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ABSTRACT Acute liver failure is a serious, life‐threatening disease. Although the gut microbiota has been considered to play a role in liver failure, the extent to which it is involved in the pathogenesis of this disease has not been fully elucidated to date. Therefore, we here analyzed the importance of the presence of intestinal microbiota in the pathogenesis of acute liver injury, using D‐galactosamine (D‐GalN)/lipopolysaccharide (LPS)‐treated mice, which is a widely used experimental model of acute liver injury. First, administration of the antibiotic polymyxin B markedly alleviated liver injury. Liver injury was also reduced in germ‐free mice, leading to the conclusion that the presence of intestinal microbiota aggravates D‐GalN/LPS‐induced liver injury. The amount of bacteria and LPS transferred from the gut to the blood was not increased by D‐GalN/LPS, suggesting that the worsening of liver injury was not simply owing to the entry of bacteria into the circulation. In conclusion, acute liver injury in polymyxin B‐pretreated or germ‐free mice was ameliorated by modulation of the gut microbiota. Modification of the gut microbiota using polymyxin B may hence have the potential to alleviate acute liver injury in human patients. [ABSTRACT FROM AUTHOR]

Muonium (Mu) is a hydrogenlike atom comprising a positive muon and an electron, both pointlike leptons. Spectroscopy of Mu is a promising method in the search for new physics in particle-physics research, superior to that of hydrogen for which the uncertainty in the proton radius and its internal structure gives limitations. Microwave spectroscopy of the Mu hyperfine structure (HFS) provides the most precise estimation of the magnetic moment and the mass of the muon, opening a way to search for a physics beyond the Standard Model. MuSEUM Collaboration is studying Mu-HFS at the J-PARC muon facility in Japan, aiming at a precision one order of magnitude better than before. With our new spectroscopic technique which does not require any frequency sweep or Fourier transformation, the resonance frequency can be obtained directly by fitting a simulated function to the time evolution of the Rabi oscillation at a fixed microwave frequency. This method, named Rabi-oscillation spectroscopy, can improve the precision by eliminating systematic uncertainties due to power fluctuations. After a decade of our study under zero magnetic field with fruitful results, we are about to start our experiment under a high magnetic field. [ABSTRACT FROM AUTHOR]

Background/Objectives: Actin plays a crucial role not only in the cytoplasm, but also in the nucleus, influencing various cellular behaviors, including cell migration and gene expression. Recent studies reveal that nuclear actin dynamics is altered by cellular stresses, such as DNA damage; however, the effect of heat shock on nuclear actin dynamics, particularly in the nucleolus, remains unclear. This study aims to elucidate the contribution of nucleolar actin to cellular responses under heat shock conditions. Methods: Nuclear actin dynamics in response to heat shock were investigated using nAC-GFP, a GFP-tagged actin chromobody, to visualize nuclear actin in HeLa cells. Bioinformatic analyses were also performed. Results: Heat shock induced the reversible assembly of nAC-GFP in the nucleolus, with disassembly occurring upon recovery in a heat shock protein (Hsp) 70-dependent manner. Because the nucleolus, formed via liquid–liquid phase separation (LLPS), sequesters misfolded proteins under heat shock to prevent irreversible aggregation, we hypothesized that nucleolar actin-binding proteins might also be sequestered in a similar manner. Using several databases, we identified 47 actin-binding proteins localized in the nucleolus and determined the proportion of intrinsically disordered regions (IDRs) known to promote LLPS. Our analysis revealed that many of these 47 proteins exhibited high levels of IDRs. Conclusions: The findings from our bioinformatics analysis and further cellular studies may help elucidate new roles for actin in the heat shock response. [ABSTRACT FROM AUTHOR]

SUMMARY: Photosynthetic electron transport is carried out by the electron carrier, plastoquinone (PQ). Recently, another form of PQ, acylplastoquinol (APQ), was discovered in Synechocystis sp. PCC 6803 (Synechocystis), but its physiological function in photosynthesis is unclear. In the present study, we identified a lipase encoded in sll0482 gene in Synechocystis that deacylates APQ and releases a free fatty acid and a reduced PQ (plastoquinol, PQH2), which we named acylplastoquinol lipase (APL). Disruption of apl gene increased APQ content, and recovery of photodamaged PSII under low light (LL) after the exposure to very high light (vHL) at 2500 μmol photons m−2 sec−1 without aeration (vHL) for 60 min, was suppressed in the Δapl cells. Δapl cells also show the slow rate of de novo synthesis of D1, a reaction center of PSII under such condition. Under high light, the cellular growth of Δapl was inhibited; however, disruption of apl gene did not affect the photosynthetic activity or photoinhibition of PSII. In wild‐type cells, APQ content increased under vHL condition. Also, APQ was converted to PQH2 after transfer to LL with aeration by ambient air. Such striking changes in APQ were not observed in Δapl cells. The deacylation of APQ by APL may help repair PSII when PSII cannot drive photosynthetic electron transport efficiently. Significance Statement: The physiological role of recently discovered acylplastoquinol (APQ) in photosynthesis is unclear. APQ content was increased under severe photo‐oxidative stress. It was deacylated by APQ lipase to produce a plastoquinol (PQH2) and a free fatty acid. Produced PQH2 may be required for the efficient repair of PSII when PSII cannot drive photosynthetic electron transport efficiently. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to evaluate the prevalence of tethered cord among patients in the postoperative period of open and occult spina bifida. To identify warning signs for its early diagnosis, as well as outcomes after the new surgical approach. Methods: Retrospective study of patients followed at the Pediatric Neurosurgery Department of the Federal University of São Paulo with spinal dysraphism. Signs and symptoms indicating reoperation were collected, and postoperative results were classified as improved, unchanged, or worsened. Results: 222 medical records of patients diagnosed with spinal dysraphism were evaluated. Symptomatic Tethered Cord Syndrome (STCS) was identified in 30 patients (13.51%), with clinical manifestations related to orthopedic deformities (66.7%), neurological deficits (56.7%), urological dysfunction (50%), and intestinal dysfunction (40%). 20 cases underwent surgery for tethered cord release. The mean age at the time of surgery was 7.7 ± 4.9 years, with 13 female patients (65%). In the postoperative evaluation, improvement in low back pain (90.9%), urological pattern, and urinary tract infection episodes (45.4%) were particularly noteworthy. 3 patients (33.3%) with constipation showed improvement, and one worsened (11.1%). Improvement in ambulation was seen in two cases (16.7%). Low back pain was the first symptom to improve after surgery, with an average time of 1.3 months, followed by changes in the urological pattern at 15.6 months. Improvement in constipation was observed in the first month in 2 cases (66.7%), positive changes in ambulation were observed around 7 months after surgery, and only one case showed improvement in clubfoot correction. Conclusions: The prevalence of tethered cord recurrence after primary correction surgery for open or occult neural tube closure defects was similar to that found in the literature. The results were encouraging, with good postoperative evolution of patients, especially in the improvement of low back pain and urological symptoms. [ABSTRACT FROM AUTHOR]

