bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors contributing to university dropout: a review
Authors: Lorenzo-Quiles Oswaldo , Galdón-López Samuel , Lendínez-Turón Ana
Published: March 2023

Introduction

Dropout is one of the problems that the university education system has to face every year. The educational community is involved in the reasons for its trajectory as a social problem, which does not exempt any student in the world. Its study and improvement of the education system is a key element in changing the course of university dropout and alleviating its rapid growth in society.

Methodology

Using a quantitative and qualitative methodology, an attempt is made to provide answers to the objectives pursued by the research.

Objectives

To analyze student satisfaction, to specify the causes of dropout, and to determine the most appropriate authors on dropout by means of literature and different databases.

Conclusions

It is concluded that, are five main major components would be behind university dropout: student adaptation, personality, socio-economic level, teacher–student relationship, and quality in university education. With them come certain sub-causes that must be taken into account for a better understanding of the reasons for university dropout, such as demotivation, low self-esteem, frustration, pregnancy, among others, reasons why their study is essential for their future eradication.
Psychometric properties and invariance of the scale to measure attitude of researchers for university-industry collaboration
Authors: Pérez-Morán Juan Carlos , Morales-Páez Marcela , Bernal-Baldenebro Brandon , Cano-Gutiérrez Julio César
Published: March 2023

The psychometric properties of the Scale to measure the attitude of researchers for scientific-technological collaboration between universities and industry (EA-COOPTEC, for its acronym in Spanish) were analyzed, specifically evidence of construct validity of the internal structure and invariance for gender and age was obtained. The EA-COOPTEC was administered to 179 academic Teachers–Researchers (T-Rs) involved in Universities-Industry Collaboration (UIC) activities: 50 women and 129 men. Participants had a median age of 36–40 years. A descriptive analysis was implemented, as well as an Exploratory and Confirmatory Factor Analysis (EFA and CFA), and a method of succession of nested models for invariance testing. A four-factor model explaining the perception of UIC activities was generated and evidence of invariance for gender and partial invariance for age was obtained. Acceptable fit indices were obtained for the configurational, weak, strong and strict. Given the results, we recommend the use of the EA-COOPTEC v0.1 for the analysis of the mean differences between genders and age in T-Rs.
Assessment and quantification of ovarian reserve on the basis of machine learning models
Authors: Ding Ting , Ren Wu , Wang Tian , Han Yun , Ma Wenqing , Wang Man , Fu Fangfang , Li Yan , Wang Shixuan
Published: March 2023

Background

Early detection of ovarian aging is of huge importance, although no ideal marker or acknowledged evaluation system exists. The purpose of this study was to develop a better prediction model to assess and quantify ovarian reserve using machine learning methods.

Methods

This is a multicenter, nationwide population-based study including a total of 1,020 healthy women. For these healthy women, their ovarian reserve was quantified in the form of ovarian age, which was assumed equal to their chronological age, and least absolute shrinkage and selection operator (LASSO) regression was used to select features to construct models. Seven machine learning methods, namely artificial neural network (ANN), support vector machine (SVM), generalized linear model (GLM), K-nearest neighbors regression (KNN), gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), and light gradient boosting machine (LightGBM) were applied to construct prediction models separately. Pearson’s correlation coefficient (PCC), mean absolute error (MAE), and mean squared error (MSE) were used to compare the efficiency and stability of these models.

Results

Anti-Müllerian hormone (AMH) and antral follicle count (AFC) were detected to have the highest absolute PCC values of 0.45 and 0.43 with age and held similar age distribution curves. The LightGBM model was thought to be the most suitable model for ovarian age after ranking analysis, combining PCC, MAE, and MSE values. The LightGBM model obtained PCC values of 0.82, 0.56, and 0.70 for the training set, the test set, and the entire dataset, respectively. The LightGBM method still held the lowest MAE and cross-validated MSE values. Further, in two different age groups (20–35 and >35 years), the LightGBM model also obtained the lowest MAE value of 2.88 for women between the ages of 20 and 35 years and the second lowest MAE value of 5.12 for women over the age of 35 years.

Conclusion

Machine learning methods combining multi-features were reliable in assessing and quantifying ovarian reserve, and the LightGBM method turned out to be the approach with the best result, especially in the child-bearing age group of 20 to 35 years.
Development and validation of a diabetic retinopathy risk prediction model for middle-aged patients with type 2 diabetes mellitus
Authors: Wang Gao-Xiang , Hu Xin-Yu , Zhao Heng-Xia , Li Hui-Lin , Chu Shu-Fang , Liu De-Liang
Published: March 2023

Objectives

The study aims to establish a predictive nomogram of diabetic retinopathy(DR) for the middle-aged population with type 2 diabetes mellitus (T2DM).

Methods

This retrospective study screened 931 patients with T2DM between 30 and 59 years of age from the 2011-2018 National Health and Nutrition Examination Survey database. The development group comprised 704 participants from the 2011-2016 survey, and the validation group included 227 participants from the 2017-2018 survey. The least absolute shrinkage and selection operator regression model was used to determine the best predictive variables. The logistic regression analysis built three models: the full model, the multiple fractional polynomial (MFP) model, and the stepwise (stepAIC) selected model. Then we decided optimal model based on the receiver operating characteristic curve (ROC). ROC, calibration curve, Hosmer-Lemeshow test, and decision curve analysis (DCA) were used to validate and assess the model. An online dynamic nomogram prediction tool was also constructed.

