bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient demographics and characteristics from an ambispective, observational study of patients with duchenne muscular dystrophy in Saudi Arabia
Authors: AlSaman Abdulaziz S. , Al Ghamdi Fouad , Bamaga Ahmed K. , AlShaikh Nahla , Al Muqbil Mohammed , Muthaffar Osama , Bashiri Fahad A. , Ali Baleegh , Mulayim Arzu , Heider Elena , Alshahrani Abdullah A. , Al Muhaizea Mohammed A.
Published: September 2022

Duchenne muscular dystrophy (DMD) is a rare neuromuscular disorder that is characterized by progressive muscle weakness, resulting in disability and premature death. Onset of symptoms typically occurs at 2–3 years of age, and disease progression is managed through treatment with corticosteroids. The aim of this interim analysis is to increase disease awareness and improve patient management in Saudi Arabia (SA) through the use of data from an ongoing ambispective, observational, multicenter study evaluating characteristics of patients aged 1–14 years with genetically confirmed DMD in SA. This interim analysis examined the secondary outcomes from the study–the demographics and clinical characteristics of patients included retrospectively [data recorded (enrollment visit) between January 2014 and September 2020] and prospectively between September 2020 and April 2021. The primary outcome–the list of DMD gene mutations for the study population–will be reported at a later date. There were 177 eligible patients. Mean, standard deviation (SD) age at enrollment was 7.5 (3.0) years. Median (min, max) age at diagnosis was 7.0 (1.3, 13.8) years. At enrollment, 28.9% of patients were full-time wheelchair users, 50.0% of ambulatory patients could run, and 63.9% could climb stairs. The mean (SD) ages of patients at enrollment who were unable to run and climb stairs were 8.0 (2.7) and 7.6 (3.0) years, respectively. Speech delay (19.4%) and learning difficulties (14.9%) were the most commonly reported intellectual impairments. Physical therapy (84.2%) was the most common choice for initial management of DMD. Only 40.7% of patients received corticosteroid therapy as part of their initial management plan, rising to 59.1% at enrollment. Devices were given to 28.8% of patients for initial management, most commonly ankle-foot orthoses (26.0%) and wheelchairs (6.2%). This analysis reports data from the largest study to date to capture demographics and clinical characteristics of DMD patients in SA. The interim results show a relatively late DMD diagnosis age compared with that in other countries, and a need for improved adherence to international DMD standard of care guidelines. Therefore, there is an urgent requirement for improved DMD education and awareness among healthcare professionals and the public in SA.
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

Introduction

Pediatric 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.

Methods

We 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.

Results

We 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.

Discussion

Many 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 registration

https://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

Introduction

Understanding 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.

Methods

We 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)

Results

Thirty-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 (<1 month) at first embolization, 45% infants (1 month ≤2 years), and 13% children (>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 < 0.01; p < 0.001] and incomplete embolization [OR = 10.87; 95% CI (1.86–63.55); I2 < 0.01; p < 0.001] were associated with mortality. First embolization as a neonate [OR = 3.24; 95% CI (1.47–7.15); I2 < 0.01; p < 0.001], incomplete embolization [OR = 5.26; 95% CI (2.06–13.43); I2 < 0.01; p < 0.001], and heart failure at presentation [OR = 3.10; 95% CI (1.03–9.33); I2 < 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.

Conclusions

We 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.
External evaluation of published population pharmacokinetic models of posaconazole
Authors: Huang Shuqi , Ding Qin , Yang Nan , Sun Zexu , Cheng Qian , Liu Wei , Li Yejun , Chen Xin , Wu Cuifang , Pei Qi
Published: September 2022

