Efficacy and safety of BVAC-C in HPV type 16- or 18-positive cervical carcinoma who failed 1st platinum-based chemotherapy: a phase I/IIa study.

Background: BVAC-C, a B cell- and monocyte-based immunotherapeutic vaccine transfected with recombinant HPV E6/E7, was well tolerated in HPV-positive recurrent cervical carcinoma patients in a phase I study. This phase IIa study investigates the antitumor activity of BVAC-C in patients with HPV 16- or 18-positive cervical cancer who had experienced recurrence after a platinum-based combination chemotherapy. Patients and methods: Patients were allocated to 3 arms; Arm 1, BVAC-C injection at 0, 4, 8 weeks; Arm 2, BVAC-C injection at 0, 4, 8, 12 weeks; Arm 3, BVAC-C injection at 0, 4, 8, 12 weeks with topotecan at 2, 6, 10, 14 weeks. Primary endpoints were safety and objective response rate (ORR) as assessed by an independent radiologist according to Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included the disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: Of the 30 patients available for analysis, the ORR was 19.2% (Arm 1: 20.0% (3/15), Arm 2: 33.3% (2/6), Arm3: 0%) and the DCR was 53.8% (Arm 1: 57.1%, Arm 2: 28.6%, Arm3: 14.3%). The median DOR was 7.5 months (95% CI 7.1-not reported), the median PFS was 5.8 months (95% CI 4.2-10.3), and the median OS was 17.7 months (95% CI 12.0-not reported). All evaluated patients showed not only inflammatory cytokine responses (IFN-γ or TNF-α) but also potent E6/E7-specific T cell responses upon vaccinations. Immune responses of patients after vaccination were correlated with their clinical responses. Conclusion: BVAC-C represents a promising treatment option and a manageable safety profile in the second-line setting for this patient population. Further studies are needed to identify potential biomarkers of response. Clinical trial registration: ClinicalTrials.gov, identifier NCT02866006.

SleepMI: An AI-based screening algorithm for myocardial infarction using nocturnal electrocardiography.

Myocardial infarction (MI) is a common cardiovascular disease, the early diagnosis of which is essential for effective treatment and reduced mortality. Therefore, novel methods are required for automatic screening or early diagnosis of MI, and many studies have proposed diverse conventional methods for its detection. In this study, we aimed to develop a sleep-myocardial infarction (sleepMI) algorithm for automatic screening of MI based on nocturnal electrocardiography (ECG) findings from diagnostic polysomnography (PSG) data using artificial intelligence (AI) models. The proposed sleepMI algorithm was designed using representation and ensemble learning methods and optimized via dropout and batch normalization. In the sleepMI algorithm, a deep convolutional neural network and light gradient boost machine (LightGBM) models were mixed to obtain robust and stable performance for screening MI from nocturnal ECG findings. The nocturnal ECG signal was extracted from 2,691 participants (2,331 healthy individuals and 360 patients with MI) from the PSG data of the second follow-up stage of the Sleep Heart Health Study. The nocturnal ECG signal was extracted 3 h after sleep onset and segmented at 30-s intervals for each participant. All ECG datasets were divided into training, validation, and test sets consisting of 574,729, 143,683, and 718,412 segments, respectively. The proposed sleepMI model exhibited very high performance with precision, recall, and F1-score of 99.38%, 99.38%, and 99.38%, respectively. The total mean accuracy for automatic screening of MI using a nocturnal single-lead ECG was 99.387%. MI events can be detected using conventional 12-lead ECG signals and polysomnographic ECG recordings using our model.

Co-culture device for in vitro high throughput analysis of cancer associated fibroblast and cancer cell interactions.

Introduction Cancers in general, and specifically lung cancer, continue to have low patient survival rates when the patient is at an advanced stage when diagnosed. It appears that the local environment, especially fibroblasts and their signaling molecules, tends to induce metastasis, increase cancer cell resistance to treatment, and aid in tumor growth rates. Since 3-D models quickly become too complex and/or expensive, and therefore rarely leave the lab they are developed in, it is interesting to develop a 2-D model that more closely mimics the clustered tumor formation and bulk interaction with a surrounding fibroblast environment. Methods In the present study, we utilize an off-the-shelf stereolithography 3-D printer, standard use well plates, magnets, and metallic beads to create a customizable 2-D co-culture system capable of being analyzed quantitatively with staining and qualitatively with standard fluorescent/brightfield microscopy to determine cancer-fibroblast interactions while also being able to test chemotherapeutic drugs in a high-throughput manner with standard 96-well plates. Results Comparisons from monoculture and co-culture growth rates shows that the presence of fibroblasts allows for significantly increased growth rates for H460 cancer. Additionally, viability of cancer cells can be quantified with simple cell staining methods and morphology and cell-cell interactions can be observed and studied. Discussion The high throughput model demonstrates that boundary condition changes can be observed between cancer cells and fibroblasts based upon the different chemotherapeutics that have been administered.