Results

The MFP model was selected to be the final model, including gender, the use of insulin, duration of diabetes, urinary albumin-to-creatinine ratio, and serum phosphorus. The AUC was 0.709 in the development set and 0.704 in the validation set. According to the ROC, calibration curves, and Hosmer-Lemeshow test, the nomogram demonstrated good coherence. The nomogram was clinically helpful, according to DCA.

Conclusion

This study established and validated a predictive model for DR in the mid-life T2DM population, which can assist clinicians quickly determining who is prone to develop DR.
Interplay between strain fitness and transmission frequency determines prevalence of antimicrobial resistance
Authors: Bogri Amalia , Otani Saria , Aarestrup Frank M. , Brinch Christian
Published: March 2023

The steep rise of infections caused by bacteria that are resistant to antimicrobial agents threatens global health. However, the association between antimicrobial use and the prevalence of resistance is not straightforward. Therefore, it is necessary to quantify the importance of additional factors that affect this relationship. We theoretically explore how the prevalence of resistance is affected by the combination of three factors: antimicrobial use, bacterial transmission, and fitness cost of resistance. We present a model that combines within-host, between-hosts and between-populations dynamics, built upon the competitive Lotka-Volterra equations. We developed the model in a manner that allows future experimental validation of the findings with single isolates in the laboratory. Each host may carry two strains (susceptible and resistant) that represent the host’s commensal microbiome and are not the target of the antimicrobial treatment. The model simulates a population of hosts who are treated periodically with antibiotics and transmit bacteria to each other. We show that bacterial transmission results in strain co-existence. Transmission disseminates resistant bacteria in the population, increasing the levels of resistance. Counterintuitively, when the cost of resistance is low, high transmission frequencies reduce resistance prevalence. Transmission between host populations leads to more similar resistance levels, increasing the susceptibility of the population with higher antimicrobial use. Overall, our results indicate that the interplay between bacterial transmission and strain fitness affects the prevalence of resistance in a non-linear way. We then place our results within the context of ecological theory, particularly on temporal niche partitioning and metapopulation rescue, and we formulate testable experimental predictions for future research.
Lithological substrates influence tropical dry forest structure, diversity, and composition, but not its dynamics
Authors: Muñoz Rodrigo , Enríquez Moisés , Bongers Frans , López-Mendoza Rey David , Miguel-Talonia César , Meave Jorge A.
Published: March 2023

Introduction

Tropical dry forests (TDF) are not only the most widespread tropical forest type but also the most threatened forest ecosystem worldwide. Yet, because their dynamics have been insufficiently studied, our knowledge about the factors responsible for the spatial and temporal variability in TDF dynamics remains very limited. In this study, we aimed (1) to assess the effects of two lithological substrates on TDF structure, diversity, and species composition, and (2) to determine whether and how these substrates affect temporal dynamics on TDF attributes.

Methods

We used information gathered through a 12-year long annual monitoring of 14 old-growth TDF permanent plots in southern Mexico, seven of which were established on limestone and seven on phyllite. Previous work shows that limestone-derived soils have higher humidity, conductivity, and phosphorous and calcium contents, but lower nitrogen content.

Results

TDF structure and diversity attributes were consistently higher on limestone TDF, while canopy height was higher on phyllite TDF. By contrast, temporal variation in TDF attributes, demographic rates (recruitment, growth, and mortality) and attribute residence times were indistinguishable between substrates. We also found a strong differentiation of species composition between substrates, yet substrates did not influence the temporal behavior of composition.

Discussion

Our results suggest that limestone is a more favorable environment for TDF development (soil-effects mechanism), but the flora of the forest on phyllite seems to be better adapted to cope with harsher environmental conditions (composition-effects mechanism), which counterbalances the environmental advantage of limestone, ultimately resulting in spatially homogeneous TDF dynamics at the landscape level. Future studies should examine the role of functional attributes on old-growth TDF dynamics, as this will allow a better understanding of the impacts of extreme climatic events on forest attributes and their dynamics, as well as to foresee potential ecosystem state shifts and tipping points.
Tenascin-X as a causal gene for classical-like Ehlers-Danlos syndrome
Authors: Okuda-Ashitaka Emiko , Matsumoto Ken-ichi
Published: March 2023

Tenascin-X (TNX) is an extracellular matrix glycoprotein for which a deficiency results in a recessive form of classical-like Ehlers-Danlos syndrome (clEDS), a heritable connective tissue disorder with hyperextensible skin without atrophic scarring, joint hypermobility, and easy bruising. Notably, patients with clEDS also suffer from not only chronic joint pain and chronic myalgia but also neurological abnormalities such as peripheral paresthesia and axonal polyneuropathy with high frequency. By using TNX-deficient (Tnxb−/−) mice, well-known as a model animal of clEDS, we recently showed that Tnxb−/− mice exhibit hypersensitivity to chemical stimuli and the development of mechanical allodynia due to the hypersensitization of myelinated A-fibers and activation of the spinal dorsal horn. Pain also occurs in other types of EDS. First, we review the underlying molecular mechanisms of pain in EDS, especially that in clEDS. In addition, the roles of TNX as a tumor suppressor protein in cancer progression have been reported. Recent in silico large-scale database analyses have shown that TNX is downregulated in various tumor tissues and that high expression of TNX in tumor cells has a good prognosis. We describe what is so far known about TNX as a tumor suppressor protein. Furthermore, some patients with clEDS show delayed wound healing. Tnxb−/− mice also exhibit impairment of epithelial wound healing in corneas. TNX is also involved in liver fibrosis. We address the molecular mechanism for the induction of COL1A1 by the expression of both a peptide derived from the fibrinogen-related domain of TNX and integrin α11.
Novel QTL for chilling tolerance at germination and early seedling stages in sorghum
Authors: La Borde Niegel , Rajewski John , Dweikat Ismail
Published: March 2023

