MARCH2, a Novel Oncogene-regulated SNAIL E3 Ligase, Suppresses Triple-negative Breast Cancer Metastases.

Epithelial-mesenchymal transition (EMT) in cancer promotes metastasis and chemotherapy resistance. A subset of triple-negative breast cancer (TNBC) exhibits a mesenchymal gene signature that is associated with poor patient outcomes. We previously identified PTK6 tyrosine kinase as an oncogenic driver of EMT in a subset of TNBC. PTK6 induces EMT by stabilizing SNAIL, a key EMT-initiating transcriptional factor. Inhibition of PTK6 activity reverses mesenchymal features of TNBC cells and suppresses their metastases by promoting SNAIL degradation via a novel mechanism. In the current study, we identify membrane-associated RING-CH2 (MARCH2) as a novel PTK6-regulated E3 ligase that promotes the ubiquitination and degradation of SNAIL protein. The MARCH2 RING domain is critical for SNAIL ubiquitination and subsequent degradation. PTK6 inhibition promotes the interaction of MARCH2 with SNAIL. Overexpression of MARCH2 exhibits tumor suppressive properties and phenocopies the effects of SNAIL downregulation and PTK6 inhibition in TNBC cells, such as inhibition of migration, anoikis resistance, and metastasis. Consistent with this, higher levels of MARCH2 expression in breast and other cancers are associated with better prognosis. We have identified MARCH2 as a novel SNAIL E3 ligase that regulates EMT and metastases of mesenchymal TNBC. SIGNIFICANCE: EMT is a process directly linked to drug resistance and metastasis of cancer cells. We identified MARCH2 as a novel regulator of SNAIL, a key EMT driver, that promotes SNAIL ubiquitination and degradation in TNBC cells. MARCH2 is oncogene regulated and inhibits growth and metastasis of TNBC. These insights could contribute to novel strategies to therapeutically target TNBC.

Extraction of mandibular third molars: relationship of preoperative anxiety with body mass index, serum high-sensitivity C-reactive protein levels, and visual analog scale scores and predictors of postoperative complications.

Objectives: Patients undergoing oral surgery exhibit high anxiety, which may elevate their cortisol levels and affect postoperative recovery. Overweight patients are often encountered in the dental clinic due to the increasing prevalence of overweight. We aimed to investigate the relationships between preoperatively assessed body mass index (BMI), serum cortisol and high-sensitivity C-reactive protein (hs-CRP) levels, and visual analog scale (VAS) scores and preoperative anxiety in patients undergoing mandibular third molar (MM3) extraction and to identify predictors of postoperative complications. Patients and Methods: We analyzed 43 patients (age, 20-42 years) undergoing MM3 extraction. At the first visit, patients completed the Modified Dental Anxiety Scale (MDAS) and Amsterdam Preoperative Anxiety and Information Scale (APAIS) questionnaires. Their BMI and VAS scores were also calculated. The participants underwent blood tests 1 hour before MM3 extraction. On the first postoperative day, the participants' VAS scores and serum hs-CRP levels were reevaluated. Results: We found that BMI was significantly correlated with preoperative VAS scores. Further, BMI and preoperative hs-CRP levels were significantly correlated among women and patients undergoing extractions of fully impacted MM3s. No correlations were found between serum cortisol and other variables. The preoperative MDAS and VAS scores were significantly positively correlated, especially among patients undergoing extractions of fully impacted MM3s. Multiple linear regression showed that BMI and the eruption status of the MM3 were significant predictors of postoperative hs- CRP levels and VAS scores, respectively. Conclusion: In MM3 removals, patients with higher BMI showed elevated hs-CRP and higher VAS scores before surgery. Patients with higher anxiety among those undergoing extractions of fully impacted MM3s showed higher preoperative VAS scores. The two main predictors of postoperative complications were BMI and MM3 eruption status.

A deep attention LSTM embedded aggregation network for multiple histopathological images.

