bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioelectrical impedance spectroscopy can assist to identify the parathyroid gland during thyroid surgery
Authors: Wang Bin , Liu Zaoyang , Wu Jian , Liu Ying , Wang Pin , Liu Hong , Wang Haobin , Wang Tielin , Wang Juan , Tang Yan , Zhang Junyan
Published: September 2022

Objective

This study aimed to explore the effectiveness of bioelectrical impedance spectroscopy in the identification of parathyroid glands during thyroid surgeries.

Method

All patients who received thyroid surgeries at our department from January 2018 to February 2020 were recruited for this study. The bioelectrical impedance spectroscopy analyzer was applied to analyze on following tissues: thyroid tissues, lymph nodes, adipose tissues, and the tissues suspected to be parathyroid glands. Postoperative pathological reports were obtained as the golden standard to compare with the characteristic parameters obtained from bioelectrical impedance spectroscopy. The receiver operating characteristic curve analysis was used to assess the diagnostic value and the selection of the optimal threshold of these parameters from bioelectrical impedance spectroscopy.

Results

A total of 512 patients were enrolled in the study and 1898 specimens were measured by the bioelectrical impedance spectroscopy analyzer. There were significant differences in the parameter of fc among parathyroid glands, thyroid tissues, lymph nodes, and adipose tissues (252.2 ± 45.8 vs 144.7 ± 26.1, 491.7 ± 87.4, 602.3 ± 57.3; P<0.001, P<0.001, P<0.001). The area under the receiver operating characteristic curves was 0.993 (95%CI: 0.989-0.996) for fc. When the diagnostic criterion of fc was set at 188.85 kHz~342.55 kHz, the sensitivity and specificity to identify parathyroid glands from lymph nodes and adipose tissues were both 100%. At this fc, the sensitivity and specificity to identify parathyroid glands from thyroid tissues were 91.1% and 99.0%, respectively.

Conclusion

In conclusion, bioelectrical impedance spectroscopy could assist to differentiate parathyroid glands from peripheral tissues during thyroid surgeries.
Profile of crosstalk between glucose and lipid metabolic disturbance and diabetic cardiomyopathy: Inflammation and oxidative stress
Authors: Chen Meng-Yuan , Meng Xiang-Fei , Han Yu-Peng , Yan Jia-Lin , Xiao Chi , Qian Ling-Bo
Published: September 2022

In recent years, the risk, such as hypertension, obesity and diabetes mellitus, of cardiovascular diseases has been increasing explosively with the development of living conditions and the expansion of social psychological pressure. The disturbance of glucose and lipid metabolism contributes to both collapse of myocardial structure and cardiac dysfunction, which ultimately leads to diabetic cardiomyopathy. The pathogenesis of diabetic cardiomyopathy is multifactorial, including inflammatory cascade activation, oxidative/nitrative stress, and the following impaired Ca2+ handling induced by insulin resistance/hyperinsulinemia, hyperglycemia, hyperlipidemia in diabetes. Some key alterations of cellular signaling network, such as translocation of CD36 to sarcolemma, activation of NLRP3 inflammasome, up-regulation of AGE/RAGE system, and disequilibrium of micro-RNA, mediate diabetic oxidative stress/inflammation related myocardial remodeling and ventricular dysfunction in the context of glucose and lipid metabolic disturbance. Here, we summarized the detailed oxidative stress/inflammation network by which the abnormality of glucose and lipid metabolism facilitates diabetic cardiomyopathy.
Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion
Authors: Jing Li , Zhang Qiang
Published: September 2022

Thyroid hormones (THs), including T4 and T3, are produced and released by the thyroid gland under the stimulation of thyroid-stimulating hormone (TSH). The homeostasis of THs is regulated via the coordination of the hypothalamic-pituitary-thyroid axis, plasma binding proteins, and local metabolism in tissues. TH synthesis and secretion in the thyrocytes-containing thyroid follicles are exquisitely regulated by an elaborate molecular network comprising enzymes, transporters, signal transduction machineries, and transcription factors. In this article, we synthesized the relevant literature, organized and dissected the complex intrathyroidal regulatory network into structures amenable to functional interpretation and systems-level modeling. Multiple intertwined feedforward and feedback motifs were identified and described, centering around the transcriptional and posttranslational regulations involved in TH synthesis and secretion, including those underpinning the Wolff-Chaikoff and Plummer effects and thyroglobulin-mediated feedback regulation. A more thorough characterization of the intrathyroidal network from a systems biology perspective, including its topology, constituent network motifs, and nonlinear quantitative properties, can help us to better understand and predict the thyroidal dynamics in response to physiological signals, therapeutic interventions, and environmental disruptions.
Holistic evaluation of aircraft detection lighting systems for wind turbines in Germany using a multi-method evaluation framework
Authors: Weigel Paul , Viebahn Peter , Fischedick Manfred
Published: September 2022