Sorghum (Sorghum bicolor L.) a drought tolerant staple crop for half a billion people in Africa and Asia, an important source of animal feed throughout the world and a biofuel feedstock of growing importanceorghum’s originated from tropical regions rendering the crop to be cold sensitive. Low temperature stresses such as chilling and frost greatly affect the agronomic performance of sorghum and limit its geographical distribution, posing a major problem in temperate environments when sorghum is planted early. Understanding the genetic basis of wide adaptability and of sorghum would facilitate molecular breeding programs and studies of other C4 crops. The objective of this study is to conduct quantitative trait loci analysis using genotying by sequencing for early seed germination and seedling cold tolerance in two sorghum recombinant inbred lines populations. To accomplish that, we used two populations of recombinant inbred lines (RIL) developed from crosses between cold-tolerant (CT19, ICSV700) and cold-sensitive (TX430, M81E) parents. The derived RIL populations were evaluated for single nucleotide polymorphism (SNP) using genotype-by-sequencing (GBS) in the field and under controlled environments for their response to chilling stress. Linkage maps were constructed with 464 and 875 SNPs for the CT19 X TX430 (C1) and ICSV700 X M81 E (C2) populations respectively. Using quantitative trait loci (QTL) mapping, we identified QTL conferring tolerance to chilling tolerance at the seedling stage. A total of 16 and 39 total QTL were identified in the C1 and C2 populations, respectively. Two major QTL were identified in the C1 population, and three major QTL were mapped in the C2 population. Comparisons between the two populations and with previously identified QTL show a high degree of similarity in QTL locations. Given the amount of co-localization of QTL across traits and the direction of allelic effect supports that these regions have a pleiotropic effect. These QTL regions were also identified to be highly enriched for genes encoding chilling stress and hormonal response genes. This identified QTL can be useful in developing tools for molecular breeding of sorghums with improved low-temperature germinability.
Metrics for maternity unit staffing in low resource settings: Scoping review and proposed core indicator
Authors: Stones William , Nair Anjali
Published: March 2023

Background

The lack of usable indicators and benchmarks for staffing of maternity units in health facilities has constrained planning and effective program implementation for emergency obstetric and newborn care (EmONC) globally.

Objectives

To identify potential indicator(s) and benchmarks for EmONC facility staffing that might be applicable in low resource settings, we undertook a scoping review before proceeding to develop a proposed set of indicators.

Eligibility criteria

Population: women attending health facilities for care around the time of delivery and their newborns. Concept: reports of mandated norms or actual staffing levels in health facilities.

Context

studies conducted in healthcare facilities of any type that undertake delivery and newborn care and those from any geographic setting in both public and private sector facilities.

Sources of evidence and charting

Searches were limited to material published since 2000 in English or French, using Pubmed and a purposive search of national Ministry of Health, non-governmental organization and UN agency websites for relevant documents. A template for data extraction was designed.

Results

Data extraction was undertaken from 59 papers and reports including 29 descriptive journal articles, 17 national Ministry of Health documents, 5 Health Care Professional Association (HCPA) documents, two each of journal policy recommendation and comparative studies, one UN Agency document and 3 systematic reviews. Calculation or modelling of staffing ratios was based on delivery, admission or inpatient numbers in 34 reports, with 15 using facility designation as the basis for staffing norms. Other ratios were based on bed numbers or population metrics.

Conclusions

Taken together, the findings point to a need for staffing norms for delivery and newborn care that reflect numbers and competencies of staff physically present on each shift. A Core indicator is proposed, “Monthly mean delivery unit staffing ratio” calculated as number of annual births/365/monthly average shift staff census.
Expression patterns of eight RNA-modified regulators correlating with immune infiltrates during the progression of osteoarthritis
Authors: Chen Ziyi , Wang Wenjuan , Hua Yinghui
Published: March 2023

Background

RNA modifications in eukaryotic cells have emerged as an exciting but under-explored area in recent years and are considered to be associated with many human diseases. While several studies have been published relating to m6A in osteoarthritis (OA), we only have limited knowledge of other kinds of RNA modifications. Our study investigated eight RNA modifiers’ specific roles in OA including A-to-I, APA, m5C, m6A, m7G, mcm5s2U, Nm and Ψ together with their relationship with immune infiltration.

