bluuebunny/crossref_metadata_2025 huggingface dataset:
The mir-21 Inhibition Enhanced HUVEC Cellular Viability during Hypoxia-Reoxygenation Injury by Regulating PDCD4
Authors: Ali Sheikh Md Sayed
Published: June 2022

The purpose of this study was to explore the clinical value of altered plasma mir-21 expression level as a biomarker for the severity of coronary artery disease (CAD) and its molecular impact on HUVEC cellular injuries. Angiographically validated 56 patients with single-vessel CAD disease, 92 patients with double-vessel CAD, 139 complex coronary artery stenosis patients, and 56 healthy individuals (

n
=
343

) were enrolled in this study. The expressions of plasma mir-21 were evidently and progressively higher while PDCD4 levels were significantly and steadily lower in single-, dual-, and multivessel occluded CAD patients than in healthy participants (

P
<
0.001

). The relative expressions of mir-21 in hypoxia-reoxygenation- (HR-) exposed HUVECs were markedly upregulated, but PDCD4 concentrations were obviously downregulated as compared with normal control cells (

P
<
0.001

). Moreover, altered circulatory mir-21 expression levels were able to significantly differentiate single- (AUC 0.893), double- (AUC 0.914), and multivessel stenosis CAD (AUC 0.933) patients from healthy subjects. Besides, the plasma mir-21 expressions in elderly (66-85 years) groups were remarkably higher than those in younger aged (25-45 years) subjects. Caspase-3 and ROS expression levels were remarkably elevated, but cellular viability noticeably declined in HR-induced HUVECs than in normoxic cells (

P
<
0.001

). In contrast, mir-21 inhibition markedly reduced caspase-3 activity and ROS concentrations while significantly ameliorating HUVEC cellular viability in HR conditions. PDCD4 expressions in HR-exposed HUVECs were prominently decreased whereas mir-21 inhibition significantly enhanced PDCD4 levels (

P
<
0.001

). Upregulated plasma mir-21 can be a valuable clinical biomarker for the detection of the severity of coronary artery stenosis patients. Elevated circulatory mir-21 concentrations have a positive correlation with aging. Inhibitory mir-21 evidently increased HUVEC cellular viability through upregulation of targeting PDCD4 and recommended a newer possible therapeutic molecule for the management of CAD patients.
Optimization of Self-Compacting Concrete Containing Blast-Furnace Slag Compositions
Authors: Zhitkovsky Vadim , Dvorkin Leonid , Ribakov Yuri
Published: June 2022

The paper deals with composition design of self-compacting concrete containing blast furnace granulated slag and polycarboxylate type superplasticizer in a wide range of concrete strength classes. Optimal superplasticizer content, cement, and blast furnace slag consumptions are obtained from the viewpoint of minimum water demand and water-cement ratio, maximum self-compacting concrete mixture workability retention, and concrete strength. A significant effect of joint influence of superplasticizer and blast furnace slag is demonstrated. The possibility of minimizing the cement consumption at optimal superplasticizer content and slag consumption of 100–120 kg/m3 is shown. Dependences for calculating SCC strength at 1, 7, and 28 days vs. the water-cement ratio are obtained. It is found that the nature of correlation dependences for SCC splitting and compression strengths when using the blast furnace slag and the superplasticizer is linear. Optimization of SCC compositions using mathematical programming enables to obtain compositions with a lowest possible cost while providing a set of specified parameters.
Pricing Israeli Option with Time-changed Compensation by an FFT-Based High-order Multinomial Tree in Lévy Markets
Authors: Wang Weiwei , Hu Xiaoping
Published: June 2022

The problem for pricing the Israel option with time-changed compensation was studied based on the high-order recombined multinomial tree by using a fast Fourier transform to approximate a Lévy process. First, the Lévy option pricing model and Fourier transform are introduced. Then, a network model based on FFT (Markov chain) is presented. After that, an FFT-based multinomial tree construction method is given to solve the problem of difficult parameter estimation when approximating the Lévy process with high-order multinomial trees. It is proved that the discrete random variables corresponding to the multinomial tree converge to the Lévy-distributed continuous random variable. Next, an algorithm based on a reverse recursion algorithm for pricing the Israel option with time-changed compensation was presented. Finally, an example was illustrated, and the relationship between the price of the Israel option and the time-changed compensation was discussed. The results show that the method of constructing a high-order recombined multinomial tree based on FFT has very high calculation precision and calculation speed, which can solve the problem of traditional risk-neutral multinomial tree construction, and it is a promising pricing method for pricing Israel options.
Effects of Income and Price on Household’s Charcoal Consumption in Three Cities of Tanzania
Authors: Nyamoga G. Z. , Sjølie H. K. , Latta G. , Ngaga Y. M. , Malimbwi R. , Solberg B.
Published: June 2022

