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Abstract Peripheral nerve injury (PNI) often leads to retrograde cell death in the spinal cord and dorsal root ganglia (DRG), hindering nerve regeneration and functional recovery. Repetitive magnetic stimulation (rMS) promotes nerve regeneration following PNI. Therefore, this study aimed to investigate the effects of rMS on post-injury neuronal death and nerve regeneration. Seventy-two rats underwent autologous sciatic nerve grafting and were divided into two groups: the rMS group, which received rMS and the control (CON) group, which received no treatment. Motor neuron, DRG neuron, and caspase-3 positive DRG neuron counts, as well as DRG mRNA expression analyses, were conducted at 1-, 4-, and 8-weeks post-injury. Functional and axon regeneration analyses were performed at 8-weeks post-injury. The CON group demonstrated a decreased DRG neuron count starting from 1 week post-injury, whereas the rMS group exhibited significantly higher DRG neuron counts at 1- and 4-weeks post-injury. At 8-weeks post-injury, the rMS group demonstrated a significantly greater myelinated nerve fiber density in autografted nerves. Furthermore, functional analysis showed significant improvements in latency and toe angle in the rMS group. Overall, these results suggest that rMS can prevent DRG neuron death and enhance nerve regeneration and motor function recovery after PNI.

Abstract Possible local influence of an extreme marine heatwave is investigated on unprecedentedly hot summer around northern Japan in 2023. Sea-surface temperatures (SSTs) and subsurface ocean temperatures around northern Japan were also unprecedentedly high in the summer. This was especially the case off the east coast of Japan, where cool Oyashio water was replaced with much warmer water due to a striking poleward meander of the Kuroshio Extension persistent from the spring. Particularly amplified near-surface air temperature anomalies and even stronger warm anomalies in the subsurface ocean suggest that the marine heatwave acted to sustain the atmospheric heatwave. Anomalous upward of latent and sensible heat fluxes from the warmed sea surface are indicative of local oceanic impact. The warm SST anomalies reduced the lower-tropospheric stratification to maintain unfavourable condition for low-level cloud formation, which in turn led to increased surface insolation for further SST warming as positive feedback. The increased moisture in the warmed lower troposphere contributed to the enhanced surface downward longwave radiation. This enhanced greenhouse effect acted not only as positive feedback on the warm SST anomalies that increased evaporation but also as a contributor for the extreme warmth over northern Japan landmass.

Previous studies on deep-learning-based side-channel attacks (DL-SCAs) have shown that traditional performance evaluation metrics commonly used in DL, like accuracy and F1 score, are not effective in evaluating DL-SCA performance. Therefore, some previous studies have proposed new alternative metrics for evaluating the performance of DL-SCAs. Notably, perceived information (PI) and effective perceived information (EPI) are major metrics based on information theory. While it has been experimentally confirmed that these metrics can give the attack success rate (SR) for DL-SCAs, their theoretical validity remains unclear. In this paper, we propose a new theoretically valid performance evaluation metric called latent perceived information (LPI), which serves as an alternative to the existing metrics. LPI is defined as the mutual information between the output of the feature extractor of a neural network (NN) model and the intermediate value, representing the potential attack performance of the trained model. First, we prove that LPI provides an upper bound on the SR of a DL-SCA by modeling and formulating DL-SCA as a communication channel. Additionally, we clarify the conditions under which PI and EPI theoretically provide an upper bound on the SR from the perspective of LPI. For practical computation of LPI, we present two methods. One utilizes the Kraskov (KSG) estimator, a common mutual information estimator, and the other is based on logistic regression. While the KSG estimator is computationally intensive, it yields accurate LPI values. In contrast, the logistic regression is faster but provides a lower bound for LPI. Through experimental attacks on AES software and hardware implementations with masking countermeasures, we demonstrate that the LPI values estimated by these two methods are significantly similar, indicating the reliability and soundness of our proposed estimation techniques. Furthermore, we show that, by using the logistic regression as a classifier, we can significantly improve the attack performance of the trained model when the difference between the SR upper bound by the LPI and its actual SR is large. This indicates that LPI represents the potential for performance improvement in the trained model. Therefore, our study contributes to optimizing the distinguisher for attack performance using the trained model.

