bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of Clinical Factors and Blood Groups With the Severity of COVID-19 Infection in Makkah City, Saudi Arabia
Authors: Shesha Nashwa , Melebari Sami , Alghamdi Saad , Refaat Bassem , Naffadi Hind , Alquthami Khalid
Published: June 2022

Context

The possible associations between the different blood groups and clinical factors with COVID-19 infection among patients in Makkah city.

Objective

To investigate the relationship between ABO blood groups and COVID-19 infection in patients who were tested positive and to elucidate the most common ABO blood groups with a higher infectivity of COVID-19 and disease association.

Materials and Methods

This was an observational cross-sectional study that included COVID-19 patients diagnosed with PCR and who were hospitalized in Al-Noor Specialist Hospital (Makkah) during the period between March to November 2020. The ABO and Rhesus blood groups alongside the clinical characteristics were determined and retrieved from medical records and HESN of the Ministry of Health of the Kingdom of Saudi Arabia (KSA).

Results

The overall confirmed COVID-19 cases included in this study were 1,583 patients who underwent positive PCR testing between March and November 2020. The frequencies of blood groups were as follows: group O+ (37%), group A+ (29.2%), group B+ (22.6%), group AB+ (5.1%), group O- (2.8%), group B- (1.8%), group A- (1.1%), and group AB- (0.4%). However, no significant correlations were observed for ABO groups and Rh types with the severity of COVID-19 illness. Conversely, signs and symptoms of respiratory distress syndrome (RDS), pneumonia, and respiratory failure symptoms, alongside a history of diabetes mellitus, hypertension, chronic kidney diseases, and congestive heart failure significantly increased the risk of death from COVID-19 infection. Moreover, the rates of fever, cough, and asthma were markedly lower in the deceased group compared with the recovered group of patients.

Conclusion

The association between the different blood groups with the prevalence and mortality of COVID-19 among infected patients has yet to be elucidated as we found no significant differences in the observed versus expected distribution of ABO phenotypes among the included cases. The prevalence of RDS, pneumonia, and respiratory failure was found higher among hospitalized COVID-19 patients in the deceased group. However, other factors such as fever, cough, and asthma appeared to be more significantly lower than in the recovered group.
A Novel Approach for Repetitive Dislocation of Transvenous Left Ventricular Leads During Cardiac Resynchronization Therapy Implantation by the Loop Technique
Authors: Wu Hao-Yu , Li Shang-Jian , Yang Zheng , Chen Hai-Chao , You Peng-Hua , Cheng Gong
Published: June 2022

Cardiac resynchronization therapy (CRT) for heart failure requires transvenous insertion of a left ventricular pacing lead through the coronary sinus. However, repeated intraoperative dislocations often occur. Therefore, we describe a novel technique that uses the loop technique to treat patients with repeated intraoperative dislocations during transvenous left ventricular lead implantation to stabilize the lead in its final position. In five patients with repeated intraoperative dislocation during transvenous left ventricular lead implantation, the loop technique was successfully used to stabilize the lead in its final position. The pacing and sensing parameters were satisfactory in all patients at implantation and 12 months post-operatively. Compared with the pre-operative values, the 12-month post-operative values for the left ventricular ejection fraction were significantly increased and the left ventricular end systolic dimension and left ventricular end diastolic dimension were significantly decreased (P < 0.05). The left ventricular ejection fraction of these 5 patients increased by more than 15%. CRT significantly improved the left ventricular structure and function of these 5 patients. During the 1-, 3-, 6-, and 12-month follow-ups, no left ventricular lead dislocations were observed. This loop technique is safe and effective and can be considered for repeated intraoperative dislocation during transvenous left ventricular lead implantation through the coronary sinus of a CRT device.
Changes in Impaired Fasting Glucose and Borderline High Low-Density Lipoprotein-Cholesterol Status Alter the Risk of Cardiovascular Disease: A 9-Year Prospective Cohort Study
Authors: Wang Xianxuan , Zhou Yan-Feng , Huang Zegui , Yu Xinran , Chen Zekai , Cai Zefeng , Lan Yulong , Li Werijian , Cai Zhiwei , Fang Wei , Chen Guanzhi , Wu Weiqiang , Wu Shouling , Chen Youren
Published: June 2022

Background

We aimed to characterize the relationships of the changes in impaired fasting glucose (IFG) and borderline high low-density lipoprotein-cholesterol (LDL-C) status with cardiovascular disease (CVD).

Methods

A total of 36,537 participants who did not have previous CVD, diabetes mellitus, or high LDL-C (≥ 4.1 mmol/L), nor were taking lipid-lowering drugs were recruited from the Kailuan study. The participants were allocated to six groups according to their baseline and follow-up fasting blood glucose (FBG) and LDL-C concentrations: (1) both were normal; (2) both normal at baseline, one abnormality subsequently; (3) both normal at baseline, both abnormal subsequently; (4) at least one abnormality that became normal; (5) at least one abnormality at baseline, a single abnormality subsequently; and (6) at least one abnormality, two abnormalities subsequently. The outcomes were CVD and subtypes of CVD (myocardial infarction and stroke). Multiple Cox regression models were used to calculate adjusted hazard ratio (HR) and confidence interval (95% CI).

