bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying potential biomarkers and molecular mechanisms related to arachidonic acid metabolism in vitiligo
Authors: Li Xiaoqing , Yang Li , Zhu Longfei , Sun Jingying , Xu Cuixiang , Sun Lijun 
Published: February 2025

BackgroundNumerous studies have reported that dysregulation of fatty acid metabolic pathways is associated with the pathogenesis of vitiligo, in which arachidonic acid metabolism (AAM) plays an important role. However, the molecular mechanisms of AAM in the pathogenesis of vitiligo have not been clarified. Therefore, we aimed to identify the biomarkers and molecular mechanisms associated with AAM in vitiligo using bioinformatics methods.MethodsThe GSE75819 and GSE65127 datasets were used in this study as the training and validation sets, respectively, along with 58 AAM-related genes (AAM-RGs). The differentially expressed genes (DEGs) between the lesional and control groups in the training set were identified through differential expression analysis. A biomarker-based nomogram was constructed to predict the risk of vitiligo.Results15 overlapping candidate genes were obtained between the DEGs and AAM-RGs. Machine-learning algorithms were used to identify six key genes as PTGDS, PNPLA8, FAAH, ABHD12, PTGS1, and MGLL. In both the training and validation sets, PTGDS, PNPLA8, and MGLL. In both the training and validation sets, PTGDS, PNPLA8, and MGLL were regarded as biomarkers. A nomogram based on these biomarkers showed potential for predicting the risk of vitiligo. Functional enrichment, immune cell infiltration, and regulatory network analyses were used to elucidate the molecular mechanisms.ConclusionIn conclusion, PTGDS, PNPLA8, and MGLL were implicated in AAM to influence the pathogenesis of vitiligo. These findings offer insights into vitiligo treatment, although further research is needed for a comprehensive understanding.
Neutrophil-related immune-inflammatory biomarkers influence the early progression of medial medullary infarction
Authors: Li Li-Min , Cai Hao 
Published: February 2025

BackgroundMedial medullary infarction (MMI) is a rare type of posterior circulation stroke for which accurate prognostication remains a challenge because of the limited predictive ability of the current models. Blood-derived biomarkers may provide valuable insights that extend beyond established prognostic factors. The aim of this study was to identify rapid and accessible biomarkers for predicting the early progression of MMI.MethodsSeventy patients with MMI and 83 sex- and age-matched healthy controls (HCs) were recruited for this study. Among them, 20 patients were allocated to the early progression cohort, and 50 patients were assigned to the nonprogression cohort. The laboratory blood indices were subsequently compared across these different cohorts. Receiver operating characteristic (ROC) curves were used to evaluate the predictive values of blood-derived indicators.ResultsThe white blood cell (WBC) count, neutrophil count, monocyte count, low-density lipoprotein cholesterol (LDL-C) level, total cholesterol (TC) concentration, WBC-to-high-density lipoprotein cholesterol (HDL-C) ratio (WHR), neutrophil-to-HDL-C ratio (NHR), monocyte-to-HDL-C ratio (MHR), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were significantly greater in patients with MMI than in HCs (p &lt; 0.05). The WBC count, neutrophil count, monocyte count, WHR, NHR, MHR, MLR, NLR and PLR were markedly higher in MMI patients with progression than in MMI patients without progression (p &lt; 0.05). ROC curve analysis revealed that the WBC count, neutrophil count, monocyte count, MLR, NLR, PLR, NHR, and WHR were significant predictors of early progression. However, among these factors, the WBC count (AUC = 0.854, p &lt; 0.001), neutrophil count (AUC = 0.878, p &lt; 0.001), NLR (AUC = 0.861, p &lt; 0.001), and NHR (AUC = 0.848, p &lt; 0.001) had the highest levels of accuracy for predicting early progression in patients with MMI.ConclusionThe efficacy of the WBC count, neutrophil count, NLR and NHR is superior in predicting progression in patients with MMI. The current findings suggest that these indicators may serve as reliable, cost-effective, and innovative prognostic markers for MMI.
Sex differences in the prediction of metabolic abnormalities via body mass index in an Eastern Chinese population
Authors: Gao Yingjie , Jin Kaimeng , Chen Jin , Chen Ben , Guo Yan , Lu Jin 
Published: February 2025

