bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elucidating the pharmacological foundations and mechanisms of the Sihai Shuyu formula in treating Graves’ disease through integrated serum metabolomics and network pharmacology with molecular docking techniques
Authors: Liu Xiaoju , Li Xingjia , Huang Wenbin , Cui Yifan , Cheng Fengyun , Chen Guofang , Mao Xiaodong , Liu Chao , Xu Shuhang 
Published: January 2025

Ethnopharmacological relevanceThe Sihai Shuyu Formula (SHSY) shows promising potential for treating Graves’ disease (GD), although the therapeutic mechanisms and pharmacological basis of SHSY have not been thoroughly evaluated.ObjectiveThis work is aim to investigate the pharmacological basis and mechanism of SHSY in the treatment of GD by integrating non-targeted serum metabolomics and network pharmacology coupled with molecular docking technology.Materials and methodsGD was induced in mice through injections of Ad-TSH289. Treatments included methimazole, inorganic iodine, and both low and high doses of SHSY administered via gavage. At the end of the treatment period, serum levels of thyroxine (T4) and thyrotropin receptor antibody (TRAb) were measured. Hematoxylin-Eosin (H&amp;E) staining assessed the effects of these pharmacological interventions on thyroid gland tissues. Ultra-High Performance Liquid Chromatography with Quadrupole Time-of-Flight Mass Spectrometry (UPLC-Q-TOF-MS) was used in conjunction with network pharmacology and molecular docking to identify and predict SHSY’s active chemical components and targets. A comprehensive analysis of the multi-level bioinformatic analysis, including protein-protein interactions (PPI) and functional pathways of the targets, was conducted, followed by verification through immunohistochemistry (IHC) to clarify SHSY’s pharmacological basis and action mechanisms in treating GD.ResultsAfter 8 weeks of treatment, SHSY significantly reduced serum T4 and TRAb levels in GD mice and enhanced the morphology of thyroid tissues. Comparative analysis of rat blood samples and SHSY using UPLC-Q-TOF-MS identified 19 blood-entry components, the potential active components of SHSY acting on GD. Further network pharmacological analysis indicated that SHSY targets the PI3K/Akt signaling pathway through components such as PIK3CD, SRC, PIK3CA, HRAS, EGFR, PIK3R1, AKT1, PTPN11, and PIK3CB. Molecular docking confirmed the effective binding of SHSY’s components to these targets. IHC confirmed that the IGF1R/PI3K/Akt signaling pathway is a significant therapeutic target of SHSY, with key substances including Guggulsterone, Betulinic aldehyde, and Forsythoside H.ConclusionsSHSY appears to effectively treat GD through the IGF1R/PI3K/Akt signaling pathway, with Guggulsterone, Betulinic aldehyde, and Forsythoside H as the critical pharmacological components. It may serve as an adjunctive treatment for GD alongside traditional therapies such as antithyroid medications, surgery, and radioiodine therapy.
Tocilizumab modulates the activity of the classical and alternative complement pathways in rheumatoid arthritis patients
Authors: Ferraz-Amaro Iván , Santos-Concepción Sergio , Castro-Hernández Javier , Hernández-Hernández Maria Vanesa , Tejera Segura Beatriz , Luna Cristina , Delgado-Frias Esmeralda , Díaz-González Federico 
Published: January 2025

BackgroundTocilizumab (TCZ) is a monoclonal antibody that neutralizes interleukin (IL)-6 and is indicated for diseases characterized by markedly elevated inflammatory markers, such as rheumatoid arthritis (RA). The complement system has been implicated in the etiopathogenesis of RA.ObjectiveTo evaluate the effect of systemic IL-6 inhibition on complement pathways functional activity in RA patients treated with TCZ.DesingProspective non-interventional study.MethodsTwenty-seven RA patients included in the TOCRIVAR study who received TCZ (8mg/kg IV/q4w) were evaluated at baseline and at weeks 12, 24 and 52 of treatment. Disease activity, as assessed by composite indices, acute phase reactants, and new-generation functional assays of the three complement pathways, was evaluated at baseline and at each follow-up visit. Multivariable linear mixed models were used to determine changes in the complement system cascades over time.ResultsAfter adjustment for disease activity, basal levels of the classical and alternative pathways decreased significantly after TCZ treatment. The effect on the classical pathway remained significant after 52 weeks. The decrease in the alternative pathway was significant at weeks 12 and 24, but not at week 52 of TCZ treatment. TCZ had no effect on the lectin cascade throughout the follow-up.ConclusionTCZ reduces the activity of the classical and alternative pathways of the complement system in RA patients regardless of the improvement in disease activity. This finding may contribute to a better understanding of the mechanisms by which the IL-6 blockade reduces disease activity in RA patients.
Exploration of the diagnostic and prognostic roles of decreased autoantibodies in lung cancer
Authors: Ye Ying , Huang Yi , Pan Jianbo 
Published: January 2025

