bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal Fusion Transformer for thermal load prediction in district heating and cooling networks
Authors: Behrens Fabian , Leiprecht Stefan , Brantl Jonas , Finkenrath Matthias
Published: October 2022

Accurate forecasting of thermal loads is a critical factor for operating district heating and cooling networks economically, efficiently and with minimized emissions. If thermal loads are known with high accuracy in advance, use of renewable energies can be maximized, and fossil generation, in particular in peaking units, can be avoided. Machine learning has already proven to be an efficient tool for time series forecasting in this context. One recent advancement in machine learning is the "Temporal Fusion Transformer" (TFT), which shows especially good results in the area of time series forecasting. This paper examines the performance of TFT in the concrete context of thermal load forecasting for district heating and cooling networks. First, a brief summary of differences between TFT and other machine learning methods is given. Secondly, it is described how the method can be adopted to train a machine learning model for thermal load forecasting. The data to train and evaluate the neural network is based on 8 years of hourly operating data made available from the district heating network of the city of Ulm in Germany. The presented technique is used to produce 72 hours of heating load forecasts for three different district heating grids in the city of Ulm. The results are compared to forecasts of other machine learning methods that have been previously made as part of the publicly funded research project "deepDHC", in order to evaluate if TFT is an improvement to further reduce forecasting uncertainties.
Simulation and optimization of screw feeder in a bubbling fluidized bed gasification reactor
Authors: Thapa Rajan K , Vaa Trym Fehn , Vaa Oddvin , Jaiswal Rajan , Jecmenica Mladen
Published: October 2022

A fluidized bed biomass gasification reactor is used to produce syngas from biomass and municipal wastes. Gasification is a flexible technology where many different types of feedstocks can be used. The University of South-Eastern Norway has a 20kW gasification reactor which is used to investigate the quality and quantity of the syngas produced using different types of feedstocks. At the present, the reactor has the challenge to supply feedstock to the reactor via transport screws. The main challenge consists of achieving continuous feeding and reduction in the feed rate. Therefore, this work is focused on the optimization of the screw feeder in the gasification reactor to obtain a reduced feed rate while maintaining a continuous feeding rate. The aim is to reduce the feed rate from approximately 8 kg/h to 3-4 kg/h without missing continuity of the feeding.A model of the screw feeder is developed using CAD software SolidWorks and the model is simulated using open-source simulation software LIGGGHTS to investigate feed rate and continuity using different combinations of transport screw parameters. The simulation results are processed using Excel and viewed graphically with the open-source visualization software ParaView. The simulation results are compared to the experimental measurements in the gasification reactor. The validated model is further used to investigate the feed rate with different combinations of transport screw parameters and the results are compared and discussed.
Enhanced oil recovery using CO2 injection and inflow control devices
Authors: Sørensen Stian Juvet , Knarrum Joachim Rød , Sannes Ole Christian Kristoffersen , Lia Lars , Timsina Ramesh , Aakre Haavard , Moldestad Britt M. E.
Published: October 2022

CO2 capture is an important aid to achieve the goals of reduced emissions. Today the market for captured CO2 is limited. Injection of CO2 in oil reservoirs is one way of utilizing the captured CO2 and provide permanent storage of the CO2. By injecting CO2, the mobility of oil is increased, and the amount of residual oil is reduced. This is called enhanced oil recovery. The goal of this study is to show the effects of CO2 injection combined with autonomous inflow control valves on oil production. Simulations are carried out using the software OLGA in combination with ROCX. The input data to the simulations are based on information obtained from a literature study. To show the effect of the autonomous inflow control valves and CO2 injection, the simulations were compared with simulations performed without autonomous inflow control valves and CO2 injection. The results from the simulations show that CO2 injection contributes to increase the mobility of both oil and water which leads to an increase in both oil and water/CO2 production. Autonomous inflow control valves reduce the amount of water produced by choking the production in areas with water breakthrough. The combination of CO2 injection and autonomous inflow control valves results in a higher oil-water ratio and a considerably lower water production.
Formulation of a novel antibacterial topical treatment based on Magnetite-Buforin-II-silver nanobioconjugates
Authors: Muñoz Laura N. , Jaramillo Valentina , Gantiva-Diaz Mónica , Cifuentes Javier , Muñoz-Camargo Carolina , Cruz Juan C. , González Barrios Andrés Fernando
Published: October 2022

