bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal transplant: gender differences
Authors: Fantuzzi Anna Laura , Berri Elisa , Tartaglione Lida , Giannini Rossella , Dominjanni Sara , Porreca Silvia
Published: September 2023

Renal transplantation represents the best treatment for end-stage kidney disease, leading to improved quality of life and life-expectancy for most of the patients. However, gender disparities are evident both in access and in outcomes of kidney transplantation. Women on dialysis are less likely to be on the waiting list for kidney transplantation and to receive an organ from a deceased donor or living donor. Several biological and sociocultural aspects could explain this disparity. On the contrary, more women than men are living kidney donors. Italian women are the first organ donors for living transplants in Europe. The gender difference in living donation is certainly affected by different comorbidities, but such a marked trend highlights a greater predisposition to donate of women, especially in the family context. Some differences are also found in kidney outcomes, even not fully understood. Our paper analyzes the main differences in different aspects of kidney transplantation related to gender, including nutritional aspects.
Gender and sex in the development and progression of renal diseases
Authors: Mandreoli Marcora
Published: September 2023

Sex-based disparities in nephrology have been a historically understudied area.
In nephrology, gender differences exist with regard to the epidemiology, evolution and prognosis of chronic kidney disease (CKD). In some cases, these differences run contrary to the general population trends. We discuss such gender and sex disparities, including differing impact of traditional and novel risk factors, as well as hormonal factors, all of them potentially influencing propensity, progression and biochemical and psychological aspects of CKD. The factors involved in this gender disparity may include diet, kidney and glomerular size, differences in glomerular hemodynamics, and the direct effects of sex hormones.
The progression rate of many renal diseases is affected by sex. In polycystic kidney disease, membranous nephropathy, immunoglobulin A nephropathy, and “chronic renal disease of unknown etiology”, men progress at a faster rate to end-stage renal failure than women do. In many, but not all, animal models of renal disease, estrogens slow progression rate. Animal and experimental studies have tried to offer further mechanistic explanations for gender differences in disease progression. It has been suggested that the gender dimorphism of CKD progression may represent the effects of the interaction of circulating steroids with specific kidney receptors. Endogenous estrogens have in general been considered to have anti-fibrotic and anti-apoptotic effects on the kidney. On the other hand, the faster decline of kidney function in men has been attributed to the specific pro-apoptotic and pro-fibrotic properties of androgens.
Enterococcal Prosthetic Valve Infective Endocarditis Presenting as Complete Heart Block with Intramyocardial Abscess Causing Asystolic Cardiac Arrest
Authors:   Internal Medicine, Lehigh Valley Health Network, PA, USA, Borokhovsky Benjamin
Published: September 2023

The extension of an intracardiac abscess causing complete heart block is a rare complication of infective endocarditis that is associated with a high mortality. Early identification of conduction abnormalities and a low threshold for suspecting infective endocarditis is crucial to provide prompt management to prevent intracardial extension of infection. We report a case of a patient presenting with complete heart block in the setting of profound hyperkalemia, and was then found to have enterococcal prosthetic valve endocarditis, which was complicated by an intracardiac aortic root abscess which led to asystolic cardiac arrest. The development of heart block in endocarditis serves as a marker for poor prognosis and can signify progression of infection. Management therefore requires immediate pacing, antibiotic delivery to lessen infectious burden, and evaluation for consideration of surgical options such as valve replacement. It is therefore recommended for patients with endocarditis complicated by conduction abnormalities or intracardial abscesses to be treated by a multi-disciplinary team consisting of cardiologists, cardiothoracic surgeons, and infectious disease specialists.
DESIGN AND DEVELOPMENT OF HMI IN SIMULATOR FOR FRESH FUEL HANDLING SYSTEM
Authors: Sankar Bindu , kumar K Vijaya , Rajan j , Rajeswari s ,   ndira Gandhi Centre for Atomic Research
Published: September 2023

KALBRSIM operator training simulator is used for training Prototype Fast Breeder Reactor (PFBR) nuclear power plant operators. In simulator, using virtual panel HMI which is an exact replica of actual hardware panels, all the essential fresh fuel operations can be done. Visualization power is also provided by 3D models which aid in quicker understanding of the complex process involved in Fresh Fuel Handling System (FFHS). Operation using Virtual Panel is an excellent tool for system developers to test the logic and process models of FFHS in KALBRSIM before integration with hardware panels. Also, operator training through virtual panel HMI can enable operator to monitor and control FFHS by running multiple screens at once at a central location. Teaching operators their effect of actions using 3D models is an add on with virtual panels which help the operator visualize the system accurately. This paper discuss the design and development of virtual panel HMI and 3D models of fresh fuel handling system used in full scope replica PFBR operator training simulator. Advantage of using HMI in simulator is also covered.
STRAIN RATE DEPENDENCY OF NEOHOOKEAN MATERIAL USING KELVIN-VOIGT VISCOELASTIC MODEL
Authors: Makwana Harsh , Deshmukh Dr. Girish P , Pandey Dr. Laxman Kumar ,   Jawahar Education Society’s, A C Patil College of Engineering
Published: September 2023

