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AbstractPhleboliths are calcified thrombi that occur in vascular channels associated with venous malformations. When phleboliths are located in the salivary gland, they are difficult to differentiate from sialolithiasis due to the similarities in their clinical and radiological features. We present the case of a patient who complained of left parotid pain and was found to have multiple calcified bodies, interpreted as sialolithiasis, in the parotid gland on plain computed tomography (CT). T2-weighted magnetic resonance imaging (MRI) showed a hyper-intense signal region in and around the parotid gland, and this finding suggested the possibility of venous malformations. A superficial parotidectomy was performed, and the histological diagnosis was venous malformations containing phleboliths. MRI was useful in differentiating between the aforementioned diseases. We describe the clinical course and review the literature.

Abstract Background Outcome measures during acute cardiovascular disease (CVD) phases, such as quality of death, have not been thoroughly evaluated. This is the first study that compared the family members’ perceptions of quality of death in deceased CVD patients and in deceased cancer patients using a bereaved family survey. Methods Retrospectively sent questionnaire to consecutive family members of deceased patients with CVD from ten tertiary hospitals from October 2017 to August 2018. We used the short version of the Good Death Inventory (GDI) and assessed overall care satisfaction. Referencing the GDI, the quality of death was compared between CVD patients admitted to a non-palliative care unit (non-PCU) and cancer patients in palliative care units (PCU) and non-PCUs in the Japan Hospice and Palliative Care Evaluation Study (J-HOPE Study). Additionally, in the adjusted analysis, multivariable linear regression was performed for total GDI score adjusted by the patient and participant characteristics to estimate the difference between CVD and other patients. Results Of the 243 bereaved family responses in agreement (response rate: 58.7%) for CVD patients, deceased patients comprised 133 (54.7%) men who were 80.2 ± 12.2 years old on admission. The GDI score among CVD patients (75.0 ± 15.7) was lower (worse) than that of cancer patients in the PCUs (80.2 ± 14.3), but higher than in non-PCUs (74.4 ± 15.2). After adjustment, the total GDI score for CVD patients was 7.10 points lower [95% CI: 5.22–8.97] than for cancer patients in PCUs and showed no significant differences compared with those in non-PCUs (estimates, 1.62; 95% CI [-0.46 to 5.22]). Conclusions The quality of death perceived by bereaved family members among deceased acute CVD patients did not differ significantly from that of deceased cancer patients in general wards, however, was significantly lower than that of deceased cancer patients admitted in PCUs.

Abstract Familial platelet disorder with associated myeloid malignancies (FPDMM) is an autosomal dominant disease caused by heterozygous germline mutations in RUNX1. It is characterized by thrombocytopenia, platelet dysfunction, and a predisposition to hematological malignancies. Although FPDMM is a precursor for diseases involving abnormal DNA methylation, the DNA methylation status in FPDMM remains unknown, largely due to a lack of animal models and challenges in obtaining patient-derived samples. Here, using genome editing techniques, we established two lines of human induced pluripotent stem cells (iPSCs) with different FPDMM-mimicking heterozygous RUNX1 mutations. These iPSCs showed defective differentiation of hematopoietic progenitor cells (HPCs) and megakaryocytes (Mks), consistent with FPDMM. The FPDMM-mimicking HPCs showed DNA methylation patterns distinct from those of wild-type HPCs, with hypermethylated regions showing the enrichment of ETS transcription factor (TF) motifs. We found that the expression of FLI1, an ETS family member, was significantly downregulated in FPDMM-mimicking HPCs with a RUNX1 transactivation domain (TAD) mutation. We demonstrated that FLI1 promoted binding-site-directed DNA demethylation, and that overexpression of FLI1 restored their megakaryocytic differentiation efficiency and hypermethylation status. These findings suggest that FLI1 plays a crucial role in regulating DNA methylation and correcting defective megakaryocytic differentiation in FPDMM-mimicking HPCs with a RUNX1 TAD mutation.

Abstract Background Thymic mucosa-associated lymphoid tissue (MALT) lymphoma is rare and is known to be associated with Sjögren’s syndrome (SjS). SjS is rarely accompanied by serositis. Here, we describe the first case of postoperative cardiac tamponade and acute pleuritis in a patient with thymic MALT lymphoma associated with SjS. Case presentation A 33-year-old woman with SjS presented with an anterior mediastinal mass on chest computed tomography, which was performed for further examination of the condition. Suspecting a thymic MALT lymphoma or thymic epithelial tumor, total thymectomy was performed. The mediastinal mass was histopathologically diagnosed as a thymic MALT lymphoma. The patient was discharged with a good postoperative course but visited the hospital 30 days after surgery for dyspnea. Cardiac tamponade was observed and drainage was performed. Four days after pericardial drainage, chest radiography revealed massive left pleural effusion, and thoracic drainage was performed. The patient was diagnosed with serositis associated with SjS and treated with methylprednisolone, which relieved cardiac tamponade and pleuritis. Conclusions Surgical invasion of thymic MALT lymphomas associated with SjS may cause serositis. Postoperative follow-up should be conducted, considering the possibility of cardiac tamponade or acute pleuritis due to serositis as postoperative complications.

A 74-year-old woman, who had been receiving olaparib for the treatment of ovarian cancer for more than a year, visited the emergency department complaining of a fever that had lasted for 1 month. She had been taking antipyretics and antibiotics for her fever, but without any effect. Although she had no symptoms other than fever, she had stopped taking olaparib for 1 week before her visit because she had developed anemia caused by myelosuppression from olaparib. After discontinuing olaparib, her maximum body temperature decreased. On admission, chest X-ray revealed no abnormalities, but chest CT showed diffuse ground-glass opacities. Chest CT taken 5 days later showed partial improvement; therefore, we diagnosed her with interstitial lung disease (ILD) associated with olaparib. After short-term steroid treatment, the ground-glass opacities disappeared, and the patient became afebrile. The CT scan taken for tumor evaluation 2 days before the onset of fever showed a few centrilobular nodular opacities and small patchy ground-glass opacities. These findings could indicate early lesions of ILD, but they seemed inconspicuous and nonspecific, and it might have been difficult to diagnose ILD then. To date, few cases of ILD associated with olaparib have been reported. However, based on previous reports, fever is often seen, and CT findings mainly comprise diffuse ground-glass opacities, and in some cases, centrilobular nodular shadows. Thus, in conjunction with the findings of the present case, these characteristics may be representative of olaparib-induced ILD.