Recent advancements in computer vision and neural networks have facilitated the medical imaging survival analysis for various medical applications. However, challenges arise when patients have multiple images from multiple lesions, as current deep learning methods provide multiple survival predictions for each patient, complicating result interpretation. To address this issue, we developed a deep learning survival model that can provide accurate predictions at the patient level. We propose a deep attention long short-term memory embedded aggregation network (DALAN) for histopathology images, designed to simultaneously perform feature extraction and aggregation of lesion images. This design enables the model to efficiently learn imaging features from lesions and aggregate lesion-level information to the patient level. DALAN comprises a weight-shared CNN, attention layers, and LSTM layers. The attention layer calculates the significance of each lesion image, while the LSTM layer combines the weighted information to produce an all-encompassing representation of the patient's lesion data. Our proposed method performed better on both simulated and real data than other competing methods in terms of prediction accuracy. We evaluated DALAN against several naive aggregation methods on simulated and real datasets. Our results showed that DALAN outperformed the competing methods in terms of c-index on the MNIST and Cancer dataset simulations. On the real TCGA dataset, DALAN also achieved a higher c-index of 0.803±0.006 compared to the naive methods and the competing models. Our DALAN effectively aggregates multiple histopathology images, demonstrating a comprehensive survival model using attention and LSTM mechanisms.

Kissing Viabahn VBX stent graft reconstruction of thoracic central veins for management of superior vena cava syndrome.

OBJECTIVE: In the present study, we evaluated the technical and clinical outcomes of thoracic central vein reconstruction for superior vena cava (SVC) syndrome using kissing Viabahn VBX stent grafts (W.L. Gore & Associates, Flagstaff, AZ). METHODS: All adult patients with SVC syndrome who had undergone attempted bilateral brachiocephalic vein-to-SVC reconstruction using kissing VBX stent grafts at an academic hospital between August 2019 and February 2021 were reviewed. The technical results, adverse events, imaging follow-up findings, and clinical outcomes were recorded. Patency over time was assessed using Kaplan-Meier analysis. RESULTS: A total of 28 patients (16 women and 12 men; mean age, 52.0 years) constituted the study cohort. Of the 28 patients, 17 (60.7%) had had benign and 11 (39.3%) malignant etiologies. The presenting symptoms included neck swelling (n = 17; 60.7%), bilateral upper extremity swelling (n = 15; 53.6%), dyspnea (n = 7; 25%), unilateral upper extremity swelling (n = 4; 14.3%), and dysphagia (n = 1; 3.6%). SVC reconstruction with VBX stent grafts in a kissing configuration was successfully completed in 27 of the 28 patients (96.4%). Four major adverse events were noted in the benign etiology subgroup (23.5%), including intraprocedural hemopericardium (n = 3) and delayed pneumothorax (n = 1). Of the 28 patients, 27 (96.4%) had experienced resolution of their presenting symptoms. The mean clinical follow-up for the living patients was 358.8 ± 77.2 days (range, 78-645 days). The mean imaging follow-up for the living patients was 272.6 ± 91 days (range, 26-594 days). The primary, primary-assisted, and secondary patency rates at 12 months were 71.8%, 88.8%, and 100%, respectively. CONCLUSIONS: For the management of SVC syndrome, thoracic central vein reconstruction with kissing VBX stent grafts was feasible with a high rate of symptom resolution and acceptable patency. However, this technique should not be recommended for those with benign SVC syndrome owing to the high risk of cardiac tamponade.

In situ microenvironment remodeling using a dual-responsive system: photodegradable hydrogels and gene activation by visible light.

