Search

Background: Infants aged <1 year with confirmed food allergies generally need to avoid causative foods completely for a certain period. Low‐dose oral food challenges (LD‐OFCs) may be an effective strategy for safely introducing small amounts of causative foods to individuals with food allergies. This study clarified the safety of LD‐OFCs in infants aged <1 year with food allergies. Methods: We retrospectively analyzed the clinical records of LD‐OFCs performed in infants aged <1 year allergic to hen's egg, cow's milk, or wheat between April 2014 and October 2017. Approximately 1/25th–1/20th of the egg white from a heated whole hen's egg, 3 mL heated cow's milk, and 2 g wheat noodles (udon) were used as challenge foods. We examined the LD‐OFC results, including the induced symptoms and treatment required for positive LD‐OFC results. Results: The LD‐Egg, LD‐Milk, and LD‐Wheat OFC groups comprised 68, 42, and 13 participants, respectively. The positivity rates for the LD‐Egg, LD‐Milk, and LD‐Wheat OFC groups were 7%, 24%, and 0%, respectively. Patients predominantly exhibited skin symptoms, and most were treated with oral antihistamines alone. None of the patients experienced anaphylaxis or required adrenaline injections. Conclusions: Infants aged <1 year with food allergies can safely undergo LD‐OFCs by consuming low doses of causative foods. Avoiding the complete elimination of causative foods is an important strategy for managing infants with food allergies when initially introducing causative foods. [ABSTRACT FROM AUTHOR]

Local translation in growth cones plays a critical role in responses to extracellular stimuli, such as axon guidance cues. We previously showed that brain-derived neurotrophic factor activates translation and enhances novel protein synthesis through the activation of mammalian target of rapamycin complex 1 signaling in growth cones of dorsal root ganglion neurons. In this study, we focused on 40S ribosomal protein S6 (RPS6), 60S ribosomal protein P0/1/2 (RPP0/1/2), and actin filaments to determine how localization of ribosomal proteins changes with overall protein synthesis induced by neurotrophins. Our quantitative analysis using immunocytochemistry and super-resolution microscopy indicated that RPS6, RPP0/1/2, and actin tend to colocalize in the absence of stimulation, and that these ribosomal proteins tend to dissociate from actin and associate with each other when local protein synthesis is enhanced. We propose that this is because stimulation causes ribosomal subunits to associate with each other to form actively translating ribosomes (polysomes). This study further clarifies the role of cytoskeletal components in local translation in growth cones. Schematic representation of ribosomal protein localization in the the growth cone. a Ribosomal proteins RPS6 and RP0/1/2 are associated with actin in the absence of stimulation. b Upon stimulation by neurotrophins, these two subunit proteins dissociate from actin and bind to each other to form the 80S ribosome initiation complex [ABSTRACT FROM AUTHOR]

The credibility of public versus private threats in international crisis bargaining has received scholarly attention. While public threats are often believed to be more credible than private ones because of audience costs, others contend that private threats should be equally credible or even more. Also, the effect of public threats can be conditioned by other domestic factors such as domestic hawkishness and a leader's unpopularity. To test these competing expectations, I conducted a conjoint survey experiment that examines how observers assess resolve to fight in an international crisis with a sample of US citizens (N  = 1,203). Three major findings stand out. First, evidence suggests that both types of threats increase the perceived likelihood that a country will stand firm. Second, though their effect size is small, public threats are more effective than private ones. Lastly, I find support for the conditional effect of public threats, indicating that the underlying mechanism of the credibility of public threats is domestic audience costs. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to investigate treatment options for older women with pelvic organ prolapse (POP) and postoperative outcomes based on their long‐term care (LTC) status. Methods: We used the medical and LTC insurance claims databases of Tochigi Prefecture in Japan, covering 2014 to 2019. We included women 65 years and older with POP and evaluated their care status and treatment, excluding women with an observation period <6 months. Among women with a postsurgical interval ≥6 months, we compared care level changes and deaths within 6 months and complications within 1 month postoperatively between those with and without LTC using Fisher exact test. Results: We identified 3406 eligible women. Of the 447 women with LTC and 2959 women without LTC, 16 (3.6%) and 415 (14.0%), respectively, underwent surgery. Among 393 women with a postsurgical interval ≥6 months, 19 (4.8%) required LTC at surgery. Two of the 19 women with LTC (10.5%) and eight of 374 women without LTC (2.1%) experienced worsening care–needs level. No deaths were recorded. Urinary tract infection (UTI) was significantly more frequent in women with LTC than in women without LTC (36.8% vs 8.6%). Other complications were rare in both groups. Conclusion: The proportion of patients who underwent surgery for POP was lower in women with LTC than in women without LTC. Postoperative UTI was common and 11% had a worsening care–needs level postoperatively, whereas other complications were infrequent. Further detailed studies would contribute to providing optimal treatment to enhance patients' quality of life. Synopsis: The proportion of patients who underwent surgery for pelvic organ prolapse was low in women requiring long‐term care. Postoperative urinary tract infection was common in this patient population. [ABSTRACT FROM AUTHOR]

Blood lactate concentration during exercise is a reliable indicator of energy metabolism and endurance performance. Lactate is also present in sweat, and sweating plays an important role in thermoregulation, especially in hot conditions. Recently, wearable sensors have enabled the real-time and noninvasive measurement of sweat lactate concentration, potentially serving as an alternative indicator of blood lactate response. However, the evidence regarding the relationship between sweat and blood lactate responses during incremental exercise in hot conditions is lacking. In a randomized cross-over design, six highly trained male runners completed two incremental treadmill tests under normal (20°C/50%RH) or hot (30°C/50%RH) conditions. The tests include 3-min running stages and 1-min recovery, starting at 12 km/h and increasing by 1 km/h at each stage. Blood and sweat lactate concentrations were measured at each stage to determine blood and sweat lactate thresholds (LT). Blood lactate concentrations were higher under hot conditions (p < 0.01), but there was no difference in the response pattern or velocity at blood LT between conditions. Significant early increase (p < 0.01) in sweat lactate and low velocity at sweat LT (p < 0.05) were observed under hot conditions. A significant correlation between blood and sweat lactate concentrations was found under normal conditions (p < 0.001) but not under hot conditions, and no significant correlations were observed between the velocity at blood and sweat LT. In conclusion, sweat lactate concentration does not consistently reflect blood lactate concentration during incremental exercise. [ABSTRACT FROM AUTHOR]

Emerging infectious diseases, cancer, and other diseases are quickly tested mainly via immune reactions based on specific molecular recognition between antigens and antibodies. By changing the diameter of solid-state pores, biomolecules of various sizes can be rapidly detected at the single-molecule level. The combination of immunoreactions and solid-state pores paves the way for an efficient testing method with high specificity and sensitivity. The challenge in developing this method is achieving quantitative analysis using solid-state pores. Here, we demonstrate a method with a low limit of detection for testing tumor markers using a combination of immunoreactions and solid-state pore technology. Quantitative analysis of the mixing ratio of two and three beads with different diameters was achieved with an error rate of up to 4.7%. The hybrid solid-state pore and immunoreaction methods with prostate-specific antigen (PSA) and anti-PSA antibody-modified beads achieved a detection limit of 24.9 fM PSA in 30 min. The hybrid solid-state pore and immunoreaction enabled the rapid development of easy-to-use tests with lower limit of detection and greater throughput than commercially available immunoassay for point-of-care testing. [ABSTRACT FROM AUTHOR]

