bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of choroidal structural changes in patients with pre- and early-stage clinical diabetic retinopathy using wide-field SS-OCTA
Authors: Xu Fabao , Li Zhiwen , Yang Xueying , Gao Yang , Li Zhiwei , Li Guihua , Wang Shaopeng , Ning Xiaolin , Li Jianqiao
Published: January 2023

Purpose

To investigate the micro-vascular changes in choroidal structures in patients with pre- and early-stage clinical diabetic retinopathy (DR) using wide-field Swept-Source Optical Coherence Tomography Angiography (SS-OCTA).

Method

This observational cross-sectional study included 131 eyes of 68 subjects that were divided into healthy controls (group 1, n = 46), pre-DR (group 2, n = 43), early-stage DR (group 3, n = 42) cohorts. All participants that underwent SS-OCTA examination were inpatients in the department of Ophthalmology and the department of Endocrinology, Qilu Hospital, Shandong University, and Department of Ophthalmology, Aier Eye Hospital, Jinan, from July 11, 2021 to March 17, 2022. The choroidal vascularity index (CVI), choroidal thickness (ChT) and central macular thickness (CMT) in the whole area (diameter of 12 mm) and concentric rings with different ranges (0–3, 3–6, 6–9, and 9–12 mm) were recorded and analyzed from the OCTA image.

Result

Compared with healthy eyes, decreases in CVI and ChT were found in the eyes of patients with pre-or early-stage DR. The changes were more significant in the peripheral choroid, with the most prominent abnormalities in the 9-12mm area (P < 0.001). However, there was no obvious difference in the average CMT value. Furthermore, CVI and ChT were significantly correlated with the duration of diabetes in the range of 6–9 and 9–12 mm (Ps < 0.05; Correlation coefficient = -0.549, -0.395, respectively), with the strongest correlation (Ps < 0.01; Correlation coefficient = -0.597, -0.413, respectively) observed at 9–12 mm.

Conclusion

The CVI and ChT values of diabetic patients are significantly lower than in healthy controls, especially in patients with early-stage DR. In addition, the peripheral choroidal capillaries are more susceptible to early DM-induced injury than in the central area.
Can probiotics enhance fertility outcome? Capacity of probiotics as a single intervention to improve the feminine genital tract microbiota in non-symptomatic reproductive-aged women
Authors: Blancafort Claudia , Llácer Joaquín
Published: January 2023

Modifications in vaginal and endometrial microbiome and microbiota have been associated with fewer implantation rates and poorest pregnancy outcomes. Therefore, its study has emerged as a new biomarker in reproductive medicine. Despite the numerous papers published on probiotic use for vaginal dysbiosis and their actual wide empiric use especially for infertile patients, there is still no clear answer to justify their recommendation. The impact of probiotics on the vaginal or endometrial microbiota has often been investigated under a symptomatic altered vaginal microbial ecosystem, such as bacterial vaginosis. However 50% of women with bacterial vaginosis are asymptomatic. Actual clinical practice guidelines clearly recommend the use of specific antimicrobial agents for the management of symptomatic vaginal infections. Assuming this should be the management as well for an infertile population, what should be the treatment for the 50% non-symptomatic women presenting unfavorable vaginal/endometrial microbiota? The aim of this review is to assess the capacity of probiotics as a single intervention to alter the feminine genital tract microbiota in non-symptomatic reproductive-aged women.
Type 2 Diabetes Mellitus and its comorbidity, Alzheimer’s disease: Identifying critical microRNA using machine learning
Authors: Alamro Hind , Bajic Vladan , Macvanin Mirjana T. , Isenovic Esma R. , Gojobori Takashi , Essack Magbubah , Gao Xin
Published: January 2023

MicroRNAs (miRNAs) are critical regulators of gene expression in healthy and diseased states, and numerous studies have established their tremendous potential as a tool for improving the diagnosis of Type 2 Diabetes Mellitus (T2D) and its comorbidities. In this regard, we computationally identify novel top-ranked hub miRNAs that might be involved in T2D. We accomplish this via two strategies: 1) by ranking miRNAs based on the number of T2D differentially expressed genes (DEGs) they target, and 2) using only the common DEGs between T2D and its comorbidity, Alzheimer’s disease (AD) to predict and rank miRNA. Then classifier models are built using the DEGs targeted by each miRNA as features. Here, we show the T2D DEGs targeted by hsa-mir-1-3p, hsa-mir-16-5p, hsa-mir-124-3p, hsa-mir-34a-5p, hsa-let-7b-5p, hsa-mir-155-5p, hsa-mir-107, hsa-mir-27a-3p, hsa-mir-129-2-3p, and hsa-mir-146a-5p are capable of distinguishing T2D samples from the controls, which serves as a measure of confidence in the miRNAs’ potential role in T2D progression. Moreover, for the second strategy, we show other critical miRNAs can be made apparent through the disease’s comorbidities, and in this case, overall, the hsa-mir-103a-3p models work well for all the datasets, especially in T2D, while the hsa-mir-124-3p models achieved the best scores for the AD datasets. To the best of our knowledge, this is the first study that used predicted miRNAs to determine the features that can separate the diseased samples (T2D or AD) from the normal ones, instead of using conventional non-biology-based feature selection methods.
Burden in primary informal caregivers of children and adolescents with type 1 diabetes: Is it associated with depression, family dysfunction, and glycemic control?
Authors: Balcázar-Hernández Lourdes , Huerta-Martínez Hebert , Garrido Magaña Eulalia , Nishimura-Meguro Elisa , Jiménez Márquez Abigail , Rivera-Hernández Aleida
Published: January 2023

Objective

The requirement of a chronic treatment and the increase in life expectancy in children with type 1 diabetes (T1D) leads to the possibility of caregiver burden. The aim of our study was to evaluate the burden in primary informal caregivers (PIC) of children and adolescents with type 1 diabetes and its association with depression, family dysfunction, and glycemic control.

