bluuebunny/crossref_metadata_2025 huggingface dataset:
Social network sites as learning environments and their implications for mental health
Authors: Hussenoeder Felix S.
Published: October 2022

Social network sites (SNSs) have become ubiquitous around the globe and interwoven with all aspects of life. In this article, I will argue that the communicative infrastructure of SNSs, i.e., all SNS-elements that allow users to communicate, is a key element for understanding their impact as it creates environments in which users, their behaviors, and social interactions are embedded. These digital environments facilitate and encourage fundamental mechanisms of implicit learning from feedback as well as observation in an unprecedented way. I will discuss how these technology-based learning environments impact the mental health of their users, e.g., by linking negative online feedback to depression and following influencers to disturbed eating. The article ends with a conclusion that emphasizes the advantages of understanding SNSs as environments in order to reflect the complexity, relevance, and ubiquitousness of the phenomenon.
Effectiveness and tolerability of Poliprotect, a natural mucosal protective agent for gastroesophageal reflux disease and dyspepsia: Surveys from patients, physicians, and pharmacists
Authors: Cioeta Roberto , Muti Paola , Rigoni Marta , Morlando Luigi , Siragusa Filippo , Cossu Andrea , Giovagnoni Emiliano
Published: October 2022

Background: Gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) are very common in the general population. GERD prevalence is considerably high in pregnant women, and it increases at a young age, alongside obesity. Mucosal protective agents (MPAs) are over-the-counter (OTC) treatments for FD and GERD commonly used alone or as add-on therapy to proton pump inhibitors (PPIs). Real-world data through surveys allow a clinical evaluation of marketed products that also complies with the new regulation on substance-based medical devices (SBMDs).

Aim: The study aimed to evaluate perceived effectiveness, safety, and pattern of usage among patients, physicians, and pharmacists of the natural MPA Poliprotect, as assessed by a validated survey methodology.

Methods: Questionnaire repeatability was first assessed, resulting in the intraclass correlation coefficient agreement level >0.9 in the three validation cohorts of physicians, pharmacists, and patients. All questions were closed multiple-choice, allowing measuring variations in frequency, quality, or magnitude of effect on a 5-point Likert-like verbal scale.

Results: Three different surveys were performed in Italy and Spain on a total of 3,471 physicians, including 77 gastroenterologists, 848 patients, and 146 pharmacists who had an experience with Poliprotect in the previous year. Over 90% of general practitioners (GPs) rated Poliprotect effectiveness as good/excellent in controlling pyrosis, 80% for epigastric pain, and approximately 70% for digestion difficulties. GPs reported Poliprotect as very or extremely useful as an alternative to PPIs (73%) and for pregnancy-associated GERD symptoms (61%), almost unanimously (99.5%) reporting an excellent to good tolerability; 79% of the gastroenterologists answered to be extremely or very satisfied with the improvement of typical GERD symptoms, whereas improvement of dyspepsia and pregnancy- and breast-feeding-associated GERD symptoms was rated as highly satisfactory for 69, 52, and 62%, respectively, among GI specialists. Its use because of painful dyspeptic symptoms was reported by over 80% of patients, who rated symptom relief as excellent/good, and reported a marked quality-of-life improvement in 73% and in 65% of their answers, respectively. The product was used as monotherapy by 63% of patients. Conclusion: Large-scale, validated surveys support the safety and effectiveness of Poliprotect in the treatment of common functional upper GI disorders.
Exploring inclusive education in times of COVID-19: An international comparison of German, Austrian and Portuguese teachers
Authors: Letzel-Alt Verena , Pozas Marcela , Schwab Susanne , Schneider Christoph , Lindner Katharina-Theresa , Dias Paulo , Cadime Irene
Published: October 2022

With the start of the Coronavirus (COVID-19) pandemic, the global education system has a faced immense challenges and disruptions resulting in and the necessity for an immediate redesign of teaching and learning in the school context. Face-to-face classroom instruction had to be replaced by ‘emergency remote teaching’, requiring teacher to adapt their daily routines to a new and unprecedented educational reality. Researchers and policymakers worldwide have agreed that, despite the fact that efforts were made to immediately adapt to emergency remote teaching, disadvantaged and vulnerable students may be especially at risk in emergency remote teaching. Given the differences in schooling organization across countries during the COVID-19 pandemic it can be expected that teachers performed inclusive instructional practices significantly different. Against the unpredictable situation, cross-country research has been urgently required to provide data that could inform education policy. Thus, this study explored teachers’ perceptions of supporting at risk students during the first COVID-19 school closures, as well as examining teachers’ inclusive teaching practices in three countries: Germany, Austria and Portugal. ANOVA results revealed important country differences. In general, it appears that teachers in Germany and Austria reported to have implemented less practices to address vulnerable and at-risk students compared to Portuguese teachers. Implications of the results, as well as further lines of research are outlined.
Evaluating the role of type 2 diabetes mellitus in rotator cuff tendinopathy: Development and analysis of a novel rat model
Authors: Xu Kuishuai , Zhang Liang , Ren Zhongkai , Wang Tianrui , Zhang Yingze , Zhao Xia , Yu Tengbo
Published: October 2022

Objective

To establish and validate an intact rotator cuff rat model for exploring the pathophysiological effects of type 2 diabetes on the rotator cuff tendon in vivo.