Community acquired infections caused by Meticillin-resistant Staphylococcus aureus (MRSA) have become a growing concern due to its impact on the world public health. This microorganism is a commonly spreading pathogen associated predominantly with skin infections and connected to other more severe conditions (septic shock, and generalized infection). The lack of highly effective antibiotics and treatments to control skin infections with S. aureus has led to the search of novel therapies using alternative agents such as antimicrobial peptides (AMPs). In order to obtain a viable administration route to counteract superficial skin infections (impetigo, abscesses, furuncles, and cellulitis), a topical formulation based on Magnetite-Buforin-II-silver nanobioconjugates as active antibacterial agents was designed by their dispersion in O/W concentrated emulsions. The prepared topical characterization indicated that O/W emulsions were stable in time, the droplets size remained within the appropriate values (∼1 µm) and their rheological properties, such as pseudoplastic and shear-thinning behavior, remained unchanged for up to 3 months. Additionally, hemolysis and platelet aggregation tests were acceptable (i.e., 14.72 ± 2.62% and 8.06 ± 2.90%, respectively) in compliance with the ISO-10993 standard. Furthermore, the treatment reduced significantly (p < 0.0001) the growth of both clinical isolated MRSA and wild Type S. aureus strains as evidenced by the contact diffusion method. These results are important in the context of proposing new alternatives that allow manage effectively the threat posed by the antibiotic resistant bacterial strains, which jeopardize the lives of thousands of people every year.
OMIXCARE: OMICS technologies solved about 33% of the patients with heterogeneous rare neuro-developmental disorders and negative exome sequencing results and identified 13% additional candidate variants
Authors: Colin Estelle , Duffourd Yannis , Tisserant Emilie , Relator Raissa , Bruel Ange-Line , Tran Mau-Them Frédéric , Denommé-Pichon Anne-Sophie , Safraou Hana , Delanne Julian , Jean-Marçais Nolwenn , Keren Boris , Isidor Bertrand , Vincent Marie , Mignot Cyril , Heron Delphine , Afenjar Alexandra , Heide Solveig , Faudet Anne , Charles Perrine , Odent Sylvie , Herenger Yvan , Sorlin Arthur , Moutton Sébastien , Kerkhof Jennifer , McConkey Haley , Chevarin Martin , Poë Charlotte , Couturier Victor , Bourgeois Valentin , Callier Patrick , Boland Anne , Olaso Robert , Philippe Christophe , Sadikovic Bekim , Thauvin-Robinet Christel , Faivre Laurence , Deleuze Jean-François , Vitobello Antonio
Published: October 2022

Purpose: Patients with rare or ultra-rare genetic diseases, which affect 350 million people worldwide, may experience a diagnostic odyssey. High-throughput sequencing leads to an etiological diagnosis in up to 50% of individuals with heterogeneous neurodevelopmental or malformation disorders. There is a growing interest in additional omics technologies in translational research settings to examine the remaining unsolved cases.

Methods: We gathered 30 individuals with malformation syndromes and/or severe neurodevelopmental disorders with negative trio exome sequencing and array comparative genomic hybridization results through a multicenter project. We applied short-read genome sequencing, total RNA sequencing, and DNA methylation analysis, in that order, as complementary translational research tools for a molecular diagnosis.

Results: The cohort was mainly composed of pediatric individuals with a median age of 13.7 years (4 years and 6 months to 35 years and 1 month). Genome sequencing alone identified at least one variant with a high level of evidence of pathogenicity in 8/30 individuals (26.7%) and at least a candidate disease-causing variant in 7/30 other individuals (23.3%). RNA-seq data in 23 individuals allowed two additional individuals (8.7%) to be diagnosed, confirming the implication of two pathogenic variants (8.7%), and excluding one candidate variant (4.3%). Finally, DNA methylation analysis confirmed one diagnosis identified by genome sequencing (Kabuki syndrome) and identified an episignature compatible with a BAFopathy in a patient with a clinical diagnosis of Coffin-Siris with negative genome and RNA-seq results in blood.

Conclusion: Overall, our integrated genome, transcriptome, and DNA methylation analysis solved 10/30 (33.3%) cases and identified a strong candidate gene in 4/30 (13.3%) of the patients with rare neurodevelopmental disorders and negative exome sequencing results.
RETRACTED: Survivin knockdown alleviates pathological hydrostatic pressure-induced bladder smooth muscle cell dysfunction and BOO-induced bladder remodeling via autophagy
Authors: Chen Guo , Chen Shuang , Di Xingpeng , He Shengyin , Liu Yugao , Qu Rui , Luo Yi , Liu Yuebai , Yang Luo
Published: October 2022

Aim: Bladder outlet obstruction (BOO) leads to bladder wall remodeling accompanying the progression from inflammation to fibrosis where pathological hydrostatic pressure (HP)-induced alteration of bladder smooth muscle cells (BSMCs) hypertrophic and excessive extracellular matrix (ECM) deposition play a pivotal role. Recently, we have predicted survivin (BIRC5) as a potential hub gene that might be critical during bladder fibrosis by bioinformatics analyses from rat BOO bladder, but its function during BOO progression remains unknown. Here, we investigated the role of survivin protein on bladder dysfunction of BOO both in vitro and in vivo.

Methods: Sprague-Dawley female rats were divided into three groups: control group, BOO group, and BOO followed by the treatment with YM155 group. Bladder morphology and function were evaluated by Masson staining and urodynamic testing. To elucidate the underlying mechanism, hBSMCs were subjected to pathological HP of 200 cm H2O and co-cultured with the presence or absence of survivin siRNA and/or autophagy inhibitor 3-MA. Autophagy was evaluated by the detection of Beclin1 and LC3B-II expression, proliferation was conducted by the EdU analysis and PCNA expression, and fibrosis was assessed by the examination of Col 1 and Fn expression.

Results: BOO led to a gradual alteration of hypertrophy and fibrosis of the bladder, and subsequently induced bladder dysfunction accompanied by increased survivin expression, while these histological and function changes were attenuated by the treatment with YM155. HP significantly increased survivin expression, upregulated Col1 and Fn expression, enhanced proliferation, and downregulated autophagy markers, but these changes were partially abolished by survivin siRNA treatment, which was consistent with the results of the BOO rat experiment. In addition, the anti-fibrotic and anti-proliferative effects of the survivin siRNA treatment on hBSMCs were diminished after the inhibition of autophagy by the treatment with 3-MA.

