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Introduction: The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib is associated with a high incidence of neutropenia. Treatment continuation using the standard dosing schedule (3 consecutive weeks of oral administration followed by 1-week off-treatment: 3/1 schedule) can be difficult and other dosing schedules have been previously adopted. We aimed to investigate whether alternative dosing schedules can be used effectively to continue palbociclib., Methods: This study included all patients who received palbociclib for hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (HR+/HER2-MBC) at Ogaki Municipal Hospital between January 2018 and November 2023. Reasons for treatment discontinuation, changes in treatment administration, treatment duration, relative dose intensity (RDI), overall response rate (ORR), clinical benefit rate (CBR), and adverse events were retrospectively investigated using electronic medical records., Results: On November 30, 2023 (a data censor date), patients who discontinued or continued palbociclib on the 3/1 schedule were classified into the 3/1 schedule group (n=20), and those who started a 3/1 schedule (partly on a 2/2 schedule) and then switched to the 3/2 schedule or the 2/2 schedule (2 consecutive weeks of oral administration followed by 2 weeks off) were classified into the 3/2 (n=10) or 2/2 schedule groups (n=18), respectively. For the 3/1, 3/2, and 2/2 schedule groups, respectively, the median treatment duration was 255.5, 1253.0, and 923.0 days (p=0.0013), the median RDI (%) was 71.0%, 69.2%, and 40.8% (p<0.001), and the ORR was 15.0%, 80.0%, and 50.0% (p=0.002), while the CBR was 55.0%, 100%, and 72.2% (p=0.028)., Conclusion: Dosing schedules other than the standard 3/1 schedule can be used to continue palbociclib with HR+/HER2-MBC while ensuring therapeutic efficacy. Alternative dosing schedules look promising and need further research (preferably, prospective studies) with a larger sample size and longer follow-up to validate treatment efficacy., (S. Karger AG, Basel.)

Background: Myofibroblasts are primary cells involved in chronic response-induced cardiac fibrosis. Fibroblast activation protein (FAP) is a relatively specific marker of activated myofibroblasts and a potential target molecule. This study aimed to clarify whether a vaccine targeting FAP could eliminate myofibroblasts in chronic cardiac stress model mice and reduce cardiac fibrosis., Methods: We coadministered a FAP peptide vaccine with a cytosine-phosphate-guanine (CpG) K3 oligonucleotide adjuvant to male C57/BL6J mice and confirmed an elevation in the anti-FAP antibody titer. After continuous angiotensin II and phenylephrine administration for 28 days, we evaluated the degree of cardiac fibrosis and the number of myofibroblasts in cardiac tissues., Results: We found that cardiac fibrosis was significantly decreased in the FAP-vaccinated mice compared with the angiotensin II and phenylephrine control mice (3.45±1.11% versus 8.62±4.79%; P =4.59×10 -3 ) and that the accumulation of FAP-positive cells was also significantly decreased, as indicated by FAP immunohistochemical staining (4077±1746 versus 7327±1741 cells/mm 2 ; FAP vaccine versus angiotensin II and phenylephrine control; P =6.67×10 - 3 ). No systemic or organ-specific inflammation due to antibody-dependent cell cytotoxicity induced by the FAP vaccine was observed. Although the transient activation of myofibroblasts has an important role in maintaining the structural robustness in the process of tissue repair, the FAP vaccine showed no adverse effects in myocardial infarction and skin injury models., Conclusions: Our study demonstrates the FAP vaccine can be a therapeutic tool for cardiac fibrosis.

