bluuebunny/crossref_metadata_2025 huggingface dataset:
New working fluids for the use of heat secondary sources in mining technologies
Authors: Kirsanov Mykhailo , Gupalo Olena , Podoliak Kostiantyn
Published: April 2023

Production cost of mining enterprises can be significantly reduced when using secondary heat. A large volume of secondary heat sources has a temperature potential of no higher than 50°C. To generate additional electricity using secondary heat it has been proposed to use installations with the Rankine thermodynamic cycle in mining enterprises. The paper aim is to study the thermodynamic efficiency of using R-1234yf and R-744 in the equipment, which uses the secondary heat of mining technologies for evaporation of these working fluids. R-1234yf is a freon that belongs to the class of hydrofluoroolefins and has a much lower level of global warming potential than other ozone-depleting substances. R-744 is carbon dioxide, which belongs to a natural, non-toxic and non-flammable working substance. It has been determined that the thermodynamic efficiencies of using R-1234yf and R-744 are 10% and 6.3%, respectively. The thermodynamic efficiency has been calculated for the temperature range from 50° to 20°C, which is typical for a large volume of secondary heat sources in mining technologies.
Enhancement of the quality of marketable iron ore products of Kryvyi Rih iron ore basin
Authors: Stupnik Mykola , Oliinyk Tetiana , Pochtarev Alexey , Kalinichenko Olena , Kalinichenko Vsevolod
Published: April 2023

The main indicators of the iron ore quality are the content of iron, silica, phosphorus and other components. It is ascertained that the quality of ore depends on its grain-size composition. The article proves that when crushing 16-0 mm fraction ore to 5-0 mm, Fe content is reclassified by sizes due to liberation of both martite and hematite at this grain size. To reduce energy consumption during grinding, it is recommended to install high pressure grinding rolls for crushing the 16-1 mm fraction and consider this operation as the first stage of grinding. Martite liberation in the -1.0+0.0 mm material shows that significant predominance (87.0 vs. 13.0%) of free grains over aggregates is observed in the -0.071+0.05 mm fraction material. Free martite aggregates make 57.12% in the -0.16+0.071 mm material. Complete (100%) liberation of martite is observed in the -0.05 mm material. Sieve analysis of the A56 sinter ore sample crushed to 5-0 mm in the industrial roll crusher enables ascertaining that the greatest increase in recovery (Fetot = 60.05%) of sinter ore occurs at the -0.16+0.071 mm grain size.
Electrochemical production of hydrogen in reactors with reduced energy costs
Authors: Nefedov Volodymyr , Matveev Vadim , Sukhyy Kostiantyn , Polishchuk Yuliya , Bulat Anatolii , Bluss Borys , Mukhachev Anatoliy
Published: April 2023

To reduce climate change and carbonization of the atmosphere, today it is proposed to switch to green energy and use hydrogen as an energy source. When hydrogen burns, water forms, and carbon oxides are not released. Methods for processing solid, liquid, and gaseous fuels, as well as water electrolysis, are proposed for hydrogen production. The electrolysis of water ensures the production of chemically pure hydrogen. Its disadvantage is significant energy consumption and, as a result, high cost. The condition for the economically beneficial use of hydrogen is to reduce its cost to $1/kg. The existing designs of reactors and technologies for producing hydrogen do not allow achieving such efficiency, which is limited by the thermodynamics of the process. To reduce energy consumption, this paper proposes designs of reactors in which the process of oxygen evolution is replaced by the process of dissolving anodes made from production waste - iron and aluminium scrap. As a result of the measures taken, it is possible to reduce the voltage on the electrolyzers from 1.8 V to 0.5-0.6 V. This makes the hydrogen production process economically viable.
Study of the efficiency of using renewable hydrogen in heating equipment to reduce carbon dioxide emissions
Authors: Gupalo Olena , Yeromin Oleksandr , Kabakova Liudmyla , Kulikov Andrii , Sukhyi Mykhailo , Romanko Yaroslav
Published: April 2023

The results of theoretical study of operation of continuous furnaces heated by natural gas, renewable hydrogen, and their mixture are presented. The furnaces have the same design, but significantly different energy efficiencies due to different heat losses and capability of recuperative fume gas heat utilization system. The measures to reduce heat losses and to increase air temperature for fuel combustion can reduce specific fuel consumption for metal heating and carbon dioxide emissions by 25.8% for natural gas furnaces. For furnaces operating on mixture of natural gas and hydrogen, a greater reduction in carbon dioxide emissions is achieved in furnaces with worse energy efficiency, but with greater fuel consumption for metal heating. The paper shows the possibility of converting a furnace with better energy efficiency indicators to be heated by mixture of natural gas (75%) and hydrogen (25%). The measure reduces the natural gas consumption and carbon dioxide emissions to 9.2% due to the use of hydrogen with specific consumption 13.81 m3 per ton of metal. To ensure the same costs for metal heating when transferring continuous furnaces from natural gas to hydrogen, or their mixture, the ratio of prices for natural gas and hydrogen should not exceed 0.301-0.312.
Mathematical modeling of rocks plasma disintegration process at borehole reaming
Authors: Potapchuk Iryna , Zhevzhyk Oleksandr , Kholiavchenko Leonid , Pertsevyi Vitalii , Bosyi Dmytro , Drubetska Tetiana , Potapchuk Anna
Published: April 2023

