bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical significance of the tumor microenvironment on immune tolerance in gastric cancer
Authors: He Xiangyang , Guan Xin-Yuan , Li Yan
Published: February 2025

In the realm of oncology, the tumor microenvironment (TME)—comprising extracellular matrix components, immune cells, fibroblasts, and endothelial cells—plays a pivotal role in tumorigenesis, progression, and response to therapeutic interventions. Initially, the TME exhibits tumor-suppressive properties that can inhibit malignant transformation. However, as the tumor progresses, various factors induce immune tolerance, resulting in TME behaving in a state that promotes tumor growth and metastasis in later stages. This state of immunosuppression is crucial as it enables TME to change from a role of killing tumor cells to a role of promoting tumor progression. Gastric cancer is a common malignant tumor of the gastrointestinal tract with an alarmingly high mortality rate. While chemotherapy has historically been the cornerstone of treatment, its efficacy in prolonging survival remains limited. The emergence of immunotherapy has opened new therapeutic pathways, yet the challenge of immune tolerance driven by the gastric cancer microenvironment complicates these efforts. This review aims to elucidate the intricate role of the TME in mediating immune tolerance in gastric cancer and to spotlight innovative strategies and clinical trials designed to enhance the efficacy of immunotherapeutic approaches. By providing a comprehensive theoretical framework, this review seeks to advance the understanding and application of immunotherapy in the treatment of gastric cancer, ultimately contributing to improved patient outcomes.
Disruption of the moonlighting function of CTF18 in a patient with T-lymphopenia
Authors: Sertori Robert , Truong Billy , Singh Manoj K. , Shinton Susan , Price Rachael , Sharo Andrew , Shultes Paulameena , Sunderam Uma , Rana Sadhna , Srinivasan Rajgopal , Datta Sutapa , Font-Burgada Joan , Brenner Steven E. , Puck Jennifer M. , Wiest David L.
Published: February 2025

Introduction

Newborn screening for immunodeficiency has led to the identification of numerous cases for which the causal etiology is unknown.

Methods

Here we report the diagnosis of T lymphopenia of unknown etiology in a male proband. Whole exome sequencing (WES) was employed to nominate candidate variants, which were then analyzed functionally in zebrafish and in mice bearing orthologous mutations.

Results

WES revealed missense mutations in CHTF18 that were inherited in an autosomal recessive manner. CTF18, encoded by the CHTF18 gene, is a component of a secondary clamp loader, which is primarily thought to function by promoting DNA replication. We determined that the patient’s variants in CHTF18 (CTF18 R751W and E851Q) were damaging to function and severely attenuated the capacity of CTF18 to support hematopoiesis and lymphoid development, strongly suggesting that they were responsible for his T lymphopenia; however, the function of CTF18 appeared to be unrelated to its role as a clamp loader. DNA-damage, expected when replication is impaired, was not evident by expression profiling in murine Chtf18 mutant hematopoietic stem and progenitor cells (HSPC), nor was development of Ctf18-deficient progenitors rescued by p53 loss. Instead, we observed an expression signature suggesting disruption of HSPC positioning and migration. Indeed, the positioning of HSPC in ctf18 morphant zebrafish embryos was perturbed, suggesting that HSPC function was impaired through disrupted positioning in hematopoietic organs.

Discussion

Accordingly, we propose that T lymphopenia in our patient resulted from disturbed cell-cell contacts and migration of HSPC, caused by a non-canonical function of CHTF18 in regulating gene expression.
Detargeting the target in phoneme detection: aiming the task at phonological representations rather than backgrounds
Authors: Scott John H. G.
Published: February 2025

One challenge of learning a second or additional language (L2+) is learning to perceive and interpret its sounds. This includes acquiring the target language (TL) contrastive phonemic inventory, the sounds' systematic behavior in the TL phonology, and novel relationships between spelling and sound (GPCs; grapheme-phoneme correspondences). Many perception tasks require stipulation of written labels for target speech sounds (e.g., phoneme detection). Listening for this target is not necessarily, or even frequently, an equivalent cognitive task between participant groups. The incongruence of phonological and orthographic domains and their GPCs poses a methodological challenge for L2+ research. The author argues that phoneme detection tasks should avoid the phone of investigative interest (x) as the direct target of listener attention and redirect focus to an adjacent listening target (y). Ideally, this target should not trigger or otherwise be implicated in the phonological process or phonotactic constraint under investigation. The careful choice of listening target (y) with both a familiar sound and a congruent orthographic label for both (or all) language groups of the experiment yields an equivalent task and better indicates implicit knowledge of the phenomenon under study. This approach opens up potential choices of phonological objects of interest (x). The two phoneme detection experiments reported here employ this novel adjacent-congruent listening target approach, which the author calls the Persean approach. Experiment 1 establishes baseline performance in two assimilation types and replicates processing inhibition in first-language (L1) German speakers in response to violations of regressive nasal assimilation. It also uses [t] as the Persean listening target to test sensitivity to preceding violations of progressive dorsal fricative assimilation (DFA). Experiment 2 investigates sensitivity to violations of DFA in both L1 German speakers and L1 English L2+ German learners. Experiment 2 also uses the Persean method for the first phoneme detection investigation demonstrating sensitivity to violation of a prosodic/phonotactic constraint banning /h/ in syllable codas. The study demonstrates that phoneme detection with Persean listening targets is a viable instrument for investigating regressive and progressive assimilation, prosodic/phonotactic constraints, and prelexical perceptual repair strategies in different language background groups and proposes statistical best practices for future phoneme detection research.
Evaluation of extraction-oxidation synergistic remediation of contaminated dredged sediment and plant suitability effects
Authors: Yang Wenchao , Liu Jize , Sun Yuanshu , Wang Zhaowei , Han Chengwei , Han Jianbo
Published: February 2025

