Brain-targeted delivery of neuroprotective survival gene minimizing hematopoietic cell contamination: implications for Parkinson's disease treatment.

BACKGROUND: Neurodegenerative diseases, including Parkinson's disease, Amyotropic Lateral Sclerosis (ALS) and Alzheimer's disease, present significant challenges for therapeutic development due to drug delivery restrictions and toxicity concerns. Prevailing strategies often employ adeno-associated viral (AAV) vectors to deliver neuroprotective survival genes directly into the central nervous system (CNS). However, these methods have been limited by triggering immunogenic responses and risk of tumorigenicity, resulting from overexpression of survival genes in peripheral blood mononuclear cells (PBMC), thereby increasing the risk of tumorigenicity in specific immune cells. Thus, by coding selectively suppressive microRNA (miRNA) target sequences in AAV genome, we designed CNS-targeted neuroprotective gene expression vector system without leakage to blood cells. METHODS: To minimize the potential for transgene contamination in the blood, we designed a CNS-specific AAV system. Our system utilized a self-complementary AAV (scAAV), encoding a quadruple repeated target sequence of the hematopoietic cell-specific miR142-3p at the 3' untranslated region (UTR). As a representative therapeutic survival gene for Parkinson's disease treatment, we integrated DX2, an antagonistic splice variant of the apoptotic gene AIMP2, known to be implicated in Parkinson's disease, into the vector. RESULTS: This configuration ensured that transgene expression was stringently localized to the CNS, even if the vector found its way into the blood cells. A single injection of scAAV-DX2 demonstrated marked improvement in behavior and motor activity in animal models of Parkinson's disease induced by either Rotenone or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Importantly, comprehensive preclinical data adhering to Good Laboratory Practice (GLP) standards revealed no adverse effects in the treated animals. CONCLUSIONS: Our CNS-specific vector system, which encodes a survival transgene DX2, signifies a promising avenue for safe gene therapy, avoiding unintended expression of survival gene in blood cells, applicable to various neurodegenerative diseases.

Radiation Major Hepatectomy Using Ablative Dose Yttrium-90 Radioembolization in Patients with Hepatocellular Carcinoma 5 cm or Larger.

PURPOSE: To evaluate the safety and effectiveness of ablative radioembolization for large hepatocellular carcinoma (HCC) while preserving a small future liver remnant (FLR). MATERIALS AND METHODS: Twenty-five patients with large HCC of ≥5 cm requiring treatment for >60% of the total liver volume and having well-preserved liver function were treated with ablative glass microsphere radioembolization at a single institution from January 2017 to December 2021. Radioembolization was performed with a mean absorbed dose of >150 Gy, and the FLR per nontumor liver volume (NTLV) was set at >30%. Changes in liver function, adverse events, duration of response (DoR) in a treated area, time-to-progression (TTP), and overall survival (OS) were retrospectively investigated. RESULTS: The largest tumor diameter and planned dose per treated volume were 11.4 cm ± 3.9 and 242.3 Gy ± 63.6 (169.4 Gy ± 45.9 per whole liver volume), respectively. All patients remained at Child-Pugh Class A for 90 days. No patient experienced Grade 3‒4 hyperbilirubinemia or new ascites. One patient (lung dose, 27.8 Gy) developed radiation pneumonitis requiring transient steroid treatment. According to the posttreatment dosimetry, the tumorous and nontumorous liver absorbed doses were 418.8 Gy ± 227.4 and 69.0 Gy ± 32.1, respectively. The median DoR in a treated area and TTP were 22.0 and 17.1 months, respectively. The 5-year OS rate was 83.2%. CONCLUSIONS: Ablative radioembolization of large HCC of ≥5 cm can be performed safely and effectively in patients with preserved liver function when FLR/NTLV exceeds 30%.

Deep learning algorithm for automatically measuring Cobb angle in patients with idiopathic scoliosis.

