bluuebunny/crossref_metadata_2025_split huggingface dataset:
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 aimSubcutaneous 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.MethodsA 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.ResultsThe 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.ConclusionThe 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

BackgroundProteinase 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.MethodsImmunohistochemistry 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.ResultsPRTN3 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.ConclusionAnti-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

BackgroundModern 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 methodsPatients 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.ResultsOf 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 &lt;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&lt;0.001) or ICI (N=69; P=0.015), but not in BRAF-wildtype patients who received ICI (N=161; P=0.47).ConclusionsLow 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.
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

IntroductionBurn-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.MethodsBioinformatics 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.ResultsMLIP-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.ConclusionsMLIP 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

BackgroundTo evaluate the efficacy and safety of sintilimab in combination with trastuzumab and chemotherapy for HER2-positive advanced gastric/gastroesophageal junction cancer (GC/GEJC).MethodsHER2-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.ResultsA 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.ConclusionSintilimab 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

IntroductionThis 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.MethodsWe 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 DiscussionThe 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

ObjectivesTo 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.MethodsThis 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.ResultsNo 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.ConclusionThe NFI immunization would be considered as an alternative immunization method to replace the traditional NI for the Ad5-nCoV.
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

BackgroundBladder 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.MethodsGene 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.ResultsWe 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.ConclusionThese 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

PurposeTo explore the phytochemical composition of Schleichera oleosa bark and evaluate its potential antimalarial activity through in vitro and in silico analyses.MethodsThe 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.ResultsThe 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.ConclusionThis 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.
A narrative review of autophagy in migraine
Authors: Huang Yanan , Li Hongyan , Yu Qijun , Pan Yonghui 
Published: February 2025

Background and objectiveAutophagy 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.MethodsA 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.ResultsIn 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.ConclusionThese 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.
Solitary fibrous tumors: radiologic features with clinical and histopathologic correlation
Authors: Xiao Ying , Chen Jiaer , Yang Wenbin , Yan Hongfei , Chen Ruowei , Li Yangkang 
Published: February 2025

ObjectiveSolitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm that exhibits a broad spectrum of biological behaviors. Few studies relative to clinical-pathologic features and radiologic manifestations of SFTs have been reported. This study aimed to correlate the radiologic findings of SFTs with the clinical and histopathologic features.MethodsThe clinical, surgical, and histopathologic records; and CT or MR images in 38 pathologically proved cases of SFTs were retrospectively evaluated.ResultsAll tumors were seen as oval (n=18) or irregular (n=20), well-defined (n=36) or ill-defined (n=2) masses with a mean size of 11.0 cm. On CT images, most tumors showed a heterogeneous density on precontrast image, and the mean density of the tumor parenchyma was 40.7 hounsfield units. Intratumoral calcification was seen in 6 tumors. After contrast media administration, most tumors showed moderate to marked enhancement (n=34). Multiple intratumoral vessels were seen in 23 tumors. Collateral feeding vessels were seen in 19 tumors. On MR images, all 6 tumors showed a low signal intensity on T1 weighted images and high signal intensity with separate foci of hypointensity on T2 weighted images, as well as significantly imhomogeneous enhancement after contrast administration.ConclusionThe presence of a large, well-defined, highly vascular soft tissue tumor with map-like enhancement and prominent collateral feeding vessels should alert the radiologist to the possible diagnosis of SFT. Diagnostic imaging coupled with clinicopathologic analysis allows accurate localization, identification, and resection of SFTs.