bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of genetic polymorphisms in the C19orf66 gene and biochemical indices of HBV infected individuals in Yunnan
Authors: Liu Ni , Liu Min , Yang Jun , Dong Shuwei , Yue Ming , Huang Peng , Xia Xueshan , Zhang A-Mei 
Published: May 2023

IntroductionHepatitis B virus (HBV) infection causes serious liver diseases and is a healthy problem worldwide. Although vaccines are administered to infants after birth, there is no effective medicine for HBV infection. The interferon-stimulated genes (ISGs) are important factors in the host that can aid in restraining the virus, and the C19orf66 gene has a wide-antiviral spectrum.MethodsIn this study, three SNPs in the C19orf66 gene were sequenced and genotyped, and their potential function were predicted and further verified by dual-luciferase reporter assay.ResultsAlthough no significant difference of genotype and allele frequency was observed between HBV patients and the controls, the genotype and allele frequency showed significant difference between HBV patients with HBsAg-positive and HBV patients with HBsAg-negative or controls. Genotype AA (P= 0.009) and AT (P= 0.019) of rs77076061 showed higher and lower frequency in HBV patients with HBsAg-positive than in patients with HBsAg-negative, respectively. Genotype AG of rs1979262 played a risk role in HBV patients with HBsAg-positive (13.22%) than in patients with HBsAg-negative (7.53%, P= 0.036) or controls (8.48%, P= 0.033). The frequency of allele A of rs1979262 was higher in patients with HBsAg-positive (6.61%) than in patients with HBsAg-negative (3.77%, P= 0.042), while it was the opposite for the allele G. Moreover, the associations between genotypes of SNPs in the C19orf66 gene and the ALT, AST, and DBIL level were also identified. The functional assay suggested that the SNPs might influence the C19orf66 expression by changing the connection of transcriptional factors.ConclusionIn summary, the association between genetic polymorphisms in the C19orf66 gene and HBV infection/biochemical indices of patients was firstly identified in Yunnan Province.
Lipoprotein(a) induces caspase-1 activation and IL-1 signaling in human macrophages
Authors: Lorey Martina B. , Youssef Amer , Äikäs Lauri , Borrelli Matthew , Hermansson Martin , Assini Julia M. , Kemppainen Aapeli , Ruhanen Hanna , Ruuth Maija , Matikainen Sampsa , Kovanen Petri T. , Käkelä Reijo , Boffa Michael B. , Koschinsky Marlys L. , Öörni Katariina 
Published: May 2023

IntroductionLipoprotein(a) (Lp(a)) is an LDL-like particle with an additional apolipoprotein (apo)(a) covalently attached. Elevated levels of circulating Lp(a) are a risk factor for atherosclerosis. A proinflammatory role for Lp(a) has been proposed, but its molecular details are incompletely defined.Methods and resultsTo explore the effect of Lp(a) on human macrophages we performed RNA sequencing on THP-1 macrophages treated with Lp(a) or recombinant apo(a), which showed that especially Lp(a) induces potent inflammatory responses. Thus, we stimulated THP-1 macrophages with serum containing various Lp(a) levels to investigate their correlations with cytokines highlighted by the RNAseq, showing significant correlations with caspase-1 activity and secretion of IL-1β and IL-18. We further isolated both Lp(a) and LDL particles from three donors and then compared their atheroinflammatory potentials together with recombinant apo(a) in primary and THP-1 derived macrophages. Compared with LDL, Lp(a) induced a robust and dose-dependent caspase-1 activation and release of IL-1β and IL-18 in both macrophage types. Recombinant apo(a) strongly induced caspase-1 activation and IL-1β release in THP-1 macrophages but yielded weak responses in primary macrophages. Structural analysis of these particles revealed that the Lp(a) proteome was enriched in proteins associated with complement activation and coagulation, and its lipidome was relatively deficient in polyunsaturated fatty acids and had a high n-6/n-3 ratio promoting inflammation.DiscussionOur data show that Lp(a) particles induce the expression of inflammatory genes, and Lp(a) and to a lesser extent apo(a) induce caspase-1 activation and IL-1 signaling. Major differences in the molecular profiles between Lp(a) and LDL contribute to Lp(a) being more atheroinflammatory.
Case report: Torsade de pointes induced by the bigeminy result from retrograde ventriculoatrial activation in VVI pacing and resolved by intentional atrial pacing
Authors: Chu Song-Yun , Sheng Qin-Hui , Shi Qiu-Ping , Qiu Lin , Wu Lin , Zhou Jing 
Published: May 2023