Population pharmacokinetic (PopPK) models of posaconazole have been established to promote the precision dosing. However, the performance of these models extrapolated to other centers has not been evaluated. This study aimed to conduct an external evaluation of published posaconazole PopPK models to evaluate their predictive performance. Posaconazole PopPK models screened from the PubMed and MEDLINE databases were evaluated using an external dataset of 213 trough concentration samples collected from 97 patients. Their predictive performance was evaluated by prediction-based diagnosis (prediction error), simulation-based diagnosis (visual predictive check), and Bayesian forecasting. In addition, external cohorts with and without proton pump inhibitor were used to evaluate the models respectively. Ten models suitable for the external dataset were finally included into the study. In prediction-based diagnostics, none of the models met pre-determined criteria for predictive indexes. Only M4, M6, and M10 demonstrated favorable simulations in visual predictive check. The prediction performance of M5, M7, M8, and M9 evaluated using the cohort without proton pump inhibitor showed a significant improvement compared to that evaluated using the whole cohort. Consistent with our expectations, Bayesian forecasting significantly improved the predictive per-formance of the models with two or three prior observations. In general, the applicability of these published posaconazole PopPK models extrapolated to our center was unsatisfactory. Prospective studies combined with therapeutic drug monitoring are needed to establish a PopPK model for posaconazole in the Chinese population to promote individualized dosing.
The optimal first-line treatment for patients with left-sided RAS wild-type metastatic colorectal cancer: Double-drug regimen or triple-drug regimen therapy
Authors: Cai Changjing , Luo Qingqing , Liu Yihan , Peng Yinghui , Zhang Xiangyang , Jiang Zhaohui , Feng Ziyang , Qi Yaru , Gao Yan , Liu Yongting , Liu Ping , Chen Yihong , Guo Cao , Shen Hong , Zeng Shan , Han Ying
Published: September 2022

There are many treatments for metastatic colorectal cancer (mCRC). Among them, uncertainty remains especially concerning the clinical benefit of different regimens for left-sided RAS wild-type (WT) mCRC in the triple-drug therapy era. No studies have been conducted to answer this critical clinical issue. We performed a comprehensive analysis of published data and real-world data. First, we conducted analyses of the published trials to show the landscape of efficacy and safety in the treatments of left-sided RAS WT mCRC. Then, we initiated a multicenter real-world study as the validation dataset. This study included six published randomized controlled trials (RCTs) and a total of 1925 patients. The double-drug regimen plus cetuximab/panitumumab (D + C/P) achieved the longest overall survival (OS) in patients with left-sided mCRC (HR = 0.74, 95%CI: 0.57–0.98), while triple-drug regimen with bevacizumab (T + B, HR = 1.1, 95%CI: 0.63–2.0), compared with double-drug with bevacizumab (D + B). The D + C/P had the highest overall response rate (ORR) in patients with left-sided mCRC (OR = 1.8, 95%CI: 0.89–3.8), while T + B (OR = 1.8, 95%CI: 0.70–4.8), compared with D + B. The multicenter real-world cohort showed the double-drug regimen plus cetuximab had longer progression-free survival (PFS) in left-sided mCRC patients than the triple-drug regimen with bevacizumab. The safety analysis showed the incidence of the adverse events (grade≥3) in the triple-drug therapy plus bevacizumab was higher than that in the double-drug therapy plus cetuximab/panitumumab. This work demonstrates the ranking of three regimens for therapeutic efficacy and safety in patients with left-sided RAS WT mCRC. The double-drug regimen plus cetuximab/panitumumab appears more effective and safer than double-drug and triple-drug based regimens with bevacizumab. Further trials and cohort analyses on this topic would increase confidence in these results.
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 < 0.00001]; disease control rate (DCR) [OR = 2.45, p < 0.00001]; Karnofsky performance status (KPS) score [OR = 3.21, p < 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 < 0.00001]; interleukin-6 (IL-6) [MD = −13.00, p < 0.00001]; C-reaction protein (CRP) [MD = −5.80, p < 0.00001]. Xiaoaiping could enhance immune function, significantly reducing myeloid-derived suppressor cells (MDSCs) [MD = −6.20, p < 0.00001] and Treg [MD = −1.70, p < 0.00001]. Xiaoaiping injection combined with chemotherapy could significantly decrease tumor markers, including carcinoembryonic antigen (CEA) [MD = −11.64, p < 0.00001]; CA199 [MD = −33.57, p = 0.02]; CA242 [MD = −20.66, p < 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 YXJYD

Results: 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.
Comparative efficacy and safety of antiplatelet or anticoagulant therapy in patients with chronic coronary syndromes after percutaneous coronary intervention: A network meta-analysis of randomized controlled trials
Authors: Lin Yaowang , Cai Zhigang , Dong Shaohong , Liu Huadong , Pang Xinli , Chen Qiuling , Yuan Jie , Geng Qingshan
Published: September 2022