Methods

A total of 45 adult male rats were randomly divided into a control group (n = 9) and type 2 diabetes group (n=36). The rats were sacrificed at 2 weeks (T2DM-2w group, n=9), 4 weeks (T2DM-4w group, n=9), 8 weeks (T2DM-8w group, n=9), and 12 weeks (T2DM-12w group, n=9) after successful modeling of type 2 diabetes. Bilateral shoulder samples were collected for gross observation and measurement, protein expression(enzyme-linked immunosorbent assay,ELISA), histological evaluation, biomechanical testing, and gene expression (real-time quantitative polymerase chain reaction, qRT-PCR).

Results

Protein expression showed that the expression of IL-6 and Advanced glycation end products (AGEs)in serum increased in type 2 diabetic group compared with the non-diabetic group. Histologically, collagen fibers in rotator cuff tendons of type 2 diabetic rats were disorganized, ruptured, and with scar hyperplasia, neovascularization, and extracellular matrix disturbances, while Bonar score showed significant and continuously aggravated tendinopathy over 12 weeks. The biomechanical evaluation showed that the ultimate load of rotator cuff tendons in type 2 diabetic rats gradually decreased, and the ultimate load was negatively correlated with AGEs content. Gene expression analysis showed increased expression of genes associated with matrix remodeling (COL-1A1), tendon development (TNC), and fatty infiltration (FABP4) in tendon specimens from the type 2 diabetic group.

Conclusion

Persistent type 2 diabetes is associated with the rupture of collagen fiber structure, disturbance in the extracellular matrix, and biomechanical decline of the rotator cuff tendon. The establishment of this new rat model of rotator cuff tendinopathy provides a valuable research basis for studying the cellular and molecular mechanisms of diabetes-induced rotator cuff tendinopathy.
Analysis of serum bone turnover markers in female cynomolgus monkeys of different ages
Authors: Li Ying , Cai Qijun , Dong Chenchen , Hou Lu , Li Yingxin , Guo Bin , Zeng Chunyuan , Cheng Yong , Shang Jingjie , Ling Xueying , Gong Jian , Xu Hao
Published: October 2022

Objective

The purpose of this study was to examine bone turnover markers, estradiol, parathyroid hormone, and 25 hydroxyvitamin D, in cynomolgus monkeys at different ages to improve our understanding of the changes in bone turnover markers throughout the life cycle of cynomolgus monkeys and to provide a basis for the establishment of a non-human primate model of osteoporosis.

Methods

Total Body Bone Mineral Density and Total Body Bone Mineral Content were measured using Dual-Energy X-Ray Absorptiometry in cynomolgus monkeys at different ages. Serum bone turnover marker' levels were measured using enzyme immunoassays at each age group, and the relationship between bone turnover markers and age was assessed by Spearman rank correlation analysis to investigate the relationship between bone turnover markers and age in female cynomolgus monkeys.

Results

Total Body Bone Mineral Density in female cynomolgus monkeys peaked at 10 years of age and then formed a plateau that was maintained until old age. Procollagen I Aminoterminal Propeptide, Bone Alkaline Phosphatase, Osteocalcin, and C-Terminal Telopeptide Of Type I Collagen peaked at 1 to 3 years of age and gradually decreased with age, leveling off by 10 years of age. Estradiol, parathyroid hormone, and 25 hydroxyvitamin D, follicle-stimulating hormone, luteinizing hormone, were not significantly different among age groups.

Conclusion

This paper provides data on trends in bone turnover markers throughout the life cycle of female cynomolgus monkeys, which are similar to human changes.
Compositional, genetic and functional characterization of soil culturable microbial communities in polychlorinated dibenzo-p-dioxins/furans contaminated soil
Authors: Mahfouz Sabrin , Mansour Gaytha , Hanano Abdulsamie
Published: October 2022

Dioxins (PCDD/Fs) are one of the most toxic environmental pollutants known to date. Due to their structural stability and extreme hydrophobicity dioxins persist in the ecosystems and can be bioaccumulated to critical levels in both human and animal food chains. Soils are the most important reservoirs of dioxins, thus soil microbes are highly exposed to dioxins, impacting their diversity, genetics and functional characteristics. To experimentally evaluate these effects, the diversity and functionality of soil microbes were assessed in seven local sites potentially exposed to PCDD/Fs.

Concentration of dioxins in soils samples was firstly determined and the soils cultivable microbes were identified and molecularly characterized as a function of their in vitro ability to degrade the TCDD. Our results revealed that the diversity of microbial communities largely varied among the sites and was likely inversely proportional to their level of contamination with PCDD/Fs. Furthermore, the genetics profiling of dioxin-degrading bacteria revealed that the Cytochrome P450 CYPBM3-positive species largely belong to the genus Bacillus and were randomly distributed among the soils samples, while the angular dioxygenase (AD)-positive species were mainly found in highly polluted soils with a major presence of the genus Pseudomonas. Finally, the functionality of dioxin-biodegrading genes (AD or CYPBM3), was confirmed by the ability of bacteria to consume 2,3,7,8-TCDD, and this was synchronized with an induced level of both pathways. Our results suggest that different dioxin-metabolizing pathways exist under the same environmental conditions and work differentially for an effective removal of PCDD/Fs.
Evaluation of the factors affecting arsenic distribution using geospatial analysis techniques in Dongting Plain, China
Authors: Malik Muhammad Akhtar , Tang Zhonghua , Xiao Tianyun
Published: October 2022