IntroductionWhile pacing has been used for long QT syndrome (LQTs), the optimal pacing modality is controversial.CaseWe report a woman with bradycardia and a recently implanted single-chamber pacemaker experienced multiple syncope. No device dysfunction was found. Multiple Torsade de Pointes (TdP) induced by the bigeminy result from retrograde ventriculoatrial (VA) activation in VVI pacing were demonstrated in the scenario of previously unidentified LQTs. Replacement for a dual-chamber ICD and intentional atrial pacing eliminated the VA conduction and symptoms.ConclusionPacing without atrioventricular sequence might be catastrophic in LQTs. Atrial pacing and atrioventricular synchrony should be highlighted.
Analysis of Japanese consumers' attitudes toward the digital transformation of OTC medicine purchase behavior and eHealth literacy: an online survey for digital experience design
Authors: Tang Guyue , Izumi Kairi , Izumisawa Megumi , Koyama Shinichi 
Published: May 2023

IntroductionSince the enactment of the revised Pharmaceutical Affairs Act in Japan in 2009, self-medication practices have increased in the country. However, studies report that consumers pay little attention to the medication facts and risks indicated on the packages of over-the-counter (OTC) medicines, which could be a potential risk. Since the COVID-19 pandemic, the digital transformation of purchasing OTC medicines has progressed. As an appropriate design for the digital transformation is likely to improve consumers' literacy and them obtaining medical information, this study systematically examines Japanese consumers' attitudes toward the digital transformation of OTC medicine purchase behavior and its correlation to eHealth literacy, exploring an appropriate digital experience design in purchasing OTC medicine.MethodsParticipants from the Greater Tokyo Area of Japan participated in an online survey. Consumers' current behavior and preferences in accessing OTC medicine, receiving medication guidance, and obtaining medical information were examined. eHealth literacy was assessed using the J-eHEALS. Descriptive statistics, text mining, and thematic analysis were conducted to answer research questions.ResultsOver 89% of the respondents who had experience in purchasing OTC medicines preferred local pharmacies or stores rather than online purchasing, p &lt; 0.001. Obtaining medicine guidance in pharmacies or stores was the main preference over other approaches, p &lt; 0.001. Furthermore, most of the participants accepted selecting medicine on shelves and digital screens in-store. However, they were accustomed to using smartphones to obtain additional information at the pharmacy or drug store, p &lt; 0.001; this behavior was positively correlated with eHealth literacy, p &lt; 0.001.ConclusionsJapanese consumers are seeking a combination of conventional and digital behaviors for purchasing OTC medicine rather than opting for a particular method. Most consumers prefer purchasing and receiving instructions in-store while searching for additional decision-making information online. eHealth literacy is positively associated with digital behaviors of OTC medicine information acquisition but less associated with medicine purchases and selections. The hybrid digital experience design may enhance the OTC medicine purchase experience and reduce potential risks by providing appropriate information.
Two web-based dynamic prediction models for the diagnosis and prognosis of gastric cancer with bone metastases: evidence from the SEER database
Authors: Liu Bo , Li Kangpeng , Ma Rui , Zhang Qiang 
Published: May 2023

PurposeOur aim was to identify the clinical characteristics and develop and validate diagnostic and prognostic web-based dynamic prediction models for gastric cancer (GC) with bone metastasis (BM) using the SEER database.MethodOur study retrospectively analyzed and extracted the clinical data of patients aged 18-85 years who were diagnosed with gastric cancer between 2010 and 2015 in the SEER database. We randomly divided all patients into a training set and a validation set according to the ratio of 7 to 3. Independent factors were identified using logistic regression and Cox regression analyses. Furthermore, we developed and validated two web-based clinical prediction models. We evaluated the prediction models using the C-index, ROC, calibration curve, and DCA.ResultA total of 23,156 patients with gastric cancer were included in this study, of whom 975 developed bone metastases. Age, site, grade, T stage, N stage, brain metastasis, liver metastasis, and lung metastasis were identified as independent risk factors for the development of BM in GC patients. T stage, surgery, and chemotherapy were identified as independent prognostic factors for GC with BM. The AUCs of the diagnostic nomogram were 0.79 and 0.81 in the training and test sets, respectively. The AUCs of the prognostic nomogram at 6, 9, and 12 months were 0.93, 0.86, 0.78, and 0.65, 0.69, 0.70 in the training and test sets, respectively. The calibration curve and DCA showed good performance of the nomogram.ConclusionsWe established two web-based dynamic prediction models in our study. It could be used to predict the risk score and overall survival time of developing bone metastasis in patients with gastric cancer. In addition, we also hope that these two web-based applications will help physicians comprehensively manage gastric cancer patients with bone metastases.
Impact of short and long exposure to cafeteria diet on food intake and white adipose tissue lipolysis mediated by glucagon-like peptide 1 receptor
Authors: Mattar Pamela , Jaque Cristian , Teske Jennifer A. , Morselli Eugenia , Kerr Bredford , Cortés Víctor , Baudrand Rene , Perez-Leighton Claudio E. 
Published: May 2023

