bluuebunny/crossref_metadata_2025 huggingface dataset:
Compounded effects of sea urchin grazing and physical disturbance on macroalgal canopies in the lagoon of Moorea, French Polynesia
Authors: Bulleri F , Pozas-Schacre C , Bischoff H , Bramanti L , D’agata S , Gasc J , Nugues MM
Published: August 2022

Release from herbivory is a factor underpinning coral replacement by macroalgae. Once macroalgae have achieved dominance, shifts back to the coral-dominated state can be hindered by stabilizing feedbacks. Thus, restoring herbivore assemblages alone can be insufficient to trigger coral recovery. However, herbivores could control macroalgal recovery in the aftermath of physical disturbances removing macroalgae. Diadematid urchins at Moorea (French Polynesia) have collapsed in the last decade. By means of a manipulative field experiment, we tested the interactive effects of physical disturbance and increased diadematid densities on macroalgae inside the lagoon. Massive Porites colonies, referred to as ‘bommies’, were assigned to 3 different macroalgal removal treatments (removal of stipes and fronds of the canopy-forming macroalgae Turbinaria ornata and Sargassum pacificum, total removal of erect macroalgae or untouched) and exposed to 3 different urchin densities (absent, low [~0.5 ind. m-2], and intermediate [~1 ind. m-2]). After 1 yr, sea urchins had no effect on the covers of S. pacificum and T. ornata when macroalgal canopies were left untouched. Urchins could control the recovery of S. pacificum on total macroalgal removal bommies, but not that of T. ornata. However, urchins, even when at intermediate densities, did not generate major changes in the structure of benthic assemblages on experimental bommies. Our study indicates that a moderate increase in diadematid densities is unlikely to reduce the extent of macroalgal stands in Moorea back reefs unless associated with the recovery of other herbivore guilds able to remove adult macroalgae (i.e. browsers).
Seasonal and fishery impacts on the nutritional condition of the Caribbean spiny lobster Panulirus argus in Florida, USA
Authors: Butler CB , Butler J , Ross EP , Matthews TR
Published: August 2022

The sublethal effects of fisheries (e.g. reduced nutritional condition or injuries) on the target species population are poorly understood, yet have the potential to reduce fishery efficiency and sustainability. The Caribbean spiny lobsterPanulirus argustrap fishery in Florida (USA) uses live, sublegal-size lobsters as bait to lure other lobsters into the ~462000 traps employed by the fishery. Long-term confinement of lobsters used as live bait causes stress, leading to the degradation of their nutritional condition or mortality; however, cumulative effects of confinement on nutritional condition throughout the fishing season and the effect on the population were unknown. We sampled sublegal- and legal-size lobsters hand-caught from a fished area (potentially affected by traps) and caught in commercial lobster traps in the fished area to determine how lobster health varies throughout the year and whether the intense recreational and commercial fisheries exhibit sublethal effects on lobster health. We compared the health of lobsters monthly for 1 yr using 2 nutritional indices (hepatopancreas dry weight and blood serum protein), and by the presence of external injuries and shell disease. Lobster blood serum protein and dry weight index varied throughout the year, peaking in late summer to early fall, dropping sharply during the winter, and rising again through the spring, likely in response to seasonal changes in environmental factors, such as water temperature. Both legal and sublegal lobsters within actively fished traps showed lower nutritional condition than lobsters from the surrounding population throughout the fishing season, suggesting that few lobsters escape traps.
Comparison of video and traps for detecting reef fishes and quantifying species richness in the continental shelf waters of the southeast USA
Authors: Bacheler NM , Gillum ZD , Gregalis KC , Pickett EP , Schobernd CM , Schobernd ZH , Teer BZ , Smart TI , Bubley WJ
Published: August 2022

The management of reef-associated fish species is challenging due to their life history characteristics and occurrence in rocky reef habitats that are difficult to sample using traditional sampling gears. We compared 2 common sampling gears for reef fish species, chevron traps and underwater video, using 5 yr of comprehensive paired sampling data (N = 7034) collected at reef habitats between North Carolina and Florida along the southeast United States Atlantic continental shelf. Most fish families (80%) and species (85%) were observed significantly more often on video than caught in traps, and only 2 species out of 40 (5%)—black sea bass Centropristis striata and bank sea bass C.ocyurus—were caught significantly more often in traps than observed on video. Moreover, site-specific species richness was approximately 3-4 times higher on average for video compared to traps. We also used a generalized additive model to show that the ratio of trap-caught species to video-observed species was higher in shallower waters off North and South Carolina, especially when water clarity was low. Results demonstrate that video can be an efficient gear to sample most reef fishes around the world but may provide even greater benefits when paired with traditional sampling gears like traps to leverage the strengths of each gear for estimating relative abundance and species richness with more certainty.
As reformas neoliberais no Brasil e os seus impactos na ação sindical e na precarização do trabalho rural
Authors: Picolotto Everton , Lazzaretti Mateus , Trindade Eduarda
Published: August 2022

