bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Profile and Prognosis of Hereditary Transthyretin Amyloid Cardiomyopathy: A Single-Center Study in South China
Authors: Wang Shuai , Peng Wenke , Pang Min , Mao Ling , Peng Daoquan , Yu Bilian , Wu Sha , Hu Die , Yang Yang , He Jia , Ouyang Mingqi
Published: June 2022

Background

Hereditary transthyretin amyloid cardiomyopathy (ATTR-CM) is a genotypically heterogeneous disorder with a poor prognosis. There is limited literature describing the variants responsible for ATTRv in areas outside the United State, the United Kingdom and Europe. This study was performed to describe the clinical characteristics and genotypic profiles of this disease in South China.

Methods

This was a single-center retrospective study that evaluated 29 patients with a confirmed diagnosis of hereditary transthyretin amyloid cardiomyopathy enrolled from January 2016 to November 2021.

Results

93.1% patients were male and the median age of symptom onset was 53 (46, 62.5) years old. The initial manifestations of ATTR-CM were cardiovascular symptoms (55.2%), neuropathy (41.4%) and vitreous opacity (3.4%). Phenotypes at diagnosis were mixed (82.8%), predominant cardiac (6.9%), neurological (6.9%) and ophthalmic (3.4%). Poor R-wave progression (41%), pseudo-infarct (31%) and low-voltage (31%) patterns were common findings on electrocardiogram. Unexplained increased wall thickness was observed in all 29 patients, with mean septal and posterior wall thicknesses of 14.25 ± 6.26 mm and 15.34 ± 2.84 mm, respectively. Diastolic dysfunction was also seen in all 29 patients, and 17 (58%) had a restrictive fill pattern at diagnosis. Nine different missense mutations of the TTR gene were found in 29 patients from 23 families, with c.349G>T (p.Ala117Ser) the most common mutation. The median survival time after diagnosis was 47.6 (95% CI 37.9-57.4) months, with 1, 3 and 5-year survival rates of 91.2%, 74% and 38% respectively. Patients with advanced heart failure (National Amyloidosis Staging stage II/III) had worse survival than stage I [Breslow (Generalized Wilcoxon), χ2 = 4.693, P = 0.03)].

Conclusions

ATTR amyloidosis genotypes and phenotypes are highly heterogeneous. Advanced heart failure predicts a poor prognosis. Understanding the different clinical profiles of ATTR cardiac amyloidosis with different genotype is important to its early recognition.
Examining Social Media Experiences and Attitudes Toward Technology-Based Interventions for Reducing Social Isolation Among LGBTQ Youth Living in Rural United States: An Online Qualitative Study
Authors: Escobar-Viera César G. , Choukas-Bradley Sophia , Sidani Jaime , Maheux Anne J. , Roberts Savannah R. , Rollman Bruce L.
Published: June 2022

Purpose

Lesbian, gay, bisexual, transgender, and queer (LGBTQ) youth living in rural areas who feel isolated are at high risk of depression and suicidality. Given the lack of support in their offline communities, many rural-living LGBTQ youth turn to social media for social support. In this qualitative study, we examined rural LGBTQ youth's social media experiences and attitudes toward technology-based interventions for reducing perceived isolation.

Method

In Spring 2020, we conducted online interviews with LGBTQ youth aged 14-19, living in rural areas of the United States, who screened positive for perceived social isolation (n = 20; 11 cisgender sexual minority, 9 transgender). Interviews examined (1) supportive social media experiences, (2) personal strategies to improve social media experiences, and (3) perspective on potential digital intervention delivery modalities. Data were analyzed using thematic analysis.

Findings

Related to supportive content and interactions, themes included (1) positive representation of and connecting with LGBTQ groups on social media are important; (2) content from people with shared experience feels supportive, and (3) lack of feedback to one's experiences is isolating. Regarding personal strategies to improve social media experiences, themes were (1) selecting platforms to connect with different audiences helps make for a more enjoyable social media experience, and (2) several social media platform features can help make for a safer social media experience. Youth discussed advantages and disadvantages of intervention delivery via a mobile app, social media pages or groups, conversational agents (chatbots), and a dedicated website.

Conclusion

Viewing positive representation of and connecting with LGBTQ groups, content from people shared experiences, and utilizing a wide array of platform features to increase the likelihood of positive connections are key to a positive social media experience among this group. Combining delivery modalities is key to engaging rural-living LGBTQ youth in digitally delivered support interventions to reduce perceived isolation. Our results inform future intervention research and conversations about social determinants of health between providers and rural LGBTQ patients.
Evaluation of Three Blended Learning Courses to Strengthen Health Professionals' Capacity in Primary Health Care, Management of Sexual and Reproductive Health Services and Research Methods in Guinea
Authors: Millimouno Tamba Mina , Delvaux Thérèse , Kolié Jean Michel , Kourouma Karifa , Van Bastelaere Stefaan , Tsunami Carlos Kiyan , Béavogui Abdoul Habib , Garcia Marlon , Van Damme Wim , Delamou Alexandre
Published: June 2022

Background

Three blended courses on Primary Health Care (eSSP), Management of Sexual and Reproductive Health Services (eSSR), and Research Methods (eMR) were developed and implemented between 2017 and 2021 by the Maferinyah National Training and Research Center in Rural Health, a training and research institution of the Ministry of Health in Guinea. The study objectives were to evaluate the reasons for dropout and abstention, the learners' work behavior following the training, and the impact of the behavior change on the achievements of learners' organizations or services.