Generally, marine dredged sediments often exhibit co-pollution with heavy metals and petroleum hydrocarbons. This work investigates the extraction-oxidation synergistic remediation treatment of heavy metals (Cu and Pb) and total petroleum hydrocarbon (TPH) in the contaminated dredged sediments. The leachability of heavy metals, the oxidation of TPH, the physicochemical properties of the treated sediment, and the fertility of the treated sediment for barley growth are compared among different combinations of extractants [ethylene diamine tetraacetic acid (EDTA), citric acid (CA) and ferric chloride (FeCl3)] and oxidant [potassium persulfate (K2S2O8)]. The results show that the extraction-oxidation synergistic remediation treatment significantly reduces the Cu and Pb contents. The total removal performances of heavy metals and TPH in the contaminated dredged sediments by each co-remediation treatment group are FeCl3+Ox > EDTA-Ox > CA-Ox. Specifically, FeCl3+Ox and EDTA-Ox achieve the highest removal rates of 91.10% and 96.95% for Cu and Pb, respectively. The extractant affects the activation of K2S2O8 by transition metals, enhancing the removal efficiency of TPH. The EDTA-Ox treatment group demonstrates the optimal treatment efficiency (37.42%) for TPH in the dredged sediment in 30 min. In the barley planting experiment, both shoot and root germinations in the EDTA-Ox treatment group reach their maximum values of 100% and 90%, respectively. Additionally, the CA-Ox treatment group exhibits maximal shoot and root lengths of 11.6 cm and 12.1 cm, respectively. The stress caused by salinity on seeds is also mitigated by the treatment. This study can provide technical support for the beneficial use of the dredged sediment.
A comparative cross-sectional study of the impact of COVID-19 pandemic on obstetrics and gynecology admissions in Croatia
Authors: Kalanj Karolina , Mikuš Mislav , Peček Mirta , Orbanić Ante , Marshall Rick , Orešković Stjepan , Orešković Slavko
Published: February 2025

Background

The COVID-19 pandemic placed unprecedented pressure on healthcare systems worldwide and altered patients' perceptions of the system's ability to protect them from virus transmission. One significant consequence was a marked decline in hospital activity, a trend observed globally. This study aims to evaluate the impact of COVID-19 on hospitalization rates among patients with gynecological disorders in Croatia. It compares the number of patients treated surgically vs. conservatively before the pandemic (2017–2019) and during the pandemic (2020–2022) using the Diagnostic-Related Group (DRG) patient classification system. The DRG system is designed to group patients based on similar clinical conditions, complexity, and resource utilization. Hospital activity categorized by DRGs was analyzed to assess the impact of the COVID-19 pandemic on case volumes within DRG groups associated with gynecological and obstetric disorders.

Materials and methods

We conducted a comparative descriptive cross sectional study of the pre-post type according to STROBE guidelines to determine the impact of COVID-19 pandemic on hospital admission rates for patients with conditions associated with illnesses and abnormalities of the female reproductive system, as well as pregnancy, delivery, and the puerperium. The publicly available data collected by Croatian Institute of Public Health (CIPH) and the Croatian Health Insurance Fund (CHIF) were the main data source for this study. All gynecological hospital admissions in Croatia were grouped based on the Australian Refined Diagnosis Related Groups (AR-DRGs) and analyzed over two time periods: before (2017–2019) and during the pandemic (2020–2022).

Results

The average number of gynecological patients in all hospitals during the pandemic was 62,257 compared to pre-pandemic when the average number of patients was 71,519, a decrease of 15.5%. The results show a 10.56% decrease in the total number of non-surgical admissions and 12.8% decrease of surgical admissions across the hospital network during the pandemic (2020–2022).

Conclusion

The COVID-19 pandemic led to a significant decline in inpatient treatments in gynecology and obstetrics departments in Croatia. Our findings highlight the need for obstetrics and gynecology practitioners to develop innovative strategies to maintain or enhance patient access to appropriate care while ensuring stringent infection prevention measures for both patients and healthcare personnel. Furthermore, investing in healthcare system resilience is crucial to maintaining core functions during future crises. The lessons learned from the COVID-19 pandemic provide a valuable opportunity to fortify healthcare systems and must not be ignored.
Development and implementation of the international AIDA network spondylarthritis registry
Authors: Caggiano Valeria , Vitale Antonio , Hinojosa-Azaola Andrea , Guaracha-Basañez Guillermo Arturo , Ruscitti Piero , Cipriani Paola , Tharwat Samar , Elberashi Hanan M. , Othman Esraa E. , Conforti Alessandro , Gimignani Giancarlo , Erten Sukran , Barone Patrizia , Thabet Maissa , Sota Jurgen , Hernández-Rodríguez José , Gómez-Caverzaschi Verónica , Ragab Gaafar , Maher Amina , Batu Ezgi Deniz , Kawakami-Campos Perla Ayumi , Torres-Ruiz Jiram , Gaggiano Carla , Tufan Abdurrahman , Kucuk Hamit , Mayrink Giardini Henrique A. , Ahmed Guiga , Eksin Mehmet Akif , Fotis Lampros , Panahi Azadeh Shariat , Gentileschi Stefano , Almaghlouth Ibrahim A. , Sfikakis Petros P. , Fragoulis George E. , Monterosso Costanza , Opris-Belinski Daniela , Hashad Soad , Di Meglio Nunzia , Sica Cristian , Ulusoy Bahar Özdemir , de-la-Torre Alejandra , Wiesik-Szewczyk Ewa , Rybak Katarzyna , Balistreri Alberto , Fabiani Claudia , Mazzei Maria Antonietta , Frediani Bruno , Cantarini Luca
Published: February 2025