Transponder-based Aircraft Detection Lighting Systems (ADLS) are increasingly used in wind turbines to limit beacon operation times, reduce light emissions, and increase wind energy acceptance. The systems use digital technologies such as receivers of digital transponder signals, LTE/5G, and other information and communication technology. The use of ADLS will be mandatory in Germany both for new and existing wind turbines with a height of >100 m from 2023 (onshore) and 2024 (offshore), so a nationwide rollout is expected to start during 2022. To fully realize the benefits while avoiding risks and bottlenecks, a thorough and holistic understanding of the efforts required and the impacts caused along the life cycle of an ADLS is essential. Therefore, this study presents the first multi-aspect holistic evaluation of an ADLS. A framework for evaluating digital applications in the energy sector, previously developed by the authors, is refined and applied. The framework is based on multi-criteria analysis (MCA), life cycle assessment (LCA), and expert interviews. On an aggregated level, the MCA results show an overall positive impact from all stakeholders’ perspectives. Most positive impacts are found in the society and politics category, while most negative impacts are of technical nature. The LCA of the ADLS reveals a slightly negative impact, but this impact is negligible when compared to the total life cycle impact of the wind turbines of which the ADLS is a part. Besides the aggregated evaluation, detailed information on potential implementation risks, bottlenecks, and levers for life cycle improvement are presented. In particular, the worldwide scarcity of the required semiconductors, in combination with the general lack of technicians in Germany, lead to the authors’ recommendation for a limited prolongation of the planned rollout period. This period should be used by decision-makers to ensure the availability of technical components and installation capacities. A pooling of ADLS installations in larger regions could improve plannability for manufacturers and installers. Furthermore, an ADLS implementation in other countries could be supported by an early holistic evaluation using the presented framework.
Potential distribution prediction of Deyeuxia angustifolia in the Tumen River Basin and analysis of major impact factors
Authors: Zong Jin , Cao Guanglan , Jin Xuemei , Jin Ri , Zhu Weihong
Published: September 2022

Deyeuxia angustifolia acts as an indicator of the changes in wetland ecosystems and plays an important ecological role in their functions. Previous studies have shown that the Tumen River Basin is of wide global interest as a transboundary basin area with abundant wetland ecological resources. Despite the implementation of wetland conservation measures in recent years, the distribution area of D. angustifolia in this basin has been reduced due to climate change and anthropogenic activities. Therefore, we used MaxEnt and geographic information system to model a suitable habitat for this species, simulated changes in the habitat, and applied Jackknife to assess the influencing environmental variables. The Jackknife tests showed that slope orientation, solar radiation in September, and total nitrogen were the dominant environmental factors affecting the potential distribution of D. angustifolia. Compared to the current distribution, the total area of land highly and moderately suitable for this species will decrease in the 2050’s and 2070’s, respectively, under two representative concentration paths (RCPs), shifting the centroid of its suitable area and direction of wetland degradation to the northeast. Our study of the projected potential distribution of D. angustifolia in the basin under future climate change could provide important information for its conservation, management, sustainable use, and early warning to prevent its extinction.
Vertical and spatial evaluation of the groundwater chemistry in the Central Nile Delta Quaternary aquifer to assess the effects of human activities and seawater intrusion
Authors: Salem Zenhom E. , ElNahrawy Abdelaziz , Attiah Abdullah M. , Edokpayi Joshua N.
Published: September 2022

Contaminants can be found in the groundwater through natural processes, such as seawater intrusion, or due to human activities that can adversely affect the quantity, quality, and distribution of the groundwater. In order to assess the influence of human activities and seawater intrusion on the groundwater chemistry in the Central Nile Delta region, groundwater was collected from 167 production wells, with depths of 15–120 m. In addition, eight soil-water samples were collected from depths of about 1 m. The groundwater samples were divided based on well depths into three zones: shallow zone (<40 m depth), intermediate zone (41–60 m depth), and deep zone (>60 m depth). The TDS, EC, pH, K+, Na+, Mg2+, Ca2+, Cl−, HCO3−, and SO42- were determined for all water samples. The groundwater samples with Cl of 100–200 mg/L and EC of 600–2,000 μs/cm represent mixing between freshwater and saltwater. The increase in TDS and concentrations of all major ions toward the northern parts reflected the impact of the seawater intrusion. The groundwater had an Na/Cl ratio of 0.46–2.75, indicating the influence of both seawater intrusion and anthropogenic activities on groundwater chemistry. In addition, the high Ca/Mg, Ca/SO4, and Ca/HCO3 ratios (>1) indicated that the groundwater was intruded by seawater. The obtained water types, the ionic ratios, and the saturation index results suggested that anthropogenic activities, water-rock interaction, infiltration, mineral weathering, and seawater intrusion are the main processes controlling the variation and evolution of groundwater chemistry.
Mixed infections of fungal trunk pathogens and induced systemic phenolic compound production in grapevines
Authors: Wallis Christopher M. , Gorman Zachary , Galarneau Erin R. -A. , Baumgartner Kendra
Published: September 2022