Materials and methods

A retrospective study was performed in PIC of children and adolescents with T1D. Zarit Burden Interview Scale (ZBIS) was used to evaluate caregiver burden. Beck Depression Inventory (BDI-II) was used to evaluate depression in PIC, and the Family APGAR questionnaire was used to evaluate the family functionality.

Results

A total of 100 PIC of children and adolescents with T1D were included. Caregiver burden was found in 33% of caregivers. The total score of the Zarit scale was 41 (34–49); 19% had mild caregiver burden, and 14% had severe caregiver burden. According to the BDI-II, 82% had minimal depression, 11% mild depression, 5% moderate depression, and 2% severe depression. Family function was good in 69%; 13% had moderate dysfunction, and 18% had severe dysfunction. A positive correlation between caregiver burden and BDI-II score (r = 0.84; p = 0.001) and the grade of depression (r = 0.87; p = 0.001) was found. A logistic regression model showed that BDI-II score was associated with caregiver burden (OR 1.14; 95% CI 1.061–1.23; p = 0.001). A BDI-II cut off of 9 or more had a sensibility and specificity of 58% and 28%, respectively, for caregiver burden [AUC 0.751 (0.64–0.85); p = 0.001]. A BDI-II score ≥9 was a predictor of caregiver burden (OR 3.4; 95% CI 1.4–8.1; p = 0.008).

Conclusion

Caregiver burden is present in more than one third of the PIC of patients with T1D and is associated with depression. A BDI-II score ≥9 is a predictor of caregiver burden which may be a point to take into account in the integral approach to the patient with T1D and his or her family nucleus.
Circulating levels and the bioactivity of miR-30b increase during pubertal progression in boys
Authors: Mørup Nina , Stakaitis Rytis , Main Ailsa Maria , Golubickaite Ieva , Hagen Casper P. , Juul Anders , Almstrup Kristian
Published: January 2023

Background

Puberty marks the transition from childhood to adulthood and is initiated by activation of a pulsatile GnRH secretion from the hypothalamus. MKRN3 functions as a pre-pubertal break on the GnRH pulse generator and hypothalamic expression and circulating levels of MKRN3 decrease peri-pubertally. In rodents, microRNA miR-30b seems to directly target hypothalamic MKRN3 expression – and in boys, circulating levels of miR-30b-5p increase when puberty is pharmacologically induced. Similarly, miR-200b-3p and miR-155-5p have been suggested to inhibit expression of other proteins potentially involved in the regulation of GnRH secretion. Here we measure circulating levels of these three miRNAs as boys progress through puberty.

Materials and Methods

Forty-six boys from the longitudinal part of the Copenhagen Puberty Study were included. All boys underwent successive clinical examinations including estimation of testis size by palpation. miR-30b-5p, miR-200b-3p, and miR-155-5p were measured in serum by RT-qPCR using a kit sensitive to the phosphorylation status of the miRNAs. Thirty-nine boys had miRNA levels measured in three consecutive samples (pre-, peri-, and post-pubertally) and seven boys had miR-30b-5p levels measured in ten consecutive samples during the pubertal transition.

Results

When circulating levels of miR-30b-5p in pre- and peri-pubertal samples were compared with post-pubertal levels, we observed a significant increase of 2.3 and 2.2-fold (p-value<6.0×10-4), respectively, and a larger fraction of miR-30b-5p appeared to be phosphorylated post-pubertally indicating an increase in its bioactivity. We also observed a negative correlation between circulating levels of miR-30b-5p and MKRN3. The inter-individual variation in circulating miR-30b levels was substantial and we could not define a clinical threshold for miR-30b-5p suggestive of imminent puberty. Also, miR-155-5p showed significantly increasing levels from the peri- to the post-pubertal stage (p=3.0×10-3), whereas miR-200b-3p did not consistently increase.

Conclusion

Both circulating levels of miR-30b-5p and its bioactivity increase during the pubertal transition in boys supporting its role in the activation of the HPG axis at the onset of physiologically normal puberty.
Static voltage stability analysis and evaluation of vector controlled offshore wind farm considering cable capacitance parameters
Authors: Tan Hongtao , Li Hui , Yao Ran , Liu Renkuan , Zhou Zhiting , Zhang Xiuqi
Published: January 2023