Impact of supradiaphragmatic lymphadenectomy on the survival of patients in stage IVB ovarian cancer with thoracic lymph node metastasis.

Introduction: To evaluate the survival impact of supradiaphragmatic lymphadenectomy as part of debulking surgery in stage IVB ovarian cancer with thoracic lymph node metastasis (LNM). Methods: We retrospectively enrolled patients diagnosed with stage IVB ovarian, fallopian or primary peritoneal cancer between 2010 and 2020, carrying cardiophrenic, parasternal, anterior mediastinal or supraclavicular lymph nodes ≥5 mm on axial chest computed tomography. All tumors were classified into the abdominal (abdominal tumors and cardiophrenic lymph nodes) and supradiaphragmatic (parasternal, anterior mediastinal or supraclavicular lymph nodes) categories depending on the area involved. Residual tumors were classified into <5 vs ≥5 mm in the abdominal and supradiaphragmatic areas. Based on the site of recurrence, they were divided into abdominal, supradiaphragmatic and other areas. Results: A total of 120 patients underwent primary debulking surgery (PDS, n=68) and interval debulking surgery after neoadjuvant chemotherapy (IDS/NAC, n=53). Residual tumors in the supradiaphragmatic area ≥5 mm adversely affected progression-free survival (PFS) and overall survival (OS) with marginal significance after PDS despite the lack of effect on survival after IDS/NAC (adjusted hazard ratios [HRs], 6.478 and 6.370; 95% confidence intervals [CIs], 2.224-18.864 and 0.953-42.598). Further, the size of residual tumors in the abdominal area measuring ≥5 mm diminished OS after IDS/NAC (adjusted HR, 9.330; 95% CIs, 1.386-62.800). Conclusion: Supradiaphragmatic lymphadenectomy during PDS may improve survival in patients diagnosed with stage IVB ovarian cancer manifesting thoracic LNM. Further, suboptimal debulking surgery in the abdominal area may be associated with poor OS after IDS/NAC. Trial registration: ClinicalTrials.gov (NCT05005650; https://clinicaltrials.gov/ct2/show/NCT05005650; first registration, 13/08/2021).Research Registry (Research Registry UIN, researchregistry7366; https://www.researchregistry.com/browse-the-registry#home/?view_2_search=researchregistry7366&view_2_page=1).

Clinical Relevance of Red Blood Cell Distribution Width (RDW) in Endometrial Cancer: A Retrospective Single-Center Experience from Korea.

BACKGROUND: Red blood cell distribution width (RDW) is a standard parameter of complete blood count and indicates the variability in red blood cell size. This study aimed to determine whether preoperative RDW can be used to predict the recurrence and prognosis of endometrial carcinoma. METHODS: The medical records of 431 patients diagnosed with endometrial carcinoma were retrospectively reviewed between May 2006 and June 2018. In addition to RDW, the clinicopathological factors, survival curves, and prognoses of the patients with endometrial carcinoma were compared between the high (n = 213) and low (n = 218) groups according to the median RDW value (12.8%). RESULTS: The patients with high RDW had significantly advanced-stage (p = 0.00) pelvic lymph node metastasis (p = 0.01) and recurrence (p = 0.01) compared to those in the low-RDW group. In univariate analysis with DFS as the endpoint, surgical stage, type II histology, grade, RDW, and lymph node metastasis were independently associated with survival. Patients with high RDW values had significantly shorter disease-free survival and overall survival than those with low RDW values (log-rank p = 0.03, log-rank p = 0.04, respectively). CONCLUSION: Our results demonstrate that RDW is a simple and convenient indicator of endometrial carcinoma recurrence. Prospective studies are needed to validate the findings of the current study.

The Role of Adjuvant Therapy Following Surgical Resection of Small Cell Lung Cancer: A Multi-Center Study.