A 3D microenvironment with dynamic cell-biomaterial interactions was developed using a dual-responsive system for in situ microenvironment remodeling and control of cellular function. A visible-light-responsive polymer was utilized to prepare a hydrogel with photodegradation properties, enabling in situ microenvironment remodeling. Additionally, a vascular endothelial growth factor (VEGF) gene activation unit that was responsive to the same wavelength of light was incorporated to support the potential application of the system in regenerative medicine. Following light exposure, the mechanical properties of the photodegradable hydrogel gradually deteriorated, and product analysis confirmed the degradation of the hydrogel, and thereby, 3D microenvironment remodeling. In situ microenvironment remodeling influenced stem cell proliferation and enlargement within the hydrogel. Furthermore, stem cells engineered to express light-activated VEGF and incorporated into the dual-responsive system were applied to wound healing and an ischemic hindlimb model, proving their potential application in regenerative medicine.

Integrative network analysis of early-stage lung adenocarcinoma identifies aurora kinase inhibition as interceptor of invasion and progression.

Here we focus on the molecular characterization of clinically significant histological subtypes of early-stage lung adenocarcinoma (esLUAD), which is the most common histological subtype of lung cancer. Within lung adenocarcinoma, histology is heterogeneous and associated with tumor invasion and diverse clinical outcomes. We present a gene signature distinguishing invasive and non-invasive tumors among esLUAD. Using the gene signatures, we estimate an Invasiveness Score that is strongly associated with survival of esLUAD patients in multiple independent cohorts and with the invasiveness phenotype in lung cancer cell lines. Regulatory network analysis identifies aurora kinase as one of master regulators of the gene signature and the perturbation of aurora kinases in vitro and in a murine model of invasive lung adenocarcinoma reduces tumor invasion. Our study reveals aurora kinases as a therapeutic target for treatment of early-stage invasive lung adenocarcinoma.

A therapeutic convection-enhanced macroencapsulation device for enhancing ß cell viability and insulin secretion.

Islet transplantation for type 1 diabetes treatment has been limited by the need for lifelong immunosuppression regimens. This challenge has prompted the development of macroencapsulation devices (MEDs) to immunoprotect the transplanted islets. While promising, conventional MEDs are faced with insufficient transport of oxygen, glucose, and insulin because of the reliance on passive diffusion. Hence, these devices are constrained to two-dimensional, wafer-like geometries with limited loading capacity to maintain cells within a distance of passive diffusion. We hypothesized that convective nutrient transport could extend the loading capacity while also promoting cell viability, rapid glucose equilibration, and the physiological levels of insulin secretion. Here, we showed that convective transport improves nutrient delivery throughout the device and affords a three-dimensional capsule geometry that encapsulates 9.7-fold-more cells than conventional MEDs. Transplantation of a convection-enhanced MED (ceMED) containing insulin-secreting ß cells into immunocompetent, hyperglycemic rats demonstrated a rapid, vascular-independent, and glucose-stimulated insulin response, resulting in early amelioration of hyperglycemia, improved glucose tolerance, and reduced fibrosis. Finally, to address potential translational barriers, we outlined future steps necessary to optimize the ceMED design for long-term efficacy and clinical utility.

An Unusual Pediatric Case of Seronegative Systemic Lupus Erythematosus Presented With Acute Abdominal Pain and Gross Hematuria.

ABSTRACT: A child with acute abdomen with gross hematuria occasionally visits the emergency department (ED). Usually, such a condition is subject to differential diagnosis for stones, injuries, or sometimes malignancies in the urinary tract. Here we introduce an unusual case of a 9-year-old girl who presented to ED with acute lower abdominal pain and gross hematuria. She had no medical history. An urgent computed tomographic image revealed a renal vein thrombosis. Laboratory tests for autoimmune diseases and coagulaopathies were performed, and the results were within normal ranges. At the time, she did not fulfil the criteria for systemic lupus erythematosus or antiphospholipid syndrome. Later at follow-up, however, she had a recurrent episode of renal vein thrombosis. A kidney biopsy was performed to reveal histology of membranous lupus nephropathy. The case emphasizes the importance for both ED physicians and pediatricians to have a clinical suspicion of autoimmune diseases in cases with major vessel thrombosis, even when the patient is seronegative.

