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Abstract Because of shifting social circumstances, a growing number of businesses are implementing work at home options. Working at home enhances work-life balance but blurs the line between work and personal life, making it challenging for workers to psychologically detach from work outside of their designated hours. This blurring of boundaries between work and personal life is thought to potentially increase work engagement. Moreover, achieving psychological detachment from work and disengaging from work-related thoughts outside of working hours are thought to demand high levels of thought control ability. This study hypothesized that (1) compared to office workers, those who work at home struggle more to detach from work and exhibit higher levels of work engagement, (2) higher levels of thought control ability reduce work-related thoughts. This study employed a combination of a cross-sectional survey design and an experimental approach using a cognitive task to examine the research questions. Focusing on Japanese workers, the results confirmed that home workers face challenges in detaching from work and show higher work engagement, identifying work from home as a potential stressor and a factor that may increase work involvement. On the other hand, the study found no link between elevated thought control ability and reduced work-related thoughts during cognitive tasks.

In the veterinary field, the utility of disease-identification models that use comprehensive circulating microRNA (miRNA) profiles produced through measurements based on next-generation sequencing (NGS) remains unproven. To integrate NGS technology with automated machine learning (autoML) to create a comprehensive circulating miRNA profile and to assess the clinical utility of a disease-screening model derived from this profile. The study involved dogs diagnosed with or being treated for various diseases, including tumors, across multiple veterinary clinics (n = 254), and healthy dogs without apparent diseases (n = 91). miRNA was extracted from EDTA-treated plasma, and a comprehensive analysis was conducted of one million reads per sample using NGS. Then autoML technology was applied to develop a diagnostic model based on miRNA. Among these models, the one with the highest performance was chosen for evaluation. The diagnostic model, based on the comprehensive circulating miRNA profile developed in this study, achieved an AUC score of 0.89, with a sensitivity of 85 % and a specificity of 88 % for the disease samples. The miRNA-based diagnostic model demonstrated high sensitivity for disease groups and has the potential to be an effective screening test. This study indicates that a comprehensive miRNA profile in dog plasma could serve as a highly sensitive blood biomarker.

Abstract Background Satisfactory treatment for patients with unresectable advanced lung cancer has not yet been established. We report a case of unresectable advanced lung cancer (stage IIIb: T2aN3M0) treated with a total of 15 doses of dendritic cells pulsed with a Wilms’ tumor 1 and mucin 1 vaccine in combination with erlotinib, a small molecule epidermal growth factor receptor tyrosine kinase inhibitor, for more than 699 days without recurrence or metastasis. Case presentation A 63-year-old Korean woman was diagnosed with lung adenocarcinoma by pathology and computed tomography. The adenocarcinoma showed an epidermal growth factor receptor (EGFR) mutation, no anaplastic lymphoma kinase expression, and less than 1% expression of programmed death ligand 1. She received erlotinib alone for approximately 1 month. She then received erlotinib and the dendritic cells pulsed with Wilms’ tumor 1 and mucin 1 vaccine. The diameter of the erythema at the vaccinated sites was 30 mm at 48 hours after the first vaccination. Moreover, it was maintained at more than 20 mm during the periods of vaccination. These results suggested the induction of antitumor immunity by the vaccine. Remarkably, the tumor size decreased significantly to 12 mm, a 65.7% reduction, after combined therapy with eight doses of the dendritic cells pulsed with Wilms’ tumor 1 and mucin 1 vaccine and erlotinib for 237 days based on fluorodeoxyglucose uptake by positron emission tomography/computed tomography and computed tomography. Interestingly, after 321 days of combination therapy, the clinical findings improved, and no tumor was detected based on computed tomography. Validation of the tumor’s disappearance persisted for at least 587 days after treatment initiation, without any indication of recurrence or metastasis. Conclusion Standard anticancer therapy combined with the dendritic cells pulsed with Wilms’ tumor 1 and mucin 1 vaccine may have therapeutic effects for such patients with unresectable lung adenocarcinoma.