Abstract Metaplastic breast carcinoma (MBC), a category of breast cancer, includes different histological types, which are occasionally mixed and heterogeneous. Considering the heterogeneity of cancer cells in a tumour mass has become highly significant, not only from a biological aspect but also for clinical management of recurrence. This study aimed to analyse the immunohistochemical and molecular profiles of each MBC component of a tumour mass. Twenty-five MBC tumours were histologically evaluated, and the most frequent MBC component (c) was squamous cell carcinoma (SCC), followed by spindle cell carcinoma (SpCC). A total of 69 components of MBC and non-MBC in formalin-fixed paraffin-embedded sections were examined for 7 markers by immunohistochemistry. SCC(c) were significantly PTEN negative and CK14 positive, and SpCC(c) were significantly E-cadherin negative and vimentin positive. Multivariate analyses revealed that immunohistochemical profiles of normal/intraductal (IC)(c), no special type (NST)(c), and MBC(c) differed; moreover, SCC(c) and SpCC(c) were distinctly grouped. PTEN gene mutation was detected only in SCC(c) (2/7), but not in SpCC(c). Next-generation sequence analyses for 2 cases with tumours containing SCC(c) demonstrated that PTEN gene mutation increased progressively from IC(c) to NST(c) to SCC(c). In conclusion, the immunohistochemical and molecular profiles of the SCC(c) of MBC are distinct from those of the SpCC(c).

BackgroundPalilalia is a type of speech characterized by compulsive repetition of words, phrases, or syllables. Several reports have noted that palilalia can occur in response to external verbal stimuli. Here, we report, for the first time, a patient with palilalia induced by gait, which we call “movement-related palilalia.”Case presentationEleven months after the onset of cerebral infarction sparing the right precentral gyrus and its adjacent subcortical regions, a 63-year-old, left-handed Japanese man was referred for psychiatric consultation because of a complaint of irritability caused by the stress of compulsive repetition of a single meaningless word, “wai.” The repetition of a word, palilalia, in this case, was characterized by its predominant occurrence during walking and by its melodic tones. The palilalia during walking disappeared almost completely after 5 months of treatment with carbamazepine 600 mg.ConclusionPalilalia induced by gait can occur in patients with a history of cerebral infarction. This palilalia during walking may be due to the reorganization of networks in areas nearby or surrounding cerebral infarcts.

Summary: Muscle fiber type composition (% slow-twitch and % fast-twitch fibers) is associated with metabolism, with increased slow-twitch fibers alleviating metabolic disorders. Previously, we reported that dietary fish oil intake induced a muscle fiber-type transition in a slower direction in rats. The aim of this study was to determine the functionality of eicosapentaenoic acid (EPA), a unique fatty acid in fish oil, to skeletal muscle fiber type and metabolism in rats. Here, we showed that dietary EPA promotes whole-body oxidative metabolism and improves muscle function by increasing proportion of slow-twitch type 1 fibers in rats. Transcriptomic and metabolomic analyses revealed that EPA supplementation activated the peroxisome proliferator-activated receptor δ (PPARδ) and AMP-activated protein kinase (AMPK) pathways in L6 myotube cultures, which potentially increasing slow-twitch fiber share. This highlights the role of EPA as an exercise-mimetic dietary component that improves metabolism and muscle function, with potential benefits for health and athletic performance.

Developing dedicated hardware for each application in future optical access network systems causes significant initial investment costs. Thus, these costs are alleviated by optical access networks using general-purpose devices related to software-defined networking (SDN) and network function virtualization (NFV). We have studied physical layer virtualization to bring the advantages of SDN and NFV in optical access networks. We have focused on digital coherent technology to enhance capacity and extend reach within optical access networks. However, the future virtualized coherent access faces stringent frequency characteristics and the impact of chromatic dispersion (CD). The number of taps of finite impulse response (FIR) filters in the receiver increases rapidly for the CD compensation. The previously proposed DSP algorithm may not operate in this situation because the processing time exceeds the requirement. Therefore, this paper proposes and implements software for a lightweight multi-input-to-multi-output (MIMO) adaptive equalizer that separates FIR filters depending on the tap update period. The proposed method uses two types of FIR filters; one is used for polarization demultiplexing with short taps, and the other is a filter with long taps for the compensation of the CD in the fiber channel and the frequency distortion from the transceiver. Owing to filter separation, the calculation cost can be reduced. We indicate the processing time meeting desired requirements through real-time transmission experiments, even with increased taps. Additionally, we conduct offline simulations and experiments at a higher symbol rate than the real-time experiment.

Factory networks are typically implemented using dedicated network protocols due to their strict accuracy and latency requirements. However, these protocols tie the factory to specific equipment vendors, making it difficult to introduce other protocols. In response to this challenge, we propose a novel architecture to build a full software-defined factory network by softwarization of industrial Ethernet protocol functions, implementation of a motion control application in a general language, and control of the data plane from the network controller. We demonstrate advanced motion control from a software-defined control system utilizing an industrial Ethernet protocol on a general-purpose server and verify the effectiveness of the proposed architecture. Our proposal makes it possible to control various industrial devices from different vendors without changing applications by mediating the data stored in various protocols through drivers for each protocol. Our experimental findings demonstrate that the PROFINET software-based motion control system can be successfully implemented. The results also show that the proposed architecture can achieve successful motor control within 11.5 s by utilizing the delay compensation method.

With the evolution of access systems by network function virtualization (NFV) and the software-defined network (SDN), further softwarization including transmission functions is required in order to fully utilize the advantages that softwarization offers to network operators in terms of more flexible and rapid service creation and migration. The softwarization of digital signal processing (DSP) is a prime target, but frequency offset compensation (FOC) has serial processing, which makes its softwarization difficult. In particular, the pre-decision-based angle differential estimator (PADE) of wide-range FOC needs long serial iterations since it obtains stable solutions by using small loop gain in the loop filter. This paper proposes a multiplication-based FOC implementation and a novel multi-thread PADE algorithm for real-time softwarization. The multiplication-based implementation enables parallel compensation of phase rotation by multiplying the estimated CFOs by sampling numbers for Viterbi-and-Viterbi (VV) method and PADE. In addition, our multi-thread PADE algorithm significantly reduces the iterations needed for FOC estimation; using multi-threading, it estimates multiple frequency offsets using the loop filters with large loop gain. This calculation needs relatively few iterations, but its outputs are very noisy, and final frequency offset estimates are obtained after removing the noise by clustering and averaging the results. The results of simulations and experiments, which use a general-purpose server with a graphic processing unit, show that our PADE algorithm is 1,308 times faster than the conventional implementation and 5-Gb/s real-time processing is achieved while maintaining the FOC performance.

