bluuebunny/crossref_metadata_2025 huggingface dataset:
Moderating effect of teacher–student relationship and mediating role of self-efficacy on the relationship between peer-assisted learning and mathematics performance
Authors: Asare Bright
Published: January 2025

Purpose

The teacher–student relationship and self-efficacy will amplify the positive effect of peer-assisted learning on mathematics performance. A strong teacher–student relationship provides a supportive foundation, while higher self-efficacy equips students with the confidence and resilience to fully benefit from peer-assisted learning. This study examined the effect peer peer-assisted learning on mathematics performance as well as the moderating effect of the teacher–student relationship and the mediating effect of self-efficacy on the relationship between students’ mathematics performance and peer-assisted learning among students.

Design/methodology/approach

For this study, a descriptive-correlation design was used. Three hundred and fifty-one students made up the study’s sample size. Stratified simple random sampling techniques were used to select respondents for this study. A structured questionnaire was employed to collect data from targeted respondents. Structural Equation Modeling (SEM) run in Amos (v.23) was used to address the proposed hypothesized paths for this study.

Findings

This study’s findings revealed that teacher–student relationship, self-efficacy, and peer-assisted learning had a positive and statistically influenced mathematics performance. Moreover, self-efficacy somewhat mediates the relationship between peer-assisted learning and mathematics performance. Finally, the association between peer-assisted learning and students’ mathematics performance was positively and considerably moderated by the teacher–student relationship.

Originality/value

Previous research has looked at how peer-assisted learning, teacher–student relationships, and self-efficacy influence mathematics performance. To contribute to the literature, this study examines the moderating and mediating effects of teacher–student relationships and self-efficacy on the relationship between peer-assisted learning and mathematics performance.
Metabolic dysfunction-associated fatty liver disease and risk of nephrolithiasis: a sizeable cross-sectional study
Authors: Zheng Shengqi , Hua Tianchi , Yin Guicao , Zhang Wei , Wang Xiaoxiang , Qi Lezhong , Jing Xiayong , Fan Qibing , Yu Xiaoping , Li Yifan
Published: January 2025

Objective

Metabolic dysfunction-associated fatty liver disease (MAFLD) and nephrolithiasis are two common metabolic diseases, but their relationship has not yet been thoroughly studied. Therefore, this study aimed to explore the association between MAFLD and nephrolithiasis and to assess the effect of MAFLD on the risk of nephrolithiasis.

Materials and methods

This cross-sectional study included 96,767 adults from China. All participants underwent medical examinations, including physical examinations, medical history tests, and laboratory tests. Based on ultrasound examination, participants were divided into MAFLD and non-MAFLD groups, and the severity of liver steatosis was determined based on ultrasound images. The relationship between MAFLD and nephrolithiasis was analyzed using a multivariate logistic regression model and subgroup analysis was performed.

Results

The proportion of participants with MAFLD was significantly higher in the nephrolithiasis group compared to the non-nephrolithiasis group (47.70% vs. 30.45%, P < 0.001). Multivariate logistic regression analysis showed a significant positive association between MAFLD and nephrolithiasis (adjusted OR=1.38, 95% CI: 1.29 to 1.47). Subgroup analyses indicated that, even after accounting for various factors such as age, diabetes, hypertension, obesity, lipid profiles, and renal function, the positive association between MAFLD and an increased risk of nephrolithiasis remained consistent. Further subgroup analysis revealed that in male patients with MAFLD, the risk of nephrolithiasis increased progressively with increasing severity of liver steatosis. The adjusted multivariable odds ratios were 1.43 (95% CI: 1.33 to 1.53) for mild, 1.48 (95% CI: 1.32 to 1.67) for moderate, and 1.94 (95% CI: 1.47 to 2.58) for severe hepatic steatosis.

Conclusions

This study found a significant positive association between MAFLD and nephrolithiasis. The risk of nephrolithiasis in males with MAFLD increased substantially with increasing severity of liver steatosis. Therefore, it is essential to strengthen prevention and screening for nephrolithiasis in individuals with MAFLD. More research is needed to elucidate the physiological and pathological mechanisms between MAFLD and nephrolithiasis.
Analyzing the impact of glycemic metabolic status on cardiovascular mortality and all-cause mortality related to the estimated glucose disposal rate: a nationwide cohort study
Authors: He Shiming , Wang Chao , Huang Xin , Jian Guoan , Lu Zihao , Jiang Kun , Xie Guobo , Sheng Guotai , Zou Yang
Published: January 2025

Objective

The Estimated Glucose Disposal Rate (eGDR) serves as a surrogate marker for insulin resistance, with numerous studies highlighting its significant prognostic value. This paper aims to analyze the impact of eGDR on cardiovascular and all-cause mortality across different glycemic metabolic statuses, including normal fasting glucose (NFG), prediabetes, and diabetes.

Methods

This study included 46,016 American adults who underwent health examinations as part of the National Health and Nutrition Examination Survey from 1999 to 2018. Multivariable Cox regression was employed to explore the relationships between eGDR and mortality rates under varying glycemic states. Additionally, Kaplan-Meier curves were used to compare the cumulative incidence of cardiovascular and all-cause mortality across different metabolic statuses. Finally, the predictive value of eGDR for mortality was assessed using receiver operating characteristic curves.

