bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of turbulence modeling and rotor-stator interaction modeling for predicting complex flows in a transonic axial compressor
Authors:   School of Energy and Power Engineering, Beihang University National Key Laboratory of Science and Technology on Aero-Engine Aero- Thermodynamics, Beihang University, Wei Xindi , Tang Yumeng ,   School of Energy and Power Engineering, Beihang University National Key Laboratory of Science and Technology on Aero-Engine Aero- Thermodynamics, Beihang University, Liu* Yangwei ,   School of Energy and Power Engineering, Beihang University National Key Laboratory of Science and Technology on Aero-Engine Aero- Thermodynamics, Beihang University
Published: February 2024

The choice of numerical methods, including turbulence model and rotor-stator interface (RSI) treatments method largely affects the Reynolds-averaged Navier-Stokes (RANS) simulation of the multistage compressor. This paper presents a numerical study of the TUDa-GLR-OpenStage compressor using the shear stress transport (SST) turbulence model and SST-Helicity turbulence model. In addition, validations for rotor-stator interface treatment methods, including the unsteady sliding mesh and nonlinear harmonic methods (NLH), are also conducted to study the unsteady effect on the flow field. Results show that the effect of the turbulence model is most significant. The SST model showed a noticeable underestimation in the stall margin compared with experimental data, while SST-Helicity model improves the stall margin by about 85.5% compared with the original SST model. Flow field analysis shows that the prediction of the stator suction separation determines the accuracy of the prediction. While, the effect of the rotor-stator interaction on the performance and time-averaged radial profile is not very significant in this case.
An enhanced compressor map extension method suited for spool speeds down to 1%
Authors:   Kurzke Consulting, Kurzke Joachim
Published: February 2024

Physically sound compressor maps are the key to accurate simulations of aircraft engine performance. The simulation of ground starting and windmilling requires maps which include speeds down to 1% as well as pressure ratios less than unity. The author has described a physics-based compressor map extension method in his ISABE Paper 2019-24299. The map tables use auxiliary coordinates – so-called ß-lines – to make reading values from them unambiguous. A single set of parabolas as auxiliary coordinates is well-suited for usual performance simulation tasks. During practical application of the method, it became obvious that extending the map to spool speeds less than 10% is difficult because the use of correlations between work and flow coefficient becomes extremely sensitive. The problem is resolved by introducing a second set of ß-lines, in which all parabolas begin at the map origin (flow=0; pressure ratio=1) and end on a grid-dividing speed line. The shape of the primary ß-line grid, for speeds greater than the grid dividing speed, can be freely selected. The author has already described starting and windmilling simulations using maps generated with the enhanced methodology in an article published in the GPPS Journal 2023.
Validation of Helicity-Corrected Spalart-Allmaras Model for Corner Separation Prediction in Incompressible Flow with OpenFOAM
Authors:   Turbomachinery and Unsteady Flows Research Group, University of Windsor, Yu Zhifan , Defoe Jeff ,   Turbomachinery and Unsteady Flows Research Group, University of Windsor
Published: February 2024

Steady Reynolds-averaged Navier-Stokes (RANS) computations save significant computational resources compared to unsteady RANS and large eddy simulation (LES). However, the ability of most RANS models to accurately predict flow separation in compressor/fan blade rows is limited. Recent research has focused on reducing the computational cost of predicting compressor/fan stall points with steady computations has shown that the helicity-corrected Spalart-Allmaras (SA) turbulence model is able to avoid over-predicting corner separations and thus lead to converged RANS up to the actual stall point. To date, this model has mostly been implemented in in-house codes or in commercial codes as a user add-on, where the source code is not available. In a recent paper, the authors implemented the helicity-corrected SA model in OpenFOAM, an open-source CFD package. In this paper, the differences in the flow field for RANS solutions with the original SA model, the helicity-corrected SA model, and Menter’s shear stress transport (SST) model are highlighted for a linear cascade with incompressible flow. A NACA 65-1810 cascade is used, and computational results are compared to experimental data.
Mach number influence on low-pressure turbine flutter
Authors:   School of Aeronautics and Space Universidad Politécnica de Madrid, Corral Roque , Escudero† Alvaro ,   School of Aeronautics and Space Universidad Politécnica de Madrid, Blando Yago ,   School of Aeronautics and Space Universidad Politécnica de Madrid
Published: February 2024

The effect of the Mach number on the vibration amplitude trends of an isolated low-pressure turbine rotor is described. The study utilizes an analytical model correlating the aerodynamic work and the dry-friction work. Aerodynamic damping has been obtained using a frequency domain linearized Navier-Stokes solver, whereas friction damping has been modeled using a heuristic micro-slip model calibrated with the experimental data. In order to validate the analytical predictions, an extensive experimental campaign was conducted. Unsteady pressure transducers flushed mounted in the outer casing, one chord downstream of the trailing edge of the rotor, were used to characterize the vibration of the rotor. The analysis reveals a significant influence of the Mach number on the work balance between aerodynamic and mechanical components. It is observed that the vibration amplitude and the flutter-induced unsteady pressure perturbations of low-pressure turbine rotor blades notably increases when exit Mach number does.
The Effect of Condensation on One-dimensional Supercritical CO2 Flow
Authors:   National Key Laboratory of Science and Technology on Aero-Engine Aero-thermodynamics School of Energy & Power Engineering, Beihang University, Xu Pengcheng , Wang Yifan ,   National Key Laboratory of Science and Technology on Aero-Engine Aero-thermodynamics School of Energy & Power Engineering, Beihang University, Zou Zhengping ,   National Key Laboratory of Science and Technology on Aero-Engine Aero-thermodynamics School of Energy & Power Engineering, Beihang University
Published: February 2024

