bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of ICT-integrated pedagogy on pre-service teachers’ teaching competence in mathematics
Authors: Samantray Ashapurna , Behera Rashmi Ranjan , Acharya Amulya Kumar
Published: June 2024

The influence of teachers’ teaching competence on students’ academic performance is pivotal, prompting an examination of the efficacy of ICT-integrated pedagogy in enhancing the teaching competence of pre-service mathematics teachers. This quasi-experimental research employed a pre-test, and post-test control group design involving 30 pre-service teachers, with 15 participants assigned to both the experimental and control groups. Throughout a four-week duration, the experimental group received instruction utilizing ‘ICT-integrated pedagogy,’ while the control group was taught applying traditional ‘Lecture-based pedagogy.’ Employing a ‘Mathematics Teaching Competence Scale,’ both cohorts were assessed prior to and following the intervention, with data subjected to analysis using descriptive statistics and t-tests in SPSS version 20. The results revealed that pre-service teachers in the experimental group, exposed to ‘ICT-integrated pedagogy,’ demonstrated superior mathematics teaching competency compared to their counterparts in the control group. These findings advocate for the positive impact of ICT-integrated pedagogical approaches in nurturing the teaching proficiency of pre-service teachers. Consequently, this study suggests the widespread implementation of this approach by Teacher Educators, envisioning its potential to engender competent and high-quality teachers.
Sex differences in the effects of aromatherapy on anxiety and salivary oxytocin levels
Authors: Nakajima Daisuke , Yamachi Megumi , Misaka Shingen , Shimomura Kenju , Maejima Yuko
Published: June 2024

Objective

Aromatherapy is a holistic healing method to promote health and well-being by using natural plant extracts. However, its precise mechanism of action and influence on the endocrine system remains unclear. Since recent studies reported that a neuropeptide, oxytocin, can attenuate anxiety, we hypothesized that if oxytocin secretion is promoted through aromatherapy, it may improve mood and anxiety. The present study is aimed to investigate the relationship between oxytocin and the effects of aromatherapy with lavender oil on anxiety level, by measuring salivary oxytocin levels in healthy men and women.

Methods

We conducted a randomized open crossover trial in 15 men and 10 women. Each participant received a placebo intervention (control group) and aromatherapy with lavender oil (aromatherapy group). For the aromatherapy group, each participant spent a 30-min session in a room with diffused lavender essential oil, followed by a 10-min hand massage using a carrier oil containing lavender oil. Anxiety was assessed using the State-Trait Anxiety Inventory (STAI) before the intervention, 30-min after the start of intervention, and after hand massage, in both groups. Saliva samples were collected at the same time points of the STAI.

Results

In women, either aromatherapy or hand massage was associated with a reduction in anxiety levels, independently. Moreover, salivary oxytocin levels were increased after aromatherapy. On the other hand, in men, anxiety levels were decreased after aromatherapy, as well as after hand massage, regardless of the use of lavender oil. However, there were no significant differences in changes of salivary oxytocin levels between the control and aromatherapy groups during the intervention period. Interestingly, there was a positive correlation between anxiety levels and salivary oxytocin levels before the intervention, but a negative correlation was observed after hand massage with lavender oil.

Conclusion

The results of the present study indicate that in women, aromatherapy with lavender oil attenuated anxiety with increase in oxytocin level in women, whereas in men, there was no clear relationship of aromatherapy with anxiety or oxytocin levels but, there was a change in correlation between anxiety and oxytocin. The results of the present study suggest that the effect of aromatherapy can vary depending on sex.
Risk factors of acute ischemic stroke and the role of angiotensin I in predicting prognosis of patients undergoing endovascular thrombectomy
Authors: Yang Shengkai , Li Kemian , Huang Zhengqian , Xu Yingda , Liang Jingshan , Sun Yong , Li Aimin
Published: June 2024

Purpose

The interaction between the renin-angiotensin system (RAS) and the acute ischemic stroke (AIS) is definite but not fully understood. This study aimed to analyze the risk factors of AIS and explore the role of serum indicators such as angiotensin I (Ang I) in the prognosis of patients undergoing endovascular thrombectomy (EVT).

Patients and methods

Patients with AIS who underwent EVT and healthy controls were retrospectively enrolled in this study, and the patients were divided into a good or a poor prognosis group. We compared Ang I, blood routine indexes, biochemical indexes, electrolyte indexes, and coagulation indexes between patients and controls. We used univariate and multivariate logistic regression analyses to evaluate possible risk factors for AIS and the prognosis of patients undergoing EVT. Independent risk factors for the prognosis of patients undergoing EVT were identified through multifactorial logistic regression analyses to construct diagnostic nomograms, further assessed by receiver operating characteristic curves (ROC).

Results

Consistent with previous studies, advanced age, high blood glucose, high D-dimer, and high prothrombin activity are risk factors for AIS. In addition, Ang I levels are lower in AIS compared to the controls. The level of Ang I was higher in the good prognosis group. Furthermore, we developed a nomogram to evaluate its ability to predict the prognosis of AIS after EVT. The AUC value of the combined ROC model (Ang I and albumin-globulin ratio (AGR)) was 0.859.