Cysteinyl RGD-peptidyl cysteinyl prolyl esters, which have different configurations at the cysteine and proline residues, were synthesized by the solid-phase method and cyclized by the native chemical ligation reaction. Cyclization efficiently proceeded to give cyclic peptides, regardless of the difference in the configuration. The peptides were further derivatized to the corresponding desulfurized or methylated cyclic peptides at the Cys residues. The inhibition activity to avp6 integrin binding was then analyzed by ELISA. The results showed that the activity varied depending on the difference in the configuration and modification of the cysteinyl prolyl ester (CPC) moiety, demonstrating the usefulness of this method in the search for a good inhibitor of the protein-protein interaction. [ABSTRACT FROM AUTHOR]

Transposable elements (TEs) contribute to plant evolution, development, and adaptation to environmental changes, but the regulatory mechanisms are largely unknown. RNA-directed DNA methylation (RdDM) is 1 TE regulatory mechanism in plants. Here, we identified that novel ARGONAUTE 1 (AGO1)-binding Tudor domain proteins Precocious dissociation of sisters C/E (PDS5C/E) are involved in 24-nt siRNA production to establish RdDM on TEs in Arabidopsis thaliana. PDS5 family proteins are subunits of the eukaryote-conserved cohesin complex. However, the double mutant lacking angiosperm-specific subfamily PDS5C and PDS5E (pds5c/e) exhibited different developmental phenotypes and transcriptome compared with those of the double mutant lacking eukaryote-conserved subfamily PDS5A and PDS5B (pds5a/b), suggesting that the angiosperm-specific PDS5C/E subfamily has a unique function in angiosperm plants. Proteome and imaging analyses revealed that PDS5C/E interact with AGO1. The pds5c/e double mutant had defects in 24-nt siRNA accumulation and CHH DNA methylation on TEs. In addition, some lncRNAs that accumulated in the pds5c/e mutant were targeted by AGO1-loading 21-nt miRNAs and 21-nt siRNAs. These results indicate that PDS5C/E and AGO1 participate in 24-nt siRNA production for RdDM in the cytoplasm. These findings indicate that angiosperm plants evolved a new regulator, the PDS5C/E subfamily, to control the increase in TEs during angiosperm evolution. A subfamily of Tudor domain proteins participates in 24-nucleotide small interfering RNA production to establish RNA-directed DNA methylation on transposable elements. [ABSTRACT FROM AUTHOR]

Background: Stump appendicitis—a rare, delayed complication of appendectomy—is most commonly managed with surgical exploration and stump appendectomy. Conservative management in the pediatric population is poorly characterized in the literature. Case Report: We report a case of a 10-year-old male who was diagnosed with stump appendicitis and initially treated nonoperatively. He received intravenous antibiotics and supportive therapy while in the hospital, was discharged on a course of oral antibiotics, and remained asymptomatic for the following 9 weeks until he underwent an elective interval stump appendectomy. We also review the literature on this uncommon condition and treatment plan. Conclusion: Considering stump appendicitis in the differential of children with history of appendectomy is imperative. Nonoperative management of stump appendicitis may be successful and beneficial in select pediatric cases compared to the standard surgical management. [ABSTRACT FROM AUTHOR]

Mycobacteroides (Mycobacterium) abscessus, which causes a variety of infectious diseases in humans, is becoming detected more frequently in clinical specimens as cases are spreading worldwide. Taxonomically, M. abscessus is composed of three subspecies of M. abscessus subsp. abscessus, M. abscessus subsp. bolletii, and M. abscessus subsp. massiliense, with different susceptibilities to macrolides. In order to identify rapidly these three subspecies, we determined useful biomarker proteins, including ribosomal protein L29, L30, and hemophore-related protein, for distinguishing the subspecies of M. abscessus using the matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) profiles. Thirty-three clinical strains of M. abscessus were correctly identified at the subspecies-level by the three biomarker protein peaks. This study ultimately demonstrates the potential of routine MALDI-MS-based laboratory methods for early identification and treatment for M. abscessus infections. [ABSTRACT FROM AUTHOR]

Purpose: The present study investigated potential access vessels in patients receiving hemodialysis who underwent surgical aortic valve replacement and determined which approaches were most suitable for performing transcatheter aortic valve implantation. Methods: Consecutive patients undergoing hemodialysis with aortic valve stenosis who underwent surgical aortic valve replacement were included. Preoperative computed tomography data were analyzed to assess the vessel diameter and calcification. Simulations were conducted to determine the feasibility of inserting the 14-F eSheath of Sapien 3 via transfemoral, trans-cervical, trans-subclavian, and direct aorta approaches. Results: A total of 72 patients were included in this study. The access route was characterized by severe calcification of the common iliac artery. The transfemoral approach was feasible in 77.8% of the cases, but the rate decreased to 33% when the calculations were based on the maximum sheath extension diameter. The trans-cervical, trans-subclavian, and direct aortic approaches were suitable for many patients. Lower extremity artery disease was identified as a risk factor for the unsuitability of the transfemoral approach. Conclusions: Common iliac artery calcification in patients undergoing hemodialysis restricts the use of the transfemoral approach. Therefore, some patients require alternative approaches. [ABSTRACT FROM AUTHOR]

Summary: Group 2 Innate Lymphoid Cells (ILC2s) are innate lymphocytes involved in type 2 immunity. ILC2s are abundant at the barrier tissues and upon allergen exposure, respond to epithelial‐derived alarmins by producing type 2 cytokines (e.g., IL‐5 and IL‐13). Upon activation, some of these activated ILC2s acquire immunological memory and can mount enhanced responses upon further allergen encounters. Here, we review recent findings of the cellular and molecular mechanisms underlying immune memory in ILC2s both in mice and humans and discuss the implications of memory ILC2s in the context of allergic diseases. [ABSTRACT FROM AUTHOR]

As the number of articles on postsecondary topics expands, new methods are required to quantitatively understand the literature. Previous scholars looking at the higher education literature use manual coding, which limits the number of years that can be studied, or network analysis of citations and words, which does not yield groupings of articles by topic area. Instead, we use topic modeling to understand the subject areas that scholars investigate, as well as changes in these subject areas over time. Topic modeling assumes that a group of abstracts contains a mix of topics that are hidden (or latent) because we can only observe abstracts and the words that appear within abstracts, but not the underlying topics. Each abstract and word are then viewed as having a probability of belonging to a topic or subject area. Our data consist of abstracts from the set of articles published in The Journal of Higher Education, Research in Higher Education, and Review of Higher Education between 1991 and 2020. We find 24 main topics in the postsecondary literature in the past three decades. The most common topics in the literature during the past three decades are research usage and research methodology (18%), followed by college access (9%), identities and experiences (9%), student engagement (9%), and academic careers (8%). The research topics that became more popular over time are all student related: identities and experiences, college access, financial aid, student experiences with diversity, and student success. Topics that became less popular over time include academic misconduct, research usage and research methodology, and academic careers. [ABSTRACT FROM AUTHOR]

Information regarding Klebsiella aerogenes haboring carbapenemase in Japan is limited. A comprehensive nationwide survey was conducted from September 2014 to December 2022, and 67 non-duplicate strains of carbapenem-resistant K. aerogenes were isolated from 57 healthcare facilities in Japan. Through genetic testing and whole-genome sequencing, six strains were found to possess carbapenemases, including imipenemase (IMP)-1, IMP-6, New Delhi metallo-β-lactamase (NDM)-1, and NDM-5. The strain harboring blaNDM-5 was the novel strain ST709, which belongs to the clonal complex of the predominant ST4 in China. The novel integron containing blaIMP-1 featured the oxacillinase-101 gene, which is a previously unreported structure, with an IncN4 plasmid type. However, integrons found in the strains possessing blaIMP-6, which were the most commonly identified, matched those reported domestically in Klebsiella pneumoniae, suggesting the prevalence of identical integrons. Transposons containing blaNDM are similar or identical to the transposon structure of K. aerogenes harboring blaNDM-5 previously reported in Japan, suggesting that the same type of transposon could have been transmitted to K. aerogenes in Japan. This investigation analyzed mobile genetic elements, such as integrons and transposons, to understand the spread of carbapenemases, highlighting the growing challenge of carbapenem-resistant Enterobacterales in Japan and underscoring the critical need for ongoing surveillance to control these pathogens. [ABSTRACT FROM AUTHOR]

