bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated Bioinformatics Algorithms and Experimental Validation to Explore Robust Biomarkers and Landscape of Immune Cell Infiltration in Dilated Cardiomyopathy
Authors: Zhang Qingquan , Fan Mengkang , Cao Xueyan , Geng Haihua , Su Yamin , Wu Chunyu , Pan Haiyan , Pan Min
Published: April 2022

Background

The etiology of dilated cardiomyopathy (DCM) is unclear. Bioinformatics algorithms may help to explore the underlying mechanisms. Therefore, we aimed to screen diagnostic biomarkers and identify the landscape of immune infiltration in DCM.

Methods

First, the CIBERSORT algorithm was used to excavate the proportion of immune-infiltration cells in DCM and normal myocardial tissues. Meanwhile, the Pearson analysis and principal component analysis (PCA) were used to identify immune heterogeneity in different tissues. The Wilcoxon test, LASSO regression, and machine learning method were conducted to identify the hub immune cells. In addition, the differentially expressed genes (DEGs) were screened by the limma package, and DEGs were analyzed for functional enrichment. In the protein–protein interaction (PPI) network, multiple algorithms were used to calculate the score of each DEG for screening the hub genes. Subsequently, external datasets were used to further validate the expression of hub genes, and the receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy. Finally, we examined the expression of hub biomarkers in animal models.

Results

A total of 108 DEGs were screened, and these genes may be related to biological processes such as cytolysis, positive regulation of cytokine secretion, etc. Two types of hub immune cells [activated natural killer (NK) cells and eosinophils] and four hub genes (ASPN, CD163, IL10, and LUM) were identified in DCM myocardial tissues. CD163 was verified to have the capability to diagnose DCM with the most excellent specificity and sensitivity. It is worth mentioning that the combined CD163 and eosinophils may have better diagnostic efficacy. Moreover, the correlation analysis showed CD163 was negatively correlated with activated NK cells. Finally, the results of the mice model also indicated that CD163 might be involved in the occurrence of DCM.

Conclusion

ASPN, CD163, IL10, and LUM may have a potential predictive ability for DCM, and especially CD163 showed the most robust efficacy. Furthermore, activated NK cells and eosinophils may relate to the occurrence of DCM.
The Associations Between Preoperative Anthropometry and Postoperative Outcomes in Infants Undergoing Congenital Heart Surgery
Authors: Lim Jia Yi Joel , Wee Rui Wen Bryan , Gandhi Mihir , Lim Yee Phong , Tan Li Nien Michelle , Quek Swee Chye , Aw Marion M. , Chen Ching Kit
Published: April 2022

Aim:

We explored the association between preoperative anthropometry and biochemistry, and postoperative outcomes in infants with CHD after cardiac surgery, as infants with congenital heart disease (CHD) often have feeding difficulties and malnutrition.

Methodology

This was a retrospective review of infants (≤ 1-year-old) who underwent congenital heart surgery. Preoperative anthropometryin terms of preoperative weight-for-age z-score (WAZ), length-for-age z-score (LAZ), as well as preoperative serum albumin and hemoglobin concentrations, were evaluated against 6-month mortality, and morbidity outcomes including postoperative complications, vasoactive inotrope score, duration of mechanical ventilation, length of stay in the pediatric intensive care unit and in hospital, using the logistic regression or median regression models accounting for infant-level clustering.

Results

One hundred and ninety-nine operations were performed in 167 infants. Mean gestational age at birth was 38.0 (SD 2.2) weeks (range 26 to 41 weeks). Thirty (18.0%) infants were born preterm (<37 weeks). The commonest acyanotic and cyanotic lesions were ventricular septal defect (26.3%, 44/167), and tetralogy of Fallot (13.8%, 23/167), respectively. Mean age at cardiac surgery was 94 (SD 95) days. Feeding difficulties, including increased work of breathing during feeding, diaphoresis, choking or coughing during feeding, and inability to complete feeds, was present in 54.3% (108/199) of infants prior to surgery, of which 21.6% (43/199) required tube feeding. The mean preoperative WAZ was−1.31 (SD 1.79). Logistic regression models showed that low preoperative WAZ was associated with increased risk of postoperative complications (odds ratio 1.82; p = 0.02), and 6-month mortality (odds ratio 2.38; p = 0.008) following CHD surgery. There was no meaningful association between the other preoperative variables and other outcomes.

Conclusion

More than 50% of infants with CHD undergoing cardiac surgery within the first year of life have feeding difficulties, of which 22% require to be tube-fed. Low preoperative WAZ is associated with increased postoperative complications and 6-month mortality.
Big Data in Cardiology: State-of-Art and Future Prospects
Authors: Dai Haijiang , Younis Arwa , Kong Jude Dzevela , Puce Luca , Jabbour Georges , Yuan Hong , Bragazzi Nicola Luigi
Published: April 2022

Cardiological disorders contribute to a significant portion of the global burden of disease. Cardiology can benefit from Big Data, which are generated and released by different sources and channels, like epidemiological surveys, national registries, electronic clinical records, claims-based databases (epidemiological Big Data), wet-lab, and next-generation sequencing (molecular Big Data), smartphones, smartwatches, and other mobile devices, sensors and wearable technologies, imaging techniques (computational Big Data), non-conventional data streams such as social networks, and web queries (digital Big Data), among others. Big Data is increasingly having a more and more relevant role, being highly ubiquitous and pervasive in contemporary society and paving the way for new, unprecedented perspectives in biomedicine, including cardiology. Big Data can be a real paradigm shift that revolutionizes cardiological practice and clinical research. However, some methodological issues should be properly addressed (like recording and association biases) and some ethical issues should be considered (such as privacy). Therefore, further research in the field is warranted.
Study on the Effect of Jet Position and Size on Heat Transfer in a Small Containment
Authors: Xiong Wang , Fang Yuan , Lin Shengsheng , Wang Shengfei
Published: April 2022

