bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular and humoral immunogenicity of the COVID-19 vaccine and COVID-19 disease severity in individuals with immunodeficiency
Authors: Murray C. E. , O’Brien C. , Alamin S. , Phelan S. H. , Argue R. , Kiersey R. , Gardiner M. , Naughton A. , Keogh E. , Holmes P. , Naughton S. , Scanlon A. , Sloan A. , McCrea P. , Sui J. , Dunne J. , Conlon N. 
Published: March 2023

BackgroundA well-coordinated adaptive immune response is crucial for limiting COVID-19 disease. Some individuals with immunodeficiency are at a high risk of developing severe COVID-19. Therefore, the development of standardized methods for measuring different arms of the vaccine response in the setting of immunodeficiency is of particular interest. In this study, we compared the vaccine response of individuals living with immunodeficiency with healthy controls in terms of interferon gamma (IFN-γ) production and spike protein-specific antibody level post primary COVID-19 vaccination and booster vaccines. Additionally, the disease severity of those individuals who contracted COVID-19 was assessed.MethodsWhole blood was stimulated overnight from 71 participants and 99 healthy controls. Commercially available PepTivator® peptide pool and trimeric spike protein stimulation were used. ELISA was used to analyze IFN-γ levels. The total SARS-CoV-2 spike protein antibody titre was measured using a Roche Elecsys® S total antibody assay. Patient characteristics, COVID-19 infection status and IDDA 2.1 ‘Kaleidoscope’ scores were recorded. Vaccine responses were scored from zero to three.Results99% of healthy controls, 89% of individuals with IEI and 76% with secondary immunodeficiency (SID) had an IFN-γ level above the validated reference range after peptide mix stimulation following primary vaccination. There was an increase in IFN-γ levels in patients with inborn errors of immunity (IEI) following the booster vaccine (p = 0.0156). 100% of healthy controls, 70% of individuals living with IEI and 64% of individuals living with SID had detectable spike protein-specific antibody levels following the primary vaccination. 55% of immunodeficiency patients who had mild COVID-19 and 10% with moderate/severe COVID-19 had detectable antibody and IFN-γ levels post vaccine. The mean pre-infection IDDA 2.1 scores were higher in individuals who developed moderate/severe COVID-19 (25.2 compared to 9.41).ConclusionsCovid whole-blood IGRA is a highly accurate, straightforward and robust assay and can be easily adapted to measure cellular response to COVID-19. A complete evaluation of the vaccine response may be particularly important for individuals living with immunodeficiency. A clinical immunodeficiency score and a validated vaccine response score may be valuable tools in estimating COVID-19 disease risk and identifying individuals living with immunodeficiency who may benefit from enhanced vaccination schedules.
Targeting NK-1R attenuates renal fibrosis via modulating inflammatory responses and cell fate in chronic kidney disease
Authors: Zhu Enyi , Liu Yang , Zhong Ming , Liu Yu , Jiang Xi , Shu Xiaorong , Li Na , Guan Hui , Xia Yin , Li Jinhong , Lan Hui-yao , Zheng Zhihua 
Published: March 2023

BackgroundRenal fibrosis is the final common pathway of chronic kidney disease (CKD), which is clinically irreversible and without effective therapy. Renal tubules are vulnerable to various insults, and tubular injury is involving in the initiation and evolution of renal inflammation and fibrosis. Neurokinin-1 receptor (NK-1R) functions by interacting with proinflammatory neuropeptide substance P (SP), exerting crucial roles in various neurological and non-neurological diseases. However, its roles in renal inflammation and fibrosis are still unknown.MethodsWe collected renal biopsy specimens and serum samples of individuals with or without CKD. Additionally, knockout mice lacking NK-1R expression, SP addition and NK-1R pharmacological antagonist treatment in the unilateral ureteral obstruction (UUO) model, and NK-1R-overexpressed HK-2 cells were employed.ResultsRenal SP/NK-1R and serum SP were increased in patients with CKD and mice experiencing UUO and correlated with renal fibrosis and function. SP addition enhanced UUO-induced progressive inflammatory responses and renal fibrosis, whereas genetically or pharmacologically targeting NK-1R attenuated these effects. Mechanistically, TFAP4 promoted NK-1R transcription by binding to its promoter, which was abolished by mutation of the binding site between TFAP4 and NK-1R promoter. Furthermore, SP acted through the NK-1R to activate the JNK/p38 pathways to modulate cell fate of tubular epithelial cells including growth arrest, apoptosis, and expression of profibrogenic genes.ConclusionOur data reveals that SP/NK-1R signaling promotes renal inflammatory responses and fibrosis, suggesting NK-1R could be a potential therapeutic target for the patients with CKD.
Adherence to the therapeutic guidelines recommendations among the people with type 2 diabetes mellitus and obesity, frailty, or recent diagnosis, attended in primary health care centers in Spain: A cross-sectional study
Authors: Vlacho Bogdan , Mata-Cases Manel , Fernandez-Camins Berta , Romera Liébana Laura , Barrot-de la Puente Joan , Franch-Nadal Josep 
Published: March 2023