Results

During a median follow-up period of 9.00 years, 1,753 participants experienced a CVD event. After adjustment for covariates, participants with IFG in combination with a borderline high LDL-C status at baseline and follow-up had higher risks of CVD (HR: 1.52; 95% CI: 1.04–2.23 and HR: 1.38, 95% CI: 1.13–1.70, respectively) compared with those with normal fasting blood glucose and LDL-C. Compared with participants that remained normal, those who changed from normality to having two abnormalities were at a higher risk of CVD (HR: 1.26; 95% CI: 0.98–1.61), as were those who changed from at least one abnormality to two abnormalities (HR: 1.48, 95% CI: 1.02–2.15).

Conclusion

Changes in IFG and borderline high LDL-C status alter the risk of CVD and its subtype, implying that it is important to focus on such individuals for the prevention and control of CVD.
Aquifer-Peatland Hydrological Connectivity and Controlling Factors in Boreal Peatlands
Authors: Lambert C. , Larocque M. , Gagné S. , Garneau M.
Published: June 2022

The conditions in which groundwater inflow occurs in boreal peatlands and its contribution to peatland water balance are still poorly understood. The objectives of this research were to quantify the hydrological connectivity between a surficial aquifer and a peatland, and to identify the controlling factors in boreal peatlands of north-central Quebec (Canada). The peatlands were instrumented with piezometers and groundwater levels were monitored during two growing seasons. Hydraulic conductivities were measured on peat cores andin situ,groundwater inflows and outflows were calculated using the Darcy equation. The peatland water budgets were simulated for the two peatlands with a steady-state groundwater flow model to verify flow hypotheses, to quantify unmeasured flows and to explore recharge scenarios leading to changes in connectivity. The two peatlands have contrasted water budgets, with recharge representing the largest inflow (78%) and subsurface runoff representing the largest outflow (85%) the peatland with the smallest catchment area (Misask). The peatland with the largest catchment area (Cheinu) is also located downgradient within the regional watershed. Its inflows are dominated by groundwater (56%) and its outflows are mostly towards subsurface runoff (74%). The two peatlands are in conditions of precipitation excess and a recharge reduction would not affect their peatland heads markedly (<10 cm). However, recharge changes could induce larger modifications in groundwater inflows and outflows for the peatland with a larger catchment area. The dominating peatland hydrological functions are thus contrasted at the two sites, and it is hypothesized that the water table depths thresholds triggering changes between storage, transmission and runoff functions are also different. Although further studies remain to be done to understand how hydrological conditions change through time, and ultimately what are the long-term impacts of a changing climate on hydrology, vegetation and carbon accumulation, this work shows that understanding peatland hydrology requires to consider hydrological conditions beyond the peatland limits.
Long-Term Trends in Black Carbon and Aerosol Optical Depth Over the Central Himalayas: Potential Causes and Implications
Authors: Joshi Hema , Naja Manish , Srivastava Priyanka , Gupta Tarun , Gogoi Mukunda M. , Suresh Babu S.
Published: June 2022

Continuous ground-based observations of aerosols over the Himalayan region are highly beneficial in studying aerosol trends over the complex geographic terrain. This study presents the results from continuous long-term observations (2004–2016) of aerosols over a high-altitude site in the central Himalayas – Nainital, quantifying multihued aspects of black carbon (BC) and columnar aerosol optical depth (AOD). The results reveal that BC and AOD have a positive trend of 23.04 ± 3.00 ng m−3 year−1 and 0.0076 ± 0.0003 year−1, respectively. Simultaneously, a positive trend of 0.0066 ± 0.0059 year−1 is observed in the Angstrom exponent, thus indicating an increase in anthropogenic aerosols. The satellite observations covering a broader region around Nainital also depicted increasing trends in AOD (0.0042–0.0074 year−1), absorbing aerosol optical depth (0.0001 ± 0.0001 year−1) and aerosol index (0.0131 ± 0.0019 year−1), along with a slight decline in single scattering albedo (−0.0004 year−1). These results suggest that aerosols of absorbing nature might have increased over this region in recent times. Investigation of the AOD ratio, obtained from aerosol vertical profiles, revealed an increasing trend in aerosol load below 1 km. The observed trends in aerosols are found to be associated with enhanced biomass burning activity, reflected in terms of the positive trend in fire count ∼38.65 ± 5.88 year−1 over the region.
How Might We Raise Interest in Robotics, Coding, Artificial Intelligence, STEAM and Sustainable Development in University and On-the-Job Teacher Training?
Authors: Henze Jannik , Schatz Carina , Malik Shalina , Bresges André
Published: June 2022

Schools are searching for strategies to foster 4C competencies (Creativity, Cooperation, Communication and Critical Thinking) in children. Scientific Reasoning, Critical Thinking, and the ability to debunk myths are already important competencies that can be fostered with science education. How can we approach the majority of seventh grade students in a given school to create innovative approaches for the future, and leverage their skills in science, art and (digital) technology along the path? And are the teachers ready to guide them on this path? This article focuses on the questions: how did the teachers adopt both the STEAM approach, and the use of digital tools while being supervised by researchers and student teachers and how did this change their beliefs about technology in education. As a pathway, we aimed to connect Robotics, Coding, Artificial Intelligence (AI) with the Sustainable Development Goals (SDGs) of the United Nations. To end poverty, protect the environment, and ensure that all people enjoy peace and prosperity by 2030, the SDGs are incorporated into national policies and school curricula. With this, citizens, teachers, and governments alike struggle with strategies on how these goals can be reached by 2030, facing the growing challenges in an ever increasingly complex and insecure world. It is clear that technology will take a dominant role in this development. Based on the STEAM paradigm and the 5E approach of the Biological Sciences Curriculum Study (BSCS), we have developed a pedagogical concept that encompasses both the technological aspects, AI and the SDGs. We tested this concept as part of an on-the-job teacher training project with 60 education science student teachers and 8 teachers in their classrooms, together with their 116 7th grade students and found out that STEAM-based projects with a sixth phase in addition to the 5E approach can be carried out promisingly with the help of digital creativity tools. We found that the 5E model with an additional sixth phase is well suited for bringing STEAM into the classroom.
Discovering a Four-Gene Prognostic Model Based on Single-Cell Data and Gene Expression Data of Pancreatic Adenocarcinoma
Authors: Huang Weizhen , Li Jun , Zhou Siwei , Li Yi , Yuan Xia
Published: June 2022

