bluuebunny/crossref_metadata_2025_split huggingface dataset:
Admission risk factors and predictors of moderate or severe pediatric acute pancreatitis: A systematic review and meta-analysis
Authors: Juhász Márk Félix , Sipos Zoltán , Ocskay Klementina , Hegyi Péter , Nagy Anikó , Párniczky Andrea 
Published: September 2022

IntroductionPediatric acute pancreatitis (PAP) has an increasing incidence and is now estimated to be almost as common as in adults. Up to 30% of patients with PAP will develop moderate or severe disease course (M/SPAP), characterized by organ failure, local or systemic complications. There is still no consensus regarding on-admission severity prediction in these patients. Our aim was to conduct a systematic review and meta-analysis of available predictive score systems and parameters, and differences between on-admission parameters in mild and M/SPAP.MethodsWe conducted a systematic search on the 14th February, 2022 in MEDLINE, Embase and CENTRAL. We performed random-effects meta-analysis of on-admission differences between mild and M/SPAP in laboratory parameters, etiology, demographic factors, etc. calculating risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI) and created forest plots. For the meta-analysis of predictive score systems, we generated hierarchical summary receiver operating characteristic curves using a bivariate model. Chi-squared tests were performed and I2 values calculated to assess statistical heterogeneity.ResultsWe included 44 studies – mostly retrospective cohorts – in our review. Among predictive score systems examined by at least 5 studies, the modified Glasgow scale had the highest specificity (91.5% for values ≥3), and the Pediatric Acute Pancreatitis Severity score the highest sensitivity (63.1% for values ≥3). The performance of other proposed score systems and values were summarized. Traumatic (RR: 1.70 95% CI: 1.09–2.67) and drug–induced (RR: 1.33 95% CI: 0.98–1.87) etiologies were associated with a higher rate of M/SPAP, while anatomical (RR: 0.6195% CI: 0.38–0.96) and biliary (RR: 0.72 95% CI: 0.53–0.99) PAP tended to be less severe.DiscussionMany predictive score systems were proposed to assess the possibility of M/SPAP course. The most commonly used ones exhibit good specificity, but subpar sensitivity. Our systematic review provides a rigorous overview of predictive options assessed thus far, that can serve as a basis for future improvement of scores via the addition of parameters with a better observed sensitivity: e.g., lipase exceeding 7-times the upper threshold, hemoglobin, etc. The addition of etiological factors is another possibility, as they can herald a more severe disease course.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=307271, PROSPERO, identifier: CRD42022307271.
Outcomes of endovascular embolization for Vein of Galen malformations: An individual participant data meta-analysis
Authors: Savage Cody , Hale Andrew T. , Parr Matthew S. , Hedaya Alexander , Saccomano Benjamin W. , Tsemo Georges Bouobda , Hafeez Muhammad U. , Tanweer Omar , Kan Peter , Solomon Laurent J. , Meila Dan , Dirks Peter B. , Blount Jeffrey P. , Johnston James M. , Rocque Brandon G. , Rozzelle Curtis J. , Bhatia Kartik , Muthusami Prakash , Krings Timo , Jones Jesse 
Published: September 2022

