bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship between the 3D electroanatomical mapping parameters of the left atrial posterior wall and the recurrence of paroxysmal atrial fibrillation
Authors: Chen Yuqiao , Zhuang Jun , Li Xiaolong , Zhang Chunqin , Cao Xinfu , Xu Zhiwei , Feng Xiu
Published: February 2025

Background

Pulmonary vein isolation (PVI) remains the cornerstone of catheter ablation in paroxysmal atrial fibrillation (PAF). However, the recurrence of AF after PVI needs further investigation. The left atrial posterior wall (LAPW) is embryologically related to the pulmonary vein and plays an important role in the initiation and maintenance of AF. This study aims to explore the relationship between the 3D electroanatomical mapping parameters of the LAPW and recurrence in patients with PAF.

Methods

A retrospective analysis was conducted on patients with PAF who underwent PVI. Both clinical and procedural characteristics from the enrolled subjects were collected before PVI. 3D electroanatomical mapping anatomical and electrical parameters were measured and calculated in the CARTO system. Intergroup comparisons and multivariate logistic regression analysis were performed to demonstrate the relationship between the parameters of LAPW and AF recurrence. A combined prediction model for AF recurrence was constructed in this study.

Results

A total of 120 patients were included in the final analysis. Among procedural characteristics, compared with Group 1 (no recurrence), there was a significantly larger posterior wall surface area (PWSA) (p = 0.013) and a percentage of very low-voltage area (PVLVA) (p < 0.001) in Group 2 (recurrence). Further analysis revealed that there was a significant difference between the two groups in terms of the distribution of VLVA (p = 0.026). Subsequently, in a multivariate logistic regression analysis, both PWSA and PVLVA were found to be independent risk factors for AF recurrence [odds ratio (OR): 1.457, 95% confidence interval (CI): 1.037–2.049, p = 0.030; OR: 1.059, 95% CI: 1.013–1.107, p = 0.012, respectively]. Finally, a prediction model that combined the PWSA with the PVLVA for AF recurrence was constructed to draw the receiver operating characteristic curve. The area under the curve of this model was 0.900 (0.827–0.973) (p < 0.001). The result, evaluated by using the Hosmer–Lemeshow goodness-of-fit test, showed that χ2 = 4.643 (p = 0.796).

Conclusions

This study demonstrates that both PWSA and PVLVA were independent risk factors for AF recurrence. Moreover, we proposed a model that combined the PWSA with the PVLVA to predict the recurrence of AF, which may provide an approach for screening patients with PAF who may require attention for the LAPW.
The mediating influence of self-efficacy and self-regulation in the relationship between perfectionism and listening anxiety
Authors: Movafagh Ardestani Elham , Barjesteh Hamed , Dehqan Mahmood
Published: February 2025

Introduction

This study investigates the complex relationship between perfectionism and Listening Anxiety (LA) in the context of English as a Foreign Language (EFL), with a focus on the mediating roles of Listening Self-Efficacy (LS) and Self-Regulated Learning (SRL).

Method

A sample of 350 EFL learners from various language institutes in Iran was selected through cluster random sampling and completed four validated questionnaires measuring SRL, LS, perfectionism, and LA. Structural Equation Modeling (SEM) was employed to analyze the data and provide detailed insights into the interrelationships among these variables.

Results

The results revealed significant linear relationships between the variables under study. Specifically, LS, perfectionism, and SRL were found to directly influence LA, with LS and SRL serving as stronger predictors of LA than perfectionism. In terms of predictive power, SRL ranked just behind LS.

Discussion

Both SRL and LS were significant mediators in the relationship between perfectionism and LA, suggesting that learners’ self-regulation and listening self-efficacy play key roles in how perfectionism affects LA. The findings have important implications for EFL instruction: by prioritizing LS and SRL, educators can create a more supportive, enjoyable, and effective learning environment for EFL students, ultimately reducing LA.
Cu/Co meta-interconnects for 112 Gbps high speed applications
Authors: Kim Hae-in , Wilcher Alexander , Bowrothu Renuka , Yoon Yong-Kyu
Published: February 2025

This paper presents an innovative interconnect approach called “meta-interconnect,” which utilizes a combination of copper (Cu) and cobalt (Co) metaconductor (Cu/Co-MC) to enhance signal integrity in the millimeter-wave (mm-wave) spectrum. The primary objective is to demonstrate reduced conductor losses from the skin effect compared to Cu at the 112 Gbps Nyquist frequency of 28 GHz. For the first time, a comprehensive parametric analysis is conducted using both simulation and experimentation methods to suppress the skin effect with Cu/Co-MC. Based on the optimization of Cu/Co-MC-based coplanar waveguide (CPW) transmission lines, a minimum insertion loss of only 0.08 dB/mm at 28 GHz, which is 0.06 dB/mm less than that of the Cu counterpart, has been demonstrated, which represents a 42.86% reduction in conductor power losses. Additionally, Cu/Co-MC-based CPWs meet the sub-0.1 dB/mm channel loss target. The study verifies the impact that the thickness and number of Cu/Co-MC layers have on device performances. This provides valuable insights into the optimizing MC configurations, which in this study are 250 nm thick Cu and 40 nm thick Co. Cu/Co-MC pairs with optimized layers and total thicknesses demonstrate significant improvements in insertion loss and thermal noise. These findings highlight the potential benefits of the Cu/Co-MC-based meta-interconnect technology for data center high-speed serial bus applications, offering a promising solution for achieving high signal integrity in the mm-wave spectrum, contributing to the overall understanding and its MCs translation to commercial applications.
Association between LDL/HDL ratio and hypertension in Chinese middle-aged and older adults: a cross-sectional and longitudinal analysis based on CHARLS LDL/HDL ration and hypertension
Authors: Lai Weicheng , Chen Xiao , Wang Lerui , Wu Liangxiu , Li Xin , Zhou Boda
Published: February 2025

Introduction

Hypertension is a global public health issue and major risk factor for cardiovascular disease (CVD). Low-density lipoprotein/high-density lipoprotein ratio (LDL/HDL Ratio, LHR) is an important indicator of lipid metabolism related to CVD. However, the relationship between LHR and the prevalence and incidence of hypertension has not been reported in large populations. This study aims to investigate the association between LHR and hypertension in middle-aged and elderly population.