This research paper examines the strain rate dependency of a Neo-Hookean material using the Kelvin-Voigt viscoelastic model. The Neo-Hookean model is widely used to describe the mechanical behavior of rubber-like materials, but it fails to consider the timedependent response observed in many materials. To overcome this limitation, the Kelvin-Voigt viscoelastic model, which incorporates a viscosity term into the NeoHookean model, is employed to capture the strain rate dependency. The paper commences by introducing the Neo-Hookean material model and its assumptions. It then elucidates the rationale behind incorporating the Kelvin-Voigt model to account for the time-dependent behavior. To validate the strain rate dependency of the KelvinVoigt model, tensile test is performed using experimental data. The experimental data comprises stress-strain curves, from which the material parameters of both the Neo-Hookean and Kelvin-Voigt models are determined using curve-fitting techniques. The study presents and analyzes the results, with a specific focus on the material's strain rate sensitivity. The stress-strain curves obtained from the Kelvin-Voigt model are compared with the experimental data, and the model's accuracy is evaluated. Additionally, the material parameters obtained from the curve-fitting process are examined to explore the influence of strain rate on the mechanical response of the material.
Influencing Factors on Self-Efficacy and Active Stress Coping Strategies on Resilience in Dental Hygiene Students
Authors:   The Korean Society of Oral Health Science, Park Young-Nam , Lee Hye-Jin
Published: September 2023

Objectives: The study aimed to investigate resilience and the factors impacting resilience among dental hygiene students.
Methods: Data were collected from 199 dental hygiene students in Chungcheong and Kyungsang from July 1 to 30, 2022 using the resilience scale, self-efficacy scale, and stress coping strategies scale.
Results: Factors that significantly impacted the resilience of dental hygiene students were stress coping method, self-efficacy, and grade_dummy 2(2/3) in the order, and the most influential factor was active stress coping strategies, and the explanation power was 51.0%.
Conclusions: There is a need for a systematic, tailored education program that can enhance resilience by strengthening protective factors such as self-efficacy, stress coping strategies.
Effects of Workplace Bullying on Dental Hygienists’ Competency at Work
Authors:   The Korean Society of Oral Health Science, Shin Myong-Suk , Jun Mi-Kyoung , Lee Sun-Mi
Published: September 2023

Objectives: This study aimed to investigate the current state of bullying in dental hygienists’ workplaces, to understand the impact of bullying on workplace competency, and to provide basic data about preventing workplace bullying in dental clinics.
Methods: In this study, 239 dental hygienists with more than six months of work experience each were surveyed. The amount of bullying participants experienced was analyzed according to demographic characteristics, and differences in the impact of bullying on work competency were analyzed using a t-test and a one-way analysis of variance.
Results: Of the 239 participants, 61.9% had experienced bullying at work, Workplace bullying had a significantly greater effect on work competency among participants under the age of 25, those with less than one year of experience, those employed as staff, and those working at dental clinics.
Conclusions: To minimize bullying in the workplace, it is necessary to improve the work ability of new dental hygienists and management staff. More research is needed on ways to improve workplace ethics and prevent bullying.
Character state diversity of Litsea (Lauraceae) leaves in Cianjur Herbarium Hortus Botanicus Tjibodensis
Authors: Suherman Dadang
Published: September 2023

Herbarium serves as a storage place for plants that have been preserved, both in the form of dry and wet preserves. The specimen material is useful in determining the taxonomic status or identity of a plant. Litsea is one of the genera of the Lauraceae tribe (kamper-kamperan) which has similar leaf morphological characters among the species in it or even with other genera that are still in one tribe. The study aims to explain the variation of leaf morphological characters of species of Litsea clan members derived from herbarium specimens of the Cianjur Herbarium Hortus Botanicus Tjibodensis (CHTJ) collection. The research method uses direct observation of specimens in a careful, detailed, high concentration, and still refer to the information data contained in the herbarium sheet. The results showed that the petiole length ranged from 0.7 cm to 3 cm, the petiole surface was hairy (glabrescent) and glabrous. Species of the genus Litsea have leaf shape (circumscriptio): oval (ovalis/ellipticus), elongated (oblongus), and lobed (lanceolatus); The leaf tip (apex folii) is pointed (acutus) in 5 species, and tapered (acuminatus) in 4 species, obtuse (obtusus) in 3 species; the leaf base (base folii) is rounded (rotundatus) in 4 species, obtuse (obtusus) in 5 species, and pointed (acutus) in 3 species; while the arrangement of leaf bones (nervatio or venation) is pinnate (penninervis). The species also have flat leaf margins (margo folii) (integer), with the leaf blade (intervenium) being paper-like and parchment-like, the leaf color is green, and the leaf surface has pilosus.
Construction of three-dimensional, homogeneous regenerative cartilage tissue based on the ECG-DBM complex
Authors: Liu Jingwen , Chen Feifan , Song Daiying , Zhang Qixin , Li Peizhe , Ci Zheng , Zhang Wei , Zhou Guangdong
Published: September 2023

Introduction: The feasibility of using a steel decalcified bone matrix (DBM)-reinforced concrete engineered cartilage gel (ECG) model concept for in vivo cartilage regeneration has been demonstrated in preliminary experiments. However, the regenerated cartilage tissue contained an immature part in the center. The present study aimed to achieve more homogeneous regenerated cartilage based on the same model concept.