Background

Pancreatic cancer has a 5-year overall survival lower than 8%. Pancreatic adenocarcinoma (PAAD) is the most common type. This study attempted to explore novel molecular subtypes and a prognostic model through analyzing tumor microenvironment (TME).

Materials and Methods

Single-cell RNA sequencing (scRNA-seq) data and expression profiles from public databases were downloaded. Three PAAD samples with single-cell data and 566 samples with gene expression data were included. Seurat was used to identify cell subsets. SVA merged and removed batch effects from multichip datasets. CIBERSORT was used to evaluate the components of different cells in transcriptome, ConsensusClusterPlus was used to identify molecular subtypes, and gene set enrichment analysis was used for functional enrichment analysis. LASSO Cox was performed to construct dimensionality reduction and prognosis model.

Results

Memory B cells (MBCs) were identified to be significantly with PAAD prognosis. Two immune subtypes (IS1 and IS2) with distinct overall survival were constructed. Forty-one DEGs were identified between IS1 and IS2. Four prognostic genes (ANLN, ARNTL2, SERPINB5, and DKK1) were screened to develop a prognostic model. The model was effective in classifying samples into high-risk and low-risk groups with distinct prognosis. Three subgroups of MBCs were identified, where MBC_0 and MBC_1 were differentially distributed between IS1 and IS2, high-risk and low-risk groups.

Conclusions

MBCs were closely involved in PAAD progression, especially MBC_0 and MBC_1 subgroups. The four-gene prognostic model was predictive of overall survival and could guide immunotherapy for patients with PAAD.
Global Trends in Research of Androgen Receptor Associated With Breast Cancer From 2011 to 2020: A Scientometric Analysis
Authors: Chen Lingzhi , Liu Yiyuan , Cai Jiehui , Ji Zeqi , Zou Juan , Chen Yaokun , Wu Jinyao , Zheng Daitian , Zheng Jiehua , Chen Yexi , Li Zhiyang
Published: June 2022

Recently, the androgen receptor has been found as a potential prognostic index and therapeutic target for breast cancer. To reveal the current research status and hotspots in this area, we analyzed the characteristics of related publications from 2011 to 2020. All related publications from 2011 to 2020 were retrieved from the Web of Science. Biblioshiny, VOSviewer, and CiteSpace V were applied to obtain the information on annual publications and citations, the highest yielding countries and authors, influential journals and articles, as well as hot keywords. In total, 2,118 documents, including 1,584 original articles and 534 reviews, were retrieved. Annual publication output was rich from 2014 to 2018, reaching the top in 2017. A systematic review written by Lehman et al. in 2011 was the most-cited document and reference. The United States was the leading country with the maximum number of publications, citations, and link strengths with other countries. The journal publishing the most was Oncotarget. Lehmann was the author who had the highest link strengths with other authors. The most highlighted keywords were “androgen receptor” (n = 1,209), “breast cancer” (n = 690), “expression” (n = 545), “breast cancer” (n = 410), “prostate cancer” (n = 290), and so on, revealing the trend from molecular mechanism level to therapeutic use level. The androgen receptor plays a significant role in the development of breast cancers, whereas its therapeutic value seems to be controversial and needs further study. With the help of a scientometric analysis in this field, researchers can clarify the current research status and hotspots worth fully exploring.
Tell Us a Story Granddad: Age and Origin of an Iconic Australian Lungfish
Authors: Mayne Benjamin , Espinoza Tom , Roberts David
Published: June 2022

The modern discovery of the Australian lungfish (Neoceratodus forsteri) by European settlers in 1870 was considered one of the most important events in natural history by leading international scientists and naturalists of that time. Its distinct evolutionary lineage and unique extant morphological characteristics fostered the romantic zoological moniker “living fossil”. Although N. forsteri were suspected of being long-lived, a reliable estimate of maximum age has remained elusive. Maximum age is critical to inform wildlife management and conservation efforts, including the use of population viability models. To estimate the maximum age for N. forsteri, we sourced DNA from “Granddad”, the presumed longest-living lungfish known in a zoological park and utilised an epigenetic ageing clock developed for N. forsteri. This lungfish specimen was gifted to the Chicago John G. Shedd Aquarium from Australia in 1933 and lived there for 84 years until death in 2017. We estimated the age of Granddad at death to be 109 years (±6 years), confirming N. forsteri as a true centenarian species. Genotyping also revealed the natal origin of Granddad to be the Burnett River, Queensland, Australia, the location of the species’ original discovery in 1870. We demonstrate the application of novel molecular techniques to a unique long-lived and captive-raised specimen, to improve estimates of maximum age for the species, and to identify natal origin. This information will support future conservation efforts for this iconic yet endangered species.
Adsorption Characteristics of Three Types of Soils on Biogas Slurry Ammonium Nitrogen
Authors: Wang Zichen , Zhang Liping , Sun Guofeng , Zhou Wei , Sheng Jing , Ye Xiaomei , Olaniran Ademola O. , Kana E. B. Gueguim
Published: June 2022