Conclusion: In summary, the upregulation of survivin increased cell proliferation and fibrotic protein expression of hBSMC and drove the onset of bladder remodeling through autophagy during BOO. Targeting survivin in pathological hBSMCs could be a promising way to anti-fibrotic therapeutic approach in bladder remodeling secondary to BOO.
Gallium ions incorporated silk fibroin hydrogel with antibacterial efficacy for promoting healing of Pseudomonas aeruginosa-infected wound
Authors: Zheng Hui , Huang Zhida , Chen Tongxin , Sun Yafeng , Chen Shouqing , Bu Guangming , Guan Hongcai
Published: October 2022

The continual resistance to antibiotics and the generation of a series of bacterial infections has emerged as a global concern, which requires appropriate measures and therapeutics to address such a menace. Herein, we report on Silk fibroin (SF) hydrogel with good biocompatibility and biodegradability fabricated through the crosslinking of the SF of different concentrations with Gallium nitrate (Ga (NO3)3) against Pseudomonas aeruginosa. However, the SF: Ga = 500: 1 (w/w) (SF/Ga) demonstrated a good bactericidal and wound healing effect as a result of the moderate and prolonged release of the Ga3+ following the gradual degradation of the hydrogel. The Ga3+, known for its innovative nature acted as a crosslinked agent and a therapeutic agent employing the “Trojan horse” strategy to effectively deal with the bacteria. Also, the Ga3+, which is positively charged neutralizes the negative potential value of the SF particles to reduce the charge and further induce the β-sheet formation in the protein structure, a characteristic of gelation in SF. The morphology showed a fabricated homogenous structure with greater storage modulus- G’ with low loss modulus- G'' modulus demonstrating the mechanical performance and the ability of the SF/Ga hydrogel to hold their shape, at the same time allowing for the gradual release of Ga3+. A demonstration of biocompatibility, biodegradability, bactericidal effect and wound healing in in vitro and in vivo present the SF/Ga hydrogel as an appropriate platform for therapeutic and for antibacterial wound dressing.
Immunomodulatory effect of extracellular vesicles from Entamoeba histolytica trophozoites: Regulation of NETs and respiratory burst during confrontation with human neutrophils
Authors: Díaz-Godínez César , Ríos-Valencia Diana G. , García-Aguirre Samuel , Martínez-Calvillo Santiago , Carrero Julio César
Published: October 2022

Parasites release extracellular vesicles (EVs) which, in some cases, modulate the host’s immune response contributing to the establishment of the infection. In this work we have isolated and characterized the EVs released by trophozoites of the human protozoan parasite Entamoeba histolytica, the causal agent of amoebiasis, when alone or in coculture with human neutrophils, and determined their effect on neutrophil NETs and ROS production. Nanoparticle tracking analysis showed that amoebic EVs are variable in size, ranging from less than 50 nm to nearly 600 nm in diameter (average of 167 nm), whereas neutrophil EVs are more uniform in size, with an average of 136 nm. In cocultures amoeba:neutrophil (1:100) most EVs are 98 nm in size, which is the typical size of exosomes. EVs from amoebae and neutrophils showed almost equal levels of ROS, which were considerably increased in EVs from cocultures. Uptake of amoebic EVs by neutrophils was demonstrated by fluorescence and resulted in a significant reduction in the oxidative burst and NET release triggered by PMA, ionophore A23187, or the amoebae itself used as stimuli. Interestingly, uptake of EVs from cocultures did not affect ROS production, but instead caused a greater delay in the onset of NETs release and in their quantity. A comparative proteomic analysis between the EVs of amoebae and neutrophils separately vs the cocultures showed a similar distribution of protein categories in the GO analysis, but differences in the expression and abundance of proteins such as the N-acetyl-D-galactosamine (GalNAc) inhibitable surface lectin and calreticulin in amoeba EVs, and various antimicrobial molecules in neutrophil EVs, such as lactoferrin and myeloperoxidase. These results highlight the importance of EVs in the immunomodulatory effects exerted by amoeba on human neutrophils.
A maximum-type microbial differential abundance test with application to high-dimensional microbiome data analyses
Authors: Li Zhengbang , Yu Xiaochen , Guo Hongping , Lee TingFang , Hu Jiyuan
Published: October 2022

Background

High-throughput metagenomic sequencing technologies have shown prominent advantages over traditional pathogen detection methods, bringing great potential in clinical pathogen diagnosis and treatment of infectious diseases. Nevertheless, how to accurately detect the difference in microbiome profiles between treatment or disease conditions remains computationally challenging.

Results

In this study, we propose a novel test for identifying the difference between two high-dimensional microbiome abundance data matrices based on the centered log-ratio transformation of the microbiome compositions. The test p-value can be calculated directly with a closed-form solution from the derived asymptotic null distribution. We also investigate the asymptotic statistical power against sparse alternatives that are typically encountered in microbiome studies. The proposed test is maximum-type equal-covariance-assumption-free (MECAF), making it widely applicable to studies that compare microbiome compositions between conditions. Our simulation studies demonstrated that the proposed MECAF test achieves more desirable power than competing methods while having the type I error rate well controlled under various scenarios. The usefulness of the proposed test is further illustrated with two real microbiome data analyses. The source code of the proposed method is freely available at https://github.com/Jiyuan-NYU-Langone/MECAF.