Methods: For this, we optimized the culture conditions for the engineered cartilage gel-decalcified bone matrix (ECG-DBM) complex based on the previous model and systematically compared the in vitro chondrogenic abilities of ECG in the cartilage slice and ECG-DBM complex states. We then compared the in vivo cartilage regeneration effects of the ECG-DBM complex with those of an equivalent volume of ECG and an equivalent ECG content.

Results and discussion: Significant increases in the DNA content and cartilage-specific matrix content were observed for the ECG-DBM complex compared with the ECG cartilage slice, suggesting that the DBM scaffold significantly improved the quality of ECG-derived cartilage regeneration in vitro. In the in vivo experiments, high-quality cartilage tissue was regenerated in all groups at 8 weeks, and the regenerated cartilage exhibited typical cartilage lacunae and cartilage-specific extracellular matrix deposition. Quantitative analysis revealed a higher chondrogenic efficiency in the ECG-DBM group. Specifically, the ECG-DBM complex achieved more homogeneous and stable regenerated cartilage than an equivalent volume of ECG and more mature regenerated cartilage than an equivalent ECG content. Compared with ECG overall, ECG-DBM had a more controllable shape, good morphology retention, moderate mechanical strength, and high cartilage regeneration efficiency. Further evaluation of the ECG-DBM complex after in vitro culture for 7 and 14 days confirmed that an extended in vitro preculture facilitated more homogeneous cartilage regeneration.
Association between FIB-4, all-cause mortality, cardiovascular mortality, and cardiovascular disease risk among diabetic individuals: NHANES 1999–2008
Authors: Guan Lihua , Li Lei , Zou Yutong , Zhong Jian , Qiu Ling
Published: September 2023

Background

Diabetes is prevalent worldwide and is associated with cardiovascular disease (CVD). Furthermore, due to the insulin resistance, diabetic populations are vulnerable to liver fibrosis, which increases the risk of CVD. Fibrosis-4 index (FIB-4)—a non-invasive biomarker for liver fibrosis—is crucial in predicting CVD among patients with liver diseases. However, the association between FIB-4, death, and CVD in the US diabetic population has not yet been investigated.

Method

We conducted a cross-sectional study using the data from the National Health and Nutrition Examination Survey (NHANES) 1999–2008. The mortality status was obtained from the National Death Index through December 31, 2015. Participants were divided into survivor and mortality group to compare the basic characteristics. The association between FIB-4, death, and CVD was analyzed using the restricted cubic spline method and Cox proportional hazards models. In stratified analysis, Participants were stratified based on age, sex, BMI, hypertension, or eGFR respectively.

Results

The participants (N = 3,471) were divided into survivor (N = 1,785) and mortality groups (N = 1,632), with the mortality group exhibiting significantly higher FIB-4 values. Moreover, the risk of all-cause mortality (HR 1.24; 95% CI, 1.17–1.32) and CVD mortality (HR 1.17; 95% CI, 1.04–1.31) increased with each FIB-4 SD increase after adjusting for all covariates. However, except for myocardial infarction, FIB-4 had no significant effect on the incidence of the other three CVD subtypes (congestive heart failure, coronary heart disease, and angina pectoris). In stratified analysis, we found that the effect of FIB-4 on CVD mortality was influenced by age, and FIB-4 is a risk factor for people older than 60 years (HR 1.14; 95% CI, 1.01–1.29).

Conclusion

Using data from NHANES 1999–2008, FIB-4 was found to be associated with all-cause and CVD mortality in the diabetic population, and this association was significantly affected by age. However, FIB-4 only affected the incidence of myocardial infarction. Future work should investigate the association between FIB-4 and CVD in the diabetic population.
Ventricular fibrillation induced by fever in structurally normal hearts
Authors: Ma Ji-Fang , Zhou You , Fu Hai-Xia
Published: September 2023

Ventricular fibrillation (VF) is a life-threatening arrhythmia that usually happens in patients with structural heart diseases. However, fever-induced ventricular fibrillation in structurally normal hearts was reported, and the four main diseases associated with these cases were Brugada syndrome, long QT syndrome, idiopathic ventricular fibrillation, and non-cardiovascular diseases. In this review, we analyzed this phenomenon and its clinical characteristics.
Effects of rhythm control on left atrial structure remodeling in atrial fibrillation and heart failure with preserved ejection fraction
Authors: Bai Lin , Sun Yuxi , Si Jiping , Ding Zijie , Zhang Xinxin , Zhang Yanli , Xia Yunlong , Liu Ying
Published: September 2023

Background

The benefits of rhythm control for atrial fibrillation (AF) in heart failure with preserved ejection fraction (HFpEF) have not been conclusively determined. We assessed the effects of rhythm control on left atrial (LA) structure remodeling and prognosis in patients with AF and HFpEF.

Methods

This was a retrospective, real-world, observational study involving patients diagnosed with AF and HFpEF. The cohort was divided into rhythm-control and rate-control groups depending on their treatment strategies. The primary outcomes were all-cause mortality, rehospitalization for any cause, HF-related rehospitalization, and stroke. Differences in follow-up LA structure parameters were also analyzed.

Results

Compared to the rate-control group, patients in the rhythm-control group had a lower risk of HF-related rehospitalization even after adjusting for potential confounders (adjusted HR 0.605, 95% CI 0.413–0.887, p = 0.010). Moreover, rhythm-control therapy led to marked reductions in LA echocardiographic indicators and a higher proportion of LA reverse remodeling (LARR).

