bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analysis of FOXM1 immune infiltrates, m6a, glycolysis and ceRNA network in human hepatocellular carcinoma
Authors: Xu Ziwu , Pei Chaozhu , Cheng Haojie , Song Kaixin , Yang Junting , Li Yuhang , He Yue , Liang Wenxuan , Liu Biyuan , Tan Wen , Li Xia , Pan Xue , Meng Lei 
Published: May 2023

BackgroundForkhead box M1 (FOXM1) is a member of the Forkhead box (Fox) transcription factor family. It regulates cell mitosis, cell proliferation, and genome stability. However, the relationship between the expression of FOXM1 and the levels of m6a modification, immune infiltration, glycolysis, and ketone body metabolism in HCC has yet to be fully elucidated.MethodsTranscriptome and somatic mutation profiles of HCC were downloaded from the TCGA database. Somatic mutations were analyzed by maftools R package and visualized in oncoplots. GO, KEGG and GSEA function enrichment was performed on FOXM1 co-expression using R. We used Cox regression and machine learning algorithms (CIBERSORT, LASSO, random forest, and SVM-RFE) to study the prognostic value of FOXM1 and immune infiltrating characteristic immune cells in HCC. The relationship between FOXM1 and m6A modification, glycolysis, and ketone body metabolism were analyzed by RNA-seq and CHIP-seq. The competing endogenous RNA (ceRNA) network construction relies on the multiMiR R package, ENCORI, and miRNET platforms.ResultsFOXM1 is highly expressed in HCC and is associated with a poorer prognosis. At the same time, the expression level of FOXM1 is significantly related to the T, N, and stage. Subsequently, based on the machine learning strategies, we found that the infiltration level of T follicular helper cells (Tfh) was a risk factor affecting the prognosis of HCC patients. The high infiltration of Tfh was significantly related to the poor overall survival rate of HCC. Besides, the CHIP-seq demonstrated that FOXM1 regulates m6a modification by binding to the promoter of IGF2BP3 and affects the glycolytic process by initiating the transcription of HK2 and PKM in HCC. A ceRNA network was successfully obtained, including FOXM1 - has-miR-125-5p – DANCR/MIR4435-2HG ceRNA network related to the prognosis of HCC.ConclusionOur study implicates that the aberrant infiltration of Tfh associated with FOXM1 is a crucial prognostic factor for HCC patients. FOXM1 regulates genes related to m6a modification and glycolysis at the transcriptional level. Furthermore, the specific ceRNA network can be used as a potential therapeutic target for HCC.
Tertiary lymphoid structures predict the prognosis and immunotherapy response of cholangiocarcinoma
Authors: Shang Taiyu , Jiang Tianyi , Lu Tao , Wang Hui , Cui Xiaowen , Pan Yufei , Xu Mengyou , Pei Mengmiao , Ding Zhiwen , Feng Xiaofan , Lin Yunkai , Li Xin , Tan Yexiong , Feng Feiling , Dong Hui , Wang Hongyang , Dong Liwei 
Published: May 2023

IntroductionCholangiocarcinoma (CCA) is a malignant tumor of the biliary epithelium with a poor prognosis. The lack of biomarkers to predict therapeutic response and prognosis is one of the major challenges for CCA treatment. Tertiary lymphoid structures (TLS) provide a local and pivotal microenvironment for tumor immune responses. The prognostic value and clinical relevance of TLS in CCA remain unclear. We aimed to explore the characteristics and clinical significance of TLS in CCA.MethodsWe investigated the prognostic value and clinical relevance of TLS in CCA using a surgery cohort containing 471 CCA patients (cohort 1) and an immunotherapy cohort containing 100 CCA patients (cohort 2). Hematoxylin and eosin (H&amp;E) and immunohistochemical (IHC) staining were used to evaluate the maturity of TLS. Multiplex IHC (mIHC) was employed to characterize the composition of TLS.ResultsDifferent maturity of TLS were observed in CCA tissue sections. Strong staining of the four-gene signature including PAX5, TCL1A, TNFRSF13C, and CD79A were found in TLS regions. A high density of intra-tumoral TLS (T-score high) were significantly correlated with longer overall survival (OS) both in CCA cohort 1 (p = 0.002) and cohort 2 (p = 0.01), whereas a high density of peri-tumoral TLS (P-score high) were associated with shorter OS in these two cohorts (p = 0.003 and p = 0.03, respectively).ConclusionThe established four-gene signature efficiently identified the TLS in CCA tissues. The abundance and spatial distribution of TLS were significantly correlated with the prognosis and immune checkpoint inhibitors (ICIs) immunotherapy response of CCA patients. The presence of intra-tumoral TLS are positive prognostic factors for CCA, which provide a theoretical basis for the future diagnosis and treatment of CCA.
Immunoglobulin E-virus phenotypes of infant bronchiolitis and risk of childhood asthma
Authors: Shibata Ryohei , Zhu Zhaozhong , Ooka Tadao , Freishtat Robert J. , Mansbach Jonathan M. , Pérez-Losada Marcos , Ramos-Tapia Ignacio , Teach Stephen , Camargo Carlos A. , Hasegawa Kohei 
Published: May 2023