Conclusions

In conclusion, advanced age, high blood glucose, high D-dimer, and high prothrombin activity are risk factors for AIS. The combined Ang I and AGR model has a good predictive ability for the prognosis of AIS patients undergoing arterial thrombectomy.
Critically evaluated key points on hereditary medullary thyroid carcinoma
Authors: Zhang Daqi , Liang Nan , Sun Hui , Frattini Francesco , Sui Chengqiu , Yang Mingyu , Wang Hongbo , Dionigi Gianlorenzo
Published: June 2024

Medullary thyroid carcinoma (MTC) accounts for only 3% of all thyroid carcinomas: 75% as sporadic MTC (sMTC) and 25% as hereditary MTC (hMTC) in the context of multiple endocrine neoplasia type 2 (MEN2). Early diagnosis is possible by determining the tumour marker calcitonin (Ctn) when clarifying nodular goitre and by detecting the mutation in the proto-oncogene RET in the MEN2 families. If the Ctn level is only slightly elevated, up to 30 pg/ml in women and up to 60 pg/ml in men, follow-up checks are advisable. At higher levels, surgery should be considered; at a level of > 100 pg/ml, surgery is always advisable. The treatment of choice is total thyroidectomy, possibly with central lymphadenectomy. In the early stage, cure is possible with adequate surgery; in the late stage, treatment with tyrosine kinase inhibitors is an option. RET A mutation analysis should be performed on all patients with MTC. During follow-up, a biochemical distinction is made between: healed (Ctn not measurably low), biochemically incomplete (Ctn increased without tumour detection) and structural tumour detection (metastases on imaging). After MTC surgery, the following results should be available for classification in follow-up care: (i) histology, Ctn immunohistology if necessary, (ii) classification according to the pTNM scheme, (iii) the result of the RET analysis for categorisation into the hereditary or sporadic variant and (iiii) the postoperative Ctn value. Tumour progression is determined by assessing the Ctn doubling time and the RECIST criteria on imaging. In most cases, “active surveillance” is possible. In the case of progression and symptoms, the following applies: local (palliative surgery, radiotherapy) before systemic (tyrosine kinase inhibitors).
Automatic prediction of non-iodine-avid status in lung metastases for radioactive I131 treatment in differentiated thyroid cancer patients
Authors: Gao Xinyi , Chen Haoyi , Wang Yun , Xu Feijia , Zhang Anni , Yang Yong , Gu Yajia
Published: June 2024

Objectives

The growing incidence of differentiated thyroid cancer (DTC) have been linked to insulin resistance and metabolic syndrome. The imperative need for developing effective diagnostic imaging tools to predict the non-iodine-avid status of lung metastasis (LMs) in differentiated thyroid cancer (DTC) patients is underscored to prevent unnecessary radioactive iodine treatment (RAI).

Methods

Primary cohort consisted 1962 pretreated LMs of 496 consecutive DTC patients with pretreated initially diagnosed LMs who underwent chest CT and subsequent post-treatment radioiodine SPECT. After automatic lesion segmentation by SE V-Net, SE Net deep learning was trained to predict non-iodine-avid status of LMs. External validation cohort contained 123 pretreated LMs of 24 consecutive patients from other two hospitals. Stepwise validation was further performed according to the nodule’s largest diameter.

Results

The SE-Net deep learning network yielded area under the receiver operating characteristic curve (AUC) values of 0.879 (95% confidence interval: 0.852–0.906) and 0.713 (95% confidence interval: 0.613–0.813) for internal and external validation. With the LM diameter decreasing from ≥10mm to ≤4mm, the AUCs remained relatively stable, for smallest nodules (≤4mm), the model yielded an AUC of 0.783. Decision curve analysis showed that most patients benefited using deep learning to decide radioactive I131 treatment.

Conclusion

This study presents a noninvasive, less radioactive and fully automatic approach that can facilitate suitable DTC patient selection for RAI therapy of LMs. Further prospective multicenter studies with larger study cohorts and related metabolic factors should address the possibility of comprehensive clinical transformation.
Evaluation of electrical load demand forecasting using various machine learning algorithms
Authors: Jain Akanksha , Gupta S. C.
Published: June 2024

The energy sector heavily relies on a diverse array of machine learning algorithms for power load prediction, which plays a pivotal role in shaping policies for power generation and distribution. The precision of power load prediction depends on numerous factors that reflect nonlinear traits within the data. Notably, machine learning algorithms and artificial neural networks have emerged as indispensable components in contemporary power load forecasting. This study focuses specifically on machine learning algorithms, encompassing support vector machines (SVMs), long short-term memory (LSTM), ensemble classifiers, recurrent neural networks, and deep learning methods. The research meticulously examines short-term power load prediction by leveraging Chandigarh UT electricity utility data spanning the last 5 years. The assessment of prediction accuracy utilizes metrics such as normalized mean square error (NMSE), root mean squared error (RMSE), mean absolute error (MAE), and mutual information (MI). The prediction results demonstrate superior performance in LSTM compared to other algorithms, with the prediction error being the lowest in LSTM and 13.51% higher in SVMs. These findings provide valuable insights into the strengths and limitations of different machine learning algorithms. Validation experiments for the proposed method are conducted using MATLAB R2018 software.
Evaluation of cholera surveillance systems in Africa: a systematic review
Authors: Mercy Kyeng , Pokhariyal Ganesh , Takah Fongwen Noah , Kivuti-Bitok Lucy
Published: June 2024

Introduction

Despite several interventions on the control of cholera, it still remains a significant public health problem in Africa. According to the World Health Organization, 251,549 cases and 4,180 deaths (CFR: 2.9%) were reported from 19 African countries in 2023. Tools exist to enhance the surveillance of cholera but there is limited evidence on their deployment and application. There is limited evidence on the harmonization of the deployment of tools for the evaluation of cholera surveillance. We systematically reviewed available literature on the deployment of these tools in the evaluation of surveillance systems in Africa.

