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Abstract Artificial neural networks are becoming an integral part of digital solutions to complex problems. However, employing neural networks on quantum processors faces challenges related to the implementation of non-linear functions using quantum circuits. In this paper, we use repeat-until-success circuits enabled by real-time control-flow feedback to realize quantum neurons with non-linear activation functions. These neurons constitute elementary building blocks that can be arranged in a variety of layouts to carry out deep learning tasks quantum coherently. As an example, we construct a minimal feedforward quantum neural network capable of learning all 2-to-1-bit Boolean functions by optimization of network activation parameters within the supervised-learning paradigm. This model is shown to perform non-linear classification and effectively learns from multiple copies of a single training state consisting of the maximal superposition of all inputs.

Past efforts to synthesize and quantify the magnitude and change in carbon dioxide (CO2) fluxes in terrestrial ecosystems across the rapidly warming Arctic–boreal zone (ABZ) have provided valuable information but were limited in their geographical and temporal coverage. Furthermore, these efforts have been based on data aggregated over varying time periods, often with only minimal site ancillary data, thus limiting their potential to be used in large-scale carbon budget assessments. To bridge these gaps, we developed a standardized monthly database of Arctic–boreal CO2 fluxes (ABCflux) that aggregates in situ measurements of terrestrial net ecosystem CO2 exchange and its derived partitioned component fluxes: gross primary productivity and ecosystem respiration. The data span from 1989 to 2020 with over 70 supporting variables that describe key site conditions (e.g., vegetation and disturbance type), micrometeorological and environmental measurements (e.g., air and soil temperatures), and flux measurement techniques. Here, we describe these variables, the spatial and temporal distribution of observations, the main strengths and limitations of the database, and the potential research opportunities it enables. In total, ABCflux includes 244 sites and 6309 monthly observations; 136 sites and 2217 monthly observations represent tundra, and 108 sites and 4092 observations represent the boreal biome. The database includes fluxes estimated with chamber (19 % of the monthly observations), snow diffusion (3 %) and eddy covariance (78 %) techniques. The largest number of observations were collected during the climatological summer (June–August; 32 %), and fewer observations were available for autumn (September–October; 25 %), winter (December–February; 18 %), and spring (March–May; 25 %). ABCflux can be used in a wide array of empirical, remote sensing and modeling studies to improve understanding of the regional and temporal variability in CO2 fluxes and to better estimate the terrestrial ABZ CO2 budget. ABCflux is openly and freely available online (Virkkala et al., 2021b, https://doi.org/10.3334/ORNLDAAC/1934).

Abstract The preparation of thermal equilibrium states is important for the simulation of condensed matter and cosmology systems using a quantum computer. We present a method to prepare such mixed states with unitary operators and demonstrate this technique experimentally using a gate-based quantum processor. Our method targets the generation of thermofield double states using a hybrid quantum-classical variational approach motivated by quantum-approximate optimization algorithms, without prior calculation of optimal variational parameters by numerical simulation. The fidelity of generated states to the thermal-equilibrium state smoothly varies from 99 to 75% between infinite and near-zero simulated temperature, in quantitative agreement with numerical simulations of the noisy quantum processor with error parameters drawn from experiment.

Quantum computers with tens to hundreds of noisy qubits are being developed today. To be useful for real-world applications, we believe that these near-term systems cannot simply be scaled-down non-error-corrected versions of future fault-tolerant large-scale quantum computers. These near-term systems require specific architecture and design attributes to realize their full potential. To efficiently execute an algorithm, the quantum coprocessor must be designed to scale with respect to qubit number and to maximize useful computation within the qubits' decoherence bounds. In this work, we employ an application-system-qubit co-design methodology to architect a near-term quantum coprocessor. To support algorithms from the real-world application area of simulating the quantum dynamics of a material system, we design a (parameterized) arbitrary single-qubit rotation instruction and a two-qubit entangling controlled-Z instruction. We introduce dynamic gate set and paging mechanisms to implement the instructions. To evaluate the functionality and performance of these two instructions, we implement a two-qubit version of an algorithm to study a disorder-induced metal-insulator transition and run 60 random instances of it, each of which realizes one disorder configuration and contains 40 two-qubit instructions (or gates) and 104 single-qubit instructions. We observe the expected quantum dynamics of the time-evolution of this system.

Background: The Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. Methods and results: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012–2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P

As part of the terrestrial branch of the Japan-funded Arctic Climate Change Research Project (GRENE-TEA), which aims to clarify the role and function of the terrestrial Arctic in the climate system and assess the influence of its changes on a global scale, this model intercomparison project (GTMIP) is designed to (1) enhance communication and understanding between the modelling and field scientists and (2) assess the uncertainty and variations stemming from variability in model implementation/design and in model outputs using climatic and historical conditions in the Arctic terrestrial regions. This paper provides an overview of all GTMIP activity, and the experiment protocol of Stage 1, which is site simulations driven by statistically fitted data created using the GRENE-TEA site observations for the last 3 decades. The target metrics for the model evaluation cover key processes in both physics and biogeochemistry, including energy budgets, snow, permafrost, phenology, and carbon budgets. Exemplary results for distributions of four metrics (annual mean latent heat flux, annual maximum snow depth, gross primary production, and net ecosystem production) and for seasonal transitions are provided to give an outlook of the planned analysis that will delineate the inter-dependence among the key processes and provide clues for improving model performance.

Free-running and Q-switched infrared Er:YAG laser radiations, ultrasonic ball tip, and classical hand piece drilling machine were compared in the case of hard dental tissues preparation. For the radiation delivery, a special waveguide transfer system was used. Light-cured, high viscosity flowable HDR microfilled hybrid composite material was used for restorations. The longitudinal sections of extracted human teeth with filling material were compared from the point of view of prepared cavity shape and filling material in scanning electron microscope.

