bluuebunny/crossref_metadata_2025_split huggingface dataset:
β-catenin attenuation leads to up-regulation of activating NKG2D ligands and tumor regression in BrafV600E-driven thyroid cancer cells
Authors: Zou Minjing , Al-Yahya Suhad , Al-Alwan Monther , BinEssa Huda A. , Khabar Khalid S. A. , Almohanna Falah , Assiri Abdullah M. , Altaweel Abdulmohsen , Qattan Amal , Meyer Brian F. , Alzahrani Ali S. , Shi Yufei 
Published: July 2023

IntroductionBRAFV600E mutations frequently occur in papillary thyroid cancer (PTC). β-catenin, encoded by CTNNB1, is a key downstream component of the canonical Wnt signaling pathway and is often overexpressed in PTC. BRAFV600E-driven PTC tumors rely on Wnt/β-catenin signaling to sustain growth and progression.MethodsIn the present study, we investigated the tumorigenicity of thyroid cancer cells derived from BRAFV600E PTC mice following Ctnnb1 ablation (BVE-Ctnnb1null).ResultsRemarkably, the tumorigenic potential of BVE-Ctnnb1null tumor cells was lost in nude mice. Global gene expression analysis of BVE-Ctnnb1null tumor cells showed up-regulation of NKG2D receptor activating ligands (H60a, H60b, H60c, Raet1a, Raet1b, Raet1c, Raet1d, Raet1e, and Ulbp1) and down-regulation of inhibitory MHC class I molecules H-2L and H-2K2 in BVE-Ctnnb1null tumor cells. In vitro cytotoxicity assay demonstrated that BVE-Ctnnb1wt tumor cells were resistant to NK cell-mediated cytotoxicity, whereas BVE-Ctnnb1null tumor cells were sensitive to NK cell-mediated killing. Furthermore, the overexpression of any one of these NKG2D ligands in the BVE-Ctnnb1wt cell line resulted in a significant reduction of tumor growth in nude mice. ConclusionsOur results indicate that active β-catenin signaling inhibits NK cell-mediated immune responses against thyroid cancer cells. Targeting the β-catenin signaling pathway may have significant therapeutic benefits for BRAF-mutant thyroid cancer by not only inhibiting tumor growth but also enhancing host immune surveillance.
Assessment of BoHV-4-based vector vaccine intranasally administered in a hamster challenge model of lung disease
Authors: Park Seok-Chan , Conti Laura , Franceschi Valentina , Oh Byungkwan , Yang Myeon-Sik , Ham Gaeul , Di Lorenzo Antonino , Bolli Elisabetta , Cavallo Federica , Kim Bumseok , Donofrio Gaetano 
Published: July 2023

IntroductionBovine herpesvirus 4 (BoHV-4) is a bovine Rhadinovirus not associated with a specific pathological lesion or disease and experimentally employed as a viral vector vaccine. BoHV-4-based vector (BoHV-4-BV) has been shown to be effective in immunizing and protecting several animal species when systemically administrated through intramuscular, subcutaneous, intravenous, or intraperitoneal routes. However, whether BoHV-4-BV affords respiratory disease protection when administered intranasally has never been tested.MethodsIn the present study, recombinant BoHV-4, BoHV-4-A-S-ΔRS-HA-ΔTK, was constructed to deliver an expression cassette for the SARS-CoV-2 spike glycoprotein, and its immunogenicity, as well as its capability to transduce cells of the respiratory tract, were tested in mice. The well-established COVID-19/Syrian hamster model was adopted to test the efficacy of intranasally administered BoHV-4-A-S-ΔRS-HA-ΔTK in protecting against a SARS-CoV-2 challenge.ResultsThe intranasal administration of BoHV-4-A-S-ΔRS-HA-ΔTK elicited protection against SARS-CoV-2, with improved clinical signs, including significant reductions in body weight loss, significant reductions in viral load in the trachea and lungs, and significant reductions in histopathologic lung lesions compared to BoHV-4-A-S-ΔRS-HA-ΔTK administered intramuscularly.DiscussionThese results suggested that intranasal immunization with BoHV-4-BV induced protective immunity and that BoHV-4-BV could be a potential vaccine platform for the protection of other animal species against respiratory diseases.
Insight of a lipid metabolism prognostic model to identify immune landscape and potential target for retroperitoneal liposarcoma
Authors: Wang Zhenyu , Tao Ping , Fan Peidang , Wang Jiongyuan , Rong Tao , Hou Yingyong , Zhou Yuhong , Lu Weiqi , Hong Liang , Ma Lijie , Zhang Yong , Tong Hanxing 
Published: July 2023

