bluuebunny/crossref_metadata_2025 huggingface dataset:
Metatranscriptome-based strategy reveals the existence of novel mycoviruses in the plant pathogenic fungus Fusarium oxysporum f. sp. cubense
Authors: Ye Yiting , Liu Yingying , Zhang Yifei , Wang Xin , Li Huaping , Li Pengfei
Published: May 2023

Fusarium oxysporum f. sp. cubense (Foc) is a devastating plant pathogen that caused a great financial loss in the banana’s source area. Metatranscriptomic analysis was used to determine the diversity of mycoviruses in 246 isolates of F. oxysporum f. sp. cubense. Partial or nearly complete genomes of 20 mycoviruses were obtained by BLASTp analysis of RNA sequences using the NCBI database. These 20 viruses were grouped into five distinct lineages, namely Botourmiaviridae, Endornaviridae, Mitoviridae, Mymonaviridae, Partitiviridae, and two non-classified mycoviruses lineages. To date, there is no report of the presence of mycoviruses in this pathogen. In this study, we demonstrate the presence of mycoviruses isolated from Foc. These findings enhance our overall knowledge of viral diversity and taxonomy in Foc. Further characterization of these mycoviruses is warranted, especially in terms of exploring these novel mycoviruses for innovative biocontrol of banana Fusarium wilt disease.
Functional diversity of staphylococcal surface proteins at the host-microbe interface
Authors: Schwermann Nicoletta , Winstel Volker
Published: May 2023

Surface proteins of Gram-positive pathogens are key determinants of virulence that substantially shape host-microbe interactions. Specifically, these proteins mediate host invasion and pathogen transmission, drive the acquisition of heme-iron from hemoproteins, and subvert innate and adaptive immune cell responses to push bacterial survival and pathogenesis in a hostile environment. Herein, we briefly review and highlight the multi-facetted roles of cell wall-anchored proteins of multidrug-resistant Staphylococcus aureus, a common etiological agent of purulent skin and soft tissue infections as well as severe systemic diseases in humans. In particular, we focus on the functional diversity of staphylococcal surface proteins and discuss their impact on the variety of clinical manifestations of S. aureus infections. We also describe mechanistic and underlying principles of staphylococcal surface protein-mediated immune evasion and coupled strategies S. aureus utilizes to paralyze patrolling neutrophils, macrophages, and other immune cells. Ultimately, we provide a systematic overview of novel therapeutic concepts and anti-infective strategies that aim at neutralizing S. aureus surface proteins or sortases, the molecular catalysts of protein anchoring in Gram-positive bacteria.
Genome sequencing with comprehensive variant calling identifies structural variants and repeat expansions in a large fraction of individuals with ataxia and/or neuromuscular disorders
Authors: Ek Marlene , Nilsson Daniel , Engvall Martin , Malmgren Helena , Thonberg Håkan , Pettersson Maria , Anderlid Britt-Marie , Hammarsjö Anna , Helgadottir Hafdis T. , Arnardottir Snjolaug , Naess Karin , Nennesmo Inger , Paucar Martin , Hjartarson Helgi Thor , Press Rayomand , Solders Göran , Sejersen Thomas , Lindstrand Anna , Kvarnung Malin
Published: May 2023

Introduction

Neuromuscular disorders (NMDs) have a heterogeneous etiology. A genetic diagnosis is key to personalized healthcare and access to targeted treatment for the affected individuals.

Methods

In this study, 861 patients with NMDs were analyzed with genome sequencing and comprehensive variant calling including single nucleotide variants, small insertions/deletions (SNVs/INDELs), and structural variants (SVs) in a panel of 895 NMD genes, as well as short tandem repeat expansions (STRs) at 28 loci. In addition, for unsolved cases with an unspecific clinical presentation, the analysis of a panel with OMIM disease genes was added.

Results

In the cohort, 27% (232/861) of the patients harbored pathogenic variants, of which STRs and SVs accounted for one-third of the patients (71/232). The variants were found in 107 different NMD genes. Furthermore, 18 pediatric patients harbored pathogenic variants in non-NMD genes.

Discussion

Our results highlight that for children with unspecific hypotonia, a genome-wide analysis rather than a disease-based gene panel should be considered as a diagnostic approach. More importantly, our results clearly show that it is crucial to include STR- and SV-analyses in the diagnostics of patients with neuromuscular disorders.
The incidence of vestibular neuritis in Italy
Authors: Mandalà Marco , Salerni Lorenzo , Ferretti Fabio , Bindi Ilaria , Gualtieri Giacomo , Corallo Giulia , Viberti Francesca , Gusinu Roberto , Fantino Claudio , Ponzo Silvia , Astore Serena , Boccuzzi Simone , Nuti Daniele
Published: May 2023

Objective

This study aims to estimate the incidence of Vestibular neuritis (VN) in three different districts in Italy, its epidemiological features, and the prevalence of comorbidities associated with it.

Methods

An observational prospective study of 198 patients referred to ENT departments in Siena, Grosseto, and Cuneo was carried out over a 2-year period. Each patient underwent a complete otoneurologic examination in the first 48 h from the onset of symptoms and a brain MRI in the early stages of the disease. The follow-up lasted for 1 year.