During the last decade, spondyloarthritis (SpA) has increasingly been considered a disease at the crossroads between autoimmunity and autoinflammation. Some patients may even present with autoinflammatory-related manifestations, including fever, hidradenitis suppurativa, other neutrophilic dermatoses, and an unusually high increase in inflammatory markers. Therefore, a subgroup of SpA patients may be identified, and specific details about this cluster need to be investigated. In this regard, the AutoInflammatory Disease Alliance (AIDA) Network has developed a registry primarily aimed at better understanding the autoinflammatory aspects of SpA. The development of this Registry favors the systematic assessment of SpA through the lens of autoinflammation, giving a voice to patients with atypical presentations, and favoring a personalized treatment approach. By supporting research and facilitating the transfer of new evidence to clinical practice, this specific registry has the potential to significantly advance the field of rheumatology and enhance the lives of patients suffering from this complex and multifaceted disease.
Burden of rheumatoid arthritis in India from 1990 to 2021: insights from the Global Burden of Disease Database
Authors: Shi Wei , Liang Xinyu , Zhang Huafeng , Li Hui
Published: February 2025

Objective

Rheumatoid arthritis (RA) significantly impacts individual health and society. This study aims to analyze the burden of RA in India from 1990 to 2021 and provide predictions to inform national prevention and control strategies.

Methods

Utilizing data from the 2021 Global Burden of Disease (GBD) database, this study describes changes in incidence, prevalence, and disability-adjusted life years (DALY) related to RA in India from 1990 to 2021, while also observing variations across 31 geographical regions.

Results

From 1990 to 2021 in India, the incidence, prevalence, and DALY rates of RA showed an increasing trend, with all age-standardized rates being significantly higher in females than in males. The age group of 65–69 years showed the highest incidence rate, while the prevalence peaked at 75–79 years. The forecast results indicate that the age-standardized incidence and DALY rates of RA in India will show an upward trend from 2022 to 2036. There were considerable differences in prevalence across different regions. In 2021, the highest male prevalence was in Uttarakhand, while Goa had the lowest. For females, Tamil Nadu had the highest prevalence, and Madhya Pradesh had the lowest. Overall, areas with high Socio-Demographic Index (SDI) showed a higher disease burden, whereas Kerala, despite a higher SDI, had the lowest burden.

Conclusion

Using the GBD database, our findings show that the disease burden of RA in India is on the rise from 1990 to 2021. The prevalence of RA in different regions of India is significantly different, which may be related to local economy and development. The high prevalence of RA in Indian women requires more attention to the early diagnosis and treatment of RA.
Inter- and intra-species interactions between meat plant environmental bacteria and a non-biofilm-forming Escherichia coli O157:H7 strain in co-culture biofilms
Authors: Visvalingam Jeyachchandran , Zhang Peipei , Yang Xianqin
Published: February 2025

This study evaluated the impact of meat-processing environmental bacteria (MPB) on biofilm formation by Escherichia coli O157:H7 in dual-species cultures. Biofilm development by 50 MPB and E. coli O157:H7 was assessed using crystal violet staining. Four MPB and E. coli O157:H7 combinations were evaluated further for viable cell numbers. A chlorinated alkaline agent and a quaternary ammonium-based agent were evaluated for their ability to remove biofilms. The E. coli O157:H7 strain was a non-biofilm former. In dual-species biofilms, if the companion MPB did not produce detectable biofilm, then the pairing did not produce measurable biofilms either. The interaction effect between MPB and E. coli O157:H7 was predominantly no-effect (neutral). Among the four MPB isolates tested by viable cell enumeration method, only generic E. coli genotype 136 reduced viable numbers of E. coli O157:H7 in dual-strain biofilm. Sequential treatment with cleaning and sanitizing treatment provided a better removal of biofilm than a single-agent treatment.
Characterization of green-synthesized zinc oxide nanoparticles and its influence on post-harvest shelf-life of garlic against black mold disease caused by Aspergillus niger
Authors: Kumawat Govind , Rajpurohit Deepak , Vyas Divya , Bhojiya Ali Asger , Upadhyay Sudhir Kumar , Jain Devendra
Published: February 2025