Methods

This study utilized the China Health and Retirement Longitudinal Study (CHARLS) database from 2011 to 2020. Cross-sectional study was employed to analyze the association between LHR and the prevalence of hypertension; longitudinal analysis was used to examine the association between LHR and the incidence of hypertension. Eligible participants were adults aged 45 years and older with complete LHR and self-reported hypertension records. Multivariate logistic regression, smooth curve fitting, threshold effect analysis was performed.

Results

In the cross-sectional study, we included 13,150 participants. After adjusting for potential confounders, each one-unit increase in LHR was associated with a 22% increase in the prevalence of hypertension (OR = 1.22, 95% CI: 1.15-1.30, P < 0.0001). The association between LHR and hypertension was consistent across different subgroups, with higher LHR being more strongly associated with increased hypertension prevalence in females and non-smokers. Our results revealed a linear relationship between LHR and hypertension prevalence. Longitudinal analysis showed that, among participants without hypertension in 2011, after 7 years of follow-up, the association between LHR and hypertension incidence remained robust after adjusting for a wide range of demographic, clinical, and biochemical variables (P < 0.05).

Conclusions

These results demonstrated significant positive association between LHR and the prevalence & incidence of hypertension, in a nationwide representative middle-aged and elderly population in China.
Adults with Phenylketonuria have suboptimal bone mineral density apart from vitamin D and calcium sufficiency
Authors: Hanusch Beatrice , Schlegtendal Anne , Grasemann Corinna , Lücke Thomas , Sinningen Kathrin
Published: February 2025

Introduction

Improvement of early diagnosis and treatment in patients with Phenylketonuria (PKU) allowed for healthy survival into adulthood of these patients, but non-neurological health impairments of unknown etiology emerged. One of these is impaired bone health that manifests in adolescence and adulthood, potentially depending not only on treatment adherence but also on additional lifestyle factors and nutrition.

Methods

Eighteen adults with PKU (18.3–51.6 years, ♀ n = 11) and 19 age- and gender-matched controls (18.3–54.9 years, ♀ n = 10) participated in the study. Bone metabolism–related parameters (BMRPs) in plasma, serum, and urine were analyzed. Dietary habits and lifestyle factors were obtained from questionnaires; a 6-min walk test and a dual X-ray absorptiometry measurement at two sites were performed. Phenylalanine (Phe) serum concentrations from the 5 years prior to study participation were collected from the patients’ charts.

Results

Patients had reduced bone mineral density (BMD) T-score in hips (−0.67 ± 1.05) and lumbar spine (−0.71 ± 1.11, both p = 0.018). Most BMRPs in plasma, serum, and urine, as well as markers of oxidative stress did not differ from healthy controls. Whereas 89% of adults with PKU were vitamin D–sufficient, only 68% of controls reached vitamin D sufficiency. 25-Hydroxy vitamin D concentration was significantly higher in adults with PKU than that in controls [33.1 ng/mL (26.2–40.3) vs. 23.4 ng/mL (17.2–24.9); p < 0.001], whereas parathyroid hormone concentrations showed no difference [PKU: 27.6 pg/mL (19.6–42.8) vs. Co: 36.1 pg/mL (29.2–40.8); p = 0.089]. Neither Phe blood concentration nor dietary habits or lifestyle factors were associated with BMD in regression analysis.

Conclusion

Neither dietary habits nor lifestyle factors showed an association with BMD in this group of adults with PKU, whereas BMD was reduced.
Profile of DHX37 gene defects in human genetic diseases: 46,XY disorders of sex development
Authors: Peng Huifang , Peng Wenyuan , Chen Jiali , Hu Keyan , Zhang Yingyu , Ma Yujin , Jiang Hongwei
Published: February 2025

The RNA helicase DHX37 gene is involved in ribosomal biological processes, and linked to human genetic diseases associated with 46,XY disorders of sex development (46,XY DSD) or neurodevelopment. Recently, relevant reports have primarily focused on 46,XY DSD. However, there is still a lack of overall understanding of the genetic characteristics, phenotype, etc. of the DHX37 gene in human genetic diseases, and its molecular mechanism is not fully understood. We searched literature databases and summarized and analyzed all the literature related to DHX37 to date, including case reports, cohort studies, and molecular mechanism studies, to comprehensively demonstrate the role of DHX37 in human genetic diseases. Sixty patients were reported to have DHX37-related 46,XY DSD, with p.R308Q, p.R674W variants being the two most common mutation hotspots, accounting for 36.67% and 11.67% of cases respectively. In DSD cohorts, DHX37 gene mutations have different detection frequencies (0.77%–45.45%), whereas in testicular regression syndrome and 46,XY gonadal dysgenesis cohorts, they have a high detection rate. The gonadal development and fertility of female (46,XX) carriers with DHX37 gene mutations are not affected; however, incomplete penetrance may be observed in males (46,XY). The treatments are primarily surgical intervention and hormone replacement therapy administered at appropriate times; however, the long-term prognosis remains unknown. Although the molecular mechanism of DHX37 mutation related 46,XY DSD is unclear, ribosome synthesis, cell cycle regulation, and the NF-κB and Wnt pathways may be affected. This review summarizes the profile of DHX37 defects in human genetic diseases.
Porphyromonas gingivalis: a potential trigger of neurodegenerative disease
Authors: Huang Ziyan , Hao Miao , Shi Naixu , Wang Xinyu , Yuan Lin , Yuan Haotian , Wang Xiaofeng
Published: February 2025