Conclusions

MECAF is a flexible differential abundance test and achieves statistical efficiency in analyzing high-throughput microbiome data. The proposed new method will allow us to efficiently discover shifts in microbiome abundances between disease and treatment conditions, broadening our understanding of the disease and ultimately improving clinical diagnosis and treatment.
Conservation through connection: Approaches to engaging communities in applied grizzly bear research
Authors: Hughes Courtney , Elmeligi Sarah , Morehouse Andrea
Published: October 2022

Human-wildlife dynamics is a growing field and one of considerable importance to conservation. Wild spaces are in short supply, and consequently wildlife and people increasingly share the landscape, though not necessarily by choice. As a result, peoples’ needs might not be prioritized over those of wildlife, even in cases of human-wildlife conflict. For wildlife conservation to be effective and human-wildlife coexistence possible, the needs of both wildlife and people must be simultaneously addressed. Rather than an afterthought or a sentence in the conservation/management implications section of a paper, community engagement should be addressed before, during, and after a research project. However, this can be a difficult and often complicated task, for multiple reasons. Building relationships founded on trust, respect and reciprocity with community members takes commitment, time, skill, and a willingness by researchers to be open-minded in terms of methodologies and new ideas. Different cultural norms, beliefs, perspectives and biases can further exacerbate these challenges. Here, we share three short case studies reflecting our own research experiences engaging with communities in the field of grizzly bear (Ursus arctos) ecology and conservation science. We conclude with guidelines for advancing effective community engagement and suggestions for tackling some common barriers. Overall, we offer considerations for a practical and more holistic approach to large carnivore conservation, established on a foundation of strong community support.
The relationship between mean platelet volume lymphocyte ratio and collateral circulation in patients with chronic total coronary occlusion
Authors: Niu Ming-Hui , Liu Peng-Hui , Liu Ze-Hua , Zhu Jun-Wei , Guo Rong , He Fei
Published: October 2022

Objective

To correlate mean platelet volume lymphocyte ratio (MPVLR) and coronary collateral circulation (CCC) in patients with chronic total occlusion (CTO).

Materials and methods

A total of 643 patients who were hospitalized at a single large academic medical center from January 2020 to October 2021 and had CTO lesions in at least one major coronary artery confirmed by coronary angiography were retrospectively analyzed. Patients were divided according to the Rentrop criteria into poorly formed CCC (Rentrop grade 0–1, n = 235) and well-formed CCC (Rentrop grade 2–3, n = 408) groups. Mean platelet volume lymphocyte ratio (MPVLR) was calculated from routine laboratory data (MPV divided by lymphocyte count). The clinical data of the two groups were compared, and relationships between MPVLR and CCC formation were analyzed.

Results

The MPVLR of patients with poorly formed CCC was significantly higher than that of patients with well-formed CCC (7.82 ± 3.80 vs. 4.84 ± 1.42, P < 0.01). The prevalence of diabetes mellitus and C-reactive protein levels were significantly higher in the poor CCC group than in the good CCC group (P < 0.01), while the proportions of patients with CTO or multivessel lesions in the right coronary artery were significantly lower in the poor CCC group than in the good CCC group (P < 0.01). Multivariate logistic regression analysis identified MPVLR (OR: 2.101, 95% CI: 1.840–2.399, P < 0.01), C-reactive protein level (OR: 1.036, 95% CI: 1.008–1.064, P < 0.05), a history of diabetes mellitus (OR: 2.355, 95% CI: 1.532–3.621, P < 0.01), and right coronary CTO ratio (OR: 0.313, 95% CI: 0.202–0.485, P < 0.01) as independent risk factors for CCC formation. The area under the ROC curve of MPVLR for predicting poorly formed CCC was 0.82 (95% CI: 0.784–0.855, P < 0.01), the best cut-off point was 6.02 and the sensitivity and specificity of MPVLR for predicting poorly formed CCC were 72.3 and 82.4%, respectively.

Conclusion

In patients with coronary CTO, MPVLR was negatively correlated with CCC and a high MPVLR level was an independent predictor of poorly formed CCC.
Trigger related outcomes of takotsubo syndrome in a cancer population
Authors: Safdar Ayesha , Ahmed Talha , Liu Victor Y. , Addoumieh Antoine , Agha Ali M. , Giza Dana E. , Balanescu Dinu V. , Donisan Teodora , Dayah Tariq , Lopez-Mattei Juan C. , Kim Peter Y. , Hassan Saamir , Karimzad Kaveh , Palaskas Nicolas , Tsai January Y. , Iliescu Gloria D. , Yang Eric H. , Herrmann Joerg , Marmagkiolis Konstantinos , Angelini Paolo , Iliescu Cezar A.
Published: October 2022

Background

Takotsubo syndrome (TTS) occurs more frequently in cancer patients than in the general population, but the effect of specific TTS triggers on outcomes in cancer patients is not well studied.

Objectives

The study sought to determine whether triggering event (chemotherapy, immune-modulators vs. procedural or emotional stress) modifies outcomes in a cancer patient population with TTS.

Methods

All cancer patients presenting with acute coronary syndrome (ACS) between December 2008 and December 2020 at our institution were enrolled in the catheterization laboratory registry. Demographic and clinical data of the identified patients with TTS were retrospective collected and further classified according to the TTS trigger. The groups were compared with regards to major adverse cardiac events, overall survival and recovery of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) after TTS presentation.