IntroductionUnderstanding outcomes after Vein of Galen malformation (VOGM) embolization has been limited by small sample size in reported series and predominantly single center studies. To address these limitations, we perform an individual-participant meta-analysis (IPMA) to identify risk factors associated with all-cause mortality and clinical outcome after VOGM endovascular embolization.MethodsWe performed a systematic review and IPMA of VOGM endovascular outcomes according to PRISMA guidelines. Individual patient characteristics including demographic, intra/post-operative adverse events, treatment efficacy (partial or complete occlusion), and clinical outcome were collected. Mixed-effects logistic regression with random effects modeling and Bonferroni correction was used (p ≤ 0.003 threshold for statistical significance). The primary and secondary outcomes were all-cause mortality and poor clinical outcome (moderate/severe developmental delay or permanent disabling injury), respectively. Data are expressed as (mean ± standard deviation (SD)) or (odds ratio (OR), 95% confidence interval (CI), I2, p-value)ResultsThirty-five studies totaling 307 participants quantifying outcomes after endovascular embolization for VOGM were included. Follow up time was 42 (±57) months. Our analysis contained 42% neonates (&lt;1 month) at first embolization, 45% infants (1 month ≤2 years), and 13% children (&gt;2 years). Complete occlusion was reported in 48% of participants. Overall all-cause mortality was 16%. Overall, good clinical outcome was achieved in 68% of participants. First embolization as a neonate [OR = 6.93; 95% CI (1.99–24.08); I2 &lt; 0.01; p &lt; 0.001] and incomplete embolization [OR = 10.87; 95% CI (1.86–63.55); I2 &lt; 0.01; p &lt; 0.001] were associated with mortality. First embolization as a neonate [OR = 3.24; 95% CI (1.47–7.15); I2 &lt; 0.01; p &lt; 0.001], incomplete embolization [OR = 5.26; 95% CI (2.06–13.43); I2 &lt; 0.01; p &lt; 0.001], and heart failure at presentation [OR = 3.10; 95% CI (1.03–9.33); I2 &lt; 0.01; p = 0.002] were associated with poor clinical outcomes. Sex, angioarchitecture of lesion, embolization approach (transvenous vs. transarterial), and single or multistage embolization were not associated with mortality or clinical outcome.ConclusionsWe identify incomplete VOGM embolization independently associated with mortality and poor clinical outcome. While this study provides the highest level of evidence for VOGM embolization to date, prospective multicenter studies are needed to understand the optimal treatment strategies, outcomes, and natural history after VOGM embolization.
Olanzapine induces weight gain in offspring of prenatally exposed poly I:C rats by reducing brown fat thermogenic activity
Authors: Chen Xiaoying , Liu Lu , Zeng Yanping , Li Dejuan , Liu Xuemei , Hu Changhua 
Published: September 2022

Background: Olanzapine (OLZ) is an antipsychotic with a high risk of metabolic syndrome, and its induced metabolic disturbance may be related to the thermogenic function of brown adipose tissue (BAT). Of note is that schizophrenia itself appears to be associated with a higher incidence of metabolic syndrome. However, whether OLZ affects metabolic disorders by regulating BAT function and its mechanism in animal models of schizophrenia have not been reported.Methods: We induced maternal immune activation (MIA) in pregnant rodents by injection of synthetic double-stranded RNA-poly I:C (a virus-like substance), and rats were injected with poly I:C, 10 mg/kg) or saline on day 13 of gestation. Rat offspring received OLZ (1 mg/kg, tid) or vehicle from adulthood for 28 days, and body weight and food intake were recorded. Morphological alterations of white adipose tissue (WAT) and BAT were analyzed by HE and oil red staining, and expression of BAT-specific marker proteins/genes was detected by western blot and qRT-PCR. In addition, embryonic stem cells C3H10T1/2 were used to direct differentiation into brown-like adipocytes, and C3H10T1/2 cells were treated with OLZ for the differentiation process. The effects of OLZ on brown-like adipocyte differentiation and activity were analyzed using oil red staining, immunofluorescence and flow cytometry.Results: Compared with the Veh (saline) group, the TG, pWAT weight, adipocyte size and liver weight of the Veh (poly I:C) group were significantly increased, suggesting that the offspring of Poly I:C rats had obvious dyslipidemia and lipid accumulation, which were risk factors for metabolic abnormalities such as obesity. In addition, OLZ treatment resulted in altered WAT and BAT morphology in poly I:C or saline exposed offspring, causing lipid accumulation and weight gain and reducing the expression of the BAT-specific marker molecule UCP1 protein/gene. At the same time, OLZ inhibited the directional differentiation and mitochondrial activity of C3H10T1/2 brown-like adipocytes.Conclusion: Poly I:C-elicited MIA and OLZ differentially inhibited BAT activity and mitochondrial biogenesis, leading to weight gain in adult rats, a process involving PPAR-γ/UCP1-related thermogenic proteins.
Atovaquone for treatment of COVID-19: A prospective randomized, double-blind, placebo-controlled clinical trial
Authors: Jain Mamta K. , De Lemos James A. , McGuire Darren K. , Ayers Colby. , Eitson Jennifer L. , Sanchez Claudia L. , Kamel Dena , Meisner Jessica A. , Thomas Emilia V. , Hegde Anita A. , Mocherla Satish , Strebe Joslyn K. , Li Xilong , Williams Noelle S. , Xing Chao , Ahmed Mahmoud S. , Wang Ping , Sadek Hesham A. , Schoggins John W. 
Published: September 2022