Conclusions

Rhythm-control therapy reverses LA structure remodeling and is associated with improved clinical outcomes; therefore, it is an optimal treatment approach for AF in HFpEF patients.
Lithium in felsic magmas: a volcanological perspective
Authors: Dupont de Dinechin Maylis , Balcone-Boissard Hélène , Martel Caroline , Rusiecka Monika
Published: September 2023

Volcanic eruptions are unpredictable phenomena that pose a challenge to crisis management, owing to the fact that contrasted eruptive styles (explosive versus effusive) exhibited at the surface depend on unobservable deep processes occurring in the reservoir and the volcanic conduit. Constricting the behaviour of magma during ascent, and the degassing in particular, allows for a clearer understanding of the relationships between petrological and volcano monitoring signals, and hence a better description of the volcanic hazard. To this aim, lithium (Li) has been used to track magmatic and post-eruptive processes, as a geospeedometer for processes operating on short time scales due to its high mobility in silicate melts and crystals. Yet, the accurate use of Li to assess syn- and post-eruptive processes still lack complete dataset. We propose a review of our current knowledge on Li behavior, with an emphasis on felsic (andesitic to rhyolitic) magmas whose explosive behavior during volcanic eruptions is still poorly understood. We present current knowledge regarding the Li concentration and isotopic compositions, intracrystalline diffusion, and crystal-melt-fluid partition coefficients discovered in felsic magmas and primary crystals. We describe difficulties in interpreting Li data to investigate the differentiation, degassing, ascent rate, volatile fluxing, and cooling of magmas. Finally, we suggest future directions for expanding our understanding of Li behavior.
Uric acid levels correlate with disease activity in growth hormone-secreting pituitary adenoma patients
Authors: Mo Caiyan , Chen Han , Wang Fang , Guo Ying , Wang Yao , Tong Tao , Zhong Liyong
Published: September 2023

Objective

Few studies reported the effects of growth hormone-secreting pituitary adenoma (GHPA) on uric acid (UA) metabolism and the relationship between growth hormone (GH)/insulin-like growth factor-1 (IGF-1) levels and UA are controversial. This study aimed to evaluate the relationship between IGF-1 and UA in patients with GHPA and to further clarify whether UA levels are associated with GHPA disease activity by follow-up.

Methods

A longitudinal study of 424 GHPA patients presenting to Beijing Tiantan Hospital, Capital Medical University between January 2015 and January 2023 was conducted. Spearman’s correlation tests were performed to examine the relationship between IGF-1 and UA at baseline. Univariate and multivariate linear regression analysis was conducted to investigate the independent association between UA and IGF-1. Changes in postoperative IGF-1 and UA levels were followed prospectively, and the differences in UA levels between the biochemical remission and nonremission groups were compared.

Results

At baseline, male patients, the lower the age, the higher the IGF-1 and body mass index (BMI), and the higher the UA levels. IGF-1 was significantly associated with UA after controlling for sex, age, and BMI (r = 0.122, P = 0.012). In adjusted multiple linear regression analysis, IGF-1 was independently associated with UA, and UA levels increased significantly with increasing IGF-1. During postoperative follow-up, UA decreased gradually as IGF-1 levels decreased. At 12 months postoperatively, UA levels were significantly lower in the biochemical remission group than in the nonremission group (P = 0.038).

Conclusions

In patients with GHPA, UA levels are associated with disease activity. Changes in UA levels should be taken into account in the comprehensive treatment of GHPA, patients presenting with HUA should be given lifestyle guidance and appropriate urate-lowering treatment according to their condition to better improve their prognosis.
Description of thyroid disorders the year before conception: a population-based study
Authors: Tena Vivó Glòria , Parellada Esquius Neus , Cunillera Puértolas Oriol , Albareda Riera Mercè , Isidro Albaladejo Mónica , Vila Ballester Lluís
Published: September 2023

Objective

This study aimed to monitoring the prevalence of previously identified thyroid disorders and hypothyroidism monitoring before pregnancy.

Material and methods

A retrospective cross-sectional study of women whose pregnancies occurred between 2014 and 2016 was conducted, including 120,763 pregnancies in Catalonia (Spain). The presence of thyroid disorders in women was based on disease diagnostic codes and/or prescription of levothyroxine or antithyroid drugs. To evaluate the thyroid disorder diagnosis and monitoring, thyrotropin (TSH), free T4 (FT4), antiperoxidase antibody (TPOAb), and anti-TSH receptor antibody (TRAb) records were gathered and categorised according to the reference values of each laboratory.

Results

The prevalence of recorded thyroid disorders before the last menstrual period was 5.09% for hypothyroidism and 0.64% for hyperthyroidism,showing a significant increase with age. A thyroid monitoring test was not performed in the year before the last menstrual period in approximately 40% of women with a known thyroid disorder. Amongst the women with hypothyroidism who underwent a TSH test, 31.75% showed an above-normal result. Amongst women previously unknown to have thyroid disorders, 3.12% had elevated TSH levels and 0.73% had low TSH levels.