Most of the modern natural language processing (NLP) techniques are based on the vector space models of language, in which each word is represented by a vector in a high dimensional space. One of the earliest successes was demonstrated by the four-term analogical reasoning task: what is to C as B is to A? The trained word vectors form "parallelograms" representing the quadruple of words in analogy. This discovery in NLP offers us insight into our understanding of human semantic representation of words via analogical reasoning. Despite successful applications of the large-scale language models, it has not been fully understood why such parallelograms emerge by learning through natural language data. As the vector space model is not optimized to form parallelograms, the key structure related to geometric shapes of word vectors is expected to be in the data, rather than the models. In the present article, we test our hypothesis that such parallelogram arrangement of word vectors readily exists in the co-occurrence statistics of language. Our approach focuses more on the data itself, and it is different from the existing theoretical approach trying to find the mechanism of parallelogram formation in the algorithms and/or vector arithmetic operations on word vectors. First, our analysis suggested that analogical reasoning is possible by decomposition of the bigram co-occurrence matrix. Second, we demonstrated the formation of a parallelepiped, a more structured geometric object than a parallelogram, by creating a small artificial corpus and its word vectors. With these results, we propose a refined form of distributional hypothesis pointing out an isomorphism between a sort of symmetry or exchangeability and word co-occurrence statistics. [ABSTRACT FROM AUTHOR]

Background/Objectives: Lipid metabolism and adiponectin modulate erythropoiesis in vitro and in general population studies and may also affect responsiveness to erythropoietin in patients undergoing haemodialysis (HD). However, little is known about the impact of lipid-associated biomarkers on reticulocyte production and erythropoietin resistance index (ERI) in patients undergoing HD. Therefore, we aimed to investigate their impacts in 167 stable patients undergoing HD. Methods: Pre-dialysis blood samples were collected and analysed for reticulocyte counts and serum lipid profiles by routine analyses and serum carnitine profiles (C0–C18) by LC-MS/MS. ERI was calculated as erythropoietin dose/kg/week normalized for haemoglobin levels. Results: The independent positive determinants of reticulocyte count were log [Triglyceride (TG)] and logC18:1. A large proportion of longer-chain acylcarnitines was positively correlated with reticulocyte counts, possibly resulting from the accumulation of acylcarnitines in mitochondria undergoing fateful exocytosis from reticulocytes. These results indicate a possible association between reticulocyte formation and reduced β-oxidation, which occurs during the peripheral phase of erythroblast enucleation. Total cholesterol (TC) and log [C2/(C16 + C18:1)] as a putative marker of β-oxidation efficiency were negative independent determinants of ERI. Moreover, acyl chain length had a significantly positive impact on the correlation coefficients of individual acylcarnitines with ERI, suggesting that enhanced β-oxidation may be associated with reduced ERI. Finally, adiponectin had no independent association with reticulocyte counts or ERI despite its negative association with HDL-C levels. Conclusions: Enhanced fatty acid β-oxidation and higher TC levels may be associated with lower ERI, whereas higher TG levels and longer acylcarnitines may be related to the latest production of reticulocytes in stable patients undergoing HD. [ABSTRACT FROM AUTHOR]

The present study analyzed the effect of temperature, pH, pre-treatment and mixing ratio on the anaerobic digestion process. The parameters during the anaerobic co-digestion of cow manure and food waste were then optimized using the Taguchi experimental design method. ANOVA was carried out to find the significant parameters which influence biogas production. Experimental tests were carried out at laboratory-scale reactors kept at different temperatures (28 °C, 35 °C, and 50 °C). The specific methanogenic performance (SMP) during anaerobic digestion at higher temperatures was characterized with the analysis of acetate, propionate, butyrate, hydrogen, glucose, and formate, and was validated with the literature. The improvement of biogas production with different pre-treatments, i.e., ultrasonic, autoclave, and microwave techniques, was also analyzed. The results showed that the reactor that was maintained at 35 °C showed the highest biogas production, while the reactor that was maintained at a lower temperature (28 °C) produced the lower volume of biogas. As the retention time increases, the amount of biogas production increases. Methanogenic activities of microorganisms were reduced at higher temperature conditions (65 °C). Biogas production increased by 28.1%, 20.23%, and 13.27% when the substrates were treated with ultrasonic, autoclave, and microwave, respectively, compared to the untreated substrate. The optimized condition for the highest biogas production during anaerobic co-digestion of food waste and cow manure is a temperature of 35 °C, a pH of 7 and a mixing ratio (CM:FW = 1.5:0.5). ANOVA showed that temperature is the most important input parameter affecting biogas production, followed by mixing ratio. [ABSTRACT FROM AUTHOR]

The formation of stomata presents a compelling model system for comprehending the initiation, proliferation, commitment and differentiation of de novo lineage‐specific stem cells. Precise, timely and robust cell fate and identity decisions are crucial for the proper progression and differentiation of functional stomata. Deviations from this precise specification result in developmental abnormalities and nonfunctional stomata. However, the molecular underpinnings of timely cell fate commitment have just begun to be unravelled. In this review, we explore the key regulatory strategies governing cell fate commitment, emphasizing the distinctions between embryonic and postembryonic stomatal development. Furthermore, the interplay of transcription factors and cell cycle machineries is pivotal in specifying the transition into differentiation. We aim to synthesize recent studies utilizing single‐cell as well as cell‐type‐specific transcriptomics, epigenomics and chromatin accessibility profiling to shed light on how master‐regulatory transcription factors and epigenetic machineries mutually influence each other to drive fate commitment and maintenance. Summary statement: In this review, we delve into the molecular mechanisms underlying timely and precise cell fate commitment during stomatal development. Emphasis is made on the differences between embryonic and postembryonic stomatal differentiation. We highlight recent discoveries on the transcriptional circuits that initiate and fortify stomatal fate transitions, as well as the epigenetic processes that facilitate fate commitment and maintenance. [ABSTRACT FROM AUTHOR]

During myelination, large quantities of proteins are synthesized and transported from the endoplasmic reticulum (ER)‐trans‐Golgi network (TGN) to their appropriate locations within the intracellular region and/or plasma membrane. It is widely believed that oligodendrocytes uptake neuronal signals from neurons to regulate the endocytosis‐ and exocytosis‐mediated intracellular trafficking of major myelin proteins such as myelin‐associated glycoprotein (MAG) and proteolipid protein 1 (PLP1). The small GTPases of the adenosine diphosphate (ADP) ribosylation factor (Arf) family constitute a large group of signal transduction molecules that act as regulators for intracellular signaling, vesicle sorting, or membrane trafficking in cells. Studies on mice deficient in Schwann cell–specific Arfs‐related genes have revealed abnormal myelination formation in peripheral nerves, indicating that Arfs‐mediated signaling transduction is required for myelination in Schwann cells. However, the complex roles in these events remain poorly understood. This review aims to provide an update on signal transduction, focusing on Arf and its activator ArfGEF (guanine nucleotide exchange factor for Arf) in oligodendrocytes and Schwann cells. Future studies are expected to provide important information regarding the cellular and physiological processes underlying the myelination of oligodendrocytes and Schwann cells and their function in modulating neural activity. [ABSTRACT FROM AUTHOR]

