bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of Ferroptosis-Related Genes Shapes Tumor Microenvironment and Pharmacological Profile in Gastric Cancer
Authors: Xiao Shilang , Liu Xiaoming , Yuan Lingzhi , Chen Xiao , Wang Fen 
Published: October 2021

Background: Ferroptosis is a form of regulated cell death that occurs as a consequence of lethal lipid peroxidation. A wealth of studies has demonstrated that ferroptosis profoundly modulated numerous biological behaviors of tumor. However, its natural functions in gastric cancer (GC) remain to be explored.Methods: Firstly, a total of over 1,000 GC patients from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database were included in our study. Secondly, 32 ferroptosis-related genes were extracted from the ferrDb website. Then, unsupervised clustering was performed to classify patients into three distinct ferroptosis-related clusters. Subsequently, we systematically and comprehensively explored the biological characteristics of each cluster. Finally, we constructed a scoring system, named ferroptosis score, to quantify each cluster and also investigated the predictive therapeutic value of the ferroptosis score for chemotherapy and immunotherapy.Results: Based on the expressions of 32 ferroptosis-related genes, three distinct ferroptosis-related subtypes with various biological characteristics were determined. Integrated analysis showed that cluster 1 is a microsatellite instability (MSI)-like subtype, cluster 2 is an epithelial–mesenchymal transition (EMT)-like subtype, while cluster 3 tends to be a metabolic-like subtype. Prognostic analysis revealed that patients in cluster 2 had a worse overall survival and relapse-free survival. The distribution of the ferroptosis score was significantly different in clusters and gene clusters. The ferroptosis score could predict the biological characteristics of each cluster, the stromal activity, and progression of tumor. The low ferroptosis score group was characterized by the activation of antigen processing and presentation, DNA damage repair pathways, and metabolic pathways, while the high ferroptosis score group was characterized by stromal activation. In response to anticancer drugs, the ferroptosis score was highly negatively associated with drugs targeting MAPK signaling and PI3K/mTOR signaling, while it was positively correlated with drugs targeting the cell cycle, mitosis, and metabolism. Finally, we also proved that the ferroptosis score could serve as a reliable biomarker to predict response to immunotherapy.Conclusion: This work revealed that tumor cells and their surrounding microenvironment could be shaped by varying the activation degrees of ferroptosis. Establishing ferroptosis-related subtypes would guide in predicting the biological features of individual tumors and selecting appropriate treatment protocols for patients.
4-Hydroxy-2-Nonenal Promotes Cardiomyocyte Necroptosis via Stabilizing Receptor-Interacting Serine/Threonine-Protein Kinase 1
Authors: Zhai Xiaoxuan , Wang Wenjun , Sun Shukun , Han Yu , Li Jiaxin , Cao Shengchuan , Li Ruochuan , Xu Tonghui , Yuan Qiuhuan , Wang Jiali , Wei Shujian , Chen Yuguo 
Published: October 2021

Background: Necroptosis is a vital regulator of myocardial ischemia/reperfusion (MI/R) injury. Meanwhile, 4-hydroxy-2-nonenal (4-HNE) is abundantly increased during MI/R injury. However, whether 4-HNE induces cardiomyocyte necroptosis during MI/R remains unknown.Methods: To observe the relationship between 4-HNE and necroptosis during MI/R, C57BL/6 mice and aldehyde dehydrogenase 2-transgenic (ALDH2-Tg) mice were both exposed to left anterior descending artery ligation surgery to establish MI/R injury models. For further study, isolated mouse hearts and H9c2 cells were both treated with 4-HNE to elucidate the underlying mechanisms.Results: Necroptosis and 4-HNE were both upregulated in I/R-injured hearts. Cardiomyocyte necroptosis was significantly decreased in I/R-injured hearts from ALDH2-Tg mice as compared with that of wild-type mice. In vitro studies showed that necroptosis was enhanced by 4-HNE perfusion in a time- and concentration-dependent manner. Knockdown of receptor-interacting serine/threonine-protein kinase 1 (RIP1) using small interfering RNA (siRNA) prevented 4-HNE-induced cardiomyocyte necroptosis, manifesting that RIP1 played a key role in the upregulation of cell necroptosis by 4-HNE. Further studies found that 4-HNE reduced the protein degradation of RIP1 by preventing K48-polyubiquitination of RIP1.Conclusion: 4-HNE contributes to cardiomyocyte necroptosis by regulating ubiquitin-mediated proteasome degradation of RIP1.
De Novo Hepatocellular Carcinoma in Hepatitis C-Related Cirrhosis: Are Advanced Glycation End Products a Key Driver?
Authors: Abdel-Razik Ahmed , Shabana Walaa , El Nakib Ahmed Mohamed , Abdelsalam Mostafa , Abdelwahab Ahmed , Hasan Ahmad S. , Elzehery Rasha , Elhelaly Rania , Fathy Aya Ahmed , Mostafa Sally Abdallah , El-Wakeel Niveen , Moemen Dalia , Eldars Waleed , Yassen Ahmed H. 
Published: October 2021