Conclusion

A high percentage of Catalan women with a known thyroid disorder were not properly monitored during the year before pregnancy. Amongst those monitored, more than one-third had TSH values outside the reference range. Therefore, it is important to evaluate women with thyroid disorders during pre-pregnancy visits.
Modeling and assessing load redistribution attacks considering cyber vulnerabilities in power systems
Authors: Shi Xingyu , Guo Huan , Wang Weiyu , Yin Banghuang , Cao Yijia
Published: September 2023

Introduction: Load Redistribution (LR) attacks, as a common form of false data injection attack, have emerged as a significant cybersecurity threat to power system operations by manipulating load buses’ measurements at substations. Existing LR attack methods typically assume that any substation can be equally attacked, contributing to the analysis of LR attacks in power systems. However, the diversity of cyber vulnerabilities in substation communication links implies varying costs associated with falsifying load buses’ measurements. Thus, quantitatively evaluating these costs and analyzing the impact of LR attacks on power systems within cost constraints holds practical significance.

Methods: In this paper, we employ a Bayesian attack graph model to characterize the intrusion process through cyber vulnerabilities. The costs of falsifying load buses’ measurements at substations are quantitatively evaluated using the mean time-to-compromise model. Subsequently, from the attacker’s perspective, we propose a bi-level optimization model for LR attacks, considering the mean time to compromise in conjunction with limited attack resources and power flow constraints.

Results: Simulations conducted on the IEEE 14-bus system illustrate the influence of cyber vulnerabilities on LR attacks within power systems. Furthermore, we verify that the attack scenario of the existing LR attack model aligns with a case of the proposed bi-level LR attack model when there is sufficient attack time to compromise all communication links.

Discussion: The findings of this research demonstrate that the impact of cyber vulnerabilities on LR attacks can be quantified by assessing the attack costs. Effective management of LR attacks can be achieved under cost constraints through optimization methods. These insights contribute to enhancing network security strategies for power systems, mitigating potential threats posed by LR attacks in power system operations.
Transformation of reverse marketing model for electrical appliances based on Markov chain optimization with information technology support
Authors: Liu Qingyun
Published: September 2023

Inverters are widely used in the military, industrial production and defense fields as current conversion devices that convert direct current to alternating current. If the inverter fails, it can cause damage to other equipment, resulting in financial losses and, in extreme cases, compromising the safety of users. In this study, by integrating neural networks, the input signals of inverters are quickly converted to Fourier spectrum amplitudes, and from fault signals (such as load phase voltage) to feature vectors. In order to realize automatic extraction and fault detection of inverters, an optimization method is used to determine the appropriate number of nodes in the hidden layer of complex neural networks. The ability to efficiently allocate limited computing, storage, and network resources to meet user demand for services; Continuously optimize quality of service (QoS), including reducing latency, improving bandwidth, and increasing reliability. These problems directly affect the performance and user experience of MEC systems. By studying these issues and proposing corresponding solutions, we aim to improve the performance of MEC systems and provide higher quality services. The accuracy of defect diagnosis can reach higher than 99%, and the method has a high remission rate, demonstrating its effectiveness and benefits.
Increase in Arctic Oscillations explains most interannual variability in Russia’s wildfires
Authors: Lapenis Andrei G. , Yurganov Leonid N.
Published: September 2023

Over the past two decades, the escalating emissions of greenhouse gases from boreal wildfires in the Northern Hemisphere have drawn significant attention, underscoring an unprecedented wildfire season in 2021. Our calculations indicate that between 2002 and 2020, wildfires in Russia released approximately 726 ± 280 Tg CO2eqv yr−1. This aligns closely with similar estimates derived from remote sensing data, far surpassing the earlier approximations found in the Russian National Inventory Report (NIR) by a factor of 2 to 3. Notably, in 2021 alone, Russia’s wildfires emitted an exceptionally high amount of 1,700 Tg CO2eqv, exceeding the carbon emissions from the country’s fossil fuel consumption. Consequently, this situation led to an almost complete counterbalance of carbon assimilation by Russian forests. Our analysis attributes over 50% of the variation in wildfire frequency between 2002 and 2021 to shifts in the Arctic Oscillation (AO). This suggests a potential for utilizing AO as a predictive variable for wildfires. It’s noteworthy that the AO itself is influenced by the sustained regression of Arctic sea-ice. From this, it can be inferred that in the foreseeable future, Russian forests might undergo a transition from their role as carbon sinks to the potential net contributors of carbon to the atmosphere.
Myeloid-derived suppressor cells exacerbate poly(I:C)-induced lung inflammation in mice with renal injury and older mice
Authors: Xie Zhiqi , Zhou Haoyang , Obana Masanori , Fujio Yasushi , Okada Naoki , Tachibana Masashi
Published: September 2023