The mathematical model of thermal disintegration of rocks during the reaming of boreholes, which takes into account the compatibility of the thermogas dynamic problem for a high-temperature heat transfer agent and the thermal problem for the rock heated by this heat transfer agent, has been developed. The mathematical model is based on the laws of conservation of mass, quantity of motion and energy and takes into account the dependences for determining the thermal stresses and the temperature of brittle fracture of rocks. As a result of solving the equations of the mathematical model, the temperature distribution in the rock mass (magnetite quartzite) during heating in the process of borehole plasma reaming and productivity of the borehole plasma reaming process are obtained. Calculated and experimentally determined productivity of the process of plasma reaming of the borehole were compared.
Summary statistics-based association test for identifying the pleiotropic effects with set of genetic variants
Authors: Bu Deliang , Wang Xiao , Li Qizhai
Published: April 2023

Motivation

Traditional genome-wide association study focuses on testing one-to-one relationship between genetic variants and complex human diseases or traits. While its success in the past decade, this one-to-one paradigm lacks efficiency because it does not utilize the information of intrinsic genetic structure and pleiotropic effects. Due to privacy reasons, only summary statistics of current genome-wide association study data are publicly available. Existing summary statistics-based association tests do not consider covariates for regression model, while adjusting for covariates including population stratification factors is a routine issue.

Results

In this work, we first derive the correlation coefficients between summary Wald statistics obtained from linear regression model with covariates. Then, a new test is proposed by integrating three-level information including the intrinsic genetic structure, pleiotropy, and the potential information combinations. Extensive simulations demonstrate that the proposed test outperforms three other existing methods under most of the considered scenarios. Real data analysis of polyunsaturated fatty acids further shows that the proposed test can identify more genes than the compared existing methods.

Availability and implementation

Code is available at https://github.com/bschilder/ThreeWayTest.
Financial Education in Secondary Education: A Cross-Country Analysis
Authors: Lopez-Agudo Luis Alejandro , Marcenaro-Gutierrez Oscar David
Published: April 2023

We live in a society in which knowing how to manage money is a necessity, since it is required in our everyday life. In this context, financial literacy is a competence which people should develop in order to improve their money-related decisions. In order to analyse the contribution of financial education to this competence, we go beyond the previous literature in respect to correlation by using student fixed-effects and PISA (Programme for International Student Assessment) 2018 data for 15-year-old students in 20 countries. Our results show that, in most of the countries under analysis, the financial education that students receive in the subject of mathematics may contribute to the development of their financial literacy competences. Nevertheless, the lack of an effective subject in economics is still an issue in most of the educational systems under analysis. (JEL codes: I20, I21, I28, and C10)
Skeletal muscle transcriptomics dissects the pathogenesis of Friedreich’s ataxia
Authors: Indelicato Elisabetta , Kirchmair Alexander , Amprosi Matthias , Steixner Stephan , Nachbauer Wolfgang , Eigentler Andreas , Wahl Nico , Apostolova Galina , Krogsdam Anne , Schneider Rainer , Wanschitz Julia , Trajanoski Zlatko , Boesch Sylvia
Published: April 2023

Objective: In Friedreich’s ataxia (FRDA), the most affected tissues are not accessible to sampling and available transcriptomic findings originate from blood-derived cells and animal models. Herein, we aimed at dissecting for the first time the pathophysiology of FRDA by means of RNA-sequencing in an affected tissue sampled in vivo. Methods: Skeletal muscle biopsies were collected from seven FRDA patients before and after treatment with recombinant human Erythropoietin (rhuEPO) within a clinical trial. Total RNA extraction, 3′-mRNA library preparation and sequencing were performed according to standard procedures. We tested for differential gene expression with DESeq2 and performed gene set enrichment analysis with respect to control subjects. Results: FRDA transcriptomes showed 1873 genes differentially expressed from controls. Two main signatures emerged: (1) a global downregulation of the mitochondrial transcriptome as well as of ribosome/translational machinery and (2) an upregulation of genes related to transcription and chromatin regulation, especially of repressor terms. Downregulation of the mitochondrial transcriptome was more profound than previously shown in other cellular systems. Furthermore, we observed in FRDA patients a marked upregulation of leptin, the master regulator of energy homeostasis. RhuEPO treatment further enhanced leptin expression. Interpretation: Our findings reflect a double hit in the pathophysiology of FRDA: a transcriptional/translational issue and a profound mitochondrial failure downstream. Leptin upregulation in the skeletal muscle in FRDA may represent a compensatory mechanism of mitochondrial dysfunction, which is amenable to pharmacological boosting. Skeletal muscle transcriptomics is a valuable biomarker to monitor therapeutic interventions in FRDA.
Genetic analyses reveal a non-panmictic genetic structure in the sablefishAnoplopoma fimbriain the northern Pacific
Authors: Orozco-Ruiz A M , Galván-Tirado C , Orlov A M , Orlova S Y , García-De León F J
Published: April 2023