Identification of Let-7 miRNA Activity as a Prognostic Biomarker of SHH Medulloblastoma.

Medulloblastoma (MB) is the most common pediatric embryonal brain tumor. The current consensus classifies MB into four molecular subgroups: sonic hedgehog-activated (SHH), wingless-activated (WNT), Group 3, and Group 4. MYCN and let-7 play a critical role in MB. Thus, we inferred the activity of miRNAs in MB by using the ActMiR procedure. SHH-MB has higher MYCN expression than the other subgroups. We showed that high MYCN expression with high let-7 activity is significantly associated with worse overall survival, and this association was validated in an independent MB dataset. Altogether, our results suggest that let-7 activity and MYCN can further categorize heterogeneous SHH tumors into more and less-favorable prognostic subtypes, which provide critical information for personalizing treatment options for SHH-MB. Comparing the expression differences between the two SHH-MB prognostic subtypes with compound perturbation profiles, we identified FGFR inhibitors as one potential treatment option for SHH-MB patients with the less-favorable prognostic subtype.

Reporting and Abstracting Variability in Technical Standards for Breast Cancer Operations.

BACKGROUND: The American College of Surgeons Commission on Cancer has incorporated documentation of critical elements outlined in Operative Standards for Cancer Surgery into revised standards for cancer center accreditation. This study assessed the current documentation of critical elements in partial mastectomy (PM) and sentinel lymph node biopsy (SLNB) operative reports. MATERIALS AND METHODS: Operative reports for PM + SLNB at a single academic institution from 2013 to 2018 were reviewed for compliance and surveyor interobserver reliability with the Oncologic Elements of Operative Record defined in Operative Standards and compared with a nonredundant American Society of Breast Surgeons Mastery of Breast Surgery (MBS) quality measure for specimen orientation. RESULTS: Ten reviewers each evaluated 66 PM + SLNB operative reports for 13 Oncologic Elements and one MBS measure. No operative records reported all critical elements for PM + SLNB or PM alone. Residents completed 36.4% of operative reports: Element documentation was similar for PM but varied significantly for SLNB between resident and attending authorship. Combined reporting performance and interrater reliability varied across all elements and was highest for the use of SLNB tracer (97.1% and κ = 0.95, respectively) and lowest for intraoperative assessment of SLNB (30.6%, κ = 0.43). MBS specimen orientation had both high proportion reported (87.0%) and interrater reliability (κ = 0.84). CONCLUSIONS: Adherence to reporting critical elements for PM and SLNB varied. Whether differential compliance was tied to discrepancies in documentation or reviewer abstraction, clarification of synoptic choices may improve reporting consistency. Evolving techniques or technologies will require continuous appraisal of mandated reporting for breast surgery.

Lung T1 mapping magnetic resonance imaging in the assessment of pulmonary disease in children with cystic fibrosis: a pilot study.

BACKGROUND: Assessment tools for early cystic fibrosis (CF) lung disease are limited. Detecting early pulmonary disease is crucial to increasing life expectancy by starting interventions to slow the progression of the pulmonary disease with the many treatment options available. OBJECTIVE: To compare the utility of lung T1-mapping MRI with ultrashort echo time (UTE) MRI in children with cystic fibrosis in detecting early stage lung disease and monitoring pulmonary exacerbations. MATERIALS AND METHODS: We performed a prospective study in 16 children between September 2017 and January 2018. In Phase 1, we compared five CF patients with normal spirometry (mean 11.2 years) to five age- and gender-matched healthy volunteers. In Phase 2, we longitudinally evaluated six CF patients (median 11 years) in acute pulmonary exacerbation. All children had non-contrast lung T1-mapping and UTE MRI and spirometry testing. We compared the mean normalized T1 value and percentage lung volume without T1 value in CF patients and healthy subjects in Phase 1 and during treatment in Phase 2. We also performed cystic fibrosis MRI scoring. We evaluated differences in continuous variables using standard statistical tests. RESULTS: In Phase 1, mean normalized T1 values of the lung were significantly lower in CF patients in comparison to healthy controls (P=0.02) except in the right lower lobe (P=0.29). The percentage lung volume without T1 value was also significantly higher in CF patients (P=0.006). UTE MRI showed no significant differences between CF patients and healthy volunteers (P=0.11). In Phase 2, excluding one outlier case who developed systemic disease in the course of treatment, the whole-lung T1 value increased (P=0.001) and perfusion scoring improved (P=0.02) following therapy. We observed no other significant changes in the MRI scoring. CONCLUSION: Lung T1-mapping MRI can detect early regional pulmonary CF disease in children and might be helpful in the assessment of acute pulmonary exacerbations.