Background: An in silico screen was performed to identify FDA approved drugs that inhibit SARS-CoV-2 main protease (Mpro), followed by in vitro viral replication assays, and in vivo pharmacokinetic studies in mice. These studies identified atovaquone as a promising candidate for inhibiting viral replication.Methods: A 2-center, randomized, double-blind, placebo-controlled trial was performed among patients hospitalized with COVID-19 infection. Enrolled patients were randomized 2:1 to atovaquone 1500 mg BID versus matched placebo. Patients received standard of care treatment including remdesivir, dexamethasone, or convalescent plasma as deemed necessary by the treating team. Saliva was collected at baseline and twice per day for up to 10 days for RNA extraction for SARS-CoV-2 viral load measurement by quantitative reverse-transcriptase PCR. The primary outcome was the between group difference in log-transformed viral load (copies/mL) using a generalized linear mixed-effect models of repeated measures from all samples.Results: Of the 61 patients enrolled; 41 received atovaquone and 19 received placebo. Overall, the population was predominately male (63%) and Hispanic (70%), with a mean age of 51 years, enrolled a mean of 5 days from symptom onset. The log10 viral load was 5.25 copies/mL vs. 4.79 copies/mL at baseline in the atovaquone vs. placebo group. Change in viral load did not differ over time between the atovaquone plus standard of care arm versus the placebo plus standard of care arm. Pharmacokinetic (PK) studies of atovaquone plasma concentration demonstrated a wide variation in atovaquone levels, with an inverse correlation between BMI and atovaquone levels, (Rho −0.45, p = 0.02). In post hoc analysis, an inverse correlation was observed between atovaquone levels and viral load (Rho −0.54, p = 0.005).Conclusion: In this prospective, randomized, placebo-controlled trial, atovaquone did not demonstrate evidence of enhanced SARS-CoV-2 viral clearance compared with placebo. However, based on the observed inverse correlation between atovaquone levels and viral load, additional PK-guided studies may be warranted to examine the antiviral effect of atovaquone in COVID-19 patients.
Xiaoaiping injection combined with chemotherapy for advanced gastric cancer: An updated systematic review and meta-analysis
Authors: Zhou Xing Qin , Chang Ya Zhou , Shen Chao Yan , Han Jie , Chang Ren An 
Published: September 2022

Aim: To evaluate the clinical efficacy and safety of Xiaoaiping injection combined with chemotherapy in the treatment of advanced gastric cancer by meta-analysis.Methods: Seven databases, including China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, Cochrane Library, PubMed, Embase, and Web of Science, were searched by computer for randomized controlled clinical trials of Xiaoaiping injection combined with chemotherapy in the treatment of gastric cancer. Risk of bias assessment and meta-analysis were performed by Review Manager 5.3 software.Results: There were 16 articles that met the inclusion criteria, with a total of 1,236 patients, 617 in the observation group and 619 in the control group. The results of meta-analysis showed that the observation group was better than chemotherapy alone control group in RR [OR = 1.86, p &lt; 0.00001]; disease control rate (DCR) [OR = 2.45, p &lt; 0.00001]; Karnofsky performance status (KPS) score [OR = 3.21, p &lt; 0.00001] or [MD = 7.73, p = 0.001]. In terms of biochemical indicators, Xiaoaiping significantly reduced inflammation factors level, including tumor necrosis factor alpha (TNF-α) [MD = −15.00, p &lt; 0.00001]; interleukin-6 (IL-6) [MD = −13.00, p &lt; 0.00001]; C-reaction protein (CRP) [MD = −5.80, p &lt; 0.00001]. Xiaoaiping could enhance immune function, significantly reducing myeloid-derived suppressor cells (MDSCs) [MD = −6.20, p &lt; 0.00001] and Treg [MD = −1.70, p &lt; 0.00001]. Xiaoaiping injection combined with chemotherapy could significantly decrease tumor markers, including carcinoembryonic antigen (CEA) [MD = −11.64, p &lt; 0.00001]; CA199 [MD = −33.57, p = 0.02]; CA242 [MD = −20.66, p &lt; 0.00001]; CA125 [MD = −12.50, p = 0.0005]. In the comparison of adverse reactions, the incidence rate of Xiaoaiping injection group was significantly lower than that of control group. The funnel plot showed that the left and right sides are basically symmetrical, and it can be considered that there is no obvious publication bias.Conclusion: Xiaoaiping injection combined with chemotherapy has better curative effect and less adverse reactions in the treatment of gastric cancer. However, limited by the quality of the included studies, more high-quality studies are still needed to be verified.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022353842], identifier [CRD42022353842].
Cost-effectiveness analysis of lenvatinib plus pembrolizumab compared with chemotherapy for patients with previously treated mismatch repair proficient advanced endometrial cancer in China
Authors: Zheng Zhiwei , Yang Liu , Xu Siqi , Zhu Huide , Cai Hongfu 
Published: September 2022