Abstract Skeletal muscle is one of the largest metabolic tissues in mammals and is composed of four different types of muscle fibers (types 1, 2A, 2X, and 2B); however, type 2B is absent in humans. Given that slow-twitch fibers are superior to fast-twitch fibers in terms of oxidative metabolism and are rich in mitochondria, shift of muscle fiber types in direction towards slower fiber types improves metabolic disorders and endurance capacity. We previously had reported that oleic acid supplementation increases type 1 fiber formation in C2C12 myotubes; however, its function still remains unclear. This study aimed to determine the effect of oleic acid on the muscle fiber types and endurance capacity. An in vivo mouse model was used, and mice were fed a 10% oleic acid diet for 4 weeks. Two different skeletal muscles, slow soleus muscle with the predominance of slow-twitch fibers and fast extensor digitorum longus (EDL) muscle with the predominance of fast-twitch fibers, were used. We found that dietary oleic acid intake improved running endurance and altered fiber type composition of muscles, the proportion of type 1 and 2X fibers increased in the soleus muscle and type 2X increased in the EDL muscle. The fiber type shift in the EDL muscle was accompanied by an increased muscle TAG content. In addition, blood triacylglycerol (TAG) and non-esterified fatty acid levels decreased during exercise. These changes suggested that lipid utilization as an energy substrate was enhanced by oleic acid. Increased proliferator-activated receptor γ coactivator-1β protein levels were observed in the EDL muscle, which potentially enhanced the fiber type transitions towards type 2X and muscle TAG content. In conclusion, dietary oleic acid intake improved running endurance with the changes of muscle fiber type shares in mice. This study elucidated a novel functionality of oleic acid in skeletal muscle fiber types. Further studies are required to elucidate the underlying mechanisms. Our findings have the potential to contribute to the field of health and sports science through nutritional approaches, such as the development of supplements aimed at improving muscle function.

Oxidative stress results from an imbalance between the production and accumulation of reactive oxygen species (ROS), which can impede plant growth under various environmental stresses. While waterlogging is a well-known inducer of oxidative stress, the effects of oxidative stress on plant roots grown using the deep flow technique (DFT) hydroponic system remain poorly understood. In this study, we demonstrate that N-acetylcysteine (NAC) enhances the growth of lettuce seedlings transplanted into a DFT system. NAC application significantly improved both shoot and root growth, with the most pronounced effects observed at a concentration of 0.3 mM. Moreover, NAC mitigated the accumulation of hydrogen peroxide in roots following transplantation. It also reduced a temporary increase in lipid peroxidation and total phenolic content in both roots and shoots. These results suggest that NAC functions as an antioxidant, alleviating oxidative stress by scavenging hydrogen peroxide in the roots. Importantly, NAC’s protective effects may extend to other hydroponically grown crops, offering broader potential for reducing oxidative stress across various cultivation systems.

BackgroundThe Philippines bears health and economic burden caused by high dengue cases annually. Presently, the Philippines still lack an effective and sustainable vector management. The use of Wolbachia, a maternally transmitted bacterium, that mitigate arbovirus transmission has been recommended. Cytoplasmic incompatibility and viral blocking, two characteristics that make Wolbachia suitable for vector control, depend on infection prevalence and density. There are no current Wolbachia release programs in the Philippines, and studies regarding the safety of this intervention. Here, we screened for Wolbachia in Aedes aegypti collected from Metropolitan Manila, Philippines. We designed location-specific primers for qPCR to test whether this improved Wolbachia detection in Ae. aegypti. We explored if host sex and Wolbachia strain could be potential factors affecting Wolbachia density.MethodsAe. aegypti mosquitoes (n=429) were screened for natural Wolbachia by taqman qPCR using location-specific Wolbachia surface protein primers (wspAAML) and known 16S rRNA primers. Samples positive for wspAAML (n=267) were processed for Sanger sequencing. We constructed a phylogenetic tree using IQ-TREE 2 to further characterize Wolbachia present in the Philippine Ae. aegypti. We then compared Wolbachia densities between Wolbachia groups and host sex. Statistical analyses were done using GraphPad Prism 9.0.ResultsWolbachia prevalence for 16S rRNA (40%) and wspAAML (62%) markers were high. Wolbachia relative densities for 16S rRNA ranged from −3.84 to 2.71 and wspAAML from −4.02 to 1.81. Densities were higher in male than female mosquitoes. Wolbachia strains detected in Ae. aegypti clustered into supergroup B. Some 54% (123/226) of these sequences clustered under a group referred to here as “wAegML,” that belongs to the supergroup B, which had a significantly lower density than wAegB/wAlbB, and wAlbA strains.ConclusionLocation-specific primers improved detection of natural Wolbachia in Ae. aegypti and allowed for relative quantification. Wolbachia density is relatively low, and differed between host sexes and Wolbachia strains. An economical way of confirming sporadic or transient Wolbachia in Ae. aegypti is necessary while considering host sex and bacterial strain.

Abstract Samples from the carbonaceous asteroid (162173) Ryugu provide information on the chemical evolution of organic molecules in the early solar system. Here we show the element partitioning of the major component ions by sequential extractions of salts, carbonates, and phyllosilicate-bearing fractions to reveal primordial brine composition of the primitive asteroid. Sodium is the dominant electrolyte of the salt fraction extract. Anions and NH4 + are more abundant in the salt fraction than in the carbonate and phyllosilicate fractions, with molar concentrations in the order SO4 2− > Cl− > S2O3 2− > NO3 − > NH4 +. The salt fraction extracts contain anionic soluble sulfur-bearing species such as S n -polythionic acids (n

Abstract Primary sclerosing cholangitis (PSC) is characterized by progressive biliary inflammation and fibrosis. Although gut commensals are associated with PSC, their causative roles and therapeutic strategies remain elusive. Here we detect abundant Klebsiella pneumoniae (Kp) and Enterococcus gallinarum in fecal samples from 45 PSC patients, regardless of intestinal complications. Carriers of both pathogens exhibit high disease activity and poor clinical outcomes. Colonization of PSC-derived Kp in specific pathogen-free (SPF) hepatobiliary injury-prone mice enhances hepatic Th17 cell responses and exacerbates liver injury through bacterial translocation to mesenteric lymph nodes. We developed a lytic phage cocktail that targets PSC-derived Kp with a sustained suppressive effect in vitro. Oral administration of the phage cocktail lowers Kp levels in Kp-colonized germ-free mice and SPF mice, without off-target dysbiosis. Furthermore, we demonstrate that oral and intravenous phage administration successfully suppresses Kp levels and attenuates liver inflammation and disease severity in hepatobiliary injury-prone SPF mice. These results collectively suggest that using a lytic phage cocktail shows promise for targeting Kp in PSC.

As electrochemical energy storage continues to gain importance, researchers have been exploring novel materials and electrode designs to enhance performance. While these innovations have significantly improved the performance of energy storage devices, the specific mechanisms responsible for their success remain unclear. One powerful tool for gaining insights into how modifications to the electrode can enhance cell performance is cyclic voltammetry (CV). However, interpreting CV data can be challenging, and simple analytical relations are often inadequate for accurate assessment. Moreover, different analytical methods can yield conflicting results, leading to confusion within the research community and hindering progress in the field. To address these challenges, our study aims to investigate the contributions of surface and diffusion-controlled processes to charge storage in supercapacitor applications. We will employ conventional methods to examine how these processes can lead to the misinterpretation of CV data and identify the advantages and limitations of different analytical approaches. Our research underscores the importance of developing models that faithfully replicate the system of interest to gain insights into charge storage mechanisms. By identifying these key factors, our findings could pave the way for the development of more efficient and effective energy storage technologies.