A Reforma Trabalhista e a Lei da Terceirização, ambas de 2017, tiveram grande impacto na vida dos trabalhadores e seus sindicatos. Estabelecem que o negociado prevalece sobre o legislado, permitem a terceirização irrestrita, dão fim às contribuições sindicais obrigatórias, entre outras mudanças. O objetivo do artigo é analisar as práticas adotadas pelos sindicatos rurais para mitigar os impactos das reformas e como estas últimas afetam os trabalhadores rurais. Fez-se uso de entrevistas com lideranças sindicais, análise dos textos das Convenções Coletivas de Trabalho (CCT), documentos e reportagens sobre o tema. Os sindicatos têm conseguido manter alguns direitos dos seus associados e as contribuições sindicais nas negociações das CCT. No entanto, percebeu-se certa tendência de redução da assistência aos trabalhadores mais precarizados e mais sujeitos a condições de trabalho degradantes, uma vez que a fiscalização e os sindicatos foram impactados negativamente pelas reformas, situação que piorou durante a pandemia de Covid-19.
Depoimento especial e trabalho escravo: da necessidade de ampliação das hipóteses de proteção especial às vítimas de trabalho escravo na Justiça do Trabalho
Authors: Campos Pereira Aline Fabiana
Published: August 2022

O presente artigo trata do depoimento especial, normatizado pela Lei 13.431/2017 em casos de crianças e adolescentes vítimas ou testemunhas de violência sexual. O depoimento especial deve primar pela proteção, acolhimento e privacidade da criança, que deve receber assistência qualificada jurídica e psicossocial especializada, durante e após procedimentos perante autoridade policial ou judiciária. Defende-se que as hipóteses de depoimento especial devem ser expandidas para além dos marcadores cronológicos da infância e da adolescência, de modo a contemplar também outras pessoas, em especial as vítimas de condições análogas à de escravo. O princípio da dignidade da pessoa humana e a teorias da justiça procedimental conferem lastro a esta proposta.
Three-Dimensional Poly-(ε-Caprolactone) Nanofibrous Scaffolds Promote the Maturation of Human Pluripotent Stem Cells-Induced Cardiomyocytes
Authors: Zhang Mingming , Xu Yuerong , Chen Yan , Yan Qinru , Li Xiaoli , Ding Lu , Wei Ting , Zeng Di
Published: August 2022

Although pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have been proved to be a new platform for heart regeneration, the lack of maturity significantly hinders the clinic application. Recent researches indicate that the function of stem cell is associated with the nanoscale geometry/topography of the extracellular matrix (ECM). However, the effects of 3D nanofibrous scaffolds in maturation of iPSC-CMs still remain unclear. Thus, we explored the effects of restructuring iPSC-CMs in 3D nano-scaffolds on cell morphology, cardiac-specific structural protein, gap junction and calcium transient kinetics. Using the electrospinning technology, poly-(ε-caprolactone) (PCL) nanofibrous scaffold were constructed and iPSC-CMs were seeded into these forms. As expected, strong sarcolemmal remodeling processes and myofilament reorientation were observed in 3D nano-scaffolds culture, as well as more expression of cardiac mature proteins, such as β-MHC and MLC2v. The mature morphology of 3D-shaped iPSC-CMs leaded to enhanced calcium transient kinetics, with increased calcium peak transient amplitude and the maximum upstroke velocity (Vmax). The results revealed that the maturation of iPSC-CMs was enhanced by the electrospun 3D PCL nanofibrous scaffolds treatment. These findings also proposed a feasible strategy to improve the myocardium bioengineering by combining stem cells with scaffolds.
Key Considerations in Targeted Protein Degradation Drug Discovery and Development
Authors: Qin Liena , Dai Han , Wang Junfeng
Published: August 2022

Targeting proteins’ enzymatic functions with small molecule inhibitors, as well as functions of receptor proteins with small-molecule agonists and antagonists, were the major forms of small-molecule drug development. These small-molecule modulators are based on a conventional occupancy-driven pharmacological approach. For proteome space traditionally considered undruggable by small-molecule modulators, such as enzymes with scaffolding functions, transcription factors, and proteins that lack well-defined binding pockets for small molecules, targeted protein degraders offer the opportunity to drug the proteome with an event-driven pharmacological approach. A degrader molecule, either PROTAC or molecular glue, brings the protein of interest (POI) and E3 ubiquitin ligase in close proximity and engages the ubiquitin-proteasome system (UPS), the cellular waste disposal system for the degradation of the POI. For the development of targeted protein degraders to meet therapeutic needs, several aspects will be considered, namely, the selective degradation of disease-causing proteins, the oral bioavailability of degraders beyond Lipinski’s rule of five (bRo5) scope, demands of new E3 ubiquitin ligases and molecular glue degraders, and drug resistance of the new drug modality. This review will illustrate several under-discussed key considerations in targeted protein degradation drug discovery and development: 1) the contributing factors for the selectivity of PROTAC molecules and the design of PROTACs to selectively degrade synergistic pathological proteins; 2) assay development in combination with a multi-omics approach for the identification of new E3 ligases and their corresponding ligands, as well as molecular glue degraders; 3) a molecular design to improve the oral bioavailability of bRo5 PROTACs, and 4) drug resistance of degraders.
Salivary Microbiome Profile of Diabetes and Periodontitis in a Chinese Population
Authors: Lu Chunting , Zhao Qingtong , Deng Jianwen , Chen Kexiao , Jiang Xinrong , Ma Fengyu , Ma Shuyuan , Li Zejian
Published: August 2022

Aim

There is a bidirectional association between diabetes and periodontitis. However, the effect of diabetes on the periodontitis salivary microbiota has not been elucidated. The aim of this study was to determine the effect of the presence of diabetes on the microbiota among Chinese patients with periodontitis.