Methods

RNA modification patterns in OA samples were identified based on eight-type RNA modifiers and their correlation with the degree of immune infiltration was also methodically investigated. Receiver operating characteristic curves (ROC) and qRT-PCR was performed to confirm the abnormal expression of hub genes. The RNA modification score (Rmscore) was generated by the applications of principal component analysis (PCA) algorithm in order to quantify RNA modification modes in individual OA patients.

Results

We identified 21 differentially-expressed RNA modification related genes between OA and healthy samples. For example, CFI, CBLL1 and ALKBH8 were expressed at high levels in OA (P<0.001), while RPUSD4, PUS1, NUDT21, FBL and WDR4 were expressed at low levels (P<0.001). Two candidate RNA modification regulators (WDR4 and CFI) were screened out utilizing a random forest machine learning model. We then identified two distinctive RNA modification modes in OA which were found to display distinctive biological features. High Rmscore, characterized by increased immune cell infiltration, indicated an inflamed phenotype.

Conclusions

Our study was the first to systematically reveal the crosstalk and dysregulations eight-type of RNA modifications in OA. Assessing individuals’ RNA modification patterns will be conductive to enhance our understanding of the properties of immune infiltration, provide novel diagnostic and prognostic biomarkers, and guide more effective immunotherapy strategies in the future.
Molecules promoting circulating clusters of cancer cells suggest novel therapeutic targets for treatment of metastatic cancers
Authors: Rozenberg Julian M. , Buzdin Anton A. , Mohammad Tharaa , Rakitina Olga A. , Didych Dmitry A. , Pleshkan Victor V. , Alekseenko Irina V.
Published: March 2023

Treatment of metastatic disease remains among the most challenging tasks in oncology. One of the early events that predicts a poor prognosis and precedes the development of metastasis is the occurrence of clusters of cancer cells in the blood flow. Moreover, the presence of heterogeneous clusters of cancerous and noncancerous cells in the circulation is even more dangerous. Review of pathological mechanisms and biological molecules directly involved in the formation and pathogenesis of the heterotypic circulating tumor cell (CTC) clusters revealed their common properties, which include increased adhesiveness, combined epithelial-mesenchymal phenotype, CTC-white blood cell interaction, and polyploidy. Several molecules involved in the heterotypic CTC interactions and their metastatic properties, including IL6R, CXCR4 and EPCAM, are targets of approved or experimental anticancer drugs. Accordingly, analysis of patient survival data from the published literature and public datasets revealed that the expression of several molecules affecting the formation of CTC clusters predicts patient survival in multiple cancer types. Thus, targeting of molecules involved in CTC heterotypic interactions might be a valuable strategy for the treatment of metastatic cancers.
Oncolytic immunovirotherapy for high-grade gliomas: A novel and an evolving therapeutic option
Authors: Asija Sweety , Chatterjee Abhishek , Goda Jayant S. , Yadav Sandhya , Chekuri Godhanjali , Purwar Rahul
Published: March 2023

Glioblastoma is one of the most difficult tumor types to manage, having high morbidity and mortality with available therapies (surgery, radiotherapy and chemotherapy). Immunotherapeutic agents like Oncolytic Viruses (OVs), Immune Checkpoint Inhibitors (ICIs), Chimeric Antigen Receptor (CAR) T cells and Natural Killer (NK) cell therapies are now being extensively used as experimental therapies in the management of glioblastoma. Oncolytic virotherapy is an emerging form of anti-cancer therapy, employing nature’s own agents to target and destroy glioma cells. Several oncolytic viruses have demonstrated the ability to infect and lyse glioma cells by inducing apoptosis or triggering an anti-tumor immune response. In this mini-review, we discuss the role of OV therapy (OVT) in malignant gliomas with a special focus on ongoing and completed clinical trials and the ensuing challenges and perspectives thereof in subsequent sections.
Phosducin-like 3 is a novel prognostic and onco-immunological biomarker in glioma: A multi-omics analysis with experimental verification
Authors: Peng Zesheng , Wang Jiajing , Tong Shiao , Wu Yuxi , Yi Dongye , Xiang Wei
Published: March 2023

Malignant glioma is the most frequent primary tumor of the central nervous system. PDCL3 is a member of the phosducin-like protein family, and its imbalance has been shown to be associated with several human diseases. However, the underlying role of PDCL3 in human malignant cancers, especially in malignant gliomas, is unclear. In this study, we combined public database analysis and experimental verification to explore the differential expression, prognostic value and potential functions and mechanisms of PDCL3. The results revealed that PDCL3 is upregulated in multiple cancers and acts as a potential prognostic biomarker of glioma. Mechanistically, PDCL3 expression is associated with epigenetic modifications and genetic mutations. PDCL3 may directly interact with the chaperonin-containing TCP1 complex, regulating cell malignancy, cell communication and the extracellular matrix. More importantly, the association of PDCL3 with the infiltration of immune cells, immunomodulatory genes, immune checkpoints, cancer stemness and angiogenesis suggested that PDCL3 may regulate the glioma immune landscape. Furthermore, PDCL3 interference also decreased the proliferation, invasion and migration of glioma cells. In conclusion, PDCL3 is a novel oncogene and can be adopted as a biomarker with value in assisting clinical diagnosis, predicting patient outcomes and assessing the immune landscape of the tumor microenvironment in glioma.
Humoral and cellular immunity to SARS-COV-2 after vaccination with mRNA vaccines in PLWH with discordant immune response. Influence of the vaccine administered
Authors: López-Cortés Luis F. , Saborido-Alconchel Abraham , Trujillo-Rodríguez María , Serna-Gallego Ana , Llaves-Flores Silvia , Muñoz-Muela Esperanza , Pérez-Santos María Jesús , Lozano Carmen , Mejias-Trueba Marta , Roca Cristina , Espinosa Nuria , Gutiérrez-Valencia Alicia
Published: March 2023

Background

Data on SARS-CoV-2 mRNA vaccine immunogenicity in people living with human immunodeficiency virus (PLWH) and discordant immune response (DIR) are currently limited. Therefore, we compare the immunogenicity of these vaccines in DIR and immunological responders (IR).