Methods

We evaluated the three implemented courses in 2021, focusing on levels 3 and 4 of the Kirkpatrick training evaluation model. Quantitative and qualitative data were collected through an open learning platform (Moodle), via an electronic questionnaire, during the face-to-face component of the courses (workshops), and at learners' workplaces. Descriptive statistics and thematic analysis were performed for quantitative and qualitative data, respectively.

Results

Out of 1,016 applicants, 543 including 137 (25%) women were enrolled in the three courses. Over the three courses, the completion rates were similar (67–69%) along with 20–29% dropout rates. Successful completion rates were 72% for eSSP, 83% for eMR and 85% for eSSR. Overall success rate (among all enrollees) ranged from 50% (eSSP) to 58% (eSSR). The majority (87%) of the learners reported applying the knowledge and skills they acquired during the courses through activities such as supervision (22%), service delivery (20%), and training workshops (14%). A positive impact of the training on utilization/coverage of services and increased revenues for their health facilities were also reported by some trainees.

Conclusion

These findings showed fair success rates and a positive impact of the training on learners' work behavior and the achievements of their organizations.
New Facies Model and Carbon Isotope Stratigraphy for an Ediacaran Carbonate Platform From South America (Tamengo Formation—Corumbá Group, SW Brazil)
Authors: Ramos Maria E. A. F. , Giorgioni Martino , Walde Detlef H. G. , do Carmo Dermeval A. , Fazio Gabriella , Vieira Lucieth C. , Denezine Matheus , V. Santos Roberto , R. Adôrno Rodrigo , Lage Guida Lucas
Published: June 2022

The Ediacaran is a period characterized by the diversification of early animals and extensive neritic carbonate deposits. These deposits are still not well understood in terms of facies and carbon isotope composition (δ13C). In this study we focus on the Tamengo Formation, in southwestern Brazil, which constitutes one of the most continuous and well-preserved sedimentary record of the late Ediacaran in South America. We present new detailed lithofacies and stable isotopes data from two representative sections (Corcal and Laginha) and revise the paleoenvironmental and stratigraphic interpretation of the Tamengo Formation. The Corcal section consists of neritic deposits including shallow-water limestone beds, alternated with shale and subordinate marl beds. These facies yield specimens of the Ediacaran fossils Cloudina lucianoi and Corumbella werneri. On the other hand, the Laginha section shows more heterogeneous facies, such as impure carbonates, breccias, marls, and subordinate mudstone beds, as well as no evidence of Corumbella werneri. The stable carbon isotope record is also different between the two sections, despite belonging to the same unit. The Corcal section displays higher and more homogeneous δ13C values, consistent with those of Ediacaran successions worldwide. The Laginha section, instead, displays more variable δ13C values, which suggest the influence of local and post depositional processes. The difference between the two sections was attributed to the different distance from the shore. We propose that the difference is due to topographic variations of the continental platform, which, at the Laginha site, was steeper and controlled by extensional faults. Therefore, the Corcal section is a better reference for the Tamengo Formation, whereas the Laginha is more particular and influenced by local factors. Besides, the lithofacies associations of the Tamengo Formation are like those of the Doushantuo and Dengying formatios, in South China, with no significant biogenic carbonate buildups, and different from those of other important Ediacaran units, such as the Nama Group in Nmibia and the Buah Formation in Oman. Our work highlights the complexity and heterogeneity of Ediacaran carbonate platforms and of their carbon isotopic composition. In addition, we characterize the Corcal section as a possible reference for the Ediacaran in South America.
Numerical Modeling on Blasting Stress Wave in Interbedding Rheological Rockmass for the Stability of the Main Shaft of Mine
Authors: Li Shuai , Zheng Chao , Zhao Yong
Published: June 2022

High rheological property and strong mining disturbance are prominent conditions in deep rock projects, and often present a coupled process to induce rockbursts, collapse and land subsidence. This paper aims to investigate the effect of surrounding rheological rockmass on the main shaft of mine with interbedding structure under coupled blasting stress wave condition. Based on elastic damage theory and the constitutive equation of rheological rockmass, considering the total strain rate in tensor form, a double-rock model was established. The model was then validated by comparing the numerical simulations with the test results. Matlab was used to develop the COMSOL software, allowing numerical simulation of the failure of shaft rock sequentially subjected to this complex loading path. The results from the rheology-impact numerical simulations show that the double-rock rheology was greatly affected by the dynamic disturbance. Under high creep stress and constant impact stress wave, the last failure of the double-rock with higher creep stress is more severe than that of double-rock with lower creep stress. The numerical simulation of the shaft in situ stress was used to predict the collapse of the rheological rockmass with interbedding structure. The preliminary results suggest that one contribution to this phenomenon is likely related to irreversible damage in the rock during the creep-disturbance process. Dynamic disturbance also promoted the failure of the rock near the interbedding structure, but also increased the strain and stress. This may reflect the initial compaction and elastic phase the rock near the interbedding structure related to the large compressive strength of the hard rock during the dynamic disturbance. The numerical results indicate that a circle-shaped spalling damage zone is prone to develop around the shaft with increased time. We discuss the reason for the decreased stress on point A2 near the interbedding structure of the shaft by visco-elastic theory. The results clearly showed insufficient stability of surrounding rockmass, thus the initial design of shaft is not reasonable. This study has important referential significance for main shaft design for similar mines.
Facilitating Systems Thinking Through Arts-Based STEM Integration
Authors: Danielson Robert William , Grace Elizabeth , White Alison Joanne , Kelton Molly Louise , Owen Jeb P. , Saba Fisher Kristin , Diaz Martinez AnaMaria , Mozo Maria
Published: June 2022