IntroductionTumor-associated antigens (TAA) are proteins expressed during the growth and development of tumor cells, and TAA autoantibodies (TAAbs) can be detected in the serum of lung cancer patients, which can be utilized in the early screening of lung cancer. Almost all the TAAbs applied for diagnosis are those elevated, however, there are still large numbers of autoantibodies detected to decrease in tumor serums, and their functions were rarely known. Diagnosing malignant small lung nodules (≤3cm) in CT scans remains a challenge in clinical practice.MethodsIn this study, we applied the HuProt array and the bioinformatics analysis to assess the diagnostic values of the decreased autoantibodies in lung cancers.ResultsIn total, 15 types of decreased autoantibodies were identified, and 6 of them were constructed into a predictive model for early lung cancer, reaching a sensitivity of 76.19% and a specificity of 55.74%. We combined with 4 elevated TAAbs, the sensitivity and the specificity of the 10-marker model can attain 80.0% and 87.0%, respectively, which is higher than that of the commonly used 7-TAAbs model in diagnosis for early-stage lung cancer. Moreover, 5 of the decreased autoantibodies can also be applied for supervising bone metastasis in lung adenocarcinoma. A follow-up process for 13 patients diagnosed with early-stage lung cancer revealed that 10 of the 15 decreased autoantibodies would recover to a higher level after the tumor was resected. Bioinformatic analysis indicated that the 15 biomarkers were strongly correlated with the prognosis of lung cancer patients.ConclusionWe confirmed the importance of the decreased autoantibodies in lung cancer, providing new diagnostic and therapeutic strategies.
Dynamics and drivers of the carbonate system: response to terrestrial runoff and upwelling along the Northeastern Colombian Caribbean coast
Authors: Ricaurte-Villota Constanza , Murcia-Riaño Magnolia , Hernádez-Ayón José Martín 
Published: January 2025

IntroductionThis study investigated the variability and main drivers of the carbonate system in Gayraca Bay and Chengue Bay, located on the northeastern Caribbean coast of Colombia, through monthly measurements of partial pressure of CO2 (pCO2), pH, total alkalinity (TA), and dissolved inorganic carbon (DIC) from 2017 to 2022. Statistical analyses and Taylor series decomposition were employed to determine the seasonal and interannual contributions of sea surface temperature, salinity, TA, and DIC to changes in pCO2, pH, and calcium carbonate saturation state (Ω).ResultsThe results showed significant seasonal variability influenced by annual changes in coastal upwelling, rainfall, and river runoff. Low/high pH and Ω values were associated with high/low DIC and TA values during the dry and wet seasons, respectively, while pCO2 exhibited an opposite pattern. During El Niño, negative anomalies in coastal upwelling produced negative anomalies in pCO2 and positive anomalies in Ω, DIC, and TA. Conversely, during La Niña, alternating periods of positive rainfall and upwelling anomalies were observed. Higher rainfall corresponded to negative anomalies in pCO2, DIC, and TA and positive anomalies in Ω, whereas stronger upwelling led to opposite trends. In early 2022, undersaturated levels of Ωcalc and Ωarag (&lt;1) were observed, which could affect coral calcification and pose risks in future climate change scenarios. Taylor series decomposition analysis identified TA and DIC as primary drivers of carbonate system variability, modulated by seasonal and interannual changes in rainfall and river runoff, which are influenced by ENSO events. The observed trends in pH and pCO2 were driven by a decrease in DIC and TA, attributed to increased river runoff, contrasting with typical ocean acidification trends driven by rising atmospheric CO2 levels.DiscussionThis highlights the region's unique dynamics and underscores the importance of local studies. This study provides a novel 6-year time-series dataset for the carbonate system in the Colombian Caribbean, offering a valuable baseline for assessing the impacts of global warming and ocean acidification in the region.
Sepsis in Internal Medicine: blood culture-based subtypes, hospital outcomes, and predictive biomarkers
Authors: Zizzo Gaetano , Guazzardi Gabriele , Bompane Daniela , Di Terlizzi Francesco , Rotola Giorgio , Stefani Ilario , Medugno Michela , Bucalo Mario , Mazzone Antonino 
Published: January 2025