In the main steam line break (MSLB) accident, the rise in temperature and pressure threatens the integrity of the containment, which is caused by a large amount of mixed gas injected into the containment rapidly. Due to the structural difference between small and large containment, it is necessary to study the heat transfer in the complex space of the small containment. Based on the research method, which is from simple to complex, in this study, a series of experiments and numerical simulations are carried out with different jet positions and sizes using hot air without phase change as the working medium. The results show that the temperature field above the jet is complex and affected by many factors such as buoyancy, initial kinetic energy, and internal structure. When the jet flow rate is constant, the jet size is smaller and the velocity is faster, which results in a large circulation and stronger heat exchange with the wall of containment. This means that the temperature above the jet is lower than the large jet size, and the temperature below the jet is slightly higher. The jet position mainly affects the relative position of the jet and the complex space in the containment. When the jet is located in a narrow space, the overall temperature in the containment is higher than the jet located in a large space. In addition, when it is close to the obstacle, the core region of the jet will shift slightly toward the obstacle.
Keeping Up with Phosphorus Dynamics: Overdue Conceptual Changes in Vegetative Filter Strip Research and Management
Authors: Ramler David , Stutter Marc , Weigelhofer Gabriele , Quinton John N. , Hood-Nowotny Rebecca , Strauss Peter
Published: April 2022

Vegetative filter strips (VFS) are best management practices with the primary aim of protecting surface waters from eutrophication resulting from excess nutrient inputs from agricultural sources. However, we argue that there is a substantial time and knowledge lag from the science underpinning VFS to policy and implementation. Focussing on phosphorus (P), we strive to introduce a holistic view on VFS that accounts for the whole functional soil volume, temporal and seasonal effects, the geospatial context, the climatic and physico-chemical basic conditions, and the intricate bio-geochemical processes that govern nutrient retention, transformation, and transport. Specifically, we suggest a step-wise approach to custom VFS designs that links and matches the incoming P from event to multi-annual timescales from the short- and mid-term processes of P retention in the effective soil volume and to the longer-term P retention and offtake coupled to the soil-vegetation system. An a priori assessment of the P export potential should be followed by bespoke VFS designs, in line with local conditions and socio-economic and ecological constraints. To cope with increasingly nutrient saturated or functionally insufficient VFS installed over the last decades, concepts and management strategies need to encompass the transition in understanding of VFS as simple nutrient containers to multifunctional buffer zones that have a complex inner life. We need to address these associated emerging challenges and integrate their implications more thoroughly into VFS research, monitoring, policy, and implementation than ever before. Only then we may get VFS that are effective, sustainable, and persistent.
Clinical Characteristics and CD4+ T Cell Subsets in IgG4-Related Disease
Authors: Yang Yan , Wang Chen , Shi Lei , Yang Shuoran , Liu Yan , Luo Jing , Wang Caihong
Published: April 2022

Objectives

To characterize the clinical features of IgG4-related disease (IgG4-RD) and analyze the peripheral T lymphocyte subsets and cytokine levels.

Methods

A total of 52 patients with newly diagnosed IgG4-RD were enrolled in the retrospective study. Baseline clinical characteristics and examinational findings were systematically reviewed.

Results

IgG4-RD patients had a male predominance, with an average age of 57.4 ± 10.3 years (range 27-81). The mean number of involved organs was 2.7 (range 1-8). Submandibular gland (57.7%) and lacrimal gland/orbit (40.4%) were the most commonly involved organs. Serum IgG4 increased in 97.9% of the patients, the median level was 1300 (585.25, 1975) mg/dl. Decreased C3 and C4 accounted for 77.8% and 55.6% of this patient cohort, respectively. Receiver operating characteristic (ROC) test indicated the possibility of lung/pleura involvement when C3 was less than 0.570 g/l (AUC = 0.788, P = 0.014), and kidney involvement when C3 was less than 0.545 g/l (AUC = 0.796, P = 0.014). Compared with healthy controls (HC), the absolute Th1 counts were higher in IgG4-RD patients (157.58 cells/μl vs. 130.54 cells/μl, P = 0.038), while the absolute counts of Th2, Th17 and T regulatory (Treg) cells, as well as Th17/Treg ratio were not statistically different. The levels of serum IL-4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ were higher in patients with IgG4-RD as compared with HC (P < 0.001). Serum IL-10 was positively correlated with IL-4, TNF-α and IFN-γ, but uncorrelated with Treg cells. Serum IgG4 level was positively associated with the number of affected organs, eosinophil counts, and ESR, whereas inversely associated with C3, C4, IgM, and IgA.