In today's globalized society, ophthalmologists can examine people of different ethnicities regardless of where they live. The frequency of disease-causing genes varies according to a patient's ethnic background. We explain genetic findings for Japanese patients with inherited eye diseases. Ocular genetics has made great advances over the past 30 years. For example, detecting mutations at nucleotide position 11778 in mitochondrial DNA was useful in the genetic diagnosis of Leber's hereditary optic neuropathy (LHON). I evaluated the genotype-phenotype relationship in cases of corneal dystrophy and inherited retinal dystrophy (IRD). I identified the entire exon sequence of the eyes shut homolog (EYS) gene in patients with autosomal recessive retinitis pigmentosa (RP). EYS gene mutations are the most frequent cause of autosomal recessive RP. RPGRIP1 may be a common causative gene with early-onset severe retinal dystrophy, including Leber congenital amaurosis. However, some genes have complex structures that are difficult to analyze, including the OPN1LW/OPN1MW gene cluster in blue cone monochromacy and the IKBKG/NEMO genes in incontinentia pigmenti. This review will also present two cases with uniparental disomy, a case of IRD with double mutations, and a case with RP complicated with LHON-like neuropathy. Precise understanding of the effects of genetic variants may reveal differences in the clinical characteristics of patients with the same variant. When starting genome medicine, accurately diagnosing the patient, making accurate prediction, determining the genetic pattern, and providing genetic counseling are important. Above all, that both the doctors and patients understand genetic diseases correctly is important. [ABSTRACT FROM AUTHOR]

Endovascular treatment has become the standard therapy for cerebral aneurysms, while the effective treatment for middle cerebral artery (MCA) bifurcation aneurysms remains a challenge. Current flow-diverting techniques with endovascular coils cover the aneurysm orifice as well as adjacent vessel branches, which may lead to branch occlusion. Novel endovascular flow disruptors, such as the Contour device (Cerus Endovascular), are of great potential to eliminate the risk of branch occlusion. However, there is a lack of valid comparison between novel flow disruptors and conventional (intraluminal) flow-diverters. In this study, two in silico MCA bifurcation aneurysm models were treated by specific Contour devices and flow-diverters using fast-deployment algorithms. Computational fluid dynamic simulations were used to examine the performance and efficiency of deployed devices. Hemodynamic parameters, including aneurysm inflow and wall shear stress, were compared among each Contour device, conventional flow-diverter, and untreated condition. Our results show that the placement of devices can effectively reduce the risk of aneurysm rupture, while the deployment of a Contour device causes more flow reduction than using flow-diverters (e.g. Silk Vista Baby). Besides, the Contour device presents the flow diversion capability of targeting the aneurysm neck without occluding the daughter vessel. In summary, the in silico aneurysm models presented in this study can serve as a powerful pre-planning tool for testing new treatment techniques, optimising device deployment, and predicting the performance in patient-specific aneurysm cases. Contour device is proved to be an effective treatment of MCA bifurcation aneurysms with less daughter vessel occlusion. [ABSTRACT FROM AUTHOR]

Management of large pediatric kidney calculi (PKC) is challenging. This study aimed to evaluate the efficacy and safety of miniature endoscopic combined intrarenal surgery (mini-ECIRS) for PKC. We retrospectively analyzed mini-ECIRS in 16 pediatric patients undergoing kidney stone treatment between November 2014 and October 2023 to determine its safety, efficacy, and associated outcomes. The median age was 50.50 (interquartile range: 36.75, 84.75) months, and the mean stone size was 21.63 ± 11.65 mm. The stone-free rate was 81.25%. The median decrease in hemoglobin level on the day after surgery was 1.10 (0.80, 1.55), and no patient required a blood transfusion. The median number of general anesthesia procedures was 2.00 (2.00, 2.00). Postoperative complications included fever in two patients and difficulty in removing the ureteral stent in one patient. In this cohort, five patients underwent pre-stenting under general anesthesia before mini-ECIRS. Age was significantly lower in the pre-stenting group than in the non-pre-stenting (P < 0.01); however, there were no significant differences in operative time, stone-free rate, total number of general anesthesia procedures, hemoglobin loss, or postoperative hospital stay between the groups. Mini-ECIRS was found to be a safe and efficient treatment method with a high stone removal rate in pediatric patients. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the safety of robot-assisted screw placement in 125 cases after introducing a spinal robotics system and to identify the situations where deviation was likely to occur. The subjects were 125 consecutive patients who underwent robotic-assisted screw placement using a spinal robotics system (Mazor X Stealth Edition, Medtronic) from April 2021 to January 2023. The 1048 screws placed with robotic assistance were evaluated. We investigated intraoperative adverse events of the robotics system and complications occurring within 30 days after surgery. We evaluated screw accuracy and deviation and compared them for vertebral levels, screw insertion methods (open traditional pedicle screw [Open-PS], cortical bone trajectory screw [CBT], percutaneous pedicle screw [PPS], and S2 alar iliac screw [S2AIS]), diagnosis, and phases of surgical cases. The deviation rate of robotic-assisted screw placement for spine surgery was 2.2%. Complications were reoperation due to implant-related neurological deficit in 0.8% and surgical site infection in 0.8%. There was significant difference in the deviation rate between vertebral levels. The deviation rate of the T1–T4 level was high at 10.0%. There was significant difference in the deviation rate between Open-PS, CBT, PPS, and S2AIS. The PPSs had a high deviation rate of 10.3%. The deviation rates were not significantly different between patients with and without deformity. The deviation rate did not change depending on the experience of surgical cases, and the deviation rate was favorable from the onset. Although the robotic-assisted screw placement was safe, we should be extra vigilant when placing screws in the upper thoracic region (deviation rate 10.0%) and when using PPSs (deviation rate 10.3%). [ABSTRACT FROM AUTHOR]

There are two dual equivalences between the ∞-category of O-monoidal ∞-categories with right adjoint lax O-monoidal functors and that with left adjoint oplax O-monoidal functors, where O is an ∞-operad. We study the space of equivalences between these two ∞-categories, and show that the two equivalences equipped with compatible O-monoidal presheaf functors are canonically equivalent. [ABSTRACT FROM AUTHOR]

Solute carrier family 26 (Slc26) is a family of anion exchangers with 11 members in mammals (named Slc26a1‐a11). Here, we identified a novel member of the slc26 family, slc26a12, located in tandem with slc26a2 in the genomes of several vertebrate lineages. BLAST and synteny analyses of various jawed vertebrate genome databases revealed that slc26a12 is present in coelacanths, amphibians, reptiles, and birds but not in cartilaginous fishes, lungfish, mammals, or ray‐finned fishes. In some avian and reptilian lineages such as owls, penguins, egrets, and ducks, and most turtles examined, slc26a12 was lost or pseudogenized. Phylogenetic analysis showed that Slc26a12 formed an independent branch with the other Slc26 members and Slc26a12, Slc26a1 and Slc26a2 formed a single branch, suggesting that these three members formed a subfamily in Slc26. In jawless fish, hagfish have two genes homologous to slc26a2 and slc26a12, whereas lamprey has a single gene homologous to slc26a2. African clawed frogs express slc26a12 in larval gills, skin, and fins. These results show that slc26a12 was present at least before the separation of lobe‐finned fish and tetrapods; the name slc26a12 is appropriate because the gene duplication occurred in the distant past. [ABSTRACT FROM AUTHOR]