Background and PurposeThe advanced glycation end products (AGEs) have been implicated in different diseases’ pathogenesis, but their role in hepatocellular carcinoma (HCC) is still a matter of debate. This study aims to investigate the association of AGEs with HCC development in patients with hepatitis C-related cirrhosis.MethodsOnly 153 of the 181 non-diabetic patients with cirrhosis were consecutively involved in this pilot cohort prospective study, along with 34 healthy control participants. Demographic characteristics, biochemical parameters, clinical data, and AGEs levels in all subjects at the starting point and every year after that for two years were assessed. Multivariable Cox regression analysis was used to settle variables that could predict HCC development within this period.ResultsHCC developed in 13 (8.5%) patients. Univariate Cox regression analysis reported that body mass index (P=0.013), homeostatic model assessment-insulin resistance (P=0.006), alpha-fetoprotein (P &lt;0.001), and AGEs levels (P &lt;0.001) were related to HCC development. After adjusting multiple confounders, the multivariable Cox regression model has revealed that AFP and AGEs were the powerful parameters related to the HCC occurrence (all P&lt;0.05). AGEs at a cutoff value of more than 79.6 ng/ml had 100% sensitivity, 96.4% specificity, and 0.999 area under the curve (all P&lt;0.001), using the receiver operating characteristic curve, for prediction of HCC development.ConclusionThis work suggests that AGEs are associated with an increased incidence of HCC, particularly in cirrhosis, which is encouraging in decreasing the risk of HCC in these patients.
Impact of Bead-Beating Intensity on the Genus- and Species-Level Characterization of the Gut Microbiome Using Amplicon and Complete 16S rRNA Gene Sequencing
Authors: Zhang Bo , Brock Matthew , Arana Carlos , Dende Chaitanya , van Oers Nicolai Stanislas , Hooper Lora V. , Raj Prithvi 
Published: October 2021

Bead-beating within a DNA extraction protocol is critical for complete microbial cell lysis and accurate assessment of the abundance and composition of the microbiome. While the impact of bead-beating on the recovery of OTUs at the phylum and class level have been studied, its influence on species-level microbiome recovery is not clear. Recent advances in sequencing technology has allowed species-level resolution of the microbiome using full length 16S rRNA gene sequencing instead of smaller amplicons that only capture a few hypervariable regions of the gene. We sequenced the v3-v4 hypervariable region as well as the full length 16S rRNA gene in mouse and human stool samples and discovered major clusters of gut bacteria that exhibit different levels of sensitivity to bead-beating treatment. Full length 16S rRNA gene sequencing unraveled vast species diversity in the mouse and human gut microbiome and enabled characterization of several unclassified OTUs in amplicon data. Many species of major gut commensals such as Bacteroides, Lactobacillus, Blautia, Clostridium, Escherichia, Roseburia, Helicobacter, and Ruminococcus were identified. Interestingly, v3-v4 amplicon data classified about 50% of Ruminococcus reads as Ruminococcus gnavus species which showed maximum abundance in a 9 min beaten sample. However, the remaining 50% of reads could not be assigned to any species. Full length 16S rRNA gene sequencing data showed that the majority of the unclassified reads were Ruminococcus albus species which unlike R. gnavus showed maximum recovery in the unbeaten sample instead. Furthermore, we found that the Blautia hominis and Streptococcus parasanguinis species were differently sensitive to bead-beating treatment than the rest of the species in these genera. Thus, the present study demonstrates species level variations in sensitivity to bead-beating treatment that could only be resolved with full length 16S rRNA sequencing. This study identifies species of common gut commensals and potential pathogens that require minimum (0-1 min) or extensive (4-9 min) bead-beating for their maximal recovery.
Microbiome Compositions From Infertile Couples Seeking In Vitro Fertilization, Using 16S rRNA Gene Sequencing Methods: Any Correlation to Clinical Outcomes?
Authors: Okwelogu Somadina I. , Ikechebelu Joseph I. , Agbakoba Nneka R. , Anukam Kingsley C. 
Published: October 2021