BackgroundSepsis is a challenging condition increasingly managed in medical wards, however literature and clinical evidence in this hospital setting are lacking.MethodsUsing the computational i2b2 framework, we retrospectively analyzed data from patients admitted to internal medicine units of four hospitals in Lombardy (Italy) between January 2012 and December 2023, with a discharge diagnosis of sepsis, septic shock, or septicemia.ResultsA total of 4,375 patients were recruited. Median length of stay (LOS) was 14 days, and mean ward-to-intensive care unit (ICU) transfer and in-hospital mortality rates were 11 and 26%, respectively; significant differences were observed over the years, with LOS peaks preceding mortality peaks by 1 year. Blood culture-negative sepses showed shorter stays and higher mortality (acute kidney injury and fast deterioration) compared to culture-positive ones; polymicrobial sepses showed higher ICU transfer rates (acute respiratory distress); while multidrug-resistant (MDR+) and/or polymicrobial sepses showed longer stays and higher mortality (complicated course) compared to drug-sensitive or monomicrobial ones. C-reactive protein elevation predicted rapidly evolving culture-negative sepsis, whereas lower leukocyte counts predicted prolonged hospitalization; higher fractions of inspired oxygen predicted polymicrobial sepsis, while lactate elevation predicted ICU transfer; ferritin elevation and increased leukocyte counts predicted MDR+ sepsis, while further ferritin elevation and decreased platelet counts predicted death. From 2016 to 2023, MDR+ sepsis frequency declined, due to decreased resistance to several antibiotic classes, such as cephalosporins, fluoroquinolones, and aminoglycosides; however, carbapenemase- and extended-spectrum beta-lactamase-producing Gram-negative bacteria, as well as vancomycin-resistant enterococci, increased, as did the frequency of polymicrobial sepsis following the COVID-19 outbreak.ConclusionThis work provides novel insights into sepsis management in internal medicine units, highlighting the need for validated biomarkers and implemented therapies in this scenario.
Diagnostic value and safety of contact laser-assisted endobronchial ultrasound-guided tunnel drilling biopsy in mediastinal and hilar lymphadenopathy: a retrospective study
Authors: Zhan Wenyu , Wang Tian , Yang Changqing , Wang Yubao , Wan Nansheng , Feng Jing 
Published: January 2025

IntroductionMediastinal and hilar lymphadenopathies are primarily diagnosed pathologically. Contact laser-assisted endobronchial ultrasound-guided tunnel drilling biopsy (EBUS-TDB), which uses a laser as a tunneling and incision tool, may yield more satisfactory specimens than conventional endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), thereby improving the diagnostic yield. This study aims to evaluate the diagnostic value and safety of contact laser-assisted EBUS-TDB compared to EBUS-TBNA in the assessment of mediastinal and hilar lymph nodes.MethodsThis retrospective study included patients who presented to our hospital between October 2022 and April 2024 with mediastinal or hilar lymph nodes of short diameter ≥ 1 cm on computed tomography (CT) or abnormally increased lymph node metabolism on positron emission tomography (PET)-CT. All patients underwent both EBUS-TBNA and EBUS-TDB procedures successively.ResultsOverall, 278 patients were included in the study, and 244 cases were confirmed. The diagnostic rates (p-values) for EBUS-TDB and EBUS-TBNA in pulmonary and extrapulmonary malignancies, lymphoma, sarcoidosis, and lymph node tuberculosis were 96.6% vs. 76.3% (0.043), 100% vs. 67.7% (−), 88.9% vs. 31.1% (0.555), and 69.2% vs. 30.8% (0.049), respectively. No serious adverse events occurred during or after either procedure.ConclusionContact laser-assisted EBUS-TBNB demonstrates superior diagnostic performance compared to EBUS-TBNA for the evaluation of mediastinal or hilar lymph nodes, making it an alternative to EBUS-TBNA for enhanced diagnostic precision.
Development and validation of a LAMP-based method for rapid and reliable detection of Xanthomonas albilineans, the causal agent of sugarcane leaf scald
Authors: Chakraborty Moutoshi , Bhuiyan Shamsul Arafin , Strachan Simon , Shiddiky Muhammad J. A. , Nguyen Nam-Trung , Ford Rebecca 
Published: January 2025