Using farmland to digest biogas slurry is an effective measure to overcome the bottleneck of sewage treatment in livestock and poultry farms. However, there is limited research on the soil adsorption characteristics of biogas slurry ammonium nitrogen (NH4+-N). In addition, the maximum adsorption capacity (Qm) of farm soil is unclear. In this study, three typical farmland tillage layer soils (silty loam, loam, and sandy loam) were used to analyze adsorption characteristics through adsorption kinetics experiments (adsorption for 0.25, 0.5, 1, 2, 4, 6, 12, 18, or 24 h with NH4+-N concentrations of 42.90 mg/L) and thermodynamic experiments (adsorption for 3 days with NH4+-N concentrations of 54.25, 88.66, 105.85, 133.71, 178.80, 273.54, and 542.87 mg/L). The Qm value was fitted by models, and its relationship with soil properties was discussed. The results showed the following: 1) the adsorption of biogas slurry NH4+-N by the three types of soils was a composite kinetic process that comprised two stages of rapid and slow reactions. Rapid adsorption predominantly occurred within 0–1 h, and the adsorption capacity accounted for 35.24%–43.55% of the total adsorption. The ExpAssoc equation produced a good fit for the adsorption kinetic behavior in the three soil types. 2) The equilibrium adsorption could be described by the Langmuir equation, the Freundlich equation, the PlPlatt model, and the Langevin model isotherm, among which the Langevin model had the best fit, with a coefficient of determination R2 close to 1. The theoretical saturated Qm fitting results of NH4+-N were 1038.41–1372.44 mg/kg in silty loam, 840.85–1157.60 mg/kg in loam, and 412.33–481.85 mg/kg in sandy loam. The optimal values were 1108.55, 874.86, and 448.35 mg/kg for silty loam, loam, and sandy loam, respectively. 3) The Qm value was significantly positively correlated with soil organic matter, total nitrogen, available phosphorus, available potassium, cation exchange capacity, and particle content of 0.02–0.002 mm (p < 0.01), but significantly negatively correlated with soil pH (p < 0.05). This study can provide a reference for the safe application of biogas slurry on farmland.
Evaluating the Causal Effects of Gestational Diabetes Mellitus, Heart Disease, and High Body Mass Index on Maternal Alzheimer’s Disease and Dementia: Multivariable Mendelian Randomization
Authors: Sheng Jie , Liu Jundong , Chan Kei Hang Katie
Published: June 2022

Introduction: Gestational diabetes mellitus (GDM), heart disease (HD) and high body mass index (BMI) are strongly related to Alzheimer’s disease (AD) dementia in pregnant women. Therefore, we aimed to determine the total effects of GDM, heart disease, and high BMI on maternal AD dementia.

Methods: We used data from the genome-wide association studies of European populations including more than 30,000 participants. We performed two-sample Mendelian randomization (MR) and multivariable MR (MVMR) to systematically estimate the direct effects of GDM, HD, and high BMI on maternal AD and dementia. Multiple sensitivity analyses involving classical MR approaches and expanded MR-pleiotropy residual sum and outlier analysis.

Results: In two-sample MR analysis, the inverse-variance weighted method in our study demonstrated no significant causality between GDM and maternal dementia (β = −0.006 ± 0.0026, p = 0.82). This method also revealed no significant causality between high BMI and maternal dementia (β = 0.0024 ± 0.0043, p = 0.57), and it was supported by the MR-Egger regression results, which showed no causal effect of high BMI on maternal Alzheimer’s disease and dementia (β = 0.0027 ± 0.0096, p = 0.78). The IVW method showed no significant causal relationship between maternal HD and maternal Alzheimer’s disease and dementia (β = −0.05 ± 0.0042, p = 0.117) and MR-Egger regression analysis gave a similar result (β = −0.12 ± 0.0060, p = 0.079). In MVMR analysis, we found no significant causal relationship between GDM, high BMI, or HD and maternal Alzheimer’s disease and dementia (p = 0.94, 0.82, and 0.13, respectively). Thus, the MVMR estimates were consistent with our results from the two-sample MR analysis. We confirmed that these results showed no horizontal pleiotropy and enhanced the robustness of our results through multiple sensitivity analyses.

Conclusion: In two-sample MR analysis, we found no significant causal relationship between GDM, HD, high BMI and maternal AD and dementia. These results differed from previous observational studies showing HD is a significant predictor of dementia. MVMR analysis supported no significant causal relationship between GDM, HD, high BMI and maternal AD and dementia. Sensitivity analysis broadly increased the robustness of two-sample MR and MVMR analysis results.
The Hypoxic Landscape Stratifies Gastric Cancer Into 3 Subtypes With Distinct M6a Methylation and Tumor Microenvironment Infiltration Characteristics
Authors: Ning Zhi-kun , Hu Ce-gui , Liu Jiang , Tian Hua-kai , Yu Zhong-lin , Zhou Hao-nan , Li Hui , Zong Zhen
Published: June 2022

