bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-cell multiomics revealed the dynamics of antigen presentation, immune response and T cell activation in the COVID-19 positive and recovered individuals
Authors: Chattopadhyay Partha , Khare Kriti , Kumar Manish , Mishra Pallavi , Anand Alok , Maurya Ranjeet , Gupta Rohit , Sahni Shweta , Gupta Ayushi , Wadhwa Saruchi , Yadav Aanchal , Devi Priti , Tardalkar Kishore , Joshi Meghnad , Sethi Tavpritesh , Pandey Rajesh
Published: December 2022

Introduction

Despite numerous efforts to describe COVID-19's immunological landscape, there is still a gap in our understanding of the virus's infections after-effects, especially in the recovered patients. This would be important to understand as we now have huge number of global populations infected by the SARS-CoV-2 as well as variables inclusive of VOCs, reinfections, and vaccination breakthroughs. Furthermore, single-cell transcriptome alone is often insufficient to understand the complex human host immune landscape underlying differential disease severity and clinical outcome.

Methods

By combining single-cell multi-omics (Whole Transcriptome Analysis plus Antibody-seq) and machine learning-based analysis, we aim to better understand the functional aspects of cellular and immunological heterogeneity in the COVID-19 positive, recovered and the healthy individuals.

Results

Based on single-cell transcriptome and surface marker study of 163,197 cells (124,726 cells after data QC) from the 33 individuals (healthy=4, COVID-19 positive=16, and COVID-19 recovered=13), we observed a reduced MHC Class-I-mediated antigen presentation and dysregulated MHC Class-II-mediated antigen presentation in the COVID-19 patients, with restoration of the process in the recovered individuals. B-cell maturation process was also impaired in the positive and the recovered individuals. Importantly, we discovered that a subset of the naive T-cells from the healthy individuals were absent from the recovered individuals, suggesting a post-infection inflammatory stage. Both COVID-19 positive patients and the recovered individuals exhibited a CD40-CD40LG-mediated inflammatory response in the monocytes and T-cell subsets. T-cells, NK-cells, and monocyte-mediated elevation of immunological, stress and antiviral responses were also seen in the COVID-19 positive and the recovered individuals, along with an abnormal T-cell activation, inflammatory response, and faster cellular transition of T cell subtypes in the COVID-19 patients. Importantly, above immune findings were used for a Bayesian network model, which significantly revealed FOS, CXCL8, IL1β, CST3, PSAP, CD45 and CD74 as COVID-19 severity predictors.

Discussion

In conclusion, COVID-19 recovered individuals exhibited a hyper-activated inflammatory response with the loss of B cell maturation, suggesting an impeded post-infection stage, necessitating further research to delineate the dynamic immune response associated with the COVID-19. To our knowledge this is first multi-omic study trying to understand the differential and dynamic immune response underlying the sample subtypes.
Novel organic selenium source hydroxy-selenomethionine counteracts the blood-milk barrier disruption and inflammatory response of mice under heat stress
Authors: Zheng Yuhui , Zhao Yanyan , He Wenjun , Wang Yajing , Cao Zhijun , Yang Hongjian , Wang Wei , Li Shengli
Published: December 2022

Heat stress (HS) in summer has caused huge economic losses to animal husbandry production recently. When mammary gland is exposed to high temperatures, it will cause blood-milk barrier damage. Hydroxy-selenomethionine (HMSeBA) is a new selenium source with better guarantee of animals’ production performance under stress, but whether it has protective effect on heat stress-induced blood-milk damage is still unclear. We established mammary epithelial cells and mice heat stress injury models to fill this research gap, and hope to provide theoretical basis for using HMSeBA to alleviate heat stress damage mammary gland. The results showed that (1) Heat stress significantly decreases in vitro transepithelial electrical resistance (TEER) and cell viability (P < 0.01), and significantly decreases clinical score, histological score, and total alveoli area of mice mammary gland tissue (P < 0.01). (2) HMSeBA significantly increases TEER and fluorescein sodium leakage of HS-induced monolayer BMECs (P < 0.01), significantly improves the milk production and total area of alveoli (P < 0.01), and reduces clinical score, histological score, mRNA expression of heat stress-related proteins, and inflammatory cytokines release of heat-stressed mice (P < 0.01). (3) HMSeBA significantly improves tight junction structure damage, and significantly up-regulated the expression of tight junction proteins (ZO-1, claudin 1, and occludin) as well as signal molecules PI3K, AKT, and mTOR (P < 0.01) in heat-stressed mammary tissue. (4) HMSeBA significantly increases glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), and superoxide dismutase release (SOD) (P < 0.01) and significantly reduce malondialdehyde (MDA) expression (P < 0.01) in heat-stressed mammary tissue. In conclusion, this study implemented heat-stressed cell and mice model and showed that HMSeBA significantly regulate antioxidant capacity, inhibited inflammation, and regulate tight junction proteins expression in blood-milk barrier via PI3K/AKT/mTOR signaling pathway, so as to alleviate mammary gland damage and ensure its structure and function integrity.
Predicting diagnostic gene expression profiles associated with immune infiltration in patients with lupus nephritis
Authors: Wang Lin , Yang Zhihua , Yu Hangxing , Lin Wei , Wu Ruoxi , Yang Hongtao , Yang Kang
Published: December 2022

Objective

To identify potential diagnostic markers of lupus nephritis (LN) based on bioinformatics and machine learning and to explore the significance of immune cell infiltration in this pathology.