Viral pneumonia is a global health burden with a high mortality rate, especially in the elderly and in patients with underlying diseases. Recent studies have found that myeloid-derived suppressor cells (MDSCs) are abundant in these patient groups; however, their roles in the progression of viral pneumonia remain unclear. In this study, we observed a substantial increase in MDSCs in a mouse model of renal ischemia/reperfusion (I/R) injury and in older mice. When intranasal polyinosinic-polycytidylic acid (poly(I:C)) administration was used to mimic viral pneumonia, mice with renal I/R injury exhibited more severe lung inflammation than sham mice challenged with poly(I:C). In addition, MDSC depletion attenuated lung inflammation in mice with I/R injury. Similar results were obtained in older mice compared with those in young mice. Furthermore, adoptive transfer of in vitro-differentiated MDSCs exacerbated poly(I:C)-induced lung inflammation. Taken together, these experimental results suggest that the increased proportion of MDSCs in mice with renal I/R injury and in older mice exacerbates poly(I:C)-induced lung inflammation. These findings have important implications for the treatment and prevention of severe lung inflammation caused by viral pneumonia.
Regulatory T-cell deficiency leads to features of autoimmune liver disease overlap syndrome in scurfy mice
Authors: Yilmaz Kaan , Haeberle Stefanie , Kim Yong Ook , Fritzler Marvin J. , Weng Shih-Yen , Goeppert Benjamin , Raker Verena K. , Steinbrink Kerstin , Schuppan Detlef , Enk Alexander , Hadaschik Eva N.
Published: September 2023

Introduction

Scurfy mice have a complete deficiency of functional regulatory T cells (Treg) due to a frameshift mutation in the Foxp3 gene. The impaired immune homeostasis results in a lethal lymphoproliferative disorder affecting multiple organs, including the liver. The autoimmune pathology in scurfy mice is in part accompanied by autoantibodies such as antinuclear antibodies (ANA). ANA are serological hallmarks of several autoimmune disorders including autoimmune liver diseases (AILD). However, the underlying pathogenesis and the role of Treg in AILD remain to be elucidated. The present study therefore aimed to characterize the liver disease in scurfy mice.

Methods

Sera from scurfy mice were screened for ANA by indirect immunofluorescence assay (IFA) and tested for a wide range of AILD-associated autoantibodies by enzyme-linked immunosorbent assay, line immunoassay, and addressable laser bead immunoassay. CD4+ T cells of scurfy mice were transferred into T cell-deficient B6/nude mice. Monoclonal autoantibodies from scurfy mice and recipient B6/nude mice were tested for ANA by IFA. Liver tissue of scurfy mice was analyzed by conventional histology. Collagen deposition in scurfy liver was quantified via hepatic hydroxyproline content. Real-time quantitative PCR was used to determine fibrosis-related hepatic gene expression. Hepatic immune cells were differentiated by flow cytometry.

Results

All scurfy mice produced ANA. AILD-associated autoantibodies, predominantly antimitochondrial antibodies, were detected at significantly higher levels in scurfy sera. CD4+ T cells from scurfy mice were sufficient to induce anti-dsDNA autoantibodies and ANA with an AILD-related nuclear envelope staining pattern. Liver histology revealed portal inflammation with bile duct damage and proliferation, as in primary biliary cholangitis (PBC), and interface hepatitis with portal-parenchymal necroinflammation, as found in autoimmune hepatitis (AIH). In scurfy liver, TNFα and fibrosis-related transcripts including Col1a1, Timp1, Acta2, Mmp2, and Mmp9 were upregulated. The level of proinflammatory monocytic macrophages (Ly-6Chi) was increased, while M2-type macrophages (CD206+) were downregulated compared to wildtype controls. Despite severe hepatic inflammation, fibrosis did not develop within 25 days, which is close to the lifespan of scurfy mice.

Discussion

Our findings suggest that Treg-deficient scurfy mice spontaneously develop clinical, serological, and immunopathological characteristics of AILD with overlapping features of PBC and AIH.
Type 1 invariant natural killer T cells in chronic inflammation and tissue fibrosis
Authors: Kumar Vipin , Hertz Marc , Agro Albert , Byrne Adam J.
Published: September 2023

Chronic tissue inflammation often results in fibrosis characterized by the accumulation of extracellular matrix components remodeling normal tissue architecture and function. Recent studies have suggested common immune mechanisms despite the complexity of the interactions between tissue-specific fibroblasts, macrophages, and distinct immune cell populations that mediate fibrosis in various tissues. Natural killer T (NKT) cells recognizing lipid antigens bound to CD1d molecules have been shown to play an important role in chronic inflammation and fibrosis. Here we review recent data in both experimental models and in humans that suggest a key role of type 1 invariant NKT (iNKT) cell activation in the progression of inflammatory cascades leading to recruitment of neutrophils and activation of the inflammasome, macrophages, fibroblasts, and, ultimately, fibrosis. Emerging evidence suggests that iNKT-associated mechanisms contribute to type 1, type 2 and type 3 immune pathways mediating tissue fibrosis, including idiopathic pulmonary fibrosis (IPF). Thus, targeting a pathway upstream of these immune mechanisms, such as the inhibition of iNKT activation, may be important in modulating various fibrotic conditions.
The role of perivascular adipose tissue-secreted adipocytokines in cardiovascular disease
Authors: Cai Meichao , Zhao Dongsheng , Han Xiao , Han Shuang , Zhang Wenxin , Zang Zhennan , Gai Chenchen , Rong Rong , Gao Tian
Published: September 2023

Perivascular adipose tissue and the vessel wall are connected through intricate bidirectional paracrine and vascular secretory signaling pathways. The secretion of inflammatory factors and oxidative products by the vessel wall in the diseased segment has the ability to influence the phenotype of perivascular adipocytes. Additionally, the secretion of adipokines by perivascular adipose tissue exacerbates the inflammatory response in the diseased vessel wall. Therefore, quantitative and qualitative studies of perivascular adipose tissue are of great value in the context of vascular inflammation and may provide a reference for the assessment of cardiovascular ischemic disease.
Immunometabolic regulation during the presence of microorganisms and parasitoids in insects
Authors: Li Shirong , Wang Jing , Tian Xing , Toufeeq Shahzad , Huang Wuren
Published: September 2023