The study compares four different procedures of selective preparation of hard dental tissues: ablation by Er:YAG laser radiation (with long and short pulses), preparation by an ultrasound extension with a ball and a classical dental drill. In the long pulses the authors employed interaction energy of 40mJ, duration of the pulse 200 μs and interaction intensity 62kW/cm2; in short pulses the energy was 20mJ, pulse duration 100ns and interaction energy 62kW/cm2. The laser methods were compared with the ultrasound preparation (Sonixflex cariex TV, D - Sonicsys micro) and with the classical preparation. The longitudinal sections through the dentin and the samples of ivory were evaluated after the creation of cavity and administration of the filling by means of electron scanning microscope.

The aim of this study is to evaluate the interation effect of Q-switched, and free running Er:YAG laser radiations, sonic, and classical drilling machine preparation on the hard dental tissues.

Zinc finger protein 36, C3H type-like 1 (ZFP36L1) is one of several Zinc Finger Protein 36 (Zfp36) family members, which bind AU rich elements within 3' untranslated regions (UTRs) to negatively regulate the post-transcriptional expression of targeted mRNAs. The prototypical member of the family, Tristetraprolin (TTP or ZFP36), has been well-studied in the context of inflammation and plays an important role in repressing pro-inflammatory transcripts such as TNF-α. Much less is known about the other family members, and none have been studied in the context of infection. Using macrophage cell lines and primary alveolar macrophages we demonstrated that, like ZFP36, ZFP36L1 is prominently induced by infection. To test our hypothesis that macrophage production of ZFP36L1 is necessary for regulation of the inflammatory response of the lung during pneumonia, we generated mice with a myeloid-specific deficiency of ZFP36L1. Surprisingly, we found that myeloid deficiency of ZFP36L1 did not result in alteration of lung cytokine production after infection, altered clearance of bacteria, or increased inflammatory lung injury. Although alveolar macrophages are critical components of the innate defense against respiratory pathogens, we concluded that myeloid ZFP36L1 is not essential for appropriate responses to bacteria in the lungs. Based on studies conducted with myeloid-deficient ZFP36 mice, our data indicate that, of the Zfp36 family, ZFP36 is the predominant negative regulator of cytokine expression in macrophages. In conclusion, these results imply that myeloid ZFP36 may fully compensate for loss of ZFP36L1 or that Zfp36l1-dependent mRNA expression does not play an integral role in the host defense against bacterial pneumonia.

The basic protein protamine strongly inhibited hydrolysis of triolein emulsified with soybean phosphatidylcholine (PC) by pancreatic and carboxylester lipases; 10 micrograms/ml protamine, about 1000 times lower than the concentration of bovine serum albumin for the same effect, inhibited triolein hydrolysis completely. This inhibition was not affected by the incubation pH or bile salt concentration. Two other basic proteins, histone and purothionin, also inhibited hydrolysis of triolein emulsified with soybean PC, but they did not inhibit triolein hydrolysis by gastric lipase. When gum arabic was used as an emulsifier instead of soybean PC, these basic proteins did not affect triolein hydrolysis by pancreatic or carboxylester lipases. The effects of protamine on triolein hydrolysis by pancreatic and carboxylester lipases was studied using various phospholipids as emulsifiers. Protamine (10 micrograms/ml) did not inhibit hydrolysis of triolein emulsified with dicaproyl PC (DCPC), phosphatidic acid (PA), or phosphatidylserine (PS) by pancreatic and carboxylester lipases. Conversely, protamine at high concentrations slightly stimulated hydrolysis of triolein emulsified with DCPC or PA. Hydrolysis of triolein-phosphatidylethanolamine (PE) emulsion was inhibited slightly by protamine. The profiles of protamine inhibition of triolein-phosphatidyl-N,N-dimethyl ethanolamine (PDME) and triolein-phosphatidyl-N-monomethyl ethanolamine (PMME) emulsions were intermediate between those of PC and PE emulsions. These results suggest that the phospholipid species, especially choline moieties and fatty acid chain length, affect the lipase inhibitory activity of protamine profoundly. In vivo, oral administration of protamine to rats reduced and delayed the peak plasma triacylglycerol concentration, but neither bovine serum albumin nor an amino acid mixture with an amino acid composition identical to protamine affected plasma triacylglycerol levels.

The Zcchc11 enzyme is implicated in microRNA (miRNA) regulation. It can uridylate let-7 precursors to decrease quantities of the mature miRNA in embryonic stem cell lines, suggested to mediate stem cell maintenance. It can uridylate mature miR-26 to relieve silencing activity without impacting miRNA content in cancer cell lines, suggested to mediate cytokine and growth factor expression. Broader roles of Zcchc11 in shaping or remodeling the miRNome or in directing biological or physiological processes remain entirely speculative. We generated Zcchc11-deficient mice to address these knowledge gaps. Zcchc11 deficiency had no impact on embryogenesis or fetal development, but it significantly decreased survival and growth immediately following birth, indicating a role for this enzyme in early postnatal fitness. Deep sequencing of small RNAs from neonatal livers revealed roles of this enzyme in miRNA sequence diversity. Zcchc11 deficiency diminished the lengths and terminal uridine frequencies for diverse mature miRNAs, but it had no influence on the quantities of any miRNAs. The expression of IGF-1, a liver-derived protein essential to early growth and survival, was enhanced by Zcchc11 expression in vitro, and miRNA silencing of IGF-1 was alleviated by uridylation events observed to be Zcchc11-dependent in the neonatal liver. In neonatal mice, Zcchc11 deficiency significantly decreased IGF-1 mRNA in the liver and IGF-1 protein in the blood. We conclude that the Zcchc11-mediated terminal uridylation of mature miRNAs is pervasive and physiologically significant, especially important in the neonatal period for fostering IGF-1 expression and enhancing postnatal growth and survival. We propose that the miRNA 3' terminus is a regulatory node upon which multiple enzymes converge to direct silencing activity and tune gene expression.

