bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of adding empagliflozin to the standard therapy for Heart Failure with Preserved Ejection Fraction from the perspective of healthcare systems in China
Authors: Jiang Yaohui , Xie Jun 
Published: September 2022

BackgroundThe Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction (EMPEROR-Preserved) is the first randomized controlled trial to provide promising evidence on the efficacy of adding empagliflozin to the standard therapy in patients with Heart Failure with Preserved Ejection Fraction (HFpEF), but the cost-effectiveness of add-on empagliflozin treatment remains unclear.MethodA Markov model using data from the EMPEROR-Preserved trial and national database was constructed to assess lifetime costs and utility from a China healthcare system perspective. The time horizon was 10 years and a 5% discount rate was applied. Incremental cost-effectiveness ratio (ICER) against willingness to pay (WTP) threshold was performed to evaluate the cost-effectiveness. A series of sensitivity analyses was applied to ensure the robustness of the results.ResultsCompared to standard therapy, the increased cost of adding empagliflozin from $4,645.23 to $5,916.50 was associated with a quality-adjusted life years (QALYs) gain from 4.70 to 4.81, projecting an ICER of $11,292.06, which was lower than a WTP threshold of $12,652.5. Univariate sensitivity analysis revealed that the parameters with the largest impact on ICER were cardiovascular mortality in both groups, followed by the cost of empagliflozin and the cost of hospitalization for heart failure. Probabilistic sensitivity analysis indicated that when the WTP threshold was $12,652.5 and $37,957.5, the probability of being cost-effective for adding empagliflozin was 52.7% and 67.6%, respectively. Scenario analysis demonstrated that the cost of empagliflozin, the cost of hospitalization for heart failure, NYHA functional classes, and time horizon had a greater impact on the ICER.ConclusionAt a WTP threshold of $12,652.5, the add-on empagliflozin treatment for HFpEF was cost-effective in healthcare systems in China, which promoted the rational use of empagliflozin for HFpEF.
Thyroid diseases are associated with coronavirus disease 2019 infection
Authors: Tian Yutian , Zhao Junyu , Wang Tingting , Wang Haipeng , Yao Jinming , Wang Song , Mou Yaru 
Published: September 2022

BackgroundIn 2019, there was a global outbreak of new coronary pneumonia. Studies have found that the severity of patients with new coronary pneumonia may be related to their comorbidities. This article discusses the impact of thyroid disease on the severity of new coronary pneumonia through a meta-analysis and provides new treatment ideas for the later treatment and recovery of new coronary pneumonia.MethodsDatabases including PubMed, Embase, Cochrane Library, SINOMED, China national knowledge infrastructure (CNKI), and Wanfang for coronavirus disease 2019 (COVID-19) infection and thyroid diseases were searched. Reference lists of all eligible articles and related previous review articles were handsearched. Fifty-three articles were included to conduct the meta-analysis.ResultsFifty-three articles with 12,022 COVID-19 infection patients were included in this meta-analysis. The proportion of patients with thyroid diseases in all COVID-19 infection patients fluctuates between 0% and 88.46%. Of the 53 included studies, 22 studies reported the severity of COVID-19 infection and grouped. The fixed-effects model was used to merge odds ratio (OR) values, and the pooled effect size in favor of non-severe patients is 2.62 (95% CI = 1.96–3.49, P &lt; 0.0001), which means that patients with severe COVID-19 infection are more likely to have thyroid diseases. The analysis subgrouped into Asia and Europe shows that patients with COVID-19 severe infection in Asia are 3.77 times more likely to have thyroid diseases than non-severe patients (fixed-effects model: OR = 3.77, 95% CI = 2.66–5.35, P &lt; 0.00001). No significant statistical heterogeneity was found by the heterogeneity analysis (chi-square = 19.85, P = 0.34, I2 = 9%). Severe COVID-19 infection patients are more likely to be complicated by hypothyroidism and low T3 syndrome. The pooled ORs with fixed-effects model are 3.72 (95% CI = 1.62–8.58, P = 0.002) and 5.86 (95% CI = 2.79–12.33, P &lt; 0.00001), respectively.ConclusionCOVID-19 infection patients with thyroid diseases are very common, and severe patients are more likely to have thyroid diseases. Asian COVID-19 infection, hypothyroidism patients, and patients with low T3 syndrome are more likely to progress to severe condition.Systematic Review Registrationhttps://inplasy.com, identifier INPLASY202190079.
The efficacy and safety of luteal phase support with progesterone following ovarian stimulation and intrauterine insemination: A systematic review and meta-analysis
Authors: Casarramona G. , Lalmahomed T. , Lemmen CHC. , Eijkemans MJC. , Broekmans FJM. , Cantineau AEP. , Drechsel KCE. 
Published: September 2022