Multicellular organisms live in environments containing diverse nutrients and a wide variety of microbial communities. On the one hand, the immune response of organisms can protect from the intrusion of exogenous microorganisms. On the other hand, the dynamic coordination of anabolism and catabolism of organisms is a necessary factor for growth and reproduction. Since the production of an immune response is an energy-intensive process, the activation of immune cells is accompanied by metabolic transformations that enable the rapid production of ATP and new biomolecules. In insects, the coordination of immunity and metabolism is the basis for insects to cope with environmental challenges and ensure normal growth, development and reproduction. During the activation of insect immune tissues by pathogenic microorganisms, not only the utilization of organic resources can be enhanced, but also the activated immune cells can usurp the nutrients of non-immune tissues by generating signals. At the same time, insects also have symbiotic bacteria in their body, which can affect insect physiology through immune-metabolic regulation. This paper reviews the research progress of insect immune-metabolism regulation from the perspective of insect tissues, such as fat body, gut and hemocytes. The effects of microorganisms (pathogenic bacteria/non-pathogenic bacteria) and parasitoids on immune-metabolism were elaborated here, which provide guidance to uncover immunometabolism mechanisms in insects and mammals. This work also provides insights to utilize immune-metabolism for the formulation of pest control strategies.
From the modeling of diadromous species’ marine distributions to the characterization of their current and future marine habitats
Authors: Navarro Clara , Janc Anais , Lassalle Géraldine , Lambert Patrick , Dambrine Chloé
Published: September 2023

Introduction

Many diadromous fish species are currently facing the threat of generalized population extirpations across their range, and conservation efforts implemented primarily within the continental domain may not be sufficient to ensure their viability. In consequence, better understanding the use of the marine environment by these species turned out to be critical.

Material and method

We developed marine species distribution models for two species, Allis shad (Alosa alosa) and the European flounder (Platichthys flesus), and proposed a way to interpret the habitat suitability from a more functional perspective. Our approach defined marine habitats as highly suitable environments that remained with a high potential through the species life stage duration at sea. First, a species-specific probabilistic threshold was applied to select for highly suitable environments each year of the simulations. Then, annual maps of high suitability were combined into recurrence maps showing areas were the environmental conditions remained the most suitable across the life at sea of the given species, these areas being called ‘marine habitats’. We applied this approach to study the current and future marine habitats of Allis shad and European flounder under climate change scenarios.

Results

The main current marine habitats of these species were coastal, primarily in the Bay of Biscay for Allis shad and in the English Channel-North Sea for European flounder. These habitats are expected to experience minimal changes by mid-century, and the species may even benefit from new habitats at higher latitudes. However, the European flounder is likely to face greater challenges in the central part of its range by the end of the century, as potential spawning grounds may be threatened.

Discussion

This study provided a way to rethink ‘traditional’ suitability maps by integrating basic knowledge on the diadromous species life at sea. Our findings were part of a larger effort to link continental and marine habitats in improving management of diadromous species.
Clinical significance of the C-reactive protein-to-bilirubin ratio in patients with ulcerative colitis
Authors: Huang Xijing , Liu Ya , Zhou Zhou , Pan Yan , Zhang Yinghui , Gao Caiping , He Chong
Published: September 2023

Background

Ulcerative colitis (UC) is a chronic relapsing remitting disease of the colon. Appropriate monitoring of the disease status is necessary for patients to adopt optimal therapy and obtain a better prognosis. Finding an ideal non-invasive biomarker, which is suitable for long-term monitoring in clinical settings will bring a significant benefit to the individualized management of patients with UC. The aim of this study is to determine the clinical significance of a novel optimizing serological biomarker by integrating C-reactive protein (CRP) and bilirubin levels in monitoring disease activity.

Methods

A total of 182 patients with UC were retrospectively enrolled. Clinical characteristics and laboratory parameters of the subjects were retrieved from the electronic medical record database of our hospital. The CRP-to-bilirubin ratio (CBR) was computed for clinical activity of UC defined by the partial Mayo score and endoscopic activity by the Mayo endoscopic score (MES).

Results

CBR was significantly elevated in patients with UC than that in healthy controls. Patients with clinically or endoscopically active UC showed evidently higher CBR levels compared to those with inactive disease, even in a subset of patients with normal CRP levels. Receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of CBR was higher than that of CRP or bilirubin alone for determining clinical remission and endoscopic mucosal improvement. Furthermore, CBR levels were significantly decreased when patients achieved mucosal improvement compared with when they had active endoscopic inflammation.

Conclusion

CBR could be useful to reflect disease activity in patients with UC.
The evaluation of cardiac functions in deep Trendelenburg position during robotic-assisted laparoscopic prostatectomy
Authors: Kılınç Emir , Yildirim Serap Aktas , Ulugöl Halim , Büyüköner Elif Eroğlu , Güçyetmez Bülent , Toraman Fevzi
Published: September 2023

Objective

This study aimed to demonstrate the reliability of the cardiac cycle efficiency value through its correlation with longitudinal strain by observing the effect of the deep Trendelenburg position.