Materials and Methods

Unstimulated whole saliva samples were collected from the periodontitis with diabetes group (TC), chronic periodontitis group (CP), and periodontally healthy and systemically healthy group (H) by spitting method. Bacterial genomic DNA was PCR-amplified at the V4 variable region of 16S rRNA gene. The library was constructed according to the obtained sequence results, and biological analysis and statistical analysis were carried out. Functional prediction of three groups of microbial communities was performed by the PICRUSt algorithm.

Results

There was no significant difference in bacterial diversity between the TC and CP groups. Compared with the H group, the TC group and CP group presented a higher diversity of salivary flora. Firmicutes, Streptococcus, Haemophilus, Veillonella, and Haemophilus parainfluenzae dominated the H group. Corynebacterium, Leptotrichia, Dialister, Comamonas, Capnocytophaga, Catonella, Filifactor, Campylobacter, Treponema, Campylobacter concisus, Prevotella oralis, and Porphyromonas gingivalis were significantly enriched in the TC and CP groups. Among them, Treponema and P. oralis were the most abundant in the TC group. The PICRUSt results showed that many pathways related to cell motility and functional metabolism of the salivary microbial flora changed in the TC group and the CP group.

Conclusions

Diabetes was not the main factor causing the altered diversity of salivary microbiota in patients with periodontitis; however, the presence of diabetes altered the abundance of some microbiota in saliva.
Effect of blood pressure on the mortality of the elderly population with (pre)frailty: Results from NHANES 1999–2004
Authors: Li Menghuan , Su Zhenyang , Su Hu , Zuo Zhi , He Yuan , Yao Wenming , Yang Jiaming , Zhang Kerui , Wang Hui , Kong Xiangqing
Published: August 2022

Backgrounds

The optimal blood pressure of elderly people with frailty or prefrailty is still unclear. We aimed to explore the relationship between blood pressure and mortality in the elderly with (pre)frailty.

Methods

A total of 528 participants aged 60 years and older were exacted for analyses of the association between blood pressure and mortality from the database of the National Health and Nutrition Examination Survey (NHANES) (1999–2004). Kaplan–Meier curves and log-rank tests were used to investigate the differences in survival between groups. Multivariable Cox regression and restricted cubic spline (RCS) analyses were applied to explore the relationship between blood pressure and mortality.

Results

During the median follow-up time of 116.5 [interquartile range (IQR) of 60–186] months, 363 all-cause deaths and 122 cardiac deaths were documented. For all-cause mortality, more participants died with systolic blood pressure (SBP) < 110 mmHg and SBP ≥ 170 mmHg (log-rank p = 0.004). After adjusting for confounders, SBP < 110 mmHg [hazard ratio (HR) 1.52, 95% CI: 0.96–2.41] and SBP ≥ 170 mmHg (HR 1.53, 95% CI: 1.09–2.15) had higher risks of all-cause mortality compared with SBP within 130–150 mmHg. There were no significant differences in all-cause mortality among DBP categories. A J-curve association was identified between the SBP and hazard ratio for all-cause mortality (p for non-linear = 0.028), with 138.6 mmHg as the lowest hazard ratio of all-cause mortality; each 10 mmHg of SBP rise was associated with a 9% increased risk in all-cause mortality (HR 1.09, 95% CI 1.00–1.18). Additionally, a non-linear relationship was determined between SBP and the hazard ratio for cardiac deaths (p for non-linear = 0.030), with 140.1 mmHg as the lowest hazard ratio of cardiac deaths. When SBP was higher than 140.1 mmHg, each 10 mmHg rise in SBP was associated with a 17% increased risk of cardiac deaths (HR 1.17, 95% CI: 1.02–1.34).

Conclusion

Both lower and higher SBP levels are associated with higher risks of all-cause mortality in older individuals with (pre)frailty. There are J-shaped associations between SBP and mortality, with the optimal SBP being approximately 140 mmHg for this population specifically.
Off-pump or on-pump coronary artery bypass at 30 days: A propensity matched analysis
Authors: Wang Chen , Jiang Yefan , Song Yu , Wang Qingpeng , Tian Rui , Wang Dashuai , Dong Nianguo , Jiang Xionggang , Chen Si , Chen Xinzhong
Published: August 2022

Introduction

This study was to determine whether coronary artery bypass grafting without cardiopulmonary bypass (off-pump CABG, OPCAB) could reduce early postoperative mortality and major complications compared with conventional coronary artery bypass grafting with cardiopulmonary bypass (on-pump CABG, ONCAB) by experienced surgeons.

Material and methods

From January 2016 to June 2020, isolated CABG was performed in 1200 patients (ONCAB 429, OPCAB 771) in Wuhan Union Hospital. The propensity score matching was used to adjust for differences in baseline characteristics between the ONCABG and OPCABG groups. After 1:1 matching, 404 pairs for each group were selected to compare outcomes within 30 days after surgery. All the operations were completed by experienced surgeons that had completed more than 500 on-pump and 200 off-pump CABG, respectively.

