bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of fecal sample collection methods for feline gut microbiome profiling: fecal loop vs. litter box
Authors: Ma Xiaolei , Brinker Emily , Lea Christopher R. , Delmain Diane , Chamorro Erin D. , Martin Douglas R. , Graff Emily C. , Wang Xu
Published: May 2024

Introduction

Microbial population structures within fecal samples are vital for disease screening, diagnosis, and gut microbiome research. The two primary methods for collecting feline fecal samples are: (1) using a fecal loop, which retrieves a rectal sample using a small, looped instrument, and (2) using the litter box, which collects stool directly from the litter. Each method has its own advantages and disadvantages and is suitable for different research objectives.

Methods and results

Whole-genome shotgun metagenomic sequencing were performed on the gut microbiomes of fecal samples collected using these two methods from 10 adult cats housed in the same research facility. We evaluated the influence of collection methods on feline microbiome analysis, particularly their impact on DNA extraction, metagenomic sequencing yield, microbial composition, and diversity in subsequent gut microbiome analyses. Interestingly, fecal sample collection using a fecal loop resulted in a lower yield of microbial DNA compared to the litterbox method (p = 0.004). However, there were no significant differences between the two groups in the proportion of host contamination (p = 0.106), virus contamination (p = 0.232), relative taxonomy abundance of top five phyla (Padj > 0.638), or the number of microbial genes covered (p = 0.770). Furthermore, no significant differences were observed in alpha-diversity, beta-diversity, the number of taxa identified at each taxonomic level, and the relative abundance of taxonomic units.

Discussion

These two sample collection methods do not affect microbial population structures within fecal samples and collecting fecal samples directly from the litterbox within 6 hours after defecation can be considered a reliable approach for microbiome research.
Development and biological characterization of an infectious cDNA clone of NADC34-like PRRSV
Authors: Lin Yafang , Zhou Lujia , Xiao Changguang , Li Zongjie , Liu Ke , Li Beibei , Shao Donghua , Qiu Yafeng , Ma Zhiyong , Wei Jianchao
Published: May 2024

Introduction

Porcine Reproductive and Respiratory Syndrome virus (PRRSV) causes high abortion rates in gestating sows and stillbirths, as well as high piglet mortality, seriously jeopardizing the pig industry in China and worldwide.

Methods

In this study, an infectious clone containing the full-length genome of NADC34-like PRRSV was constructed for the first time using reverse genetic techniques. The gene was amplified segmentally onto a plasmid, transfected into BHK-21 cells, and the transfected supernatant was harvested and transfected into PAM cells, which showed classical cytopathic effects (CPE).

Results

The virus rJS-KS/2021 was successfully rescued which could be demonstrated by Western Blot and indirect immunofluorescence assays. Its growth curve was similar to the original strain. Replace the 5’UTR and 3’UTR of rJS-KS/2021 with 5’UTR and 3’UTR of HP-PRRSV (strain SH1) also failed to propagate on MARC-145.

Discussion

In this study, an infectious clone of NADC34-like was constructed by reverse genetics, replacing the UTR and changing the cellular tropism of the virus. These findings provide a solid foundation for studying the recombination of different PRRSVs and the adaption of PRRSVs on MARC-145 in the future.
Ammonium sulfate denatures transport medium less dependent on guanidinium isothiocyanate and enables SARS-CoV-2 RNA and antigen detection compatibility
Authors: Liu Ge , Xu Jiapeng , Huang Yuanyuan , Ye Wei , Li Jieyu , Yan Ran , Luo Qiting , Zhou Xinrui , Cai Yingna , Jiang Hanfang , Lu Xiujing , Zheng Kai , He Zhendan , Zhu Qinchang
Published: May 2024

Introduction

Rapid identification of infected individuals through viral RNA or antigen detection followed by effective personal isolation is usually the most effective way to prevent the spread of a newly emerging virus. Large-scale detection involves mass specimen collection and transportation. For biosafety reasons, denaturing viral transport medium has been extensively used during the SARS-CoV-2 pandemic. However, the high concentrations of guanidinium isothiocyanate (GITC) in such media have raised issues around sufficient GITC supply and laboratory safety. Moreover, there is a lack of denaturing transport media compatible with SARS-CoV-2 RNA and antigen detection.

Methods

Here, we tested whether supplementing media containing low concentrations of GITC with ammonium sulfate (AS) would affect the throat-swab detection of SARS-CoV-2 or a viral inactivation assay targeting coronavirus and other enveloped and non-enveloped viruses. The effect of adding AS to the media on RNA stability and its compatibility with SARS-CoV-2 antigen detection were also tested.

Results and discussion

We found that adding AS to the denaturing transport media reduced the need for high levels of GITC, improved SARS-COV-2 RNA detection without compromising virus inactivation, and enabled the denaturing transport media compatible with SARS-CoV-2 antigen detection.
Bacterial–fungal interactions and response to heavy metal contamination of soil in agricultural areas
Authors: Li Jia , Zheng Qiwen , Liu Jiangyun , Pei Shuwei , Yang Zhen , Chen Rentong , Ma Li , Niu Jingping , Tian Tian
Published: May 2024

Introduction

Long-term heavy metal contamination of soil affects the structure and function of microbial communities. The aim of our study was to investigate the effect of soil heavy metal contamination on microorganisms and the impact of different heavy metal pollution levels on the microbial interactions.