Abstract Background Modulating atrial fibrillation (AF) drivers has been proposed as one of the effective ablation strategies for non‐paroxysmal AF (non‐PAF). However, the optimal non‐PAF ablation strategy is still under debate because the exact mechanisms of AF persistence including focal activity and/or rotational activity, are not well‐understood. Recently, spatiotemporal electrogram dispersion (STED) assumed to indicate rotors in the form of rotational activity is proposed as an effective target for non‐PAF ablation. We aimed to clarify the effectiveness of STED ablation for modulating AF drivers. Methods STED ablation plus pulmonary vein isolation was applied in 161 consecutive non‐PAF patients not undergoing previous ablation. STED areas within the entire left and right atria were identified and ablated during AF. After the procedures, the STED ablation's acute and long‐term outcomes were investigated. Results (1) Despite a more effective acute outcome of the STED ablation for both AF termination and non‐inducibility of atrial tachyarrhythmias (ATAs), Kaplan–Meier curves showed that the 24‐month freedom ratio from ATAs was 49%, which resulted from the higher recurrence ratio of atrial tachycardia (AT) rather than AF. (2) A multivariate analysis showed that the determinant of ATA recurrences was only a non‐elderly age, not long‐standing persistent AF, and an enlarged left atrium, which were conventionally considered as key factors. Conclusions STED ablation targeting rotors was effective in elderly non‐PAF patients. Therefore, the main mechanism of AF persistency and the component of the fibrillatory conduction might vary between elders and non‐elders. However, we should be careful about post‐ablation ATs following substrate modification.

Abstract Background The acute success rate of pulmonary vein isolation (PVI) with cryoballoon (CB) is reported to be lower in the right inferior pulmonary vein (RIPV). This study aimed to investigate the utility of the “balloon lever technique (BLT)” for RIPV CB ablation. Methods We retrospectively studied consecutive patients who underwent CB‐PVI for atrial fibrillation between February 21, 2020 and June 3, 2022. RIPV cryoablation was performed according to a specific protocol. The patients underwent RIPV cryoablation using the conventional method. If the method was found ineffective, BLT cryoablation was performed. The acute success rate of RIPV CB ablation was examined. We also investigated the RIPV isolation rate and procedural parameters during conventional and BLT cryoablation. Results Ninety‐three patients were included in the analysis. RIPV isolation was achieved in 89.2% (83/93) of the patients using conventional method and subsequent BLT cryoablation. Meanwhile, 68 patients underwent BLT cryoablation because the conventional method was ineffective. RIPV was isolated with BLT in 85.3% (58/68) of patients. Additionally, BLT was found to be superior to conventional cryoablation in terms of nadir balloon temperature, freezing time, and thawing time to a specific temperature in patients who underwent both conventional and BLT cryoablations. Conclusions BLT is useful in RIPV cryoablation when the conventional method is ineffective. BLT cryoablation may be helpful, mainly because of the BLT‐mediated contact of the balloon with the bottom of the RIPV, which leads to optimal RIPV occlusion.

We provide an overview of our understanding of the dust environment at Mercury and the role that dust plays in shaping the planet's surface and exosphere. Our understanding of the role that dust impacts play in the generation of Mercury's atmosphere has evolved considerably with continued analysis of results from the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) mission. Recent models have provided evidence for the probable release of refractory species into Mercury's exosphere via impacts. However, there remain significant questions regarding the relative contributions of atoms released via impacts versus other mechanisms (e.g., photon-stimulated desorption) to the overall exospheric budget. We also discuss the state of observational and modeling efforts to constrain the dust environment at Mercury, including sources from the zodiacal cloud, cometary trails, and interstellar dust. We describe the advancements that will be made in our characterization of dust at Mercury with BepiColombo, providing observational constraints on the dust clouds themselves and the role that impacts play in exospheric generation. On Mercury's surface, there remain outstanding questions regarding the role that dust impacts play in the regolith cycling and development. We review how improved modeling efforts to understand grain lifetimes as a function of impactor flux will further our understanding of Mercury's regolith. Finally, there are few constraints on the role of dust impacts on the space weathering of Mercury's surface, particularly the expected chemical, physical, and spectral alterations to the regolith. Here we discuss the importance of laboratory experiments to simulate these processes for the interpretation of data from MESSENGER and BepiColombo.