While the supercritical carbon dioxide (SCO2) compressor works near the critical point, possible phase change in the compressor inducer will lead to unusual flow behavior that is quite different from ideal gases. Special attention is paid to the possible condensation when the inflow is supercooled. This condition arises with compressor overspeed and increased stagnation pressure loss. The problem is studied by one-dimensional flow analysis and validated against results from high-fidelity computations. Flow choking and pressure loss caused by the condensation are discussed. Results show that the effects of condensation are twofold. First, the mass and energy transfer between the phases during the condensation process tends to accelerate the flow, thus limiting the swallowing capacity. Second, condensation is a thermodynamically irreversible process which leads to loss of the total pressure.
Experimental investigation on the effect of impingement hole location on vane impingement/film cooling
Authors:   Key Laboratory of Thermo- Fluid Science and Engineering of MOE, Xi’an Jiaotong University, Cheng Xiang , Ji Wen-Tao ,   Key Laboratory of Thermo- Fluid Science and Engineering of MOE, Xi’an Jiaotong University, Ding Yu-Zhong ,   Key Laboratory of Thermo- Fluid Science and Engineering of MOE, Xi’an Jiaotong University, He Ya-Ling ,   Key Laboratory of Thermo- Fluid Science and Engineering of MOE, Xi’an Jiaotong University, Wan Hong-Niu ,   Key Laboratory of Thermo- Fluid Science and Engineering of MOE, Xi’an Jiaotong University, Tao Wen-Quan ,   Key Laboratory of Thermo- Fluid Science and Engineering of MOE, Xi’an Jiaotong University
Published: February 2024

In order to study the effect of impingement hole location on the ICE (Integrated Cooling Effectiveness) of turbine vanes, the heat transfer experiments of vanes with low thermal conductivity were conducted. The test vanes include typical film cooling without jets (Vane 0), typical impingement/film cooling with centerline normal jets (Vane 1), and swirl impingement/film cooling with offset jets (Vane 2). When the BR (Blowing Ratio) was relatively higher, the heat transfer between the coolant and the target surface was enhanced by jet impingement, and the ICE of Vanes 1 and 2 was 3.6-8.6% higher than that of Vane 0. The jet impingement enhanced region was relatively independent of the film hole coverage region because the offset impingement holes were located at the film hole inlet upstream. It made the vane surface temperature distribution more uniform and ICE of Vane 2 slightly higher. However, when the BR was relatively small, the ICE of Vane 1 with centerline jets was larger than that of Vane 0, and the ICE of Vane 2 with offset jets was lower than that of Vane 0.
Nonlinear frequency response analysis of a rotating structure via the hyper-reduction
Authors:   Seoul National University, Kang Seung-Hoon , Kim Yongse ,   Republic of Korea Air Force, Lee Sangmin ,   Seoul National University, Hwang Minho ,   Seoul National University, Cho Haeseong ,   Jeonbuk National University, Shin SangJoon ,   Seoul National University
Published: February 2024

Linear frequency response (LFR) analysis is the efficient approach to obtain the periodic vibratory response of the rotating structure, in which centrifugal effect is included by the preliminary nonlinear static analysis. However, LFR analysis is not capable of reflecting the coupling effect among the harmonic responses. Harmonic balance (HB) method overcomes such limitation by assuming the structural response as the truncated Fourier expansion. In this paper, HB analysis will be applied for the vibration prediction of the rotating structure. The difference from LFR analysis will be investigated. In addition, the hyper-reduction approach will be presented to treat the magnified degrees of freedom (DOFs) due to the harmonically coupled assumption. Proper orthogonal decomposition basis will be combined with the energy-conserving sampling and weighting method. Application on the example of 0.9-million DOFs will be conducted.
Modelling practices for axial compressors - assessment of contemporary enhancements of k−ω shear stress transport turbulence model
Authors:   Cranfield University, Zawadzki Natan , Szymański Artur ,   Cranfield University, Igie Uyioghosa ,   Cranfield University
Published: February 2024