IntroductionClinical practice guidelines are helpful for clinicians, and their proper implementation could improve the quality of care and management of participants with diabetes. This study aimed to evaluate the degree of adherence to the Clinical Practice Guidelines (CPG) recommendations among obese, frail, or recently diagnosed type 2 diabetes mellitus (T2DM) participants in primary care centers in Spain.MethodsWe perform a cross-sectional study on a national level in two phases. In the first phase, study participants were recruited, and their clinical data were collected. In the second phase, data related to the participating physicians were collected.ResultsIn total, 882 participants from 240 physicians were analyzed. According to the study questionnaire, most participants from all three clinical groups had adequate adherence to the CPG. This percentage was highest among the recently diagnosed T2DM (91.6%) and lowest percent of frail T2DM persons (74.7%). The inadequate adherence to the guidelines was observed mainly among the obese and frail participants with T2DM from medical doctors with low CPG knowledge (3.4% and 3.5%, respectively). Regarding the patient's characteristics and degree of adherence to the guidelines, the participants with inadequate adherence were generally older, with higher BMI, poorer HbA1c control, and fewer visits with primary care physicians. Most (57%) primary care physicians had moderate CPG knowledge. In our multivariable logistic model, we did not observe statistically significant odds ratios for different characteristics related to the physicians/consultation and low CPG knowledge.DiscussionThe results of our cross-sectional study observe adequate adherence to the clinical guidelines by the primary care physicians for the majority of the participants with obesity, frailty, or newly diagnosed with T2DM.
Improving the accuracy of revised cardiac risk index with HbA1C: Hemoglobin ratio (HH ratio) – A retrospective cohort study
Authors: Ke Yuhe , Shannon Nicholas Brian , Abdullah Hairil Rizal 
Published: March 2023

BackgroundThe current Lee’s Revised cardiac risk index (RCRI) was created in 1999. Validation studies have found RCRI to be only moderately discriminant. The “Diabetes Mellitus on insulin” component of the score does not accurately reflect the severity of the disease. A previously studied HbA1C:Hemoglobin ratio shows an improved association with outcomes than individual components alone.Study designA retrospective cohort study was performed in diabetic patients undergoing non-cardiac surgery. Ethics approval was obtained. The study compares the predictive value of RCRI and substitution of the “DM on insulin” component with HH ratio for 30- and 90-day mortality, and postoperative acute myocardial injury (AMI) and acute kidney injury (AKI).ResultsA total of 20,099 adult patients were included in the final analysis. The incidence of 30- and 90-day mortality was at 4.2 and 6.5%, respectively. Substitution of HH ratio in RCRI resulted in 687 more patients being in the moderate to high-risk category. The substituted HH-RCRI score had better prediction for 30-day (AUC 0.66 vs. 0.69, p &lt; 0.001) and 90-day mortality (AUC 0.67 vs. 0.70, p &lt; 0.001), and postoperative AMI (AUC 0.69 vs. 0.71, p &lt; 0.001) and AKI (AUC 0.57 vs. 0.62, p &lt; 0.001).ConclusionAlthough currently not an universal practice, substitution of “DM on insulin” with HbA1C:Hemoglobin ratio in RCRI score improves the accuracy of the RCRI risk prediction model in diabetic patients going for non-cardiac surgery.
RNA silencing proteins and small RNAs in oomycete plant pathogens and biocontrol agents
Authors: Piombo Edoardo , Kelbessa Bekele Gelena , Sundararajan Poorva , Whisson Stephen C. , Vetukuri Ramesh Raju , Dubey Mukesh 
Published: March 2023