Garlic is an important spice crop used for flavoring food and has a long history of use in traditional medicine. However, black mold is a common fungal disease affecting garlic, which was caused by an Aspergillus infection. This disease significantly impacts both the production and quality of garlic. Therefore, this study aimed to evaluate the antifungal activity of novel green-synthesized zinc oxide nanoparticles (ZnO-NPs) against black mold diseases in garlic. An environmentally friendly green synthesis technique was used to produce ZnO-NPs using zinc-tolerant bacteria Serratia sp. (ZTB24). In the present study the experimental analysis viz. UV-Vis spectroscopy at 380 nm, transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential confirmed the successful biosynthesis of green ZnO-NPs from Serratia sp. The poisoned food technique and spore germination test revealed the antifungal activities of ZnO-NPs against A. niger under in vitro conditions. The presence of disease-causing A. niger fungus was confirmed through its isolation from infected garlic bulbs, and it was further identified at the molecular level using inter-transcribed sequence (ITS) rDNA sequencing. ZnO-NPs reduced the mycelial growth up to 90% and the 73% spore germination at 250 μg ml−1 concentration of ZnO-NPs. The ZnO-NPs were further used in vivo at different concentrations (50, 100, 250, and 500 ppm) in the post-harvest treatment of garlic. The percentage of disease severity was assessed after 7 and 14 days, and the application of 500 ppm of ZnO-NPs exhibited 0% disease severity in the pre-inoculation method, while disease severity of black mold disease in garlic plant was recorded at 1.10% after 7 days and 0.90% after 14 days in the post-inoculation method, compared to the control group. Hence, the antifungal activity of ZnO-NPs synthesized using the green technique paves the way for the development of natural fungicides, offering a sustainable and renewable alternative to traditional chemical control methods.
Predictive value of early neutrophil-to-lymphocyte ratio and C-reactive protein in pediatric steroid-sensitive nephrotic syndrome
Authors: Maimaititusvn Gulinuer , Jvnaiti Nilupaer , Kulaixi Maierhaba , Liu Fang
Published: February 2025

Objective

This study aims to investigate the predictive value of early neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) levels for relapse and adverse prognosis within one year in children diagnosed with steroid-sensitive nephrotic syndrome (SSNS).

Methods

This study included a total of 145 pediatric patients diagnosed with steroid-sensitive nephrotic syndrome (SSNS) between January 2016 and December 2021. We collected early neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) levels, along with relevant clinical data, and conducted a one-year follow-up of the patients. Based on the follow-up outcomes, the patients were categorized into two groups: those who experienced a relapse and those who did not. We assessed the diagnostic and predictive value of NLR and CRP for relapse within one year using receiver operating characteristic (ROC) curve analysis and the Cox proportional hazards regression model.

Results

After an average follow-up period of one year, 95 patients (65.52%) experienced relapse, while 50 patients (34.48%) did not. Significant differences were noted between the relapse and non-relapse groups regarding neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), 24-hour urinary protein levels, age at onset, and parental education level (P < 0.05). Cox proportional hazards regression analysis identified age at onset, NLR, CRP, and 24-hour urinary protein levels as significant risk factors for relapse in patients with steroid-sensitive nephrotic syndrome (SSNS). Receiver operating characteristic (ROC) curve analysis for the combined prediction of relapse using NLR, CRP, and 24-hour urinary protein levels demonstrated good predictive value, with an area under the curve (AUC) of 0.858 (95% CI: 0.80–0.916, P < 0.001). Kaplan-Meier survival analysis indicated that patients with elevated NLR (≥ 2.90) and CRP (≥ 25.30) exhibited the highest relapse rates and shorter survival times. Further Cox proportional hazards analysis revealed that children in the high NLR and high CRP groups were at an increased risk of relapse, rehospitalization, infection, prolonged cumulative steroid use, renal insufficiency, secondary hypertension, and other adverse outcomes within one year.

Conclusion

Early levels of Neutrophil-to-Lymphocyte Ratio (NLR) and C-Reactive Protein (CRP) demonstrate significant predictive value for relapse and adverse prognosis within one year in children with Steroid-Sensitive Nephrotic Syndrome (SSNS). These markers can serve as effective tools for auxiliary clinical assessment.
Pyrotinib-assisted whole brain radiotherapy alleviates HER2-positive advanced breast cancer and brain metastases: a prospective study in patients
Authors: Zhou Fulin , Zhang Cui , He Mingyuan , Ren Yu , Yue Hongshuang , Tan Zhihua , Zhang Shaolin , Li Yong , Liu Shu
Published: February 2025

Purpose

The whole-brain radiotherapy (WRBT)-based therapeutic efficacy is often limited against human epidermal growth factor receptor 2 (HER2+)-positive advanced breast cancer (BC) and brain metastases (BM), requiring more effective treatment options. This prospective study evaluates the effectiveness and safety of combining WBRT with pyrotinib in patients with HER2+ advanced BC and BM.

Methods

The enrolled patients (n = 26, from April 2019 to March 2022) were divided into two treatment groups. Group 1 (p-WBRT) received pyrotinib initially, followed by subsequent WBRT. Group 2 (WBRT-p) received WBRT concurrently with pyrotinib. The intracranial progression-free survival (iPFS) was determined.

Results

In the WBRT-p group (n = 11), the median iPFS was recorded as 25.0 months (95% CI, 15.3–34.7), while the overall survival (OS) rates in 1–4 years were 100, 54.5, 9.1, and 0%, respectively. The intracranial objective response rate (iORR) and intracranial clinical benefit rate (iCBR) were 63.6 and 90.9%, respectively. In the p-WBRT group (n = 15), the median iPFS was around 22.0 months (95% CI, 4.3–39.7), and the OS rates in 1–4 years were 100, 53.3, 33.3, and 6.7%, respectively. The iORR and iCBR values were 66.7 and 80.0%, respectively. Notably, no significant differences in iPFS, OS, iORR, and iCBR were observed between treatment groups. Although some instances of adverse events, such as vomiting and reduced white blood cells and neutrophil counts, were evident, these adverse events were grades 1–3.