Results

After propensity matching, the two groups were comparable in terms of preoperative characteristics. The OPCAB group had less vein graft (2.5 ± 1.0 vs. 2.7 ± 0.9; P < 0.001) and a higher rate of incomplete revascularization (12.4 vs. 8.2%; P < 0.049) than the ONCAB group. There was no significant difference in early postoperative mortality between ONCAB and OPCAB groups (2.2 vs. 2.2%; P = 1.00). However, patients in the OPCAB group had a lower risk of postoperative stroke (1.5 vs. 4.7%; P = 0.008), new-onset renal insufficiency (8.9 vs. 18.8%; P < 0.001), respiratory failure (2.2 vs. 7.2%; P = 0.001), reoperation for bleeding (0.5 vs. 2.7%; P = 0.001), and required less ventilator assistance time (33.4 ± 37.9 h vs. 51.0 ± 66.1 h; P < 0.001) and intensive care unit (ICU) time (3.7 ± 2.7 days vs. 4.8 ± 4.3 days; P < 0.001).

Conclusions

In our study, patients undergoing OPCAB had fewer postoperative complications and a faster recovery. It is a feasible and safe surgical approach to achieve revascularization when performed by experienced surgeons.
Repeatable enhancement of healthcare data with social determinants of health
Authors: Greer Melody L. , Zayas Cilia E. , Bhattacharyya Sudeepa
Published: August 2022

Background

Social and behavioral aspects of our lives significantly impact our health, yet minimal social determinants of health (SDOH) data elements are collected in the healthcare system.

Methods

In this proof-of-concept study we developed a repeatable SDOH enrichment and integration process to incorporate dynamically evolving SDOH domain concepts from consumers into clinical data. This process included SDOH mapping, linking compiled consumer data to patient records in Electronic Health Records, data quality analysis and preprocessing, and storage.

Results

Consumer compilers data coverage ranged from ~90 to ~54% and the percentage match rate between compilers was between ~21 and 64%. Our preliminary analysis showed that apart from demographic factors, several SDOH factors like home-ownership, marital-status, presence of children, number of members per household, economic stability and education were significantly different between the COVID-19 positive and negative patient groups while estimated family-income and home market-value were not.

Conclusion

Our preliminary analysis shows commercial consumer data can be a viable source of SDOH factor at an individual-level for clinical data thus providing a path for clinicians to improve patient treatment and care.
Luteinizing hormone supplementation in women with hypogonadotropic hypogonadism seeking fertility care: Insights from a narrative review
Authors: Di Segni Noemi , Busnelli Andrea , Secchi Matteo , Cirillo Federico , Levi-Setti Paolo Emanuele
Published: August 2022

The management of infertile women affected by hypogonadotropic hypogonadism (HH) or conditions mimicking it is particularly challenging. In the present narrative review, we aimed to synthesize the available evidence on the benefit (if any) of exogenous luteinizing hormone (LH) supplementation in this group of patients. Available data support LH supplementation in women with organic or functional HH. On the contrary, the benefit of exogenous LH on reproductive outcomes both in advanced maternal age patients and in cases of depletion of FSH and LH levels induced by GnRH analogues has not been demonstrated. unfortunately, the inhomogeneous study populations as well as the methodological heterogeneity between studies focused on women affected by conditions mimicking HH do not allow reliable conclusions to be drawn.
Association between Chinese visceral adiposity index and metabolic-associated fatty liver disease in Chinese adults with type 2 diabetes mellitus
Authors: Tang Min , Wei Xiao-Hui , Cao Han , Zhen Qin , Liu Fang , Wang Yu-Fan , Fan Neng-Guang , Peng Yong-De
Published: August 2022

Objective

The purpose of the study was to determine the correlation of the Chinese visceral adiposity index (CVAI) with metabolic-associated fatty liver disease (MAFLD) in Chinese adults with type 2 diabetes mellitus (T2DM).

Materials/methods

In this cross-sectional study, data on sociodemographic characteristics, laboratory test results, coexisting diseases, and medical therapy were collected and analyzed. Multivariate logistic regression analyses were used to examine the correlation between CVAI and MAFLD. In order to investigate the correlation between CVAI on a continuous scale and MAFLD, a restricted cubic spline (RCS) was used.

Results

A total of 679 participants were included in this study. There were 251 female participants and 428 male participants, with a median age of 55 years. In the multivariate logistic regression model, diastolic blood pressure, duration of diabetes, glycated hemoglobin, hemoglobin, alanine transaminase, aspartate aminotransferase, gamma -glutamyl transferase, albumin, blood urea nitrogen, total cholesterol, low-density lipoprotein cholesterol, statin use and metformin use were adjusted, and an evident increase in the odds ratios of MAFLD from the lowest to the highest CVAI quartile was found (P value for trend < 0.001). Moreover, the RCS curves revealed a positive correlation between CVAI and MAFLD.