As grapevines mature in California vineyards they accumulate chronic wood infections by the Ascomycete fungi that cause trunk diseases, including Botryosphaeria dieback (caused by Diplodia seriata and Neofusicoccum parvum) and Esca (caused by Phaeomoniella chlamydospora). It is thought that such mixed infections become localized to separate internal lesions/cankers of the permanent, woody structure of an individual vine, but nonetheless the fungi all colonize the same vascular system. In response to infection by one pathogen, the host may initiate systemic biochemical changes, which in turn may affect the extent of subsequent infections by other pathogens. To test this hypothesis, we measured changes in phenolic compounds in the wood and lesion lengths of the pathogens, during sequential co-inoculations with different or identical pair-wise sequences of infection by D. seriata, N. parvum, or P. chlamydospora. Prior fungal infections only affected the development of subsequent D. seriata infections. Effects of fungal infections on phenolic compounds were variable, yet initial infection by D. seriata was associated with significantly higher concentrations of most phenolic compounds distally, compared to all other initial inoculation treatments. It was hypothesized that pre-existing phenolic levels can slow initial lesion development of fungal trunk pathogens, especially for D. seriata, but over time the pathogens appeared to overcome or neutralize phenolic compounds and grow unimpeded. These results demonstrate that effects of one fungal trunk pathogen infection is generally unable to distally affect another long-term, albeit shifts in host phenolics and other plant defenses do occur.
Super-Enhancer–Associated nine-gene prognostic score model for prediction of survival in chronic lymphocytic leukemia patients
Authors: Liang Xue , Meng Ye , Li Cong , Liu Linlin , Wang Yangyang , Pu Lianfang , Hu Linhui , Li Qian , Zhai Zhimin
Published: September 2022

Chronic lymphocytic leukemia (CLL) is a type of highly heterogeneous mature B-cell malignancy with various disease courses. Although a multitude of prognostic markers in CLL have been reported, insights into the role of super-enhancer (SE)–related risk indicators in the occurrence and development of CLL are still lacking. A super-enhancer (SE) is a cluster of enhancers involved in cell differentiation and tumorigenesis, and is one of the promising therapeutic targets for cancer therapy in recent years. In our study, the CLL-related super-enhancers in the training database were processed by LASSO-penalized Cox regression analysis to screen a nine-gene prognostic model including TCF7, VEGFA, MNT, GMIP, SLAMF1, TNFRSF25, GRWD1, SLC6AC, and LAG3. The SE-related risk score was further constructed and it was found that the predictive performance with overall survival and time-to-treatment (TTT) was satisfactory. Moreover, a high correlation was found between the risk score and already known prognostic markers of CLL. In the meantime, we noticed that the expressions of TCF7, GMIP, SLAMF1, TNFRSF25, and LAG3 in CLL were different from those of healthy donors (p < 0.01). Moreover, the risk score and LAG3 level of matched pairs before and after treatment samples varied significantly. Finally, an interactive nomogram consisting of the nine-gene risk group and four clinical traits was established. The inhibitors of mTOR and cyclin-dependent kinases (CDKs) were considered effective in patients in the high-risk group according to the pRRophetic algorithm. Collectively, the SE-associated nine-gene prognostic model developed here may be used to predict the prognosis and assist in the risk stratification and treatment of CLL patients in the future.
Poor prognosis, hypomethylation, and immune infiltrates are associated with downregulation of INMT in head and neck squamous cell carcinoma
Authors: Cui Kun , Yao Xi , Wei Zhengbo , yang Yujia , Liu Xinli , Huang Zhongheng , Huo Huimin , Tang Jinping , Xie Ying
Published: September 2022

Background: Indiolethylamine-N-methyltransferase (INMT) is a methyltransferase responsible for transferring methyl groups from methyl donor SAM to its substrate. S-adenosyl-l-methionine (SAM), obtained from the methionine cycle, is a naturally occurring sulfonium compound that is vital to cellular metabolism. The expression of INMT is down-regulated in many tumorous tissues, and it may contribute to tumor invasion and metastasis. Nevertheless, the expression of INMT and its relationship to methylation and immune infiltrates in head and neck squamous cell carcinoma (HNSC) remains a mystery. Thus, we evaluated expression, clinicopathological features, prognosis, several critical pathways, DNA methylation, and immune cell infiltration for the first time.

Methods: Analysis of the clinicopathological characteristics of INMT expression, several tumor-related bioinformatics databases were utilized. In addition, the role of INMT expression was analyzed for prognosis. Several INMT-related pathways were enriched on the LinkedOmics website. In addition, we have analyzed the methylation of INMT in HNSC in detail by using several methylation databases. Lastly, the relationship between INMT gene expression and immune infiltration was analyzed with ssGSEA, Timer, and TISIDB.

Results: In HNSC, mRNA and protein levels were significantly lower than in normal tissues. The low expression of INMT was statistically associated with T stage, histological grade, gender, smoking history, and alcohol consumption. HNSC patients with low INMT expression have a poorer OS (overall survival) compared to those with high levels of expression. In addition, the multivariate analysis revealed INMT expression to be a remarkable independent predictor of prognosis in HNSC patients. An analysis of gene enrichment showed that several pathways were enriched in INMT, including the Ras signaling pathway, the cGMP-PKG signaling pathway, and others. Moreover, methylation patterns of INMT detected in a variety of methylation databases are closely associated with mRNA expression and prognosis. Finally, INMT was significantly correlated with immune infiltration levels.

Conclusion: HNSC with low levels of INMT exhibits poor survival, hypomethylation, and immune infiltration. For HNSC, this study presented evidence that INMT is both a biomarker of poor prognosis and a target of immunotherapy.
A novel necroptosis-related gene signature associated with immune landscape for predicting the prognosis of papillary thyroid cancer
Authors: Wang Zhiyuan , Wu Pu , Shi Jinyuan , Ji Xiaoyu , He Liang , Dong Wenwu , Wang Zhihong , Zhang Hao , Sun Wei
Published: September 2022

Background: Necroptosis, a type of programmed cell death, has been implicated in a variety of cancer-related biological processes. However, the roles of necroptosis-related genes in thyroid cancer yet remain unknown.