IntroductionThe exploration of lipid metabolism dysregulation may provide novel perspectives for retroperitoneal liposarcoma (RPLS). In our study, we aimed to investigate potential targets and facilitate further understanding of immune landscape in RPLS, through lipid metabolism-associated genes (LMAGs) based prognostic model.MethodsGene expression profiles and corresponding clinical information of 234 cases were enrolled from two public databases and the largest retroperitoneal tumor research center of East China, including cohort-TCGA (n=58), cohort-GSE30929 (n=92), cohort-FD (n=50), cohort-scRNA-seq (n=4) and cohort-validation (n=30). Consensus clustering analysis was performed to identify lipid metabolism-associated molecular subtypes (LMSs). A prognostic risk model containing 13 LMAGs was established using LASSO algorithm and multivariate Cox analysis in cohort-TCGA. ESTIMATE, CIBERSORT, XCELL and MCP analyses were performed to visualize the immune landscape. WGCNA was used to identify three hub genes among the 13 model LMAGs, and preliminarily validated in both cohort-GSE30929 and cohort-FD. Moreover, TIMER was used to visualize the correlation between antigen-presenting cells and potential targets. Finally, single-cell RNA-sequencing (scRNA-seq) analysis of four RPLS and multiplexed immunohistochemistry (mIHC) were performed in cohort-validation to validate the discoveries of bioinformatics analysis.ResultsLMS1 and LMS2 were characterized as immune-infiltrated and -excluded tumors, with significant differences in molecular features and clinical prognosis, respectively. Elongation of very long chain fatty acids protein 2 (ELOVL2), the enzyme that catalyzed the elongation of long chain fatty acids, involved in the maintenance of lipid metabolism and cellular homeostasis in normal cells, was identified and negatively correlated with antigen-presenting cells and identified as a potential target in RPLS. Furthermore, ELOVL2 was enriched in LMS2 with significantly lower immunoscore and unfavorable prognosis. Finally, a high-resolution dissection through scRNA-seq was performed in four RPLS, revealing the entire tumor ecosystem and validated previous findings.DiscussionThe LMS subgroups and risk model based on LMAGs proposed in our study were both promising prognostic classifications for RPLS. ELOVL2 is a potential target linking lipid metabolism to immune regulations against RPLS, specifically for patients with LMS2 tumors.
Ozone therapy as a novel complementary therapeutic approach in refractory idiopathic granulomatous mastitis
Authors: Cabioglu Neslihan , Trabulus Didem Can , Emiroglu Selman , Ozkurt Enver , Yalcin Nesli , Dinc Nagehan , Tukenmez Mustafa , Muslumanoglu Mahmut , Igci Abdullah , Ozmen Vahit , Dinccag Ahmet Sait , Guven Yusuf Izzettin 
Published: July 2023