Voltage stability region assessment is the key to ensuring the reliable operation of offshore wind farms However, the traditional analysis method, which treats the WFs as a PQ node and directly connected to the infinite power grid, fails to take the cable capacitance and the dynamics of the converter into account, resulting an inaccurate evaluation of voltage stability. The contribution of this paper is to propose a more accurate method for assessing the voltage stability of OWFs. Firstly, based on the equivalent circuit method, the point of common coupling (PCC) and internal voltage characterization models of OWF considering the cable capacitance parameters are derived. Then, the coupling interface between the dynamic of the converter and the voltage characteristics of the system is designed, and the transfer function of the power injection from the DC side of the converter to the voltage of the collector system is established, which fully reflects the OWF Pin→Udc→Id→Upcc→Pout transitive relationship. Finally, a voltage stability criterion based on dPw, out/dId&dUdc/dt direction discrimination is proposed, and the influence of cable parameters, output power, and grid impedance on the voltage stability margin is analyzed. The accuracy of the proposed method is verified based on the RT-LAB platform.
The dynamic impact of green finance and renewable energy on sustainable development in China
Authors: Chen Jiahui , Li Lun , Yang Dechun , Wang Zuogong
Published: January 2023

In recent years, sustainable development has become a focal issue in the globalization process due to environmental uncertainty in the global context, which has attracted the extensive attention of scholars. This study explores the dynamic transmission mechanism and time-varying impacts among green finance, renewable energy and sustainable development in China on the basis of a stochastic volatile time-varying vector autoregressive (TVP-VAR-SV) model using time-series data from January 4, 2013, to October 14, 2022. The results revealed that there is an interaction among green finance, renewable energy and sustainable development in China, and the degree of influence and direction of action at different points in time show time-varying and heterogeneous characteristics. Further, this study subdivides renewable energy into hydro, wind, geothermal and solar energy. The dynamic impact of these types of energy on sustainable development is heterogeneous, and this relationship is affected by relevant economic events.
Living on the edge: Reservoirs facilitate enhanced interactions among generalist and rheophilic fish species in tributaries
Authors: Šmejkal Marek , Bartoň Daniel , Duras Jindřich , Horký Pavel , Muška Milan , Kubečka Jan , Pfauserová Nikola , Tesfaye Million , Slavík Ondřej
Published: January 2023

Most lotic ecosystems have been heavily modified in recent centuries to serve human needs, for example, by building dams to form reservoirs. However, reservoirs have major impacts on freshwater ecosystem functions and severely affect rheophilic fishes. The aim of this review is to gather evidence that aside from direct habitat size reductions due to reservoir construction, competition for food and space and predation from generalist fishes affect rheophilic community compositions in tributaries (river/stream not directly affected by water retention). River fragmentation by reservoirs enables the establishment of generalist species in altered river sections. The settlement of generalist species, which proliferate in reservoirs and replace most of the native fish species formerly present in pristine river, may cause further diversity loss in tributaries. Generalist migrations in tributaries, spanning from tens of metres to kilometres, affect fish communities that have not been directly impacted by reservoir construction. This causes “edge effects” where two distinct fish communities meet. Such interactions temporarily or permanently reduce the effective sizes of available habitats for many native specialized rheophilic fish species. We identified gaps that need to be considered to understand the mechanistic functioning of distinct fauna at habitat edges. We call for detailed temporal telemetry and trophic interaction studies to clarify the mechanisms that drive community changes upstream of reservoirs. Finally, we demonstrate how such knowledge may be used in conservation to protect the remnants of rheophilic fish populations.
Study on the characteristics of embodied carbon emission transfer in China’s power sector based on input-output networks
Authors: Ma Xiaodi , Fan Fengyan , Liu Qunyi
Published: January 2023

Electricity is an essential factor of production. The trade of goods and services between different industrial sectors in different regions may lead to the transfer of embodied carbon emissions in the power sector, which makes the problem of “carbon leakage” widespread. As the world’s largest CO2 emitter, China’s systematic identification of the patterns and structural characteristics of embodied carbon transfer in its power sector is essential for reasonably defining emission reduction responsibilities and scientifically formulating emission reduction policies. Few studies have focused on interprovincial transfer characteristics of embodied carbon emissions in the power sector. Based on the multi-regional input-output tables of China in 2010, 2012, 2015, and 2017, this paper combined the complex network theory to construct the interprovincial power embodied carbon transfer networks (PECTNs1) of China, analyzed the topological nature, community structure and identified the key provinces in the networks with the help of complex network indicators. The results indicate that both direct and embodied carbon emissions from China’s power sector present an increasing trend during the study period. The scale and scope of power carbon emission transfer between provinces have been expanding, showing an transfer trend from west to east and north to south. China’s PECTNs have small-world characteristics. From 2010 to 2017, the sub-regional phenomenon in China’s PECTNs gradually decreased. In the network community, the provinces with stable relationships are close to each other and have closer carbon correlation. Coal resource-based and large economic provinces with high power demand tend to be the core of the networks. The position of Xinjiang in the networks is gradually prominent. According to the results of the study, differentiated carbon emission reduction schemes are formulated based on the roles played by different provinces to provide ideas for embodied carbon reduction among provinces in China’s power sector.
Characterizing urban growth and land surface temperature in the western himalayan cities of India using remote sensing and spatial metrics
Authors: Gupta Rajman , Sharma Mani , Singh Garima , Joshi Rajendra Kr
Published: January 2023