Conclusion

Submandibular and lacrimal glands are the most commonly involved organs in IgG4-RD. Serum C3 level could be a predictor of lung/pleura and kidney involvement in the disease process. Elevated Th1 cells are probably related to chronic inflammation and fibrosis. Treg cells are unlikely to play an important role in the pathogenesis of IgG4-RD.
An Update of Cutaneous Melanoma Patients Treated in Adjuvancy With the Allogeneic Melanoma Vaccine VACCIMEL and Presentation of a Selected Case Report With In-Transit Metastases
Authors: Mordoh Ana , Aris Mariana , Carri Ibel , Bravo Alicia Inés , Podaza Enrique , Pardo Juan Carlos Triviño , Cueto Gerardo Rubén , Barrio María Marcela , Mordoh José
Published: April 2022

The CSF-470 vaccine (VACCIMEL) plus BCG and GM-CSF as adjuvants has been assayed in cutaneous melanoma patients. In the adjuvant randomized Phase II study CASVAC-0401, vaccinated patients had longer distant metastasis-free survival (DMFS) than those treated with IFNα2b. Five years after locking the data, an actualization was performed. The benefit in DMFS was maintained in the vaccinated group versus the IFNα2b-treated group (p = 0.035), with a median DMFS of 96 months for VACCIMEL and 13 months for IFNα2b. The favorable risk–benefit ratio was maintained. DMFS was also analyzed as a single cohort in all the IIB, IIC, and III patients (n = 30) who had been treated with VACCIMEL. The median DMFS was 169 months, and at 48 months follow-up, it was 71.4%, which was not statistically different from DMFS of previously published results obtained in adjuvancy with ipilimumab, pembrolizumab, nivolumab, or dabrafenib/trametinib. The possible toxicity of combining VACCIMEL with anti-immune checkpoint inhibitors (ICKi) was analyzed, especially since VACCIMEL was co-adjuvated with BCG in every vaccination. A patient with in-transit metastases was studied to produce a proof of concept. During treatment with VACCIMEL, the patient developed T-cell clones reactive towards tumor-associated antigens. Three years after ending the VACCIMEL study, the patient progressed and was treated with ICKi. During ICKi treatment, the patient did not reveal any toxicity due to previous BCG treatment. When she recurred after a 4-year treatment with nivolumab, a biopsy was obtained and immunohistochemistry and RNA-seq were performed. The tumor maintained expression of tumor-associated antigens and HLA-I and immune infiltration, with immunoreactive and immunosuppressive features. VACCIMEL plus BCG and GM-CSF is an effective treatment in adjuvancy for stages IIB, IIC, and III cutaneous melanoma patients, and it is compatible with subsequent treatments with ICKi.
Emerging Roles of Platelets in Allergic Asthma
Authors: Yue Ming , Hu Mengjiao , Fu Fangda , Ruan Hongfeng , Wu Chengliang
Published: April 2022

Allergic asthma is a complex chronic inflammatory disease of the airways, driven by Th2 immune responses and characterized by eosinophilic pulmonary inflammation, airway hyperresponsiveness, excessive mucus production, and airway remodeling. Overwhelming evidence from studies in animal models and allergic asthmatic patients suggests that platelets are aberrantly activated and recruited to the lungs. It has been established that platelets can interact with other immune cells and secrete various biochemical mediators to promote allergic sensitization and airway inflammatory response, and platelet deficiency may alleviate the pathological features and symptoms of allergic asthma. However, the comprehensive roles of platelets in allergic asthma have not been fully clarified, leaving attempts to treat allergic asthma with antiplatelet agents questionable. In this review, we summarize the role of platelet activation and pulmonary accumulation in allergic asthma; emphasis is placed on the different interactions between platelets with crucial immune cell types and the contribution of platelet-derived mediators in this context. Furthermore, clinical antiplatelet approaches to treat allergic asthma are discussed. This review provides a clearer understanding of the roles of platelets in the pathogenesis of allergic asthma and could be informative in the development of novel strategies for the treatment of allergic asthma.
Alginate Oligosaccharide Alleviated Cisplatin-Induced Kidney Oxidative Stress via Lactobacillus Genus-FAHFAs-Nrf2 Axis in Mice
Authors: Zhang Yubing , Qin Song , Song Yipeng , Yuan Jingyi , Hu Shanliang , Chen Min , Li Lili
Published: April 2022

Alginate oligosaccharide is the depolymerized product of alginate, a natural extract of brown algae, which is associated with beneficial health effects. Here, we aimed to investigate the mechanism via which alginate oligosaccharides improve kidney oxidative damage and liver inflammation induced by cisplatin chemotherapy via the gut microbiota. C57BL/6J mice were treated with cisplatin were administered alginate oligosaccharide via gavage for 3 weeks. Compared to that observed in the cisplatin chemotherapy group without intragastric administration of alginate oligosaccharide, liver inflammation improved in the alginate oligosaccharide group, indicated by reduction in lipopolysaccharide and interleukin-1β (IL-1β) levels. This was accompanied by improvement in the oxidative stress of mice kidneys, indicated by the increase in the levels of superoxide dismutase (SOD), catalase (CAT) and nuclear NF-E2-related factor 2 (Nrf2) in renal tissue, and reduction in the levels of malondialdehyde (MDA) in renal tissue and serum creatinine (Cr) to the levels of the normal control group. Alginate oligosaccharide intervention increased the concentration of fatty acid esters of hydroxy fatty acids (FAHFAs). Alginate oligosaccharide regulated the composition of the intestinal microbial community and promoted Lactobacillus stains, such as Lactobacillus johnsonii and Lactobacillus reuteri. Spearman analysis showed that 5 members of FAHFAs concentrations were positively correlated with Lactobacillus johnsonii and Lactobacillus reuteri abundance. We observed that alginate oligosaccharide increased FAHFAs producing-related bacterial abundance and FAHFAs levels, enhanced the levels of SOD and CAT in kidney tissue, and reduced the levels of MDA via activating Nrf2, thereby ameliorating the renal redox injury caused by cisplatin chemotherapy.
Intracellular Complement Component 3 Attenuated Ischemia-Reperfusion Injury in the Isolated Buffer-Perfused Mouse Heart and Is Associated With Improved Metabolic Homeostasis
Authors: Torp M-K. , Ranheim T. , Schjalm C. , Hjorth M. , Heiestad C.M. , Dalen K. T. , Nilsson P. H. , Mollnes T. E. , Pischke S. E. , Lien E. , Vaage J. , Yndestad A. , Stensløkken K-O.
Published: April 2022

