bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends and challenges for balanced scoring in cybersecurity exercises: A case study on the example of Locked Shields
Authors: Mäses Sten , Maennel Kaie , Brilingaitė Agnė
Published: September 2022

Cybersecurity exercises (CSXs) enable raising organizational awareness, testing capabilities, identifying strengths and weaknesses, and gaining hands-on practice in building resilience against attacks. Typical CSX execution is designed as a competition or a challenge with gamification features to increase participant engagement. Also, it requires a significant amount of human resources to ensure up-to-date attack simulation and proper feedback. The usual concerns related to CSXs are how many points the team or participant received and the reason behind the particular evaluation. Properly balanced scoring can provide valuable feedback and keep CSX participants engaged. An inadequate scoring system might have the opposite effect—spread disorder, cause discontent, decrease motivation, and distract the participants from the event's primary goal. Combining both technical and soft sides in CSX makes it increasingly complex and challenging to ensure a balanced scoring. This paper defines scoring challenges and trends based on the case study of one of the largest international live-fire cyber defense exercises, Locked Shields (LS). It reviews the CSX scoring categories of the recent LS executions and provides the most common participant concerns related to scoring. The feedback shows that clarity and transparency of the scoring system together with providing feedback and justification to the scores are one of the top concerns. The design choices of the scoring system are explored to demonstrate the subtle variations of balanced category scoring and make a basis for future discussions. The chosen contrast and comparison approach enabled distinguishing four parameters for design decision categories: complexity, transparency, level of competition, and automatization. The research results demonstrate that learning facilitation requires system simplification and decisions regarding trends of the scoring curve. Even though transparency is a critical issue, concealing some scoring logic details can ensure more flexibility during the event to stimulate participants, support learning experiences, and cope with unexpected situations. Time as a central dimension enables the implementation of complex scoring curves for automated assessment. Our study contributes to the community of higher education institutions and all organizers of cybersecurity challenges for skill development and assessment.
Genetic testing of sperm donors at a human sperm bank in China
Authors: Huang Chuan , Wu Hui-Lan , Zhou Wen-Jun , Huang Zeng-Hui , Luo Xue-Feng , Tang Yu-Ling , Liu Qian , Fan Li-Qing , Nie Hong-Chuan , Zhu Wen-Bing
Published: September 2022

Background

In China, numerous human sperm banks only perform three-generation family history evaluation to exclude genetic diseases with clinical symptoms; therefore, many inherited risks cannot be detected before donor qualification even when a thorough genetic family history evaluation has been performed. Hence, the risk of recessive disease inheritance persists with the current eligibility guidelines in China regarding the donor selection process.

Methods

Retrospective study that reviewed the genetic test analyses and clinical outcomes of young adult men who were qualified sperm donors at the Hunan Province Human Sperm Bank of China from January 1, 2018, to May 1, 2021. We included a total of 3231 qualified sperm donors: all donors underwent primary screening for thalassemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Whereafter, 278 of donors underwent genetic testing for specific genes, and 43 donors underwent whole exome sequencing.

Results

2.4% of 3231 qualified sperm donors might have thalassemia and 1.4% might have G6PD deficiency. Sperm donors with thalassemia and G6PD deficiency would be eliminated. Specific gene testing identified 7 of the 278 donors (2.5%) as carriers of at least one pathogenic or likely pathogenic variant in a gene, including 1.9% of 154 donors (3/154) as carrier variants in α-Like or β-Like globin genes, 17.6% of 17 donors (3/17) as carrier variants in GJB2, 12.5% of 8 donors (1/8) as carrier variants in SMN1. In addition, among the 43 sperm donors carrying the 111 pathogenic/likely pathogenic variants, eight (18.6%) were carriers of pathogenic variants of the GJB2 gene. The frequency, therefore, was approximately 1 in 5.

Conclusions

The data suggest that used blood routine and RDT can make a preliminary screening of sperm donors, and special gene testing should be performed for sperm donors according to the regional incidence of specific genetic diseases. Meanwhile, whole exome sequencing can be used as a supplementary application in sperm donor genetic testing, and aid a successful and healthy pregnancy. However, industry guidelines must be modified to incorporate its use.
Development and validation of a novel diagnostic tool for predicting the malignancy probability of thyroid nodules: A retrospective study based on clinical, B-mode, color doppler and elastographic ultrasonographic characteristics
Authors: Xu Shangyan , Ni Xiaofeng , Zhou Wei , Zhan Weiwei , Zhang Huan
Published: September 2022

Background

Clinicians estimate the risk of thyroid nodules and make subsequently decision on the basis of clinical and ultrasonographic findings. Currently, there is no comprehensive diagnostic tool for predicting the malignancy rates of thyroid nodules. Our aim was to develop and validate a novel integrate diagnostic tool for predicting the malignancy probability of thyroid nodules based on clinical, B-mode, Color Doppler and elastographic ultrasonographic characteristics.

Methods

A total of 1016 nodules in 1016 patients who underwent thyroid ultrasonography and surgery from July 2021 to December 2021 were included in this retrospective study. All nodules were confirmed by pathology and randomly classified into the training and validation groups. Clinical, B-mode, Color Doppler and elastographic (CBCE) ultrasonographic characteristics of nodules were recorded. Univariate and multivariate analyses were performed to screen independent predictors associated with thyroid cancer. A multivariate model containing the extracted predictors was constructed and presented in the form of a nomogram. The validation and applicability of the CBCE nomogram was evaluated using the receiver operating characteristic (ROC) curve. Diagnostic performances were calculated to compare the CBCE nomogram with ACR-TIRADS (Thyroid Imaging Reporting Data System by American College of Radiology) and EU-TIRADS (Thyroid Imaging Reporting Data System by European Thyroid Association).