BackgroundBronchiolitis is the leading cause of infant hospitalization in U.S. and is associated with increased risk for childhood asthma. Immunoglobulin E (IgE) not only plays major roles in antiviral immune responses and atopic predisposition, but also offers a potential therapeutic target.ObjectiveWe aimed to identify phenotypes of infant bronchiolitis by using total IgE (tIgE) and virus data, to determine their association with asthma development, and examine their biological characteristics.MethodsIn a multicenter prospective cohort study of 1,016 infants (age &lt;1 year) hospitalized for bronchiolitis, we applied clustering approaches to identify phenotypes by integrating tIgE and virus (respiratory syncytial virus [RSV], rhinovirus [RV]) data at hospitalization. We examined their longitudinal association with the risk of developing asthma by age 6 years and investigated their biological characteristics by integrating the upper airway mRNA and microRNA data in a subset (n=182).ResultsIn infants hospitalized for bronchiolitis, we identified 4 phenotypes: 1) tIgElowvirusRSV-high, 2) tIgElowvirusRSV-low/RV, 3) tIgEhighvirusRSV-high, and 4) tIgEhighvirusRSV-low/RV phenotypes. Compared to phenotype 1 infants (resembling “classic” bronchiolitis), phenotype 4 infants (tIgEhighvirusRSV-low/RV) had a significantly higher risk for developing asthma (19% vs. 43%; adjOR, 2.93; 95% CI, 1.02–8.43; P=.046). Phenotypes 3 and 4 (tIgEhigh) had depleted type I interferon and enriched antigen presentation pathways; phenotype 4 also had depleted airway epithelium structure pathways.ConclusionsIn this multicenter cohort, tIgE-virus clustering identified distinct phenotypes of infant bronchiolitis with differential risks of asthma development and unique biological characteristics.
Biocrust carbon exchange varies with crust type and time on Chihuahuan Desert gypsum soils
Authors: Hoellrich Mikaela R. , James Darren K. , Bustos David , Darrouzet-Nardi Anthony , Santiago Louis S. , Pietrasiak Nicole 
Published: May 2023

IntroductionIn dryland systems, biological soil crusts (biocrusts) can occupy large areas of plant interspaces, where they fix carbon following rain. Although distinct biocrust types contain different dominant photoautotrophs, few studies to date have documented carbon exchange over time from various biocrust types. This is especially true for gypsum soils. Our objective was to assess the carbon exchange of biocrust types established at the world’s largest gypsum dune field at White Sands National Park.MethodsWe sampled five different biocrust types from a sand sheet location in three different years and seasons (summer 2020, fall 2021, and winter 2022) for carbon exchange measurements in controlled lab conditions. Biocrusts were rehydrated to full saturation and light incubated for 30 min, 2, 6, 12, 24, and 36 h. Samples were then subject to a 12-point light regime with a LI-6400XT photosynthesis system to determine carbon exchange.ResultsBiocrust carbon exchange values differed by biocrust type, by incubation time since wetting, and by date of field sampling. Lichens and mosses had higher gross and net carbon fixation rates than dark and light cyanobacterial crusts. High respiration rates were found after 0.5 h and 2 h incubation times as communities recovered from desiccation, leveling off after 6 h incubation. Net carbon fixation of all types increased with longer incubation time, primarily as a result of decreasing respiration, which suggests rapid recovery of biocrust photosynthesis across types. However, net carbon fixation rates varied from year to year, likely as a product of time since the last rain event and environmental conditions preceding collection, with moss crusts being most sensitive to environmental stress at our study sites.DiscussionGiven the complexity of patterns discovered in our study, it is especially important to consider a multitude of factors when comparing biocrust carbon exchange rates across studies. Understanding the dynamics of biocrust carbon fixation in distinct crust types will enable greater precision of carbon cycling models and improved forecasting of impacts of global climate change on dryland carbon cycling and ecosystem functioning.
The unhealthy-tasty intuition in dining out situations: the role of health inferences and taste expectations
Authors: Garaus Marion , Wolfsteiner Elisabeth , Hu Jennifer 
Published: May 2023