Mesoporous silica-alkali earth (Mg, Ca, or Sr) hybrids were prepared from waste glass as a silica source. Mesoporous silica containing no alkali earth succeeded in preparing a perfect pore structure arranged hexagonally. On increasing the alkali-earth element, mesoporous structures are preserved on a small amount of the alkali-earth element as a substituent and tend to diminish with an increase in the substituent, reducing the surface area. We examined a scale-up experiment for the production of a large amount of hybrids. The scale-up system factor we proposed was relatively small, indicating relatively high production efficiency. The hybrids were also examined for the ion-exchangeability of rare-earth metals. The tendency of the amount for ion-exchange showed a positive convex tetrad effect, which means a decrease in the ionicity of the rare-earth metals during an exchange. Since XANES spectra confirm the trivalent state of each rare-earth metal in ion-exchanged hybrids, the rare-earth metals are found to exchange from the alkali-earth elements because the exchanged amount is 2/3 of the alkaliearth element leached. [ABSTRACT FROM AUTHOR]

This study provides the quantitative assessment of the effect of melt on the polycrystal anelasticity by grain boundary sliding, which is necessary to evaluate the effect of melt on seismic wave velocity and attenuation. We measured elasticity, anelasticity, and viscosity of rock analog samples by changing temperature continuously from subsolidus to supersolidus. Our previous studies have shown that when homologous temperature exceeds 0.9, anelastic relaxation by grain boundary sliding is significantly enhanced, probably due to the increase in grain boundary disorder called pre‐melting. In this study, we found that when homologous temperature exceeds 1, grain boundary sliding is further enhanced by melt and that the viscoelastic property at supersolidus temperatures shows the combined total effect of disordered grain boundaries and melt. The relaxation strength due to melt depends on melt fraction, while that due to disordered grain boundaries does not. When melt fraction is very small (≪1%), the melt effect is negligibly small and the effect of disordered grain boundaries is dominant. Based on these experimental results, we present a new viscoelasticity model seamlessly applicable for a broad temperature range from subsolidus to supersolidus temperatures and for a broad frequency range from seismic waves to geodetic deformation. The new model covers an upper mantle region where a moderate amount of melt exists (e.g., near subduction zones). We further compare our data with those of rock samples and infer that a common physical mechanism, subsolidus and supersolidus enhancements on grain boundary sliding, may be dominant in these two data sets. Plain Language Summary: Low seismic velocity and high attenuation are observed beneath volcanoes where a certain amount of melt may be present. However, quantitative analyses of such seismic anomalies are still difficult. This is because the effect of melt on rock anelasticity, which causes velocity dispersion and attenuation of seismic waves, is not well understood due to insufficient experimental data. This study investigated the effect of melt on polycrystal anelasticity by using binary organic aggregates as rock analog in laboratory experiments. Our previous studies have shown that anelastic relaxation by the grain boundary sliding mechanism is significantly enhanced at near solidus temperatures probably due to the increase in grain boundary disorder called premelting. This study shows that grain boundary sliding is further enhanced by melt and that the effect of melt systematically increases with increasing melt fraction. We combine the present result with our previous data and present a new model of viscoelasticity which is seamlessly applicable from subsolidus to supersolidus temperatures. We further compare the anelasticity data from the present analog samples with those of rock samples. The two data sets are similar, suggesting a common anelastic mechanism between these polycrystalline materials. Key Points: We assess the effect of melt on grain boundary sliding and develop a model of viscoelasticity seamlessly applicable across the solidusA very small amount of melt has a negligibly small effect on polycrystal viscoelasticityAnelasticity of partially molten rock and rock analog commonly shows the combined total effect of disordered grain boundaries and melt [ABSTRACT FROM AUTHOR]

This study aimed to determine the safety, feasibility, and acceptability of physiotherapy (PT) combined with strength training using active video games (AVG) for older patients with musculoskeletal conditions. Sixteen patients underwent AVG + PT on day 1 and only conventional physiotherapy (CPT) on day 2. The AVG was conducted in 6 upper- and lower-limb training performed in standing position using Ring Fit Adventure (RFA) on Nintendo Switch. Outcome measured adverse events and deviant movements associated with the AVG as safety, execution rate of each AVG programme as feasibility, and questionnaires (4-point Likert scale) regarding enjoyment, motivation to continue, and feeling of efficacy as acceptability. The berg balance scale/functional independence measure indicated 45 ± 8/90 ± 16. No adverse events occurred. Some of deviant movements were observed that could be an injury risk, such as a slight forward movement during the stepping exercise. The execution rate for each AVG programme ranged from 81% to 100%. The categories of enjoyment, motivation to continue, and feeling of efficacy had >90% of positive responses (strongly agree, slightly agree) in AVG + PT, and enjoyment tended to be higher in AVG + PT than in CPT. Strength training using RFA was considered to be a safe and feasible exercise tool enough to be applicable as part of a rehabilitation programme in older patients with musculoskeletal conditions. However, should be supervised, at least during the introductory phase. It was also positively accepted by older adults, suggesting enhanced enjoyment. Active video games (AVG) training with Ring Fit Adventure (RFA) was found to be safe enough to be considered for application as part of a rehabilitation programme for older patients with musculoskeletal conditions, but should be supervised, at least during the introductory phase. AVG training comprising strength training with RFA was found to be a highly feasible exercise tool for rehabilitation in older patients with musculoskeletal conditions. Physiotherapy combined with AVG training using RFA was also well received, suggesting enhanced enjoyment for older patients with musculoskeletal conditions. [ABSTRACT FROM AUTHOR]

Hypoxic exercise, which can induce arterial and tissue deoxygenation, promotes physiological adaptations. However, reduced oxygen availability can lower the absolute training intensity (i.e., mechanical stress). Adding normoxic recovery to sprint interval exercise (SIE) is one potential approach to strike a balance between providing a hypoxic stimulus and maintaining the absolute training intensity. However, the effects of adding normoxic recovery to SIE on performance and physiological responses are uncertain. We tested the hypothesis that hypoxic SIE with normoxic recovery enhances arterial deoxygenation and muscle deoxygenation levels without impeding performance compared to an entirely normoxic condition. On separate days, seven male sprinters performed 4 × 30‐s 'all‐out' cycle sprints with 4.5‐min recovery with hypoxic exposure (FiO2: 12.7%O2) applied continuously (hypoxia, HYP), intermittently during sprint periods only (intermittent, INT), or not at all (normoxia, NOR). Power output, oxygen saturation, muscle oxygenation, surface electromyography (EMG) activity, heart rate, blood lactate concentration, and ratings of perceived exertion were measured. The total work significantly decreased in HYP than NOR (p < 0.05) and INT (p < 0.01). The aTrterial oxygen saturation was lower during HYP than NOR (∼86% vs. ∼97%; p < 0.001), while lower values were also obtained for INT than NOR during sprint periods (∼85% vs. ∼97%; p < 0.001) but not during recovery periods (∼96% vs. ∼97%). The heart rate differed (p < 0.05) between conditions (NOR: ∼164 bpm; INT: ∼160 bpm; HYP: ∼156 bpm). No other variables demonstrated significant differences between conditions. Adding hypoxia during exercise while recovering in normoxia did not compromise exercise capacity during SIE, despite inducing larger arterial deoxygenation levels compared to normoxia. Highlights: Utilizing severe hypoxia during exercise and normoxia during recovery induces a substantial hypoxic stimulus while safeguarding mechanical performance in sprinters.This approach maintains neuromuscular, metabolic, and perceptual parameters without any detrimental effects, ensuring athletes can perform at their best.Alternating hypoxia and normoxia during active and passive phases shows potential for optimizing hypoxic training, striking an ideal balance between the hypoxic stimulus and training intensity and load. [ABSTRACT FROM AUTHOR]