Methods

A prospective cohort that enrolled 89 participants. Finally, 22 IR and 24 DIR were analyzed before vaccination (T0), one (T1) and six months (T2) after receiving BNT162b2 or mRNA-1273 vaccine. Additionally, 10 IR and 16 DIR were evaluated after a third dose (T3). Anti-S-RBD IgG, neutralizing antibodies (nAb), neutralization activity, and specific memory B cells were quantified. Furthermore, specific CD4+ and CD8+ responses were determined by intracellular cytokine staining and polyfunctionality indexes (Pindex).

Results

At T1, all participants developed anti-S-RBD. 100% IR developed nAb compared to 83.3% DIR. Spike-specific B cells were detected in all IR and 21/24 DIR. Memory CD4+ T cells responded in 5/9 IR and 7/9 DIR, mainly based on the expression of IFN-γ and TNF-α, with a higher Pindex in DIR. Memory CD8+ T cells responded in only four participants in each group. At T2, anti-S-RBD and nAb titers were higher in DIR than in IR. In both groups, there was an increase in specific B memory cells, higher in DIR. Six IR and five DIR maintained a specific memory CD4+ response. Memory CD8+ response was preserved in IR but was lost in DIR. In a multivariate linear regression analysis, receiving mRNA-1273 instead of BNT162b2 played a prominent role in the results.

Conclusions

Our data suggest that PLWH with DIR can mount an immune response similar to those with higher CD4+, provided they receive the mRNA-1273 vaccine instead of others less immunogenic.
T-cell exhaustion signatures characterize the immune landscape and predict HCC prognosis via integrating single-cell RNA-seq and bulk RNA-sequencing
Authors: Chi Hao , Zhao Songyun , Yang Jinyan , Gao Xinrui , Peng Gaoge , Zhang Jinhao , Xie Xixi , Song Guobin , Xu Ke , Xia Zhijia , Chen Shi , Zhao Jinqiu
Published: March 2023

Background

Hepatocellular carcinoma (HCC), the third most prevalent cause of cancer-related death, is a frequent primary liver cancer with a high rate of morbidity and mortality. T-cell depletion (TEX) is a progressive decline in T-cell function due to continuous stimulation of the TCR in the presence of sustained antigen exposure. Numerous studies have shown that TEX plays an essential role in the antitumor immune process and is significantly associated with patient prognosis. Hence, it is important to gain insight into the potential role of T cell depletion in the tumor microenvironment. The purpose of this study was to develop a trustworthy TEX-based signature using single-cell RNA-seq (scRNA-seq) and high-throughput RNA sequencing, opening up new avenues for evaluating the prognosis and immunotherapeutic response of HCC patients.

Methods

The International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases were used to download RNA-seq information for HCC patients. The 10x scRNA-seq. data of HCC were downloaded from GSE166635, and UMAP was used for clustering descending, and subgroup identification. TEX-related genes were identified by gene set variance analysis (GSVA) and weighted gene correlation network analysis (WGCNA). Afterward, we established a prognostic TEX signature using LASSO-Cox analysis. External validation was performed in the ICGC cohort. Immunotherapy response was assessed by the IMvigor210, GSE78220, GSE79671, and GSE91061cohorts. In addition, differences in mutational landscape and chemotherapy sensitivity between different risk groups were investigated. Finally, the differential expression of TEX genes was verified by qRT-PCR.

Result

11 TEX genes were thought to be highly predictive of the prognosis of HCC and substantially related to HCC prognosis. Patients in the low-risk group had a greater overall survival rate than those in the high-risk group, according to multivariate analysis, which also revealed that the model was an independent predictor of HCC. The predictive efficacy of columnar maps created from clinical features and risk scores was strong.

Conclusion

TEX signature and column line plots showed good predictive performance, providing a new perspective for assessing pre-immune efficacy, which will be useful for future precision immuno-oncology studies.
Heterologous prime-boost immunisation with mRNA- and AdC68-based 2019-nCoV variant vaccines induces broad-spectrum immune responses in mice
Authors: Li Xingxing , Liu Jingjing , Li Wenjuan , Peng Qinhua , Li Miao , Ying Zhifang , Zhang Zelun , Liu Xinyu , Wu Xiaohong , Zhao Danhua , Yang Lihong , Cao Shouchun , Huang Yanqiu , Shi Leitai , Xu Hongshan , Wang Yunpeng , Yue Guangzhi , Suo Yue , Nie Jianhui , Huang Weijin , Li Jia , Li Yuhua
Published: March 2023