Abstract Bioluminescence generated by luciferase and luciferin has been extensively used in biological research. However, detecting signals from deep tissues in vivo poses a challenge to traditional methods. To overcome this, the Akaluc and AkaLumine bioluminescent systems were developed, resulting in improved signal detection. We evaluate the potential of Akaluc/AkaLumine in Drosophila melanogaster to establish a highly sensitive, non-invasive, and temporal detection method for gene expression. Our results show that oral administration of AkaLumine to flies expressing Akaluc provided a higher luminescence signal than Luc/D-luciferin, with no observed harmful effects on flies. The Akaluc/AkaLumine system allows for monitoring of dynamic temporal changes in gene expression. Additionally, using the Akaluc fusion gene allows for mRNA splicing monitoring. Our findings indicate that the Akaluc/AkaLumine system is a powerful bioluminescence tool for analyzing gene expression in deep tissues and small numbers of cells in Drosophila.

Abstract Peripheral nerve injury causes long-term motor dysfunction. Ultrasound (US) therapy is expected to accelerate peripheral nerve regeneration. However, its optimal usage and effects on macrophage phenotypes during peripheral nerve regeneration remain unknown. In this study, we investigated the optimal duration of US therapy and its effects on macrophage phenotype. Twenty-seven rats with autologous sciatic nerve grafting were divided into three groups: two received US therapy (1 MHz frequency, intensity of 140 mW/cm2, 20% duty cycle, 5 min/day) for one (US1) or 4 weeks (US4), and one group received sham stimulation. Immunohistochemistry was performed 3 and 7 days after injury in another set of 12 rats. Eight weeks after the injury, the compound muscle action potential amplitude of the gastrocnemius in the US1 and US4 groups was significantly higher than that in the sham group. The toe-spreading test showed functional recovery, whereas the gait pattern during treadmill walking did not recover. There were no significant differences in motor function, histomorphometry, or muscle weight between groups. Immunohistochemistry showed that US therapy decreased the number of pro-inflammatory macrophages seven days after injury. Therefore, US therapy for both one or 4 weeks can similarly promote reinnervation and reduce proinflammatory macrophages in autograft model rats.

Abstract COVID‐19 outbreaks occurred in several hospitals, and the National Institute of Infectious Diseases, local authorities, and universities carried out investigations into ventilation in hospitals. The results indicated that ventilation performance was insufficient to prevent aerosol infection due to poor air conditioning, equipment maintenance, and existing ventilation design guidelines. The authors investigated guidelines for ventilation measures for general patient wards with the cooperation of The Society of Air‐Conditioning and Sanitary Engineers of Japan and the Japanese Society for Infection Prevention and Control. Based on a survey of COVID‐19 outbreaks in hospitals, ventilation countermeasure plans for 3 stages (a. normal conditions, b. increased risk of outbreaks, and c. infected patients treated) were compiled.

Matrix stiffening is a quintessential feature of aged tissues. Authors show that an aged (stiff) matrix epigenetically represses the gene encoding the longevity factor, α-Klotho, resulting in chondrocyte dysfunction, a leading cause of osteoarthritis.

Abstract Biobanking of pancreatic islets for transplantation could solve the shortage of donors, and cryopreservation of vitrified islets is a possible approach. However, a technological barrier is rewarming of large volumes both uniformly and rapidly to prevent ice formation due to devitrification. Here, we describe successful recovery of islets from the vitrified state using a volumetric rewarming technology called “nanowarming,” which is inductive heating of magnetic nanoparticles under an alternating magnetic field. Convective warming using a 37°C water bath as the gold standard for rewarming of vitrified samples resulted in a decrease in the viability of mouse islets in large volumes (>1 ml) owing to devitrification caused by slow warming. Nanowarming showed uniform and rapid rewarming of vitrified islets in large volumes. The viability of nanowarmed islets was significantly improved and islets transplanted into streptozotocin‐induced diabetic mice successfully lowered serum glucose. The results suggest that nanowarming will lead to a breakthrough in biobanking of islets for transplantation.