The aim of this systematic review and meta-analysis was to update the current evidence for the efficacy and safety of progesterone luteal phase support (LPS) following ovarian stimulation and intrauterine insemination treatment (OS-IUI) for unexplained or mild male infertility. Four additional studies were identified compared to the previous review in 2017. Twelve RCTs (2631 patients, 3262 cycles) met full inclusion criteria. Results from quantitative synthesis suggest that progesterone LPS after OS-IUI leads to higher live birth (RR 1.38, 95%CI [1.09, 1.74]; 7 RCTs, n=1748) and clinical pregnancy rates (RR 1.38, 95% CI [1.21, 1.59]; 11 RCTs, n=2163) than no LPS or placebo. This effect is specifically present in protocols using gonadotropins for OS-IUI (RR 1.41, 95%CI [1.17, 1.71]; 7 RCTs, n=1114), and unclear in protocols involving clomiphene citrate (RR 1.01, 95% CI [0.05, 18.94]; 2 RCTs, n=138). We found no effect of progesterone LPS on multiple pregnancy or miscarriage rates. No correlation between drug-dosage or duration of treatment and effect size was seen. Though our results suggest both benefit and safety of progesterone LPS in OS-IUI, evidence is of low to moderate quality and additional well-powered trials are still mandatory to confirm our findings and justify implementation in daily practice.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=292325, identifier CRD42021292325.
Hydrogen saline water accelerates fracture healing by suppressing autophagy in ovariectomized rats
Authors: Guo Jialiang , Tian Siyu , Wang Zhongzheng , Wang Yuchuan , Zhang Xiaojuan , Zhang Yingze , Hou Zhiyong , Dong Weichong 
Published: September 2022

ObjectiveThe treatment of osteoporotic fractures is difficult, and to minimize the negative result or poor functional rehabilitation, this study focuses on hydrogen water (HRW) to test its effect on the process of menopausal osteoporotic fracture healing and its relationship with autophagy and to try to reveal the potential mechanism of action of HRW on osteoporotic fractures.Materials and methodsA rat osteoporotic fracture model was established, and HRW was systematically applied with or without 3MA. The results were analyzed with X-rays, micro-CT scans, serum biomarker analysis, biomechanical tests, histopathology, immunohistochemistry, and Western blotting. The sham, OVX, OH (OVX+HRW) and OHA (OVX+HRW+3MA) groups were formed and compared.ResultsIncreased oxidative stress and autophagy levels were necessary physiological responses in the process of fracture healing. It was found that systemic HRW treatment slightly suppressed autophagy and then activated the Keap1-Nrf2 signaling pathway by maintaining the Keap1-Nrf2-P62 interaction and improved the osteoporotic fracture healing process.ConclusionHRW treatment activated the Keap1-Nrf2 signaling pathway to antagonize cellular stress by suppressing autophagy levels, especially at the early stage of the fracture healing process, and this was beneficial to osteoporotic fracture healing in rats.
Potential biomarkers for clinical outcomes of IVF cycles in women with/without PCOS: Searching with metabolomics
Authors: Guan Shang-yue , Liu Yuan-yuan , Guo Yuhan , Shen Xiao-xue , Liu Yan , Jin Hai-xia 
Published: September 2022