The electronic structure of the organic semiconductor titanyl phthalocyanine (TiO-Pc) has been investigated using synchrotron radiation-excited X-ray emission and absorption spectroscopies. The C and N K-edge spectra display similarities with those recorded from other metal-Pcs, while the O K-edge and Ti L-edge spectra support the premise that the titanyl species are spatially isolated. Good agreement is found between a calculation of the partial density of states and the measured spectra, although the Ti L-edge spectra differ from a previous study. Two energy loss features are reported from resonant X-ray inelastic scattering at the Ti L-edge associated with O 2p–Ti 3d* and N 2p–Ti 3d* charge transfer transitions. [ABSTRACT FROM AUTHOR]

The electronic structure of thin films of the organic semiconductor vanadyl phthalocyanine has been studied using synchrotron radiation-excited resonant soft X-ray emission spectroscopy, resonant inelastic soft X-ray scattering, X-ray absorption spectroscopy, and X-ray photoemission spectroscopy. The C, N, V, and O partial densities of states for both the valence and conduction bands have been determined, as well as the core level electronic structure. Good agreement was found between the experimental measurements of the valence and conduction bands, and the results of a density functional calculation. [ABSTRACT FROM AUTHOR]

The yeast nucleoporin Nup2p is associated primarily with the nuclear basket of nuclear pore complexes and is required for efficient importin-α:β-mediated nuclear protein import as well as efficient nuclear export of Kap60p/importin-α. Residues 1-51 of Nup2p bind tightly to Kap60p and are required for Nup2p function in vivo. We have determined the 2.6 Å resolution crystal structure of a complex between this region of Nup2p and the armadillo repeat domain of Kap60p. Nup2p binds along the inner concave groove of Kap60p, but its interaction interface is different from that employed for nuclear localization signal (NLS) recognition although there is some overlap between them. Nup2p binds Kap60p more strongly than NLSs and accelerates release of NLSs from Kap60p. Nup2p itself is released from Kap60p by Cse1p:RanGTP only in the presence of the importin-β binding (IBB) domain of Kap60p. These data indicate that Nup2p increases the overall rate of nuclear trafficking by coordinating nuclear import termination and importin recycling as a concerted process. [ABSTRACT FROM AUTHOR]

Sumoylation is involved in mediating protein-protein interactions, subcellular compartmentalization and protein stability. Our analysis of various Wnt signaling molecules revealed that one of them, Tcf-4, is sumoylated at the endogenous level. At least one sumoylation site, Lys297, of Tcf-4 was identified. The sumoylation of Tcf-4 was enhanced by PIASy, a SUMO E3 enzyme, and inhibited by Axam, a desumoylation enzyme. Although PIASy did not affect the interaction of Tcf-4 with β-catenin or DNA, Tcf-4, SUMO-1 and PIASy were co-localized in the nucleus and present in a complex in the PML body. PIASy enhanced β-catenin-dependent transcriptional activity of Tcf-4, whereas Axam inhibited it. Reduction of the protein level of Axam by RNA interference led to an increase in sumoylation of Tcf-4 and activation of Tcf-4. Furthermore, β-catenin and PIASy activated Tcf-4K297R, in which Lys297 was changed to arginine, less than wild-type Tcf-4. These results suggest that sumoylation of Tcf-4 is involved in β-catenin-dependent and Tcf-4-mediated gene expression in the Wnt signaling pathway. [ABSTRACT FROM AUTHOR]

A photoacoustic imaging system composed of a flexible bundle of thin hollow-optical fibers is proposed for endoscopic diagnosis. In this system, a bundle of 127 hollow-optical fibers with an inner diameter of 100 μm was fabricated. The total diameter of the bundle was 2.1 mm, and the minimum bending radius was around 10 mm. Owing to the small numerical aperture of hollow optical fibers, a high resolution image was obtained without using a lens array at the distal end. In the imaging system, the hollow fibers in the bundle were aligned at the input end, so the hollow fibers were sequentially excited by linearly scanning the laser beam at the input end. Photoacoustic imaging systems consisting of the bundled fibers for excitation of acoustic wave and piezoelectric probes for detection of photoacoustic signals were built. By using the systems, photoacoustic images of blood vessels in the ovarian membrane of fish were taken to test the feasibility of the system. As a result, photoacoustic images of the vessel were successfully obtained with a laser fluence of around 6.6 mJ cm−2. [ABSTRACT FROM AUTHOR]

Purpose: Despite a global decrease in the number of COVID-19 patients, early prediction of the clinical course for optimal patient care remains challenging. Recently, the usefulness of image generation for medical images has been investigated. This study aimed to generate short-term follow-up chest CT images using a latent diffusion model in patients with COVID-19., Materials and Methods: We retrospectively enrolled 505 patients with COVID-19 for whom the clinical parameters (patient background, clinical symptoms, and blood test results) upon admission were available and chest CT imaging was performed. Subject datasets (n = 505) were allocated for training (n = 403), and the remaining (n = 102) were reserved for evaluation. The image underwent variational autoencoder (VAE) encoding, resulting in latent vectors. The information consisting of initial clinical parameters and radiomic features were formatted as a table data encoder. Initial and follow-up latent vectors and the initial table data encoders were utilized for training the diffusion model. The evaluation data were used to generate prognostic images. Then, similarity of the prognostic images (generated images) and the follow-up images (real images) was evaluated by zero-mean normalized cross-correlation (ZNCC), peak signal-to-noise ratio (PSNR), and structural similarity (SSIM). Visual assessment was also performed using a numerical rating scale., Results: Prognostic chest CT images were generated using the diffusion model. Image similarity showed reasonable values of 0.973 ± 0.028 for the ZNCC, 24.48 ± 3.46 for the PSNR, and 0.844 ± 0.075 for the SSIM. Visual evaluation of the images by two pulmonologists and one radiologist yielded a reasonable mean score., Conclusions: The similarity and validity of generated predictive images for the course of COVID-19-associated pneumonia using a diffusion model were reasonable. The generation of prognostic images may suggest potential utility for early prediction of the clinical course in COVID-19-associated pneumonia and other respiratory diseases., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing interests. Ethical statement: This retrospective multicenter study was approved by the Institutional Review Boards of Chiba University (No. 4074 Date 2021/11/24) and Chiba Aoba Municipal Hospital (No. 20200301). The study was conducted in accordance with the principles of the Declaration of Helsinki. The institutional review boards of all hospital institutions included in the present study provided ethical approval. The requirement for written informed consent was waived due to the characteristics of the retrospective study., (© 2024. The Author(s).)