In this study, a novel rat model of knee joint adhesion was developed, and its formation was analyzed quantitatively over time. Thirty-nine Wistar rats were randomly divided into intact control (n = 3) and experimental (n = 36) groups. The latter was equally divided into three groups according to the experimental intervention: fixed with deep bending of the knee joint (group I), fixed after incision of the capsule (group II), and fixed after exposure of the patellofemoral joint to artificial patellar subluxation (group III). All rats were subdivided according to their joint immobilization period (1, 2, or 4 weeks). Thereafter, the limited range of motion of the knee joint with (limited knee range of motion) and without (limited knee joint intrinsic range of motion) skin and muscles were measured. The lengths of adhesions of the anterior knee joint and posterior capsules were evaluated histologically. The limited intrinsic range of motion of the knee joint was found to be increased in groups II and III compared to that in group I 4 weeks after immobilization. Adhesions were confirmed within 1 week after immobilization in groups II and III. The length of the adhesions in group III was significantly longer than in other groups at 2 weeks and remained longer than in group I at 4 weeks. This model may contribute to the assessment of the adhesion process and development of new therapeutic avenues following trauma or surgical invasion.

Background. Percutaneous coronary intervention using a drug-eluting stent (DES) is a common therapeutic option for acute coronary syndrome (ACS). However, stent-associated complications, such as bleeding associated with dual antiplatelet therapy, in-stent restenosis, stent thrombosis, and neoatherosclerosis, remain. Drug-coated balloons (DCBs) are expected to reduce stent-associated complications. This study aimed to assess the efficacy of DCB therapy and compare it with that of DES therapy in patients with ACS. Materials and Methods. In this single-center, retrospective, observational study, we examined all patients with ACS treated with DCB or DES between July 2014 and November 2020. Patients with left main trunk lesions were excluded. The primary outcome was a composite of major adverse cardiovascular events (MACE: cardiac death, myocardial infarction, and target lesion revascularization) at one year. Results. Three hundred and seventy-two patients were treated with DES, and 83 patients were treated with DCB. MACE occurred in 10 (12.0%) patients in the DCB group and in 50 (13.4%) patients in the DES group (P=0.73). Conclusions. DCB is a valuable and effective therapy for patients with ACS. Moreover, DCB may become an alternative therapy for DES in patients with ACS.

Abstract Recently, trans-radial intervention has gained popularity as a common procedure to reduce hemorrhagic complications. However, the cuff-type hemostatic device (TR Band) previously used at our institution required 6 h to achieve hemostasis. Since July 2016, we have been using the VasoSTAT, a new hemostatic device that could achieve hemostasis in 4 h. In a verification study, we found that prolonged activated clotting time (ACT) was related to transient hemorrhage occurrence after the hemostatic procedure. Therefore, we designed a hemostatic protocol based on ACT and evaluated its efficacy. In this retrospective and observational study, 78 and 111 patients used the VasoSTAT and TR Band, respectively, from July 2015 to May 2017. In the VasoSTAT group, the ACTs were significantly lower in the hemostasis success (246 ± 46 s) than in the failure group patients (327 ± 59 s) (P