A Reynolds-Averaged Navier-Stokes (RANS) analysis requires turbulence models, such as the Shear Stress Transport (SST). Their limitations are particularly evident in compressor applications due to the inherent flow complexity. Several modifications were proposed to enhance the SST predictive capability, but only a handful of validation examples exist for axial turbomachinery. Furthermore, the reproducibility of the available work is frequently restricted by proprietary geometrical data that cannot be published. The aim of this study was to present a comprehensive account of the Computational Fluid Dynamics (CFD) process to analyse an axial compressor. Particular attention was paid to validating the recent enhancement of the SST model and their applicability to axial compressors. Best practices for selecting an adequate numerical setup were evaluated and discussed in detail, including aspects of discretisation, modelling errors, and challenges encountered in the post-processing phase. RANS simulations of a single blade passage of NASA Rotor 67 (R67) were performed at design speed. The turbulence model study was conducted using the SST model along with five enhancements: increased shear stress limiter (SST-a1), streamline curvature correction (SST-CC), reattachment modification (SST-RM), the γ -Reθ laminar-turbulent boundary layer transition (SST-T), and a blend of the latter two (SST-RM-T). The study showed that while the analysed turbulence models gave reasonably consistent results at stable compressor operation, they exhibited marked differences towards the stall. Combining the transition model with reattachment modification allowed for the best agreement with the experiment across the entire operating range. Thus, it was recommended for transonic rotor simulations. Further findings reiterate the importance of careful and consistent development of the CFD methodology and can serve as helpful guidance for similar applications. We demonstrated that mesh distribution is of primary importance to achieve gird independence in sensitive regions such as hub corner stall and tip gap clearance. It was also found that inadequate flow sampling and averaging can significantly distort the simulated compressor characteristic.
Quasi-steady state CFD simulation method for the ac/deceleration process of gas turbine engine
Authors:   Tsinghua University, Xu YiBing , Cao Ruizhe ,   Tsinghua University, Gao Lei ,   Tsinghua University, Wang Qiujun ,   Tsinghua University, Yan Chong ,   Tsinghua University, Piao Ying ,   Tsinghua University
Published: February 2024

Acceleration and deceleration characteristics reflect the ability of the engine to switch operating states, which is an important performance parameter of gas turbine engine. The development of computational fluid dynamics (CFD) technology provides a new paradigm for engine simulation and makes it possible to carry out unsteady simulations of gas turbine engine in a more physical way. From the perspective of physical equations, three feasible schemes for simulating the ac/deceleration process are presented and analysed: transient coupled scheme, transient decoupled scheme and quasi-steady state scheme. The difference between the three methods lies in the level of the coupling between the rotor motion equation and N-S equations. The quasi-steady state simulation method can realize rapid simulation of engine transient process by considering rotor motion inertia while ignoring the fluid inertia in the engine. Taking KJ66 micro turbojet as an example, the ac/deceleration process is simulated based on the quasi-steady state CFD simulation. With different ac/deceleration fuel supply rules, the duration time from the idling state to the design state is estimated and the whole engine flow field is obtained. This simulation of the engine ac/deceleration characteristics can provide an important forecasting method for designing the ac/deceleration control rules of the gas turbine engine.
Antibiotic Resistance-An institutional questionnaire study
Authors: Kolli Sai Sri , Manjusha S. Sethu , Samata Y. , Rao Naik N. Purna Chandra , Shruthi P. , Sanjana M.
Published: February 2024

To determine the pattern of antibiotic prescription and to assess the knowledge of antibiotic resistance among dentists.

Material and Methods
An electronic version of the questionnaire regarding antibiotic use and knowledge on antibiotic resistance was created using google forms and a link was mailed to dental surgeons and their response was recorded. Data obtained was recorded and analysed using descriptive statistics.

Results
Out of 130 responses recorded 45.4% of dentists prefer prescribing antibiotics daily. Amoxicillin was the most often recommended antibiotic by majority (49.6%) of the practitioners, While 54.6% of dentists considered a duration of 3 days course of antibiotics for odontogenic infections. 43.7% of the respondent’s considered clindamycin as an alternative in penicillin-allergic patients. Abscess was the most common (67.2%) condition considered for antibiotic prescription ,49.6% of the participants stated that availability of a particular brand as a primary factor for prescription of antibiotics. 40.3% of dental surgeons felt that failure to prescribe antibiotics was the main reason for the spread of infection. Almost 91.8% of dental surgeons were aware that antibiotic resistance was becoming a global concern.

Conclusion
Antibiotics revolutionized the way infections are being treated, Although incorrect and inappropriate use of antibiotics could be a contributing factor for the development of Antibiotic Resistance. Anti-microbial stewardship should be deeply integrated into dental practice and oral health care, to reduce the number of unnecessary prescriptions and educational intervention is utmost essential to limit non-medical prescriptions.

Key Words
Anti-microbial resistance in dentistry, Antibiotic prescribing patterns, Antibiotic resistance, Over-prescription
Self-Assessment of Emotional Intelligence amongst Medical and Dental
Students: A Questionnaire-Based Study
Authors: Sakthivel Abhipreethi , Hyder Aamina , Anandan Soumya , Varadarajan S , Chelvan H Thamizh
Published: February 2024

Emotional intelligence (EI) has never been spoken in the field of dentistry ever since our profession has taken its shape by itself. The traditional Intelligent IQ assessments which are used as tools for testing the knowledge of the students have been carried out and updated in various curriculum updates of our Dental council of India (DCI regulations).

Material and Methods: This objective was studied using a self-assessment questionnaire, which all the students of our college and other colleges who volunteered to participate were collected. This questionnaire used a standardized objective scale of evaluation and was validated. Following which the students were sensitized who showed willingness to participate. Then each of them was subjected to self-assessment. The results of the questionnaire were divided into four components of analysis such as self- awareness, self- management, social- awareness and relationship-management.

Results: The total number of students who were subjected included 309 from colleges around Chennai. The results thus obtained were classified into 2 categories based on the EQ as low EQ and Normal EQ. The results were tabulated based on gander, in comparison to each component of the analysis. Thereby we found statistically significant results in components such self- awareness and self-management to male gender.

Conclusion: We conclude from this study that the mentioned ways of practice implementation as a curricular aspect into dentistry would empower the students to have an overall outcome as a dentist and not merely a dentist with the strength of knowledge and without the power to apply this into practical life practices.