The innate immune system is rapidly activated during myocardial infarction and blockade of extracellular complement system reduces infarct size. Intracellular complement, however, appears to be closely linked to metabolic pathways and its role in ischemia-reperfusion injury is unknown and may be different from complement activation in the circulation. The purpose of the present study was to investigate the role of intracellular complement in isolated, retrogradely buffer-perfused hearts and cardiac cells from adult male wild type mice (WT) and from adult male mice with knockout of complement component 3 (C3KO). Main findings: (i) Intracellular C3 protein was expressed in isolated cardiomyocytes and in whole hearts, (ii) after ischemia-reperfusion injury, C3KO hearts had larger infarct size (32 ± 9% in C3KO vs. 22 ± 7% in WT; p=0.008) and impaired post-ischemic relaxation compared to WT hearts, (iii) C3KO cardiomyocytes had lower basal oxidative respiration compared to WT cardiomyocytes, (iv) blocking mTOR decreased Akt phosphorylation in WT, but not in C3KO cardiomyocytes, (v) after ischemia, WT hearts had higher levels of ATP, but lower levels of both reduced and oxidized nicotinamide adenine dinucleotide (NADH and NAD+, respectively) compared to C3KO hearts. Conclusion: intracellular C3 protected the heart against ischemia-reperfusion injury, possibly due to its role in metabolic pathways important for energy production and cell survival.
Sources and Behavior of Particulate Organic Carbon in the Yellow Sea and the East China Sea Based on 13C, 14C, and 234Th
Authors: Seo Junhyeong , Kim Guebuem , Hwang Jeomshik
Published: April 2022

The cycling of particulate organic carbon (POC) in continental shelf regions of the Yellow Sea (YS) and the East China Sea (ECS) was investigated by analyzing the concentrations and carbon isotope signatures (δ13C, Δ14C) of POC, together with the particulate aluminum (Al) concentration and 234Th activity over the period 10–20 August 2020. POC concentrations in the surface layer (0–20 m) were twice as high as those in the middle layer (20–50 m); the highest concentrations of all were observed in the bottom layer (> 50 m) of the YS and the region affected by Changjiang Diluted Water (CDW). Particulate Al concentrations in the bottom layer were three times higher than those in the overlying water column, indicating extensive sediment resuspension. Based on the three-endmember mixing model for the dual carbon isotopes, the estimated contribution of resuspended sedimentary organic carbon to POC ranged from 18% in the surface layer to 65% in the bottom layer. The contribution of riverine input to POC ranged from < 5% in the CDW region to ∼45% in the surface layer of the YS region, whereas that of in situ production was ∼40% in the entire study region. A deficiency of 234Th relative to 238U indicates short residence times of particles in the entire water column (2.6 ± 2.2 d). The flux of POC settling to the seafloor, calculated based on 234Th–238U disequilibrium, was 47–125 mmol m–2 d–1. The POC settling flux was one to two orders of magnitude higher than the burial rate of POC in the underlying sediment, implying the rapid decomposition of POC before incorporation into the sediment. Thus, sediment resuspension is prevalent and an important component of the POC cycling in this shelf region. Overall, our study revealed the complex nature of POC cycling on this shelf, quantified the relative importance of each source of POC, and determined POC flux to the sediment.
Characterization and Genomic Analysis of the First Podophage Infecting Shewanella, Representing a Novel Viral Cluster
Authors: Dong Yue , Zheng Kaiyang , Zou Xiao , Liang Yantao , Liu Yundan , Li Xiang , Shao Hongbing , Sung Yeong Yik , Mok Wen Jye , Wong Li Lian , McMinn Andrew , Wang Min
Published: April 2022

Shewanella is a common bacterial genus in marine sediments and deep seas, with a variety of metabolic abilities, suggesting its important roles in the marine biogeochemical cycles. In this study, a novel lytic Shewanella phage, vB_SInP-X14, was isolated from the surface coastal waters of Qingdao, China. The vB_SInP-X14 contains a linear, double-strand 36,396-bp with the G + C content of 44.1% and harbors 40 predicted open reading frames. Morphological, growth, and genomic analysis showed that it is the first isolated podovirus infecting Shewanella, with a short propagation time (40 min), which might be resulted from three lytic-related genes. Phylogenetic analysis suggested that vB_SInP-X14 could represent a novel viral genus, named Bocovirus, with four isolated but not classified phages. In addition, 14 uncultured viral genomes assembled from the marine metagenomes could provide additional support to establish this novel viral genus. This study reports the first podovirus infecting Shewanella, establishes a new interaction system for the study of virus–host interactions, and also provides new reference genomes for the marine viral metagenomic analysis.
The Interference Mechanism of Basil Essential Oil on the Cell Membrane Barrier and Respiratory Metabolism of Listeria monocytogenes
Authors: Li Changzhu , Zhang Chenghui , Chen Xiaochen , Cui Haiying , Lin Lin
Published: April 2022