Many attempts were made in recent years to create effective heat exchange devices in an effort to save energy and raw resources while also taking economic and environmental concerns into account. A compacted cooling component called a liquid-cooled microchannel heat sink was utilized to provide electronic components higher heat dissipation rates and low temperatures. In this study, the finite volume method in three dimensions was used to simulate laminar flow of water/Al2O3 nanofluid (NF) with volume fractions (φ) ranging from 0 to 4 vol% at Reynolds numbers of 50, 100, 200, and 400 in steady states inside the microchannel (MC) under the influence of a homogeneous magnetic field with Ha = 0–40. When pure water was used as the working fluid, the numerical findings demonstrated that fins increase the rate of heat transfer (HT) by a factor of four. In contrast, water-Al2O3 doubled the HT rate in the bare MC. Ansys Fluent simulation software was utilized to consider the laminar, steady state, and incompressible flow of NF with constant thermophysical characteristics. The findings indicated that Fins create the HT 3.9 times greater than the smooth MC in pure water flow. When 4% of nanoparticles were added to the base fluid in a smooth wall MC, the pressure drop (∆P) in comparison to the flow of pure water increased 1.25 times. The pressure drop in the finned MC was double that of the NF flow at the same flow condition. The maximum performance evaluation criterion (PEC) for NF flow in a smooth channel was 2. The maximum PEC in a finned MC flowing pure water is 3, whereas the maximum PEC in a finned MC flowing NF was 7.5. The fins had a significantly greater impact on HT than the magnetic field. [ABSTRACT FROM AUTHOR]

It is widely recognized that electrostatics plays a central role in the intermolecular interactions in condensed phases, as evidenced by the "electrostatics + Lennard-Jones" form of the potential functions that are commonly used in classical molecular dynamics simulations. Then, do we understand all about electrostatics in condensed phases? In this review, recent theoretical advances in relation to this topic will be discussed: (1) vibrational spectroscopic probing of the electrostatics in condensed phases, and (2) some phenomena affected by deviation from the scheme of isotropic fixed atomic partial charges, i.e., anisotropy and intermolecular transfer of electron distributions. A theoretical basis for better understanding on them and some theoretical models for practical calculations will be shown with some typical example cases of hydrogen- and halogen-bonded systems. [ABSTRACT FROM AUTHOR]

In response to the problems of high mass and high thermal resistance in traditional cold plate collectors, the author proposes a shaped and efficient micro-channel collector structure design for non-normal temperature control scenarios such as high power, multiple heat sources, and highly non-uniform power density. The author conducted numerical and experimental studies on the laminar heat transfer in a highly efficient micro-channel shaped collector for non-normal temperature control scenarios such as high power, multiple heat sources, and highly non-uniform power density, the results show that: The relative deviation between the simulated and experimental values of the pressure drop of the micro-channel collector using perfluorotriethylamine as the working fluid is within -20%, and the relative deviation between the simulated and experimental values of the surface temperature is within +3 ° C, the predicted trend of the pressure drop and temperature field of the collector is in good agreement with the experimental values, indicating the feasibility of using numerical simulation methods for performance analysis and design optimization of 3-D printed micro-channel collectors. As the flow rate increases, the pressure drop of the collector increases approximately linearly, while the value increase of the total heat transfer coefficient gradually decreases, and increasing inlet temperature or heating power will reduce pressure drop of collector and increase total heat transfer coefficient. The influence of gravity on the pressure drop and total heat transfer coefficient of micro-channel collectors is less than 1. The straight through micro-channel collector has lower pressure drop and stronger heat transfer ability compared to the folded type collector. [ABSTRACT FROM AUTHOR]

Congenital cytomegalovirus (cCMV) infection can damage the central nervous system in infants; however, its prognosis cannot be predicted from clinical evaluations at the time of birth. Urinary exosomes can be used to analyze neuronal damage in neuronal diseases. To investigate the extent of neuronal damage in patients with cCMV, exosomal miRNA expression in the urine was investigated in cCMV-infected infants and controls. Microarray analysis of miRNA was performed in a cohort of 30 infants, including 11 symptomatic cCMV (ScCMV), 7 asymptomatic cCMV (AScCMV), and one late-onset ScCMV cases, and 11 healthy controls (HC). Hierarchical clustering analysis revealed the distinct expression profile of ScCMV. The patient with late-onset ScCMV was grouped into the ScCMV cluster. Pathway enrichment analysis of the target mRNAs differed significantly between the ScCMV and HC groups; this analysis also revealed that pathways related to brain development were linked to upregulated pathways. Six miRNAs that significantly different between groups (ScCMV vs. HC and ScCMV vs. AScCMV) were selected for digital PCR in another cohort for further validation. Although these six miRNAs seemed insufficient for predicting ScCMV, expression profiles of urine exosomal miRNAs can reveal neurological damage in patients with ScCMV compared to those with AcCMV or healthy infants. [ABSTRACT FROM AUTHOR]

Human–wildlife conflict involves diverse stakeholders with conflicting values. Resolving such conflicts necessitates the development of management plans rooted in scientific knowledge and establishing of social consensus. In Nara City, situated within the Japanese Archipelago, wild sika deer (Cervus nippon) hold sacred significance due to religious reasons and have been protected for over a millennium, resulting in a distinct genetic identity. However, the escalating deer population has caused significant agricultural damage in the areas surrounding the sanctuary. Consequently, a debate has arisen regarding the advantages and disadvantages of implementing lethal measures to address individuals that might be considered sacred deer but are regarded as pests in the vicinity of the sanctuary. Here, we used mitochondrial DNA (mtDNA) control region and nuclear simple sequence repeat (SSR) markers to detect the origin of deer in the areas neighboring the sanctuary (management areas). As a result, two genetic populations of deer were detected in Nara City. In the sanctuary, we detected only one specific mtDNA haplotype (S4). On the other hand, seven haplotypes, including S4, were detected in the management area. SSR analysis also suggested that the sika deer in the management area may be an admixed population of multiple origins from the sanctuary and out of Nara City. Interbreeding populations may expand into the sanctuary, and unique genetic populations for more than 1000 years may disappear. This study suggests that ordinary deer could soon replace the deer revered and protected by the people of Nara. Additionally, the proximity of sanctuary deer to tourists worldwide and the interaction with wild deer in other areas pose a potential risk of spreading zoonotic diseases. Urgent decisions are required to determine whether to advocate for extermination in managed areas for 'conservation' purposes or risk losing the genetic identity of the sacred deer. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to clarify the learning curve for robotic-assisted spine surgery. We analyzed the workflow in robotic-assisted spine surgery and investigated how much experience is required to become proficient in robotic-assisted spine surgery. Methods: The data were obtained from consecutive 125 patients who underwent robotic-assisted screw placement soon after introducing a spine robotic system at a single center from April 2021 to January 2023. The 125 cases were divided into phases 1–5 of sequential groups of 25 cases each and compared for screw insertion time, robot setting time, registration time, and fluoroscopy time. Results: There were no significant differences in age, body mass index, intraoperative blood loss, number of fused segments, operation time, or operation time per segment between the 5 phases. There were significant differences in screw insertion time, robot setting time, registration time, and fluoroscopy time between the 5 phases. The screw insertion time, robot setting time, registration time, and fluoroscopy time in phase 1 were significantly longer than those in phases 2, 3, 4, and 5. Conclusion: In an analysis of 125 cases after the introduction of the spine robotic system, the screw insertion time, robot setting time, registration time, and fluoroscopy time were significantly longer in the 25 cases in the period initially after introduction. The times were not significantly different in the subsequent 100 cases. Surgeons can be proficient in robotic-assisted spine surgery after their experience with 25 cases. [ABSTRACT FROM AUTHOR]