Porphyromonas gingivalis (P. gingivalis) is a gram-negative bacterium and the main causative agent of periodontitis, a disease closely associated with the development of periodontal disease. The progression of periodontitis, a chronic infectious disease, is intricately linked to the inflammatory immune response. Inflammatory cytokines act on periodontal tissues via immunomodulation, resulting in the destruction of the periodontal tissue. Recent studies have established connections between periodontitis and various systemic diseases, including cardiovascular diseases, tumors, and neurodegenerative diseases. Neurodegenerative diseases are neurological disorders caused by immune system dysfunction, including Alzheimer’s and Parkinson’s diseases. One of the main characteristics of neurodegenerative diseases is an impaired inflammatory response, which mediates neuroinflammation through microglial activation. Some studies have shown an association between periodontitis and neurodegenerative diseases, with P. gingivalis as the primary culprit. P. gingivalis can cross the blood-brain barrier (BBB) or mediate neuroinflammation and injury through a variety of pathways, including the gut-brain axis, thereby affecting neuronal growth and survival and participating in the onset and progression of neurodegenerative diseases. However, comprehensive and systematic summaries of studies on the infectious origin of neurodegenerative diseases are lacking. This article reviews and summarizes the relationship between P. gingivalis and neurodegenerative diseases and its possible regulatory mechanisms. This review offers new perspectives into the understanding of neurodegenerative disease development and highlights innovative approaches for investigating and developing tailored medications for treating neurodegenerative conditions, particularly from the viewpoint of their association with P. gingivalis.
Interactions between the metabolic reprogramming of liver cancer and tumor microenvironment
Authors: Yang Haoqiang , Li Jinghui , Niu Yiting , Zhou Tao , Zhang Pengyu , Liu Yang , Li Yanjun
Published: February 2025

Metabolic reprogramming is one of the major biological features of malignant tumors, playing a crucial role in the initiation and progression of cancer. The tumor microenvironment consists of various non-cancer cells, such as hepatic stellate cells, cancer-associated fibroblasts (CAFs), immune cells, as well as extracellular matrix and soluble substances. In liver cancer, metabolic reprogramming not only affects its own growth and survival but also interacts with other non-cancer cells by influencing the expression and release of metabolites and cytokines (such as lactate, PGE2, arginine). This interaction leads to acidification of the microenvironment and restricts the uptake of nutrients by other non-cancer cells, resulting in metabolic competition and symbiosis. At the same time, metabolic reprogramming in neighboring cells during proliferation and differentiation processes also impacts tumor immunity. This article provides a comprehensive overview of the metabolic crosstalk between liver cancer cells and their tumor microenvironment, deepening our understanding of relevant findings and pathways. This contributes to further understanding the regulation of cancer development and immune evasion mechanisms while providing assistance in advancing personalized therapies targeting metabolic pathways for anti-cancer treatment.
Interactions with and activation of immune cells by CD41a+ extracellular vesicles
Authors: Tamagne Marie , Khelfa Mehdi , Many Souganya , Neyrinck-Leglantier Deborah , Delorme Adèle Silane , Pinheiro Marion Klea , Andrieu Muriel , Cleophax Sabine , Pirenne France , Vingert Benoît
Published: February 2025

Introduction

The immunological profiles of CD4+ T lymphocytes (TLs) from patients with hematological malignancies differ between patients who have and have not received transfusions. There may be several reasons for these differences, including the presence of extracellular vesicles (EVs) derived from plasma membrane budding and present in the platelet concentrates. Indeed, EVs can modulate the immune system through interactions with many immune cells, but the underlying mechanisms remain incompletely understood.

Methods

We therefore investigated how interactions with CD41a+ EVs cause immune cells to change phenotype and function. CD41a+ EVs were cultured with TLs, B lymphocytes, and monocytes. Given the potential involvement of monocytes in leukemia progression, we performed a new original multi-omics study to confirm the protein changes and gene activation observed following interaction with CD41a+ EVs

Results

The CD41a+ EVs had immunomodulatory effects on all these cell types but this effect depended on the numbers of EVs. CD4+ TLs required large numbers of CD41a+ EVs for activation, whereas monocytes were the most sensitive. With the new multi-omics technique, we confirmed the direct effects of CD41a+ EVs on protein phenotype and gene activation.