IntroductionIncreasing obesity rates around the globe have challenged policymakers to find strategies to prompt healthier eating habits. While unhealthy eating takes place in many different contexts, dining out is a context where individuals often choose an unhealthy option despite the availability of healthier alternatives. One possible explanation for this behavior is the unhealthy-tasty intuition, which refers to the belief that unhealthy food is tastier than healthy food. Nevertheless, many policymakers and restaurant managers follow the – in this context – counterintuitive approach of using health claims to nudge people towards more healthy eating choices or habits.MethodsThe current research employs an online experiment with 137 participants and investigates how health claims and sensory claims impact on the purchase intention of healthy options for desserts. Furthermore, it explores how health inferences and taste expectations mediate the intention to purchase.Results and discussionFindings from the online experiment confirm that health claims prompt positive health inferences, while also stimulating unfavorable taste expectations, resulting in a lower intention to purchase. Surprisingly, we found no effect of a sensory claim on taste expectations. The findings of our experiment contradict the unhealthy-tasty intuition by revealing a significant positive correlation between taste expectations and health inferences. While both health inferences and taste expectations impact positively on purchasing intentions for the health-claim condition, the indirect effect of taste expectations was stronger than the indirect effect of health inferences.
Activity of TNT: a phase 2 study using talimogene laherparepvec, nivolumab and trabectedin for previously treated patients with advanced sarcomas (NCT# 03886311)
Authors: Chawla Sant P. , Tellez Walter Andree , Chomoyan Hripsime , Valencia Chrysler , Ahari Amir , Omelchenko Nadezhda , Makrievski Stefan , Brigham Don A. , Chua-Alcala Victoria , Quon Doris , Moradkhani Ania , Gordon Erlinda M. 
Published: May 2023

BackgroundIntratumoral injection of talimogene laherparepvec evokes a cytotoxic immune response. Therefore, the combination of talimogene laherparepvec with trabectedin and nivolumab may have synergistic effects in advanced sarcomas.Patients and methodsThis phase 2 trial was conducted from May 30, 2019 to January 31, 2022. Endpoints: Primary: Progression free survival rate at month 12. Secondary: Best overall response, progression free survival rate at 6 and 9 months, overall survival rate at 6, 9, and 12 months, incidence of conversion of an unresectable tumor to a resectable tumor, and incidence of adverse events. Eligible patients had to be ≥ 18 years of age, have advanced histologically proven sarcoma, at least 1 previous chemotherapy regimen, and at least one accessible tumor for intratumoral injection. Treatment: Trabectedin intravenously (1.2 mg/m2 q3 weeks), nivolumab intravenously (3 mg/kg q2 weeks), and intratumoral talimogene laherparepvec (1x108 plaque forming units/ml q2 weeks).ResultsMedian time of follow-up: 15.2 months. Efficacy analysis: Thirty-nine patients who had completed at least one treatment cycle and had a follow-up computerized tomography were evaluable for efficacy analysis. Median number of prior therapies: 4 (range 1-11). Progression free survival rate at month 12, 36.7%. Confirmed Best Overall Response by Response Evaluation Criteria in Solid Tumors v1.1 = 3 partial responses, 30 stable disease, 6 progressive disease. Best Overall Response Rate, 7.7%, Disease Control Rate, 84.6%; median progression free survival, 7.8 (95% Confidence Intervals: 4.1-13.1) months; 6-, 9-, 12-month progression free survival rates, 54.5%/45.9%/36.7%; median overall survival 19.3 (95% Confidence Intervals: 12.8 -.) months; 6-, 9- and 12-month overall survival rate, 86.9%/73.3%/73.3%. One patient had a complete surgical resection. Fifty percent of patients had a ≥ grade 3 treatment related adverse events which included anemia (6%), thrombocytopenia (6%), neutropenia (4%), increased alanine transaminase (4%), decreased left ventricular ejection fraction (4%), dehydration (4%), hyponatremia (4%).ConclusionsTaken together these data suggest that the TNT regimen is effective and safe for advanced previously treated sarcomas, and is worth being further studied in a randomized phase 3 trial as first- or second- line treatment for patients with advanced sarcomas.
The clinical relevance and prediction efficacy from therapy of tumor microenvironment related signature score in colorectal cancer
Authors: Jun Xiang , Gao Shengnan , Yu Lei , Wang Guiyu 
Published: May 2023