Recent advancements in genome analysis technology have revealed the presence of read-through transcripts in which transcription continues by skipping the polyA signal. We here identified and characterized a new read-through transcript, TOMM40-APOE. With cDNA amplification from THP-1 cells, the TOMM40-APOE3 product was successfully generated. We also generated TOMM40-APOE4, another isoform, by introducing point mutations. Notably, while APOE3 and APOE4 exhibited extracellular secretion, both TOMM40-APOE3 and TOMM40-APOE4 were localized exclusively to the mitochondria. But functionally, they did not affect mitochondrial membrane potential. Cell death induction studies illustrated increased cell death with TOMM40-APOE3 and TOMM40-APOE4, and we did not find any difference in cellular function between the two isoforms. These findings indicated that the new mitochondrial protein TOMM40-APOE has cell toxic ability. [ABSTRACT FROM AUTHOR]

Water is essential in our daily lives, and conserving and monitoring its quality is crucial. Biological assessment is one of the methods for evaluating water quality. This study aimed at predicting the average score per taxon (ASPT), a biological assessment of the water quality index, for 109 Japanese rivers, mainly by machine learning using extreme gradient boosting and random forest. To this end, we extracted and utilized freshwater macroinvertebrate distribution data collected during 1991–2017 under the "National Census on River Environments" (NCRE) by the Ministry of Land, Infrastructure, and Transport. Five factors (average temperature, biochemical oxygen demand, elevation, slope, and human impact index) were addressed as environmental data affecting the macroinvertebrate distribution. Based on the biological data and five factors, predictive models were developed for 71 taxa used for ASPT. To confirm the accuracy of the prediction model, we compared the ASPT values that were predicted to the actual values. The actual values were within the range of the predicted values at elevations below 200 m, and the actual and predicted values diverged at elevations above 200 m, probably because 91% of the biological data used in the model were gathered at elevations lower than 200 m. Thus, the model is applicable at elevations below 200 m. This study is the first to show that it is possible to predict ASPT values for Japanese sites that have not been surveyed. These results suggest that accumulating biological data, such as NCRE data, will enable the preliminary screening of ecological predictions in freshwater areas. [ABSTRACT FROM AUTHOR]

Percutaneous chemonucleolysis with condoliase has been available for painful lumbar disc herniation since 2018 in Japan. This study investigated clinical and radiographic outcomes three months after the administration because the secondary surgical removal is most required during this period for the insufficient pain relief, and analyzed whether the differences of intradiscal injection areas affected the clinical outcomes. We retrospectively investigated 47 consecutive patients (males, 31; median age, 40 years) three months after the administration. Clinical outcomes were evaluated using the Japanese Orthopaedic Association Back Pain Questionnaire (JOABPEQ), a visual analog scale (VAS) score for low back pain, and VAS scores for pains and numbness in the lower limbs. Radiographic outcomes were analyzed in 41 patients, using parameters such as mid-sagittal disc height and maximal protrusion length of herniation on MRI preoperatively and at the final follow-up. Postoperative median evaluation period was 90 days. The effective rate of low back pain based on the pain-related disorders at baseline and the last follow-up in the JOABPEQ reached 79.5%. The postoperative proportion of VAS scores recovery ≥ 2 points and ≥ 50% for pains in the lower limbs were 80.9% and 66.0%, respectively, revealing satisfactory effectiveness. Preoperative median mid-sagittal disc height significantly reduced from 9.5 to 7.6 mm postoperatively. There were no significant differences in pain relief in the lower limbs by injection areas in the center and the dorsal 1/3rd near the herniation of nucleus pulposus. Chemonucleolysis with condoliase revealed satisfactory short-term outcomes after the administration regardless of intradiscal injection areas. [ABSTRACT FROM AUTHOR]

This study focuses on the shaft power at the neutral angle of a controllable pitch propeller to analyze the change in the required power due to propeller fouling. It is named and defined as a power for keeping propeller's rotation (RP) because a propeller does not generate the net thrust to push the hull but dissipates the power to keep its constant speed. Statistical analysis was conducted using a decade of the observed data from a research vessel. This study assumed that the change in RP can be considered as an indicator showing the state of propeller fouling. In addition, the state of fouling on the hull can be estimated indirectly based on RP because the data correlated the shaft power under several operating conditions with RP on the same voyage. The fouling state was classified into three conditions based on RP. The comparison of shaft power at the same ship speed between the clean condition and the serious fouled condition showed that the shaft power was increased by 35% on average due to fouling. When the ship navigates under 10 knots, propeller fouling has a larger impact on the increase in shaft power than hull fouling. [ABSTRACT FROM AUTHOR]

We give another proof of the fact that there is a dual equivalence between the \infty-category of monoidal \infty-categories with left adjoint oplax monoidal functors and that with right adjoint lax monoidal functors by constructing a perfect pairing between them. [ABSTRACT FROM AUTHOR]

Introduction: The bone metabolism of male endurance runners during a competitive season has been little studied. Furthermore, Japanese runners have a special competitive season. This study aimed to investigate the change of bone turnover markers (BTMs) and other hormones in Japanese male endurance runners. Materials and methods: We investigated biochemical markers, bone formation and resorption markers and sex hormones, body composition using dual-energy X-ray absorptiometry (DXA), and training volume during a competitive season. 11 (age: 24.0 ± 4.3 years) Japanese male endurance runners were analyzed in this study. They participated in all measurements three times a year: the baseline (BL), the post-track period (PT), and the road race period (RR). Results: Fat mass (FM) and percentage of body fat (% body fat) at RR (p = 0.009, p = 0.009) were lower than at BL. Specific bone alkaline phosphatase (BAP) decreased at PT (p = 0.004) and RR (p = 0.004) compared with BL. However, the bone resorption marker did not change. Free testosterone at PT (p = 0.032) was lower than BL. There was no correlation with blood variables and body composition or training volume. Conclusion: BAP and testosterone in Japanese male endurance runners decreased during the competitive season. However, there was no correlation between blood variables and training volume. [ABSTRACT FROM AUTHOR]

Leber congenital amaurosis (LCA) is the most severe form of inherited retinal dystrophy. RPGRIP1-related LCA accounts for 5–6% of LCA. We performed whole-exome sequencing and whole-genome sequencing (WGS) on 29 patients with clinically suspected LCA and examined ophthalmic findings in patients with biallelic pathogenic variants of RPGRIP1. In addition to five previously reported cases, we identified five cases from four families with compound heterozygous RPGRIP1 variants using WGS. Five patients had null variants comprising frameshift variants, an Alu insertion, and microdeletions. A previously reported 1339 bp deletion involving exon 18 was found in four cases, and the deletion was relatively prevalent in the Japanese population (allele frequency: 0.002). Microdeletions involving exon 1 were detected in four cases. In patients with RPGRIP1 variants, visual acuity remained low, ranging from light perception to 0.2, and showed no correlation with age. In optical coherence tomography images, the ellipsoid zone (EZ) length decreased with age in all but one case of unimpaired EZ. The retinal structure was relatively preserved in all cases; however, there were cases with great differences in visual function compared to their siblings and a 56-year-old patient who still had a faint EZ line. Structural abnormalities may be important genetic causes of RPGRIP1-related retinal dystrophy in Japanese patients, and WGS was useful for detecting them. [ABSTRACT FROM AUTHOR]