In order to prevent food-borne diseases caused by Listeria monocytogenes (L. monocytogenes) safely and effectively, plant essential oils that have no toxic side effects and are not prone to drug resistance have become the focus of research. This article takes basil (Ocimum basilicum L.) essential oil (BEO) as the research object and explores its antibacterial mechanism against L. monocytogenes. The site of action was preliminarily determined to provide a theoretical basis for the development of natural antibacterial agents. The results show that BEO has good antibacterial activity against L. monocytogenes. After 8 h of treatment with BEO (1 mg/ml), the number of remaining bacteria reached an undetectable level. Combining spectroscopic analysis techniques (Raman, UV, and fluorescence spectroscopy) and fluorescence microscopy imaging techniques, it was found that BEO increased the disorder of the hydrocarbyl chain of phospholipid tail, which in turn led to increased cell membrane permeability, thereby causing the leakage of intracellular proteins and DNA. Meanwhile, respiratory metabolism experiments showed that BEO inhibited the EMP pathway by inhibiting the activity of key enzymes. From the molecular docking results, this inhibition may be attributed to the hydrophobic interaction between α-bergamotene and the amino acid residues of phosphofructokinase (PFK) and pyruvate kinase (PK). In addition, BEO can also cause oxidative stress, and reactive oxygen species (ROS) may also be related to the damage of cell membranes and enzymes related to respiratory metabolism.
COPD and Gut–Lung Axis: How Microbiota and Host Inflammasome Influence COPD and Related Therapeutics
Authors: Qu Ling , Cheng Qing , Wang Yan , Mu Hui , Zhang Yunfeng
Published: April 2022

The exact pathogenesis of chronic obstructive pulmonary disease (COPD) remains largely unknown. While current management strategies are effective at stabilizing the disease or relief the symptoms, new approaches are required to target underlying disease process and reverse lung function deterioration. Recent research showed that pneumonia bacteria is critical in disease progression and gut microbiome is likely perturbed in COPD, which is usually accompanied by a decreased intestinal microbial diversity and a disturbance in immune system, contributing to a chronic inflammation. The cross-talk between gut microbes and lungs, termed as the “gut-lung axis,” is known to impact immune response and homeostasis in the airway. Although the gut and respiratory microbiota exhibit compositional differences, the gut and lung showed similarities in the origin of epithelia of both gastrointestinal and respiratory tracts, the anatomical structure, and early-life microbial colonization. Evidence showed that respiratory infection might be prevented, or at least dampened by regulating gut microbial ecosystem; thus, a promising yet understudied area of COPD management is nutrition-based preventive strategies. COPD patient is often deficient in nutrient such as antioxidant, vitamins, and fiber intake. However, further larger-scale randomized clinical trials (RCTs) are required to establish the role of these nutrition-based diet in COPD management. In this review, we highlight the important and complex interaction of microbiota and immune response on gut-lung axis. Further research into the modification and improvement of the gut microbiota and new interventions through diet, probiotics, vitamins, and fecal microbiota transplantation is extreme critical to provide new preventive therapies for COPD.
A Rapid, Highly Sensitive and Open-Access SARS-CoV-2 Detection Assay for Laboratory and Home Testing
Authors: Kellner Max J. , Ross James J. , Schnabl Jakob , Dekens Marcus P. S. , Matl Martin , Heinen Robert , Grishkovskaya Irina , Bauer Benedikt , Stadlmann Johannes , Menéndez-Arias Luis , Straw Andrew D. , Fritsche-Polanz Robert , Traugott Marianna , Seitz Tamara , Zoufaly Alexander , Födinger Manuela , Wenisch Christoph , Zuber Johannes , Vienna COVID-19 Detection Initiative (VCDI)  , Pauli Andrea , Brennecke Julius
Published: April 2022

RT-qPCR-based diagnostic tests play important roles in combating virus-caused pandemics such as Covid-19. However, their dependence on sophisticated equipment and the associated costs often limits their widespread use. Loop-mediated isothermal amplification after reverse transcription (RT-LAMP) is an alternative nucleic acid detection method that overcomes these limitations. Here, we present a rapid, robust, and sensitive RT-LAMP-based SARS-CoV-2 detection assay. Our 40-min procedure bypasses the RNA isolation step, is insensitive to carryover contamination, and uses a colorimetric readout that enables robust SARS-CoV-2 detection from various sample types. Based on this assay, we have increased sensitivity and scalability by adding a nucleic acid enrichment step (Bead-LAMP), developed a version for home testing (HomeDip-LAMP), and identified open-source RT-LAMP enzymes that can be produced in any molecular biology laboratory. On a dedicated website, rtlamp.org (DOI: 10.5281/zenodo.6033689), we provide detailed protocols and videos. Our optimized, general-purpose RT-LAMP assay is an important step toward population-scale SARS-CoV-2 testing.
Resting-State Functional Network Topology Alterations of the Occipital Lobe Associated With Attention Impairment in Isolated Rapid Eye Movement Behavior Disorder
Authors: Geng Chaofan , Wang Shenghui , Li Zhonglin , Xu Pengfei , Bai Yingying , Zhou Yao , Zhang Xinyu , Li Yongli , Zhang Jiewen , Zhang Hongju
Published: April 2022

Purpose

This study investigates the topological properties of brain functional networks in patients with isolated rapid eye movement sleep behavior disorder (iRBD).