More than 80% of the urban and periurban population in Tanzania depend on charcoal as their main source of energy for cooking. This charcoal is supplied from natural forests, mainly Miombo woodlands, and the high charcoal consumption is a main trigger for deforestation, forest degradation, and climate gas emissions. The country’s urban population is increasing at an annual rate of 5-6%, and better understanding of the urban demand for charcoal is of high interest regarding the country’s energy development, climate mitigation, and land use. We surveyed 360 households situated in the Tanzanian cities Dodoma, Morogoro, and Mtwara and analyzed statistically the impacts of household income, charcoal prices, and household size on the per capita charcoal consumption. For the total sample, statistically significant elasticities were found to be 0.03, −0.13, and −0.62 for per capita income, charcoal price, and household size, respectively. In the low-income group, the elasticities of charcoal price and household size were found to be statistically significant with the values of −0.44 and −0.59, respectively, whereas in the middle-income group, the household size was the only statistically significant variable, with elasticity −0.81. In the high-income group, we got statistically significant elasticities of 0.17 for per capita income and −0.44 for household size. These results are based on small samples and should be followed up by larger surveys.
CHD1 Promotes Sensitivity to Aurora Kinase Inhibitors by Suppressing Interaction of AURKA with Its Coactivator TPX2
Authors: Li Haoyan , Wang Yin , Lin Kevin , Venkadakrishnan Varadha Balaji , Bakht Martin , Shi Wei , Meng Chenling , Zhang Jie , Tremble Kaitlyn , Liang Xin , Song Jian H. , Feng Xu , Van Vivien , Deng Pingna , Burks Jared K. , Aparicio Ana , Keyomarsi Khandan , Chen Junjie , Lu Yue , Beltran Himisha , Zhao Di
Published: June 2022

Clinical studies have shown that subsets of patients with cancer achieve a significant benefit from Aurora kinase inhibitors, suggesting an urgent need to identify biomarkers for predicting drug response. Chromodomain helicase DNA binding protein 1 (CHD1) is involved in chromatin remodeling, DNA repair, and transcriptional plasticity. Prior studies have demonstrated that CHD1 has distinct expression patterns in cancers with different molecular features, but its impact on drug responsiveness remains understudied. Here, we show that CHD1 promotes the susceptibility of prostate cancer cells to inhibitors targeting Aurora kinases, while depletion of CHD1 impairs their efficacy in vitro and in vivo. Pan-cancer drug sensitivity analyses revealed that high expression of CHD1 was associated with increased sensitivity to Aurora kinase A (AURKA) inhibitors. Mechanistically, KPNA2 served as a direct target of CHD1 and suppressed the interaction of AURKA with the coactivator TPX2, thereby rendering cancer cells more vulnerable to AURKA inhibitors. Consistent with previous research reporting that loss of PTEN elevates CHD1 levels, studies in a genetically engineered mouse model, patient-derived organoids, and patient samples showed that PTEN defects are associated with a better response to AURKA inhibition in advanced prostate cancer. These observations demonstrate that CHD1 plays an important role in modulating Aurora kinases and drug sensitivities, providing new insights into biomarker-driven therapies targeting Aurora kinases for future clinical studies.

Significance:

CHD1 plays a critical role in controlling AURKA activation and promoting Aurora kinase inhibitor sensitivity, providing a potential clinical biomarker to guide cancer treatment.
Metabolic Reprogramming in Hematologic Malignancies: Advances and Clinical Perspectives
Authors: Yu Zhuoya , Zhou Xiangxiang , Wang Xin
Published: June 2022

Metabolic reprogramming is a hallmark of cancer progression. Metabolic activity supports tumorigenesis and tumor progression, allowing cells to uptake essential nutrients from the environment and use the nutrients to maintain viability and support proliferation. The metabolic pathways of malignant cells are altered to accommodate increased demand for energy, reducing equivalents, and biosynthetic precursors. Activated oncogenes coordinate with altered metabolism to control cell-autonomous pathways, which can lead to tumorigenesis when abnormalities accumulate. Clinical and preclinical studies have shown that targeting metabolic features of hematologic malignancies is an appealing therapeutic approach. This review provides a comprehensive overview of the mechanisms of metabolic reprogramming in hematologic malignancies and potential therapeutic strategies to target cancer metabolism.
A Therapeutically Actionable Protumoral Axis of Cytokines Involving IL-8, TNFα, and IL-1β
Authors: Olivera Irene , Sanz-Pamplona Rebeca , Bolaños Elixabet , Rodriguez Inmaculada , Etxeberria Iñaki , Cirella Assunta , Egea Josune , Garasa Saray , Migueliz Itziar , Eguren-Santamaria Iñaki , Sanmamed Miguel F. , Glez-Vaz Javier , Azpilikueta Arantza , Alvarez Maite , Ochoa María C. , Malacrida Beatrice , Propper David , de Andrea Carlos E. , Berraondo Pedro , Balkwill Frances R. , Teijeira Álvaro , Melero Ignacio
Published: June 2022

Interleukin-8 (CXCL8) produced in the tumor microenvironment correlates with poor response to checkpoint inhibitors and is known to chemoattract and activate immunosuppressive myeloid leukocytes. In human cancer, IL8 mRNA levels correlate with IL1B and TNF transcripts. Both cytokines induced IL-8 functional expression from a broad variety of human cancer cell lines, primary colon carcinoma organoids, and fresh human tumor explants. Although IL8 is absent from the mouse genome, a similar murine axis in which TNFα and IL-1β upregulate CXCL1 and CXCL2 in tumor cells was revealed. Furthermore, intratumoral injection of TNFα and IL-1β induced IL-8 release from human malignant cells xenografted in immunodeficient mice. In all these cases, the clinically used TNFα blockers infliximab and etanercept or the IL-1β inhibitor anakinra was able to interfere with this pathogenic cytokine loop. Finally, in paired plasma samples of patients with cancer undergoing TNFα blockade with infliximab in a clinical trial, reductions of circulating IL-8 were substantiated.

Significance:

IL-8 attracts immunosuppressive protumor myeloid cells to the tumor microenvironment, and IL-8 levels correlate with poor response to checkpoint inhibitors. TNFα and IL-1β are identified as major inducers of IL-8 expression on malignant cells across cancer types and models in a manner that is druggable with clinically available neutralizing agents.