Method

Three electronic databases (PubMed, Medline and Embase) were used to search articles published in English between January 2012 to May 2023. Grey literature was also searched using Google and Google Scholar. Only articles that addressed a framework used in cholera surveillance in Africa were included. The quality of articles was assessed using the appropriate tools. Data on the use of surveillance tools and frameworks were extracted from articles for a coherent synthesis on their deployment.

Result

A total of 13 records (5 frameworks and 8 studies) were fit for use for this study. As per the time of the study, there were no surveillance frameworks specific for the evaluation of surveillance systems of cholera in Africa, however, five frameworks for communicable diseases and public health events could be adapted for cholera surveillance evaluation. None (0%) of the studies evaluated capacities on cross border surveillance, multisectoral one health approach and linkage of laboratory networks to surveillance systems. All (100%) studies assessed surveillance attributes even though there was no synergy in the attributes considered even among studies with similar objectives. There is therefore the need for stakeholders to harmoniously identify a spectrum of critical parameters and attributes to guide the assessment of cholera surveillance system performance.
Management of pregnancy in women with monogenic diabetes due to mutations in GCK, HNF1A and HNF4A genes
Authors: Crowley M. T. , Paponette B. , Bacon S. , Byrne M. M.
Published: June 2024

Women with maturity-onset diabetes of the young (MODY) need tailored antenatal care and monitoring of their offspring. Each MODY subtype has different implications for glycaemic targets, treatment choices and neonatal management. Hyperglycaemia of MODY is often first diagnosed in adolescence or early adulthood and therefore is clinically relevant to pregnant women. MODY remains an under-recognised and undiagnosed condition. Pregnancy represents an opportune time to make a genetic diagnosis of MODY and provide precision treatment. This review describes the nuance of antenatal care in women with MODY and the implications for pregnancies affected by a positive paternal genotype. Mutations in hepatic nuclear factor 1-alpha (HNF1A) and 4-alpha (HNF4A) genes are associated with progressive β-cell dysfunction resulting in early onset diabetes. Patients are largely managed with sulphonylureas outside of pregnancy. Macrosomia and persistent neonatal hypoglycaemia are reported in 54% and 15% of HNF4A genotype positive offspring respectively with a median increase in birthweight of 790 g. Close observation of foetal growth in utero allows optimal timing of delivery to minimise peri- and postpartum materno-foetal complications. Glucokinase (GCK)-MODY causes mild fasting hyperglycaemia which does not require treatment outside of pregnancy. Birthweight of offspring of maternal carriers is dependent on foetal genotype; heterozygous mutation carriers are usually normal weight while genotype negative offspring are large for gestational age (600 g heavier). Affected offspring of paternal carriers may be small for gestational age (500 g lighter). Serial growth scans with measurement of the abdominal circumference indirectly differentiate foetal genotype. Measurement of cell free foetal DNA in maternal blood from the late first trimester is superior to traditionally used ultrasound to distinguish foetal genotype. Cost and accessibility may limit its use.
Comparison of the classifiers based on mRNA, microRNA and lncRNA expression and DNA methylation profiles for the tumor origin detection
Authors: Feng Yun , Wang Yilin
Published: June 2024

Background

Tumor tissue origin detection is of great importance in determining the appropriate course of treatment for cancer patients. Classifiers based on gene expression and DNA methylation profiles have been confirmed to be feasible and reliable to predict the tumor primary. However, few works have been performed to compare the performance of these classifiers based on different profiles.

Methods

Using gene expression and DNA methylation profiles from The Cancer Genome Atlas (TCGA) project, eight machine learning methods were employed for the tumor tissue origin detection. We then evaluated the predictive performance using DNA methylation, mRNA, microRNA (miRNA) and long non-coding RNA (lncRNA) expression profiles in a comparative manner. A statistical method was introduced to select the most informative CpG sites.

Results

We found that LASSO is the most predictive models based on various profiles. Further analyses indicated that the results derived from DNA methylation (overall accuracy: 97.77%) are better than those derived from mRNA expression (overall accuracy: 88.01%), microRNA expression (overall accuracy: 91.03%) and lncRNA expression (overall accuracy: 95.7%). It has been suggested that we can achieve an overall accuracy >90% using only 1,000 methylated CpG sites for prediction.

Conclusion

In this work, we comprehensively evaluated the performance of classifiers based on different profiles for the tumor origin detection. Our findings demonstrated the effectiveness of DNA methylation as biomarker for tracing tumor tissue origin using LASSO and neural network.
miRNA signatures underlie chemoresistance in the gemcitabine-resistant pancreatic ductal adenocarcinoma cell line MIA PaCa-2 GR
Authors: Fuller Ryan N. , Vallejos Paul A. , Kabagwira Janviere , Liu Tiantian , Wang Charles , Wall Nathan R.
Published: June 2024

Introduction: Chemotherapy resistance remains a significant challenge in the treatment of pancreatic adenocarcinoma (PDAC), particularly in relation to gemcitabine (Gem), a commonly used chemotherapeutic agent. MicroRNAs (miRNAs) are known to influence cancer progression and chemoresistance. This study investigates the association between miRNA expression profiles and gemcitabine resistance in PDAC.