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) variants has been associated with the transmission and pathogenicity of COVID-19. Therefore, exploring the optimal immunisation strategy to improve the broad-spectrum cross-protection ability of COVID-19 vaccines is of great significance. Herein, we assessed different heterologous prime-boost strategies with chimpanzee adenovirus vector-based COVID-19 vaccines plus Wuhan-Hu-1 (WH-1) strain (AdW) and Beta variant (AdB) and mRNA-based COVID-19 vaccines plus WH-1 strain (ARW) and Omicron (B.1.1.529) variant (ARO) in 6-week-old female BALB/c mice. AdW and AdB were administered intramuscularly or intranasally, while ARW and ARO were administered intramuscularly. Intranasal or intramuscular vaccination with AdB followed by ARO booster exhibited the highest levels of cross-reactive IgG, pseudovirus-neutralising antibody (PNAb) responses, and angiotensin-converting enzyme-2 (ACE2)-binding inhibition rates against different 2019-nCoV variants among all vaccination groups. Moreover, intranasal AdB vaccination followed by ARO induced higher levels of IgA and neutralising antibody responses against live 2019-nCoV than intramuscular AdB vaccination followed by ARO. A single dose of AdB administered intranasally or intramuscularly induced broader cross-NAb responses than AdW. Th1-biased cellular immune response was induced in all vaccination groups. Intramuscular vaccination-only groups exhibited higher levels of Th1 cytokines than intranasal vaccination-only and intranasal vaccination-containing groups. However, no obvious differences were found in the levels of Th2 cytokines between the control and all vaccination groups. Our findings provide a basis for exploring vaccination strategies against different 2019-nCoV variants to achieve high broad-spectrum immune efficacy.
Bioinformatics analysis reveals the potential role of matrix metalloproteinases in immunity and urolithiasis
Authors: Hong Sen-Yuan , Jiang Hong-Cheng , Xu Wen-Chao , Zeng He-Song , Wang Shao-Gang , Qin Bao-Long
Published: March 2023

Background

The pathogenesis of urolithiasis remains unclear, making the development of medications for treatment and prevention stagnant. Randall’s plaques (RPs) begin as interstitial calcium phosphate crystal deposits, grow outward and breach the renal papillary surface, acting as attachment for CaOx stones. Since matrix metalloproteinases (MMPs) can degrade all components of extracellular matrix (ECM), they might participate in the breach of RPs. Besides, MMPs can modulate the immune response and inflammation, which were confirmed to be involved in urolithiasis. We aimed to investigate the role of MMPs in the development of RPs and stone formation.

Methods

The public dataset GSE73680 was mined to identify differentially expressed MMPs (DEMMPs) between normal tissues and RPs. WGCNA and three machine learning algorithms were performed to screen the hub DEMMPs. In vitro experiments were conducted for validation. Afterwards, RPs samples were classified into clusters based on the hub DEMMPs expression. Differentially expressed genes (DEGs) between clusters were identified and functional enrichment analysis and GSEA were applied to explore the biological role of DEGs. Moreover, the immune infiltration levels between clusters were evaluated by CIBERSORT and ssGSEA.

Results

Five DEMMPs, including MMP1, MMP3, MMP9, MMP10, and MMP12, were identified between normal tissues and RPs, and all of them were elevated in RPs. Based on WGCNA and three machine learning algorithms, all of five DEMMPs were regarded as hub DEMMPs. In vitro validation found the expression of hub DEMMPs also increased in renal tubular epithelial cells under lithogenic environment. RPs samples were divided into two clusters and cluster A exhibited higher expression of hub DEMMPs compared to cluster B. Functional enrichment analysis and GSEA found DEGs were enriched in immune-related functions and pathways. Moreover, increased infiltration of M1 macrophages and enhanced levels of inflammation were observed in cluster A by immune infiltration analysis.

Conclusion

We assumed that MMPs might participate in RPs and stone formation through ECM degradation and macrophages-mediated immune response and inflammation. Our findings offer a novel perspective on the role of MMPs in immunity and urolithiasis for the first time, and provide potential biomarkers to develop targets for treatment and prevention.
Valve movements indicate rhythm and survival potential of scallop
Authors: Xun Xiaogang , Wang Jingru , Liu Fengqing , Chen Long , Zou Yan , Liu Yan , Kong Xiangfeng , Hu Xiaoli
Published: March 2023

Yesso scallop, Patinopecten yessoensis, is one of the most economically important marine bivalves that has been extensively cultured on the northern coast of China. Unfortunately, recurrent mass scallop mortalities have caused enormous economic losses to farmers and industries. Therefore, the exploration of indicators to assess the survival potential of scallops is conducive to breeding new varieties for a high survival rate. However, traditional indicators related to scallop health are generally measured using laborious and time-consuming methods that often involve killing the scallops. In this study, we developed a non-invasive and real-time method for monitoring Yesso scallop valve movements. Our research demonstrated a close correlation between the behavior of valve movements and the survival potential of scallops. The frequency of valve movements was found to have a circadian rhythm with elevated frequency during 7:00–9:00 and 17:00–19:00, showing a coincident rhythm with cardiac activity. Moreover, the patterns of valve behavior indicated that intense valve movements appeared to be more equally distributed in the lifespan of long-surviving individuals. Velocity estimation of valve movement was further applied to assess its correlation with scallop vitality and mortality. The top valve movement velocity was the most important determinant of the scallop vitality coefficient, which was positively correlated with scallop survival time (R2 = 0.873, P < 0.01). The prominent variables in predicting scallop survival potential, including the scallop top velocity and thickness, were presumed to be linked to the movement associated attributes of the shell ligament and muscle, which are important determinants of valve behavior intensity. Our findings demonstrate that an understanding of the valve movements of bivalves can be of great benefit, not only in exploring scallop vitality but also in developing scallop breeding strategies.
Biological soil crust development affects bacterial communities in the Caragana microphylla community in alpine sandy areas
Authors: Zhou Hong , Li Lun , Liu Yunxiang
Published: March 2023