This article is highlighted in the In This Issue feature, p. 2007
SENP3 Aggravates Renal Tubular Epithelial Cell Apoptosis in Lipopolysaccharide-Induced Acute Kidney Injury via deSUMOylation of Drp1
Authors: Wang Lirui , Li Jiangtao , Yu Chen
Published: June 2022

Background: Sepsis causes acute kidney injury (AKI) in critically ill patients, although the mechanisms underlying the pathophysiology are not fully understood. SUMO-specific proteases 3 (SENP3), a member of the deSUMOylating enzyme family, is known as a redox sensor and could regulate multiple cellular signaling pathways. However, the role of SENP3 in septic AKI remains unclear. Objectives: The purpose of this study was to investigate the role of SENP3 in lipopolysaccharide (LPS)-induced AKI model. Methods: C57BL/6 mice were given intraperitoneal injection of LPS (10 mg/kg). NRK-52E cells were treated with LPS in vitro. The SENP3 protein expression was analyzed by Western blotting. The levels of reactive oxygen species (ROS) in cells were measured using DCFH-DA. SENP3-siRNA or SENP3-plasmid was, respectively, transfected into NRK-52E cells to knock down or overexpress the SENP3 expression. Western blotting was performed to analyze the protein expression of cleaved caspase 3, cytochrome c, and dynamin-related protein 1 (Drp1). The mitochondrial membrane potential was measured using JC-1 assay kit. Co-immunoprecipitation was used to determine the interaction of Drp1 and SMUO2/3. Results: SENP3 protein expression was obviously increased in renal tissues from the mouse model of LPS-induced AKI. Accordingly, SENP3 expression was upregulated in NRK-52E cells treated with LPS in a ROS-dependent manner in vitro. Knockdown of SENP3 dramatically ameliorated LPS-induced apoptosis of NRK-52E cells, whereas overexpression of SENP3 further aggravated LPS-induced apoptosis of NRK-52E cells. Mechanistically, SENP3 triggered Drp1 recruitment to mitochondria by increasing the deSUMOylation of Drp1. Conclusion: SENP3 aggravated renal tubular epithelial cell apoptosis in LPS-induced AKI via Drp1 deSUMOylation manner.
Reduction of Cardiac Fibrosis by Interference With YAP-Dependent Transactivation
Authors: Garoffolo Gloria , Casaburo Manuel , Amadeo Francesco , Salvi Massimo , Bernava Giacomo , Piacentini Luca , Chimenti Isotta , Zaccagnini Germana , Milcovich Gesmi , Zuccolo Estella , Agrifoglio Marco , Ragazzini Sara , Baasansuren Otgon , Cozzolino Claudia , Chiesa Mattia , Ferrari Silvia , Carbonaro Dario , Santoro Rosaria , Manzoni Martina , Casalis Loredana , Raucci Angela , Molinari Filippo , Menicanti Lorenzo , Pagano Francesca , Ohashi Toshiro , Martelli Fabio , Massai Diana , Colombo Gualtiero I. , Messina Elisa , Morbiducci Umberto , Pesce Maurizio
Published: June 2022

Background:

Conversion of cardiac stromal cells into myofibroblasts is typically associated with hypoxia conditions, metabolic insults, and/or inflammation, all of which are predisposing factors to cardiac fibrosis and heart failure. We hypothesized that this conversion could be also mediated by response of these cells to mechanical cues through activation of the Hippo transcriptional pathway. The objective of the present study was to assess the role of cellular/nuclear straining forces acting in myofibroblast differentiation of cardiac stromal cells under the control of YAP (yes-associated protein) transcription factor and to validate this finding using a pharmacological agent that interferes with the interactions of the YAP/TAZ (transcriptional coactivator with PDZ-binding motif) complex with their cognate transcription factors TEADs (TEA domain transcription factors), under high-strain and profibrotic stimulation.

Methods:

We employed high content imaging, 2-dimensional/3-dimensional culture, atomic force microscopy mapping, and molecular methods to prove the role of cell/nuclear straining in YAP-dependent fibrotic programming in a mouse model of ischemia-dependent cardiac fibrosis and in human-derived primitive cardiac stromal cells. We also tested treatment of cells with Verteporfin, a drug known to prevent the association of the YAP/TAZ complex with their cognate transcription factors TEADs.

Results:

Our experiments suggested that pharmacologically targeting the YAP-dependent pathway overrides the profibrotic activation of cardiac stromal cells by mechanical cues in vitro, and that this occurs even in the presence of profibrotic signaling mediated by TGF-β1 (transforming growth factor beta-1). In vivo administration of Verteporfin in mice with permanent cardiac ischemia reduced significantly fibrosis and morphometric remodeling but did not improve cardiac performance.