Aedes mosquitoes are well-known vectors of arthropod-borne viruses (arboviruses). Mosquitoes are more frequently infected with insect-specific viruses (ISVs) that cannot infect vertebrates. Some ISVs interfere with arbovirus replication in mosquito vectors, which has gained attention for potential use against arbovirus transmission. Cell-fusing agent virus (CFAV), a widespread ISV, can reduce arbovirus dissemination in Ae. aegypti. However, vectorial capacity is largely governed by other parameters than pathogen load, including mosquito survival and biting behaviour. Understanding how ISVs impact these mosquito fitness-related traits is critical to assess the potential risk of using ISVs as biological agents. Here, we examined the effects of CFAV infection on Ae. aegypti mosquito fitness. We found no significant reduction in mosquito survival, blood-feeding behaviour and reproduction, suggesting that Ae. aegypti is tolerant to CFAV. The only detectable effect was a slight increase in human attraction of CFAV-infected females in one out of eight trials. Viral tolerance is beneficial for introducing CFAV into natural mosquito populations, whereas the potential increase in biting activity must be further investigated. Our results provide the first insight into the link between ISVs and Aedes mosquito fitness and highlight the importance of considering all aspects of vectorial capacity for arbovirus control using ISVs.

Background: The utility of using indirect calorimetry (IC) to estimate energy needs and methods for its application to this purpose remain unclear. This systematic review investigated whether using IC to estimate energy expenditure in critically ill patients is more meaningful for improving survival than other estimation methods. Methods: Comprehensive searches were conducted in MEDLINE using PubMed, Cochrane Central Register of Controlled Trials, and Igaku-Chuo-Zasshi up to March 2023. Results: Nine RCTs involving 1178 patients were included in the meta-analysis. The evidence obtained suggested that energy delivery by IC improved short-term mortality (risk ratio, 0.86; 95% confidence interval [CI], 0.70 to 1.06). However, the use of IC did not appear to affect the length of ICU stay (mean difference [MD], 0.86; 95% CI, −0.98 to 2.70) or the duration of mechanical ventilation (MD, 0.66; 95% CI, −0.39 to 1.72). Post hoc analyses using short-term mortality as the outcome found no significant difference by target calories in resting energy expenditure, whereas more frequent IC estimates were associated with lower short-term mortality and were more effective in mechanically ventilated patients. Conclusions: This updated meta-analysis revealed that the use of IC may improve short-term mortality in patients with critical illness and did not increase adverse events.

Despite evacuation on foot being recommended by authorities, evacuation in practice is assumed to include evacuation on foot and evacuation by car, as a certain amount of evacuation by car is to be expected. We developed a tsunami evacuation training application operating on smartphones and tablets, and a tsunami evacuation training simulator to evaluate the effect of this application. We then conducted an experiment in Nishio City to evaluate the application. We found that the subjects were able to quickly grasp the attention targets that were present near them but had difficulty grasping attention targets that were far away. This suggests that participants need to be trained repeatedly on distant objects of attention to be able to locate them instantaneously.

Remarkable advancements have been made in the treatment outcomes of multiple myeloma (MM) patients; however, for frail elderly patients, these treatment outcomes are still insufficient. Elderly MM patients are increasing, as are their treatment regimens. There is a heightened demand to assess these patients in order to provide optimized treatments. While continuous treatment is more common for MM patients when compared to fixed-duration treatment, due to the risk of treatment interruption causing reduced survival rates, effectiveness and safety are essential. Treatment goals vary for each patient, but must preserve their quality of life (QOL). When planning treatments for these patients, frailty evaluation is increasingly emphasized as a stratification factor which helps develop accurate screening tools. Daratumumab (DARA) therapy, used globally, is not only effective in frail elderly MM patients, but also has QOL benefits. Proficiency in utilizing DARA regimens is potentially advantageous for patients not included in clinical trials, and innovative usage can further broaden its scope. The development of tools to accurately assess frailty and the establishment of optimal treatments for frail elderly MM patients are imperative. This review is an overview, challenging the frailty assessments for MM patients, re-examining the evidence for DARA regimens in frail elderly MM patients, and discussing potential areas for improvement.

Abstract Hepatocytes are a major parenchymal cell type in the liver and play an essential role in liver function. Hepatocyte-like cells can be differentiated in vitro from induced pluripotent stem cells (iPSCs) via definitive endoderm (DE)-like cells and hepatoblast-like cells. Here, we explored the in vitro differentiation time-course of hepatocyte-like cells. We performed methylome and transcriptome analyses for hepatocyte-like cell differentiation. We also analyzed DE-like cell differentiation by methylome, transcriptome, chromatin accessibility, and GATA6 binding profiles, using finer time-course samples. In this manuscript, we provide a detailed description of the dataset and the technical validations. Our data may be valuable for the analysis of the molecular mechanisms underlying hepatocyte and DE differentiations.

Abstract Background Anticoagulation using heparin is generally used to prevent thrombus formation during mechanical circulatory support, such as veno-arterial extracorporeal membrane oxygenation (VA-ECMO). However, during the early period following cardiac surgery, anticoagulation becomes more difficult due to the greater risk of critical bleeding complications. Case presentation A 71-year-old man presented with acute prosthetic valve occlusion caused by left atrial thrombus formation and bioprosthetic valve thrombosis during peripheral VA-ECMO following mitral valve replacement (MVR) despite continuous heparin administration and loading of antiplatelet agents. The VA-ECMO flow rate decreased 10 h after the intensive care unit (ICU) admission after MVR. Exploratory transesophageal echocardiography (TEE) examination revealed a left atrial thrombus, prosthetic valve obstruction by the thrombus, and an intrapericardial hematoma. Conclusions Intracardiac thrombus formation might occur during VA-ECMO despite appropriate anticoagulation and loading of antiplatelet agents. Exploratory TEE examination was helpful in the detection of intra-atrial thrombus formation after cardiac surgery and surgical decision-making.

Smooth muscle cells are widely distributed in the digestive organs of chickens. They exist as single cells, but adhere to each other to function synchronously. In this study, the expression of the gap junction protein connexin 43 (Cx43) in chicken gizzards was investigated at embryonic days (E) 10, E15, and E18. Gizzards have an abundance of smooth muscle cells because of their thick muscle layers, which enable easy analysis of the cells. Morphological observations and expression patterns of smooth muscle markers were confirmed. Next, we observed where the markers were localized in the gizzard tissue at E10, E15, and E18. Finally, the expression pattern of Cx43 in primary cultured smooth muscle cells from E15 gizzards was investigated. The analysis revealed the expression and localization of Cx43 and calponin 1 in the smooth muscle layers, and 3D analysis revealed dynamic changes in the localization pattern of Cx43 from E10 to E15. Cultured smooth muscle cells confirmed that Cx43 was expressed in the cell membrane and cytosol. In conclusion, Cx43 expression was identified in chicken gizzards at E10, E15, and E18, which was localized differently during development. The expression was broad at E10, and became restricted at E15 and E18. Primary culture of smooth muscle cells showed that Cx43 was present in the cell membrane and cytosol. This suggests that Cx43 is actively translated into the cytosol at E10, forming a hexamer, and shuttling the cell membrane to function as a gap junction.