Oncogenic transformation of normal cells is caused by mutations and chromosomal abnormalities in cancer-related genes. Enzootic bovine leukosis (EBL) is a malignant B-cell lymphoma caused by bovine leukemia virus (BLV) infection in cattle. Although a small fraction of BLV-infected cattle develops EBL after a long latent period, the mechanisms for oncogenesis in EBL cattle remain largely unknown. In this study, we analyzed the types and patterns of somatic mutations in cancer cells from 36 EBL cases, targeting 21 cancer-related genes. Various somatic mutations were identified in eight genes, TP53 , KMT2D , CREBBP , KRAS , PTEN , NOTCH1 , MYD88 , and CARD11 . In addition, TP53 gene was found to be mutated in 69.4% of EBL cases, with most being biallelic mutations. In some cases, associations were observed between the ages at which cattle had developed EBL and somatic mutation patterns; young onset of EBL possibly occurs due to high impact mutations affecting protein translation and biallelic mutations. Furthermore, nucleotide substitution patterns indicated that cytosine at CpG sites tended to be converted to thymine in many EBL cases, which was considered to be the result of spontaneous deamination of 5-methylcytosine. These results demonstrate how somatic mutations have occurred in cancer cells leading to EBL development, thereby explaining its pathogenic mechanism. These findings will contribute to a better understanding and future elucidation of disease progression in BLV infection.IMPORTANCEEnzootic bovine leukosis (EBL) is a malignant and lethal disease in cattle. Currently, there are no effective vaccines or therapeutic methods against bovine leukemia virus (BLV) infection, resulting in severe economic losses in livestock industry. This study provides a renewed hypothesis to explain the general mechanisms of EBL onset by combining the previous finding that several integration sites of BLV provirus can affect the increase in survival and proliferation of infected cells. We demonstrate that two additional random events are necessary for oncogenic transformation in infected cell clones, elucidating the reason why only few infected cattle develop EBL. Further exploration of somatic mutation and BLV integration sites could support this hypothesis more firmly, potentially contributing to the development of novel control methods for EBL onset., Competing Interests: The authors declare no conflict of interest.

Background: The Kerlan-Jobe Orthopaedic Clinic shoulder and elbow score (KJOC) is sensitive enough to detect subtle changes in the functional level of the shoulder or elbow in overhead athletes. However, a Japanese version of the KJOC is not yet available. Moreover, the original KJOC uses a visual analog scale (VAS) assessment format that requires a print version so that users can add a check mark along a horizontal line. The KJOC can be completed using online tools such as Google Forms if a 10-point scale format can be used with comparable results., Purposes: To (1) translate and cross-culturally adapt the KJOC into Japanese (KJOC-J) and assess its validity and (2) evaluate the correlation between a standard VAS format and a 10-point scale format (KJOC-J10)., Study Design: Cohort study (Diagnosis); Level of evidence, 3., Methods: In total, 318 athletes participated in the validation study, 255 in the test-retest reliability study for the KJOC-J, and 273 in the validation study for the KJOC-J10. Internal consistency was evaluated using the Cronbach alpha. Validity was evaluated by calculating the correlation between the KJOC-J and the Disability of the Arm, Shoulder and Hand (DASH). Test-retest reliability was assessed using the intraclass correlation coefficient (ICC). The validity of the KJOC-J10 was evaluated by calculating the correlation between the KJOC-J10 and KJOC-J., Results: The Cronbach alpha was 0.914, indicating good internal consistency. The KJOC-J was moderately correlated with the DASH ( r = -0.581; P < .001) and had good test-retest reliability (ICC, 0.874). A strong correlation was found between the KJOC-J and KJOC-J10 ( r = 0.846; P < .001)., Conclusion: The study results demonstrated good internal consistency, validity, and reliability for the KJOC-J, indicating that it is a valid assessment tool for shoulder and elbow functions in Japanese overhead athletes. Moreover, a strong correlation was found between the VAS and 10-point formats of the KJOC-J., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: Research support was received from the Project for Establishment of Sports Medicine and Science Support System in Local Communities 2023 through the Japan Sports Agency. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

Purpose: In a cadaveric model, a comparison was made of the strength of a suture method for collateral ligaments (the N method) with that of simple sutures using suture anchors for the repair of collateral ligaments in the proximal interphalangeal joint., Methods: We obtained 72 fingers from 18 upper limbs of fresh-frozen cadavers and compared the left and right sides of the same specimens. In experiment 1, we examined the rupture strength and rupture sites of intact collateral ligaments in 24 fingers. In experiment 2, we compared the rupture strength and failure modes of the N method (three locking sutures) with those of simple sutures (S group) on 32 fingers. In experiment 3, we examined the rupture strength and failure modes between the N method with three locking sutures (N3 group) and the N method with two locking sutures (N2 group) on 16 fingers. All the experiments involved mechanical testing by applying lateral stress to the collateral ligaments at a rate of 1 mm/s using testing equipment., Results: In Experiment 1, the mean rupture strength of intact collateral ligaments was 80.6 ± 27.5 N. Proximal tears were the most common rupture sites. In Experiment 2, the mean rupture strength was significantly higher in the N group (46.3 ± 19.2 N) than in the S group (24.1 ± 12.7 N). In the N group, suture breakage occurred more frequently than in the S group, whereas in the S group, there was a higher incidence of suture cut out. In Experiment 3, the N3 and N2 groups exhibited nearly identical rupture strength values., Conclusions: This study showed that the N method had better rupture strength than the simple suture method following finger collateral ligament repair., Clinical Relevance: The outcome provides useful information for informing the choice of suture method in clinical practice., Competing Interests: Conflicts of Interest No benefits in any form have been received or will be received related directly to this article., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