Key Words: Assessments, Emotional intelligence, Self awareness.
A role for TRPC3 in mammalian testis development
Authors: Ming Zhenhua , Bagheri-Fam Stefan , Frost Emily R. , Ryan Janelle M. , Vining Brittany , Harley Vincent R.
Published: February 2024

SOX9 is a key transcription factor for testis determination and development. Mutations in and around the SOX9 gene contribute to Differences/Disorders of Sex Development (DSD). However, a substantial proportion of DSD patients lack a definitive genetic diagnosis. SOX9 target genes are potentially DSD-causative genes, yet only a limited subset of these genes has been investigated during testis development. We hypothesize that SOX9 target genes play an integral role in testis development and could potentially be causative genes in DSD. In this study, we describe a novel testicular target gene of SOX9, Trpc3. Trpc3 exhibits high expression levels in the SOX9-expressing male Sertoli cells compared to female granulosa cells in mouse fetal gonads between embryonic day 11.5 (E11.5) and E13.5. In XY Sox9 knockout gonads, Trpc3 expression is markedly downregulated. Moreover, culture of E11.5 XY mouse gonads with TRPC3 inhibitor Pyr3 resulted in decreased germ cell numbers caused by reduced germ cell proliferation. Trpc3 is also expressed in endothelial cells and Pyr3-treated E11.5 XY mouse gonads showed a loss of the coelomic blood vessel due to increased apoptosis of endothelial cells. In the human testicular cell line NT2/D1, TRPC3 promotes cell proliferation and controls cell morphology, as observed by xCELLigence and HoloMonitor real-time analysis. In summary, our study suggests that SOX9 positively regulates Trpc3 in mouse testes and TRPC3 may mediate SOX9 function during Sertoli, germ and endothelial cell development.
How great thou ART: biomechanical properties of oocytes and embryos as indicators of quality in assisted reproductive technologies
Authors: Fluks Monika , Collier Rebecca , Walewska Agnieszka , Bruce Alexander W. , Ajduk Anna
Published: February 2024

Assisted Reproductive Technologies (ART) have revolutionized infertility treatment and animal breeding, but their success largely depends on selecting high-quality oocytes for fertilization and embryos for transfer. During preimplantation development, embryos undergo complex morphogenetic processes, such as compaction and cavitation, driven by cellular forces dependent on cytoskeletal dynamics and cell-cell interactions. These processes are pivotal in dictating an embryo’s capacity to implant and progress to full-term development. Hence, a comprehensive grasp of the biomechanical attributes characterizing healthy oocytes and embryos is essential for selecting those with higher developmental potential. Various noninvasive techniques have emerged as valuable tools for assessing biomechanical properties without disturbing the oocyte or embryo physiological state, including morphokinetics, analysis of cytoplasmic movement velocity, or quantification of cortical tension and elasticity using microaspiration. By shedding light on the cytoskeletal processes involved in chromosome segregation, cytokinesis, cellular trafficking, and cell adhesion, underlying oogenesis, and embryonic development, this review explores the significance of embryo biomechanics in ART and its potential implications for improving clinical IVF outcomes, offering valuable insights and research directions to enhance oocyte and embryo selection procedures.
In vivo PSC differentiation as a platform to identify factors for improving the engraftability of cultured muscle stem cells
Authors: Xie Ning , Robinson Kathryn , Sundquist Timothy , Chan Sunny S. K.
Published: February 2024

Producing an adequate number of muscle stem cells (MuSCs) with robust regenerative potential is essential for the successful cell therapy of muscle-wasting disorders. We have recently developed a method to produce skeletal myogenic cells with exceptional engraftability and expandability through an in vivo pluripotent stem cell (PSC) differentiation approach. We have subsequently mapped engraftment and gene expression and found that leukemia inhibitory factor receptor (Lifr) expression is positively correlated with engraftability. We therefore investigated the effect of LIF, the endogenous ligand of LIFR, on cultured MuSCs and examined their engraftment potential. We found that LIF-treated MuSCs exhibited elevated expression of PAX7, formed larger colonies from single cells, and favored the retention of PAX7+ “reserve cells” upon myogenic differentiation. This suggested that LIF promoted the maintenance of cultured MuSCs at a stem cell stage. Moreover, LIF enhanced the engraftment capability of MuSCs that had been expanded in vitro for 12 days by 5-fold and increased the number of MuSCs that repopulated the stem cell pool post-transplantation. These results thereby demonstrated the effectiveness of our in vivo PSC differentiation platform to identify positive regulators of the engraftability of cultured MuSCs.
Predictive functional control for separation processes by liquid-liquid extraction
Authors: Vanel V. , Mallet J. , Dinh B. , Michaud S. , Montuir M. , Vilpini F.
Published: February 2024