Conclusion

WBRT combined with pyrotinib exhibited exceptional tolerability, showing long iPFS in patients with HER2+ advanced BC and BM.
Evaluation of fluxon synapse device based on superconducting loops for energy efficient neuromorphic computing
Authors: Kumar Ashwani , Goteti Uday S. , Cubukcu Ertugrul , Dynes Robert C. , Kuzum Duygu
Published: February 2025

With Moore’s law nearing its end due to the physical scaling limitations of CMOS technology, alternative computing approaches have gained considerable attention as ways to improve computing performance. Here, we evaluate performance prospects of a new approach based on disordered superconducting loops with Josephson-junctions for energy efficient neuromorphic computing. Synaptic weights can be stored as internal trapped fluxon states of three superconducting loops connected with multiple Josephson-junctions (JJ) and modulated by input signals applied in the form of discrete fluxons (quantized flux) in a controlled manner. The stable trapped fluxon state directs the incoming flux through different pathways with the flow statistics representing different synaptic weights. We explore implementation of matrix–vector-multiplication (MVM) operations using arrays of these fluxon synapse devices. We investigate the energy efficiency of online-learning of MNIST dataset. Our results suggest that the fluxon synapse array can provide ~100× reduction in energy consumption compared to other state-of-the-art synaptic devices. This work presents a proof-of-concept that will pave the way for development of high-speed and highly energy efficient neuromorphic computing systems based on superconducting materials.
Association between advanced lung cancer inflammation index and acute gouty arthritis in Dalian, China: a cross-sectional study
Authors: Xiu Ziran , Gao Zhengnan , Luo Lan
Published: February 2025

Introduction

Acute gouty arthritis (AGA) is an inflammatory joint disease. The advanced lung cancer inflammation index (ALI) evaluates inflammation. This study investigates the association between ALI and AGA.

Methods

We included 652 participants in this cohort study, dividing them into two groups: those with AGA and a control group without AGA. We employed logistic regression to examine the ALI-AGA relationship, using restricted cubic splines (RCS) to assess dose–response relationships, performing subgroup analyses, and conducting interaction tests. K-fold cross-validation was applied for model assessment. Receiver operating characteristic (ROC) curves were applied to visualize and compare the predictive value of ALI and other inflammatory indices for AGA.

Results

Among the 652 participants, the AGA group exhibited significantly lower ALI values compared to the control group. Multivariate logistic regression identified an inverse relationship between ALI and AGA. RCS analysis indicated an L-shaped non-linear relationship between ALI levels and AGA, with inflection points at an ALI of 23.38. Subgroup analyses showed no significant interactions between ALI levels and AGA after stratifying by age, hypertension, coronary heart disease (CHD), and diabetes (DM). The results from the ROC curves indicate that ALI may serve as a better predictor of AGA.

Conclusion

This cross-sectional study found a significant inverse correlation between ALI levels and AGA prevalence. Moreover, the ALI could serve as a more accurate diagnostic tool for AGA and offer a novel approach for further investigating the relationship between inflammation and AGA.
Wnt/β-catenin signaling pathway: an attractive potential therapeutic target in osteosarcoma
Authors: Ding Yi , Chen Qin
Published: February 2025

Osteosarcoma (OS) is the most common bone malignancy in children and adolescents, and although current neoadjuvant chemotherapy has shown efficacy against OS, the long-term survival rate for patients with OS remains low, highlighting the need to find more effective treatments. In cancer cells, abnormal activation of signaling pathways can widely affect cell activity from growth and proliferation to apoptosis, invasion and metastasis. Wnt/β-catenin is a complex and unique signaling pathway that is considered to be one of the most important carcinogenic pathways in human cancer. Research have confirmed that the Wnt/β-catenin signaling pathway is an important driving factor for the occurrence and development of osteosarcoma, and abnormal activation of this pathway can promote the pathological processes of cell proliferation, invasion, migration, tumor angiogenesis and chemical resistance of osteosarcoma. However, inhibition of Wnt/β-catenin signaling pathway can effectively inhibit or reverse the above pathological processes. Therefore, manipulating the expression or function of the Wnt/β-catenin pathway may be a potential targeted pathway for the treatment of OS. In this review, we describe the characteristics of the Wnt/β-catenin signaling pathway and summarize the role and mechanism of this pathway in OS. This paper discusses the therapeutic significance of inhibiting or targeting Wnt/β-catenin pathway in OS and the shortcomings of current studies on this pathway in OS and the problems to be solved. This review helps us to understand the role of Wnt/β-catenin on OS, and provides a theoretical basis and new ideas for targeting Wnt/β-catenin pathway as a therapeutic target for OS.
Global research prospects and trends in TFH cells and tumors: a bibliometric analysis
Authors: Lei Hao , Hu Jin , Zhu Junpeng , Li Runze , Zhao Yu , Zhao Yaqi , He Guisheng , Song Tao , Lu Chong , Zheng Wuping , Li Lei , Liu Chunping , Chen Hengyu
Published: February 2025

Background

T follicular helper (TFH) cells, a subset of CD4+Th cells, play a critical role in B cell activation, proliferation, and differentiation primarily within B follicles in secondary lymphoid organs, essential processes for effective antibody responses. TFH cells are also implicated in various conditions, including autoimmune diseases, cancer, infectious diseases, allergies, and vaccine reactions. Despite their broad impact, a review of the literature on TFH cells and tumors has not been conducted. We aimed to fill this gap by providing a detailed analysis of the research landscape concerning TFH cells and tumors.