The sablefish Anoplopoma fimbria is distributed on the continental shelf of the North Pacific, has a high commercial value for both fisheries and aquaculture, and represents a shared resource between countries in the North Pacific basin. In the present study, we extend the geographic range surveyed in previous studies and reexamine the population’s genetic structure by integrating phylogeographic patterns of mitochondrial DNA and microsatellite DNA markers. Our results contradict the proposal that sablefish constitute a single population throughout their distributional range. We observed a signal of ancient divergence in mtDNA that differentiates the North Pacific West Coast from the rest of the sample sites, and microsatellite markers reveal a contemporary isolation of Mexican sablefish. Our findings show genetic differences between localities that should be explored in more detail to fully understand the interconnectedness that appears to exist between populations.
Activation of mTORC1 Signaling Cascade in Hippocampus and Medial Prefrontal Cortex Is Required for Antidepressant Actions of Vortioxetine in Mice
Authors: Li Wei-Yu , Shi Tian-Shun , Huang Jie , Chen Yan-Mei , Guan Wei , Jiang Bo , Wang Cheng-Niu
Published: April 2023

Background

Although thought of as a multimodal-acting antidepressant targeting the serotonin system, more molecules are being shown to participate in the antidepressant mechanism of vortioxetine. A previous report has shown that vortioxetine administration enhanced the expression of rapamycin complex 1 (mTORC1) in neurons. It has been well demonstrated that mTORC1 participates in not only the pathogenesis of depression but also the pharmacological mechanisms of many antidepressants. Therefore, we speculate that the antidepressant mechanism of vortioxetine may require mTORC1.

Methods

Two mouse models of depression (chronic social defeat stress and chronic unpredictable mild stress) and western blotting were first used together to examine whether vortioxetine administration produced reversal effects against the chronic stress–induced downregulation in the whole mTORC1 signaling cascade in both the hippocampus and medial prefrontal cortex (mPFC). Then, LY294002, U0126, and rapamycin were used together to explore whether the antidepressant effects of vortioxetine in mouse models of depression were attenuated by pharmacological blockade of the mTORC1 system. Furthermore, lentiviral-mTORC1-short hairpin RNA-enhanced green fluorescence protein (LV-mTORC1-shRNA-EGFP) was adopted to examine if genetic blockade of mTORC1 also abolished the antidepressant actions of vortioxetine in mice.

Results

Vortioxetine administration produced significant reversal effects against the chronic stress–induced downregulation in the whole mTORC1 signaling cascade in both the hippocampus and mPFC. Both pharmacological and genetic blockade of the mTORC1 system notably attenuated the antidepressant effects of vortioxetine in mice.

Conclusions

Activation of the mTORC1 system in the hippocampus and mPFC is required for the antidepressant actions of vortioxetine in mice.
Being in a Horror Movie
Authors: Falconer Pete
Published: April 2023

This article takes as its starting point a recurring complaint in the popular reception of horror movies: that the characters in them behave foolishly. I argue that such complaints fail to recognize that the horror genre exploits a fundamental tension in fiction, between the perspective on a fictional world offered to its audience and that available to its characters. This distinction is highlighted in horror, which often depicts characters with everyday expectations facing extraordinary threats. Horror characters are frequently taken by surprise, and even the better prepared can be thwarted by the malevolence of the generic world. The extent of characters’ misfortunes can resemble deliberate persecution, self-consciously flaunting authorial manipulation. I draw on Todorov’s notion of “pan-determinism” and suggest that a more sinister variant operates in horror. Occasionally, a character’s experiences can help equip them to survive; I argue that this can be inflected politically in films where the malevolent horror world is placed alongside forms of real-life persecution and abuse. Critical attention to the world of horror, and how it is understood from both the outside and within, can clarify the connections between different theoretical understandings of the genre and bring out important but overlooked generic conventions.
Graph convolutional network-based fusion model to predict risk of hospital acquired infections
Authors: Tariq Amara , Lancaster Lin , Elugunti Praneetha , Siebeneck Eric , Noe Katherine , Borah Bijan , Moriarty James , Banerjee Imon , Patel Bhavik N
Published: April 2023

Objective

Hospital acquired infections (HAIs) are one of the top 10 leading causes of death within the United States. While current standard of HAI risk prediction utilizes only a narrow set of predefined clinical variables, we propose a graph convolutional neural network (GNN)-based model which incorporates a wide variety of clinical features.

Materials and Methods

Our GNN-based model defines patients’ similarity based on comprehensive clinical history and demographics and predicts all types of HAI rather than focusing on a single subtype. An HAI model was trained on 38 327 unique hospitalizations while a distinct model for surgical site infection (SSI) prediction was trained on 18 609 hospitalization. Both models were tested internally and externally on a geographically disparate site with varying infection rates.

Results

The proposed approach outperformed all baselines (single-modality models and length-of-stay [LoS]) with achieved area under the receiver operating characteristics of 0.86 [0.84–0.88] and 0.79 [0.75–0.83] (HAI), and 0.79 [0.75–0.83] and 0.76 [0.71–0.76] (SSI) for internal and external testing. Cost-effective analysis shows that the GNN modeling dominated the standard LoS model strategy on the basis of lower mean costs ($1651 vs $1915).

Discussion

The proposed HAI risk prediction model can estimate individualized risk of infection for patient by taking into account not only the patient’s clinical features, but also clinical features of similar patients as indicated by edges of the patients’ graph.

Conclusions

The proposed model could allow prevention or earlier detection of HAI, which in turn could decrease hospital LoS and associated mortality, and ultimately reduce the healthcare cost.
A predictive model for lung cancer screening nonadherence in a community setting health-care network
Authors: Bastani Mehrad , Chiuzan Codruta , Silvestri Gerard , Raoof Suhail , Chusid Jesse , Diefenbach Michael , Cohen Stuart L
Published: April 2023

Background

Lung cancer screening (LCS) decreases lung cancer mortality. However, its benefit may be limited by nonadherence to screening. Although factors associated with LCS nonadherence have been identified, to the best of our knowledge, no predictive models have been developed to predict LCS nonadherence. The purpose of this study was to develop a predictive model leveraging a machine learning model to predict LCS nonadherence risk.