Methods

We collected soil samples and determined soil properties. Microbial diversity was analyzed in two groups of samples using high-throughput sequencing technology. Additionally, we constructed microbial networks to analyze microbial interactions.

Results

The pollution load index (PLI) < 1 indicates that the area is not polluted. 1 < PLI < 2 represents moderate pollution. PLI was 1.05 and 0.14 for the heavy metal contaminated area and the uncontaminated area, respectively. Cd, Hg, Pb, Zn, and Cu were identified as the major contaminants in the contaminated area, with the contamination factors were 30.35, 11.26, 5.46, 5.19, and 2.46, respectively. The diversities and compositions of the bacterial community varied significantly between the two groups. Compared to the uncontaminated area, the co-occurrence network between bacterial and fungal species in the contaminated area was more complex. The keystone taxa of the co-occurrence network in the contaminated area were more than those in the uncontaminated area and were completely different from it.

Discussion

Heavy metal concentrations played a crucial role in shaping the difference in microbial community compositions. Microorganisms adapt to long-term and moderate levels of heavy metal contamination through enhanced interactions. Bacteria resistant to heavy metal concentrations may play an important role in soils contaminated with moderate levels of heavy metals over long periods of time.
Mapping the evolution of neurofeedback research: a bibliometric analysis of trends and future directions
Authors: Wider Walton , Mutang Jasmine Adela , Chua Bee Seok , Pang Nicholas Tze Ping , Jiang Leilei , Fauzi Muhammad Ashraf , Udang Lester Naces
Published: May 2024

Introduction

This study conducts a bibliometric analysis on neurofeedback research to assess its current state and potential future developments.

Methods

It examined 3,626 journal articles from the Web of Science (WoS) using co-citation and co-word methods.

Results

The co-citation analysis identified three major clusters: “Real-Time fMRI Neurofeedback and Self-Regulation of Brain Activity,” “EEG Neurofeedback and Cognitive Performance Enhancement,” and “Treatment of ADHD Using Neurofeedback.” The co-word analysis highlighted four key clusters: “Neurofeedback in Mental Health Research,” “Brain-Computer Interfaces for Stroke Rehabilitation,” “Neurofeedback for ADHD in Youth,” and “Neural Mechanisms of Emotion and Self-Regulation with Advanced Neuroimaging.

Discussion

This in-depth bibliometric study significantly enhances our understanding of the dynamic field of neurofeedback, indicating its potential in treating ADHD and improving performance. It offers non-invasive, ethical alternatives to conventional psychopharmacology and aligns with the trend toward personalized medicine, suggesting specialized solutions for mental health and rehabilitation as a growing focus in medical practice.
Clinical and genetic analyses of APMR4 syndrome caused by novel biallelic LSS variants
Authors: Kang Qingyun , Kang Hui , Tang Jingwen , Wang Miao , Jiang Haojiang , Ning Zeshu , Wu Liwen
Published: May 2024

Alopecia intellectual disability syndromes 4 (APMR4) caused by Lanosterol synthase (LSS) gene variants is a very rare autosomal recessive neuroectodermal syndrome. It is characterized by congenital alopecia and variable degrees of intellectual disability (ID), frequently associated with developmental delay (DD) and epilepsy. Currently, only three studies regarding LSS-related APMR4 have been reported, the pathogenesis of APMR4 is poorly understood. We studied one patient with LSS-related APMR4 who presented with severe intellectual disability, alopecia, early-onset epilepsy and developmental delay. She is absence of hair on the eyebrows, eyelashes, and scalp. Two novel LSS variants (c.401 T > G and c.369C > G) were detected with whole-exome sequencing (WES). Analysis via WB experiment indicated that c.369 > G reduced the protein expression level of LSS. Analysis of protein stability prediction showed a destabilizing for LSS caused by the variant c.401 T > G. This study is the first study in Asia to date. These findings expanded the variantal spectrum of LSS-related APMR4 and revealed the potential pathogenic mechanism of LSS gene variants.
Case report: Regression of in-transit metastases of cutaneous squamous cell carcinoma with combination pembrolizumab and topical diphencyprone
Authors: Poplausky Dina , Young Jade N. , Block Brandon R. , Estrada Yeriel , Singer Giselle K. , Wong Vicky , Cabral Patricia , Suemitsu Yamato , Kim Randie H. , Friedlander Philip , Gulati Nicholas
Published: May 2024