Methods

Seven LN gene expression datasets were downloaded from the GEO database, and the larger sample size was used as the training group to obtain differential genes (DEGs) between LN and healthy controls, and to perform gene function, disease ontology (DO), and gene set enrichment analyses (GSEA). Two machine learning algorithms, least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE), were applied to identify candidate biomarkers. The diagnostic value of LN diagnostic gene biomarkers was further evaluated in the area under the ROC curve observed in the validation dataset. CIBERSORT was used to analyze 22 immune cell fractions from LN patients and to analyze their correlation with diagnostic markers.

Results

Thirty and twenty-one DEGs were screened in kidney tissue and peripheral blood, respectively. Both of which covered macrophages and interferons. The disease enrichment analysis of DEGs in kidney tissues showed that they were mainly involved in immune and renal diseases, and in peripheral blood it was mainly enriched in cardiovascular system, bone marrow, and oral cavity. The machine learning algorithm combined with external dataset validation revealed that C1QA(AUC = 0.741), C1QB(AUC = 0.758), MX1(AUC = 0.865), RORC(AUC = 0.911), CD177(AUC = 0.855), DEFA4(AUC= 0.843)and HERC5(AUC = 0.880) had high diagnostic value and could be used as diagnostic biomarkers of LN. Compared to controls, pathways such as cell adhesion molecule cam, and systemic lupus erythematosus were activated in kidney tissues; cell cycle, cytoplasmic DNA sensing pathways, NOD-like receptor signaling pathways, proteasome, and RIG-1-like receptors were activated in peripheral blood. Immune cell infiltration analysis showed that diagnostic markers in kidney tissue were associated with T cells CD8 and Dendritic cells resting, and in blood were associated with T cells CD4 memory resting, suggesting that CD4 T cells, CD8 T cells and dendritic cells are closely related to the development and progression of LN.

Conclusion

C1QA, C1QB, MX1, RORC, CD177, DEFA4 and HERC5 could be used as new candidate molecular markers for LN. It may provide new insights into the diagnosis and molecular treatment of LN in the future.
The spatial distribution of cystic echinococcosis in Italian ruminant farms from routine surveillance data
Authors: Entezami Mahbod , Nocerino Martina , Widdicombe Jo , Bosco Antonio , Cringoli Giuseppe , Casulli Adriano , Iacono Giovanni Lo , Rinaldi Laura , Prada Joaquin M.
Published: December 2022

Introduction

Cystic echinococcosis (CE) is a zoonotic parasite caused by the cestode Echinococcus granulosus sensu lato (s.l.) which predominantly affects livestock. The disease is endemic in central-southern and insular Italy, with CE particularly infecting sheep, goats, cattle, and water buffalo. The spatial distribution of CE in endemic regions is not widely understood, with surveillance efforts varying across the region.

Methods

In this study, we investigated the spatial distribution of CE in livestock using samples from farms across different livestock species using a Stochastic Partial Differential Equations (SPDE) model. Samples were collected during a survey conducted in the area of central-southern and insular Italy between the years 2019 – 2021.

Results

A total of 3141 animal samples (126 goats, 601 sheep and 2414 cattle and water buffalo) were inspected for Echinococcus s.l. cysts through routine surveillance in abattoirs by postmortem visual examination, palpation and incision of target organs. The geographic location of the farm of origin (a total of 2,878) for each sample was recorded. CE prevalence of 46.0% (1,323/2,878) was estimated at the farm level with 78.3% (462/590) of farms with sheep, 28.6% (36/126) of farms with goats, 36.5% (747/2,049) of farms with cattle, and 23.5% (102/434) of farms with water buffalo infected.

Discussion

The spatial model evaluated the probability of infection in farms across the sampled regions, with the distribution of CE showing high clustering of infected cattle farms in Sardinia and Sicily regions, and sheep farms in Salerno province (Campania region). The output of this study can be used to identify CE hot-spots and to improve surveillance and control programs in endemic areas of Italy.
Two canonically aerobic foraminifera express distinct peroxisomal and mitochondrial metabolisms
Authors: Powers Christopher , Gomaa Fatma , Billings Elizabeth B. , Utter Daniel R. , Beaudoin David J. , Edgcomb Virginia P. , Hansel Colleen M. , Wankel Scott D. , Filipsson Helena L. , Zhang Ying , Bernhard Joan M.
Published: December 2022

Certain benthic foraminifera thrive in marine sediments with low or undetectable oxygen. Potential survival avenues used by these supposedly aerobic protists include fermentation and anaerobic respiration, although details on their adaptive mechanisms remain elusive. To better understand the metabolic versatility of foraminifera, we studied two benthic species that thrive in oxygen-depleted marine sediments. Here we detail, via transcriptomics and metatranscriptomics, differential gene expression of Nonionella stella and Bolivina argentea, collected from Santa Barbara Basin, California, USA, in response to varied oxygenation and chemical amendments. Organelle-specific metabolic reconstructions revealed these two species utilize adaptable mitochondrial and peroxisomal metabolism. N. stella, most abundant in anoxia and characterized by lack of food vacuoles and abundance of intracellular lipid droplets, was predicted to couple the putative peroxisomal beta-oxidation and glyoxylate cycle with a versatile electron transport system and a partial TCA cycle. In contrast, B. argentea, most abundant in hypoxia and contains food vacuoles, was predicted to utilize the putative peroxisomal gluconeogenesis and a full TCA cycle but lacks the expression of key beta-oxidation and glyoxylate cycle genes. These metabolic adaptations likely confer ecological success while encountering deoxygenation and expand our understanding of metabolic modifications and interactions between mitochondria and peroxisomes in protists.
Exploratory analysis of radiomic as prognostic biomarkers in 18F-FDG PET/CT scan in uterine cervical cancer
Authors: Alencar Nadja Rolim Gonçalves de , Machado Marcos Antônio Dórea , Mourato Felipe Alves , Oliveira Mércia Liane de , Moraes Thauan Fernandes , Mattos Junior Luiz Alberto Reis , Chang Tien-Man Cabral , Azevedo Carla Rameri Alexandre Silva de , Brandão Simone Cristina Soares
Published: December 2022

Objective

To evaluate the performance of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) radiomic features to predict overall survival (OS) in patients with locally advanced uterine cervical carcinoma.

