bluuebunny/crossref_metadata_2025 huggingface dataset:
Helical flow in tortuous aortas and its relationship to turbulence: A whole-aorta 4D flow MRI study
Authors: Dyverfeldt Petter , Trenti Chiara , Ziegler Magnus , Bjarnegård Niclas , Lindenberger Marcus
Published: March 2023

Background

Increased vascular tortuosity is a hallmark of ageing of the vascular system, including the aorta. However, the impact of tortuosity on aortic blood flow is unknown. We hypothesized that increased tortuosity would be associated with increased blood flow helicity and with decreased degree of blood flow turbulence as measured by the turbulent kinetic energy (TKE).

Methods

4D Flow MR images covering the entire aorta from the aortic valve to the iliac bifurcation were acquired in 23 normal volunteers aged 18–30 years (“Young”) and 23 normal volunteers aged 66–76 years (“Old”) without aortic disease. The aorta was segmented and divided into four regions: the ascending, descending, suprarenal abdominal and infrarenal abdominal aorta. Tortuosity, helicity, TKE, flow velocity, and Reynolds number were computed for the whole aorta and for each section.

Results

Tortuosity and helicity were higher whereas TKE, velocity, and Reynolds number were lower in Old than in Young, for all aortic regions (p < 0.05) except for helicity in the descending aorta. Tortuosity correlated positively with helicity and negatively with TKE for all aortic regions (Spearman rho=±0.45–±0.72, p < =0.002) except for TKE in the ascending aorta. Further, helicity correlated with TKE in the descending, suprarenal abdominal and infrarenal abdominal aorta (Spearman rho=−0.56–−0.77).

Conclusion

Tortuosity increases with age and blood flow in tortuous aortas is more helical. Increasing helicity, in turn, is associated with decreasing TKE.
Facilitating engagement of universal school-based digital mental health solutions through user experience: A qualitative exploration
Authors: Badawi Erfan , Coursaris Constantinos K. , Sénécal Sylvain , Léger Pierre-Majorique
Published: March 2023

Digital mental health intervention (DMHI) programs offered in schools present a readily-accessible and flexible means for educating, empowering, and supporting adolescents in maintaining a balanced mental health, especially during uncertain and stressful times such as the COVID-19 pandemic. Recent studies indicate that the effectiveness of DMHI programs in improving students’ mental well-being and in preventing from their mental health complications depends on the users’ engagement. This study focuses on identifying the user experience factors that can facilitate user engagement with universal school-based DMHI programs (i.e., the DMHI programs delivered to the students regardless of their mental health risks or conditions). To identify said factors, we sought to gain a deeper understanding of perceptions, opinions, and preferences of actual end-users (i.e., the adolescents) regarding their experiences with both digital and non-digital mental health resources. Specifically, interviews were conducted with two participant groups to uncover the reasons that could lead the adolescents to better engage with school-based DMHI programs, as well as the shortcomings that could prevent that from happening: (a) adolescent users who had either a high or a low level of engagement with universal DMHI programs of a specific school-based digital mental health solution; and (b) adolescents who had voluntarily used non-digital or non-school-based digital mental health resources for purposes other than treatment. Through a thematic analysis of interview data, the most important (or primary) and the additionally desirable (or secondary) factors that could lead to a higher engagement level for school-based DMHI programs were identified. Lastly, using the evidence gathered from our interviews, specific recommendations are proposed that could help in targeting each identified engagement factor and in increasing the likelihood that school-based DMHI programs achieve their desired outcome for high school students.
Machine learning based ground motion site amplification prediction
Authors: Wang Xiangqi , Wang Zifa , Wang Jianming , Miao Pengyu , Dang Haotian , Li Zhaoyan
Published: March 2023

Site condition impact on seismic ground motion has been a complex but important subject in earthquake hazard analysis. Traditional studies on site amplification effect are either based on site response via wave propagation simulation or regression analysis using parameters such as Vs30, bedrock ground motion and site response period. Ground Motion Prediction Equations (GMPEs) are used for regions where there is limited data of seismic records. The main issues with these approaches are that they cannot demonstrate the complex relationship between site amplification and its various affecting parameters, thus there exists large uncertainty in the results. Recent studies based on machine learning have shown significant improvement in predicting the site amplification, but the result is not well explained. This study assembled the information on 6 parameters including Vs30, magnitude, epicentral distance, earthquake source depth, bedrock ground motion, and altitude of 353,327 records observed during 1997 and 2019 from 698 KiK-net stations. Three machine learning algorithms of Random Forest (RF), XGBoost, and Deep Neural Networks (DNN) were implemented to predict the site amplification factor using these 6 selected parameters. Shapley Additive explanation (SHAP) was used to explain the importance of the 6 parameters. The results show that all three machine learning algorithms performed much better than the traditional GMPE approach with XGBoost’s performance the best. The explanation provided by the SHAP analysis further enhanced the reasonability of this study. It is anticipated that the combination of machine learning and SHAP analysis can provide better assessment for site amplification of ground motion with better potential of future application in seismic hazard analysis.
Integrated approach using petrophysical, gravity, and magnetic data to evaluate the geothermal resources at the Rahat Volcanic Field, Saudi Arabia
Authors: Alqahtani Faisal , Ehsan Muhsan , Aboud Essam , Abdulfarraj Murad , El-Masry Nabil
Published: March 2023