Abstract Martian moons exploration, MMX, is the new sample return mission planned by the Japan Aerospace Exploration Agency (JAXA) targeting the two Martian moons with the scheduled launch in 2024 and return to the Earth in 2029. The major scientific objectives of this mission are to determine the origin of Phobos and Deimos, to elucidate the early Solar System evolution in terms of volatile delivery across the snow line to the terrestrial planets having habitable surface environments, and to explore the evolutionary processes of both moons and Mars surface environment. To achieve these objectives, during a stay in circum-Martian space over about 3 years MMX will collect samples from Phobos along with close-up observations of this inner moon and carry out multiple flybys of Deimos to make comparative observations of this outer moon. Simultaneously, successive observations of the Martian atmosphere will also be made by utilizing the advantage of quasi-equatorial spacecraft orbits along the moons’ orbits. Graphical Abstract

Abstract The science operations of the spacecraft and remote sensing instruments for the Martian Moon eXploration (MMX) mission are discussed by the mission operation working team. In this paper, we describe the Phobos observations during the first 1.5 years of the spacecraft’s stay around Mars, and the Deimos observations before leaving the Martian system. In the Phobos observation, the spacecraft will be placed in low-altitude quasi-satellite orbits on the equatorial plane of Phobos and will make high-resolution topographic and spectroscopic observations of the Phobos surface from five different altitudes orbits. The spacecraft will also attempt to observe polar regions of Phobos from a three-dimensional quasi-satellite orbit moving out of the equatorial plane of Phobos. From these observations, we will constrain the origin of Phobos and Deimos and select places for landing site candidates for sample collection. For the Deimos observations, the spacecraft will be injected into two resonant orbits and will perform many flybys to observe the surface of Deimos over as large an area as possible. Graphical Abstract

Abstract The Martian Moons Exploration (MMX) spacecraft is a JAXA mission to Mars and its moons Phobos and Deimos. MMX will be equipped with the Circum-Martian Dust Monitor (CMDM) which is a newly developed light-weight ( $$\mathrm {650\,g}$$ 650 g ) large area ( $$1\,\mathrm {m}^{2}$$ 1 m 2 ) dust impact detector. Cometary meteoroid streams (also referred to as trails) exist along the orbits of comets, forming fine structures of the interplanetary dust cloud. The streams consist predominantly of the largest cometary particles (with sizes of approximately $$100\,\mu \mathrm { m}$$ 100 μ m to 1 cm) which are ejected at low speeds and remain very close to the comet orbit for several revolutions around the Sun. The Interplanetary Meteoroid Environment for eXploration (IMEX) dust streams in space model is a new and recently published universal model for cometary meteoroid streams in the inner Solar System. We use IMEX to study the detection conditions of cometary dust stream particles with CMDM during the MMX mission in the time period 2024 to 2028. The model predicts traverses of 12 cometary meteoroid streams with fluxes of $$100\,\mu \mathrm { m}$$ 100 μ m and bigger particles of at least $$10^{-3}\,\mathrm {m}^{-2}\,\mathrm {day}^{-1}$$ 10 - 3 m - 2 day - 1 during a total time period of approximately 90 days. The highest flux of $$0.15\,\mathrm {m}^{-2}\,\mathrm {day}^{-1}$$ 0.15 m - 2 day - 1 is predicted for comet 114P/Wiseman-Skiff in October 2026. With its large detection area and high sensitivity CMDM will be able to detect cometary meteoroid streams en route to Phobos. Our simulation results for the Mars orbital phase of MMX also predict the occurrence of meteor showers in the Martian atmosphere which may be observable from the Martian surface with cameras on board landers or rovers. Finally, the IMEX model can be used to study the impact hazards imposed by meteoroid impacts onto large-area spacecraft structures that will be particularly necessary for crewed deep space missions.

Abstract In contrast to conventional X-ray therapy, proton beam therapy (PBT) can confine radiation doses to tumours because of the presence of the Bragg peak. However, the precision of the treatment is currently limited by the uncertainty in the beam range. Recently, a unique range verification methodology has been proposed based on simulation studies that exploit spherical ionoacoustic waves with resonant frequency (SPIREs). SPIREs are emitted from spherical gold markers in tumours initially introduced for accurate patient positioning when the proton beam is injected. These waves have a remarkable property: their amplitude is linearly correlated with the residual beam range at the marker position. Here, we present proof-of-principle experiments using short-pulsed proton beams at the clinical dose to demonstrate the feasibility of using SPIREs for beam-range verification with submillimetre accuracy. These results should substantially contribute to reducing the range uncertainty in future PBT applications.