A separation process by liquid-liquid extraction is a well-known and widespread industrial technology implemented to quantitatively recover valuable chemical elements. In the nuclear industry, such processes have been used for decades to recover uranium and plutonium from spent fuel. The process is non-linear and time constants vary over a wide range. Former studies on a simplified model showed linear controllers such as PID were not adapted to regulate these separation processes. The objective of this study is to propose process monitoring by using available physical models within the PAREX code and to validate the feasibility to monitor a separation process by using directly the PAREX code as a black box. The Predictive Functional Control (PFC) command law manages to monitor non-linear separation processes by liquid-liquid extraction, when using an existing physical model implemented in the PAREX code. An online alignment of the model on process values is necessary to keep the model sufficiently representative to predict the future behaviour of the process. As a reference benchmark, the PID control loop is also simulated with the physical model. The PFC and PID regulations are compared to evaluate the gain of using physical models implemented in the PAREX code. A simulation tool has been developed to implement the PID and Predictive Functional Control (PFC) controllers for separation processes by liquid-liquid extraction. The PFC command law manages to monitor non-linear separation processes, when using a physical model connected to the PAREX code. Even if the PID controller may be locally more efficient, the great strength of the PFC controller is to enable good performances on wider operating conditions, with an easier parametrization. The PFC algorithm is a mean to deal with the process characteristic features, like non-linearity and time constant change. The PFC controller appears to be a good candidate for experimental tests. A mid-term objective is to include the state estimator tool in the control loop to consolidate the controlled variable measurements. These developments may be regarded as an add-on module in a digital factory concept. Results shown in this article are only from simulation. For the sake of data confidentiality, studies with the PAREX code cannot be published and numerical parameters of the process are normalized. These simulations will be validated during further experimental tests.
Education and cardiovascular diseases: a Mendelian randomization study
Authors: Liu Wei , Lin Quan , Fan Zongjing , Cui Jie , Wu Yang
Published: February 2024

Background

Observational studies have indicated a potential association between education and cardiovascular diseases (CVDs). However, uncertainties regarding the causal relationship persist. Therefore, this study aimed to investigate whether higher levels of education causally reduce the risks of CVDs.

Methods

Employing a two-sample Mendelian randomization (MR) design, our study examined the relationship between education and ten different CVDs. Utilizing data from the IEU Open GWAS database, relevant single nucleotide polymorphisms (SNPs) were identified through stringent screening criteria. Causality was assessed using the inverse-variance weighted (IVW), ME-Egger regression, and weighted median methods. Sensitivity analyses, including heterogeneity and pleiotropy tests, were conducted to ensure the robustness of our findings.

Results

Our study identified a genetic predisposition associated with an additional 3.6 years of education, which significantly reduced the risk of various CVDs. Specifically, this genetic factor was found to lower the risk of type 2 diabetes by 46.5%, coronary heart disease by 37.5%, ischemic stroke by 35.4%, cardiac-related mortality by 28.6%, heart failure by 28.2%, transient ischemic attack by 24%, atrial fibrillation by 15.2%, peripheral artery disease by 0.3%, and hypertension by 0.3%. However, no significant evidence revealed a causal relationship between education and pulmonary embolism.

Conclusion

Our study provides robust evidence supporting the role of higher educational attainment in reducing the incidence of various cardiovascular diseases, including type 2 diabetes, coronary heart disease, ischemic stroke, cardiac-related mortality, heart failure, transient ischemic attack, atrial fibrillation, peripheral artery disease, and hypertension. However, the impact of education on pulmonary embolism remains inconclusive.
Genetic insights into repurposing statins for hyperthyroidism prevention: a drug-target Mendelian randomization study
Authors: Huang Anqi , Wu Xinyi , Lin Jiaqi , Wei Chiju , Xu Wencan
Published: February 2024

Background

Current therapeutic measures for thyroid dysfunction are limited and often accompanied by adverse effects. The use of lipid-lowering drugs like statins has recently been associated with lower thyroid eye diseases risk.

Objective

To investigate the implications of genetically proxied lipid-lowering drugs on thyroid dysfunction.

Methods

In this drug-target Mendelian randomization (MR) study, we utilized genetic variants within drug target genes associated with low-density lipoprotein (LDL) or triglyceride (TG), derived from a genome-wide association study (GWAS) meta-analysis (N ≤ 188,577), to simulate lifelong drug interventions. Genetic summary statistics for thyroid dysfunction outcomes were retrieved from GWAS datasets of Thyroid Omics Consortium (N ≤ 54,288) and UK Biobank (N = 484,598). Inverse-variance-weighted MR (IVW-MR) method was performed as primary analysis, followed by validation in colocalization analysis. A subsequent two-step MR analysis was conducted to identify biomarkers mediating the identified drug-outcome association.

Results

In IVW-MR analysis, genetic mimicry of 3-hydroxy-3-methylglutarylcoenzyme reductase (HMGCR) inhibitors (e.g. statins) was significantly associated with lower risk of hyperthyroidism in two independent datasets (OR1, 0.417 per 1-mmol/L lower in LDL-C; 95% CI 0.262 to 0.664; P1 = 2.262 × 10-4; OR2 0.996; 95% CI 0.993-0.998; P2 = 0.002). Two-step MR analysis revealed eighteen biomarkers linked to genetic mimicry of HMGCR inhibition, and identified insulin-like growth factor 1 (IGF-1) levels mediating 2.108% of the negative causal relationship between HMGCR inhibition and hyperthyroidism.