Objective: Mechanical stimulation is a risk factor for knee osteoarthritis. Non-surgical compression has been used to study the effects of mechanical stimulation in vivo. However, the long-term effects of low-force compression on knee joint had not been studied. Therefore, we sought to identify the long-term effects of low-force cyclic compression on the rat knee joint. Design: In this study, we applied one session cyclic compression with a peak load of 20 ​N for 60 cycles to the rat knee joint in an approximately 140-degree flexion position (Wistar, male, 12 weeks old), followed by 1 year of observation (including data from 1 week, 2 weeks, 4 weeks, 8 weeks, 6 months, and 1 year after compression), and then performed a sub-regional analysis with hematoxylin-eosin, Safranin O and Fast Green, and MMP13 immunohistochemical staining. Results: We observed osteoarthritis-like cartilage damage, synovial inflammation, and high expression of MMP13 within 1 year after compression. However, these changes progressed slowly, with obvious matrix cracks that did not appear until 1 year after compression. In the regional analysis, we found that low-force compression caused a much slower development of injury at the compression contact site, and no significant structural cartilage damage was observed after 1 year of compression. In contrast, the non-contact site during compression at tibial cartilage in the same joint was the first to show significant structural damage. Conclusion: This study demonstrates that one session of 20 ​N cyclic compression induces a chronic osteoarthritis-like phenotype in the rat knee in the long term.

Recovery of motor function after peripheral nerve injury requires treatment of the neuromuscular junction (NMJ), as well as the injured nerve and skeletal muscle. The purpose of this study was to examine the effects of ultrasound (US) stimulation on NMJ degeneration after denervation using a rat model of peroneal nerve transection. Twelve-week-old male Wistar rats were randomly assigned to 3 groups: US stimulation, sham stimulation, and intact. US or sham stimulation was performed on the left tibialis anterior (TA) muscle starting the day after peroneal nerve transection for 5 minutes daily under anesthesia. Four weeks later, the number and morphology of the motor endplates were analyzed to assess NMJ in the TA muscle. The endplates were classified as normal, partially fragmented, or fully fragmented for morphometric analysis. In addition, the number of terminal Schwann cells (tSCs) per endplate and percentage of endplates with tSCs (tSC retention percentage) were calculated to evaluate the effect of tSCs on NMJs. Our results showed that endplates degenerated 4 weeks after transection, with a decrease in the normal type and an increase in the fully fragmented type in both the US and sham groups compared to the intact group. Furthermore, the US group showed significant suppression of the normal type decrease and a fully fragmented type increase compared to the sham group. These results suggest that US stimulation inhibits endplate degeneration in denervated TA muscles. In contrast, the number of endplates and tSC and tSC retention percentages were not significantly different between the US and sham groups. Further investigations are required to determine the molecular mechanisms by which US stimulation suppresses degeneration.

In this study, we present new analytical metrics for evaluating the performance of side-channel attacks (SCAs) by revisiting the perceived information (PI), which is defined using cross-entropy (CE). PI represents the amount of information utilized by a probability distribution that determines a distinguishing rule in SCA. Our analysis partially solves an important open problem in the performance evaluation of deep-learning based SCAs (DL-SCAs) that the relationship between neural network (NN) model evaluation metrics (such as accuracy, loss, and recall) and guessing entropy (GE)/success rate (SR) is unclear. We first theoretically show that the conventional CE/PI is non-calibrated and insufficient for evaluating the SCA performance, as it contains uncertainty in terms of SR. More precisely, we show that an infinite number of probability distributions with different CE/PI can achieve an identical SR. With the above analysis result, we present a modification of CE/PI, named effective CE/PI (ECE/EPI), to eliminate the above uncertainty. The ECE/EPI can be easily calculated for a given probability distribution and dataset, which would be suitable for DL-SCA. Using the ECE/EPI, we can accurately evaluate the SR hrough the validation loss in the training phase, and can measure the generalization of the NN model in terms of SR in the attack phase. We then analyze and discuss the proposed metrics regarding their relationship to SR, conditions of successful attacks for a distinguishing rule with a probability distribution, a statistic/asymptotic aspect, and the order of key ranks in SCA. Finally, we validate the proposed metrics through experimental attacks on masked AES implementations using DL-SCA.