18F-Choline PET/mpMRI for Detection of Clinically Significant Prostate Cancer: Part 1. Improved Risk Stratification for MRI-Guided Transrectal Prostate Biopsies.

A prospective single-arm clinical trial was conducted to determine whether 18F-choline PET/mpMRI can improve the specificity of multiparametric MRI (mpMRI) of the prostate for Gleason ≥ 3+4 prostate cancer. Methods: Before targeted and systematic prostate biopsy, mpMRI and 18F-choline PET/CT were performed on 56 evaluable subjects with 90 Likert score 3-5 mpMRI target lesions, using a 18F-choline target-to-background ratio of greater than 1.58 to indicate a positive 18F-choline result. Prostate biopsies were performed after registration of real-time transrectal ultrasound with T2-weighted MRI. A mixed-effects logistic regression was applied to measure the performance of mpMRI (based on prospective Likert and retrospective Prostate Imaging Reporting and Data System, version 2 [PI-RADS], scores) compared with 18F-choline PET/mpMRI to detect Gleason ≥ 3+4 cancer. Results: The per-lesion accuracy of systematic plus targeted biopsy for mpMRI alone was 67.8% (area under receiver-operating-characteristic curve [AUC], 0.73) for Likert 4-5 and 70.0% (AUC, 0.76) for PI-RADS 3-5. Several PET/MRI models incorporating 18F-choline with mpMRI data were investigated. The most promising model selected all high-risk disease on mpMRI (Likert 5 or PI-RADS 5) plus low- and intermediate-risk disease (Likert 4 or PI-RADS 3-4), with an elevated 18F-choline target-to-background ratio greater than 1.58 as positive for significant cancer. Using this approach, the accuracy on a per-lesion basis significantly improved to 88.9% for Likert (AUC, 0.90; P < 0.001) and 91.1% for PI-RADS (AUC, 0.92; P < 0.001). On a per-patient basis, the accuracy improved to 92.9% for Likert (AUC, 0.93; P < 0.001) and to 91.1% for PI-RADS (AUC, 0.91; P = 0.009). Conclusion:18F-choline PET/mpMRI improved the identification of Gleason ≥ 3+4 prostate cancer compared with mpMRI, with the principal effect being improved risk stratification of intermediate-risk mpMRI lesions.

Ultrasonography for chairside evaluation of periodontal structures: A pilot study.