In Japan, the switch from branded to generic infusion fluids has been promoted as a national policy. Recently, as generic products have been in short supply, the switch from generic to branded infusion fluids has increased. However, certain additives for injectable infusion fluids, such as nonvolatile acids like acetic acid and hydrochloric acid, are not required to be listed in the package insert. We hypothesized that the addition of nonvolatile acids may be one of the reasons for the differences in physicochemical properties between the branded and generic infusion fluids. We have previously reported that in other types of electrolyte infusion fluids, a variation in pH can cause incompatibility with other drugs, and variation in titratable acidity and osmolality can lead to phlebitis. Glucose-added maintenance hypotonic infusion fluid (listed as type-3G) is commonly used as a maintenance solution when energy support is needed. However, nonvolatile acid is added to prevent the caramelization of glucose, resulting in higher osmolality and titratable acidity and lower pH. Therefore, we hypothesized that both phlebitis and incompatibility with other drugs are likely to occur; hence, we measured and evaluated the physicochemical properties of branded and generic type-3G infusion fluids. We show that the osmolality, pH, and titratable acidity of all evaluated branded and generic products differed significantly and that these properties should be evaluated together to avoid phlebitis and incompatibility with other drugs when switching between branded and generic type-3G infusion fluids. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the efficacy and safety of hydroxychloroquine (HCQ) in patients with rheumatoid arthritis (RA). Methods: Patients with active RA, despite conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), were recruited. HCQ was administered for 24 weeks, in addition to prior treatment. The primary end-point was the proportion of patients achieving American College of Rheumatology (ACR) 20 at Week 24, compared to that of a propensity score–matched historical control group. Results: Sixty patients were enrolled and administered HCQ. We also identified 276 patients as candidates for the historical control group. Propensity score matching yielded 46 patients in each group. The proportion of patients achieving ACR20 at Week 24 was significantly higher in the HCQ group than in the control group (54.4% vs. 28.3%, P = .007). The proportion of patients achieving ACR50 and ACR70 at Week 24 were also higher in the HCQ group than in the control group (ACR50, 30.4% vs. 4.3%, P = .006; ACR70, 17.4% vs. 0%, P = .005). Neither HCQ retinopathy nor any new safety signal was observed during the study. Conclusion: The addition of HCQ to csDMARDs was effective, with no new safety signal in patients with RA. [ABSTRACT FROM AUTHOR]

Simple Summary: Although body composition-related biomarkers are associated with the prognosis of patients with cancer, whether they are associated with the therapeutic effects of immune checkpoint inhibitors remains unclear. We found that among body composition-related biomarkers, sarcopenia based on skeletal muscle mass was strongly associated with the treatment efficacy of immune checkpoint inhibitors in patients with metastatic renal cell carcinoma. However, body composition-related biomarkers based on subcutaneous or visceral fat were not associated with treatment efficacy. The skeletal muscle releases myokines to activate the immune system. Therapeutic interventions for sarcopenia may not only improve patients' quality of life but also improve the therapeutic effects of immune checkpoint inhibitors and prolong the prognosis of patients. Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic renal cell carcinoma (mRCC); however, validating body composition-related biomarkers for their efficacy remains incomplete. We evaluated the association between body composition-related markers and the prognosis of patients with mRCC who received ICI-based first-line therapies. Patients and Methods: We retrospectively investigated 60 patients with mRCC who underwent ICI-based therapy as their first-line treatment between 2019 and 2023. Body composition variables, including skeletal muscle, subcutaneous fat, and visceral fat indices, were calculated using baseline computed tomography scans. Sarcopenia was defined according to sex-specific cut-off values of the skeletal mass index. The associations between body composition indices and objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated. Results: Patients with sarcopenia had lower ORR and DCR than those without sarcopenia (33.3% vs. 61.1%, p = 0.0436 and 52.4% vs. 94.4%, p = 0.0024, respectively). Patients with sarcopenia had a significantly shorter median PFS (14 months vs. not reached, p = 0.0020) and OS (21 months vs. not reached, p = 0.0023) than patients without sarcopenia did. Sarcopenia was a significant predictor of PFS (hazard ratio [HR], 4.31; 95% confidence interval [CI], 1.65–14.8; p = 0.0018) and OS (HR, 5.44; 95% CI, 1.83–23.4; p = 0.0013) along with poor IMDC risk. No association was found between the subcutaneous, visceral, and total fat indices and the therapeutic effect of ICI-based therapy. Conclusions: Sarcopenia was associated with a lower response and shorter survival rates in patients with mRCC who received first-line ICI-based therapy. [ABSTRACT FROM AUTHOR]

We visualized a dynamic process of fatty acid uptake of brown adipocytes using a time-lapse ultra-broadband multiplex coherent anti-Stokes Raman scattering (CARS) spectroscopic imaging system with an onstage incubator. Combined with the deuterium labeling technique, the intracellular uptake of saturated fatty acids was traced up to 9 h, a substantial advance over the initial multiplex CARS system, with an analysis time of 80 min. Characteristic metabolic activities of brown adipocytes, such as resistance to lipid saturation, were elucidated, supporting the utility of the newly developed system. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is associated with coagulopathy. However, the underlying mechanisms are not completely understood. We evaluated the association between COVID-19 coagulopathy and extracellular vesicle (EV) levels. We hypothesized that several EV levels would be higher in COVID-19 coagulopathy patients than in non-coagulopathy patients. This prospective observational study was conducted in four tertiary care faculties in Japan. We enrolled 99 COVID-19 patients (48 with coagulopathy and 51 without coagulopathy) aged ≥20 years who required hospitalization, and 10 healthy volunteers; we divided the patients into coagulopathy and non-coagulopathy groups according to the D-dimer levels (≥1 μg/mL and <1 μg/mL, respectively). We used flow cytometry to measure the tissue-factor-bearing, endothelium-derived, platelet-derived, monocyte-derived, and neutrophil-derived EV levels in platelet-free plasma. The EV levels were compared between the two COVID-19 groups as well as among the coagulopathy patients, non-coagulopathy patients, and healthy volunteers. No significant difference was found in EV levels between the two groups. Meanwhile, the cluster of differentiation (CD) 41 + EV levels were significantly higher in COVID-19 coagulopathy patients than in healthy volunteers (549.90 [255.05–984.65] vs. 184.3 [150.1–254.1] counts/µL, p = 0.011). Therefore, CD41+ EVs might play an essential role in COVID-19 coagulopathy development. [ABSTRACT FROM AUTHOR]