PURPOSE: This multi-center, retrospective study was conducted to evaluate the long-term survival in patients who underwent surgical resection for small cell lung cancer (SCLC) and to identify the benefit of adjuvant therapy following surgery. MATERIALS AND METHODS: The data of 213 patients who underwent surgical resection for SCLC at four institutions were retrospectively reviewed. Patients who received neoadjuvant therapy or an incomplete resection were excluded. RESULTS: The mean patient age was 65.29±8.93 years, and 184 patients (86.4%) were male. Lobectomies and pneumonectomies were performed in 173 patients (81.2%), and 198 (93%) underwent systematic mediastinal lymph node dissections. Overall, 170 patients (79.8%) underwent adjuvant chemotherapy, 42 (19.7%) underwent radiotherapy to the mediastinum, and 23 (10.8%) underwent prophylactic cranial irradiation. The median follow-up period was 31.08 months (interquartile range, 13.79 to 64.52 months). The 5-year overall survival (OS) and disease-free survival were 53.4% and 46.9%, respectively. The 5-year OS significantly improved after adjuvant chemotherapy in all patients (57.4% vs. 40.3%, p=0.007), and the survival benefit of adjuvant chemotherapy was significant in patients with negative node pathology (70.8% vs. 39.7%, p=0.004). Adjuvant radiotherapy did not affect the 5-year OS (54.6% vs. 48.5%, p=0.458). Age (hazard ratio [HR], 1.032; p=0.017), node metastasis (HR, 2.190; p < 0.001), and adjuvant chemotherapy (HR, 0.558; p=0.019) were associated with OS. CONCLUSION: Adjuvant chemotherapy after surgical resection in patients with SCLC improved the OS, though adjuvant radiotherapy to the mediastinum did not improve the survival or decrease the locoregional recurrence rate.

A parametric metamodel of the vehicle frontal structure accounting for material properties and strain-rate effect: application to full frontal rigid barrier crash test.

In the automotive industry, building parametric surrogate models is a fundamental tool to evaluate, in real time, the performance of newly designed car components. Such models allow to compute any Quantity of Interest -QoI-, such as a specific safety protocol index, for any choice of material and/or geometrical parameters characterizing the component, within the stringent real time constraint. For instance, they can be exploited to guarantee safer designs (e.g., maximizing energy absorption by the crash boxes) or to reduce manufacturing costs (e.g., minimizing the mass of a specific structure under some safety protocol constraints). In general, these parametric simulation tools allow a significant gain in terms of manufacturing costs and time delays during the investigation phase. In this study, we focus on the vehicle frontal structure system considering its performance in a full-frontal crash scenario. In the front structure system we parameterize the crash boxes (left and right) and the inner/outer side front members (left and right, front and rear) with respect to the part thickness and the material parameters characterizing the Krupkowski plasticity curve. Moreover, Strain Rate Effect is also taken into account via Neural Network based regressions, whose training dataset comes from experimental data. The parametric metamodel is built via Non-Intrusive PGD -NI-PGD- strategies, relying on a sparse sampling of the parametric space, and allowing a quite reduced number of High Fidelity -HiFi- simulations. A novel strategy based on clustering and classification, known as Multi-PGD, is also applied and numerically verified.

Expression Profiles of ID and E2A in Ovarian Cancer and Suppression of Ovarian Cancer by the E2A Isoform E47.

The E2A and inhibitor of DNA binding (ID) proteins are transcription factors involved in cell cycle regulation and cellular differentiation. Imbalance of ID/E2A activity is associated with oncogenesis in various tumors, but their expression patterns and prognostic values are still unknown. We evaluated ID and E2A expression in ovarian cancer cells, and assessed the possibility of reprogramming ovarian cellular homeostasis by restoring the ID/E2A axis. We analyzed copy number alterations, mutations, methylations, and mRNA expressions of ID 1-4 and E2A using The Cancer Genome Atlas data of 570 ovarian serous cystadenocarcinoma patients. Incidentally, 97.2% cases exhibited gain of ID 1-4 or loss of E2A. Predominantly, ID 1-4 were hypomethylated, while E2A was hypermethylated. Immunohistochemical analysis revealed that ID-3 and ID-4 expressions were high while E2A expression was low in cancerous ovarian tissues. Correlation analysis of ID and E2A levels with survival outcomes of ovarian cancer patients indicated that patients with high ID-3 levels had poor overall survival. We also determined the effect of E2A induction on ovarian cancer cell growth in vitro and in vivo using SKOV-3/Luc cells transduced with tamoxifen-inducible E47, a splice variant of E2A. Interestingly, E47 induced SKOV-3 cell death in vitro and inhibited tumor growth in SKOV-3 implanted mice. Therefore, restoring ID/E2A balance is a promising approach for treating ovarian cancer.