Engaging with socio-scientific issues often involves making sense of how – and for whom – actions, choices, and policies might affect aspects of daily life. Understanding the complexity of socio-scientific issues also requires recognizing the interconnectedness of – and working across – multiple communities and professions. We suggest that art, whether musical composition, illustrations, or sculpture / collage across materials would promote the synthesis of different types of knowledge across different scales and systems. The present investigation seeks to understand how arts integration into STEM curriculum could support systems thinking around socio-scientific issues, specifically around the issue of pathogen transmission in rural-agricultural communities. Our after-school program, which works with 3rd – 5th grade students in rural-agricultural communities, leverages the arts to promote systems-level understanding of zoonotic diseases and ecosystem dynamics. A total of 23 students across two sites located in rural communities in the Western United States participated in our afterschool program. We found that after completing the program students expanded their understanding of both the connections between concepts and an understanding of careers related to ecosystem dynamics. We suggest that educators can integrate both arts and sciences together to enhance systems thinking and expand student perception of the interconnectedness of STEM disciplines and their everyday lives.
Metabolic Syndrome-Related Kidney Injury: A Review and Update
Authors: Lin Lirong , Tan Wei , Pan Xianfeng , Tian En , Wu Zhifeng , Yang Jurong
Published: June 2022

Metabolic syndrome (MetS) includes visceral obesity, hyperglycemia, dyslipidemia, and hypertension. The prevalence of MetS is 20-25%, which is an important risk factor for chronic kidney disease (CKD). MetS causes effects on renal pathophysiology, including glomerular hyperfiltration, RAAS, microalbuminuria, profibrotic factors and podocyte injury. This review compares several criteria of MetS and analyzes their differences. MetS and the pathogenesis of CKD includes insulin resistance, obesity, dyslipidemia, inflammation, oxidative stress, and endothelial dysfunction. The intervention of MetS-related renal damage is the focus of this article and includes controlling body weight, hypertension, hyperglycemia, and hyperlipidemia, requiring all components to meet the criteria. In addition, interventions such as endoplasmic reticulum stress, oxidative stress, gut microbiota, body metabolism, appetite inhibition, podocyte apoptosis, and mesenchymal stem cells are reviewed.
Pathogenesis of Primary Aldosteronism: Impact on Clinical Outcome
Authors: Santana Lucas S. , Guimaraes Augusto G. , Almeida Madson Q.
Published: June 2022

Primary aldosteronism (PA) is the most common form of secondary arterial hypertension, with a prevalence of approximately 20% in patients with resistant hypertension. In the last decade, somatic pathogenic variants in KCNJ5, CACNA1D, ATP1A1 and ATP2B3 genes, which are involved in maintaining intracellular ionic homeostasis and cell membrane potential, were described in aldosterone-producing adenomas (aldosteronomas). All variants in these genes lead to the activation of calcium signaling, the major trigger for aldosterone production. Genetic causes of familial hyperaldosteronism have been expanded through the report of germline pathogenic variants in KCNJ5, CACNA1H and CLCN2 genes. Moreover, PDE2A and PDE3B variants were associated with bilateral PA and increased the spectrum of genetic etiologies of PA. Of great importance, the genetic investigation of adrenal lesions guided by the CYP11B2 staining strongly changed the landscape of somatic genetic findings of PA. Furthermore, CYP11B2 staining allowed the better characterization of the aldosterone-producing adrenal lesions in unilateral PA. Aldosterone production may occur from multiple sources, such as solitary aldosteronoma or aldosterone-producing nodule (classical histopathology) or clusters of autonomous aldosterone-producing cells without apparent neoplasia denominated aldosterone-producing micronodules (non-classical histopathology). Interestingly, KCNJ5 mutational status and classical histopathology of unilateral PA (aldosteronoma) have emerged as relevant predictors of clinical and biochemical outcome, respectively. In this review, we summarize the most recent advances in the pathogenesis of PA and discuss their impact on clinical outcome.
The Efficacy of Li-ESWT Combined With VED in Diabetic ED Patients Unresponsive to PDE5is: A Single-Center, Randomized Clinical Trial
Authors: Tao Rongzhen , Chen Jianhuai , Wang Dujian , Li Yunpeng , Xiang Jun , Xiong Lei , Ji Junbiao , Wu Jie , Zhou Shuang , Jia Chunping , Lv Jianlin , Yang Jie , Tang Qinglai
Published: June 2022

Introduction

Phosphodiesterase type 5-inhibitors (PDE5is) are the first-line treatment for patients with diabetes mellitus-induced erectile dysfunction (DMED), however, some patients are non-responser to PDE5is. We performed a perspective, randomized, comparative study to explore the efficacy of low intensity extracorporeal shock wave treatment (Li-ESWT) combined with vacuum erectile device (VED) in the treatment of DMED patients who were unresponsive to PDE5is.

Methods

One hundred and five eligible patients were randomly divided into three groups: group A (VED), group B (Li-ESWT) and group C (VED plus Li-ESWT). Follow-up was conducted at 4 weeks, 8 weeks and 12 weeks after the end of treatment. The erectile function was estimated by the international index of erectile function-erectile function domain (IIEF-EF), erection hardness score (EHS), sexual encounter profile questions 2 and 3 (SEP2 and SEP3) and global assessment question 1 and 2 (GAQ1 and GAQ2) before and after treatment. The changes of five points in IIEF-EF were calculated as the minimal clinical important difference (MCID), which was considered as the main index of efficacy.