PURPOSE: The Cobb angle is a standard measurement to qualify and track the progression of scoliosis. However, the Cobb angle has high inter- and intra-observer variability. Consequently, its measurement varies with vertebrae and may even differ when the same vertebra is measured. Therefore, it is not constant and differs with measurements. This study aimed to develop a deep learning model that automatically measures the Cobb angle. The deep learning model for identifying vertebrae on spine radiographs was developed. METHODS: The dataset consisted of 297 images that were divided into two subsets for training and validation. Two hundred and twenty-seven images (76.4%) were used to train the model, while 70 images (23.6%) were used as the validation dataset. Absolut error between the measurements by the observer and developed deep learning model and intraclass correlation coefficient (ICC). RESULTS: The average absolute error between the measurements was 1.97° with a standard deviation of 1.57°. In addition, 95.9% of the angles had an absolute error of less than 5°. The ICC was calculated to assess the model's reliability further. The ICC was 0.981, indicating excellent reliability. CONCLUSIONS: The authors believe the model will be useful in clinical practice by relieving clinicians of the burden of having to manually compute the Cobb angle. Further studies are needed to enhance the accuracy and versatility of this deep learning model.

Mechanism of action of genicular artery embolization in a rabbit model of knee osteoarthritis.

OBJECTIVES: To establish a rabbit osteoarthritis model for genicular artery embolization (GAE) experiments and to investigate the cellular mechanism of action of this novel procedure for interventional radiologists. METHODS: Rabbit knee osteoarthritis was surgically modeled by anterior cruciate ligament transection and medial partial meniscectomy of the bilateral hindlimbs followed by 10 weeks of incubation. Rabbits exhibiting synovitis on magnetic resonance imaging were randomly divided into two groups: the bilateral GAE group and the control (sham procedure) group. Four weeks later, the rabbits' mobility (moving time, sec/10 min) and the histopathological features of each knee were assessed, and inter-group differences were evaluated using Student's t-test and ordinal/linear logistic models with generalized estimating equations. RESULTS: Osteoarthritis modeling and endovascular procedures were successful in 15 of 20 rabbits (8 and 7 in the GAE and control groups, respectively). There was no significant difference in moving times between the two groups (p = .958). The degree of structural cartilage damage was similar in both groups (p = .780). However, the synovial proliferation (p = .016), synovial hypertrophy (p < .001), and villous hyperplasia of the synovial stroma (p = .002) scores were significantly lower in the GAE group than in the control group. The CD3+ cell density (p = .018) and CD3 + cell-infiltrated area (p = .019) were also significantly lower in the GAE group than in the control group. CONCLUSION: GAE can limit inflammatory processes in the synovium of osteoarthritis-affected knees. KEY POINTS: Surgical transection of the anterior cruciate ligament and medial partial meniscectomy of rabbit knees provides a useful animal model for research of genicular artery embolization. Osteoarthritic knees treated by genicular artery embolization showed milder synovial proliferation (p = .016), synovial hypertrophy (p < .001), and villous hyperplasia of the synovial stroma (p = .002) than the untreated knees. Osteoarthritic knees treated by genicular artery embolization presented lower CD3+ cell density (p = .018) and CD3+ cell-infiltrated area (p = .019) in the synovium than the untreated knees.

Safety of Radioembolization via the Cystic Artery in Patients with Hepatocellular Carcinoma and Parasitized Arterial Supply.

PURPOSE: To evaluate the safety and effectiveness of radioembolization through the cystic artery supplying hepatocellular carcinoma (HCC) adjacent to the gallbladder. MATERIALS AND METHODS: This retrospective, single-center study included 24 patients who underwent radioembolization via the cystic artery between March 2017 and October 2022. The median tumor size was 8.3 cm (range, 3.4-20.4 cm). Twenty-two (92%) patients had Child-Pugh Class A disease, and 2 (8%) patients had Class B cirrhosis. Technical issues, adverse events, and tumor response were analyzed. RESULTS: Infusion of radioactive microspheres was performed from the main cystic artery (n = 6), the deep cystic artery (n = 9), and small feeders from the cystic artery (n = 9). The cystic artery supplied the primary index tumor in 21 patients. The median radiation activity delivered via the cystic artery was 0.19 GBq (range, 0.02-0.43 GBq). The median total radiation activity administered was 4.1 GBq (range, 0.9-10.8 GBq). There was no case of symptomatic cholecystitis requiring invasive intervention. One patient experienced abdominal pain during injection of radioactive microspheres via the cystic artery. Eleven (46%) patients received pain medication during or within 2 days of the procedure. Twelve (50%) patients had gallbladder wall thickening on a 1-month follow-up computed tomography scan. Based on follow-up imaging, 23 (96%) patients showed an objective response (complete or partial response) of the tumor supplied by the cystic artery. CONCLUSION: Radioembolization via the cystic artery may be safe in patients with HCC partially supplied by the cystic artery.