Results

The total VN incidence rate of the three municipalities was 48.497 (95% CI: 48.395–48.598) and its standardized value was 53.564 (95% CI: 53.463–53.666). The total VN incidence rate for the whole sample (municipality and district of the three centers) was 18.218 (95% CI: 18.164–18.272), and its standardized value was 20.185 (95% CI: 20.129–20.241). A significant difference was highlighted between patients living in the city compared to those living in the surrounding area (p < 0.000), this may be due to the ease of reaching the otoneurological referral center.

Conclusion

The total incidence rate for the three municipalities was 48.497. This result is higher than previously reported studies.
Drosophila melanogaster as a model to study autophagy in neurodegenerative diseases induced by proteinopathies
Authors: Santarelli Stefania , Londero Chiara , Soldano Alessia , Candelaresi Carlotta , Todeschini Leonardo , Vernizzi Luisa , Bellosta Paola
Published: May 2023

Proteinopathies are a large group of neurodegenerative diseases caused by both genetic and sporadic mutations in particular genes which can lead to alterations of the protein structure and to the formation of aggregates, especially toxic for neurons. Autophagy is a key mechanism for clearing those aggregates and its function has been strongly associated with the ubiquitin-proteasome system (UPS), hence mutations in both pathways have been associated with the onset of neurodegenerative diseases, particularly those induced by protein misfolding and accumulation of aggregates. Many crucial discoveries regarding the molecular and cellular events underlying the role of autophagy in these diseases have come from studies using Drosophila models. Indeed, despite the physiological and morphological differences between the fly and the human brain, most of the biochemical and molecular aspects regulating protein homeostasis, including autophagy, are conserved between the two species.In this review, we will provide an overview of the most common neurodegenerative proteinopathies, which include PolyQ diseases (Huntington’s disease, Spinocerebellar ataxia 1, 2, and 3), Amyotrophic Lateral Sclerosis (C9orf72, SOD1, TDP-43, FUS), Alzheimer’s disease (APP, Tau) Parkinson’s disease (a-syn, parkin and PINK1, LRRK2) and prion diseases, highlighting the studies using Drosophila that have contributed to understanding the conserved mechanisms and elucidating the role of autophagy in these diseases.
Extracellular vesicles highlight many cases of photoreceptor degeneration
Authors: Spencer William J.
Published: May 2023

The release of extracellular vesicles is observed across numerous cell types and serves a range of biological functions including intercellular communication and waste disposal. One cell type which stands out for its robust capacity to release extracellular vesicles is the vertebrate photoreceptor cell. For decades, the release of extracellular vesicles by photoreceptors has been documented in many different animal models of photoreceptor degeneration and, more recently, in wild type photoreceptors. Here, I review all studies describing extracellular vesicle release by photoreceptors and discuss the most unifying theme among them–a photoreceptor cell fully, or partially, diverts its light sensitive membrane material to extracellular vesicles when it has defects in the delivery or morphing of this material into the photoreceptor’s highly organized light sensing organelle. Because photoreceptors generate an enormous amount of light sensitive membrane every day, the diversion of this material to extracellular vesicles can cause a massive accumulation of these membranes within the retina. Little is known about the uptake of photoreceptor derived extracellular vesicles, although in some cases the retinal pigment epithelial cells, microglia, Müller glia, and/or photoreceptor cells themselves have been shown to phagocytize them.
Increased selenium and decreased iron levels in relation to risk of coronary artery disease in patients with diabetes
Authors: Tian Mengyun , Hu Teng , Ying Jiajun , Cui Hanbin , Huangfu Ning
Published: May 2023

Background

Observational studies have reported inconsistent associations between micronutrient levels and the risk of coronary artery disease (CAD) in diabetic patients. We aim to explore the causal association between genetically predicted concentrations of micronutrients (phosphorus, magnesium, selenium, iron, zinc, and copper) and CAD in patients with diabetes.

Methods

Single nucleotide polymorphisms (SNPs) connected to serum micronutrient levels were extracted from the corresponding published genome-wide association studies (GWASs). Summary-level statistics for CAD in diabetic patients were obtained from a GWAS of 15,666 patients with diabetes. The primary analysis was carried out with the inverse variance weighted approach, and sensitivity analyses using other statistical methods were further employed to assess the robustness of the results.

Results

Genetically predicted selenium level was causally associated with a higher risk of CAD in diabetic patients (odds ratio [OR]: 1.25; 95% confidence interval [CI]: 1.10–1.42; p = 5.01 × 10−4). While, genetically predicted iron concentrations in patients with diabetes were inversely associated with the risk of CAD (OR: 0.82; 95% CI: 0.75–0.90; p = 2.16 × 10−5). The association pattern kept robust in most sensitivity analyses. Nominally significant associations were observed for magnesium and copper with the risk of CAD in patients with diabetes. No consistent evidence was found for the causal associations between phosphorus and zinc levels, and the risk of CAD in patients with diabetes.