IntroductionThe modern food environment facilitates excessive calorie intake, a major driver of obesity. Glucagon-like peptide 1 (GLP1) is a neuroendocrine peptide that has been the basis for developing new pharmacotherapies against obesity. The GLP1 receptor (GLP1R) is expressed in central and peripheral tissues, and activation of GLP1R reduces food intake, increases the expression of thermogenic proteins in brown adipose tissue (BAT), and enhances lipolysis in white adipose tissue (WAT). Obesity decreases the efficiency of GLP1R agonists in reducing food intake and body weight. Still, whether palatable food intake before or during the early development of obesity reduces the effects of GLP1R agonists on food intake and adipose tissue metabolism remains undetermined. Further, whether GLP1R expressed in WAT contributes to these effects is unclear.MethodsFood intake, expression of thermogenic BAT proteins, and WAT lipolysis were measured after central or peripheral administration of Exendin-4 (EX4), a GLP1R agonist, to mice under intermittent-short exposure to CAF diet (3 h/d for 8 days) or a longer-continuous exposure to CAF diet (24 h/d for 15 days). Ex-vivo lipolysis was measured after EX4 exposure to WAT samples from mice fed CAF or control diet for 12 weeks. .ResultsDuring intermittent-short exposure to CAF diet (3 h/d for 8 days), third ventricle injection (ICV) and intra-peritoneal administration of EX4 reduced palatable food intake. Yet, during a longer-continuous exposure to CAF diet (24 h/d for 15 days), only ICV EX4 administration reduced food intake and body weight. However, this exposure to CAF diet blocked the increase in uncoupling protein 1 (UCP1) caused by ICV EX4 administration in mice fed control diet. Finally, GLP1R expression in WAT was minimal, and EX4 failed to increase lipolysis ex-vivo in WAT tissue samples from mice fed CAF or control diet for 12 weeks. .DiscussionExposure to a CAF diet during the early stages of obesity reduces the effects of peripheral and central GLP1R agonists, and WAT does not express a functional GLP1 receptor. These data support that exposure to the obesogenic food environment, without the development or manifestation of obesity, can alter the response to GLP1R agonists. .
Bone morphogenetic protein-7 attenuates pancreatic damage under diabetic conditions and prevents progression to diabetic nephropathy via inhibition of ferroptosis
Authors: Song Sang Hyun , Han Dawool , Park Kyeonghui , Um Jo Eun , Kim Seonghun , Ku Minhee , Yang Jaemoon , Yoo Tae-Hyun , Yook Jong In , Kim Nam Hee , Kim Hyun Sil 
Published: May 2023

BackgroundApproximately 30% of diabetic patients develop diabetic nephropathy, a representative microvascular complication. Although the etiological mechanism has not yet been fully elucidated, renal tubular damage by hyperglycemia-induced expression of transforming growth factor-β (TGF-β) is known to be involved. Recently, a new type of cell death by iron metabolism called ferroptosis was reported to be involved in kidney damage in animal models of diabetic nephropathy, which could be induced by TGF-β. Bone morphogenetic protein-7 (BMP7) is a well-known antagonist of TGF-β inhibiting TGF-β-induced fibrosis in many organs. Further, BMP7 has been reported to play a role in the regeneration of pancreatic beta cells in diabetic animal models.MethodsWe used protein transduction domain (PTD)-fused BMP7 in micelles (mPTD-BMP7) for long-lasting in vivo effects and effective in vitro transduction and secretion.ResultsmPTD-BMP7 successfully accelerated the regeneration of diabetic pancreas and impeded progression to diabetic nephropathy. With the administration of mPTD-BMP7, clinical parameters and representative markers of pancreatic damage were alleviated in a mouse model of streptozotocin-induced diabetes. It not only inhibited the downstream genes of TGF-β but also attenuated ferroptosis in the kidney of the diabetic mouse and TGF-β-stimulated rat kidney tubular cells.ConclusionBMP7 impedes the progression of diabetic nephropathy by inhibiting the canonical TGF-β pathway, attenuating ferroptosis, and helping regenerate diabetic pancreas.
Analysis of retinal and choroidal characteristics in patients with early diabetic retinopathy using WSS-OCTA
Authors: Qi Zhihao , Si Yuanyuan , Feng Feng , Zhu Jing , Yang Xuepeng , Wang Wenjuan , Zhang Yuting , Cui Yan 
Published: May 2023