Results

During an average follow-up of 115 months, a total of 6,906 (15.01%) participants experienced all-cause mortality, with 1,798 (3.91%) deaths attributed to cardiovascular causes. Kaplan-Meier analysis revealed that higher eGDR levels were associated with gradually reduced mortality rates. After adjusting for confounders, elevated eGDR levels were protective against both cardiovascular and all-cause mortality; the protective effect was notably stronger for cardiovascular mortality [Cardiovascular mortality hazard ratio: 0.92; All-cause mortality hazard ratio: 0.94]. Further interaction tests indicated that glycemic status significantly modified the protective effect of eGDR (P-interaction<0.0001); specifically, high eGDR conferred stronger protection against cardiovascular and all-cause mortality in individuals with NFG and prediabetes compared to those with diabetes. Receiver operating characteristic analysis suggested that eGDR had superior predictive value for mortality in the NFG and prediabetic populations compared to the diabetic group.

Conclusion

eGDR is a straightforward surrogate for insulin resistance, acting as a protective factor against cardiovascular and all-cause mortality in American adults, with glycemic status modifying this protective effect. Specifically, high eGDR levels offer stronger protection in individuals with NFG and prediabetes compared to those with diabetes; moreover, eGDR appears to be more suitable for predicting mortality events in the NFG and prediabetic populations.
Immortalized Schwann cell lines as useful tools for pathogenesis-based therapeutic approaches to diabetic peripheral neuropathy
Authors: Sango Kazunori , Yako Hideji , Niimi Naoko , Takaku Shizuka
Published: January 2025

Growing evidence suggests that hyperglycemia-related abnormalities in Schwann cells play a pivotal role in the development and progression of diabetic peripheral neuropathy (DPN). Several immortalized Schwann cell lines have been established in our laboratory and utilized for the study of DPN; IMS32 from normal ICR mice, 1970C3 from normal C57BL/6 mice, IWARS1 and IKARS1 from wild-type and aldose reductase-deficient C57BL/6 mice, and IFRS1 from normal Fischer 344 rats. These cell lines retain biological features of Schwann cells and display high proliferative activities that enable us to perform molecular and biochemical analyses. In addition, these cells have exhibited metabolic alterations under exposure to diabetes-associated conditions, such as hyperglycemia, dyslipidemia, glycative and oxidative stress load. Herein, recent studies with these cell lines regarding the pathogenic factors of DPN (augmentation of the polyol and other collateral glycolysis pathways, glycative and oxidative stress-induced cell injury, autophagic and proteostatic disturbances, etc.) and therapeutic strategies targeting these factors are introduced.
Comparison of the lower genital tract microbiome composition in patients with benign gynecological disease
Authors: Shi Yonghui , Li Jun , Xie Jinjing , Yang Tianye , Ma Qiongyan , Chen Hua , Guo Wenwei
Published: January 2025

Objective

Lower genital tract microbiome dysbiosis has been associated with several gynecological diseases. However, the differences in microbiome composition among patients with several gynecological diseases, such as endometrial polyps and uterine myoma, are poorly understood. Studying the lower genital tract microbiome composition in patients with benign gynecological diseases could provide new insights for interpreting the complex interplay between the microbiome and pathogenesis and finding new targets for preventive measures.

Methods

A total of 16 patients with endometrial polyps (EPs), 11 patients with uterine myoma (UM), 6 patients with ovarian cysts (OC) and 36 healthy women (HWs) were recruited for this study. Samples were obtained from vaginal secretions. The DNA was isolated from the samples, and the V3-V4 regions were amplified. The sequencing libraries were generated and sequenced on an Illumina NovaSeq 6000 platform.

Results

Firmicutes, Actinobacteria and Bacteroidota were the most common phyla in all four groups, whereas OC presented the highest abundance of Firmicutes and the lowest abundance of Bacteroidota. At the genus level, Lactobacillus in the OC group was significantly greater than that in the HW group, and Atopobium in the UM group was significantly lower than that in the HW group. The abundance of Gardnerella was greater in the UM group than in the EP group, and the abundance of Streptococcus was greater in the EP group. The richness and evenness of the microbiome were generally consistent among the HW, EP, UM, and OC groups. Principal component analysis (PCA), principal coordinate analysis (PCoA) and nonmetric multidimensional scaling (NMDS) revealed no distinct separation trends among the four groups. According to ANOSIM, there was no significant difference in community structure among the four groups.

Conclusions

A nonsignificant result was obtained from the microbiome diversity comparison among the different groups. However, we demonstrated that the OC group had a greater abundance of Lactobacillus and that the UM group had a lower abundance of Atopobium, which might contribute to the occurrence of diseases, providing new clues for preventive measures.
Association of ERAP1 and ERAP2 gene polymorphisms and ERAP2 protein with the susceptibility and severity of rheumatoid arthritis in the Ukrainian population
Authors: Kril Iryna , Wiśniewski Andrzej , Tarnowska Agnieszka , Lishchuk-Yakymovych Khrystyna , Bojko Yaryna , Kuśnierczyk Piotr , Chopyak Valentyna V. , Nowak Izabela
Published: January 2025

Introduction

Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. Although RA is chiefly associated with HLA class II, nevertheless some HLA class I associations have also been observed. These molecules present antigenic peptides to CD8+ T lymphocytes and natural killer cells. HLA-I molecules bind their peptide cargo (8–10 amino acids long) in the endoplasmic reticulum. Peptides longer than 10 amino acids are trimmed by the endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 to fit the peptide binding groove of the HLA-I molecule. Here, we investigated the possible association of ERAP1 and ERAP2 polymorphisms with RA, and also any possible correlation between serum levels of the ERAP2 protein with disease severity.