Results

The MCID was achieved in 14.7%, 14.7% and 17.6% patients in group A at the follow up on 4 weeks, 8 weeks and 12 weeks, respectively (36.4%, 39.4% and 36.4% in group B; 36.4%, 51.5%, and 66.7% in group C). There were significant differences in the percentage of MCID cases between group A and group C at the follow up on 12 weeks (P<0.001), as well as that between group B and group C (P=0.014). Additionally, comparison in MCID within group C showed that there were significant differences between 4 weeks and 12 weeks follow-up (P=0.014).

Conclusion

Our findings indicated the combined therapy Li-ESWT and VED was more beneficial to shift turn PDE5is non-responders to responders for moderate patients with DMED than VED or Li-ESWT monotherapy. Moreover, this study provided evidence that patients with DMED who failed after taking oral PDE5is could attempt to opt for an alternative physicotherapy (Li-ESWT or VED) prior to more invasive alternatives.
Long-Term Effects of Biochar Application With Reduced Chemical Fertilizer on Paddy Soil Properties and japonica Rice Production System
Authors: Gu Wenqi , Wang Yuning , Feng Zhibo , Wu Di , Zhang Honggui , Yuan Hechong , Sun Yuanyuan , Xiu Liqun , Chen Wenfu , Zhang Weiming
Published: June 2022

To clarify the effects of co-application of rice-straw biochar and different chemical fertilizer doses on paddy soil properties and japonica rice production in Northeast China, a located-field experiment was adopted for 5 years. The treatments included fertilization (F, no biochar, control) and rice-straw biochar (7.5 t ha−1) combined with different chemical fertilizer doses (100, 80, and 60% that of F) set as CF, CF1, and CF2, respectively. The results showed that the co-application of biochar and chemical fertilizers after 5 years reduced soil bulk density, increased soil total and capillary porosity, changed the soil solid–liquid–gas ratio (increased the liquid and air ratios and decreased the solid ratio), and increased soil macroaggregates (>0.25 mm) and aggregate stability, which enhanced the soil’s physical properties. Furthermore, the co-application improved soil pH and soil enzyme activity (urease, sucrase, and catalase) and had a significant effect on promoting SOM. The soil total N, P, and K of CF and CF1, were 23.48, %, 47.28%, and 26.59% and 9.47%, 43.98%, and 27.87% higher than those of the control, respectively. The soil available nutrients (N, P, and K) increased in the co-application treatment, shown as the nitrogen was promoted higher in the early growth of rice, while phosphorus and potassium were exhibited greater in the late growth. With the soil amendment, the co-application increased the rice plant height and dry matter accumulation, and the CF and CF1 increased yields by 5.78 and 2.41%, respectively, by increasing the rice effective panicles, grains per panicle, and seed-setting rate. The co-application of biochar and chemical fertilizers could significantly amend soil properties and reduce chemical fertilizer use to ensure rice–grain output, which has an important significance for enhancing sustainable soil and crop productivity.
Evaluation of Association Studies and Meta-Analyses of eNOS Polymorphisms in Type 2 Diabetes Mellitus Risk
Authors: Wang Di , Liu Liangshu , Zhang Chengyu , Lu Wensheng , Wu Feifei , He Xiaofeng
Published: June 2022

Background: Numerous studies reported the associations between endothelial nitric oxide synthase (eNOS) polymorphisms (4b/a VNTR (rs869109213), G894T (rs1799983) and T786C (rs2070744)) and type 2 diabetes mellitus (T2DM) risk. However, the conclusions were incongruent. Moreover, since no published meta-analyses were performed, a key issue regarding false-positive results needs to be addressed. Furthermore, four new articles have been published on these issues. Therefore, an updated meta-analysis was conducted to further explore these associations.

Objectives: To investigate the association between eNOS 4b/a, G894T and T786C polymorphisms and T2DM risk.

Methods: Studies were searched by using the PubMed, China National Knowledge Infrastructure (CNKI), Medline, Embase, International Statistical Institute (ISI) and the China Wanfang databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the associations using five genetic models. Furthermore, the false-positive report probability (FPRP), Bayesian false discovery probability (BFDP), and the Venice criteria were employed to assess the credibility of statistically significant associations.

Results: Overall, the eNOS 4b/a polymorphism was associated with a significantly decreased T2DM risk in Asians (bb vs. aa: OR = 0.44, 95% CI = 0.23–0.84; ab + bb vs. aa: OR = 0.45, 95% CI = 0.24–0.86; bb vs. aa + ab: OR = 0.73, 95% CI = 0.59–0.91; b vs. a: OR = 0.71, 95% CI = 0.57–0.88); the eNOS G894T polymorphism was associated with a significantly increased T2DM risk in Asians (GT vs. GG: OR = 1.52, 95% CI = 1.15–2.01; GT + TT vs. GG: OR = 1.52, 95% CI = 1.15–2.01; T vs. G: OR = 1.39, 95% CI = 1.09–1.76); the eNOS T786C polymorphism was associated with a significantly increased T2DM risk in Indian (TC vs. TT: OR = 1.93, 95% CI = 1.27–2.94; TC + CC vs. TT: OR = 2.06, 95%CI = 1.26–3.36; C vs. T: OR = 1.90, 95%CI = 1.17–3.08). However, when a sensitivity analysis was performed after excluding low quality and Hardy–Weinberg Disequilibrium (HWD) studies, no significant association was found for the eNOS G894T polymorphism. After credibility assessment, we identified “less-credible positive results” for the statistically significant associations in the current meta-analysis.