Conclusions

The CVAI is positively correlated with MAFLD and may be an indicator with diagnostic value for MAFLD in clinical practice in type 2 diabetic patients.
New evidence for SPX2 in regulating the brain-pituitary reproductive axis of half-smooth tongue sole (Cynoglossus semilaevis)
Authors: Wang Bin , Wang Kaijie , Tian Zhenfang , Cui Aijun , Liu Xin , Jin Zhixin , Liu Xuezhou , Jiang Yan , Xu Yongjiang
Published: August 2022

Spexin (SPX) is an evolutionarily conserved neuropeptide, which was first identified in human proteome by data mining. Two orthologs (SPX1 and SPX2) are present in some non-mammalian species, including teleosts. It has been demonstrated that SPX1 is involved in reproduction and food intake, whereas the functional role of SPX2 is still absent in any vertebrate. The aim of the current study was to evaluate the actions of intraperitoneal injection of endogenous SPX2 peptide on the expression levels of some key reproductive genes of the brain-pituitary axis in half-smooth tongue sole. Our data showed an inhibitory action of SPX2 on brain gnih, spx1, tac3 and pituitary gthα, lhβ mRNA levels. However, SPX2 had no significant effect on brain gnihr, gnrh2, gnrh3, kiss2, kiss2r, spx2 expression or pituitary gh expression. On the other hand, SPX2 induced an increase in pituitary fshβ expression. Taken together, our results provide initial evidence for the involvement of SPX2 in the regulation of reproduction in vertebrates, which is in accordance with previous studies on SPX1.
Modes of Selection in Tumors as Reflected by Two Mathematical Models and Site Frequency Spectra
Authors: Kurpas Monika K. , Kimmel Marek
Published: August 2022

The tug-of-war model was developed in a series of papers of McFarland and co-authors to account for existence of mutually counteracting rare advantageous driver mutations and more frequent slightly deleterious passenger mutations in cancer. In its original version, it was a state-dependent branching process. Because of its formulation, the tug-of-war model is of importance for tackling the problem as to whether evolution of cancerous tumors is “Darwinian” or “non-Darwinian.” We define two Time-Continuous Markov Chain versions of the model, including identical mutation processes but adopting different drift and selection components. In Model A, drift and selection process preserves expected fitness whereas in Model B it leads to non-decreasing expected fitness. We investigate these properties using mathematical analysis and extensive simulations, which detect the effect of the so-called drift barrier in Model B but not in Model A. These effects are reflected in different structure of clone genealogies in the two models. Our work is related to the past theoretical work in the field of evolutionary genetics, concerning the interplay among mutation, drift and selection, in absence of recombination (asexual reproduction), where epistasis plays a major role. Finally, we use the statistics of mutation frequencies known as the Site Frequency Spectra (SFS), to compare the variant frequencies in DNA of sequenced HER2+ breast cancers, to those based on Model A and B simulations. The tumor-based SFS are better reproduced by Model A, pointing out a possible selection pattern of HER2+ tumor evolution. To put our models in context, we carried out an exploratory study of how publicly accessible data from breast, prostate, skin and ovarian cancers fit a range of models found in the literature.
Soil Bacterial Community Structure in Different Micro-Habitats on the Tidal Creek Section in the Yellow River Estuary
Authors: Wang Zhikang , Yang Kaixin , Yu Junbao , Zhou Di , Li Yunzhao , Guan Bo , Yu Yang , Wang Xuehong , Ren Zhonghua , Wang Wei , Chen Xin , Yang Jisong
Published: August 2022

Tidal creeks have attracted considerable attention in estuary wetland conservation and restoration with diverse micro-habitats and high hydrological connectivity. Bacterial communities act effectively as invisible engines to regulate nutrient element biogeochemical processes. However, few studies have unveiled the bacterial community structures and diversities of micro-habitats soils on the tidal creek section. Our study selected three sections cross a tidal creek with obviously belt-like habitats “pluff mudflat – bare mudflat – Tamarix chinensis community – T. chinensis-Suaeda salsa community– S. salsa community” in the Yellow River estuarine wetland. Based on soil samples, we dissected and untangled the bacterial community structures and special bacterial taxa of different habitats on the tidal creek section. The results showed that bacterial community structures and dominant bacterial taxa were significantly different in the five habitats. The bacterial community diversities significantly decreased with distance away from tidal creeks, as well as the dominant bacteria Flavobacteriia and δ-Proteobacteria, but in reverse to Bacteroidetes and Gemmatimonadetes. Moreover, the important biomarkers sulfate-reducing bacteria and photosynthetic bacteria were different distributions within the five habitats, which were closely associated with the sulfur and carbon cycles. We found that the bacterial communities were heterogeneous in different micro-habitats on the tidal creek section, which was related to soil salinity, moisture, and nutrients as well as tidal action. The study would provide fundamental insights into understanding the ecological functions of bacterial diversities and biogeochemical processes influenced by tidal creeks.
Single-cell RNA sequencing to decipher the immunogenicity of ChAdOx1 nCoV-19/AZD1222 and mRNA-1273 vaccines in patients with autoimmune rheumatic diseases
Authors: Chen Yen-Ju , Cheng Po-Liang , Huang Wen-Nan , Chen Hsin-Hua , Chen Hong-Wei , Chen Jun-Peng , Lin Ching-Tsai , Tang Kuo-Tung , Hung Wei-Ting , Hsieh Tsu-Yi , Chen Yi-Hsing , Chen Yi-Ming , Hsiao Tzu-Hung
Published: August 2022

Objectives

To investigate the differences between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna) in patients with autoimmune rheumatic diseases (AIRD), and to explore the cell-cell interactions between high and low anti-SARS-CoV-2 IgG levels in patients with rheumatic arthritis (RA) using single-cell RNA sequencing (scRNA-seq).