Conclusion

Transfusion EVs should be considered during the immunological follow-up of patients after transfusion to detect immunological effects on malignant hemopathies, and during the development of new immunotherapies.
Patient-centered outcomes with subcutaneous immunoglobulin use for infection control in primary and secondary immunodeficiencies: data of a GEIE Spanish Registry
Authors: Martínez Mercader Sandra , Garcia-Bustos Victor , Moral Moral Pedro , Martínez Buenaventura Carmen , Escudero Vergara Elisa , Montaner Bosch María Carmen , Balastegui-Martín Héctor , Galindo Maycas Sonia , Palací Mur Berta , Escobar Palazón Marian , Moreno Mulet María , Campanero Carrasco Ignacio , López Alicia , Hernández Ruiz Carlos Daniel , Ruiz-López Laura , Guzmán Guzmán Rocío , Cabañero-Navalon Marta Dafne
Published: February 2025

Background and aim

Subcutaneous immunoglobulin (SCIg) has emerged as an alternative to intravenous administration for patients with primary (PID) and secondary immunodeficiencies (SID), offering benefits such as fewer systemic adverse reactions and greater patient autonomy. However, comprehensive real-world data on SCIg use, including clinical and patient-centered outcomes, remain scarce. This study, conducted by expert immunodeficiency nursing teams, assesses the clinical characteristics, reported adverse effects, and quality-of-life outcomes associated with SCIg therapy with different formulations in patients with PID and SID across Spain.

Methods

A multicenter, cross-sectional study was conducted across 8 immunodeficiency nursing units in Spain, involving 223 adult patients treated with SCIg from 2004 to 2024. Data on demographics, comorbidities, SCIg treatment characteristics, reported adverse events, and quality-of-life metrics (EuroQol-5D-3L, Gijón Scale) were collected and analyzed.

Results

The cohort (61.4% female, mean age: 47.1 years) included 65% PID patients, with common variable immunodeficiency being the most frequent diagnosis (39.8%). SCIg demonstrated good tolerability overall, with no significant differences in global adverse event rates between facilitated 10% (fSCIg) and 20% formulations. However, 10% fSCIg was associated with higher reported frequencies of mild local rash (58.7% vs. 36.9%, p=0.002) and fever (10.6% vs. 1.7%, p=0.01). Quality-of-life scores indicated minimal limitations in mobility and self-care, with a mean subjective health rating of 72.7/100. Patients using 20% SCIg required fewer educational sessions for self-administration compared to the 10% group.

Conclusion

The different SCIg formulations in this large, multicenter cohort was effective and generally well-tolerated, supporting its use for maintaining adequate IgG levels and promoting patient independence in PID and SID. The study’s findings advocate for tailored approaches that optimize patient satisfaction and address individual needs, emphasizing the critical role of dedicated immunodeficiency nursing teams in ensuring safe, effective, and patient-centered SCIg administration.
Plasma anti-PRTN3 IgG and IgM autoantibodies: novel biomarkers for early detection of lung adenocarcinoma
Authors: Li Yutong , Wang Linhong , Chen Fengqi , Liao Rulan , Li Jing , Cao Xiaobin , Ouyang Songyun , Dai Liping , Du Renle
Published: February 2025

Background

Proteinase 3 (PRTN3) has been recognized as a crucial target for anti-neutrophil cytoplasmic autoantibody. However, the relationship between anti-PRTN3 autoantibody and cancer remains largely unexplored.

Methods

Immunohistochemistry was used to detect the level of PRTN3 in lung adenocarcinoma (LUAD) tissue array. Enzyme-linked immunosorbent assay was conducted to measure anti-PRTN3 IgG and IgM autoantibodies in plasma from patients with early- and advanced-stage LUAD, benign pulmonary nodules (BPN) and normal control (NC). Western blotting and immunofluorescence staining were performed to confirm the presence of plasma immune response to PRTN3.

Results

PRTN3 protein was highly expressed in LUAD tissues. Elevated plasma levels of anti-PRTN3 IgG and IgM autoantibodies were also detected in LUAD, especially in early LUAD. The AUC of anti-PRTN3 IgG autoantibodies in the diagnosis of early LUAD from NC was 0.782, and from BPN was 0.761. When CEA and anti-PRTN3 autoantibodies were combined, the AUC for the diagnosis of early LUAD was significantly higher than that of CEA alone. The presence of a plasma immune response to PRTN3 in LUAD was also confirmed.

Conclusion

Anti-PRTN3 IgG and IgM autoantibodies maybe early biomarkers to differentiate LUAD from NC and BPN.
Presence of brain metastasis differentially impacts long-term survival after first-line therapy in melanoma depending on BRAF mutation status
Authors: Placke Jan-Malte , Rajcsanyi Luisa Sophie , Herbst Rudolf , Terheyden Patrick , Utikal Jochen , Pföhler Claudia , Kreuter Alexander , Mohr Peter , Gutzmer Ralf , Weichenthal Michael , Meier Friedegund , Berking Carola , Leiter Ulrike , Seier Johanna , Krefting Frederik , Tasdogan Alpaslan , Lodde Georg C. , Livingstone Elisabeth , Zimmer Lisa , Roesch Alexander , Griewank Klaus , Schadendorf Dirk , Ugurel Selma
Published: February 2025

Background

Modern therapeutic strategies have significantly improved the prognosis of advanced melanoma patients. Predictive factors of therapy response include serum LDH; however, predictive markers for long-term survival are currently largely lacking.

Patients and methods

Patients diagnosed with stage IV melanoma (AJCCv8) of cutaneous origin or unknown primary were identified from the prospective multicenter German Dermatologic Cooperative Oncology Group (DeCOG) skin cancer registry ADOREG. Baseline characteristics were compared between patient groups with short-term versus long-term survival. Statistical analysis included ROC analysis and multinomial regression analysis.