Introduction

Biological soil crusts (BSCs) constitute a substantial portion of primary production in dryland ecosystems. They successionally mature to deliver a series of ecosystem services. Bacteria, as an important community in BSCs, play critical roles in maintaining the structure and functions of BSCs. However, the process by which bacterial diversity and community are altered with BSC development is not fully understood.

Methods

In this study, amplicons sequencing was used to investigate bacterial diversity and community compositions across five developmental stages of BSCs (bare sand, microbial crusts, algae crusts, lichen crusts, and moss crusts) and their relationship with environmental variables in the Gonghe basin sandy land in Qinghai-Tibet Plateau, northwestern China.

Results

The results showed that Proteobacteria, Actinobacteria, Cyanobacteria, Acidobacteria, Bacteroidetes, and Firmicutes were predominant in different developmental stages of BSCs, accounting for more than 77% of the total relative abundance. The phyla of Acidobacteria and Bacteroidetes were abundant in this region. With BSC development, bacterial diversity significantly increased, and the taxonomic community composition significantly altered. The relative abundance of copiotrophic bacteria, such as Actinobacteria, Acidobacteria, Bacteroidetes, Verrucomicrobia, Planctomycetes, and Gemmatimonadetes significantly increased, whereas the relative abundance of oligotrophic bacteria, such as Proteobacteria and Firmicutes significantly decreased. The relative abundance of Cyanobacteria in the algae crusts was significantly higher than that in the other developmental stages (p < 0.05).

Conclusion

Variations in bacterial composition suggested that the potential ecological functions of the bacterial community were altered with BSC development. The functions varied from enhancing soil surface stability by promoting soil particle cementation in the early stages to promoting material circulation of the ecosystem by fixing carbon and nitrogen and decomposing litter in the later stages of BSC development. Bacterial community is a sensitive index of water and nutrient alterations during BSC development. SWC, pH value, TC, TOC, TN, NO3−, TP and soil texture were the primary environmental variables that promoted changes in the bacterial community composition of BSCs.
Cell-type-specific densities in mouse somatosensory cortex derived from scRNA-seq and in situ RNA hybridization
Authors: Keller Daniel , Verasztó Csaba , Markram Henry
Published: March 2023

Cells in the mammalian cerebral cortex exhibit layer-dependent patterns in their distribution. Classical methods of determining cell type distributions typically employ a painstaking process of large-scale sampling and characterization of cellular composition. We found that by combining in situ hybridization (ISH) images with cell-type-specific transcriptomes, position-dependent cortical composition in P56 mouse could be estimated in the somatosensory cortex. The method uses ISH images from the Allen Institute for Brain Science. There are two novel aspects of the methodology. First, it is not necessary to select a subset of genes that are particular for a cell type of interest, nor is it necessary to only use ISH images with low variability among samples. Second, the method also compensated for differences in soma size and incompleteness of the transcriptomes. The soma size compensation is particularly important in order to obtain quantitative estimates since relying on bulk expression alone would overestimate the contribution of larger cells. Predicted distributions of broader classes of cell types agreed with literature distributions. The primary result is that there is a high degree of substructure in the distribution of transcriptomic types beyond the resolution of layers. Furthermore, transcriptomic cell types each exhibited characteristic soma size distributions. Results suggest that the method could also be employed to assign transcriptomic cell types to well-aligned image sets in the entire brain.
Exploring the use of Granger causality for the identification of chemical exposure based on physiological data
Authors: Difrancesco S. , van Baardewijk J. U. , Cornelissen A. S. , Varon C. , Hendriks R. C. , Brouwer A. M.
Published: March 2023