Objective: This study aimed to compare the effects of a combination of sodium fluoride, soluble calcium, and pyrophosphate (FCaP) versus fluoride alone in inhibiting enamel caries progression., Design: Different FCaP solutions were prepared, and two were selected for testing (FCaP-1: F = 76 mmol/L, Ca = 7.6 mmol/L, P = 7.6 mmol/L, FCaP-5: F = 76 mmol/L, Ca = 23 mmol/L, P = 23 mmol/L). Fluoride solution (F = 76 mmol/L) was used as a control. Fluoride and calcium bioavailability in the solutions were measured, and NMR analysis was used to identify fluorine-containing complexes. Sound bovine enamel samples (n = 24 / group) underwent a 4-day pH cycling protocol followed by an additional 3 days of demineralization. Micro-hardness testing and fluoride concentration measurements were performed., Results: FCaP-1 and FCaP-5 demonstrated nearly 100 % fluoride and calcium bioavailability. NMR analysis confirmed the formation of fluorine-containing complex. Enamel treated with FCaP-5 exhibited significantly less reduction in subsurface hardness after pH cycling and additional demineralization compared to fluoride alone. Interestingly, fluoride concentration and acid resistance on enamel surfaces treated with FCaP-5 was lower than with fluoride alone (Steel's multiple comparison test, p < 0.05)., Conclusions: FCaP effectively inhibits caries progression in subsurface enamel layers under pH cycling conditions by providing bioavailable calcium, indicating that FCaP increases the effectiveness of fluoride in caries management. FCaP may be a valuable addition to clinical practice, particularly for improving the effectiveness of fluoride-containing oral care products in individuals with low salivary calcium levels., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. The authors are employees of LION Corporation., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Foot rock-paper-scissors and towel-gathering exercises are widely used for isometric strengthening of intrinsic foot muscles. An initial trial demonstrated that foot rock-paper-scissors and towel-gathering exercises affected skeletal muscles associated with the medial longitudinal arch and toe pressure force, respectively. However, no quantitative reports of interosseous muscle activity after continuous training exist. We aimed to quantitatively assess and compare the impact of foot rock-paper-scissors and towel-gathering exercises on skeletal muscle activity in university athletes over a 3-month period using FDG-PET 3 imaging., Methods: This randomized controlled clinical trial was conducted in a university hospital with pre- and post-training PET measurements of muscle activity changes. Eight healthy university athletes were subjected to two 3-month-long exercise regimens: foot rock-paper-scissors and towel-gathering. Skeletal muscle activity changes were quantitatively evaluated using FDG-PET imaging. We defined regions of interest across 25 specific muscles and conducted measurements of toe pressure strength and vertical jump height., Results: The foot rock-paper-scissors exercise initially impacted medial muscles and later intrinsic foot muscles, including lateral longitudinal arch muscles. The towel-gathering exercise improved toe pressure force and vertical jump. Therefore, each exercise targets specific muscle groups differently., Conclusions: Foot rock-paper-scissors and towel-gathering exercises have distinct effects on skeletal muscle activity. The former primarily enhances medial intrinsic muscles, while the latter improves toe pressure force and vertical jump ability. This highlights the importance of selecting specific exercises for targeted muscle training in athletic and rehabilitation settings. Further research is suggested to extend these findings to broader athletic populations and clinical applications.

Neurons receive, process, and integrate inputs. These operations are organized by dendrite arbor morphology, and the dendritic arborization (da) neurons of the Drosophila peripheral sensory nervous system are an excellent experimental model for examining the differentiation processes that build and shape the dendrite arbor. Studies in da neurons are enabled by a wealth of fly genetic tools that allow targeted neuron manipulation and labeling of the neuron's cytoskeletal or organellar components. Moreover, as da neuron dendrite arbors cover the body wall, they are highly accessible for live imaging analysis of arbor patterning. Here, we outline the structure and function of different da neuron types and give examples of how they are used to elucidate central mechanisms of dendritic arbor formation., (© 2024 Cold Spring Harbor Laboratory Press.)

Live imaging approaches are essential for monitoring how neurons go through a coordinated series of differentiation steps in their native mechanical and chemical environment. These imaging approaches also allow the study of dynamic subcellular processes such as cytoskeleton remodeling and the movement of organelles. Drosophila dendritic arborization (da) neurons are a powerful experimental system for studying the dendrite arbor in live animals. da neurons are located on the internal surface of the body wall and, therefore, are easily accessible for imaging. Moreover, many genetic tools target da neurons to disrupt genes or proteins of interest and allow the investigator to visualize fluorescent markers and endogenously tagged proteins in the neurons. This protocol introduces methods for preparing and mounting intact Drosophila embryos, larvae, and pupae, allowing live imaging of dynamic cellular processes in da neurons., (© 2024 Cold Spring Harbor Laboratory Press.)