BackgroundBacterial infections are usually suspected in infertile couples seeking IVF with no clear understanding of the microbial compositions present in the seminal fluids and vaginal niche of the patients. We used next-generation sequencing technology to correlate microbiota compositions with IVF clinical outcomes.MethodsThirty-six couples were recruited to provide seminal fluids and vaginal swabs. Bacterial DNA was extracted, and V4 region of the 16S rRNA was amplified and sequenced in a pair-end configuration on the Illumina MiSeq platform rendering 2 × 150 bp sequences. Microbial taxonomy to species level was generated using the Greengenes database. Linear discriminant analysis (LDA) effect size (LEfSe) was used to identify biologically and statistically significant differences in relative abundance.ResultsSeminal fluid microbiota compositions had lower bacterial concentrations compared with the vagina, but species diversity was significantly higher in seminal fluid samples. Azoospermic subjects had more relative abundance of Mycoplasma and Ureaplasma. In Normospermic semen, Lactobacillus (43.86%) was the most abundant, followed by Gardnerella (25.45%), while the corresponding vaginal samples, Lactobacillus (61.74%) was the most abundant, followed by Prevotella (6.07%) and Gardnerella (5.86%).ConclusionsSemen samples with positive IVF were significantly colonized by Lactobacillus jensenii (P=0.002), Faecalibacterium (P=0.042) and significantly less colonized by Proteobacteria, Prevotella, Bacteroides, and lower Firmicutes/Bacteroidetes ratio compared with semen samples with negative IVF. Vaginal samples with positive IVF clinical outcome were significantly colonized by Lactobacillus gasseri, less colonized by Bacteroides and Lactobacillus iners. This study has opened a window of possibility for Lactobacillus replenishments in men and women before IVF treatment.
Diversity of Cardiologic Issues in a Contemporary Cohort of Women With Breast Cancer
Authors: Tini Giacomo , Ameri Pietro , Buzzatti Giulia , Sarocchi Matteo , Murialdo Roberto , Guglielmi Giulia , Arboscello Eleonora , Ballestrero Alberto , Del Mastro Lucia , Spallarossa Paolo , Porto Italo 
Published: October 2021

Background: Women with breast cancer (BC) represent a special population particularly exposed to cardiovascular disease (CVD) risk. However, cardiologic assessment in BC is mostly limited to detection of left ventricular dysfunction cardiotoxicity (LVD-CTX) due to anticancer treatments. Our aim was to comprehensively investigate CV profile and events in a contemporary BC cohort.Methods and Results: Records of BC patients referred for a Cardio-Oncologic evaluation before starting anticancer treatments, between 2016 and 2019, were retrospectively reviewed (n = 508). Information regarding prevalence and control of CV risk factors, and novel CVD diagnoses were extracted. Occurrence of LVD-CTX, CV events other than LVD-CTX and mortality was assessed. Mean age of study population was 64 ± 13 years; 287 patients were scheduled to receive anthracycline and 165 anti-HER2 therapy. Overall, 53% of BC women had ≥2 CV risk factors, and 67% had at least one of arterial hypertension, dyslipidaemia or diabetes mellitus not adequately controlled. Eighteen (4%) patients were diagnosed a previously unknown CVD. Over a mean follow-up of 2.5 ± 1 years, 3% of BC patients developed LVD-CTX, 2% suffered from other CV events and 11% died. CV risk factors were not associated with LVD-CTX, except for family history of CAD. On the contrary, patients with other CV events exhibited a worse CV profile. Those who died more commonly experienced CV events other than LVD-CTX (p = 0.02).Conclusions: BC women show a suboptimal CV risk profile and are at risk of CV events not limited to LVD-CTX. A baseline Cardio-Oncologic evaluation was instrumental to implement CV prevention and to optimize CV therapies.
Troponin T Elevation After Percutaneous Left Atrial Appendage Occlusion
Authors: Wang Xiaoyan , Chen Xueying , Ye Yong , Peng Juan , Lin Jinyi , Deng Xin , Lin Li , You Jieyun , Wang Xingxu , Zhou Daxin , Chen Qingxing , Ge Junbo 
Published: October 2021