BACKGROUND: The crestal bone level and soft tissue dimension are essential for periodontal diagnosis and phenotype determination; yet, existing measurement methods have limitations. The aim of this clinical study was to evaluate the correlation and accuracy of ultrasound in measuring periodontal dimensions, compared to direct clinical and cone-beam computed tomography (CBCT) methods. METHODS: A 24-MHz ultrasound probe prototype, specifically designed for intraoral use, was employed. Periodontal soft tissue dimensions and crestal bone levels were measured at 40 teeth and 20 single missing tooth gaps from 20 patients scheduled to receive a dental implant surgery. The ultrasound images were interpreted by two calibrated examiners. Inter-rater agreement was calculated by using inter-rater correlation coefficient (ICC). Ultrasound readings were compared with direct clinical and CBCT readings by using ICC and Bland-Altman analysis. RESULTS: The following six parameters were measured: 1) interdental papilla height (tooth), 2) mid-facial soft tissue height (tooth), 3) mucosal thickness (tooth), 4) soft tissue height (edentulous ridge), 5) mucosal thickness (edentulous ridge), and 6) crestal bone level (tooth). Intra-examiner calibrations were exercised to achieve an agreement of at least 0.8. ICC between the two readers ranged from 0.482 to 0.881. ICC between ultrasound and direct readings ranged from 0.667 to 0.957. The mean difference in mucosal thickness (tooth) between the ultrasound and direct readings was -0.015 mm (95% CI: -0.655 to 0.624 mm) without statistical significance. ICC between ultrasound and CBCT ranged from 0.654 to 0.849 among the measured parameters. The mean differences between ultrasound and CBCT range from -0.213 to 0.455 mm, without statistical significance. CONCLUSION: Ultrasonic imaging can be valuable for accurate and real-time periodontal diagnosis without concerns about ionizing radiation.

A Network Analysis of Multiple Myeloma Related Gene Signatures.

Multiple myeloma (MM) is the second most prevalent hematological cancer. MM is a complex and heterogeneous disease, and thus, it is essential to leverage omics data from large MM cohorts to understand the molecular mechanisms underlying MM tumorigenesis, progression, and drug responses, which may aid in the development of better treatments. In this study, we analyzed gene expression, copy number variation, and clinical data from the Multiple Myeloma Research Consortium (MMRC) dataset and constructed a multiple myeloma molecular causal network (M3CN). The M3CN was used to unify eight prognostic gene signatures in the literature that shared very few genes between them, resulting in a prognostic subnetwork of the M3CN, consisting of 178 genes that were enriched for genes involved in cell cycle (fold enrichment = 8.4, p value = 6.1 × 10-26). The M3CN was further used to characterize immunomodulators and proteasome inhibitors for MM, demonstrating the pleiotropic effects of these drugs, with drug-response signature genes enriched across multiple M3CN subnetworks. Network analyses indicated potential links between these drug-response subnetworks and the prognostic subnetwork. To elucidate the structure of these important MM subnetworks, we identified putative key regulators predicted to modulate the state of these subnetworks. Finally, to assess the predictive power of our network-based models, we stratified MM patients in an independent cohort, the MMRF-CoMMpass study, based on the prognostic subnetwork, and compared the performance of this subnetwork against other signatures in the literature. We show that the M3CN-derived prognostic subnetwork achieved the best separation between different risk groups in terms of log-rank test p-values and hazard ratios. In summary, this work demonstrates the power of a probabilistic causal network approach to understanding molecular mechanisms underlying the different MM signatures.

A probabilistic multi-omics data matching method for detecting sample errors in integrative analysis.

BACKGROUND: Data errors, including sample swapping and mis-labeling, are inevitable in the process of large-scale omics data generation. Data errors need to be identified and corrected before integrative data analyses where different types of data are merged on the basis of the annotated labels. Data with labeling errors dampen true biological signals. More importantly, data analysis with sample errors could lead to wrong scientific conclusions. We developed a robust probabilistic multi-omics data matching procedure, proMODMatcher, to curate data and identify and correct data annotation and errors in large databases. RESULTS: Application to simulated datasets suggests that proMODMatcher achieved robust statistical power even when the number of cis-associations was small and/or the number of samples was large. Application of our proMODMatcher to multi-omics datasets in The Cancer Genome Atlas and International Cancer Genome Consortium identified sample errors in multiple cancer datasets. Our procedure was not only able to identify sample-labeling errors but also to unambiguously identify the source of the errors. Our results demonstrate that these errors should be identified and corrected before integrative analysis. CONCLUSIONS: Our results indicate that sample-labeling errors were common in large multi-omics datasets. These errors should be corrected before integrative analysis.

The polarity protein Scrib limits atherosclerosis development in mice.