Methods

We used Real-Time PCR to genotype ERAP1 and ERAP2 and ELISA test to detect ERAP2 protein.

Results

We found significant associations of ERAP1 rs30187, rs27044, and rs26618, as well as ERAP2 rs2248374, with susceptibility to RA. ERAP1 rs26653 and ERAP2 rs2248374 were also associated with the Disease Activity Score (DAS28), and some polymorphisms were also associated with anti-citrullinated protein or anti-mutated citrullinated vimentin antibodies. RA patients secreted higher concentrations of ERAP2 than controls. Patients with mild disease activity (DAS28 < 3.2) released a concentration of ERAP2 four times lower than that of patients with severe disease activity (DAS28 > 5.1). We detected a higher level of ERAP2 in rheumatoid factor (RF)-positive patients than in RF-negative patients. ERAP2 concentration above 5.85 ng/mL indicated a severe phase of RA.

Conclusions

Some ERAP1 and ERAP2 polymorphisms seem to be related to susceptibility to RA or the severity of the disease. The ERAP2 protein tested in serum could be a valuable biomarker of RA severity.
Pan-cancer analysis of the transcriptional expression of histone acetylation enzymes in solid tumors defines a new classification scheme for gliomas
Authors: Zhang Junhao , Li Lingbo , Tang Aiwei , Wang Chucheng , Wang Yupeng , Hu Yongqi , He Guangting , Liao Wangjun , Zhou Rui
Published: January 2025

Introduction

The altered expression of genes encoding histone acetyltransferases (HATs) and histone deacetylases (HDACs) has been implicated in the tumorigenesis and progression of various solid tumors. However, systematic characterization of the transcriptomic landscape and clinical relevance of HATs and HDACs in pan-cancer contexts remains lacking.

Methods

Transcriptome and clinical data of 9,483 patients across 31 tumor types from The Cancer Genome Atlas were collected for systematic pan-cancer analysis. Additional glioma-specific datasets (Chinese Glioma Genome Atlas, GlioVis, GSE43378, and GSE182109) were also collected to validate the transcriptional characteristics of HATs and HDACs in gliomas. Consensus clustering analysis was applied to identify distinct expression patterns of HATs and HDACs.

Results

Based on the transcriptomic data of 25 genes encoding 9 HATs and 16 HDACs, we identified five major subtypes across 31 cancer types (AC-I to AC-V). Notably, the AC-V subtype comprised over 95% of glioma patients, suggesting glioma patients exhibited distinct expression patterns of histone acetylation-modifying enzymes compared to patients with other solid tumors. Therefore, we re-conducted the consensus clustering analysis specifically within the context of gliomas and identified five subtypes, denoted “AC-GI” to “AC-GV”, which were characterized by differences in HATs/HDACs expression patterns, biological and immune status, genetic alterations, and clinical outcomes. The AC-GII patients exhibited the best prognosis and were sensitive to temozolomide, while AC-GV patients had the poorest prognosis and the lowest sensitivity to temozolomide among all subtypes. Moreover, based on the Connectivity Map database analysis and experimental verification, we identified several pan-HDAC inhibitors that could serve as sensitizers for temozolomide therapy in AC-GV patients, such as panobinostat and scriptaid. Considering the distinctive clinical characteristics of patients with AC-GII and AC-GV, we constructed the “ACG score” model capable of effectively recognizing patients with these subtypes and predicting patient prognosis.

Conclusion

Herein, we established novel biologically and clinically relevant molecular classifications for pan-solid tumors and gliomas based on transcriptional expression profiles of HATs and HDACs. Moreover, the ACG score model, calculated by the transcriptional expression of 29 genes, was not only an independent prognostic factor for glioma patients, but can also provide valuable references for promoting more effective therapeutic strategies.
Marine fungi as a goldmine for novel antibiotics: a 2024 perspective
Authors: Pan Chengqian , Hassan Syed Shams ul , Muhammad Ishaq , Jin Huizi
Published: January 2025

The microbial diversity in oceans is considerable, widely distributed in seawater, marine sediments, and marine organisms. Compared with terrestrial resources in traditional natural product research, the living environments of marine microorganisms are starkly different. The drastic differences in survival conditions, such as high salinity, oligotrophic conditions, lack of light, and limited oxygen, determine that microorganisms exhibit distinctive characteristics in metabolism, survival modes, and adaptive mechanisms. These factors contribute to significant distinctions in secondary metabolic pathways and enzymatic reaction mechanisms between marine and terrestrial microorganisms. In this review, we summarized a total of 72 novel natural products with antibacterial activity, published in 2024, which are derived from marine-derived fungi. These products (polyketides, alkaloids, terpenoids, and peptides) are emphasized in terms of their structures and biological activities. This article aims to provide useful information for the research and development of novel antibiotics.
Explainable AutoML models for predicting the strength of high-performance concrete using Optuna, SHAP and ensemble learning
Authors: Khan Muhammad Salman , Peng Tianbo , Khan Muhammad Adeel , Khan Asad , Ahmad Mahmood , Aziz Kamran , Sabri Sabri Mohanad Muayad , Abd EL-Gawaad N. S.
Published: January 2025