Mosaic analysis with a repressible cell marker (MARCM) is used in Drosophila research to create labeled homozygous mutant clones of cells in an otherwise heterozygous fly. It allows the study of the effect of embryonically lethal genes and the determination of cell autonomy for a mutant phenotype. When used in dendritic arborization (da) neurons with a fluorescent protein targeted to the plasma membrane, MARCM allows the identification of homozygous mutant neurons and clear imaging of the dendrite arbor in both live and fixed preparations. Previous protocols that outlined experimental procedures to create MARCM clones in da neurons used a heat shock promoter to drive Flippase (FLP) expression; such an approach requires laborious embryo collection and heat shock steps, and it creates clones in other tissues besides the da neurons. The updated protocol described here outlines the use of FLP expression driven by a sensory organ precursor promoter (SOP-FLP); it requires no embryo collection or manipulation steps and creates clones exclusively in the peripheral sensory neuron lineage., (© 2024 Cold Spring Harbor Laboratory Press.)

Neurons have a complex dendritic architecture that governs information flow through a circuit. Manual quantification of dendritic arbor morphometrics is time-consuming and can be inaccurate. Automated quantification systems such as DeTerm help to overcome these limitations. DeTerm is a software tool that automatically recognizes dendrite branch terminals with high precision. It uses an artificial neural network to label the terminals, count them, and provide each terminal's positional data. DeTerm can recognize the dendritic terminals of Drosophila dendritic arborization (da) neurons, and it can also examine other types of neurons, including mouse Purkinje cells. It is freely available and works on Mac, Windows, and Linux. Here, we describe the use of DeTerm., (© 2024 Cold Spring Harbor Laboratory Press.)

Background: Ischemic priapism is a rare pathological condition, and delayed intervention can result in irreversible sequelae. Most cases are attributed to the use of antipsychotics. The blockade of α1-adrenergic receptors is thought to be associated with the disease onset, although data supporting this hypothesis are lacking. No consensus regarding the optimal choice of medication is available., Case Presentation: A 59-year-old man with schizophrenia, who had been receiving long-acting injections of risperidone, developed ischemic priapism after receiving paliperidone treatment. Following improvement in ischemic priapism, we administered a combination of aripiprazole and olanzapine, which improved his psychiatric symptoms. We did not observe any recurrence of ischemic priapism., Conclusions: Switching the antipsychotic drug causing ischemic priapism to patients having a relatively low affinity for α1-adrenergic receptors may enable the treatment of schizophrenia without recurrence of ischemic priapism. In addition to the affinity for α1-adrenergic receptor, differences in metabolic enzyme types and antipsychotic doses may be involved in the occurrence of ischemic priapism. Accumulating evidence is necessary to establish guidelines for selecting medication of patients with ischemic priapism., (© 2024 The Author(s). Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Competing Interests: The authors declare that they have no conflict of interest.