Methods

Longitudinal and retrospective study that evaluated 50 patients with cervical epidermoid carcinoma (clinical stage IB2 to IVA according to FIGO). Segmentation of the 18F-FDG PET/CT tumors was performed using the LIFEx software, generating the radiomic features. We used the Mann–Whitney test to select radiomic features associated with the clinical outcome (death), excluding the features highly correlated with each other with Spearman correlation. Subsequently, ROC curves and a Kaplan–Meier analysis were performed. A p-value < 0.05 were considered significant.

Results

The median follow-up was 23.5 months and longer than 24 months in all surviving patients. Independent predictors for OS were found–SUVpeak with an AUC of 0.74, sensitivity of 77.8%, and specificity of 72.7% (p = 0.006); and the textural feature gray-level run-length matrix GLRLM_LRLGE, with AUC of 0.74, sensitivity of 72.2%, and specificity of 81.8% (p = 0.005). When we used the derived cut-off points from these ROC curves (12.76 for SUVpeak and 0.001 for GLRLM_LRLGE) in a Kaplan–Meier analysis, we can see two different groups (one with an overall survival probability of approximately 90% and the other with 30%). These biomarkers are independent of FIGO staging.

Conclusion

By radiomic 18F-FDG PET/CT data analysis, SUVpeak and GLRLM_LRLGE textural feature presented the best performance to predict OS in patients with cervical cancer undergoing chemo-radiotherapy and brachytherapy.
Manual and semi-automated approaches to MIBG myocardial scintigraphy in patients with Parkinson’s disease
Authors: Boccalini Cecilia , Carli Giulia , Vanoli Emilia Giovanna , Cocco Antoniangela , Albanese Alberto , Garibotto Valentina , Perani Daniela
Published: December 2022

Objective

This study investigates the effects of manual and semi-automatic methods for assessing MIBG semi-quantitative indices in a clinical setting.

Materials and methods

We included 123I-MIBG scans obtained in 35 patients with idiopathic Parkinson’s Disease. Early and late heart-to-mediastinum (H/M) ratios were calculated from 123I-MIBG images using regions of interest (ROIs) placed over the heart and the mediastinum. The ROIs were derived using two approaches: (i) manually drawn and (ii) semi-automatic fixed-size ROIs using anatomical landmarks. Expert, moderate-expert, and not expert raters applied the ROIs procedures and interpreted the 123I-MIBG images. We evaluated the inter and intra-rater agreements in assessing 123I-MIBG H/M ratios.

Results

A moderate agreement in the raters’ classification of pathological and non-pathological scores emerged regarding early and late H/M ratio values (κ = 0.45 and 0.69 respectively), applying the manual method, while the early and late H/M ratios obtained with the semi-automatic method reached a good agreement among observers (κ = 0.78). Cohen-Kappa values revealed that the semi-automatic method improved the agreement between expert and inexpert raters: the agreement improved from a minimum of 0.29 (fair, for early H/M) and 0.69 (substantial, in late H/M) with the manual method, to 0.90 (perfect, in early H/M) and 0.87 (perfect, in late H/M) with the semi-automatic method.

Conclusion

The use of the semi-automatic method improves the agreement among raters in classifying’ H/M ratios as pathological or non-pathological, namely for inexpert readers. These results have important implications for semi-quantitative assessment of 123I-MIBG images in clinical routine.
Mucocutaneous manifestations of Behçet’s disease: Pathogenesis and management from perspectives of vasculitis
Authors: Kim Doyoung , Nakamura Koichiro , Kaneko Fumio , Alpsoy Erkan , Bang Dongsik
Published: December 2022

Behçet’s disease (BD) is a systemic inflammatory disorder characterized by vasculitis affecting blood vessels of any caliber or type. It can present with a wide spectrum of vasculitic lesions, including erythema nodosum-like lesions and retinal vasculitis, and may also lead to larger vessel diseases, such as aortic aneurysm and deep vein thrombosis. The full etiology of BD remains unclear, but it is considered a polygenetic disease with multiple genetic risk factors that promote immune dysregulation and thrombophilia. Inflammation can be triggered by environmental factors, such as bacteria or viruses, and the dysregulation of innate and adaptive immune cell subsets. Neutrophils and lymphocytes are the primary players involved in BD pathogenesis, with specific innate (i.e., neutrophil-derived reactive oxygen species and neutrophil extracellular traps) and adaptive (i.e., anti-endothelial cell antibodies) processes inducing endothelial cell activation and chemotaxis of inflammatory cells, leading to coagulation and vasculitis. These inflammation-induced vasculitic or vasculopathic features are observed in most mucocutaneous BD lesions, although vasculitis per se is often pathologically evident only during a brief period of the disease process. Due to the multifactorial nature of BD-associated inflammation, broad-spectrum anti-inflammatory medications, including glucocorticoids and immunosuppressive drugs, have been the mainstay for managing BD. In addition, inhibitors of interleukin (IL)-1, tumor necrosis factor (TNF)-α, and IL-17, which target innate and adaptive immune functions dysregulated in BD, have emerged as promising new therapeutics. In this review, we discuss the muco-cutaneous manifestations of BD by focusing on the underlying vasculitic components in their pathologies, as well as the current array of treatment options.
Rapid visual detection of anisakid nematodes using recombinase polymerase amplification and SYBR Green I
Authors: Chen Xiuqin , Zhao Lianjing , Wang Jiahui , Wang Haolu , Qiu Yangyuan , Dong Zijian , Zhang Chunling , Liu Mingyuan , Wang Xuelin , Bai Xue
Published: December 2022