Ideal Size Range for Embolic Agents in Interventional Oncology Experiments Involving Rat Models of Hepatocellular Carcinoma.

PURPOSE: To optimize future translational research, this study aimed to determine the ideal range of sizes for embolic agents in interventional oncology experiments utilizing rat models of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Fifty-five male Sprague-Dawley rats were divided into 2 groups to evaluate the distribution of microparticles and tumor response rates. After implanting hepatoma cells into the rodent liver, fluorescent microparticles of sizes ranging from 5 to 35 µm were administered via the hepatic artery. In the first group, the distribution of microparticles was evaluated in hepatoma-free rats, and the tumor necrosis rates following administration of a predetermined aliquot of microparticles (0.4 mL) were measured in tumor-bearing rats. Thereafter, the 3 microparticle sizes associated with the best tumor response rates were chosen for analysis of the tumor necrosis rates following hepatic artery embolization until angiographic stasis is achieved in the second group. RESULTS: The tendency for microparticles to distribute in nontarget organs increased as the microparticle size decreased below 15 µm. Tumor necrosis rates tended to be higher in rats treated with 15-19-µm microparticles than in those treated with 19-24-µm or 19-24-µm microparticles. The in-group deviation of the tumor necrosis rates was highest for microparticle sizes of 19-24 and 25-35 µm, which implies the proximal embolization of the hepatic artery for larger microparticle sizes. However, there was no statistical significance among the 3 groups (P = .095). CONCLUSIONS: The 15-19-µm embolic agents were the most favorable for causing tumor necrosis without nontarget toxicity in the transarterial treatments of rat HCC models.

Hepatocellular Carcinoma Supplied by the Inferior Phrenic Artery or Cystic Artery: Anatomic and Technical Considerations.

Intra-arterial treatment has been identified as one of the mainstays in the management of unresectable hepatocellular carcinoma. A thorough knowledge of tumor arterial supply enables selective therapy, which improves both safety and efficacy. The inferior phrenic artery (IPA) is the most common extrahepatic collateral artery that feeds hepatocellular carcinoma. The bilateral IPAs are known to have a specific vascular anatomy. A systemic-to-pulmonary shunt and a gastric branch from the IPAs may be present and should not be confused with tumor blush. The supraceliac aorta and celiac trunk are the common origin sites of the IPAs, and their orifice may be compressed by the diaphragm. Various techniques and catheters are used for catheterization of the IPAs, depending on their origin sites. Because the IPA is normally connected with the intercostal, internal mammary, retroperitoneal, and hepatic arteries, its hemodynamics may be altered when its orifice is occluded. In general, superselective chemoembolization via the target branch of the IPA is safe and effective. When a systemic-to-pulmonary shunt from the IPA is adequately embolized with coils or particles, radioembolization through the IPA can be performed safely in most cases. The cystic artery branches into deep and superficial cystic arteries; deep cystic arteries often supply tumors near the gallbladder. Chemoembolization through the cystic artery is relatively safe, with transient embolic materials. Radioembolization through the cystic artery has been recently tried, with acceptable efficacy and toxicity results, but it requires further investigation. ©RSNA, 2022.

Prognostic value of collateral perfusion estimation by arterial spin labeling for acute anterior circulation ischemic stroke.

PURPOSE: This study aimed to verify the value of arterial spin labeling (ASL) collateral perfusion estimation for predicting functional outcomes in acute anterior circulation ischemic stroke. METHODS: This secondary analysis of an ongoing prospective observational study included data from participants with acute ischemic stroke due to steno-occlusion of the internal carotid artery and/or the middle cerebral artery within 8 h of symptom onset. We compared the collateral map, which is a 5-phase collateral imaging derived from dynamic contrast-enhanced magnetic resonance angiography, and ASL to validate the ASL collateral perfusion estimation. Multiple logistic regression analyses were conducted to identify independent predictors of favorable functional outcomes. RESULTS: One hundred forty-eight participants (68 ± 13 years, 96 men) were evaluated. The ASL collateral perfusion grade was positively correlated with the collateral perfusion grade of the collateral map (P < .001). Younger age (OR = 0.53, 95% CI = 0.36-0.78, P = .002), lower baseline NIHSS score (OR = 0.85, 95% CI = 0.78-0.92, P < .001), intermediate ASL collateral perfusion grade (OR = 4.02, 95% CI = 1.43-11.26, P = .008), good ASL collateral perfusion grade (OR = 26.37, 95% CI = 1.06-655.01, P = .046), and successful reperfusion (OR = 5.84, 95% CI = 2.08-16.42, P < .001) were independently associated with favorable functional outcomes. CONCLUSION: ASL collateral perfusion estimation provides prognostic information, which can be helpful in guiding management decisions.