Diffusion of a Lifelog-Based Digital Healthcare Platform for Future Precision Medicine: Data Provision and Verification Study.

We propose a method for data provision, validation, and service expansion for the spread of a lifelog-based digital healthcare platform. The platform is an operational cloud-based platform, implemented in 2020, that has launched a tool that can validate and de-identify personal information in a data acquisition system dedicated to a center. The data acquired by the platform can be processed into products of statistical analysis and artificial intelligence (AI)-based deep learning modules. Application programming interfaces (APIs) have been developed to open data and can be linked in a programmatic manner. As a standardized policy, a series of procedures were performed from data collection to external sharing. The proposed platform collected 321.42 GB of data for 146 types of data. The reliability and consistency of the data were evaluated by an information system audit institution, with a defects ratio of approximately 0.03%. We presented definitions and examples of APIs developed in 17 functional units for data opening. In addition, the suitability of the de-identification tool was confirmed by evaluating the reduced risk of re-identification using quasi-identifiers. We presented specific methods for data verification, personal information de-identification, and service provision to ensure the sustainability of future digital healthcare platforms for precision medicine. The platform can contribute to the diffusion of the platform by linking data with external organizations and research environments in safe zones based on data reliability.

Physical Forces in Glioblastoma Migration: A Systematic Review.

The invasive capabilities of glioblastoma (GBM) define the cancer's aggressiveness, treatment resistance, and overall mortality. The tumor microenvironment influences the molecular behavior of cells, both epigenetically and genetically. Current forces being studied include properties of the extracellular matrix (ECM), such as stiffness and "sensing" capabilities. There is currently limited data on the physical forces in GBM-both relating to how they influence their environment and how their environment influences them. This review outlines the advances that have been made in the field. It is our hope that further investigation of the physical forces involved in GBM will highlight new therapeutic options and increase patient survival. A search of the PubMed database was conducted through to 23 March 2022 with the following search terms: (glioblastoma) AND (physical forces OR pressure OR shear forces OR compression OR tension OR torsion) AND (migration OR invasion). Our review yielded 11 external/applied/mechanical forces and 2 tumor microenvironment (TME) forces that affect the ability of GBM to locally migrate and invade. Both external forces and forces within the tumor microenvironment have been implicated in GBM migration, invasion, and treatment resistance. We endorse further research in this area to target the physical forces affecting the migration and invasion of GBM.

Fabrication of junction-free Cu nanowire networks via Ru-catalyzed electroless deposition and their application to transparent conducting electrodes.

Over the past few years, metal nanowire networks have attracted attention as an alternative to transparent conducting oxide materials such as indium tin oxide for transparent conducting electrode applications. Recently, electrodeposition of metal on nanoscale template is widely used for formation of metal network. In the present work, junctionless Cu nanowire networks were simply fabricated on a substrate by forming a nanostructured Ru with 80 nm width as a seed layer, followed by direct electroless deposition of Cu. By controlling the density of Ru nanowires or the electroless deposition time, we readily achieve desired transmittance and sheet resistance values ranging from ∼1 kΩ sq-1at 99% to 9 Ω sq-1at 89%. After being transferred to flexible substrates, the nanowire networks exhibited no obvious increase in resistance during 8000 cycles of a bending test to a radius of 2.5 mm. The durability was verified by evaluation of its heating performance. The maximum temperature was greater than 180 °C at 3 V and remained constant after three repeated cycles and for 10 min. Transmission electron microscopy and x-ray diffraction studies revealed that the adhesion between the electrolessly deposited Cu and the seed Ru nanowires strongly influenced the durability of the core-shell structured nanowire-based heaters.

Physical confinement during cancer cell migration triggers therapeutic resistance and cancer stem cell-like behavior.