Anisakidosis is a food-borne parasitic disease (FBPD) caused by the third-stage larvae of the family Anisakidae. Therefore, it is important to develop a simple, rapid and equipment-free detection method for anisakids in fish samples or seafood since current methods are time-consuming and require complex instruments. In this study, a recombinase polymerase amplification (RPA)-based method was established for the first time to detect anisakids by targeting the internal transcribed spacer (ITS) regions. The detection results were visualized by including SYBR Green I (SG) in the method. The sensitivity of RPA-SG assay was 102 copies per reaction of recombinant plasmid (within 20 min at 37°C), similar to quantitative real-time PCR (qPCR). The assay had high specificity for detecting anisakids against other related parasites and host fish. In addition, the assay was further used to detect fresh marine fish contaminated with anisakids and it showed high precision. These results indicate that the novel RPA-SG assay suitable for visual detection of anisakids in the field and food safety control.
Antifungal metabolites, their novel sources, and targets to combat drug resistance
Authors: Choudhary Megha , Kumar Vijay , Naik Bindu , Verma Ankit , Saris Per Erik Joakim , Kumar Vivek , Gupta Sanjay
Published: December 2022

Excessive antibiotic prescriptions as well as their misuse in agriculture are the main causes of antimicrobial resistance which poses a growing threat to public health. It necessitates the search for novel chemicals to combat drug resistance. Since ancient times, naturally occurring medicines have been employed and the enormous variety of bioactive chemicals found in nature has long served as an inspiration for researchers looking for possible therapeutics. Secondary metabolites from microorganisms, particularly those from actinomycetes, have made it incredibly easy to find new molecules. Different actinomycetes species account for more than 70% of naturally generated antibiotics currently used in medicine, and they also produce a variety of secondary metabolites, including pigments, enzymes, and anti-inflammatory compounds. They continue to be a crucial source of fresh chemical diversity and a crucial component of drug discovery. This review summarizes some uncommon sources of antifungal metabolites and highlights the importance of further research on these unusual habitats as a source of novel antimicrobial molecules.
Real-time reverse transcription recombinase polymerase amplification for rapid detection of murine hepatitis virus
Authors: Wang Xiao , Sui Xin , Ma Yueyu , Li Ming , Zhang Xu , Fei Dongliang , Ma Mingxiao
Published: December 2022

Murine hepatitis virus (MHV) is a highly infectious murine coronavirus that has a high potential for causing harm to host animals. This study aimed to develop a real-time reverse transcription recombinase polymerase amplification (RT-RPA) method for rapid detection of MHV in laboratory mice.

Methods

Specific primers and probes for RT-RPA assay were designed targeting the conserved region in the M gene of the MHV reference strain (accession no. FJ6647223) according to the TwistDx manual instructions. The specificity, sensitivity, and reproducibility of the RT-RPA method were evaluated and compared with those of the standard RT-qPCR method. The clinical applicability of this assay was evaluated using 68 field samples.

Results

Amplification using the newly developed RT-RPA assay was completed within 20 min at 37°C, while that using the RT-qPCR method required nearly 60 min. The RT-RPA method exhibited an obvious time-saving advantage. Both RT-RPA and RT-PCR methods had the same limit of detection, which was 4.45 × 101 copies/μL. The specificity was indicated by a lack of cross-reaction with MHV, pneumonia virus of mice, Sendai virus, hantavirus, minute virus of mice, and reovirus type III. The MHV detection rate of RT-RPA assays was 13.63% (9/66) and RT-qPCR assays was 15.15% (10/66). Cohen’s “kappa” (κ) analysis results exhibited a very good agreement between two methods with the value of κ ≥ 0.750(since κ = 0.939) and p < 0.0005 (since p = 0.000).

Conclusion

The RT-RPA assay offers an alternative tool for simple, rapid, and reliable detection of MHV in laboratory mice and has significant potential for application in laboratories.
Global phylogenomic novelty of the Cas1 gene from hot spring microbial communities
Authors: Salgado Oscar , Guajardo-Leiva Sergio , Moya-Beltrán Ana , Barbosa Carla , Ridley Christina , Tamayo-Leiva Javier , Quatrini Raquel , Mojica Francisco J. M. , Díez Beatriz
Published: December 2022

The Cas1 protein is essential for the functioning of CRISPR-Cas adaptive systems. However, despite the high prevalence of CRISPR-Cas systems in thermophilic microorganisms, few studies have investigated the occurrence and diversity of Cas1 across hot spring microbial communities. Phylogenomic analysis of 2,150 Cas1 sequences recovered from 48 metagenomes representing hot springs (42–80°C, pH 6–9) from three continents, revealed similar ecological diversity of Cas1 and 16S rRNA associated with geographic location. Furthermore, phylogenetic analysis of the Cas1 sequences exposed a broad taxonomic distribution in thermophilic bacteria, with new clades of Cas1 homologs branching at the root of the tree or at the root of known clades harboring reference Cas1 types. Additionally, a new family of casposases was identified from hot springs, which further completes the evolutionary landscape of the Cas1 superfamily. This ecological study contributes new Cas1 sequences from known and novel locations worldwide, mainly focusing on under-sampled hot spring microbial mat taxa. Results herein show that circumneutral hot springs are environments harboring high diversity and novelty related to adaptive immunity systems.
Factors associated with antidepressant responses to repetitive transcranial magnetic stimulation in antidepressant-resistant depression
Authors: Li Cheng-Ta , Su Tung-Ping , Cheng Chih-Ming , Chen Mu-Hong , Bai Ya-Mei , Tsai Shih-Jen
Published: December 2022

Background

A significant proportion of patients with major depressive disorder (MDD) failed to respond to antidepressant medications. Repetitive transcranial magnetic stimulation (rTMS) is an effective option for treating such treatment-resistant patients with MDD (TRD). Reliable clinical predictors for antidepressant responses to rTMS remain elusive.