BackgroundPolycystic ovary syndrome (PCOS) is a heterogeneous endocrinological and metabolic disorder which is the common cause of female infertility. The dysmetabolism displayed in it has not been completely ascertained. Metabonomics may shed light on understanding many small molecule endogenous metabolites and their associated metabolic pathways.ObjectiveTo analyze the different metabolites and related metabolic pathways in follicular fluid and embryo culture fluid of PCOS and non-PCOS groups. Finding markers predictable for clinical outcomes of in vitro fertilization-embryo transfer (IVF-ET) treatment.Population and sample60 women who underwent IVF-ET were selected, including 30 with PCOS and 30 with the fallopian tubal issues only. We collected the first tube follicular fluid (FF) of all patients at the time of oocyte pick up and the waste embryo culture medium (ECM) after D3 high-quality embryo transplant.MethodsAll samples were performed nontargeted Ultra High Performance Liquid Chromatography-Mass Spectrometry (UHPLC-QE-MS) analysis. Related metabolic pathways were screened by KEGG annotation. To search potential indicators, the logistic regression was made combined with clinical data.Mean outcome measuresPredictive performance of markers of clinical outcomes (pregnancy rate, delivery rate, live birth rate, miscarriage rate) of assisted reproductive technology (ART).ResultsComparing the PCOS group against the non-PCOS group, we found 11 significantly different metabolites in the FF and 56 in the ECM. There are a total of 11 kinds of biomarkers associated with clinical outcomes. Androsterone sulfate, Glycerophosphocholine, and Elaidic carnitine seem robust to predict the abortion rate of the PCOS group, with an AUC of 0.941, 0.933, 0.933, respectively. The glycerol phospholipid metabolic pathway is enriched in both the follicular fluid and embryo culture fluid.ConclusionsThe differential metabolites were mainly a variety of lipids. Some of them can predict clinical outcomes to a certain extent.
Experimental study for thermal methane cracking reaction to generate very pure hydrogen in small or medium scales by using regenerative reactor
Authors: Yousefi Mahdi , Donne Scott 
Published: September 2022

Non-catalytic thermal methane cracking (TMC) is an alternative for hydrogen manufacturing and traditional commercial processes in small-scale hydrogen generation. Supplying the high-level temperatures (850–1800°C) inside the reactors and reactor blockages are two fundamental challenges for developing this technology on an industrial scale (Mahdi Yousefi and Donne, 2021). A regenerative reactor could be a part of a solution to overcome these obstacles. This study conducted an experimental study in a regenerative reactor environment between 850 and 1,170°C to collect the conversion data and investigate the reactor efficiency for TMC processes. The results revealed that the storage medium was a bed for carbon deposition and successfully supplied the reaction’s heat, with more than 99.7% hydrogen yield (at more than 1,150°C). Results also indicated that the reaction rate at the beginning of the reactor is much higher, and the temperature dependence in the early stages of the reaction is considerably higher. However, after reaching a particular concentration of Hydrogen at each temperature, the influence of temperature on the reaction rate decreases and is almost constant. The type of produced carbon in the storage medium and its auto-catalytic effect on the reactions were also investigated. Results showed that carbon black had been mostly formed but in different sizes from 100 to 2000 nm. Increasing the reactor temperature decreased the size of the generated carbon. Pre-produced carbon in the reactor did not affect the production rate and is almost negligible at more than 850°C.
Sorption of benzo(a)pyrene and of a complex mixture of petrogenic polycyclic aromatic hydrocarbons onto polystyrene microplastics
Authors: Martínez-Álvarez Ignacio , Le Menach Karyn , Devier Marie-Hélène , Cajaraville Miren P. , Orbea Amaia , Budzinski Hélène 
Published: September 2022

Microplastics (MPs) largely occur in aquatic ecosystems due to degradation of larger plastics or release from MP-containing products. Due to the hydrophobic nature and large specific surface of MPs, other contaminants, such as polycyclic aromatic hydrocarbons (PAHs), can potentially sorb onto MPs. Several studies have addressed the potential impact of MPs as vectors of PAHs for aquatic organisms. Therefore the role of MPs as sorbents of these compounds should be carefully investigated. The present study aimed to determine the sorption capacity of benzo(a)pyrene (B(a)P), as a model pyrolytic PAH, to polystyrene (PS) MPs of different sizes (4.5 and 0.5 μm). In addition, the sorption of PAHs present in the water accommodated fraction (WAF) of a naphthenic North Sea crude oil to 4.5 μm MPs was also studied as a model of a complex mixture of petrogenic PAHs that could appear in oil-polluted environments. The results indicated that 0.5 μm MPs showed higher maximum sorption capacity (Qmax) for B(a)P (145–242.89 μg/g) than 4.5 μm MPs (30.50–67.65 μg/g). From the WAF mixture, naphthalene was sorbed at a higher extent than the other PAHs to 4.5 μm MPs but with weak binding interactions (Kf = 69.25 L/g; 1/n = 0.46) according to the analysis of the aqueous phase, whereas phenanthrene showed stronger binding interactions (Kf = 0.24 L/g; 1/n = 0.98) based on the analysis of the solid phase. Sorption of PAHs of the complex WAF mixture to 4.5 μm MPs was relatively limited and driven by the hydrophobicity and initial concentration of each PAH. Overall, the results indicate that sorption estimations based solely on the analysis of the aqueous phase could overestimate the capacity of MPs to carry PAHs. Therefore, controlled laboratory assays assessing the “Trojan Horse effect” of MPs for aquatic organisms should consider these findings in order to design accurate and relevant experimental procedures.
Residues, dissipation, and dietary risk assessment of oxadixyl and cymoxanil in cucumber
Authors: Fan Jiqiao , Li Li 
Published: September 2022