Methods: A necroptosis-related gene signature was constructed using the least absolute shrinkage and selection operator (LASSO) regression analysis and Cox regression analysis. The predictive value of the prognostic signature was validated in an internal cohort. Additionally, the single-sample gene set enrichment analysis (ssGSEA) was used to examine the relationships between necroptosis and immune cells, immunological functions, and immune checkpoints. Next, the modeled genes expressions were validated in 96 pairs of clinical tumor and normal tissue samples. Finally, the effects of modeled genes on PTC cells were studied by RNA interference approaches in vitro.

Results: In this study, the risk signature of seven necroptosis-related genes was created to predict the prognosis of papillary thyroid cancer (PTC) patients, and all patients were divided into high- and low-risk groups. Patients in the high-risk group fared worse in terms of overall survival than those in the low-risk group. The area under the curve (AUC) of the receiving operating characteristic (ROC) curves proved the predictive capability of created signature. The risk score was found to be an independent risk factor for prognosis in multivariate Cox analysis. The low-risk group showed increased immune cell infiltration and immunological activity, implying that they might respond better to immune checkpoint inhibitor medication. Next, GEO database and qRT-PCR in 96 pairs of matched tumorous and non-tumorous tissues were used to validate the expression of the seven modeled genes in PTCs, and the results were compatible with TCGA database. Finally, overexpression of IPMK, KLF9, SPATA2 could significantly inhibit the proliferation, invasion and migration of PTC cells.

Conclusion: The created necroptosis associated risk signature has the potential to have prognostic capability in PTC for patient outcome. The findings of this study could pave the way for further research into the link between necroptosis and tumor immunotherapy.
A construction and comprehensive analysis of the immune-related core ceRNA network and infiltrating immune cells in peripheral arterial occlusive disease
Authors: Chen Zhiyong , Xu Jiahui , Zha Binshan , Li Jun , Li Yongxiang , Ouyang Huan
Published: September 2022

Background: Peripheral arterial occlusive disease (PAOD) is a peripheral artery disorder that increases with age and often leads to an elevated risk of cardiovascular events. The purposes of this study were to explore the underlying competing endogenous RNA (ceRNA)-related mechanism of PAOD and identify the corresponding immune cell infiltration patterns.

Methods: An available gene expression profile (GSE57691 datasets) was downloaded from the GEO database. Differentially expressed (DE) mRNAs and lncRNAs were screened between 9 PAOD and 10 control samples. Then, the lncRNA-miRNA-mRNA ceRNA network was constructed on the basis of the interactions generated from the miRcode, TargetScan, miRDB, and miRTarBase databases. The functional enrichment and protein–protein interaction analyses of mRNAs in the ceRNA network were performed. Immune-related core mRNAs were screened out through the Venn method. The compositional patterns of the 22 types of immune cell fraction in PAOD were estimated through the CIBERSORT algorithm. The final ceRNA network and immune infiltration were validated using clinical tissue samples. Finally, the correlation between immune cells and mRNAs in the final ceRNA network was analyzed.

Results: Totally, 67 DE_lncRNAs and 1197 DE_mRNAs were identified, of which 130 DE_mRNAs (91 downregulated and 39 upregulated) were lncRNA-related. The gene ontology enrichment analysis showed that those down- and upregulated genes were involved in dephosphorylation and regulation of translation, respectively. The final immune-related core ceRNA network included one lncRNA (LINC00221), two miRNAs (miR-17-5p and miR-20b-5p), and one mRNA (CREB1). Meanwhile, we found that monocytes and M1 macrophages were the main immune cell subpopulations in PAOD. After verification, these predictions were consistent with experimental results. Moreover, CREB1 was positively correlated with naive B cells (R = 0.55, p = 0.035) and monocytes (R = 0.52, p = 0.049) and negatively correlated with M1 macrophages (R = −0.72, p = 0.004), resting mast cells (R = −0.66, p = 0.009), memory B cells (R = −0.55, p = 0.035), and plasma cells (R = −0.52, p = 0.047).

Conclusion: In general, we proposed that the immune-related core ceRNA network (LINC00221, miR-17-5p, miR-20b-5p, and CREB1) and infiltrating immune cells (monocytes and M1 macrophages) could help further explore the molecular mechanisms of PAOD.
The paradoxical role of MDSCs in inflammatory bowel diseases: From bench to bedside
Authors: Zhao Fan , Gong Wenbin , Song Jiaojiao , Shen Zhe , Cui Dawei
Published: September 2022

Myeloid-derived suppressor cells (MDSCs) are a group of bone marrow derived heterogeneous cells, which is known for their immunosuppressive functions especially in tumors. Recently, MDSCs have receiving increasing attention in pathological conditions like infection, inflammation and autoimmune diseases. Inflammatory bowel diseases (IBD) are a series of immune-dysfunctional autoimmune diseases characterized by relapsing intestinal inflammation. The role of MDSCs in IBD remains controversial. Although most studies in vitro demonstrated its anti-inflammatory effects by inhibiting the proliferation and function of T cells, it was reported that MDSCs failed to relieve inflammation but even promoted inflammatory responses in experimental IBD. Here we summarize recent insights into the role of MDSCs in the development of IBD and the potential of MDSCs-targeted therapy.
V-Set and immunoglobulin domain containing (VSIG) proteins as emerging immune checkpoint targets for cancer immunotherapy
Authors: Zhou Xia , Khan Sohail , Huang Dabing , Li Lu
Published: September 2022