Methods

In total, 212 patients with MDD who failed to respond to at least one adequate antidepressant trial and had a detailed evaluation before rTMS were recruited for chart review. Demographic data, clinical characteristics, psychiatric comorbidities, symptom ratings [e.g., objective and subjective depression, life stress, depression refractoriness by Maudsley Staging Method (MSM)], and antidepressant treatment responses were analyzed.

Results

MSM-subitem1 (duration of current depressive episode; Beta = 0.209, p = 0.004), MSM-subitem5 (a history of ECT treatment; Beta = –0.210, p = 0.004), and psychiatric admissions (Beta = 0.241, p = 0.001) predicted antidepressant response of rTMS treatment. ECT was underutilized (only 3.3%). Psychiatric admissions [Exp(B) = 1.382, p = 0.021], a comorbidity of OCD [0.047, 0.005], and life stress level [0.984, 0.029] predicted the history of ECT treatment.

Conclusion

Several clinical variables (e.g., number of psychiatric admissions, OCD as a comorbidity, and life stress level) were reliable clinical factors associated with antidepressant responses of rTMS treatment and may be utilized in combination with MSM subitems to evaluate levels of TRD.
Optimisation of the chemical oxidation reduction process (CORD) on surrogate stainless steel in regards to its efficiency and secondary wastes
Authors: Rivonkar Aditya , Katona Richárd , Robin Mathurin , Suzuki-Muresan Tomo , Abdelouas Abdessalam , Mokili Marcel , Bátor Gergő , Kovács Tibor
Published: December 2022

Nuclear Power is a decarbonated technology of electrical energy generation. Using nuclear energy as a power source is currently considered as the best option in the fight against climate change. But the radioactive waste generated from nuclear power plants and their related facilities are matter of concern. Though the high level and intermediate level activity wastes are contained in small volumes (≤10%), significant volumes of lower activity wastes are generated. Metallic wastes are a major component of these radioactive wastes with about 500,000 tons expected in France alone, including 130,000 tons from steam generators. Majority of these metals are made of Stainless steel 316 alloy or Inconel 600. Under the effect of the primary circuit thermal-hydraulic constraints and irradiation, these the resulting corrosion products may be activated when close to the fuel, and be transported throughout the circuit. These products can be deposited on the surface of other metal components, causing contamination of the latter. The contamination can be adsorbed on the surface but can also diffuse in the oxide layers and sub-surface. The oxide layer is composed of an inner layer of Cr oxide under a layer of Ni and Fe oxide. Chemical decontamination is preferred due to the possibility of decontamination of difficult geometries and tube bends. In order to decontaminate these materials, it is important to dissolve the oxide layers chemically and a few micrometers of base metal where it could have diffused. An existing chemical method used to treat these materials is studied in this article, Chemical Oxidation Reduction Decontamination (CORD). Surrogate steel samples were prepared using high temperature induction heating and water vapour after sample preparation and cleaning. The oxide layer was characterised before treatment of the samples in the batch method at different concentrations and its effects are observed on the dissolution of the oxide layers. A protocol is being developed for the treatment of secondary waste effluents by multi-stage precipitation with a goal to reduce the total waste volumes and thus the volumes of ion exchange resins that would otherwise be needed.
The potential role of preventive and therapeutic immunonutrition strategies for pediatric food allergy: A mini-review
Authors: Coppola Serena , Carucci Laura , De Michele Roberta , Berni Canani Roberto
Published: December 2022

Food allergy (FA) represents one of the main chronic conditions of the pediatric population. The gut microbiome (GM)-immune system axis is a milestone in affecting FA susceptibility. The dynamic and bidirectional crosstalk between the GM and immune system starts early in life, and it is deeply modulated during the first 1,000 days of life. Nutritional factors during this crucial period mainly influence the proper GM-immune system development and function across the lifespan, with potential beneficial or detrimental effects on health status. Immunonutrition strategies, applied from conception, could represent an innovative target for prevention and treatment of pediatric FA. Here we described the potential role of preventive and therapeutic immunonutrition strategies for pediatric FA, highlighting putative future perspectives in this field.
Patients with dysphagia: How to supply nutrition through non-tube feeding
Authors: Shen Zhean , Hou Yingze , Huerman Ayideng , Ma Aiqin
Published: December 2022

Objective

Dysphagia has become one of the important factors that cause malnutrition in the whole age group. At present, tube feeding is still the mainstream means to solve the problem of dysphagia. However, tube feeding has physical and mental harm to people, and the ways of non-tube feeding are relatively diversified. The significance of the thickening mechanism described in some articles to solve the problem of dysphagia is not clear.

Setting and participants

All patients with dysphagia worldwide, including oropharyngeal dysphagia (OD) and non-oropharyngeal dysphagia.

Methods

We searched the literature in Pubmed, Web of Science and Cochrane Library and initially browsed the titles and abstracts. We reviewed the full text of the articles that met our topic, and the language of the article was limited to English.