BackgroundAutoimmunity may play a major role in the pathogenesis of idiopathic granulomatous mastitis (IGM). The therapeutic potential of ozone therapy has recently been shown in rheumatological diseases, and this study aimed to assess the clinical efficacy of ozone therapy (OT) in refractory IGM.MethodsPatients with biopsy-verified IGM and incomplete response after steroid therapy (n = 47) between 2018 and 2021 were enrolled. Of these, 23 cases in cohort A had standard treatment with further steroid therapy (ST), and 24 were treated with systemic OT via autohemotherapy (AHT) in addition to steroid therapy (cohort B).ResultsThe median age was 33 years (range, 24–45). Patients in cohort B had a higher complete response rate after completion of a four-month ozone therapy than those in the ST-group (OT-group, 37.5% vs. ST-group, 0%; p = 0.002). At a median follow-up of 12 months (range, 12–35), the patients treated with OT had a lower one-year recurrence in the affected breast than cases in cohort A treated with ST (OT-group, 21% vs. ST-group, 70%; p = 0.001). No significant side effects were observed in patients in cohort B related to AHT. Furthermore, OT significantly decreased the total steroid treatment duration (median week of steroid use; 26  weeks in cohort A vs. 12 weeks in cohort B; p = 0.001).ConclusionSystemic OT increases the complete response rate and decreases the duration of steroid treatment in patients with refractory IGM. Therefore, ozone therapy is an effective, well-tolerated, and safe novel complementary therapeutic modality.
Spokewise iridotomy combined with Descemet stripping automated endothelial keratoplasty in iridocorneal endothelial syndrome
Authors: Zhang Jiaxin , Peng Rongmei , Xiao Gege , Wang Minshu , Hong Jing 
Published: July 2023

PurposeIridocorneal endothelial (ICE) syndrome is a progressive anterior segment disorder that can be tricky to treat. Keratoplasty is commonly used to treat corneal edema in ICE syndrome. However, glaucoma is an important risk factor affecting graft survival. To address this question, we designed a retrospective cohort study to evaluate the effect of Spokewise Iridotomy (SI) on Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) Grafts in Iridocorneal Endothelial (ICE) Syndrome.MethodsThis was a retrospective cohort study. A total of 29 patients were included; 31 eyes with ICE syndrome underwent DSAEK at Peking University Third Hospital between June 2015 and June 2022, including 11 eyes with combined SI during DSAEK. The aim was to explore the effect of SI on vision, glaucoma control, complications, peripheral anterior synechiae recurrence, endothelial cell count, and graft survival.ResultsThe median follow-up time was 30.83 months (mo.) in the SI+Endothelial Keratoplasty (EK) group and 6.17 mo in the EK group. The 2-year cumulative survival rate of grafts in the SI+EK group was 100%, compared with the 6-month and 1-year cumulative survival rates of 80.2 and 63.2%, respectively, in the EK group (p = 0.043). The SI+EK group had a lower incidence of immediate postoperative complications (p = 0.005), fewer postoperative anti-glaucoma medications (AGMs) (p = 0.029), smaller peripheral anterior synechiae recurrence (p = 0.001), and significant visual acuity improvement (p &lt; 0.05). More AGMs were used in failed grafts (p = 0.002).ConclusionSI can help control intraocular pressure, improve visual acuity, and increase graft survival after DSAEK in ICE syndrome patients.
Comparison of the gut microbiota and metabolites between Diannan small ear pigs and Diqing Tibetan pigs
Authors: Guan Xuancheng , Zhu Junhong , Yi Lanlan , Sun Haichao , Yang Minghua , Huang Ying , Pan Hongbin , Wei Hongjiang , Zhao Hongye , Zhao Yanguang , Zhao Sumei 
Published: July 2023