Results

Of 3066 stage IV melanoma patients entered into the ADOREG between 05/2014 and 06/2021, 395 were identified for this study, of whom 301 (76.2%) survived ≤1 year, and 94 (23.8%) survived ≥5 years after stage IV diagnosis. The median follow-up time was 6 months (range 0-129 months). Regarding the baseline characteristics, only elevated serum LDH (P <0.001) was found to be independently predicting survival ≤1 year. Type of first-line therapy, immune checkpoint inhibition (ICI) versus BRAF/MEK targeted therapy (TT), was not predictive of long-term survival ≥5 years. For survival ≤1 year, the presence of brain metastases at treatment start was an independent predictor in BRAF-mutated patients regardless if they received TT (N=113; P=0<0.001) or ICI (N=69; P=0.015), but not in BRAF-wildtype patients who received ICI (N=161; P=0.47).

Conclusions

Low serum LDH independently predicts long-term survival of stage IV melanoma patients in every subgroup of treatment type and BRAF status. Brain metastasis has a negative impact on long-term survival in BRAF-mutated, but not in BRAF-wildtype patients. Investigation of molecular features of brain metastases in BRAF-mutated vs. BRAF-wildtype melanomas may lead to new insights in tumor biology and may yield new therapeutic approaches.
CCR7A defines a subpopulation of IgD+IgM- B cells with higher IgD secreting capacity in the rainbow trout skin
Authors: Morel Esther , Herranz-Jusdado Juan German , Simón Rocío , Vicente-Gil Samuel , González Lucía , Tafalla Carolina
Published: February 2025

B cells exclusively expressing IgD on the cell surface (IgD+IgM− B cells) have been identified in mammals, where they seem to play a still not well-defined role in peripheral tolerance. These cells have also been reported in catfish (Ictalurus punctatus) peripheral blood and in several mucosal tissues of rainbow trout (Oncorhynchus mykiss), including gut, gills and skin. As in mammals, the precise function of these cells remains obscure, yet, in rainbow trout mucosal surfaces, these cells have been shown to be differentiated to plasma-like cells. Interestingly, in the gills, these IgD+IgM− B cells expressed high levels of the CC chemokine receptor 7 (CCR7), receptor that in mammals controls the migration of B and T cells to secondary lymphoid organs. In this work, we have established that this is also true for the trout skin, where CCR7 defines a specific subset of IgD+IgM− B cells that are further differentiated to a plasma-like profile than those not expressing CCR7. These findings increase the current understanding of this enigmatic B cell population and point to CCR7 as a key differentiation marker for these cells.
Role of MLIP in burn-induced sepsis and insights into sepsis-associated cancer progression
Authors: Li Zhiwei , Wang Qian , Liu Yezi , Yang Shuting , Zhao Jin , Wu Changdong , Wang Changmin
Published: February 2025

Introduction

Burn-induced sepsis is a critical clinical challenge marked by systemic inflammation, immune dysregulation, and high mortality. Macrophage-driven inflammatory pathways are central to sepsis pathogenesis, while immune cell metabolic reprogramming plays a key role in both sepsis and cancer progression.

Methods

Bioinformatics analyses using GEO, TCGA, and GTEx datasets identified MLIP-modulated genes linked to immune responses and prognosis. In vitro, LPS-stimulated HUVEC cells were used to study MLIP’s effects on inflammation and macrophage function through cell viability, ROS levels, cytokine expression, qRT-PCR, and immunofluorescence assays.

Results

MLIP-modulated genes were associated with immune-related metabolic pathways in both sepsis and cancer. Epigenetic analysis showed MLIP expression is regulated by promoter methylation and chromatin accessibility. Prognostic analyses revealed MLIP’s impact on survival outcomes across cancer types. In vitro, MLIP reduced inflammation, oxidative stress, and macrophage hyperactivation.

Conclusions

MLIP regulates immune-metabolic dynamics in burn-induced sepsis, influencing macrophage activity and oxidative stress. Its role in metabolic reprogramming suggests MLIP as a potential therapeutic target linking immune modulation and cancer progression. Further research on MLIP’s role in immune evasion and tumor metabolism may inform novel therapeutic strategies.
Efficacy and safety of sintilimab combined with trastuzumab and chemotherapy in HER2-positive advanced gastric or gastroesophageal junction cancer
Authors: Liu Zeyu , Liu Aina , Li Ming , Xiang Jinyu , Yu Guohua , Sun Ping
Published: February 2025

Background

To evaluate the efficacy and safety of sintilimab in combination with trastuzumab and chemotherapy for HER2-positive advanced gastric/gastroesophageal junction cancer (GC/GEJC).

Methods

HER2-positive advanced GC/GEJC patients admitted to our department between January 2018 and October 2024 were included in this study. Patients who received sintilimab in combination with trastuzumab and chemotherapy were assigned to cohort A, while patients who received trastuzumab and chemotherapy alone were assigned to cohort B. The primary endpoints were progression-free survival (PFS) and overall survival (OS), while the secondary endpoints included disease control rate (DCR), objective response rate (ORR), and safety.

Results

A total of 103 patients were analyzed, with 46 in cohort A and 57 in cohort B. The ORR was 65.2% in cohort A compared to 40.4% in cohort B, while the DCR was 87.0% in cohort A and 70.2% in cohort B. The median follow-up duration was 14.0 months. Median PFS (mPFS) was 9.4 months (95% CI: 5.6–13.2) for cohort A and 7.4 months (95% CI: 6.1–8.7) for cohort B (p = 0.089). Median OS (mOS) was 16.4 months (95% CI: 11.5–21.3) in cohort A versus 14.2 months (95% CI: 11.2–17.2) in cohort B (p = 0.069). Adverse events were predominantly mild, and no treatment-related deaths occurred.