The development of immune checkpoint inhibitors is becoming a promising approach to fight cancers. Antibodies targeting immune checkpoint proteins such as CTLA-4 and PD-1 can reinvigorate endogenous antitumor T-cell responses and bring durable advantages to several malignancies. However, only a small subset of patients benefit from these checkpoint inhibitors. Identification of new immune checkpoints with the aim of combination blockade of multiple immune inhibitory pathways is becoming necessary to improve efficiency. Recently, several B7 family-related proteins, TIGIT, VSIG4, and VSIG3, which belong to the VSIG family, have attracted substantial attention as coinhibitory receptors during T-cell activation. By interacting with their corresponding ligands, these VSIG proteins inhibit T-cell responses and maintain an immune suppressive microenvironment in tumors. These results indicated that VSIG family members are becoming putative immune checkpoints in cancer immunotherapy. In this review, we summarized the function of each VSIG protein in regulating immune responses and in tumor progression, thus providing an overview of our current understanding of VSIG family members.
Macrophage activation syndrome in adults: Characteristics, outcomes, and therapeutic effectiveness of etoposide-based regimen
Authors: He Lingbo , Yao Shuyan , Zhang Ruoxi , Liu Menghan , Hua Zhengjie , Zou Heshan , Wang Zhao , Wang Yini
Published: September 2022

Objectives

To describe the clinical characteristics and outcomes of adult macrophage activation syndrome (MAS) patients and to provide experience for the treatment.

Methods

Adult patients with MAS admitted to Beijing Friendship Hospital from December 2014 to September 2021 were enrolled in this study. Clinical data of patients were collected and analyzed.

Results

A total of 118 adult MAS patients entered this study. MAS was the first manifestation in 43 (36.4%) patients, while 75 (63.6%) developed MAS after the diagnosis of autoimmune disease (AID) with a median diagnostic interval of 2 (0.5–359) months. Eighty-two patients were initially treated with glucocorticoid-based regimen; the overall response (OR) rate at the 2-week posttreatment was 37.8%. Forty-five patients switched to etoposide-based regimen, and the OR rate was 84.4%. Thirty-six patients were initially treated with etoposide-based regimen, and the OR rate at the 2-week posttreatment was 80.6%. Serum IL-18 (P = 0.021), IFN-γ (P = 0.013), IP-10 (P = 0.001), IL-10 (P = 0.041), IL-1RA (P < 0.001), and TNF-α (P = 0.020) levels of patients were significantly decreased in the remission phase than in the active phase. Levels of SDF-1α (P = 0.018) and IL-7 (P = 0.022) were higher in refractory patients, while the GRO-α level had a strong tendency toward statistical significance (P = 0.050). The probability of overall survival (OS) at 3, 6, and 36 months after HLH diagnosis were 89.8%, 89.0%, and 87.9%, retrospectively. The active MAS status at the 2-week post initial treatment [P = 0.009, HR = 15.281, 95% CI, (0.1.972, 118.430)] and baseline neutrophil count (Neu) <1.5 × 109/l [P = 0.017, HR = 3.678, 95% CI, (1.267, 10.672)] were negative prognostic factors.

Conclusion

MAS typically occurs within 2 months after the onset of autoimmune disease in adults. SDF-1α, IL-7, and GRO-α could be used to predict refractory MAS. The etoposide-based regimen is effective and tolerable for adult MAS.
Complement-mediated serum bactericidal activity of antibodies elicited by the Shigella sonnei GMMA vaccine in adults from a shigellosis-endemic country: Exploratory analysis of a Phase 2a randomized study
Authors: Kapulu Melissa C. , Nakakana Usman , Sciré Antonella S. , Sarakinou Eleanna , Conti Valentino , Rossi Omar , Acquaviva Alessandra , Necchi Francesca , Obiero Christina W. , Martin Laura B. , Bejon Philip , Njuguna Patricia , Micoli Francesca , Podda Audino
Published: September 2022

Shigella is associated with a significant burden of disease worldwide among individuals of all ages and is the major cause of moderate and severe diarrhea in children under five years of age in low- and middle-income countries. Several candidate vaccines against Shigella species are currently under clinical development. The investigational 1790GAHB vaccine against Shigella sonnei is based on GMMA (Generalized Modules for Membrane Antigens) technology. The vaccine was well tolerated and induced high antibody levels in early-phase clinical trials in both Shigella-endemic and non-endemic settings. The present analysis assessed the bactericidal activity of antibodies induced by 1790GAHB in healthy Kenyan adults during a phase 2a, controlled, randomized study (NCT02676895). Participants received two doses of 1790GAHB 4 weeks apart containing either 1.5/25 µg or 6/100 µg O antigen/protein, or active comparator vaccines (Control). Serum bactericidal activity (SBA) against S. sonnei was assessed at pre-vaccination (D1), 28 days post-first dose (D29) and 28 days post-second dose (D57), using a luminescence-based assay. Most participants had SBA titers above the lower limit of quantification of the assay at D1. SBA geometric mean titers increased 3.4-fold in the 1.5/25 µg group and 6.3-fold in the 6/100 µg group by D29 and were maintained at D57. There was no increase in SBA geometric mean titers in the Control group. A strong correlation was observed between SBA titers and anti-S. sonnei lipopolysaccharide serum immunoglobulin G antibody concentrations (Pearson correlation coefficient = 0.918), indicating that SBA can effectively complement enzyme-linked immunosorbent assay data by indicating the functionality of 1790GAHB-induced antibodies.
Molecular pathogenesis: Connections between viral hepatitis-induced and non-alcoholic steatohepatitis-induced hepatocellular carcinoma
Authors: Tian Zelin , Xu Chen , Yang Peijun , Lin Zhibin , Wu Wenlong , Zhang Wenjie , Ding Jian , Ding Rui , Zhang Xuan , Dou Kefeng
Published: September 2022