Background: Cardiac troponin T (cTNT) has been widely used in detecting cardiac damage. Elevated cTNT level has been reported to be associated with increased mortality in multiple cardiac conditions. It is not uncommon to observe an increased level of cTNT in patients after left atrial appendage occlusion (LAAO). The objective of the study is to study the incidence, significance, and factors associated with cTNT elevation after LAAO.Methods: We prospectively included patients who underwent LAAO from January 2019 to July 2020 in Fudan Zhongshan Hospital. Patients were divided into those with elevated cTNT after procedure and those with normal postprocedure cTNT. All individuals were followed up for 1 year. The primary outcome is major adverse cardiovascular events, which include myocardial infarction, heart failure, cardiac death, and stroke. The second outcome is periprocedure complication, including chest pain, tachycardia, cardiac tamponade, change of electrocardiograph, and atrial thrombus.Results: A total of 190 patients were enrolled. Of the patients, 85.3% had elevated cTNT after LAAO, while 14.7% of them did not. Exposure time, dosage of contrast, types of devices, shapes, and sizes of LAA could contribute to elevated postprocedure cTNT. We found that patients with a Watchman device were more likely to have elevated postprocedure cTNT than those with a Lambre device (89.2 vs. 76.7%, p = 0.029). LAAO shapes were associated with cTNT levels in patients with a Watchman device, while the diameter of the outer disc and LAA depth mattered for the Lambre device. There was no significant difference in the primary and second outcome between the two groups (p-value: 0.619, 0.674).Conclusion: LAAO was found to be commonly accompanied with cTNT elevation, which might not to be related to the complications and adverse cardiac outcomes within 1 year of follow-up. Moreover, eGFR at baseline, exposure time, dosage of contrast, types of LAAO device, and LAA morphology could contribute to cTNT elevation.
Hydrological Evolution of a Lake Recharged by Groundwater in the Badain Jaran Desert Over the Past 140 years
Authors: Jiang Gaolei , Wang Nai’ang , Mao Xin , Zhao Hua , Liu Linjing , Shen Jianmei , Nie Zhenlong , Wang Zhe 
Published: October 2021

Understanding the evolution of lakes in arid areas is very important for water resource management. Previous studies have mainly focused on lakes with runoff recharge, while the evolution of groundwater recharge lakes in hyper-arid areas is still less known. In this study, an 86 cm-long sediment core was extracted from Sayinwusu Lake, one of groundwater-recharge lakes in the southeastern Badain Jaran Desert, Northwest China. 210Pb and 137Cs dating, total organic carbon (TOC) and total nitrogen (TN) contents, and mineral content analysis were used to reconstruct the lake evolution over the past 140 years. The evolution of Sayinwusu Lake since 1880 can be divided into two periods. In the first period from 1880 to 1950, the TOC and TN contents were low, and the minerals consisted of all detrital minerals, which indicate that the lake’s primary productivity and salinity were low. During the second period from 1950 to 2018, the contents of TOC, TN, and carbonate minerals increased rapidly at the beginning of the 1950s, indicating that the lake’s primary productivity and salinity increased. Comprehensive analysis of regional climate data suggests that the increase in evaporation caused by rising temperature is an important factor affecting lake evolution in the desert. Although precipitation has increased in the arid region of Northwest China in recent decades with increasing temperature, the enhancement of the evaporation effect is much greater. As a record from groundwater recharge lakes in deserts, our study provides new insight into projecting future lake changes in hyper-arid areas.
Spatio-Temporal Evolution of Intermediate-Depth Seismicity Beneath the Himalayas: Implications for Metamorphism and Tectonics
Authors: Michailos Konstantinos , Carpenter N. Seth , Hetényi György 
Published: October 2021

Intermediate-depth earthquakes (&gt;40 km) have been observed beneath the central Himalayas over decades, with little known about their nature and characteristics. Here, we apply a state-of-the-art systematic processing routine, starting from continuous waveform data, to obtain the most comprehensive high-quality earthquake catalog with a focus on the intermediate-depth seismicity beneath the central Himalayas. We construct a catalog containing 414 robust earthquake locations with depths ranging from 40 to 110 km spanning from late 2001 till mid-2003. We calculate earthquake magnitudes in a consistent way and obtain values ranging between ML0.8 and 4.5 with a magnitude of completeness of Mc2.4. This information allows us to study the spatiotemporal characteristics of the seismicity in great detail. Earthquakes mainly take place in a cluster, consisting of two linear segments at ca. 35° azimuth difference, situated beneath the high Himalayas in NE Nepal and adjacent S. Tibet. Seismicity there does not feature any mainshock-aftershock patterns but presents a few sequences with potential seismicity migration rates compatible with linear or diffusive migration. This result, along with previous studies in the lower Indian crust, allows interpreting these events as related to metamorphic reactions involving dehydration processes. However, given the geodynamic context, a tectonic interpretation with a dextral basement fault zone propagating beneath the Himalaya and continuing as a westward propagating tear fault would also be possible. This represents a continuous fault zone from the deep crust in S. Tibet, across the Himalaya along the Dhubri-Chungthang fault zone (DCFZ) to the Shillong plateau, which could be an inherited tectonic feature.
Investigation on Thermal Characteristics of the Oil-Circulating Hydraulic Energy Storage System for Hybrid Mining Trucks
Authors: Yi Tong , Ma Fei , Jin Chun , Hong Jichao , Liu Yanbo 
Published: October 2021

