Toxic leukoencephalopathy with axonal spheroids caused by chemotherapeutic drugs other than methotrexate

Background The objective of this report is to share the clinicopathological features of chemotherapy-induced toxic leukoencephalopathy, which is a rare and under-recognized disease, clinically characterized by rapidly progressive cognitive loss that often leads to sudden death. Case presentation A 64-year-old woman and a 63-year-old man, who had both suffered from a rapid deterioration of consciousness, were autopsied under the clinical impressions of either the central nervous system graft versus host disease (CNS-GVHD), infectious encephalitis, or autoimmune encephalitis. Both patients had been treated with multiple chemotherapy regimens, including adriamycin, cytarabine arabinoside, daunorubicin, fludarabine, azacitidine, and allogeneic peripheral blood stem cell transplantation to treat hematological malignancies (acute myelogenous leukemia and myelodysplastic syndrome). Neuropathological findings at autopsy revealed rarefaction and vacuolar changes of the white matter with axonal spheroids, reactive gliosis, and foamy macrophage infiltration, predominantly in the visual pathways of the occipital and temporal lobes. Damaged axons exhibited immunoreactivity to beta-amyloid, consistent with axonopathy. However, there was no lymphocyte infiltration that suggested CNS-GVHD or any type of encephalitis. Conclusion The neuropathology found in the presented cases had the characteristic features of toxic leukoencephalopathy (chemobrain). Our cases showed that toxic leukoencephalopathy can also be caused by chemotherapy drugs other than methotrexate.This research was supported by a fund (2021-ER1001-01) by the Research of Korea Disease Control and Prevention Agency. The role of the funder is financial support for the operation of the brain bank of Seoul National University Hospital and the operation of the brain donation program for the research

Autophagy deficiency leads to protection from obesity and insulin resistance by inducing Fgf21 as a mitokine

Despite growing interest and a recent surge in papers, the role of autophagy in glucose and lipid metabolism is unclear. We produced mice with skeletal muscle–specific deletion of Atg7 (encoding autophagy-related 7). Unexpectedly, these mice showed decreased fat mass and were protected from diet-induced obesity and insulin resistance; this phenotype was accompanied by increased fatty acid oxidation and browning of white adipose tissue (WAT) owing to induction of fibroblast growth factor 21 (Fgf21). Mitochondrial dysfunction induced by autophagy deficiency increased Fgf21 expression through induction of Atf4, a master regulator of the integrated stress response. Mitochondrial respiratory chain inhibitors also induced Fgf21 in an Atf4-dependent manner. We also observed induction of Fgf21, resistance to diet-induced obesity and amelioration of insulin resistance in mice with autophagy deficiency in the liver, another insulin target tissue. These findings suggest that autophagy deficiency and subsequent mitochondrial dysfunction promote Fgf21 expression, a hormone we consequently term a 'mitokine', and together these processes promote protection from diet-induced obesity and insulin resistance

Study on Optimal Generative Network for Synthesizing Brain Tumor-Segmented MR Images

Due to institutional and privacy issues, medical imaging researches are confronted with serious data scarcity. Image synthesis using generative adversarial networks provides a generic solution to the lack of medical imaging data. We synthesize high-quality brain tumor-segmented MR images, which consists of two tasks: synthesis and segmentation. We performed experiments with two different generative networks, the first using the ResNet model, which has significant advantages of style transfer, and the second, the U-Net model, one of the most powerful models for segmentation. We compare the performance of each model and propose a more robust model for synthesizing brain tumor-segmented MR images. Although ResNet produced better-quality images than did U-Net for the same samples, it used a great deal of memory and took much longer to train. U-Net, meanwhile, segmented the brain tumors more accurately than did ResNet

Techno-economic and environmental assessments for sustainable bio-methanol production as landfill gas valorization

With the regular increase in global solid waste, landfilling is intensively used for waste disposal. However, landfill gas (LFG) produced as a byproduct during waste decomposition in the landfills is a serious problem since it leads to damage to the eco-systems. Accordingly, it has been highlighted to convert LFG into other value-added chemicals. In this study, LFG utilization was studied in terms of conversion into methanol (MeOH) by considering different scenarios of LFG utilization. Techno-economic analysis and environmental assessment were performed to identify the economic feasibility and environmental impact of each case. From the economic analysis, bio-MeOH production costs of 879.16, 724.52, and 1,130.74 $ton-1 for case 1, 2, and 3 was estimated with the economic infeasibility, while substantial cost reduction through projected cost analysis can lead to economic competitiveness (449.52$ ton(-1) for case 2 and 595.76 $ ton-1 for case 3). In sequence, the quantitative envi-ronmental impacts in terms of climate change impact were 2.360, 0.835, and 0.605 kg CO2-eq kg MeOH-1 for cases 1, 2, and 3, respectively. Based on the results of two analyses, a multi-criteria decision analysis was conducted to investigate the acceptable case of bio-MeOH production in the economic and environmental as-pects. It can be concluded that the most feasible case depends on decision-makers if only economic and envi-ronmental criteria were considered. Therefore, dry reforming and membrane separation of LFG have considerable potential for bio-MeOH production in terms of LFG utilization for high weighting of economic and environmental aspects, respectively

The Pepper RING Finger E3 Ligase, CaDIR1, Regulates the Drought Stress Response via ABA-Mediated Signaling