Conclusion

This study supports HMGCR inhibition as a promising therapeutic strategy for hyperthyroidism and suggests its underlying mechanisms may extend beyond lipid metabolism. Further investigations through laboratory studies and clinical trials are necessary to confirm and elucidate these findings.
X-ray chemical imaging for assessing redox microsites within soils and sediments
Authors: Noël Vincent , Boye Kristin , Naughton Hannah R. , Lacroix Emily M. , Aeppli Meret , Kumar Naresh , Fendorf Scott , Webb Samuel M.
Published: February 2024

Redox reactions underlie several biogeochemical processes and are typically spatiotemporally heterogeneous in soils and sediments. However, redox heterogeneity has yet to be incorporated into mainstream conceptualizations and modeling of soil biogeochemistry. Anoxic microsites, a defining feature of soil redox heterogeneity, are non-majority oxygen depleted zones in otherwise oxic environments. Neglecting to account for anoxic microsites can generate major uncertainties in quantitative assessments of greenhouse gas emissions, C sequestration, as well as nutrient and contaminant cycling at the ecosystem to global scales. However, only a few studies have observed/characterized anoxic microsites in undisturbed soils, primarily, because soil is opaque and microsites require µm-cm scale resolution over cm-m scales. Consequently, our current understanding of microsite characteristics does not support model parameterization. To resolve this knowledge gap, we demonstrate through this proof-of-concept study that X-ray fluorescence (XRF) 2D mapping can reliably detect, quantify, and provide basic redox characterization of anoxic microsites using solid phase “forensic” evidence. First, we tested and developed a systematic data processing approach to eliminate false positive redox microsites, i.e., artefacts, detected from synchrotron-based multiple-energy XRF 2D mapping of Fe (as a proxy of redox-sensitive elements) in Fe-“rich” sediment cores with artificially injected microsites. Then, spatial distribution of FeII and FeIII species from full, natural soil core slices (over cm-m lengths/widths) were mapped at 1–100 µm resolution. These investigations revealed direct evidence of anoxic microsites in predominantly oxic soils such as from an oak savanna and toeslope soil of a mountainous watershed, where anaerobicity would typically not be expected. We also revealed preferential spatial distribution of redox microsites inside aggregates from oak savanna soils. We anticipate that this approach will advance our understanding of soil biogeochemistry and help resolve “anomalous” occurrences of reduced products in nominally oxic soils.
Rising awareness to improve conservation of microorganisms in terrestrial ecosystems: advances and future directions in soil microbial diversity from Chile and the Antarctic Peninsula
Authors: Lavergne Céline , Cabrol Léa , Cuadros-Orellana Sara , Quinteros-Urquieta Carolina , Stoll Alexandra , Yáñez Carolina , Tapia Joseline , Orlando Julieta , Rojas Claudia
Published: February 2024

Soil ecosystems are important reservoirs of biodiversity, as they are the most diverse habitat on Earth. Microbial biodiversity plays key roles in many ecosystem services, including the support to biogeochemical cycles. However, despite great advances in the understanding of the role of soil microbiota in providing benefits to nature and humankind, there is still much knowledge to be gained from understudied areas across the globe. Indeed, underrepresentation of the Global South in ecological studies has been suggested as an important gap that could compromise global solutions to conservation and the current biodiversity and climate crisis. In the Southern hemisphere, the southwest of South America, which includes Chile, runs behind the rest of the continent on studies related to soil microbial diversity and ecosystem functions. Therefore, to gain a better understanding of the global biodiversity and environment crisis, essential perspectives and knowledge from underrepresented regions need to be acknowledged to avoid biases in the scientific community. The main objective of this work is to understand how soil microbial diversity has been studied in Chile and the Antarctic Peninsula since 1975 to identify main knowledge gaps and funding opportunities for future research. Our survey consists of 343 articles representing 1,335 sampling points from Continental Chile to the Antarctic Peninsula. It revealed a better representation of articles studying bacterial and fungal diversity in the extreme regions of Chile funded by both international funds and the National Agency for Research and Development (ANID). To study microbial diversity, cultivation-based methods are still the most commonly used, whereas molecular studies are increasing but insufficiently applied. We have identified and argued the need to enhance collaborative multi- and interdisciplinary efforts, fundings for sequencing effort, and long-term studies to provide robust and informative knowledge about soil microbial communities.
Synergistic interplay between arbuscular mycorrhizal fungi and fern manure compost tea suppresses common tomato phytopathogens and pest attacks on-farm
Authors: Mbogning Sylviane , Okiobe Simon Thierry , Theuerl Susanne , Nwaga Dieudonne
Published: February 2024

Actually, there are intensive efforts towards eco-friendly integrated agricultural management measures to control plant diseases and pests. One of the most promising approaches is the use of arbuscular mycorrhizal fungi (AMF) in combination with organic biopesticides such as eagle fern manure (FM) compost tea. However, their effects have been mainly studied independently from each other. The potential interactions between belowground plant-associated microorganisms such as AMF and aboveground foliar application of biopesticide to mitigate common tomato phytopathogens and pests remain untapped, particularly under on-farm conditions. In a randomized complete block design, the impact of inoculating tomato seedlings with a selected AMF consortium and beyond that the impact of mycorrhized plants receiving three different doses of FM compost tea (0%, 5%, and 10%) on the control of tomato-specific plant diseases and pests and subsequently on the crop yield were examined. The present study demonstrated a sevenfold increase in the rate of mycorrhizal root colonization (from 10% to 70%) in tomato plants that received the combined application of AMF and 10% FM compost tea compared to the control plants that did not receive AMF inoculum and FM compost tea. The combination of AMF and FM compost tea application led to positive synergistic effects that promoted beneficial effects in suppressing the incidence and severity of common tomato diseases and pests. The magnitude of these synergistic effects increased with AMF inoculation and FM compost tea dosage, culminating in greater suppression of tomato plant diseases and pests and, moreover, in an increase in fruit yield compared to control plants. The combination of AMF and 10% FM compost tea revealed a higher suppressive ability against most pathogens and insect attacks. This was evidenced by a 71.3% and 94.7% total reduction in incidence and severity, respectively, compared to control plants. This is the first time that pre-inoculation of AM, combined with FM compost tea application, has been reported as a potential biocontrol alternative to suppress common tomato pathogens and pests while increasing cherry tomato yields sustainably.
Enhancing immune regulation in vitro: the synergistic impact of 3′-sialyllactose and osteopontin in a nutrient blend following influenza virus infection
Authors: Guo Zhengtao , Xie Qinggang , Ren Qiqi , Liu Yang , Li Kaifeng , Li Bailiang , Li Jufang
Published: February 2024