Hypomyelinating leukodystrophies (HLDs) represent a group of congenital rare diseases for which the responsible genes have been identified in recent studies. In this review, we briefly describe the genetic/molecular mechanisms underlying the pathogenesis of HLD and the normal cellular functions of the related genes and proteins. An increasing number of studies have reported genetic mutations that cause protein misfolding, protein dysfunction, and/or mislocalization associated with HLD. Insight into the mechanisms of these pathways can provide new findings for the clinical treatments of HLD. [ABSTRACT FROM AUTHOR]

Chlorine disinfection is commonly applied to inactivate pathogenic viruses in drinking water treatment plants. However, the role of water quality in chlorine disinfection of viruses has not been investigated thoughtfully. In this study, we investigated the inactivation efficiency of coxsackievirus B5 (CVB5) by free chlorine using actual water samples collected from four full-scale drinking water treatment plants in Japan under strict turbidity management (less than 0.14 NTU) over a 12-month period. It was found that chlorine disinfection of CVB5 might not be affected by water quality. Japanese turbidity management might play an indirect role in controlling the efficiency of chlorine disinfection. [ABSTRACT FROM AUTHOR]

The purpose of this study was to verify whether a spine robotic system was useful for junior surgeons. Twenty-seven patients underwent posterior spinal fusion with open surgery using a spine robotic system (Mazor X Stealth Edition, Medtronic Inc., Dublin, Ireland) from April to August 2021. Pedicle screw insertions were performed by five surgeons. The surgeon and insertion time were recorded for each pedicle screw. Two surgeons who are board-certified spine surgeons by the Japanese Society for Spine Surgery and Related Research (JSSR) were defined as the expert surgeon group. Three surgeons who were training to acquire qualifications as JSSR board certified spine surgeons were defined as the junior surgeon group. In postoperative CT images, the deviation of 255 pedicle screws was evaluated using the Gertzbein-Robbins (GR) grades. In the expert surgeon group, the GR grades were Grade A for 79 screws (90.8%), Grade B for 6 (6.9%), Grade C for 2 (2.3%), and 0 (0%) for Grades D and E. I In the junior surgeon group, the GR grades were Grade A for 162 screws (96.4%), Grade B for 6 (3.6%), and 0 (0%) for Grades C, D, and E. There was no significant difference in the deviation rate between surgeon groups (p = 0.08). The mean insertion times were 174.5 ± 83.0 s in the expert surgeon group and 191.0 ± 111.0 s in the junior surgeon group. There was no significant difference in the insertion time between surgeon groups (p = 0.22). There were no significant differences in the deviation rate and the insertion time of robotic-assisted pedicle screw placement between expert surgeons and junior surgeons who were training to acquire qualifications as JSSR board certified spine surgeons. Robotic-assisted pedicle screw placement can be effectively employed by junior surgeons. [ABSTRACT FROM AUTHOR]

Polymethylmethacrylate (PMMA) hollow fiber membranes are one of the synthetic polymer hollow fiber membranes used to the hollow fiber artificial kidney. A PMMA hollow fiber membrane (PMMA membrane) has unique properties including the uniform structure and the adsorption property. Hemodialyzers using PMMA membranes, Filtryzer®, were approved in Japan in 1977 and have been used worldwide for over 40 years and so is a historical hemodialyzer.Various types in Filtryzer® having different pore sizes are developed and used in the clinical field. Filtryzer® B3 is a low-flux dialyzer. Filtryzer® BK has three types having different pore sizes, and above all, BK-F has the largest pores in the Filtryzer® series. Filtryzer® BG has a more uniform membrane structure by using weak anionic polymers compared with the earlier Filtryzer® series to remove β2-MG more. Filtryzer® NF is the latest Filtryzer® series and was developed as a dialyzer having improved antithrombogenicity compared with previous models and having protein adsorption property as the same with them. There have been many reports concerning Filtryzer® including improvement of patients' symptoms such as pruritus and nutrition on the advantages for dialysis patients. Although PMMA membranes are historic dialysis tools used for over 40 years, they are also modern dialysis membranes that have been updated to respond to dialysis therapy at those time. [ABSTRACT FROM AUTHOR]

A camera captures multidimensional information of the real world by convolving it into two dimensions using a sensing matrix. The original multidimensional information is then reconstructed from captured images. Traditionally, multidimensional information has been captured by uniform sampling, but by optimizing the sensing matrix, we can capture images more efficiently and reconstruct multidimensional information with high quality. Although compressive video sensing requires random sampling as a theoretical optimum, when designing the sensing matrix in practice, there are many hardware limitations (such as exposure and color filter patterns). Existing studies have found random sampling is not always the best solution for compressive sensing because the optimal sampling pattern is related to the scene context, and it is hard to manually design a sampling pattern and reconstruction algorithm. In this paper, we propose an end-to-end learning approach that jointly optimizes the sampling pattern as well as the reconstruction decoder. We applied this deep sensing approach to the video compressive sensing problem. We modeled the spatio–temporal sampling and color filter pattern using a convolutional neural network constrained by hardware limitations during network training. We demonstrated that the proposed method performs better than the manually designed method in gray-scale video and color video acquisitions. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to elucidate the influential predictive risk factors of Osgood–Schlatter disease (OSD) on the support (non-kicking) leg among adolescent soccer players considering peak height velocity (PHV) age and investigate the cut-off values of the predictive variables. Methods: A cohort of 302 Japanese adolescent male soccer players aged 12–13 years were followed over 6 months. All players underwent physical examination, tibial tubercle ultrasonography, anthropometric and whole-body composition measurements, and muscle flexibility test of the support leg at the baseline. The developmental stage was evaluated from the PHV age. The OSD of the support leg was diagnosed 6 months later; players were divided into the OSD and control (CON) groups. The predictive risk factors were analyzed by multivariate logistic regression analysis. Results: There were 42 players who had developed OSD at baseline and they were excluded from the study. Among the 209 players, 43 and 166 belonged to the OSD and CON groups, respectively. The predictive risk factors of OSD development were PHV age ± 6 months at baseline (p = 0.046), apophyseal stage of tibial tuberosity maturity at baseline (p < 0.001), quadriceps flexibility ≥ 35° at baseline (p = 0.017), and decrease in gastrocnemius flexibility in 6 months (p = 0.009). Conclusion: PHV age ± 6 months at baseline, apophyseal stage of the tibial tuberosity at baseline, quadriceps flexibility ≥ 35° at baseline, and decrease in gastrocnemius flexibility in 6 months are predictive risk factors of OSD development in the support leg among adolescent male soccer players. It is crucial to know the PHV age of each player, and not only the flexibility of quadriceps muscle but also the gastrocnemius should be monitored to predict OSD. Level of evidence: II. [ABSTRACT FROM AUTHOR]