Participants and Methods

A total of 21 patients with iRBD (iRBD group) and 22 healthy controls (HCs) were evaluated using resting-state functional MRI (rs-fMRI) and neuropsychological measures in cognitive and motor function. Data from rs-fMRI were analyzed using graph theory, which included small-world properties, network efficiency, network local efficiency, nodal shortest path, node efficiency, and network connectivity, as well as the relationship between behavioral characteristics and altered brain topological features.

Results

Rey-Osterrieth complex figure test (ROCFT-copy), symbol digital modalities test (SDMT), auditory verbal learning test (AVLT)-N1, AVLT-N2, AVLT-N3, and AVLT-N1-3 scores were significantly lower in patients with iRBD than in HC (P < 0.05), while trail making test A (TMT-A), TMT-B, and Unified Parkinson’s Disease Rating Scale Part-III (UPDRS-III) scores were higher in patients with iRBD (P < 0.05). Compared with the HCs, patients with iRBD had no difference in the small-world attributes (P > 0.05). However, there was a significant decrease in network global efficiency (P = 0.0052) and network local efficiency (P = 0.0146), while an increase in characteristic path length (P = 0.0071). There was lower nodal efficiency in occipital gyrus and nodal shortest path in frontal, parietal, temporal lobe, and cingulate gyrus. Functional connectivities were decreased between the nodes of occipital with the regions where they had declined nodal shortest path. There was a positive correlation between TMT-A scores and the nodal efficiency of the right middle occipital gyrus (R = 0.602, P = 0.014).

Conclusion

These results suggest that abnormal behaviors may be associated with disrupted brain network topology and functional connectivity in patients with iRBD and also provide novel insights to understand pathophysiological mechanisms in iRBD.
Olfactory Senses Modulate Food Consumption and Physiology in Drosophila melanogaster
Authors: He Jianzheng , Tuo Wenjuan , Zhang Xueyan , Dai Yuting , Fang Ming , Zhou Ting , Xiu Minghui , Liu Yongqi
Published: April 2022

Both sensory and metabolic processes guide food intake. Olfactory inputs help coordinate food appreciation and selection, but their role in food consumption and post-feeding physiology remains poorly understood. In this study, using Drosophila melanogaster as a model system, we investigated the effects of olfactory sensory neurons (OSNs) on food consumption, metabolism, and stress responses. We found that dysfunction of OSNs affects diverse processes, including decreased food consumption, increased triacylglycerol level, enhanced stress resistance to starvation or desiccation, and decreased cold resistance. Decreased neuropeptide F receptor (NPFR) level or increased insulin activity in OSNs inhibited food consumption, while impaired NPF signaling or insulin signaling in OSNs increased resistance to starvation and desiccation. These studies provide insights into the function of the olfactory system in control of feeding behaviors and physiology.
Combination of Radiological and Clinical Baseline Data for Outcome Prediction of Patients With an Acute Ischemic Stroke
Authors: Ramos Lucas A. , Os Hendrikus van , Hilbert Adam , Olabarriaga Silvia D. , Lugt Aad van der , Roos Yvo B. W. E. M. , Zwam Wim H. van , Walderveen Marianne A. A. van , Ernst Marielle , Zwinderman Aeiko H. , Strijkers Gustav J. , Majoie Charles B. L. M. , Wermer Marieke J. H. , Marquering Henk A.
Published: April 2022

Background

Accurate prediction of clinical outcome is of utmost importance for choices regarding the endovascular treatment (EVT) of acute stroke. Recent studies on the prediction modeling for stroke focused mostly on clinical characteristics and radiological scores available at baseline. Radiological images are composed of millions of voxels, and a lot of information can be lost when representing this information by a single value. Therefore, in this study we aimed at developing prediction models that take into account the whole imaging data combined with clinical data available at baseline.

Methods

We included 3,279 patients from the MR CLEAN Registry; a prospective, observational, multicenter registry of patients with ischemic stroke treated with EVT. We developed two approaches to combine the imaging data with the clinical data. The first approach was based on radiomics features, extracted from 70 atlas regions combined with the clinical data to train machine learning models. For the second approach, we trained 3D deep learning models using the whole images and the clinical data. Models trained with the clinical data only were compared with models trained with the combination of clinical and image data. Finally, we explored feature importance plots for the best models and identified many known variables and image features/brain regions that were relevant in the model decision process.

Results

From 3,279 patients included, 1,241 (37%) patients had a good functional outcome [modified Rankin Scale (mRS) ≤ 2] and 1,954 (60%) patients had good reperfusion [modified Thrombolysis in Cerebral Infarction (eTICI) ≥ 2b]. There was no significant improvement by combining the image data to the clinical data for mRS prediction [mean area under the receiver operating characteristic (ROC) curve (AUC) of 0.81 vs. 0.80] above using the clinical data only, regardless of the approach used. Regarding predicting reperfusion, there was a significant improvement when image and clinical features were combined (mean AUC of 0.54 vs. 0.61), with the highest AUC obtained by the deep learning approach.