ObjectiveHost genetics and environment participate in the shaping of gut microbiota. Diannan small ear pigs and Diqing Tibetan pigs are excellent native pig breeds in China and live in different environments. However, the gut microbiota of Diannan small ear pigs and Diqing Tibetan pigs were still rarely understood. Therefore, this study aimed to analyze the composition characteristics of gut microbiota and metabolites in Diannan small ear pigs and Diqing Tibetan pigs.MethodsFresh feces of 6 pigs were randomly collected from 20 4-month-old Diannan small ear pigs (DA group) and 20 4-month-old Diqing Tibetan pigs (TA group) for high-throughput 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC-MS) non-targeted metabolome analysis.ResultsThe results revealed that Firmicutes and Bacteroidetes were the dominant phyla in the two groups. Chao1 and ACE indices differed substantially between DA and TA groups. Compared with the DA group, the relative abundance of Prevotellaceae, and Ruminococcus was significantly enriched in the TA group, while the relative abundance of Lachnospiraceae, Actinomyces, and Butyricicoccus was significantly reduced. Cholecalciferol, 5-dehydroepisterol, stigmasterol, adrenic acid, and docosahexaenoic acid were significantly enriched in DA group, which was involved in the steroid biosynthesis and biosynthesis of unsaturated fatty acids. 3-phenylpropanoic acid, L-tyrosine, phedrine, rhizoctin B, and rhizoctin D were significantly enriched in TA group, which was involved in the phenylalanine metabolism and phosphonate and phosphinate metabolism.ConclusionWe found that significant differences in gut microbiota composition and metabolite between Diannan small ear pigs and Diqing Tibetan pigs, which provide a theoretical basis for exploring the relationship between gut microbiota and pig breeds.
Anti-Vibrio parahaemolyticus compounds from Streptomyces parvus based on Pan-genome and subtractive proteomics
Authors: Liu Wenbin , Ou Peiyu , Tian Fangyuan , Liao Jingyang , Ma Yan , Wang Jie , Jin Xiaobao 
Published: July 2023

IntroductionVibrio parahaemolyticus is a foodborne pathogen commonly found in seafood, and drug resistance poses significant challenges to its control. This study aimed to identify novel drug targets for antibacterial drug discovery.MethodsTo identify drug targets, we performed a pan-genome analysis on 58 strains of V. parahaemolyticus genomes to obtain core genes. Subsequently, subtractive proteomics and physiochemical checks were conducted on the core proteins to identify potential therapeutic targets. Molecular docking was then employed to screen for anti-V. parahaemolyticus compounds using a in-house compound library of Streptomyces parvus, chosen based on binding energy. The anti-V. parahaemolyticus efficacy of the identified compounds was further validated through a series of experimental tests.Results and DiscussionPangenome analysis of 58 V. parahaemolyticus genomes revealed that there were 1,392 core genes. After Subtractive proteomics and physiochemical checks, Flagellar motor switch protein FliN was selected as a therapeutic target against V. parahaemolyticus. FliN was modeled and docked with Streptomyces parvus source compounds, and Actinomycin D was identified as a potential anti-V. parahaemolyticus agent with a strong binding energy. Experimental verification confirmed its effectiveness in killing V. parahaemolyticus and significantly inhibiting biofilm formation and motility. This study is the first to use pan-genome and subtractive proteomics to identify new antimicrobial targets for V. parahaemolyticus and to identify the anti-V. parahaemolyticus effect of Actinomycin D. These findings suggest potential avenues for the development of new antibacterial drugs to control V. parahaemolyticus infections.
Evaluation of iron deposition in the motor CSTC loop of a Chinese family with paroxysmal kinesigenic dyskinesia using quantitative susceptibility mapping
Authors: Xie Fangfang , Mao Ting , Tang Jingyi , Zhao Linmei , Guo Jiuqing , Lin Huashan , Wang Dongcui , Zhou Gaofeng 
Published: July 2023