While typically low-risk, cutaneous squamous cell carcinoma (cSCC) can infrequently progress to metastatic disease with in-transit lesions, localized to the dermis or subcutaneous tissue between the primary tumor and draining regional lymph nodes. These lesions are associated with poor prognostic values, including decreased survival rates and increased risk of recurrence. We present the case of a 75-year-old male with cSCC and in-transit metastases on his scalp treated with the immune checkpoint inhibitor (ICI) pembrolizumab in conjunction with diphencyprone (DPCP), a topical hapten that induces a delayed-type hypersensitivity reaction in the skin. The patient was enrolled in a clinical trial (NCT05481658) that involved the twice-weekly application of DPCP 0.04% ointment to four of the in-transit metastases on his frontal scalp, concurrent with pembrolizumab 300 mg administered every three weeks. Following effective sensitization and a twelve-week treatment course, complete clearance of all lesions, DPCP-treated and non-DPCP treated, was achieved, with no adverse events. The immunologic profiles of the post-treatment biopsies were analyzed by TaqMan Low Density Array quantitative real-time polymerase chain reaction to measure immune marker gene expression. Relative to the non-DPCP-treated lesion, the DPCP-treated lesion demonstrated increased pro-inflammatory genetic markers and T-cell activation. This case represents the first reported instance of in-transit metastases of cSCC successfully treated with DPCP and an ICI. It highlights the potential safety and efficacy of DPCP with systemic immunotherapy for the management of in-transit metastases of cSCC in patients for whom surgery and radiation may be contraindicated.
Minimally invasive esophagectomy with non-invasive ventilation by laryngeal mask-assisted anesthesia for esophageal squamous cell carcinoma: case report
Authors: Che Weibi , Zhong Jian , Huang Jiawei , Chen Huilong , Feng Caihou , Xie Yujie , He Haiquan , Chen Ying , Li Cui , Wu Bomeng , Ding Wei , Lin Wanli
Published: May 2024

Minimally invasive esophagectomy for cancer surgery remains associated with significant morbidity and surgical complications across the globe. Non-intubation video-assisted thoracic surgery (NIVATS) has been successfully employed in lung resection in recent years, but there are few reported cases with regard to the safety and feasibility of this approach in radical esophagectomy for patients with esophageal cancers. We present 4 consecutive cases with esophageal squamous cell carcinoma (ESCC) who received minimally invasive McKeown’s esophagectomy under non-intubation general anesthesia from November 2022 to April 2023. All these patients were aged from 55 to 75 years old and were pathologically diagnosed with ESCC. All procedures of McKeown’s esophagectomy in these patients were completed with non-invasive ventilation by laryngeal mask-assisted anesthesia. Operation duration ranged from 185 to 395 minutes and the estimated blood loss ranged from 25 to 60 ml in these 4 cases. No severe hypoxia was observed and transient hypercapnia was resolved intraoperatively. None of them was converted to endotracheal intubation with mechanical ventilation or to thoracotomy. The number of retrieved lymph nodes in mediastinum were 21-27 and all patients received R0 surgery with pathological stage as T1bN0M0 to T3N2M0. There was no serious complication (Clavien-Dindo grade III-IV) observed perioperatively and they were all discharged 11-14 days after the surgery with resumption of oral feeding. They are all alive without tumor recurrence at the date of data collection. The safety and efficacy of minimally invasive esophagectomy with non-invasive ventilation by laryngeal mask-assisted anesthesia for patients with ESCC are warranted for explored in a larger cohort study.
An analysis of the influencing factors of false negative autoantibodies in patients with non-small cell lung cancer
Authors: Wang Ailin , Hao Ying , Huo Yunlong , Xu Xiaoman , Zhang Yi
Published: May 2024

Objectives

To analyze the clinical significance of seven autoantibodies (P53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGE, and CAGE) in patients with non-small cell lung cancer (NSCLC) and the factors that influence false-negative results.

Methods

Seven autoantibodies were measured in the serum of 502 patients with non-small cell lung cancer (NSCLC) using ELISA, and their correlations with age, sex, smoking history, pathological type, clinical stage, and PD-L1 gene expression were analyzed. The clinicopathological data of the false-negative and positive groups for the seven autoantibodies were compared to determine the influencing factors.

Results

P53 antibody expression level was correlated with lobulation sign, PGP9.5 antibody expression level with sex and vascular convergence; SOX2 antibody expression level with pathological type, clinical stage, and enlarged lymph nodes; and MAGE antibody expression level with the pathological type (P<0.05). False-negative autoantibodies are prone to occur in lung cancer patients with ground-glass nodules, no enlarged lymph nodes, no vascular convergence, and PD-L1 gene expression <1% (P <0.05).

Conclusion

Detection of seven autoantibodies was clinically significant in patients with NSCLC. However, poor sensitivity should be considered in clinical diagnoses to prevent missed diagnoses.
MicroRNA-875-5p inhibits the growth and metastasis of cervical cancer cells by promoting autophagy and apoptosis and inhibiting the epithelial-mesenchymal transition
Authors: Liang Yingxiu , Li Chunyang , Hou Xiaohong , Lin Yiguang , Cheng Jing
Published: May 2024

Introduction

MicroRNA-875-5p (miR-875-5p) is a cancer-related microRNA. It has been demonstrated that miR−875−5p participates in the development of various types of cancer such as hepatocellular carcinoma, gastric carcinoma, prostate and bladder cancer. Previous research suggested that miR-875 is implicated in the development of cervical cancer cells. However, the exact role and function of miR−875−5p in cervical cancer remain unexplored. It is important to examine the role and function of miR-875-5p and the associated signaling pathway, as the findings may have diagnostic and therapeutic significance. Thus, in this study, we investigated the effect of miR-875-5p on the growth and metastasis of cervical cancer cells and the possible underlying mechanisms.