Results

We found that food thickening to a certain degree (350–1,750 cP) can reduce the complications of choking, aspiration, reflux, and other complications in patients with dysphagia, and reduce the social disorder, anxiety, and other psychological problems caused by catheterization and surgery. Significantly, food science engineers should invite clinicians to intervene in the development of specialty foods from different perspectives such as clinical pathophysiology and fluid mechanics.

Conclusion and implications

It is necessary to develop special foods for patients with dysphagia, which requires scientists from different disciplines to work together.
3D vs. 2D MRI radiomics in skeletal Ewing sarcoma: Feature reproducibility and preliminary machine learning analysis on neoadjuvant chemotherapy response prediction
Authors: Gitto Salvatore , Corino Valentina D. A. , Annovazzi Alessio , Milazzo Machado Estevāo , Bologna Marco , Marzorati Lorenzo , Albano Domenico , Messina Carmelo , Serpi Francesca , Anelli Vincenzo , Ferraresi Virginia , Zoccali Carmine , Aliprandi Alberto , Parafioriti Antonina , Luzzati Alessandro , Biagini Roberto , Mainardi Luca , Sconfienza Luca Maria
Published: December 2022

Objective

The extent of response to neoadjuvant chemotherapy predicts survival in Ewing sarcoma. This study focuses on MRI radiomics of skeletal Ewing sarcoma and aims to investigate feature reproducibility and machine learning prediction of response to neoadjuvant chemotherapy.

Materials and methods

This retrospective study included thirty patients with biopsy-proven skeletal Ewing sarcoma, who were treated with neoadjuvant chemotherapy before surgery at two tertiary sarcoma centres. 7 patients were poor responders and 23 were good responders based on pathological assessment of the surgical specimen. On pre-treatment T1-weighted and T2-weighted MRI, 2D and 3D tumour segmentations were manually performed. Features were extracted from original and wavelet-transformed images. Feature reproducibility was assessed through small geometrical transformations of the regions of interest mimicking multiple manual delineations, and intraclass correlation coefficient >0.75 defined feature reproducibility. Feature selection also consisted of collinearity and significance analysis. After class balancing in the training cohort, three machine learning classifiers were trained and tested on unseen data using hold-out cross-validation.

Results

1303 (77%) 3D and 620 (65%) 2D radiomic features were reproducible. 4 3D and 4 2D features passed feature selection. Logistic regression built upon 3D features achieved the best performance with 85% accuracy (AUC=0.9) in predicting response to neoadjuvant chemotherapy.

Conclusion

Compared to 2D approach, 3D MRI radiomics of Ewing sarcoma had superior reproducibility and higher accuracy in predicting response to neoadjuvant chemotherapy, particularly when using logistic regression classifier.
Detection of somatic copy number deletion of the CDKN2A gene by quantitative multiplex PCR for clinical practice
Authors: Tian Yuan , Zhou Jing , Qiao Juanli , Liu Zhaojun , Gu Liankun , Zhang Baozhen , Lu Youyong , Xing Rui , Deng Dajun
Published: December 2022

Background

A feasible method to detect somatic copy number deletion (SCND) of genes is still absent to date.

Methods

Interstitial base-resolution deletion/fusion coordinates for CDKN2A were extracted from published articles and our whole genome sequencing (WGS) datasets. The copy number of the CDKN2A gene was measured with a quantitative multiplex PCR assay P16-Light and confirmed with whole genome sequencing (WGS).

Results

Estimated common deletion regions (CDRs) were observed in many tumor suppressor genes, such as ATM, CDKN2A, FAT1, miR31HG, PTEN, and RB1, in the SNP array-based COSMIC datasets. A 5.1 kb base-resolution CDR could be identified in >90% of cancer samples with CDKN2A deletion by sequencing. The CDKN2A CDR covers exon-2, which is essential for P16INK4A and P14ARF synthesis. Using the true CDKN2A CDR as a PCR target, a quantitative multiplex PCR assay P16-Light was programmed to detect CDKN2A gene copy number. P16-Light was further confirmed with WGS as the gold standard among cancer tissue samples from 139 patients.

Conclusion

The 5.1 kb CDKN2A CDR was found in >90% of cancers containing CDKN2A deletion. The CDKN2A CDR was used as a potential target for developing the P16-Light assay to detect CDKN2A SCND and amplification for routine clinical practices.
Immunogenicity of SARS-CoV-2 vaccination in patients undergoing autologous stem cell transplantation. A multicentric experience
Authors: Autore Francesco , Stirparo Luca , Innocenti Idanna , Papa Elena , Marchesi Francesco , Togni Chiara , Mariani Sabrina , Torrieri Lorenzo , Salvatori Martina , Fazio Francesca , Metafuni Elisabetta , Giammarco Sabrina , Sora Federica , Falcucci Paolo , Ferrari Antonella , Trisolini Silvia Maria , Capria Saveria , Tafuri Agostino , Chiusolo Patrizia , Sica Simona , Laurenti Luca
Published: December 2022