It is necessary to develop and explore geothermal resources to achieve sustainable development and clean renewable energy around the Globe. Geothermal energy is crucial to the future energy supply to meet the environmentally friendly energy demand of the World. The Rahat Volcanic Field (Kingdom of Saudi Arabia) is the oldest and lengthiest Cenozoic Volcanic Field in the World. It is a dominantly a mature mafic Volcanic Field that holds three major geological events; the historic eruption (1256 C.E.), the five fingers (∼4500–1500 BP), and the seismic swarm (1999 C.E.). These incidents were studied by utilizing geological information and geophysical data sets. Geophysical and geostatistical research includes gravity and magnetic survey data, including different log curves and major elements, obtained from water samples as well as of volcanic rocks obtained by X-ray fluorescence (XRF). To gain an understanding of the subsurface thermal structure, these datasets were analyzed. The primary goal of this study is to identify the prominent potential geothermal resources with the help of an available data set. Findings suggest that beneath the historic eruption site along with the fissure eruption, on the western side, there is a geothermal anomaly with a surface footprint of about 35 km2. Analyzing gravity and magnetic data as well as density and magnetic susceptibility variations in rock samples led to the mapping of this anomaly. It has been inferred through integrated study that statistical analysis of major elements will be helpful to validate the results of the outcome.
Clinical efficacy of weight loss herbal intervention therapy and lifestyle modifications on obesity and its association with distinct gut microbiome: A randomized double-blind phase 2 study
Authors: Cao Ming-Zhuo , Wei Chun-Hua , Wen Ming-Chun , Song Ying , Srivastava Kamal , Yang Nan , Shi Yan-Mei , Miao Mingsan , Chung Danna , Li Xiu-Min
Published: March 2023

Goals

To assess the efficacy and safety of Chinese Medicine Prescription “W-LHIT” in subjects with simple obesity, and to explore its potential mechanism of action.

Methods

Thirty-seven patients aged 18 to 60 from Wei-En hospital (Weifang City, Shandong, China), participated in a double blinded, placebo-controlled study. Subjects were randomly divided into 2 groups, 18 in treatment and 19 in placebo group. The treatment group took the “W-LHIT” capsules for two months, while the control group received placebo capsules. Both groups accepted healthy lifestyle education materials. After a 2-month treatment, the placebo group transferred to open-label treatment after unblinding.

Results

72.22% participants in the treatment group lost more than 5% of their body weight, compared with 36.84% in the placebo group (p < 0.001). Body weight loss and body mass index reduction of the treatment group were also significantly higher than those of the placebo group (p < 0.05). These changes were accompanied by increased abundance of Akkermansia muciniphila and Enterococcus faecium, and decreased abundance of Proteobacteria in gut microbiota. Furthermore, the treatment group also showed improvement in obesity-related comorbidities such as hypertension and elevation of liver enzymes. No serious adverse reactions were found during the study period. Weight did not rebound at a follow-up visit 2 months after treatment.

Conclusion

W-LHIT significantly improved body weight and comorbid conditions without obvious adverse reaction or rebound weight gain. These effects were associated with increased abundance of probiotics in gut microbiota. W-LHIT may have a potential for treating obesity in conjunction with healthy lifestyle modifications.
Circulating liver function markers and the risk of COPD in the UK Biobank
Authors: Du Wencong , Guan Haoyu , Wan Xinglin , Zhu Zheng , Yu Hao , Luo Pengfei , Chen Lulu , Su Jian , Lu Yan , Hang Dong , Tao Ran , Wu Ming , Zhou Jinyi , Fan Xikang
Published: March 2023

Objective

To investigate the associations of circulating liver function marker levels with the risk of chronic obstructive pulmonary disease (COPD).

Methods

We leveraged the data of 372,056 participants from the UK Biobank between 2006 and 2010. The assessed circulating liver function markers included alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total bilirubin (TBIL), albumin (ALB), and total protein (TP). Incident COPD was identified through linkage to the National Health Service registries. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

During a median follow-up period of 12.3 (interquartile range:11.4-13.2) years, we documented 10,001 newly diagnosed COPD cases. Lower levels of ALT, TBIL, ALB, and TP and higher levels of GGT and ALP were nonlinearly associated with elevated COPD risk. The HR (95% CI) for decile 10 vs. 1 was 0.92 (0.84-1.01) for ALT, 0.82 (0.75-0.89) for TBIL, 0.74 (0.67-0.81) for ALB, 0.96 (0.88-1.04) for TP, 1.45 (1.31-1.62) for GGT, and 1.31 (1.19-1.45) for ALP. Restricted cubic spline analyses suggested a U-shaped relationship between AST levels and COPD risk (P for nonlinearity <0.05).

Conclusion

We observed that all seven circulating liver function markers were nonlinearly associated with the risk of COPD, indicating the importance of liver function in COPD.
Log odds of negative lymph nodes/T stage ratio (LONT): A new prognostic tool for differentiated thyroid cancer without metastases in patients aged 55 and older
Authors: Wang Xuezhen , Wu Yufan , Li Xiaoxia , Hong Jinsheng , Zhang Mingwei
Published: March 2023

Background

The optimal approach to assess the postoperative status of lymph nodes in differentiated thyroid cancer (DTC) remains controversial. Our aim was to determine if the log odds of negative lymph nodes/T stage ratio (LONT) could serve as a new prognostic and predictive tool for DTC without metastases in patients aged ≥ 55 years.