Conclusions:

Our study indicates that preventing molecular translation of mechanical cues in cardiac stromal cells reduces the impact of cardiac maladaptive remodeling with a positive effect on fibrosis.
‘Humanizing’ the Law of Self-Determination – the Chagos Island Case
Authors: Hilpold Peter
Published: June 2022

Human rights are perceived more and more as a set of norms of all-encompassing effects determining all international action, in particular also those by the United Nations. The recent icj Opinion in the Chagos case seems to suggest, however, that the field of self-determination is not yet really affected by this development. The icj has dealt with this case in a very traditional manner declaring, as it was foreseeable, that the de-colonisation process of the Chagos Islands has not been lawfully completed. At the same time, the icj widely ignored the direful lot of the Chagossians. This article investigates whether it is still tenable to deal with a decolonisation case exclusively from the perspective of ‘classic colonial self-determination’ while barely considering the lot of the people directly affected by these events. The main proposition of this article is that the process of humanization of international law must not stop short from affecting also the law of self-determination. It is suggested, on the contrary, that in the 21th century the law of self-determination has to set the individuals composing the people in the forefront.
Access to Information and Data in International Law
Authors: Mazur Joanna , Słok-Wódkowska Magdalena
Published: June 2022

The sharing of data between States, particularly during a transnational public emergency, is essential for, e.g., monitoring adequate responses. Yet, in the digital economy, it is the private sector that leads in the collection and processing of huge amounts of data on a global scale, while the public sector often lags behind. We begin the article by examining the shortcomings of the solutions developed in human rights law and in international economic law concerning access to public sector information and data. Afterwards, we propose three possibilities to provide adjustments of the regulatory framework governing data sharing in the era of big data: sectoral approach to data sharing, establishment of common standards for public sector information re-use, and the idea of ‘data altruism’ introduced in the Data Governance Act. We indicate how these solutions could facilitate the development of an international regulatory framework for data sharing on an international level.
Heat Transfer on a Chemically Reacting Non-Newtonian Casson Fluid Over a Vertically Stretched Magnetized Surface
Authors: Aloliga Golbert , Seini Yakubu Ibrahim , Musah Rabiu
Published: June 2022

An extensive investigation into heat transfer through Casson fluid on a stretched magnetized surface with presence of chemical reactants has been conducted. The magnetic strength influence at the plate surface and within the body of the fluid has been analysed as well as effects of
radiation and convection fields are considered. The methods of similarity analysis have been used to transform the multivariable dependent equations modelling the flow to a single variable dependent equation. The emerged dimensionless parameters describing the flow have been presented numerically.
The effects of magnetization of the surface along with the bulk fluid are presented in tables and graphs. It is evident that magnetizing the surface enhances the temperature distribution near the surface. Similar results can be seen with the coefficient of wall resistance, and the mass and
transfer rate on the magnitised plate. From the study, it is recommended that surface magnetization can influence flow kinematics involving Casson fluids for efficient control.
Enhanced Thermo-Fluidic Performance of Aqueous SiO2 Nanofluid Flow Through a Horizontal Tube—An Experimental Investigation
Authors: Mukherjee S. , Panda S. R. , Mishra P. C. , Sen S. , Chaudhuri P.
Published: June 2022

The thermo-fluidic performance of SiO2-water nanofluid (NF) flow inside a horizontal tube of circular cross section were examined applying constant heat flux. An aqua based dispersion of SiO2 nanopowders with 16.58 nm average particle diameter were used as the
working fluid with 0.15–0.35 vol.%. Experiments are conducted in the Reynolds number (Re) range of 2798.96–27989.62 maintaining the bulk temperature of the flow at 45 °C. Thermo-physical properties namely conductivity (k) and viscosity (μ) of NF were
determined at various temperatures range of 25–65 °C. Maximum 13% enhancement in k and a maximum of 20% enhancement in μ were obtained at 0.35 vol.% as compared to basefluid. Heat transfer and friction factor (f) were increased with enhancing concentration
and Re. The Nusselt number (Nu) increased upto 40% along with a maximum increase of 28.57% in f as compared to their basefluid. New empirical correlations for Nu and f of nanofluids were developed. Finally, a figure of merit (FOM) was determined, which reveals
the potency of nanofluids as working fluid for rapid cooling applications.
Cerium Compound-Loaded Poly(lactic co glycolic acid) Nanospheres in Improving Diabetic Retinopathy
Authors: Chen Han , Li Zhihong , Zhou Zhenbao , Zhuang Jingyi
Published: June 2022

This research tested a nanoparticle biomaterial in improving diabetic retinopathy (DR). Poly(lactic co glycolic acid) (PLGA)-CeO2, composed of cerium oxide (CeO2) and PLGA, was chosen as the new nanocomposite for DR treatment. DR mouse models were constructed to
test the anti-DR efficiency of polyethylenimine (PEI)-CeO2 and PLGA-CeO2. The infiltration efficiency test was conducted to study the transport performance of the delivery system, and the clinical effect of CeO2 was observed regarding the structural integrity,
oxidative stress response, inflammatory reaction, and retinal ganglion cell (RGC) apoptosis in the retina tissue. We observed that the infiltration efficiency of PLGA-CeO2 was higher than that of PEI-CeO2, and PLGA-CeO2 could inhibit oxidative stress and inflammatory
reaction. Furthermore, the clinical efficacy of PLGA-CeO2 in rescuing amotio retinae and reducing RGC apoptosis was superior to PEI-CeO2. Conclusively, PLGA-CeO2 has a significant capacity for antioxidation and reducing RGC apoptosis in mouse models, which
can be a potential compound nanodrug for DR treatment in the future.
Observed Characteristics of the Tornadic Supercells of 27–28 April 2011 in the Southeast United States
Authors: Lyza Anthony W. , Flournoy Matthew D. , Rasmussen Erik N.
Published: June 2022