Method

We conducted a bibliometric analysis of literature on TFH cells and tumors from 2012 to 2024 using the Web of Science Core Collection (WoSCC). For an analysis of the global research landscape, we employed VOSviewer (version 1.6.20), CiteSpace 6.2.R6 software, and the “bibliometric” package in R language (version 4.3.2) to evaluate data on countries/regions, authors and cited authors, institutions, journals, references, and keywords. We also conducted a systematic review to summarize the global research trends, prospects, and hotspots in this field.

Results

Our analysis included contributions from 60 countries/regions, 7,864 authors, 35,853 cited authors, 1,756 institutions, 385 academic journals, 50883 references, 222 keywords, and 1,181published papers. Over the past decade, the volume of research on TFH cells and tumors had consistently increased. China published the most papers, more than double that of the United States. The top 2 authors ranked by publication volume were Gaulard, Philippe (14 articles, 379 citations), and De leval, Laurence (12 articles, 236 citations) Notably, 9 of the top 10 most published institutions were from China. Frontiers in Immunology and Immunity were the leading journals in publications and citations. A cluster analysis revealed a shift in research focus from “expression”,”B cells” and “survival” to “tumor microenvironment”, “tumor infiltrating immune cells” and “immune infiltration” in recent years.

Conclusion

This bibliometric analysis suggests that TFH cells hold significant research value and potential clinical applications in tumor immunotherapy. Moreover, the bibliometric analysis offers valuable references and guidance for related research endeavors. It also points out the prevailing issues and challenges in TFH cell research, and underscores the need for further basic and clinical research to advance the related fields.
Survival prognostic nomogram for young metastatic non-small cell lung cancer: a study of the US SEER database and a Chinese cohort
Authors: Li Yu , Cao Lei , Ding Yawen , Liu Lei , Zhu Yonggang , Cao Feng
Published: February 2025

Objective

Young patients diagnosed with non-small cell lung cancer (NSCLC) present unique clinical, pathological, and genetic features, resulting in a highly heterogeneous patient population. The current TNM staging system is insufficient for accurately predicting their prognosis. This study aims to develop a nomogram model for survival prediction in young patients with metastatic NSCLC at initial diagnosis and further verify the effectiveness of the model.

Methods

This study enrolled 961 young patients diagnosed with metastatic NSCLC in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2017. The patients were allocated into a training cohort (n = 673) and an internal validation cohort (n = 288). An additional 215 patients from the Fourth Hospital of Hebei Medical University were included as a Chinese external validation cohort. Univariate and multivariate Cox regression analyses were conducted in the training cohort to identify independent risk factors influencing survival, which were used to develop a nomogram model. The model’s effectiveness was evaluated using C-index, calibration curve, receiver operating characteristic (ROC) curve, decision curve analysis (DCA) curve, and Kaplan–Meier survival curve.

Results

The multifactorial Cox regression model identified eight independent risk factors influencing overall survival (OS): race, marital status, histological type, T stage, N stage, liver metastasis, chemotherapy, and radiotherapy (all P < 0.05). These factors were incorporated into the nomogram, which achieved a C-index of 0.673 [95% confidence interval (CI) = 0.661–0.685]. The nomogram exhibited excellent prognostic value in both internal (C-index = 0.662, 95% CI = 0.643–0.681) and external (C-index = 0.724, 95% CI = 0.702–0.746) validation cohorts. In addition, calibration curves for 0.5-,1-, 2-, 3-, and 5-year OS probabilities showed close agreement between predicted and observed survival outcomes across various time points. Additionally, ROC curve analysis and Kaplan–Meier curves highlighted the robust discriminatory power of the model based on survival outcomes. Moreover, the DCA analysis revealed that the incremental net benefit of this model was significantly superior to that of the TNM staging system alone.

Conclusions

A nomogram model has been developed and validated to accurately predict the OS of young patients with metastatic NSCLC at initial diagnosis, demonstrating superior performance compared to the traditional TNM staging system. This model offers valuable guidance for precise predictions and making rational treatment decisions in clinical practice.
Identification of potential diagnostic targets and therapeutic strategies for anoikis-related biomarkers in lung squamous cell carcinoma using machine learning and computational virtual screening
Authors: Zhang Xin , Zou Jing , Ning Jinghua , Zhao Yanhong , Qu Run , Zhang Yuzhe
Published: February 2025

Objective

Lung squamous cell carcinoma (LUSC) is a common subtype of non-small cell lung cancer (NSCLC) characterized by high invasiveness, high metastatic potential, and drug resistance, resulting in poor patient prognosis. Anoikis, a specific form of apoptosis triggered by cell detachment from the extracellular matrix (ECM), plays a crucial role in tumor metastasis. Resistance to anoikis is a key mechanism by which cancer cells acquire metastatic potential. Although several studies have identified biomarkers related to LUSC, the role of anoikis-related genes (ARGs) remains largely unexplored.