Results

Eighty one of the 373 cancer patients who presented with ACS met the Mayo criteria for TTS. The triggering event was determined to be “cancer specific triggers” (use of chemotherapy in 23, immunomodulators use in 7, and radiation in 4), and “traditional triggers” (medical triggers 22, and procedural 18 and emotional stress in 7). Of the 81 patients, 47 died, all from cancer-related causes (no cardiovascular mortality). Median survival was 11.9 months. Immunomodulator (IM) related TTS and radiation related TTS were associated with higher mortality during the follow-up. Patients with medical triggers showed the least recovery in LVEF and GLS while patients with emotional and chemotherapy triggers, showed the most improvement in LVEF and GLS, respectively.

Conclusion

Cancer patients presenting with ACS picture have a high prevalence of TTS due to presence of traditional and cancer specific triggers. Survival and improvement in left ventricular systolic function seem to be related to the initial trigger for TTS.
Culprit vessel revascularization first with primary use of a dedicated transradial guiding catheter to reduce door to balloon time in primary percutaneous coronary intervention
Authors: Guo Jincheng , Wang Guozhong , Li Zixuan , Liu Zijing , Wang Yujie , Wang Senhu , Wang Yuntao , Wu Yongxia , Wang Haotian , Wang Yuping , Zhang Libin , Hua Qi
Published: October 2022

Background

The effect of a single transradial guiding catheter (STGC) for culprit vessel percutaneous coronary intervention (PCI) first on door-to-balloon (D2B) time remains unclear.

Materials and methods

Between February 2017 and July 2019, 560 patients with ST-elevation myocardial infarction (STEMI) were randomized into either the STGC group (n = 280) or the control group (n = 280) according to direct culprit vessel PCI with a STGC. In the STGC group, a dedicated transraidal guiding catheter (6F either MAC3.5 or JL3.5) was used for the treatment of electrocardiogram (ECG)-guided culprit vessel first and later contralateral angiography. In the control group, a universal diagnostic catheter (5F Tiger II) was used for complete coronary angiography, followed by guiding catheter selection for culprit vessel PCI. The primary endpoint was D2B time, and the secondary endpoint included catheterization laboratory door-to-balloon (C2B), procedural, fluoroscopy times, and major adverse cardiac events (MACE) at 30 days.

Results

The median D2B time was significantly shorter in the STGC group compared to the control group (53.9 vs. 58.4 min; p = 0.003). The C2B, procedural, and fluoroscopy times were also shorter in the STGC group (C2B: 17.3 vs. 24.5 min, p < 0.001; procedural: 45.2 vs. 49.0 min, p = 0.012; and fluoroscopy: 9.7 vs. 11.3 min, p = 0.025). More patients achieved the goal of D2B time within 90 min (93.9% vs. 87.1%, p = 0.006) and 60 min (61.4% vs. 51.1%, p = 0.013) in the STGC group. Radial artery perforation (RAP) was significantly reduced in the STGC group compared with the control group (0.7% vs. 3.2%, P = 0.033). MACE at 30 days was similar (2.5% vs. 4.6%, P = 0.172) between the two groups.

Conclusion

ECG-guided immediate intervention on culprit vessel with a STGC can reduce D2B, C2B, procedural, and fluoroscopy times (ECG-guided Immediate Primary PCI for Culprit Vessel to Reduce Door to Device Time; NCT03272451).
Methyltransferase like 3-mediated N6-methylatidin methylation inhibits vascular smooth muscle cells phenotype switching via promoting phosphatidylinositol 3-kinase mRNA decay
Authors: Zhao Yongchao , Xia Aichao , Li Chaofu , Long Xianping , Bai Zhixun , Qiu Zhimei , Xiong Weidong , Gu Ning , Shen Youcheng , Zhao Ranzun , Shi Bei
Published: October 2022

N6-methylatidine (m6A) is involved in post-transcriptional metabolism and a variety of pathological processes. However, little is known about the role of m6A in vascular proliferative diseases, particularly in vascular smooth muscle cells (VSMCs) phenotype switching-induced neointimal hyperplasia. In the current study, we discovered that methyltransferase like 3 (METTL3) is a critical candidate for catalyzing a global increase in m6A in response to carotid artery injury and various VSMCs phenotype switching. The inhibited neointimal hyperplasia was obtained after in vivo gene transfer to knock-down Mettl3. In vitro overexpression of Mettl3 resulted in increased VSMC proliferation, migration, and reduced contractile gene expression with a global elevation of m6A modification. In contrast, Mettl3 knockdown reversed this facilitated phenotypic switch in VSMCs, as demonstrated by downregulated m6A, decreased proliferation, migration, and increased expression of contractile genes. Mechanistically, Mettl3 knock-down was found to promote higher phosphatidylinositol 3-kinase (Pi3k) mRNA decay thus inactivating the PI3K/AKT signal to inhibit VSMCs phenotype switching. Overall, our findings highlight the importance of METTL3-mediated m6A in VSMCs phenotype switching and offer a novel perspective on targeting METTL3 as a therapeutic option for VSMCs phenotype switching modulated pathogenesis, including atherosclerosis and restenosis.
Bivalirudin vs. heparin on a background of ticagrelor and aspirin in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: A multicenter prospective cohort study
Authors: Yu Xiao-Fan , Chen Hong-Wu , Xu Jie , Xu Qi-Zhi , Zhang Xiao-Hong , Li Bin-Bin , Xu Bang-Long , Ma Li-Kun
Published: October 2022

Objective

Current guidelines recommend potent P2Y12 inhibitors such as ticagrelor over clopidogrel as part of the dual antiplatelet therapy (DAPT) after ST-segment elevation myocardial infarction (STEMI), irrespective of final management strategy. The aim of this multicenter prospective cohort study was to examine the efficacy and safety of bivalirudin with background ticagrelor and aspirin therapy in patients with STEMI undergoing primary percutaneous coronary intervention (PPCI).