C-Arm Computed Tomographic Image Fusion for Repetitive Transarterial Chemoembolization of Hepatocellular Carcinoma.

OBJECTIVE: The aim of this study was to evaluate the potential implications of fusion imaging with C-arm computed tomography (CACT) scans for repetitive conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma. MATERIALS AND METHODS: Fifty-six cTACE sessions were performed using fusion CACT images from September 2020 to June 2021 in a tertiary referral center, and the data were retrospectively analyzed. Fusion of unenhanced and enhanced CACT images was considered when previously accumulated iodized oil hampered the identification of local tumor progression or intrahepatic distant metastasis (indication A), when a tumor was supplied by multiple arteries with different origins from the aorta and missing tumor enhancement was suspected (indication B), or when iodized oil distribution on immediate post-cTACE CACT images needed to be precisely compared with the pre-cTACE images (indication C). Fusion image quality, initial tumor response, time to local progression (TTLP) of index tumors, and time to progression (TTP) were evaluated. RESULTS: The fusion quality was satisfactory with a mean misregistration distance of 1.4 mm. For the 40 patients with indication A, the initial tumor responses at 3 months were nonviable, equivocal, and viable in 27 (67.5%), 4 (10.0%), and 9 (22.5%) index tumors, respectively. The median TTLP and TTP were 14.8 months and 4.5 months, respectively. For 10 patients with indication B, the median TTLP and TTP were 8.3 months and 2.6 months, respectively. Among the 6 patients with indication C, 2 patients were additionally treated at the same cTACE session after confirming incomplete iodized oil uptake on fusion imaging. CONCLUSIONS: Fusion CACT images are useful in patients with hepatocellular carcinoma undergoing repetitive cTACE.

A Motion Artifact Correction Algorithm for Cone-Beam CT in Patients with Hepatic Malignancies Treated with Transarterial Chemoembolization.

PURPOSE: To evaluate the effect of a motion artifact correction algorithm (MACA) on cone-beam computed tomography (CT) during transarterial chemoembolization for hepatic malignancies. MATERIALS AND METHODS: From June 2020 to March 2021, 42 patients with mild-to-severe motion artifacts detected using single cone-beam CT scans were evaluated retrospectively. The image quality of native and motion-corrected data was compared. The maximum intensity, sharpness, and full width at half maximum (FWHM) of 5 segmental hepatic arteries were quantitatively measured. The overall quality of maximum intensity projection (MIP) images, conspicuity of tumor-supplying arteries, and need for selective angiography to ascertain the vascular anatomy were qualitatively evaluated by multiple readers. Paired t and Wilcoxon signed rank tests were used to compare the parameters. RESULTS: The mean maximum intensity and sharpness increased from 2,792.01 HU ± 451.36 to 3,148.40 HU ± 594.46 and from 0.31 ± 0.02/mm to 0.34 ± 0.02/mm, respectively, using the MACA (both P < .001). The MACA decreased the mean FWHM from 2.02 mm ± 0.27 to 1.78 mm ± 0.26 (P < .001). The overall quality of the MIP images and the conspicuity of the tumor-supplying artery were enhanced from 2.5 to 3.0 points and from 3.0 to 4.0 points, respectively (both P < .001). Selective angiography was expected to be omitted in 7 cases (16.7%, 7/42) after using the MACA. CONCLUSIONS: The MACA significantly improved both quantitative and qualitative image quality of cone-beam CT in selected patients with motion artifacts during transarterial chemoembolization for hepatic malignancies.

Outcomes of Venoplasty-Assisted, Peripherally Inserted Central Catheter Placement in Patients with Upper-Arm Venous Stenosis: Comparison with Midlines and Contralateral Placement.