Methods

From September 16 to December 10, 2021, we consecutively enrolled 445 participants (389 patients with AIRD and 56 healthy controls), of whom 236 were immunized with AZD1222 and 209 with mRNA-1273. The serum IgG antibodies to the SARS-CoV-2 receptor-binding domain was quantified by electrochemiluminescence immunoassay at 4-6 weeks after vaccination. Moreover, peripheral blood mononuclear cells (PBMCs) were isolated from RA patients at 4-6 weeks after vaccination for scRNA-seq and further analyzed by CellChat. ScRNA-seq of PBMCs samples from GSE201534 in the Gene Expression Omnibus (GEO) database were also extracted for analysis.

Results

The anti-SARS-CoV-2 IgG seropositivity rate was 85.34% for AIRD patients and 98.20% for healthy controls. The anti-SARS-CoV-2 IgG level was higher in patients receiving mRNA-1273 than those receiving AZD1222 (β: 35.25, 95% CI: 14.81-55.68, p=0.001). Prednisolone-equivalent dose >5 mg/day and methotrexate use in AIRD patients, and non-anti-tumor necrosis factor-α biologics and Janus kinase inhibitor use in RA patients were associated with inferior immunogenicity. ScRNA-seq revealed CD16-monocytes were predominant in RA patients with high anti-SARS-CoV2-IgG antibodies, and enriched pathways related to antigen presentation via MHC class II were found. HLA-DRA and CD4 interaction was enhanced in high anti-SARS-CoV2-IgG group.

Conclusions

mRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity in AIRD patients. Enriched pathways related to antigen presentation via MHC class II in CD16-monocytes might be associated with higher anti-SARS-CoV2-IgG level in RA patients and further study is warranted.
Application value of blood metagenomic next-generation sequencing in patients with connective tissue diseases
Authors: Su Rui , Yan Huanhuan , Li Na , Ding Tingting , Li Baochen , Xie Yuhuan , Gao Chong , Li Xiaofeng , Wang Caihong
Published: August 2022

Objective

This study aimed to analyze the application value of blood metagenomic next-generation sequencing (mNGS) in patients with connective tissue diseases (CTDs) to provide a reference for infection diagnosis and guidance for treatment.

Methods

A total of 126 CTD patients with suspected infections who were hospitalized in the Department of Rheumatology, the Second Hospital of Shanxi Medical University from January 2020 to December 2021 were enrolled in this study. We retrospectively reviewed the results of mNGS and conventional diagnostic tests (CDTs).

Results

Systemic lupus erythematosus (SLE) and polymyositis/dermatomyositis (DM/PM) had the highest incidence of infections. The positive pathogen detection rates of mNGS were higher than those of CDT. The virus infections are the most common type in CTD patients with single or mixed infection, especially Human gammaherpesvirus 4 (EBV), Human betaherpesvirus 5 (CMV), and Human alphaherpesvirus 1. The incidence of prokaryote and eukaryote infections is secondary to viruses. Bloodstream infections of rare pathogens such as Pneumocystis jirovecii should be of concern. Meanwhile, the most common mixed infection was bacterial–virus coinfection.

Conclusion

mNGS has incremental application value in patients with CTD suspected of co-infection. It has a high sensitivity, and a wide detection range for microorganisms in CTD patients. Furthermore, the high incidence of opportunistic virus infections in CTD patients should be of sufficient concern.
Vaccine adjuvants to engage the cross-presentation pathway
Authors: Lee Woojong , Suresh M.
Published: August 2022

Adjuvants are indispensable components of vaccines for stimulating optimal immune responses to non-replicating, inactivated and subunit antigens. Eliciting balanced humoral and T cell-mediated immunity is paramount to defend against diseases caused by complex intracellular pathogens, such as tuberculosis, malaria, and AIDS. However, currently used vaccines elicit strong antibody responses, but poorly stimulate CD8 cytotoxic T lymphocyte (CTL) responses. To elicit potent CTL memory, vaccines need to engage the cross-presentation pathway, and this requirement has been a crucial bottleneck in the development of subunit vaccines that engender effective T cell immunity. In this review, we focus on recent insights into DC cross-presentation and the extent to which clinically relevant vaccine adjuvants, such as aluminum-based nanoparticles, water-in oil emulsion (MF59) adjuvants, saponin-based adjuvants, and Toll-like receptor (TLR) ligands modulate DC cross-presentation efficiency. Further, we discuss the feasibility of using carbomer-based adjuvants as next generation of adjuvant platforms to elicit balanced antibody- and T-cell based immunity. Understanding of the molecular mechanism of DC cross-presentation and the mode of action of adjuvants will pave the way for rational design of vaccines for infectious diseases and cancer that require balanced antibody- and T cell-based immunity.
Platelets in the NETworks interweaving inflammation and thrombosis
Authors: Wienkamp Ann-Katrin , Erpenbeck Luise , Rossaint Jan
Published: August 2022