Methods

Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-875-5p in cervical cancer cells and normal cervical epithelium. After overexpression or co-expression of miR-875-5p in cells, the changes in cell function were analyzed. Western blot was used to detect the expression changes of epithelial-mesenchymal transition (EMT) -related proteins and autophagy-related proteins.

Results

Functional studies demonstrated that miR-875-5p overexpression significantly inhibited the proliferation, migration, invasion, and EMT, and promotes apoptosis and autophagy of cervical cancer cells., while miR-875-5p knockdown promoted the proliferation, migration, invasion, and EMT, and inhibited apoptosis and autophagy cervical cancer cells. Furthermore, Western blot results showed that overexpression of miR-875-5p downregulated the expressions of N-cadherin, Snail, Vimentin and microtubule-associated protein 1 light chain 3B I (LC3B I). Conversely, miR-875-5p upregulated the expression of E-cadherin.

Conclusion

In conclusion, our findings suggest that miR-875-5p functions as a tumor inhibitor suppressing the growth and metastasis of cervical cancer. Overexpression of miR-875-5p inhibits malignant behavior and promotes autophagy and apoptosis in cervical cancer cells. These findings advance our understanding of the role and function of miR-875-5p in cervical cancer and could facilitate the development of early genetic markers or biomarkers and therapeutic targets for cervical cancer.
The updated surgical steps of gasless transaxillary endoscopic thyroidectomy with neck level and region orientation for thyroid cancer
Authors: Zhou Yuqiu , Shui Chunyan , Ma Linjie , Cai Yongcong , Sun Ronghao , Jiang Jian , Zeng Dingfen , Wang Xu , Xu Xiaoli , Huang Pei , Li Chao
Published: May 2024

Introduction

We previously made a detailed expansion to the gasless transaxillary endoscopic thyroidectomy(GTET) procedure described in the previous literatures. In this study, we optimized the procedure focused on the limitation of the approach in terms of trauma and lymph node dissection and made a comparison with the early procedure.

Materials and methods

This paper gave a detailed description of the updated procedure and prospectively collected data about patients with papillary thyroid carcinoma(PTC) performed by the two procedures from December 2020 to April 2023. The differences in surgical outcome, surgical trauma and parathyroid gland(PG) function protection were analyzed.

Results

Of the 302 patients, 184 underwent with early procedure(EP), and 118 underwent with updated procedure(UP). The surgical outcomes of operative time, time of thyroidectomy and central neck dissection, blood loss, drainage and postoperative hospital stay were shorter in UP than that of the EP. The mean number of lymph nodes retrieved and weight of dissection lymphatic tissue in the UP were significantly more than that in EP without increasing the mean number of metastatic lymph nodes. Postoperative complications did not differ between the two procedures. The UP had more advantages in the identification and preservation of the superior parathyroid gland, however, it did not improve the preservation in situ of the inferior parathyroid gland. The visual analog scale score for pain and the changes among inflammation factors was lower in the UP.

Conclusion

The UP of GTET could perform safely and efficiently while reducing surgical trauma in selected patients.
Incidence and risk factors for bone metastases at presentation in solid tumors
Authors: Knapp Brendan J. , Cittolin-Santos Giordano F. , Flanagan Mary E. , Grandhi Nikhil , Gao Feng , Samson Pamela P. , Govindan Ramaswamy , Morgensztern Daniel
Published: May 2024

Introduction

Bone metastases are associated with increased morbidity and decreased quality of life in patients with solid tumors. Identifying patients at increased risk of bone metastases at diagnosis could lead to earlier interventions. We sought to retrospectively identify the incidence and predictive factors for bone metastases at initial diagnosis in a large population-based dataset.

Methods

The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients 18 years-old or older diagnosed with solid cancers from 2010 to 2019. Patients with hematologic malignancies and primary tumors of the bone were excluded. We calculated the incidence and predictive factors for bone metastases according to demographic and tumor characteristics.

Results

Among 1,132,154 patients identified, 1,075,070 (95.0%) had known bone metastasis status and were eligible for the study. Bone metastases were detected in 55,903 patients (5.2% of those with known bone metastases status). Among patients with bone metastases, the most common primary tumors arose from lung (44.4%), prostate (19.3%), breast (12.3%), kidney (4.0%), and colon (2.2%). Bone metastases at presentation were most common in small cell lung cancer (25.2%), non-small cell lung cancer (18.0%), and esophageal adenocarcinoma (9.4%). In addition to stage classification, predictors for bone metastases included Gleason score (OR 95.7 (95% CI 73.1 – 125.4) for Grade Group 5 vs 1 and OR 42.6 (95% CI 32.3 – 55.9) for Group 4 vs 1) and PSA (OR 14.2 (95% CI 12.6 – 16.0) for PSA > 97 vs 0 – 9.9) for prostate cancer, HER2 and hormonal receptor (HR) status (OR 2.2 (95% CI 1.9 – 2.6) for HR+/HER2+ vs HR-/HER2-) for breast cancer, histology (OR 2.5 (95% CI 2.3 – 2.6) for adenocarcinoma vs squamous) for lung cancer, and rectal primary (OR 1.2 (95% 1.1 – 1.4) vs colon primary) and liver metastases (OR 8.6 (95% CI 7.3 – 10.0) vs no liver metastases) for colorectal tumors.