Background The management of pancreatic injury is not well‐established. Recently, endoscopic therapy has been reported as a treatment option for main pancreatic duct disruption. Case Presentation A 68‐year‐old man presented to our hospital and was diagnosed with severe traumatic pancreatic injury that developed 2 days prior. Endoscopic retrograde cholangiopancreatography revealed main pancreatic duct disruption. Although initial stenting to the distal main pancreatic duct was not achieved because of the widespread intermediate fluid collection, an endoscopic naso‐pancreatic drainage tube was successfully inserted into via the main duodenal papilla. After drainage, the endoscopic naso‐pancreatic drainage tube was replaced with an endoscopic retrograde pancreatic drainage tube, and a stent was successfully placed into the distal main pancreatic duct via the minor papilla. Conclusion We report a case of severe pancreatic injury managed using multi‐stage endoscopic therapy that could be a possible treatment strategy for pancreatic injury with total main pancreatic duct disruption.

Three-dimensional printing technology holds marked promise for the pharmaceutical industry and is now under intense investigation. Most research is aimed at a greater efficiency in printing oral dosage forms using powder bed printing or fused deposition modeling (FDM). Oral dosage forms printed by FDM tend to be hard objects, which reduce the risk of cracking and chipping. However, one challenge in printing oral dosage forms via FDM is achieving rapid drug release, because the materials for FDM are basically thermoplastic polymers with slow drug release properties. In this study, we investigated printing a fast-dissolving oral dosage form by adding sugar alcohol to a poly(vinyl alcohol)-based formulation for FDM. Filaments which contain sugar alcohol were successfully prepared, and objects were printed with them as oral dosage forms by FDM. On drug release testing, a printed oral dosage form in a ring shape which contained 55% maltitol showed a more than 85% drug release in 15 min. In vivo oral absorption of this printed oral dosage form in dogs was comparable to that of a conventional fast-dissolving tablet. Of particular interest, the drug release profile and drug amount of the oral dosage forms can be easily controlled by a change in shape using 3D Computer Aided Design. These characteristics will encourage the prevalence of FDM by the pharmaceutical industry, and contribute to the promotion of personalized medicine.

Abstract Background The purpose of this study is to investigate if a laryngeal mask could improve respiratory condition during radiofrequency catheter ablation (RFCA). Methods Twenty-four consecutive patients who underwent RFCA for atrial fibrillation were divided into two groups (Facemask group; n = 10, Laryngeal mask group; n = 14). All patients were completely sedated under intravenous anesthesia and fitted with artificial respirators during the RFCA. The capnography waveforms and their differential coefficients were analyzed to evaluate the changes of end-tidal CO2 (ETCO2) values, respiratory intervals, expiratory durations, and inspiratory durations. Results During the RFCA, ETCO2 values of the laryngeal mask group were higher than those of the facemask group (36.0 vs. 29.2 mmHg, p = 0.005). The respiratory interval was significantly longer in the laryngeal mask group than those in the facemask group (4.28 s vs.5.25 s, p

Abstract Background Despite advances in chemotherapy, curing multiple liver metastases is quite rare. Even when response is obtained, regrowth of the tumors is almost inevitable. We aimed to evaluate the efficacy and adverse events of helical tomotherapy for chemo‐refractory multiple liver metastases. Methods Forty‐five patients with chemo‐refractory multiple (3‐10) liver metastases after standard systemic chemotherapy entered the single‐institutional prospective study. Liver metastases were the major disease; however, 31 also had uncontrolled primary lesions and/or other metastases. The prescribed dose was 55 Gy in 25 fractions. The median planning target volume (PTV) and normal liver volume (NLV) of first treatment were 128 cm3 and 1175 cm3, respectively. The median of V15Gy, V30Gy, and mean dose to NLV were 45%, 23%, and 19.4 Gy, respectively. Results Forty‐two patients (93%) completed the planned treatment. Median survival time (MST) for all patients was 8 months, and the 1‐year survival rate was 29%. The median local control (LC) period was 5 months and the 6‐month control rate of irradiated tumors was 33%. A ≥30% decrease in tumor markers was observed in 31%. The most common grade 3 toxicity was lymphocytopenia (40%), followed by fatigue (6%). Radiation‐induced liver disease (RILD) was not observed. Pancreatic cancer as the primary tumor, distant metastases outside the liver, low pretreatment neutrophil‐to‐lymphocyte ratio (NLR), and low pretreatment monocyte‐to‐lymphocyte ratio (MLR) were associated with poorer prognoses. Conclusions Helical tomotherapy for chemo‐refractory multiple liver metastases is a feasible and potentially effective treatment. Incorporating tomotherapy into the first‐line treatment in combination with systemic chemotherapy should be considered. Trial registration number CROG 12005.