An historic outbreak of tornadoes impacted a large swath of the eastern United States on 26–28 April 2011. The most severe series of tornadoes was associated with numerous classic supercell thunderstorms that developed across the Southeast during the afternoon and evening of 27 April and continued into the predawn of 28 April. This study documents characteristics of these storms with respect to tornado production and mesocyclone strength during different periods of each storm’s life cycle. The supercells initiated in four quasi-distinct spatiotemporal regions, with each cluster exhibiting slightly different evolutionary traits and tornado production. These included differences in the mean times between convection initiation and the time of first tornadogenesis for each supercell, as well as variations in overall and significant tornado production. This suggests that mesoscale environmental differences, such as proximity to a mesoscale boundary, and/or storm-scale events strongly influenced the variety of supercell evolutionary paths that were observed during this event, even in the presence of a synoptic-scale background environment extremely favorable for supercell and tornado production. The azimuthal shear products from the Multi-Year Reanalysis of Remotely Sensed Storms database perform well in discriminating between mesocyclones associated with ongoing weak, strong, and violent tornadoes during the event. Furthermore, mean azimuthal shear values during pre-tornadic (e.g., within 30 min of tornadogenesis) and tornadic phases are significantly larger than those during nontornadic phases. This warrants further study of azimuthal shear characteristics in different environments and its potential usefulness in aiding real-time forecasting efforts.

Significance Statement

This study documents the prolific supercell tornado outbreak that occurred in the southeastern United States on 27–28 April 2011. We associate tornado families with their parent supercells and use a radar-derived database to quantify changes in mesocyclone strength. We show that a variety of supercell evolutionary paths occurred during the event that were somewhat distinct based on where and when each supercell initiated. We also find significant differences between supercell intensity, characterized using azimuthal shear as a measure of mesocyclone strength, during nontornadic periods as opposed to the 30-min window prior to tornadogenesis. These findings are relevant for both researchers and operational forecasters and motivate future work to better understand relationships and processes influencing supercells and their background environments.
Benefits, Barriers and Determinants of Clinical Pathway Use in Germany, Austria and Switzerland. A pilot study
Authors: Noehammer Elisabeth , Ponweiser Matthias , Romeyke Tobias , Eibinger Florian
Published: June 2022

Background

Performance-oriented financing of healthcare aims at demand-based and efficient resource allocation. Often, clinical pathways (CPs) are introduced in this context.

Purpose

For CP success (a) the degree of utilization of and divergence, (b) cost effects and (c) health professionals’ acceptance rate of and satisfaction are relevant. There are gaps in research regarding these issues in general, and more specifically in the German speaking part of Europe.

Methodology/Approach

Employing a two-stage mixed-methods pilot study, we studied (a) and (b) quantitatively in Germany, Austria, and Switzerland, and (c) qualitatively in Germany and Austria.

Results

Many hospitals already implemented CPs, but the utilization varies. They are expected to yield middle-range savings, but intangible benefits are more important. In general, employees are in favor of CPs, but several conditions need to be met, e.g. adaptability to local requirements.

Conclusion

Linking the results to the Consolidated Framework for Implementation Research showed many criteria are covered, which might lead to the positive evaluations, but also highlights the complexity of the intervention.

Practice Implication

As enhanced acceptance rates are expected to lead to higher benefits and vice versa, management team should safeguard employee participation and perceived benefits in all phases of the CP cycle.
Comparison of Clinical Characteristics and Genetic Aberrations of Plasma Cell Disorders in Thailand Population
Authors: Jirabanditsakul Chutirat , Dakeng Sumana , Kunacheewa Chutima , U-pratya Yaowalak , Owattanapanich Weerapat
Published: June 2022

Multiple myeloma is an incurable malignancy of plasma cells resulting from impaired terminal B cell development. Almost all patients with multiple myeloma eventually have a relapse. Many studies have demonstrated the importance of the various genomic mutations that characterize multiple myeloma as a complex heterogeneous disease. In recent years, next-generation sequencing has been used to identify the genomic mutation landscape and clonal heterogeneity of multiple myeloma. This is the first study, a prospective observational study, to identify somatic mutations in plasma cell disorders in the Thai population using targeted next-generation sequencing. Twenty-seven patients with plasma cell disorders were enrolled comprising 17 cases of newly diagnosed multiple myeloma, 5 cases of relapsed/refractory multiple myeloma, and 5 cases of other plasma cell disorders. The pathogenic mutations were found in 17 of 27 patients. Seventy percent of those who had a mutation (12/17 patients) habored a single mutation, whereas the others had more than one mutation. Fifteen pathogenic mutation genes were identified: ATM, BRAF, CYLD, DIS3, DNMT3A, FBXW7, FLT3, GNA13, IRF4, KMT2A, NRAS, SAMHD1, TENT5C, TP53, and TRAF3. Most have previously been reported to be involved in the RAS/MAPK pathway, the nuclear factor kappa B pathway, the DNA-repair pathway, the CRBN pathway, tumor suppressor gene mutation, or an epigenetic mutation. However, the current study also identified mutations that had not been reported to be related to myeloma: GNA13 and FBXW7. Therefore, a deep understanding of molecular genomics would inevitably improve the clinical management of plasma cell disorder patients, and the increased knowledge would ultimately result in better outcomes for the patients.
Research and application of XGBoost in imbalanced data
Authors: Zhang Ping , Jia Yiqiao , Shang Youlin
Published: June 2022