Conclusions

Bone metastases at presentation are commonly seen in solid tumors, particularly lung, prostate, breast, and kidney cancers. Clinical and pathologic factors are associated with a significantly increased risk for bone metastases.
Primary squamous cell carcinoma and adenocarcinoma simultaneously occurring in the same lung lobe: a case report and literature review
Authors: Zhang Tianyu , He Ruyuan , Xiao Yongguang , Geng Qing
Published: May 2024

The co-occurrence of distinct lung cancer types within the same lobe is an exceedingly rare phenomenon. Here, we present a unique case wherein primary invasive squamous cell carcinoma and invasive adenocarcinoma concurrently manifested in the identical lung lobe. Additionally, we provide a comprehensive overview of the diagnosis and treatment approaches for multiple primary lung cancers, along with highlighting existing challenges based on the most recent guidelines. Our case underscores the importance of sampling each lesion individually, conducting separate diagnostic procedures, and determining the histological subtype for effective treatment planning irrespective of their location or size.
Reappraising the psychosomatic approach in the study of “chronic orofacial pain”: looking for the essential nature of these intractable conditions
Authors: Toyofuku Akira , Matsuoka Hirofumi , Abiko Yoshihiro
Published: May 2024

As burning mouth syndrome (BMS) and atypical odontalgia (AO) continue to remain complex in terms of pathophysiology and lack explicit treatment protocol, clinicians are left searching for appropriate solutions. Oversimplification solves nothing about what bothers us in clinical situations with BMS or AO. It is important to treat a complicated phenomenon as complex. We should keep careful observations and fact-finding based on a pragmatic approach toward drug selection and prescription with regular follow-up. We also need to assess the long-term prognosis of treatment with a meticulous selection of sample size and characteristics. Further investigation of BMS and AO from a psychosomatic perspective has the potential to provide new insight into the interface between brain function and “chronic orofacial pain.”
A comprehensive bibliometric analysis (2000–2022) on the mapping of knowledge regarding immunotherapeutic treatments for advanced, recurrent, or metastatic cervical cancer
Authors: Duan Yuanqiong , Yang Lin , Wang Wenxiang , Zhang Peixuan , Fu Kaiyu , Li Wen , Yin Rutie
Published: May 2024

Background

Despite extensive literature on therapeutic strategies for cervical cancer, a bibliometric analysis specifically focused on immunotherapy for advanced, recurrent, or metastatic (A/R/M) cervical malignancies remains unexplored. This study aims to address this gap by presenting a comprehensive overview that includes general characteristics, research focal points, the trajectory of evolution, and current emerging trends in this under-researched area.

Methods

A systematic search was conducted using the Web of Science Core Collection (WOSCC) to identify articles related to A/R/M cervical cancer published between 2000 and 2022. Citespace and VOS viewer were the primary tools used to identify research focal points, intriguing future patterns, and to evaluate contributions and co-occurrences among authors, institutions, countries, and journals.

Results

A total of 1,001 original articles were identified, involving 6,387 authors from 66 countries and 1,474 institutions, and published across 366 academic journals. The United States contributed most significantly. The most productive researcher was Van der Burg SH from Leiden University Medical Center. The International Journal of Cancer and Cancer Research were identified as the most productive and influential journals, respectively. Analysis of co-citation clusters highlighted 25 clusters, primarily focusing on potential predictive biomarkers, dendritic cell-based tumor vaccines, therapeutic HPV vaccinations, peptide-based cancer vaccines, tumor immune microenvironments, and adoptive cell transfer (ACT). The latest significant trends in A/R/M cervical cancer immunotherapy research included ACT, CAR-T, and immune checkpoint inhibitors (ICIs), as revealed by keyword and reference burst detection.

Conclusion

This pioneering study provides a detailed landscape of immunotherapy research in A/R/M cervical cancer. It underscores the importance of global collaboration, enriches our understanding of the immunology of A/R/M cervical cancer, expands on potential beneficiaries of immunotherapy, and explores clinical applications of various therapies, including therapeutic vaccines, adoptive cell transfer, and ICIs, particularly in combination with established treatments such as chemotherapy, radiotherapy, and targeted therapy.
Knowledge mapping of graph neural networks for drug discovery: a bibliometric and visualized analysis
Authors: Yao Rufan , Shen Zhenhua , Xu Xinyi , Ling Guixia , Xiang Rongwu , Song Tingyan , Zhai Fei , Zhai Yuxuan
Published: May 2024

Introduction

In recent years, graph neural network has been extensively applied to drug discovery research. Although researchers have made significant progress in this field, there is less research on bibliometrics. The purpose of this study is to conduct a comprehensive bibliometric analysis of graph neural network applications in drug discovery in order to identify current research hotspots and trends, as well as serve as a reference for future research.

Methods

Publications from 2017 to 2023 about the application of graph neural network in drug discovery were collected from the Web of Science Core Collection. Bibliometrix, VOSviewer, and Citespace were mainly used for bibliometric studies.