IntroductionXanthomonas albilineans (Xalb)-induced leaf scald (LS) is a significant bacterial disease affecting sugarcane and posing a global threat to the sugarcane industry. The presence of irregular symptoms makes traditional phenotypic detection difficult, and molecular methods necessitate costly equipment, labor, and extended sample-to-answer processing times.MethodsThis study introduces an innovative rapid DNA isolation method requiring no reagents, combined with an isothermal amplification-based assay for efficient detection of Xalb DNA in sugarcane xylem sap, leaf tissue, and meristematic tissue samples. Sugarcane samples from infected plants were subjected to heat lysis, followed by loop-mediated isothermal amplification (LAMP)-based fluorescence and colorimetric quantification within a single microcentrifuge tube.ResultsThe method exhibited exceptional detection sensitivity (detecting as low as 1 cell/μL), reproducibility [with a standard deviation (SD) of &lt;5% for n = 3], and a broad linear dynamic range (10 pM to 1 aM or 107–100 copies/μL, r = 0.99). Quantification of Xalb was accurately correlated with sugarcane cultivar disease ratings. Validation using qPCR showed 91–98% agreement. This assay also effectively determined optimal sampling times and plant parts by monitoring the progression of the disease over time.DiscussionThis diagnostic assay holds significant potential as a commercial opportunity for a kit-based DNA extraction/purification-free molecular detection alternative. It can be adapted into a handheld device, enabling on-farm detection and quantification of the pathogen responsible for LS disease.
Cerebellar-cerebral circuits functional connectivity in patients with cognitive impairment after basal ganglia stroke: a pilot study
Authors: Zuo Lijun , Lan Xinlong , Zhou Yijun , Liu Hao , Hu Yang , Wang Yongjun , Liu Tao , Li Zixiao 
Published: January 2025

IntroductionThis study aims to assess the pattern of functional connectivity (FC) between cerebellar subregions, the basal ganglia (BG), and the cortex, and explore the relationship between FC patterns and cognitive function after stroke with BG infarcts.MethodsA total of 39 stroke patients and 29 healthy controls were recruited. Four cerebellar seed points were selected, and the FC of each seed point with other voxels in the whole brain was calculated. FC and cognitive performance were compared between the two groups, and their correlations were analyzed.ResultsStroke patients exhibited increased FC between the bilateral cerebellum IX and BG (particularly the head of the caudate nucleus), which was positively correlated with episodic memory, visuospatial ability, and attention. Increased FC was also observed between the right cerebellum Crus I/II and BG, as well as the bilateral cerebellum VI and BG, correlating positively with episodic memory. Conversely, decreased FC was identified between the bilateral cerebellum IX and the right caudal cuneus, which negatively correlated with episodic memory, language, and attention but positively correlated with executive function. Additionally, increased FC between the bilateral cerebellum VI and the bilateral inferior parietal lobule was associated with improvements in episodic memory, language, and attention. Decreased FC was observed between the right cerebellum VI and the left insula, as well as between the right cerebellum Crus I/II and the left insula, which negatively correlated with episodic memory.DiscussionThe enhanced FC between the cerebellum and BG, along with the reorganization of new neural circuits involving the cerebellar cortex, may contribute to cognitive recovery following stroke. These changes may represent compensatory mechanisms of the cerebellum in response to stroke injury.
Evaluating NfL and NTproBNP as predictive biomarkers of intracranial injuries after mild traumatic brain injury in children presenting to emergency departments
Authors: Chiollaz Anne-Cécile , Pouillard Virginie , Seiler Michelle , Habre Céline , Romano Fabrizio , Ritter Schenck Céline , Spigariol Fabian , Korff Christian , Maréchal Fabienne , Wyss Verena , Gruaz Lyssia , Montaner Joan , Sanchez Jean-Charles , Manzano Sergio 
Published: January 2025