IntroductionPrevious studies have revealed structural, functional, and metabolic changes in brain regions inside the cortico-striatal-thalamo-cortical (CSTC) loop in patients with paroxysmal kinesigenic dyskinesia (PKD), whereas no quantitative susceptibility mapping (QSM)-related studies have explored brain iron deposition in these areas.MethodsA total of eight familial PKD patients and 10 of their healthy family members (normal controls) were recruited and underwent QSM on a 3T magnetic resonance imaging system. Magnetic susceptibility maps were reconstructed using a multi-scale dipole inversion algorithm. Thereafter, we specifically analyzed changes in local mean susceptibility values in cortical regions and subcortical nuclei inside the motor CSTC loop.ResultsCompared with normal controls, PKD patients had altered brain iron levels. In the cortical gray matter area involved with the motor CSTC loop, susceptibility values were generally elevated, especially in the bilateral M1 and PMv regions. In the subcortical nuclei regions involved with the motor CSTC loop, susceptibility values were generally lower, especially in the bilateral substantia nigra regions.ConclusionOur results provide new evidence for the neuropathogenesis of PKD and suggest that an imbalance in brain iron levels may play a role in PKD.
Periventricular and juxtacortical characterization of UManitoba-JHU functionally defined human white matter atlas networks
Authors: Figley Chase R. , Figley Teresa D. , Wong Kaihim , Uddin Md Nasir , Dalvit Carvalho da Silva Rodrigo , Kornelsen Jennifer 
Published: July 2023

BackgroundThe open-access UManitoba-JHU functionally defined human white matter (WM) atlas contains specific WM pathways and general WM regions underlying 12 functional brain networks in ICBM152 template space. However, it is not known whether any of these WM networks are disproportionately co-localized with periventricular and/or juxtacortical WM (PVWM and JCWM), which could potentially impact their ability to infer network-specific effects in future studies—particularly in patient populations expected to have disproportionate PVWM and/or JCWM damage.MethodsThe current study therefore identified intersecting regions of PVWM and JCWM (defined as WM within 5 mm of the ventricular and cortical boundaries) and: (1) the ICBM152 global WM mask, and (2) all 12 UManitoba-JHU WM networks. Dice Similarity Coefficient (DSC), Jaccard Similarity Coefficient (JSC), and proportion of volume (POV) values between PVWM (and JCWM) and each functionally defined WM network were then compared to corresponding values between PVWM (and JCWM) and global WM.ResultsBetween the 12 WM networks and PVWM, 8 had lower DSC, JSC, and POV; 1 had lower DSC and JSC, but higher POV; and 3 had higher DSC, JSC, and POV compared to global WM. For JCWM, all 12 WM networks had lower DSC, JSC, and POV compared to global WM.ConclusionThe majority of UManitoba-JHU functionally defined WM networks exhibited lower than average spatial similarity with PVWM, and all exhibited lower than average spatial similarity with JCWM. This suggests that they can be used to explore network-specific WM changes, even in patient populations with known predispositions toward PVWM and/or JCWM damage.
Learning from pseudo-labels: deep networks improve consistency in longitudinal brain volume estimation
Authors: Zhan Geng , Wang Dongang , Cabezas Mariano , Bai Lei , Kyle Kain , Ouyang Wanli , Barnett Michael , Wang Chenyu 
Published: July 2023