Methods

A retrospective cohort of patients who enrolled in our LCS program between 2015 and 2018 was used to develop a model to predict the risk of nonadherence to annual LCS after the baseline examination. Clinical and demographic data were used to fit logistic regression, random forest, and gradient-boosting models that were internally validated on the basis of accuracy and area under the receiver operating curve.

Results

A total of 1875 individuals with baseline LCS were included in the analysis, with 1264 (67.4%) as nonadherent. Nonadherence was defined on the basis of baseline chest computed tomography (CT) findings. Clinical and demographic predictors were used on the basis of availability and statistical significance. The gradient-boosting model had the highest area under the receiver operating curve (0.89, 95% confidence interval = 0.87 to 0.90), with a mean accuracy of 0.82. Referral specialty, insurance type, and baseline Lung CT Screening Reporting & Data System (LungRADS) score were the best predictors of nonadherence to LCS.

Conclusions

We developed a machine learning model using readily available clinical and demographic data to predict LCS nonadherence with high accuracy and discrimination. After further prospective validation, this model can be used to identify patients for interventions to improve LCS adherence and decrease lung cancer burden.
Comparison of plastid proteomes points towards a higher plastidial redox turnover in vascular tissues than in mesophyll cells
Authors: Boussardon Clément , Carrie Chris , Keech Olivier
Published: April 2023

Plastids are complex organelles that vary in size and function depending on the cell type. Accordingly, they can be referred to as amyloplasts, chloroplasts, chromoplasts, etioplasts, or proplasts, to only cite a few. Over the past decades, methods based on density gradients and differential centrifugation have been extensively used for the purification of plastids. However, these methods need large amounts of starting material, and hardly provide a tissue-specific resolution. Here, we applied our IPTACT (Isolation of Plastids TAgged in specific Cell Types) method, which involves the biotinylation of plastids in vivo using one-shot transgenic lines expressing the Translocon of the Outer Membrane 64 (TOC64) gene coupled with a biotin ligase receptor particle and the BirA biotin ligase, to isolate plastids from mesophyll and companion cells of Arabidopsis using tissue specific pCAB3 and pSUC2 promoters, respectively. Subsequently, a proteome profiling was performed, which allowed the identification of 1672 proteins, among which 1342 were predicted to be plastidial, and 705 were fully confirmed according to the SUBA5 database. Interestingly, although 92% of plastidial proteins were equally distributed between the two tissues, we observed an accumulation of proteins associated with jasmonic acid biosynthesis, plastoglobuli (e.g. NAD(P)H dehydrogenase C1, vitamin E deficient 1, plastoglobulin of 34 kDa, ABC1-like kinase 1) and cyclic electron flow in plastids originating from vascular tissue. Besides demonstrating the technical feasibility of isolating plastids in a tissue-specific manner, our work provides strong evidence that plastids from vascular tissue have a higher redox turnover to ensure optimal functioning, notably under high solute strength as encountered in vascular cells.
TheEscherichia coliFur pan-regulon has few conserved but many unique regulatory targets
Authors: Gao Ye , Bang Ina , Seif Yara , Kim Donghyuk , Palsson Bernhard O
Published: April 2023

While global transcription factors (TFs) have been studied extensively in Escherichia coli model strains, conservation and diversity in TF regulation between strains is still unknown. Here we use a combination of ChIP-exo–to define ferric uptake regulator (Fur) binding sites–and differential gene expression–to define the Fur regulon in nine E. coli strains. We then define a pan-regulon consisting of 469 target genes that includes all Fur target genes in all nine strains. The pan-regulon is then divided into the core regulon (target genes found in all the strains, n = 36), the accessory regulon (target found in two to eight strains, n = 158) and the unique regulon (target genes found in one strain, n = 275). Thus, there is a small set of Fur regulated genes common to all nine strains, but a large number of regulatory targets unique to a particular strain. Many of the unique regulatory targets are genes unique to that strain. This first-established pan-regulon reveals a common core of conserved regulatory targets and significant diversity in transcriptional regulation amongst E. coli strains, reflecting diverse niche specification and strain history.
CDK12/13 promote splicing of proximal introns by enhancing the interaction between RNA polymerase II and the splicing factor SF3B1
Authors: Panzeri Valentina , Pieraccioli Marco , Cesari Eleonora , de la Grange Pierre , Sette Claudio
Published: April 2023