Aims: This study aimed to evaluate the cost-effectiveness of lenvatinib plus pembrolizumab (LP) vs. chemotherapy for patients with previously treated mismatch repair proficient advanced endometrial cancer in China.Methods: A lifetime of partitioned survival Markov was used to evaluate the overall lifetime, total costs, quality adjusted life years (QALYs), and incremental cost effectiveness ratio (ICER) across a 10-years time horizon in the study 309–KEYNOTE-775 clinical trial. Direct costs and utility values were gathered from available literature. The willingness to pay (WTP) was defined at $37,663.26 per QALY. Sensitivity analyses were carried out to determine the model’s uncertainty.Results: According to the baseline analysis, the LP group gained 4.02 total life years and 3.13 QALYs for $93,496.69, whereas the chemotherapy group gained 2.86 total life years and 2.24 QALYs for $30,578.04. LP versus chemotherapy resulted in an incremental cost of $62,918.65, with an ICER of $70,962.09/QALY, which was higher than China’s WTP threshold ($37,663.26/QALY). The ICERs were most sensitive to the cost of pembrolizumab and the cycle of LP delivered, according to the sensitivity analysis. However, changing the range of those parameters has no influence on the model’s results.Conclusion: Our present analysis suggests that LP treatment is not cost-effective for patients with previously treated mismatch repair proficient advanced endometrial cancer. However, LP treatment may be a cost-effective treatment option if the price is reduced.
Integrated 16S rRNA sequencing and metabolomics analysis to investigate the antidepressant role of Yang-Xin-Jie-Yu decoction on microbe-gut-metabolite in chronic unpredictable mild stress-induced depression rat model
Authors: Liang Xing-Qiu , Mai Peng-Yu , Qin Hui , Li Sen , Ou Wen-Juan , Liang Jian , Zhong Jing , Liang Ming-Kun 
Published: September 2022

Objectives: Our goals were to evaluate the antidepressant efficacy of Yang-Xin-Jie-Yu Decoction (YXJYD) in Chronic Unpredictable Mild Stress (CUMS)-induced depression rat model and to investigate the underlying mechanisms.Design: We used CUMS-induced depression rat model to evaluate whether oral administration of YXJYD with different doses (2.1 g/kg, 1.05 g/kg and 0.525 g/kg, respectively) improve the depressive-like symptoms, and then performed UHPLC-Q-TOF-MS to explore the active ingredients of YXJYD. Subsequently, rat’s cecal contents, serum, and urine were collected from the control group, CUMS model group, and YXJYD high-dose (2.1 g/kg) treatment group. The 16S rRNA sequencing was performed on the cecal contents, based on Illumina MiSeq platform, and ANOVA analysis were used to analyze the composition variety and screen differential expression of gut bacteria in the three groups. 1H Nuclear Magnetic Resonance (NMR) analysis was used for analyzing the metabolites obtained from cecal contents, serum, and urine, and KEGG enrichment analysis was used to identify pathways of differential metabolites. An integrated 16S rRNA sequencing and metabolomic data were conducted to characterize the underlying mechanisms of YXJYDResults: The gut microbial communities, and serum, cecal content, urine metabolic compositions were significantly significantly altered in CUMS-induced depressive rats, while YXJYD effectively ameliorated the CUMS-associated gut microbiota dysbiosis, especially of Monoglobus, and alleviated the disturbance of serum, cecal content, urine metabolome and reversed the changes of key depressive and gut microbiota-related metabolites, such as succinic acid, taurine, hippuric acid, melatonin. With an integrated study of the gut microbiota and metabolomes, we identified the pathway of tricarboxylic acid cycle (TCA cycle) and propanoate metabolism as the regulated target of YXJYD on host-microbiome interaction.Conclusion: Our findings further confirmed the imbalance of metabolism and intestinal microbial is closely related to CUMS-induced depression. YXJYD regulates gut microbiome to affect body metabolomes and then produce antidepressant-like effect in CUMS-induced depressive rats while its molecular mechanism possibly be increased Monoglobus abundance in gut microbiota and regulated the TCA cycle pathway and propanoate metabolism in host.
Understanding plant to extract ratios in botanical extracts
Authors: Monagas Maria , Brendler Thomas , Brinckmann Josef , Dentali Steven , Gafner Stefan , Giancaspro Gabriel , Johnson Holly , Kababick James , Ma Cuiying , Oketch-Rabah Hellen , Pais Pilar , Sarma Nandu , Marles Robin 
Published: September 2022