Conclusion: In conclusion, this article suggests that all substantial relationships between eNOS 4b/a, G894T, and T786C polymorphisms and T2DM risk are most likely due to false positive results rather than real connections or biological variables.
Immune- and Stemness-Related Genes Revealed by Comprehensive Analysis and Validation for Cancer Immunity and Prognosis and Its Nomogram in Lung Adenocarcinoma
Authors: Chen Mengqing , Wang Xue , Wang Wenjun , Gui Xuemei , Li Zhan
Published: June 2022

Objective

Lung adenocarcinoma (LUAD) is a familiar lung cancer with a very poor prognosis. This study investigated the immune- and stemness-related genes to develop model related with cancer immunity and prognosis in LUAD.

Method

The Cancer Genome Atlas (TCGA) was utilized for obtaining original transcriptome data and clinical information. Differential expression, prognostic value, and correlation with clinic parameter of mRNA stemness index (mRNAsi) were conducted in LUAD. Significant mRNAsi-related module and hub genes were screened using weighted gene coexpression network analysis (WGCNA). Meanwhile, immune-related differential genes (IRGs) were screened in LUAD. Stem cell index and immune-related differential genes (SC-IRGs) were screened and further developed to construct prognosis-related model and nomogram. Comprehensive analysis of hub genes and subgroups, involving enrichment in the subgroup [gene set enrichment analysis (GSEA)], gene mutation, genetic correlation, gene expression, immune, tumor mutation burden (TMB), and drug sensitivity, used bioinformatics and reverse transcription polymerase chain reaction (RT-PCR) for verification.

Results

Through difference analysis, mRNAsi of LUAD group was markedly higher than that of normal group. Clinical parameters (age, gender, and T staging) were ascertained to be highly relevant to mRNAsi. MEturquoise and MEblue were found to be the most significant modules (including positive and negative correlations) related to mRNAsi via WGCNA. The functions and pathways of the two mRNAsi-related modules were mainly enriched in tumorigenesis, development, and metastasis. Combining stem cell index–related differential genes and immune-related differential genes, 30 prognosis-related SC-IRGs were screened via Cox regression analysis. Then, 16 prognosis-related SC-IRGs were screened to construct a LASSO regression model at last. In addition, the model was successfully validated by using TCGA-LUAD and GSE68465, whereas c-index and the calibration curves were utilized to demonstrate the clinical value of our nomogram. Following the validation of the model, GSEA, immune cell correlation, TMB, clinical relevance, etc., have found significant difference in high- and low-risk groups, and 16-gene expression of the SC-IRG model also was tested by RT-PCR. ADRB2, ANGPTL4, BDNF, CBLC, CX3CR1, and IL3RA were found markedly different expression between the tumor and normal group.

Conclusion

The SC-IRG model and the prognostic nomogram could accurately predict LUAD survival. Our study used mRNAsi combined with immunity that may lay a foundation for the future research studies in LUAD.
Gut Microbiota-Derived Indole-3-Carboxylate Influences Mucosal Integrity and Immunity Through the Activation of the Aryl Hydrocarbon Receptors and Nutrient Transporters in Broiler Chickens Challenged With Eimeria maxima
Authors: Park Inkyung , Nam Hyoyoun , Goo Doyun , Wickramasuriya Samiru S. , Zimmerman Noah , Smith Alexandra H. , Rehberger Thomas G. , Lillehoj Hyun S.
Published: June 2022

Two studies were conducted to evaluate the effects of indole-3-carboxylate (ICOOH) as a postbiotic on maintaining intestinal homeostasis against avian coccidiosis. In the first study, an in vitro culture system was used to investigate the effects of ICOOH on the proinflammatory cytokine response of chicken macrophage cells (CMCs), gut integrity of chicken intestinal epithelial cells (IECs), differentiation of quail muscle cells (QMCs), and primary chicken embryonic muscle cells (PMCs) and anti-parasitic effect against Eimeria maxima. Cells to be tested were seeded in the 24-well plates and treated with ICOOH at concentrations of 0.1, 1.0, and 10.0 µg. CMCs were first stimulated by lipopolysaccharide (LPS) to induce an innate immune response, and QMCs and PMCs were treated with 0.5% and 2% fetal bovine serum, respectively, before they were treated with ICOOH. After 18 h of incubation, cells were harvested, and RT-PCR was performed to measure gene expression of proinflammatory cytokines of CMCs, tight junction (TJ) proteins of IECs, and muscle cell growth markers of QMCs and PMCs. In the second study, in vivo trials were carried out to study the effect of dietary ICOOH on disease parameters in broiler chickens infected with E. maxima. One hundred twenty male broiler chickens (0-day-old) were allocated into the following four treatment groups: 1) basal diet without infection (CON), 2) basal diet with E. maxima (NC), 3) ICOOH at 10.0 mg/kg feed with E. maxima (HI), and 4) ICOOH at 1.0 mg/kg feed with E. maxima (LO). Body weights (BWs) were measured on 0, 7, 14, 20, and 22 days. All groups except the CON chickens were orally infected with E. maxima on day 14. Jejunal samples were collected for lesion score and the transcriptomic analysis of cytokines and TJ proteins. In vitro, ICOOH increased the expression of TJ proteins in IECs and decreased IL-1β and IL-8 transcripts in the LPS-stimulated CMCs. In vivo, chickens on the HI diet showed reduced jejunal IL-1β, IFN-γ, and IL-10 expression and increased expression of genes activated by aryl hydrocarbon receptors and nutrient transporters in E. maxima-infected chickens. In conclusion, these results demonstrate the beneficial effects of dietary ICOOH on intestinal immune responses and barrier integrity in broiler chickens challenged with E. maxima. Furthermore, the present finding supports the notion to use microbial metabolites as novel feed additives to enhance resilience in animal agriculture.
Immune Responses Against SARS-CoV-2 WT and Delta Variant in Elderly BNT162b2 Vaccinees
Authors: Jäger Michael , Sonnleitner Sissy Therese , Dichtl Stefanie , Lafon Eliott , Diem Gabriel , Walder Gernot , Lass-Flörl Cornelia , Wilflingseder Doris , Posch Wilfried
Published: June 2022

Background

Residents of nursing homes are one of the most vulnerable groups during the severe acute syndrome coronavirus 2 (SARS-CoV-2) pandemic. The aim of this study was to characterize cellular and humoral immune responses in >70-year-old participants before vaccination, after first and second vaccination with BNT162b2, in contrast to second-dose-vaccinated participants younger than 60 years.