PURPOSE: To compare the effectiveness and safety of percutaneous transluminal angioplasty and peripherally inserted central catheter (PTA + PICC), contralateral PICC, and midline catheterization (MC) in patients with venous stenosis. MATERIALS AND METHODS: A total of 7,327 PICC procedures were performed in 5,421 patients at a single institution between 2013 and 2019. Among them, 87 patients had upper-arm venous stenoses and were managed with PTA + PICC, contralateral PICC, or MC. Data on catheter-dwell time, clinical success rate, and adverse events were recorded. The procedure was considered to have clinically succeeded when a PICC was removed from the patient just before discharge or after the completion of therapy. Catheter survival time and the chance of adverse events were compared among the groups using the Kaplan-Meier method and log-rank test. RESULTS: PTA + PICC, contralateral PICC, and MC procedures were performed for 57 (65.5%, 57/87), 10 (11.5%, 10/87), and 20 (23.0%, 23/87) patients, respectively. The mean catheter-dwell time in the PTA + PICC, contralateral PICC, and MC groups was 49.7, 28.7, and 15.1 days, respectively, and the clinical success rate of each group was 86.0% (49/57), 80.0% (8/10), and 50.0% (10/20). The PTA + PICC group had a significantly longer catheter survival time than the MC group (P < .001). The chance of a catheter-related infection (P = .008) was significantly lower in the PTA + PICC group than in the MC group. CONCLUSIONS: PTA + PICC or contralateral PICC should be considered prior to ipsilateral MC when venous stenosis is encountered during PICC procedures.

A practical evaluation of machine learning for classification of ultrasound images of ovarian development in channel catfish (Ictalurus punctatus).

Machine learning is a powerful tool to improve efficiency of industrial processes, but it has not yet been well utilized in aquacultural and hatchery applications. The goal of the present study was to evaluate the feasibility of using a broad array of machine learning approaches (testing of > 200 vectorization and model combinations, reporting on 20) to classify ultrasound images spanning annual ovarian development (i.e., from undeveloped to mature) of channel catfish (Ictalurus punctatus). The specific objectives were to: 1) establish dataset preprocessing to standardize image features; 2) develop and train image classification models with deep learning methods; 3) develop and train models with traditional machine learning methods; 4) compare performance of deep learning and traditional methods on two classification problems (2-class and 5-class), and 5) propose insights to deploy models in practical aquaculture applications for research and hatchery use. A total of 931 ultrasound images of catfish ovaries were used to train and evaluate models for a 2-class problem (as a 'yes' or 'no' answer) to support hormone-injection decisions for spawning management in hatcheries, and a 5-class problem for classifying gonadal development stages for research. By using feature extraction, cropping, dimension reduction, and histogram normalization, a preprocessing method was created to standardize images to develop traditional (i.e., vector input), and deep learning convolutional neural network (CNN) (i.e., image input) approaches. Traditional machine learning models with image classification achieved 100% median accuracy on the 2-class problem (with the models RN-50 and RN-152), and 96% median accuracy for the 5-class problem (with VGG-19 image vectorization). The deep learning approach for the 2-class problem had a median accuracy of > 98% for 15models. The 5-class deep learning models produced a steady increase in median accuracy with training net size, achievable through expansion of the dataset. These models can be developed further, but traditional models (using CNN architectures to simply calculate image vectors) outperformed the deep learning approach. These models can be directly applicable to aquaculture in hatcheries and reproductive biology research, in addition to a wide variety of other image-based applications.

Design and Development of a Battery State of Health Estimation Model for Efficient Battery Monitoring Systems.

An uninterruptible power supply (UPS) is a device that can continuously supply power for a certain period when a power outage occurs. UPS devices are used by national institutions, hospitals, and servers, and are located in numerous public places that require continuous power. However, maintaining such devices in good condition requires periodic maintenance at specific time points. Efficient monitoring can currently be achieved using a battery management system (BMS). However, most BMSs are administrator-centered. If the administrator is not careful, it becomes difficult to accurately grasp the data trend of each battery cell, which in turn can lead to a leakage or heat explosion of the cell. In this study, a deep-learning-based intelligent model that can predict battery life, known as the state of health (SoH), is investigated for the efficient operation of a BMS applied to a lithium-based UPS device.

A Fabricated Force Glove That Measures Hand Forces during Activities of Daily Living.

Understanding hand and wrist forces during activities of daily living (ADLs) are pertinent when modeling prosthetics/orthotics, preventing workplace-related injuries, and understanding movement patterns that make athletes, dancers, and musicians elite. The small size of the wrist, fingers, and numerous joints creates obstacles in accurately measuring these forces. In this study, 14 FlexiForce sensors were sewn into a glove in an attempt to capture forces applied by the fingers. Participants in this study wore the glove and performed grasp and key turn activities. The maximal forces produced in the study were 9 N at the distal middle finger phalanx and 24 N at the distal thumb phalanx, respectively, for the grasp and key turn activities. Results from this study will help in determining the minimal forces of the hand during ADLs so that appropriate actuators may be placed at the appropriate joints in exoskeletons, orthotics, and prosthetics.