Due to high toxicity, arsenic is regarded as a major global environmental pollutant. The present study is investigated the potential factors influencing to elevate concentration of arsenic in groundwater, surface water, and soil of the Dongting basin. The arsenic contamination potential prediction map and categories were developed using various GIS techniques such as Ordinary Kriging and the Quantile method. Then the “Raster calculator” tool was applied to verify the impact of the factors on arsenic. Eighty-four single-factor, bi-factor, and multi-factor models were established to investigate effective combinations among factors of each phase. Additionally, statistical tests were computed to evaluate arsenic between classes and factors. The arsenic value varies in groundwater from 0.0001 to 0.1582 mg/l, while in surface water between 0.0001–0.0287 mg/l and soil sediments range from 1.8–45.69 mg/kg. JunShan and GongAn groundwater resources have been identified as posing a high risk to human health. The single factors showed the best match frequency of arsenic with a population density of 66.86% in water and land use depicted match frequency of arsenic 73.19% in soil. The statistical calculations with percentage frequency factors also depicted positive trends. The correlation of the factors with arsenic in soil and water showed slow oxidation and reduction in the groundwater system. Treated portable water could be the best option to reduce the health risk of the local community.
Aragonite saturation states in estuaries along a climate gradient in the northwestern Gulf of Mexico
Authors: Hu Xinping , Yao Hongming , McCutcheon Melissa R. , Dias Larissa , Staryk Cory J. , Wetz Michael S. , Montagna Paul A.
Published: October 2022

In the northwestern Gulf of Mexico (nwGOM), the coastal climate shifts abruptly from the humid northeast to the semiarid southwest within a narrow latitudinal range. The climate effect plays an important role in controlling freshwater discharge into the shallow estuaries in this region. In addition to diminishing freshwater runoff down the coast, evaporation also increases substantially. Hence, these estuaries show increasing salinity along the coastline due to the large difference in freshwater inflow balance (river runoff and precipitation minus evaporation and diversion). However, this spatial gradient can be disrupted by intense storm events as a copious amount of precipitation leads to river flooding, which can cause temporary freshening of these systems in extreme cases, in addition to freshwater-induced ephemeral stratification. We examined estuarine water aragonite saturation state (Ωarag) data collected between 2014 and 2018, covering a period of contrasting hydrological conditions, from the initial drought to multiple flooding events, including a brief period that was influenced by a category 4 hurricane. Based on freshwater availability, these estuaries exhibited a diminishing Ωarag fluctuation from the most freshwater enriched Guadalupe Estuary to the most freshwater-starved Nueces Estuary. While Ωarag values were usually much higher than the threshold level (Ωarag = 1), brief freshwater discharge events and subsequent low oxygen levels in the lower water column led to episodic corrosive conditions. Based on previously obtained Ωarag temporal trends and Ωarag values obtained in this study, we estimated the time of emergence (ToE) for Ωarag. Not only did estuaries show decreasing ToE with diminishing freshwater availability but the sub-embayments of individual estuaries that had a less freshwater influence also had shorter ToE. This spatial pattern suggests that planning coastal restoration efforts, especially for shellfish organisms, should emphasize areas with longer ToE.
Comparative osteomorphological criteria for differentiating mandibular teeth and post-cranial skeletons of takins (Budorcas taxicolor) from Bovini species on Tibetan Plateau
Authors: Zhang Zhengwei , Li Fan , Marshall Fiona
Published: October 2022

For centuries, hunting and herding of large bovids were important for human survival at high altitudes on the Tibetan Plateau. However, little is known about past human relations with iconic plateau animals, such as takins (Budorcas taxicolorHodgson, 1850) or yaks (Bos grunniensLinnaeus, 1766). Takins were widely hunted historically for subsistence and social reasons, but an understanding of ancient relationships has been hampered by the difficulty of distinguishing takins from other large wild or domestic bovids, e.g., gaurs (Bos gaurus), yaks, cattle (Bos taurus), water buffalo (Bubalus bubalis). Through the comparative and systematic study of modern specimens, comprising 80 mandibles and 53–78 skeletons curated across five institutions in China and the United States, this research proposes a new set of osteomorphological criteria for differentiating large bovids from the Tibetan Plateau and tests previously published criteria. The results show that takins can be easily differentiated from yaks, cattle, gaurs, and water buffalos using readily identifiable shape differences, non-metric characteristics, and specific landmarks of mandibular teeth and post-cranial elements. Criteria with especially high-reliability scores include mandibular teeth and 14 postcranial elements: scapula, humerus, femur, tibia, fibula, metapodials, lunate, scaphoid, magnum, unciform, and astragalus. Providing a reproducible field method for distinguishing takins from other large bovids in this region, the osteomorphological criteria established in this study will further archaeological investigations of Holocene hunting on the Tibetan Plateau, as well as early usage of domesticated yaks and cattle. These criteria can also be used in conservation to aid field identification of illegally hunted takins.
Reconstructing diets of hunted sika deer from Torihama Shell Midden site (ca. 6,000 years ago) by dental microwear texture analysis
Authors: Sato Koyo , Sato Takao , Kubo Mugino O.
Published: October 2022