Results

The following factors were included in the CBCE nomogram: patient gender, age, shape, margin, composition and echogenicity, calcification, vascularization distribution, vascularization degree, suspicious lymph node metastases and elastography. The area under the curve (AUC) values were 0.978 and 0.983 for the training and validation groups, respectively. Compared with ACR-TIRADS and EU-TIRADS, the CBCE nomogram showed improved accuracy (0.944) and specificity (0.913) without sacrificing sensitivity (0.963) and showed the highest AUC with an optimal cutoff value of 0.55.

Conclusion

The CBCE nomogram has good and high clinical practicability in predicting the malignancy probability of thyroid nodules.
Effectiveness of core needle biopsy in the diagnosis of thyroid lymphoma and anaplastic thyroid carcinoma: A systematic review and meta-analysis
Authors: Vander Poorten Vincent , Goedseels Nathan , Triantafyllou Asterios , Sanabria Alvaro , Clement Paul M. , Cohen Oded , Golusinski Pawel , Guntinas-Lichius Orlando , Piazza Cesare , Randolph Gregory W. , Rinaldo Alessandra , Ronen Ohad , Cabanillas Maria E. , Shaha Ashok R. , Teng Yong , Tufano Ralph P. , Williams Michelle D. , Zafereo Mark , Ferlito Alfio
Published: September 2022

Background

Both anaplastic thyroid carcinoma (ATC) and thyroid lymphoma (TL) clinically present as rapidly enlarging neck masses. Unfortunately, in this situation, like in any other thyroid swelling, a routine fine-needle aspiration (FNA) cytology is the first and only diagnostic test performed at the initial contact in the average thyroid practice. FNA, however, has a low sensitivity in diagnosing ATC and TL, and by the time the often “inconclusive” result is known, precious time has evolved, before going for core-needle biopsy (CNB) or incisional biopsy (IB) as the natural next diagnostic steps.

Objectives

To determine the diagnostic value of CNB in the clinical setting of a rapidly enlarging thyroid mass, via a systematic review and meta-analysis of the available data on CNB reliability in the differential diagnosis of ATC and TL.

Methods

A PubMed, Embase and Web of Science database search was performed on June 23th 2021. Population of interest comprised patients who underwent CNB for clinical or ultrasonographical suspicion of ATC or TL, patients with a final diagnosis of ATC or TL after CNB, or after IB following CNB.

Results

From a total of 17 studies, 166 patients were included. One hundred and thirty-six were diagnosed as TL and 14 as ATC following CNB. CNB, with a sensitivity and positive predictive value of 94,3% and 100% for TL and 80,1% and 100% for ATC respectively, proved to be superior to FNA (reported sensitivity for TL of 48% and for ATC of 61%). Furthermore, the need for additional diagnostic surgery after CNB was only 6.2% for TL and 17.6% for ATC.

Conclusions

Immediately performing CNB for a suspected diagnosis of ATC and TL in a rapidly enlarging thyroid mass is more appropriate and straightforward than a stepped diagnostic pathway using FNA first and awaiting the result before doing CNB.
Quantitative assessment of lumbar spine bone marrow in patients with different severity of CKD by IDEAL-IQ magnetic resonance sequence
Authors: Xiong Yan , He Tongxiang , Liu Weiyin Vivian , Zhang Yao , Hu Shuang , Wen Donglin , Wang Yanan , Zhang Peisen , He Fan , Li Xiaoming
Published: September 2022

Background

Chronic kidney disease (CKD) has a significant negative impact on bone health. Bone marrow is an essential component of bone, mainly composed of trabecular bone and fat. The IDEAL-IQ sequence of MRI allows indirect quantification of trabecular bone mass by R2* and direct quantification of bone marrow fat content by FF map, respectively.

Objective

Our objective was to explore the association of CKD severity with bone marrow using IDEAL-IQ and whether mineral and bone metabolism markers alter this association.

Method

We recruited 68 CKD patients in this cross-sectional research (15 with CKD stages 3-4, 26 with stage 5, and 27 with stage 5d). All patients underwent lumbar spine IDEAL-IQ, BMD, and several bone metabolism markers (iPTH, 25-(OH)-VitD, calcium and phosphorus). Multiple linear regression analysis was used to examine the association of CKD severity with MRI measurements (R2* and FF).

Results

More severe CKD was associated with a higher R2* value [CKD 5d versus 3-4: 30.077 s-1 (95% CI: 12.937, 47.217), P for trend < 0.001], and this association was attenuated when iPTH was introduced [CKD 5d versus 3-4: 19.660 s-1 (95% CI: 0.205, 39.114), P for trend = 0.042]. Furthermore, iPTH had an association with R2* value [iPTH (pg/mL): 0.033 s-1 (95% CI: 0.001, 0.064), P = 0.041]. Besides, FF was mainly affected by age and BMI, but not CKD.