Platelets are well characterized for their indispensable role in primary hemostasis to control hemorrhage. Research over the past years has provided a substantial body of evidence demonstrating that platelets also participate in host innate immunity. The surface expression of pattern recognition receptors, such as TLR2 and TLR4, provides platelets with the ability to sense bacterial products in their environment. Platelet α-granules contain microbicidal proteins, chemokines and growth factors, which upon release may directly engage pathogens and/or contribute to inflammatory signaling. Additionally, platelet interactions with neutrophils enhance neutrophil activation and are often crucial to induce a sufficient immune response. In particular, platelets can activate neutrophils to form neutrophil extracellular traps (NETs). This specific neutrophil effector function is characterized by neutrophils expelling chromatin fibres decorated with histones and antimicrobial proteins into the extracellular space where they serve to trap and kill pathogens. Until now, the mechanisms and signaling pathways between platelets and neutrophils inducing NET formation are still not fully characterized. NETs were also detected in thrombotic lesions in several disease backgrounds, pointing towards a role as an interface between neutrophils, platelets and thrombosis, also known as immunothrombosis. The negatively charged DNA within NETs provides a procoagulant surface, and in particular NET-derived proteins may directly activate platelets. In light of the current COVID-19 pandemic, the topic of immunothrombosis has become more relevant than ever, as a majority of COVID-19 patients display thrombi in the lung capillaries and other vascular beds. Furthermore, NETs can be found in the lung and other tissues and are associated with an increased mortality. Here, virus infiltration may lead to a cytokine storm that potently activates neutrophils and leads to massive neutrophil infiltration into the lung and NET formation. The resulting NETs presumably activate platelets and coagulation factors, further contributing to the subsequent emergence of microthrombi in pulmonary capillaries. In this review, we will discuss the interplay between platelets and NETs and the potential of this alliance to influence the course of inflammatory diseases. A better understanding of the underlying molecular mechanisms and the identification of treatment targets is of utmost importance to increase patients’ survival and improve the clinical outcome.
Successful first-line treatment of simultaneous multiple primary malignancies of lung adenocarcinoma and renal clear cell carcinoma: A case report
Authors: Ye Xiaojun , Liu Xiangliang , Yin Na , Song Wei , Lu Jin , Yang Yi , Chen Xiao
Published: August 2022

Background

Multiple Primary Malignancies (MPMs) refer to the occurrence of two or more primary malignancies in the same organ or multiple organs and tissues of the same patient simultaneously or sequentially, with an incidence rate ranging from 2-17%. According to the difference in the time of occurrence of each primary tumor, MPMs can be classified as simultaneous malignancies and heterochronic malignancies. The former refers to the occurrence of two or more malignancies one after another within 6 months, while the latter refers to the occurrence of two malignancies at an interval of more than 6 months. Currently, there is a lack of effective treatment options for MPMs both nationally and internationally.

Case presentation

The patient was a 65-year-old male smoker with a definite diagnosis of advanced lung adenocarcinoma with kirsten rat sarcoma viral oncogene (KRAS) mutation, concomitant with primary renal clear cell carcinoma (RCCC), who had a progression-free survival (PFS) for 7 months after first-line treatment with albumin-bound paclitaxel and cisplatin in combination with sintilimab.

Conclusion

In this paper, we report a case of advanced lung adenocarcinoma combined with RCCC as a concurrent double primary malignancy, which achieved a satisfactory outcome after first-line chemotherapy combined with immunotherapy, with the aim of exploring effective treatment modalities for this type of MPMs, in order to improve the survival and prognosis of the patient.
Autophagy activation by dietary piceatannol enhances the efficacy of immunogenic chemotherapy
Authors: Wang Shuang , Wang Guangsuo , Wu Weiqing , Xu Zhenglei , Yang Jing , Cao Min , Wang Qi , Wang Jigang , Yang Chuanbin , Zhang Wei
Published: August 2022

Immunogenic cell death (ICD) promotes the immune antitumor response via releasing damage-associated molecular patterns (DAMPs) from dying tumor cells. The induction of autophagy improves the efficacy of multiple immunogenic chemotherapies. Here, we show that piceatannol, a dietary phenolic compound that is widely distributed in multiple fruits and vegetables such as grapes, blueberries, and mushrooms, induces autophagy and enhances oxaliplatin (OXA)-induced anticancer immune response. Specifically, piceatannol enhanced OXA-induced release of DAMPs, several key hallmarks of ICD including ATP release, cell surface exposure of calreticulin, and high-mobility group box 1 (HMGB1) release. Mechanistically, piceatannol promoted autophagy via activating TFEB/TFE3, two key transcription factors of the autophagy-lysosome pathway, and inhibiting autophagy attenuated piceatannol plus OXA-induced ATP release. Furthermore, piceatannol induced endoplasmic reticulum stress, which is critical for its role in enhancing OXA-induced cell surface exposure of calreticulin, another key hallmark of ICD. Consistently, the combination of piceatannol with OXA promoted the anticancer effects in immunocompetent mice. Taken together, our results indicate the importance and great potential of dietary piceatannol in cancer immunotherapy. Therefore, piceatannol may be used as an ICD enhancer that improves the efficacy of chemotherapeutics such as OXA in cancer treatment with minimized toxicity.
Genetic basis of defects in immune tolerance underlying the development of autoimmunity
Authors: Hocking Anne M. , Buckner Jane H.
Published: August 2022

Genetic variants associated with susceptibility to autoimmune disease have provided important insight into the mechanisms responsible for the loss of immune tolerance and the subsequent development of autoantibodies, tissue damage, and onset of clinical disease. Here, we review how genetic variants shared across multiple autoimmune diseases have contributed to our understanding of global tolerance failure, focusing on variants in the human leukocyte antigen region, PTPN2 and PTPN22, and their role in antigen presentation and T and B cell homeostasis. Variants unique to a specific autoimmune disease such as those in PADI2 and PADI4 that are associated with rheumatoid arthritis are also discussed, addressing their role in disease-specific immunopathology. Current research continues to focus on determining the functional consequences of autoimmune disease-associated variants but has recently expanded to variants in the non-coding regions of the genome using novel approaches to investigate the impact of these variants on mechanisms regulating gene expression. Lastly, studying genetic risk variants in the setting of autoimmunity has clinical implications, helping predict who will develop autoimmune disease and also identifying potential therapeutic targets.
Forecasting seasonal sargassum events across the tropical Atlantic: Overview and challenges
Authors: Marsh Robert , Oxenford Hazel A. , Cox Shelly-Ann L. , Johnson Donald R. , Bellamy Joshua
Published: August 2022