Transcription-associated cyclin-dependent kinases (CDKs) regulate the transcription cycle through sequential phosphorylation of RNA polymerase II (RNAPII). Herein, we report that dual inhibition of the highly homologous CDK12 and CDK13 impairs splicing of a subset of promoter-proximal introns characterized by weak 3′ splice sites located at larger distance from the branchpoint. Nascent transcript analysis indicated that these introns are selectively retained upon pharmacological inhibition of CDK12/13 with respect to downstream introns of the same pre-mRNAs. Retention of these introns was also triggered by pladienolide B (PdB), an inhibitor of the U2 small nucelar ribonucleoprotein (snRNP) factor SF3B1 that recognizes the branchpoint. CDK12/13 activity promotes the interaction of SF3B1 with RNAPII phosphorylated on Ser2, and disruption of this interaction by treatment with the CDK12/13 inhibitor THZ531 impairs the association of SF3B1 with chromatin and its recruitment to the 3′ splice site of these introns. Furthermore, by using suboptimal doses of THZ531 and PdB, we describe a synergic effect of these inhibitors on intron retention, cell cycle progression and cancer cell survival. These findings uncover a mechanism by which CDK12/13 couple RNA transcription and processing, and suggest that combined inhibition of these kinases and the spliceosome represents an exploitable anticancer approach.
Provider Referral Patterns and Surgical Utilization Among New Patients Seen in Spine Clinic
Authors: Araghi Kasra , Subramanian Tejas , Haque Nawaal , Merrill Robert , Amen Troy B. , Shahi Pratyush , Singh Sumedha , Maayan Omri , Sheha Evan , Dowdell James , Iyer Sravisht , Qureshi Sheeraz A.
Published: April 2023

Study Design.

Retrospective chart review.

Objective:

The objective of this study was to elucidate the demographics of patient referrals from different sources and identify factors that affect a patient’s likelihood of undergoing surgery.

Summary of Background Data.

Despite baseline factors for surgical consideration, such as attempting conservative management, surgeons encounter many patients who are not surgically indicated. Overreferrals, that is, a patient referred to a surgeon that does not need surgery, can result in long wait times, delayed care, worse outcomes, and resource waste.

Materials and Methods.

All new patients at a single academic institution seen in the clinic by eight spine surgeons between January 1, 2018, and January 1, 2022, were analyzed. Referral types included self-referral, musculoskeletal (MSK), and non-MSK provider referral. Patient demographics included age, body mass index (BMI), zip code as a proxy for socioeconomic status, sex, insurance type, and surgical procedures undergone within 1.5 years postclinic visit. Analysis of variance and a Kruskal-Wallis test was used to compare means among normally and non-normally disturbed referral groups, respectively. Multivariable logistic regressions were run to assess demographic variables associated with undergoing surgery.

Results.

From 9356 patients, 84% (7834) were self-referred, 3% (319) were non-MSK, and 13% (1203) were MSK. A statistically significant association with ultimately undergoing surgery was observed with MSK referral type compared with non-MSK referral [odds ratio (OR)=1.37, CI: 1.04–1.82, P=0.0246]. Additional independent variables observed to be associated with patients undergoing surgery included older age (OR=1.004, CI: 1.002–1.007, P=0.0018), higher BMI (OR=1.02, CI: 1.011–1.029, P<0.0001), high-income quartile (OR=1.343, CI: 1.177–1.533, P<0.0001), and male sex (OR=1.189, CI: 1.085–1.302, P=0.0002).

Conclusions.

A statistically significant association with undergoing surgery was observed with a referral by an MSK provider, older age, male sex, high BMI, and a high-income quartile home zip code. Understanding these factors and patterns is critical for optimizing practice efficiency and reducing the burdens of inappropriate referrals.
Severity of non-alcoholic fatty liver disease is a risk factor for developing hypertension from prehypertension
Authors: Song Qirui , Ling Qianhui , Fan Luyun , Deng Yue , Gao Qiannan , Yang Ruixue , Chen Shuohua , Wu Shouling , Cai Jun
Published: April 2023

Background:

There is little published evidence about the role of non-alcoholic fatty liver disease (NAFLD) in the progression from prehypertension to hypertension. This study was conducted to investigate the association of NAFLD and its severity with the risk of hypertension developing from prehypertension.

Methods:

The study cohort comprised 25, 433 participants from the Kailuan study with prehypertension at baseline; those with excessive alcohol consumption and other liver diseases were excluded. NAFLD was diagnosed by ultrasonography and stratified as mild, moderate, or severe. Univariable and multivariable Cox proportional hazard regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension according to the presence and 3 categories of severity of NAFLD.

Results:

During a median of 12.6 years of follow-up, 10,638 participants progressed to hypertension from prehypertension. After adjusting for multiple risk factors, patients with prehypertension and NAFLD had a 15% higher risk of incident hypertension than those without NAFLD (HR = 1.15, 95% CI 1.10–1.21). Moreover, the severity of NAFLD was associated with the incidence of hypertension, which was higher in patients with more severe NAFLD (HR = 1.15 [95% CI 1.10–1.21] in the mild NAFLD group; HR = 1.15 [95% CI 1.07–1.24] in the moderate NAFLD group; and HR = 1.20 [95% CI 1.03–1.41] in the severe NAFLD group). Subgroup analysis indicated that age and baseline systolic blood pressure may modify this association.

Conclusions:

NAFLD is an independent risk factor for hypertension in patients with prehypertension. The risk of incident hypertension increases with the severity of NAFLD.
Integrative pan-cancer analysis of cuproplasia-associated genes for the genomic and clinical characterization of 33 tumors
Authors: Li Xinyu , Ma Weining , Liu Hui , Wang Deming , Su Lixin , Yang Xitao
Published: April 2023

Background:

The molecular mechanisms driving tumorigenesis have continually been the focus of researchers. Cuproplasia is defined as copper-dependent cell growth and proliferation, including its primary and secondary roles in tumor formation and proliferation through signaling pathways. In this study, we analyzed the differences in the expression of cuproplasia-associated genes (CAGs) in pan-cancerous tissues and investigated their role in immune-regulation and tumor prognostication.