The interaction between hypoxia and RNA N6-methyladenosine (m6A) is an emerging focus of investigation. However, alterations in m6A modifications at distinct hypoxia levels remain uncharacterized in gastric cancer (GC). Unsupervised hierarchical clustering was performed to stratify samples into different clusters. Differentially expressed gene analysis, univariate Cox proportional hazards regression analysis, and hazard ratio calculations were used to establish an m6A score to quantify m6A regulator modification patterns. After using an algorithm integrating Least absolute shrinkage and selection operator (LASSO) and bootstrapping, we identified the best candidate predictive genes. Thence, we established an m6A-related hypoxia pathway gene prognostic signature and built a nomogram to evaluate its predictive ability. The area under the curve (AUC) value of the nomogram was 0.811, which was higher than that of the risk score (AUC=0.695) and stage (AUC=0.779), suggesting a high credibility of the nomogram. Furthermore, the clinical response of anti-PD-1/CTLA-4 immunotherapy between high- and low-risk patients showed a significant difference. Our study successfully explored a brand-new GC pathological classification based on hypoxia pathway genes and the quantification of m6A modification patterns. Comprehensive immune analysis and validation demonstrated that hypoxia clusters were reliable, and our signature could provide a new approach for clinical decision-making and immunotherapeutic strategies for GC patients.
Selective Expansion of Tregs Using the IL-2 Cytokine Antibody Complex Does Not Reverse Established Alopecia Areata in C3H/HeJ Mice
Authors: Lee Eunjin , Kim Mingyu , Lee You Jeong
Published: June 2022

Alopecia areata (AA) is an autoimmune disease mediated by NKG2D-expressing cytotoxic T lymphocytes destroying hair follicles in the skin. It is one of the most common autoimmune diseases, but there is no effective treatment modality approved by the FDA. Regulatory T cells (Tregs) are crucial for suppressing autoreactive T cells, and in the skin, they promote hair growth by inducing anagen. Based on this, we tested the therapeutic potential of expanded Tregs in AA using the C3H/HeJ mouse model. In mice with AA, NKG2D-expressing CD8 T cells widely infiltrate both haired and hairless skin areas, which have tissue-resident memory T-cell phenotypes. Tregs in the skin express CD25, CTLA-4, GATA-3, and Jagged1 and efficiently proliferate with IL-2 cytokine antibody complex. However, expanding Tregs in the skin did not induce anagen in normal mice, indicating that they are necessary but not sufficient for anagen induction. Also, they fail to suppress autoreactive CD8 T cells in the skin to reverse established AA in C3H/HeJ mice. These results suggest that Treg expansion alone is not sufficient for AA treatment, and combined immunotherapy is required.
Non-HLA Gene Polymorphisms in the Pathogenesis of Type 1 Diabetes: Phase and Endotype Specific Effects
Authors: Laine Antti-Pekka , Valta Milla , Toppari Jorma , Knip Mikael , Veijola Riitta , Ilonen Jorma , Lempainen Johanna
Published: June 2022

The non-HLA loci conferring susceptibility to type 1 diabetes determine approximately half of the genetic disease risk, and several of them have been shown to affect immune-cell or pancreatic β-cell functions. A number of these loci have shown associations with the appearance of autoantibodies or with progression from seroconversion to clinical type 1 diabetes. In the current study, we have re-analyzed 21 of our loci with prior association evidence using an expanded DIPP follow-up cohort of 976 autoantibody positive cases and 1,910 matched controls. Survival analysis using Cox regression was applied for time periods from birth to seroconversion and from seroconversion to type 1 diabetes. The appearance of autoantibodies was also analyzed in endotypes, which are defined by the first appearing autoantibody, either IAA or GADA. Analyzing the time period from birth to seroconversion, we were able to replicate our previous association findings atPTPN22,INS, andNRP1.Novel findings included associations withERBB3,UBASH3A,PTPN2, andFUT2. In the time period from seroconversion to clinical type 1 diabetes, prior associations withPTPN2,CD226, andPTPN22were replicated, and a novel association withSTAT4was observed. Analyzing the appearance of autoantibodies in endotypes, thePTPN22association was specific for IAA-first. In the progression phase,STAT4was specific for IAA-first andERBB3to GADA-first. In conclusion, our results further the knowledge of the function of non-HLA risk polymorphisms in detailing endotype specificity and timing of disease development.
Type-2 Cytokines Promote the Secretion of the Eosinophil–Attractant CCL26 by Intestinal Epithelial Cells in Food-Sensitized Patients
Authors: Vaccaro Julián , Canziani Karina Eva , Guzmán Luciana , Bernedo Viviana , García Marcela , Altamirano Eugenia Margarita , Feregotti Emanuel , Curciarello Renata , Muglia Cecilia Isabel , Docena Guillermo Horacio
Published: June 2022

Several inflammatory processes of the bowel are characterized by an accumulation of eosinophils at inflammation sites. The mechanisms that govern mucosal infiltration with eosinophils are not fully understood. In this work, we studied the colorectal polyp-confined tissue containing eosinophils and we hypothesized that intestinal epithelial cells are the cell source of eotaxin-3 or CCL26, a potent chemoattractant for eosinophils. We analyzed colorectal polyps (n=50) from pediatric patients with rectal bleeding by H&E staining and eosin staining, and different pro-inflammatory cytokines were assessed by RT-qPCR and ELISA. IgE and CCL26 were investigated by RT-qPCR, ELISA and confocal microscopy. Finally, the intracellular signaling pathway that mediates the CCL26 production was analyzed using a kinase array and immunoblotting in human intestinal Caco-2 cell line. We found a dense cell agglomeration within the polyps, with a significantly higher frequency of eosinophils than in control adjacent tissue. IL-4 and IL-13 were significantly up-regulated in polyps and CCL26 was elevated in the epithelial compartment. Experiments with Caco-2 cells showed that the type-2 cytokine IL-13 increased STAT3 and STAT6 phosphorylation and eotaxin-3 secretion. The addition of the blocking antibody Dupilumab or the inhibitor Ruxolitinib to the cytokine-stimulated Caco-2 cells diminished the CCL26 secretion to basal levels in a dose-dependent manner. In conclusion, our findings demonstrate a high frequency of eosinophils, and elevated levels of type-2 cytokines and eotaxin-3 in the inflammatory stroma of colorectal polyps from pediatric patients. Polyp epithelial cells showed to be the main cell source of CCL26, and IL-13 was the main trigger of this chemokine through the activation of the STAT3/STAT6/JAK1-2 pathway. We suggest that the epithelial compartment actively participates in the recruitment of eosinophils to the colonic polyp-confined inflammatory environment.
The Next Decade of Seismic Oceanography: Possibilities, Challenges and Solutions
Authors: Dickinson Alex , Gunn Kathryn L.
Published: June 2022