ObjectiveBody mass index (BMI) is important for predicting the occurrence of metabolic abnormality, but sex differences exist. We aimed to investigate potential sex differences in the predictive value of BMI for metabolic abnormality and to calculate the optimal BMI cut-offs for predicting metabolic abnormality for each sex.MethodsParticipants (n = 4,623) who attended a health check-up centre continuously in Eastern China between January 2022 and December 2023 were evaluated for metabolic abnormalities. We calculated the proportions of different metabolic abnormalities in different sexes. Receiver operating characteristic (ROC) curves were calculated to determine the optimal BMI cut-off values for predicting metabolic abnormality in males and females. The recognition rate of each metabolic abnormality using different BMI cut-off values for men and women were evaluated.ResultsAmong 4,623 participants (2,234 men and 2,389 women), the age-adjusted prevalence of all metabolic abnormalities was significantly greater among males than among females (p &lt; 0.001). The optimal cut-off values for predicting metabolic abnormalities were 23.5 kg/m2 (males) and 21.8 kg/m2 (females). When BMI ≥24 kg/m2 was used as the cut-off value the recognition rates of each abnormal metabolic factor in the male group were all above 50%, while they were mostly below 50% in the female group, except for the recognition of hyperglycaemia and hypertriglyceridemia. However, in females, when BMI ≥22 kg/m2 was used as the cut-off value, the recognition rates for each abnormal metabolic factor were all above 50%, greater than that when BMI ≥24 kg/m2 was used (p &lt; 0.001).ConclusionThere were sex differences in the BMI thresholds for predicting metabolic abnormalities in the health check-up population.
AI models for the identification of prognostic and predictive biomarkers in lung cancer: a systematic review and meta-analysis
Authors: AlOsaimi Hind M. , Alshilash Aseel M. , Al-Saif Layan K. , Bosbait Jannat M. , Albeladi Roaa S. , Almutairi Dalal R. , Alhazzaa Alwaleed A. , Alluqmani Tariq A. , Al Qahtani Saud M. , Almohammadi Sara A. , Alamri Razan A. , Alkurdi Abdullah A. , Aljohani Waleed K. , Alraddadi Raghad H. , Alshammari Mohammed K. 
Published: February 2025

IntroductionThis systematic review and meta-analysis aim to evaluate the efficacy of artificial intelligence (AI) models in identifying prognostic and predictive biomarkers in lung cancer. With the increasing complexity of lung cancer subtypes and the need for personalized treatment strategies, AI-driven approaches offer a promising avenue for biomarker discovery and clinical decision-making.MethodsA comprehensive literature search was conducted in multiple electronic databases to identify relevant studies published up to date. Studies investigating AI models for the identification of prognostic and predictive biomarkers in lung cancer were included. Data extraction, quality assessment, and meta-analysis were performed according to PRISMA guidelines.ResultsA total of 34 studies met the inclusion criteria, encompassing diverse AI methodologies and biomarker targets. AI models, particularly deep learning and machine learning algorithms demonstrated high accuracy in predicting biomarker status. Most of the studies developed models for the prediction of EGFR, followed by PD-L1 and ALK biomarkers in lung cancer. Internal and external validation techniques confirmed the robustness and generalizability of AI-driven predictions across heterogeneous patient cohorts. According to our results, the pooled sensitivity and pooled specificity of AI models for the prediction of biomarkers of lung cancer were 0.77 (95% CI: 0.72 – 0.82) and 0.79 (95% CI: 0.78 – 0.84).ConclusionThe findings of this systematic review and meta-analysis highlight the significant potential of AI models in facilitating non-invasive assessment of prognostic and predictive biomarkers in lung cancer. By enhancing diagnostic accuracy and guiding treatment selection, AI-driven approaches have the potential to revolutionize personalized oncology and improve patient outcomes in lung cancer management. Further research is warranted to validate and optimize the clinical utility of AI-driven biomarkers in large-scale prospective studies.
Real-life evidence of encorafenib plus binimetinib in patients with unresectable advanced or metastatic BRAFV600-mutant melanoma in Spain: the BECARE (GEM-2002) trial
Authors: Soria Ainara , Sanchez Mauriño Pedro , Serrano Domingo Juan José , García Galindo Regina , Sequero Silvia , Gutiérrez Sanz Lourdes , Crespo Guillermo , Díaz-Beveridge Roberto , Puértolas Teresa , López Pedro , Fra Rodríguez Joaquín , López Castro Rafael , Aguayo Cristina , Valdivia Javier , Cunquero-Tomás Alberto Jacobo , Benítez Gretel , Ayala de Miguel Pablo , Espinosa Enrique , Muñoz-Couselo Eva , Campos Begoña , García Sánchez Lourdes , Cerezuela-Fuentes Pablo 
Published: February 2025