Sika deer (Cervus nippon) is the most abundant ruminant in the Japanese archipelago and has been the primary hunting target, including during the prehistoric ages. Abundant skeletal remains of sika deer have been excavated from archeological sites of the Jomon periods (ca. 15,000–2,400 BP). We reconstructed the feeding habits of sika deer from the Torihama Shell Midden site in Fukui Prefecture, western Japan. The Torihama site is one of the most well-preserved archeological sites of the Jomon period, and we investigated materials from the layers of the Early Jomon period (ca. 6,000 BP). In this study, we obtained three-dimensional tooth surface texture from the lower molars of excavated deer and measured microwear texture using international surface roughness parameters (ISO 25178-2) to infer their habitat use. Next, we estimated the percentage of grasses in the diet by using the reference dataset for extant sika deer with known diets. The results show that the Torihama deer overlapped with mixed feeding and grazing sika deer populations. Moreover, the proportion of grasses in the diet was estimated to be 50.7% on average but showed a wide range among the Torihama deer. This result implied that Torihama deer were mixed feeders of dicot leaves and grasses and had a flexible diet adapted to the vegetation of its habitat. Our results support the paleoenvironmental estimation that the Torihama Shell Midden site contained mixed vegetation of evergreen, deciduous, and coniferous trees around the Mikata Five Lakes in the Early Jomon period. These findings provide insights into the highly plastic diets of the extant sika deer in the Japanese archipelago.
Integrated analysis of bulk and single-cell RNA-seq reveals the role of MYC signaling in lung adenocarcinoma
Authors: Hao Lu , Chen Qiuyan , Chen Xi , Zhou Qing
Published: October 2022

MYC is one of the well-known oncogenes, and its important role in cancer still remains largely unknown. We obtained lung adenocarcinoma (LUAD) multi-omics data including genome, transcriptome, and single-cell sequencing data from multiple cohorts. We calculated the GSVA score of the MYC target v1 using the ssGSEA method, and obtained the genes highly correlated with this score by Spearman correlation analysis. Subsequent hierarchical clustering divided these genes into two gene sets highly associated with MYC signaling (S1 and S2). Unsupervised clustering based on these genes divided the LUAD samples into two distinct subgroups, namely, the MYC signaling inhibition group (C1) and activation group (C2). The MCP counter package in R was used to assess tumor immune cell infiltration abundance and ssGSEA was used to calculate gene set scores. The scRNA-seq was used to verify the association of MYC signaling to cell differentiation. We observed significant differences in prognosis, clinical characteristics, immune microenvironment, and genomic alterations between MYC signaling inhibition and MYC signaling activation groups. MYC-signaling is associated with genomic instability and can mediate the immunosuppressive microenvironment and promote cell proliferation, tumor stemness. Moreover, MYC-signaling activation is also subject to complex post-transcriptional regulation and is highly associated with cell differentiation. In conclusion, MYC signaling is closely related to the genomic instability, genetic alteration and regulation, the immune microenvironment landscape, cell differentiation, and disease survival in LUAD. The findings of this study provide a valuable reference to revealing the mechanism of cancer-promoting action of MYC in LUAD.
Linear high-dimensional mediation models adjusting for confounders using propensity score method
Authors: Luo Linghao , Yan Yuting , Cui Yidan , Yuan Xin , Yu Zhangsheng
Published: October 2022

High-dimensional mediation analysis has been developed to study whether epigenetic phenotype in a high-dimensional data form would mediate the causal pathway of exposure to disease. However, most existing models are designed based on the assumption that there are no confounders between the exposure, the mediators, and the outcome. In practice, this assumption may not be feasible since high-dimensional mediation analysis (HIMA) tends to be observational where a randomized controlled trial (RCT) cannot be conducted for some economic or ethical reasons. Thus, to deal with the confounders in HIMA cases, we proposed three propensity score-related approaches named PSR (propensity score regression), PSW (propensity score weighting), and PSU (propensity score union) to adjust for the confounder bias in HIMA, and compared them with the traditional covariate regression method. The procedures mainly include four parts: calculating the propensity score, sure independence screening, MCP (minimax concave penalty) variable selection, and joint-significance testing. Simulation results show that the PSU model is the most recommended. Applying our models to the TCGA lung cancer dataset, we find that smoking may lead to lung disease through the mediation effect of some specific DNA-methylation sites, including site Cg24480765 in gene RP11-347H15.2 and site Cg22051776 in gene KLF3.
Integration of RNA molecules data with prior-knowledge driven Joint Deep Semi-Negative Matrix Factorization for heart failure study
Authors: Ma Zhihui , Chen Bin , Zhang Yongjun , Zeng Jinmei , Tao Jianping , Hu Yu
Published: October 2022

Heart failure (HF) is the main manifestation of cardiovascular disease. Recent studies have shown that various RNA molecules and their complex connections play an essential role in HF’s pathogenesis and pathological progression. This paper aims to mine key RNA molecules associated with HF. We proposed a Prior-knowledge Driven Joint Deep Semi-Negative Matrix Factorization (PD-JDSNMF) model that uses a hierarchical nonlinear feature extraction method that integrates three types of data: mRNA, lncRNA, and miRNA. The PPI information is added to the model as prior knowledge, and the Laplacian constraint is used to help the model resist the noise in the genetic data. We used the PD-JDSNMF algorithm to identify significant co-expression modules. The elements in the module are then subjected to bioinformatics analysis and algorithm performance analysis. The results show that the PD-JDSNMF algorithm can robustly select biomarkers associated with HF. Finally, we built a heart failure diagnostic model based on multiple classifiers and using the Top 13 genes in the significant module, the AUC of the internal test set was up to 0.8714, and the AUC of the external validation set was up to 0.8329, which further confirmed the effectiveness of the PD-JDSNMF algorithm.
Adaptive immunity to SARS-CoV-2 infection: A systematic review
Authors: Silva Marcos Jessé Abrahão , Ribeiro Layana Rufino , Lima Karla Valéria Batista , Lima Luana Nepomuceno Gondim Costa
Published: October 2022

Background

There is evidence that the adaptive or acquired immune system is one of the crucial variables in differentiating the course of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This work aimed to analyze the immunopathological aspects of adaptive immunity that are involved in the progression of this disease.