ObjectiveBlood-biomarkers have the potential to aid clinicians in pediatric emergency departments (PED) in managing children with mild traumatic brain injury (mTBI) acutely. However, studies focusing on pediatric populations remain limited. We aim to assess the performances of two routinely used biomarkers in other fields: the neurofilament light chain protein (NfL), and the N-terminal prohormone of brain natriuretic peptide (NTproBNP), to safely discharge children without intracranial injuries (ICIs).MethodsA prospective multicenter cohort study was conducted, enrolling children suffering from mTBI, both with and without imaging during their acute management in the PED. A blood sample was collected within 24 h post-trauma for biomarker analysis. Inclusion criteria followed the PECARN (Pediatric Emergency Care Applied Research Network) guidelines for the diagnosis of mTBI and for ICI on CT as the primary outcome (CT+).ResultsA total of 302 mTBI patients were analyzed comparing children with ICI (18 CT+) versus all the other children without ICI (54 CT− and 230 in-hospital-observation patients without CT). NfL and NTproBNP were increased in the CT+ group and their performances to safely rule-out patient without ICI reached up to 30% specificity with 100% sensitivity. Equivalent performances were observed whether selecting patients with blood collection within 6 h or 24 h post-trauma.ConclusionNfL and NTproBNP were described for the first time in children suffering mTBI. Their performances were comparable to well-known biomarkers, such as S100b, GFAP, or HFABP, with the benefit of already being used in routine tests for other diseases. Further large-scale studies are necessary to verify and validate these results.
Network analysis of headache diagnoses using international classification of headache disorders, 3rd edition
Authors: Zhang Pengfei , Berk Thomas 
Published: January 2025

Background and objectiveThe International Classification of Headache Disorders, Third Edition (ICHD-3), significantly influences clinicians’ understanding of headache disorders. In this study, we aim to elucidate how the hierarchical structure of ICHD-3 shapes the understanding of interconnectivity among headache disorders.MethodsA network comprises elements known as “nodes,” with the connections between them referred to as “edges.” In our study, a node represents a headache diagnosis that meets at least one ICHD-3 diagnostic criterion of the ICHD-3. We developed two network models for ICHD-3: a non-hierarchical model, where edges are only formed by cross-references found within the text of diagnoses, and a hierarchical model that incorporates the ICHD-3’s structural organization by adding extra edges between sections and their subsections. We identified the top 10 disorders in terms of their centrality, which assesses their popularity, their role as bridges in the network, and their proximity to other disorders. These measurements are calculated using the network’s degree, betweenness, and closeness centrality.ResultsBoth our models contain 387 nodes. The choice between a non-hierarchical or hierarchical model affects which diagnoses occupy the top 10 centrality nodes. In both models, migraine and medication-overuse headaches consistently rank among the top 10 diagnoses according to all three centrality metrics. The hierarchical model includes a greater number of secondary headache diagnoses among its top 10 compared to the non-hierarchical model.ConclusionMigraine and medication overuse headaches are the most interconnected nodes in ICHD-3. The addition of a diagnostic hierarchy facilitates the unification of secondary headaches, which would otherwise be considered isolated, miscellaneous diagnoses. When interconnected hierarchically, these secondary headache diagnoses become the majority of the most well-connected nodes in our field.
Value of the systemic immunoinflammatory index, nutritional risk index, and triglyceride-glucose index in predicting the condition and prognosis of patients with hypertriglyceridemia-associated acute pancreatitis
Authors: Wang Yuan Zhen , Yun Ya Ling , Ye Ting , Yao Wen Tun , Guo Yu Feng , Huang Li Ya 
Published: January 2025

ObjectiveThe study aimed to investigate the function and prognosis of pancreatitis in patients with hypertriglyceridemia-associated acute pancreatitis (HTGAP), as assessed by the systemic immunoinflammatory index (SII), nutritional risk index (NRI), and triglyceride-glucose index (TyG).MethodsA total of 300 patients with HTGAP who were admitted to the General Hospital of Ningxia Medical University from January 2022 to June 2023 were selected. These patients were divided into three groups based on the severity of their condition: the mild acute pancreatitis (MAP) group, the moderate-to-severe acute pancreatitis (MSAP) group, and the severe acute pancreatitis (SAP) group. The SII, NRI, and TyG index in the three groups were recorded and compared. The value of these indices in predicting the occurrence of HTGAP was analyzed using a receiver operating characteristic (ROC) curve.ResultsThe SII and TyG index values in the SAP group (3259.4 ± 2795.8, 4.5 ± 1.1) were higher than those in the MSAP group (2563.7 ± 1614.1, 4.3 ± 0.8) and MAP group (1991.1 ± 1566.8, 4.1 ± 0.8), and the difference was statistically significant (p &lt; 0.005). The ROC curve analysis showed that the AUC value of the combined SII, NRI, and TyG index for predicting SAP occurrence was 0.705 (95%CI:0.632 ~ 0.778).ConclusionThe SII, NRI, and TyG index are related to the severity of HTGAP, and a combination of the three can better predict the occurrence of SAP.