Conclusions

The bone marrow R2* value measured by IDEAL-IQ sequence is associated with CKD severity and iPTH. The R2* of IDEAL-IQ has the potential to reflect lumbar bone changes in patients with CKD.
Female reproductive functions of the neuropeptide PACAP
Authors: Koppan Miklos , Nagy Zsuzsanna , Bosnyak Inez , Reglodi Dora
Published: September 2022

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide originally isolated as a hypothalamic peptide. It has a widespread distribution in the body and has a diverse spectrum of actions. Among other processes, PACAP has been shown to be involved in reproduction. In this review we summarize findings related to the entire spectrum of female reproduction. PACAP is a regulatory factor in gonadal hormone production, influences follicular development and plays a role in fertilization and embryonic/placental development. Furthermore, PACAP is involved in hormonal changes during and after birth and affects maternal behavior. Although most data come from cell cultures and animal experiments, increasing number of evidence suggests that similar effects of PACAP can be found in humans. Among other instances, PACAP levels show changes in the serum during pregnancy and birth. PACAP is also present in the human follicular and amniotic fluids and in the milk. Levels of PACAP in follicular fluid correlate with the number of retrieved oocytes in hyperstimulated women. Human milk contains very high levels of PACAP compared to plasma levels, with colostrum showing the highest concentration, remaining steady thereafter for the first 7 months of lactation. All these data imply that PACAP has important functions in reproduction both under physiological and pathological conditions.
Trends in hospital admissions for adrenal insufficiency in adolescents and young adults in the 21st century
Authors: Chrisp Georgina L. , Quartararo Maria , Torpy David J. , Falhammar Henrik , Rushworth R. Louise
Published: September 2022

Background

Very little is known about the epidemiology of adrenal crises (AC) and adrenal insufficiency (AI) in adolescents and young adults.

Methods

Data on all admissions to Australian hospitals between 2000/1 to 2019/20 for a principal diagnosis of AI (including AC) in 10-24 year olds were extracted from a national repository. Age and sex-specific rates and age-adjusted rates were compared.

Findings

Over the study, there were 3386 admissions for a principal diagnosis of AI; 24.0% (n=812) were for an AC and 50·7% (n=1718) were for secondary AI. Age-adjusted AI admissions increased from 31·70/million in 2000/1 to 54·68/million in 2019/20 (p<0·0001). Age-adjusted AC admissions also increased, most notably in the second decade (from 5·80/million in 2010/11 to 15·75/million in 2019/20) (p<0·00001). Average AI and AC admission rates were comparable between the sexes, but rates increased significantly in females, especially in those aged 20 to 24 years, whose AC rate in 2019/20 (39·65/million) was significantly higher than the corresponding rate in 2000/1 (3·15/million) (p<0·00001). Average age-adjusted SAI admission rates were higher in males (23·92/million) than females (15·47/million) (p<0·00001). However, SAI admission rates increased only among females (from 11·81/million to 22·12/million in 2019/20), with an increase in 20-24 year old females in the second decade from 5·07/million in 2010 to 20·42/million (p<0·00001). Age adjusted admissions for congenital adrenal hyperplasia, primary AI (PAI) and drug-induced AI did not change significantly over the study.

Interpretation

AC/AI admissions increased over the first two decades of this century in the emerging adult population, particularly among females who also experienced a marked increase in AC admission rates, most evident in the second decade. Although uncertain, possible explanations include: dose of glucocorticoid replacement; non-adherence to therapy; psychosocial factors; and difficulty in transition to adult services. Admissions for SAI also increased, while rates of PAI and CAH remained constant.
A novel grid-connected microgrid energy management system with optimal sizing using hybrid grey wolf and cuckoo search optimization algorithm
Authors: Jasim Ali M. , Jasim Basil H. , Bureš Vladimír
Published: September 2022

Renewable energy systems, particularly in countries with limited fossil fuel resources, are promising and environmentally sustainable sources of electricity generation. Wind, solar Photovoltaic (PV), and biomass gasifier-based systems have gotten much attention recently for providing electricity to energy-deficient areas. However, due to the intermittent nature of renewable energy, a completely renewable system is unreliable and may cause operation problems. Energy storage systems and volatile generation sources are the best way to combat the problem. This paper proposes a hybrid grid-connected wind-solar PV generation Microgrid (MG) with biomass and energy storage devices to meet the entire value of load demand for the adopted buildings in an intended region and ensure economic dispatch as well as make a trade in the electricity field by supplying/receiving energy to/from the utility grid. The control operation plan uses battery storage units to compensate energy gap if the priority resources (wind turbine and solar PV) are incapable of meeting demand. Additionally, the biomass gasifier is used as a fallback option if the batteries fail to perform their duty. At any time, any excess of energy can be utilized to charge the batteries and sell the rest to the utility. Additionally, if the adopted resources are insufficient to meet the demand, the required energy is acquired from the utility. A Hybrid Grey Wolf with Cuckoo Search Optimization (GWCSO) algorithm is adopted for achieving optimal sizing of the proposed grid-connected MG. To assess the proposed technique’s robustness, the results are compared to those obtained using the Grey Wolf Optimization (GWO) algorithm. The GWCSO method yielded a lower total number of component units, annual cost, total Net Present Cost (NPC), and Levelized Cost Of Energy (LCOE) than the GWO algorithm, whereas the GWCSO algorithm has the lowest deviation, indicating that it is more accurate and robust than the GWO algorithm.
Spatiotemporal distribution of physicochemical parameters and toxic elements in Lake Pomacochas , Amazonas, Peru
Authors: Leiva-Tafur Damaris , Goñas Malluri , Culqui Lorenzo , Santa Cruz Carlos , Rascón Jesús , Oliva-Cruz Manuel
Published: September 2022