Methods:

Raw data from 11,057 cancer samples were acquired from multiple databases. Pan-cancer analysis was conducted to analyze the CAG expression, single-nucleotide variants, copy number variants, methylation signatures, and genomic signatures of micro RNA (miRNA)–messenger RNA (mRNA) interactions. The Genomics of Drug Sensitivity in Cancer and the Cancer Therapeutics Response Portal databases were used to evaluate drug sensitivity and resistance against CAGs. Using single-sample Gene Set Enrichment Analysis (ssGSEA) and Immune Cell Abundance Identifier database, immune cell infiltration was analyzed with the ssGSEA score as the standard.

Results:

Aberrantly expressed CAGs were found in multiple cancers. The frequency of single-nucleotide variations in CAGs ranged from 1% to 54% among different cancers. Furthermore, the correlation between CAG expression in the tumor microenvironment and immune cell infiltration varied among different cancers. ATP7A and ATP7B were negatively correlated with macrophages in 16 tumors including breast invasive carcinoma and esophageal carcinoma, while the converse was true for MT1A and MT2A. In addition, we established cuproplasia scores and demonstrated their strong correlation with patient prognosis, immunotherapy responsiveness, and disease progression (P < 0.05). Finally, we identified potential candidate drugs by matching gene targets with existing drugs.

Conclusions:

This study reports the genomic characterization and clinical features of CAGs in pan-cancers. It helps clarify the relationship between CAGs and tumorigenesis, and may be helpful in the development of biomarkers and new therapeutic agents.
The long non-coding RNA colon cancer-associated transcript 1-Vimentin axis promoting the migration and invasion of HeLa cells
Authors: Li Zhangfu , Yuan Jiangbei , Da Qingen , Yan Zilong , Qu Jianhua , Li Dan , Liu Xu , Zhan Qimin , Liu Jikui
Published: April 2023

Background:

Long non-coding RNA colon cancer-associated transcript 1 (CCAT1) is involved in transforming multiple cancers into malignant cancer types. Previous studies underlining the mechanisms of the functions of CCAT1 primarily focused on its decoy for miRNAs (micro RNAs). However, the regulatory mechanism of CCAT1–protein interaction associated with tumor metastasis is still largely unknown. The present study aimed to identify proteome-wide CCAT1 partners and explored the CCAT1–protein interaction mediated tumor metastasis.

Methods:

CCAT1–proteins complexes were purified and identified using RNA antisense purification coupled with the mass spectrometry (RAP-MS) method. The database for annotation, visualization, and integrated discovery and database for eukaryotic RNA binding proteins (EuRBPDB) websites were used to bioinformatic analyzing CCAT1 binding proteins. RNA pull-down and RNA immunoprecipitation were used to validate CCAT1–Vimentin interaction. Transwell assay was used to evaluate the migration and invasion abilities of HeLa cells.

Results:

RAP-MS method worked well by culturing cells with nucleoside analog 4-thiouridine, and cross-linking was performed using 365 nm wavelength ultraviolet. There were 631 proteins identified, out of which about 60% were RNA binding proteins recorded by the EuRBPDB database. Vimentin was one of the CCAT1 binding proteins and was participated in the tumor metastasis pathway. Knocked down VIM and rescued the downregulation by overexpressing CCAT1 demonstrated that CCAT1 could enhance tumor migration and invasion abilities by stabilizing Vimentin protein.

Conclusion:

CCAT1 may bind with and stabilize Vimentin protein, thus enhancing cancer cell migration and invasion abilities.
Superiority of sugammadex in preventing postoperative pulmonary complications
Authors: Liu Haibei , Luo Rong , Cao Shuangjiao , Zheng Bixing , Ye Ling , Zhang Wensheng
Published: April 2023

Background:

Postoperative pulmonary complications often lead to increasing mortality and financial burden. Residual paralysis plays a critical role in postoperative pulmonary complications. This meta-analysis was performed to determine whether sugammadex overmatch neostigmine in reducing postoperative pulmonary complications.

Methods:

PubMed, Embase, Web of Science, Medline through Ovid, Cochrane Library, Wan fang, China National Knowledge Infrastructure, and Chinese BioMedical Literature Databases were searched from their inception to 24 June 2021. Random effects models were used for all analyses. Cochrane risk of bias tool was used to assess the quality of RCTs, while Newcastle Ottawa Quality Assessment Scale was used to assess for the quality of cohort studies.

Results:

Seventeen studies were included in the meta-analysis. Pooled data from cohort studies showed reversing neuromuscular blocking with sugammadex had less risk of compound postoperative pulmonary complications [relative risk (RR): 0.73; 95% confidence interval (CI): 0.60–0.89; P = 0.002; I
2 = 81%], pneumonia (RR: 0.64; 95% CI: 0.48–0.86; I
2 = 42%) and respiratory failure (RR: 0.48, 95% CI: 0.41–0.56, I
2 = 0%). However, pooled data from RCTs did not show any difference between the two groups in pneumonia (RR: 0.58; 95% CI: 0.24–1.40; I
2 = 0%) and respiratory failure. The difference was not found between sugammadex and neostigmine about atelectasis in pooled data from either RCTs (RR: 0.85; 95% CI: 0.69–1.05; I
2 = 0%) or cohort studies (RR: 1.01; 95% CI: 0.87 to 1.18; I
2 = 0%).

Conclusion:

The evidence of superiority of sugammadex was limited by the confounding factors in cohort studies and small scale of RCTs. Whether sugammadex precedes neostigmine in preventing pulmonary complications after surgery is still unknown. Well-designed RCTs with large scale are needed.