Dietary supplement current good manufacturing practice (cGMP) requires establishment of quality parameters for each component used in the manufacture of a dietary supplement to ensure that specifications for the identity, purity, strength, composition, and limits on contaminants are met.* Compliance with botanical extract ingredient specifications is assured by using scientifically valid methods of analysis, the results of which are reported on certificates of analysis (CoAs). However, CoAs routinely include additional data that are not amenable to verification through methods of analysis. Such descriptive information may include Plant to Extract ratios, which are ratios of the quantity of botanical article used in the manufacture of the extract to the quantity of extract obtained. Plant to Extract ratios can be misleading when their meaning is not clearly understood.Plant to Extract ratios do not completely describe botanical extracts because other important factors influence the make-up of final extracts, such as the quality of the raw starting material (as can defined by pharmacopeial standards), extraction solvent(s) used, duration and temperature of extraction, and percentage and type of excipients present. Other important qualitative descriptions may include constituent “fingerprinting.” Despite these issues, Plant to Extract ratios are often used as a measure of extract strength for dosage calculations. This article defines and clarifies the meaning of Plant to Extract ratios and their proper use in describing and labeling botanical extract ingredients and finished products containing them.
Potentially inappropriate medications in older Chinese outpatients based on the Beers criteria and Chinese criteria
Authors: Zhang Ying , Chen Zhaoyan , Tian Fangyuan 
Published: September 2022

Objective: Polypharmacy increases the prevalence of potentially inappropriate drugs potentially inappropriate medications among older persons, lowering their quality of life. PIMs use can lead to higher mortality in older patients. This study aimed to compare the prevalence of PIMs in older Chinese outpatients according to the Beers criteria and the Chinese criteria and to analyze the risk factors. Second, we describe the differences between the two criteria, focusing on the inappropriate prescription of drugs in older outpatients.Methods: In Chengdu, Southwest China, a cross-sectional study was undertaken using electronic medical data from 9 general hospitals s. Outpatients above the age of 60 who were treated in the Geriatrics Center of these medical institutions were included. The 2019 Beers criteria and the 2017 Chinese criteria were used to evaluate the PIM status of older outpatients, and binary logistic regression was used to identify potential risk factors for PIMs.Results: There were 44,458 prescriptions from 2016 to 2018. The prevalence of PIMs among older outpatients was 30.05% (according to the Beers criteria) and 35.38% (according to the Chinese criteria), with statistical difference. Estazolam, hydrochlorothiazide and alprazolam were the top three PIMs in the Beers criteria, while the top three PIMs in the Chinese criteria were clopidogrel, estazolam and insulin. The prevalence of PIMs was associated with age, the number of diseases and the number of drugs. PIMs were shown to be more common in patients aged 70 and above, with more than 2 kinds of diseases and more than 4 kinds of drugs.Conclusion: PIMs were shown to be common among older outpatients in China, according to this study. The detection rate of the Chinese criteria was higher than that of the Beers criteria.