The improved hydraulic energy storage system (IHESS) is a novel compact hydraulic ESS with only 10% of oil and 64.78% of installation space of the regular ones. However, its novel circulating structure and lightweight material result in poor heat dissipation. The thermodynamic and heat transfer model of IHESS with an oil-circulating layout is proposed. Based on the mining trucks’ dynamic model, thermal characteristics of IHESSs with different parameters under the actual and simplified working conditions are studied and the factors causing overheating are analyzed. Finally, a feasible thermal design is put forward, and its efficiency is analyzed. The simulation shows that more accumulators and higher recovery power lead to higher system temperature and vice versa. Under the standard simplified working condition at 40°C ambient temperature, the highest oil temperature reached is 93.13°C. About 90% of the generated heat is converted into the internal energy of nitrogen and oil. On this basis, by adopting an energy-saving passive cooling system with a cooling power of 6.68 kW, the highest temperature of the oil drops to 52.79°C and 28% of the generated heat is released through the cooling system.
Common Statin Intolerance Variants in ABCB1 and LILRB5 Show Synergistic Effects on Statin Response: An Observational Study Using Electronic Health Records
Authors: Melhem Alaa’ Lutfi , Chourasia Mehul Kumar , Bigossi Margherita , Maroteau Cyrielle , Taylor Alasdair , Pola Roberto , Dawed Adem Y. , Tornio Aleksi , Palmer Colin N. A. , Siddiqui Moneeza K. 
Published: October 2021

Background: Statin intolerance impacts approximately 10% of statin users, with side effects ranging from mild myalgia to extreme intolerance resulting in myopathy and rhabdomyolysis. Statin intolerance results in poor adherence to therapy and can impact statin efficacy. Many genetic variants are associated with statin intolerance. The effect of these variants on statin efficacy has not been systematically explored.Methods: Using longitudinal electronic health records and genetic biobank data from Tayside, Scotland, we examined the effect of seven genetic variants with previously reported associations with simvastatin or atorvastatin intolerance on the outcome of statin response. Statin response was measured by the reduction achieved when comparing pre- and post-statin non-high-density lipoprotein-cholesterol (non-HDL-C). Post-treatment statin response was limited to non-HDL-C measured within 6months of therapy initiation. Univariate and multivariable linear regression models were used to assess the main and adjusted effect of the variants on statin efficacy.Results: Around 9,401 statin users met study inclusion criteria, of whom 8,843 were first prescribed simvastatin or atorvastatin. The average difference in post-treatment compared to pre-treatment non-HDL-cholesterol was 1.45 (±1.04) mmol/L. In adjusted analyses, only two variants, one in the gene ATP-binding cassette transporter B1 (ABCB1; rs1045642), and one in leukocyte immunoglobulin like receptor B5 (LILRB5; rs12975366), were associated with statin efficacy. In ABCB1, homozygous carriers of the C allele at rs1045642 had 0.06mmol/L better absolute reduction in non-HDL-cholesterol than carriers of the T allele (95% CI: 0.01, 0.1). In LILRB5 (rs12975366), carriers of the C allele had 0.04mmol/L better absolute reduction compared to those homozygous for the T allele (95% CI: 0.004, 0.08). When combined into a two-variant risk score, individuals with both the rs1045642-CC genotype and the rs12975366-TC or CC genotype had a 0.11mmol/L greater absolute reduction in non-HDL-cholesterol compared to those with rs1045642-TC or TT genotype and the rs12975366-TT genotype (95% CI: 0.05, 0.16; p&lt;0.001).Conclusion: We report two genetic variants for statin adverse drug reactions (ADRs) that are associated with statin efficacy. While the ABCB1 variant has been shown to have an association with statin pharmacokinetics, no similar evidence for LILRB5 has been reported. These findings highlight the value of genetic testing to deliver precision therapeutics to statin users.