Methods

The Surveillance, Epidemiology, and End Results (SEER) database was used to study the role of LONT in patients aged ≥55 years diagnosed with DTC without metastases. The primary outcome was overall survival (OS). The Kaplan-Meier method and the Cox proportional hazard regression model were used to calculate the outcome. Moreover, the robustness of research findings was evaluated using sensitivity analyses.

Results

A total of 21,172 DTC patients aged ≥55 years without distant metastasis were enrolled. Multivariate Cox regression analyses and a “floating absolute risk” analysis showed that a LONT ≥0.920 (vs. -0.56 to 0.92) was a protective factor for OS in DTC patients. Sensitivity analyses revealed an E-value of 1.98 for the obtained LONT value. In subgroup analyses, LONT was correlated significantly with OS in different subgroups of negative lymph nodes, stage-I–II subgroups and the N0 subgroup. The conditional probability of survival of DTC improved with prolonged survival time in the LONT ≥0.920 group.

Conclusion

A high LONT was associated with longer OS compared with low LONT in patients aged ≥55 years with non-metastatic DTC. LONT could provide valuable information for undertaking postoperative evaluations.
Serum afamin levels in predicting gestational diabetes mellitus and preeclampsia: A systematic review and meta-analysis
Authors: Yuan Ying , He Wenyin , Fan Xuejiao , Liang Junyu , Cao Zhen , Li Lei
Published: March 2023

Objectives

The association between biomarkers and the risk of gestational diabetes mellitus (GDM) or preeclampsia (PE) has been extensively studied. However, there is still a lack of convenient, specific, and sensitive indicators for early identification of GMD and PE. Therefore, we conducted a meta-analysis of published articles to investigate the value of afamin circulating levels in the early diagnosis of GDM and PE.

Methods

We searched the PubMed, Embase, Cochrane Library, and Web of Science databases for English studies published before November 16, 2022, that examined the association between afamin and GDM or PE. In addition, we searched Clinicaltrials.gov for the relevant completed and ongoing clinical trials. Pooled standard mean differences (SMDs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were used to compare the levels of afamin in different groups.

Results

Eleven studies were included in our analysis (N = 3047 participants: 1195 GDM, 1407 non-GDM, 195 PE, and 250 non-PE). Subgroup analysis based on different blood collection periods found that the plasma afamin levels in pregnant women with GDM in the first trimester were significantly higher than those in healthy pregnant women (SMD = 0.481, 95% CI: 0.280-0.682), but the analysis showed the opposite results in the second and late stages (SMD = 0.292, 95% CI: -0.092-0.676). The plasma afamin levels of pregnant women with PE in the first trimester (SMD = 0.808, 95% CI: 0.558-1.059) and second/third trimesters (SMD = 0.904, 95% CI: 0.570-1.239) were significantly higher than those in healthy pregnant women.

Conclusion

The plasma afamin levels in pregnant women with GDM in the first trimester were significantly higher than those in healthy pregnant women, but the analysis showed the opposite results in the second and third trimesters. The plasma afamin levels in pregnant women with PE in the first, second, and third trimesters were significantly higher than those in healthy pregnant women. Additional large-scale prospective studies are desired to verify these findings, and it is recommended that afamin should be included as a routine diagnostic test for women with GDM and PE.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=339171, identifier CRD42022339171.
Research on minimum height above ground considering total and ionized field when ± 800 kV power lines at the high altitude cross the residential areas
Authors: Guo Zhijian , Yu Jian , Wang Xia , Zhang Yuexian
Published: March 2023

Recently, in order to reduce carbon emissions and meet climate change targets set by governments worldwide, which has led to the growth of renewable energy sources, such as wind, solar and hydropower energy, more and more ± 800 kV power lines have been built for more than 1500 km long-distance transmission, and the total and ionized field under it serve as important assessment indicators of an electromagnetic field. To calculate the total electric field and ionized field under UHVDC power lines, based on the upwind difference idea proposed by Takuma, the boundary condition and initial value selection are improved with the Kaptzov hypothesis as the boundary condition, and the difference between the surface field strength on the wire and the critical coronal voltage is used as the benchmark to estimate the initial value of charge density. By adopting the improved method, the calculation results of the total electric field and ionized field under the ± 800 kV power lines in typical high altitude regions suggest that the total electric field on the ground increases with the decrease in the wire’s height above ground, while the ion current density goes up with the reduction in the roughness coefficient of the wire; when the ± 800 kV power lines stipulated by national standards go through the residential areas, and the wire’s minimum height above ground is 21 m, total electric field and ionized field under the power lines are less than the limits set by national standards. Also, the calculation method proposed in this paper is suitable for the calculation of ground total electric field for future ± 1,200 kV power lines, which can provide reference for UHVDC power line designing and carbon emission target realization.
Weighted shapley value: A cooperative game theory for loss allocation in distribution systems
Authors: Singh Vijay Pal , Ahmad Aijaz , Jagtap Kushal Manoharrao
Published: March 2023