PurposeCombined BRAF/MEK inhibition with encorafenib (E) plus binimetinib (B) has demonstrated efficacy and tolerability in phase III clinical trials, and is the standard of care for advanced/metastatic BRAFV600-mutant melanoma. However, real-life evidence is limited, particularly in patients pre-treated with immune checkpoint inhibitors (ICI).Patients and methodsBECARE GEM 2002 was a retrospective, non-interventional study aimed at investigating the real-world effectiveness and tolerability of EB in patients with unresectable or metastatic BRAFV600-mutant melanoma conducted at 21 sites in Spain. The primary objective of this study was to characterise the population of patients receiving EB and assess the efficacy and tolerability of EB in real life. The study included patients treated according to standard clinical practice with EB as the 1st line or 2nd line after progression to ICI for an unresectable or metastatic stage. Patients who previously received treatment with BRAF and/or MEK inhibitor, other than as adjuvants, that ended ≥ 6 m before EB were not eligibleResultsFrom September 2021 to March 2023, 117 patients were included; 89 (76.1%) and 28 (23.9%) patients received EB as 1st line and 2nd line, respectively. The median follow-up was 13.8 months (95% CI: 12.0-17.4). In patients with EB as 1st line treatment, ORR and median PFS were 75% and 12 months (95% CI: 9.4-18.6), respectively. In patients with EB as 2nd line treatment after ICI, ORR and median PFS were 77.8% and 12.5 months (95% CI: 6.6-NA), respectively. In patients with brain metastasis ORR and median PFS were 70.8% and 6.3 months (95% CI: 6.1-10.3). Treatment-related adverse events of grade ≥3 were reported in 17 (14.5%) patients; transaminitis (9.4%) and diarrhoea (2.6%) were the most frequent adverse events.ConclusionIn this real-world study, EB treatment demonstrated effectiveness and a consistent safety profile in patients with BRAFV600-mutant melanoma treated according to standard clinical practice, including in those with prior ICI treatment and of brain metastasis; therefore, EB is a feasible treatment option for unresectable and metastatic melanoma.Clinical trial identification: REec: 0004-2021-OBSClinical trial identificationREec: 0004-2021-OBS.
Significance of mouse xenograft tumor model using patient-derived cancer organoids for clinical drug development
Authors: Ogawa Hisataka , Yoshida Keiichi , Hasegawa Shinichiro , Wada Hiroshi , Yasui Masayoshi , Tahara Hideaki 
Published: February 2025

BackgroundIn vitro and in vivo preclinical examinations of cancer cell lines are performed to determine the effectiveness of new drugs before initiating clinical trials. However, there is often a significant disparity between the promising results observed in preclinical evaluations and actual outcomes in clinical trials. Therefore, we hypothesized that this inconsistency might be due to the differences between the characteristics of cell lines and actual cancers in patients. Therefore, we screened drugs for bile duct cancer to test our hypotheses.MethodsWe established patient-derived cancer organoids (PDCOs) from the surgical samples of patients with bile duct cancer and conducted multiple in vitro drug screening tests.ResultsWe identified proteasome inhibitors (Bortezomib and Carfilzomib) as promising drugs in the screening. Bortezomib has demonstrated a significant antitumor effect on bile duct cancer cell-derived xenografts, as previously reported in preclinical trials. However, although Bortezomib showed significant proliferation inhibition in PDCOs in three-dimensional culture in vitro, it did not exhibit significant anti-tumor effects in mouse xenograft tumor models using our PDCOs. Bile duct cancer cell-line-derived xenografts are characterized by structurally uniform, irregular glandular structures surrounded by simple and sparse stromal components. However, organoid-derived xenografts exhibit a spectrum of differentiation levels within irregular glandular structures and consist of a complex and rich stromal microenvironment similar to those observed in surgical specimens.ConclusionThese findings suggest that in vivo studies using PDCO xenograft tumor models may be more suitable than conventional mouse tumor models for determining the clinical development of drugs.
Clinical factors influencing residual subcutaneous tissue after skin-sparing and nipple-sparing mastectomy with immediate breast reconstruction
Authors: Turna Menekse , Caglar Hale Basak 
Published: February 2025