The proper development and function of stomata — turgor-driven valves for efficient gas-exchange and water control — impact plant survival and productivity. It has become apparent that various receptor kinases regulate stomatal development and immunity. Although stomatal development and immunity occur over different cellular time scales, their signaling components and regulatory modules are strikingly similar, and often shared. In this review, we survey the current knowledge of stomatal development and immunity signaling components, and provide a synthesis and perspectives on the key concepts to further understand the conservation and specificity of these two signaling pathways. Receptor–kinase signaling pathways in stomatal development and immunity are strikingly similar. This review highlights recent studies in both pathways that have identified the shared and unique components and suggest that potential signal crosstalk or specificity maintenance may occur in multiple levels of signal transduction. [ABSTRACT FROM AUTHOR]

Purpose: To verify whether robotics was useful for surgeons who had less experience with spinal deformity surgery. Methods: A retrospective review was conducted of 70 consecutive patients who underwent robotic-assisted pedicle screw placements with open procedures using a spine robotic system (Mazor X Stealth Edition) at a single institution from April 2021 to April 2022. Gertzbein–Robbins grades were used to assess the deviation of the 599 pedicle screws in the postoperative CT images. The rate of Grade A was considered the perfect accuracy rate, and the rate of Grades C, D, and E was calculated as the deviation rate. The perfect accuracy rate and deviation rate were compared between the spinal deformity and the non-deformity groups. The perfect accuracy rate, deviation rate, and screw insertion time were compared in the spinal deformity cases between the expert surgeon group and the less-experienced surgeon group. Results: The deviation rate of the spinal deformity group was higher than that of the non-deformity group even though there was no statistically significant difference (spinal deformity group: 2.3%, non-deformity group: 1.2%, p = 0.350). In the spinal deformity cases, there was no significant difference in the perfect accuracy rate between the expert surgeon group and the less-experienced surgeon group, but the deviation rate was significantly lower in the less-experienced surgeon group (expert surgeon group: 5.0%, less-experienced surgeon group: 0%, p = 0.008). The screw insertion time was significantly shorter in the less-experienced surgeon group. Conclusion: Robotics is particularly useful for surgeons with less experience in spinal deformity surgery. [ABSTRACT FROM AUTHOR]

Adverse ventricular remodeling after myocardial infarction (MI) is progressive ventricular dilatation associated with heart failure for weeks or months and is currently regarded as the most critical sequela of MI. It is explained by inadequate tissue repair due to dysregulated inflammation during the acute stage; however, its pathophysiology remains unclear. Tenascin-C (TNC), an original member of the matricellular protein family, is highly up-regulated in the acute stage after MI, and a high peak in its serum level predicts an increased risk of adverse ventricular remodeling in the chronic stage. Experimental TNC-deficient or -overexpressing mouse models have suggested the diverse functions of TNC, particularly its pro-inflammatory effects on macrophages. The present study investigated the roles of TNC during human myocardial repair. We initially categorized the healing process into four phases: inflammatory, granulation, fibrogenic, and scar phases. We then immunohistochemically examined human autopsy samples at the different stages after MI and performed detailed mapping of TNC in human myocardial repair with a focus on lymphangiogenesis, the role of which has recently been attracting increasing attention as a mechanism to resolve inflammation. The direct effects of TNC on human lymphatic endothelial cells were also assessed by RNA sequencing. The results obtained support the potential roles of TNC in the regulation of macrophages, sprouting angiogenesis, the recruitment of myofibroblasts, and the early formation of collagen fibrils during the inflammatory phase to the early granulation phase of human MI. Lymphangiogenesis was observed after the expression of TNC was down-regulated. In vitro results revealed that TNC modestly down-regulated genes related to nuclear division, cell division, and cell migration in lymphatic endothelial cells, suggesting its inhibitory effects on lymphatic endothelial cells. The present results indicate that TNC induces prolonged over-inflammation by suppressing lymphangiogenesis, which may be one of the mechanisms underlying adverse post-infarct remodeling. [ABSTRACT FROM AUTHOR]

This review summarizes the evidence for the management of sarcopenia in patients with rheumatoid arthritis (RA) in terms of drugs, exercise, and nutrition. Sarcopenia is a decrease in skeletal muscle mass and muscle strength or physical function. The prevalence of sarcopenia in patients with RA is higher than that in the general population. The treatment and management of sarcopenia in patients with RA are clinically important for long-term prognosis. One of the mechanisms of muscle metabolism is the pro-inflammatory cytokine pathway, which involves tumour necrosis factor α and interleukin-6, and is a common pathway in the pathogenesis of RA. Thus, tumour necrosis factor α and interleukin-6 inhibitors may play a potential role in controlling sarcopenia. In exercise therapy, a combination of moderate resistance and aerobic exercise may be effective in improving muscle strength, muscle mass, and physical function; however, intense exercise may exacerbate the inflammatory response in RA. Regarding nutrition, protein intake is generally considered beneficial, but other nutrients such as vitamin D and carotenoids have also been studied. Overall, there remains a lack of concrete evidence on sarcopenia treatment and management in patients with RA from any perspective; more longitudinal and intervention studies are needed in the future. [ABSTRACT FROM AUTHOR]

This review summarizes the evidence for the management of sarcopenia in patients with rheumatoid arthritis (RA) in terms of drugs, exercise, and nutrition. Sarcopenia is a decrease in skeletal muscle mass and muscle strength or physical function. The prevalence of sarcopenia in patients with RA is higher than that in the general population. The treatment and management of sarcopenia in patients with RA are clinically important for long-term prognosis. One of the mechanisms of muscle metabolism is the pro-inflammatory cytokine pathway, which involves tumour necrosis factor α and interleukin-6, and is a common pathway in the pathogenesis of RA. Thus, tumour necrosis factor α and interleukin-6 inhibitors may play a potential role in controlling sarcopenia. In exercise therapy, a combination of moderate resistance and aerobic exercise may be effective in improving muscle strength, muscle mass, and physical function; however, intense exercise may exacerbate the inflammatory response in RA. Regarding nutrition, protein intake is generally considered beneficial, but other nutrients such as vitamin D and carotenoids have also been studied. Overall, there remains a lack of concrete evidence on sarcopenia treatment and management in patients with RA from any perspective; more longitudinal and intervention studies are needed in the future. [ABSTRACT FROM AUTHOR]