Drought stress from soil or air limits plant growth and development, leading to a reduction in crop productivity. Several E3 ligases positively or negatively regulate the drought stress response. In the present study, we show that the pepper (Capsicum annuum) Drought Induced RING type E3 ligase 1, CaDIR1, regulates the drought stress response via abscisic acid (ABA)-mediated signaling. CaDIR1 contains a C3HC4-type RING finger domain in the N-terminal region; this domain functions during protein degradation via attachment of ubiquitins to the substrate target proteins. The expression levels of the CaDIR1 gene were suppressed and induced by ABA and drought treatments, respectively. We conducted loss-of-function and gain-of function genetic studies to examine the in vivo function of CaDIR1 in response to ABA and drought stress. CaDIR1-silenced pepper plants displayed a drought-tolerant phenotype characterized by a low level of transpirational water loss via increased stomatal closure and elevated leaf temperatures. CaDIR1-overexpressing (OX) Arabidopsis plants exhibited an ABA-hypersensitive phenotype during the germination stage, but an ABA-hyposensitive phenotype—characterized by decreased stomatal closure and reduced leaf temperatures—at the adult stage. Moreover, adult CaDIR1-OX plants exhibited a drought-sensitive phenotype characterized by high levels of transpirational water loss. Our results indicate that CaDIR1 functions as a negative regulator of the drought stress response via ABA-mediated signaling. Our findings provide a valuable insight into the plant defense mechanism that operates during drought stress

An innovative high energy efficiency-based process enhancement of hydrogen liquefaction: Energy, exergy, and economic perspectives

Hydrogen liquefaction can be one of the effective and viable solutions to enhance its energy contents for storage and transportation purposes. However, liquefaction of H-2 is highly energy intensive where precooling is the most significant energy consumption section (similar to 50% of overall process) due to huge reduction in temperature (25 to-159.4 degrees C). In this context, in proposed study the precooling cycle is split into two cycles for reducing the energy consumption, 1) Hydrofluoroolefin-based mixed refrigerant stream which reduces the H-2 temperature to -30 degrees C and 2) Mixed refrigerant stream which tends to reduce the H-2 temperature up to-159.4 degrees C. This is the first study which utilizes the four refrigeration cycles with unique selection of HFO-based mixed refrigerants in precooling section to reduce the gaseous H-2 temperature. Results of proposed study reveal that the specific energy consumption of proposed process was reduced by 55.2 % and 29.5%, as compared to base case-I (10.15 kWh/kgLH(2)) and base case-II (6.45 kWh/kgLH(2)), respectively. The exergy efficiency of the proposed process was increased by 67%. In addition, results of economic evaluation depicted that the total annualized cost of proposed process was obtained as $1.89 x 10(6)/y where the CAPEX has share of similar to 71.7$5.18/kg of LH2 at the capacity of 1TPD. The simplicity and less energy consumption of proposed model built a basis for its development to commercial scale adoption

Collapse pressure measurement of single hollow glass microsphere using single-beam acoustic tweezer

Microbubbles are widely used in medical ultrasound imaging and drug delivery. Many studies have attempted to quantify the collapse pressure of microbubbles using methods that vary depending on the type and population of bubbles and the frequency band of the ultrasound. However, accurate measurement of collapse pressure is difficult as a result of non-acoustic pressure factors generated by physical and chemical reactions such as dissolution, cavitation, and interaction between bubbles. In this study, we developed a method for accurately measuring collapse pressure using only ultrasound pulse acoustic pressure. Under the proposed method, the collapse pressure of a single hollow glass microsphere (HGM) is measured using a high-frequency (20–40 MHz) single-beam acoustic tweezer (SBAT), thereby eliminating the influence of additional factors. Based on these measurements, the collapse pressure is derived as a function of the HGM size using the microspheres’ true density. We also developed a method for estimating high-frequency acoustic pressure, whose measurement using current hydrophone equipment is complicated by limitations in the size of the active aperture. By recording the transmit voltage at the moment of collapse and referencing it against the corresponding pressure, it is possible to estimate the acoustic pressure at the given transmit condition. These results of this study suggest a method for quantifying high-frequency acoustic pressure, provide a potential reference for the characterization of bubble collapse pressure, and demonstrate the potential use of acoustic tweezers as a tool for measuring the elastic properties of particles/cells.11Nsciescopu

Thermal Ablation and High-Resolution Imaging Using a Back-to-Back (BTB) Dual-Mode Ultrasonic Transducer: In Vivo Results

We present a back-to-back (BTB) structured, dual-mode ultrasonic device that incorporates a single-element 5.3 MHz transducer for high-intensity focused ultrasound (HIFU) treatment and a single-element 20.0 MHz transducer for high-resolution ultrasound imaging. Ultrasound image-guided surgical systems have been developed for lesion monitoring to ensure that ultrasonic treatment is correctly administered at the right locations. In this study, we developed a dual-element transducer composed of two elements that share the same housing but work independently with a BTB structure, enabling a mode change between therapy and imaging via 180-degree mechanical rotation. The optic fibers were embedded in the HIFU focal region of ex vivo chicken breasts and the temperature change was measured. Images were obtained in vivo mice before and after treatment and compared to identify the treated region. We successfully acquired B-mode and C-scan images that display the hyperechoic region indicating coagulation necrosis in the HIFU-treated volume up to a depth of 10 mm. The compact BTB dual-mode ultrasonic transducer may be used for subcutaneous thermal ablation and monitoring, minimally invasive surgery, and other clinical applications, all with ultrasound only.11Nsciescopu