Methods

This is a systematic review based on articles that included experimental evidence from in vitro assays, cohort studies, reviews, cross-sectional and case-control studies from PubMed, SciELO, MEDLINE, and Lilacs databases in English, Portuguese, or Spanish between January 2020 and July 2022.

Results

Fifty-six articles were finalized for this review. CD4+ T cells were the most resolutive in the health-disease process compared with B cells and CD8+ T lymphocytes. The predominant subpopulations of T helper lymphocytes (Th) in critically ill patients are Th1, Th2, Th17 (without their main characteristics) and regulatory T cells (Treg), while in mild cases there is an influx of Th1, Th2, Th17 and follicular T helper cells (Tfh). These cells are responsible for the secretion of cytokines, including interleukin (IL) - 6, IL-4, IL-10, IL-7, IL-22, IL-21, IL-15, IL-1α, IL-23, IL-5, IL-13, IL-2, IL-17, tumor necrosis factor alpha (TNF-α), CXC motivating ligand (CXCL) 8, CXCL9 and tumor growth factor beta (TGF-β), with the abovementioned first 8 inflammatory mediators related to clinical benefits, while the others to a poor prognosis. Some CD8+ T lymphocyte markers are associated with the severity of the disease, such as human leukocyte antigen (HLA-DR) and programmed cell death protein 1 (PD-1). Among the antibodies produced by SARS-CoV-2, Immunoglobulin (Ig) A stood out due to its potent release associated with a more severe clinical form.

Conclusions

It is concluded that through this study it is possible to have a brief overview of the main immunological biomarkers and their function during SARS-CoV-2 infection in particular cell types. In critically ill individuals, adaptive immunity is varied, aberrantly compromised, and late. In particular, the T-cell response is also an essential and necessary component in immunological memory and therefore should be addressed in vaccine formulation strategies.
Could inflammation contribute to salivary gland dysfunction in patients with chronic heart failure?
Authors: Klimiuk Anna , Zalewska Anna , Knapp Małgorzata , Skutnik-Radziszewska Anna , Maciejczyk Mateusz
Published: October 2022

Heart failure (HF) is one of the leading causes of death worldwide. HF results not only in cardiovascular dysfunction, but also numerous pathologies in the oral cavity and salivary glands. The present study is the first to evaluate whether salivary inflammatory and anti-inflammatory factors may be related with the occurrence of hyposalivation in HF patients. We also evaluated the potential of salivary biomarkers in the diagnostics of HF. The study included 30 women with HF and 30 sex- and age-matched healthy controls. We demonstrated significantly higher levels of pro-inflammatory cytokines, anti-inflammatory cytokines, Th1, Th2, Th17, chemokines and growth factors in unstimulated saliva of HF patients compared to controls. However, the results do not indicate dominance of either branch of the immune response. The concentration of selected biomarkers is significantly higher in patients with HF and salivary gland dysfunction compared to patients with normal saliva secretion and healthy subjects (IL-1β, TNF-α, IL-7, IL-13, INF-γ, IL-12, IL-15, IL-5, IL-6, IL-9, IL-17, MCP-1/CCL-2, EOTAXIN/CCL11, RANTES/CCL5, GM-CSF, VEGF, FGF basic, PDFG-BB). Multivariate regression analysis showed that the content of salivary cytokines, chemokines and growth factors is highly dependent on salivary gland function, i.e. salivary flow rate, total protein content and amylase activity. Using receiver operating characteristic (ROC) analysis, we showed that salivary TNF-α, INF-γ, IL-12 and EOTAXIN/CCL11 differentiated patients with HF and hyposalivation with the highest sensitivity and specificity compared to patients with normal salivary secretion and controls. Interestingly, the content of some pro- and anti-inflammatory mediators in saliva significantly exceeds their concentration in plasma. In addition, salivary biomarker levels do not reflect their plasma content, which may suggest a different nature/severity of inflammatory changes at the central (blood) and local (salivary) levels. Although our study was purely observational, the significantly higher concentration of inflammatory parameters in saliva compared to plasma, as well as the lack of saliva-blood correlation, may suggest increased production/secretion of these compounds in salivary cells of HF patients. ROC analysis did not confirm the diagnostic utility of salivary cytokines and chemokines in the differential diagnosis of HF patients.
ATF6α contributes to rheumatoid arthritis by inducing inflammatory cytokine production and apoptosis resistance
Authors: Ge Luna , Wang Ting , Shi Dandan , Geng Yun , Fan Huancai , Zhang Ruojia , Zhang Yuang , Zhao Jianli , Li Shufeng , Li Yi , Shi Haojun , Song Guanhua , Pan Jihong , Wang Lin , Han Jinxiang
Published: October 2022

Objective

The contribution of activating transcription factor 6α (ATF6α) in rheumatoid arthritis (RA) pathogenesis, especially on fibroblast-like synoviocytes (FLSs), has been suggested by its sensitivity to inflammatory stimulus. However, the exact role and therapeutic potential of ATF6α in RA remains to be fully elucidated.