Hepatocellular carcinoma(HCC) is the sixth most common cancer in the world and is usually caused by viral hepatitis (HBV and HCV), alcoholic, and non-alcoholic fatty liver disease(NAFLD). Viral hepatitis accounts for 80% of HCC cases worldwide. In addition, With the increasing incidence of metabolic diseases, NAFLD is now the most common liver disease and a major risk factor for HCC in most developed countries. This review mainly described the specificity and similarity between the pathogenesis of viral hepatitis(HBV and HCV)-induced HCC and NAFLD-induced HCC. In general, viral hepatitis promotes HCC development mainly through specific encoded viral proteins. HBV can also exert its tumor-promoting mechanism by integrating into the host chromosome, while HCV cannot. Viral hepatitis-related HCC and NASH-related HCC differ in terms of genetic factors, and epigenetic modifications (DNA methylation, histone modifications, and microRNA effects). In addition, both of them can lead to HCC progression through abnormal lipid metabolism, persistent inflammatory response, immune and intestinal microbiome dysregulation.
Life factors acting on systemic lupus erythematosus
Authors: Chen Jiaxuan , Liao Shuzhen , Pang Wanxian , Guo Fengbiao , Yang Lawei , Liu Hua-feng , Pan Qingjun
Published: September 2022

Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease that primarily affects women. Currently, in the search for the mechanisms of SLE pathogenesis, the association of lifestyle factors such as diet, cigarette smoking, ultraviolet radiation exposure, alcohol and caffeine-rich beverage consumption with SLE susceptibility has been systematically investigated. The cellular and molecular mechanisms mediating lifestyle effects on SLE occurrence, including interactions between genetic risk loci and environment, epigenetic changes, immune dysfunction, hyper-inflammatory response, and cytotoxicity, have been proposed. In the present review of the reports published in reputable peer-reviewed journals and government websites, we consider the current knowledge about the relationships between lifestyle factors and SLE incidence and outline directions of future research in this area. Formulation of practical measures with regard to the lifestyle in the future will benefit SLE patients and may provide potential therapy strategies.
Influence of graft composition in patients with hematological malignancies undergoing ATG-based haploidentical stem cell transplantation
Authors: Zhang Ran , Lu Xuan , Tang Liang V. , Wang Huafang , Yan Han , You Yong , Zhong Zhaodong , Shi Wei , Xia Linghui
Published: September 2022

To determine the influence of graft composition in haplo-HSCT, we summarized the long-term consequences of 251 consecutive transplantations from haploidentical donors. For donor-recipient HLA3/6-matched setting, 125 cases used G-CSF-mobilized BM and PBSCs mixtures, while 126 cases only used G-CSF-mobilized PBSCs in HLA4/6-matched transplantation. On the one hand, we wanted to explore the effect of harvests (CD34+ cells and TNCs dosages) on transplantation outcome in the context of haplo-HSCT no matter HLA4/6 or HLA3/6-matched setting. On the other hand, for patients using G-CSF-mobilized BM and PBSCs combination in HLA3/6-matched setting, we attempted to analyze whether TNCs or CD34+ cells from G-CSF-mobilized BM or G-CSF-mobilized PBSCs play the most paramount role on transplantation prognosis. Collectively, patients with hematologic malignancies receiving G-CSF-primed BM and PBSCs harvests had comparable consequences with patients only receiving G-CSF-mobilized PBSCs. Moreover, when divided all patients averagely according to the total amount of transfused nucleated cells, 3-year TRM of the intermediate group (13.06-18.05×108/kg) was only 4.9%, which was remarkably reduced when compared to lower and higher groups with corresponding values 18.3%, 19.6% (P=0.026). The 3-year probabilities of OS and DFS of this intermediate group were 72.6% and 66.5%, which were slightly improved than the lower and higher groups. Most importantly, these data suggest that the transfused nucleated cells from G-CSF-primed BM above than 5.20×108/kg could achieve remarkably lower TRM in haplo-HSCT receiving G-CSF-mobilized BM and PBSCs harvests. These encouraging results suggested that we could improve the efficacy of haplo-HSCT by adjusting the component and relative ratio of transfused graft cells. Nevertheless, the above findings should be confirmed in a randomized prospective comparative research with adequate follow-up.
A combined analysis of bulk and single-cell sequencing data reveals that depleted extracellular matrix and enhanced immune processes co-contribute to fluorouracil beneficial responses in gastric cancer
Authors: Dong Shaowei , Zhang Siyu , Zhao Pan , Lin Guanchuan , Ma Xiaoshi , Xu Jing , Zhang Hao , Hu Jiliang , Zou Chang
Published: September 2022