AIMS: The protein Scrib (Scribble 1) is known to control apico-basal polarity in epithelial cells. The role of polarity proteins in the vascular system remains poorly characterized; however, we previously reported that Scrib maintains the endothelial phenotype and directed migration. On this basis, we hypothesized that Scrib has anti-atherosclerotic functions. METHODS AND RESULTS: Tamoxifen-induced Scrib-knockout mice were crossed with ApoE-/- knockout mice and spontaneous atherosclerosis under high-fat diet (HFD), as well as accelerated atherosclerosis in response to partial carotid artery ligation and HFD, was induced. Deletion of Scrib resulted in increased atherosclerosis development in both models. Mechanistically, flow- as well as acetylcholine-induced endothelium-dependent relaxation and AKT phosphorylation was reduced by deletion of Scrib, whereas vascular permeability and leucocyte extravasation were increased after Scrib knockout. Scrib immune pull down in primary carotid endothelial cells and mass spectrometry identified Arhgef7 (Rho Guanine Nucleotide Exchange Factor 7, ßPix) as interaction partner. Scrib or Arhgef7 down-regulation by siRNA reduced the endothelial barrier function in human umbilical vein endothelial cells. Gene expression analysis from murine samples and from human biobank material of carotid endarterectomies indicated that loss of Scrib resulted in endothelial dedifferentiation with a decreased expression of endothelial signature genes. CONCLUSIONS: By maintaining a quiescent endothelial phenotype, the polarity protein Scrib elicits anti-atherosclerotic functions.

Intra-arterial ampicillin and gentamicin and the incidence of splenic abscesses following splenic artery embolization: A 20-year case control study.

PURPOSE: Splenic abscesses represent a major complication following splenic artery embolization. The purpose of this study was to assess the effectiveness of intra-arterial antibiotics administered during splenic artery embolization in reducing splenic abscess formation. MATERIALS AND METHODS: 406 patients were screened. 313 (77.1%) patients who underwent splenic artery embolization and were >18 years old were included. Mean age of the cohort was 58 ±â€¯15 years (range: 18-88 years). There were 205 (65.5%) male patients and 108 (34.5%) female patients. 197 (62.9%) patients underwent embolization without intra-arterial antibiotics and 116 (37.1%) patients underwent embolization with 1 g ampicillin and 80 mg gentamicin administered in an intra-arterial fashion. Primary outcome was splenic abscess formation. Secondary outcomes included type of splenic artery embolization, embolic agent, and technical success. RESULTS: Partial splenic embolization was performed in 229 (73.1%) patients. Total splenic embolization was performed in 84 (26.8%) patients. Platinum coils were the most commonly used embolic agent overall (n = 178; 56.9%) followed by particulates (n = 114; 36.4%). Embolization technical success was achieved in 312 (99.7%) patients. 7 (3.6%) splenic abscesses were detected in the non-intra-arterial antibiotic group and 1 (0.9%) in the intra-arterial antibiotic cohort (P = 0.27). Coils were found to be statistically more likely to result in splenic abscesses than any other embolic agent (P = 0.03). Mean time to abscess identification was 74 days ±120 days (range: 9-1353 days). CONCLUSION: Splenic abscesses occurred more frequently in patients who did not receive intra-arterial antibiotics during splenic embolization; however, this did not reach statistical significance.

Trends in Interventional Radiology Through the Eye of the Journal of Vascular and Interventional Radiology: A 27-Year History.