This paper proposes a new method for assigning distribution system (DS) losses to consumers and distributed generations in the framework of a liberalized energy market. The architecture of the proposed method is based on a synthesis of electrical network analytical theory and cooperative game theory (CGT). Weighted shapely value (WSV) is a solution idea that is regarded to be efficient in CGT for n-player games with characteristic function form. By retaining the notion of electrical networks, the axioms of game theory will be preserved while employing the WSV in loss allocation theory. To allocate system losses, the proposed method estimates the average marginal contribution of each participant to all conceivable coalitions and also determines the weight of the marginal contribution of each participant based on its power rating. Rather than a sequential branch-oriented approach, the proposed methodology is node-oriented. Additionally, a majority rule game is used to constrain the population of a coalition without jeopardizing the efficacy of the solutions to achieve a fair allocation of losses. The results of the proposed method are presented and contrasted with those obtained using the conventional pro-rata method and the well-known Shapley value solution concept in CGT.
Trade-off between environment and economy: The relationship between carbon and inflation
Authors: Xu Yingying , Li Xiang , Yuan Peng , Zhang Yinpeng
Published: March 2023

Introduction: The global pandemic since 2019 has caused crushing blow to healthy economic developments, particularly the harmonious development of environment and economy. Given the violent contradiction between health and economy, this study focuses on the controversial relationship between inflation and important environmental indicators.

Methods: Specifically, we collect monthly data on inflation and carbon returns from three representative pilots in China and make a comprehensive investigation of the relationship between carbon and inflation within the framework of the Environmental Kuznets Curve (EKC).

Results: Some significant empirical results are found. First, inflation shows a linear impact on carbon returns, despite the signals of inflation vary in pilots. Second, there exists an inverted U-shape connection in Shenzhen and Guangdong pilots. Third, inflation appears to be a non-negligible factor in pilot fluctuations, despite differences exist among pilots.

Discussion: Considering the pressing targets of carbon peaking and carbon neutrality in China, this investigation provides important implications to policy makers in implementing differentiated policies across regions, particularly in the turbulent situations caused by frequent climate policy changes and global pandemic developments.
Urban expansion impacts on agricultural land and thermal environment in Larkana, Pakistan
Authors: Rahman Ghani , Chandio Noor Hussain , Moazzam Muhammad Farhan Ul , Al Ansari Nadhir
Published: March 2023

Urban area expansion and the increase in the built-up area are major threats to agriculture, the natural environment, and ecology throughout the world. The population of the city of Larkana is rapidly increasing due to natural growth and uncontrolled migration from the surrounding areas, which have resulted in a haphazard increase in the built-up area over the fertile agricultural land and affected the city’s thermal environment. This research aims to evaluate the impacts of urban area expansion on agricultural land and the thermal environment of the study area by assessing the change in land use/ land cover (LULC) from 1990 to 2020 and land surface temperature (LST). For this purpose, the Random Forest (RF) algorithm was applied, and LST was calculated in Google Earth Engine (GEE) using Landsat imageries for the years 1990, 2000, 2010, and 2020. For the RF classifier algorithm, 3500 reference random points were generated for each year, which were then randomly divided into two datasets, i.e., a training sample consisting of 70% of the points and a validation dataset (30% of the points). After LULC classification, the results were validated for 1990, 2000, 2010, and 2020, and the accuracy was 88.3%, 89%, 90.01%, and 90.8%, respectively. The study results showed that the built-up area increased from 12.31 to 43.83 km2while the barren land in the study region decreased from 56.51 km2to 11.62 km2. The agricultural land was 66.66 km2in 1990, expanded to 101.38 km2, and then decreased to 79.49 km2in 2020. The results also revealed that most of the urban expansion in the last decade (2010-2020) took place on agricultural land. The urban thermal environment also showed a gradual increase in surface temperatur,e as recorded by the LST results. The LST results revealed that the maximum LST was 33.4°C in 1990, which increased to 36.1°C in 2020, and similarly, the minimum LST was 25.1°C, which also increased to 26.6°C in 2020. This study provides useful results for stakeholders to devise better policies and plans to control further haphazard urban expansion on fertile agricultural land in the study area.
The establishment of the national key ecological functional zone and the county’s ecological green development
Authors: Rong-bo Zhang , Chang-biao Zhong
Published: March 2023

Ecological green development is the development of conforming to nature and promoting the harmonious coexistence of man and nature. As the most basic and supportive grassroots political unit, the county level occupies a special key position in the overall national green development strategy. How to evaluate the ecological green development of the county, protect the green earth, and respond to climate change, have become a new problem facing various countries around the world. To this end, China is determined to implement the establishment of a national key ecological functional zone pilot policy to study its ecological green development from the perspective of the county. Based on the literature review and theoretical mechanism, this paper selects 1997 county-level data indicators in mainland China from 2007 to 2019 to explore the role of the establishment of national key ecological function areas on the ecological green development of counties. The implementation of the national key ecological function zone policy can significantly increase the vegetation normalization index by about 0.035–0.037 units. The implementation of the policy has greatly expanded the capacity and range of above-ground and below-ground biomass. The reduction of large-scale investment by the government, the improvement of quality and efficiency of enterprises in the region, and the increase artificial afforestation are important transmission mechanisms for the implementation of policies to affect the green development of counties. The implementation of the policy has a positive green spillover effect on adjacent areas, which can realize regional coordinated ecological governance. Each additional hectare of artificial afforestation can absorb about 134,800 tons of carbon emissions each year, bringing additional benefits of 730 million yuan. It releases about 98,000 tons of oxygen a year, which can be used for 1.312 billion people for oxygen respiration consumption every year.
CD300b regulates intestinal inflammation and promotes repair in colitis
Authors: Avlas Shmuel , Kassis Hala , Itan Michal , Reichman Hadar , Dolitzky Avishay , Hazut Inbal , Grisaru-Tal Sharon , Gordon Yaara , Tsarfaty Ilan , Karo-Atar Danielle , Rozenberg Perri , Bitton Almog , Munitz Ariel
Published: March 2023

