bluuebunny/crossref_metadata_2025 huggingface dataset:
The Interplay Between Inflammation and Stromal Components in Pancreatic Cancer
Authors: Li Ying , Wang Jing , Wang Haiyan , Zhang Shaoqiang , Wei Yingxin , Liu Shanglong
Published: April 2022

Inflammation involves interactions between various immune cells, inflammatory cells, chemokines and cytokines in pancreatic cancer. Cancer cells as well as surrounding stromal and inflammatory cells establish an inflammatory tumor microenvironment (TME). Inflammation is closely associated with immunity. Meanwhile, immune cells are involved in both inflammation and immune response. Tumor-promoting inflammation and tumor-suppressive immunity are two main characteristics of the tumor microenvironment in pancreatic cancer. Yet, the mechanism of inflammation and immune response in pancreatic cancer development is still unclear due to the dual role of some cytokines and the complicated crosstalk between tumor and stromal components in TME. In this review, we outline the principal cytokines and stromal cells in the pancreatic TME that are involved in the tumor-promoting and immunosuppressive effects of inflammation, and discuss the interaction between inflammation and stromal components in pancreatic cancer progression. Moreover, the clinical approaches based on targeting TME in pancreatic cancer are also summarized. Defining the mechanisms of interplay between inflammation and stromal components will be essential for further development of anti-cancer therapies.
Joint Analysis of Microbial and Immune Cell Abundance in Liver Cancer Tissue Using a Gene Expression Profile Deconvolution Algorithm Combined With Foreign Read Remapping
Authors: Ai Dongmei , Xing Yonglian , Zhang Qingchuan , Wang Yishu , Liu Xiuqin , Liu Gang , Xia Li C.
Published: April 2022

Recent transcriptomics and metagenomics studies showed that tissue-infiltrating immune cells and bacteria interact with cancer cells to shape oncogenesis. This interaction and its effects remain to be elucidated. However, it is technically difficult to co-quantify immune cells and bacteria in their respective microenvironments. To address this challenge, we herein report the development of a complete a bioinformatics pipeline, which accurately estimates the number of infiltrating immune cells using a novel Particle Swarming Optimized Support Vector Regression (PSO-SVR) algorithm, and the number of infiltrating bacterial using foreign read remapping and the GRAMMy algorithm. It also performs systematic differential abundance analyses between tumor-normal pairs. We applied the pipeline to a collection of paired liver cancer tumor and normal samples, and we identified bacteria and immune cell species that were significantly different between tissues in terms of health status. Our analysis showed that this dual model of microbial and immune cell abundance had a better differentiation (84%) between healthy and diseased tissue. Caldatribacterium sp., Acidaminococcaceae sp., Planctopirus sp., Desulfobulbaceae sp.,Nocardia farcinica as well as regulatory T cells (Tregs), resting mast cells, monocytes, M2 macrophases, neutrophils were identified as significantly different (Mann Whitney Test, FDR< 0.05). Our open-source software is freely available from GitHub at https://github.com/gutmicrobes/PSO-SVR.git.
Immunologic Gene Sets Reveal Features of the Tumor Immune Microenvironment and Predict Prognosis and Immunotherapy Response: A Pan-Cancer Analysis
Authors: Pan Hongda , Pan Jingxin , Li Pei , Wu Jianghong
Published: April 2022

In the treatment of cancer, anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) immunotherapy has achieved unprecedented clinical success. However, the significant response to these therapies is limited to a small number of patients. This study aimed to predict immunotherapy response and prognosis using immunologic gene sets (IGSs). The enrichment scores of 4,872 IGSs in 348 patients with metastatic urothelial cancer treated with anti-PD-L1 therapy were computed using gene set variation analysis (GSVA). An IGS-based classification (IGSC) was constructed using a nonnegative matrix factorization (NMF) approach. An IGS-based risk prediction model (RPM) was developed using the least absolute shrinkage and selection operator (LASSO) method. The IMvigor210 cohort was divided into three distinct subtypes, among which subtype 2 had the best prognosis and the highest immunotherapy response rate. Subtype 2 also had significantly higher PD-L1 expression, a higher proportion of the immune-inflamed phenotype, and a higher tumor mutational burden (TMB). An RPM was constructed using four gene sets, and it could effectively predict prognosis and immunotherapy response in patients receiving anti-PD-L1 immunotherapy. Pan-cancer analyses also demonstrated that the RPM was capable of accurate risk stratification across multiple cancer types, and RPM score was significantly associated with TMB, microsatellite instability (MSI), CD8+ T-cell infiltration, and the expression of cytokines interferon-γ (IFN-γ), transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α), which are key predictors of immunotherapy response. The IGSC strengthens our understanding of the diverse biological processes in tumor immune microenvironment, and the RPM can be a promising biomarker for predicting the prognosis and response in cancer immunotherapy.
Aspects of the Complement System in New Era of Xenotransplantation
Authors: Miyagawa Shuji , Maeda Akira , Toyama Chiyoshi , Kogata Shuhei , Okamatsu Chizu , Yamamoto Riho , Masahata Kazunori , Kamiyama Masafumi , Eguchi Hiroshi , Watanabe Masahito , Nagashima Hiroshi , Ikawa Masahito , Matsunami Katsuyoshi , Okuyama Hiroomi
Published: April 2022