We previously reported that hepatitis C virus (HCV) infection or HCV core protein expression induces HOX gene expression by impairing histone H2A monoubiquitination via a proteasome-dependent reduction in the level of RNF2, a key catalytic component of polycomb repressive complex 1 (H. Kasai, K. Mochizuki, T. Tanaka, A. Yamashita, et al., J Virol 95:e01784-20, 2021, https://doi.org/10.1128/jvi.01784-20). In this study, we aimed to investigate the mechanism by which HCV infection accelerates RNF2 degradation. Yeast two-hybrid screening and an immunoprecipitation assay revealed that RNF2 is a PA28γ-binding protein. The proteasome activator PA28γ destabilized the RNF2 protein in a proteasome-dependent manner, since RNF2 degradation was impaired by PA28γ knockout or MG132 treatment. HCV infection or core protein expression reduced the levels of RNF2 and histone H2A K119 monoubiquitination and induced the expression of HOX genes in the presence of PA28γ, while PA28γ knockout reversed these changes. Treatment with a lysine acetyltransferase inhibitor inhibited the acetylation of PA28γ at K195 and the degradation of the RNF2 protein, while treatment with a lysine deacetylase inhibitor accelerated these events in a PA28γ-dependent manner. RNF2 protein degradation was increased by expression of the acetylation mimetic PA28γ mutant but not by expression of the acetylation-defective mutant or the proteasome activation-defective mutant. Furthermore, HCV infection or core protein expression facilitated the interaction between PA28γ and the lysine acetyltransferase CBP/p300 and then accelerated PA28γ acetylation and heptazmerization to promote RNF2 degradation. These data suggest that HCV infection accelerates the acetylation-dependent heptamerization of PA28γ to increase the proteasomal targeting of RNF2.IMPORTANCEHCV is a causative agent of HCV-related liver diseases, including hepatic steatosis, cirrhosis, and hepatocellular carcinoma. PA28γ, which, in heptameric form, activates the 20S core proteasome for the degradation of PA28γ-binding proteins, is responsible for HCV-related liver diseases. HCV core protein expression or HCV infection accelerates RNF2 degradation, leading to the induction of HOX gene expression via a decrease in the level of H2Aub on HOX gene promoters. However, the mechanism of RNF2 degradation in HCV-infected cells has not been clarified. The data presented in this study suggest that PA28γ acetylation and heptamerization are promoted by HCV infection or by core protein expression to activate the proteasome for the degradation of RNF2 and are responsible for HCV propagation. This study provides novel insights valuable for the development of therapies targeting both HCV propagation and HCV-related diseases., Competing Interests: The authors declare no conflict of interest.

Competing Interests: The authors declare no conflict of interest.

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Pelvis experiences changes in its orientation due to the alignment of the hip joint and spine, and its orientation might affect both joints. Pelvic tilt on the sagittal plane has been widely discussed; however, the pelvis is oriented also on the coronal and horizontal planes. This study aimed to examine how stress distribution on intact hip joint changes under the three-dimensional pelvic orientation., Methods: Computed tomography data of five patients with unilateral pelvic girdle were analyzed. Thirteen models were evaluated by the MECHANICAL FINDER: neutral position at 0°; 10° and 20° anterior and posterior pelvic tilt; 10° and 20° pelvic hike and drop; 10° and 20° pelvic forward and backward rotation. Stress assessment was performed in four parts of the acetabulum: anterosuperior, posterosuperior, posteroinferior, and central parts., Results: Compared with the neutral position, the mean value of the equivalent stress and maximum principal stress in the anterosuperior part significantly increased by 1.51 times and 1.57 times at 20° posterior tilt, respectively. The maximum principal stress in the anterosuperior part significantly increased by 1.44 times at 20° hike. A significant increase of 1.45 times was found in the maximum principal stress in the anterosuperior part at 20° forward rotation., Conclusions: Local stress accumulated in the anterosuperior acetabulum at the posterior pelvic tilt, pelvic hike, and pelvic forward rotation, which might lead to hip overload. The effect of posterior pelvic tilt appears to be greater for the hip joint than at the pelvic hike or forward rotation., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Importance: This report details a case of effectively managing severe panic attacks in a panic disorder (PD) patient with agoraphobia by acupuncture treatment., Case Presentation: A 38-year-old Japanese woman suffering from PD with agoraphobia presented at our acupuncture clinic with complaints of repeated panic attacks and anxiety. Initially starting to experience symptoms in her late teens, she avoided psychiatric consultation due to reluctance toward psychotropic medications. An unbiased psychiatrist used the Panic Disorder Severity Scale (PDSS) to assess her PD severity. The PDSS score decreased from 21 on the first to 12 points on the sixth visit. The patient experienced reduced frequency and severity of panic attacks, with restored confidence to go into public despite agoraphobia., Conclusions and Relevance: This is the first report to demonstrate the effectiveness of acupuncture on PD with agoraphobia using PDSS, suggesting its potential as a nonpharmacological treatment for patients with PD and agoraphobia.