IntroductionOomycetes cause several damaging diseases of plants and animals, and some species also act as biocontrol agents on insects, fungi, and other oomycetes. RNA silencing is increasingly being shown to play a role in the pathogenicity of Phytophthora species, either through trans-boundary movement of small RNAs (sRNAs) or through expression regulation of infection promoting effectors.MethodsTo gain a wider understanding of RNA silencing in oomycete species with more diverse hosts, we mined genome assemblies for Dicer-like (DCL), Argonaute (AGO), and RNA dependent RNA polymerase (RDRP) proteins from Phytophthora plurivora, Ph. cactorum, Ph. colocasiae, Pythium oligandrum, Py. periplocum, and Lagenidium giganteum. Moreover, we sequenced small RNAs from the mycelium stage in each of these species.Results and discussionEach of the species possessed a single DCL protein, but they differed in the number and sequence of AGOs and RDRPs. SRNAs of 21nt, 25nt, and 26nt were prevalent in all oomycetes analyzed, but the relative abundance and 5’ base preference of these classes differed markedly between genera. Most sRNAs mapped to transposons and other repeats, signifying that the major role for RNA silencing in oomycetes is to limit the expansion of these elements. We also found that sRNAs may act to regulate the expression of duplicated genes. Other sRNAs mapped to several gene families, and this number was higher in Pythium spp., suggesting a role of RNA silencing in regulating gene expression. Genes for most effector classes were the source of sRNAs of variable size, but some gene families showed a preference for specific classes of sRNAs, such as 25/26 nt sRNAs targeting RxLR effector genes in Phytophthora species. Novel miRNA-like RNAs (milRNAs) were discovered in all species, and two were predicted to target transcripts for RxLR effectors in Ph. plurivora and Ph. cactorum, indicating a putative role in regulating infection. Moreover, milRNAs from the biocontrol Pythium species had matches in the predicted transcriptome of Phytophthora infestans and Botrytis cinerea, and L. giganteum milRNAs matched candidate genes in the mosquito Aedes aegypti. This suggests that trans-boundary RNA silencing may have a role in the biocontrol action of these oomycetes.
EEGformer: A transformer–based brain activity classification method using EEG signal
Authors: Wan Zhijiang , Li Manyu , Liu Shichang , Huang Jiajin , Tan Hai , Duan Wenfeng 
Published: March 2023

BackgroundThe effective analysis methods for steady-state visual evoked potential (SSVEP) signals are critical in supporting an early diagnosis of glaucoma. Most efforts focused on adopting existing techniques to the SSVEPs-based brain–computer interface (BCI) task rather than proposing new ones specifically suited to the domain.MethodGiven that electroencephalogram (EEG) signals possess temporal, regional, and synchronous characteristics of brain activity, we proposed a transformer–based EEG analysis model known as EEGformer to capture the EEG characteristics in a unified manner. We adopted a one-dimensional convolution neural network (1DCNN) to automatically extract EEG-channel-wise features. The output was fed into the EEGformer, which is sequentially constructed using three components: regional, synchronous, and temporal transformers. In addition to using a large benchmark database (BETA) toward SSVEP-BCI application to validate model performance, we compared the EEGformer to current state-of-the-art deep learning models using two EEG datasets, which are obtained from our previous study: SJTU emotion EEG dataset (SEED) and a depressive EEG database (DepEEG).ResultsThe experimental results show that the EEGformer achieves the best classification performance across the three EEG datasets, indicating that the rationality of our model architecture and learning EEG characteristics in a unified manner can improve model classification performance.ConclusionEEGformer generalizes well to different EEG datasets, demonstrating our approach can be potentially suitable for providing accurate brain activity classification and being used in different application scenarios, such as SSVEP-based early glaucoma diagnosis, emotion recognition and depression discrimination.
Systematic review of craniofacial osteosarcoma regarding different clinical, therapeutic and prognostic parameters
Authors: Weber Verena , Stigler Robert , Lutz Rainer , Kesting Marco , Weber Manuel 
Published: March 2023