Design

A prospective, observational study.

Setting

Single center.

Participants

Between May and September 2022, the hemodynamic parameters of 30 patients who underwent robotic assisted laparoscopic prostatectomy under general anesthesia were prospectively evaluated.

Measurements and main results

All invasive cardiac monitoring parameters and longitudinal strain achieved transesophageal echocardiography were recorded in pre-deep Trendelenburg position (T3) and 10th minute of deep Trendelenburg position (T4). Delta values were calculated for the cardiac cycle efficiency and longitudinal strain (values at T4 minus values at T3). The estimated power was calculated as 0.99 in accordance with the cardiac cycle efficiency values at T3 and T4 (effect size: 0.85 standard deviations of the mean difference: 0.22, alpha: 0.05). At T4, heart rate, pulse pressure variation, cardiac cycle efficiency, dP/dt and longitudinal strain were significantly lower than those at T3 (p = 0.009, p < 0.001, p < 0.001, and p < 0.001, respectively). There was a positive correlation between the delta-cardiac cycle efficiency and delta-longitudinal strain (R2 = 0.36, p < 0.001).

Conclusion

Although the absence of significant changes in mean arterial pressure and cardiac index after Trendelenburg position suggests that cardiac workload has not changed, changes in cardiac cycle efficiency and longitudinal strain indicate increased cardiac workload due to increased ventriculo-arterial coupling.
Activation of multiple stress responses in Staphylococcus aureus substantially lowers the minimal inhibitory concentration when combining two novel antibiotic drug candidates
Authors: Singleton Amanda Holstad , Bergum Olaug Elisabeth Torheim , Søgaard Caroline Krogh , Røst Lisa Marie , Olsen Cecilie Elisabeth , Blindheim Fredrik Heen , Ræder Synnøve Brandt , Bjørnstad Frithjof A. , Sundby Eirik , Hoff Bård Helge , Bruheim Per , Otterlei Marit
Published: September 2023

The past few decades have been plagued by an increasing number of infections caused by antibiotic resistant bacteria. To mitigate the rise in untreatable infections, we need new antibiotics with novel targets and drug combinations that reduce resistance development. The novel β-clamp targeting antimicrobial peptide BTP-001 was recently shown to have a strong additive effect in combination with the halogenated pyrrolopyrimidine JK-274. In this study, the molecular basis for this effect was examined by a comprehensive proteomic and metabolomic study of the individual and combined effects on Staphylococcus aureus. We found that JK-274 reduced activation of several TCA cycle enzymes, likely via increasing the cellular nitric oxide stress, and BTP-001 induced oxidative stress in addition to inhibiting replication, translation, and DNA repair processes. Analysis indicated that several proteins linked to stress were only activated in the combination and not in the single treatments. These results suggest that the strong additive effect is due to the activation of multiple stress responses that can only be triggered by the combined effect of the individual mechanisms. Importantly, the combination dose required to eradicate S. aureus was well tolerated and did not affect cell viability of immortalized human keratinocyte cells, suggesting a species-specific response. Our findings demonstrate the potential of JK-274 and BTP-001 as antibiotic drug candidates and warrant further studies.
Clethra fimbriata hexanic extract triggers alteration in the energy metabolism in epimastigotes of Trypanosoma cruzi
Authors: Pardo-Rodriguez Daniel , Lasso Paola , Santamaría-Torres Mary , Cala Mónica P. , Puerta Concepción J. , Méndez Arteaga Jonh Jairo , Robles Jorge , Cuervo Claudia
Published: September 2023

Chagas disease (ChD), caused by Trypanosoma cruzi, is endemic in American countries and an estimated 8 million people worldwide are chronically infected. Currently, only two drugs are available for therapeutic use against T. cruzi and their use is controversial due to several disadvantages associated with side effects and low compliance with treatment. Therefore, there is a need to search for new tripanocidal agents. Natural products have been considered a potential innovative source of effective and selective agents for drug development to treat T. cruzi infection. Recently, our research group showed that hexanic extract from Clethra fimbriata (CFHEX) exhibits anti-parasitic activity against all stages of T. cruzi parasite, being apoptosis the main cell death mechanism in both epimastigotes and trypomastigotes stages. With the aim of deepening the understanding of the mechanisms of death induced by CFHEX, the metabolic alterations elicited after treatment using a multiplatform metabolomics analysis (RP/HILIC-LC-QTOF-MS and GC-QTOF-MS) were performed. A total of 154 altered compounds were found significant in the treated parasites corresponding to amino acids (Arginine, threonine, cysteine, methionine, glycine, valine, proline, isoleucine, alanine, leucine, glutamic acid, and serine), fatty acids (stearic acid), glycerophospholipids (phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine), sulfur compounds (trypanothione) and carboxylic acids (pyruvate and phosphoenolpyruvate). The most affected metabolic pathways were mainly related to energy metabolism, which was found to be decrease during the evaluated treatment time. Further, exogenous compounds of the triterpene type (betulinic, ursolic and pomolic acid) previously described in C. fimbriata were found inside the treated parasites. Our findings suggest that triterpene-type compounds may contribute to the activity of CFHEX by altering essential processes in the parasite.