Methods

ATF6α expression was determined in joint tissues and FLS, and gain-of-function and loss-of-function analyses were applied to evaluate the biological roles of ATF6α in RA FLSs. A murine collagen-induced arthritis (CIA) model, combining both gene deletion of ATF6α and treatment with the ATF6α inhibitor Ceapin-A7, was employed. Joint inflammation, tissue destruction, circulating levels of inflammatory cytokines were assessed in CIA mice. Transcriptome sequencing analysis (RNASeq), molecular biology, and biochemical approaches were performed to identify target genes of ATF6α.

Results

ATF6α expression was significantly increased in synovium of RA patients and in synovium of mice subjected to CIA. ATF6α silencing or inhibition repressed RA FLSs viability and cytokine production but induced the apoptosis. CIA-model mice with ATF6α deficiency displayed decreased arthritic progression, leading to profound reductions in clinical and proinflammatory markers in the joints. Pharmacological treatment of mice with Ceapin-A7 reduced arthritis severity in CIA models. RNA-sequencing of wild-type and knockdown of ATF6α in RA FLSs revealed a transcriptional program that promotes inflammation and suppresses apoptosis, and subsequent experiments identified Baculoviral IAP Repeat Containing 3 (BIRC3) as the direct target for ATF6α.

Conclusion

This study highlights the pathogenic role of ATF6α-BIRC3 axis in RA and identifies a novel pathway for new therapies against RA.
LigA formulated in AS04 or Montanide ISA720VG induced superior immune response compared to alum, which correlated to protective efficacy in a hamster model of leptospirosis
Authors: Varma Vivek P. , Kadivella Mohammad , Kumar Ajay , Kavela Sridhar , Faisal Syed M.
Published: October 2022

Leptospirosis is a zoonotic disease of global importance. The current vaccine provides serovar-specific and short-term immunity and does not prevent bacterial shedding in infected animals. Subunit vaccines based on surface proteins have shown to induce protection in an animal model. However, these proteins were tested with non-clinical adjuvants and induced low to moderate protective efficacy. We formulated a variable region of Leptospira immunoglobulin-like protein A (LAV) in clinical adjuvants, AS04 and Montanide ISA720VG, and then evaluated the immune response in mice and protective efficacy in a hamster model. Our results show that animals immunized with LAV-AS04 and LAV-Montanide ISA720VG (LAV-M) induced significantly higher levels of LAV-specific antibodies than LAV-Alum. While LAV-Alum induced Th2 response with the induction of IgG1 and IL-4, AS04 and LAV-M induced a mixed Th1/Th2 response with significant levels of both IgG1/IL-4 and IgG2c/IFN-γ. Both LAV-AS04 and LAV-M induced the generation of a significantly higher number of cytotoxic T cells (CTLs). The immune response in LAV-AS04- and LAV-M-immunized animals was maintained for a long period (>180 days) with the generation of a significant level of B- and T-cell memory. The strong immune response by both vaccines correlated to enhanced recruitment and activation of innate immune cells particularly DCs at draining lymph nodes and the formation of germinal centers (GCs). Furthermore, the immune response generated in mice correlated to protective efficacy in the hamster model of leptospirosis. These results indicate that LAV-AS04 and LAV-M are promising vaccines and can be further evaluated in clinical trials.
Gemcitabine-mediated depletion of immunosuppressive dendritic cells enhances the efficacy of therapeutic vaccination
Authors: Repáraz David , Ruiz Marta , Silva Leyre , Aparicio Belén , Egea Josune , Guruceaga Elizabeth , Ajona Daniel , Senent Yaiza , Conde Enrique , Navarro Flor , Barace Sergio , Alignani Diego , Hervás-Stubbs Sandra , Lasarte Juan José , Llopiz Diana , Sarobe Pablo
Published: October 2022

Vaccination using optimized strategies may increase response rates to immune checkpoint inhibitors (ICI) in some tumors. To enhance vaccine potency and improve thus responses to ICI, we analyzed the gene expression profile of an immunosuppressive dendritic cell (DC) population induced during vaccination, with the goal of identifying druggable inhibitory mechanisms. RNAseq studies revealed targetable genes, but their inhibition did not result in improved vaccines. However, we proved that immunosuppressive DC had a monocytic origin. Thus, monocyte depletion by gemcitabine administration reduced the generation of these DC and increased vaccine-induced immunity, which rejected about 20% of LLC-OVA and B16-OVA tumors, which are non-responders to anti-PD-1. This improved efficacy was associated with higher tumor T-cell infiltration and overexpression of PD-1/PD-L1. Therefore, the combination of vaccine + gemcitabine with anti-PD-1 was superior to anti-PD-1 monotherapy in both models. B16-OVA tumors benefited from a synergistic effect, reaching 75% of tumor rejection, but higher levels of exhausted T-cells in LLC-OVA tumors co-expressing PD-1, LAG3 and TIM3 precluded similar levels of efficacy. Our results indicate that gemcitabine is a suitable combination therapy with vaccines aimed at enhancing PD-1 therapies by targeting vaccine-induced immunosuppressive DC.
Advancing parameter estimation with Characteristic Finite Difference Method (CFDM) for a marine ecosystem model by assimilating satellite observations: Spatial distributions
Authors: Xu Minjie , Liu Yongzhi , Zhao Zihan , Fu Kai , Lv Xianqing
Published: October 2022