Methods: The miRNA expression profiles of a gemcitabine-sensitive (GS) PDAC cell line, MIA PaCa-2, and its gemcitabine-resistant (GR) progeny, MIA PaCa-2 GR, were analyzed. miRNA sequencing (miRNA-seq) was employed to identify miRNAs expressed in these cell lines. Differential expression analysis was performed, and Ingenuity Pathway Analysis (IPA) was utilized to elucidate the biological functions of the differentially expressed miRNAs.

Results: A total of 1867 miRNAs were detected across both cell lines. Among these, 97 (5.2%) miRNAs showed significant differential expression between the GR and GS cell lines, with 65 (3.5%) miRNAs upregulated and 32 (1.7%) miRNAs downregulated in the GR line. The most notably altered miRNAs were implicated in key biological processes such as cell proliferation, migration, invasion, chemosensitization, alternative splicing, apoptosis, and angiogenesis. A subset of these miRNAs was further analyzed in patient samples to identify potential markers for recurrent tumors.

Discussion: The differential miRNA expression profiles identified in this study highlight the complex regulatory roles of miRNAs in gemcitabine resistance in PDAC. These findings suggest potential targets for improving prognosis and tailoring treatment strategies in PDAC patients, particularly those showing resistance to gemcitabine. Future research should focus on validating these miRNAs as biomarkers for resistance and exploring their therapeutic potential in overcoming chemoresistance.
Transcriptomics and metabolomics analyses provide insights into resistance genes of tree ferns
Authors: Yang Weicheng , He Qinqin , Zhang Lijun , Xiao Jiaxing , Yang Jiao , Che Bingjie , Zhang BingChen , Chen Handan , Li Jiang , Jiang Yu
Published: June 2024

As ancient organisms, tree ferns play a crucial role as an evolutionary bridge between lower and higher plant species, providing various utilitarian benefits. However, they face challenges such as overexploitation, climate change, adverse environmental conditions, and insect pests, resulting in conservation concerns. In this study, we provide an overview of metabolic and transcriptomic resources of leaves in two typical tree ferns, A. spinulosa and A. metteniana, and explore the resistance genes for the first time. The landscape of metabolome showed that the compound skimmin may hold medicinal significance. A total of 111 differentially accumulated metabolites (DAMs) were detected, with pathway enrichment analysis highlighting 14 significantly enriched pathways, including 2-oxocarboxylic acid metabolism possibly associated with environmental adaptations. A total of 14,639 differentially expressed genes (DEGs) were found, among which 606 were resistance (R) genes. We identified BAM1 as a significantly differentially expressed R gene, which is one of the core genes within the R gene interaction network. Both the maximum-likelihood phylogenetic tree and the PPI network revealed a close relationship between BAM1, FLS2, and TMK. Moreover, BAM1 showed a significant positive correlation with neochlorogenic acid and kaempferol-7-O-glucoside. These metabolites, known for their antioxidant and anti-inflammatory properties, likely play a crucial role in the defense response of tree ferns. This research provides valuable insights into the metabolic and transcriptomic differences between A. spinulosa and A. metteniana, enhancing our understanding of resistance genes in tree ferns.
Uncovering periodontitis-associated markers through the aggregation of transcriptomics information from diverse sources
Authors: Peng Chujun , Huang Jinhang , Li Mingyue , Liu Guanru , Liu Lingxian , Lin Jiechun , Sun Weijun , Liu Hongtao , Huang Yonghui , Chen Xin
Published: June 2024

Introduction

Periodontitis, a common chronic inflammatory disease, significantly impacted oral health. To provide novel biological indicators for the diagnosis and treatment of periodontitis, we analyzed public microarray datasets to identify biomarkers associated with periodontitis.

Method

The Gene Expression Omnibus (GEO) datasets GSE16134 and GSE106090 were downloaded. We performed differential analysis and robust rank aggregation (RRA) to obtain a list of differential genes. To obtain the core modules and core genes related to periodontitis, we evaluated differential genes through enrichment analysis, correlation analysis, protein-protein interaction (PPI) network and competing endogenous RNA (ceRNA) network analysis. Potential biomarkers for periodontitis were identified through comparative analysis of dual networks (PPI network and ceRNA network). PPI network analysis was performed in STRING. The ceRNA network consisted of RRA differentially expressed messenger RNAs (RRA_DEmRNAs) and RRA differentially expressed long non-coding RNAs (RRA_DElncRNAs), which regulated each other’s expression by sharing microRNA (miRNA) target sites.

Results

RRA_DEmRNAs were significantly enriched in inflammation-related biological processes, osteoblast differentiation, inflammatory response pathways and immunomodulatory pathways. Comparing the core ceRNA module and the core PPI module, C1QA, CENPK, CENPU and BST2 were found to be the common genes of the two core modules, and C1QA was highly correlated with inflammatory functionality. C1QA and BST2 were significantly enriched in immune-regulatory pathways. Meanwhile, LINC01133 played a significant role in regulating the expression of the core genes during the pathogenesis of periodontitis.