Methods

A total of 800 patients with STEMI who were undergoing PPCI and receiving treatment with aspirin and ticagrelor from three Hospitals between April 2019 and September 2021 were included in this study. The patients were assigned, according to the perioperative anticoagulant, to the bivalirudin group (n = 456) or the heparin group (n = 344). In this study, the primary endpoint was 30-day net adverse clinical events (NACEs), a composite of major adverse cardiac or cerebral events (MACCEs, a composite of cardiac death, recurrent myocardial infarction, ischemia-driven target vessel revascularization, or stroke), or any bleeding as defined by the Bleeding Academic Research Consortium (BARC) definition (grades 1–5).

Results

The patients were followed up for 30 days after PPCI. The incidence of NACE was significantly lower in the bivalirudin group than in the heparin group (11.2 vs. 16.0%, P = 0.042), and this significance was mainly a consequence of the reduction in BARC 1 bleeding events in the bivalirudin group compared to the heparin group (3.2 vs. 7.1%, P = 0.010). Results from multivariate Cox regression analysis showed that bivalirudin significantly reduced 30-day NACE (HR: 0.676, 95% CI: 0.462–0.990, P = 0.042) and BARC1 bleeding events (HR: 0.429, 95% CI: 0.222–0.830, P = 0.010). No significant between-group differences were observed for MACCE, all-cause mortality, cardiac death, recurrent myocardial infarction, stroke, target vessel revascularization, stent thrombosis, and BARC2-5 bleeding events at 30 days.

Conclusion

In patients with STEMI who were undergoing primary PCI and receiving treatment with aspirin and ticagrelor, bivalirudin was associated with decreased rates in NACE and minimal bleeding events without significant differences in the rates of MACCE or stent thrombosis when compared with heparin. Nevertheless, large randomized trials are warranted to confirm these observations.

Clinical trial registration

The trial was registered at the Chinese Clinical Trial Registry (ChiCTR, http://www.chictr.org.cn; identifier [ChiCTR1900022529]). Registered on 15 April 2019. Registration title: Effect of bivalirudin combined with ticagrelor in patients with ST-segment elevation myocardial infarction during primary percutaneous coronary intervention.
Nabiximols effect on blood pressure and heart rate in post-stroke patients of a randomized controlled study
Authors: Rosa Gian Marco , Puce Luca , Mori Laura , Currà Antonio , Fattapposta Francesco , Porto Italo , Bragazzi Nicola Luigi , Trompetto Carlo , Marinelli Lucio
Published: October 2022

Background

Cannabinoids may be useful to treat pain, epilepsy and spasticity, although they may bear an increased risk of cardiovascular events. This study aims to evaluate the cardiovascular safety of nabiximols, a cannabis-based drug, in patients with spasticity following stroke, thus presenting an increased cardiovascular risk.

Methods

This is an ancillary study stemming from the SativexStroke trial: a randomized double-blind, placebo-controlled, crossover study aimed at assessing the effect of nabiximols on post-stroke spasticity. Patients were treated with nabiximols oromucosal spray or placebo and assessed before and after two phases of 1-month duration each. Only the phase with the active treatment was considered for each patient who completed the study. The average values of blood pressure (diastolic, systolic, differential) and heart rate from the first 5 days of the phase (lowest nabiximols dosage) were compared to the average values recorded during the last 5 days at the end of the phase (highest nabiximols dosage). Baseline comparisons between gender, stroke type and affected side and correlation between age and blood pressure and heart rate were performed. The study was registered with the EudraCT number 2016-001034-10.

Results

Thirty-four patients completed the study and were included in the analysis. Thirty-one were taking antihypertensive drugs and, among these, 12 were taking beta-blockers. During the study, no arrhythmic events were recorded, blood pressure and heart rate did not show pathological fluctuations, and no cardiovascular or cerebrovascular events occurred. At baseline blood pressure and heart rate were comparable concerning gender, stroke type and affected side. A significant direct correlation emerged between differential blood pressure and age and an inverse correlation between diastolic blood pressure and age. No correlation emerged between systolic blood pressure or heart rate and age. Blood pressure and heart rate did not change during nabiximols treatment compared to the baseline condition.

Conclusion

This ancillary study adds evidence that, in patients who already underwent a cerebrovascular accident, nabiximols does not determine significant blood pressure and heart rate variation or cardiovascular complications. These data support the cardiovascular safety of nabiximols, encouraging more extensive studies involving cannabinoids characterized by slow absorption rates.
Population pharmacokinetic analysis for dabigatran etexilate in Chinese patients with non-valvular atrial fibrillation
Authors: Liu Ya-ou , Xie Qiu-fen , Liu Zhi-yan , Wang Zhe , Mu Guang-yan , Zhang Ya-tong , Zhao Zi-nan , Yuan Dong-dong , Guo Li-ping , Wang Na , Xiang Jing , Song Hong-tao , Jiang Jie , Xiang Qian , Cui Yi-min
Published: October 2022