Natural components of breast milk, human milk oligosaccharides (HMOs) and osteopontin (OPN) have been shown to have a variety of functional activities and are widely used in infant formulas. However, the preventive and therapeutic effects of both on influenza viruses are not known. In this study, antiviral assays using a human laryngeal carcinoma cell line (HEP-2) showed that 3′-sialyllactose (3′-SL) and OPN had the best antiviral ability with IC50 values of 33.46 μM and 1.65 μM, respectively. 3′-SL (10 μM) and OPN (4 μM) were used in combination to achieve 75% inhibition. Further studies found that the combination of 200 μg/mL of 3′-SL with 500 μg/mL of OPN exerted the best antiviral ability. The reason for this was related to reduced levels of the cytokines TNF-α, IL-6, and iNOS in relation to mRNA expression. Plaque assay and TCID50 assay found the same results and verified synergistic effects. Our research indicates that a combination of 3′-SL and OPN can effectively reduce inflammatory storms and exhibit anti-influenza virus effects through synergistic action.
From immune checkpoints to therapies: understanding immune checkpoint regulation and the influence of natural products and traditional medicine on immune checkpoint and immunotherapy in lung cancer
Authors: Zhou Yibin , Wang Fenglan , Li Guangda , Xu Jing , Zhang Jingjing , Gullen Elizabeth , Yang Jie , Wang Jing
Published: February 2024

Lung cancer is a disease of global concern, and immunotherapy has brought lung cancer therapy to a new era. Besides promising effects in the clinical use of immune checkpoint inhibitors, immune-related adverse events (irAEs) and low response rates are problems unsolved. Natural products and traditional medicine with an immune-modulating nature have the property to influence immune checkpoint expression and can improve immunotherapy’s effect with relatively low toxicity. This review summarizes currently approved immunotherapy and the current mechanisms known to regulate immune checkpoint expression in lung cancer. It lists natural products and traditional medicine capable of influencing immune checkpoints or synergizing with immunotherapy in lung cancer, exploring both their effects and underlying mechanisms. Future research on immune checkpoint modulation and immunotherapy combination applying natural products and traditional medicine will be based on a deeper understanding of their mechanisms regulating immune checkpoints. Continued exploration of natural products and traditional medicine holds the potential to enhance the efficacy and reduce the adverse reactions of immunotherapy.
Case report: Identification of Hepatitis B Virus in the cerebrospinal fluid of neuromyelitis optica spectrum disorders and successful treatment with ofatumumab and inebilizumab
Authors: Cai Linjun , Liu Xu , Zhou Hongyu , Li Jinmei , Zhou Dong , Hong Zhen
Published: February 2024

Neuromyelitis optica spectrum disorder (NMOSD) is a rare demyelinating disease of the central nervous system primarily affecting the optic nerves, spinal cord, and brainstem. Viral infection may trigger NMOSD. Here, we report the case of a 34-year-old female presenting with a range of symptoms including nausea, vomiting, dysphagia, choking, and fatigue with unsteady gait, diplopia, hearing loss, left-sided facial paralysis, breathing difficulties, and hoarseness of voice. Her HBV DNA concentration, as determined by quantitative PCR analysis, exceeded 5×107 IU/ml in serum and 4.48×102 IU/ml in CSF. Next-generation sequencing of CSF revealed 1,528 HBV sequences in DNA analysis and 6 sequences in RNA analysis. Serum aquaporin-4 antibody (AQP4-Ab) titer was 1:10, and the CSF titer was 1:3.2. Brain magnetic resonance imaging showed high signal intensities in the brain stem, medulla oblongata, and left middle cerebellar peduncle with mild restricted-diffusion. The patient received antiviral and hepatoprotective medications before the high-dose methylprednisolone pulse therapy. However, the patient did not respond well to the first-line treatment. Subsequently, the patient received ofatumumab and inebilizumab. Throughout the follow-up period, there was a gradual improvement in her neurological symptoms, with no reactivation of hepatitis B or deterioration of liver function observed. Thereby, to the best of our knowledge, we report the first case of successful treatment with ofatumumab and inebilizumab in a patient with NMOSD concurrent with HBV infection.
Ratio of hemoglobin to red cell distribution width: an inflammatory predictor of survival in AIDS-related DLBCL
Authors: Chen Juanjuan , Wu Yihua , Zhao Han , Ruan Guangjing , Qin Shanfang
Published: February 2024

Background

Despite the introduction of combined antiretroviral therapy, AIDS-related diffuse large B-cell lymphoma (AR-DLBCL) remains a prominent cancer among individuals living with HIV with a suboptimal prognosis. Identifying independent prognostic markers could improve risk stratification.