Metastasized cancer cells have an increased resistance to therapies leading to a drastic decrease in patient survival rates. However, our understanding of the cause for this enhanced resistance is lacking. In this study, we report that physically tight confinement during cancer cell migration triggers therapeutic resistance and induces cancer stem cell-like behavior including up-regulation in efflux proteins and in cancer stem cell related markers. Moreover, the re-localization of Yes-associated protein (YAP) to the cell nucleus indicated an elevated level of cytoskeletal tension. The increased cytoskeletal tension suggested that mechanical interactions between cancer cells and tight surroundings during metastasis is one of the factors that contributes to therapeutic resistance and acquisition of cancer stem cell (CSC) like features. With this system and supporting data, we are able to study cells with therapeutic resistance and CSC-like properties for the future purpose of developing new strategies for the treatment of metastatic cancer.

Use of bevacizumab before or after radiotherapy increases the risk of fistula formation in patients with cervical cancer.

OBJECTIVE: Several reports have documented the risk of fistula formation after bevacizumab in patients previously treated with radiation therapy. The aim of this study was to investigate the risk of fistula formation with bevacizumab and radiotherapy compared with radiotherapy alone. METHODS: We retrospectively analyzed patients with stage I-IV cervical cancer between January 2013 and December 2018. Patients who had a history of pelvic radiotherapy, who were treated with intracavitary brachytherapy alone, received radiotherapy at another hospital, received concurrent bevacizumab and radiotherapy, or had missing follow-up data or a short follow-up period (<6 months) were excluded. The fistula rates were compared between the groups using the Cox proportional hazards model and propensity score analyses. RESULTS: A total of 302 patients were included in the study: 249 patients were treated with definitive or adjuvant radiotherapy, and 53 patients were treated with radiotherapy before or after bevacizumab. With a median follow-up of 35.9 (IQR 22.8-53.5) months, the 3 year cumulative fistula incidence rate was significantly higher in the radiotherapy + bevacizumab group than in the radiotherapy group (27.0% vs 3.0%, p<0.001). Bevacizumab administration was significantly associated with fistula formation in the multivariable adjusted model (HR 4.76, 95% CI 1.71 to 13.23) and three propensity score adjusted model (all p<0.05). Biologically equivalent dose in 2 Gy fractions for 2 cc of the rectum more than 76 Gy was also associated with fistula formation (HR 4.30, 95% CI 1.52 to 12.18). Additionally, a 10 month interval between radiotherapy and bevacizumab reduced the incidence of fistula formation in the radiotherapy + bevacizumab group (p=0.032). CONCLUSIONS: In patients with cervical cancer treated with pelvic radiotherapy, the addition of bevacizumab substantially increased the risk of fistula formation. Physicians should perform pelvic radiotherapy in combination with bevacizumab with caution; moreover, close monitoring for fistula formation is warranted in these patients.

Single-cell-level screening method for migratory cancer cells and its potential feasibility in high-throughput manner.

High-throughput screening (HTS) is a well-established approach for tumor-specific drug development because of its high efficiency and customizable selection of antineoplastic drugs. However, there is still a lack of an appropriate cell-based HTS specific for migratory cancer cells. In the study presented here, we created a novel assay (mHTS): a single-cell-level screening method targeting migratory cancer cells and can be applied in a high-throughput manner. This mHTS platform is based on microchannel devices (providing physical confinement during cell migration and limit migrating cells' proliferation rate) assembled 96-well plate (fitting to HTS manner). To determine the feasibility of this assay, we quantified the anti-migratory and anti-viability effects of several molecules (Cytochalasin D, Doxorubicin and AZD-6244) on migrating (creeping inside microchannel) glioblastoma multiforme (GBM) cells. After analyzing migration screening data that was collected on a single-cell-level, we were able to compare those drug's effects on cancer cells' migration velocity and uncovered the migration inhibiting potential of AZD (500 nM and 1000 nM). Viability data based on single-cell-level screening also allowed us to further understand the same drug's different lethality toward migrating and normal 2D cultured cancer cells. The Pre-classification of subpopulations enables us to study the heterogeneity of cancer and ensures our method's feasibility for a high-throughput manner. All these results proved our mHTS platform is suitable for single-cell-level anti-migration drug screening and has potential feasibility in promoting the development of anti-migratory-cancer-drug in a high-throughput manner.

Comparison of outcomes between the one-step and two-step sentinel lymph node mapping techniques in endometrial cancer.

