox2) induced by Aβ oligomers. Antidepressant pre-treatment was also able to rescue the mRNA expression of glutathione peroxidase 1 (Gpx1) antioxidant enzyme. FLX and VTX also prevented Aβ-induced neurodegeneration in mixed neuronal cultures treated with Aβ oligomers. Our data represent the first evidence that the long-term treatment with the antidepressants FLX or VTX can prevent the oxidative stress phenomena related to the cognitive deficits and depressive-like phenotype observed in a non-transgenic animal model of AD.
AnDHN, a Dehydrin Protein From Ammopiptanthus nanus, Mitigates the Negative Effects of Drought Stress in Plants
Authors: Sun Yibo , Liu Linghao , Sun Shaokun , Han Wangzhen , Irfan Muhammad , Zhang Xiaojia , Zhang Li , Chen Lijing 
Published: December 2021

Dehydrins (DHNs) play crucial roles in a broad spectrum of abiotic stresses in model plants. However, the evolutionary role of DHNs has not been explored, and the function of DHN proteins is largely unknown in Ammopiptanthus nanus (A. nanus), an ancient and endangered legume species from the deserts of northwestern China. In this study, we isolated a drought-response gene (c195333_g1_i1) from a drought-induced RNA-seq library of A. nanus. Evolutionary bioinformatics showed that c195333_g1_i1 is an ortholog of Arabidopsis DHN, and we renamed it AnDHN. Moreover, DHN proteins may define a class of proteins that are evolutionarily conserved in all angiosperms that have experienced a contraction during the evolution of legumes. Arabidopsis plants overexpressing AnDHN exhibited morpho-physiological changes, such as an increased germination rate, higher relative water content (RWC), higher proline (PRO) content, increased peroxidase (POD) and catalase (CAT) activities, lower contents of malondialdehyde (MDA), H2O2 and O2–, and longer root length. Our results showed that the transgenic lines had improved drought resistance with deep root system architecture, excellent water retention, increased osmotic adjustment, and enhanced reactive oxygen species (ROS) scavenging. Furthermore, the transgenic lines also had enhanced salt and cold tolerance. Our findings demonstrate that AnDHN may be a good candidate gene for improving abiotic stress tolerance in crops.Key Message: Using transcriptome analysis in Ammopiptanthus nanus, we isolated a drought-responsive gene, AnDHN, that plays a key role in enhancing abiotic stress tolerance in plants, with strong functional diversification in legumes.
Improving Health of People With Multiple Sclerosis From a Multicenter Randomized Controlled Study in Parallel Groups: Preliminary Results on the Efficacy of a Mindfulness Intervention and Intention Implementation Associated With a Physical Activity Program
Authors: Torkhani Eya , Dematte Emilie , Slawinski Jean , Csillik Antonia , Gay Marie-Claire , Bensmaïl Djamel , Heinzlef Olivier , de Marco Giovanni 
Published: December 2021

Objectives: The objective of this study is to investigate the efficacy of psychological Interventions – Mindfulness or Implementation Intention – associated with a Physical Activity program, delivered via internet, in reducing Multiple Sclerosis symptoms.Method: Thirty-five adults were randomly assigned to one of the three groups: a Mindfulness-Based Intervention group (N = 12), Implementation Intention group (N = 11), and a Control Group (N = 12). All the groups received the same Physical Activity program. The Mindfulness condition group received daily training in the form of pre-recorded sessions while the Implementation group elaborated their specific plans once a week. Mobility, fatigue, and the impact of the disease on the patient’s life were measured. Two measurement times are carried out in pre-post intervention, at baseline and after eight weeks.Results: Overall, after 8 weeks intervention, results show that there was a significant increase in Walking distance in the three groups. In addition, the within-group analysis showed a statistically significant improvement between pre and post intervention on the physical component of the Disease Impact scale in the Implementation Intention group (p = 0.023) with large effect size, in the Mindfulness-Based Intervention group (p = 0.008) with a medium effect size and in the control group (p = 0.028) with small effect size. In the Implementation Intention group, all physical, psychosocial and cognitive Fatigue Impact subscales scores decreased significantly (p = 0.022, p = 0.023, and p = 0.012, respectively) and the physical component was statistically and negatively correlated (r = −0.745; p = 0.008) when Implementation Intention group practice a mild to moderate physical activity. In the Mindfulness-Based Intervention group, the physical component (MFIS) showed a statistically significant improvement (p = 0.028) but no correlation with moderate-to-vigorous physical activity (MVPA); the control group outcomes did not reveal any significant change.Conclusion: The results of this study are very encouraging and show the feasibility of Mindfulness interventions associated with physical activity to improve the health of people with MS. Further study should assess Mindfulness interventions tailored to MS condition and using both hedonic and eudemonic measures of happiness.
Multi-Family Therapy for First Episode Psychosis: Experiences of Families in Singapore
Authors: Loh Christopher , Liang Wilfred , Lee Helen , Koh Astelle 
Published: December 2021