Methods

Peripheral blood mononuclear cells of 45 elderly and 40 younger vaccinees were analyzed by IFNγ ELISpot, specific immunoglobulin G antibody titers against SARS-CoV-2 spike protein, and neutralization abilities against SARS-CoV-2 wild-type (WT) and Delta variant (B.1.617.2).

Results

Our results clearly demonstrate a significantly increased T cell response, IgG titers, and neutralization activities against SARS-CoV-2 WT and Delta between first and second vaccination with BNT162b2 in elderly vaccinees, thereby highlighting the importance of the second booster. Interestingly, similar cellular and humoral immune responses against SARS-CoV-2 WT and Delta were found after the second vaccine dose in the young and elderly groups.

Conclusions

Our data demonstrate a full picture of cellular and humoral immune responses of BNT162b2-vaccinees in two age cohorts. In all vaccines, SARS-CoV-2 WT-specific antibodies with similar neutralizing activity were detected in all vaccinees. After the second vaccination, neutralization titers against SARS-CoV-2 Delta were impaired in both age groups compared with SARS-CoV-2 WT, thereby emphasizing the need for an additional booster to overcome rising variants of SARS-CoV-2.
Lack of Association Between Sex Hormones, MDSCs, LDGs and pDCs in Males and Females With Systemic Lupus Erythematosus
Authors: Jones Jessica M. , Smith Frances , Littlejohn Emily , Jorgensen Trine N.
Published: June 2022

Plasmacytoid dendritic cells (pDCs) and low-density granulocytes (LDGs) are interferon-alpha producing cells that create a pro-inflammatory response in Systemic Lupus Erythematosus (SLE) leading to auto antibody production and organ damage. Both pDCs and LDGs have been shown to be dysfunctional in patients with active SLE. Myeloid-derived suppressor cells (MDSCs) have the capacity to control T and B cell activation and differentiation, and have recently been identified as cells of interest in SLE as well. While not fully understood, previous studies have suggested that pDCs are regulated in part by both X chromosome inactivation and estradiol. Whether sex chromosomes or sex hormones regulate MDSCs and LDGs remain to be determined. We aimed to explore the relative role of sex and sex hormones on pDC, MDSC and LDG frequency and function in SLE patients. We recruited patients with SLE as defined by ACR or SLICC classification criteria and healthy controls in conjunction with the Cleveland Clinic Lupus Cohort and Clinical Research Unit. We analyzed serum sex hormone levels by ELISA, and frequencies of pDCs, MDSCs, and LDGs among PBMCs and serum cytokine levels by flow cytometry. PBMCs were further analyzed for expression of genes involved in or induced by toll-like receptor (TLR)7 or TLR9 stimulation. In all SLE patients, the serum estradiol/testosterone ratio and levels of granulocytic MDSCs and LDGs were increased, while levels of pDCs were decreased. Furthermore, pDCs from active SLE patients expressed lower levels of TLR7 and TLR9 and showed diminished production of TLR9-induced IFNα and TNFα as compared to healthy controls. LDGs from healthy controls and SLE patients expressed very low levels of TLR7 and TLR9 and largely failed to respond to TLR9 stimulation. Thus, regardless of sex and sex-hormone levels, frequencies of pDCs, MDSCs and LDGs, TLR7 and TLR9 expression, and TLR9-driven cytokine production were similarly altered in male and female SLE patients.
N-Glycosylation and Inflammation; the Not-So-Sweet Relation
Authors: Radovani Barbara , Gudelj Ivan
Published: June 2022

Chronic inflammation is the main feature of many long-term inflammatory diseases such as autoimmune diseases, metabolic disorders, and cancer. There is a growing number of studies in which alterations of N-glycosylation have been observed in many pathophysiological conditions, yet studies of the underlying mechanisms that precede N-glycome changes are still sparse. Proinflammatory cytokines have been shown to alter the substrate synthesis pathways as well as the expression of glycosyltransferases required for the biosynthesis of N-glycans. The resulting N-glycosylation changes can further contribute to disease pathogenesis through modulation of various aspects of immune cell processes, including those relevant to pathogen recognition and fine-tuning the inflammatory response. This review summarizes our current knowledge of inflammation-induced N-glycosylation changes, with a particular focus on specific subsets of immune cells of innate and adaptive immunity and how these changes affect their effector functions, cell interactions, and signal transduction.
Nationwide Effectiveness of First and Second SARS-CoV2 Booster Vaccines During the Delta and Omicron Pandemic Waves in Hungary (HUN-VE 2 Study)
Authors: Kiss Zoltán , Wittmann István , Polivka Lőrinc , Surján György , Surján Orsolya , Barcza Zsófia , Molnár Gergő Attila , Nagy Dávid , Müller Veronika , Bogos Krisztina , Nagy Péter , Kenessey István , Wéber András , Pálosi Mihály , Szlávik János , Schaff Zsuzsa , Szekanecz Zoltán , Müller Cecília , Kásler Miklós , Vokó Zoltán
Published: June 2022

Background

In Hungary, the pandemic waves in late 2021 and early 2022 were dominated by the Delta and Omicron SARS-CoV-2 variants, respectively. Booster vaccines were offered with one or two doses for the vulnerable population during these periods.