COVID-19 disease has a strong impact on hematological patients; those receiving autologous hematopoietic stem cell transplantation (aHSCT) represent a particularly vulnerable group, in which the effectiveness of vaccination is very variable. Chiarucci et al. showed that patients affected by non-Hodgkin lymphoma (NHL) and treated with rituximab experienced a lower rate of immunization against SARS-CoV-2 (54%), as well as significantly lower IgG antibody titers. In our multicenter retrospective observational study, we included 82 patients who underwent aHSCT, divided into two groups: 58 patients vaccinated after aHSCT (group A) and 24 vaccinated before getting transplantation (group B). In group A, 39 (67%) patients had positive serology, and the rate of positivity increased with time after aHSCT. In the subgroup of patients with NHL, the administration of rituximab predicted negative serology, particularly when administered in the 6 months before vaccination (13% response rate). Patients affected by plasma cells had a higher rate of positivity (83% overall), independently of the time to aHSCT. In group B, no patient who initially showed positive serology became negative after transplantation, so the aHSCT did not affect the response to the vaccination. Our study confirmed the role of rituximab as a negative predictor of response to SARS-CoV-2 vaccination, whereas the conditioning and transplantation procedure itself seemed to be less important.
Immune-based treatment re-challenge in renal cell carcinoma: A systematic review and meta-analysis
Authors: Papathanassiou Maria , Tamposis Ioannis , Exarchou-Kouveli Kalliopi K. , Kontou Panagiota I. , de Paz Anna Tzortzi , Mitrakas Lampros , Samara Maria , Bagos Pantelis G. , Tzortzis Vassilios , Vlachostergios Panagiotis J.
Published: December 2022

Introduction

The use of immune checkpoint inhibitors (ICIs) as a front-line treatment for metastatic renal cell carcinoma (RCC) has significantly improved patient’ outcome. However, little is known about the efficacy or lack thereof of immunotherapy after prior use of anti-PD1/PD-L1 or/and anti-CTLA monoclonal antibodies.

Methods

Electronic databases, including PubMed, EMBASE, Medline, Web of Science, and Cochrane Library, were comprehensively searched from inception to July 2022. Objective response rates (ORR), progression-free survival (PFS), and ≥ grade 3 adverse events (AEs) were assessed in the meta-analysis, along with corresponding 95% confidence intervals (CIs) and publication bias.

Results

Ten studies which contained a total of 500 patients were included. The pooled ORR was 19% (95% CI: 10, 31), and PFS was 5.6 months (95% CI: 4.1, 7.8). There were ≥ grade 3 AEs noted in 25% of patients (95% CI: 14, 37).

Conclusion

This meta-analysis on different second-line ICI-containing therapies in ICI-pretreated mRCC patients supports a modest efficacy and tolerable toxicity.
A review on the socio-environmental impacts of lithium supply for electric aircraft
Authors: Chen-Glasser Melodie , DeCaluwe Steven C.
Published: December 2022

Electrified aircraft have gained traction as a promising approach to emissions abatement in the aviation sector. This transition will require overcoming numerous technical challenges related to increasing battery energy density, as well as logistic challenges related to the lithium supply chain, which is already stressed due to high demand for electric vehicles. We have estimated that lithium demand for electrified aviation may raise lithium demand in the range of 10–250%. The uncertainty in these estimates show the importance of quantifying the impacts of electrified aviation and designing batteries to mitigate additional demand. In addition, most reviews on electrified aviation do not include information on the localized social and environmental impacts caused by lithium demand, despite their importance to enabling technology necessary for emissions reductions. This review seeks to fill this gap by presenting an overview of environmental and social research in context with one another to encourage researchers in the field to consider these dynamics as part of electrified aircraft design. Given that the high energy density batteries necessary to enable large-scale electrification of aircraft are still under development, continued progress in this field should emphasize sustainable governance for lithium extraction and a circular battery economy to reduce social and environmental stressors.
Potential mechanisms of Lian-Zhi-Fan solution for TNBS-induced ulcerative colitis in rats via a metabolomics approach
Authors: Bai Junyi , Xiong Tingting , Wang Xiao , Cheng Yanfen , Luo Ruifeng , Yang Xiangdong , Fu Chaomei
Published: December 2022

Lian-Zhi-Fan (LZF) decoction is a hospital-prescribed traditional Chinese medicine botanical drug prepared by the fermentation of decocted Coptidis Rhizome (Huanglian), Gardeniae Fructus (Zhizi), and alum (Baifan). It has been used clinically in China for the treatment of anal fistula, perianal abscess, ulcerative colitis (UC), and other anorectal diseases for hundreds of years. However, due to the complexity of traditional Chinese medicine, the potential mechanisms of LZF in the treatment of UC have remained unknown. This study primarily investigated the remarkable pharmacological effects of LZF on TNBS-induced UC rats. To explore the complex targets and regulatory mechanisms of metabolic networks under LZF intervention, a metabolomics approach mediated by HPLC/Q-TOF-MS analysis was used to screen the different metabolites and their metabolic pathways in the serum in order to characterize the possible anti-UC mechanisms of LZF. After rectal administration of LZF for seven consecutive days, significant amelioration effects on body weight loss, DAI score, and colon inflammation were found in UC rats. Based on this, further metabolomics identified 14 potential biomarkers in the treatment of UC with LZF, of which five possessed diagnostic significance: L-alanine, taurocholic acid, niacinamide, cholic acid, and L-valine. These metabolites are mainly involved in 12 metabolic pathways, including nicotate and nicotinamide metabolism, glycospholipid metabolism, arginine and proline metabolism, primary bile acid biosynthesis, and pantothenate and CoA biosynthesis. These metabolic pathways suggest that LZF ameliorates UC by regulating amino acid metabolism, fat metabolism, and energy production. This study provides a useful approach for exploring the potential mechanisms of herbal prescription in UC treatment mediated by metabolomics.
Human matters in asthma: Considering the microbiome in pulmonary health
Authors: Marathe Sandesh J. , Snider Mark A. , Flores-Torres Armando S. , Dubin Patricia J. , Samarasinghe Amali E.
Published: December 2022