Conclusion

The identified biomarkers C1QA, CENPK, CENPU, BST2 and LINC01133 provided valuable insight into periodontitis pathology.
Long-term outcomes and predictive factors of achieving low disease activity status in childhood systemic lupus erythematosus: a Chinese bicentric retrospective registered study
Authors: Yu Xi Xi , Deng Jia , Chen Qiu Xia , Qiu Shi Yuan , Jiang Chao Hui , Wu Yi Qian , Yang Qin , Zhang Gao Fu , Yang Hai Ping , Zhao Fei , Li Qiu , Zhang Ai Hua , Wang Mo
Published: June 2024

Background

This study aims to explore the clinical value of low disease activity state (LDAS) in the treat-to-target strategy of pediatric systemic lupus erythematosus (pSLE) and find the risk factors for never reaching LDAS.

Methods

A total of 272 children with SLE who were diagnosed and followed up in two tertiary hospitals in China during the period from January 2012 to December 2019 were involved in this study, and the clinical presentation, pathology, and treatment were retrospectively studied.

Results

The male-to-female ratio was 1:5.2, the age at diagnosis was 11.1 years (IQR, 9.8–13.1 years), the disease duration was 1.0 month (IQR, 0.5–2.0 months), and follow-up was 36.5 months (IQR, 25.7–50.9 months). During follow-up, 230 children achieved LDAS, and 42 were never been in. Male (P = 0.018), mucosal ulcer (P = 0.048), liver function damage (P = 0.026), cardiac effusion (P = 0.034), anemia (P = 0.048), urine red blood cells (P = 0.017), urinary leukocytes (P = 0.032), and endothelial cell proliferation in renal biopsy (P = 0.004)—these indexes have statistical differences between the two groups in the baseline. At baseline, endothelial cell proliferation (P = 0.02) is an independent risk factor for never achieving LDAS by multivariate logistic analysis. During follow-up, non-compliance was a risk factor for never achieving LDAS by comparing between groups. Children with biologics achieved LDAS at a higher rate than children without biologics (P = 0.038). The proportion of organ damage in patients never been in LDAS was significantly higher than that in patients who achieved LDAS (P < 0.001).

Conclusion

Endothelial cell proliferation in renal biopsy and non-compliance during follow-up were independent risk factors for never achieving LDAS. At the end of the follow-up, the organ damage in the remission group was similar to that in the LDAS group, indicating that LDAS can be used as a target for pSLE treatment.
NLRP3 promotes allergic responses to birch pollen extract in a model of intranasal sensitization
Authors: Bauer Renate , Dang Hieu-Hoa , Neureiter Daniel , Unger Michael Stefan , Neuper Theresa , Jensen Melanie , Taliento Alice Emma , Strandt Helen , Gratz Iris , Weiss Richard , Sales Angelika , Horejs-Hoeck Jutta
Published: June 2024

Introduction & Objective

Allergic sensitization is an essential step in the development of allergic airway inflammation to birch pollen (BP); however, this process remains to be fully elucidated. Recent scientific advances have highlighted the importance of the allergen context. In this regard, microbial patterns (PAMPs) present on BP have attracted increasing interest. As these PAMPs are recognized by specialized pattern recognition receptors (PRRs), this study aims at investigating the roles of intracellular PRRs and the inflammasome regulator NLRP3.

Methods

We established a physiologically relevant intranasal and adjuvant-free sensitization procedure to study BP-induced systemic and local lung inflammation.

Results

Strikingly, BP-sensitized Nlrp3-deficient mice showed significantly lower IgE levels, Th2-associated cytokines, cell infiltration into the lung, mucin production and epithelial thickening than their wild-type counterparts, which appears to be independent of inflammasome formation. Intriguingly, bone-marrow chimera revealed that expression of NLRP3 in the hematopoietic system is required to trigger an allergic response.

Conclusion

Overall, this study identifies NLRP3 as an important driver of BP-induced allergic immune responses.
Necroptosis in bacterial infections
Authors: Yu Xing , Yuan Jin , Shi Linxi , Dai Shuying , Yue Lei , Yan Min
Published: June 2024

Necroptosis, a recently discovered form of cell-programmed death that is distinct from apoptosis, has been confirmed to play a significant role in the pathogenesis of bacterial infections in various animal models. Necroptosis is advantageous to the host, but in some cases, it can be detrimental. To understand the impact of necroptosis on the pathogenesis of bacterial infections, we described the roles and molecular mechanisms of necroptosis caused by different bacterial infections in this review.
Expansion of effector memory Vδ2neg γδ T cells associates with cytomegalovirus reactivation in allogeneic stem cell transplant recipients
Authors: Huang Yiwen , Jiang Cen , Zhu Jiacheng , Lin Lin , Mao Minjing , Yin Tong , Cai Gang
Published: June 2024

Background

Cytomegalovirus (CMV) reactivation is a significant concern following allogeneic stem cell transplantation. While previous research has highlighted the anti-CMV reactivation effect of γδ T cells in immunocompromised transplant patients, their characterization in recipients at high risk of CMV reactivation remains limited.

Methods

This study focused on D+/R+ recipients (where both donor and recipient are CMV seropositive) at high risk of CMV reactivation. We analyzed 28 patients who experienced CMV recurrence within 100 days post-allogeneic hematopoietic stem cell transplantation, along with 36 matched recipients who did not experience CMV recurrence. Clinical data from both groups were compared, and risk factors for CMV reactivation were identified. Additionally, CMV viral load was measured, and flow cytometric analysis was conducted to assess changes in peripheral blood γδ T cell proportions, subpopulation distribution, and differentiation status. We also analyzed the CDR3 repertoire of the TCR δ chain in different γδ T cell subsets. Functional analysis was performed by measuring the lysis of CMV-infected cells upon stimulation.