Introduction: The SARS-CoV-2 pandemic has had a widespread and severe impact on society, yet there have also been instances of remarkable recovery, even in critically ill patients., Materials and Methods: In this study, we used single-cell RNA sequencing to analyze the immune responses in recovered and deceased COVID-19 patients during moderate and critical stages., Results: Expanded T cell receptor (TCR) clones were predominantly SARS-CoV-2-specific, but represented only a small fraction of the total repertoire in all patients. In contrast, while deceased patients exhibited monoclonal B cell receptor (BCR) expansions without COVID-19 specificity, survivors demonstrated diverse and specific BCR clones. These findings suggest that neither TCR diversity nor BCR monoclonal expansions are sufficient for viral clearance and subsequent recovery. Differential gene expression analysis revealed that protein biosynthetic processes were enriched in survivors, but that potentially damaging mitochondrial ATP metabolism was activated in the deceased., Conclusion: This study underscores that BCR repertoire diversity, but not TCR diversity, correlates with favorable outcomes in COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Paran, Oyama, Khasawneh, Ai, Ismanto, Sherif, Saputri, Ono, Saita, Takei, Horiuchi, Yagi, Matsuura, Okazaki, Takahashi, Standley, Tabe and Naito.)

KEGG (https://www.kegg.jp/) is a database resource for representation and analysis of biological systems. Pathway maps are the primary dataset in KEGG representing systemic functions of the cell and the organism in terms of molecular interaction and reaction networks. The KEGG Orthology (KO) system is a mechanism for linking genes and proteins to pathway maps and other molecular networks. Each KO is a generic gene identifier and each pathway map is created as a network of KO nodes. This architecture enables KEGG pathway mapping to uncover systemic features from KO assigned genomes and metagenomes. Additional roles of KOs include characterization of conserved genes and conserved units of genes in organism groups, which can be done by taxonomy mapping. A new tool has been developed for identifying conserved gene orders in chromosomes, in which gene orders are treated as sequences of KOs. Furthermore, a new dataset called VOG (virus ortholog group) is computationally generated from virus proteins and expanded to proteins of cellular organisms, allowing gene orders to be compared as VOG sequences as well. Together with these datasets and analysis tools, new types of pathway maps are being developed to present a global view of biological processes involving multiple organism groups., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy. We report an extremely rare case of CTS associated with a bifid median nerve and palmaris profundus muscle. A 68-year-old man presented with numbness and pain in the right hand. Intraoperatively, a bifid median nerve was identified, with the ulnar branch severely compressed by the palmaris profundus muscle. The muscle was resected, leading to symptom resolution. Anatomical variations of the median nerve and anomalous muscles should be considered in CTS. Preoperative imaging and open carpal tunnel release are recommended to identify and address such variations., Competing Interests: The authors have no financial interest to declare in relation to the content of this article. During the preparation of this work, the author used ChatGPT4 to convert the text from Japanese to English. After using this tool, the author reviewed and edited the content as needed. Subsequently, the author takes full responsibility for the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background and Objectives: A recent Japanese phase three clinical trial for lung cancer suggested a possible advantage of segmentectomy over lobectomy in terms of death from other diseases. This study aimed to compare the risk of death from other diseases based on surgical procedures in lung cancer patients without recurrence., Methods: We retrospectively reviewed 2121 patients without disease recurrence after curative resection for lung cancer at our institution. Patient characteristics and overall survival were compared between sublobar resection and lobectomy., Results: The sublobar group (n = 595) had a significantly higher proportion of women, non-smokers, patients without comorbidities, patients with a history of other cancers, and patients with earlier-staged disease when compared with the lobectomy group (n = 1526). The overall survival was significantly longer in the sublobar group than in the lobectomy group (p = 0.0034). After adjusting for background characteristics in an analysis of 488 patients, the overall survival had a trend to be longer in the sublobar group than in the lobectomy group (p = 0.071)., Conclusions: Our results suggested that the risk of death from other diseases was potentially higher after lobectomy than after sublobar resection. Although several clinical factors could influence the results, these results may support the benefit of sublobar resection, assuming that the curability of both procedures is similar., (© 2024 Wiley Periodicals LLC.)

Objectives: Being a school teacher is highly stressful. This study aimed to clarify the prevalence of menopausal symptoms and explore the association between these symptoms and job-related stress among Japanese school teachers., Study Design: A cross-sectional study was conducted among randomly selected elementary and junior high school teachers in Japan. Data from 284 teachers aged 45-60 years were analyzed., Main Outcome Measures: Menopausal symptoms were measured using the Greene Climacteric Scale, and the Brief Job Stress Questionnaire was used to assess job stressors, social support, and job/family satisfaction. Associations between scores on the Greene Climacteric Scale and on the Brief Job Stress Questionnaire, and demographic information were analyzed., Results: The most common menopausal symptom was "feeling tired or lacking in energy" (reported by 94.4 % of respondents). The total intensity of menopausal, psychological, and somatic symptoms was significantly correlated with the total level of job stress. Moderate correlations were found between depressive symptoms and job stress regarding suitable jobs, job control, and rewarding jobs, while weak correlations were evident between depressive symptoms and job stress regarding quantitative job overload, interpersonal conflict, and poor physical environment. Higher levels of perceived support from supervisors or co-workers and job satisfaction were associated with less severe psychological and somatic symptoms., Conclusions: Most middle-aged school teachers felt tired or lacking in energy. Higher job-related stress and lower levels of support from supervisors or co-workers were correlated with more severe menopausal symptoms. A supportive work environment and stress management are essential for such teachers., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: The appropriate extent of hilar lymph node (LN) dissection in segmentectomy for lung cancer has not yet been fully investigated. Herein, we assessed the patterns of LN metastasis using network analyses., Methods: Patients with nodal metastases of non-small-cell lung cancer measuring ≤30 mm in diameter who underwent anatomical resection were included. The assumed pathways of metastasis were visualized using Cytoscape software. Metastasis to hilar (#10) or interlobar (#11) LNs but not to more peripheral ones was defined as skip N1 metastasis., Results: A total of 322 patients were included, with 123 of them having pleural invasive tumors and 32 having intrapulmonary metastases. There were 130 patients with pN1 disease and 192 with pN2 disease. The overall proportion of patients with skip N1 metastasis was 17%. Patients with lower lobe tumors had more frequent skip N1 metastasis than those with upper lobe tumors (31% vs. 10%, P<0.001) but had less frequent skip N2 metastasis (10% vs. 20%, P=0.02). The rates of skip metastasis to #11i in the right S6 tumor and right S9-10 tumor were unexpectedly high (22% and 17%, respectively). Similarly, skip metastasis to #11 in the left S6 tumor was relatively high (16%). There was a significant difference in the frequency of skip LN metastasis between tumors with and without pleural invasion (44% vs. 27%, P=0.001)., Conclusions: The pattern of LN metastasis differed according to the localized segment of the tumor and the pleural invasion status., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-944/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