Seismic reflection profiling of thermohaline structure has the potential to transform our understanding of oceanic mixing and circulation. This profiling, which is known as seismic oceanography, yields acoustic images that extend from the sea surface to the sea bed and which span horizontal distances of hundreds of kilometers. Changes in temperature and salinity are detected in two, and sometimes three, dimensions at spatial resolutions of ~O(10) m. Due to its unique combination of extensive coverage and high spatial resolution, seismic oceanography is ideally placed to characterize the processes that sustain oceanic circulation by transferring energy between basin-scale currents and turbulent flow. To date, more than one hundred research papers have exploited seismic oceanographic data to gain insight into phenomena as varied as eddy formation, internal waves, and turbulent mixing. However, despite its promise, seismic oceanography suffers from three practical disadvantages that have slowed its development into a widely accepted tool. First, acquisition of high-quality data is expensive and logistically challenging. Second, it has proven difficult to obtain independent observational constraints that can be used to benchmark seismic oceanographic results. Third, computational workflows have not been standardized and made widely available. In addition to these practical challenges, the field has struggled to identify pressing scientific questions that it can systematically address. It thus remains a curiosity to many oceanographers. We suggest ways in which the practical challenges can be addressed through development of shared resources, and outline how these resources can be used to tackle important problems in physical oceanography. With this collaborative approach, seismic oceanography can become a key member of the next generation of methods for observing the ocean.
Compact Fano-Type Liquid Metamaterial Resonator for High-Precision Temperature Sensing
Authors: Chen Haotian
Published: June 2022

In this paper, a liquid metal mercury (Hg) based high quality-factor (Q-factor) liquid electromagnetic metamaterial unit, the Hg Fano resonator, is designed for the high-precision temperature sensing application. Such Fano resonance in the Hg-resonator is excited by the microstrip-line coupling and the resonance frequency is sensitive to the background temperature changes. Based on the high Q-factor and the temperature-sensitive features of Hg-Fano resonator, the high-precision temperature sensing performance is discussed and achieved, with numerical and experimental demonstrations. The experimental sensitivity of 11.7 MHz/°C and figure-of-merit (FOM) of 0.4/°C are obtained. The proposed compact Hg-Fano resonator-based sensor can be widely used for the wireless temperature sensing area.
Oral Tofacitinib and Systemic Corticosteroids, Alone or in Combination, in Patients With Moderate-to-Severe Alopecia Areata: A Retrospective Study
Authors: Zhang Wenxin , Li Xiangqian , Chen Baifu , Zhang Jianzhong , Torres-Culala Kara Melissa T. , Zhou Cheng
Published: June 2022

Introduction

Alopecia areata (AA) is an autoimmune hair loss mediated by CD8 + T cells. Treatment for moderate-to-severe AA is still challenging. Janus kinase inhibitors, such as tofacitinib, have been recently investigated as a promising treatment option for AA. Evidence on the combination use of oral tofacitinib and systemic corticosteroids (SCs) for AA is still lacking.

Objective

To compare the efficacy and safety of monotherapy of oral tofacitinib and SCs, as well as their combination in patients with moderate-to-severe AA.

Methods

Patients with moderate-to-severe AA, who have been treated with at least 3 months of monotherapy of tofacitinib or SCs, or in their combination, were included in this study. The efficacy and adverse events of these treatments were retrospectively analyzed.

Results

Sixty-one patients with moderate-to-severe AA were included in this study. There were 12 (66.7%) of 18 patients in the SCs group, 12 (60.0%) of 20 patients in the tofacitinib group, and 18 (78.3%) of 23 patients achieved SALT50, with no significant difference among the three groups. The ratio of patients who achieved SALT50 was significantly higher in patients with a short duration of current hair loss episode (≤2 years) than in those with a duration of current hair loss episode (>2 years) in all the three groups. There were 66.7% patients in the SCs group, 35.0% patients in the tofacitinib group, and 56.5% patients in the combined group that showed adverse effects.