Abstract Background Acute kidney injury (AKI) remains a frequent complication in children undergoing hematopoietic stem cell transplantation (HSCT) and an independent risk factor of the patient’s survival and a prognostic factor of progression to chronic kidney disease (CKD). However, the causes of these complications are diverse, usually overlapping, and less well understood. Methods This retrospective analysis was performed in 43 patients (28 boys, 15 girls; median age, 5.5 years) undergoing HSCT between April 2006 and March 2019. The main outcome was the development of AKI defined according to the Pediatric Risk, Injury, Failure, Loss, End-stage Renal Disease (pRIFLE) criteria as ≥ 25% decrease in estimated creatinine clearance. The secondary outcome was the development of CKD after a 2-year follow-up. Results AKI developed in 21 patients (49%) within 100 days after HSCT. After adjusting for possible confounders, posttransplant AKI was associated with matched unrelated donor (MUD) (HR, 6.26; P = 0.042), but not total body irradiation (TBI). Of 37 patients who were able to follow-up for 2 years, 7 patients died, but none had reached CKD during the 2 years after transplantation. Conclusions Posttransplant AKI was strongly associated with HSCT from MUD. Although the incidence of AKI was high in our cohort, that of posttransplant CKD was lower than reported previously in adults. TBI dose reduced, GVHD minimized, and infection prevented are required to avoid late renal dysfunction after HSCT in children since their combinations may contribute to the occurrence of AKI.

Abstract Background Ulcerative colitis (UC) developing during chemotherapy is very rare. Here, we describe a case of acute onset during chemoradiotherapy for lung adenocarcinoma, requiring a total proctocolectomy. Case presentation A 52-year-old man was admitted to the hospital for chemoradiotherapy of lung cancer. He had no obvious history of gastrointestinal diseases, and concurrent chemoradiotherapy was initiated. Thirteen days after 2 cycles of cisplatin and vinorelbine, he experienced persistent hematochezia. Findings of the colonoscopy revealed edematous thickening from the rectum to the transverse colon, suggesting UC, drug-induced colitis, or infectious colitis. Results from bacterial culture were negative for Clostridium difficile and methicillin-resistant Staphylococcus aureus (MRSA). Immunohistological staining for cytomegalovirus was also negative. Although he was clinically diagnosed with UC and treated with intravenous glucocorticoid, his symptoms gradually worsened and an abdominal X-ray revealed megacolon. Thirty-five days after conservative therapy, a total proctocolectomy with end permanent ileostomy was performed. Based on pathological findings and clinical course, he was diagnosed with UC. Conclusion Although the pathogenesis of UC during chemotherapy has been unknown, chemotherapy could be one of the causes of UC in this case. UC should be included in the differential diagnosis in patients with progressive colitis during chemotherapy.

Objective: To assess the status of 10 patients with advanced osteonecrosis of the femoral head who underwent mesenchymal stromal cell transplants and a 12-week rehabilitation program 10 years earlier. Design: Retrospective study. Setting: University clinical research laboratory. Participants: Patients (N=10) who had undergone mesenchymal stromal cell transplantation and rehabilitation for a single hip osteonecrosis of the femoral head 10 years prior to the current study were recruited by telephone. The average age was 31.7 years and all participants were men; radiographic stages were 3A in 6 patients and 3B in 4 patients before treatment. Intervention: A 12-week rehabilitation program with follow-up once every 1 to 2 years was performed after mesenchymal stromal cell transplantation. Main Outcome Measures: Radiographic analysis, clinical score, timed Up and Go test, hip function (range of motion, muscle strength), and Short Form-36 scores were assessed before treatment and 1 and 10 years after treatment. Results: Upon imaging, 5 hips were found to be stable (stable group) and 5 had progressed (progressed group); 2 of the latter group required a total hip arthroplasty. The pretreatment radiographic stage of the progressed group was more advanced than that of the stable group. Body mass index was higher in the progressed group than in the stable group. Hip function and clinical score at 1 and 10 years after treatment improved in the hips of 8 patients without total hip arthroplasty. There were no severe adverse events during the rehabilitation. Conclusions: The 12-week rehabilitation program and annual follow-up after mesenchymal stromal cell transplantation for osteonecrosis of the femoral head was associated with pain reduction, maintaining hip muscle strength, widening range of motion, and improving quality of life. The level and timing of weight-bearing and social activity should be planned according to the individual's lifestyle and body composition.