Conclusion

We provide consistent evidence for the causal effect of increased selenium and decreased iron levels on CAD in patients with diabetes, highlighting the necessity of micronutrient monitoring and application in these patients.
Underutilized legumes: nutrient status and advanced breeding approaches for qualitative and quantitative enhancement
Authors: Samal Ipsita , Bhoi Tanmaya Kumar , Raj M. Nikhil , Majhi Prasanta Kumar , Murmu Sneha , Pradhan Asit Kumar , Kumar Dilip , Paschapur Amit Umesh , Joshi Dinesh Chandra , Guru P. N.
Published: May 2023

Underutilized/orphan legumes provide food and nutritional security to resource-poor rural populations during periods of drought and extreme hunger, thus, saving millions of lives. The Leguminaceae, which is the third largest flowering plant family, has approximately 650 genera and 20,000 species and are distributed globally. There are various protein-rich accessible and edible legumes, such as soybean, cowpea, and others; nevertheless, their consumption rate is far higher than production, owing to ever-increasing demand. The growing global urge to switch from an animal-based protein diet to a vegetarian-based protein diet has also accelerated their demand. In this context, underutilized legumes offer significant potential for food security, nutritional requirements, and agricultural development. Many of the known legumes like Mucuna spp., Canavalia spp., Sesbania spp., Phaseolus spp., and others are reported to contain comparable amounts of protein, essential amino acids, polyunsaturated fatty acids (PUFAs), dietary fiber, essential minerals and vitamins along with other bioactive compounds. Keeping this in mind, the current review focuses on the potential of discovering underutilized legumes as a source of food, feed and pharmaceutically valuable chemicals, in order to provide baseline data for addressing malnutrition-related problems and sustaining pulse needs across the globe. There is a scarcity of information about underutilized legumes and is restricted to specific geographical zones with local or traditional significance. Around 700 genera and 20,000 species remain for domestication, improvement, and mainstreaming. Significant efforts in research, breeding, and development are required to transform existing local landraces of carefully selected, promising crops into types with broad adaptability and economic viability. Different breeding efforts and the use of biotechnological methods such as micro-propagation, molecular markers research and genetic transformation for the development of underutilized crops are offered to popularize lesser-known legume crops and help farmers diversify their agricultural systems and boost their profitability.
Effects of early introduction of solid foods on nutrient intake in preterm infants during their 1st year of life: a secondary outcome analysis of a prospective, randomized intervention study
Authors: Gsoellpointner Melanie , Eibensteiner Fabian , Thanhaeuser Margarita , Ristl Robin , Jilma Bernd , Berger Angelika , Haiden Nadja
Published: May 2023

Very low birth weight (VLBW) infants have higher nutritional needs even after hospital discharge. However, data concerning current nutrient intakes at different time points after the introduction of solid foods and whether dietary reference values are being met are scarce. To adress this issue, this secondary analysis of a prospective, two-arm interventional study in 177 VLBW infants 21 investigates dietary intake comparing early and late (early: 10–12 weeks corrected for gestational age, late: 16–18 weeks corrected for gestational age) introduction of standardized complementary food during the first year of life. Nutritional intake was assessed using self-reported monthly 3-day dietary records from 3 until 12 months, corrected for gestational age. The time point of the introduction of solid foods did not influence nutrient intake, but the early introduction of solids tended toward a higher proportional intake of protein and carbohydrates and a lower intake of fat as a percentage of total energy) during the 1st year of life, corrected for gestational age. The results of this study indicate that this standardized feeding concept was sufficient for zinc, calcium, and phosphorus intake. However, dietary iron and vitamin D intakes did not meet the recommendations. Thus, prolonged iron supplementation should be considered beyond the introduction of meat and vitamin D supplementation at least until 12 months, corrected for gestational age.

Trial registration number

ClinicalTrials.gov: NCT01809548.
Lindera pulcherrima var. attenuata leaves: a nutritious and economically promising staple food in the Baiku Yao community in China
Authors: Luo Binsheng , Nong You , Hu Renchuan
Published: May 2023

The Baiku Yao community in China has traditionally used the Lindera pulcherrima var. attenuate (LPA) leaves as a staple food source, diverging from the common reliance on grains and plant roots worldwide. This study comprehensively analyzes LPA’s nutritional composition and local usage practices through field observations and laboratory testing. Our results show that LPA contains significant levels of starch, protein, and dietary fiber and is rich in trace elements, vitamin E, and flavonoids. These findings not only support the community’s traditional knowledge of LPA as a valuable food and feed source but also highlight its potential as a sustainable and innovative ingredient for new food and feed products. By filling a gap in our scientific understanding of LPA, this study may contribute to developing novel and eco-friendly agricultural practices and promote regional economic growth.
Prediction of angiogenesis in extrahepatic cholangiocarcinoma using MRI-based machine learning
Authors: Liu Jiong , Liu Mali , Gong Yaolin , Su Song , Li Man , Shu Jian
Published: May 2023

Purpose

Reliable noninvasive method to preoperative prediction of extrahepatic cholangiocarcinoma (eCCA) angiogenesis are needed. This study aims to develop and validate machine learning models based on magnetic resonance imaging (MRI) for predicting vascular endothelial growth factor (VEGF) expression and the microvessel density (MVD) of eCCA.

Materials and methods

In this retrospective study from August 2011 to May 2020, eCCA patients with pathological confirmation were selected. Features were extracted from T1-weighted, T2-weighted, and diffusion-weighted images using the MaZda software. After reliability testing and feature screening, retained features were used to establish classification models for predicting VEGF expression and regression models for predicting MVD. The performance of both models was evaluated respectively using area under the curve (AUC) and Adjusted R-Squared (Adjusted R2).

Results

The machine learning models were developed in 100 patients. A total of 900 features were extracted and 77 features with intraclass correlation coefficient (ICC) < 0.75 were eliminated. Among all the combinations of data preprocessing methods and classification algorithms, Z-score standardization + logistic regression exhibited excellent ability both in the training cohort (average AUC = 0.912) and the testing cohort (average AUC = 0.884). For regression model, Z-score standardization + stochastic gradient descent-based linear regression performed well in the training cohort (average Adjusted R2 = 0.975), and was also better than the mean model in the test cohort (average Adjusted R2 = 0.781).