Registration:

PROSPERO CRD 42020191575
Trans-ethnic Mendelian randomization study of systemic lupus erythematosus and common female hormone-dependent malignancies
Authors: Zhu Tingting , Ding Yantao , Xu Xiaoli , Zhang Liyin , Zhang Xuejun , Cui Yong , Liu Lu
Published: April 2023

Background:

Observational research has reported that systemic lupus erythematosus (SLE) is related to common female hormone-dependent cancers, but the underlying causal effect remains undefined. This study aimed to explore the causal association of these conditions by Mendelian randomization (MR) analysis.

Methods:

We selected instrumental variables for SLE from genome-wide association studies (GWASs) conducted in European and East Asian populations. The genetic variants for female malignant neoplasms were obtained from corresponding ancestry GWASs. We utilized inverse variance weighted (IVW) as the primary analysis, followed by sensitivity analysis. Furthermore, we conducted multivariable MR (MVMR) to estimate direct effects by adjusting for the body mass index and estradiol. Finally, we implemented reverse direction MR analysis and gave a negative example to test the reliability of MR results.

Results:

We found SLE was significantly negatively associated with overall endometrial cancer risk (odds ratio [OR] = 0.961, 95% confidence interval [CI] = 0.935–0.987, P = 3.57E−03) and moderately inversely related to endometrioid endometrial cancer (ENEC) (OR = 0.965, 95% CI = 0.936–0.995, P = 0.024) risk in the European population by IVW. We replicated these results using other MR models and detected a direct effect by MVMR (overall endometrial cancer, OR = 0.962, 95% CI = 0.941–0.983, P = 5.11E−04; ENEC, OR = 0.964, 95% CI = 0.940–0.989, P = 0.005). Moreover, we revealed that SLE was correlated with decreased breast cancer risk (OR = 0.951, 95% CI = 0.918–0.986, P = 0.006) in the East Asian population by IVW, and the effect was still significant in MVMR (OR = 0.934, 95% CI = 0.859–0.976, P = 0.002). The statistical powers of positive MR results were all >0.9.

Conclusion:

This finding suggests a possible causal effect of SLE on the risk of overall endometrial cancer and breast cancer in European and East Asian populations, respectively, by MR analysis, which compensates for inherent limitations of observational research.
Effect of intra-operative chemotherapy with 5-fluorouracil and leucovorin on the survival of patients with colorectal cancer after radical surgery: a retrospective cohort study
Authors: Hu Xuhua , Zheng Zhaoxu , Han Jing , Li Baokun , Guo Ganlin , Guo Peiyuan , Yang Yang , Li Daojuan , Yan Yiwei , Niu Wenbo , Zhou Chaoxi , Meng Zesong , Feng Jun , Yu Bin , Liu Qian , Wang Guiying
Published: April 2023

Background:

The effect of intra-operative chemotherapy (IOC) on the long-term survival of patients with colorectal cancer (CRC) remains unclear. In this study, we evaluated the independent effect of intra-operative infusion of 5-fluorouracil in combination with calcium folinate on the survival of CRC patients following radical resection.

Methods:

1820 patients were recruited, and 1263 received IOC and 557 did not. Clinical and demographic data were collected, including overall survival (OS), clinicopathological features, and treatment strategies. Risk factors for IOC-related deaths were identified using multivariate Cox proportional hazards models. A regression model was developed to analyze the independent effects of IOC.

Results:

Proportional hazard regression analysis showed that IOC (hazard ratio [HR]=0.53, 95% confidence intervals [CI] [0.43, 0.65], P < 0.001) was a protective factor for the survival of patients. The mean survival time in IOC group was 82.50 (95% CI [80.52, 84.49]) months, and 71.21 (95% CI [67.92, 74.50]) months in non-IOC group. The OS in IOC-treated patients were significantly higher than non-IOC-treated patients (P < 0.001, log-rank test). Further analysis revealed that IOC decreased the risk of death in patients with CRC in a non-adjusted model (HR=0.53, 95% CI [0.43, 0.65], P < 0.001), model 2 (adjusted for age and gender, HR=0.52, 95% CI [0.43, 0.64], P < 0.001), and model 3 (adjusted for all factors, 95% CI 0.71 [0.55, 0.90], P = 0.006). The subgroup analysis showed that the HR for the effect of IOC on survival was lower in patients with stage II (HR = 0.46, 95% CI [0.31, 0.67]) or III disease (HR=0.59, 95% CI [0.45, 0.76]), regardless of pre-operative radiotherapy (HR=0.55, 95% CI [0.45, 0.68]) or pre-operative chemotherapy (HR=0.54, 95% CI [0.44, 0.66]).

Conclusions:

IOC is an independent factor that influences the survival of CRC patients. It improved the OS of patients with stages II and III CRC after radical surgery.

Trial registration:

chictr.org.cn, ChiCTR 2100043775.
Identification of the metabolic state of surviving cardiomyocytes in the human infarcted heart by spatial single-cell transcriptomics
Authors: Shen Yan , Kim Il-man , Weintraub Neal L. , Tang Yaoliang
Published: April 2023

Background and purpose:

The metabolic status of surviving cardiomyocytes (CM) in the myocardial tissues of patients who sustained myocardial infarction (MI) is largely unknown. Spatial single-cell RNA-sequencing (scRNA-seq) is a novel tool that enables the unbiased analysis of RNA signatures within intact tissues. We employed this tool to assess the metabolic profiles of surviving CM in the myocardial tissues of patients post-MI.