Abstract Poly-ubiquitin (poly-Ub) is involved in various cellular processes through the linkage-specific recognition of Ub-binding domains (UBD). In this study, using molecular dynamics (MD) simulation together with an enhanced sampling method, we demonstrated that K63-linked di-Ub recognizes the NZF domain of TAB2, a zinc finger UBD, in an ensemble of highly dynamic structures that form from the weak interactions between UBD and the flexible linker connecting the two Ubs. However, the K63 di-Ub/TAB2 NZF complex showed a much more compact and stable ensemble than the non-native complexes, linear di-Ub/TAB2 NZF and K33 di-Ub/TAB2 NZF, that were modeled from linear di-Ub/HOIL-1L NZF and K33 di-Ub/TRABID NZF1, respectively. We further demonstrated the importance of the length and position of the Ub-Ub linker in the results of MD simulations of K63 di-Ub/TAB2 NZF by changing the Ub linkage from the native K63 to four different non-native linkages, linear, K6, K11, and K48, while maintaining inter-molecular contacts in the native complex. No systems with non-native linkage maintained the native binding configuration. These simulation results provide an atomistic picture of the linkage specific recognition of poly-Ubs leading to the biological functions such as cellular colocalization of various component proteins in the signal transduction pathways.

(3200) Phaethon is a near-Earth asteroid discovered in 1983 that has large inclination and eccentricity. Here, the authors perform polarimetric observation of Phaethon over a wide range of solar phase angle and report that the asteroid exhibits a very strong linear polarization.

Human infections caused by the H5 highly pathogenic avian influenza virus (HPAIV) sporadically threaten public health. The susceptibility of HPAIVs to baloxavir acid (BXA), a new class of inhibitors for the influenza virus cap-dependent endonuclease, has been confirmed in vitro, but it has not yet been fully characterized. Here, the efficacy of BXA against HPAIVs, including recent H5N8 variants, was assessed in vitro. The antiviral efficacy of baloxavir marboxil (BXM) in H5N1 virus-infected mice was also investigated. BXA exhibited similar in vitro activities against H5N1, H5N6, and H5N8 variants tested in comparison with seasonal and other zoonotic strains. Compared with oseltamivir phosphate (OSP), BXM monotherapy in mice infected with the H5N1 HPAIV clinical isolate, the A/Hong Kong/483/1997 strain, also caused a significant reduction in viral titers in the lungs, brains, and kidneys, thereby preventing acute lung inflammation and reducing mortality. Furthermore, compared with BXM or OSP monotherapy, combination treatments with BXM and OSP using a 48-h delayed treatment model showed a more potent effect on viral replication in the organs, accompanied by improved survival. In conclusion, BXM has a potent antiviral efficacy against H5 HPAIV infections.

Sleep-disordered breathing (SDB) is one of the most common complications among heart failure (HF) patients. Changes of respiratory patterns during the various stages in patients with HF have not been fully investigated. In this case, the algorism using thoracic impedance sensor and minute ventilation (sleep apnea monitoring [SAM] algorithm) with implanted pacemaker (REPLY 200 SR or DR, Sorin CRM SAS, Clamart, France) was used to monitor respiration. Impedance data from the implanted pacemaker can be converted into respiratory data, which can be used to calculate the respiratory disturbance index (RDI) per unit of time. Using this algorithm, we observed a sudden appearance of abnormal breathing at the onset of HF, followed by gradual improvement of respiratory patterns during the recovery stage. The results from respiratory monitoring using the SAM algorithm were strongly correlated with those from the positive airway pressure device. This case report could imply that proper utilization of this sensor could facilitate the early detection and therapeutic control of HF. Keywords: Heart failure, Pacemaker, Respiratory monitoring