Background: Doubly labeled water is gold standard for measuring total energy expenditure (TEE). Measurements using the method are sensitive to the isotope dilution space ratio (DSR). Accuracy and precision of the method might be improved if we could identify factors influencing DSR., Objectives: We evaluated the potential associations of age, sex, ethnicity, anthropometry, body composition, turnover rates of the isotopes, and geographical elevation with DSR., Methods: We used univariate regression analysis to explore the relationships between the continuous variables and analysis of variance to test the relationships between the categorical variables with DSR. Subsequently, we used general linear model (GLM) and 1-way analysis of variance to evaluate the simultaneous associations of age, sex, ethnicity, fat-free mass (FFM) and fat mass (FM) on DSR., Results: From 5678 measurements complied from studies around the world with diverse ethnicity and living at various elevations, the mean DSR was 1.0364 ± 0.0141. No meaningful physiologic effect of any of the continuous and categorical variable on DSR was detected. General linear model analysis revealed no effect of FFM and FM (P > 0.33) on DSR, but DSR decreased with age (P < 0.001) among those aged 60 y and older regardless of sex. Among the Whites who were younger than 60 y, DSR was not related to FFM and FM (P = 0.73) but was affected by both age and sex (P < 0.001)., Conclusions: Previous estimates of age-related decline in TEE may have overestimated TEE at age 90 y. Validation studies on older participants are required to confirm this finding., Competing Interests: Conflict of interest WWW reports administrative support was provided by Baylor College of Medicine. JRS reports administrative support and article publishing charges were provided by University of Aberdeen. MLN is a Deputy Editor of the Journal of Nutrition but played no role in the Journal’s evaluation of the manuscript. The other authors report no conflicts of interest., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Previous reports focusing on cefiderocol susceptibility against Stenotrophomonas maltophilia have included a large number of noninvasive or colonized isolates, and data focusing on invasive S. maltophilia strains are still lacking. We retrospectively investigated the cefiderocol susceptibility of stored S. maltophilia strains that caused bacteremia at two Japanese hospitals. The MIC 50 and MIC 90 were 0.06 μg/mL and 0.25 μg/mL, respectively, while the susceptibility rate was 99.3% (current CLSI breakpoint criteria). Our results provide the MIC distribution of bacteremic S. maltophilia isolates in Japan and show the preserved cefiderocol susceptibility of S. maltophilia among clinically invasive pathogenic strains., Competing Interests: Declarations. Ethical approval: Not applicable. This article does not contain any studies with human participants or animals performed by any of the authors. Consent to publish: The authors consent to the publication of the manuscript. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The effect of trivalent cation Fe 3+ on the gelation process of a sodium salt form of gellan (DG, deacylated gellan gum) was investigated by rheology and DSC studies. On addition of a fairly low concentration of Fe 3+ (1 mM), both the complex modulus (G*) of a 1.0 % DG solution in gel state and the sol-gel transition temperature (T gel ) slightly decreased. At higher Fe 3+ concentrations (2 and 3 mM), however, a slight increase in the G* and T gel was observed. In the coexisting monovalent cation (K + ) solutions, addition of Fe 3+ always improved the G* in gel state and the T gel in a concentration-dependent manner. Moreover, for all Fe 3+ DG solutions, the ordered structure formation temperature (T order ) was always lower than T gel and increased with increasing Fe 3+ concentration. This finding indicates that the network formation in the DG solutions should occur in advance of the ordered structure formation of the DG chains and that the presence of Fe 3+ unfavorably affected the conformational transition of DG. In coexisting cation solution, the presence of K + ion made a favorable contribution to the binding of Fe 3+ to the disordered DG chains and to the subsequent ordered structure formation of the DG chains., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Long-term care (LTC) residents are susceptible to falling and the risk of subsequent morbidity and mortality may be compounded with concurrent anticoagulation use. Uncertainty exists around the benefit and harm of anticoagulation use for residents with a high risk for falls because of concerns of major bleeding complications. We aimed to examine if anticoagulant use increases mortality risk among LTC residents who fall., Design: A retrospective cohort study., Setting and Participants: Older adults (≥65 years) admitted to a LTC facility in Ontario, Canada between January 1, 2010, and December 1, 2019, who were transferred to emergency departments for fall-related injuries., Methods: The exposure was the use of an oral anticoagulant (OAC). The primary outcome was mortality within 30 