Conclusion

Sintilimab combined with trastuzumab and chemotherapy showed promising efficacy and acceptable safety in HER2-positive advanced GC/GEJC. However, no statistically significant improvement in survival outcomes was observed compared to trastuzumab and chemotherapy alone.
Comprehensive transcriptome profiling of silvertip tetra (Hasemania nana), a new freshwater fish model for gender classification based on color and establishment of a caudal fin-derived cell line
Authors: Lee Hwa Jin , Lee Mi-Gi , Cho Jeong-Hyeon , Kim Min Sun , Lee Sang Yoon
Published: February 2025

Introduction

This study aimed to propose the silvertip tetra (Hasemania nana) as a new experimental fish model. The silvertip tetra is a freshwater species that exhibits clear sexual dimorphism, with distinct differences in body coloration between males and females.

Methods

We analyzed the embryonic development of silvertip tetra and investigated transcriptome-level differences in gene expression between male and female brain-pituitary, caudal fin, and gonadal tissues. Additionally, we established a primary cell line derived from the caudal fin of male silvertip tetra and optimized the culture conditions for this cell line.

Results and Discussion

The optimal cell growth temperature was identified as 32°C, with a doubling time of approximately 28 hours. Successful transfection of foreign genes was confirmed by fluorescent protein expression, which was observed within 48 hours of transfection. RNA-seq analysis identified differentially expressed genes (DEGs) between sexes and tissues, particularly those involved in pigmentation, and protein interaction networks were examined to explore sex-related differences. The RNA-seq results validated by qRT-PCR suggest that the transcriptome-level gene expression patterns observed in silvertip tetra play critical roles in physiological functions and sexual dimorphism. Our findings highlight the potential of silvertip tetra as a valuable experimental model for studying pigmentation and sexual dimorphism.
Safety and immunogenicity of Ad5-nCoV administered intradermally by needle-free injector in rats
Authors: Chen Li , Zhang Xiaoyin , Jin Lairun , Hou Lihua , Zhu Fengcai , Li Jingxin
Published: February 2025

Objectives

To evaluate the safety and immunogenicity of adenovirus type 5 vectored COVID-19 vaccine (Ad5-nCoV), by intradermal immunization with a needle-free injector in rats.

Methods

This study was divided into two parts. In study A, 105 rats were randomly assigned to seven groups, to receive the low-dose, medium-dose, or high-dose vaccine by needle-free intradermal injections (NFI), or needle-based intramuscular injections (NI), or needle-free intradermal injections with saline solution as a control group. Blood samples were collected on day 0 before vaccination, and day 7, day 14, day 21 and day 28 after vaccination. Binding antibody, pseudovirus neutralizing antibody as well as cellular immune response were measured. The safety endpoints included weight changes and skin reactions. In study B, 32 rats were randomly assigned to four groups to receive low-dose, or medium-dose vaccine by NFI or NI, to observe pathological changes at the injection site following immunization.

Results

No safety concern was noted associated with NFI of Ad5-nCoV. Comparable levels of neutralizing antibodies against various variants induced by NFI compared to NI at the same dosage.

Conclusion

The NFI immunization would be considered as an alternative immunization method to replace the traditional NI for the Ad5-nCoV.
Yearlong analysis of bacterial diversity in hospital sink drains: culturomics, antibiotic resistance and implications for infection control
Authors: Laço José , Martorell Sergi , Gallegos Maria del Carmen , Gomila Margarita
Published: February 2025

Hospitals can carry high levels of bacterial diversity from all types of origins, such as human skin, outside environment and medical equipment. Sink drains in clinical settings are considered reservoirs for pathogenic bacteria and potential sources of hospital-acquired infections (HAI’s) and antibiotic resistance genes (ARGs). Therefore, infection control measures are crucial to minimizing the risks associated with these reservoirs. Recent research has focused primarily on intensive care units (ICUs) and known pathogens, often employing metagenomic approaches that do not include bacterial isolation. This study aims to evaluate bacterial diversity using culturomics, extending the investigation beyond the ICU to identify antibiotic-resistant bacteria. A total of four samplings were conducted over 1 year (March 2022 to March 2023) in five different hospital wards [ICU, General Medicine (GM), Hematology (H), Short stay unit (UCE), and Microbiology laboratory (MS)]. All samples were cultured on selective and non-selective culture media, resulting in 1,058 isolates identified using MALDI-TOF MS, with a subset confirmed through 16S rRNA gene sequencing. Isolates retrieved from antibiotic supplemented agar were subjected to antibiotic susceptibility testing. The highest bacterial diversity, as measured by the Shannon index, was observed in the ICU and GM wards, posing significant risks to patients in these areas. While bacterial genera were largely similar across wards and sampling times, with Pseudomonas and Stenotrophomonas being the most prevalent, different species were detected in each sampling, indicating no loss of diversity. This suggests that these environments undergo dynamic changes over time, influenced by their surroundings. The results also indicate a relationship between human activity and drain usage and the presence of Pseudomonas aeruginosa, the most commonly found species across most wards. Antibiotic susceptibility testing revealed that all tested isolates, except for one, were multi-resistant, including clinically relevant species, such as P. aeruginosa and K. pneumoniae. Hospital drains may serve as reservoirs for both known and emerging pathogens exhibiting high antibiotic resistance phenotypes. Their dynamic nature may provide insights into strategies for preventing the colonization of these environments by such species.
Development of diagnostic tools and discovery of two novel Indian citrus ringspot virus species: insights into global mandarivirus phylogeography
Authors: Bharsakale Rushikesh D. , Gubyad Mrugendra G. , Mukherjee Krishanu , Kokane Amol D. , Kokane Sunil B. , Misra Pragati , Ghosh Dilip Kumar
Published: February 2025