Conclusion

Two machine learning models based on MRI can accurately predict VEGF expression and the MVD of eCCA respectively.
A novel technique for endoscope progression in gastroscopy resection: forward-return way for dissection of stromal tumor in the muscularis propria of the gastric fundus
Authors: Guo Hai-Mei , Sun Ying , Cai Shuang , Miao Feng , Zheng Yan , Yu Yang , Zhao Zhi-Feng , Liu Lu
Published: May 2023

Background

The fundus of the stomach is a challenging region for endoscopic resection of gastrointestinal stromal tumors (GISTs), especially in the anterior wall of the fornix at the side of the greater curvature. This study aimed to introduce the Forward-Return Way (FRW) technique in gastric fundus operations and provide evidence of its advantages. The FRW technique allows the gastroscope to access the stomach fornix without entering the gastric antrum after passing through the gastric cardia. Using FRW, the gastroscope body makes a forward return along the wall of the posterior wall of the upper gastric body and the wall of the greater curvature.

Methods

The clinical data of patients with stromal tumors in muscularis propria at the gastric fundus (STMF) at the Fourth Hospital of China Medical University between May 2020- March 2021 were reviewed. The novel FRW technique was used in the procedures, and the beneficial effects, suitability, applicable lesion site, and success rates of FRW were analyzed.

Results

A total of 10 cases were reviewed, and the FRW technique was successfully performed in 7 cases (70%). The gastroscope’s tip reached the area just below the gastric cardia, allowing endoscopists to successfully access all angles and sites of the stomach’s fundus in all seven patients. The lesion was easily accessed, and the gastroscope was stable with good left-right and forward-backwards movements.

Conclusion

The FRW technique significantly facilitates the resection of the GISTs by aligning the endoscopy body movement direction with the observation direction. Gastrointestinal Stromal Tumor; forward-return of gastroscopy along the gastric body wall; muscularis propria; gastric fundus.
Ampulla of Vater carcinoma: advancement in the relationships between histological subtypes, molecular features, and clinical outcomes
Authors: Liang Hao , Zhu Yu , Wu Ya-kun
Published: May 2023

The incidence of ampulla of Vater carcinoma, a type of periampullary cancer, has been increasing at an annual percentage rate of 0.9%. However, patients with ampulla of Vater carcinoma have quite different prognoses due to the heterogeneities of the tissue origin of this carcinoma. In addition to TNM staging, histological subtypes and molecular features of ampulla of Vater carcinoma are the key factors for predicting the clinical outcomes of patients. Fortunately, with the development of testing technology, information on the histological subtypes and molecular features of ampulla of Vater carcinoma is increasingly being analyzed in-depth. Patients with the pancreaticobiliary subtype have shorter survival times. In immunohistochemical examination, high cutoff values of positive MUC1 staining can be used to accurately predict the outcome of patients. Mutant KRAS, TP53, negative SMAD4 expression, and microsatellite stability are related to poor prognosis, while the clinical value of BRCA1/BRCA2 mutations is limited for prognosis. Testing the histological subtypes and molecular characteristics of ampulla of Vater carcinoma not only is the key to prognosis analysis but also provides extra information for targeted treatment to improve the clinical outcomes of patients.
Construction of the structural equation model of stigma, self-disclosure, social support, and quality of life of breast cancer patients after surgery—a multicenter study
Authors: Bu Liuxiu , Chen Xisui , Zheng Shaoyan , Fan Guanhua
Published: May 2023

Purpose

Stigma is common in patients with breast cancer after surgery, which has a negative impact on the quality of life (QOL). This study aimed to investigate the QOL of breast cancer patients after surgery and to analyze the multiple chains mediating effects of self-disclosure and social support between stigma and QOL.

Methods

A total 292 patients of breast cancer patients after operation were recruited in this study. A questionnaire survey was conducted using the general information questionnaire, the consumer experiences of stigma questionnaire (CESQ), the distress disclosure index(DDI), the perceived social support scale(PSSS), and the functional assessment of cancer therapy-breast(FACT-B). Path analysis was conducted to test the hypothesized serial multiple mediation model.

Results

The total scores of stigma, self-disclosure, social support and QOL were 15 (10 ~ 22), 39 (31 ~ 46), 58 (50 ~ 67) and 88 (74 ~ 104) respectively. QOL of breast cancer patients after the operation was negatively correlated with stigma (p < 0.01), and positively correlated with self-disclosure and social support (p < 0.01). Self-disclosure and social support played a complete mediating effect between stigma and QOL, and the total mediating effect value was 85. 87%.

Conclusions

Self-disclosure and social support play a complete intermediary role between stigma and QOL. In order to improve the quality of life of patients, medical staff should pay attention to the assessment of stigma, encourage patients to express their emotions, and encourage their families and friends to respond to their expression and needs of patients.
Association between preoperative diagnosis of sarcopenia and postoperative pneumonia in resectable esophageal squamous cell carcinoma patients: a retrospective cohort study
Authors: Xu Zhiyun , Wang Qianwei , Zhang Zhenzhong , Zhu Yaning , Chen Yunyun , Tang Derong , Zhao Jianqiang
Published: May 2023

Background

Postoperative outcomes for patients suffering from resectable esophageal squamous cell carcinoma (ESCC) are related to sarcopenia. In patients with resectable ESCC, this study investigated the link between sarcopenia and postoperative pneumonia.