Methods

In this multicenter retrospective cohort study spanning years 2011 to 2019, 153 eligible patients with AR-DLBCL were examined. Overall survival (OS) factors were analyzed using Kaplan–Meier curves, and univariate and multivariate Cox proportional hazards models. The discriminatory ability of the risk score was evaluated by examining the area under the receiver operating characteristic curve.

Results

The study included 153 patients with a median age of 47 years (interquartile range [IQR] 39–58), 83.7% of whom were men. The median follow-up was 12.0 months (95% confidence interval [CI], 8.5–15.5), with an OS rate of 35.9%. Among the potential inflammatory markers examined, only the ratio of hemoglobin (g/dL) to red cell distribution width (%) (Hb/RDW) emerged as an independent prognostic parameter for OS in the training (hazard ratios [HR] = 2.645, 95% CI = 1.267–5.522, P = 0.010) and validation cohorts (HR = 2.645, 95% CI = 1.267–5.522, P = 0.010). A lower Hb/RDW ratio was strongly correlated with adverse clinical factors, including advanced Ann Arbor stage, increased extranodal sites, reduced CD4 count, elevated lactate dehydrogenase levels, poorer Eastern Cooperative Oncology Group performance status (ECOG PS), and a higher International Prognostic Index (IPI) score. The addition of the Hb/RDW ratio to the IPI produced a highly discriminatory prognostic composite score, termed Hb/RDW-IPI.

Conclusion

We identified a cost-effective and readily available inflammatory biomarker, the Hb/RDW ratio, as an independent predictor of outcomes in patients with AR-DLBCL. Its integration into the IPI score partially improves prognostic accuracy.
Endothelial cells in tumor microenvironment: insights and perspectives
Authors: Leone Patrizia , Malerba Eleonora , Susca Nicola , Favoino Elvira , Perosa Federico , Brunori Giuliano , Prete Marcella , Racanelli Vito
Published: February 2024

The tumor microenvironment is a highly complex and dynamic mixture of cell types, including tumor, immune and endothelial cells (ECs), soluble factors (cytokines, chemokines, and growth factors), blood vessels and extracellular matrix. Within this complex network, ECs are not only relevant for controlling blood fluidity and permeability, and orchestrating tumor angiogenesis but also for regulating the antitumor immune response. Lining the luminal side of vessels, ECs check the passage of molecules into the tumor compartment, regulate cellular transmigration, and interact with both circulating pathogens and innate and adaptive immune cells. Thus, they represent a first-line defense system that participates in immune responses. Tumor-associated ECs are involved in T cell priming, activation, and proliferation by acting as semi-professional antigen presenting cells. Thus, targeting ECs may assist in improving antitumor immune cell functions. Moreover, tumor-associated ECs contribute to the development at the tumor site of tertiary lymphoid structures, which have recently been associated with enhanced response to immune checkpoint inhibitors (ICI). When compared to normal ECs, tumor-associated ECs are abnormal in terms of phenotype, genetic expression profile, and functions. They are characterized by high proliferative potential and the ability to activate immunosuppressive mechanisms that support tumor progression and metastatic dissemination. A complete phenotypic and functional characterization of tumor-associated ECs could be helpful to clarify their complex role within the tumor microenvironment and to identify EC specific drug targets to improve cancer therapy. The emerging therapeutic strategies based on the combination of anti-angiogenic treatments with immunotherapy strategies, including ICI, CAR T cells and bispecific antibodies aim to impact both ECs and immune cells to block angiogenesis and at the same time to increase recruitment and activation of effector cells within the tumor.
Successful pregnancy using oral DHEA treatment for hypoandrogenemia in a 30-year-old female with 5 recurrent miscarriages, including fetal demise at 24 weeks: a case report
Authors: Boyle Phil C. , Pandalache Codruta , Turczynski Craig
Published: February 2024

Hypoandrogenemia is not usually considered as a potential cause of recurrent miscarriage. We present the case of a 30-year-old female with 6 previous pregnancies resulting in one live birth and 5 pregnancy losses, including fetal demise at 24 weeks gestation. She had standard investigations after her 4th loss, at a specialized miscarriage clinic. Lupus anticoagulant, anticardiolipin antibodies, thyroid function, parental karyotypes were all normal. Fetal products confirmed triploidy for her 4th miscarriage at 16 weeks gestation. She was reassured and advised to conceive again but had fetal demise after 24 weeks gestation. This was her 5th pregnancy loss with no explanation. She attended our Restorative Reproductive Medicine (RRM) clinic in January 2022. In addition to poor follicle function, we found hypoandrogenemia for the first time. Treatment included follicle stimulation with clomiphene and DHEA 25 mg twice daily pre-conception with DHEA 20 mg once daily maintained throughout pregnancy. She delivered a healthy baby boy by cesarean section at 36 weeks gestation in November 2023. Hypoandrogenemia should be considered as a contributory factor for women with recurrent miscarriage or late pregnancy loss. Restoration of androgens to normal levels with oral DHEA is safe and can improve pregnancy outcome.