Background. Previous reports have revealed various endovascular intervention techniques for prosthetic femoropopliteal bypass occlusion (PFPBO); however, treatment for PFPBO remains challenging for most interventionalists and vascular surgeons because the procedure is complicated. Most of the reported techniques involve device implantation. In the present study, we performed a combination of surgical graft thrombectomy and drug-coated balloon angioplasty for PFPBO without implanting any additional devices. Furthermore, we determined the favorable long-term results of this treatment using follow-up angiography. Case Presentation. A 77-year-old man with a history of chronic kidney disease and coronary artery disease presented to our clinic with rest pain on his left leg. Seven years prior to the current consult, he underwent femoropopliteal bypass (FPB) surgery using a prosthetic graft due to in-stent occlusion of the left superficial femoral artery (SFA). Four years after surgery, a duplex ultrasound scan revealed stenosis of the proximal anastomosis site; hence, medical therapy was continued. On the current consult, diagnostic angiography revealed occlusion of the FPB and infrapopliteal vessels. In the first attempt at recanalization, the guidewire was unable to pass through the occluded SFA. Therefore, another technique was performed to revascularize the FPBO and infrapopliteal vessels. We obtained an angiography of the left leg after inserting the guiding sheath via the right common femoral artery (CFA). First, surgical thrombectomy using a Fogarty catheter via the exposed left CFA was performed. Following endovascular therapy via the right CFA, we performed drug-coated balloon angioplasty for anastomotic stenosis and recanalized occlusive infrapopliteal vessels. Restenosis was not observed on follow-up angiograms. On further follow-up angiography, there was notable regression of the residual stenosis at the proximal anastomosis of the prosthetic graft. Conclusion. This novel revascularization strategy may be a viable treatment option for PFPBO. [ABSTRACT FROM AUTHOR]

Dendritic cell (DC)-based immunotherapy has been applied to glioblastoma (GBM); however, biomarkers informing response remain poorly understood. We conducted a phase I/IIa clinical trial investigating tumor-fused DC (TFDC) immunotherapy following temozolomide-based chemoradiotherapy in patients with newly diagnosed GBM and determined prognostic factors in patients receiving TFDC immunotherapy. Twenty-eight adult patients with GBM isocitrate dehydrogenase (IDH) wild-type (IDH-WT) were enrolled; 127 TFDC vaccine injections (4.5 ± 2.6 times/patient) were administered. Patients with GBM IDH-WT had a respectable 5-year survival rate (24%), verifying the clinical activity of TFDC immunotherapy, particularly against O6-methylguanine-DNA methyltransferase (MGMT) unmethylated GBM (5-year survival rate: 33%). To identify novel factors influencing overall survival (OS) in GBM IDH-WT treated with TFDC immunotherapy, clinical parameters were assessed and comprehensive molecular profiling involving transcriptome and exome analyses was performed. MGMT promoter methylation status, extent of tumor resection, and vaccine parameters (administration frequency, DC and tumor cell numbers, and fusion ratio) were not associated with survival following TFDC immunotherapy. Old age and pre- and post-operative Karnofsky performance status were significantly correlated with OS. Low HLA-A expression and lack of CCDC88A, KRT4, TACC2, and TONSL mutations in tumor cells were correlated with better prognosis. We validated the activity of TFDC immunotherapy against GBM IDH-WT, including chemoresistant, MGMT promoter unmethylated cases. The identification of molecular biomarkers predictive of TFDC immunotherapy efficacy in GBM IDH-WT will facilitate the design of and patient stratification in a phase-3 trial to maximize treatment benefits. [ABSTRACT FROM AUTHOR]

Strigolactones (SLs) were initially discovered as germination inducers for root parasitic plants. In 2015, three groups independently reported the characterization of the SL receptor in the root parasitic plant Striga hermonthica , which causes significant damage to crop production, particularly in sub-Saharan Africa. The characterized receptors belong to HYPOSENSITIVE TO LIGHT/KARRIKIN INSENSITIVE2 (HTL/KAI2), which is a member of the α/β-hydrolase protein superfamily. In non-parasitic plants, HTL/KAI2 perceives the smoke-derived germination inducer karrikin and a yet-unidentified endogenous ligand. However, root parasitic plants evolved a specific clade of HTL/KAI2 that has diverged from the KAI2 clade of non-parasitic plants. The S. hermonthica SL receptors are included in this specific clade, which is called KAI2 divergent (KAI2d). Orobanche minor is an obligate root holoparasitic plant that grows completely dependent on the host for water and nutrients because of a lack of photosynthetic ability. Previous phylogenetic analysis of KAI2 proteins in O. minor has demonstrated the presence of at least five KAI2d clade genes. Here, we report that KAI2d3 and KAI2d4 in O. minor have the ability to act as the SL receptors. They directly interact with SLs in vitro, and when expressed in Arabidopsis , they rescue thermo-inhibited germination in response to the synthetic SL analog GR24. In particular, KAI2d3 showed high sensitivity to GR24 when expressed in Arabidopsis , suggesting that this receptor enables highly sensitive SL recognition in O. minor. Furthermore, we provide evidence that these KAI2d receptors are involved in the perception of sesquiterpene lactones, non-strigolactone-type germination inducers. [ABSTRACT FROM AUTHOR]

Endobronchial metastasis (EBM) of hepatocellular carcinoma (HCC) is rare though HCC often metastasizes to the lungs. In this case report, a 74‐year‐old man with a history of HCC with chronic hepatitis C experienced hemoptysis and a dry cough. During immunotherapy for postoperative recurrent HCC, chest computed tomography (CT) revealed soft tissue shadows in the right upper and lower lobe bronchi, and we pathologically diagnosed as EBM of HCC using bronchoscopy. Although the prognosis of HCC with EBM is poor, lenvatinib, a tyrosine kinase inhibitor, was administered and resulted in improved symptoms, decreased tumour markers, and reduced EBM shadows on chest CT scans. To the best of our knowledge, this is the first case of lenvatinib monotherapy for EBM of HCC. It is important to perform a bronchoscopy for early diagnosis of EBM, followed by lenvatinib treatment. [ABSTRACT FROM AUTHOR]

Background: It remains unclear how the salivary flow and the fat content of food affect bolus formation during mastication. Objectives: We aimed to clarify: (1) how hyposalivation affects jaw‐closing and hyoid‐elevating muscle activities in bolus formation, and (2) if the effect of hyposalivation on muscle activity depends on the fat content of food. Methods: Eighteen healthy male volunteers were instructed to freely ingest four test foods: Plain, Fat without seasoning, Fat with seasoning, and Soft rice crackers. Masseter and suprahyoid electromyographic activities were recorded before and 30 min after the administration of atropine sulfate, a muscarinic receptor antagonist that induces hyposalivation. Results: Hyposalivation extended the masticatory duration significantly in all the test foods except Fat with seasoning. Masticatory cycle time was significantly longer with vs without hyposalivation for the Soft (p =.011). Suprahyoid activity/cycle was significantly greater with vs without hyposalivation (p =.013). Masticatory cycle time was significantly longer at the late stage with vs without hyposalivation for the Soft (p <.001). Suprahyoid activity/cycle was significantly greater at the middle (p =.045) and late stages (p =.002) with vs without hyposalivation for the Soft and greater at the late stage with vs without hyposalivation for the Plain (p =.043). Changes in masticatory cycle time and suprahyoid activity/cycle for these foods had significantly positive relationship (p <.001). Conclusion: Hyposalivation‐induced changes in masticatory behaviours resulted from the middle and late stage suprahyoid activity. Fat content and seasoning compensate for salivary flow inhibition. [ABSTRACT FROM AUTHOR]