INTRODUCTION: Fluorescence image-guided sentinel lymph node (SLN) biopsy using a two-step mapping technique incorporates sequential injection of indocyanine green into the bilateral uterine cornus, followed by cervical injection. Outcomes were compared with the conventional cervical (one-step) method . METHODS: Patients with FIGO stage I-III endometrial cancer who underwent laparoscopic or robotic staging, including SLN biopsy, from May 2014 to December 2018, were retrospectively reviewed. Patient characteristics, pre-operative imaging, SLN detection pattern, pathologic result, adjuvant, and recurrence locations were analyzed. RESULTS: A total of 199 patients received one-step (n=123) and two-step (n=76) SLN biopsy. Para-aortic SLN were more frequently identified in the two-step group. Lower and upper para-aortic SLN were identified in 67.1% and 38.2%, respectively, in the two-step group and in 18.7% and 5.7% in the one-step group (p<0.001). The number of para-aortic SLN harvested was superior in the two-step group (p<0.001). Metastatic para-aortic SLN were found in 7.9% of the two-step group and 2.4% of the one-step group (p=0.070). In detecting nodal metastasis, the sensitivities of the one- and two-step methods were 91.7% and 100.0%, negative predictive values were 99.0% and 100.0%, false-negative rates were 8.3% and 0%, and accuracy rates were 99.1% and 100.0%, respectively. The one-step method identified only three out of eight para-aortic lymph node metastases and missed five para-aortic lymph node metastases. There was no missed para-aortic lymph node metastasis in the two-step group. Recurrence was observed in two patients (2.6%; vaginal vault and adrenal gland) in the two-step group and seven patients (5.7%) including three nodal recurrences in the one-step group (p=0.307). DISCUSSION: Two-step SLN mapping improved the para-aortic SLN detection rate, a known pitfall of conventional cervical injection. Proper evaluation of aortic nodal status will assist in the tailoring of adjuvant and prevent undertreatment of patients with isolated para-aortic metastasis.

Differences in creep response of GBM cells migrating in confinement.

Using a microfluidic platform to apply negative aspiration pressure (-20, -25, -30, -35 and -40 cm H2O), we compared the differences in creep responses of Glioblastoma Multiforme (GBM) cells while migrating in confinement and at a stationary state on a 2D substrate. Cells were either migrating in a channel of 5 x 5 µm cross-section or stationary at the entrance to the channel. In response to aspiration pressure, we found actively migrating GBM cells exhibited a higher stiffness than stationary cells. Additionally, migrating cells absorbed more energy elastically with a relatively small dissipative energy loss. At elevated negative pressure loads up to - 30 cm H2O, we observed a linear increase in elastic deformation and a higher distribution in elastic storage than energy loss, and the response plateaued at further increasing negative pressure loads. To explore the underlying cause, we carried out immuno-cytochemical studies of these cells and found a polarized actin and myosin distribution at the front and posterior ends of the migrating cells, whereas the distribution of the stationary group demonstrated no specific regional differences. These differences in creep response and cytoskeletal protein distribution demonstrate the importance of a migrating cell's kinematic state to the mechanism of cell migration.

Does Tranexamic Acid Increase the Incidence of Thromboembolism After Spinal Fusion Surgery?

STUDY DESIGN: This was a retrospective analysis of prospectively collected data. OBJECTIVE: To investigate the incidence of thromboembolism in patients who received tranexamic acid (TXA) after lumbar spine fusion and determine the diagnostic value of lower limb duplex sonography as a screening test. SUMMARY OF BACKGROUND DATA: TXA is effective in reducing blood drainage in spine fusion surgery but some studies have reported increased incidence of venous thromboembolism associated with TXA. MATERIALS AND METHODS: One hundred twenty-two patients who underwent lumbar fusion for degenerative spinal disease received intravenous TXA in doses equivalent to 10 mg/kg for 48 hours after surgery. As a control group, 85 patients received intravenous administration of the same amount of normal saline. D-dimer levels were checked on the day of admission and the seventh postoperative day (POD#7). All patients underwent duplex sonography on POD#7, and patients with abnormal results were further evaluated with computed tomography angiography and pulmonary arterial angiography. RESULTS: None of the patients showed symptoms of deep vein thrombosis (DVT). Suspicious signs of DVT were observed in 5 patients in the TXA group and 4 patients in the control group in lower limb duplex sonography. Finally, DVT was confirmed by computed tomography angiography in one of 122 patients (0.8%) in the TXA group and in one of 85 patients (1.2%) in the control group. D-dimer levels on POD#7 were higher in the patients with DVT than in patients without DVT. Average postoperative blood drain was 421.3±133.1 mL in the TXA group and 635.2±151.2 mL in the control group (P<0.001), which showed TXA was effective to reduce postoperative hemorrhage. CONCLUSIONS: The incidence of thromboembolism after using TXA in lumbar fusion surgery was 0.8%, as comparable as the incidence of thromboembolism in the control group. Lower limb duplex sonography is not recommended for screening test of DVT because of high false-positive rate. LEVEL OF EVIDENCE: Level III.