Proliferation of sargassum across the tropical Atlantic since 2011 has motivated a range of forecasting methods. Statistical methods based on basin-scale satellite data are used to address seasonal timescales. Other methods involve explicit Lagrangian calculations of trajectories for particles that are representative of drifting sargassum over days-months. This computed sargassum drift is attributed to the combined action of surface currents, winds and waves, individually or in various combinations. Such calculations are undertaken with both observed surface drift and simulated currents, each involving strengths and weaknesses. Observed drift implicitly includes the action on sargassum of winds and waves, assumed equivalent between drifters and sargassum mats. Simulated currents provide large gridded datasets that facilitate computation of ensembles, enabling some quantification of the uncertainty inherent in an eddy-rich ocean, further subject to interannual variability. A more limited number of forecasts account for in situ growth or loss of sargassum biomass, subject to considerable uncertainty. Forecasts provide either non-dimensional indices or quantities of sargassum, accumulated in specified areas or counted across specified transects over a given time interval. Proliferation of different forecast methodologies may reduce uncertainty, if predictions for given seasons are consistent in broad terms, but there is scope to coordinate different approaches with common geographical foci and predicted variables, to facilitate direct inter-comparisons. In an example of forecasting westward sargassum flux into the Caribbean during the first half of 2022, challenges and opportunities are highlighted. In conclusion, prospects for closer alignment of complementary forecasting methods, and implications for sargassum management, are identified.
Variations in nutrients and microbes during the occurrence and extinction of algal blooms: A mesocosm experiment with the addition of marine aquaculture sediment
Authors: Sun Yuanmin , Tang Kunxian , Ma Yong , Zhu Xuan , Li Heyang , Zhang Fei , Chen Shan , Huang Haiping
Published: August 2022

The release of pollutants in sediment often causes secondary pollution of seawater. In this paper, marine aquaculture sediment was added to seawater in a coastal land–based mesocosm, and the changes in microbial and physicochemical parameters were measured to study the influence of sediment disturbance on seawater. The results showed that sediment disturbance had adverse effects on seawater. After adding and stirring the aquaculture sediment, the concentration of dissolved oxygen (DO) gradually decreased, and those of nutrients gradually increased; in particular, the concentrations of ammonia and dissolved inorganic phosphorus (DIP) increased most sharply. After day 9, a bloom dominated by Chaetoceros occurred. Concentrations of chlorophyll a (Chl-a) increased, and two obvious Chl-a peaks were observed; the trends of DO and pH were similar to that of Chl-a during the bloom period; and DIP and ammonia were exhausted during periods of Chl-a peaks. During the extinction of algal blooms, the concentrations of Chl-a and DO decreased, whereas those of DIP and ammonia increased. The variation trends of bacteria and viruses were similar to that of Chl-a, with two obvious peaks, which were later than those of Chl-a. There were close connections between Chl-a and nutrients, bacteria and viruses and they showed a trend of changes in turn from nutrients to phytoplankton to bacteria to viruses during the experiment. We concluded that bloom formation was mainly affected by nutrients and weather, and the main reason for bloom decline was the depletion of nutrients. The increase in zooplankton, bacteria, and virus abundance was the ecological effect after the occurrence of algal blooms, and they affected the development of algal blooms.
Assessment of communication skills using telehealth: considerations for educators
Authors: Wright Hattie H. , O’Shea Marie-Claire , Sekula Julia , Mitchell Lana J.
Published: August 2022

Objective

The main aim of this study was to explore the views and perceptions of dietetic educators on their ability to assess communication skills of undergraduate student dietitians in a telehealth setting. A secondary aim was to provide recommendations to educators when assessing these skills using telehealth.

Methods

A descriptive qualitative study design was used. Australian and New-Zealand dietetic educators used a validated global communication rating scale to evaluate three pre-recorded telehealth encounters. Educators then answered a series of open-ended questions on their ability to assessed communication skills in the telehealth environment.

Analysis

Inductive analysis allowed the emergence of themes and sub-themes independent of a specific framework or theory. Peer debriefing and triangulation increased research rigor.

Results

Twenty-four educators were included in this study with the majority (87.5%) having > 10 years experience as a dietetic educator, and 41.6% (n = 10) with experience in assessing dietetics student using telehealth. Most (76%) educators reported the assessment of non-verbal communication skills were challenging in the telehealth environment. Five themes and 15 subthemes emerged relating to advice for students and educators when assessing communication skills and a checklist was developed from recommendations that students and educators can use when preparing, planning, implementing, and assessing telehealth consultations.

Conclusion

Assessing student communication skills via telehealth provides a useful opportunity with the growing use of the online environment, however, it also presents challenges that must be taken into consideration. While verbal communication skills are easier to assess than non-verbal, both need to be adapted for the telehealth setting.