IntroductionAs the top 3 cancer in terms of incidence and mortality, the first-line treatment for CRC includes FOLFOX, FOLFIRI, Cetuximab or immunotherapy. However, the drug sensitivity of patients to regimens is different. There has been increasing evidence that immune components of TME can affect the sensitivity of patients to drugs. Therefore, it is necessary to define novo molecular subtypes of CRC based on TME immune components, and screen patients who are sensitive to the treatments, to make personalized therapy possible. MethodsWe analyzed the expression profiles and 197 TME-related signatures of 1775 patients using ssGSEA, univariate Cox proportional risk model and LASSO-Cox regression model, and defined a novo molecular subtype (TMERSS) of CRC. Simultaneously, we compared the clinicopathological factors, antitumor immune activity, immune cell abundance and differences of cell states in different TMERSS subtypes. In addition, patients sensitive to the therapy were screened out by correlation analysis between TMERSS subtypes and drug responses.ResultsCompared with low TMERSS subtype, high TMERSS subtype has a better outcome, which may be associated to higher abundance of antitumor immune cell in high TMERSS subtype. Our findings suggested that the high TMERSS subtype may have a higher proportion of respondents to Cetuximab agent and immunotherapy, while the low TMERSS subtype may be more suitable for treatment with FOLFOX and FOLFIRI regimens.DiscussionIn conclusion, the TMERSS model may provide a partial reference for the prognosis evaluation of patients, the prediction of drug sensitivity, and the implementation of clinical decision-making.
Intraoperative microscopic autofluorescence detection and characterization in brain tumors using stimulated Raman histology and two-photon fluorescence
Authors: Fürtjes Gina , Reinecke David , von Spreckelsen Niklas , Meißner Anna-Katharina , Rueß Daniel , Timmer Marco , Freudiger Christian , Ion-Margineanu Adrian , Khalid Florian , Watrinet Konstantin , Mawrin Christian , Chmyrov Andriy , Goldbrunner Roland , Bruns Oliver , Neuschmelting Volker 
Published: May 2023

IntroductionThe intrinsic autofluorescence of biological tissues interferes with the detection of fluorophores administered for fluorescence guidance, an emerging auxiliary technique in oncological surgery. Yet, autofluorescence of the human brain and its neoplasia is sparsely examined. This study aims to assess autofluorescence of the brain and its neoplasia on a microscopic level by stimulated Raman histology (SRH) combined with two-photon fluorescence.MethodsWith this experimentally established label-free microscopy technique unprocessed tissue can be imaged and analyzed within minutes and the process is easily incorporated in the surgical workflow. In a prospective observational study, we analyzed 397 SRH and corresponding autofluorescence images of 162 samples from 81 consecutive patients that underwent brain tumor surgery. Small tissue samples were squashed on a slide for imaging. SRH and fluorescence images were acquired with a dual wavelength laser (790 nm and 1020 nm) for excitation. In these images tumor and non-tumor regions were identified by a convolutional neural network that reliably differentiates between tumor, healthy brain tissue and low quality SRH images. The identified areas were used to define regions.of- interests (ROIs) and the mean fluorescence intensity was measured.ResultsIn healthy brain tissue, we found an increased mean autofluorescence signal in the gray (11.86, SD 2.61, n=29) compared to the white matter (5.99, SD 5.14, n=11, p&lt;0.01) and in the cerebrum (11.83, SD 3.29, n=33) versus the cerebellum (2.82, SD 0.93, n=7, p&lt;0.001), respectively. The signal of carcinoma metastases, meningiomas, gliomas and pituitary adenomas was significantly lower (each p&lt;0.05) compared to the autofluorescence in the cerebrum and dura, and significantly higher (each p&lt;0.05) compared to the cerebellum. Melanoma metastases were found to have a higher fluorescent signal (p&lt;0.01) compared to cerebrum and cerebellum.DiscussionIn conclusion we found that autofluorescence in the brain varies depending on the tissue type and localization and differs significantly among various brain tumors. This needs to be considered for interpreting photon signal during fluorescence-guided brain tumor surgery.
Effects of isolated central nervous system involvement evaluated by multiparameter flow cytometry prior to allografting on outcomes of patients with acute lymphoblastic leukemia
Authors: Ma Ling , Xu Lan-Ping , Wang Yu , Zhang Xiao-Hui , Chen Huan , Chen Yu-Hong , Wang Feng-Rong , Han Wei , Sun Yu-Qian , Yan Chen-Hua , Lv Meng , Tang Fei-Fei , Mo Xiao-Dong , Wang Zhi-Dong , Jiang Qian , Lu Jin , Jiang Hao , Liu Yan-Rong , Liu Kai-Yan , Chang Ying-Jun , Huang Xiao-Jun 
Published: May 2023

IntroductionAllogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a major strategy to cure patients with acute lymphoblastic leukemia (ALL). The aim of this study was to evaluate whether isolated flow cytometry (FCM)-positive central nervous system (CNS) involvement before allo-HSCT is clinically significant.MethodsThe effects of isolated FCM-positive CNS involvement prior to transplantation on the outcomes of 1406 ALL patients with complete remission (CR) were retrospectively investigated.ResultsPatients were classified into isolated FCM-positive CNS involvement (n=31), cytology-positive CNS involvement (n = 43), and negative CNS involvement (n = 1332) groups. Among the three groups, the 5-year cumulative incidence of relapse (CIR) values were 42.3%, 48.8%, and 23.4%, respectively (P&lt;0.001). The 5-year leukemia-free survival (LFS) values were 44.7%, 34.9%, and 60.8%, respectively (P&lt;0.001). Compared with the negative CNS group (n=1332), the 5-year CIR of the pre-HSCT CNS involvement group (n=74) was higher (46.3% vs. 23.4%, P&lt;0.001], and the 5-year LFS was inferior (39.1% vs. 60.8%, P&lt;0.001). Multivariate analysis indicated that four variables, T-cell ALL, in second complete remission or beyond (CR2+) at HSCT, pre-HSCT measurable residual disease positivity, and pre-HSCT CNS involvement, were independently associated with a higher CIR and inferior LFS. A new scoring system was developed using the following four variables: low-risk, intermediate-risk, high-risk, and extremely high-risk groups. The 5-year CIR values were 16.9%, 27.8%, 50.9%, and 66.7%, respectively (P&lt;0.001), while the 5-year LFS values were 67.6%, 56.9%, 31.0%, and 13.3%, respectively (P&lt;0.001).ConclusionOur results suggest that ALL patients with isolated FCM-positive CNS involvement are at a higher risk of recurrence after transplantation. Patients with pre-HSCT CNS involvement had higher CIR and inferior survival outcomes.
Automated machine learning to predict the difficulty for endoscopic resection of gastric gastrointestinal stromal tumor
Authors: Liu Luojie , Zhang Rufa , Shi Dongtao , Li Rui , Wang Qinghua , Feng Yunfu , Lu Fenying , Zong Yang , Xu Xiaodan 
Published: May 2023

BackgroundAccurate preoperative assessment of surgical difficulty is crucial to the success of the surgery and patient safety. This study aimed to evaluate the difficulty for endoscopic resection (ER) of gastric gastrointestinal stromal tumors (gGISTs) using multiple machine learning (ML) algorithms.MethodsFrom December 2010 to December 2022, 555 patients with gGISTs in multi-centers were retrospectively studied and assigned to a training, validation, and test cohort. A difficult case was defined as meeting one of the following criteria: an operative time ≥ 90 min, severe intraoperative bleeding, or conversion to laparoscopic resection. Five types of algorithms were employed in building models, including traditional logistic regression (LR) and automated machine learning (AutoML) analysis (gradient boost machine (GBM), deep neural net (DL), generalized linear model (GLM), and default random forest (DRF)). We assessed the performance of the models using the areas under the receiver operating characteristic curves (AUC), the calibration curve, and the decision curve analysis (DCA) based on LR, as well as feature importance, SHapley Additive exPlanation (SHAP) Plots and Local Interpretable Model Agnostic Explanation (LIME) based on AutoML.ResultsThe GBM model outperformed other models with an AUC of 0.894 in the validation and 0.791 in the test cohorts. Furthermore, the GBM model achieved the highest accuracy among these AutoML models, with 0.935 and 0.911 in the validation and test cohorts, respectively. In addition, it was found that tumor size and endoscopists’ experience were the most prominent features that significantly impacted the AutoML model’s performance in predicting the difficulty for ER of gGISTs.ConclusionThe AutoML model based on the GBM algorithm can accurately predict the difficulty for ER of gGISTs before surgery.