The structural change in Pt networks composed of multiple chain connections among grains was observed in air at 1 atm using atomic-resolution environmental cell scanning transmission electron microscopy. An aberration-corrected incident electron probe with a wide convergence angle made it possible to increase the depth resolution that contributes to enhancing the signal-to-noise ratio of Pt network samples in air in an environmental cell, resulting in the achievement of atomic-resolution imaging. The exposure of the Pt networks to gas molecules under Brownian motion, stimulated by electron beams in the air, increases the collision probability between gas molecules and Pt networks, and the Pt networks are more intensely stressed from all directions than in a situation without electron irradiation. By increasing the electron beam dose rate, the structural change of the Pt networks became significant. Dynamic observation on an atomic scale suggested that the structural change of the networks was not attributed to the surface atomic-diffusion-induced step motion but mainly caused by the movement and deformation of unstable grains and grain boundaries. The oxidized surface layers may be one of the factors hindering the surface atomic step motion, mitigating the change in the size of the grains and grain boundaries. [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]

Some hydrogen-poor supernovae (SNe) are found to undergo interaction with dense circumstellar matter (CSM) that may originate from mass eruption(s) just prior to core-collapse. We model the interaction between the remaining star and the bound part of the erupted CSM that eventually falls back to the star. We find that while fallback initially results in a continuous CSM down to the star, feedback processes from the star can push the CSM to large radii of ≳1015 cm for several years after the eruption. In the latter case, a tenuous bubble surrounded by a dense and detached CSM extending to ≳1016 cm is expected. Our model offers a natural unifying explanation for the diverse CSM structures seen in hydrogen-poor SNe, such as Type Ibn/Icn SNe that show CSM signatures soon after explosion, and the recently discovered Type Ic SNe 2021ocs and 2022xxf (the "Bactrian") with CSM signatures seen only at late times. [ABSTRACT FROM AUTHOR]

Cancer stemness and immunosuppressive tumor microenvironment (TME) in accordance with tumor oxygenation are variable during bevacizumab (Bev) therapy for glioblastoma (GBM). Positron emission tomography (PET) using 18F-fluoromisonidazole (FMISO) reflects hypoxic TME. The aim of this study was to compare FMISO-PET and immunohistochemical findings of tumor oxygenation in the TME of GBM during Bev treatment. Seven patients with newly diagnosed IDH-wildtype GBM underwent FMISO-PET during follow-up. Three patients received preoperative neoadjuvant Bev (neo-Bev) and subsequently underwent surgical resection. Reoperation was performed at the recurrence. FMISO-PET was performed before and after neo-Bev. Four patients who underwent tumor resection without neo-Bev were included as the control group. Expressions of hypoxic markers (carbonic anhydrase; CA9), stem cell markers (nestin, FOXM1), and immunoregulatory molecules (CD163, FOXP3, PD-L1) in tumor tissues were analyzed by immunohistochemistry (IHC). All 3 patients treated with neo-Bev showed decrease in FMISO accumulation in accordance with expressions of CA9 and FOXM1 compared with the control group. Two of these 3 patients at the recurrence showed increase in FMISO accumulation. IHC showed increased CA9-and FOXM1-positive cells in recurrent tumors. Expression of PD-L1 tended to be lower after neo-Bev compared with the control group. FMISO-PET effectively visualized TME oxygenation after neo-Bev. Increased FMISO accumulation at the time of recurrence, even under Bev treatment, suggests that FMISO-PET might be useful for monitoring the duration of Bev efficacy by reflecting tumor oxygenation. [ABSTRACT FROM AUTHOR]

We have developed a SERS stamp that can be pressed directly onto a solid surface for characterization of surface-adsorbed target molecules. The stamp was fabricated by transfer of a dense monolayer of SiO2 nanospheres from a glass surface onto a piece of adhesive tape and subsequent evaporation of silver. The performance of the resulting SERS stamps was evaluated by their exposure to methyl mercaptan vapor, and immersion in rhodamine 6G and ferbam solutions. It was found that beside the nanosphere diameter and metal deposition thickness, the extent of burial of the nanospheres into the adhesive tape, dictated by the pressure during the nanosphere transfer process, had a significant effect. We carried out FDTD calculations of the near field. Models are based on morphological information obtained from helium ion microscopy, which can provide high-resolution images of poor electrical conductors such as our SERS stamp. While one of our main eventual goals is detection of pesticides on agricultural produce, we have begun to take a careful step by testing our SERS stamp on better characterized surfaces such as a porous gel surface, having been immersed in fungicides such as ferbam. We also present our preliminary results with ferbam on oranges. It is expected that our well-characterized SERS stamp will play a role in shedding light on the poorly studied transfer process of target molecules onto a SERS surface as well as serving as a new SERS platform. [ABSTRACT FROM AUTHOR]

In this study, an optical sensor using thermo-sensitive phosphor and its measurement system for visualizing and measuring the temperature distribution in an arbitrary cross-section of transmission oil using one type of phosphor, whose peak wavelength changes with temperature, is proposed. Because the intensity of the excitation light is gradually attenuated by the scattering of the laser light owing to microscopic impurities in the oil, we attempted to reduce the scattering effect by increasing the excitation light wavelength. Therefore, Pyrromethene 597 was selected as the optical sensor using thermo-sensitive phosphor, and a DPSS (Diode Pumped Solid State) laser with a wavelength of 532 nm was used as the excitation light. Using this measurement system, we measured the temperature distribution of a vertical buoyant jet of transmission oil and validated the measurement method. In addition, it was shown that this measurement system could be applied to the measurement of the temperature distribution in transmission oil with cavitation foaming. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated that hamster sperm hyperactivation is suppressed by extracellular Na+ by lowering intracellular Ca2+ levels, and Na+/Ca2+-exchanger (NCX) specific inhibitors canceled the suppressive effects of extracellular Na+. These results suggest the involvement of NCX in the regulation of hyperactivation. However, direct evidence of the presence and functionality of NCX in hamster spermatozoa is still lacking. This study aimed to reveal that NCX is present and is functional in hamster spermatozoa. First, NCX1 and NCX2 transcripts were detected via RNA-seq analyses of hamster testis mRNAs, but only the NCX1 protein was detected. Next, NCX activity was determined by measuring the Na+-dependent Ca2+ influx using the Ca2+ indicator Fura-2. The Na+-dependent Ca2+ influx was detected in hamster spermatozoa, notably in the tail region. The Na+-dependent Ca2+ influx was inhibited by the NCX inhibitor SEA0400 at NCX1-specific concentrations. NCX1 activity was reduced after 3 h of incubation in capacitating conditions. These results, together with authors' previous study, showed that hamster spermatozoa possesses functional NCX1 and that its activity was downregulated upon capacitation to trigger hyperactivation. This is the first study to successfully reveal the presence of NCX1 and its physiological function as a hyperactivation brake. [ABSTRACT FROM AUTHOR]

Optimizing the bias modulation of a fiber-optic gyroscope is crucial to improving its precision. In this study, we propose and demonstrate the use of multiple harmonics of sinusoidal modulation as an intermediate alternative to the widely used modulation methods: sinusoidal and square-wave modulation. We show that this alternative integrates the advantages of each modulation method by providing a smooth modulation that produces a clean, spike-free output and a satisfactory signal-to-noise ratio. By using three harmonics of modulation in combination with a high frequency to reduce thermal phase noise, we obtained an angular random walk of 5.2 (2) μ deg / h and a bias instability of ∼ 10 μ deg / h . This is the highest performance ever reported for fiber-optic gyroscopes. [ABSTRACT FROM AUTHOR]