After producing triple (Gal, H-D and Sda)-KO pigs, hyperacute rejection appeared to no longer be a problem. However, the origin of xeno-rejection continues to be a controversial topic, including small amounts of antibodies and subsequent activation of the graft endothelium, the complement recognition system and the coagulation systems. The complement is activated via the classical pathway by non-Gal/H-D/Sda antigens and by ischemia-reperfusion injury (IRI), via the alternative pathway, especially on islets, and via the lectin pathway. The complement system therefore is still an important recognition and effector mechanism in xeno-rejection. All complement regulatory proteins (CRPs) regulate complement activation in different manners. Therefore, to effectively protect xenografts against xeno-rejection, it would appear reasonable to employ not only one but several CRPs including anti-complement drugs. The further assessment of antigens continues to be an important issue in the area of clinical xenotransplantation. The above conclusions suggest that the expression of sufficient levels of human CRPs on Triple-KO grafts is necessary. Moreover, multilateral inhibition on local complement activation in the graft, together with the control of signals between macrophages and lymphocytes is required.
Cumulative Evidence for Associations Between Genetic Variants in Interleukin 6 Receptor Gene and Human Diseases and Phenotypes
Authors: Zhang Min , Bai Ye , Wang Yutong , Cui Huijie , Tang Mingshuang , Wang Lanbing , Wang Xin , Gu Dongqing
Published: April 2022

Background

Genetic studies have linked polymorphisms in the interleukin 6 receptor (IL6R) gene to the risk of multiple human diseases and phenotypes, yet have reported inconsistent results. We aimed to synthesize current knowledge of variants in the IL6R gene on the risk of diseases and phenotypes.

Methods

We searched the Medline and Embase databases to identify relevant publications. Meta-analysis was performed utilizing DerSimonian and Laird random-effects model. We also graded cumulative evidence for significant associations. Furthermore, phenome-wide analyses and functional annotations were performed for variants with strong evidence.

Results

We included 155 studies for evaluating the associations between 80 polymorphisms in the IL6R gene and the risk of 102 human diseases and 98 phenotypes. We conducted 58 main meta-analyses, and 41 significant associations were identified. Strong evidence was assigned to 29 associations that investigated ten variants (rs2228145, rs4129267, rs7529229, rs4537545, rs7518199, rs4845625, rs4553185, rs4845618, rs4845371, and rs6667434) related to the risk of four cardiovascular diseases (coronary heart disease, coronary artery disease, atherosclerosis, and abdominal aortic aneurysms), four inflammatory diseases (rheumatoid arthritis, Crohn’s disease, dermatitis, and asthma), and concentration of four phenotypes (C-reactive protein, fibrinogen, IL-6, and sIL-6R). Furthermore, phenome-wide analysis verified that rs2228145 associated with asthma and dermatitis risk. Functional analyses indicated that these polymorphisms fall within exon, enhancer regions.

Conclusions

Our study comprehensively summarizes current data on the genetic architecture of the IL6R gene and highlights the pharmacological targeting potential of IL-6R on cardiovascular and inflammatory diseases.
Neonatal Immune Responses to Respiratory Viruses
Authors: Eddens Taylor , Parks Olivia B. , Williams John V.
Published: April 2022

Respiratory tract infections are a leading cause of morbidity and mortality in newborns, infants, and young children. These early life infections present a formidable immunologic challenge with a number of possibly conflicting goals: simultaneously eliminate the acute pathogen, preserve the primary gas-exchange function of the lung parenchyma in a developing lung, and limit long-term sequelae of both the infection and the inflammatory response. The latter has been most well studied in the context of childhood asthma, where multiple epidemiologic studies have linked early life viral infection with subsequent bronchospasm. This review will focus on the clinical relevance of respiratory syncytial virus (RSV), human metapneumovirus (HMPV), and rhinovirus (RV) and examine the protective and pathogenic host responses within the neonate.
Four Decades of Prophylactic EBV Vaccine Research: A Systematic Review and Historical Perspective
Authors: Escalante Gabriela M. , Mutsvunguma Lorraine Z. , Muniraju Murali , Rodriguez Esther , Ogembo Javier Gordon
Published: April 2022

Background

Epstein-Barr virus (EBV) is the causal agent of infectious mononucleosis and has been associated with various cancers and autoimmune diseases. Despite decades of research efforts to combat this major global health burden, there is no approved prophylactic vaccine against EBV. To facilitate the rational design and assessment of an effective vaccine, we systematically reviewed pre-clinical and clinical prophylactic EBV vaccine studies to determine the antigens, delivery platforms, and animal models used in these studies.

Methods

We searched Cochrane Library, ClinicalTrials.gov, Embase, PubMed, Scopus, Web of Science, WHO’s Global Index Medicus, and Google Scholar from inception to June 20, 2020, for EBV prophylactic vaccine studies focused on humoral immunity.

Results

The search yielded 5,614 unique studies. 36 pre-clinical and 4 clinical studies were included in the analysis after screening against the exclusion criteria. In pre-clinical studies, gp350 was the most commonly used immunogen (33 studies), vaccines were most commonly delivered as monomeric proteins (12 studies), and mice were the most used animal model to test immunogenicity (15 studies). According to an adaptation of the CAMARADES checklist, 4 pre-clinical studies were rated as very high, 5 as high, 13 as moderate quality, 11 as poor, and 3 as very poor. In clinical studies, gp350 was the sole vaccine antigen, delivered in a vaccinia platform (1 study) or as a monomeric protein (3 studies). The present study was registered in PROSPERO (CRD42020198440).

