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Abnormal spindle-like microcephaly associated (ASPM) is a causative gene of primary autosomal recessive microcephaly. Microcephaly is considered to be a consequence of a small brain, but the associated molecular mechanisms are not fully understood. In this study, we generated brain-specific Aspm knockout mice to evaluate the fetal brain phenotype and observed cortical reduction in the late stage of murine cortical development. It has been reported that the total number of neurons is regulated by the number of neural stem and progenitor cells. In the Aspm knockout mice, no apparent change was shown in the neural progenitor cell proliferation and there was no obvious effect on the number of newly generated neurons in the developing cortex. On the other hand, the knockout mice showed a constant increase in apoptosis in the cerebral cortex from the early through the late stages of cortical development. Furthermore, apoptosis occurred in the neural progenitor cells associated with DNA damage. Overall, these results suggest that apoptosis of the neural progenitor cells is involved in the thinning of the mouse cerebral cortex, due to the loss of the Aspm gene in neocortical development.

Following carbon ion beam irradiation in mammalian cells, such as used in carbon ion radiotherapy (CIRT), it has been suggested that the balance between whether nonhomologous end joining (NHEJ) or homologous recombination (HR) is utilized depends on the DNA double‐strand break (DSB) complexity. Here, we quantified DSB distribution and identified the importance of each DSB repair pathway at increasing depths within the carbon ion spread‐out Bragg peak (SOBP) beam range. Chinese hamster ovary (CHO) cell lines were irradiated in a single biological system capable of incorporating the full carbon ion SOBP beam range. Cytotoxicity and DSB distribution/repair kinetics were examined at increasing beam depths using cell survival as an endpoint and γ‐H2AX as a surrogate marker for DSBs. We observed that proximal SOBP had the highest number of total foci/cell and lowest survival, while distal SOBP had the most dense tracks. Both NHEJ‐ and HR‐deficient CHO cells portrayed an increase in radiosensitivity throughout the full carbon beam range, although NHEJ‐deficient cells were the most radiosensitive cell line from beam entrance up to proximal SOBP and demonstrated a dose‐dependent decrease in ability to repair DSBs. In contrast, HR‐deficient cells had the greatest ratio of survival fraction at entrance depth to the lowest survival fraction within the SOBP and demonstrated a linear energy transfer (LET)‐dependent decrease in ability to repair DSBs. Collectively, our results provide insight into treatment planning and potential targets to inhibit, as HR was a more beneficial pathway to inhibit than NHEJ to enhance the cell killing effect of CIRT in targeted tumor cells within the SOBP while maintaining limited unwanted damage to surrounding healthy cells. This is the first study to demonstrate that homologous recombination is the most beneficial pathway to inhibit over nonhomologous end joining to enhance the cell killing effect of carbon ion radiotherapy in the targeted tumor cells within the carbon ion spread‐out Bragg peak.

Among the celestial bodies in the Solar System, Mars currently represents the main target for the search for life beyond Earth. However, its surface is constantly exposed to high doses of cosmic rays (CRs) that may pose a threat to any biological system. For this reason, investigations into the limits of resistance of life to space relevant radiation is fundamental to speculate on the chance of finding extraterrestrial organisms on Mars. In the present work, as part of the STARLIFE project, the responses of dried colonies of the black fungus Cryomyces antarcticus Culture Collection of Fungi from Extreme Environments (CCFEE) 515 to the exposure to accelerated iron (LET: 200 keV/μm) ions, which mimic part of CRs spectrum, were investigated. Samples were exposed to the iron ions up to 1000 Gy in the presence of Martian regolith analogues. Our results showed an extraordinary resistance of the fungus in terms of survival, recovery of metabolic activity and DNA integrity. These experiments give new insights into the survival probability of possible terrestrial-like life forms on the present or past Martian surface and shallow subsurface environments.

Space travel has advanced significantly over the last six decades with astronauts spending up to 6 months at the International Space Station. Nonetheless, the living environment while in outer space is extremely challenging to astronauts. In particular, exposure to space radiation represents a serious potential long-term threat to the health of astronauts because the amount of radiation exposure accumulates during their time in space. Therefore, health risks associated with exposure to space radiation are an important topic in space travel, and characterizing space radiation in detail is essential for improving the safety of space missions. In the first part of this review, we provide an overview of the space radiation environment and briefly present current and future endeavors that monitor different space radiation environments. We then present research evaluating adverse biological effects caused by exposure to various space radiation environments and how these can be reduced. We especially consider the deleterious effects on cellular DNA and how cells activate DNA repair mechanisms. The latest technologies being developed, e.g., a fluorescent ubiquitination-based cell cycle indicator, to measure real-time cell cycle progression and DNA damage caused by exposure to ultraviolet radiation are presented. Progress in examining the combined effects of microgravity and radiation to animals and plants are summarized, and our current understanding of the relationship between psychological stress and radiation is presented. Finally, we provide details about protective agents and the study of organisms that are highly resistant to radiation and how their biological mechanisms may aid developing novel technologies that alleviate biological damage caused by radiation. Future research that furthers our understanding of the effects of space radiation on human health will facilitate risk-mitigating strategies to enable long-term space and planetary exploration.