Objective: To determine whether a gout polygenic risk score (PRS) is associated with age at gout onset and tophaceous disease in European, East Polynesian, and West Polynesian men and women with gout. Methods: A 19‐variant gout PRS was produced in 7 European gout cohorts (N = 4,016), 2 East Polynesian gout cohorts (N = 682), and 1 West Polynesian gout cohort (N = 490). Sex‐stratified regression models were used to estimate the relationship between the PRS and age at gout onset and tophaceous disease. Results: The PRS was associated with earlier age at gout onset in men (β = –3.61 in years per unit PRS [95% confidence interval (95% CI) –4.32, –2.90] in European men; β = –6.35 [95% CI –8.91, –3.80] in East Polynesian men; β = –3.51 [95% CI –5.46, –1.57] in West Polynesian men) but not in women (β = 0.07 [95% CI –2.32, 2.45] in European women; β = 0.20 [95% CI –7.21, 7.62] in East Polynesian women; β –3.33 [95% CI –9.28, 2.62] in West Polynesian women). The PRS showed a positive association with tophaceous disease in men (odds ratio [OR] for the association 1.15 [95% CI 1.00, 1.31] in European men; OR 2.60 [95% CI 1.66, 4.06] in East Polynesian men; OR 1.53 [95% CI 1.07, 2.19] in West Polynesian men) but not in women (OR for the association 0.68 [95% CI 0.42, 1.10] in European women; OR 1.45 [95% CI 0.39, 5.36] in East Polynesian women). The PRS association with age at gout onset was robust to the removal of ABCG2 variants from the PRS in European and East Polynesian men (β = –2.42 [95% CI –3.37, –1.46] and β = –6.80 [95% CI –10.06, –3.55], respectively) but not in West Polynesian men (β = –1.79 [95% CI –4.74, 1.16]). Conclusion: Genetic risk variants for gout also harbor risk for earlier age at gout onset and tophaceous disease in European and Polynesian men. Our findings suggest that earlier gout onset involves the accumulation of gout risk alleles in men but perhaps not in women, and that this genetic risk is shared across multiple ancestral groups. [ABSTRACT FROM AUTHOR]

Bone metastases frequently occur in patients with cancer. Skeletal-related events (SREs), including pain, impaired mobility, hypercalcemia, pathological fracture, spinal cord and nerve root compression, and bone marrow infiltration, can decrease the quality of life of the patients and increase the risk of morbidity. The mechanism of pain due to bone metastasis is complicated and involves various interactions among tumor cells, bone cells, activated inflammatory cells, and bone-innervating neurons. Cancer pain due to bone metastasis can be crippling and a chronic state that causes sarcopenia. For pain management, it is important to diagnose whether the pain is based on background pain or breakthrough pain due to bone metastasis. In addition, the management goal of cancer pain due to bone metastasis is not only to achieve pain relief but also to prevent pain progression and SREs. Pain mechanisms should be applied to achieve optimal management. This review aims to discuss the mechanisms of cancer pain due to bone metastasis and review the recommended drug therapies. [ABSTRACT FROM AUTHOR]

Levy et al. (2015) propose that inconsistency audience costs are caused in two ways: backing out of military commitment or backing into foreign conflicts. We replicate their experiment in July–August, 2021. Like many other studies, we find evidence for audience costs caused by backing out. However, our findings indicate that, unlike Levy et al. citizens are no less supportive of a leader who backs into a military conflict despite an initial commitment to stay out than one who behaves consistently. This study has significant theoretical and methodological implications. Theoretically, the importance of inconsistency in audience cost literature may be overstated or inconsistency audience costs may be bounded by temporal domains or contexts. Methodologically, our study emphasizes the necessity of replications because major findings can become conventional wisdom without such additional analysis. [ABSTRACT FROM AUTHOR]

Introduction: In this study, we examined the effect of switching dialysis membranes on the response to influenza virus vaccination in HD patients. Methods: This study consisted of two phases. In phase 1, antibody titers were measured and compared between HD patients and healthy volunteers (HVs) before and after vaccination against influenza virus. Using antibody titers 4 weeks after vaccination, HD patients and HVs were classified according to seroconversion (i.e., antibody titers against all four strains were >20-fold) or non-seroconversion (i.e., antibody titer against at least one strain was <20-fold). In the phase 2, we examined whether the change in the dialysis membrane from a polysulfone (PS) to a polymethyl methacrylate (PMMA) membrane affected the response to vaccination in HD patients without seroconversion in response to the vaccine the previous year. Patients with seroconversion and non-seroconversion were classified as responders and nonresponders, respectively. Additionally, we compared clinical data. Results: In the phase 1, 110 HD patients and 80 HVs were enrolled, and their seroconversion rates were 58.6% and 72.5%, respectively. In the phase 2, 20 HD patients without seroconversion in response to the vaccine the previous year were enrolled, and the dialyzer membrane was changed to PMMA 5 months before annual vaccination. After annual vaccination, 5 and 15 HD patients were categorized as responders and nonresponders, respectively. In the responders, β2-microglobulin, white blood cell counts, platelet counts, and serum albumin levels (Alb) were all higher than in the nonresponders. Conclusion: The responsiveness to vaccination against influenza virus was lower in HD patients compared with HVs. Changing the dialysis membrane from PS to PMMA appeared to affect the response to vaccination in HD patients. [ABSTRACT FROM AUTHOR]

Background: Relugolix, an oral gonadotrophin-releasing hormone receptor antagonist, was launched in Japan in 2019. Although there have been several studies on relugolix for leiomyomas, few have focused on submucosal leiomyomas. Submucosal leiomyomas cause bleeding more frequently than leiomyomas in other locations. There is only one case report described a patient treated for a submucosal leiomyoma with relugolix who developed severe hemorrhage. However, it remains unclear which characteristics of submucosal leiomyomas can lead to severe hemorrhage. Thus, the aim of this study was to investigate the characteristics of submucosal leiomyomas that would cause severe hemorrhage when treated with relugolix. Methods: We retrospectively reviewed records of patients who underwent treatment for submucosal leiomyoma with relugolix (40 mg once daily for up to 6 months) in our institute between December 2019 and September 2021. We evaluated the clinical course and characteristics of submucosal leiomyoma in patients who developed severe hemorrhage. Results: A total of 17 patients were treated for submucosal leiomyoma with relugolix. Two patients developed severe hemorrhage and required emergent surgery and blood transfusions. Only those two of the 17 patients had a submucosal leiomyoma of the International Federation of Gynecology and Obstetrics (FIGO) type 0, which has a stalk. In the remaining 15 patients who had FIGO type 1 or 2 leiomyoma, hemorrhage did not occur. Conclusions: Our study suggests that the use of relugolix for FIGO type 0 leiomyomas may be associated with a risk of hemorrhage. However, relugolix may be a safe and effective treatment option for patients with FIGO type 1 or 2 leiomyomas. [ABSTRACT FROM AUTHOR]

Ladderane lipids (found in the membranes of anaerobic ammonium-oxidizing [anammox] bacteria) have unique ladder-like hydrophobic groups, and their highly strained exotic structure has attracted the attention of scientists. Although enzymes encoded in type II fatty acid biosynthesis (FASII) gene clusters in anammox bacteria, such as S-adenosyl-l-methionine (SAM)-dependent enzymes, have been proposed to construct a ladder-like structure using a substrate connected to acyl carrier protein from anammox bacteria (AmxACP), no experimental evidence to support this hypothesis was reported to date. Here, we report the crystal structure of a SAM-dependent methyltransferase from anammox bacteria (AmxMT1) that has a substrate and active site pocket between a class I SAM methyltransferase-like core domain and an additional α-helix inserted into the core domain. Structural comparisons with homologous SAM-dependent C-methyltransferases in polyketide synthase, AmxACP pull-down assays, AmxACP/AmxMT1 complex structure predictions by AlphaFold, and a substrate docking simulation suggested that a small compound connected to AmxACP could be inserted into the pocket of AmxMT1, and then the enzyme transfers a methyl group from SAM to the substrate to produce branched lipids. Although the enzymes responsible for constructing the ladder-like structure remain unknown, our study, for the first time, supports the hypothesis that biosynthetic intermediates connected to AmxACP are processed by SAM-dependent enzymes, which are not typically involved in the FASII system, to produce the ladder-like structure of ladderane lipids in anammox bacteria. [ABSTRACT FROM AUTHOR]