Conclusions

Four major obstacles have prevented the development of an effective prophylactic EBV vaccine: undefined correlates of immune protection, lack of knowledge regarding the ideal EBV antigen(s) for vaccination, lack of an appropriate animal model to test vaccine efficacy, and lack of knowledge regarding the ideal vaccine delivery platform. Our analysis supports a multivalent antigenic approach including two or more of the five main glycoproteins involved in viral entry (gp350, gB, gH/gL, gp42) and a multimeric approach to present these antigens. We anticipate that the application of two underused challenge models, rhesus macaques susceptible to rhesus lymphocryptovirus (an EBV homolog) and common marmosets, will permit the establishment ofin vivocorrelates of immune protection and attainment of more generalizable data.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=198440, identifier PROSPERO I.D. CRD4202019844.
Islet Encapsulation: New Developments for the Treatment of Type 1 Diabetes
Authors: Zhang Qi , Gonelle-Gispert Carmen , Li Yanjiao , Geng Zhen , Gerber-Lemaire Sandrine , Wang Yi , Buhler Leo
Published: April 2022

Islet transplantation is a promising approach for the treatment of type 1 diabetes (T1D). Currently, clinical islet transplantation is limited by allo - and autoimmunity that may cause partial or complete loss of islet function within a short period of time, and long-term immunosuppression is required to prevent rejection. Encapsulation into semipermeable biomaterials provides a strategy that allows nutrients, oxygen and secreted hormones to diffuse through the membrane while blocking immune cells and the like out of the capsule, allowing long-term graft survival and avoiding long-term use of immunosuppression. In recent years, a variety of engineering strategies have been developed to improve the composition and properties of encapsulation materials and to explore the clinical practicality of islet cell transplantation from different sources. In particular, the encapsulation of porcine islet and the co-encapsulation of islet cells with other by-standing cells or active ingredients for promoting long-term functionality, attracted significant research efforts. Hydrogels have been widely used for cell encapsulation as well as other therapeutic applications including tissue engineering, cell carriers or drug delivery. Here, we review the current status of various hydrogel biomaterials, natural and synthetic, with particular focus on islet transplantation applications. Natural hydrophilic polymers include polysaccharides (starch, cellulose, alginic acid, hyaluronic acid, chitosan) and peptides (collagen, poly-L-lysine, poly-L-glutamic acid). Synthetic hydrophilic polymers include alcohol, acrylic acid and their derivatives [poly (acrylic acid), poly (methacrylic acid), poly(acrylamide)]. By understanding the advantages and disadvantages of materials from different sources and types, appropriate materials and encapsuling methods can be designed and selected as needed to improve the efficacy and duration of islet. Islet capsule transplantation is emerging as a promising future treatment for T1D.
Case Report: Fulminant Celiac Disease With Combination Immune Checkpoint Therapy
Authors: Falade Ayo S. , Reynolds Kerry L. , Zubiri Leyre , Deshpande Vikram , Fintelmann Florian J. , Dougan Michael , Mooradian Meghan J.
Published: April 2022

Since the first approval of immune checkpoint inhibitors (ICIs) in 2011, these agents have rapidly become an integral treatment option across tumor types. However, with the increased adoption of ICIs, the incidence of immune-related adverse events (irAEs) continues to rise, and rare toxicity continues to be reported. Here, we present a case of a 70-year-old male patient with widespread metastatic melanoma who developed rapid onset anasarca and transaminitis after initiation of dual anti-PD-1/CTLA-4 inhibition with nivolumab and ipilimumab. An extensive workup was performed with serologies returning positive for anti-tissue transglutaminase immunoglobulin (tTG-IgA) and endoscopy revealing duodenal mucosal atrophy with duodenal biopsies confirming celiac disease. All symptoms resolved after initiation of a gluten-free diet without the addition of immunosuppression. This case highlights the importance of considering celiac disease in patients with suspected protein-losing enteropathy on ICI, the fulminant nature this uncommon irAE can present with, and underscores the broad differential clinicians must maintain when managing presumed irAEs.
Clinical Features and T Cell Immune Characteristics of Postpartum Hepatitis Flare in Pregnant Women With HBeAg-Positive Chronic HBV Infection
Authors: Song Aixin , Liu Yisi , Cao Zhenhuan , Lu Junfeng , Ren Shan , Zheng Sujun , Ma Lina , Hu Zhongjie , Lin Xiao , Li Hong , Zheng Yanhong , Chen Xinyue
Published: April 2022

Background

The extent of the increase in postpartum alanine transaminase (ALT) varies significantly among pregnant women in the immune tolerance stage of nucleoside analogue (NA) intervention, so this study is an attempt to analyze the clinical features of patients with and without postpartum hepatitis flare and preliminarily explore the differences in their immune functions.

Methods

Pregnant women with a gestational age of 24–28 w and in the immune tolerance stage of NA intervention for hepatitis B virus (HBV) infection were included and divided into a hepatitis group (Group 1) and a nonhepatitis group (Group 2) according to the ALT level at 6–12 w after childbirth. The clinical features were analyzed, and the phenotypes, functions, and cytokines of clusters of differentiation CD8+ T cells in the two groups of patients were detected using flow cytometry before and after childbirth.