Results and Discussion

In this paper, a total of 652 papers from 48 countries/regions were included. Research interest in this field is continuously increasing. China and the United States have a significant advantage in terms of funding, the number of publications, and collaborations with other institutions and countries. Although some cooperation networks have been formed in this field, extensive worldwide cooperation still needs to be strengthened. The results of the keyword analysis clarified that graph neural network has primarily been applied to drug-target interaction, drug repurposing, and drug-drug interaction, while graph convolutional neural network and its related optimization methods are currently the core algorithms in this field. Data availability and ethical supervision, balancing computing resources, and developing novel graph neural network models with better interpretability are the key technical issues currently faced. This paper analyzes the current state, hot spots, and trends of graph neural network applications in drug discovery through bibliometric approaches, as well as the current issues and challenges in this field. These findings provide researchers with valuable insights on the current status and future directions of this field.
Comprehensive spectroscopic and computational insight into the binding of vanillin with human transferrin: targeting neuroinflammation in Alzheimer’s disease therapeutics
Authors: Alrouji Mohammed , Yasmin Sabina , Alhumaydhi Fahad A. , Sharaf Sharaf E. , Shahwan Moyad , Furkan Mohammad , Khan Rizwan Hasan , Shamsi Anas
Published: May 2024

In present times, vanillin stands out as a promising therapeutic molecule that can be implicated in the treatment of neurodegenerative disorders (NDs), notably Alzheimer’s disease (AD). This can be attributed to the highly potent scavenging activity of vanillin against reactive oxygen species (ROS). Oxidative stress leads to generation of ROS that serves a critical role in AD’s pathological progression. It is apparent from various studies that diets rich in polyphenols prevent oxidative stress associated with AD development, implying the crucial role of vanillin in AD therapeutics. It is crucial to maintain iron balance to manage AD associated oxidative stress, unveiling the significance of human transferrin (hTf) that maintains iron homeostasis. Here, we have performed an integrated study of spectroscopic and computational approaches to get insight into the binding mechanism of vanillin with hTf. In the preliminary study, molecular docking deciphered that vanillin primarily occupies the hTf binding pocket, forming multiple interactions with its key residues. Moreover, the binding mechanism was evaluated at an atomistic level employing comprehensive molecular dynamic (MD) simulation. MD analysis demonstrated that binding of vanillin to hTf stabilizes its structure, without inducing any significant alterations in its native conformation. The docked complex was maintained throughout the simulations without changing its original conformation. Essential dynamics analysis further confirms that hTf achieved a stable conformation with vanillin. The outcomes were further supplemented by fluorescence spectroscopy which confirms the formation of stable hTf-vanillin complex. Taken together, the current study unveils the interaction mechanism of vanillin with hTf and providing a platform to use vanillin in AD therapeutics in the context of iron homeostasis.
Field screening and identification of biochemical indices of pod borer (Helicoverpa armigera) resistance in chickpea mutants
Authors: Noreen Asima , Hameed Amjad , Shah Tariq Mahmud
Published: May 2024

Chickpea pod borer (CPB) (Helicoverpa armigera) is one of the major pests, causing significant yield losses. The objectives were to screen chickpea mutants for pod borer resistance/tolerance under field conditions and identification of biochemical markers of tolerance. Chickpea mutant CM216-A/15 had highest leaf (25 trichomes/mm2) and stem trichome density (17 trichomes/mm2) with least pod damage at Kallur Kot and highest pod weight per plant (22.8 ± 2.6g) at AZRI. Higher total phenolic contents (TPCs) and antioxidant capacity were detected in tolerant mutants, i.e., CM216-A/15 and CM664/15. TPC was positively associated with pod yield and had negative correlation with pod damage. Mutants CM216-A/15, CM664/15, and CM766/15 depicted the highest resilience to CPB, owing to higher hairiness, better antioxidant defense response, and lower levels of hydrolytic enzymes and sugars. Identified biochemical markers like TPC, total oxidant status, superoxide dismutase, and pigments can be used for screening of CPB-tolerant/resistant mutants.
The global development of value orientations, political support and democracy since the 1990s
Authors: Hoffmann-Lange Ursula
Published: May 2024

This article analyzes the global development of democracy since the 1990s. The theoretical introduction is followed by a descriptive analysis of several indices of political support based on survey results for 89 countries that participated at least twice in the World Values Survey (WVS) or the European Values Study (EVS). The analysis focuses on emancipative value orientations measured by Welzel's Choice Index and several indicators of political support. The scores of these indicators are broken down by five regime types and seven world regions. The results confirm that the global decline of democratic quality since the mid-2000s has not been as dramatic as the pessimistic analyses of Freedom House and the V-Dem project have claimed. It has primarily taken place in a limited number of populous countries on which these publications have focused. When countries are treated equally, the quality of democracy has remained remarkably stable since the early 1990s. Emancipative values are globally on the rise, but their increase has been considerably higher in the established democracies. This supports the skeptical argument that they cannot be considered as the major cause of the third wave of democratization. The descriptive analysis is complemented by regression analyses for confidence in regime institutions and support for democracy as dependent variables. The evaluation of democratic regime performance is the strongest predictor of confidence in regime institutions. An intrinsic conception of democracy and the importance assigned to living in a democracy have the strongest influence on support for democracy. Emancipative value orientations have a minor influence on political support even in consolidated democracies. Finally, the analysis does not confirm the suspected relationship between the different levels of political support. Easton's theory of political support assumed that they mutually influence each other via a generalization of experiences or an overflow of values. Instead, it seems that confidence in regime institutions and support for democracy follow different cognitive logics.
Civilians at war: focusing on the Israeli-Palestinian conflict and scrutinizing the doctrine of non-combatant immunity
Authors: Liu Xia
Published: May 2024