Methods

Anoikis-related genes were obtained from the Harmonizome and GeneCards databases, and 222 differentially expressed genes (DEGs) in LUSC were identified via differential expression analysis. Univariate Cox regression analysis identified 74 ARGs significantly associated with survival, and a prognostic model comprising 8 ARGs was developed using LASSO and multivariate Cox regression analyses. The model was internally validated using receiver operating characteristic (ROC) curves and Kaplan-Meier (K-M) survival curves. Differences in immune cell infiltration and gene expression between high- and low-risk groups were analyzed. Virtual drug screening and molecular dynamics simulations were performed to evaluate the therapeutic potential of CSNK2A1, a key gene in the model. Finally, in vitro experiments were conducted to validate the therapeutic effects of the identified drug on LUSC.

Results

The 8-gene prognostic model demonstrated excellent predictive performance and stability. Significant differences in immune cell infiltration and immune microenvironment characteristics were observed between the high- and low-risk groups, suggesting the critical role of ARGs in shaping the immune landscape of LUSC. Virtual drug screening identified Dihydroergotamine as having the highest binding affinity for CSNK2A1. Molecular dynamics simulations confirmed that the CSNK2A1-Dihydroergotamine complex exhibited strong binding stability. Further in vitro experiments demonstrated that Dihydroergotamine significantly inhibited LUSC cell viability, migration, and invasion, and downregulated CSNK2A1 expression.

Conclusion

This study is the first to construct an anoikis-related prognostic model for LUSC, highlighting its role in the tumor immune microenvironment and providing insights into personalized therapy. Dihydroergotamine exhibited significant anti-LUSC activity and holds promise as a potential therapeutic agent. CSNK2A1 emerged as a robust candidate for early diagnosis and a therapeutic target in LUSC.
Cordycepin attenuates NLRP3/Caspase-1/GSDMD-mediated LPS-induced macrophage pyroptosis
Authors: Liu Zige , Lv Li , Wei Jiao , Xie Yuli , Jili Mujia , Huang Yian , Yang Rirong , Luo Yu
Published: February 2025

Pyroptosis, a form of programmed cell death driven by the NLRP3 inflammasome, is a key contributor to inflammation in various diseases. This study aimed to investigate the anti-inflammatory mechanisms of cordycepin, focusing on its role in macrophage pyroptosis. Molecular docking analysis was performed to evaluate the binding affinity of cordycepin to key pyroptosis-related proteins, including NLRP3, Caspase-1, and GSDMD. RAW264.7 cells were pre-treated with cordycepin to assess its effects on pyroptosis. Key measurements included reactive oxygen species (ROS) levels, xanthine oxidase (XO) activity, and the expression of NLRP3, Caspase-1, and GSDMD. Additionally, lactate dehydrogenase (LDH) release, interleukin (IL)-1β and IL-18 levels in the culture supernatant, and macrophage cell death rates were evaluated using Hoechst 33342/PI dual staining. The results demonstrated that cordycepin exhibits strong binding affinity for NLRP3, Caspase-1, and GSDMD. Cordycepin pre-treatment significantly reduced ROS levels and XO activity, inhibited the expression of NLRP3, cleaved-Caspase-1, and cleaved-GSDMD, and decreased pyroptosis-associated inflammatory cytokines IL-1β and IL-18, along with Caspase-1 activity. Furthermore, cordycepin reduced the macrophage pyroptosis rate. In conclusion, cordycepin inhibits macrophage pyroptosis by reducing XO activity, suppressing ROS production, and regulating the expression of key molecules in the NLRP3/Caspase-1/GSDMD pathway. These findings provide a strong experimental basis for the potential development of cordycepin as a novel anti-inflammatory agent.
Navigating exercise attitudes and emotional positivity in adulthood during the COVID-19 pandemic: evidence from Shandong Province
Authors: Meng Ran , Dong Chen
Published: February 2025

Introduction

During the onset of the COVID-19 pandemic, understanding public attitudes and emotional responses towards physical exercise became crucial. This study aimed to explore the relationship between positive emotions and attitudes towards physical exercise among adults in Shandong Province, China, and to identify the influence of demographic factors such as gender, age, and education levels on these attitudes and emotions.

Methods

A cross-sectional study was conducted among 404 adults in Shandong Province, China. Data were collected through surveys that assessed participants’ attitudes towards physical exercise and their emotional positivity. Quantitative analysis was performed to examine the correlations and differences based on demographic variables, including gender, age, and education levels.

Results

A robust positive correlation was found between positive emotions and attitudes towards physical exercise, with an emotional positivity ratio of 2.01±1.38% among respondents. Significant differences in attitudes and emotional positivity were observed based on demographic factors. Specifically, male participants had a higher mean score in behavioral intention and control compared to females. Older adults (>41 years) demonstrated more positive exercise attitudes, with a higher total score of 4.05 ± 0.54 compared to younger age groups. Additionally, respondents with a graduate degree and above reported the highest emotional positivity rate, outpacing those with lower educational levels.