Aimed to evaluate and compare the interactive effects of different antiplatelet or anticoagulation strategies in patients with chronic coronary syndromes (CCS) after percutaneous coronary intervention (PCI). Randomized controlled trials comparing different antiplatelet or anticoagulant strategies in patients with CCS after PCI were included. The primary outcomes were major adverse cardiovascular event (MACE), mortality, ischemic and bleeding events. Compared to aspirin alone, addition of prasugrel or ticagrelor to aspirin resulted in lower risk of myocardial infarction (MI) [odds ratio (OR): 0.38 (95% confidence interval 0.38–0.62); 0.810–0.84 (0.69–0.98)] and any stroke [0.56 (0.42–0.75)] at the expense of increased risk of major bleeding [1.79 (1.34–2.39); 2.08–2.38 (1.56–3.28)], whereas, clopidogrel monotherapy reduced the risk of any stroke, major bleeding, and intracranial bleeding. On subgroup analysis, compared with aspirin alone, addition of prasugrel resulted in lower MACE [0.72 (0.60–0.86)], MI [0.48 (0.38–0.62)], and stent thrombosis [0.29 (0.09–0.91)], whereas, addition of rivaroxaban 2.5 mg resulted in lower risk of MACE [0.72 (0.60–0.87)], cardiac death [0.71 (0.52–0.98)] and any stroke [0.65 (0.45–0.95)], but not reduced MI. Both prasugrel and rivaroxaban 2.5 mg increased major bleeding [1.79 (1.34–2.39); 1.72 (1.33–2.22)]. Clopidogrel monotherapy was associated with lower MACE [0.72 (0.58–0.90)], any stroke [0.42 (0.24–0.73)], and major bleeding [0.62 (0.40–0.96)]. Adding prasugrel or ticagrelor led to a reduced incidence of MI and prasugrel was also found to reduce the risk of MACE and stent thrombosis in CCS patients with low risk of bleeding after PCI. Clopidogrel monotherapy has advantage in reducing MACE, stroke, and major bleeding events in CCS patients at high risk of bleeding after PCI.

Systematic Review Registration:https://clinicaltrials.gov/, PROSPERO Identifier: CRD 42021291050.
Preclinical studies of NOS inhibitor T1059 vasopressor activity on the models of acute hemorrhagic shock in rats and dogs
Authors: Filimonova Marina , Shevchenko Ljudmila , Makarchuk Victoria , Saburova Alina , Shegay Petr , Kaprin Andrey , Ivanov Sergey , Filimonov Alexander
Published: September 2022

The development of new effective and safe vasopressors is one of the ways to increase the effectiveness of the treatment of hypotensive disorders, the severe forms of which remain a common cause of death in all countries of the world. Previously, we synthesized the original compound T1059, a selective inhibitor of eNOS/iNOS which has a pronounced vasoconstrictive effect. Here we show its vasopressor activity in models of the early stage of acute hemorrhagic shock in rats and dogs, as part of preclinical studies. The results indicate NOS inhibitor T1059 as a potent long-acting vasopressor. Its single parenteral administration in sufficiently safe doses (1/50–1/9 LD10), caused in rats and dogs a rapid increase in vascular tone, accompanied by a prolonged hypertensive effect (within 90–120 min in rats, and within 115 min in dogs). The repeated administration of T1059 at low doses (1/3 of the first dose) made it possible to considerably (by at least 60 min) prolong a significant vasopressor effect. In all schemes, T1059 administration considerably inhibited the development of threatening cardiorespiratory disorders and significantly (p = 0.0026–0.0098) increased the short-term survival of experimental animals, formally extending the duration of the “golden hour” by 2 times. These data indicate that NOS inhibitors and, in particular, compound T1059, are able to create new opportunities in the treatment of hypotensive disorders, including the provision of assistance at the prehospital stage of treatment of such pathologies.
Statin uses in adults with non-dialysis advanced chronic kidney disease: Focus on clinical outcomes of infectious and cardiovascular diseases
Authors: Hsiao Ching-Chung , Yeh Jih-Kai , Li Yan-Rong , Sun Wei-Chiao , Fan Pei-Yi , Yen Chieh-Li , Chen Jung-Sheng , Lin Chihung , Chen Kuan-Hsing
Published: September 2022

Background: Statins are commonly used for cardiovascular disease (CVD) prevention. Observational studies reported the effects on sepsis prevention and mortality improvement. Patients with chronic kidney disease (CKD) are at high risk for CVD and infectious diseases. Limited information is available for statin use in patients with non-dialysis CKD stage V.