Methods

The McKewon procedure was the only one used to treat resectable ESCC patients from January 2018 to December 2021 in this retrospective analysis. Sarcopenia was assessed using skeletal muscles at L3 and planning CT scans. It was defined when PMI was below 6.36 cm2/m2 and 3.92 cm2/m2 for men and women, separately. Analyses of multivariate and univariate logistic regression were applied for identifying the risk factors for postoperative pneumonia.

Results

The study included 773 patients with resectable ESCC in total. Sarcopenia was an independent risk factor for postoperative pneumonia in individuals with resectable ESCC based on univariate and multivariate analysis (P < 0.05). The stratified analysis indicated that neither of the clinical outcomes in the logistic regression model were affected by gender, age, BMI, smoking, or pre-albumin (P for interaction > 0.006).

Conclusion

Following the McKewon procedure, patients with resectable ESCC who were sarcopenic had a higher postoperative pneumonia rate. To prevent the development of postoperative pneumonia during the perioperative period, it may be important to control the incidence of sarcopenia.
FMO family may serve as novel marker and potential therapeutic target for the peritoneal metastasis in gastric cancer
Authors: Gong Xumeng , Hou Dong , Zhou Shengning , Tan Jianan , Zhong Guangyu , Yang Bing , Xie Lang , Han Fanghai , Zhong Lin
Published: May 2023

Objective

To explore the relationship between flavin-containing monooxygenases (FMOs) and peritoneal metastasis (PM) in gastric cancer (GC).

Materials and methods

TIMER 2.0 was used to perform pan-cancer analysis and assess the correlation between the expression of FMOs and cancers. A dataset from The Cancer Genome Atlas (TCGA) was used to analyze the correlation between FMOs and clinicopathological features of GC. PM is well established as the most common mode of metastasis in GC. To further analyze the correlation between FMOs and PM of GC, a dataset was obtained from the National Center for Biotechnology Information Gene Expression Omnibus (GEO) database. The results were validated by immunohistochemistry. The relationship between FMOs and PM of GC was explored, and a novel PM risk signature was constructed by least absolute shrinkage and selection operator (LASSO) regression analysis. The regression model’s validity was tested by multisampling. A nomogram was established based on the model for predicting PM in GC patients. The mechanism of FMOs in GC patients presenting with PM was assessed by conducting Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses in TCGA and GEO datasets. Finally, the potential relationship between FMOs and immunotherapy was analyzed.

Results

The pan-cancer analysis in TCGA and GEO datasets showed that FMO1 was upregulated, while FMO2 and FMO4 were downregulated in GC. Moreover, FMO1 and FMO2 correlated positively with the T and N stage of GC in the TCGA dataset. FMO1 and FMO2 expression was a risk factor for GC (hazard ratio: 1.112 and 1.185). The overexpression of FMO1 was significantly correlated with worse disease-free-survival (DFS) and overall survival (OS). However, no relationship was found between FMO2 expression in GC and DFS and OS. PM was highly prevalent among GC patients and typically associated with a worse prognosis. FMO1 was highly expressed in GC with PM. FMO1 and FMO2 were positively correlated with PM in GC. We identified a 12-gene panel for predicting the PM risk signature by LASSO (Area Under Curve (AUC) = 0.948, 95%CI: 0.896–1.000). A 10-gene panel for PM prediction was identified (AUC = 0.932, 95%CI: 0.874–0.990), comprising FMO1 and FMO2. To establish a model for clinical application, a 7-gene panel was established (AUC = 0.927, 95% CI: 0.877–0.977) and successfully validated by multisampling. (AUC = 0.892, 95% CI: 0.878–0.906). GO and KEGG analyses suggest that FMO1 and FMO2 regulate the extracellular matrix and cell adhesion. FMO1 and FMO2 were positively correlated with the immune score of GC, and their expression was associated with the infiltration of immune cells.

Conclusion

PM in GC is strongly correlated with FMOs. Overall, FMO1 and FMO2 have huge prospects for application as novel diagnostic and therapeutic targets.
Blood immune cells as potential biomarkers predicting relapse-free survival of stage III/IV resected melanoma patients treated with peptide-based vaccination and interferon-alpha
Authors: Moschella Federica , Buccione Carla , Ruspantini Irene , Castiello Luciano , Rozo Gonzalez Andrea , Iacobone Floriana , Ferraresi Virginia , Palermo Belinda , Nisticò Paola , Belardelli Filippo , Proietti Enrico , Macchia Iole , Urbani Francesca
Published: May 2023

Introduction

Despite the recent approval of several therapies in the adjuvant setting of melanoma, tumor relapse still occurs in a significant number of completely resected stage III-IV patients. In this context, the use of cancer vaccines is still relevant and may increase the response to immune checkpoint inhibitors. We previously demonstrated safety, immunogenicity and preliminary evidence of clinical efficacy in stage III/IV resected melanoma patients subjected to a combination therapy based on peptide vaccination together with intermittent low-dose interferon-α2b, with or without dacarbazine preconditioning (https://www.clinicaltrialsregister.eu/ctr-search/search, identifier: 2008-008211-26). In this setting, we then focused on pre-treatment patient immune status to highlight possible factors associated with clinical outcome.