Oxadixyl and cymoxanil are widely used for controlling downy mildew in cucumber; however, there are few systematic studies on monitoring residue levels of these two pesticides in cucumber under greenhouse and open field conditions. In this study, a simplified quick, easy, cheap, effective, rugged, and safe (QuEChERS) method was applied to analyze target compounds in cucumber. The average recoveries of oxadixyl and cymoxanil in cucumber ranged from 96% to 102%, with relative standard deviations (RSDs) of 1.8%–4.0%. The limits of quantification (LOQs) for two pesticides were both 0.01 mg/kg. The dissipation of oxadixyl was in accordance with a first-order kinetics equation, with half-lives ranging from 1.8 to 3.1 days. At the pre-harvest interval (PHI) of 3 or 5 days, the residue levels of oxadixyl in cucumber under open field conditions were higher than those under greenhouse conditions. Compared to oxadixyl, the cymoxanil degraded quickly, and its residues were below LOQ on the 3rd or 5th day after the last application. The terminal residues of oxadixyl and cymoxanil in the cucumber were both lower than the maximum residue limits (MRLs) in China. The risk quotient (RQ) used for dietary risk assessment was 1.8%–3.5% and 0.26%–0.51% for oxadixyl and cymoxanil, respectively. The results showed that the risks of these two pesticides used on cucumber at the experimental dosages are comparably acceptable for Chinese consumers of different gender and age groups. This study provides a reference data to use oxadixyl and cymoxanil scientifically and rationally.
Integrative analysis of synovial sarcoma transcriptome reveals different types of transcriptomic changes
Authors: Sun Zhengwang , Yin Mengchen , Ding Yi , Zhu Zixu , Sun Yangbai , Li Kun , Yan Wangjun 
Published: September 2022

Background: Synovial sarcoma (SS) is a rare and aggressive cancer that can come from distinct soft tissue types including muscle and ligaments. However, the transcriptomic landscape of SS is still poorly understood. This study aimed to systematically dissect the changes in SS transcriptome from different perspectives.Methods: We performed deep total RNA sequencing on ten paired Synovial sarcoma and tumor-adjacent tissues to systematically dissect the transcriptomic profile of SS in terms of gene expression, alternative splicing, gene fusion, and circular RNAs.Results: A total of 2,309 upregulated and 1,977 downregulated genes were identified between SS and tumor-adjacent tissues. Those upregulated genes could lead to the upregulation of the cell cycle, ribosome, and DNA replication pathways, while the downregulated genes may result in the downregulation of a set of metabolic biological processes and signaling pathways. Moreover, 2,511 genes (including 21 splicing factors) were differentially alternative spliced, indicating that the deregulation of alternative splicing could be one important factor that contributes to tumorigenesis. Additionally, we identified the known gene fusions of SS18-SSX1/SSX2 as well as 11 potentially novel gene fusions. Interestingly, 49 circular RNAs were differentially expressed and their parental genes could function in muscle contraction and muscle system processes.Conclusions: Collectively, our comprehensive dissection of the transcriptomic changes of SS from both transcriptional and post-transcriptional levels provides novel insights into the biology and underlying molecular mechanism of SS.
Evaluating the effect of tanning response to sun exposure on the risk of skin diseases through Mendelian randomization
Authors: Ping Weidong , Zhao Qiming , Ge Shuhong , Wang Xin , Li Fei , Huang Xiaoxiang 
Published: September 2022