Urban heat islands (UHI) are developing due to increasing urbanization and loss of vegetation in major cities in India. Increased urbanization modifies the urban microclimate that leads to significant land-use changes resulting in surface conversion and heat release, which poses serious risks to human health, environment and the ecosystem of the Himalayan ecosystem. Hence, mitigating UHI becomes important and requires a better understanding of underlying associated biophysical processes. In the study an attempt has been made to demonstrate the impact of urbanization on land surface temperature (LST) in Shimla and Dehradun, capitals of the Western Himalayan states, India using satellite data and spatial metrics. The process was analyzed using urban coverage patterns obtained from Landsat 5, 7, and 8 and corresponding sensors from TM, ETM+, and OLI. The Built-up and Non-Built-up areas were extracted and the biophysical parameters NDVI, NDBI, NDWI and LST were calculated to capture different features of urban growth. The result indicated, that the built-up area increased from 32.19 km2 (2000) to 68.37 km2 (2016) in Dehradun and from 12.38 km2 (2000) to 29.47 km2 (2016) in Shimla during the study period, resulting in an increase in NDBI and LST and Reduction and NDVI and NDWI. Results showed that temperature hotspots were largest in urban areas, followed by vegetation and water bodies. A significant correlation (p < 0.05) was observed between LST and biophysical parameters -NDVI, NDBI, NDWI. Spatial metrics at the class and landscape levels show that increased urban growth from 2000 to 2016 has made the landscape fragmented and more heterogeneous. The Identified trends and changes in landscape patterns and their impact on heterogeneous urban areas suggest that the study is feasible to estimate LST, NDVI, NDBI and NDWI with reasonable accuracy that will likely have influence on policy interventions.
Climate change enhanced the positive contribution of human activities to net ecosystem productivity from 1983 to 2018
Authors: Liu Min , Bai Xiaoyong , Tan Qiu , Luo Guangjie , Zhao Cuiwei , Wu Luhua , Chen Fei , Li Chaojun , Yang Yujie , Ran Chen , Luo Xuling , Zhang Sirui
Published: January 2023

Introduction

Accurate assessment of the net ecosystem productivity (NEP) is very important for understanding the global carbon balance. However, it remains unknown whether climate change (CC) promoted or weakened the impact of human activities (HA) on the NEP from 1983 to 2018.

Methods

Here, we quantified the contribution of CC and HA to the global NEP under six different scenarios based on a boosted regression tree model and sensitivity analysis over the last 40 years.

Results and discussion

The results show that (1) a total of 69% of the areas showed an upward trend in the NEP, with HA and CC controlled 36.33 and 32.79% of the NEP growth, respectively. The contribution of HA (HA_con) far exceeded that of CC by 6.4 times. (2) The CO2 concentration had the largest positive contribution (37%) to NEP and the largest influence area (32.5%). It made the most significant contribution to the NEP trend in the range of 435–440 ppm. In more than 50% of the areas, the main loss factor was solar radiation (SR) in any control area of the climate factors. (3) Interestingly, CC enhanced the positive HA_con to the NEP in 44% of the world, and in 25% of the area, the effect was greater than 50%. Our results shed light on the optimal range of each climatic factor for enhancing the NEP and emphasize the important role of CC in enhancing the positive HA_con to the NEP found in previous studies.
Phenotypic and genetic parameters of circadian rhythms from core body temperature profiles and their relationships with beef steers’ production efficiency profiles during successive winter feeding periods
Authors: Durunna Obioha , Carroll Jeffery A. , Dailey Jeff W. , Damiran Daalkhaijav , Larson Kathy A. , Timsit Edouard , Parsons Rex , Manafiazar Ghader , Lardner Herbert A.
Published: January 2023

This 2-year study evaluated differences in circadian parameters obtained from measures of core body temperatures using telemetric reticulo-rumen and rectal devices during two winter feeding regimes in western Canada. The study also estimated phenotypic correlations and genetic parameters associated with circadian parameters and other production traits in each feeding regime. Each year, 80 weaned steer calves (initial age: 209 ± 11 days; BW: 264 ± 20 kg) from the same cohort were tested over two successive regimes, Fall-Winter (FW) and Winter-Spring (WS) at Lanigan, Saskatchewan, Canada. The steers received forage-based rations in both regimes where the individual feed intake was measured with automatic feeding units. During the trial, the reticulo-rumen (RTMP) and rectal (RCT) temperatures were simultaneously measured every 5 min using telemetric devices. These were used to calculate the circadian parameters (Midline Estimating Statistic Of Rhythms, amplitude, and acrophase/peak time) for both temperature measures. Growth and efficiency performance traits were also determined for all steers. Each steer was assigned into inefficient, neutral, and efficient classes based on the SD of the residual feed intake (RFI), residual gain (RG), and residual intake and gain (RIG) within each year and feeding regime. Higher (p < 0.0003) RTMP and rectal temperature MESORs were observed in the Fall-Winter compared to the Winter-Spring regime. While the two test regimes were different (p < 0.05) for the majority of the RTMP or RCT temperature parameters, they did not differ (p > 0.10) with the production efficiency profiles. The heritability estimates were higher in FW (0.78 ± 0.18 vs. 0.56 ± 0.26) than WS (0.50 ± 0.18 vs. 0.47 ± 0.22) for the rumen and rectal MESORs, respectively. There were positive genetic correlations between the two regimes for the RTMP (0.69 ± 0.21) and RCT (0.32 ± 0.59). There was a negative correlation (p < 0.001) between body temperature and ambient temperature. The high heritability estimates and genetic correlations for rumen and rectal temperature parameters demonstrate their potential as beef genetic improvement tools of economic traits associated with the parameters. However, there are limited practical implications of using only the core-body temperature as a proxy for production efficiency traits for beef steers during winter.
PseU-ST: A new stacked ensemble-learning method for identifying RNA pseudouridine sites
Authors: Zhang Xinru , Wang Shutao , Xie Lina , Zhu Yuhui
Published: January 2023

Background: Pseudouridine (Ψ) is one of the most abundant RNA modifications found in a variety of RNA types, and it plays a significant role in many biological processes. The key to studying the various biochemical functions and mechanisms of Ψ is to identify the Ψ sites. However, identifying Ψ sites using experimental methods is time-consuming and expensive. Therefore, it is necessary to develop computational methods that can accurately predict Ψ sites based on RNA sequence information.