Bile acids are a category of steroids biosynthesized from cholesterol in the liver. Inborn errors of their metabolism are inherited in an autosomal recessive manner, resulting in enzyme deficiencies affecting the bile acid biosynthetic pathway. These defects in the pathway cause accumulation of unusual bile acids or bile alcohols. Unusual bile acids are highly cytotoxic, causing injury to the liver. These unusual bile acids damage hepatocytes, resulting in cholestatic liver injury beginning in infancy. Except for cerebrotendinous xanthomatosis and some secondary defects, various inborn errors of bile acid metabolism (IEBAM) have been reported from Japan, affecting eight patients including three with 3β‐hydroxy‐Δ5‐C27‐steroid dehydrogenase/isomerase deficiency, three with Δ4‐3‐oxosteroid 5β‐reductase deficiency, one with oxysterol 7α‐hydroxylase deficiency, and one with bile acid‐CoA: amino acid N‐acyltransferase deficiency. Distinctive laboratory findings in patients with 3β‐hydroxy‐Δ5‐C27‐steroid dehydrogenase/isomerase deficiency, Δ4‐3‐oxosteroid 5β‐reductase deficiency, and oxysterol 7α‐hydroxylase deficiency include normal serum γ‐glutamyltransferase and total bile acids concentrations despite presence of cholestasis (elevated serum direct bilirubin) from infancy. Pediatricians and pediatric surgeons who suspect a case of IEBAM should obtain urinary and serum bile acid analyses using gas or liquid chromatography‐mass spectrometry as well as genetic analyses. Available treatments include oral cholic acid, chenodeoxycholic acid, glycocholic acid, and ursodeoxycholic acid; fat‐soluble vitamin supplementation; and liver transplantation. Early diagnosis and treatment can offer a good outcome. [ABSTRACT FROM AUTHOR]

Fruit shape is an important trait that attracts consumers, and the regulation of genes related to cell division is crucial for shaping multicellular organs. In Arabidopsis, MYB3R transcription factors, which harbor three imperfect repeats in the N-terminus, control organ growth by regulating cell division. However, the function of MYB3Rs in tomato remains unknown. Here, we characterized tomato SlMYB3R3 , which was preferentially expressed in flowers and placed in a subclade with two Arabidopsis cell cycle suppressors (MYB3R3/5). slmyb3r3 knockout mutants were generated using the CRISPR/Cas9 system. Morphological observation of the slmyb3r3 mutants showed that fruits that were elongated and occasionally peanut-like in shape were formed, which was caused by significantly increased cell numbers in the longitudinal direction. Transcriptome and yeast one-hybrid assay results suggested that SlMYB3R3 acted as a suppressor of cell-cycle-related genes by binding to the mitosis-specific activator (MSA) motifs in their promoters. Taken together, knock out of the suppressor SlMYB3R3 leads to elongated fruit, which results from the altered cell division pattern at the ovary stage, by regulating cell-cycle-related genes in an MSA-dependent manner. Our results suggest that SlMYB3R3 and its orthologs have the potential to change fruit shape as part of the molecular breeding of fruit crops. [ABSTRACT FROM AUTHOR]

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global pandemic of coronavirus disease 19. Coronaviruses, including SARS-CoV-2, use RNA-dependent RNA polymerase (RdRP) for viral replication and transcription. Since RdRP is a promising therapeutic target for infection of SARS-CoV-2, it would be beneficial to develop new experimental tools for analysis of the RdRP reaction of SARS-CoV-2. Here, we succeeded to develop novel mouse monoclonal antibodies (mAbs) that recognize SARS-CoV-2 nsp12, catalytic subunit of the RdRP. These anti-nsp12 mAbs, RdMab-2, -13, and -20, specifically recognize SARS-CoV-2 nsp12 by western blotting analysis, while they exhibit less or no cross-reactivity to SARS-CoV nsp12. In addition, SARS-CoV-2 nsp12 was successfully immunoprecipitated using RdMab-2 from lysates of cells overexpressing SARS-CoV-2 nsp12. RdMab-2 was able to detect SARS-CoV-2 nsp12 transiently expressed in established culture cells such as HEK293T cells by indirect immunofluorescence technique. These novel mAbs against SARS-CoV-2 nsp12 are useful to elucidate the RdRP reaction of SARS-CoV-2 and biological cell response against it. [ABSTRACT FROM AUTHOR]

Background: Accurate tumor stage diagnosis during laparoscopic surgery remains difficult. We clarify the impact of new diagnostic strategy using narrow-band imaging (NBI) during laparoscopic surgery for colorectal cancer compared with other strategies. Methods: We defined angiogenesis (Ag) and fibrosis (Fib) grades using NBI laparoscopy (lap-NBI), and assessed the clinicopathological features associated with these grades for 67 patients with colorectal cancer who underwent surgery. We assessed vessel density and gray scale with computer software. Results: NBI-Ag-grade and NBI-Fib-grade of the serosal surface of cancer lesions and peritoneal nodules correlated with vessel density and gray scale of those assessed by Image J computer software. NBI-Fib-grades of liver nodules also correlated with gray scale. NBI-Ag- grade and Fib-grade of the serosal surface of cancer lesions correlated with pathological depth of invasion. These NBI grades of pathological metastatic peritoneal nodules were higher than those of pathologically benign peritoneal nodules. NBI- Fib grades of pathological metastatic liver nodules were higher than those of pathologically benign liver nodules. In multivariate analysis, lap-NBI was associated with different diagnosis for T3, T4 and non-T3, and non-T4. Moreover, lap-NBI was associated with different diagnosis for T4 and non-T4. Predictive value for T4 by lap-NBI showed high sensitivity (85%) specificity (87%), positive predictive value (74%), negative predictive value (93%), and overall accuracy (87%). Sensitivity and overall accuracy of lap-NBI was superior to that of other diagnostic modalities. Conclusion: We clarified the usefulness of the new diagnostic strategy using lap-NBI during laparoscopic surgery for colorectal cancer in comparison with other strategies. [ABSTRACT FROM AUTHOR]

• A case of death due to combined use of multiple drugs is often observed. • The forensic pathologist should consider pharmacological interactions among those drugs. • This case suggests that more attention should to be paid to the interactions of multiple drugs. A case of death due to combined use of multiple drugs is reported, and the pharmacokinetic interactions are discussed. A woman in her thirties was found dead in her home. A medico-legal autopsy found no findings suggestive of injury or natural disease. Toxicological analysis using liquid chromatography tandem mass spectrometry (LC-MS/MS) identified a toxic level of fluvoxamine (0.947 µg/mL), and concentrations greater than the therapeutic levels of levomepromazine (0.238 µg/mL) and trihexyphenidyl (0.225 µg/mL) were present, while bromazepam, haloperidol, sulpiride, and 7-aminoflunitrazepam were within or below their therapeutic ranges. Fluvoxamine is mainly metabolized by cytochrome P450 2D6 (CYP2D6), and levomepromazine is a potent CYP2D6 inhibitor. A high concentration of levomepromazine may increase the blood fluvoxamine level. Since the combined use of levomepromazine and fluvoxamine induces seizures, it may have been involved in causing the subject's death. In addition, combined use of trihexyphenidyl may potentiate anticholinergic effects of fluvoxamine overdose, including convulsions and coma. It was concluded that the cause of the subject's death was the interaction of multiple drugs. [ABSTRACT FROM AUTHOR]