Abstract Background Toxic shock syndrome (TSS) caused by Staphylococcus aureus in the postpartum period is a rare but life-threatening disease. We present a case of acute heart failure as the initial presentation of TSS due to methicillin-susceptible Staphylococcus aureus (MSSA) and describe its clinical characteristics with a systematic literature review. Case presentation A 34-year-old woman, 8 days after a normal vaginal delivery presented to our hospital with dyspnea and fever. She had jugular venous distension, bilateral leg edema, and erythema. Laboratory examinations revealed elevated NT-pro-BNP level of 3,233 pg/mL. Transthoracic echocardiography showed elevated tricuspid regurgitation peak gradient, with decreased respiratory variability of the inferior vena cava diameter and bilateral pleural effusions. The patient was hospitalized with suspicion of congestive heart failure. MSSA positive for toxic shock syndrome exotoxin-1 was detected in the culture of the perineal incision wound, and we diagnosed TSS caused by MSSA. Intravenous diuretics were administered, along with eventual cefazolin plus clindamycin. After 2 weeks of antimicrobial therapy, the patient showed improvement and was discharged. No recurrence was observed at the 24-month follow-up. Conclusion This is a rare case report of acute heart failure being the initial manifestation of TSS due to MSSA in the postpartum period. Clinicians should consider TSS as a possibility in postpartum patients with acute heart failure. This systematic review provides insights into its clinical features, treatment regimens, and prognosis of TSS by S. aureus in the postpartum period. TSS requires an appropriate, prompt diagnosis, because delayed treatment can be fatal.

The commonest sites for liposarcoma are the retroperitoneum and lower extremities. Liposarcoma of the head and neck region is a rare and potentially life-threatening malignancy. Tumors originating in the right cervical space cause special diagnostic and therapeutic difficulties. In the present report, we describe a case of differentiated liposarcoma of the right cervical region. The tumor continued to grow slowly over 3 years before a definitive diagnosis was established. Extended extirpation of the tumor was performed and proved efficacious in that no recurrence has been observed for 4 years. Recommendations for earlier and accurate diagnosis and treatment of this rare neoplasm are discussed.

Chloropupukeananin is a natural product that inhibits HIV-1 replication and has antitumor activity. Its structure consists of a chlorinated tricyclo[4.3.1.03,7]decane core skeleton with an array of highly oxidized multifunctional groups. In the biosynthesis of chloropupukeananin, (+)-iso-A82775C and (−)-maldoxin are employed as biosynthetic precursors for the intermolecular Diels–Alder and carbonyl–ene reactions, followed by the migration of the p-orcellinate group. Chloropupukeanolides and chloropestolides are intermediates and isomers in biosynthesis; their unique chemical structures and biosynthetic pathways have attracted significant attention from synthetic chemists. In this review, I present the synthetic studies on chloropupukeananin and its related compounds that have been conducted thus far.

Splenosis should be suspected when a patient has a history of trauma or abdominal surgery. Intrahepatic splenosis is a rare disease that is often difficult to distinguish from liver malignancy, especially hepatocellular carcinoma. The cause of intrahepatic splenosis may be though the auto-transplantation of splenic tissue on the surface of the liver. The authors report a case of intrahepatic splenosis that presented as a liver tumour in an 81-year-old female treated for autoimmune hepatitis, who had no history of splenectomy or abdominal trauma. Laparoscopic hepatectomy was performed and the specimen demonstrated characteristic histopathological findings of the spleen. Only one case of a patient who had no history of splenectomy or abdominal trauma has been reported in the literature. It may be hypothesised that erythropoiesis induced by local hypoxia in the chronic hepatitis may cause the growth of splenic erythrocytic progenitor cells, which have migrated via portal vein to the liver.

Background & Aims: B-cell depletion therapy with an anti-CD20 is an effective treatment strategy for patients with refractory autoimmune hepatitis (AIH). However, the mechanisms underlying B-cell action are unclear. Methods: Herein, we used the adeno-associated virus IL-12 model, in which hepatic IL-12 expression triggers liver injuries characteristic of AIH. We also analysed the clinical samples of patients with AIH. Results: B-cell depletion using anti-CD20 or splenectomy was found to improve liver functions and decrease the cytotoxic CD8+ T-cell (cytotoxic T lymphocyte [CTL]) count in the liver. This improvement was reversed by the adoptive transfer of splenic B cells derived from AAV IL-12-treated mice to splenectomised mice as it caused the hepatic CTL count to increase. RNA-sequencing analysis identified IL-15 as a key factor in pathogenic B cells, which promotes CTL expansion and subsequent migration to the liver via the CXCL9/CXCR3 axis. Indeed, IL-15 neutralisation ameliorated hepatitis by suppressing splenic and hepatic CTLs in vivo. The close distribution of B220+ B cells and CD8+ T cells in the spleen of AIH mice suggested mutual interactions. Mechanistically, IFNγ and CD40L/CD40 signalling were indispensable for the expression of IL-15 in B cells, and in vitro co-culture experiments revealed that splenic CD40L+CD8+ T cells promoted IL-15 production in B cells, which led to CTL expansion. In patients with AIH, high serum IL-15 concentration and IL-15+ B-cell counts, positively correlating with serum alanine aminotransferase levels, support translation and potential therapeutic targeting in human AIH. Conclusions: This investigation elucidated the roles of IL-15-producing splenic B cells that occur in concert with pathogenic CD8+ T cells during the development of AIH. Impact and Implications: IL-15-producing B cells were shown to exacerbate experimental AIH via cytotoxic T lymphocyte expansion. CD40L+CD8+ T cells promoted IL-15 expression in B cells, indicating the mutual interaction of both cells. High serum IL-15 concentrations, IL-15+ B-cell counts, and CD40L+IL-15Rα+CD8+ T-cell counts were confirmed in the blood of patients with AIH.

Background: Unilateral diaphragmatic paralysis is a condition in which the unilateral diaphragm is paralyzed and elevated. Orthopnea due to lung compression by an elevated diaphragm in the supine position is common in patients with unilateral diaphragmatic paralysis. Although its symptom is posture-dependent, the effect of posture on lung function in unilateral diaphragmatic paralysis has not been studied. Computed tomography (CT) can be used to assess lung volume. However, conventional CT cannot be performed in the upright position. A pulmonary function test can be performed in both upright and supine positions. However, it cannot evaluate the function of each lung separately. Case presentation: We report a case of a 79-year-old man with unilateral diaphragmatic paralysis. He presented with difficulty in inspiration, specifically in the supine position, and underwent both conventional supine CT and newly developed upright CT to assess the effect of posture on the function of each lung. The difference between expiratory and inspiratory lung volumes on CT in the supine position was less than that in the upright position by 46% and 4% on affected and healthy sides, respectively. We previously reported that the difference between expiratory and inspiratory lung volumes on CT correlated with inspiratory capacity on the pulmonary function test. A 46% decline in inspiratory capacity on the affected side in the supine position likely caused orthopnea in this patient. Conclusions: Supine/upright CT is helpful to assess the influence of posture on unilateral lung function in patients with unilateral diaphragmatic paralysis.