Fluorouracil, also known as 5-FU, is one of the most commonly used chemotherapy drugs in the treatment of advanced gastric cancer (GC). Whereas, the presence of innate or acquired resistance largely limits its survival benefit in GC patients. Although accumulated studies have demonstrated the involvement of tumor microenvironments (TMEs) in chemo-resistance induction, so far little is known about the relevance of GC TMEs in 5-FU resistance. To this end, in this study, we investigated the relationship between TME features and 5-FU responses in GC patients using a combined analysis involving both bulk sequencing data from the TCGA database and single-cell RNA sequencing data from the GEO database. We found that depleted extracellular matrix (ECM) components such as capillary/stroma cells and enhanced immune processes such as increased number of M1 polarized macrophages/Memory T cells/Natural Killer T cells/B cells and decreased number of regulatory T cells are two important features relating to 5-FU beneficial responses in GC patients, especially in diffuse-type patients. We further validated these two features in the tumor tissues of 5-FU-benefit GC patients using immunofluorescence staining experiments. Based on this finding, we also established a Pro (63 genes) and Con (199 genes) gene cohort that could predict 5-FU responses in GC with an AUC (area under curve) score of 0.90 in diffuse-type GC patients, and further proved the partial applicability of this gene panel pan-cancer-wide. Moreover, we identified possible communications mediated by heparanase and galectin-1 which could regulate ECM remodeling and tumor immune microenvironment (TIME) reshaping. Altogether, these findings deciphered the relationship between GC TMEs and 5-FU resistance for the first time, as well as provided potential therapeutic targets and predicting rationale to overcome this chemo-resistance, which could shed some light on developing novel precision treatment strategies in clinical practice.
p50-associated Cyclooxygenase-2 Extragenic RNA (PACER) and Long Non-coding RNA 13 (LNC13) as potential biomarkers for monitoring tuberculosis treatment
Authors: Kameni Charleine , Mezajou Cybelle Fodieu , Ngongang Natacha Njike , Ngum Jubilate Afuoti , Simo Ulrich Stephane Fotso , Tatang Fabrice Junior , Nguengo Sarah Ngate , Nouthio Annick Prisca Chakam , Pajiep Michelle Alma Wandji , Toumeni Michelle Hako , Madjoumo Epiphanie Sorelle Takou , Tchinda Maxwell Fofou , Ngangue Roland Jethro Ekwala Misse , Koro Koro Francioli , Wade Abel , Akami Mazarin , Ngono Annie Rosalie Ngane , Tamgue Ousman
Published: September 2022

Gaps in early and accurate diagnosis, effective drug control, and treatment monitoring are hindering the global eradication effort of tuberculosis. This infectious disease has become the deadliest worldwide before the outbreak of Covid-19. The search for new molecular biomarkers of tuberculosis will help to reverse this trend. Long non-coding RNAs (lncRNAs) have emerged as important regulators of the host immune response to infection, hence their link with the etiology and diagnosis of tuberculosis has attracted some attention from the research community. However, very little is known about their potential for the monitoring of tuberculosis treatment. This study aimed at assessing the potential of two lncRNAs: p50-associated Cyclooxygenase-2 Extragenic RNA (PACER) and Long Non-coding RNA 13 (LNC13) in the monitoring of tuberculosis treatment. This was a cross-sectional study carried out in Douala, Cameroon from December 2020 to August 2021. A quantitative real-time polymerase chain reaction followed by Cq analysis using the Livak method were performed to measure the relative expression levels of PACER and LNC13 in whole blood of healthy controls, patients with active pulmonary tuberculosis at the initiation of treatment, after two, five, and six months into treatment. Receiver Operating Characteristic curves analysis was used to assess the ability of targeted lncRNAs to discriminate among those groups. The study showed that the lncRNAs PACER and LNC13 were significantly upregulated in patients with active pulmonary tuberculosis at the initiation of treatment than in healthy controls. The expression levels of the two lncRNAs were significantly downregulated in patients during the treatment as compared to the active pulmonary tuberculosis patients. However, the expression levels of the lncRNAs PACER and LNC13 in whole blood of patients after six months of treatment were similar to those in healthy controls. Similarly, lncRNAs PACER and LNC13 showed very good performance in distinguishing between active tuberculosis patients and healthy controls as well as in differentiating between newly diagnosed active tuberculosis patients and those under treatment. Interestingly, those lncRNAs could not discriminate healthy controls from patients after six months of treatment. The lncRNAs PACER and LNC13 are therefore potential biomarkers for the monitoring of tuberculosis treatment.
Threshold of surface erosion of cohesive sediments
Authors: Chen Dake , Zheng Jinhai , Zhang Chi , Guan Dawei , Li Yuan , Huang Huiming
Published: September 2022

Cohesive sediment is ubiquitous in aquatic systems, which often forms fractal aggregates due to cohesive and adhesive forces between particles and is generally eroded as aggregates at low bed shear stresses. The erosion of aggregates plays a significant role in cohesive sediment dynamics. However, the effects of fractal bed aggregation on the erosion threshold of sediment have not been well understood. The incipient motion condition of cohesive sediment is investigated, in which particle aggregation is taken into account by employing the fractal theory and the van der Waals force between particles. A formula for the critical shear stress for surface erosion of cohesive sediments composed of fractal aggregates is developed based on the balance analysis of momentums acting on an aggregate in the bed surface. The developed formula has been successfully applied to different kinds of cohesive sediment. The fractal dimension is found as a function of the solid volume fraction and the diameter of primary particles. The contribution rate of the effective weight of aggregate to the erosion threshold of cohesive sediment is quantified.
Chemotaxonomic patterns in intracellular metabolites of marine microbial plankton
Authors: Durham Bryndan P. , Boysen Angela K. , Heal Katherine R. , Carlson Laura T. , Boccamazzo Rachel , Deodato Chloe R. , Qin Wei , Cattolico Rose Ann , Armbrust E. Virginia , Ingalls Anitra E.
Published: September 2022