The ecosystem parameters are critical for precisely determining the marine ecological process and improving the simulations of the marine ecological model. In this study, based on the NPZD (nutrient, phytoplankton, zooplankton and detritus) model, the surface chlorophyll-a observations obtained from Sea-viewing Wide Field-of-view Sensor (SeaWiFS) data were assimilated to estimate spatially ecosystem parameters in the Bohai, Yellow, and East China Seas using an adjoint assimilation method with characteristic finite difference scheme. The experiments of the moving Gaussian hump indicated that the characteristic finite difference method (CFDM) can get rid of the limit of stability and permit using large time steps, which reduces long computation durations and large memory requirements. The model performance was significantly improved after data assimilation with CFDM using a large time step of 6 hours. Moreover, the distributions of parameters of the NPZD model in winter in the Bohai Sea, the Yellow Sea, and the East China Sea were simulated by our method. Overall, the developed method can efficiently optimize the ecosystem parameters and the results can be beneficial for determining reasonable parameters of the marine ecological model.
Using stacked deep learning models based on PET/CT images and clinical data to predict EGFR mutations in lung cancer
Authors: Chen Song , Han Xiangjun , Tian Guangwei , Cao Yu , Zheng Xuting , Li Xuena , Li Yaming
Published: October 2022

Purpose

To determine whether stacked deep learning models based on PET/CT images and clinical data can help to predict epidermal growth factor receptor (EGFR) mutations in lung cancer.

Methods

We analyzed data from two public datasets of patients who underwent 18F-FDG PET/CT. Three PET deep learning ResNet models and one CT deep learning ResNet model were trained as low-level predictors based on PET and CT images, respectively. A high-level Support Vector Machine model (Stack PET/CT and Clinical model) was trained using the prediction results of the low-level predictors and clinical data. The clinical data included sex, age, smoking history, SUVmax and SUVmean of the lesion. Fivefold cross-validation was used in this study to validate the prediction performance of the models. The predictive performance of the models was evaluated by receiver operator characteristic (ROC) curves. The area under the curve (AUC) was calculated.

Results

One hundred forty-seven patients were included in this study. Among them, 37/147 cases were EGFR mutations, and 110/147 cases were EGFR wild-type. The ROC analysis showed that the Stack PET/CT & Clinical model had the best performance (AUC = 0.85 ± 0.09), with 0.76, 0.85 and 0.83 in sensitivity, specificity and accuracy, respectively. Three ResNet PET models had relatively higher AUCs (0.82 ± 0.07, 0.80 ± 0.08 and 0.79 ± 0.07) and outperformed the CT model (AUC = 0.58 ± 0.12).

Conclusion

Using stack generalization, the deep learning model was able to efficiently combine the anatomic and biological imaging information gathered from PET/CT images with clinical data. This stacked deep learning model showed a strong ability to predict EGFR mutations with high accuracy.
Exploration of prognostic factors for prediction of mortality in elderly CAP population using a nomogram model
Authors: Lv Chunxin , Li Mengyuan , Shi Wen , Pan Teng , Muhith Abdul , Peng Weixiong , Xu Jiayi , Deng Jinhai
Published: October 2022

Background

The incidence and mortality rate of community-acquired pneumonia (CAP) in elderly patients were higher than the younger population. The assessment tools including CURB-65 and qSOFA have been applied in early detection of high-risk patients with CAP. However, several disadvantages exist to limit the efficiency of these tools for accurate assessment in elderly CAP. Therefore, we aimed to explore a more comprehensive tool to predict mortality in elderly CAP population by establishing a nomogram model.

Methods

We retrospectively analyzed elderly patients with CAP in Minhang Hospital, Fudan University. The least absolute shrinkage and selection operator (LASSO) logistic regression combined with multivariate analyses were used to select independent predictive factors and established nomogram models via R software. Calibration plots, decision curve analysis (DCA) and receiver operating characteristic curve (ROC) were generated to assess predictive performance.

Results

LASSO and multiple logistic regression analyses showed the age, pulse, NLR, albumin, BUN, and D-dimer were independent risk predictors. A nomogram model (NB-DAPA model) was established for predicting mortality of CAP in elderly patients. In both training and validation set, the area under the curve (AUC) of the NB-DAPA model showed superiority than CURB-65 and qSOFA. Meanwhile, DCA revealed that the predictive model had significant net benefits for most threshold probabilities.

Conclusion

Our established NB-DAPA nomogram model is a simple and accurate tool for predicting in-hospital mortality of CAP, adapted for patients aged 65 years and above. The predictive performance of the NB-DAPA model was better than PSI, CURB-65 and qSOFA.
Advancements in navigational bronchoscopy for peripheral pulmonary lesions: A review with special focus on virtual bronchoscopic navigation
Authors: Giri Mohan , Dai Haiyun , Puri Anju , Liao Jiaxin , Guo Shuliang
Published: October 2022