PURPOSE: To report the quantity, manuscript types, geographic distribution of publications, and published content trends in a major interventional radiology journal over 27 years. MATERIALS AND METHODS: Available publication data from the Journal of Vascular and Interventional Radiology was collected via Scopus from November 1990 to November 2017. Quantity, manuscript type, geographic distribution, number of citations, and publication content were analyzed. RESULTS: 6925 papers were published in JVIR during the study period. The number of publications increased by 234% from an average of 103 publications/year in the first 5 years to 344 publications/year in the last 5 years. Manuscript types included 4891 original articles (70.6%), 987 letters (14.3%), 360 review articles (5.2%), 324 notes (4.7%), 167 conference papers (2.4%), 102 editorials (1.5%), 61 errata (0.9%), 23 articles in press (0.3%), and 10 short surveys (0.1%). The majority of publications originated in the United States with 3945 articles (57.0%), followed by Canada with 366 articles (5.3%), and Japan and South Korea with 360 (5.2%) and 340 articles (4.9%), respectively. As for article content, arterial disease and interventions were discussed in 2256 publications (32.6%), followed by venous (1237; 17.9%), miscellaneous (1072; 15.5%), oncology (1006; 14.5%), genitourinary (758; 10.9%), portal (337; 4.9%), neurovascular (253; 3.7%), gastrointestinal (232; 3.4%), biliary (210; 3.0%), pediatric (130; 1.9%), clinical trials (119; 1.7%), and guideline development (119; 1.7%). CONCLUSION: There has been a marked increase in the number of publications in JVIR over 27 years. JVIR has shown continued growth since its inception and has strengthened its international reputation with more global research than ever before.

Comparison of glioblastoma (GBM) molecular classification methods.

Glioblastoma (GBM) is the most aggressive and common form of brain cancer in adults. GBM is characterized by poor survival and remarkably high tumors heterogeneity (both intertumoral and intratumoral), and lack of effective therapies. Recent high-throughput data revealed heterogeneous genetic/genomic/epigenetic features and led to multiple methods aiming to classify tumors according to the key molecular events that drive the most aggressive cellular components so that targeted therapies can be developed for individual subtypes. However, GBM molecular subtypes have not led to improvement of patients outcomes. Targeted or tailored therapies for specific mutations or subtypes largely failed due to the complexities arising from intratumoral molecular heterogeneity. Most tumors develop resistance to treatment and soon recur. GBM stem cells (GSCs) have been identified. Recent single cell sequencing studies of GBM suggest that intratumoral cellular heterogeneity can be partially explained by tumor cell hierarchy arising from GBM stem cells. Therefore, the molecular subtypes based on patient derived GSCs may potentially lead to more effective subtype-specific treatments. In this paper, we review the molecular alterations of GBM and molecular subtyping methods as well as subtype plasticity in primary and recurrent tumors emphasizing the clinical relevance of potential targets for further drug development.

Identification of microR-106b as a prognostic biomarker of p53-like bladder cancers by ActMiR.

Bladder cancers can be categorized into subtypes according to gene expression patterns. P53-like muscle-invasive bladder cancers are generally resistant to cisplatin-based chemotherapy, but exhibit heterogeneous clinical outcomes with a prognosis intermediate to that of the luminal and basal subtypes. The optimal approach to p53-like tumors remains poorly defined and better means to risk-stratify such tumors and identification of novel therapeutic targets is urgently needed. MicroRNAs (miRNAs) play a key role in cancer, both in tumorigenesis and tumor progression. In the past few years, miRNA expression signatures have been reported as prognostic biomarkers in different tumor types including bladder cancer. However, miRNA's expression does not always correlate well with its activity. We previously developed ActMiR, a computational method for explicitly inferring miRNA activities. We applied ActMiR to The Cancer Genome Atlas (TCGA) bladder cancer data set and identified the activities of miR-106b-5p and miR-532-3p as potential prognostic markers of the p53-like subtype, and validated them in three independent bladder cancer data sets. Especially, higher miR-106b-5p activity was consistently associated with better survival in these data sets. Furthermore, we experimentally validated causal relationships between miR-106-5p and its predicted target genes in p53-like cell line HT1197. HT1197 cells treated with the miR-106b-5p-specific inhibitor were more invasive while cells treated with the miR-106b-5p-specific mimic were less invasive than corresponding controls. Altogether, our results suggest that miR-106b-5p activity can categorize p53-like bladder tumors into more and less-favorable prognostic groups, which provides critical information for personalizing treatment option for p53-like bladder cancers.