We aimed to develop a pharmacokinetic (PK) and pharmacodynamic (PD) model from healthy Chinese subjects and real-world non-valvular atrial fibrillation (NVAF) patients. We also investigated meaningful intrinsic and extrinsic factors and related biomarkers for bleeding events. We characterized the integrated PK/PD models based on rich PK/PD data [dabigatran concentration, activated partial thromboplastin time (APTT), prothrombin time (PT), and anti-factor IIa (anti-FIIa) activity] from 118 healthy volunteers and sparse PD data [APTT, PT, and anti-FIIa] from 167 patients with NVAF after verifying the model extrapolation performance. We also documented the correlations between PD biomarkers and clinically relevant bleeding events over one year. Next, we used the final integrated PK/PD model (a two-compartment, linear model with first-order absorption) to evaluate the influence of dosage and individual covariates on PD parameters. The age, high-density liptein cholesterol (HDL-C), and creatinine clearance (CrCL) improved the PK model fit. The linear direct-effects PD model described the correlation between APTT, PT, and anti-FIIa and plasma concentration. CrCL improved the PD model fit. Anti-FIIa was more sensitive to the increase in dabigatran exposure than APTT and PT in the PD model. Therefore, fixed dabigatran doses could be prescribed for patients with NVAF without adjusting for age and HDL-C. We observed an elevated bleeding tendency with higher peak and trough values of APTT, PT, and anti-FIIa. Randomized studies should be performed to evaluate the efficacy and safety of low-dose dabigatran in Chinese patients with NVAF.
Toward a meaningful technology for instrumental music education: Teachers’ voice
Authors: Michałko Aleksandra , Campo Adriaan , Nijs Luc , Leman Marc , Van Dyck Edith
Published: October 2022

In musical instrument training, researchers have gradually started exploring the potential of interactive technologies supporting learning processes and teaching methods. Although numerous technological tools have been proposed to enhance instrument learning and teaching, these methods rarely find their way into daily practice and teaching routines. In this study, we report data from an online survey study administered to violin and drum kit teachers. Results reveal distinct learning profiles of novice violin and drum kit students and exhibit a variety of teaching approaches toward adults and children. Furthermore, they provide more insight into teachers’ opinions on the use of virtual reality (VR) and smart wearable technologies in early instrumental training, as well as their attitudes regarding technology design. Overall, our findings highlight the importance of involving teachers in the initial stages of technology design to facilitate technology acceptance and adoption, prevent potential mismatches between requirements regarding technological functionality and actual user needs, and promote musical growth and skill acquisition.
Back to basics: A role of reading, writing, and arithmetic teaching
Authors: Alghazo Ali M. , Abdelhamid Sherif , Alghazo Runna
Published: October 2022

This study has assessed the role of reading, writing, and arithmetic teaching among adult learners in Saudi Arabia. A quantitative approach was used by recruiting 186 students divided into three groups, namely, the write to learn (WTL) group, traditional teaching group, and individual technology use (ITU) group. Statistical Package for Social Sciences (SPSS) was used for the analysis of the arithmetic and literacy test scores of the students. The findings showed that the performance of the WTL group was most effective among the three groups. The results showed that the learning capacity of adults could be improved by refining their writing and reading skills. The formative feedback, collaborative environment, and engagement helped improve the learning scores. It shows that the use of information and communication technology (ICT) should be accurately implemented along with the formation of a collaborative environment.
A comparative analysis of eight machine learning models for the prediction of lateral lymph node metastasis in patients with papillary thyroid carcinoma
Authors: Feng Jia-Wei , Ye Jing , Qi Gao-Feng , Hong Li-Zhao , Wang Fei , Liu Sheng-Yong , Jiang Yong
Published: October 2022

Background

Lateral lymph node metastasis (LLNM) is a contributor for poor prognosis in papillary thyroid cancer (PTC). We aimed to develop and validate machine learning (ML) algorithms-based models for predicting the risk of LLNM in these patients.

Methods

This is retrospective study comprising 1236 patients who underwent initial thyroid resection at our institution between January 2019 and March 2022. All patients were randomly split into the training dataset (70%) and the validation dataset (30%). Eight ML algorithms, including the Logistic Regression, Gradient Boosting Machine, Extreme Gradient Boosting, Random Forest (RF), Decision Tree, Neural Network, Support Vector Machine and Bayesian Network were used to evaluate the risk of LLNM. The performance of ML models was evaluated by the area under curve (AUC), sensitivity, specificity, and decision curve analysis.

Results

Among the eight ML algorithms, RF had the highest AUC (0.975), with sensitivity and specificity of 0.903 and 0.959, respectively. It was therefore used to develop as prediction model. The diagnostic performance of RF algorithm was dependent on the following nine top-rank variables: central lymph node ratio, size, central lymph node metastasis, number of foci, location, body mass index, aspect ratio, sex and extrathyroidal extension

Conclusion

By combining clinical and sonographic characteristics, ML algorithms can achieve acceptable prediction of LLNM, of which the RF model performs best. ML algorithms can help clinicians to identify the risk probability of LLNM in PTC patients.
Bariatric surgery and health outcomes: An umbrella analysis
Authors: Liao Jing , Yin Yiqiong , Zhong Jing , Chen Yanjun , Chen Yanbing , Wen Yue , Cai Zhaolun
Published: October 2022

Background

There is a relative lack of data that systematically investigates the breadth and validity of the association between bariatric surgery and health-related outcomes. We aimed to evaluate the quantity, validity, and credibility of evidence regarding the association between bariatric surgery and health-related outcomes using an umbrella review of meta-analyses.