The principle of non-combatant immunity was codified in the Code of International Law and developed into an important foundation for the doctrine of just war, whose origins can be traced to the moral imperative of religious support. The doctrine advocates that persons deemed innocent should be protected from the threat of war, and it is the most widely recognized and deeply rooted moral constraint on the conduct of war. However, the principle of non-combatant immunity has not really deterred the outbreak of war, leaving the international community committed to utopian ideals. In the contemporary context of the Israeli-Palestinian conflict, the principle of non-combatant immunity has been rendered ineffective as civilians are forced to be on the frontlines of both sides of the war. The principle of “just war” seems to have taken on a new basis, with self-defense becoming the pretext for justifying war, and the international community unable to rescue civilians from the flames of war amidst the outcry. There is an urgent need for the international community to re-examine and re-evaluate the immunity of non-combatants, and to limit the use of war as a “legitimate” means of resolving international conflicts. This article calls for a critical assessment of the normativity and effectiveness of the existing law on the principle of non-combatants, and a rethinking of how to construct a more rational and high-level principle to enhance the protection of non-combatants.
Synergies of affordances and place-based relationality in Forest School practice: implications for socio-emotional well-being
Authors: Sharma-Brymer Vinathe , Brymer Eric , Willis Royce , Leach Matthew
Published: May 2024

Research shows that the human-nature relationship positively impacts human well-being. Forest School (FS) practice offers young children a structured program of nature connection through activities, aiming to enhance their self-esteem and social skills. FS is now adapted in countries such as Australia, Canada and New Zealand where a unique cultural interface occurs between European settlers and Indigenous peoples. Responding to socio-cultural diversities, geographical contexts, and the traditional ecological knowledges, FS needs to go beyond play pedagogy and incorporate theoretical perspectives that promote human-nature relationship in local context-specific environments. We argue that the synergies between Western perspectives on affordances perceived in person-environment relationship and Indigenous place-based relationality perspective provide a more suitable approach for developing reciprocal relationships between FS participants and land/place/nature. We propose that the synergies between affordances perceived in FS and place-based relationality cultivated in participants will enhance social and emotional well-being. We call for specific research investigating such synergies supporting participant well-being. Future research on FS practice should be directed toward initiating and exploring co-designed studies by Indigenous and non-Indigenous researchers incorporating methodologies that study participant experience as well as evaluating the impact of FS programs embedding affordances and place-based relationality perspectives.
Psychological factors enhanced heterogeneous learning interactive graph knowledge tracing for understanding the learning process
Authors: Wang Zhifeng , Wu Wanxuan , Zeng Chunyan , Luo Heng , Sun Jianwen
Published: May 2024

Introduction

With the rapid expansion of online education, there is a burgeoning interest within the EdTech space to offer tailored learning experiences that cater to individual student's abilities and needs. Within this framework, knowledge tracing tasks have garnered considerable attention. The primary objective of knowledge tracing is to develop a model that assesses a student's proficiency in a particular skill based on their historical performance in exercises, enabling predictions regarding the likelihood of correct responses in future exercises. While existing knowledge tracing models often incorporate information such as students' exercise answering history and skill mastery level, they frequently overlook the students' mental states during the learning process.

Methods

This paper addresses this gap by introducing a novel psychological factors-enhanced heterogeneous learning interactive graph knowledge tracing model (Psy-KT). This model delineates the interactions among students, exercises, and skills through a heterogeneous graph, supplementing it with four psychological factors that capture students' mental states during the learning process: frustration level, confusion level, concentration level, and boredom level. In the modeling of students' learning processes, we incorporate the forgetting curve and construct relevant cognitive parameters from the features. Additionally, we employ the Item Response Theory (IRT) model to predict students' performance in answering exercises at the subsequent time step. This model not only delves into the psychological aspects of students during the learning process but also integrates the simulation of forgetting, a natural phenomenon in the learning journey. The inclusion of cognitive parameters enhances the description of changes in students' abilities throughout the learning process. This dual focus allows for a more comprehensive understanding of students' learning behaviors while providing a high level of interpretability for the model.

Results and discussion

Empirical validation of the Psy-KT model is conducted using four publicly available datasets, demonstrating its superior performance in predicting students' future performance. Through rigorous experimentation, the integration of psychological and forgetting factors in the Psy-KT model not only improves predictive accuracy but also enables educators to offer more targeted tutoring and advice, enhancing the overall efficacy of the learning experience.
Clinical effectiveness of internet-based cognitive behavioral therapy for insomnia in routine secondary care: results of a randomized controlled trial
Authors: Pchelina Polina , Poluektov Mikhail , Krieger Tobias , Duss Simone B. , Berger Thomas
Published: May 2024

Introduction

Delivering cognitive behavioral therapy for insomnia over the internet bears the advantage of accessibility and uptake to many patients suffering from chronic insomnia. In the current study, we aimed to investigate the effectiveness of internet-based cognitive behavioral therapy for insomnia (iCBT-I) in routine care.