Most biological diversity on Earth is contained within microbial communities. In the ocean, these communities dominate processes related to carbon fixation and nutrient recycling. Yet, specific factors that determine community composition and metabolic activity are difficult to resolve in complex microbial populations, complicating predictions of microbial processes in a changing ocean. Microbial metabolism generates small organic molecules that reflect both the biochemical and physiological diversity as well as the taxonomic specificity of these biological processes. These small molecules serve as the conduit for taxon-specific signaling and exchange. Here, we use liquid chromatography-mass spectrometry (LC-MS)-based metabolomics to taxonomically categorize 111 metabolites that include small molecules in central and secondary metabolism across 42 taxa representing numerically dominant and metabolically important lineages of microbial autotrophs and heterotrophs. Patterns in metabolite presence-absence broadly reflected taxonomic lineages. A subset of metabolites that includes osmolytes, sulfur-containing metabolites, sugars, and amino acid derivatives provided chemotaxonomic information among phytoplankton taxa. A variety of phytohormones and signaling molecules were predominantly found in the heterotrophic bacteria and archaea, expanding knowledge of metabolites implicated in modulating interactions between microbes. This chemotaxonomic inventory of marine microbial metabolites is a key step in deciphering metabolic networks that influence ocean biogeochemical cycles.
Gregarious larval settlement mediates the responses of new recruits of the reef coral Acropora austera to ocean warming and acidification
Authors: Jiang Lei , Zhang Yu-Yang , Liu Cheng-Yue , Huang Lin-Tao , Tong Hao-Ya , Zhou Guo-Wei , Guo Ming-Lan , Yuan Tao , Huang Hui
Published: September 2022

Gregarious larval settlement represents an important window for chimera formation in reef corals, yet it remains largely unknown how aggregated settlement and early chimerism could modify the performance and responses of coral recruits under elevated temperature and pCO2. In this study, single and aggregated recruits of the broadcast spawning coral Acropora austera were exposed to contrasts of two temperatures (28 versus 30.5°C) and pCO2 levels (~500 versus 1000 μatm) for two weeks, and algal symbiont infection success, survivorship and growth were assessed. Results showed that symbiont infection success was mainly affected by temperature and recruit type, with reduced symbiont infection at increased temperature and consistently higher infection success in chimeric recruits compared to single recruits. Furthermore, although chimeric recruits with larger areal size had significantly higher survivorship in all treatments, the polyp-specific growth rates were considerably lower in chimeric entities than individual recruits. More importantly, the recruit type significantly influenced the responses of recruit polyp-specific growth rates to elevated temperature, with chimeras exhibiting lowered skeletal lateral growth under elevated temperature. These results demonstrate the benefits and costs associated with gregarious larval settlement for juvenile corals under ocean warming and acidification, and highlight the ecological role of larval settlement behavior in mediating the responses of coral recruits to climate change stressors.
The cascade of care for latent tuberculosis infection in congregate settings: A national cohort analysis, Korea, 2017–2018
Authors: Min Jinsoo , Kim Hyung Woo , Stagg Helen R. , Rangaka Molebogeng X. , Lipman Marc , Abubakar Ibrahim , Lee Yunhee , Myong Jun-Pyo , Jeong Hyunsuk , Bae Sanghyuk , Shin Ah Young , Kang Ji Young , Lee Sung-Soon , Park Jae Seuk , Yim Hyeon Woo , Kim Ju Sang
Published: September 2022

Background

In 2017, Korea implemented a nationwide project to screen and treat latent tuberculosis infection (LTBI) in high-risk for transmission public congregate settings. We aimed to assess programme success using a cascade of care framework.

Materials and methods

We undertook a cohort study of people from three congregate settings screened between March 2017 and December 2018: (1) first-grade high school students, (2) employees of educational institutions, (3) employees of social welfare facilities. We report percentages of participants with LTBI completing each step in the cascade of care model. Poisson regression models were used to determine factors associated with not visiting clinics, not initiating treatment, and not completing treatment.

Results

Among the 96,439 participants who had a positive interferon-gamma release assay result, the percentage visiting clinics for further assessment, to initiate treatment, and who then completed treatment were 50.7, 34.7, and 28.9%, respectively. Compared to those aged 20–34 years, individuals aged < 20 years and aged ≥ 65 years were less likely to visit clinics, though more likely to complete treatment once initiated. Using public health centres rather than private hospitals was associated with people “not initiating treatment” (adjusted risk ratio [aRR], 3.72; 95% confidence interval [CI], 3.95–3.86). Nine-month isoniazid monotherapy therapy was associated with “not completing treatment,” compared to 3-month isoniazid and rifampin therapy (aRR, 1.28; 95% CI, 1.16–1.41).

Conclusion

Among participants with LTBI from three congregate settings, less than one third completed treatment. Age, treatment centre, and initial regimen were important determinants of losses to care through the cascade.