Spectral CT-Based Iodized Oil Quantification to Predict Tumor Response Following Chemoembolization of Hepatocellular Carcinoma.

PURPOSE: To quantify iodized oil retention in tumors after transarterial chemoembolization using spectral computed tomography (CT) imaging in patients with hepatocellular carcinoma (HCC) and evaluate its performance in predicting 12-month tumor responses. MATERIALS AND METHODS: From September 2017 to December 2018, 111 patients with HCC underwent initial conventional transarterial chemoembolization. Immediately after the procedure, unenhanced CT was performed using a spectral CT scanner, and the iodized oil densities in index tumors were measured. In tumor-level analyses, a threshold level of iodized oil density in the tumors was calculated using clustered receiver operating characteristic curve analyses to predict the 12-month tumor responses. In patient-level analyses, significant factors associated with a 12-month complete response, including the presence of tumors below the threshold value (ie, suspected residual tumors), were evaluated by logistic regression. RESULTS: Forty-eight HCCs in 39 patients were included in the analyses. The lower 10th percentile of the iodine density was identified as the threshold for determining the 12-month nonviable responses. The area under the curve of the iodine density measurements in predicting the 12-month nonviable responses was 0.893 (95% confidence interval, 0.797-0.989). The threshold value of the iodine density of 10.68 mg/mL yielded a sensitivity of 82.76% and specificity of 94.74% (P < .001). In the patient-level analysis, the 12-month complete response was significantly associated with the presence of a suspected residual tumor, with an odds ratio of 72.0 (95% confidence interval, 7.273-712.770). CONCLUSIONS: Spectral CT imaging using quantitative analysis of the iodized oil retention in target HCCs can predict tumor responses after a conventional transarterial chemoembolization procedure.

Collateral and permeability imaging derived from dynamic contrast material-enhanced MR angiography in prediction of PH 2 hemorrhagic transformation after acute ischemic stroke: a pilot study.

PURPOSE: To evaluate the role of collateral and permeability imaging derived from dynamic contrast material-enhanced magnetic resonance angiography to predict PH 2 hemorrhagic transformation in acute ischemic stroke. METHODS: The secondary analysis of a published data from participants with acute ischemic stroke. The multiphase collateral map and permeability imaging were generated by using dynamic signals from dynamic contrast material-enhanced magnetic resonance angiography obtained at admission. To identify independent predictors of PH 2 hemorrhagic transformation, age, sex, risk factors, baseline National Institutes of Health Stoke Scale (NIHSS) score, baseline DWI lesion volume, collateral-perfusion status, mode of treatment, and successful early reperfusion were evaluated with multiple logistic regression analyses and the significance of permeability imaging in prediction of PH 2 hemorrhagic transformation was evaluated by subgroup analysis. RESULTS: In 115 participants, including 70 males (mean (SD) age, 69 (12) years), PH 2 hemorrhagic transformation occurred in 6 participants with very poor collateral-perfusion status (MAC 0). MAC 0 (OR, 0.06; 95% CI, 0.01, 0.74; P = .03) was independently associated with PH 2 hemorrhagic transformation. In 22 participants with MAC 0, the permeable signal on Kep permeability imaging was the only significant characteristic associated with PH 2 hemorrhagic transformation (P = .009). The specificity of Kep permeability imaging was 93.8% (95% confidence interval: 69.8, 99.8) in predicting PH 2 hemorrhagic transformation. CONCLUSION: Individual-based prediction of PH 2 hemorrhagic transformation in patients with acute ischemic stroke may be possible with multiphase collateral map and permeability imaging derived from dynamic contrast material-enhanced magnetic resonance angiography.

Krüppel-like factor 15 is a key suppressor of podocyte fibrosis under rotational force-driven pressure.