Aim: This qualitative study examined the experiences of families with Multi-Family Therapy (MFT) provided by the Early Psychosis Intervention Programme (EPIP) in Singapore. The MFT was piloted over a period of 2 years and findings from this study were used to further refine the MFT to better meet the needs of Singaporean families in the service.Methods: Families who completed the MFT were invited to participate in the study. Nine clients and ten carers who consented to participate in the study were allocated to two client and two carer Focus Group Discussions (FGDs) respectively. A semi-structured interview schedule was used to facilitate the discussions. The FGDs were audio recorded, transcribed, and anonymised. The data was analysed using thematic analysis.Results: Four main themes emerged from the analysis: (1) therapeutic processes of MFT, (2) positive changes in family relationships, (3) improvements in coping with psychosis, and (4) suggestions for improvement in MFT. The families suggested some structural changes to the MFT, and more carers than clients would prefer therapists to offer more expert advice.Conclusions: Findings suggest that a Western-based MFT can be adapted to work with Singaporean families. This study sheds light on the therapeutic processes that may be related to the changes in family relationships and coping with psychosis. In addition, it suggests that therapists taking an expert and authoritative approach may not fit with the needs of younger generations in Singapore. It advocates for therapists to take a flexible and fluid stance to work with Singaporean families.
Association of Negative Symptoms of Schizophrenia Assessed by the BNSS and SNS Scales With Neuropsychological Performance: A Gender Effect
Authors: Wójciak Paweł , Domowicz Klaudia , Zabłocka Marta , Michalak Michał , Rybakowski Janusz K. 
Published: December 2021

Objective: The relationship between negative symptoms and neurocognitive performance in schizophrenia is well documented, but the mechanism of these connections remains unclear. The study aims to measure the relationship between the results on the new scales for the assessment of negative symptoms such as Brief Negative Symptom Scale (BNSS) and Self-evaluation of Negative Symptoms (SNS), and the results of some neurocognition tests. The second aim is to assess a possible gender effect on these associations.Methods: The study included 80 patients (40 men, 40 women) with schizophrenia, aged 19–63 (mean 38 years), during the improvement period (total PANSS score &lt;80, unchanged pharmacological treatment in the last 3 weeks). They were assessed using the BNSS, SNS, Personal and Social Performance (PSP) scales, and the tests for neuropsychological performance such as the Trail Making Test (TMT-A, TMT-B), Stroop Color-Word Interference Test, Verbal fluency tests (VFT), Category fluency test (CFT), and Digit Symbol Substitution Test (DSST).Results: Male patients obtained higher scores than females on some PANSS and BNSS items. No gender differences were observed for the SNS scale. Female patients scored better in the PSP and CFT. In male patients, a significant positive correlation between the intensity of negative symptoms measured by the BNSS and the results of PSP with the Trail Making Test was observed. In female patients, we found a positive correlation between the results of BNSS and PSP with the Stroop Color-Word Interference Test.Conclusion: The obtained results confirm the relationship between negative symptoms and neurocognition in schizophrenia patients. However, in male and female patients such association was observed for different cognitive domains. Further research is needed to explain the nature of these differences.