Lakes are water bodies that play an essential role as water sources for humanity, as they provide a wide range of ecosystem services. Therefore, this study aimed to evaluate Lake Pomacochas, a high Andean lake in the north of Peru. A variety of parameters were studied, including physicochemical parameters such as temperature (T°C), dissolved oxygen (DO), potential hydrogen (pH), electrical conductivity (EC), turbidity, total dissolved solids (TDS), biochemical oxygen demand (BOD), alkalinity, and chlorides hardness; the concentrations of nitrates, nitrites, sulfates, and ammonium; elements such as aluminum (Al), calcium (Ca), magnesium (Mg), sodium (Na), potassium (K), and boron (B); as well as metals and metalloids such as zinc (Zn), cadmium (Cd), copper (Cu), lead (Pb), and arsenic (As). In addition, pH, Zn, and Cu were evaluated at the sediment level. It is important to note that all parameters evaluated in the water matrix showed significant differences in the seasonal period and depth levels. In comparison, the parameters evaluated at the sediment level had no significant differences between the seasonal period and sampling points. As for the seasonal period, the variables that were higher for the dry season were electrical conductivity, total dissolved solids, and lead while that for the wet season were biochemical oxygen demand, zinc, magnesium, turbidity, calcium, dissolved oxygen, temperature, and potential hydrogen. At the depth levels, parameters such as total dissolved solids, lead, and arsenic had similar behavior for the three depths evaluated. According to national standards, latent contamination by cadmium and lead was found in the lake water from the ecological risk assessment. However, by international standards, all sampling stations showed a high level of contamination by cadmium, lead, zinc, copper, and arsenic, which represents a potential risk for the development of socioeconomic activities in the lake. At the same time, the evaluation of sediments did not present any potential risk.
Identification and validation of ferroptosis-related lncRNA signatures as a novel prognostic model for glioma
Authors: Huang Liang , Zhang Juan , Gong Fanghua , Han Yuhua , Huang Xing , Luo Wanxiang , Cai Huaan , Zhang Fan
Published: September 2022

Background: Ferroptosis is a newly discovered form of regulated cell death with distinct properties and recognizing functions involved in physical conditions or various diseases, including cancers. However, the relationship between gliomas and ferroptosis-related lncRNAs (FRLs) remains unclear.

Methods: We collected a total of 1850 samples from The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEX) databases, including 698 tumor and 1,152 normal samples. A list of ferroptosis-related genes was downloaded from the Ferrdb website. Differentially expressed FRLs (DEFRLS) were analyzed using the “limma” package in R software. Subsequently, prognosis-related FRLs were obtained by univariate Cox analysis. Finally, a prognostic model based on the 3 FRLs was constructed using Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) algorithm. The prognostic power of the model was assessed using receiver operating characteristic (ROC) curve analysis and Kaplan-Meier (K-M) survival curve analysis. In addition, we further explored the relationship of the immune landscape and somatic mutations to prognostic model characteristics. Finally, we validated the function of LINC01426 in vitro.

Results: We successfully constructed a 3-FRLs signature and classified glioma patients into high-risk and low-risk groups based on the risk score calculated from this signature. Compared with traditional clinicopathological features [age, sex, grade, isocitrate dehydrogenase (IDH) status], the prognostic accuracy of this model is more stable and stronger. Additionally, the model had stable predictive power for overall survival over a 5-year period. In addition, we found significant differences between the two groups in cellular immunity, the numbers of many immune cells, including NK cells, CD4+, CD8+ T-cells, and macrophages, and the expression of many immune-related genes. Finally, the two groups were also significantly different at the level of somatic mutations, especially in glioma prognosis-related genes such as IDH1 and ATRX, with lower mutation rates in the high-risk group leading to poorer prognosis. Finally, we found that the ferroptosis process of glioma cells was inhibited after knocking down the expression of LINC01426.

Conclusion: The proposed 3-FRL signature is a promising biomarker for predicting prognostic features in glioma patients.
Microfibrillar-associated protein 2 is a prognostic marker that correlates with the immune microenvironment in glioma
Authors: Xu Wanzhen , Geng Ren , Zhao Yao , Ma Xiaoshan , Bai Yang , Jiang Yining , Zhao Liyan , Li Yunqian
Published: September 2022

Aims: microfibrillar-associated protein 2 (MFAP2), a component of the extracellular matrix, plays key roles in regulating growth factor signal transduction and various malignant tumors. However, the clinicopathological features of microfibrillar-associated protein 2 in gliomas have not been elucidated to date.

Methods: TCGA and CGGA databases were used to study the expression of microfibrillar-associated protein 2 in glioma and its relationship with clinicopathological features of patients with glioma. Western blotting was performed to detect the expression of microfibrillar-associated protein 2 protein in tissue samples from glioma patients. Gene set enrichment analysis (GSEA) was applied to detect biological processes and signal pathways related to microfibrillar-associated protein 2. Single-sample gene set enrichment analysis, TIMER 2.0, and TISIDB databases were used to evaluate the role of microfibrillar-associated protein 2 in tumor immune characteristics. The prognostic role of microfibrillar-associated protein 2 in glioma was analyzed using the Kaplan-Meier method and Cox regression. Survival data were used to establish a nomogram prediction model.