IntroductionDiabetic retinopathy (DR) is one of the most common and destructive microvascular complications of DM, and has become a major cause of irreversible visual impairment. The purpose of this study was to evaluate the changes in fundus microcirculation in non-diabetic retinopathy (NDR) and mild non-proliferative diabetic retinopathy (NPDR) in patients with type 2 diabetic mellitus (T2DM) using widefield swept-source optical coherence tomography angiography (WSSOCTA), and to investigate the correlation with laboratory indices of T2DM.MethodsEighty nine, 58 and 28 eyes were included in the NDR, NPDR and Control groups, respectively, were enrolled in this study. The 12mm×12mm fundus images obtained by WSS-OCTA were divided into 9 regions (supratemporal, ST; temporal, T; inferotemporal, IT; superior, S; central macular area, C; inferior, I; supranasal, SN; nasal, N; inferonasal, IN) to evaluate changes in vessel density (VD) of the superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris, and mid-large choroidal vessel (MLCV), as well as changes in inner retinal thickness (IRT), outer retinal thickness (ORT), and choroidal thickness (CT). Results: Compared with control group, MLCV VD (I, N, IN) was significantly decreased in NDR group, SCP VD (IT, C, I) and DCP VD (T, IT, I) were significantly decreased in NPDR group. In NPDR group, DCP VD (IT) was significantly decreased compared with that in NDR group. Compared with control group, CT (ST, T, IT, S, SN, IN) was significantly declined in NDR group, and IRT (ST, IT) and ORT (ST, N) were significantly increased in NPDR group. In NPDR group, IRT (ST) and ORT (T, S) were significantly increased compared with NDR group. Correlation analysis showed that age, body mass index, fasting blood glucose, fasting insulin, fasting C-peptide, and estimated glomerular filtration rate in T2DM patients were statistically correlated with retinal and choroidal thickness/VD. DiscussionStructural and blood flow changes in the choroid occur before the onset of DR and precede changes in the retinal microcirculation, and MLCV thickness/VD is a more sensitive imaging biomarker for the clinical detection of DR. WSS-OCTA enables large-scale non-invasive visual screening and follow-up of the retinal and choroidal vasculature in DR patients, providing a new strategy for the prevention and monitoring of DR in patients with T2DM.
The oxidative aging model integrated various risk factors in type 2 diabetes mellitus at system level
Authors: Chen Yao , Yao Lilin , Zhao Shuheng , Xu Mengchu , Ren Siwei , Xie Lu , Liu Lei , Wang Yin 
Published: May 2023

BackgroundType 2 diabetes mellitus (T2DM) is a chronic endocrine metabolic disease caused by insulin dysregulation. Studies have shown that aging-related oxidative stress (as “oxidative aging”) play a critical role in the onset and progression of T2DM, by leading to an energy metabolism imbalance. However, the precise mechanisms through which oxidative aging lead to T2DM are yet to be fully comprehended. Thus, it is urgent to integrate the underlying mechanisms between oxidative aging and T2DM, where meaningful prediction models based on relative profiles are needed.MethodsFirst, machine learning was used to build the aging model and disease model. Next, an integrated oxidative aging model was employed to identify crucial oxidative aging risk factors. Finally, a series of bioinformatic analyses (including network, enrichment, sensitivity, and pan-cancer analyses) were used to explore potential mechanisms underlying oxidative aging and T2DM.ResultsThe study revealed a close relationship between oxidative aging and T2DM. Our results indicate that nutritional metabolism, inflammation response, mitochondrial function, and protein homeostasis are key factors involved in the interplay between oxidative aging and T2DM, even indicating key indices across different cancer types. Therefore, various risk factors in T2DM were integrated, and the theories of oxi-inflamm-aging and cellular senescence were also confirmed.ConclusionIn sum, our study successfully integrated the underlying mechanisms linking oxidative aging and T2DM through a series of computational methodologies.
Cardiovascular toxicity profiles of immune checkpoint inhibitors with or without angiogenesis inhibitors: a real-world pharmacovigilance analysis based on the FAERS database from 2014 to 2022
Authors: Wang Yanfeng , Cui Chanjuan , Deng Lei , Wang Lin , Ren Xiayang 
Published: May 2023