Methods and Findings

The nationwide HUN-VE 2 study examined the effectiveness of primary immunization, single booster, and double booster vaccination in the prevention of Covid-19 related mortality during the Delta and Omicron waves, compared to an unvaccinated control population without prior SARS-CoV-2 infection during the same study periods. The risk of Covid-19 related death was 55% lower during the Omicron vs. Delta wave in the whole study population (n=9,569,648 and n=9,581,927, respectively; rate ratio [RR]: 0.45, 95% confidence interval [CI]: 0.44–0.48). During the Delta wave, the risk of Covid-19 related death was 74% lower in the primary immunized population (RR: 0.26; 95% CI: 0.25–0.28) and 96% lower in the booster immunized population (RR: 0.04; 95% CI: 0.04–0.05), vs. the unvaccinated control group. During the Omicron wave, the risk of Covid-19 related death was 40% lower in the primary immunized population (RR: 0.60; 95% CI: 0.55–0.65) and 82% lower in the booster immunized population (RR: 0.18; 95% CI: 0.16–0.2) vs. the unvaccinated control group. The double booster immunized population had a 93% lower risk of Covid-19 related death compared to those with only one booster dose (RR: 0.07; 95% CI. 0.01–0.46). The benefit of the second booster was slightly more pronounced in older age groups.

Conclusions

The HUN-VE 2 study demonstrated the significantly lower risk of Covid-19 related mortality associated with the Omicron vs. Delta variant and confirmed the benefit of single and double booster vaccination against Covid-19 related death. Furthermore, the results showed the additional benefit of a second booster dose in terms of SARS-CoV-2 infection and Covid-19 related mortality.
The Complement System and ANCA Associated Vasculitis in the Era of Anti-Complement Drugs
Authors: Kimoto Yasutaka , Horiuchi Takahiko
Published: June 2022

ANCA (anti-neutrophil cytoplasmic antibody)-associated vasculitis (AAV) is the condition in which ANCA, as an autoantibody, is associated with the pathogenesis of vasculitis in small blood vessels, mainly in the ear, nose, throat, kidney, lung, and nerves. These diseases are important because they can be fatal due to renal failure and pulmonary hemorrhage if not promptly and appropriately treated. Recently accumulated evidence has shown that C5a produced by the complement alternative pathway primes neutrophils, which in turn activate the complement alternative pathway, leading to the pathogenesis of AAV. Avacopan (CCX168), a C5aR antagonist was shown to be effective against AAV, and it has been a novel therapeutic option, becoming a novel anti-complement drug to modulate inflammatory diseases.
Phylogeny of Strombidae (Gastropoda) Based on Mitochondrial Genomes
Authors: Li Fengping , Zheng Jiawen , Ma Qingxia , Gu Zhifeng , Wang Aimin , Yang Yi , Liu Chunsheng
Published: June 2022

The marine gastropod Strombidae is widely distributed in tropical and subtropical regions all over the world and possesses high morphological diversity. In order to better understand how morphological characteristics evolved within Strombidae, a robust phylogenetic framework is needed. In the present study, the complete mitochondrial genomes ofLentigo lentiginosus,Euprotomus aratrum, andCanarium labiatumwere sequenced. The three newly sequenced mt genomes contained 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, and several non-coding regions, indicating a similar pattern with respect to genome size, gene order, and nucleotide composition compared with those of other strombids reported before. Two different datasets derived from mitochondrial genes were constructed to resolve the internal phylogenetic relationships of Stromboidea and Strombidae. Within Stromboidea, the sister group formed by Clade I [Rostellariidae + (Seraphsidae + Strombidae)] and Clade II [Xenophoridae + (Struthiolariidae + Aporrhaidae)] were fully recovered and supported by morphological synapomorphies as previously suggested. The phylogenetic positions ofL. lentiginosus,E. aratrum, andC. labiatumwere confirmed within Strombidae, and several morphological similarities were observed corresponding to the present phylogeny. A correlation between strombids speciation events and paleoclimate change was presumed. Our results indicate that complete mt genomes would be a promising tool to reconstruct a robust phylogeny of Strombidae with an increased taxon sampling in the future.
Cognitive Trajectories in Community-Dwelling Older Adults and Incident Dementia, Disability and Death: A 10-Year Longitudinal Study
Authors: Wu Zimu , Woods Robyn L. , Chong Trevor T. J. , Orchard Suzanne G. , Shah Raj C. , Wolfe Rory , Storey Elsdon , Sheets Kerry M. , Murray Anne M. , McNeil John J. , Ryan Joanne
Published: June 2022

Objective

The inter-individual variability in cognitive changes may be early indicators of major health events. We aimed to determine whether late-life cognitive trajectories were associated with incident dementia, persistent physical disability and all-cause mortality.

Methods

Data came from a cohort of older community-dwelling individuals aged 70 years or above in Australia and the United States. Global cognition, verbal fluency, episodic memory and psychomotor speed were assessed regularly at up to seven waves between 2010 and 2017. Dementia, disability in activities of daily living, and death were adjudicated between 2017 and 2020. Latent classes of cognitive trajectories over seven years were determined using group-based trajectory modeling. Multivariable logistic regression was used for the prospective associations between cognitive trajectories and these outcomes.