Conclusions

The combination of radiomics and deep learning image features with clinical data significantly improved the prediction of good reperfusion. The visualization of prediction feature importance showed both known and novel clinical and imaging features with predictive values.
Novel Immunotherapies for Osteosarcoma
Authors: Lu Yubao , Zhang Jiahe , Chen Yutong , Kang Yuchen , Liao Zhipeng , He Yuanqi , Zhang Cangyu
Published: April 2022

Osteosarcoma (OS) is the most common primary malignant bone sarcoma mainly affecting adolescents and young adults, which often progresses to pulmonary metastasis and leads to the death of OS patients. OS is characterized as a highly heterogeneous cancer type and the underlying pathologic mechanisms triggering tumor progress and metastasis are incompletely recognized. Surgery combined with neoadjuvant and postoperative chemotherapy has elevated 5-year survival to over 70% for patients with localized OS tumors, as opposed to only 20% of patients with recurrence and/or metastasis. Therefore, novel therapeutic strategies are needed to overcome the drawbacks of conventional treatments. Immunotherapy is gaining momentum for the treatment of OS with an increasing number of FDA-approved therapies for malignancies resistant to conventional therapies. Here, we review the OS tumor microenvironment and appraise the promising immunotherapies available in the management of OS.
The Comparable Microenvironment Shared by Colorectal Adenoma and Carcinoma: An Evidence of Stromal Proteomics
Authors: Yan Keqiang , Bai Bin , Ren Yan , Cheng Benliang , Zhang Xia , Zhou Haichao , Liang Yuting , Chen Lingyun , Zi Jin , Yang Qinghai , Zhao Qingchuan , Liu Siqi
Published: April 2022

Tumor microenvironment (TME) is a key factor involved in cancer development and metastasis. In the TME of colorectal cancer (CRC), the gene expression status of stromal tissues could influence the CRC process from normal to adenoma then carcinoma; however, the expression status at the protein level has not yet been well evaluated. A total of 22 CRC patients were recruited for this study, and the tissue regions corresponding with adjacent, adenoma, and carcinoma were carefully excised by laser capture microdissection (LCM), including a patient with adenoma and carcinoma. The individual proteomes of this cohort were implemented by high-resolution mass spectrometer under data-independent acquisition (DIA) mode. A series of informatic analysis was employed to statistically seek the proteomic characteristics related with the stroma at different stages of CRC. The identified proteins in the colorectal stromal tissues were much less than and almost overlapped with that in the corresponding epithelial tissues; however, the patterns of protein abundance in the stroma were very distinct from those in the epithelium. Although qualitative and quantitative analysis delineated the epithelial proteins specifically typified in the adjacent, adenoma, and carcinoma, the informatics in the stroma led to another deduction that such proteomes were only divided into two patterns, adjacent- and adenoma/carcinoma-dependent. The comparable proteomes of colorectal adenoma and carcinoma were further confirmed by the bulk preparation- or individual LCM-proteomics. The biochemical features of the tumor stromal proteomes were characterized as enrichment of CD4+ and CD8+ T cells, upregulated pathways of antigen presentation, and enhancement of immune signal interactions. Finally, the features of lymphoid lineages in tumor stroma were verified by tissue microarray (TMA). Based on the proteomic evidence, a hypothesis was raised that in the colorectal tissue, the TME of adenoma and carcinoma were comparable, whereas the key elements driving an epithelium from benign to malignant were likely decided by the changes of genomic mutations or/and expression within it.
Metagenomic Analyses Reveal Distinct Gut Microbiota Signature for Predicting the Neoadjuvant Chemotherapy Responsiveness in Breast Cancer Patients
Authors: Li Yuanyuan , Dong Bingbin , Wu Wei , Wang Jiawei , Jin Hao , Chen Kangmei , Huang Kangling , Huang Songyin , Yao Yandan
Published: April 2022

Background

Growing evidence supports the modulatory role of human gut microbiome on neoadjuvant chemotherapy (NAC) efficacy. However, the relationships among the gut microbiome, tumor-infiltrating lymphocytes (TILs), and NAC response for breast cancer (BC) patients remain unclear. We thus proposed this preliminary study to investigate the relationship between gut microbiome and BC patients’ responses to NAC treatment as well as underlying mechanisms.

Methods

Prior to receiving NAC, the fecal metagenome collected from 23 patients with invasive BC was analyzed. Patients were subsequently assigned to the NAC non-effectual group and the NAC effectual group based on their response to NAC. The peripheral T lymphocyte subset counts were examined by flow cytometry methods. CellMinor analysis was employed to explore the relationship between CD4 mRNA expression and the reaction of tumor cells to NAC drugs.

Results

The gut microbiomes of the NAC non-effectual group showed characteristics of low diversity with low abundances, distinct metagenomic composition with decreased butyrate-producing and indolepropionic acid-producing bacteria, and increased potential pathobionts compared with the NAC effectual group. The combination of Coprococcus, Dorea, and uncultured Ruminococcus sp. serves as signature bacteria for distinguishing NAC non-effectual group patients from the NAC effectual group. The absolute numbers of CD4+ and CD8+ TIL infiltration in tumors in the NAC non-effectual group were significantly lower than those in the effectual group. Similar findings were reported for the CD4+ T lymphocytes in the peripheral blood (p’s < 0.05). NAC effectual-related signature bacteria were proportional to these patients’ CD4+ T lymphocyte counts in peripheral blood and tumors (p’s < 0.05). CellMinor analysis showed that the CD4 mRNA expression level dramatically climbed with increased sensitivity of tumor cells to NAC drugs such as cyclophosphamide, cisplatin, and carboplatin (p’s < 0.05).