Methods

Multiparametric flow cytometry was used to identify baseline immune profiles in patients’ peripheral blood mononuclear cells and correlation with the patient clinical outcome. Receiver operating characteristic curve, Kaplan-Meier survival and principal component analyses were used to evaluate the predictive power of the identified markers.

Results

We identified 12 different circulating T and NK cell subsets with significant (p ≤ 0.05) differential baseline levels in patients who later relapsed with respect to patients who remained free of disease. All 12 parameters showed a good prognostic accuracy (AUC>0.7, p ≤ 0.05) and 11 of them significantly predicted the relapse-free survival. Remarkably, 3 classifiers also predicted the overall survival. Focusing on immune cell subsets that can be analyzed through simple surface staining, three subsets were identified, namely regulatory T cells, CD56dimCD16- NK cells and central memory γδ T cells. Each subset showed an AUC>0.8 and principal component analysis significantly grouped relapsing and non-relapsing patients (p=0.034). These three subsets were used to calculate a combination score that was able to perfectly distinguish relapsing and non-relapsing patients (AUC=1; p=0). Noticeably, patients with a combined score ≥2 demonstrated a strong advantage in both relapse-free (p=0.002) and overall (p=0.011) survival as compared to patients with a score <2.

Discussion

Predictive markers may be used to guide patient selection for personalized therapies and/or improve follow-up strategies. This study provides preliminary evidence on the identification of peripheral blood immune biomarkers potentially capable of predicting the clinical response to combined vaccine-based adjuvant therapies in melanoma.
Case Report: Intraoperative radiotherapy as the new standard of care for breast cancer patients with disabling health conditions or impairments
Authors: Omosule Michael , De Silva-Minor Shiroma , Coombs Nathan
Published: May 2023

In selected patients, intraoperative radiotherapy (IORT) offers an alternative to standard external beam radiotherapy (EBRT) while providing equivalent breast cancer control outcomes. After IORT, most patients do not require external beam radiotherapy and thus avoid the need to travel to and from a radiotherapy centre in the weeks after surgery. EBRT is associated with an increased risk of non-breast cancer mortality and poorer cosmetic outcomes while increasing patient travel time, emissions associated with travel and time spent in the hospital. Consequently, EBRT is associated with an overall reduction in quality of life compared to IORT. Patients with other on-going health conditions or clinical impairments are likely to be affected by the daily radiotherapy requirement. Should these patients be consulted during their pre-operative assessment as to options to undergo IORT? This paper describes a case of IORT and follow up in a functionally blind patient. Quality of life effects are elucidated and further support the use of IORT in selected breast cancer patients with health conditions or impairments.
Identification of key immune genes related to lymphatic metastasis of papillary thyroid cancer via bioinformatics analysis and experimental validation
Authors: Yu Yang , Guo Xing , Chai Jian , Han Zhuoyi , Ji Yaming , Sun Jirui , Zhang Huiqing
Published: May 2023

Objective

The current research aimed to development and validation in signature immune genes for lymphatic metastasis in papillary thyroid cancer (PTC).

Method

Weighted correlation network analysis (WGCNA) was performed to identify genes closely correlated with lymphatic metastasis in PTC from TCGA database. Information on immune-related genes (IRGs) was obtained from the ImmPort database. Crossover genes were used with the R package clusterProfiler for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment. Key genes in the protein–protein interaction network of cross-targets were obtained using Cytoscape. Lasso and Random Forest (RF) models were utilized to identify pivotal genes. We constructed a nomogram based on the hub genes. The correlation between hub genes and immune cell infiltration was explored. We collected and assessed clinical samples via immunohistochemistry to detect the expression of hub genes.

Result

In total, 122 IRGs were correlated with lymphatic metastases from PTC. There are 10 key IRGs in the protein–protein interaction network. Then, three hub genes including PTGS2, MET, and ICAM1 were established using the LASSO and RF models. The expression of these hub genes was upregulated in samples collected from patients with lymphatic metastases. The average area under the curve of the model reached 0.83 after a 10-fold and 200-time cross-validation, which had a good prediction ability. Immuno-infiltration analysis showed that the three hub genes were significantly positively correlated with resting dendritic cells and were negatively correlated with activated natural cells, monocytes, and eosinophils. Immunohistochemistry results revealed that lymph node metastasis samples had a higher expression of the three hub genes than non-metastasis samples.

Conclusion

Via bioinformatics analysis and experimental validation, MET and ICAM1 were found to be upregulated in lymph node metastasis from papillary thyroid carcinoma. Further, the two hub genes were closely correlated with activated natural killer cells, monocytes, resting dendritic cells, and eosinophils. Therefore, these two genes may be novel molecular biomarkers and therapeutic targets in lymph node metastasis from papillary thyroid carcinoma.
The multidisciplinary approach to eosinophilia
Authors: Thomsen Gunhild Nynke , Christoffersen Mette Niemann , Lindegaard Hanne Merete , Davidsen Jesper Rømhild , Hartmeyer Gitte Nyvang , Assing Kristian , Mortz Charlotte G. , Martin-Iguacel Raquel , Møller Michael Boe , Kjeldsen Anette Drøhse , Havelund Troels , El Fassi Daniel , Broesby-Olsen Sigurd , Maiborg Michael , Johansson Sofie Lock , Andersen Christen Lykkegaard , Vestergaard Hanne , Bjerrum Ole Weis
Published: May 2023