As a new and efficient ensemble learning algorithm, XGBoost has been widely applied for its multitudinous advantages, but its classification effect in the case of data imbalance is often not ideal. Aiming at this problem, an attempt was made to optimize the regularization term of XGBoost, and a classification algorithm based on mixed sampling and ensemble learning is proposed. The main idea is to combine SVM-SMOTE over-sampling and EasyEnsemble under-sampling technologies for data processing, and then obtain the final model based on XGBoost by training and ensemble. At the same time, the optimal parameters are automatically searched and adjusted through the Bayesian optimization algorithm to realize classification prediction. In the experimental stage, the G-mean and area under the curve (AUC) values are used as evaluation indicators to compare and analyze the classification performance of different sampling methods and algorithm models. The experimental results on the public data set also verify the feasibility and effectiveness of the proposed algorithm.
Flexible conservatism in the skull modularity of convergently evolved myrmecophagous placental mammals
Authors: Ferreira-Cardoso Sérgio , Claude Julien , Goswami Anjali , Delsuc Frédéric , Hautier Lionel
Published: June 2022

Background

The skull of placental mammals constitutes one of the best studied systems for phenotypic modularity. Several studies have found strong evidence for the conserved presence of two- and six-module architectures, while the strength of trait correlations (integration) has been associated with major developmental processes such as somatic growth, muscle-bone interactions, and tooth eruption. Among placentals, ant- and termite-eating (myrmecophagy) represents an exemplar case of dietary convergence, accompanied by the selection of several cranial morphofunctional traits such as rostrum elongation, tooth loss, and mastication loss. Despite such drastic functional modifications, the covariance patterns of the skull of convergently evolved myrmecophagous placentals are yet to be studied in order to assess the potential consequences of this dietary shift on cranial modularity.

Results

Here, we performed a landmark-based morphometric analysis of cranial covariance patterns in 13 species of myrmecophagous placentals. Our analyses reveal that most myrmecophagous species present skulls divided into six to seven modules (depending on the confirmatory method used), with architectures similar to those of non-myrmecophagous placentals (therian six modules). Within-module integration is also similar to what was previously described for other placentals, suggesting that most covariance-generating processes are conserved across the clade. Nevertheless, we show that extreme rostrum elongation and tooth loss in myrmecophagid anteaters have resulted in a shift in intermodule correlations in the proximal region of the rostrum. Namely, the naso-frontal and maxillo-palatine regions are strongly correlated with the oro-nasal module, suggesting an integrated rostrum conserved from pre-natal developmental processes. In contrast, the similarly toothless pangolins show a weaker correlation between the anterior rostral modules, resembling the pattern of toothed placentals.

Conclusions

These results reveal that despite some integration shifts related to extreme functional and morphological features of myrmecophagous skulls, cranial modular architectures have conserved the typical mammalian scheme.
Chronic, acute and protocol-dependent effects of exercise on psycho-physiological health during long-term isolation and confinement
Authors: Abeln V. , Fomina E. , Popova J. , Braunsmann L. , Koschate J. , Möller F. , Fedyay S. O. , Vassilieva G. Y. , Schneider S. , Strüder H. K. , Klein T.
Published: June 2022

Exercise could prevent physical and psychological deteriorations, especially during pandemic times of lock-down scenarios and social isolation. But to meet both, the common exercise protocols require optimization based on holistic investigations and with respect to underlying processes. This study aimed to explore individual chronic and acute effects of continuous and interval running exercise on physical and cognitive performance, mood, and affect and underlying neurophysiological factors during a terrestrial simulated space mission. Six volunteers (three females) were isolated for 120 days. Accompanying exercise training consisted of a continuous and interval running protocol in a cross-over design. Incremental stage tests on a treadmill were done frequently to test physical performance. Actigraphy was used to monitor physical activity level. Cognitive performance, mood (MoodMeter®), affect (PANAS), brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), vascular-endothelial growth factor (VEGF), and saliva cortisol were investigated prior to, four times during, and after isolation, pre- and post-exercise on two separate days, respectively. As a chronic effect, physical performance increased (and IGF-1 tended) in the course of isolation and training until the end of isolation. Subjective mood and affect state, as well as cognitive performance, basal BDNF and VEGF levels, were well-preserved across the intervention. No acute effects of exercise were detected, besides slower reaction time after exercise in two out of nine cognitive tests, testing sensorimotor speed and memory of complex figures. Consistently higher basal IGF-1 concentrations and faster reaction time in the psychomotor vigilance test were found for the continuous compared to the interval running protocol. The results suggest that 120 days of isolation and confinement can be undergone without cognitive and mental deteriorations. Regular, individual aerobic running training supporting physical fitness is hypothesized to play an important role in this regard. Continuous running exercise seems to trigger higher IGF-1 levels and vigilance compared to interval running. Systematic and prolonged investigations and larger sample size are required to follow up on exercise-protocol specific differences in order to optimize the exercise intervention for long-term psycho-physiological health and well-being.
Association study between polymorphisms in MIA3, SELE, SMAD3 and CETP genes and coronary artery disease in an Iranian population
Authors: Rayat Sima , Ramezanidoraki Nasim , Kazemi Nima , Modarressi Mohammad H. , Falah Masoumeh , Zardadi Safoura , Morovvati Saeid
Published: June 2022

Background

Coronary artery disease (CAD) is the most common heart disease. Several studies have shown association between some polymorphism in different genes with CAD. Finding this association can be used in order to early diagnosis and prevention of CAD.

Method

101 CAD patients with ≥ 50% luminal stenosis of any coronary vessel as case group and 111 healthy individuals as control group were selected. the polymorphisms were evaluated by ARMS-PCR and RFLP-PCR methods.

Result

The results of this study show that there is no significant association between rs17228212, rs17465637, and rs708272 and risk of CAD. But there is significant association between risk of CAD and rs5355 (p-value = 0.022) and rs3917406 (p-value = 0.006) in total cases, and rs5882 (p-value = 0.001) in male cases.