Accurately predicting key engineering properties, such as compressive and tensile strength, remains a significant challenge in high-performance concrete (HPC) due to its complex and heterogeneous composition. Early selection of optimal components and the development of reliable machine learning (ML) models can significantly reduce the time and cost associated with extensive experimentation. This study introduces four explainable Automated Machine Learning (AutoML) models that integrate Optuna for hyperparameter optimization, SHapley Additive exPlanations (SHAP) for interpretability, and ensemble learning algorithms such as Random Forest (RF), Extreme Gradient Boosting (XGB), Light Gradient Boosting Machine (LGB), and Categorical Gradient Boosting (CB). The resulting interpretable AutoML models O-RF, O-XGB, O-LGB, and O-CB are applied to predict the compressive and tensile strengths of HPC. Compared to a baseline model from the literature, O-LGB achieved significant improvements in predictive performance. For compressive strength, it reduced the Mean Absolute Error (MAE) by 87.69% and the Root Mean Squared Error (RMSE) by 71.93%. For tensile strength, it achieved a 99.41% improvement in MAE and a 96.67% reduction in RMSE, along with increases in R2. Furthermore, SHAP analysis identified critical factors influencing strength, such as cement content, water, and age for compressive strength, and curing age, water-binder ratio, and water-cement ratio for tensile strength. This approach provides civil engineers with a robust and interpretable tool for optimizing HPC properties, reducing experimentation costs, and supporting enhanced decision-making in structural design, risk assessment, and other applications.
Serum decorin and biglycan levels as predictive biomarkers for lung fibrosis severity and mortality risk in COVID-19 patients
Authors: Ahmad Shaaf , Maqsood Kaleem , Liaqat Farwa , Roohi Nabila
Published: January 2025

Introduction

Individuals experiencing severe symptoms of COVID-19 are at the greatest risk of developing post-COVID lung fibrosis, which significantly impacts long-term health outcomes. This study aims to investigate the predictive potential of serum biomarkers, specifically decorin and biglycan, in assessing the severity and mortality risk among COVID-19 patients.

Methods

For this study, healthy controls and COVID-19 patients (n = 240) among them 186 with moderate and 54 with severe symptoms from Ittefaq Hospital and Mayo Hospital, Lahore, Pakistan were recruited satisfying the inclusion and exclusion criteria. Patients were followed up for 2 months. Serum level of decorin and biglycan was evaluated by ELISA. One-way ANOVA and Independent sample “t”-test were applied at significance level p < 0.05 by using GraphPad Prism.

Results

Decorin levels significantly decreased from controls (43.36 ± 1.14 ng/mL) to moderate (40.24 ± 0.64 ng/mL) and severe COVID-19 patients (35.49 ± 1.00 ng/mL) (p = 0.0059). Biglycan levels increased from controls (66.15 ± 2.22 pg/mL) to moderate (70.02 ± 1.57 pg/mL) and severe patients (75.88 ± 1.97 pg/mL) (p = 0.0042). In follow-up, survivors had higher decorin (39.6 ± 0.59 ng/mL) than non-survivors (35.84 ± 1.61 ng/mL) (p = 0.0319). Biglycan levels were similar between survivors (70.98 ± 1.41 pg/mL) and non-survivors (73.99 ± 3.24 pg/mL) (p = 0.459). Higher decorin levels correlate with survival in COVID-19 patients.

Conclusion

Serum decorin and biglycan levels are valuable biomarkers for predicting severity and mortality in COVID-19 patients. Lower decorin and higher biglycan levels correlate with increased disease severity, emphasizing their potential to identify patients at risk for lung fibrosis and guide clinical management.
Identification of nuclear valosin-containing-protein-like as a target of anti-nuclear autoantibodies in systemic sclerosis
Authors: Zeng Zitao , Miske Ramona , Scharf Madeleine , Denno Yvonne , Ott Anthonina , Brakopp Stefanie , Teegen Bianca , Stöcker Winfried , Siegert Elise , Saschenbrecker Sandra , Probst Christian , Komorowski Lars
Published: January 2025

Objective

To identify the target antigen of an anti-nuclear autoantibody (ANA) from a patient with a suspected systemic autoimmune disease and to study the autoantibody’s clinical association.

Methods

The index patient serum was screened for autoantibodies using indirect immunofluorescence assay (IFA) and line blots (membrane strips coated with parallel lines of different purified antigens). Immunoprecipitation with fixed HEp-2 cells followed by SDS-PAGE and MALDI-TOF mass spectrometry was used to identify the autoantigen, which was verified by competitive inhibition experiments, recombinant HEK293 cell-based IFA, and Western and line blots based on the recombinant antigen. The prevalence of autoantibodies against this antigen was studied in 693 patients with systemic autoimmune rheumatic diseases (SARD) and 150 healthy controls.