Results

A total of 15 patients with postpartum hepatitis flare were enrolled in Group 1, and 10 matched patients were selected as controls for Group 2. Compared with the individuals in Group 2, the postpartum clinical features in Group 1 included a remarkable elevation of the ALT level on the basis of a relatively low HBV DNA level, usually accompanied by a decline in hepatitis B virus surface antigen levels as well as HBeAg levels. In addition, CD8+ T cell activation was enhanced after childbirth in Group 1. In particular, there was a notable difference in the activation of TEMRA subsets, and the frequency of CD8+ T cells expressing perforin and granzyme B increased.

Conclusion

The changes in the immune characteristics of CD8+ T cells may play a certain role in breaking down immune tolerance in patients with postpartum hepatitis flare, and the indexes related to activating and killing functions may help to indicate the population with hepatitis flare after childbirth.
Combining Bootstrapping Procedure and Citizen Science Data to Elucidate Waterbirds’ Dependence on Coastal Wetland
Authors: Duan Houlang , Yu Xiubo , Xia Shaoxia , Liu Yu
Published: April 2022

Coastal wetlands of the Yellow Sea and Bohai Sea, China, along the East Asian–Australasian Flyway (EAAF) migratory route provide important stopover sites for waterbirds. Natural wetland loss caused by external stress has posed serious threats to the population of waterbirds. Elucidating the extent to which species depend on natural wetland and providing conservation and management recommendations for species are important steps toward relieving such population declines. We created a natural landscape (NL) index along the coastal wetlands of the Yellow and Bohai Seas, China, using the inverse distance-weighted nearest-neighbor approach. Then, we used a bootstrapping procedure to combine the NL index with 11,485 occurrence records for 80 waterbird species attributed to four functional groups (shorebirds, ducks, herons, and gulls) to quantify species’ dependence on coastal natural wetlands. Twenty-seven out of the 80 species selected (16 shorebird, 3 duck, 4 heron, and 4 gull species) significantly depended on natural wetlands. The shorebirds [standardized effect size (SES) = 4.37] and herons (SES = 2.56) were more dependent on natural wetlands than the ducks (SES = −0.02) and gulls (SES = −3.22). The threatened species (those classified as critically endangered, endangered, vulnerable, or near threatened) showed significantly higher dependence on natural wetlands than the non-threatened species (t = 2.613, df = 78, p < 0.05). Of the 27 species showing significant dependence on natural wetlands, only nine species were listed as national protected species. Threatened species that highly depend on natural wetlands need more attention as these species could face greater risk due to natural wetland loss.
Control of Orthodontic Tooth Movement by Nitric Oxide Releasing Nanoparticles in Sprague-Dawley Rats
Authors: Crawford Derrick , Lau Tommy C. , Frost Megan C. , Hatch Nan E.
Published: April 2022

Orthodontic treatment commonly requires the need to prevent movement of some teeth while maximizing movement of other teeth. This study aimed to investigate the influence of locally injected nitric oxide (NO) releasing nanoparticles on orthodontic tooth movement in rats. Materials and Methods: Experimental tooth movement was achieved with nickel-titanium alloy springs ligated between the maxillary first molar and ipsilateral incisor. 2.2 mg/kg of silica nanoparticles containing S-nitrosothiol groups were injected into the mucosa just mesial to 1st molar teeth immediately prior to orthodontic appliance activation. NO release from nanoparticles was measured in vitro by chemiluminescence. Tooth movement was measured using polyvinyl siloxane impressions. Bones were analyzed by microcomputed tomography. Local tissue was assessed by histomorphometry. Results: Nanoparticles released a burst of NO within the first hours at approximately 10 ppb/mg particles that diminished by 10 × to approximately 1 ppb/mg particles over the next 1–4 days, and then diminished again by tenfold from day 4 to day 7, at which point it was no longer measurable. Molar but not incisor tooth movement was inhibited over 50% by injection of the NO releasing nanoparticles. Inhibition of molar tooth movement occurred only during active NO release from nanoparticles, which lasted for approximately 1 week. Molar tooth movement returned to control levels of tooth movement after end of NO release. Alveolar and long bones were not impacted by injection of the NO releasing nanoparticles, and serum cyclic guanosine monophosphate (cGMP) levels were not increased in animals that received the NO releasing nanoparticles. Root resorption was decreased and periodontal blood vessel numbers were increased in animals with appliances that were injected with the NO releasing nanoparticles as compared to animals with appliances that did not receive injections with the nanoparticles. Conclusion: Nitric oxide (NO) release from S-nitrosothiol containing nanoparticles inhibits movement of teeth adjacent to the site of nanoparticle injection for 1 week. Additional studies are needed to establish biologic mechanisms, optimize efficacy and increase longevity of this orthodontic anchorage effect.
Construction of Molybdenum Disulfide/Biological Structure Carbon Composite Photocatalysts and Their Photocatalytic Hydrogen Production
Authors: Wang Shujing , Ding Jiajing , Wang Chencheng , Li Wanfei , Chen Zhigang , Liu Chengbao , Chen Feng
Published: April 2022