This cross-sectional study investigates the association between long working hours, short sleep duration, and mental health among Japanese physicians. We enrolled 232 Japanese physicians. We used the Brief Job Stress Questionnaire to assess high-stress status, and the Japanese version of the Center for Epidemiologic Studies Depression scale to assess depressive status. Daily sleep duration (DSD) and weekly working hours (WWHs) were collected using a self-administered questionnaire. Multivariable-adjusted logistic regression analysis was performed to examine the association of the combined categories of DSD and WWHs with high-stress and depressive status. Compared to physicians with WWHs <80 h and DSD ≥6 h, the multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of high-stress status for those with WWHs ≥80 and DSD ≥6, WWHs <80 and DSD <6, and WWHs ≥80 and DSD <6 were 2.76 (0.97-7.87), 3.36 (1.53-7.40), and 3.92 (1.52-10.14), respectively. The respective ORs (CIs) of depressive status were 1.82 (0.42-7.81), 4.03 (1.41-11.53), and 4.69 (1.33-16.62). The results showed that regardless of working long hours or not, physicians with DSD <6 h had significantly higher stress and depressive status, suggesting that not only regulating long working hours but also ensuring adequate sleep duration is important for preventing physicians' mental health.

Competing Interests: None disclosed.

Whereas severe COVID-19 is often associated with elevated autoantibody titers, the underlying mechanism behind their generation has remained unclear. Here we report clonal composition and diversity of autoantibodies in humoral response to SARS-CoV-2. Immunoglobulin repertoire analysis and characterization of plasmablast-derived monoclonal antibodies uncovered clonal expansion of plasmablasts producing cardiolipin (CL)-reactive autoantibodies. Half of the expanded CL-reactive clones exhibited strong binding to SARS-CoV-2 antigens. One such clone, CoV1804, was reactive to both CL and viral nucleocapsid (N), and further showed anti-nucleolar activity in human cells. Notably, antibodies sharing genetic features with CoV1804 were identified in COVID-19 patient-derived immunoglobulins, thereby constituting a novel public antibody. These public autoantibodies had numerous mutations that unambiguously enhanced anti-N reactivity, when causing fluctuations in anti-CL reactivity along with the acquisition of additional self-reactivities, such as anti-nucleolar activity, in the progeny. Thus, potentially CL-reactive precursors may have developed multiple self-reactivities through clonal selection, expansion, and somatic hypermutation driven by viral antigens. Our results revealed the nature of autoantibody production during COVID-19 and provided novel insights into the origin of virus-induced autoantibodies., (© 2024 Sakakibara et al.)

A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes mild-to-severe respiratory symptoms, including acute respiratory distress. Despite remarkable efforts to investigate the virological and pathological impacts of SARS-CoV-2, many of the characteristics of SARS-CoV-2 infection still remain unknown. The interferon-inducible ubiquitin-like protein ISG15 is covalently conjugated to several viral proteins to suppress their functions. It was reported that SARS-CoV-2 utilizes its papain-like protease (PLpro) to impede ISG15 conjugation, ISGylation. However, the role of ISGylation in SARS-CoV-2 infection remains unclear. We aimed to elucidate the role of ISGylation in SARS-CoV-2 replication. We observed that the SARS-CoV-2 nucleocapsid protein is a target protein for the HERC5 E3 ligase-mediated ISGylation in cultured cells. Site-directed mutagenesis reveals that the residue K374 within the C-terminal spacer B-N3 (SB/N3) domain is required for nucleocapsid-ISGylation, alongside conserved lysine residue in MERS-CoV (K372) and SARS-CoV (K375). We also observed that the nucleocapsid-ISGylation results in the disruption of nucleocapsid oligomerization, thereby inhibiting viral replication. Knockdown of ISG15 mRNA enhanced SARS-CoV-2 replication in the SARS-CoV-2 reporter replicon cells, while exogenous expression of ISGylation components partially hampered SARS-CoV-2 replication. Taken together, these results suggest that SARS-CoV-2 PLpro inhibits ISGylation of the nucleocapsid protein to promote viral replication by evading ISGylation-mediated disruption of the nucleocapsid oligomerization.IMPORTANCEISG15 is an interferon-inducible ubiquitin-like protein that is covalently conjugated to the viral protein via specific Lys residues and suppresses viral functions and viral propagation in many viruses. However, the role of ISGylation in SARS-CoV-2 infection remains largely unclear. Here, we demonstrated that the SARS-CoV-2 nucleocapsid protein is a target protein for the HERC5 E3 ligase-mediated ISGylation. We also found that the residue K374 within the C-terminal spacer B-N3 (SB/N3) domain is required for nucleocapsid-ISGylation. We obtained evidence suggesting that nucleocapsid-ISGylation results in the disruption of nucleocapsid-oligomerization, thereby suppressing SARS-CoV-2 replication. We discovered that SARS-CoV-2 papain-like protease inhibits ISG15 conjugation of nucleocapsid protein via its de-conjugating enzyme activity. The present study may contribute to gaining new insight into the roles of ISGylation-mediated anti-viral function in SARS-CoV-2 infection and may lead to the development of more potent and selective inhibitors targeted to SARS-CoV-2 nucleocapsid protein., Competing Interests: The authors declare no conflict of interest.