Methods

We systematically searched PubMed, Embase, and the Web of Science databases from inception until December 2, 2021, to identify meta-analyses of observational or interventional studies that investigated the association between bariatric surgery and multiple health outcomes. We extracted the summary effect size and 95% confidence interval (CI) data. The Assessment of Multiple Systematic Reviews (AMSTAR-2) and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines were used for methodological and evidence quality assessments, respectively.

Results

Twenty-eight studies with 82 different health-related outcomes were included in this umbrella review. Beneficial effects of bariatric surgery have been observed in cancer incidence, mortality, cardiovascular risk, polycystic ovary syndrome (PCOS), anxiety symptoms, depressive symptoms, gestational diabetes mellitus, gestational hypertension, large for gestational age (LGA), macrosomia, post-term birth, risk of kidney stones, albuminuria, urinary incontinence, fecal incontinence, Barrett’s esophagus, and diabetic retinopathy. However, adverse effects of bariatric surgery were observed for maternal anemia, perinatal mortality, congenital anomalies, preterm birth, neonatal intensive care unit (NICU) admission, intrauterine growth restriction, small for gestational age (SGA), fracture risk, upper limb fracture, suicide, self-harm, and alcohol use disorder (AUD).

Conclusions

Current evidence suggests that bariatric surgery improves the majority of health-related outcomes; however, caution is advised given it may increase the risk of adverse mental effects, perinatal problems, and fractures.
Involvement of POMC neurons in LEAP2 regulation of food intake and body weight
Authors: Chu Guangpin , Peng Hualing , Yu Nana , Zhang Yuejin , Lin Xueling , Lu Yisheng
Published: October 2022

Liver-expressed antimicrobial peptide 2 (LEAP2) is a newly discovered antagonist of the growth hormone secretagogue receptor (GHSR) and is considered the first endogenous peptide that can antagonize the metabolic actions of ghrelin. The effects of ghrelin administration on feeding behavior, body weight, and energy metabolism involve the activation of orexigenic neurons in the arcuate nucleus (ARC) of the hypothalamus. It is unclear, however, if LEAP2 applied directly to the ARC of the hypothalamus affects these metabolic processes. Here, we show that overexpression of LEAP2 in the ARC through adeno-associated virus (AAV) reduced food intake and body weight in wild-type (WT) mice fed chow and a high-fat diet (HFD) and improved metabolic disorders. LEAP2 overexpression in the ARC overrides both central and peripheral ghrelin action on a chow diet. Interestingly, this AAV-LEAP2 treatment increased proopiomelanocortin (POMC) expression while agouti-related peptide (AGRP)/neuropeptide Y (NPY) and GHSR levels remained unchanged in the hypothalamus. Additionally, intracerebroventricular (i.c.v.) administration of LEAP2 decreased food intake, increased POMC neuronal activity, and repeated LEAP2 administration to mice induced body weight loss. Using chemogenetic manipulations, we found that inhibition of POMC neurons abolished the anorexigenic effect of LEAP2. These results demonstrate that central delivery of LEAP2 leads to appetite-suppressing and body weight reduction, which might require activation of POMC neurons in the ARC.
Natural cycle increases the live-birth rate compared with hormone replacement treatment for frozen-thawed single euploid blastocyst transfer
Authors: Li Xiaofang , Gao Yan’e , Shi Juanzi , Shi Wenhao , Bai Haiyan
Published: October 2022

Background

A number of studies have compared the clinical outcomes between the two endometrial preparation methods: natural cycles (NCs) and hormone replacement treatment (HRT) before frozen embryo transfer, but the results were conflicting. In order to mitigate the potential effect of embryos per se, several researchers have worked on this subject for euploid blastocyst transfer, but the results were still inconsistent. Therefore, the present study was aimed to investigate the clinical outcomes between HRT and NC for autologous single vitrified–warmed euploid blastocyst transfer based on our data.

Methods

A total of 598 frozen-thawed single euploid blastocyst transfer cycles in the assisted reproductive center of Northwest Women’s and Children’s Hospital from January 2014 to May 2021 were retrospectively analyzed. Women were stratified into the NC (n = 125) or HRT (n = 473) group according to the patient’s preference and the physician’s guidance. Multivariate regression models and subgroup analysis were constructed to analyze the association between endometrial preparation and live birth.

Results

Women in the NC group had a higher live birth rate (68.80% versus 58.35%, P = 0.034) and a lower risk of total pregnancy loss (8.51% versus 21.14%, P = 0.005) when compared with women in the HRT group. The biochemical pregnancy rate (75.20% versus 74.00%, P = 0.784) and clinical pregnancy rate (74.40% versus 69.98%, P = 0.334) were similar between the two groups (NC versus HRT). NC was associated with an increased odds of live birth compared with HRT by different multivariable analysis models (Model 1: adjusted odds ratio [aOR], 95% confidence interval [CI]: 0.57, 0.36 - 0.90; Model 2: aOR, 95%CI: 0.57, 0.35 - 0.92). In addition, the increased chance of live birth in the NC group was found in all subgroups. No major obstetrical complications and two malformation livebirths were reported.

Conclusions

In women undergoing single euploid frozen blastocyst transfers, the NC group was associated with a lower pregnancy loss rate and an ultimately higher live birth rate than the HRT group. Although HRT is convenient for both clinicians and patients, the lower live birth rate should be taken into account and NC might be the first choice of endometrial preparation method.