BackgroundImmune checkpoint inhibitors (ICIs) combined with angiogenesis inhibitors (AGIs) have become increasingly available for multiple types of cancers, although the cardiovascular safety profiles of this combination therapy in real-world settings have not been elucidated to date. Therefore, we aimed to comprehensively investigate the cardiovascular toxicity profiles of ICIs combined with AGIs in comparison with ICIs alone.MethodsThe Food and Drug Administration Adverse Event Reporting System (FAERS) database from the 1st quarter of 2014 to the 1st quarter of 2022 was retrospectively queried to extract reports of cardiovascular adverse events (AEs) associated with ICIs alone, AGIs alone and combination therapy. To perform disproportionality analysis, the reporting odds ratios (RORs) and information components (ICs) were calculated with statistical shrinkage transformation formulas and a lower limit of the 95% confidence interval (CI) for ROR (ROR025) &gt; 1 or IC (IC025) &gt; 0 with at least 3 reports was considered statistically significant.ResultsA total of 18 854 cardiovascular AE cases/26 059 reports for ICIs alone, 47 168 cases/67 595 reports for AGIs alone, and 3 978 cases/5 263 reports for combination therapy were extracted. Compared to the entire database of patients without AGIs or ICIs, cardiovascular AEs were overreported in patients with combination therapy (IC025/ROR025 = 0.559/1.478), showing stronger signal strength than those taking ICIs alone (IC025/ROR025 = 0.118/1.086) or AGIs alone (IC025/ROR025 = 0.323/1.252). Importantly, compared with ICIs alone, combination therapy showed a decrease in signal strength for noninfectious myocarditis/pericarditis (IC025/ROR025 = 1.142/2.216 vs. IC025/ROR025 = 0.673/1.614), while an increase in signal value for embolic and thrombotic events (IC025/ROR025 = 0.147/1.111 vs. IC025/ROR025 = 0.591/1.519). For outcomes of cardiovascular AEs, the frequency of death and life-threatening AEs was lower for combination therapy than ICIs alone in noninfectious myocarditis/pericarditis (37.7% vs. 49.2%) as well as in embolic and thrombotic events (29.9% vs. 39.6%). Analysis among indications of cancer showed similar findings.ConclusionOverall, ICIs combined with AGIs showed a greater risk of cardiovascular AEs than ICIs alone, mainly due to an increase in embolic and thrombotic events while a decrease in noninfectious myocarditis/pericarditis. In addition, compared with ICIs alone, combination therapy presented a lower frequency of death and life-threatening in noninfectious myocarditis/pericarditis and embolic and thrombotic events.
Circulating sepsis-related metabolite sphinganine could protect against intestinal damage during sepsis
Authors: Wang Zetian , Qi Yue , Wang Fei , Zhang Baiyin , Jianguo Tang 
Published: May 2023

IntroductionSepsis is intricately linked to intestinal damage and barrier dysfunction. At present times, there is a growing interest in a metabolite-based therapy for multiple diseases.MethodsSerum samples from septic patients and healthy individuals were collected and their metabonomics profiling assessed using Ultra-Performance Liquid Chromatography-Time of Flight Mass Spectrometry (UPLC-TOFMS). The eXtreme Gradient Boosting algorithms (XGBOOST) method was used to screen essential metabolites associated with sepsis, and five machine learning models, including Logistic Regression, XGBoost, GaussianNB(GNB), upport vector machines(SVM) and RandomForest were constructed to distinguish sepsis including a training set (75%) and validation set(25%). The area under the receiver-operating characteristic curve (AUROC) and Brier scores were used to compare the prediction performances of different models. Pearson analysis was used to analysis the relationship between the metabolites and the severity of sepsis. Both cellular and animal models were used to HYPERLINK "javascript:;" assess the function of the metabolites.ResultsThe occurrence of sepsis involve metabolite dysregulation. The metabolites mannose-6-phosphate and sphinganine as the optimal sepsis-related variables screened by XGBOOST algorithm. The XGBoost model (AUROC=0.956) has the most stable performance to establish diagnostic model among the five machine learning methods. The SHapley Additive exPlanations (SHAP) package was used to interpret the XGBOOST model. Pearson analysis reinforced the expression of Sphinganine, Mannose 6-phosphate were positively associated with the APACHE-II, PCT, WBC, CRP, and IL-6. We also demonstrated that sphinganine strongly diminished the LDH content in LPS-treated Caco-2 cells. In addition, using both in vitro and in vivo examination, we revealed that sphinganine strongly protects against sepsis-induced intestinal barrier injury.DiscussionThese findings highlighted the potential diagnostic value of the ML, and also provided new insight into enhanced therapy and/or preventative measures against sepsis.