Conclusion

Tofacitinib was an effective treatment for patients with moderate-to-severe AA, and it was more tolerated than SCs. A combination of tofacitinib and SCs may have higher efficacy than SCs alone. Efficacy significantly decreased in patients with a current episode of disease for more than 2 years.
Hypertonic Solution in Severe COVID-19 Patient: A Potential Adjuvant Therapy
Authors: Gennari-Felipe Matheus , Borges Leandro , Dermargos Alexandre , Weimann Eleine , Curi Rui , Pithon-Curi Tania Cristina , Hatanaka Elaine
Published: June 2022

Coronavirus disease 2019 (COVID-19) features hyper-inflammation, cytokine storm, neutrophil function changes, and sodium chloride (NaCl) homeostasis disruption, while the treatment with NaCl hypertonic solutions (HS) controls electrolytic body homeostasis and cell functions. HS treatment is a simple, popular, economic, and feasible therapy to regulate leukocyte function with a robust anti-inflammatory effect in many inflammatory diseases. The purpose of this narrative review is to highlight the knowledge on the use of HS approaches against viral infection over the past years and to describe the mechanisms involved in the release of neutrophil extracellular traps (NETs) and production of cytokine in severe lung diseases, such as COVID-19. We reported the consequences of hyponatremia in COVID-19 patients, and the immunomodulatory effects of HS, eitherin vitroorin vivo. We also described the relationship between electrolyte disturbances and COVID-19 infection. Although there is still a lack of clinical trials, hypertonic NaCl solutions have marked effects on neutrophil function and NETs formation, emerging as a promising adjuvant therapy in COVID-19.
A Combined Use of Rhizobacteria and Moringa Leaf Extract Mitigates the Adverse Effects of Drought Stress in Wheat (Triticum aestivum L.)
Authors: Lalarukh Irfana , Al-Dhumri Sami A. , Al-Ani Laith Khalil Tawfeeq , Hussain Rashid , Al Mutairi Khalid Awadh , Mansoora Nida , Amjad Syeda Fasiha , Abbas Mohamed H. H. , Abdelhafez Ahmed A. , Poczai Peter , Meena Khem Raj , Galal Tarek M.
Published: June 2022

Less nutrient availability and drought stress are some serious concerns of agriculture. Both biotic and abiotic stress factors have the potential to limit crop productivity. However, several organic extracts obtained from moringa leaves may induce immunity in plants under nutritional and drought stress for increasing their survival. Additionally, some rhizobacterial strains have the ability to enhance root growth for better nutrient and water uptake in stress conditions. To cover the knowledge gap on the interactive effects of beneficial rhizobacteria and moringa leaf extracts (MLEs), this study was conducted. The aim of this experimental study was to investigate the effectiveness of sole and combined use of rhizobacteria and MLEs against nutritional and drought stress in wheat. Nitrogen-fixing bacteriaPseudomonas aeruginosa(Pa) (108CFU ml–1) was inoculated to wheat plants with and without foliar-applied MLEs at two different concentrations (MLE 1 = 1:15 v/v and MLE 2 = 1:30 v/v) twice at 25 and 35 days after seed sowing (50 ml per plant) after the establishment of drought stress. Results revealed that Pa + MLE 2 significantly increased fresh weight (FW), dry weight (DW), lengths of roots and shoot and photosynthetic contents of wheat. A significant enhancement in total soluble sugars, total soluble proteins, calcium, potassium, phosphate, and nitrate contents validated the efficacious effect of Pa + MLE 2 over control-treated plants. Significant decrease in sodium, proline, glycine betaine, electrolyte leakage, malondialdehyde, hydrogen peroxide, superoxide dismutase (SOD), and peroxide (POD) concentrations in wheat cultivated under drought stress conditions also represents the imperative role of Pa + MLE 2 over control. In conclusion, Pa + MLE 2 can alleviate nutritional stress and drought effects in wheat. More research in this field is required to proclaim Pa + MLE 2 as the most effective amendment against drought stress in distinct agroecological zones, different soil types, and contrasting wheat cultivars worldwide.
Network Analysis Reveals the Combination of Controlled-Release and Regular Urea Enhances Microbial Interactions and Improves Maize Yields
Authors: Ji Peng-tao , Du Xiong , Zhou Jin-chao , Peng Yujuan , Li Xiang-ling , Tao Pei-jun , Zhang Yue-chen
Published: June 2022

Increased complexity of microbial networks can contribute to increased biodiversity and multifunctionality and thus crop productivity. However, it is not clear which combination ratio of regular and controlled-release urea will increase the soil microbial community complexity and improve maize yield in the North China Plain. To address this knowledge gap, a 2-year field experiment was conducted to explore the effects of the combination of regular (U) and controlled release (S) urea ratios [no fertilizer control (CT), regular urea alone (U), controlled-release urea alone (S), controlled-release urea mixed with regular urea 3:7 (SU3), controlled-release urea mixed with regular urea 5:5 (SU5), and controlled-release urea mixed with regular urea 7:3 (SU7)] on XianYu 688 yield and its rhizosphere and bulk soil microbial community composition and network complexity at different fertility stages. The combination of controlled-release and regular urea increased the N agronomic efficiency, N partial factors productivity, maize yield, and grain number per spike, with the maximum maize yield (9,186 kg ha–1) being achieved when the ratio of controlled-release urea to regular urea was 3:7 (SU3, p < 0.05). Maize yield increased by 13% in the SU3 treatment compared to the CT treatment. Rhizosphere soil microbial diversity remained stable at the silking stage of maize while increased at the physiological maturity stage of maize, with the increasing controlled-release to regular N fertilizer ratios (from 3:7 to 7:3, p < 0.05). This result suggests that a combination of regular and controlled-release N fertilizer can still substantially increase soil microbial diversity in the later stages of maize growth. The combination of controlled-release and regular urea is more effective in improving microbial network total links and average degree, and N agronomic efficiency (R2 = 0.79, p < 0.01), N partial factor productivity (R2 = 0.79, p < 0.01), spikes per unit area (R2 = 0.54, p < 0.05), and maize yield (R2 = 0.42, p < 0.05) increased with the microbial network complexity. This result indicates that the higher microbial network complexity is strongly associated with the higher N agronomic efficiency and N partial factors productivity and maize yield. In conclusion, the ratio of controlled-release to regular urea at SU3 not only increases the yield of maize and N agronomic efficiency but also enhances microbial diversity and network complexity in the North China Plain.
Anthropogenic Disturbance Impacts Gut Microbiome Homeostasis in a Malagasy Primate
Authors: Wasimuddin  , Malik Hina , Ratovonamana Yedidya R. , Rakotondranary Solofomalala Jacques , Ganzhorn Jörg U. , Sommer Simone
Published: June 2022