IntroductionBrain atrophy is a critical biomarker of disease progression and treatment response in neurodegenerative diseases such as multiple sclerosis (MS). Confounding factors such as inconsistent imaging acquisitions hamper the accurate measurement of brain atrophy in the clinic. This study aims to develop and validate a robust deep learning model to overcome these challenges; and to evaluate its impact on the measurement of disease progression.MethodsVoxel-wise pseudo-atrophy labels were generated using SIENA, a widely adopted tool for the measurement of brain atrophy in MS. Deformation maps were produced for 195 pairs of longitudinal 3D T1 scans from patients with MS. A 3D U-Net, namely DeepBVC, was specifically developed overcome common variances in resolution, signal-to-noise ratio and contrast ratio between baseline and follow up scans. The performance of DeepBVC was compared against SIENA using McLaren test-retest dataset and 233 in-house MS subjects with MRI from multiple time points. Clinical evaluation included disability assessment with the Expanded Disability Status Scale (EDSS) and traditional imaging metrics such as lesion burden.ResultsFor 3 subjects in test-retest experiments, the median percent brain volume change (PBVC) for DeepBVC and SIENA was 0.105 vs. 0.198% (subject 1), 0.061 vs. 0.084% (subject 2), 0.104 vs. 0.408% (subject 3). For testing consistency across multiple time points in individual MS subjects, the mean (± standard deviation) PBVC difference of DeepBVC and SIENA were 0.028% (± 0.145%) and 0.031% (±0.154%), respectively. The linear correlation with baseline T2 lesion volume werer= −0.288 (p&lt; 0.05) andr= −0.249 (p&lt; 0.05) for DeepBVC and SIENA, respectively. There was no significant correlation of disability progression with PBVC as estimated by either method (p= 0.86,p= 0.84).DiscussionDeepBVC is a deep learning powered brain volume change estimation method for assessing brain atrophy used T1-weighted images. Compared to SIENA, DeepBVC demonstrates superior performance in reproducibility and in the context of common clinical scan variances such as imaging contrast, voxel resolution, random bias field, and signal-to-noise ratio. Enhanced measurement robustness, automation, and processing speed of DeepBVC indicate its potential for utilisation in both research and clinical environments for monitoring disease progression and, potentially, evaluating treatment effectiveness.
The beneficial effect of sulforaphane on platelet responsiveness during caloric load: a single-intake, double-blind, placebo-controlled, crossover trial in healthy participants
Authors: van Steenwijk Hidde P. , Winter Evi , Knaven Edward , Brouwers Jos F. , van Baardwijk Myrthe , van Dalum Jasper B. , Luijendijk Teus J. C. , van Osch Frits H. M. , Troost Freddy J. , Bast Aalt , Semen Khrystyna O. , de Boer Alie 
Published: July 2023

Background and aimsAs our understanding of platelet activation in response to infections and/or inflammatory conditions is growing, it is becoming clearer that safe, yet efficacious, platelet-targeted phytochemicals could improve public health beyond the field of cardiovascular diseases. The phytonutrient sulforaphane shows promise for clinical use due to its effect on inflammatory pathways, favorable pharmacokinetic profile, and high bioavailability. The potential of sulforaphane to improve platelet functionality in impaired metabolic processes has however hardly been studied in humans. This study investigated the effects of broccoli sprout consumption, as a source of sulforaphane, on urinary 11-dehydro-thromboxane B2 (TXB2), a stable thromboxane metabolite used to monitor eicosanoid biosynthesis and response to antithrombotic therapy, in healthy participants exposed to caloric overload.MethodsIn this double-blind, placebo-controlled, crossover trial 12 healthy participants were administered 16g of broccoli sprouts, or pea sprouts (placebo) followed by the standardized high-caloric drink PhenFlex given to challenge healthy homeostasis. Urine samples were collected during the study visits and analyzed for 11-dehydro-TXB2, sulforaphane and its metabolites. Genotyping was performed using Illumina GSA v3.0 DTCBooster.ResultsAdministration of broccoli sprouts before the caloric load reduced urinary 11-dehydro-TXB2 levels by 50% (p = 0.018). The amount of sulforaphane excreted in the urine during the study visits correlated negatively with 11-dehydro-TXB2 (rs = −0.377, p = 0.025). Participants carrying the polymorphic variant NAD(P)H dehydrogenase quinone 1 (NQO1*2) showed decreased excretion of sulforaphane (p = 0.035).ConclusionSulforaphane was shown to be effective in targeting platelet responsiveness after a single intake. Our results indicate an inverse causal relationship between sulforaphane and 11-dehydro-TXB2, which is unaffected by the concomitant intake of the metabolic challenge. 11-Dehydro-TXB2 shows promise as a non-invasive, sensitive, and suitable biomarker to investigate the effects of phytonutrients on platelet aggregation within hours.Clinical trial registration[https://clinicaltrials.gov/], identifier [NCT05146804].