Chronic inflammation is a hallmark charataristic of various inflammatory diseases including inflammatory bowel disease. Subsequently, current therapeutic approaches target immune-mediated pathways as means for therapeutic intervention and promotion of mucosal healing and repair. Emerging data demonstrate important roles for CD300 receptor family members in settings of innate immunity as well as in allergic and autoimmune diseases. One of the main pathways mediating the activities of CD300 family members is via promotion of resolution through interactions with ligands expressed by viruses, bacteria, or dead cells (e.g., phospholipids such as PtdSer and/or ceramide). We have recently shown that the expression of CD300a, CD300b and CD300f were elevated in patients with IBD and that CD300f (but not CD300a) regulates colonic inflammation in response to dextran sodium sulphate (DSS)-induced colitis. Whether CD300b has a role in colitis or mucosal healing is largely unknown. Herein, we demonstrate a central and distinct role for CD300b in colonic inflammation and subsequent repair. We show that Cd300b-/- mice display defects in mucosal healing upon cessation of DSS treatment. Cd300b-/- mice display increased weight loss and disease activity index, which is accompanied by increased colonic histopathology, increased infiltration of inflammatory cells and expression of multiple pro-inflammatory upon cessation of DSS cytokines. Furthermore, we demonstrate that soluble CD300b (sCD300b) is increased in the colons of DSS-treated mice and establish that CD300b can bind mouse and human epithelial cells. Finally, we show that CD300b decreases epithelial EpCAM expression, promotes epithelial cell motility and wound healing. These data highlight a key role for CD300b in colonic inflammation and repair processes and suggest that CD300b may be a future therapeutic target in inflammatory GI diseases.
Towards a consensus definition of immune exclusion in cancer
Authors: Tiwari Ankur , Oravecz Tamas , Dillon Laura A. , Italiano Antoine , Audoly Laurent , Fridman Wolf Hervé , Clifton Guy Travis
Published: March 2023

Background

The immune cell topography of solid tumors has been increasingly recognized as an important predictive factor for progression of disease and response to immunotherapy. The distribution pattern of immune cells in solid tumors is commonly classified into three categories - namely, “Immune inflamed”, “Immune desert” and “Immune excluded” - which, to some degree, connect immune cell presence and positioning within the tumor microenvironment to anti-tumor activity.

Materials and methods

In this review, we look at the ways immune exclusion has been defined in published literature and identify opportunities to develop consistent, quantifiable definitions, which in turn, will allow better determination of the underlying mechanisms that span cancer types and, ultimately, aid in the development of treatments to target these mechanisms.

Results

The definitions of tumor immune phenotypes, especially immune exclusion, have largely been conceptual. The existing literature lacks in consistency when it comes to practically defining immune exclusion, and there is no consensus on a definition. Majority of the definitions use somewhat arbitrary cut-offs in an attempt to place each tumor into a distinct phenotypic category. Tumor heterogeneity is often not accounted for, which limits the practical application of a definition.

Conclusions

We have identified two key issues in existing definitions of immune exclusion, establishing clinically relevant cut-offs within the spectrum of immune cell infiltration as well as tumor heterogeneity. We propose an approach to overcome these limitations, by reporting the degree of immune cell infiltration, tying cut-offs to clinically meaningful outcome measures, maximizing the number of regions of a tumor that are analyzed and reporting the degree of heterogeneity. This will allow for a consensus practical definition for operationalizing this categorization into clinical trial and signal-seeking endpoints.
Third SARS-CoV-2 vaccination and breakthrough infections enhance humoral and cellular immunity against variants of concern
Authors: Ruhl Louisa , Kühne Jenny F. , Beushausen Kerstin , Keil Jana , Christoph Stella , Sauer Jasper , Falk Christine S.
Published: March 2023

Introduction

SARS-CoV-2 vaccination is the leading strategy to prevent severe courses after SARS-CoV-2 infection. In our study, we analyzed humoral and cellular immune responses in detail to three consecutive homologous or heterologous SARS-CoV-2 vaccinations and breakthrough infections.

Methods

Peripheral blood samples of n=20 individuals were analyzed in the time course of three SARS-CoV-2 vaccinations and/or breakthrough infection. S1-, RBD-, S2- and N-specific IgG antibodies were quantified using Luminex-based multiplex assays and electrochemiluminescence multiplex assays for surrogate neutralization in plasma. Changes in cellular immune components were determined via flow cytometry of whole blood samples.

Results

All individuals (n=20) responded to vaccination with increasing S1-/RBD-/S2-specific IgG levels, whereas specific plasma IgA displayed individual variability. The third dose increased antibody inhibitory capacity (AIC) against immune-escape variants Beta and Omicron BA.1 independently of age. The mRNA-primed vaccination induced IgG and IgA immunity more efficiently, whereas vector-primed individuals displayed higher levels of memory T and B cells. Vaccinees showed SARS-CoV-2-specific T cell responses, which were further improved and specified after Omicron breakthrough infections in parallel to the appearance of new variant-specific antibodies.