Discussion

The findings indicate that demographic factors, including gender, age, and education levels, play a crucial role in shaping attitudes and emotional responses towards exercise, especially during a global health crisis. These insights highlight the importance of considering demographic differences when promoting physical exercise and designing public health interventions. Future research should further explore the underlying mechanisms and potential interventions to enhance positive attitudes and emotional responses towards physical exercise across diverse populations.
Assessing the feasibility of using salivary microRNAs as biomarkers to distinguish between chronic stress and childhood trauma in African American young women in an exploratory pilot study
Authors: Holliday Erica , Bagasra Anisah , Bagasra Omar , Pandey Pratima
Published: February 2025

Introduction

The current study assessed the impact of self-reported stress measures on microRNA (miRNA) profiles in saliva exosomes. Saliva is one of the most accessible and non-invasive bodily fluids and exosomal miRNAs in saliva could be useful in (1) measuring stress states and (2) distinguishing between individuals suffering from high levels of chronic stress vs. adverse childhood experiences (ACEs). miRNAs are small, noncoding RNAs that act as gene regulators. Several studies have shown differential expressions of certain miRNA in neurological diseases and in stress, post-traumatic stress syndrome (PTSD) and anxiety. Detailed analyses of miRNA expressions and profiling of miRNAs among populations with various exposures to traumatic and life stressors have not been carried out. The goal of our study was to discover miRNAs associated with high chronic stress or childhood trauma.

Method

This study sought to explore miRNA expression in African American young women from a small, southern Historically Black College and University (HBCU). Twelve participants completed the social readjustment rating scale (SRRS), ACEs scale, and saliva collection and were divided into three groups based on ACE and chronic stress score: Low Chronic Stress (LCS; n = 4); High Chronic Stress (HCS; n = 4); High Chronic Stress + High ACEs (HCS+HA; n=4). A custom-made miRNA Taqman-Array tested for fold change in four miRNAs (i.e., miR-19b, miR-187, miR-34a and miR-135-3p).

Results

There was a significant downregulation of miR-19b (χ2(2, N=12) = 7.42, p < 0.01, η²= 0.915), miR-187 (χ2 (2, N = 12) = 7.36, p < 0.05, η²= 0.598), and miR-34a (χ2(2, N = 12) = 7.42, p < 0.05, η²= 0.60). in both the HCS and the HCS+HA groups vs. LCS. Interestingly, miR-135-3p (χ2(2, N = 12) = 8.00, p < 0.05, η²= 0.67. was upregulated in the HCS group vs. LCS and HCS+LA. Expression for miR-135-3p was not significantly different between LCS + HCS+HA.

Conclusion

Our analyses shows that miRNA extracted from salivary exosomes can be a reliable biomarker for stress and miR-135a-3p appears to be the most upregulated between LCS and HCS individuals and a potential candidate to corroborate self-reports on self-assessments and predict negative health outcomes. Given that HCS+HA did not show an upregulation of miR-135-3p but had similar expression in the other three miRs compared to HCS group may indicate an adaptive stress response following early life adversity. Further, downregulation in miR-135-3p in individuals with high levels of chronic stress could point to unknown childhood trauma exposure (e.g. closed adoptions, dissociative amnesia, abuse). A major limitation in this study is the small sample size and future directions include determining the predictive validity of these miRNAs in predicting onset of physical and mental health outcomes for early interventions in larger studies.
Epidemiology, outcomes, and risk factors of traumatic brain injury in Bangladesh: a prospective cohort study with a focus on road traffic injury-related vulnerability
Authors: Rahman Farah Naz , Das Sukriti , Kader Manzur , Mashreky Saidur Rahman
Published: February 2025

Background

Low-and middle-income countries bear a disproportionate burden of traumatic brain injury (TBI), with significant consequences for affected individuals and health systems. However, evidence on the incidence, risk factors, and associated vulnerability—particularly from road traffic injuries (RTIs)—remains limited in South Asia, including Bangladesh, which has one of the highest RTI burdens globally. This study aimed to investigate the epidemiology, clinical characteristics, health outcomes of TBI, and the vulnerability and risk factors associated with RTI-related TBI in Bangladesh.

Methods

A prospective observational cohort study was conducted at Dhaka Medical College and Hospital from May to June 2017. Data were collected during patient admission and at 30-day follow-up (or discharge). Registered medical practitioners used a semi-structured questionnaire to collect data, including the Glasgow Coma Scale (GCS), Glasgow Outcome Scale (GOS), and EuroQol-5D-3L. Descriptive analysis was used to present the incidence, clinical characteristics, outcomes, and pre-hospital care scenarios for TBI. The Chi-square test and multivariable logistic regression analysis were performed to identify the vulnerability of RTI-related TBI and its predictive factors for mortality.

Results

The study followed 659 TBI cases. The mean age was 32.3 years, and the majority (80.1%) were male. RTIs were the leading cause of TBI (62%), followed by physical assault (17%) and falls (16%). The mortality rate was 10.3% (n = 68). Patients with RTI-related TBI had 1.95 times higher odds (95% CI 1.21–3.14) of severe GCS scores (<8) and three times higher odds (95% CI 1.59–5.78) of mortality compared to other causes. Predictive factors for mortality included severe GCS (<8) (aOR 8.1, p < 0.01, 95% CI 4.1–16.2), loss of consciousness >1 h (aOR 4.4, p < 0.01, 95% CI 1.4–8.1), and treatment initiation delay >8 h (aOR 2.8, p < 0.01, 95% CI 1.4–5.5). Nearly all patients lacked first aid and emergency transport, and two-thirds were referred from primary and secondary facilities, with one-third receiving no treatment before referral.

Conclusion

RTI is the most vulnerables, duration of unconsciousness, and treatment delays are key predictors of mortality. These findings can inform policy for prevention and management of TBI in Bangladesh and similar settings.