The sharp high dose Bragg peak of a carbon-ion beam helps it to deliver the highest dosage to the malignant cells while leaving the normal cells relatively unharmed. However, the precise range in which it distributes dosages that significantly induce cell death or genotoxicity surrounding its Bragg peak remains unclear. To evaluate biological effects of carbon-ion radiation through entrance to post Bragg peak in a single biological system, CHO and xrs5 cells were cultured in T-175 cell culture flasks and irradiated with 290 MeV/n monoenergetic carbon-ions with initial dosages upon entrance to the flask of 1, 2, or 3 Gy for cell survival assays or 1 Gy for cytokinesis block micronuclei assays. Under all initial dosages, the biological Bragg peak and the highest micronuclei formation was observed at the depth of 14.5 cm. Moreover, as the initial dosage increased the range displaying a significant decrease in survival fraction increased as well ( P  <  0 . 0001 ). Intriguingly from 1 Gy to 3 Gy, we observed a significant increase in reappearance of colony formation depth ( P  <  0 . 05 ), possibly indicating the nuclear fragmentation lethality potential of the carbon-ion. By means of our single system approach, we can achieve a more comprehensive understanding of biological effects surrounding of carbon-ions Bragg peak.

The annual survey of the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) was sent to 4458 dialysis facilities at the end of 2018; among these facilities, 4402 facilities (98.7%) responded to the facility questionnaire, and 4222 (94.7%) responded to the patient questionnaire. The number of chronic dialysis patients in Japan continues to increase every year; as of the end of 2018, it had reached 339,841 patients, representing 2688 patients per million population. Among the prevalent dialysis patients, the mean age was 68.75 years, and diabetic nephropathy was the most common primary disease among the prevalent dialysis patients (39.0%), followed by chronic glomerulonephritis (26.8%) and nephrosclerosis (10.8%). The number of incident dialysis patients was 40,468, and a reduction by 491 from 2017. The mean age of the incident dialysis patients was 69.99 years old. Diabetic nephropathy was also the most common primary disease (42.3%), representing a 0.2 percent point reduction from 2017. The distribution of diabetic nephropathy appears to have reached a plateau. The number of deceased patients during 2018 was 33,863, and the crude annual death rate was 10.0%. Heart failure was the most common cause of death (23.5%), followed by infection (21.3%) and malignant tumor (8.4%); these causes were similar to those for 2017. The number of patients receiving hemodiafiltration has been increasing since 2012, reaching 125,793 or 37.0% of all dialysis patients at the end of 2018. The number of patients receiving peritoneal dialysis has been gradually increasing since 2017, reaching 9445, and 19.7% of these patients were treated using a combination of peritoneal dialysis and hemodialysis or hemodiafiltration. The proportion of patients receiving combination therapy has remained at around 20% of all peritoneal dialysis patients. The number of patients undergoing home hemodialysis was 720, representing an increase of 36 patients from 2017. The 2018 JRDR survey included several topics such as the present status of the patient kinetics of chronic dialysis patients at the end of 2018, water treatment and hemodiafiltration, peritoneal dialysis, treatments for diabetes, mental and physical conditions, and the present status of viral hepatitis. In this paper, we describe the patient and facility kinetics. Trial registration The JRDR was approved by the ethics committee of the JSDT (approval number 1-3) and was registered in the “University hospital Medical Information Network (UMIN) Clinical Trials Registry” under the clinical trial ID of UMIN000018641 on August 8, 2015: (Accessed June 2, 2020)

Previous work pointed to a critical role of excessive production of reactive oxygen species (ROS) in increased radiation hematopoietic death in GFP mice. Meanwhile, enhanced antioxidant capability was not demonstrated in the mouse model of radio-induced adaptive response (RAR) using rescue of radiation hematopoietic death as the endpoint. ROS induction by ex vivo X-irradiation at a dose ranging from 0.1 to 7.5 Gy in the nucleated bone marrow cells was comparatively studied using GFP and wild type (WT) mice. ROS induction was also investigated in the cells collected from mice receiving a priming dose (0.5 Gy) efficient for RAR induction in WT mice. Significantly elevated background and increased induction of ROS in the cells from GFP mice were observed compared to those from WT mice. Markedly lower background and decreased induction of ROS were observed in the cells collected from WT mice but not GFP mice, both receiving the priming dose. GFP overexpression could alter background and induction of ROS by X-irradiation in hematopoietic cells. The results provide a reasonable explanation to the previous study on the fate of cells and mice after X-irradiation and confirm enhanced antioxidant capability in RAR. Investigations involving GFP overexpression should be carefully interpreted.