Results

CMV reactivation post-transplantation was associated with acute graft-versus-host disease (aGvHD) and reactivation of non-CMV herpesviruses. Notably, CMV reactivation led to sustained expansion of γδ T cells, primarily within the Vδ2neg γδ T cell subpopulation, with a trend toward differentiation from Naive to effector memory cells. Analysis of the δ chain CDR3 repertoire revealed a delay in the reconstitution of clonal diversity in Vδ2neg γδ T cells following CMV reactivation, while Vδ2pos T cells remained unaffected. Upon stimulation with CMV-infected MRC5 cells, the Vδ2neg γδ T cell subpopulation emerged as the primary effector cell group producing IFN-γ and capable of lysing CMV-infected cells. Moreover, our findings suggest that NKG2D is not necessary involved in Vδ2neg γδ T cell-mediated anti-CMV cytotoxicity.

Conclusion

This study provides novel insights into the role of γδ T cells in the immune response to CMV reactivation in transplantation recipients at high risk of CMV infection. Specifically, the Vδ2neg γδ T cell subpopulation appears to be closely associated with CMV reactivation, underscoring their potential role in controlling infection and reflecting CMV reactivation in HSCT patients.
Whole-blood culture-derived cytokine combinations for the diagnosis of tuberculosis
Authors: Østergaard Anne Ahrens , Feddersen Søren , Barnkob Mike B. , Lynggaard Rasmus Bank , Karstoft Amanda Cecilie Annie , Borup Maria , Titlestad Ingrid Louise , Jensen Torben Tranborg , Hilberg Ole , Wejse Christian , Bjerrum Stephanie , Blaabjerg Morten , Assing Kristian , Johansen Isik Somuncu
Published: June 2024

Introduction

The diagnosis of tuberculosis (TB) disease and TB infection (TBI) remains a challenge, and there is a need for non-invasive and blood-based methods to differentiate TB from conditions mimicking TB (CMTB), TBI, and healthy controls (HC). We aimed to determine whether combination of cytokines and established biomarkers could discriminate between 1) TB and CMTB 2) TB and TBI 3) TBI and HC.

Methods

We used hemoglobin, total white blood cell count, neutrophils, monocytes, C-reactive protein, and ten Meso Scale Discovery analyzed cytokines (interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon (IFN)-ɣ, and tumor necrosis factor (TNF)-α) in TruCulture whole blood tubes stimulated by lipopolysaccharides (LPS), zymosan (ZYM), anti-CD3/28 (CD3), and unstimulated (Null) to develop three index tests able to differentiate TB from CMTB and TBI, and TBI from HC.

Results

In 52 persons with CMTB (n=9), TB (n=23), TBI (n=10), and HC (n=10), a combination of cytokines (LPS-IFN-ɣ, ZYM-IFN-ɣ, ZYM-TNF-α, ZYM-IL-1β, LPS-IL-4, and ZYM-IL-6) and neutrophil count could differentiate TB from CMTB with a sensitivity of 52.2% (95% CI: 30.9%–73.4%) and a specificity of 100 % (66.4%-100%). Null- IFN-ɣ, Null-IL-8, CD3-IL-6, CD3-IL-8, CD3-IL-13, and ZYM IL-1b discriminated TB from TBI with a sensitivity of 73.9% (56.5% - 91.3%) and a specificity of 100% (69.2-100). Cytokines and established biomarkers failed to differentiate TBI from HC with ≥ 98% specificity.

Discussion

Selected cytokines may serve as blood-based add-on tests to detect TB in a low-endemic setting, although these results need to be validated.
Profibrogenic role of IL-15 through IL-15 receptor alpha-mediated trans-presentation in the carbon tetrachloride-induced liver fibrosis model
Authors: Cloutier Maryse , Variya Bhavesh , Akbari Sara Ali , Rexhepi Fjolla , Ilangumaran Subburaj , Ramanathan Sheela
Published: June 2024

Background

Inflammatory cytokines play key pathogenic roles in liver fibrosis. IL-15 is a proinflammatory cytokine produced by myeloid cells. IL-15 promotes pathogenesis of several chronic inflammatory diseases. However, increased liver fibrosis has been reported in mice lacking IL-15 receptor alpha chain (IL-15Rα), suggesting an anti-fibrogenic role for IL-15. As myeloid cells are key players in liver fibrosis and IL-15 signaling can occur independently of IL-15Rα, we investigated the requirement of IL-15 and IL-15Rα in liver fibrosis.

Methods

We induced liver fibrosis in Il15–/–, Il15ra–/– and wildtype C57BL/6 mice by the administration of carbon tetrachloride (CCl4). Liver fibrosis was evaluated by Sirius red and Mason’s trichrome staining and α-smooth muscle acting immunostaining of myofibroblasts. Gene expression of collagens, matrix modifying enzymes, cytokines and chemokines was quantified by RT-qPCR. The phenotype and the numbers of intrahepatic lymphoid and myeloid cell subsets were evaluated by flow cytometry.