Clinical Anatomy of the Puboprostatic Ligament for the Safe Guidance for the Prostate Surgery.

OBJECTIVE: To provide the anatomy of the puboprostatic ligament and related structures to save urogenital competence after prostatectomy. MATERIALS AND METHODS: Pelvic areas of 31 adult cadavers were dissected to figure out the shape, number, and location of the puboprostatic ligaments. RESULTS: The puboprostatic ligament was the most important support structure between the pubic bone and prostate gland. Puboprostatic ligaments were bilaterally single (61.3%), bilaterally double (19.4%), or mixed (19.4%). Ligaments were mostly I-shaped (53.8%). If ligaments had extra attachment to or from the arcuate line, the ligaments were λ-shaped (36.3%), or Y-shaped (8.8%). In one case, the ligament had a central fusion with an irregular shape. I-shaped puboprostatic ligaments were observed more frequently in specimens with double ligaments, while λ-shaped puboprostatic ligaments were observed more frequently in the cases with single ligaments. The average distance between both puboprostatic ligaments was 8.1 mm at the pubic site and 14.2 mm at the prostate site. The distance was narrower when the specimen had double puboprostatic ligaments on both sides. The neurovascular bundle ran beneath the puboprostatic ligament. If the ligament was the λ-shaped type, the neurovascular bundle frequently pierced the lateral band of the ligament. CONCLUSION: Puboprostatic ligaments hold and stabilize the prostate against the pubic bone. It is believed that a pelvis with bilateral, double puboprostatic ligaments would have advantages in urogenital competence. The morphologic data of the shape, multiplicity, and location of the PPLs would help to make a plan to approach the prostate.

Highly Fluorinated Barium Titanate Nanoparticle Dispersion for Fabrication of Lithographically Patterned Thin Films.

We report the synthesis, characterization, and photopatterning of high-k inorganic nanoparticles that are covered with highly fluorinated carboxylic acid and, as a result, are solution-processable in fluorous liquids. Barium titanate (BTO) nanoparticles, 7-8 nm in diameter, were prepared under solvothermal conditions and were surface-modified with perfluoroalkyl ether-type carboxylic acid molecules via ligand-exchange reactions. Thin films with a high dielectric constant (9.27 at 1 kHz) were achieved by spin-coating homogeneous solutions of BTO nanoparticles in a fluorous solvent (HFE-7500). Additionally, electron-beam lithography and photolithography were applied to the thin films of BTO nanoparticles, yielding BTO patterns with scales of 300 nm and 5 µm, respectively. Thus, an approach for a chemically non-damaging solution process of inorganic materials for device implementation was successfully demonstrated.

Glioblastoma Multiforme heterogeneity profiling with solid-state micropores.

Glioblastoma multiforme (GBM) is the most common and lethal type of brain cancer. It is characterized by widespread heterogeneity at the cellular and molecular levels. The detection of this heterogeneity is valuable for accurate diagnosis. Herein, solid-state 20 µm diameter micropore made in thin suspended silicon dioxide membrane is used as cell sensor device. The device relies on a cell's mechano-physical properties as an indicator to differentiate between the subtypes of GBM. A library of GBM cell lines (U251, U87, D54 EGFRviii, and G55) was created by measuring the differences in cell's micropore translocation properties from their distinct electrical profiles. Each GBM subtype has distinct phenotype and this was delineated in their cell translocation behaviors. The library was used to distinguish cells from samples of brain tumor patients. The micropore device accurately profiled GBM patient samples for cell subtypes by comparing data with the GBM library. The micropore approach is simple, can be implemented at low cost and can be used in the clinical setups and operation theaters to detect and identify GBM subtypes from patient samples.