Results

The index patient serum displayed a homogeneous nucleolar staining pattern on HEp-2 cells and monkey liver by IFA but did not react with 27 known nuclear antigens. Nuclear valosin-containing-protein-like (NVL) was identified as the ANA target antigen. Preincubation with recombinant NVL abolished the reactivity of the patient serum with HEp-2 cells in IFA. Additionally, the patient serum reacted with recombinant NVL in cell-based IFA and Western blot analysis, whereas sera from 15 healthy controls were nonreactive. Using line blots coated with recombinant NVL, anti-NVL autoantibodies were exclusively found in four out of 378 patients with systemic sclerosis, but neither in 315 patients with other SARD nor in 150 healthy controls.

Conclusion

These findings indicate that autoantibodies against NVL may be a suitable marker to help narrowing the serological gap in systemic sclerosis.
Time-lapse imaging of identified granule cells in the mouse dentate gyrus after entorhinal lesion in vitro reveals heterogeneous cellular responses to denervation
Authors: Greco Davide , Drakew Alexander , Rößler Nina , Jungenitz Tassilo , Jedlicka Peter , Deller Thomas
Published: January 2025

Denervation of neurons is a network consequence of brain injury. The effects of denervation on neurons can be readily studied in vitro using organotypic slice cultures of entorhinal cortex and hippocampus. Following transection of the entorhino-dentate projection, granule cells (GCs) are denervated and show on average a transient loss of spines on their denervated distal dendrites but not on their non-denervated proximal dendrites. In the present study, we addressed the question how single GCs and their denervated and non-denervated segments react to entorhinal denervation. Local adeno-associated virus (AAV)-injections were employed to transduce dentate GCs with tdTomato and entorhinal projection neurons with EGFP. This made it possible to visualize both innervating entorhinal fibers and their target neurons and to identify dendritic segments located in the “entorhinal” and the “hippocampal” zone of the dentate gyrus. Confocal time-lapse imaging was used to image distal and proximal segments of single GCs after entorhinal denervation. Time-matched non-denervated cultures served as controls. In line with previous reports, average dendritic spine loss was ~30% (2–4 days post-lesion) in the denervated zone. However, individual GCs showed considerable variability in their response to denervation in both layers, and both decreases as well as increases in spine density were observed at the single cell level. Based on the standard deviations and the effect sizes observed in this study, a computer simulation yielded recommendations for the minimum number of neurons that should be analyzed in future studies using the entorhinal in vitro denervation model.
Effect of continuous theta burst stimulation on the glymphatic system, brain network and cognitive function in patients with cerebral small vessel disease
Authors: Dai Pei , Yu Hui-xian , Wang Zhao-xia , Liu Si-hao , Liu Chang-bin , Xu Guang-qing
Published: January 2025

Objective

We aim to investigate the impact of continuous theta burst stimulation (cTBS) on glymphatic system (GS), brain network (BN) and cognition in cerebral small vessel disease (CSVD).

Methods

This exploratory study included a small cohort of 11 patients, divided into a cTBS group (6 patients) and a sham-cTBS group (5 patients). Over a period of 2 weeks, all participants underwent cTBS to the right dorsolateral prefrontal cortex (DLPFC). The efficiency of the GS was assessed by along the perivascular space (ALPS) index. BN was measured using global efficiency (GE), characteristic path length (CPL) and clustering coefficient (Cp). Cognition was evaluated by Montreal Cognitive Assessment (MoCA).

Results

In the cTBS group, the ALPS index increased 4 out of 6 after treatment, compared to an increase in only 2 out of 5 in the control. Improvements in GE, CPL and Cp were observed in 4 out of 6 patients in the cTBS group, whereas no improvements were noted in the control group. The MoCA scores for all patients in the cTBS improved after treatment. Additionally, completion times of the Stroop color and word test C (Stroop C) were reduced for all individuals in the cTBS group, while the control saw an increase in one case. The Digital Span Test-backward (DST-backward) scores were significantly higher in the cTBS group than those in the control.

Conclusion

Applying cTBS to the DLPFC in CSVD may enhance the efficiency of brain glymphatic clearance, optimize network connectivity and improve cognitive function to a certain extent.
Advanced progress in the genetic modification of the oncolytic HSV-1 virus
Authors: Zhou Mi , Shen Zhenyu
Published: January 2025

The use of replication-competent viruses for selective tumor oncolysis while sparing normal cells marks a significant advancement in cancer treatment. HSV-1 presents several advantages that position it as a leading candidate for oncolytic virotherapies. Its large genome can accommodate insertions over 30 kb or deletions of multiple virulence genes without compromising lytic replication in tumor cells. Additionally, anti-herpes drugs can inhibit its replication during accidental infections. Importantly, HSV-1 does not integrate into the host genome and cause mutations. The HSV-1 genome can be modified through genetic engineering in two main ways: first, by reducing infectivity and toxicity to normal cells via limited replication and assembly, altered protein-virus receptor binding, and minimized immune evasion; second, by enhancing anticancer activity through disruption of tumor cell metabolism, induction of autophagy, improved immune recognition, and modification of the tumor microenvironment. In this mini-review, we systematically examine genetic modification strategies for oncolytic HSV-1 while highlighting advancements from these modifications. Certain genetic alterations have shown efficacy in improving clinical outcomes for HSV-1-based therapies. These modifications include silencing specific genes and inserting exogenous genes into the HSV-1 genome. The insertion of exogenous genes has increasingly been used to develop new oncolytic HSV-1 variants. Finally, we discuss limitations associated with oncolytic virotherapy at the conclusion of this review. As more clinical trials explore newly engineered therapies, they are likely to yield breakthroughs and promote broader adoption for cancer treatment.
Genome-wide identification and expression analysis of bHLH gene family revealed their potential roles in abiotic stress response, anthocyanin biosynthesis and trichome formation in Glycyrrhiza uralensis
Authors: Ding Guohua , Shi Yanping , Xie Kerui , Li Hongbin , Xiao Guanghui
Published: January 2025