Pecky rice incidence caused by rice stink bugs greatly decreases the quality of rice grain and has come a big problem not only in Japan but also many other rice producing countries recently. In this study, antixenosis and tolerance were examined as the factors of resistance to rice stink bugs attack of rice line CRR-99-95W. Two experiments were conducted to determine a possibility of antixenosis involvement as a factor of the resistance in CRR-99-95W. The results showed no correlation between the number of Leptocorisa chinensis parasites and pecky rice incidence. Furthermore, no significant difference was found between the sucking frequency of Nezara viridula on mature husks of CRR-99-95W and that on the check genotypes. These results suggest that CRR-99-95W does not exhibit antixenosis effect against rice stink bugs. Then, to examine the tolerance factor involved in the resistance mechanism, the husks structures were analyzed. The results showed that the packing ratio of cell wall of the sclerenchyma fibers in the palea tended to be higher in CRR-99-95-W compared to the check genotype. In addition, the width of the hook openness of the palea of CRR-99-95W was narrower than that of the check genotype. Such morphological characteristic of CRR-99-95W may play an important role in its resistance against stink bug attack.

BackgroundIn infants, respiratory syncytial virus (RSV) infection occasionally causes severe symptoms requiring respiratory support; however, supportive care is the primary treatment. This study compared the use of respiratory support among infants with RSV infection treated with or without pranlukast.MethodsThis retrospective cohort study included infants aged ResultsA total of 492 infants, including 147 propensity score-matched pairs, were included in the analysis. The use of respiratory support was significantly lower in infants treated with pranlukast (3.4% [5/147]) than those treated without pranlukast (11.6% [17/147]; P = 0.01). In the propensity score-matched analysis, pranlukast use was associated with a significantly lower chance of needing respiratory support (odds ratio: 0.27, 95% confidence interval: 0.08-0.79; P = 0.01); however, the length of hospital stay (median: 4 days) and the GRSS (median: 2.804 and 2.869 for infants treated with and without pranlukast, respectively) did not differ significantly between propensity score-matched pairs.ConclusionsPranlukast use was associated with a reduced likelihood of requiring respiratory support in infants aged

This paper presents a side-channel analysis (SCA) on key encapsulation mechanism (KEM) based on the Fujisaki–Okamoto (FO) transformation and its variants. The FO transformation has been widely used in actively securing KEMs from passively secure public key encryption (PKE), as it is employed in most of NIST post-quantum cryptography (PQC) candidates for KEM. The proposed attack exploits side-channel leakage during execution of a pseudorandom function (PRF) or pseudorandom number generator (PRG) in the re-encryption of KEM decapsulation as a plaintext-checking oracle that tells whether the PKE decryption result is equivalent to the reference plaintext. The generality and practicality of the plaintext-checking oracle allow the proposed attack to attain a full-key recovery of various KEMs when an active attack on the underlying PKE is known. This paper demonstrates that the proposed attack can be applied to most NIST PQC third-round KEM candidates, namely, Kyber, Saber, FrodoKEM, NTRU, NTRU Prime, HQC, BIKE, and SIKE (for BIKE, the proposed attack achieves a partial key recovery). The applicability to Classic McEliece is unclear because there is no known active attack on this cryptosystem. This paper also presents a side-channel distinguisher design based on deep learning (DL) for mounting the proposed attack on practical implementation without the use of a profiling device. The feasibility of the proposed attack is evaluated through experimental attacks on various PRF implementations (a SHAKE software, an AES software, an AES hardware, a bit-sliced masked AES software, and a masked AES hardware based on threshold implementation). Although it is difficult to implement the oracle using the leakage from the TI-based masked hardware, the success of the proposed attack against these implementations (even except for the masked hardware), which include masked software, confirms its practicality.