Results

Cognitive trajectories were defined for 16,174 participants (mean age: 78.9 years; 56.7% female) who were alive and without incident dementia or disability by 2017, among which 14,655 participants were included in the association analysis. Between three and five trajectory classes were identified depending on the cognitive test. Cognitive trajectories were strongly associated with the risk of dementia. For example, compared to those in the highest-functioning trajectory, the worst performers of episodic memory had a 37-fold increased risk of dementia (95% CI: 17.23–82.64). The lowest trajectories of both global cognition and episodic memory also predicted increased mortality risk (OR: 1.80, 95% CI: 1.28–2.52; OR: 1.61, 95% CI: 1.09–2.36, respectively), while only slow psychomotor speed was marginally associated with physical disability (OR: 2.39, 95% CI: 0.99–5.77).

Conclusions

In older individuals, cognitive trajectories appear to be early indicators of clinically relevant health outcomes. Systematic cognitive assessments as part of routine geriatric evaluation may facilitate early identification and interventions for those individuals at highest risk.
Effectiveness and Safety of JAK Inhibitors in Autoinflammatory Diseases: A Systematic Review
Authors: Boyadzhieva Zhivana , Ruffer Nikolas , Burmester Gerd , Pankow Anne , Krusche Martin
Published: June 2022

Introduction

Autoinflammatory diseases (AID) are rare diseases presenting with episodes of sterile inflammation. These involve multiple organs and can cause both acute organ damage and serious long-term effects, like amyloidosis. Disease-specific anti-inflammatory therapeutic strategies are established for some AID. However, their clinical course frequently includes relapsing, uncontrolled conditions. Therefore, new therapeutic approaches are needed. Janus Kinase inhibitors (JAKi) block key cytokines of AID pathogenesis and can be a potential option.

Methods

A systematic review of the literature in accordance with the PRISMA guidelines was conducted. Three databases (MEDLINE, Embase and Cochrane Central Register of Controlled Trials) were searched for publications regarding the use of JAKi for AID. Data from the included publications was extracted and a narrative synthesis was performed. Criteria for defining treatment response were defined and applied.

Results

We report data from 38 publications with a total of 101 patients describing the effects of JAKi in AID. Data on Type I Interferonopathies, Adult-Onset Still's Disease (AOSD), Systemic Juvenile Idiopathic Arthritis (sJIA), Familial Mediterranean Fever (FMF), and Behçet's Syndrome (BS) was identified. From a total of 52 patients with type I interferonopathies, in seven patients (7/52, 13.5%) a complete response was achieved, most (35/52, 67.3%) showed a partial response and a minority (10/52, 19.2%) showed no treatment response. For AOSD, a complete or a partial response was achieved by eleven (11/26, 42.3%) patients each. Two sJIA patients achieved complete response (2/4, 50%) and in two cases (2/4, 50%) a partial response was reported. Half of FMF patients showed a complete response and the other half had a partial one (3/6, 50.0%). Amongst BS patients most achieved a partial response (8/13, 61.5%). Five patients showed no response to therapy (5/13, 38.5%). Overall, the most frequent AEs were upper respiratory tract infections (17), pneumonia (10), BK virus viremia (10) and viruria (4), herpes zoster infection (5), viral gastroenteritis (2) and other infections (4).

Conclusion

The results from this systematic review show that JAKi can be beneficial in certain AID. The risk of AEs, especially viral infections, should be considered. To accurately assess the risk benefit ratio of JAKi for AID, clinical trials should be conducted.
Variable Number Tandem Repeat Profiling of Mycobacterium ulcerans Reveals New Genotypes in Buruli Ulcer Endemic Communities in Ghana and Côte d’Ivoire
Authors: Gyamfi Elizabeth , Dogbe Magdalene Amerl , Quaye Charles , Affouda Abel Adjet , Kyei-Baffour Edwin , Awuku-Asante Daisy , Sarpong-Duah Mabel , Mosi Lydia
Published: June 2022

Buruli ulcer (BU), a necrotic skin disease caused by Mycobacterium ulcerans, is mainly prevalent in West Africa, but cases have also been reported in other tropical parts of the world. It is the second most common mycobacterial disease after tuberculosis in Ghana and Côte d’Ivoire. Heterogeneity among M. ulcerans from different geographical locations has not been clearly elucidated, and some studies seem to suggest genetic differences between M. ulcerans in humans and in the environment. This study aimed at identifying genetic differences among M. ulcerans strains between two BU endemic countries: Ghana and Côte d’Ivoire. Clinical samples consisting of swabs, fine needle aspirates, and tissue biopsies of suspected BU lesions and environmental samples (e.g., water, biofilms from plants, soil, and detrital material) were analyzed. BU cases were confirmed via acid fast staining and PCR targeting the 16S rRNA, IS2404, IS2606, and ER domain genes present on M. ulcerans. Heterogeneity among M. ulcerans was determined through VNTR profiling targeting 10 loci. Eleven M. ulcerans genotypes were identified within the clinical samples in both Ghana and Côte d’Ivoire, whiles six M. ulcerans genotypes were found among the environmental samples. Clinical M. ulcerans genotypes C, D, F, and G were common in both countries. Genotype E was unique among the Ghanaian samples, whiles genotypes A, Z, J, and K were unique to the Ivorian samples. Environmental isolates were found to be more conserved compared with the clinical isolates. Genotype W was observed only among the Ghanaian environmental samples. Genotype D was found to be prominent in both clinical and environmental samples, suggesting evidence of possible transmission of M. ulcerans from the environment, particularly water bodies and biofilms from aquatic plants, to humans through open lesions on the skin.