Method: The retrospective observational study included patients with non-dialysis CKD stage V, with either de novo statin use or none. Patients who were prior statin users and had prior cardiovascular events were excluded. The key outcomes were infection-related hospitalization, major adverse cardiovascular events (MACE) (non-fatal myocardial infarction, hospitalization for heart failure, or non-fatal stroke), and all-cause mortality. The data were retrieved from the Chang Gung Research Database (CGRD) from January 2001 to December 2019. Analyses were conducted with Cox proportional hazard regression models in the propensity score matching (PSM) cohort.

Result: A total of 20,352 patients with CKD stage V were included (1,431 patients were defined as de novo statin users). After PSM, 1,318 statin users were compared with 1,318 statin non-users. The infection-related hospitalization (IRH) rate was 79.3 versus 94.3 per 1,000 person-years in statin users and statin non-users, respectively [hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.74–0.93, p = 0.002]. The incidence of MACE was 38.9 versus 55.9 per 1,000 person-years in statin users and non-users, respectively (HR, 0.72; 95% CI 0.62–0.83, p < 0.001). The all-cause mortality did not differ between statin users and non-users, but statin users had lower infection-related mortality than non-users (HR, 0.59; 95% CI 0.38–0.92, p = 0.019).

Conclusion:De novo use of statin in patients with non-dialysis CKD stage V reduced the incidence of cardiovascular events, hospitalization, and mortality for infectious disease. The study results reinforced the benefits of statin in a wide range of patients with renal impairment before maintenance dialysis.
Antihypertensive potential of Brassica rapa leaves: An in vitro and in silico approach
Authors: Abid Rohma , Islam Muhammad , Saeed Hamid , Ahmad Abrar , Imtiaz Fariha , Yasmeen Anam , Rathore Hassaan Anwer
Published: September 2022

Aim:Plants contain many essential constituents and their optimization can result in the discovery of new medicines. One such plant isBrassica rapathat is commonly used as a vegetable to fulfill daily food requirements worldwide. This study intends to screen the phytochemicals, antihypertensive potential, GC-MS, andin silicoanalysis of the leaves ofBrassica rapa.

Methods:Powdered leaves were subjected to proximate analysis followed by estimation of primary metabolites. Extracts were obtained by hot and cold extraction and investigated for secondary metabolites. All crude extracts were screened for their antihypertensive potential using an angiotensin-converting enzyme (ACE) inhibition assay. GC-MS analysis was carried out to standardize the extract, and an antihypertensive metabolite was confirmed using anin silicoapproach.

Results:Physicochemical evaluation resulted in moisture content (9.10% ± 0.1), total ash value (18.10% ± 0.6), and extractive values (water 9.46% ± 0.5 and alcohol soluble 4.99% ± 0.1), while phytochemical investigation revealed primary metabolites (total proteins 11.90 mg/g ± 0.9; total fats 3.48 mg/g ± 0.5; and total carbohydrates 57.45 mg/g ± 1.2). Methanol extract showed the highest number of secondary metabolites including polyphenols 93.63 mg/g ± 0.6; flavonoids 259.13 mg/g ± 0.6; and polysaccharides 56.63 mg/g ± 1.4, while water extract (70 mg/g ± 2) was rich in glycosaponins. Methanol extract showed the highest antihypertensive potential by inhibiting ACE (79.39%) amongst all extracts, compared to the standard drug captopril, which inhibited 85.81%. Standardization of methanol extractviaGC-MS analysis revealed potent phytoconstituents, and a molecular docking study confirmed that oleic acid is the main antihypertensive metabolite.

Conclusion:We conclude that leaves ofBrassica rapacan successfully lower hypertension by inhibiting ACE, however;in vivoinvestigations are required to confirm this antihypertensive activity.
Natural products of traditional Chinese medicine treat atherosclerosis by regulating inflammatory and oxidative stress pathways
Authors: Meng Tianwei , Li Xinghua , Li Chengjia , Liu Jiawen , Chang Hong , Jiang Nan , Li Jiarui , Zhou Yabin , Liu Zhiping
Published: September 2022