Eosinophilic granulocytes are normally present in low numbers in the bloodstream. Patients with an increased number of eosinophilic granulocytes in the differential count (eosinophilia) are common and can pose a clinical challenge because conditions with eosinophilia occur in all medical specialties. The diagnostic approach must be guided by a thorough medical history, supported by specific tests to guide individualized treatment. Neoplastic (primary) eosinophilia is identified by one of several unique acquired genetic causes. In contrast, reactive (secondary) eosinophilia is associated with a cytokine stimulus in a specific disease, while idiopathic eosinophilia is a diagnosis by exclusion. Rational treatment is disease-directed in secondary cases and has paved the way for targeted treatment against the driver in primary eosinophilia, whereas idiopathic cases are treated as needed by principles in eosinophilia originating from clonal drivers. The vast majority of patients are diagnosed with secondary eosinophilia and are managed by the relevant specialty—e.g., rheumatology, allergy, dermatology, gastroenterology, pulmonary medicine, hematology, or infectious disease. The overlap in symptoms and the risk of irreversible organ involvement in eosinophilia, irrespective of the cause, warrants that patients without a diagnostic clarification or who do not respond to adequate treatment should be referred to a multidisciplinary function anchored in a hematology department for evaluation. This review presents the pathophysiology, manifestations, differential diagnosis, diagnostic workup, and management of (adult) patients with eosinophilia. The purpose is to place eosinophilia in a clinical context, and therefore justify and inspire the establishment of a multidisciplinary team of experts from diagnostic and clinical specialties at the regional level to support the second opinion. The target patient population requires highly specialized laboratory analysis and therapy and occasionally has severe eosinophil-induced organ dysfunction. An added value of a centralized, clinical function is to serve as a platform for education and research to further improve the management of patients with eosinophilia. Primary and idiopathic eosinophilia are key topics in the review, which also address current research and discusses outstanding issues in the field.
Quantitative identification of ventral/dorsal nerves through intraoperative neurophysiological monitoring by supervised machine learning
Authors: Jiang Wenbin , Zhan Qijia , Wang Junlu , Wei Min , Li Sen , Mei Rong , Xiao Bo
Published: May 2023

Objective

This study aimed to investigate the electro-neurophysiological characteristics of the ventral and dorsal nerves at the L2 segment in a quantitative manner.

Methods

Medical records of consecutive patients who underwent single-level approach selective dorsal rhizotomy (SDR) from June 2019 to January 2022 were retrospectively reviewed. Intraoperative electro-neurophysiological data were analyzed.

Results

A total of 74 males and 27 females were included in the current study with a mean age of 6.2 years old. Quadriceps and adductors were two main muscle groups innervated by L2 nerve roots in both ventral and dorsal nerve roots. Dorsal roots have a higher threshold than that of the ventral ones, and muscles that first reached 200 µV innervated by dorsal roots have longer latency and smaller compound muscle action potential (CMAP) than those of the ventral ones. Supervised machine learning can efficiently distinguish ventral/dorsal roots using threshold + latency or threshold + CMAP as predictors.

Conclusion

Electro-neurophysiological parameters could be used to efficiently differentiate ventral/dorsal fibers during SDR.
A nomogram model to predict the risk of drug-induced liver injury in patients receiving anti-tuberculosis treatment
Authors: Ji Songjun , Lu Bin , Pan Xinling
Published: May 2023

Objectives: To establish an individualized nomogram to predict the probability of drug-induced liver injury (DILI) in tuberculosis patients receiving anti-tuberculosis treatment.

Methods: The clinical information of patients admitted to a tertiary hospital between January 2010 and December 2022 was retrospectively reviewed from the clinical records. Patients with baseline liver diseases (hepatis B or C infection and fatty liver) or taking liver protective drugs were excluded. The maximum values in liver function test within 180 days after anti-tuberculosis treatment were collected to determine the occurrence of DILI. The candidate variables used for establishing prediction model in this study were the last results within the 30 days before the treatment onset. The final variables were included after univariate and multivariate logistic regression analyses and applied to establish the nomogram model. The discrimination power and prediction accuracy of the prediction model were assessed using the area under the receiver operating characteristic (AUC) curve and a calibration chart. The clinical effectiveness was assessed via decision curve analysis (DCA). The established model was validated in two validation groups.

Results: A total of 1979 patients with 25 variables were enrolled in this study, and the incidence of DILI was 4.2% (n = 83). The patients with complete variables were divided into training group (n = 1,121), validation group I (n = 492) and validation group II (n = 264). Five variables were independent factors for DILI and included in the final prediction model presented as nomogram: age (odds ratio [OR] 1.022, p = 0.023), total bilirubin ≥17.1 μmol/L (OR 11.714, p < 0.001), uric acid (OR 0.977, p = 0.047), neutrophil count (OR 2.145, 0.013) and alcohol consumption (OR 3.209, p = 0.002). The AUCs of the prediction model in the training group, validation group I and validation group II were 0.833, 0.668, and 0.753, respectively. The p-values of calibration charts in the three groups were 0.800, 0.996, and 0.853. The DCA curves of the prediction model were above the two extreme curves.