Results

Both Il15–/– and Il15ra–/– mice developed markedly reduced liver fibrosis compared to wildtype control mice, as revealed by reduced collagen deposition and myofibroblast content. Il15ra–/– mice showed further reduction in collagen deposition compared to Il15–/– mice. However, Col1a1 and Col1a3 genes were similarly induced in the fibrotic livers of wildtype, Il15–/– and Il15ra–/– mice, although notable variations were observed in the expression of matrix remodeling enzymes and chemokines. As expected, Il15–/– and Il15ra–/– mice showed markedly reduced numbers of NK cells compared to wildtype mice. They also showed markedly less staining of CD45+ immune cells and CD68+ macrophages, and significantly reduced inflammatory cell infiltration into the liver, with fewer pro-inflammatory and anti-inflammatory monocyte subsets compared to wildtype mice.

Conclusion

Our findings indicate that IL-15 exerts its profibrogenic role in the liver by promoting macrophage activation and that this requires trans-presentation of IL-15 by IL-15Rα.
Advances in Foxp3+ regulatory T cells (Foxp3+ Treg) and key factors in digestive malignancies
Authors: Wang Wanyao , Ding Minglu , Wang Qiuhong , Song Yidan , Huo Keyuan , Chen Xiaojie , Xiang Zihan , Liu Lantao
Published: June 2024

Foxp3+ regulatory T cells (Foxp3+ Treg) play a role in regulating various types of tumors, but uncertainty still exists regarding the exact mechanism underlying Foxp3+ Treg activation in gastrointestinal malignancies. As of now, research has shown that Foxp3+ Treg expression, altered glucose metabolism, or a hypoxic tumor microenvironment all affect Foxp3+ Treg function in the bodies of tumor patients. Furthermore, it has been demonstrated that post-translational modifications are essential for mature Foxp3 to function properly. Additionally, a considerable number of non-coding RNAs (ncRNAs) have been implicated in the activation of the Foxp3 signaling pathway. These mechanisms regulating Foxp3 may one day serve as potential therapeutic targets for gastrointestinal malignancies. This review primarily focuses on the properties and capabilities of Foxp3 and Foxp3+Treg. It emphasizes the advancement of research on the regulatory mechanisms of Foxp3 in different malignant tumors of the digestive system, providing new insights for the exploration of anticancer treatments.
Human antibodies neutralizing the alpha-latrotoxin of the European black widow
Authors: Ruschig Maximilian , Nerlich Jana , Becker Marlies , Meier Doris , Polten Saskia , Cervantes-Luevano Karla , Kuhn Philipp , Licea-Navarro Alexei Fedorovish , Hallermann Stefan , Dübel Stefan , Schubert Maren , Brown Jeffrey , Hust Michael
Published: June 2024

Poisoning by widow-spider (genus Latrodectus) bites occurs worldwide. The illness, termed latrodectism, can cause severe and persistent pain and can lead to muscle rigidity, respiratory complications, and cardiac problems. It is a global health challenge especially in developing countries. Equine serum-derived polyclonal anti-sera are commercially available as a medication for patients with latrodectism, but the use of sera imposes potential inherent risks related to its animal origin. The treatment may cause allergic reactions in humans (serum sickness), including anaphylactic shock. Furthermore, equine-derived antivenom is observed to have batch-to-batch variability and poor specificity, as it is always an undefined mix of antibodies. Because latrodectism can be extremely painful but is rarely fatal, the use of antivenom is controversial and only a small fraction of patients is treated. In this work, recombinant human antibodies were selected against alpha-latrotoxin of the European black widow (Latrodectus tredecimguttatus) by phage display from a naïve antibody gene library. Alpha-Latrotoxin (α-LTX) binding scFv were recloned and produced as fully human IgG. A novel alamarBlue assay for venom neutralization was developed and used to select neutralizing IgGs. The human antibodies showed in vitro neutralization efficacy both as single antibodies and antibody combinations. This was also confirmed by electrophysiological measurements of neuronal activity in cell culture. The best neutralizing antibodies showed nanomolar affinities. Antibody MRU44–4-A1 showed outstanding neutralization efficacy and affinity to L. tredecimguttatus α-LTX. Interestingly, only two of the neutralizing antibodies showed cross-neutralization of the venom of the Southern black widow (Latrodectus mactans). This was unexpected, because in the current literature the alpha-latrotoxins are described as highly conserved. The here-engineered antibodies are candidates for future development as potential therapeutics and diagnostic tools, as they for the first time would provide unlimited supply of a chemically completely defined drug of constant quality and efficacy, which is also made without the use of animals.
NOD2 activation enhances macrophage Fcγ receptor function and may increase the efficacy of antibody therapy
Authors: Merchand-Reyes Giovanna , Bull Mikayla F. , Santhanam Ramasamy , Valencia-Pena Maria L. , Murugesan Rakesh A. , Chordia Aadesh , Mo Xiaokui-Molly , Robledo-Avila Frank H. , Ruiz-Rosado Juan De Dios , Carson William Edgar , Byrd John C. , Woyach Jennifer A. , Tridandapani Susheela , Butchar Jonathan P.
Published: June 2024

Introduction

Therapeutic antibodies have become a major strategy to treat oncologic diseases. For chronic lymphocytic leukemia, antibodies against CD20 are used to target and elicit cytotoxic responses against malignant B cells. However, efficacy is often compromised due to a suppressive microenvironment that interferes with cellular immune responses. To overcome this suppression, agonists of pattern recognition receptors have been studied which promote direct cytotoxicity or elicit anti-tumoral immune responses. NOD2 is an intracellular pattern recognition receptor that participates in the detection of peptidoglycan, a key component of bacterial cell walls. This detection then mediates the activation of multiple signaling pathways in myeloid cells. Although several NOD2 agonists are being used worldwide, the potential benefit of these agents in the context of antibody therapy has not been explored.