Krüppel-like factor 15 (KLF15) is a well-known transcription factor associated with podocyte injury and fibrosis. Recently, hypertensive nephropathy was discovered to be closely related to podocyte injury and fibrosis. However, methods to stimulate hypertension in vitro are lacking. Here, we constructed an in vitro model mimicking hypertension using a rotational force device to identify the role of KLF15 in fibrosis due to mechanically induced hypertensive injury. First, we found that KLF15 expression was decreased in patients with hypertensive nephropathy. Then, an in vitro study of hypertension due to rotational force was conducted, and an increase in fibrosis markers and decrease in KLF15 levels were determined after application of 4 mmHg pressure in primary cultured human podocytes. KLF15 and tight junction protein levels increased with retinoic acid treatment. siRNA-mediated inhibition of KLF15 exacerbated pressure-induced fibrosis injury, and KLF15 expression after treatment with angiotensin II was similar to that observed after treatment with the blood pressure modeling device. Furthermore, the reduced KLF15 levels after mechanical pressure application were restored after the administration of an antihypertensive drug. KLF15 expression was also low in vivo. We confirmed the protective role of KLF15 in fibrosis using a mechanically induced in vitro model of hypertensive injury.

Endoscopic submucosal dissection using a detachable assistant robot: a comparative in vivo feasibility study (with video).

BACKGROUND: Appropriate tissue tension and clear visibility of the dissection area using traction are essential for effective and safe endoscopic submucosal dissection (ESD). We developed a robotic assistive traction device for flexible endoscopy and compared its safety and efficiency in ESD between experienced and novice endoscopists. METHODS: Robotic ESD was performed by experienced and novice endoscopist groups (n = 2, each). The outcomes included time to complete each ESD step, total procedure time, size of the dissected mucosa, rate of en bloc resection, and major adverse events. Furthermore, incision and dissection speeds were compared between groups. RESULTS: Sixteen gastric lesions were resected from nine live pigs. The submucosal incision speed was significantly faster in the expert group than in the novice group (P = 0.002). There was no significant difference in the submucosal dissection speed between the groups (P = 0.365). No complications were reported in either group. CONCLUSIONS: When the robot was assisting in the ESD procedure, the dissection speed improved significantly, especially in the novice surgeons. Our robotic device can provide simple, effective, and safe multidirectional traction during ESD.

An Impedimetric Sensing Probe Based on Printed Circuit Board Technology for Monitoring in Cryobiology Applications.

Cryopreservation of living cells is an effective tool for protection, maintenance, and distribution of genetic resources, which involves exposure to cryogenic temperatures and requires precise control over various parameters to avoid potential cell damages. Hundreds of protocols have been reported for cryopreservation of aquatic species, but replicating them is challenging without a reliable monitoring technique during a cryopreservation process. In this work, we aim to use electrical impedance as a monitoring parameter to assist standardization of cryopreservation processes and reporting. Specifically, this paper reports an impedance sensing probe compatible with cryogenic temperatures and conventional containers in cryopreservation of aquatic species based on printed circuit board technology its characterization in cryopreservation conditions including different sperm extenders (buffer) compositions and concentrations, presence of cryoprotectant, and multiple cooling rates. The developed probe based on printed circuit board (PCB) technology shows a capability of measuring conditions during cryopreservation differentiating among samples with different buffer contents and cryoprotectants. The probe also demonstrates the capability to distinguish different cooling regimes and detect phase change phenomena. This PCB-based sensing platform provides quantitative impedance measurement data during the cryopreservation process at sample preparation, cooling, and while frozen. Technology such as this offers opportunities for improving the reproducibility of protocols generated by the aquatic species community and can be made widely available as open hardware.

Electron-hole separation in ferroelectric oxides for efficient photovoltaic responses.

Despite their potential to exceed the theoretical Shockley-Queisser limit, ferroelectric photovoltaics (FPVs) have performed inefficiently due to their extremely low photocurrents. Incorporating Bi2FeCrO6 (BFCO) as the light absorber in FPVs has recently led to impressively high and record photocurrents [Nechache R, et al. (2015) Nat Photonics 9:61-67], which has revived the FPV field. However, our understanding of this remarkable phenomenon is far from satisfactory. Here, we use first-principles calculations to determine that such excellent performance mainly lies in the efficient separation of electron-hole (e-h) pairs. We show that photoexcited electrons and holes in BFCO are spatially separated on the Fe and Cr sites, respectively. This separation is much more pronounced in disordered BFCO phases, which adequately explains the observed exceptional PV responses. We further establish a design strategy to discover next-generation FPV materials. By exploring 44 additional Bi-based double-perovskite oxides, we suggest five active-layer materials that offer a combination of strong e-h separations and visible-light absorptions for FPV applications. Our work indicates that charge separation is the most important issue to be addressed for FPVs to compete with conventional devices.