Background TAFRO syndrome is a rare disorder that causes thrombocytopenia, generalized oedema, fever, organ enlargement, and renal impairment. Few reports have suggested an association with vaccines, and few cases have undergone renal biopsy. TAFRO syndrome is often severe and fatal, and its cause is unknown. We report a case of TAFRO syndrome that occurred after vaccination with the coronavirus disease 2019 (COVID-19) vaccine. Case presentation An 82-year-old woman received two doses of the BNT162b2 mRNA vaccine 3 weeks apart. Two weeks later, she was admitted to the hospital with oedema, accompanied with renal failure and thrombocytopenia. After close examination, she was diagnosed with TAFRO syndrome. She was treated with steroids, cyclosporine, and thrombopoietin receptor agonists. The patient was discharged after several months in remission. Conclusions Although an incident of TAFRO syndrome after COVID-19 vaccination has been previously reported, this is a rare case in which the patient went into remission and was discharged. A renal biopsy was also performed in this case, which was consistent with previous reports. The favorable treatment course for TAFRO syndrome provides valuable insights.

Background Recently, virtual navigation system has been applied to hepatic surgery, enabling better visualization of intrahepatic vascular branches and location of tumor. Intraoperative ultrasonography (IOUS) is the most common form of image guidance during liver surgery. However, during laparoscopic hepatectomies (LH), IOUS has several limitations and its reliability has been poorly evaluated. The objective of this work is to evaluate VRCT (virtual real-time CT-guided volume navigation) during LH. This system aims to provide accurate anatomical orientation for surgeons enhancing the safety of LH. Methods Twenty-seven hepatic neoplasms were resected laparoscopically at our institution under reference guidance of VRCT. During operation, electromagnetic tracking of the surgical instrument was used for navigating the direction of accurate liver transection. Results Twenty-six (96.3%) of the 27 lesions (mean diameter 11 mm) were successfully performed under VRCT guidance. Average registration time was < 2 min. Average setup time was approximately 7 min per procedure. VRCT allows the surgeon to navigate liver transection with acceptable accuracy. The mean error was 12 mm. All surgical margins were negative and the mean histologic resection margin was 9 mm. Conclusions VRCT-guided LH is feasible and provides valuable real-time anatomical feedback during hepatic resections. Advancement of such systems to improve accuracy might greatly compensate for the limitation of laparoscopic IOUS.

Laparoscopic hepatectomy (LH) requires accurate visualization and appropriate handling of hepatic veins and the Glissonean pedicle that suddenly appear during liver dissection. Failure to recognize these structures can cause injury, resulting in severe bleeding and bile leakage. This study aimed to develop a novel artificial intelligence (AI) system that assists in the visual recognition and color presentation of tubular structures to correct the recognition gap among surgeons.BACKGROUND/AIMLaparoscopic hepatectomy (LH) requires accurate visualization and appropriate handling of hepatic veins and the Glissonean pedicle that suddenly appear during liver dissection. Failure to recognize these structures can cause injury, resulting in severe bleeding and bile leakage. This study aimed to develop a novel artificial intelligence (AI) system that assists in the visual recognition and color presentation of tubular structures to correct the recognition gap among surgeons.Annotations were performed on over 350 video frames capturing LH, after which a deep learning model was developed. The performance of the AI was evaluated quantitatively using intersection over union (IoU) and Dice coefficients, as well as qualitatively using a two-item questionnaire on sensitivity and misrecognition completed by 10 hepatobiliary surgeons. The usefulness of AI in medical education was qualitatively evaluated by 10 medical students and residents.PATIENTS AND METHODSAnnotations were performed on over 350 video frames capturing LH, after which a deep learning model was developed. The performance of the AI was evaluated quantitatively using intersection over union (IoU) and Dice coefficients, as well as qualitatively using a two-item questionnaire on sensitivity and misrecognition completed by 10 hepatobiliary surgeons. The usefulness of AI in medical education was qualitatively evaluated by 10 medical students and residents.The AI model was able to individually recognize and colorize hepatic veins and the Glissonean pedicle in real time. The IoU and Dice coefficients were 0.42 and 0.53, respectively. Surgeons provided a mean sensitivity score of 4.24±0.89 (from 1 to 5; Excellent) and a mean misrecognition score of 0.12±0.33 (from 0 to 4; Fail). Medical students and residents assessed the AI to be very useful (mean usefulness score, 1.86±0.35; from 0 to 2; Excellent).RESULTSThe AI model was able to individually recognize and colorize hepatic veins and the Glissonean pedicle in real time. The IoU and Dice coefficients were 0.42 and 0.53, respectively. Surgeons provided a mean sensitivity score of 4.24±0.89 (from 1 to 5; Excellent) and a mean misrecognition score of 0.12±0.33 (from 0 to 4; Fail). Medical students and residents assessed the AI to be very useful (mean usefulness score, 1.86±0.35; from 0 to 2; Excellent).The novel AI presented was able to assist surgeons in the intraoperative recognition of microstructures and address the recognition gap among surgeons to ensure a safer and more accurate LH.CONCLUSIONThe novel AI presented was able to assist surgeons in the intraoperative recognition of microstructures and address the recognition gap among surgeons to ensure a safer and more accurate LH.