Methods: In this study, we proposed a new model called PseU-ST to identify Ψ sites in Homo sapiens (H. sapiens), Saccharomyces cerevisiae (S. cerevisiae), and Mus musculus (M. musculus). We selected the best six encoding schemes and four machine learning algorithms based on a comprehensive test of almost all of the RNA sequence encoding schemes available in the iLearnPlus software package, and selected the optimal features for each encoding scheme using chi-square and incremental feature selection algorithms. Then, we selected the optimal feature combination and the best base-classifier combination for each species through an extensive performance comparison and employed a stacking strategy to build the predictive model.

Results: The results demonstrated that PseU-ST achieved better prediction performance compared with other existing models. The PseU-ST accuracy scores were 93.64%, 87.74%, and 89.64% on H_990, S_628, and M_944, respectively, representing increments of 13.94%, 6.05%, and 0.26%, respectively, higher than the best existing methods on the same benchmark training datasets.

Conclusion: The data indicate that PseU-ST is a very competitive prediction model for identifying RNA Ψ sites in H. sapiens, M. musculus, and S. cerevisiae. In addition, we found that the Position-specific trinucleotide propensity based on single strand (PSTNPss) and Position-specific of three nucleotides (PS3) features play an important role in Ψ site identification. The source code for PseU-ST and the data are obtainable in our GitHub repository (https://github.com/jluzhangxinrubio/PseU-ST).
Vam6 reduces iNKT cell function in tumor via modulating AMPK/mTOR pathways
Authors: Bai Shiyu , Wu Qielan , Zhu Shasha , Zhang Yuwei , Chen Xuran , Su Miya , Pan Jun , Li Shuhang , Yue Ting , Xu Linfeng , Xie Di , Tian Chenxi , Zhao Dan , Li Xiang , Hou Junjie , Wang Lu , Fu Sicheng , Xue Yanhong , Jiang Amin , Li Dong , Xu Tao , Tian Zhigang , Zhou Rongbin , Zhang Huimin , Bai Li
Published: January 2023

Activation of mTORC1 is essential for anti-tumor function of iNKT cells. The mechanisms underlying impaired mTORC1 activation in intratumoral iNKT cells remain unclear. Via generating Vam6+/- mice and using flow cytometry, image approach, and RNA sequencing, we studied the role of Vam6 in controlling mTORC1 activation and intratumoral iNKT cell functions. Here, we find that increased Vam6 expression in intratumoral iNKT cells leads to impaired mTORC1 activation and IFN-γ production. Mechanistically, Vam6 in iNKT cells is essential for Rab7a-Vam6-AMPK complex formation and thus for recruitment of AMPK to lysosome to activate AMPK, a negative regulator of mTORC1. Additionally, Vam6 relieves inhibitory effect of VDAC1 on Rab7a-Vam6-AMPK complex formation at mitochondria-lysosome contact site. Moreover, we report that lactic acid produced by tumor cells increases Vam6 expression in iNKT cells. Given the key roles of increased Vam6 in promoting AMPK activation in intratumoral iNKT cells, reducing Vam6 expression signifificantly enhances the mTORC1 activation in intratumoral iNKT cells as well as their anti-tumor effificacy. Together, we propose Vam6 as a target for iNKT cell-based immunotherapy.
Exploring causal correlations between inflammatory cytokines and systemic lupus erythematosus: A Mendelian randomization
Authors: Xiang Mengmeng , Wang Yilun , Gao Zhanyan , Wang Jie , Chen Qian , Sun Zhan , Liang Jun , Xu Jinhua
Published: January 2023

Objectives

Previous studies have reported that a few inflammatory cytokines have associations with systemic lupus erythematosus (SLE)—for example, IL-6, IL-17, and macrophage inflammatory protein (MIP). This Mendelian randomization was conducted to further assess the causal correlations between 41 inflammatory cytokines and SLE.

Methods

The two-sample Mendelian randomization utilized genetic variances of SLE from a large publicly available genome-wide association study (GWAS) (7,219 cases and 15,991 controls of European ancestry) and inflammatory cytokines from a GWAS summary containing 8,293 healthy participants. Causalities of exposures and outcomes were explored mainly using inverse variance weighted method. In addition, multiple sensitivity analyses including MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO were simultaneously applied to strengthen the final results.

Results

The results indicated that cutaneous T cell-attracting chemokine (CTACK) and IL-17 may be suggestively associated with the risk of SLE (odds ratio, OR: 1.21, 95%CI: 1.04–1.41, p = 0.015; OR: 1.37, 95%CI: 1.03–1.82, p = 0.029). In addition, cytokines including beta nerve growth factor, basic fibroblast growth factor, IL-4, IL-6, interferon gamma-induced protein 10, monokine induced by interferon-gamma, MIP1b, stromal cell-derived factor-1 alpha, and tumor necrosis factor-alpha are suggested to be the consequences of SLE disease (Beta: 0.035, p = 0.014; Beta: 0.021, p = 0.032; Beta: 0.024, p = 0.013; Beta: 0.019, p = 0.042; Beta: 0.040, p = 0.005; Beta: 0.046, p = 0.001; Beta: 0.021, p = 0.029; Beta: 0.019, p = 0.045; Beta: 0.029, p = 0.048).