BackgroundOsteosarcomas are the most common primary bone tumor while occurrence in the craniofacial skeleton is relatively rare. There are clinical differences of osteosarcomas regarding their location. In this regard craniofacial osteosarcomas (COS) have special characteristics. Extracranial osteosarcomas (EOS) occur mainly in the long bones of the extremities (tibia, humerus and femur). These tumors metastasize hematogenically at a very early stage. In comparison, COS are mainly localized in the mandible and maxilla, occur later in life and show significantly less and later metastasis and respond differently to adjuvant therapy. In the literature, clinical characteristics of COS and EOS are rarely compared directly. The aim of this systematic review is to answer the question whether COS and EOS exhibit fundamentally different clinical behavior and how they differ in terms of survival rates and response to different therapies.MethodsA systemic review was performed. Pubmed, Cochrane and Google Scholar were used as search engines. The literature research was done by using clearly defined terms and their links. 124 full texts were selected and evaluated for this review. The inclusion criteria were determined using the PICO model.ResultsCOS have significantly better survival rates, especially if they are located in the jawbone. Surgical R0 resection is crucial for therapeutic success. The study situation regarding the benefit of neoadjuvant chemotherapy in COS is very inhomogeneous. There is also no evidence for the benefit of adjuvant radio- or chemotherapy in COS. The large heterogeneity of the studies in terms of therapeutic concept, initial situation of the patients and outcome considered, as well as the small number of patients with craniofacial osteosarcoma were limiting factors.ConclusionThe results of this study show the clear therapeutic and prognostic differences between COS and EOS and underline the necessity to consider both types of osteosarcoma as independent tumor entities in future studies. Furthermore, the study highlights the importance of surgical R0 resection for the prognosis of COS patients. There is no evidence for therapeutic benefit of adjuvant/neoadjuvant radio-/chemotherapy in R0 resected COS cases.
Decreased expression of SCARA5 predicts a poor prognosis in melanoma using bioinformatics analysis
Authors: Ni Qinggan , Li Xia , Huang Hua , Ge Zili 
Published: March 2023

BackgroundIt has been established that the scavenger receptor class A member 5 (SCARA5) functions as a tumor suppressor gene in various cancer types. To our knowledge, no comprehensive study has hitherto investigated the expression and function of SCARA5 in melanoma. This study aimed to determine the association between SCARA5 and melanoma.MethodsAnalysis of SCARA5 mRNA expression was performed using The Cancer Genome Atlas (TCGA) data sets. To evaluate the clinical significance of SCARA5, the clinical data of 93 patients with melanoma were collected. The role of SCARA5 expression in prognosis was also analyzed. In this study, survival was evaluated by Kaplan–Meier analysis and compared using the log-rank test. Univariate and multivariate Cox proportional hazard regression analyses were used to identify independent predictors. The Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and gene set enrichment analysis (GSEA) were used to perform gene set functional annotations. Protein–protein interaction (PPI) networks were constructed to illustrate gene–gene interactions. The Tumor IMmune Estimation Resource (TIMER) database was used to explore the association between SCARA5 and immune infiltration levels.ResultsThe results showed that the SCARA5 mRNA expression in melanoma was significantly lower than in adjacent normal skin tissue (p &lt; 0.001). Moreover, decreased expression of SCARA5 in melanoma correlated with the tumor, node, and metastasis (TNM) stage and recurrence (p &lt; 0.05). The overall survival (OS) was significantly higher in melanoma with high SCARA5 expression compared with low SCARA5 expression (p &lt; 0.001). During univariate analysis, SCARA5 expression, tumor (T) stage, node (N) stage, metastasis (M) stage, and recurrence correlated with OS (p &lt; 0.05). Further multivariate Cox regression analysis showed that SCARA5 expression (p = 0.012) could be an independent prognostic factor for OS in cutaneous malignant melanoma. GSEA analysis showed that SCARA5 was significantly enriched in various pathways, such as response to developmental biology and response to antimicrobial peptides. Correlation analysis showed a positive correlation with CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells (p &lt; 0.05), and a negative correlation with tumor purity (p &lt; 0.05)ConclusionSCARA5 has significant potential as a prognostic biomarker and as a promising therapeutic target in melanoma. Furthermore, SCARA5 expression in melanoma is related to the level of immune infiltration.
Sex differences in methylation profiles are apparent in medulloblastoma, particularly among SHH tumors
Authors: Moss Rachel M. , Sorajja Natali , Mills Lauren J. , Moertel Christopher L. , Hoang Thanh T. , Spector Logan G. , Largaespada David A. , Williams Lindsay A. 
Published: March 2023