Graphical Abstract

Exogenous factors that influence the microbiome and asthma pathogenesis. External factors including a well-balanced diet and clean air support a healthy gut microbiome that releases metabolites and short-chain fatty acids (SCFA) that promote a healthy pulmonary immune system that remains non-inflammatory thereby protecting against the development of asthma or asthma exacerbations (left panel). An unhealthy diet, dirty air, and some pharmaceutical agents on the other hand can induce dysbiosis in the gut and lung microbial communities through induction of co-morbid states like obesity and aberrant immune activation. Additional confounders including modes of delivery and feeding, use of antibiotics during pregnancy and childhood also have an impact on the airway microbial homeostasis and asthma onset and pathogenesis (right panel). Figure prepared on BioRender.
Understanding inter-individual variability in pharmacokinetics/pharmacodynamics of aripiprazole in children with tic disorders: Individualized administration based on physiological development and CYP2D6 genotypes
Authors: Xin Yingying , Gao Liuliu , Tuo Yali , Nie Gang , Mei Yan , Chen Chen , Wang Jun , Li Sichan , Sun Dan , Qian Qiaoqiao , Fu Yongli , Wang Yang , Liu Zhisheng
Published: December 2022

Objective: This study aims to develop a combined population pharmacokinetic (PPK) model for aripiprazole (ARI) and its main active metabolite dehydroaripiprazole (DARI) in pediatric patients with tic disorders (TD), to investigate the inter-individual variability caused by physiological and genetic factors in pharmacokinetics of ARI and optimize the dosing regimens for pediatric patients.

Methods: A prospective PPK research was performed in Chinese children with TD. Totally 84 patients aged 4.83–17.33 years were obtained for the pharmacokinetic analysis. 27 CYP2D6 and ABCB1 gene alleles were detected. Moreover, the clinical efficacy was evaluated according to reduction rate of Yale Global Tic Severity Scale (YGTSS) score at the 12th week comparing with the baseline. Monte Carlo simulations were used to evaluate and optimize dosing regimens.

Results: The PPK model was established to predict the concentrations of ARI and DARI. Body weight and CYP2D6 genotype were the significant covariates affecting the clearance of ARI. The DARI/ARI metabolic ratios (MRs) of AUC24h, Cmin and Cmax at the steady state of results were ultra-rapid metabolizers (UMs) > normal metabolizers (NMs) > intermediated metabolizers (IMs). MRs could be used to distinguish UMs or IMs from other patients. The best predictor of clinical efficacy for TD was the trough concentration of ARI and the cut-off point was 101.636 ng/ml.

Conclusion: The pharmacokinetics of ARI and DARI in pediatric TD were significantly influenced by body weight and CYP2D6 genotype. Individualized dosing regimens were recommended for pediatric patients with TD to ensure clinical efficacy.
The iron-modulating hormone hepcidin is upregulated and associated with poor survival outcomes in renal clear cell carcinoma
Authors: Huang Jian , Liu Wang , Song Shiqi , Li Jean C. , Gan Kaimei , Shen Chunxiao , Holzbeierlein Jeffrey , Li Benyi
Published: December 2022

Background: Reliable biomarkers are rare for renal cell carcinoma (RCC) treatment selection. We aimed to discover novel biomarkers for precision medicine. The iron-regulating hormone hepcidin (HAMP) was reportedly increased in RCC patient sera and tissues. However, its potential implication as a prognostic biomarker remains exclusive.

Methods: Multiple RNA-seq and cDNA microarray datasets were utilized to analyze gene expression profiles. Hepcidin protein expression was assessed using an ELISA assay in cell culture models. Comparisons of gene expression profiles and patient survival outcomes were conducted using the R package bioinformatics software.

Results: Five (HAMP, HBS, ISCA2, STEAP2, and STEAP3) out of 71 iron-modulating genes exhibited consistent changes along with tumor stage, lymph node invasion, distal metastasis, tumor cell grade, progression-free interval, overall survival, and disease-specific survival. Of which HAMP upregulation exerted as a superior factor (AUC = 0.911) over the other four genes in distinguishing ccRCC tissue from normal renal tissue. HAMP upregulation was tightly associated with its promoter hypomethylation and immune checkpoint factors (PDCD1, LAG3, TIGIT, and CTLA4). Interleukin-34 (IL34) treatment strongly enhanced hepcidin expression in renal cancer Caki-1 cells. Patients with higher levels of HAMP expression experienced worse survival outcomes.

Conclusion: These data suggest that HAMP upregulation is a potent prognostic factor of poor survival outcomes and a novel immunotherapeutic biomarker for ccRCC patients.
Validation of a simplified-geometry model of inhaled formoterol pharmacodynamics in asthmatic patients
Authors: Panunzi Simona , Gaz Claudio , Cibella Fabio , De Gaetano Andrea
Published: December 2022

PharmacoKinetics (PK) and PharmacoDynamics (PD) mathematical models of inhaled bronchodilators represent useful tools for understanding the mechanisms of drug action and for the individuation of therapy regimens. A PK/PD model for inhaled bronchoactive compounds was previously proposed, incorporating a simplified-geometry approach: the key feature of that model is a mixed compartmental and spatially distributed representation of the kinetics, with the direct computation of representative flow rates from Ohm’s law and bronchial diameter profiles. The aim of the present work is the enrichment and validation of this simplified geometry modeling approach against clinical efficacy data. The improved model is used to compute airflow response to treatment for each single virtual patient from a simulated population and it is found to produce very good fits to observed FEV1 profiles. The model provides a faithful quantitative description of the increasing degree of improvement with respect to basal conditions with continuing administration and with increasing drug dosages, as clinically expected.