Conclusions

Our findings revealed a significant interaction between CETP SNPs and CETP activity for affecting HDL-C levels. The SELE gene is a known cell adhesion molecule with a significant role in inflammation. Studies about possible linkage between SELE gene polymorphisms and the development of CAD are conflicting. We have found a significant association between polymorphisms of SELE gene and risk of CAD.
An evaluation of ascitic calprotectin for diagnosis of ascitic fluid infection in children with cirrhosis
Authors: Honar Naser , Nezamabadipour Najmeh , Dehghani Seyed Mohsen , Haghighat Mahmood , Imanieh Mohammad Hadi , Ataollahi Maryam , Shakibazad Nader , Javaherizadeh Hazhir
Published: June 2022

Background

The most common infection in children with the hepatic disease with or without cirrhotic ascites is spontaneous bacterial peritonitis (SBP), which occurs in the absence of an evident intra-abdominal source of infection. The present study aims to assess the value of calprotectin in ascitic fluid in the diagnosis of ascitic fluid infection in children with liver cirrhosis.

Materials and methods

In this cross-section study, 80 children with underlying liver disease who attended the Hepatology and Emergency Department in Shiraz University Hospitals were studied. All the patients were evaluated by a thorough history, clinical examination, laboratory investigations, diagnostic paracentesis with PMNLs count, and Calprotectin, which was measured in 1 mL ascitic fluid by ELISA.

Results

Thirty-five patients (43.75%) were diagnosed with ascitic fluid infection. Of these children 6 cases had positive ascitic fluid culture (SBP). Calprotectin was high in AFI patients with a statistically significant difference in AFI patients compared to non-AFI patients. The cut-off levels were 91.55 mg /L and the area under the curve was 0.971. So it can serve as a sensitive and specific diagnostic test for detection of AFI in children with underlying liver disease.

Conclusion

Elevated ascitic calprotectin levels in cirrhotic patients are a diagnostic and reliable marker for the detection of AFI and are considered a surrogate marker for PMN.
Financing COVID-19 vaccination in sub-Saharan Africa: lessons from a nation-wide willingness to pay (WTP) survey in Ghana
Authors: Alhassan Robert Kaba , Nketiah-Amponsah Edward , Immurana Mustapha , Abuosi Aaron Asibi
Published: June 2022

Background

Over 13 million doses of the corona virus disease, 2019 (COVID-19) vaccines have been administered in Ghana as at March, 2022; 28.5% of the population have received one dose while 16.3% have been fully vaccinated. Cost associated with COVID-19 vaccinations in low- and middle-income countries (LMICs) requires rethinking on sustainable funding arrangements to consolidate gains made towards containing the COVID-19 pandemic.

Objective

Ascertain the determinants of willingness to pay (WTP) for COVID-19 vaccination among adult eligible population in Ghana, and prefer evidence-based policy recommendations on sustainable financing regime for COVID-19 vaccination in the global south.

Methods

Setting/design: A cross-sectional web-based survey was conducted among adult population aged 18 years and above across the sixteen (16) administrative regions of Ghana.

Participants: A sub-sample of 697 participants willing to receive the COVID-19 vaccine was used as the unit of analysis.

Outcome measures: main outcome measures of interests were willingness to pay for COVID-19 vaccination and the specific amount respondents were willing to pay. The odds of WTP and specific amount were predicted using the step-wise backward logistic regression and backward step-wise OLS, respectively.

Results

A total of 2,107 adult respondents aged 18 years and above were reached out to answer the questionnaire; 1,556 successfully completed the questionnaire, representing 74% response rate. Out of the 1,556 valid responses, 697 said they will receive the COVID-19 vaccine. Out of the 697 sub-sample willing to accept the vaccine, 386 (55%) were willing to pay an average of US$6.00 for the vaccine. Positive predictors of WTP were: being an educated male (OR = 0.55, 95% [CI = 0.366, 0.826], p = 0.004), married and educated (OR = 2.19, 95% [CI = 1.077, 4.445], p = 0.030), being a married health worker (OR = 0.43, 95% [CI = 0.217, 0.845], p = 0.015), and having positive perception of the vaccine (OR = 2.40, 95% [CI = 1.144, 5.054], p = 0.021). High WTP amounts correlated positively with adherence to COVID-19 prevention protocols (Coef. = 10.30, 95% [CI = 0.463, 20.137], p = 0.040) and being a health worker with tertiary education (Coef. = 56.339, 95% [CI = 8.524, 104.154], p = 0.021). Christians who are also health workers by occupation were less likely to pay higher amounts for the vaccine (Coef. = -71.431, 95% [CI = 118.821, -24.040], p = 0.003).

Conclusions

WTP for COVID-19 vaccination in Ghana is low relative to comparative studies in the sub-region. There is the need for accelerated, advocacy and public education on the benefits of vaccination. Likewise, there should be broader stakeholder engagement and national dialogue on sustainable financing options for COVID-19 vaccination as donor support continues to dwindle for LIMCs like Ghana.
National geographical pattern of COVID-19 hospitalization, case fatalities, and associated factors in patients covered by Iran Health Insurance Organization
Authors: Damiri Soheila , Shojaee Ali , Dehghani Mohsen , Shahali Zahra , Abbasi Sadrollah , Daroudi Rajabali
Published: June 2022

Background

Understanding the Spatio-temporal distribution and interpersonal comparisons are important tools in etiological studies. This study was conducted to investigate the temporal and geographical distribution of COVID-19 hospitalized patients in the Iran Health Insurance Organization (IHIO) insured population (the second largest social health insurance organization) and the factors affecting their case fatality rate (CFR).