The hydrothermal calcination method using bamboo leaves as the biological template, thiourea as the sulfur source, and molybdenum chloride as the molybdenum source was employed to synthesize the molybdenum disulfide/biological structure carbon (MoS2/C) photocatalytic composites with different concentrations of molybdenum chloride. The thermal decomposition behavior, surface morphology, phase structure, BET specific surface area, optical and photoluminescence properties, and photocatalytic activity of MoS2/C photocatalytic composites with different concentrations of molybdenum chloride were studied. The results showed that the optimal temperature for synthesizing MoS2/C photocatalytic composites is 700°C. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations show that the hydrothermal calcination method can be used to load MoS2 onto the biological carbon and form a structurally stable composite system. Analysis of optical and photoluminescence properties shows that the MoS2/C composites prepared by the hydrothermal calcination method with the concentration of molybdenum chloride of 0.20 mol/L exhibit a high charge transfer and separation efficiency. Photocatalytic experiments show that the MoS2/C composites prepared by the hydrothermal calcination method with the concentration of molybdenum chloride of 0.20 mol/L have a high photocatalytic activity and cyclic stability. This excellent synthesis strategy can be used to synthesize other photocatalytic hydrogen production materials.
A Novel Strategy for Predicting 72-h Mortality After Admission in Patients With Polytrauma: A Study on the Development and Validation of a Web-Based Calculator
Authors: Chen Song , Liu Meiyun , Feng Di , Lv Xin , Wei Juan
Published: April 2022

Background

Early and accessible screening of patients with polytrauma at a high risk of hospital death is essential. The purpose of this research was to seek an accurate and convenient solution to predict deaths occurring within 72 h after admission of these patients.

Methods

A secondary analysis was conducted on 3,075 patients with polytrauma from the Dryad database. We imputed missing values in eligible individuals with the k-nearest neighbor algorithm and then randomly stratified them into the training group (n = 2,461) and the validation group (n = 614) based on a proportion of 8:2. The restricted cubic spline, univariate, backward stepwise, and multivariate logistic regression methods were employed to determine the suitable predictors. Calibration and receiver operating characteristic (ROC) curves were applied to assess the calibration and discrimination of the obtained model. The decision curve analysis was then chosen as the measure to examine the clinical usage.

Results

Age, the Glasgow Coma Scale score, the Injury Severity Score, base excess, and the initial lactate level were inferred as independent prognostic factors related to mortality. These factors were then integrated and applied to construct a model. The performance of calibration plots, ROC curves, and decision curve analysis indicated that the model had satisfactory predictive power for 72-h mortality after admission of patients with polytrauma. Moreover, we developed a nomogram for visualization and a web-based calculator for convenient application (https://songandwen.shinyapps.io/DynNomapp/).

Conclusions

A convenient web-based calculator was constructed to robustly estimate the risk of death in patients with polytrauma within 72 h after admission, which may aid in further rationalization of clinical decision-making and accurate individual treatment.
Age, Sex, and Profession Difference Among Health Care Workers With Burnout and Metabolic Syndrome in Taiwan Tertiary Hospital—A Cross-Section Study
Authors: Tsai Huel-Ju , Tsou Meng-Ting
Published: April 2022

Background

This cross-sectional study aimed to analyze the association between burnout, work-related factors and metabolic syndrome (MetS) among various health-care workers (HCWs) at a tertiary hospital in Taiwan.

Methods

Relevant demographic data were obtained through written questionnaires. Information about psychosocial and work conditions, including assigned department, working hours, shifts, and sleep condition, was obtained. Burnout was evaluated according to the Chinese version of Maslach Burnout Inventory–Health Services Survey. MetS was analyzed according to the criteria of the National Cholesterol Education Program of Taiwan–Treatment Panel for Adults III.

Results

A total of 1,055 non-doctor/nurse and 2,078 doctor/nurse staff with a median age of 45.2 and 36.1 years participated in this study. The incidence of burnout was nearly 6.42 and 6.68% and that of MetS was 31.4 and 13.5% in non-doctor/nurse and doctor/nurse staff, respectively. The results showed that burnout induced a higher Odds ratio (OR) of MetS in the doctor/nurse group (OR = 1.96, p = 0.01). Other factors, such as night shift and seniority (>10 years), led to a higher OR of MetS, but a decreased risk was observed based on seniority (2–4 years). Further, young female participants and young doctors/nurses with burnout had a higher OR of MetS compare to other groups (OR = 2.43 and 2.32, p < 0.05).

Conclusion

The study results suggested positive relationship between burnout and MetS in young female staffs and young doctors/nurses. For doctor/nurse staff with higher seniority or more night shifts, strategies are needed to prevent burnout and MetS.
Music Modulates Autonomic Nervous System Activity in Human Fetuses
Authors: Massimello Francesca , Billeci Lucia , Canu Alessio , Montt-Guevara Maria Magdalena , Impastato Gaia , Varanini Maurizio , Giannini Andrea , Simoncini Tommaso , Mannella Paolo
Published: April 2022

Context

Fetal Autonomic Nervous sysTem Evaluation (FANTE) is a non-invasive tool that evaluates the autonomic nervous system activity in a fetus. Autonomic nervous system maturation and development during prenatal life are pivotal for the survival and neuropsychiatric development of the baby.

Objective

Aim of the study is to evaluate the effect of music stimulation on fetal heart rate and specific parameters linked to ANS activity, in particular fetal heart rate variability.

Methods

Thirty-two women between the 32nd and 38th week with a singleton uncomplicated pregnancy were recruited. All FANTE data collections were acquired using a 10-derivation electrocardiograph placed on the maternal abdomen. In each session (5 min basal, 10 min with music stimulus, and 5 min post-stimulus), FANTE was registered. The music stimulus was “Clair de lune” Debussy, played through headphones on the mother’s abdomen (CTR: 31927).