Summary: The fate of resolution of liver fibrosis after withdrawal of liver injury is still incompletely elucidated. Toll-like receptor 4 (TLR4) in tissue fibroblasts is pro-fibrogenic. After withdrawal of liver injury, we unexpectedly observed a significant delay of fibrosis resolution as TLR4 signaling was pharmacologically inhibited in vivo in two murine models. Single-cell transcriptome analysis of hepatic CD11b+ cells, main producers of matrix metalloproteinases (MMPs), revealed a prominent cluster of restorative Tlr4-expressing Ly6c2-low myeloid cells. Delayed resolution after gut sterilization suggested its microbiome-dependent nature. Enrichment of a metabolic pathway linking to a significant increase of bile salt hydrolase-possessing family Erysipelotrichaceae during resolution. Farnesoid X receptor-stimulating secondary bile acids including 7-oxo-lithocholic acids upregulated MMP12 and TLR4 in myeloid cells in vitro. Fecal material transplant in germ-free mice confirmed phenotypical correlations in vivo. These findings highlight a pro-fibrolytic role of myeloid TLR4 signaling after injury withdrawal and may provide targets for anti-fibrotic therapy.

An integrated analysis of human induced pluripotent stem cells differentiating into hepatocyte-like cells unveils changes in DNA methylation and relevant transcription factors (like GATA6) that may influence hepatic development.

Abstract Background The AF-201P, a new electromyography (EMG)-based neuromuscular monitor has been developed recently. The aim of this clinical study was to compare two ulnar nerve innervated muscles: the adductor pollicis (AP) muscle and the abductor digiti minimi (ADM) muscle during the recovery from rocuronium-induced neuromuscular block by using EMG AF-201P. Methods Twenty patients undergoing surgery with general anesthesia were enrolled in the study. During total intravenous general anesthesia, train-of-four (TOF) and post-tetanic counts (PTC) responses following 0.9 mg/kg rocuronium administration were concurrently monitored at the AP and the ADM muscles with EMG AF-201P on the opposite arms. At the end of the surgery, sugammadex 2 mg/kg was administered when TOF counts of 2 (TOFC2) was observed at both muscles. The primary outcome of the study was time from administration of rocuronium to first appearance of PTC response (first PTC). The secondary outcomes of the study were time from administration of rocuronium to TOF count of 1 (TOFC1), time from first PTC to TOFC1 (PTC-TOF time), time to TOFC2, and time from administration of sugammadex to TOF ratio ≥ 0.9. Agreement between the two muscles was assessed using the Bland–Altman analysis. Data are expressed as mean ± standard deviation. Results Nineteen patients were included in the analysis. Time to first PTC was significantly faster at the ADM muscle than the AP muscle (24.4 ± 11.4 min vs 32.4 ± 13.1 min, p = 0.006). PTC-TOF time was significantly longer with the ADM muscle than the AP muscle (19.4 ± 7.3 min vs 12.4 ± 10.6 min, p = 0.019). There were no significant differences in time to TOFC2 and sugammadex-facilitated recovery between the two muscles. Bland–Altman analyses showed acceptable ranges of bias and limits of agreement of the two muscles. Conclusions The ADM muscle showed a good agreement with the AP muscle during rocuronium-induced neuromuscular block but faster recovery of PTC response when using EMG. Trial registration UMIN-CTR (Registration No. UMIN000044904 ). Registered 19 July 2021 -Retrospectively registered, https://center6.umin.ac.jp/cgi-bin/ctr_e/ctr_view.cgi?recptno=R000051290 .

Abstract Electrochemical conversion and storage of unutilized renewable energy will contribute to decarbonization. Here, we create the concept of a liquid electrochemical cell that discharges between the anodic and cathodic sides by reverse reactions of the same redox couple in different solvation states, which are created by differences in the mixture ratios of two solvents called the main solvent (MS) and the transferred solvent (TS). The cell can be charged by a transfer of the TS between the discharged anolyte and catholyte. As an example, we demonstrate a cell utilizing a ferro-/ferricyanide redox couple. Stable discharging and charging via the proposed method is achieved by utilizing water (MS) and acetone (TS). Additionally, dominating factors in the design of a high-performance system are discussed, focusing on the electron acceptability of the MS and the TS. The cell voltages are successfully tuned, and a cell voltage of 0.63 V is achieved by the combination of dimethyl sulfoxide (MS) and water (TS). Moreover, the cell can be customized by various electrochemical reaction systems, which can allow multiple options for the charging processes. This concept provides new approaches for the utilization of diverse energy sources as an input for the charging of electrochemical cells.

Objectives: Plunging ranula intruding into the cervical region is rare and a standard therapy has not yet been consolidated. This paper investigates the outcomes and side effects of OK-432 treatment in patients with a ranula extending into the cervical region. Methods: The study design and setting consisted of a planned data collection at Tohoku Medical and Pharmaceutical University and Fukase Clinic. Eight patients with ranula extending into the cervical region received OK-432 treatment between January 2016 and February 2019. OK-432 treatment was performed for patients with ranula extending into the cervical region. Results: In all patients, a total shrinkage and marked reduction in lesions were observed without local scars or deformations after OK-432 treatment. Complications were local swelling and mild fever (37.5–38.5 °C), which lasted a few days in half of the patients. Conclusions: OK-432 treatment is straightforward, secure, and efficacious and can be substituted for surgery in the treatment of ranula extending into the cervical region.

It is necessary to discuss from various angles how to make the younger generation, who will be responsible for future society, aware of disasters and how to cope with them. Therefore, we designed a project-based learning class, “Media Design Project III · IV”, in which students are asked to create a game to raise their awareness of disaster prevention. This class aims to improve disaster awareness, especially tsunami evacuation, and to improve abilities that students will need in the future, i.e., time management and problem-solving, especially after they begin work. It was found that the game can increase tsunami evaluation awareness. Therefore, the projects presented here might become a new method for education, especially disaster education and career education, with games focused on disasters potentially being a new tool for raising awareness about disasters.

In the remote motion control of IoT devices, the delay adversely affects control performance. In our access edge concept, in which motion control is performed from a central office, the delay becomes large due to Dynamic Bandwidth Allocation (DBA) when the Passive Optical Network (PON) is adopted as the access system. No existing motion control method considers the delay changes of the DBA algorithm. We rectify this omission by proposing a novel real-time and high-precision motion control method that links the PON device and the controller. The proposed method can improve the control performance while maintaining the bandwidth utilization efficiency without changing the DBA delay specified to meet the requirements. In the proposed method, the delay in the PON system is calculated by using a delay model based on the setting parameter received from the communication device, and is used for delay compensation control. An experiment shows that, unlike the conventional method which becomes unstable and fails to realize control, the proposed method achieves high resolution control within 4 s, which demonstrates the feasibility of motion control for factory automation using edge computing in PON systems.