BackgroundMedulloblastoma, the most common malignant pediatric brain tumor, displays marked sex differences in prevalence of the four main molecular subgroups: SHH, WNT, Group 3 and Group 4. Males are more frequently diagnosed with SHH, Group 3 and 4 tumors, which have worse prognoses than WNT tumors. Little is known about sex differences in methylation profiles within subgroups.MethodsUsing publicly available methylation data (Illumina HumanMethylation450K array), we compared beta values for males versus females. Differentially methylated positions (DMP) by sex within medulloblastoma subgroups were identified on the autosomes. DMPs were mapped to genes and Reactome pathway analysis was run by subgroup. Kaplan-Meier survival curves (Log-Rank p-values) were assessed for each sex within subgroup. MethylCIBERSORT was used to investigate the tumor microenvironment using deconvolution to estimate the abundances of immune cell types using DNA methylation data.ResultsThere were statistically significant differences in sex by medulloblastoma subgroups (chi-squared p-value=0.00004): Group 3 (n=144; 65% male), Group 4 (n=326; 67% male), SHH (n=223; 57% male) and WNT (n=70; 41% male). Females had worse survival than males for SHH (p-value=0.02). DMPs by sex were identified within subgroups: SHH (n=131), Group 4 (n=29), Group 3 (n=19), and WNT (n=16) and validated in an independent dataset. Unsupervised hierarchical clustering showed that sex-DMPs in SHH did not correlate with other tumor attributes. Ten genes with sex DMPs (RFTN1, C1orf103, FKBP1B, COL25A1, NPDC1, B3GNT1, FOXN3, RNASEH2C, TLE1, and PHF17) were shared across subgroups. Significant pathways (p&lt;0.05) associated with DMPs were identified for SHH (n=22) and Group 4 (n=4) and included signaling pathways for RET proto-oncogene, advanced glycosylation end product receptor, regulation of KIT, neurotrophic receptors, NOTCH, and TGF-β. In SHH, we identified DMPs in four genes (CDK6, COL25A1, MMP16, PRIM2) that encode proteins which are the target of therapies in clinical trials for other cancers. There were few sex differences in immune cell composition within tumor subgroups.ConclusionThere are sexually dimorphic methylation profiles for SHH medulloblastoma where survival differences were observed. Sex-specific therapies in medulloblastoma may impact outcomes.
Survival and prognostic factors in patients with synchronous multiple primary esophageal squamous cell carcinoma receiving definitive radiotherapy: A propensity score-matched analysis
Authors: Wang Wenyi , Liu Xiaoxu , Dang Jun , Li Guang 
Published: March 2023

PurposeTo compare the lesion characteristics and radiotherapy efficacy of patients with single and multiple esophageal squamous cell carcinoma (ESCC), to evaluate the effect of multiple lesions on ESCC, and establish a nomogram survival prediction model for patients with synchronous multiple primary esophageal squamous cell carcinoma (SMPESCC) who received definitive radiotherapy.Materials and methods:The study enrolled 1,034 patients with ESCC who underwent definitive radiotherapy between 2010 and 2020. The efficacy of radiotherapy was compared between 101 patients with SMPESCC and 933 patients with single ESCC. Propensity score matching was used to control for potential confounders. For patients with SMPESCC, a nomogram prediction model was established based on the Cox regression model.ResultsThe median OS was 30.00 (95% CI = 25.08-34.92) months for the single lesion group and 19.00 (95% CI = 15.51-22.48) months for the multiple cancer group respectively. Multivariate COX regression analysis showed that multiple cancer was an independent prognostic factor for ESCC patients (HR=1.89, 95%CI=1.49-2.38, P&lt;0.001). Cox multivariate analysis of SMPESCC patients showed that T stage (P =0.002), chemotherapy (P =0.006), and lesion spacing (P =0.004) were independent prognostic factors associated with OS. The nomogram was established by combining T stage, chemotherapy, and lesion spacing, and Harrell’s C index was 0.711 after internal cross-validation. The calibration curve and decision curve analysis confirmed that the nomogram survival prediction model had a good predictive value for individual survival.ConclusionsThe survival rate of single esophageal cancer is significantly better than that of multiple lesions. Patients with SMPESCC exhibit worse survival than patients with single ESCC. Multiple lesions have a significant impact on the survival of patients with ESCC. The nomogram model established for SMPESCC patients can well predict the individual survival of patients.