Lung cancer is often diagnosed at an advanced stage and is associated with significant morbidity and mortality. Low-dose computed tomography for lung cancer screening has increased the incidence of peripheral pulmonary lesions. Surveillance and early detection of these lesions at risk of developing cancer are critical for improving patient survival. Because these lesions are usually distal to the lobar and segmental bronchi, they are not directly visible with standard flexible bronchoscopes resulting in low diagnostic yield for small lesions <2 cm. The past 30 years have seen several paradigm shifts in diagnostic bronchoscopy. Recent technological advances in navigation bronchoscopy combined with other modalities have enabled sampling lesions beyond central airways. However, smaller peripheral lesions remain challenging for bronchoscopic biopsy. This review provides an overview of recent advances in interventional bronchoscopy in the screening, diagnosis, and treatment of peripheral pulmonary lesions, with a particular focus on virtual bronchoscopic navigation.
Microbiologically influenced corrosion of FeCoNiCrMn high-entropy alloys by Pseudomonas aeruginosa biofilm
Authors: Yang Jike , Zhang Yu , Chang Weiwei , Lou Yuntian , Qian Hongchang
Published: October 2022

Pseudomonas aeruginosa is widely found in industrial water and seawater. Microbiologically influenced corrosion (MIC) caused by P. aeruginosa is a serious threat and damage to the safe service of steel materials. In this study, the MIC behavior of FeCoNiCrMn high-entropy alloy (HEA) by P. aeruginosa biofilm was investigated in the simulated marine medium. The maximum pitting depth of the HEA coupons in the P. aeruginosa-inoculated medium was ~4.77 μm, which was 1.5 times that in the sterile medium. EIS and potentiodynamic polarization results indicated that P. aeruginosa biofilm reduced the corrosion resistance of the passive film of HEA coupons and promoted its anodic dissolution process. XPS and AES results further demonstrated that P. aeruginosa interfered with the distribution of elements in the passive film and significantly promoted the dissolution of Fe.
Fermented grape seed meal promotes broiler growth and reduces abdominal fat deposition through intestinal microorganisms
Authors: Nan Shanshan , Yao Min , Zhang Xiaoyang , Wang Hailiang , Li Jiacheng , Niu Junli , Chen Cheng , Zhang Wenju , Nie Cunxi
Published: October 2022

The fermentation of grape seed meal, a non-conventional feed resource, improves its conventional nutritional composition, promotes the growth and development of livestock and fat metabolism by influencing the structure and diversity of intestinal bacteria. In this study, the nutritional components of Fermented grape seed meal (FGSM) and their effects on the growth performance, carcass quality, serum biochemistry, and intestinal bacteria of yellow feather broilers were investigated. A total of 240 male 14-day-old yellow-feathered broilers were randomly selected and divided into four groups, with three replicates of 20 chickens each. Animals were fed diets containing 0% (Group I), 2% (Group II), 4% (Group III), or 6% (Group IV) FGSM until they were 56 days old. The results showed that Acid soluble protein (ASP) and Crude protein (CP) contents increased, Acid detergent fiber (ADF) and Neutral detergent fiber (NDF) contents decreased, and free amino acid content increased in the FGSM group. The non-targeted metabolome identified 29 differential metabolites in FGSM, including organic acids, polyunsaturated fatty acids, and monosaccharides. During the entire trial period, Average daily gain (ADG) increased and Feed conversion ratio (FCR) decreased in response to dietary FGSM supplementation (p < 0.05). TP content in the serum increased and BUN content decreased in groups III and IV (p < 0.05). Simultaneously, the serum TG content in group III and the abdominal fat rate in group IV were significantly reduced (p < 0.05). The results of gut microbiota analysis showed that FGSM could significantly increase the Shannon and Simpson indices of broilers (35 days). Reducing the relative abundance of Bacteroidetes significantly altered cecal microbiota composition by increasing the relative abundance of Firmicutes (p < 0.05). By day 56, butyric acid content increased in the cecal samples from Group III (p < 0.05). In addition, Spearman’s correlation analysis revealed a strong correlation between broiler growth performance, abdominal fat percentage, SCFAs, and gut microbes. In summary, the addition of appropriate levels of FGSM to rations improved broiler growth performance and reduced fat deposition by regulating gut microbes through differential metabolites and affecting the microbiota structure and SCFA content of the gut.
Temporal proteomic analyses of human lung cells distinguish high pathogenicity influenza viruses and coronaviruses from low pathogenicity viruses
Authors: Rashid Mahamud-ur , Glover Kathleen K. M. , Lao Ying , Spicer Victor , Coombs Kevin M.
Published: October 2022

Newly re-emerging viruses are of significant global concern. In late 2019, a new coronavirus, SARS-CoV-2, emerged in China and soon spread worldwide, causing the COVID-19 pandemic, which to date has caused >6 M deaths. There has been a wealth of studies on this new virus since its emergence. The coronaviruses consist of many animal and human pathogens, with some of the human coronavirus, such as strain OC43, normally causing only mild cold-like symptoms. Viruses usurp host cellular processes to successfully replicate. We used tandem mass tag mass spectrometry-based proteomic analyses of human lung MRC-5 cells infected with OC43 for various periods of time to delineate virus-induced host cell alterations. Numerous proteins involved in lipid metabolism, molecular transport, small molecule biochemistry, cell death and survival, humoral immune response, and inflammatory response were dysregulated. Comparison of our findings to previous studies that examined a range of differentially pathogenic influenza A viruses (IAV), and to SARS-CoV-2 data, revealed that proteins involved in the cell cycle, cytokine signaling, DNA replication, and anti-inflammatory responses were generally similarly affected by virtually all tested IAV and CoV. However, proteins involved in necrosis, protein metabolism, ECM regulation, and signal transduction were generally different. In addition, the more pathogenic CoV and IAV activated Rb-dependent repression of E2F-mediated transcription, whereas less pathogenic influenza and coronaviruses either inhibited or had no effect on this pathway.