Discussion

In conclusion, the third vaccination was essential to increase IgG levels, mandatory to boost AIC against immune-escape variants, and induced SARS-CoV-2-specific T cells. Breakthrough infection with Omicron generates additional spike specificities covering all known variants.
The emerging role of neutrophil extracellular traps in endometritis
Authors: Li Hongyan , Liu Ling , Wang Junrong , Zhao Weiliang
Published: March 2023

Endometritis is a kind of common obstetric disease in women, usually caused by various pathogenic bacteria. Neutrophil infiltration is one of the most important pathological features of endometritis. Neutrophils can reach the uterine cavity through the endometrium, and make early response to the infection caused by the pathogen. Neutrophil extracellular traps (NETs), a meshwork of chromatin fibers extruded by neutrophils, have a role in entrapping microbial pathogens. It has been confirmed that NETs have a strong antibacterial effect and play crucial roles in the occurrence and development of various diseases. However, while killing pathogenic bacteria, excessive NETs formation may cause immune damage to the body. NETs are present in endometrium of female domestic animals in different physiological periods, especially post-mating, postpartum and in the presence of lesions, especially in endometritis. Meanwhile, NETs and its products might contribute to a reduction in physical clearance and persistent endometritis. In brief, NETs is a double-edged sword and it may play a different role in the development of endometritis, which may be beneficial or harmful, and its specific mechanism needs further study. Here we provide an overview of the role of NETs in the development of endometritis and the regulatory role of selenium on NETs formation and endometritis.
Analgesic drug use in patients with STEMI: Current perspectives and challenges
Authors: Chen Huaigang , Wang Hong , Li Bin , Hong Lang , Kuang Maobin , Yang Liu
Published: March 2023

Therapy for patients with ST-elevation myocardial infarction (STEMI) has been a controversial topic since the introduction of thrombolytic agents in the 1980s. The use of morphine, fentanyl and lidocaine has increased substantially during this period. However, there is still limited evidence on their advantages and limitations. In this review, the clinical application, as well as future considerations of morphine, fentanyl and lidocaine in patients with ST segment elevation myocardial infarction were discussed.
Landscape in the gallbladder mycobiome and bacteriome of patients undergoing cholelithiasis with chronic cholecystitis
Authors: Hu Junqing , Tang Jichao , Zhang Xinpeng , Yang Kaijin , Zhong Ayan , Yang Qin , Liu Yanjun , Li Yi , Zhang Tongtong
Published: March 2023

Gallstone disease (GSD) is associated with changes in the gut and gallbladder bacterial composition, but there is limited information on the role of the fungal community (mycobiome) in disease development. This study aimed to characterize the gallbladder mycobiome profiles and their interactions with bacteriome in GSD. A total of 136 bile and gallstone samples (34 paired for bacteriome, and 33 paired and extra 2 bile samples for mycobiome) were obtained from calculi patients with chronic cholecystitis. Bile and gallstone bacteriome and mycobiome were profiled by 16S and internal transcribed spacer (ITS) rRNA gene sequencing, respectively. Gallbladder bacteriome, mycobiome, and interkingdom and intrakingdom interactions were compared between bile and gallstone. In general, microbial diversity was higher in bile than in gallstone, and distinct microbial community structures were observed among them. Deep Sea Euryarchaeotic Group, Rhodobacteraceae, and Rhodobacterales were microbial biomarkers of bile, while Clostridiales and Eubacterium coprostanoligenes were biomarkers of gallstone. Five fungal taxa, including Colletotrichum, Colletotrichum sublineola, and Epicoccum, were enriched in gallstone. Further ecologic analyses revealed that intensive transkingdom correlations between fungi and bacteria and intrakingdom correlations within them observed in gallstone were significantly decreased in bile. Large and complex fungal communities inhabit the gallbladder of patients with GSD. Gallstone, compared with bile, is characterized by significantly altered bacterial taxonomic composition and strengthened bacterial–bacterial, fungal–fungal, and bacterial–fungal correlations in the gallbladder of patients with GSD.
Elevated LDL-C, high blood pressure, and low peak V̇O2 associate with platelet mitochondria function in children—The Arkansas Active Kids Study
Authors: Diaz Eva C. , Adams Sean H. , Weber Judith L. , Cotter Matthew , Børsheim Elisabet
Published: March 2023

Purpose: To evaluate the association of platelet (PL) mitochondria respiration with markers of cardiovascular health in children ages 7–10 years.

Methods: PL mitochondrial respiration (n = 91) was assessed by high resolution respirometry (HRR): Routine (R) respiration, complex (C) I linked respiration (CI), and maximal uncoupled electron transport capacity of CII (CIIE) were measured. The respiratory control ratio (RCR) was calculated as the ratio of maximal oxidative phosphorylation capacity of CI and CI leak respiration (PCI/LCI). Peak V.O2 (incremental bike test) and body composition (dual-energy X-ray absorptiometry) were measured. Multiple generalized linear regression analysis was used to model the association of measures by HRR with variables of interest: adiposity, low-density lipoprotein (LDL-C) and triglyceride (TG) status (normal vs. elevated) HOMA2-IR, blood pressure status (normal vs. high), and demographics.