Background: Until now, the relevance of the tanning response to sun exposure and skin diseases has incomplete and inconsistent epidemiological observations. In this case, it is valuable to find out the causality of tanning response to sun exposure and skin diseases, and take a step further toward developing effective therapies as well as prevention methods.Methods: We investigated the causal effect of tanning response to sun exposure on 10 major skin diseases that have been studied in recent large-scale genome-wide association studies (GWASs). Significant independent genetic variants from large-scale GWAS on ease of skin tanning (N = 453,065) are selected as the effective instrumental variables (IVs). For each skin disease, we extracted the summary statistics of those IVs (or their proxies) from the corresponding skin disease-GWAS as the valid IVs. Mendelian randomization (MR) was further performed to evaluate the causal association of ease of skin tanning with each of the skin diseases using different statistical methods, including inverse-variance weighted (IVW), the weighted median, and MR-Egger. Sensitivity analysis was also conducted to evaluate the effect of horizontal pleiotropy and heterogeneity.Results: We observe significant associations between six skin diseases with tanning response to sun exposure with adjusted p-value derived by IVW less than 0.05 and with nominal p value less than 0.05 at the same time derived by either MR-Egger or weighted median. The six skin diseases include actinic keratosis (IVW FDR = 1.71E-40, MR Egger p-value = 3.46E-22), seborrhoeic keratosis (IVW FDR = 2.97E-4, MR Egger p-value = 1.06E-3), blepharochalasis (IVW FDR = 1.30E-3, MR Egger p-value = 2.91E-4), seborrhoeic dermatitis (IVW FDR = 1.29E-2, MR Egger p-value = 1.23E-2), malignant melanoma of skin (IVW FDR = 2.95E-2, MR Egger p-value = 1.91E-2), and freckles (IVW FDR = 2.95E-2, weighted median p-value = 1.02E-3). Interestingly, we find increased trends of developing all of the six skin diseases with increased tanning response to sun exposure (beta values are positive using IVW, MR-egger, and weighted median methods). We also replicate the association on three skin diseases using an independent outcome GWAS cohort, including malignant melanoma of the skin (replication IVW p-value = 2.13E-39), actinic keratosis (replication IVW p-value = 4.64E-32), and seborrhoeic keratosis (replication IVW p-value = 1.79E-3).Conclusion: Our observation shows that the tanning response to sun exposure is positively correlated with the development of skin diseases in people of European descent by Mendelian randomization studies. But randomized controlled trials are still needed to add proof to our observations.
Family-based exome sequencing identifies candidate genes related to keratoconus in Chinese families
Authors: Xu Liyan , Yang Kaili , Yin Shanshan , Gu Yuwei , Fan Qi , Wang Yawen , Zhao Dongqing , Ren Shengwei 
Published: September 2022

Background: Keratoconus (KC) is a complex corneal disorder with a strong genetic component. The present study aimed to identify candidate genes related to KC in Chinese families.Methods: Family-based exome sequencing was performed in ten patients suffering from KC who belong to five families with two affected members in each. The candidate rare variants were identified with multi-step bioinformatics analysis. The STRING website was used to perform the protein interaction of the identified genes.Results: Our analyses identified 32 candidate rare variants in 13 genes by family-based exome sequencing. The molecular analyses of identified genes showed that EPCAM directly interacted with CTNNB1 of the Hippo signaling pathway and focal adhesion pathway, and directly interacted with CTNNB1, CDH1 of the WNT signaling pathway. SHROOM3 directly interacted with ROCK2, ROCK1 of the focal adhesion pathway. SYNE1 directly interacted with MUSK of the extracellular matrix organization pathway. TEK directly interacted with VEGFA, SHC1, PIK3R1, GRB2 of the focal adhesion pathway. TTN directly interacted with CAPN3 of the extracellular matrix organization pathway.Conclusion: The EPCAM, SHROOM3, SYNE1, TEK, and TTN genes were potential high-risk candidate pathogenic genes of familial KC. The findings might significantly improve our understanding of the genetic etiology of the disease, providing novel insights on KC pathogenesis.