Introduction

Licorice stands out as an exceptional medicinal resource with a long history of application, attributed to its substantial pharmacological potential. The basic helix-loop-helix (bHLH) transcription factors (TFs) gene family, being the second-largest in plants, is vital for plant development and adapting to environmental shifts. Despite this, the comprehensive characteristics of licorice bHLH gene family are not well-documented.

Results

In this study, a detailed and thorough genome-wide identification and expression analysis of Glycyrrhiza uralensis bHLH gene family was carried out, resulting in the identification of 139 licorice bHLH members. Our duplication analysis highlighted the significant contribution of segmental duplications to the expansion of G. uralensis bHLH genes, with GubHLH genes experiencing negative selection throughout evolution. It was discovered that GubHLH64 and GubHLH38 could be importantly linked to the licorice trichome initiation and anthocyanin biosynthesis and GubHLH64 was also involved in the abiotic stress response. Additionally, certain subfamily III (d+e) GubHLH members could be implicated in the licorice drought response. GubHLH108, GubHLH109, and GubHLH116 were suggested to form a tightly related cluster, initiating transcriptional responses via JA signaling pathway.

Discussion

In summary, our findings furnish a foundational understanding for future investigations of GubHLH gene functions and regulation mechanisms, shedding light on the potential applications of licorice in medicine and agriculture.
Integrating cotyledon-based virus-induced gene silencing with visual marker promises a rapid, highly effective validation of gene functions in Nepeta cataria
Authors: Yu Zongxia , Lv Ruo , Hong Bo , Yang Lei
Published: January 2025

Nepeta spp. generate volatile nepetalactone iridoids that have cat-attractant and insect-repellent activities. They differ from typical mint family (Lamiaceae) iridoids, which are non-volatile glucosides, and also vary from other species in the Nepetoideae sub-family, which do not generate iridoids. The chemistry and evolution of Nepeta make it suitable for further investigation. However, the lack of transgenic technology hampers the molecular and genetic investigations in Nepeta. Virus-induced gene silencing (VIGS) is a powerful tool to detect gene functions in vivo. Here, we constructed a modified VIGS method in Nepeta cataria, using cotyledon infiltration, with the gene silencing effect spreading to the first two pairs of true leaves. The VIGS efficiency reached as high as 84.4%, and the procedure takes only 3 weeks. We employed this method to validate the role of geraniol 8-hydroxylase in nepetalactone biosynthesis with ChlH as a visual marker in N. cataria. The method is also applicable to Nepeta mussinii. Thus, we developed an easy and effective VIGS approach, which will be advantageous for endogenous gene studies in two Nepeta species and holds the potential for application in other plants.
MOUD 2.0: a clinical algorithm and implementation evaluation protocol for sublingual and injectable buprenorphine treatment of opioid use disorder
Authors: Joa Brandon L. , Fung Eric N. , Weinstein Michael S. , Weinstein Lara C.
Published: January 2025

Background

Primary care is the initial contact point for most patients with opioid use disorder (OUD) but lacks tools for guiding treatment. Only a small fraction of patients access evidence-based care. Long-acting injectable buprenorphine has potential to improve medication adherence and program retention in low-barrier primary care treatment settings. We present the first clinical decision support algorithm incorporating long-acting buprenorphine (LAIB) in primary care. We include a protocol for a future evaluation of the algorithm’s implementation process, “Medication for Opioid Use Disorder (MOUD) 2.0,” at a housing and integrated care clinic at a Federally Qualified Health Center.

Methods

Literature review and expert consensus informed creation of the algorithm, which underwent iterative development with feedback from clinicians, staff, and patients. Patients are categorized by adherence to therapy and retention in the program, with recommendations for each category. Adherence is determined by urine screen supplemented by self-report. To ensure all patients in this high morbidity and mortality risk population are treated, we will treat patients as their own controls in the evaluation, with potential for multisite comparisons. We will present descriptive statistics for adherence proportion before and after MOUD 2.0 implementation, testing for differences using McNemar’s test. We will then present pre- and post-implementation unadjusted six-month survival curves for retention.