days of transfer. Secondary outcomes were major hemorrhage and care utilization. We used hierarchical logistic regression models to examine the association between the use of OAC and 30-day mortality., Results: There were 56,419 residents transferred to the hospital for a fall, of whom 9611 (17.0%) were on an OAC. At 30 days, 5794 (10.3%) of the cohort had died: 12.0% (1151) on an OAC and 9.90% (4643) not on an OAC [risk difference (RD), 2.1%; 95% CI, 1.40%-2.82%]. There were 485 major hemorrhage cases: 1.3% (125) on an OAC and 0.8% (360) not on an OAC (RD, 0.5%; 95% CI, 0.26%-0.74%). Multivariable analysis found no significant association between OAC use and 30-day mortality [odds ratio (OR), 0.98; 95% CI, 0.90-1.06], but an increased risk of major hemorrhage (OR, 1.31; 95% CI, 1.04-1.66). Both groups had similar health system and neurosurgical care utilization., Conclusions and Implications: Among LTC residents transferred to the emergency department for fall-related injuries, OACs did not increase the risk of post-fall mortality. OAC prescribing for frail older adults who experience falls should consider their individual risk profile., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Background: Appropriate adverse event (AE) management and maintenance of therapeutic intensity are necessary to achieve therapeutic benefits of CDK4/6 inhibitors (palbociclib and abemaciclib) in hormone receptor-positive, HER2-negative metastatic/recurrent breast cancer. Objective: This study was aimed at clarifying the effect of AEs associated with palbociclib and abemaciclib on treatment. Methods: A total of 62 and 49 patients were prescribed palbociclib and abemaciclib, respectively, at our hospital from January 1, 2018 to June 30, 2023. The rate and reasons for treatment discontinuation, interruption of administration, and changes in dose and dosing schedule, treatment duration, and relative dose intensity (RDI) were compared between the groups of patients prescribed the 2 treatments. Results: Treatment discontinuation due to AEs occurred more frequently with abemaciclib (12 patients) because of interstitial lung disease and hepatic and renal events than with palbociclib (5 patients; P = .008). Administration was interrupted in 57 (91.9%) and 35 (71.4%) patients treated with palbociclib and abemaciclib, respectively ( P = .004). Dose reduction occurred in 37 (67.3%) and 19 (47.5%) patients treated with palbociclib and abemaciclib, respectively ( P = .053). The median [range] treatment duration was 301 [21-1643] days for palbociclib and 238 [70-1526] days for abemaciclib (log-rank test, P = .581). The median RDI was 59.7% and 59.6% for palbociclib and abemaciclib, respectively ( P = .539). Although the AEs of palbociclib and abemaciclib affected the treatment considerably, the treatment duration and RDI were similar. Conclusion: CDK4/6 inhibitors should be selected based on the tolerability and manageability of each AE., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Human granulocytic anaplasmosis (HGA) is a tick-borne infection caused by Anaplasma phagocytophilum. Only seven cases of HGA have been reported in Japan to date. We report the case of a 61-year-old female farmer who developed HGA with rash and rhabdomyolysis. The patient had fever and erythema covering the entire body, including the palms. An induration with an eschar was observed on the right leg, indicating that the patient had been bitten by a tick. Elevated serum creatinine and creatinine kinase levels and hematuria indicated rhabdomyolysis. We suspected Japanese spotted fever, a tick-borne illness caused by Rickettsia Japonica, and administered minocycline and ciprofloxacin for a week. Transient neutropenia and thrombocytopenia were observed, but the symptoms improved. Polymerase chain reaction (PCR) and antibody tests for R. japonica and Orientia tsutsugamushi, which causes scrub typhus, were both negative. The PCR test for severe fever with thrombocytopenia syndrome virus was also negative. Antibodies against A. phagocytophilum-related proteins were detected by western blotting, indicating seroconversion of IgG with paired serum samples, and the patient was diagnosed with HGA. HGA should be suspected in acute febrile patients with a history of outdoor activity and cytopenia, with or without a rash. A testing system and the accumulation of cases in Japan are necessary for the early diagnosis and appropriate treatment of HGA., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Introduction: Burdensome care transitions may occur despite clinicians' engagement in care planning discussions with residents and their family/friend care partners. Conversations about potential hospital transfers can better prepare long-term care (LTC) residents, their families and care providers for future decision-making. Lack of such discussions increases the likelihood of transitions that do not align with residents' values. This study will examine experiences of LTC residents, family/friend care partners and staff surrounding decision-making about LTC to hospital transitions and codesign a tool to assist with transitional decision-making to help prioritise