Conclusion

This study suggested that CTACK and IL-17 are probably the factors correlated with SLE etiology, while a couple of inflammatory cytokines are more likely to be involved in SLE development downstream.
New methods for the quantification of mixed chimerism in transplantation
Authors: Picard Christophe , Frassati Coralie , Cherouat Nicem , Maioli Sandrine , Moskovtchenko Philippe , Cherel Mathilde , Chiaroni Jacques , Pedini Pascal
Published: January 2023

Background

Quantification of chimerism showing the proportion of the donor in a recipient is essential for the follow-up of hematopoietic stem cell transplantation but can also be useful to document an immune tolerance situation after solid organ transplantation. Historically, chimerism has been quantified from genomic DNA, but with technological advances, chimerism from donor-derived cell-free DNA seems particularly relevant in solid organ transplantation.

Methods

The reference method was until recently the short tandem repeat technique, but new innovative techniques as digital PCR (dPCR) and NGS, have revolutionized the quantification of chimerism, such as the so-called microchimerism analysis. After a short review of chimerism methods, a comparison of chimerism quantification data for two new digital PCR systems (QIAcuity™ dPCR (Qiagen®) and QuantStudio Absolute Q (ThermoFisher®) and two NGS-based chimerism quantification methods (AlloSeq HCT™ (CareDx®) and NGStrack™ (GenDX®)) was performed.

Results

These new methods were correlated and concordant to routinely methods (r²=0.9978 and r²=0.9974 for dPCR methods, r²=0.9978 and r²=0.9988 for NGS methods), and had similar high performance (sensitivity, reproductibility, linearity).

Conclusion

Finally, the choice of the innovative method of chimerism within the laboratory does not depend on the analytical performances because they are similar but mainly on the amount of activity and the access to instruments and computer services.
Protective roles and protective mechanisms of neutralizing antibodies against SARS-CoV-2 infection and their potential clinical implications
Authors: Abebe Endeshaw Chekol , Dejenie Tadesse Asmamaw
Published: January 2023

Neutralizing antibodies (NAbs) are central players in the humoral immunity that defends the body from SARS-CoV-2 infection by blocking viral entry into host cells and neutralizing their biological effects. Even though NAbs primarily work by neutralizing viral antigens, on some occasions, they may also combat the SARS-CoV-2 virus escaping neutralization by employing several effector mechanisms in collaboration with immune cells like natural killer (NK) cells and phagocytes. Besides their prophylactic and therapeutic roles, antibodies can be used for COVID-19 diagnosis, severity evaluation, and prognosis assessment in clinical practice. Furthermore, the measurement of NAbs could have key implications in determining individual or herd immunity against SARS-CoV-2, vaccine effectiveness, and duration of the humoral protective response, as well as aiding in the selection of suitable individuals who can donate convalescent plasma to treat infected people. Despite all these clinical applications of NAbs, using them in clinical settings can present some challenges. This review discusses the protective functions, possible protective mechanisms against SARS-CoV-2, and potential clinical applications of NAbs in COVID-19. This article also highlights the possible challenges and solutions associated with COVID-19 antibody-based prophylaxis, therapy, and vaccination.
A bacterial outer membrane vesicle-based click vaccine elicits potent immune response against Staphylococcus aureus in mice
Authors: Sun Jingjing , Lin Xuansheng , He Yige , Zhang Baozhong , Zhou Nan , Huang Jian-dong
Published: January 2023

Staphylococcus aureus infection is a severe public health concern with the growing number of multidrug-resistant strains. S. aureus can circumvent the defense mechanisms of host immunity with the aid of multiple virulence factors. An efficacious multicomponent vaccine targeting diverse immune evasion strategies developed by S. aureus is thus crucial for its infection control. In this study, we exploited the SpyCatcher-SpyTag system to engineer bacterial outer membrane vesicles (OMVs) for the development of a multitargeting S. aureus click vaccine. We decorated OMVs with surface exposed SpyCatcher via a truncated OmpA(a.a 1-155)-SpyCatcher fusion. The engineered OMVs can flexibly bind with various SpyTag-fused S. aureus antigens to generate an OMV-based click vaccine. Compared with antigens mixed with alum adjuvant, the click vaccine simultaneously induced more potent antigen-specific humoral and Th1-based cellular immune response, which afforded protection against S. aureus Newman lethal challenge in a mouse model. Our study provided a flexible and versatile click vaccine strategy with the potential for fighting against emerging S. aureus clinical isolates.
Virus induced dysbiosis promotes type 1 diabetes onset
Authors: Morse Zachary J. , Simister Rachel L. , Crowe Sean A. , Horwitz Marc S. , Osborne Lisa C.
Published: January 2023