BackgroundSkin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) have emerged as increasingly preferred alternatives to traditional mastectomy, largely due to their enhanced cosmetic outcomes and elevated levels of patient satisfaction. Nonetheless, the oncological safety and implications associated with residual breast tissue in these surgical procedures continue to raise significant concerns. The objective of this study is to evaluate the influence of various clinical and surgical factors on residual subcutaneous tissue in patients undergoing SSM and NSM.MethodsThis retrospective cohort study encompassed breast cancer patients who underwent postoperative radiotherapy following SSM and NSM with immediate breast reconstruction from November 2020 to April 2024. Clinical and demographic data, including age, tumor size, axillary staging, molecular subtype, genetic analysis, and surgical details, were systematically collected. Additionally, radiation treatment planning CT scans were assessed to measure residual subcutaneous tissue thickness at multiple anatomical regions. The correlation between residual subcutaneous tissue thickness and clinical factors was subsequently analyzed.ResultsThe median age was 45 years (range, 31-61). Among the total patients, 20 underwent SSM (52.63%), and 18 underwent NSM (47.37%). An acceptable residual subcutaneous tissue distance (≤5 mm) was observed in 21 breasts (55.26%), while 17 breasts (44.74%) did not meet this criterion. Analysis demonstrated a statistically significant but modest positive correlation between RFT thickness and age (r = 0.38, p = 0.02), minimal positive correlation was observed between RFT thickness and clinical tumor size (r = 0.08, p = 0.042). A significant effect of contralateral breast surgery on residual subcutaneous tissue thickness was noted (F = 8.38, p &lt; 0.001). Additionally, the results also revealed a statistically significant inverse correlation between RFT thickness and axillary involvement (r = -0.18, p = 0.005), suggesting that thicker flaps are associated with reduced axillary involvement. There was no significant difference in RFT thickness between NSM and SSM groups (Chi² = 0.47, p = 0.491).ConclusionA significant proportion of patients undergoing SSM and NSM exhibit residual subcutaneous tissue thickness that exceeds acceptable limits, which may vary based on clinical and pathological factors. Further research involving larger cohorts and prospective designs is essential to identify additional contributing factors and optimize indications for postoperative radiotherapy.
Prognostic impact of initial platelet count and post-induction platelet recovery in elderly AML patients: associated with circulating cytokines
Authors: Ling Chun , Cao Neng-Neng , Niu Xiao-Wei , Xu Shi-Yun , Gong Wen-Yu , Bao Wen-Qiang , Jin Qi-Chuan , Wang Yin , Wu Jing , Zhao Chang-Zhi , Fu Wen-Jing , Zhang Qi-Guo , Feng Shan-Shan , Li Dao-Yuan 
Published: February 2025

ObjectiveAcute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy, with various clinical features influencing its prognosis. The aim of this study to evaluate the impact of platelet count at diagnosis and platelet recovery after induction chemotherapy on the survival outcomes of elderly AML patients.MethodsA total of 109 elderly patients with AML who were treated in our center between 2017 and 2023 were evaluated. According to the median platelet counts at the time of new diagnosis, the cases were divided into a low platelet counts group (≤40×109/L, n=54) and a high platelet count group (&gt;40×109/L, n=55). Platelet recovery times were accepted as the periods from the beginning of induction chemotherapy to a platelet count of ≥20×109/L 3 days in a row, respectively. The median time to platelet recovery was 25 days (range12-47) for all patients. Therefore, platelet recovery in the first 25 days was defined as early platelet recovery and at &gt;25 days it was defined as late platelet recovery.ResultsLow platelet counts at diagnosis and early recovery of platelet counts after induction therapy indicate longer overall survival (OS) and Leukemia-free survival (LFS). Patients with high platelet counts at diagnosis and those with delayed platelet recovery after induction therapy exhibited elevated levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Additionally, patients with high platelet counts at diagnosis also had relatively higher levels of interleukin-8 (IL-8).ConclusionPlatelets can be used as a prognostic biomarker for elderly AML and may be associated with circulating cytokines.
SATB2 promotes radiation resistance of esophageal squamous cell carcinoma by regulating epithelial-to-mesenchymal transition via the Wnt/β-catenin pathway
Authors: Lin Chen , Wu Youyi , Qian Yuchen , Li Jiayi , He Youdi , Yu Huang , Xie Congying , Su Huafang 
Published: February 2025