Results: microfibrillar-associated protein 2 expression was significantly elevated in gliomas. receiver operating characteristic analysis revealed good discrimination of microfibrillar-associated protein 2 between glioma and normal tissues. High expression of microfibrillar-associated protein 2 was associated with malignant phenotypes, such as histological type. Based on gene set enrichment analysis, we identified pathways associated with high microfibrillar-associated protein 2 expression. High microfibrillar-associated protein 2 expression was related to the infiltration of tumor immune cells, including Th2 cells and macrophages, and correlated with key markers of T-cell exhaustion. Based on the TISIDB database, microfibrillar-associated protein 2 was observed to be associated with chemokines, chemokine receptors, and multiple immunoinhibitors in glioma. Kaplan–Meier survival analyses revealed that high microfibrillar-associated protein 2 expression predicted poor overall survival, DSS, and PFS in patients with glioma. By combining microfibrillar-associated protein 2 and other prognostic factors, a nomogram prognostic prediction model was constructed, which demonstrated an ideal prediction effect.

Conclusion: microfibrillar-associated protein 2 is a potential prognostic marker that plays a key role in glioma development given its association with malignant phenotypes, cancer-related pathways and tumor immunity.
IL-10 partly mediates the ability of MSC-derived extracellular vesicles to attenuate myocardial damage in experimental metabolic renovascular hypertension
Authors: Jiang Yamei , Hong Siting , Zhu Xiangyang , Zhang Lei , Tang Hui , Jordan Kyra L. , Saadiq Ishran M. , Huang Weijun , Lerman Amir , Eirin Alfonso , Lerman Lilach O.
Published: September 2022

Extracellular vesicles (EVs) obtain properties of immunomodulation and tissue repair from their parental mesenchymal stem cells (MSCs), and upon delivery may be associated with fewer adverse events. EVs derived from adipose-tissue MSCs restored kidney function by attenuating kidney inflammation in a swine model of metabolic syndrome (MetS) and renal artery stenosis via anti-inflammatory pathways. EVs also ameliorated myocardial injury in renovascular hypertension (RVH) secondary to inflammation in cardiorenal disease, but the mechanisms regulating this effect are unknown. We hypothesize that the anti-inflammatory cytokine interleukin (IL)-10 mediates the reparative effects of EVs on cardiovascular complications in a preclinical swine model with coexisting MetS and RVH. Twenty-three pigs established as Lean controls or RVH models were observed for 16 weeks. At 12 weeks RVH subgroups received an intrarenal delivery of 1011 either wildtype (WT) EVs or EVs after IL-10 knockdown (KD) (RVH+WT-EVs or RVH+IL-10-KD-EVs, respectively). Cardiac and renal function were studied in-vivo and myocardial tissue injury in-vitro 4 weeks later. RVH pigs showed myocardial inflammation, fibrosis, and left ventricular diastolic dysfunction. WT-EVs attenuated these impairments, increased capillary density, and decreased myocardial inflammation in-vivo. In-vitro, co-incubation with IL-10-containing WT-EVs decreased activated T-cells proliferation and endothelial cells inflammation and promoted their migration. Contrarily, these cardioprotective effects were largely blunted using IL-10-KD-EVs. Thus, the anti-inflammatory and pro-angiogenic effects of EVs in RVH may be partly attributed to their cargo of anti-inflammatory IL-10. Early intervention of IL-10-containing EVs may be helpful to prevent cardiovascular complications of MetS concurrent with RVH.
Glucose metabolism and glycosylation link the gut microbiota to autoimmune diseases
Authors: Wang Lu , Xu Haojie , Yang Huaxia , Zhou Jiaxin , Zhao Lidan , Zhang Fengchun
Published: September 2022

Carbohydrates serve as important energy sources and structural substances for human body as well as for gut microbes. As evidenced by the advances in immunometabolism, glucose metabolism and adenosine triphosphate (ATP) generation are deeply involved in immune cell activation, proliferation, and signaling transduction as well as trafficking and effector functions, thus contributing to immune response programming and assisting in host adaption to microenvironment changes. Increased glucose uptake, aberrant expression of glucose transporter 1 (e.g., GLU1), and abnormal glycosylation patterns have been identified in autoimmunity and are suggested as partially responsible for the dysregulated immune response and the modification of gut microbiome composition in the autoimmune pathogenesis. The interaction between gut microbiota and host carbohydrate metabolism is complex and bidirectional. Their impact on host immune homeostasis and the development of autoimmune diseases remains to be elucidated. This review summarized the current knowledge on the crosstalk of glucose metabolism and glycosylation in the host with intestinal microbiota and discussed their possible role in the development and progression of autoimmune diseases. Potential therapeutic strategies targeting glucose metabolism and glycosylation in modulating gut ecosystem and treating autoimmune diseases were discussed as well.
Bacteroides fragilis outer membrane vesicles preferentially activate innate immune receptors compared to their parent bacteria
Authors: Gilmore William J. , Johnston Ella L. , Bitto Natalie J. , Zavan Lauren , O'Brien-Simpson Neil , Hill Andrew F. , Kaparakis-Liaskos Maria
Published: September 2022