Background: Patients with rheumatoid arthritis (RA) are prone to muscle atrophy due to inflammatory cytokines and corticosteroid use and immobility due to joint pain and deformity. Although resistance training is effective and safe in reversing muscle atrophy in RA, some patients are unable to perform a conventional high-load exercise program due to disease-related limitations. This study aims to examine the efficacy of individualized exercise therapy on physical function in elderly patients with RA who are at a high risk for sarcopenia. Methods: This study is a single-center, parallel-group, two-arm, healthcare provider- and outcome assessor-blinded, superiority randomized controlled trial with a 1:1 allocation ratio. A total of 160 participants with RA between 60 and 85 years of age with a positive screening test for sarcopenia will be included. The intervention group will receive nutritional guidance and a four-month individualized exercise program in addition to the usual treatment. The control group will receive nutritional guidance in addition to the usual care. The primary endpoint will be physical function assessed using the Short Physical Performance Battery (SPPB) at 4 months. The data on outcome measures will be collected at baseline and at the two- and four-month follow-ups. Linear mixed-effects models for repeated measures will be conducted using the modified intention-to-treat analysis population. Discussion: This study will provide evidence on whether a personalized exercise program can improve physical function and quality of life in elderly patients with RA. Some limitations include limited generalizability due to the single-center study and lack of blinding of the patients to the intervention assignment because of the nature of the exercise. Physical therapists may use this knowledge in their daily practice to improve RA treatment. Tailored exercise may enhance the health outcomes of the RA population and contribute to a reduction in healthcare costs. Trial registration: The study protocol was retrospectively registered at the University hospital Medical Information Network-Clinical Trial Repository (UMIN-CTR) (registration number: UMIN000044930, https://www.umin.ac.jp/ctr/index-j.htm) on January 4, 2022. [ABSTRACT FROM AUTHOR]

Mutations continue to accumulate within the SARS-CoV-2 genome, and the ongoing epidemic has shown no signs of ending. It is critical to predict problematic mutations that may arise in clinical environments and assess their properties in advance to quickly implement countermeasures against future variant infections. In this study, we identified mutations resistant to remdesivir, which is widely administered to SARS-CoV-2-infected patients, and discuss the cause of resistance. First, we simultaneously constructed eight recombinant viruses carrying the mutations detected in in vitro serial passages of SARS-CoV-2 in the presence of remdesivir. We confirmed that all the mutant viruses didn't gain the virus production efficiency without remdesivir treatment. Time course analyses of cellular virus infections showed significantly higher infectious titers and infection rates in mutant viruses than wild type virus under treatment with remdesivir. Next, we developed a mathematical model in consideration of the changing dynamic of cells infected with mutant viruses with distinct propagation properties and defined that mutations detected in in vitro passages canceled the antiviral activities of remdesivir without raising virus production capacity. Finally, molecular dynamics simulations of the NSP12 protein of SARS-CoV-2 revealed that the molecular vibration around the RNA-binding site was increased by the introduction of mutations on NSP12. Taken together, we identified multiple mutations that affected the flexibility of the RNA binding site and decreased the antiviral activity of remdesivir. Our new insights will contribute to developing further antiviral measures against SARS-CoV-2 infection. Author summary: Considering the emerging Omicron strain, quick characterization of SARS-CoV-2 mutations is important. However, owing to the difficulties in genetically modifying SARS-CoV-2, limited groups have produced multiple mutant viruses. Our cutting-edge reverse genetics technique enabled construction of eight reporter-carrying SARS-CoV-2 with the mutations detected in in vitro serial passages of SARS-CoV-2 in the presence of remdesivir. We confirmed that all the mutant viruses didn't gain the virus production efficiency without remdesivir treatment. We developed a mathematical model taking into account sequential changes and identified antiviral effects against mutant viruses with differing propagation capacities and lethal effects on cells. In addition to identifying the positions of mutations, we analyzed the structural changes in SARS-CoV-2 NSP12 by computer simulation to understand the mechanism of resistance. This multidisciplinary approach promotes the evaluation of future resistance mutations. [ABSTRACT FROM AUTHOR]

An energy production system that combines biomass and fuel cells produces much energy with minimal environmental impact. However, the hydrogen sulfide (H2S) contained in gasified biomass degrades fuel cell performance, thus negating the advantages of this combination. In this study, the removal of H2S by adsorption after biomass gasification was investigated. Metal oxides with high adsorption performance are common H2S adsorbents. However, they have a significant environmental impact in terms of metal depletion, which is an environmental impact indicator. Therefore, neutralized sediment materials from mine drainage treatments can be used as H2S adsorbents. A previous study found that the adsorption performance of H2S adsorbents is equivalent to that of metal oxides, especially in the high-temperature zone (300 °C), and the environmental impact is considerably lower than that of metal oxides. However, because the neutralized sediment is a powder (Φ 4.5 μm on average), there is a possibility that the gas will not flow due to the pressure drop when it is used in a large adsorption column. Therefore, in this study, we propose the use of granulated neutralized sediments for practical plant operations. No studies have investigated the adsorption performance of granulated neutralized sediment through experiments or quantitatively investigated the effect of using waste material as a H2S adsorbent to reduce the environmental impact of hydrogen production. Based on these data, the sulfur capture capacity of the granulated neutralized sediment was experimentally investigated. The extent to which the environmental impact of the hydrogen production system could be reduced when granulated neutralized sediment was used as the H2S adsorbent was assessed. Note that the granulated neutralized sediment is formed with about a Φ 0.56–1.25 mm diameter. The granulated neutralized sediment exhibited approximately 76.8% of the adsorption performance of zinc oxide (ZnO) on a conventional adsorbent. In terms of the LCA, the global warming potential (GWP) and the abiotic depletion potential (ADP) were improved by approximately 0.89% (GWP) and 55.3% (ADP) in the entire hydrogen production process. This study demonstrated that the use of waste materials can significantly reduce the environmental impact on the entire system. [ABSTRACT FROM AUTHOR]

Coronary angiography-derived wall shear stress (WSS) may enable identification of vulnerable plaques and patients. A new recently introduced software allows seamless three-dimensional quantitative coronary angiography (3D-QCA) reconstruction and WSS computation within a single user-friendly platform carrying promise for clinical applications. This study examines for the first time the efficacy of this software in detecting vulnerable lesions in patients with intermediate non-flow limiting stenoses. This multicentre retrospective study included patients who had coronary angiography showing at least one lesion with borderline negative fractional flow reserve (FFR: 0.81–0.85). In these lesions, 3D-QCA reconstruction and blood flow simulation were performed using the CAAS Workstation WSS prototype (Pie Medical Imaging, Maastricht, Netherlands). Time averaged and multidirectional WSS were extracted across the lesion at every 3 mm segments. The primary endpoint of the study was lesion-oriented clinical events (LOCE), defined as the composite of cardiac death, target lesion related myocardial infarction (MI) or clinically indicated target lesion revascularization. 352 patients (355 lesions) were included in the analysis. Over a median follow-up of 4.1 years, 57 LOCE were recorded. Lesions causing events had a larger area stenosis (AS) [59.4 (54.6–67.7)% vs 52.8 (43.8–60.1)%, p < 0.001], maximum time averaged WSS (TAWSS) [11.56 (8.25–13.64)Pa vs 7.73 (5.41–11.51)Pa, p < 0.001], mean TAWSS at the minimum lumen area (MLA) [9.30 (5.44–11.94)Pa vs 6.19 (3.96–9.00)Pa, p < 0.001] and maximum transverse WSS [0.30 (0.21–0.45)Pa vs 0.23 (0.17–0.32)Pa, p= 0.002] than those remaining quiescent. In multivariable models, AS was the only independent predictor of LOCE. Kaplan-Meier curves demonstrated that lesions with elevated maximum TAWSS and AS had a higher rate of LOCE than those with low TAWSS and AS values (26 % vs 7 %, p < 0.001). For non-flow limiting lesions with borderline negative FFR, fast WSS computation using a dedicated software is feasible and holds potential for cardiovascular risk stratification. [Display omitted] [ABSTRACT FROM AUTHOR]