Results

Music does not change the mean value of fetal heart rate. However, indices of total fetal heart rate variability statistically increase (RRsd p = 0.037, ANNsd p = 0.039, SD2 p = 0.019) during music stimulation in comparison to the basal phase. Heart rate variability increase depends mainly on the activation of parasympathetic branches (CVI p = 0.013), meanwhile, no significant changes from basal to stimulation phase were observed for indices of sympathetic activity. All the parameters of heart rate variability and parasympathetic activity remained activated in the post-stimulus phase compared to the stimulus phase. In the post-stimulus phase, sympathetic activity resulted in a significant reduction (LFn p = 0.037).

Conclusion

Music can influence the basal activity of the fetal autonomic nervous system, enhancing heart rate variability, without changing fetal heart rate mean value. Music is enabled to induce a relaxation state in a near-to-term fetus, mediated by parasympathetic activation and by a parallel sympathetic inhibition.
Effect of First Trough Vancomycin Concentration on the Occurrence of AKI in Critically Ill Patients: A Retrospective Study of the MIMIC-IV Database
Authors: Li Longzhu , Zhang Luming , Li Shaojin , Xu Fengshuo , Li Li , Li Shuna , Lyu Jun , Yin Haiyan
Published: April 2022

Background

Vancomycin can effectively inhibit Gram-positive cocci and is widely used in critically ill patients. This study utilized a large public database to explore the effect of patients' first vancomycin trough concentration (FVTC) on the occurrence of acute kidney injury (AKI) and mortality after receiving vancomycin treatment in intensive care unit (ICU).

Methods

Critically ill patients who used vancomycin in the Medical Information Mart for Intensive Care (MIMIC) IV have been retrospectively studied. The outcomes included the occurrence of AKI during the use of vancomycin or within 72 h of withdrawal, ICU mortality and hospital mortality. Restricted cubic splines (RCS) were used to analyze the linear relationship between FVTC and the outcomes. Multivariate logistic/Cox regression analysis was used to analyze the association between patient's FVTC and the occurrence of AKI, ICU mortality, and in-hospital mortality.

Results

The study ultimately included 3,917 patients from the MIMIC-IV database who had been treated with vancomycin for more than 48 h. First of all, the RCS proved the linear relationship between FVTC and the outcomes. After controlling for all covariates as confounders in logistic/Cox regression, FVTC was a risk factor with the occurrence of AKI (OR: 1.02; 95% CI: 1.01–1.04), ICU mortality (HR: 1.02; 95% CI: 1.01–1.03), and in-hospital mortality (HR: 1.02; 95% CI: 1.01–1.03). Moreover, patients were divided into four groups in the light of the FVTC value: group1 ≤ 10 mg/L, 10 <group 2 ≤ 15 mg/L, 15  20 mg/L. Categorical variables indicated that group 3 and group 4 had a significant relationship on the occurrence of AKI [group 3: (OR: 1.36; 95% CI: 1.02–1.81); group 4: (OR: 1.76; 95% CI: 1.32–2.35)] and ICU mortality [group 3: (HR: 1.47; 95% CI: 1.03–2.09); group 4: (HR: 1.87; 95% CI: 1.33–2.62)], compared to group 1, while group 4 had a significant effect on in-hospital mortality (HR: 1.48; 95% CI: 1.15–1.91).

Conclusions

FVTC is associated with the occurrence of AKI and increased ICU and in-hospital mortality in critically ill patients. Therefore, in clinical practice, patients in intensive care settings receiving vancomycin should be closely monitored for FVTC to prevent drug-related nephrotoxicity and reduce patient mortality.
Altered Gut Microbiota as an Auxiliary Diagnostic Indicator for Patients With Fracture-Related Infection
Authors: Zhao Xingqi , Tang Wenli , Wan Haoyang , Lan Zixin , Qin Hanjun , Lin Qingrong , Hu Yanjun , Yu Guangchuang , Jiang Nan , Yu Bin
Published: April 2022

Preoperative diagnosis of fracture-related infection (FRI) is difficult for patients without obvious signs of infection. However, specific profiles of gut microbiota may be used as a potential diagnostic tool for FRI as suggested by a previous study. The fecal microbiome was compared between 20 FRI patients (FRI group), 18 fracture healed patients (FH group), and 12 healthy controls (HC group) included after collection of fecal samples and evaluation. The α and β diversity indices were used to characterize the fecal microbiome. Dysbiosis indexes were constructed based on the characteristic high-dimensional biomarkers identified in the fecal microbiota from the three groups by linear discriminant analysis and generalized linear model analysis to quantify the dysbiosis of fecal microbiota. The effectiveness of α and β diversity indices and dysbiosis indexes was assessed in distinguishing the fecal microbiome among the three groups. The influences of serum inflammatory factors on gut microbiota were also addressed. The α diversity indices were significantly different between the three groups, the highest in HC group and the lowest in FRI group (P < 0.05). The β diversity indices showed significant phylogenetic dissimilarity of gut microbiome composition among the three groups (P < 0.001). The dysbiosis indexes were significantly higher in FRI group than in FH and HC groups (P < 0.001). The area under Receiver operating characteristic curve showed the characteristics of gut microbiota and the gut microbiota was found as effective in distinguishing the three groups. The dysbiosis in the FRI patients was associated with systemic inflammatory factors. In addition, significant differences in the gut microbiota were not observed between the FRI patients versus without sinus tract or pus before operation. Since FRI patients, with or without sinus tract or pus, have a characteristic profile of gut microbiota, their gut microbiota may be used as an auxiliary diagnostic tool for suspected FRI.
Metagenomics Insights Into the Microbial Diversity and Microbiome Network Analysis on the Heterogeneity of Influent to Effluent Water
Authors: Azli Bahiyah , Razak Mohd Nasharudin , Omar Abdul Rahman , Mohd Zain Nor Azimah , Abdul Razak Fatimah , Nurulfiza I.
Published: April 2022