The release of bacterial membrane vesicles (BMVs) has become recognized as a key mechanism used by both pathogenic and commensal bacteria to activate innate immune responses in the host and mediate immunity. Outer membrane vesicles (OMVs) produced by Gram-negative bacteria can harbor various immunogenic cargo that includes proteins, nucleic acids and peptidoglycan, and the composition of OMVs strongly influences their ability to activate host innate immune receptors. Although various Gram-negative pathogens can produce OMVs that are enriched in immunogenic cargo compared to their parent bacteria, the ability of OMVs produced by commensal organisms to be enriched with immunostimulatory contents is only recently becoming known. In this study, we investigated the cargo associated with OMVs produced by the intestinal commensal Bacteroides fragilis and determined their ability to activate host innate immune receptors. Analysis of B. fragilis OMVs revealed that they packaged various biological cargo including proteins, DNA, RNA, lipopolysaccharides (LPS) and peptidoglycan, and that this cargo could be enriched in OMVs compared to their parent bacteria. We visualized the entry of B. fragilis OMVs into intestinal epithelial cells, in addition to the ability of B. fragilis OMVs to transport bacterial RNA and peptidoglycan cargo into Caco-2 epithelial cells. Using HEK-Blue reporter cell lines, we identified that B. fragilis OMVs could activate host Toll-like receptors (TLR)-2, TLR4, TLR7 and nucleotide-binding oligomerization domain-containing protein 1 (NOD1), whereas B. fragilis bacteria could only induce the activation of TLR2. Overall, our data demonstrates that B. fragilis OMVs activate a broader range of host innate immune receptors compared to their parent bacteria due to their enrichment of biological cargo and their ability to transport this cargo directly into host epithelial cells. These findings indicate that the secretion of OMVs by B. fragilis may facilitate immune crosstalk with host epithelial cells at the gastrointestinal surface and suggests that OMVs produced by commensal bacteria may preferentially activate host innate immune receptors at the mucosal gastrointestinal tract.
Disease predisposition of human leukocyte antigen class II genes influences the gut microbiota composition in patients with primary biliary cholangitis
Authors: Huang Chun-Yang , Zhang Hai-Ping , Han Wei-Jia , Zhao Dan-Tong , Liao Hui-Yu , Ma Yin-Xue , Xu Bin , Li Li-Juan , Han Ying , Liu Xiu-Hong , Wang Qi , Lou Jin-Li , Zhang Xiao-Dan , Zhao Juan , Li Wen-Juan , Liu Yan-Min , Yan Hui-Ping
Published: September 2022

Background

The human leukocyte antigen (HLA) susceptibility gene is the main genetic risk factor for primary biliary cholangitis (PBC). The prognosis of patients with PBC is linked to gut microbiota dysbiosis. However, whether the HLA alleles are associated with the gut microbiota distribution and disease severity remains unknown.

Methods

A cohort of 964 Chinese patients with PBC was enrolled at Beijing YouAn Hospital, Beijing, China. High-resolution genotyping of the HLA class I and class II loci from 151 of these patients was performed using sequence-based PCR. Stool samples were collected from 43 of the 151 fully HLA-typed patients to analyze their microbiota compositions via 16S RNA gene sequencing.

Results

Of the 964 patients, the male:female ratio was 114:850, and 342 of these patients (35.5%) had already developed liver cirrhosis (LC) before enrollment. Patients with PBC showed a significantly higher frequency of HLA DRB1*08:03 than did the controls (21.2% vs. 9.0%, P=0.0001). HLA-DRB1*03:01, DRB1*07:01, DRB1*14:05, and DRB1*14:54 frequencies were also increased but did not reach significance after Bonferroni’s correction. Conversely, the DQB1*03:01 frequency was significantly lower in patients with PBC than in the controls (24.5% vs. 39.2%, P=0.0010). The patients’ gut microbiota were analyzed from four perspectives. The microbial community abundances were significantly lower in FHRAC-positive patients (patients with a combination of five HLA DRB1 high-risk alleles) than in FHRAC-negative patients (P<0.05). Of the top 10 microbial genera, Lachnospiraceae_incertae_sedis was higher in the FHRAC-positive patients than in the FHRAC-negative patients (P<0.05). linear discriminant analysis (LDA) effect-size (LEfSe) analysis showed different microbes at different levels in the FHRAC-negative patients but not in the FHRAC-positive patients. DQB1*03:01-positive patients contained mostly Lactobacillaceae at the family level. A comparison of the FHRAC-positive patients with and without liver cirrhosis showed that the abundances of Veillonella were significantly higher in patients with cirrhosis and FHRAC than in those without cirrhosis and are FHRAC-negative.

Conclusion

The HLA class II genes may influence the gut microbiota compositions in patients with PBC. Differential gut microbiota were expressed at different taxonomic levels. Some bacterial abundances may be increased in FHRAC-positive patients with PBC and cirrhosis.
Human chorionic gonadotropin promotes murine Treg cells and restricts pregnancy-harmful proinflammatory Th17 responses
Authors: Lentz Lea S. , Stutz Annika J. , Meyer Nicole , Schubert Kristin , Karkossa Isabel , von Bergen Martin , Zenclussen Ana C. , Schumacher Anne
Published: September 2022