Emerging viral pathogens, Indian citrus ringspot virus (ICRSV) and Citrus yellow vein clearing virus (CYVCV), pose significant threats to global citrus production, a cornerstone of agriculture and trade. The rapid transboundary spread of CYVCV underscores the urgent need for effective diagnostic tools. To tackle this issue, we developed a novel RT-PCR assay capable of simultaneously detecting ICRSV and CYVCV with high sensitivity and specificity in a single reaction. This assay, targeting conserved genomic regions, provides a cost-effective, reliable, and scalable diagnostic solution. Field validation across 49 citrus samples revealed infection rates of 61.22% for ICRSV and 24.48% for CYVCV, with notable co-infections, highlighting its precision and utility. Phylogenetic analyses uncovered substantial genetic diversity, delineating two ICRSV species (ICRSV-A and ICRSV-B) and eight geographically clustered CYVCV clades, reflecting trade-driven and environmental dispersal patterns. These findings emphasize the need for region-specific diagnostics and tailored management strategies. By addressing critical diagnostic gaps, this assay enables early detection and intervention, reducing economic losses and enhancing efforts to control emerging citrus pathogens. Additionally, it provides a foundation for future epidemiological research and contributes to the sustainability of global citrus production.
An unfolded protein response (UPR)-signature regulated by the NFKB–miR-29b/c axis fosters tumor aggressiveness and poor survival in bladder cancer
Authors: Zhang Jian , Fan Xiaosong , Chen Yu , Han Yichao , Yu Weixing , Zhang Shaolin , Yang Bicheng , Zhang Junlong , Chen Yanling
Published: February 2025

Background

Bladder cancer continues to pose a substantial global health challenge, marked by a high mortality rate despite advances in treatment options. Therefore, in-depth understanding of molecular mechanisms related to disease onset, progression, and patient survival is of utmost importance in bladder cancer research. Here, we aimed to investigate the underlying mechanisms using a stringent differential expression and survival analyses-based pipeline.

Methods

Gene and miRNA expression data from TCGA and NCBI GEO databases were analyzed. Differentially expressed genes between normal vs tumor, among tumor aggressiveness groups and between early vs advanced stage were identified using Student's t-test and ANOVA. Kaplan-Meier survival analyses were conducted using R. Functional annotation, miRNA target and transcription factor prediction, network construction, random walk analysis and gene set enrichment analyses were performed using DAVID, miRDIP, TransmiR, Cytoscape, Java and GSEA respectively.

Results

We identified elevated endoplasmic reticulum (ER) stress response as key culprit, as an eight-gene unfolded protein response (UPR)-related gene signature (UPR-GS) drives aggressive disease and poor survival in bladder cancer patients. This elevated UPR-GS is linked to the downregulation of two miRNAs from the miR-29 family (miR-29b-2-5p and miR-29c-5p), which can limit UPR-driven tumor aggressiveness and improve patient survival. At further upstream, the inflammation-related NFKB transcription factor inhibits miR-29b/c expression, driving UPR-related tumor progression and determining poor survival in bladder cancer patients.

Conclusion

These findings highlight that the aberrantly activated UPR, regulated by the NFKB-miR-29b/c axis, plays a crucial role in tumor aggressiveness and disease progression in bladder cancer, highlighting potential targets for therapeutic interventions and prognostic markers in bladder cancer management.
Metabolite profiling, antimalarial potentials of Schleichera oleosa using LC-MS and GC-MS: in vitro, molecular docking and molecular dynamics
Authors: Vanaja Peetha , Moorthy N. S. Hari Narayana , Rajpoot Vivek Singh , Rao Harshawardhan , Goswami Rohit Kumar , Subash Paranthaman , Khute Sulekha , Rao Kareti Srinivasa
Published: February 2025

Purpose

To explore the phytochemical composition of Schleichera oleosa bark and evaluate its potential antimalarial activity through in vitro and in silico analyses.

Methods

The bark of S. oleosa was subjected to Soxhlet extraction using petroleum ether, chloroform, and methanol. The quantitative analysis of the extracts was performed to determine total phenolic, flavonoid, and tannin contents. Advanced analytical techniques such as Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) were employed to identify 175 phytoconstituents from the methanolic extract In-vitro antimalarial activity was assessed against Plasmodium falciparum using the candle jar method, measuring parasite growth inhibition. The inhibitory concentration (IC50) values were calculated and compared with standard antimalarial drugs, chloroquine and quinine. Furthermore, computational analyses, including molecular docking and molecular dynamics simulations, were conducted to evaluate the interactions of identified phytochemicals with key malarial targets (1CEQ and 4ZL4). The efficacy of these compounds was compared with standard drugs like artesunate and chloroquine. Additionally, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiling and drug-likeness assessments were performed.

Results

The methanolic extract of S. oleosa exhibited promising in-vitro antimalarial activity with an average IC50 value of 0.780 μg/mL, which, while higher than chloroquine (0.020 μg/mL) and quinine (0.268 μg/mL), still demonstrated significant efficacy. GC-MS and LC-MS analyses identified 175 phytoconstituents, among which two novel lead compounds, scillarenin and 4-[(Z)-(6-hydroxy-3-oxo-1-benzofuran-2(3H)-ylidene) methyl] phenyl beta-Dglucopyranoside, exhibited the highest docking scores and favorable ADMET profiles. Molecular docking and dynamics simulations confirmed strong binding affinities to malarial targets, surpassing some standard drugs in efficacy.