Abstract Background Single‐cell transcriptomics allows parallel analysis of multiple cell types in tissues. Because testes comprise somatic cells and germ cells at various stages of spermatogenesis, single‐cell RNA sequencing is a powerful tool for investigating the complex process of spermatogenesis. However, single‐cell RNA sequencing analysis needs extensive knowledge of experimental technologies and bioinformatics, making it difficult for many, particularly experimental biologists and clinicians, to use it. Methods Aiming to make single‐cell RNA sequencing analysis familiar, this review article presents an overview of experimental and computational methods for single‐cell RNA sequencing analysis with a history of transcriptomics. In addition, combining the PubMed search and manual curation, this review also provides a summary of recent novel insights into human and mouse spermatogenesis obtained using single‐cell RNA sequencing analyses. Main Findings Single‐cell RNA sequencing identified mesenchymal cells and type II innate lymphoid cells as novel testicular cell types in the adult mouse testes, as well as detailed subtypes of germ cells. This review outlines recent discoveries into germ cell development and subtypes, somatic cell development, and cell–cell interactions. Conclusion The findings on spermatogenesis obtained using single‐cell RNA sequencing may contribute to a deeper understanding of spermatogenesis and provide new directions for male fertility therapy.

Eosinophilic bronchiolitis is a disease concept reported in Japan in 2001, that presents with bronchiolitis accompanied by eosinophilia in the blood and lungs. In 2013, hypereosinophilic obliterative bronchiolitis, as a group of disease presenting with eosinophilic bronchiolitis, was proposed in France. The relationship between eosinophilic bronchiolitis and other eosinophil-related diseases has not been clarified. Herein, we report the case of a 56-year-old female patient with eosinophilic bronchiolitis without asthma, which developed into eosinophilic pneumonia. Treatment with oral prednisone improved the respiratory function. According to the clinicopathological findings in this case, eosinophilic bronchiolitis may be a different disease from asthma.

Abstract Background and Aim International consensus on the definition and classification of post‐endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) has been reached. However, the diagnosis and severity of PEP are often assessed according to the diagnostic criteria and classification for acute pancreatitis (AP). This study determined the incidence, severity, and risk factors of PEP diagnosed according to the diagnostic criteria and classification for AP in a large cohort. Methods This prospective, multicenter, observational cohort study conducted at five high‐volume centers included 1932 patients who underwent ERCP‐related procedures. The incidence, severity, and risk factors for PEP were evaluated. Results PEP occurred in 142 patients (7.3%); it was mild in 117 patients (6.0%) and severe in 25 patients (1.3%). According to the Cotton criteria, PEP occurred in 87 patients (4.5%); it was mild in 54 patients (2.8%), moderate in 20 patients (1.0%), and severe in 13 patients (0.7%). In the multivariate analysis, female sex (odds ratio [OR] 2.239; 95% confidence interval [CI] 1.546–3.243), naïve papilla (OR 3.047; 95% CI 1.803–5.150), surgically‐altered gastrointestinal anatomy (OR 2.538; 95% CI 1.342–4.802), procedure time after reaching the papilla (OR 1.009; 95% CI 1.001–1.017), pancreatic duct injection (OR 2.396; 95% CI 1.565–3.669), and intraductal ultrasonography (OR 1.641; 95% CI 1.024–2.629) were independent risk factors. Conclusion According to the diagnostic criteria and classification for AP, the incidence of PEP was higher than that according to the Cotton criteria and the severity of PEP tended to be severe.

How liver tolerance is disrupted in immune‐mediated liver injury is currently unclear. There is also insufficient information available regarding susceptibility, precipitation, escalation, and perpetuation of autoimmune hepatitis. To explore how dietary fiber influences hepatic damage, we applied the concanavalin A (ConA)‐induced acute immune‐mediated liver injury model in mice fed a diet supplemented with 6.8% inulin, a water‐soluble fermentable fiber. Twelve hours after ConA administration, inulin‐supplemented diet‐fed mice demonstrated significantly alleviated hepatic damage histologically and serologically, with down‐regulation of hepatic interferon‐γ and tumor necrosis factor and reduced myeloperoxidase (MPO)‐producing neutrophil infiltration. Preconditioning with an inulin‐supplemented diet for 2 weeks significantly reduced hepatic adenosine triphosphate (ATP) content; suramin, a purinergic P2 receptor antagonist, abolished the protective effect. Of note, the portal plasma derived from mice fed the inulin‐supplemented diet significantly alleviated ConA‐induced immune‐mediated liver injury. Mechanistically, increased portal short‐chain fatty acid (SCFA) levels, such as those of acetate and butyrate, by inulin supplementation leads to up‐regulation of hepatic γ‐type peroxisome proliferator‐activated receptor (Pparg) and uncoupling protein 2 (Ucp2), which uncouples mitochondrial ATP synthesis downstream of PPARγ. Pparg down‐regulating small interfering RNA cancelled the protective effect of inulin supplementation against MPO‐producing neutrophil infiltration and the subsequent immune‐mediated liver injury, suggesting that the SCFA–PPARγ–UCP2 axis plays a key role in the protective effect by inulin supplementation. Moreover, significant changes in the gut microbiota, including increased operational taxonomic units in genera Akkermansia and Allobaculum, also characterized the protective effect of the inulin‐supplemented diet. Conclusion: There is a possible unraveled etiopathophysiological link between the maintenance of liver tolerance and dietary fiber. The SCFA–PPARγ–UCP2 axis may provide therapeutic targets for immune‐mediated liver injury in the future.

Abstract Background Entamoeba histolytica (E. histolytica) is rarely identified as a cause of amebic pericarditis. We report a case of amebic pericarditis complicated by cardiac tamponade, in which the diagnosis was missed initially and was made retrospectively by polymerase chain reaction (PCR) testing of a stored sample of pericardial fluid. Furthermore, we performed a systematic review of the literature on amebic pericarditis. Case presentation A 71-year-old Japanese man who had a history of sexual intercourse with several commercial sex workers 4 months previously, presented to our hospital with left chest pain and cough. He was admitted on suspicion of pericarditis. On hospital day 7, he developed cardiac tamponade requiring urgent pericardiocentesis. The patient’s symptoms temporarily improved, but 1 month later, he returned with fever and abdominal pain, and multiple liver lesions were found in the right lobe. Polymerase chain reaction of the aspiration fluid of the liver lesion and pericardial and pleural fluid stored from the previous hospitalization were all positive for E. histolytica. Together with the positive serum antibody for E. histolytica, a diagnosis of amebic pericarditis was made. Notably, the diagnosis was missed initially and was made retrospectively by performing PCR testing. The patient improved with metronidazole 750 mg thrice daily for 14 days, followed by paromomycin 500 mg thrice daily for 10 days. Conclusions This case suggests that, although only 122 cases of amebic pericarditis have been reported, clinicians should be aware of E. histolytica as a potential causative pathogen. The polymerase chain reaction method was used to detect E. histolytica in the pericardial effusion and was found to be useful for the diagnosis of amebic pericarditis in addition to the positive results for the serum antibody testing for E. histolytica. Because of the high mortality associated with delayed treatment, prompt diagnosis should be made.