An equilibrium between proinflammatory and anti-inflammatory immune responses is essential for maternal tolerance of the fetus throughout gestation. To study the participation of fetal tissue-derived factors in this delicate immune balance, we analyzed the effects of human chorionic gonadotropin (hCG) on murine Treg cells and Th17 cells in vitro, and on pregnancy outcomes, fetal and placental growth, blood flow velocities and remodeling of the uterine vascular bed in vivo. Compared with untreated CD4+CD25+ T cells, hCG increased the frequency of Treg cells upon activation of the LH/CG receptor. hCG, with the involvement of IL-2, also interfered with induced differentiation of CD4+ T cells into proinflammatory Th17 cells. In already differentiated Th17 cells, hCG induced an anti-inflammatory profile. Transfer of proinflammatory Th17 cells into healthy pregnant mice promoted fetal rejection, impaired fetal growth and resulted in insufficient remodeling of uterine spiral arteries, and abnormal flow velocities. Our works show that proinflammatory Th17 cells have a negative influence on pregnancy that can be partly avoided by in vitro re-programming of proinflammatory Th17 cells with hCG.
Identification of immune-related endoplasmic reticulum stress genes in sepsis using bioinformatics and machine learning
Authors: Gong Ting , Liu Yongbin , Tian Zhiyuan , Zhang Min , Gao Hejun , Peng Zhiyong , Yin Shuang , Cheung Chi Wai , Liu Youtan
Published: September 2022

Background

Sepsis-induced apoptosis of immune cells leads to widespread depletion of key immune effector cells. Endoplasmic reticulum (ER) stress has been implicated in the apoptotic pathway, although little is known regarding its role in sepsis-related immune cell apoptosis. The aim of this study was to develop an ER stress-related prognostic and diagnostic signature for sepsis through bioinformatics and machine learning algorithms on the basis of the differentially expressed genes (DEGs) between healthy controls and sepsis patients.

Methods

The transcriptomic datasets that include gene expression profiles of sepsis patients and healthy controls were downloaded from the GEO database. The immune-related endoplasmic reticulum stress hub genes associated with sepsis patients were identified using the new comprehensive machine learning algorithm and bioinformatics analysis which includes functional enrichment analyses, consensus clustering, weighted gene coexpression network analysis (WGCNA), and protein-protein interaction (PPI) network construction. Next, the diagnostic model was established by logistic regression and the molecular subtypes of sepsis were obtained based on the significant DEGs. Finally, the potential diagnostic markers of sepsis were screened among the significant DEGs, and validated in multiple datasets.

Results

Significant differences in the type and abundance of infiltrating immune cell populations were observed between the healthy control and sepsis patients. The immune-related ER stress genes achieved strong stability and high accuracy in predicting sepsis patients. 10 genes were screened as potential diagnostic markers for sepsis among the significant DEGs, and were further validated in multiple datasets. In addition, higher expression levels of SCAMP5 mRNA and protein were observed in PBMCs isolated from sepsis patients than healthy donors (n = 5).

Conclusions

We established a stable and accurate signature to evaluate the diagnosis of sepsis based on the machine learning algorithms and bioinformatics. SCAMP5 was preliminarily identified as a diagnostic marker of sepsis that may affect its progression by regulating ER stress.
The complete paternally inherited mitochondrial genomes of three clam species in genus Macridiscus (Bivalvia: Veneridae): A TDRL model of dimer-mitogenome rearrangement of doubly uniparental inheritance
Authors: Wang Rui , Li Xuanzhao , Qi Jiwei
Published: September 2022

One of the most striking exceptions to strict maternal inheritance of mitochondrial DNA (mtDNA) in the animal kingdom is a system called doubly uniparental inheritance (DUI), which exists in several bivalve species. DUI is characterized by the presence of two distinct sex-associated mitochondrial lineages: one transmitted through eggs (F-type mtDNA) and the other through sperm (M-type mtDNA). Presently, most known species exhibiting DUI belong to the freshwater bivalve order Unionoida. Other groups with species exhibiting DUI include the orders Mytiloida, Veneroida, and Nuculanoida. In Veneroida, the complete M-type mtDNA is available for two species. We report the presence of DUI in three species belonging to genus Macridiscus (Macridiscus melanaegis, Macridiscus multifarious, and Macridiscus semicancellata), in the order Veneroida, further obtaining their complete M-type mitogenomes. The M-type mitogenome sizes for M. melanaegis, M. multifarious, and M. semicancellata were 19,019 bp, 18,694 bp, and 18,726 bp, respectively, and the mean nucleotide difference between M-type and F-type mitogenomes was 21–23%. We compared the M-type and F-type mitogenomes and found that they show roughly the same genome features, except for gene order. In phylogenetic analyses of Veneroida, a “gender-joining” pattern was revealed within Macridiscus, similar to the pattern of “partial” Mytilus complex (except Unionida). This new insight provides novel evidence supporting the theory that Veneroida and Mytiloida have a more similar DUI pattern than Unionida. A large-scale rearrangement between the sex-linked mitogenomes of the three Macridiscus species was reported. From the observed rearrangement patterns, gene rearrangement between the two sex-linked mitogenomes could be explained by the tandem duplication and random loss (TDRL) model of dimer-mitogenome. This is the first report of heterogeneous genomes with two types of large-scale arrangements in the same organism, and may be contribute significantly to the study of mitochondrial recombination mechanisms.
Transcriptional changes in the gilthead seabream (Sparus aurata) skin in response to ultraviolet B radiation exposure
Authors: Alves Ricardo N. , Agustí Susana
Published: September 2022