Results: R and CI-linked respiration positively associated with adiposity, high blood pressure (HBP), and peak V.O2. R and CI-linked respiration had inverse association with age and elevated LDL-C. CIIE was higher in children with elevated LDL-C (log-β = −0.54, p = 0.010). HBP and peak V.O2 interacted in relation to RCR (log-β = −0.01, p = 0.028). Specifically, RCR was lowest among children with HBP and low aerobic capacity (i.e., mean peak V.O2 -1SD). HOMA2-IR did not associate with measures of PL mitochondria respiration.

Conclusion: In PL, R and CI-linked mitochondrial respiration directly associate with adiposity, peak V.O2 and HBP. Elevated LDL-C associates with lower CI-linked respiration which is compensated by increasing CII respiration. PL bioenergetics phenotypes in children associate with whole-body metabolic health status.
A preliminary study of diffusion tensor imaging in root entry zone of primary trigeminal neuralgia
Authors: Wang Yiwen , Wang Danni , Wu Yingwei , Zhu Ce , Wei Wenbin , Li Yao , Li Lingzhi , Chen Wantao , Chen Minjie
Published: March 2023

Objective

Primary Trigeminal Neuralgia (PTN) is a common and refractory neurological disease. Conventional vascular compression theory could not completely explain the etiology and pathogenesis of PTN. This study used diffusion tensor imaging (DTI) to demonstrate the microstructural changes of root entry zone (REZ) region in PTN patients.

Materials and methods

DTI sequences was performed on PTN patients and healthy controls (HCs). Clinical data included affected side, disease course and visual analogue scale (VAS) were collected. Quantitative DTI variables such as FA, MD, AD and RD of the root entry/Exit zone (REZ) were measured and compared in PTN/HCs, affected/unaffected side, and pre/post operation groups. The PCoA was established to conduct overall differences between PTN group and the HCs.

Results

A total of 17 patients with PTN (mean age 59.29 ± 8.53; 5 men) and 34 HCs (mean age 57.70 ± 6.37; 10 men) were included. Lower FA value of the affected side of PTN group was observed compared to the unaffected side and the HCs (p = 0.001), whereas the values of MD, AD and RD were significantly increased (p < 0.001). Moreover, the decrease of FA value was recovered post operation. PCoA results of the comprehensive indexes can significantly distinguish PTN group from HCs (r = 0.500, p < 0.001).

Conclusion

Quantitative variables derived from DTI in REZ had significantly different profiles between PTN patients and HCs, which were associated with VAS situation and the disease course of PTN. The comprehensive index established on DTI variables were of great potential to reveal the microstructure changes in PTN patients and predict the therapeutic effect.
Measuring anxiety-like behavior in a mouse model of mTBI: Assessment in standard and home cage assays
Authors: Tseitlin Liron , Richmond-Hacham Bar , Vita Adi , Schreiber Shaul , Pick Chaim G. , Bikovski Lior
Published: March 2023

Traumatic brain injury (TBI) is a primary global health concern and one of the most common causes of neurological impairments in people under 50. Mild TBI (mTBI) accounts for the majority of TBI cases. Anxiety is the most common complaint after mTBI in humans. This study aims to evaluate behavioral tests designed to assess anxiety-like phenotypes in a mice model of mTBI. ICR mice underwent mTBI using the weight-drop model. Seven days post-injury, mice were subjected to one of five different behavioral tests: Elevated Plus Maze (EPM), Open Field apparatus (OF), Marble Burying test (MBT), Light Dark Box (LDB), and the Light Spot test within the PhenoTyper home cage (LS). In the EPM and OF tests, there were no significant differences between the groups. During the 30-min test period of the MBT, mTBI mice buried significantly more marbles than control mice. In the LDB, mTBI mice spent significantly less time on the far side of the arena than control mice. In addition, the time it took for mTBI mice to get to the far side of the arena was significantly longer compared to controls. Results of LS show significant within-group mean differences for total distance traveled for mTBI mice but not for the control. Furthermore, injured mice moved significantly more than control mice. According to the results, the anxiety traits exhibited by mTBI mice depend upon the time of exposure to the aversive stimulus, the apparatus, and the properties of the stressors used. Therefore, the characterization of anxiety-like behavior in mTBI mice is more complicated than was initially suggested. Based on our findings, we recommend incorporating a variety of stressors and test session lengths when assessing anxiety-like behavior in experimental models of mTBI.
Defining the role of TRPM4 in broadly responsive taste receptor cells
Authors: Dutta Banik Debarghya , Medler Kathryn F.
Published: March 2023