Conclusions

The composition of the gut microbial community differs between BC patients for whom NAC is effective to those that are treatment resistant. The modulation of the gut microbiota on host CD4+ T lymphocytes may be one critical mechanism underlying chemosensitivity and NAC pathologic response. Taken together, gut microbiota may serve as a potential biomarker for NAC response, which sheds light on novel intervention targets in the treatment of NAC non-effectual BC patients.
Ventilation Weaning and Extubation Readiness in Children in Pediatric Intensive Care Unit: A Review
Authors: Poletto Elisa , Cavagnero Francesca , Pettenazzo Marco , Visentin Davide , Zanatta Laura , Zoppelletto Fabrizio , Pettenazzo Andrea , Daverio Marco , Bonardi Claudia Maria
Published: April 2022

Ventilation is one of the most common procedures in critically ill children admitted to the pediatric intensive care units (PICUs) and is associated with potential severe side effects. The longer the mechanical ventilation, the higher the risk of infections, mortality, morbidity and length of stay. Protocol-based approaches to ventilation weaning could have potential benefit in assisting the physicians in the weaning process but, in pediatrics, clear significant outcome difference related to their use has yet to be shown. Extubation failure occurs in up to 20% of patients in PICU with evidences demonstrating its occurrence related to a worse patient outcome including higher mortality. Various clinical approaches have been described to decide the best timing for extubation which can usually be achieved by performing a spontaneous breathing trial before the extubation. No clear evidence is available over which technique best predicts extubation failure. Within this review we summarize the current strategies of ventilation weaning and extubation readiness evaluation employed in the pediatric setting in order to provide an updated view on the topic to guide intensive care physicians in daily clinical practice. We performed a thorough literature search of main online scientific databases to identify principal studies evaluating different strategies of ventilation weaning and extubation readiness including pediatric patients receiving mechanical ventilation. Various strategies are available in the literature both for ventilation weaning and extubation readiness assessment with unclear clear data supporting the superiority of any approach over the others.
Microbiome Analysis and Pharmacovigilance After Inhaled Glucocorticoid: Oral Dysbiosis With the Isolation of Three Rothia Species and Subsequent Sjögren’s Syndrome
Authors: Zdziarski Przemysław , Paściak Mariola , Gamian Andrzej
Published: April 2022

Background: Treatment of respiratory tract diseases with inhaled glucocorticoids is a form of therapy that has been used for many years. It shows lower potency of side effects; nevertheless, microbiome change, sinopulmonary dysbiosis, secondary immunodeficiency, and immunomodulatory effects are underestimated. The latest guideline recommendations introduce the use of empirical antibiotic and/or multiplying inhaled glucocorticoids in therapeutic intervention of asthma and chronic pulmonary obstructive disease.

Aims and objectives: The aim of the study was to describe a simple, universal, and cost-effective method of microbiome analysis for clinical trials. Such a general method for monitoring pharmacovigilance should be widely available and reliable.

Methods: The study material included two kinds of swabs, taken from the same mouth ulcerations of patients with asthma treated with a temporary quadruple dose of fluticasone. The microbiological investigation was performed, and identification of the isolates was carried out using the matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF-MS) Biotyper.

Results: The analysis of dry swab demonstrated the presence of typical oral bacteria (Neisseria spp. and Streptococcus spp.), alongside with the potentially pathogenic Actinomyces spp. and three different Rothia species, identified simultaneously: R. aeria, R. dentocariosa, and R. mucilaginosa. Although quadrupled dose of corticoids was discontinued and ulcer healing was observed, the patients required topical therapy for maintained xerostomia. Progressive systemic autoimmunity (seronegative Sjögren’s syndrome with major organ involvement) was observed later.

Conclusion: Topical steroids (especially in quadruple dose) require attention to safety, immunomodulation, and microbiological outcome. They showed systemic side effects: microbiome alteration, humoral (IgG) immunodeficiency, and systemic autoimmunity. Isolation of three species of Rothia from a patient with mouth ulcers after steroid therapy suggests their participation in infectious and inflammatory processes. The proposed a methodology using MALDI-TOF-MS may be a prototype approach for microbial diagnostics in clinical trials of immunomodulatory drugs.
Identification of Natural Products as SENP2 Inhibitors for Targeted Therapy in Heart Failure
Authors: Taghvaei Somayye , Sabouni Farzaneh , Minuchehr Zarrin
Published: April 2022

Aims: Sentrin-specific protease -2 (SENP2) is involved in deSUMOylation. Increased deSUMOylation in murine hearts by SENP2 upregulation resulted in cardiac dysfunction and congenital heart defects. Natural compounds via regulating cell proliferation and survival, induce cell cycle cessation, cell death, apoptosis, and producing reactive oxygen species and various enzyme systems cause disease prevention. Then, natural compounds can be suitable inhibitors and since SENP2 is a protein involved in heart disease, so our aim was inhibition of SENP2 by natural products for heart disease treatment. Material and methods: Molecular docking and molecular dynamics simulation of natural products i.e. Gallic acid (GA), Caffeic acid (CA), Thymoquinone (TQ), Betanin, Betanidin, Fisetin, and Ebselen were done to evaluate the SENP2 inhibitory effect of these natural products. The toxicity of compounds was also predicted. Results: The results showed that Betanin constituted a stable complex with SENP2 active site as it revealed low RMSD, high binding energy, and hydrogen bonds. Further, as compared to Ebselen, Betanin demonstrated low toxicity, formed a stable complex with SENP2 via four to seven hydrogen bonds, and constituted more stable MD plots. Therefore, depending upon the outcomes presented herein, Betanin significantly inhibited SENP2 and hence may be considered as a suitable natural compound for the treatment of heart failure. Further clinical trials must be conducted to validate its use as a potential SENP2 inhibitor.