Solar ultraviolet B radiation (UVB) has recently been described as a relevant stressor in fish confined to aquaculture cages. In gilthead seabream (Sparus aurata), UVB exposure resulted in decreased growth, epidermal sloughing, increased oxidative stress in the skin, and induced changes in behavior, physiology, and immune system. Several molecular responses should accompany such detrimental effects; however, little is known in fish about the overall UVB-mediated changes at the transcriptional level. Thus, this study aimed to investigate the effects of UVB exposure on the global gene expression profiles of S. aurata skin through transcriptome analysis. S. aurata juveniles were exposed for 43 days to two experimental groups: 1) UVB (daily dose, 6 kJ m-2; representing levels between 5 and 7 m depth); 2) Unirradiated treatment, used as a control. The comparison of skin transcriptomes between the control and UVB treatments revealed 845 differentially expressed genes (580 up-regulated and 265 down-regulated). The reliability of the transcriptome analysis was confirmed by qRT-PCR for selected genes. Functional annotation and PPI analyses revealed that genes related to the immune system and inflammatory response, cell cycle regulation, proteasome, proteolysis, and oxidative stress might be involved in the response to UVB exposure. In contrast, UVB exposure inhibited the expression of several genes related to growth factor activity, cell growth and differentiation, and pigmentation. p53 signaling pathway was enriched in fish exposed to UVB. Moreover, pathways involved in the immune system and inflammatory response (cytokine-cytokine receptor interaction, RIG-I-like receptor signaling pathway, and Toll-like receptor signaling pathway) were also enriched in the skin of UVB-exposed fish. UVB-induced skin damage and a high level of infiltration of immune-related cells were confirmed through histopathological examination. Together, our results provide noteworthy insights into the molecular changes in fish after long-term exposure to UVB. These findings will help in the future to identify biomarkers of fish reared in offshore aquaculture systems in oligotrophic and highly transparent waters.
Effects of sodium humate and probiotics on growth performance enzyme activity and microbial environment of Litopenaeus vannamei in high-density zero‐water exchange systems
Authors: Liao Wuquan , Lin Zexu , Liao Minze , Xue Yuan , Zhou Jianing , Wang Yue , Hou Danqing , Sun Chengbo
Published: September 2022

The study investigates the outcomes of adding sodium humate and sodium humate with probiotics (Lysinibacillus,Bacillus subtilis) to culture water on the growth performance, enzyme activity, and microbial environment of shrimp. The sodium humate and probiotics concentrations were 3 mg/L and 105CFU/mL in the culture water.Litopenaeus vannamei(0.31 ± 0.03 g) at a density of 300 shrimps/m3were cultured in nine buckets for a 43-days culture experiment. The results showed that the survival rate (SR) ofL. vannameiin sodium humate group and sodium humate with probiotics group were (88.44%) and (86.07%), with the sodium humate group outcome being significantly better than the control group. The shrimps’ final body weight and specific growth rate (SGR) in the two experimental groups were significantly higher than the control group. The feed conversion rate (FCR) was significantly lower than the control group. The ammonia nitrogen concentration in sodium humate with probiotics group was significantly lower than the control group on the 15th day. The activities of intestinal amylase, lipase, trypsin and hepatopancreas superoxide dismutase (SOD), phenol oxidase (PO), and catalase (CAT) in sodium humate group were significantly higher than the control group. Notably, SOD, PO, and lipase activities in sodium humate with probiotics group were significantly higher than the control group. Illumina MiSeq high-throughput sequencing showed that the Chao and Ace indices of the culture water microflora in experimental groups were higher than the control group, and the sodium humate group was significantly higher than the control group. At the phylum level, Proteobacteria, Bacteroidetes, and Actinobacteria were the dominant bacterial communities in the intestine and culture water ofL. vannamei, Proteobacteria was the most abundant phyla. At the genus level, the relative abundance ofPseudohongiellaof water microflora in the control group was significantly lower than the experimental groups.Ruggiella(15.22-19.56%) was the most abundant genera of intestinal microflora. These results infer that the addition of sodium humate enhances the growth performance, digestive enzymes, and some immune enzyme activities, improving the richness of the water microbial community ofL. vannamei.
Non-conventional interventions to prevent gonorrhea or syphilis among men who have sex with men: A scoping review
Authors: Tran Julien , Fairley Christopher K. , Bowesman Henry , Aung Ei T. , Ong Jason J. , Chow Eric P. F.
Published: September 2022

Objectives

We assessed nonconventional interventions that did not traditionally focus on increasing condom use and/or testing among men who have sex with men (MSM) and the evidence for these interventions.

Methods

Guided by the Participants, Concept and Context (PCC) framework, we searched five online databases from inception to 9 August 2021 for original research on interventions that do not focus on increasing condom use and/or testing to prevent gonorrhea and/or syphilis in MSM. Two researchers screened titles and abstracts to assess eligibility, reviewed articles' full text and resolved discrepancies through discussion. We charted relevant study information, and the included studies were critically appraised.

Results

Of 373 articles retrieved, 13 studies were included. These studies were conducted in Australia (n = 3), Belgium (n = 2), China (n = 3), the Netherlands (n = 1) and the US (n = 4). Two randomized controlled trials (RCTs) of doxycycline as pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) reduced any STI incidence (gonorrhea, syphilis, or chlamydia), but only doxycycline PEP significantly reduced syphilis incidence. Six studies of interventions that facilitated self-collection, self-examination, and self-testing, found varied evidence for gonorrhea and/or syphilis prevention. Four RCTs and one single-arm trial examined the efficacy of mouthwash, but the evidence remains inconclusive on whether mouthwash use can prevent transmission between men.

Conclusion

We found evidence for doxycycline PEP in reducing syphilis incidence, evidence on the use of mouthwash to prevent gonorrhea transmission between men remains inconclusive. More evidence is needed for interventions that do not focus on increasing condom use and/or testing to prevent gonorrhea and/or syphilis.