Illisimonin A is a new sesquiterpene isolated from Illicium simonsii, and it possesses a novel 5/5/5/5/5 pentacyclic skeleton. The tricyclic skeleton of illisimonin A, tricyclo[5.2.1.01,5]decane, is presumed to be biosynthesized from allo-cedranes via a skeletal rearrangement. Herein, we report the concise synthesis of highly oxidized allo-cedranes by an intramolecular Diels–Alder reaction using ortho-benzoquinones and demonstrate the biomimetic transformation of allo-cedranes by a retro-Claisen/aldol pathway.

Protein tyrosine residue (Y) nitration, a post-translational chemical-modification mode, has been associated with changes in protein activity and function; hence the accumulation of specific nitrated proteins in tissues may be used to monitor the onset and progression of pathological disorders. To verify the possible impact of nitration on postnatal muscle growth and regeneration, a pilot study was designed to examine the nitration/dysfunction of hepatocyte growth factor (HGF), a key ligand that is released from the extracellular tethering and activates myogenic stem satellite cells to enter the cell cycle upon muscle stretch and injury. Exposure of recombinant HGF (a hetero-dimer of α- and β-chains) to peroxynitrite induces Y nitration in HGF α-chain under physiological conditions. Physiological significance of this finding was emphasized by Western blotting that showed the NK1 segment of HGF (including a K1 domain critical for signaling-receptor c-met binding) undergoes nitration with a primary target of Y198. Peroxynitrite treatment abolished HGF-agonistic activity of the NK1 segment, as revealed by in vitro c-met binding and bromodeoxyuridine-incorporation assays. Importantly, direct-immunofluorescence microscopy of rat lower hind-limb muscles from two aged-groups (2-month-old “young” and 12-month-old “retired/adult”) provided in vivo evidence for age-related nitration of extracellular HGF (Y198). Overall, findings provide the insight that HGF/NK1 nitration/dysfunction perturbs myogenic stem cell dynamics and homeostasis; hence NK1 nitration may stimulate progression of muscular disorders and diseases including sarcopenia.

The cellular and molecular mechanisms underlying the resolution of non-alcoholic steatohepatitis remain incompletely understood. Here the authors report a single cell-based analysis that identified CD8 + tissue-resident memory T cells, which contribute to resolution of liver fibrosis potentially via elimination of hepatic stellate cells through Fas-mediated cytotoxicity.

Abstract Increased intestinal permeability and hepatic macrophage activation by endotoxins are involved in alcohol-induced liver injury pathogenesis. Long-term alcohol exposure conversely induces endotoxin immune tolerance; however, the precise mechanism and reversibility are unclear. Seventy-two alcohol-dependent patients with alcohol dehydrogenase-1B (ADH1B, rs1229984) and aldehyde dehydrogenase-2 (ALDH2, rs671) gene polymorphisms admitted for alcohol abstinence were enrolled. Blood and fecal samples were collected on admission and 4 weeks after alcohol cessation and were sequentially analyzed. Wild-type and ALDH2*2 transgenic mice were used to examine the effect of acetaldehyde exposure on liver immune responses. The productivity of inflammatory cytokines of peripheral CD14+ monocytes in response to LPS stimulation was significantly suppressed in alcohol dependent patients on admission relative to that in healthy controls, which was partially restored by alcohol abstinence with little impact on the gut microbiota composition. Notably, immune suppression was associated with ALDH2/ADH1B gene polymorphisms, and patients with a combination of ALDH2*1/*2 and ADH1B*2 genotypes, the most acetaldehyde-exposed group, demonstrated a deeply suppressed phenotype, suggesting a direct role of acetaldehyde. In vitro LPS and malondialdehyde-acetaldehyde adducted protein stimulation induced direct cytotoxicity on monocytes derived from healthy controls, and a second LPS stimulation suppressed the inflammatory cytokines production. Consistently, hepatic macrophages of ethanol-administered ALDH2*2 transgenic mice exhibited suppressed inflammatory cytokines production in response to LPS compared to that in wild-type mice, reinforcing the contribution of acetaldehyde to liver macrophage function. These results collectively provide new perspectives on the systemic influence of excessive alcohol consumption based on alcohol-metabolizing enzyme genetic polymorphisms.

There is an increasing demand for motion control of Internet of Things devices such as drones and industrial machines from large computational resources on the network side. Since the delay between communication devices adversely affects the control performance, utilization of low-latency platforms such as edge computing is promising. However, no other study focuses on architecture and control methods in optical access network for motion control. We aim at realizing the access edge that performs real-time motion control on an edge server located in a central office. This paper proposes an access edge configuration and a control method that offers time-varying delay compensation based on delay information. We evaluate control performance of our method when delay is increased and packet loss occurs under a high network load environment. We demonstrate that when the downstream traffic changes from 9 to 10 Gbps, the proposed method offers motor control settling times of 2.7 s and 8.0 s, respectively, while the conventional method cannot control the motor in either case.

Abstract Background Schlafen 11 (SLFN11) was recently identified as a dominant determinant of sensitivity to DNA-targeting agents including platinum-based drugs. SLFN11 also reportedly enhances cellular radiosensitivity. In this study, we examined the prognostic value of SLFN11 expression in esophageal squamous cell carcinoma (ESCC) patients treated with definitive chemoradiotherapy (dCRT), including the platinum derivative nedaplatin. Methods Seventy-three patients with ESCC who received dCRT were examined. SLFN11 expression was analyzed in pre-dCRT biopsies using immunohistochemistry and evaluated using a histo-score (H-score). Correlation between the H-score and overall survival was analyzed. An H-score ≥ 51 was provisionally defined as indicating high SLFN11 expression. Viability assays were performed using previously established isogenic human cell lines differentially expressing SLFN11 to test the usefulness of SLFN11 as marker of response to the dCRT regimen. Results High SLFN11 expression was independently associated with better prognosis in ESCC patients (hazard ratio = 0.295, 95% CI = 0.143–0.605, p = 0.001 for multivariate analysis). Kaplan-Meier survival curves showed that the prognostic value of high SLFN11 expression was most evident in patients at clinical stages II and III (p = 0.004). In in vitro study, SLFN11-proficient cells were highly sensitive to platinum derivatives compared to SLFN11-deficient cells. Conclusion SLFN11 expression is an independent prognostic factor for ESCC patients treated with dCRT and a potential biomarker for treatment selection of ESCC. Examination of SLFN11 may be particularly useful for clinical Stage II–III patients who wish to choose dCRT (instead of surgery) to preserve esophageal function.