Discussion

LAIB is incorporated as an alternative or adjunctive treatment for patients refractory to sublingual buprenorphine and as an initial treatment for selected patients. We developed an algorithm with 4-, 8-, and 12-week decision points to guide treatment for patients with varying levels of response to sublingual buprenorphine and LAIB. This clinical decision tool incorporates LAIB among treatment options for OUD in primary care settings. The protocol will evaluate the algorithm’s implementation, presenting a replicable method for assessing adherence and retention among high-risk patients in similar settings.
Dyadic examination of rumination and depressive symptoms in Chinese heterogeneous young couples: the differential role of gender
Authors: Liu Xiaoyu , Zhou Anji , Jin Zhuyun , Han Zhuo Rachel , Qian Jing , Wang Hui
Published: January 2025

Introduction

The relationship between rumination and depressive symptoms has been extensively studied over the past two decades. However, few studies have explored how rumination contributes to depressive symptoms within the context of heterogeneous romantic relationships, particularly regarding potential gender differences in these effects. The present study aims to investigate whether rumination is related to four key factors of depressive symptoms (i.e., depressed affect, positive affect, somatic and retarded activity, interpersonal distress) both on the intrapersonal and interpersonal levels among young couples.

Methods

Participants were 148 Chinese young couples (N = 296; males: M age = 21.94 years, SD = 2.40 years; females: M age = 21.62 years, SD = 2.26 years). Couples completed self-reported questionnaires assessing rumination and depressive symptoms separately, using the Ruminative Response Scale (RRS) and the Center for Epidemiologic Studies Depression Scale (CES-D).

Results

The results of a series of actor-partner interdependence models (APIM) showed that, on the intrapersonal level, rumination was positively and significantly associated with an individual’s own depressed affect, somatic and retarded activity, and interpersonal distress. On the interpersonal level, higher levels of rumination in males were associated with increased depressed affect and interpersonal distress in their female partners. However, no such partner effect was observed for male partners of ruminative females.

Conclusions

These findings suggest that females in romantic relationships, as compared to males, may be more susceptible to the influence of their male partners’ rumination. This study is among the firsts to demonstrate the gender-specific effect in the relationship between rumination and depressive symptoms in young couples.
Resilience and vulnerability of post-ostomy patients with early-onset colorectal cancer from the perspective of social-ecological theory: a qualitative study
Authors: Yang Fangfang , Feng Fangming , Gu Hongming , Liang Han , Zhang Jin , Cheng Yusha , Zhang Weiying
Published: January 2025

Background

The incidence rate of colorectal cancer (CRC) is rising among adults under the age of 50 (early-onset colorectal cancer, EOCRC). Post-ostomy dysfunction, along with negative perceptions due to incorrect public views and a decline in quality of life, has a significant impact on these individuals, their families, and social relationships.

Objective

By understanding the adaptation process of post-ostomy EOCRC(POEOCRC) patients, this study aims to provide information for developing targeted nursing interventions for this population.

Methods

Based on the social-ecological theory, semi-structured, in-depth interviews were conducted with 16 POEOCRC patients in China between May 2023 and January 2024.Colaizzi’s method of phenomenology was employed for data analysis.

Results

This study found two aspects of adaptation experience in POEOCRC patients. For resilience, three themes emerged:(1) Micro-Positive individual psychological experiences, (2) Meso-Positive adjustment within the family and (3) Macro-Social resource integration and utilization. In terms of vulnerability, three themes were as follows:(1) Micro-Persistent negative experiences, (2) Meso-Family crisis caused by the ostomy and (3) Macro-Urgency and fragility of social support.

Conclusion

This study based on the social-ecological theory and highlights different dimensions of resilience and vulnerability experienced by POEOCRC patients. Early and targeted interventions to promote patients’ coping skills and their ability to adapt to family and society.
The connection between climate change and perinatal mental health
Authors: Barkin Jennifer L. , van Rhijn Sanne , Johnson Chloe M.
Published: January 2025

Climate change and extreme weather events are particularly concerning for pregnant and postpartum women and have been related to negative birth outcomes. However, the impact of climate change on perinatal mental health outcomes is not well studied. Mood and anxiety disorders are among the leading comorbidities during pregnancy and the postpartum period, and they are associated with significant familial and societal burdens. It is crucial to include environmental factors in the risk profile of perinatal mental illness to optimize prevention and early intervention strategies. In the clinical experience of one of the authors, new mothers can feel particularly concerned about their baby’s physical health when faced with extreme heat or may present as agitated due to heat-related sleep deprivation. This is in line with qualitative research showing maternal worrying about a baby’s thermal dysregulation as one of the emerging themes. With extreme weather events becoming more frequent, clinicians have a role in advocating for climate adaptation in healthcare settings. Climate inequalities need to be addressed alongside health and social inequalities.
The evolutionary journey to a new normal for learning and capacity building of healthcare workers to prepare and respond to health emergencies across Africa
Authors: Bonkoungou Boukaré , Mosha Fausta , Abianuru Amarachi , Okeibunor Joseph , Utunen Heini , Balaciano Giselle , Barbosa de Lima Ana C. , Burke Lauren , McKenna Shannon , Nag Sukriti , Gueye Abdou Salam , Struminger Bruce
Published: January 2025

Background

Faced with the COVID-19 mobility restrictions, the WHO AFRO EPR program pioneered a collaborative initiative with Project ECHO to virtually educate health workers across Africa at scale. This initiative has evolved into a transformative learning journey. This paper aims to present the lessons learned.

Results

From April 2020 to February 2024, 287 virtual learning sessions were conducted with over 125,816 attendances from 173 countries and regions. This marked a significant increase compared to pre-pandemic face-to-face training, which targeted fewer than 2,000 participants annually. Survey responses (n = 43,221) indicated high relevance and applicability, with 97% of respondents planning to use the information in their work and 89% finding the sessions very or extremely relevant. Self-reported knowledge levels increased from 28 to 74% post-session.