Atherosclerosis (AS) is a prevalent arteriosclerotic vascular disease that forms a pathological basis for coronary heart disease, stroke, and other diseases. Inflammatory and oxidative stress responses occur throughout the development of AS. Treatment for AS over the past few decades has focused on administering high-intensity statins to reduce blood lipid levels, but these inevitably damage liver and kidney function over the long term. Natural medicines are widely used to prevent and treat AS in China because of their wide range of beneficial effects, low toxicity, and minimal side effects. We searched for relevant literature over the past 5 years in databases such as PubMed using the keywords, “atherosclerosis,” “traditional Chinese medicine,” “natural medicines,” “inflammation,” and “oxidative stress.” We found that the PI3K/AKT, TLR4, JAK/STAT, Nrf2, MAPK, and NF-κB are the most relevant inflammatory and oxidative stress pathways in AS. This review summarizes studies of the natural alkaloid, flavonoid, polyphenol, saponin, and quinone pathways through which natural medicines used to treat AS. This study aimed to update and summarize progress in understanding how natural medicines treat AS via inflammatory and oxidative stress-related signaling pathways. We also planned to create an information base for the development of novel drugs for future AS treatment.
A preliminary study on drug switching strategy for second-line therapy after combination treatment of tyrosine kinase inhibitors and immune checkpoint inhibitors for unresectable hepatocellular carcinoma
Authors: Guan Renguo , Yu Chengyou , Li Shaohua , Mei Jie , Wei Wei , Guo Rongping
Published: September 2022

Background: Combination treatment with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) has been widely used in patients with unresectable hepatocellular carcinoma (uHCC). As no standard guidelines exist for second-line therapy after failure of combination treatment, this study aimed to determine a better drug-switching strategy.

Methods: A total of 785 patients with uHCC who initially received a combination treatment of TKIs and ICIs between January 2017 and December 2021 at our center were screened. After applying the inclusion and exclusion criteria, a total of 102 patients were included in the study. Based on drug switching strategy, patients were divided into a single drug-switching group (A group, n = 49) and a double drug-switching group (B group, n = 53). The comparative effectiveness between groups A and B was assessed based on treatment response and survival time. Second progression-free survival (SPFS) and overall survival (OS) were compared using the Kaplan-Meier method and log-rank test.

Results: Compared to group B, group A had a higher overall response rate (16.3% vs. 3.8%; p = 0.0392) and disease control rate (61.2% vs. 49.1%; p = 0.238). The median SPFS in group A was longer than that in group B (5.47 vs. 3.8 months; HR = 1.70, p = 0.0176). In the second-line therapy, the inclusion of lenvatinib resulted in a better SPFS than other TKI treatments (5.53 vs. 2.83 months, p = 0.0038).

Conclusion: After the failure of the combination treatment of TKIs and ICIs, single-drug switching significantly prolonged median SPFS in uHCC patients, and retaining lenvatinib resulted in the survival benefit of single-drug switching.
1D Sine-Map-Coupling-Logistic-Map for 3D model encryption
Authors: Hu Yongsheng , Wang Xiaolin , Zhang Liyi
Published: September 2022

With the rise of technologies of VR technology, AR technology, and 3D printing, the application of 3D models has become more and more extensive. The data of the 3D model is the floating point and has a unique storage format, and the traditional 2D image encryption algorithms are unsuitable for 3D models. Therefore, based on 1D Sine-Map-Coupling-Logistic-Map (1D-SMCLM), a 3D model encryption algorithm is designed in this paper. The 1D-SMCLM is a new chaotic system with large parameter space and good chaotic characteristics. The keystream generated by the 1D-SMCLM has good randomness and is very suitable for cryptographic systems. In the new encryption algorithm (SMCLM-3ME), the vertices of the 3D models are divided into integer and decimal vertices. The integer part is encrypted by the strategy of simultaneous scrambling and diffusion. The 3D ciphertext model is obtained by combining the integer and fractional parts. Experimental results show that the SMCLM-IE exhibits excellent performance.
Light intensity correction for quartz-enhanced photoacoustic spectroscopy using photothermal baseline
Authors: Chen Xiang , Hu Mai , Liu Hao , Yao Lu , Xu Zhenyu , Kan Ruifeng
Published: September 2022