Autoimmune disorders are complex diseases of unclear etiology, although evidence suggests that the convergence of genetic susceptibility and environmental factors are critical. In type 1 diabetes (T1D), enterovirus infection and disruption of the intestinal microbiota are two environmental factors that have been independently associated with T1D onset in both humans and animal models. However, the possible interaction between viral infection and the intestinal microbiota remains unknown. Here, we demonstrate that Coxsackievirus B4 (CVB4), an enterovirus that accelerates T1D onset in non-obese diabetic (NOD) mice, induced restructuring of the intestinal microbiome prior to T1D onset. Microbiome restructuring was associated with an eroded mucosal barrier, bacterial translocation to the pancreatic lymph node, and increased circulating and intestinal commensal-reactive antibodies. The CVB4-induced change in community composition was strikingly similar to that of uninfected NOD mice that spontaneously developed diabetes, implying a mutual “diabetogenic” microbiome. Notably, members of the Bifidobacteria and Akkermansia genera emerged as conspicuous members of this diabetogenic microbiome, implicating these taxa, among others, in diabetes onset. Further, fecal microbiome transfer (FMT) of the diabetogenic microbiota from CVB4-infected mice enhanced T1D susceptibility and led to diminished expression of the short chain fatty acid receptor GPR43 and fewer IL-10-expressing regulatory CD4+ T cells in the intestine of naïve NOD recipients. These findings support an overlap in known environmental risk factors of T1D, and suggest that microbiome disruption and impaired intestinal homeostasis contribute to CVB-enhanced autoreactivity and T1D.
Review: Current trends, challenges, and success stories in adjuvant research
Authors: Singleton Kentner L. , Joffe Ari , Leitner Wolfgang W.
Published: January 2023

Vaccine adjuvant research is being fueled and driven by progress in the field of innate immunity that has significantly advanced in the past two decades with the discovery of countless innate immune receptors and innate immune pathways. Receptors for pathogen-associated molecules (PAMPs) or host-derived, danger-associated molecules (DAMPs), as well as molecules in the signaling pathways used by such receptors, are a rich source of potential targets for agonists that enable the tuning of innate immune responses in an unprecedented manner. Targeted modulation of immune responses is achieved not only through the choice of immunostimulator – or select combinations of adjuvants – but also through formulation and systematic modifications of the chemical structure of immunostimulatory molecules. The use of medium and high-throughput screening methods for finding immunostimulators has further accelerated the identification of promising novel adjuvants. However, despite the progress that has been made in finding new adjuvants through systematic screening campaigns, the process is far from perfect. A major bottleneck that significantly slows the process of turning confirmed or putative innate immune receptor agonists into vaccine adjuvants continues to be the lack of defined in vitro correlates of in vivo adjuvanticity. This brief review discusses recent developments, exciting trends, and notable successes in the adjuvant research field, albeit acknowledging challenges and areas for improvement.
Twenty years of in-situ monitoring in the south-eastern Mediterranean Levantine basin: Basic elements of the thermohaline structure and of the mesoscale circulation during 1995-2015
Authors: Zodiatis George , Brenner Steve , Gertman Isaac , Ozer Tal , Simoncelli Simona , Ioannou Marinos , Savva Sotiris
Published: January 2023

The in-situ data gathered over two decades since mid-1990s in the South-Eastern Levantine Basin from 34 hydrographic campaigns and from 35 bi-weekly and monthly Voluntary Observing Ships (VOS) transects, after the pioneering POEM cruises, have provided insight on the dominant meso-scale coherent circulation features of this sub-basin. The most pronounced feature, the anticyclonic Cyprus Eddy, migrates over the broad region of the Eratosthenes seamount and exhibits significant seasonal and inter-annual spatial-temporal variability. Another prominent structure of the sub-basin is the anticyclonic Shikmona Eddy generated by instabilities of the strong northward flowing jet along the south-easternmost shelf and slope of the Levantine basin. Its evolution and co-existence with the Cyprus Eddy, cause the periodic re-establishment of the Shikmona Gyre, which was first observed during the POEM cruises in mid-1980s. The offshore, cross basin, eastward flowing Mid-Mediterranean Jet (MMJ) defines the northern and southern flanks of these sub-basin scale anticyclonic eddies and transports the lower salinity Modified Atlantic Water (MAW) in the subsurface layer, through the warmest and most saline waters of the Mediterranean. Periodically, the MMJ bifurcates and/or is diverted northward, along the western coast of Cyprus due to westward and northward spatial fluctuations of the Cyprus Eddy’s western boundaries. The current long term in-situ monitoring of the sub-basin provides an overview of the extent of the main water masses and characterizes their variability throughout the period considered. The analysis of the data indicates an increase of the temperature and salinity of the Levantine Surface Water (LSW) and of the subsurface MAW. The Eastern Mediterranean Transient Water (EMTW) is shown to occupy the deep cavities in the vicinity of the Eratosthenes seamount while its upper boundary was found to be lifted to shallower depths over a period of two decades.
Proposed solutions for marine debris in the Windward Islands- perspectives from key policy makers and policy influencers
Authors: Graham Roxanne E. D.
Published: January 2023