Discussion

Integrating digital learning into WHO AFRO's education and training toolkit has facilitated immediate emergency responses and enhanced long-term resilience, adaptability, and equity among healthcare workers, especially in under-resourced regions. This initiative has reached more health professionals than pre-pandemic in-person training, facilitating more equitable access to essential knowledge and best practices.

Conclusion

The WHO AFRO and Project ECHO partnership navigated a variety of challenges, while establishing a paradigm shift in learning strategies. Emphasizing a digital learning first approach, while retaining in-person elements, this collaborative initiative offers insights for future healthcare education, highlighting adaptability, cost-efficiency, equity, and new technologies in addressing global health challenges. However, to sustain this momentum and further expand access to critical knowledge, stakeholders must commit to continued investment in digital learning infrastructure, training, and technology.
Standard of prevention for infectious diseases' prevention clinical trials during pandemics: learning lessons for global policies from biomedical HIV prevention clinical trials and a case study of COVID-19
Authors: Foláyan Moréniké Oluwátóyìn , Dubé Karine , Ndembi Nicaise
Published: January 2025

Lessons from biomedical HIV prevention research indicate that standard of prevention packages evolve over time, and require active engagement of stakeholders and community advocates to define packages accept to community members and trial participants. Using COVID-19 prevention research as an example, this paper discusses the reasons why a standard of prevention package must be defined for infectious diseases prevention research, what the minimum content of this package may be, the importance of stakeholder engagement in defining the package, the role of the government, and ethical considerations. As the experience from the HIV pandemic had shown, multiple ethics guidelines argue for a comprehensive standard of prevention package for biomedical HIV prevention trials that does not preclude the inclusion of newly developed HIV prevention tools including those experimental products listed for emergency use during health crisis. In the case of COVID-19, the standard of prevention package should include at a minimum, risk reduction counseling on physical distancing, provision of hand sanitizers, education on how to use available prevention tools, and provision for the possibility of vaccine-induced seropositivity. When pre-exposure prophylaxis studies are conducted for healthcare workers and home carers, personal protective equipment should be provided. Regional and country level regulatory provisions on these issues can provide critical guidance for research design and implementation.
Substance use and social influence as risk factors for nicotine and tobacco product use in adolescents and young adults who use electronic nicotine delivery systems
Authors: Hatz Laura E. , Courtney Kelly E. , Wallace Alexander L. , Wade Natasha E. , Baca Rachel , Doran Neal , Jacobus Joanna
Published: January 2025

Background

Nicotine and tobacco product (NTP) use in adolescence and young adulthood is associated with negative health and psychosocial outcomes. This study prospectively tested alcohol use, cannabis use, and peer and family NTP use as predictors of NTP use in adolescents and young adults (AYAs) who were NTP naïve or who primarily used electronic nicotine delivery systems (ENDS).

Method

Participants (N = 133) ages 16–22 completed a baseline laboratory visit and follow-up session 1 year later. Participants’ baseline alcohol use, cannabis use, and NTP use by peers and family were tested as risk factors for any and moderate to heavy (at least monthly) NTP use at follow-up. Logistic regressions were conducted for the full sample (N = 133) and in a subsample of participants reporting no to low NTP use at baseline (n = 76).

Results

Baseline alcohol use, cannabis use, and peer and family NTP use were associated with NTP use at 1-year follow-up, over and above baseline NTP use. Peer and family NTP use emerged as the most consistent predictor of AYA NTP use (ORs: 4.059–8.432), while recent cannabis and alcohol use exerted effects (ORs: 1.003–1.021) that varied by NTP use level.

Discussion

A confluence of variables, including prior substance use and social and familial influences, act as risk factors for NTP use in AYAs who primarily use ENDS. Identification of risk and protective factors for NTP use is necessary to inform efforts to decrease NTP use in this developmentally vulnerable population.
A conceptual ethical framework to preserve natural human presence in the use of AI systems in education
Authors: Isop Werner Alexander
Published: January 2025

In recent years, there has been a remarkable increase of interest in the ethical use of AI systems in education. On one hand, the potential for such systems is undeniable. Used responsibly, they can meaningfully support and enhance the interactive process of teaching and learning. On the other hand, there is a risk that natural human presence may be gradually replaced by arbitrarily created AI systems, particularly due to their rapidly increasing yet partially unguided capabilities. State-of-the-art ethical frameworks suggest high-level principles, requirements, and guidelines, but lack detailed low-level models of concrete processes and according properties of the involved actors in education. In response, this article introduces a detailed Unified Modeling Language (UML)-based ancillary framework that includes a novel set of low-level properties. Whilst not incorporated in related work, particularly the ethical behavior and visual representation of the actors are intended to improve transparency and reduce the potential for misinterpretation and misuse of AIS. The framework primarily focuses on school education, resulting in a more restrictive model, however, reflects on potentials and challenges in terms of improving flexibility toward different educational levels. The article concludes with a discussion of key findings and implications of the presented framework, its limitations, and potential future research directions to sustainably preserve natural human presence in the use of AI systems in education.