Methods

Primary cells from healthy-donor volunteers (PBMCs, monocytes) or CLL patients (monocytes) were treated with versus without the NOD2 agonist L18-MDP, then antibody-mediated responses were assessed. In vivo, the Eµ-TCL1 mouse model of CLL was used to test the effects of L18-MDP treatment alone and in combination with anti-CD20 antibody.

Results

Treatment of peripheral blood mononuclear cells with L18-MDP led to activation of monocytes from both healthy donors and CLL patients. In addition, there was an upregulation of activating FcγR in monocytes and a subsequent increase in antibody-mediated phagocytosis. This effect required the NF-κB and p38 signaling pathways. Treatment with L18-MDP plus anti-CD20 antibody in the Eµ-TCL model of CLL led to a significant reduction of CLL load, as well as to phenotypic changes in splenic monocytes and macrophages.

Conclusions

Taken together, these results suggest that NOD2 agonists help overturn the suppression of myeloid cells, and may improve the efficacy of antibody therapy for CLL.
The therapeutic role of γδT cells in TNBC
Authors: Li Wenjing , Zhao Xian , Ren Chuanxin , Gao Shang , Han Qinyu , Lu Min , Li Xiangqi
Published: June 2024

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that presents significant therapeutic challenges due to the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. As a result, conventional hormonal and targeted therapies are largely ineffective, underscoring the urgent need for novel treatment strategies. γδT cells, known for their robust anti-tumor properties, show considerable potential in TNBC treatment as they can identify and eliminate tumor cells without reliance on MHC restrictions. These cells demonstrate extensive proliferation both in vitro and in vivo, and can directly target tumors through cytotoxic effects or indirectly by promoting other immune responses. Studies suggest that expansion and adoptive transfer strategies targeting Vδ2 and Vδ1 γδT cell subtypes have shown promise in preclinical TNBC models. This review compiles and discusses the existing literature on the primary subgroups of γδT cells, their roles in cancer therapy, their contributions to tumor cell cytotoxicity and immune modulation, and proposes potential strategies for future γδT cell-based immunotherapies in TNBC.
Impact of assimilating satellite surface velocity observations in the Mercator Ocean International analysis and forecasting global 1/4° system
Authors: Mirouze Isabelle , Rémy Elisabeth , Lellouche Jean-Michel , Martin Matthew J. , Donlon Craig J.
Published: June 2024

Representing and forecasting global ocean velocities is challenging. Velocity observations are scarce and sparse, and are rarely assimilated in a global ocean configuration. Recently, different satellite mission candidates have been proposed to provide surface velocity measurements. To assess the impact of assimilating such data, Observing System Simulation Experiments (OSSEs) have been run in the Mercator Ocean International analysis and forecasting global 1/4° system. Results show that assimilating simulated satellite surface velocities in addition to classical observations has a positive impact on the predicted currents at the surface and below to some extent. Compared to an experiment that assimilates only the classical observations, the surface velocity root-mean-squared error (RMSE) is reduced, especially in the Tropics. From a certain depth depending on the region (e.g. 200 m in the Tropics) however, slight degradations can be spotted. Temperature and salinity RMSEs are generally slightly degraded except in the Tropics where there is a small improvement at the surface and sub-surface. Sea surface height results are mixed, with some areas having reduced RMSE and some increased. The OSSEs reported here constitute a first study and aim to provide first insights on the features that improve by assimilating surface velocity data, and those which need to be worked on.
Synthesis and characterization of polyurethane-based self-luminous pavement coatings: a performance evaluation study
Authors: Lu Qinghe , Liu Xiajun , Lu Zhen , Li Ke
Published: June 2024

Improving the nighttime vision of drivers is essential, given the growing advancements in urban transportation. In this study, polyurethane-based self-luminous pavement coatings (PSCs) were prepared by doping luminous powders (LPs) into the polyurethane materials. The superior optical properties and chemical stabilities of these coatings were ensured by synthesizing the polyurethane-based material. Then, the PSCs were evaluated for their comprehensive performances, such as luminescence, aging resistance, and abrasion resistance, using various characterization methods, including fluorescence spectral analysis, Fourier-transform infrared spectroscopy, fluorescence microscopy, and mechanical property testing. The results show that the 50-mesh LP has the optimal overall performance, with an initial luminescence that exceeds those of the 100 and 400 meshes. The initial brightness of the PSC is mainly influenced by the LP and increases with dosage. The lattice structure and luminescent properties of the luminescent material did not change after coating preparation. The peak excitation wavelength of 420 nm implies that the coating has the best excitation effect under UV light. The primer-marking coating effectively improves the abrasion resistance of the PSC, and the mass loss of the PSC with a coating thickness of 0.4 kg/m2 is 52.9% of that without the primer-marking coating, with the optimal coating thickness being 0.6 kg/m2. This research provides an innovative solution to improve nighttime roadway lighting, which provides useful support for the sustainable development of urban transportation infrastructures and construction of intelligent transportation systems.