Wearable sensors offer new opportunities for the early detection and identification of toxic chemicals in situations where medical evaluation is not immediately possible. We previously found that continuously recorded physiology in guinea pigs can be used for early detection of exposure to an opioid (fentanyl) or a nerve agent (VX), as well as for differentiating between the two. Here, we investigated how exposure to these different chemicals affects the interactions between ECG and respiration parameters as determined by Granger causality (GC). Features reflecting such interactions may provide additional information and improve models differentiating between chemical agents. Traditional respiration and ECG features, as well as GC features, were extracted from data of 120 guinea pigs exposed to VX (n = 61) or fentanyl (n = 59). Data were divided in a training set (n = 99) and a test set (n = 21). Minimum Redundancy Maximum Relevance (mRMR) and Support Vector Machine (SVM) algorithms were used to, respectively, perform feature selection and train a model to discriminate between the two chemicals. We found that ECG and respiration parameters are Granger-related under healthy conditions, and that exposure to fentanyl and VX affected these relationships in different ways. SVM models discriminated between chemicals with accuracy of 95% or higher on the test set. GC features did not improve the classification compared to traditional features. Respiration features (i.e., peak inspiratory and expiratory flow) were the most important to discriminate between different chemical’s exposure. Our results indicate that it may be feasible to discriminate between chemical exposure when using traditional physiological respiration features from wearable sensors. Future research will examine whether GC features can contribute to robust detection and differentiation between chemicals when considering other factors, such as generalizing results across species.
Feasibility and usability of a digital health technology system to monitor mobility and assess medication adherence in mild-to-moderate Parkinson's disease
Authors: Debelle Héloïse , Packer Emma , Beales Esther , Bailey Harry G. B. , Mc Ardle Ríona , Brown Philip , Hunter Heather , Ciravegna Fabio , Ireson Neil , Evers Jordi , Niessen Martijn , Shi Jian Qing , Yarnall Alison J. , Rochester Lynn , Alcock Lisa , Del Din Silvia
Published: March 2023

Introduction

Parkinson's disease (PD) is a neurodegenerative disorder which requires complex medication regimens to mitigate motor symptoms. The use of digital health technology systems (DHTSs) to collect mobility and medication data provides an opportunity to objectively quantify the effect of medication on motor performance during day-to-day activities. This insight could inform clinical decision-making, personalise care, and aid self-management. This study investigates the feasibility and usability of a multi-component DHTS to remotely assess self-reported medication adherence and monitor mobility in people with Parkinson's (PwP).

Methods

Thirty participants with PD [Hoehn and Yahr stage I (n = 1) and II (n = 29)] were recruited for this cross-sectional study. Participants were required to wear, and where appropriate, interact with a DHTS (smartwatch, inertial measurement unit, and smartphone) for seven consecutive days to assess medication adherence and monitor digital mobility outcomes and contextual factors. Participants reported their daily motor complications [motor fluctuations and dyskinesias (i.e., involuntary movements)] in a diary. Following the monitoring period, participants completed a questionnaire to gauge the usability of the DHTS. Feasibility was assessed through the percentage of data collected, and usability through analysis of qualitative questionnaire feedback.

Results

Adherence to each device exceeded 70% and ranged from 73 to 97%. Overall, the DHTS was well tolerated with 17/30 participants giving a score > 75% [average score for these participants = 89%, from 0 (worst) to 100 (best)] for its usability. Usability of the DHTS was significantly associated with age (ρ = −0.560, BCa 95% CI [−0.791, −0.207]). This study identified means to improve usability of the DHTS by addressing technical and design issues of the smartwatch. Feasibility, usability and acceptability were identified as key themes from PwP qualitative feedback on the DHTS.

Conclusion

This study highlighted the feasibility and usability of our integrated DHTS to remotely assess medication adherence and monitor mobility in people with mild-to-moderate Parkinson's disease. Further work is necessary to determine whether this DHTS can be implemented for clinical decision-making to optimise management of PwP.
Clinical features and prognosis of pediatric idiopathic sudden sensorineural hearing loss: A bi-center retrospective study
Authors: Li Yingqiang , Zhou Xiaowei , Dou Zhiyong , Deng Dongzhou , Bing Dan
Published: March 2023

Objective

Limited research has focused on the clinical features of sudden sensorineural hearing loss (SSNHL) in pediatric patients. This study is aimed to investigate the relationship between clinical features and the baseline hearing severity and outcomes of SSNHL in the pediatric population.

Method

We conducted a bi-center retrospective observational study in 145 SSNHL patients aged no more than 18 years who were recruited between November 2013 and October 2022. Data extracted from medical records, audiograms, complete blood count (CBC) and coagulation tests have been assessed for the relationship with the severity (the thresholds of the initial hearing) and outcomes (recovery rate, hearing gain and the thresholds of the final hearing).

Results

A lower lymphocyte count (P = 0.004) and a higher platelet-to-lymphocyte ratio (PLR) (P = 0.041) were found in the patient group with profound initial hearing than in the less severe group. Vertigo (β = 13.932, 95%CI: 4.082–23.782, P = 0.007) and lymphocyte count (β = −6.686, 95%CI: −10.919 to −2.454, P = 0.003) showed significant associations with the threshold of the initial hearing. In the multivariate logistic model, the probability of recovery was higher for patients with ascending and flat audiograms compared to those with descending audiograms (ascending: OR 8.168, 95% CI 1.450–70.143, P = 0.029; flat: OR 3.966, 95% CI 1.341–12.651, P = 0.015). Patients with tinnitus had a 3.2-fold increase in the probability of recovery (OR 3.222, 95% CI 1.241–8.907, P = 0.019), while the baseline hearing threshold (OR 0.968, 95% CI 0.936–0.998, P = 0.047) and duration to the onset of therapy (OR 0.942, 95% CI 0.890–0.977, P = 0.010) were negatively associated with the odds of recovery.

Conclusions

The present study showed that accompanying tinnitus, the severity of initial hearing loss, the time elapse and the audiogram configuration might be related to the prognosis of pediatric SSNHL. Meanwhile, the presence of vertigo, lower lymphocytes and higher PLR were associated with worse severity.