Sanitizing the water sources of local communities is important to control the spread of microbial resistance genes, especially those for water-borne illnesses. The activities of antibiotic resistance gene (ARG)-host pathogens pose a threat to public health, and it has been estimated that the infection will lead up to 10 million deaths globally by the year 2050. Hence, in this study, we aim to analyze the efficiency of our municipal wastewater treatment plant (WWTP) process in producing pathogen-free water by investigating the microbial composition between influent and effluent water sites. Shotgun metagenomics sequencing using the Illumina platform was performed on the influent and effluent samples of six different WWTP sites located in Johore, Malaysia. After raw data pre-processing, the non-redundant contigs library was then aligned against BLASTP for taxonomy profiling and the Comprehensive Antibiotic Resistance Database for ARG annotation. Interestingly, the alpha-diversity result reported that effluent site samples showed higher abundance and diverse heterogeneity compared to the influent site. The principal component analysis (PCA) and non-metric multidimensional scaling (NMDS) plots also suggested that effluent sites showed high variation in the genetic material due to loosely clustered sample plots, as compared to the tightly clustered influent samples. This study has successfully identified the top three abundant phyla in influent—Proteobacteria,Firmicutes, andBacteroidetes—and effluent—Proteobacteria,Actinobacteria, andBacteroidetes—water. Despite the overlap within the top three abundant phyla in influent and effluent sites (ProteobacteriaandBacteroidetes), the ARG composition heat map and drug class phenotype plot bar exhibits a general trend of a downward shift, showing the efficiency of WWTP in reducing opportunistic pathogens. Overall, it was demonstrated that our municipal WWTP efficiently eliminated pathogenic microbes from the influent water before its total discharge to the environment, though not with the total elimination of microorganisms. This metagenomics study allowed for an examination of our water source and showed the potential interaction of species and ARGs residing in the influent and effluent environment. Both microbial profile structure and co-occurrence network analysis provide integrated understanding regarding the diversity of microorganisms and interactions for future advanced water sanitation treatments.
Heat Stress Altered the Vaginal Microbiome and Metabolome in Rabbits
Authors: Shi Yu , Tang Lipeng , Bai Xue , Du Kun , Wang Haoding , Jia Xianbo , Lai Songjia
Published: April 2022

Heat stress can have an impact on parental gamete maturation and reproduction functions. According to current research, the microbial composition of the vaginal cavity is species specific. Pregnancy, menstruation, and genital diseases have been linked to the dynamics of vaginal ecology. In this study, we characterized the vaginal microbiota and metabolites after heat stress. At the phylum level, the rabbit’s vaginal microbial composition of rabbit showed high similarity with that of humans. In the Heat group, the relative abundance of the dominant microbiota Actinobacteria, Bacteroidetes, and Proteobacteria increased, while the relative abundance of Firmicutes decreased. Furthermore, heat stress significantly increased the relative abundance of W5053, Helcococcus, Thiopseudomonas, ldiomaarina, atopostipes, and facklamia, whereas the relative abundance of 12 genera significantly decreased, including Streptococcus, UCG-005, Alistipes, [Eubacterium]_xylanophilum_group, Comamonas, RB41, Fastidiosipila, Intestinimonas, Arthrobacter, Lactobacillus, Leucobacter, and Family_xlll_AD3011_group. Besides, the relative concentrations of 158 metabolites differed significantly between the Heat and Control groups. Among them, the endocrine hormone estradiol (E2) increased in the Heat group and was positively associated with a number of metabolites such as linolelaidic acid (C18:2N6T), N-acetylsphingosine, N-oleoyl glycine, trans-petroselinic acid, syringic acid, 2-(1-adamantyl)-1-morpholinoethan-1-one, 5-OxoETE, and 16-heptadecyne-1,2,4-triol. Further, the majority of the differential metabolites were enriched in steroid biosynthesis and endocrine and other factor-regulated calcium reabsorption pathways, reflecting that heat stress may affect calcium metabolism, hormone-induced signaling, and endocrine balance of vaginal ecology. These findings provide a comprehensive depiction of rabbit vaginal ecology and reveal the effects of heat stress on the vagina via the analysis of vaginal microbiome and metabolome, which may provide a new thought for low female fertility under heat stress.
Imaging Technologies Build Capacity and Accessibility in Phytoplankton Species Identification Expertise for Research and Monitoring: Lessons Learned During the COVID-19 Pandemic
Authors: Clayton Sophie , Gibala-Smith Leah , Mogatas Kathryn , Flores-Vargas Chanel , Marciniak Kayla , Wigginton Maci , Mulholland Margaret R.
Published: April 2022