With the rise of regionalization and globalized approaches to dealing with the associated sources and impacts of marine debris, it is often a challenge to properly capture the unique context and special needs of small island developing states (SIDS) worldwide. In the SIDS context, locals’ perspectives should have a voice in scientific research, as well as in devising potential solutions, at all and different scales. With the view to tailor solutions for the prevention, reduction and mitigation of marine debris, this research explores the professional opinion of local knowledge holders including policy makers from government organizations (GOs) and key policy influencers in non-governmental organizations (NGOs) in the five English-Speaking Windward Islands of the Eastern Caribbean. To achieve that objective, surveys were conducted with these two groups in Barbados, Dominica, Grenada, St. Lucia and St. Vincent and the Grenadines. On the causes of the debris problem, the survey revealed that the lack of a proper waste management systems on islands, recycling limitations and inappropriate disposal behaviors of the population are generally thought to be the main contributory factors to the accelerating problem of marine debris. Further, phenomena such asSargassuminfluxes, sea level rise and extreme weather events exacerbate the problem including most especially tropical storms and hurricanes. On the recommended solutions, over eighty percent of the participants identified monitoring and policing services as a main constraint that prohibits sound coastal and marine litter handling. Ninety-five percent identified establishing feasible recycling systems and sixty-seven percent identified changing social behaviors (including a combination of product and consumer literacy, disposal habits, compliance with laws and regulations) as national priorities for enabling on-the-ground actions for better coastal and marine litter prevention and reduction going forward. These findings reinforce recently published work which indicates the need for effective solid waste management systems in the Eastern Caribbean for cleaner and healthier oceans. An additional recommendation was proposed to address a major source of the marine litter problem- upstream producers. Furthermore, given the natural events component, this research proposes incorporating the Sendai Framework for disaster risk reduction in future proposed mitigation measures with a view to building the resilience of SIDS and local communities in combating the impacts of marine debris.
From basalt to biosphere: Early non-vent community succession on the erupting Vailulu’u deep seamount
Authors: Herrera Santiago , Chadwick William W. , Jackson Matthew G. , Konter Jasper , McCartin Luke , Pittoors Nicole , Bushta Emily , Merle Susan G.
Published: January 2023

Volcanic eruptions provide rare opportunities to witness the biological recolonization of areas covered by new lava flows by effectively resetting the ecological succession clock to zero. The role of submarine volcanic eruptions as disturbance events and the resulting patterns of ecological succession have mainly been studied in hydrothermal vent ecosystems. However, the effects of submarine volcanic eruptions as disturbance forces have rarely been studied in non-vent ecosystems, particularly on seamounts. Here, we document the early stages of ecological succession of non-vent benthic communities inhabiting the summit caldera of the active Vailulu’u submarine volcano in American Samoa. Sitting above the Samoan volcanic hotspot, Vailulu’u is the youngest volcano of the Samoan chain. Repeated mapping of Vailulu’u in 1999, 2005, 2006, 2012, and 2017 revealed the progressive growth of a new cone named Nafanua. In 18 years, the cone grew >300 meters in height from a starting depth of ~1000 meters below sea level (mbsl). The differential analyses of this time-series bathymetry dataset enabled the assignment of maximum age ranges to different portions of the new cone. High-definition ROV imagery collected in 2017 revealed patterns of community structuring consistent with ecological succession: newly erupted seafloor contained a subset of the benthic species found on older seafloor. Furthermore, individual animal sizes in the younger seafloor zones were smaller than in the older zones. This unusual interdisciplinary combination of geological and biological observations provides constraints on which deep-sea animals recolonize new seafloor after a major disturbance event and how quickly. This knowledge could be applied to identify signs and states of recovery from anthropogenic disturbances by a deep seamount ecosystem.
Water model determines thermosensitive and physicochemical properties of poly(N-isopropylacrylamide) in molecular simulations
Authors: Quoika Patrick K. , Kamenik Anna S. , Fernández-Quintero Monica L. , Zacharias Martin , Liedl Klaus R.
Published: January 2023

Poly (N-isopropylacrylamide) (PNIPAM) is a famous representative of thermosensitive polymers. Thermosensitive polymers undergo a phase transition with lower critical solution temperature. Commonly, their phase behavior is linked to a conformational collapse above a certain temperature. This thermosensitive conformational transition is called Coil-Globule transition. In contrast, most other polymers usually show inverse temperature behavior, i.e., an upper critical solution temperature, corresponding to a Globule-Coil transition. Besides their numerous possible applications, thermosensitive polymers are of interest for fundamental research, because of similarities to macromolecular conformational transitions, e.g., protein folding. The counter-intuitive behavior of thermosensitive polymers is commonly associated with solvation effects. Thus, an accurate description of the solvent is crucial for the investigation of thermosensitive polymers in molecular simulations. Here, we investigate the influence of the in silico water model on the thermosensitive Coil-Globule transition in molecular dynamics simulations. To this end, we performed extensive atomistic simulations of the syndiotactic PNIPAM 20-mer at multiple temperatures with eight different water models–four of which are 3-point water models (TIP3P-type) and four are 4-point water models (TIP4P-type). We found that the thermosensitive Coil-Globule transition is strongly influenced by the water model in the simulations. Depending on the water model, the conformational ensemble of the polymer is shifted significantly, which leads to dramatically different results: The estimated transition temperature may span between 255 and 350 K. Consequently, depending on the description of the solvent, the physicochemical and mechanical properties of these polymers, e.g., the polymer-solvent affinity and persistence length, vary. These divergent results originate from the strength of interactions between polymer and solvent, but also on the bulk state of the solvent. Both these quantities vary between water models. We found that the Lennard-Jones interaction parameter ϵ of the water model correlates with the transition temperature of the polymer. Indeed, the quadrupole moment of the water model shows an even higher correlation with this quantity. Our results suggest a connection between the phase diagram of the solvent and the thermosensitive transition of the polymer.