Peripheral taste receptor cells use multiple signaling pathways to transduce taste stimuli into output signals that are sent to the brain. We have previously identified a subpopulation of Type III taste cells that are broadly responsive (BR) and respond to multiple taste stimuli including bitter, sweet, umami, and sour. These BR cells use a PLCβ3/IP3R1 signaling pathway to detect bitter, sweet, and umami stimuli and use a separate pathway to detect sour. Currently, the downstream targets of the PLCβ3 signaling pathway are unknown. Here we identify TRPM4, a monovalent selective TRP channel, as an important downstream component in this signaling pathway. Using live cell imaging on isolated taste receptor cells from mice, we show that inhibition of TRPM4 abolished the taste-evoked sodium responses and significantly reduced the taste-evoked calcium responses in BR cells. Since BR cells are a subpopulation of Type III taste cells, they have conventional chemical synapses that require the activation of voltage-gated calcium channels (VGCCs) to cause neurotransmitter release. We found that TRPM4-dependent membrane depolarization selectively activates L-type VGCCs in these cells. The calcium influx through L-type VGCCs also generates a calcium-induced calcium release (CICR) via ryanodine receptors that enhances TRPM4 activity. Together these signaling events amplify the initial taste response to generate an appropriate output signal.
An in vitro model of drug-resistant seizures for selecting clinically effective antiseizure medications in Febrile Infection-Related Epilepsy Syndrome
Authors: Cerovic Milica , Di Nunzio Martina , Craparotta Ilaria , Vezzani Annamaria
Published: March 2023

Introduction

FIRES is a rare epileptic encephalopathy induced by acute unremitting seizures that occur suddenly in healthy children or young adults after a febrile illness in the preceding 2 weeks. This condition results in high mortality, neurological disability, and drug-resistant epilepsy. The development of new therapeutics is hampered by the lack of validated experimental models. Our goal was to address this unmet need by providing a simple tool for rapid throughput screening of new therapies that target pathological inflammatory mechanisms in FIRES. The model was not intended to mimic the etiopathogenesis of FIRES which is still unknown, but to reproduce salient features of its clinical presentation such as the age, the cytokine storm and the refractoriness of epileptic activity to antiseizure medications (ASMs).

Methods

We refined an in vitro model of mouse hippocampal/temporal cortex acute slices where drug-resistant epileptic activity is induced by zero Mg2+/100 μM 4-aminopirydine. Clinical evidence suggests that acute unremitting seizures in FIRES are promoted by neuroinflammation triggered in the brain by the preceding infection. We mimicked this inflammatory component by exposing slices for 30 min to 10 μg/ml lipopolysaccharide (LPS).

Results

LPS induced a sustained neuroinflammatory response, as shown by increased mRNA levels of IL-1β, CXCL1 (IL-8), TNF, and increased IL-1β/IL-1Ra ratio. Epileptiform activity was exacerbated by neuroinflammation, also displaying increased resistance to maximal therapeutic concentrations of midazolam (100 μM), phenytoin (50 μM), sodium valproate (800 μM), and phenobarbital (100 μM). Treatment of LPS-exposed slices with two immunomodulatory drugs, a mouse anti-IL-6 receptor antibody (100 μM) corresponding to tocilizumab in humans, or anakinra (1.3 μM) which blocks the IL-1 receptor type 1, delayed the onset of epileptiform events and strongly reduced the ASM-resistant epileptiform activity evoked by neuroinflammation. These drugs were shown to reduce ASM-refractory seizures in FIRES patients.

Discussion

The neuroinflammatory component and the pharmacological responsiveness of epileptiform events provide a proof-of-concept validation of this in vitro model for the rapid selection of new treatments for acute ASM-refractory seizures in FIRES.
Effect of switching to erenumab in non-responders to a CGRP ligand antibody treatment in migraine: A real-world cohort study
Authors: Overeem Lucas Hendrik , Lange Kristin Sophie , Fitzek Mira Pauline , Siebert Anke , Steinicke Maureen , Triller Paul , Hong Ja Bin , Reuter Uwe , Raffaelli Bianca
Published: March 2023

Background

Therapeutic options for migraine prevention in non-responders to monoclonal antibodies (mAbs) targeting Calcitonin Gene-Related Peptide (CGRP) and its receptor are often limited. Real-world data have shown that non-responders to the CGRP-receptor mAb erenumab may benefit from switching to a CGRP ligand mAb. However, it remains unclear whether, vice versa, erenumab is effective in non-responders to CGRP ligand mAbs. In this study, we aim to assess the efficacy of erenumab in patients who have previously failed a CGRP ligand mAb.

Methods

This monocentric retrospective cohort study included patients with episodic or chronic migraine in whom a non-response (< 30% reduction of monthly headache days during month 3 of treatment compared to baseline) to the CGRP ligand mAbs galcanezumab or fremanezumab led to a switch to erenumab, and who had received at least 3 administrations of erenumab. Monthly headache days were retrieved from headache diaries to assess the ≥30% responder rates and the absolute reduction of monthly headache days at 3 and 6 months of treatment with erenumab in this cohort.

Results

From May 2019 to July 2022, we identified 20 patients who completed 3 months of treatment with erenumab after non-response to a CGRP ligand mAb. Fourteen patients continued treatment for ≥6 months. The ≥30% responder rate was 35% at 3 months, and 45% at 6 months of treatment with erenumab, respectively. Monthly headache days were reduced from 18.6 ± 5.9 during baseline by 4.1 ± 3.1 days during month 3, and by 7.0 ± 4.8 days during month 6 compared to the month before treatment with erenumab (p< 0.001, respectively). Responders and non-responders to erenumab did not differ with respect to demographic or headache characteristics.

Conclusion

Switching to erenumab in non-responders to a CGRP ligand mAb might be beneficial in a subgroup of resistant patients, with increasing responder rates after 6 months of treatment. Larger prospective studies should aim to predict which subgroup of patients benefit from a switch.