As primary producers, phytoplankton play an integral role in global biogeochemical cycles through their production of oxygen and fixation of carbon. They also provide significant ecosystem services, by supporting secondary production and fisheries. Phytoplankton biomass and diversity have been identified by the Global Ocean Observing System (GOOS) as Essential Ocean Variables (EOVs), properties that need to be monitored to better understand and predict the ocean system. Phytoplankton identification and enumeration relies on the skills and expertise of highly trained taxonomic analysts. The training of new taxonomic analysts is intensive and requires months to years of supervised training before an analyst is able to independently and consistently apply identification skills to a sample. During the COVID-19 pandemic, access to laboratories was greatly restricted and social distancing requirements prevented supervised training. However, access to phytoplankton imaging technologies such as the Imaging FlowCytobot (IFCB), FlowCam, and PlanktoScope, combined with open online taxonomic identification platforms such as EcoTaxa, provided a means to continue monitoring, research, and training activities remotely when in-person activities were restricted. Although such technologies can not entirely replace microscopy, they have a great potential for supporting an expansion in taxonomic training, monitoring, surveillance, and research capacity. In this paper we highlight a set of imaging and collaboration tools and describe how they were leveraged during laboratory lockdowns to advance research and monitoring goals. Anecdotally, we found that the use of imaging tools accelerated the training of new taxonomic analysts in our phytoplankton analysis laboratory. Based on these experiences, we outline how these technologies can be used to increase capacity in taxonomic training and expertise, as well as how they can be used more broadly to expand research opportunities and capacity.
Metatranscriptomic Analysis of the Chicken Gut Resistome Response to In-Feed Antibiotics and Natural Feed Additives
Authors: Koorakula Raju , Schiavinato Matteo , Ghanbari Mahdi , Wegl Gertrude , Grabner Nikolaus , Koestelbauer Andreas , Klose Viviana , Dohm Juliane C. , Domig Konrad J.
Published: April 2022

The emergence of resistance against common antibiotics in the gut microbiota is a major issue for both human and livestock health. This highlights the need for understanding the impact of such application on the reservoir of antibiotic resistance genes in poultry gut and devising means to circumvent the potential resistome expansion. Phytogenic feed additives (PFAs) are potential natural alternative to antibiotic to improve animal health and performance, supposedly via positively affecting the gut microbial ecosystem, but there is little systematic information available. In this time-course study, we applied a shotgun meta-transcriptomics approach to investigate the impact of a PFA product as well as the commonly used antibiotic, zinc bacitracin either at AGP concentration or therapeutic concentration on the gut microbiome and resistome of broiler chickens raised for 35 days. Over the course of the trial, PFA treatments increased the abundance of Firmicutes such as Lactobacillus and resulted in a lower abundance of Escherichia, while the latter group increased significantly in the feces of chickens that received either AGP or AB doses of bacitracin. Tetracycline resistance and aminoglycoside resistance were the predominant antibiotic resistance gene (ARG) classes found, regardless of the treatment. PFA application resulted in a decrease in abundance of ARGs compared to those in the control group and other antibiotic treatment groups. In summary, the findings from this study demonstrate the potential of phytogenic feed additives could be an alternative to antibiotics in poultry farming, with the added benefit of counteracting antimicrobial resistance development.
Microbial Cross-Talk: Dissecting the Core Microbiota Associated With Flue-Cured Tobacco (Nicotiana tabacum) Plants Under Healthy and Diseased State
Authors: Ahmed Waqar , Dai Zhenlin , Liu Qi , Munir Shahzad , Yang Jun , Karunarathna Samantha C. , Li Shichen , Zhang Jinhao , Ji Guanghai , Zhao Zhengxiong
Published: April 2022

Bacterial wilt caused byRalstonia solanacearumis a devastating disease of flue-cured tobacco production which poses significant yield losses all around the world. In this study, we evaluated the rhizosphere microbiome of healthy and bacterial wilt-infected (diseased) flue-cured tobacco plants through amplification of V3-V4 and ITS1-5f variable regions of 16S and internal transcribed spacer (ITS) rRNA. The study was based on the location (Qujing, Shilin, and Wenshan), plant components (rhizosphere soil and roots), and sample types (healthy and diseased) to assess the diversity of bacterial and fungal communities. Bacterial and fungal communities present in roots primarily emanated from rhizosphere soil. Healthy flue-cured tobacco plants exhibit high microbial diversity compared to diseased plants. Among three variables, plant components significantly influence the diversity of microbial communities, whereas rhizosphere soil harbors higher microbial diversity than roots. Bacterial phyla Cyanobacteria and Proteobacteria were found in high relative abundance in roots and rhizosphere soil samples, respectively. As far as fungi is concerned, a high relative abundance of Ascomycota and Basidiomycota was found in both rhizosphere soil and root. Bacterial genera such asBacillus,Bradyrhizobium,Ensifer,Neorhizobium, andLysobacterrelated to plant growth promotion and disease suppressing abilities were dominant than fungal genera. Analysis of relative abundance at specie-level revealed that most fungal species are pathogenic to flue-cured tobacco and could provide a conducive environment for wilt infection. In conclusion,R. solanacearumsignificantly influences the microbial diversity of flue-cured tobacco plants and negatively affects the bacterial community composition. Altogether, our study demonstrates the complexity of bacterial and fungal communities that possibly interact with each other (microbe–microbe) and host (host–microbe). This cross-talk could be helpful for healthy flue-cured tobacco plant growth and to induce resistance against bacterial wilt disease.