Conclusion

This study reports, for the first time, the antimalarial potential of bioactive constituents derived from the bark of S. oleosa. The identified compounds, scillarenin and 4-[(Z)-(6-hydroxy-3-oxo-1-benzofuran-2(3H)-ylidene) methyl] phenyl beta-D-glucopyranoside, demonstrated promising antiplasmodial activity, validating traditional medicinal claims. The findings highlight the potential of S. oleosa as a source of novel antimalarial agents with fewer side effects compared to existing therapies. Further in vivo studies are warranted to confirm these results and support the development of new antimalarial drugs. This groundbreaking discovery contributes to the growing evidence supporting the role of medicinal plants in drug discovery.
Neuroplasticity-based novel brain stimulation support intervention options for autistic population
Authors: Desarkar Pushpal
Published: February 2025

Transcranial magnetic stimulation (TMS), introduced in 1985, has become a vital tool for investigating brain-behaviour relationships and therapeutic interventions. Repetitive TMS (rTMS) as a therapeutic tool has shown promise for various neuropsychiatric conditions, including autism, which affects approximately 1% of the global population. Evidence suggests that atypical neuroplasticity characterizes the neurobiology of autism. Recent studies using TMS paradigms like theta-burst stimulation (TBS) indicate an excessive neuroplasticity or hyper-plasticity in the form of an excessive long-term potentiation (LTP) in the motor cortex of autistic adults compared to neurotypical controls. Hyper-plasticity may negatively impact cognitive and behavioural outcomes. Our proposed neuroplasticity-based rTMS intervention protocols aim to address motor function, sensory sensitivities, and executive function difficulties in autistic adults. We present a testable framework to evaluate neuroplasticity in the motor, sensory, and dorsolateral prefrontal cortices, hypothesizing the presence of hyper-plasticity in autistic adults. We anticipate that this hyper-plasticity underpins motor, sensory, and executive function difficulties in autistic adults. Additionally, we propose investigating the efficacy of bilateral rTMS to reduce hyper-plasticity and improve these functions in autistic adults. This approach not only seeks to enhance therapeutic options but also provides biological insights into the brain mechanisms underlying some of the common autism-associated difficulties.
A narrative review of autophagy in migraine
Authors: Huang Yanan , Li Hongyan , Yu Qijun , Pan Yonghui
Published: February 2025

Background and objective

Autophagy is a natural process regulated by autophagy-related genes in eukaryotic cells that involves the degradation of cytoplasmic proteins and old or damaged organelles via the lysosomal pathway to help maintain cell homeostasis. Previous studies have suggested a potential association between autophagy and migraine, while the underlying mechanisms remain unclear. This review seeks to evaluate the possible involvement of autophagy in the pathophysiology of migraine, aiming to clarify its role and implications for future research and therapeutic strategies.

Methods

A search in PubMed was conducted for English-language articles until December 5, 2024. Key terms of “autophagy,” “migraine,” “microglia,” “neurogenic inflammation,” “central sensitization,” “mitophagy” and “neuropathic pain” in different combinations.

Results

In the context of migraine, the activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB/Akt) signaling pathway exerts a direct influence on the mammalian target of rapamycin (mTOR), leading to a reduction in autophagy levels. Moreover, the stimulation of purinergic ligand-gated ion channel type 7 receptor (P2X7R) in microglia can hinder autophagy by interfering with the fusion of autophagosomes and lysosomes, which impedes the degradation of substrates within the autophagolysosome. Increased levels of calcitonin gene-related peptide (CGRP) may also modulate autophagy through the Akt/mTOR or protein kinase A (PKA)/mTOR signaling pathways. Additionally, research indicates that mitophagy may be partially impaired in individuals suffering from migraine. Furthermore, autophagy could contribute to the dysregulation of synaptic plasticity by influencing the processes of long-term potentiation (LTP) and long-term depression (LTD), both of which are associated with central sensitization in chronic migraine.

Conclusion

These findings suggest that autophagy may play an important role in the pathophysiology of migraine, particularly in its development and central sensitization. Research on autophagy modulators related to migraine will provide valuable insights for treatment strategies.
Uterine carcinosarcoma with heterologous osseous elements: a case report of an extremely rare clinical occurrence with literature review
Authors: Al Dallal Hiba A. , Jacobs Taylor H. , Bergman Cody L. , Narayanan Siddharth , Kaur Arshi , Al-Quran Samer Z. , Chopra Harpreet Kaur
Published: February 2025

Carcinosarcoma is a rare and aggressive malignant neoplasm that predominantly affects elderly postmenopausal women and can involve various gynecologic organs. It is characterized by the presence of both malignant epithelial and sarcomatous components. While most uterine carcinosarcomas (UCS) are homologous (sarcomatous component consisting of elements native to the uterus), heterologous components are less common and may vary in composition. Rare heterologous elements can include lipomatous (liposarcoma) or osseous elements (osteosarcoma). We present an unusual case of a 31-year-old female with UCS exhibiting osseous heterologous elements. The patient underwent successful surgical resection and remains in remission during follow-up. This case is notable for its rarity, as highlighted by the uncommon age of the patient and the presence of rare heterologous elements in the UCS. Furthermore, it provides new insights into the diverse presentations of UCS and underscores the importance of comprehensive evaluation in understanding its clinical manifestations.