Methods:

A spatial scRNA-seq dataset was used to compare the genetic profiles of CM from patients with MI and control patients; we analyzed the metabolic adaptations of surviving CM within the ischemic niche. A standard pipeline in Seurat was used for data analysis, including normalization, feature selection, and identification of highly variable genes using principal component analysis (PCA). Harmony was used to remove batch effects and integrate the CM samples based on annotations. Uniform manifold approximation and projection (UMAP) was used for dimensional reduction. The Seurat “FindMarkers” function was used to identify differentially expressed genes (DEGs), which were analyzed by the Gene Ontology (GO) enrichment pathway. Finally, the scMetabolism R tool pipeline with parameters method = VISION (Vision is a flexible system that utilizes a high-throughput pipeline and an interactive web-based report to annotate and explore scRNA-seq datasets in a dynamic manner) and metabolism.type = Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to quantify the metabolic activity of each CM.

Results:

Analysis of spatial scRNA-seq data showed fewer surviving CM in infarcted hearts than in control hearts. GO analysis revealed repressed pathways in oxidative phosphorylation, cardiac cell development, and activated pathways in response to stimuli and macromolecular metabolic processes. Metabolic analysis showed downregulated energy and amino acid pathways and increased purine, pyrimidine, and one-carbon pool by folate pathways in surviving CM.

Conclusions:

Surviving CM within the infarcted myocardium exhibited metabolic adaptations, as evidenced by the downregulation of most pathways linked to oxidative phosphorylation, glucose, fatty acid, and amino acid metabolism. In contrast, pathways linked to purine and pyrimidine metabolism, fatty acid biosynthesis, and one-carbon metabolism were upregulated in surviving CM. These novel findings have implications for the development of effective strategies to improve the survival of hibernating CM within the infarcted heart.
Efficacy and Safety of Different Dosing Regimens of Colchicine in Patients With Coronary Artery Disease: A Network Meta-analysis of 15 Randomized Controlled Trials
Authors: Wang Shixun , Mu Yanguang , Tan Lei , Hao Junqiang
Published: April 2023

Several meta-analyses have investigated the effects of different doses of colchicine in treating coronary artery disease, but all dosing regimens were never compared in a single study. We aimed to compare the efficacy and safety of 3 dosing regimens of colchicine in patients with coronary artery disease. PubMed, EMBASE, the Cochrane Library, and SCOPUS were searched for randomized controlled trials involving different colchicine doses. Major adverse cardiac events (MACE), all-cause and cardiovascular mortality, recurrent myocardial infarction (MI), stroke, gastrointestinal adverse events (AEs), discontinuation, and hospitalization were evaluated using risk ratio (RR) with 95% confidence interval (CI). A total of 15 randomized controlled trial involving 13,539 patients were included. Pooled results calculated with STATA 14.0 showed that low-dose colchicine significantly reduced MACE (RR, 0.51; 95% CI, 0.32–0.83), recurrent MI (RR, 0.56; 95% CI, 0.35–0.89), stroke (RR, 0.48; 95% CI, 0.23–1.00), and hospitalization (RR, 0.44; 95% CI, 0.22–0.85), whereas high and loading doses significantly increased gastrointestinal AEs (RR, 2.84; 95% CI, 1.26–6.24) and discontinuation (RR, 2.73; 95% CI, 1.07–6.93), respectively. Sensitivity analyses confirmed that 3 dosing regimens did not reduce all-cause and cardiovascular mortality but significantly increased the gastrointestinal AEs, and high dose significantly increased AEs-related discontinuation; loading dose resulted in more discontinuation than low dose. Although differences between 3 dosing regimens of colchicine are not significant, low dose is more effective in reducing MACE, recurrent MI, stroke, and hospitalization than the control, whereas high and loading doses increase gastrointestinal AEs and discontinuation, respectively.
Intraoperative Fluorescein Angiography Can Efficiently Identify Biomarkers And Guide Surgical Decision Making
Authors: Cardamone Michael S , Hüning Gustavo , Scarlett Chadd , Yin Lu , Luna Alexander J , Franklin Alan J
Published: April 2023

Purpose:

We sought to develop an efficient method for fluorescein angiography (FA) during Digitally Assisted Vitreoretinal Surgery (DAVS).

Methods:

A 485 nm bandpass filter was placed into the filter holder of the accessory light sources of the Constellation Vision System with steel modified washers to produce an exciter source. A barrier filter was placed into the blank slot of a switchable laser filter with a 535 nm bandpass filter and another washer or created digitally with a specific color channel using NGENUITY Software Version 1.4. Fluorescein, 250-500 mg was then injected intravenously during retinal surgery.

Results:

These fluorescence patterns accurately detect many fluorescein angiography biomarkers such as determination of vascular filling times, ischemia, neovascularization, shunt vessels, microaneurysms, and leakage into the vitreous. This enhanced surgical visualization permitted intervention in real time such as laser or diathermy to residual microvascular abnormalities after delamination of retinal neovascularization as well as heavier panretinal laser placement in areas of retinal capillary dropout to relatively preserve areas of more intact retinal microcirculation.

Conclusion:

We are the first to report an efficient method that permits high resolution detection of many classic FA biomarkers such as during DAVS to enhance surgical visualization and intervention in real time.