PurposeRadioresistance remains a predominant factor contributing to local recurrence in esophageal squamous cell carcinoma (ESCC). SATB2, as a transcriptional co-gene, may affect the radioresistance of cancer cells. Consequently, this study aims to elucidate the mechanism by which SATB2 modulates radiotherapy resistance in esophageal cancer.MethodsWe identified highly expressed genes associated with radioresistance in ESCC using the MSigDB database and conducted survival correlation analysis. A radioresistant esophageal squamous cell carcinoma cell line (KYSE150R) was established using the gradient dose method, and RT-qPCR was used to detect the expression of SATB2 in KYSE150 and KYSE150R cells. CCK-8, Transwell, colony formation assay, and cell scratching were performed to determine and evaluate cell proliferation, cell migration, and cell invasion. Furthermore, the expression levels of mRNA and protein were correlated using WB and RT-qPCR. Mitochondrial membrane potential and apoptosis detection kits were used to evaluate the level of apoptosis. Finally, a mouse subcutaneous xenograft tumor model was employed to elucidate the role of SATB2 on the radiotherapy resistance of ESCC in vivo.ResultsBioinformatics analysis indicated that SATB2 is linked to increased drug resistance in esophageal cancer. The results demonstrated that suppression of SATB2 decelerates cell proliferation and migration, accelerates apoptosis, inhibits the GSK-3β (Ser9) phosphorylation, and reduces β-catenin and target gene C-myc. The addition of the Wnt/β-catenin signaling pathway agonist (CHIR-99021) reversed these effects. Xenograft studies in mice revealed that knockdown of SATB2 reduced ESCC radioresistance.ConclusionWe concluded that SATB2 may dysregulate the Wnt/β-catenin pathway, thereby facilitating EMT progression and conferring radioresistance.
The impact of a virtual wound on pain sensitivity: insights into the affective dimension of pain
Authors: Koopmans Ingrid , Doll Robert-Jan , Hagemeijer Maurice , van Barneveld Robert , de Kam Marieke , Groeneveld Geert Jan 
Published: February 2025

BackgroundThe perception of pain is difficult to assess due to the complex combination of various components related to nociception, experience, and cognition. There are currently no biomarkers to assess the affective component of pain in healthy volunteers. Using Virtual Reality (VR), it may be possible to assess changes in pain perception when adding an affective component to painful stimulation.MethodsIn this two-visit feasibility study, we assess the effect of a simulated wound in VR on the electrical pain detection (PDT) and tolerance (PTT) threshold in 24 healthy male study participants. The VR simulation presented a copy of the research room from first person view. Prior to each VR assessment, study participants were primed by interacting with the VR environment. Two conditions were assessed: (1) VR-Wound: a burn-wound, smoke, and electrical sparks become visible and audible with increasing stimulus intensity, and (2) VR-neutral: no additional aspects. The PDT and PTT to electrical stimuli were recorded during both VR conditions and outside of VR. VAS-Questionnaires were used to assess unpleasantness and fear.ResultsThe PDT decreased when a virtual wound is presented compared to a neutral condition. Study participants experienced the electrical stimulation as more painful and more intense during the wound simulation than during the neutral condition. The effect was more pronounced during the second visit.ConclusionVR enhanced the perception of pain, thereby providing new insights into the affective component of pain. Further testing of this methodology is warranted by performing a clinical study that evaluates drug effects on the affective component of pain.
Economic impact of individualized antimicrobial dose optimization in the critically ill patient in Spain
Authors: Grau Santiago , Luque Sonia , Ferrandez Olivia , Benitez Cano Adela , Rubio-Rodríguez Darío , Rubio-Terrés Carlos 
Published: February 2025

ObjectiveTo estimate the economic impact of individualized dose optimization guided by antimicrobial therapeutic drug monitoring (TDM) in Spain, compared to no monitoring.MethodsA cost analysis of antibiotic treatment of critically ill patients, with and without TDM, was performed using a probabilistic Markov model (with second-order Monte Carlo simulations). Three scenarios were analyzed based on three published meta-analyses (Analysis 1: Pai Mangalore, 2022; Analysis 2: Sanz-Codina, 2023; Analysis 3: Takahashi, 2023).ResultsTDM, compared to the no-TDM option, generated according to the meta-analysis, a per patient expenditure of €195 (95%CI €194; €197) in analysis 1 or savings of -€301 (95%CI -€300; -€304) and -€685 (95%CI -€685; -€684) in analyses 2 and 3. The probability of TDM (vs. no-TDM) generating savings would be 39.4%, 63.5% and 79.7% in analyses 1, 2 and 3, respectively. This discrepancy in the results is due to methodological differences, in particular in the cure rate with TDM (vs. no-TDM) obtained in the meta-analyses: 12.2%, 16.6% and 16.0% more in analyses 1, 2 and 3, respectively.ConclusionIn critically ill patients undergoing antimicrobial therapy TDM, there is an increased likelihood of cure. However, the currently available data are not conclusive on the economic impact of such a therapeutic effect.