Increasing anthropogenic disturbances in Madagascar are exerting constrains on endemic Malagasy lemurs and their habitats, with possible effects on their health and survival. An important component of health is the gut microbiome, which might be disrupted by various stressors associated with environmental change. We have studied the gut microbiome of gray-brown mouse lemurs (Microcebus griseorufus), one of the smallest Malagasy primates and an important model of the convergent evolution of diseases. We sampled two sites: one situated in a national park and the other consisting of a more disturbed site around human settlement. We found that more intense anthropogenic disturbances indeed disrupted the gut microbiome of this lemur species marked by a reduction in bacterial diversity and a shift in microbial community composition. Interestingly, we noted a decrease in beneficial bacteria (i.e., members of the Bacteroidaceae family) together with a slight increase in disease-associated bacteria (i.e., members of the Veillonellaceae family), and alterations in microbial metabolic functions. Because of the crucial services provided by the microbiome to pathogen resistance and host health, such negative alterations in the gut microbiome of mouse lemurs inhabiting anthropogenically disturbed habitats might render them susceptible to diseases and ultimately affecting their survival in the shrinking biodiversity seen in Madagascar. Gut microbiome analyses might thus serve as an early warning signal for pending threats to lemur populations.
Impact of Quorum Sensing and Tropodithietic Acid Production on the Exometabolome of Phaeobacter inhibens
Authors: Srinivas Sujatha , Berger Martine , Brinkhoff Thorsten , Niggemann Jutta
Published: June 2022

Microbial interactions shape ecosystem diversity and chemistry through production and exchange of organic compounds, but the impact of regulatory mechanisms on production and release of these exometabolites is largely unknown. We studied the extent and nature of impact of two signaling molecules, tropodithietic acid (TDA) and the quorum sensing molecule acyl homoserine lactone (AHL) on the exometabolome of the model bacterium Phaeobacter inhibens DSM 17395, a member of the ubiquitous marine Roseobacter group. Exometabolomes of the wild type, a TDA and a QS (AHL-regulator) negative mutant were analyzed via Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). Based on a total of 996 reproducibly detected molecular masses, exometabolomes of the TDA and QS negative mutant were ∼70% dissimilar to each other, and ∼90 and ∼60% dissimilar, respectively, to that of the wild type. Moreover, at any sampled growth phase, 40–60% of masses detected in any individual exometabolome were unique to that strain, while only 10–12% constituted a shared “core exometabolome.” Putative annotation revealed exometabolites of ecological relevance such as vitamins, amino acids, auxins, siderophore components and signaling compounds with different occurrence patterns in the exometabolomes of the three strains. Thus, this study demonstrates that signaling molecules, such as AHL and TDA, extensively impact the composition of bacterial exometabolomes with potential consequences for species interactions in microbial communities.
Optimal NPK Fertilizer Combination Increases Panax ginseng Yield and Quality and Affects Diversity and Structure of Rhizosphere Fungal Communities
Authors: Sun Jin , Luo Haoming , Yu Qian , Kou Baixin , Jiang Yuxin , Weng Lili , Xiao Chunping
Published: June 2022

Soil microorganisms affect crop rhizospheres via the transformation and transport of nutrients, which has important influences on soil fertility, carbon sequestration, and plant yield and health in agroecosystems. There are few reports on the effects of fertilizer application on the growth of Panax ginseng (C. A. Mey.) or the structure of its rhizosphere microbial communities. In this study, an orthogonal experimental design was used to explore the effects of nine different combinations of nitrogen (N), phosphorus (P), and potassium (K) fertilizers with different amounts and proportions on ginseng growth and accumulation of ginsenosides and the structure of rhizosphere soil fungal communities. Soil without fertilization was the control. With the combined application of NPK, ginseng growth and development increased. The fertilization scheme N3P1K3, with N fertilizer at 50 g·m−2, P fertilizer at 15 g·m−2, and K fertilizer at 60 g·m−2, had the most comprehensive benefit and significantly increased ginseng rhizome biomass and ginsenoside contents (Rg1, Re, Rf, Rg2, Rb1, Ro, Rc, Rb2, Rb3, and Rd). Amplicon sequencing showed that NPK application increased the diversity of fungal communities in ginseng rhizospheres, whereas richness was bidirectionally regulated by proportions and amounts of NPK. Ascomycota was the dominant fungal phylum in ginseng rhizosphere soil, and relative abundances decreased with combined NPK application. Combined NPK application increased the relative abundance of potential beneficial fungi, such as Mortierella, but decreased that of potentially pathogenic fungi, such as Fusarium. Correlation analysis showed that potential beneficial fungi were significantly positively correlated with ginseng rhizome yield and ginsenoside contents, whereas the opposite relation was observed with potential pathogenic fungi. Thus, in addition to directly increasing crop growth, precise NPK application can also increase crop adaptability to the environment by shaping specific microbial communities. The results of this study suggest that the combined effects of biotic and abiotic processes on agricultural production determine crop yield and quality.