Materials and methods

We conducted a two-arm non-blinded randomized controlled trial with care as usual (CAU) as a control condition. Participants were recruited in a specialized outpatient sleep medicine department. Both arms had access to other healthcare resources, and the intervention group had access to the iCBT-I program for 2 months. The primary outcome was insomnia severity, measured by the Insomnia Severity Index (ISI). Secondary outcomes were fatigue severity, daytime sleepiness, affective symptoms, dysfunctional beliefs and attitudes about sleep, sleep locus of control, sleep hygiene, sleep efficiency (SE), sleep onset latency, wake time after sleep onset (WASO), and total sleep time (TST). Linear mixed models for repeated measures were used to analyze the longitudinal data at baseline, post-treatment, and after 3 months of follow-up. The trial was registered at www.clinicaltrials.gov (NCT04300218 21.04.2020).

Results

The results showed a significant time*group interaction effect (p = 0.001) at post-treatment with between-group effect size (d = 0.51), indicating that the ISI decreased by a score of 3.8-fold in the iCBT-I group than in the CAU group. There was no significant difference in ISI between groups at follow-up. Regarding secondary outcomes, dysfunctional beliefs about sleep, SE, and WASO decreased significantly during treatment in the intervention group with between-group effect sizes d = 0.35, d = −0.51, and d = 0.47, respectively. At the follow-up, between-group effects on DBAS and SE remained significant: d = 0.36 and d = −0.63, respectively. For TST, we observed a significant time*group effect of d = −0.38 only after follow-up.

Conclusion

Our findings suggest that iCBT-I has a significant effect on insomnia severity at post-treatment compared to CAU. iCBT-I further improved dysfunctional beliefs about sleep and improved subjective sleep characteristics, such as SE, WASO, and TST during 3 months after treatment.

Clinical trial registration

www.clinicaltrials.gov, identifier (NCT04300218).
The relationship between sleeptime and depression among middle-aged and elderly Chinese participant during COVID-19 epidemic and non-epidemic phases
Authors: Du Chaonan , Wang Cong , Liu Zhiwei , Bai Nan , Zhu Junhao , Ali Alleyar , Geng Yuanming , Zeng Xinrui , Yang Yu , Li Zhenxing , Ma Chiyuan
Published: May 2024

Background

The global impact of the COVID-19 pandemic had significantly altered the daily routines of people worldwide. This study aimed to compare how sleeptime and depression among Chinese residents had differed between periods during and outside the epidemic. Furthermore, it delved into the interactive effect of age in this relationship.

Method

Utilizing data from the China Health and Retirement Longitudinal Study (CHARLS) study in 2015 and the recently released data from 2020, which covered the pandemic period. Depression was assessed using Center for Epidemiologic Studies Depression Scale (CESD-10), considering a score of 10 or higher as indicative of depression. Participants were categorized based on age, specifically those aged 60 years and older. multivariate logistic regression and interaction analyses were employed to assess the interplay of age, supported by subgroup and sensitivity analyses to reinforce our findings.

Results

The 2020 database comprised 19,331 participants, while the 2015 database had 10,507 participants. Our findings demonstrated a significant correlation between sleeptime and depression in both unadjusted models and models adjusted for all variables in both datasets (p<0.001). Upon stratifying by age and adjusting for relevant factors, we identified an interaction effect among age, sleeptime, and depression (p=0.004 for the interaction in the 2020 database, compared to 0.004 in 2015). The restricted cubic spline analysis in both datasets showcased a nonlinear relationship between sleeptime and depression.

Conclusions

During both epidemic and non-epidemic periods in China, there existed a correlation between sleep duration and depression, which interacts with age.
Associations between dietary habits and bipolar disorder: a diet-wide mendelian randomization study
Authors: Li Junyao , Hu Renqin , Luo Huirong , Guo Yanwei , Zhang Zheng , Luo Qinghua , Xia Pingyou
Published: May 2024

Background

Diet/nutrition is critically important in the pathogenesis, progression, and treatment outcomes of various mental disorders. Current research predominantly focuses on the role of diet in the development and treatment of depression, with less attention given to the relationship between diet and Bipolar Disorder (BD).

Method

We employed Mendelian Randomization (MR) to investigate the relationship between 28 dietary habits and BD. An analysis was conducted using publicly available genome-wide association study data from the UK Biobank dataset. Various dietary habits were analyzed as exposures with BD as the outcome, mainly using the Inverse Variance Weighted (IVW) method.

Results

Intake of non-oily fish and sponge pudding both have a positive association with BD. Oily fish, dried fruit, apples, salt, and cooked vegetables intake also appeared potentially risky for BD, although the possibility of false positives cannot be ruled out. Sensitivity analysis further confirmed the robustness of these findings.

Conclusion

Our research provides evidence of a relationship between various dietary habits and BD. It underscores the need for careful dietary management and balance to reduce the risk of BD, suggesting caution with dietary preferences for fish and sponge pudding. Furthermore, more detailed studies are needed to further understand the potential impacts of high-sugar and high-protein diets on BD development.