Conclusion: The nomogram model in this study could effectively predict the DILI risk among patients under anti-tuberculosis drug treatment.
Blocking TRAIL-DR5 signaling pathway with soluble death receptor 5 fusion protein mitigates radiation-induced injury
Authors: Zhao Danyang , Yang Lei , Han Peng , Zhang Haihui , Wang Fanjun , Meng Zhiyun , Gan Hui , Wu Zhuona , Sun Wenzhong , Chen Chuan , Dou Guifang , Gu Ruolan
Published: May 2023

The increasing application of nuclear technology, the high fatality of acute radiation syndrome (ARS) and its complex mechanism make ARS a global difficulty that requires urgent attention. Here we reported that the death receptor 5 (DR5), as well as its ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were both significantly upregulated after irradiation in mice with 6 Gy γ-ray single radiation. And by intravenously administrated with soluble DR5 fusion protein (sDR5-Fc), the competitive antagonist of DR5, the excessive apoptosis in the radiation-sensitive tissues such as spleen and thymus were significantly inhibited and the radiation-induced damage of spleen and thymus were mitigated, while the expression of apoptosis-inhibiting proteins such as Bcl-2 was also significantly upregulated. The biochemical indicators such as serum ALP, AST, ALT, TBIL, K, and Cl levels that affected by radiation, were improved by sDR5-Fc administration. sDR5-Fc can also regulate the number of immune cells and reduce blood cell death. For in vitro studies, it had been found that sDR5-Fc effectively inhibited apoptosis of human small intestinal mucosal epithelial cells and IEC-6 cells using flow cytometry. Finally, survival studies showed that mice administrated with sDR5-Fc after 9 Gy γ-ray single whole body radiation effectively increased the 30-day survival and was in a significant dose-dependent manner. Overall, the findings revealed that DR5/TRAIL-mediated apoptosis pathway had played important roles in the injury of ARS mice, and DR5 probably be a potential target for ARS therapeutics. And the DR5 apoptosis antagonist, sDR5 fusion protein, probably is a promising anti-ARS drug candidate which deserves further investigation.
The role of lutein-rich purple sweet potato leaf extract on the amelioration of diabetic retinopathy in streptozotocin-induced Sprague–Dawley rats
Authors: Hisamuddin Ahmad Safiyyu'd-din Bin , Naomi Ruth , Manan Khairul Aiman Bin , Bahari Hasnah , Othman Fezah , Embong Hashim , Ismail Amin , Ahmed Qamar Uddin , Jumidil Siti Hadizah , Hussain Mohd Khairi , Zakaria Zainul Amiruddin
Published: May 2023

The objective of this study is to access the effect of purple sweet potato leaf (PSPL) extract on diabetic retinopathy (DR) of streptozotocin (STZ)-induced male Sprague–Dawley (SD) rats. In this study, rats were injected intraperitoneally with a single dose of 60 mg/kg STZ, and diabetes was confirmed on day 7. Rats were further divided into a few groups, which were then orally administered with one of the following treatments: 25 mg/kg of gliclazide (D25G), 200 mg/kg of PSPL extract (DT 200), and 400 mg/kg of PSPL extract (DT 400). However, the normal control (NS) and control group for diabetic (DNS) were given normal saline (NS) for 12 weeks. The results show that the treated group demonstrated a reduction in serum oral glucose tolerance test (OGTT) levels of DT 200 and DT 400, and an increase in the serum and retinal insulin levels, and restored oxidative stress markers in serum and retina on week 12. The PSPL extract exhibited protective effects in maintaining the kidney, liver, retina, and pancreas architecture in 400 mg/kg compared to the 200 mg/kg treated group and D25G, thereby restoring fully transparent lenses in diabetes-induced rats. In conclusion, 400 mg/kg PSPL is the most effective dose for the amelioration of STZ-induced DR pathology in male SD rats.
Efficacy and safety of tacrolimus-based treatment for non-rapidly progressive IgA nephropathy
Authors: Zhao Lijuan , Yang Yanyan , Xu Hao , Leng Wei , Xu Guoshuang
Published: May 2023

In this study, we aimed to evaluate the efficacy and safety of tacrolimus-based treatment for immunoglobulin A nephropathy (IgAN). We retrospectively reviewed 127 adult patients with primary IgAN with 24 h urine total protein quantity (24 h UTP) ≥ 1 g and serum creatinine ≤3 mg/dL. All patients were divided into tacrolimus (TAC) and control (non-TAC) groups according to the treatment strategy. Proteinuria remission, remission rate, and adverse events were compared between the two groups. Among the 127 patients, 61 received TAC-based treatment and 66 received non-TAC treatment. TAC group exhibited a more rapid decline in proteinuria than the non-TAC group at 3, 9, and 12 months (p = 0.049, 0.001, and 0.018, respectively). Remission rates at 1, 3, 6, 9, and 12 months were 41.0, 68.9, 80.3, 90.2, and 88.5%, respectively, in the TAC group. These rates were higher than those in the control group at 3, 9, and 12 months (p = 0.030, 0.008, and 0.026, respectively). Complete remission rates at 1, 3, 6, 9, and 12 months were 6.56, 19.7, 37.7, 54.1, and 62.3%, respectively, in the TAC group. These rates were higher than those in the control group at 9 and 12 months (p = 0.013 and 0.008, respectively). The estimated mean time to complete remission was significantly shorter in the TAC group than in the control group (p = 0.028). TAC did not increase the incidence of adverse events. In conclusion, TAC accelerated proteinuria remission in patients with non-rapidly progressive IgAN with no increased risk of adverse events. Further prospective randomized controlled trials are necessary to validate our findings.