ObjectivesAlthough endoscopic papillectomy is useful for treating papillary tumors, it is associated with a high rate of complications including pancreatitis; therefore, safer treatment options are needed. We examined the utility of wire-guided endoscopic papillectomy by comparing the pancreatic duct stenting and pancreatitis rates before and after wire-guided endoscopic papillectomy was introduced at our institution.MethodsWe retrospectively examined the data from 16 consecutive patients who underwent conventional endoscopic papillectomy between November 1995 and July 2005 and the data from 33 patients in whom wire-guided endoscopic papillectomy was first attempted at our institution between August 2005 and April 2017. We compared the pancreatic duct stenting and pancreatitis rates between the two groups.ResultsOf the 33 patients in whom wire-guided endoscopic papillectomy was first attempted, the procedure was completed in 21. Pancreatic duct stenting was possible in 30 of the 33 patients in whom wire-guided endoscopic papillectomy was attempted (91%), and this rate was significantly higher than that before the introduction of wire-guided endoscopic papillectomy (68.8%). The incidence of pancreatitis before the introduction of wire-guided endoscopic papillectomy was 12.5%, but after August 2005, the incidence was reduced by half to 6.1%, which includes those patients in whom wire-guided endoscopic papillectomy could not be completed.ConclusionsAlthough wire-guided endoscopic papillectomy cannot be completed in some patients, we believe that this method shows some potential for reducing the total incidence of post-endoscopic papillectomy pancreatitis owing to more successful pancreatic duct stenting.

Background and aims In recent years, the short single-balloon enteroscope (SBE) has been used during endoscopic retrograde cholangiopancreatography (ERCP) for patients with surgically altered anatomy and has been reported to be useful. However, difficulties remain, and the procedures and devices need improvements. We assessed the usefulness and superiority of a new short SBE equipped with passive bending and high-force transmission by comparisons with outcomes using the conventional short SBE. Methods This study evaluated short SBE-assisted ERCP-related procedures for Roux-en-Y gastrectomy between September 2011 and October 2017. Outcomes including the procedural success rate, which was the primary outcome, were assessed to compare the conventional short SBE (SIF-Y0004 [prototype]) and the new short SBE (SIF-H290S). Results Of 74 procedures performed in 61 patients, 51 procedures in 39 patients involved the SIF-Y0004, and 23 procedures in 22 patients involved the SIF-H290S. The procedural success rates were 70.6 % for SIF-Y0004, and 95.7 % for SIF-H290S, representing better results for the new short SBE (P = 0.02). The new short SBE also had a superior diagnostic success rate (P = 0.047) and median time to reach the blind end (P

Background: CHADS2 or CHA2DS2-VASc score is used for prediction of stroke in patients with atrial fibrillation (AF). Recently, CHADS2 score is reported to have prognostic value in acute coronary syndrome without AF. However, clinical validation of CHA2DS2-VASc score for prognostic stratification in coronary heart disease (CHD) without AF remains uncertain. In this study, we evaluate whether CHA2DS2-VASc score could predict clinical outcome in CHD without known AF. Methods: SHINANO registry was a prospective, observational, multicenter cohort study, enrolling 1923 consecutive patients with CHD from August 2012 to July 2013. Two hundred nine patients were excluded because of known AF. We calculated CHA2DS2-VASc score in the remaining 1714 patients (mean age 70 ± 11 years, 23% female) without known AF. To assess the clinical validation of CHA2DS2-VASc score, we divided patients into 3 groups according to the tertiles (score 0–2, 3–4, and ≥5). The primary endpoint was MACE including death, nonfatal myocardial infarction, and ischemic stroke at 1 year. Results: One-year follow-up was completed in 1632 patients (95.2%). Cumulative incidence of MACE was 139 cases. In Kaplan–Meier analysis, incidence of MACE was significantly higher in patients with CHA2DS2-VASc score ≥5 compared to 3–4 and 0–2 (14.6% vs. 6.8% vs. 5.3%, p