Secondary spontaneous pneumothorax (SSP) due to bevacizumab has been reported in other malignancies but not in cervical cancer. We present the case of a 57-year-old woman with stage IIIB cervical cancer who developed SSP during bevacizumab chemotherapy. Despite complete remission with cisplatin-based chemoradiotherapy, she experienced a recurrence 9 months later. A thoracoscopic surgery was performed to remove a lung nodule and bulla. Subsequently, local cervical lesion recurrence and lung metastases were noted, and paclitaxel and carboplatin combined with bevacizumab were administered. After two cycles, a grade-1 left pneumothorax occurred, attributed to bevacizumab-induced tissue fragility. The patient improved within 7 days with conservative management. Bevacizumab was discontinued, and pneumothorax did not recur. This case highlights the rare occurrence of SSP in patients with cervical cancer treated with bevacizumab and underscores the importance of appropriate management of such patients, especially those who have undergone early thoracic surgery., Competing Interests: Conflict of interestNo conflicts of interest., (© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Aims: While the prevalence of transthyretin-derived amyloid cardiomyopathy (ATTR-CM) is on the rise, detailed understanding of its morphological and functional characteristics within the left ventricle (LV) across heart failure (HF) remains limited., Methods and Results: Utilizing two-dimensional (2D) speckle-tracking echocardiography, we assessed longitudinal strain (LS) in 63 histology-confirmed ATTR-CM patients. Additionally, cardiac magnetic resonance (CMR) images measured native T1 and extracellular volume (ECV), compared with LS across 18 LV segments. Patients were categorized into three groups based on HF status: Group 1 (no HF symptoms), Group 2 (HF with preserved LV ejection fraction), and Group 3 (HF with reduced LV ejection fraction). LS analysis unveiled susceptibility to deformation in the basal inferoseptal segment, persisting even in asymptomatic cases. CMR demonstrated increasing native T1 deviation, particularly evident in segments distant from the inferoseptal region. Contrastingly, maximal ECV was consistently observed in the basal and mid-ventricular inferior-septum, even in asymptomatic individuals. Segmental LS decline correlated with ECV expansion but not with native T1 values., Conclusion: Our findings suggest that the inferoseptal segment is highly susceptible to amyloid infiltration, and 2D speckle-tracking echocardiography and CMR may serve as a valuable tool for its early detection., Competing Interests: Conflict of interest: T.T. received lecture fees from Pfizer Japan Inc and Alnylam Japan. K.K. received lecture fees from Bayer Yakuhin, Daiichi-Sankyo, Novartis Pharma AG, Otsuka Pharmaceutical, Bristol-Myers K.K., and Kowa, as well as scholarship funds from Abbott Medical., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Exercise has positive effects on psychological well-being, with team sports often associated with superior mental health compared to individual sports. Augmented reality (AR) technology has the potential to convert solitary exercise into multi-person exercise. Given the role of oxytocin in mediating the psychological benefits of exercise and sports, this study aimed to investigate the impact of AR-based multi-person exercise on mood and salivary oxytocin levels., Methods: Fourteen participants underwent three distinct regimens: non-exercise (Rest), standard solitary cycling exercise (Ex), and AR-based multi-person cycling exercise (Ex+AR). In both Ex and Ex+AR conditions, participants engaged in cycling at a self-regulated pace to maintain a Rating of Perceived Exertion of 10. In the Ex+AR condition, participants' avatars were projected onto a tablet screen, allowing them to cycle alongside ten other virtual avatars in an AR environment. Mood states and saliva samples were collected before and immediately after each 10-minute regimen. Subsequently, salivary oxytocin levels were measured., Results: Notably, only the Ex+AR condition significantly improved mood states associated with depression-dejection and exhibited a non-significant trend toward suppressing anger-hostility in participants. Moreover, the Ex+AR condition led to a significant elevation in salivary oxytocin levels, while the Ex condition showed a non-significant trend toward an increase. However, changes in salivary oxytocin did not show a significant correlation with changes in mood states., Conclusions: These findings suggest that Ex+AR enhances mood states and promotes oxytocin release. AR-based multi-person exercise may offer greater psychological benefits compared to standard solitary exercise, although the relationship between oxytocin and mood changes remains inconclusive., Competing Interests: Declaration of competing interest The authors inform no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Coronavirus (CoV) possesses numerous functional cis-acting elements in its positive-strand genomic RNA. Although most of these RNA structures participate in viral replication, the functions of RNA structures in the genomic RNA of CoV in viral replication remain unclear. In this study, we investigated the functions of the higher-order RNA stem-loop (SL) structures SL5B, SL5C, and SL5D in the ORF1a coding region of Middle East respiratory syndrome coronavirus (MERS-CoV) in viral replication. Our approach, using reverse genetics of a bacterial artificial chromosome system, revealed that SL5B and SL5C play essential roles in the discontinuous transcription of MERS-CoV. In silico analyses predicted that SL5C interacts with a bulged stem-loop (BSL) in the 3' untranslated region, suggesting that the RNA structure of SL5C is important for viral RNA transcription. Conversely, SL5D did not affect transcription, but mediated the synthesis of positive-strand genomic RNA. Additionally, the RNA secondary structure of SL5 in the revertant virus of the SL5D mutant was similar to that of the wild-type, indicating that the RNA structure of SL5D can finely tune RNA replication in MERS-CoV. Our data indicate novel regulatory mechanisms of viral RNA transcription and replication by higher-order RNA structures in the MERS-CoV genomic RNA., (© 2024. The Author(s).)