A convenient method of light intensity correction for quartz-enhanced photoacoustic spectroscopy (QEPAS) using photothermal baseline is demonstrated. The laser beam passes through the prongs of the quartz tuning fork (QTF) and then focused on the root of the prongs. First harmonic (1f) analysis is utilized to process the simultaneously induced photoacoustic and photothermal signals. The optical path length for photothermal spectroscopy is minimized to millimeter level, yielding negligible gas absorption. The demodulated 1f signal can be regarded as the superposition of the photoacoustic signal and the non-absorption photothermal baseline. A good linear relationship (R2 = 0.999) is observed between amplitude of photothermal baseline and light intensity. QEPAS signal normalized by photothermal baseline shows a good immunity to light intensity variation. An excellent linear response between normalized QEPAS signal and gas concentration is achieved. According to the Allan deviation analysis, the minimum detection limit for CH4 is 0.31 ppm at an integration time of 1,200 s. With this strategy, the precise gas concentration and accurate light intensity of a QEPAS system can be simultaneously obtained with only a single QTF. Compared with the light intensity correction using a photodetector or a power meter, this method entails a low cost and small footprint. It is promising to mitigate the influence from light intensity drift in long-term field measurement of QEPAS systems.
Social contagion influenced by active-passive psychology of college students
Authors: Ye Jianmeng , Chen Yi
Published: September 2022

Educational behavioral psychology refers to the fact that college students within campus networks have various psychological cognition toward novel information and behavior. This is hardly ever taken into account or theoretically examined in weighted network research. According to psychological traits and a student’s willingness to adopt fresh behaviors, we categorize students’ behaviors into the active and passive. On this basis, a threshold models is established for the behavior of active and passive students in weighted networks, and the influence behavioral psychology on information propagation is discussed. In order to qualitatively investigate the information propagation mechanism, a partition theory based on edge-weight and behavioral psychology is developed. Active students encourage the acceptance of new behaviors and the spread of information, according to theoretical study and simulation results. However, the phase transition intersected was more significant. When the percentage of enrolled pupils is high, a continuous phase transition is present in the growth pattern of the final adoption size. In contrast, as the proportion of active students declines, the increasing pattern alterss to discontinuous phase transition. In addition, weight distribution heterogeneity facilitates the dissemination of information and does not alter phase transition pattern. Finally, the theoretical analysis is in good agreement with the simulation results.
Markers for human haematopoietic stem cells: The disconnect between an identification marker and its function
Authors: Rix Beatrice , Maduro Andres Hernandez , Bridge Katherine S. , Grey William
Published: September 2022

The haematopoietic system is a classical stem cell hierarchy that maintains all the blood cells in the body. Haematopoietic stem cells (HSCs) are rare, highly potent cells that reside at the apex of this hierarchy and are historically some of the most well studied stem cells in humans and laboratory models, with haematopoiesis being the original system to define functional cell types by cell surface markers. Whilst it is possible to isolate HSCs to near purity, we know very little about the functional activity of markers to purify HSCs. This review will focus on the historical efforts to purify HSCs in humans based on cell surface markers, their putative functions and recent advances in finding functional markers on HSCs.
Acute effects of one-leg standing on arterial stiffness in older women: Role of the vision condition and standing dose
Authors: Zhou Zhixiong , Tao Xiaoli , Zhang Yuqin , Zhu Weili
Published: September 2022

Objective: One-leg standing has been used exclusively for static balance testing and training purposes. We investigated the acute effects of one-leg standing with open or closed eyes on arterial stiffness in older women and explored the role of standing dose in arterial stiffness regulation.

Methods: Eighteen older women (60 ± 2 years) underwent non-intervention control (CON), one-leg standing with open eyes for 2 × 3 min (SO2), and one-leg standing with closed eyes for 1 × 3 min (SC1), 2 × 3 min (SC2), and 3 × 3 min trials (SC3) in a randomized self-controlled crossover fashion. Arterial stiffness in the cardio-ankle vascular index (CAVI) was measured at baseline (BL), immediately (0 min), and 10 and 20 min after standing. CAVI changes from BL in the same trial (⊿CAVI) were used for analysis.

Results: ⊿CAVI of the non-standing and standing side did not change with time in CON and SO2 trials. In SC1, SC2, and SC3 trials, ⊿CAVI of the standing side decreased significantly at 0 min compared to their corresponding BL (p < 0.01) and reverted gradually to the BL level afterward, with ⊿CAVI of the non-standing side undergoing no changes. At the time point of 0 min, only in the SC2 trial, ⊿CAVI of the standing side was significantly lower than that of CON (p < 0.01).

Conclusion: One-leg standing with closed eyes, but not with open eyes, resulted in transient arterial stiffness improvement in older women. The improvement was restricted to standing leg, and the moderate standing dose had maximal benefit on arterial stiffness.