Methods

In this descriptive-analytical cross-sectional study, the demographic and clinical data of all insured of the IHIO who were hospitalized with COVID-19 in hospitals across the country until March 2021 was extracted from the comprehensive system of handling the inpatient documents of this organization. The Excel 2019 and GeoDA software were used for descriptive reporting and geographical distribution of variables. A multiple logistic regression model was used to estimate the Odds Ratio (OR) of death in patients with COVID-19 using STATA 14 software.

Results

During the first 14 months of the COVID-19 outbreak in Iran, 0.72% of the IHIO insured (303,887 individuals) were hospitalized with COVID-19. Hospitalization per 100,000 people varied from 192.51 in East Azerbaijan to 1,277.49 in Yazd province. The overall CFR in hospitalized patients was 14%. Tehran and Kohgiluyeh & BoyerAhmad provinces had the highest and lowest CFR with 19.39% and 5.19%, respectively. The highest odds of death were in those over 80 years old people (OR = 9.65), ICU-admitted (OR = 7.49), Hospitalized in governmental hospitals (OR = 2.08), Being a foreign national (OR = 1.45), hospitalized in November (OR = 1.47) and Residence in provinces such as Sistan & Baluchestan (OR = 1.47) and Razavi Khorasan (OR = 1.66) respectively. Furthermore, the odds of death were lower in females (OR = 0.81) than in males.

Conclusions

A sound understanding of the primary causes of COVID-19 death and severity in different groups can be the basis for developing programs focused on more vulnerable groups in order to manage the crisis more effectively and benefit from resources more efficiently.
A prospective comparison of 3 hamstring ACL fixation devices—rigidfix, bioscrew, and intrafix—randomized into 4 groups with a minimum follow-up of 5 years
Authors: Metso Leena , Bister Ville , Sandelin Jerker , Harilainen Arsi
Published: June 2022

Background

ACL (anterior cruciate ligament) reconstruction remains the gold standard surgical option for patients with ACL tears. There are many fixation devices available for ACL reconstruction. Recent ACL reconstruction strategies are aiming to reproduce the native anatomy and normal kinematics of the knee. This is a five years follow-up report of some of the new devices for graft fixation. A two years follow-up data was published previously.

Methods

120 patients were randomized into four different groups (30 each) for ACL reconstruction with hamstring tendons: group I femoral Rigidfix cross-pin and Intrafix tibial extension sheath with a tapered expansion screw; group II Rigidfix femoral and BioScrew interference screw tibial fixation; group III BioScrew femoral and Intrafix tibial fixation; group IV BioScrew fixation into both tunnels. The evaluation methods were clinical examination, knee scores, and instrumented laxity measurements.

Results

In this 5 years follow-up there were 102/120 (85%) patients available, but only 77 (64,2%) attended the clinical examinations. No significant difference between the groups in the clinical results was detected. Between the 2 and 5 years follow-up there were 6 additional procedures in group I and one in group II. There was a significant difference in additional procedures between group I and the other groups (P = .041).

Conclusion

There was a statistically significant difference in the additional procedures, most in group I (six). The ACL grafts were intact. Other statistically or clinically significant differences in the 5 years follow-up results were not found.

Study design

Randomized controlled clinical trial; Level of evidence, 1.

Trial registration ISRCTN registry with study ID ISRCTN34011837. Retrospectively registered 17.4.2020.
Comparison of mini endoscopic combined intrarenal surgery and multitract minimally invasive percutaneous nephrolithotomy specifically for kidney staghorn stones: a single-centre experience
Authors: Chen Zhi-Hao , Lee Kau-Han , Tseng Wen-Hsin , Su Chia-Cheng , Hsieh Kun-Lin , Lim Chye-Yang , Huang Steven K.
Published: June 2022

Background

Staghorn stones require surgical treatment to prevent serious complications. Multitract percutaneous nephrolithotomy (PNL) causes great renal parenchymal injury and blood loss. One-stage endoscopic combined intrarenal surgery (ECIRS) entails the combined use of antegrade nephroscope and retrograde flexible ureteroscope to clear the staghorn stone, which may overcome the limitations of multitract PNL. We aimed to compare the perioperative outcomes of mini ECIRS and multitract minimally invasive PNL in staghorn stone management.

Methods

This was a retrospective single-center study of patients with staghorn stones who underwent ECIRS (n = 17) or multitract minimally invasive PNL (n = 17) between January 2018 and September 2021.

Results

There was a significant between-group difference with respect to Guy’s stone score. Stone size, stone burden (ECIRS group, 21.41 cm3; multitract minimally invasive PNL group, 20.88 cm3 [P = 0.94]), and degree of hydronephrosis were comparable in the two groups. There was no significant between-group difference with respect to one-step or final stone-free rates. The mean operative time was also not significantly different between the groups (ECIRS group, 140 min; multitract minimally invasive PNL group, 183 min [P = 0.63]). ECIRS was associated with significantly lesser postoperative pain (visual analog scale; ECIRS group: 0; multitract minimally invasive PNL group: 2.7 [P < 0.001]). Hemoglobin loss, postoperative blood transfusion rate, complications, and length of hospital stay were comparable in the two groups.

Conclusion

Both mini ECIRS and multitract minimally invasive PNL were effective and safe for the management of renal staghorn stones with comparable operation time and stone-free rate, and complications. ECIRS was associated with less severe postoperative pain.