needs and preferences of residents and their care partners., Methods and Analysis: This study will use semi-structured needs assessment interviews (duration: 1 hour), content analysis of existing decision support and discussion tools and a codesign workshop series (for residents and care partners, and for staff) at three participating LTC home research sites. This qualitative work will inform the development of a decision support tool that will subsequently be pilot tested and evaluated at three partnering LTC homes in future phases of the project. The study is guided by the Person-centred Practice in Long-term Care theoretical framework. Interview audio recordings will be transcribed verbatim and analysed using reflexive thematic analysis. Participants will be recruited in partnership with three LTC homes in Ottawa, Ontario. Eligible participants will be English or French speaking residents, family/friend care partners or staff (eg, physicians, nurses and personal support workers) who have experienced or been involved in a transition from LTC to hospital., Ethics and Dissemination: Ethical approval has been obtained from the Bruyère Health Research Ethics Board (#M16-23-030). Findings will be (1) reported to participating and funding organisations; (2) presented at national and international conferences and (3) disseminated by peer-review publications., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The accumulation of ascites is a major symptom of ovarian cancer. The volume of ascites is a pathophysiological indicator of the peritoneal environment, such as inflammation and fibrosis; however, the relationship between the volume of ascites and oncological outcomes remains unclear. We herein retrospectively examined the effects of the volume of ascites on the prognosis of epithelial ovarian cancer in a multi-institutional large cohort using the stratification of clinical characteristics and statistical adjustment methods., Methods: Of 5,268 patients with ovarian tumors in the Tokai Ovarian Tumor Study Group between 1986 and 2020, we included 1,966 cases of epithelial ovarian cancer and examined the relationship between the volume of ascites at the initial surgery and the prognosis of patients. We performed a multivariate analysis and propensity score weighting for covariate adjustments to precisely estimate the prognostic impact of ascites accumulation. A subgroup analysis was also performed to examine differences in the prognostic implications of ascites accumulation among histotypes., Results: A reservoir of 100 mL of ascites was confirmed as the cut-off value in our cohort. A Kaplan-Meyer analysis with propensity score adjustments indicated that the accumulation of more than 100 mL of ascites shortened overall survival. The multivariate analysis revealed that the increased accumulation of 100 mL of ascites was an independent prognostic factor for overall survival (HR 1.242; 95% CI 1.050-1.470; P = 0.012). The subgroup analysis showed the prognostic significance of ascites accumulation in mucinous and endometrioid histologies., Conclusions: The accumulation of even a low to intermediate volume of ascites (≥ 100 mL) was confirmed to be an independent poor prognostic factor in epithelial ovarian cancer. Furthermore, its prognostic impact differed among histotypes., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of Nagoya University (No. 2006 − 0357) in accordance with the principles of the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

There was a scarcity of data evaluating variations in treatment approaches and clinical outcomes for severe aortic stenosis (AS) between medical centers with and without availability of transcatheter aortic valve implantation (TAVI). Current study population was 2993 patients with severe AS enrolled in the CURRENT AS Registry-2 (2581 patients from 10 TAVI centers; 412 patients from 10 non-TAVI centers). TAVI centers more frequently opted for the initial aortic valve replacement (AVR) strategy compared to non-TAVI centers (60% and 40%, P < 0.001). Among patients with the initial AVR strategy, TAVI centers disproportionately favored the initial TAVI strategy compared to non-TAVI centers (71% and 23%, P < 0.001). No significant differences were observed in the risk of a composite of all-cause death or heart failure hospitalization between TAVI and non-TAVI centers in the entire study population (cumulative 3-year incidence: 32.0% and 31.0%, P = 0.37; adjusted hazard ratios: 0.92, 95% confidence intervals: 0.74-1.15, P = 0.45) or in conservative, initial AVR, initial surgical AVR, and initial TAVI strata. A substantial disparity exists in the treatment strategies for patients with severe AS between TAVI and non-TAVI centers. TAVI centers tended to perform AVR, particularly TAVI, earlier and more frequently. However, there was no discernible distinction in the risk of the composite of all-cause death or HF hospitalization between TAVI and non-TAVI centers. UMINID: UMIN000034169., Competing Interests: Declarations. Conflict of interest: K. Ono and K. Minatoya are members of Circulation Journal’s Editorial Team. S.S. reports clinical proctoring for Edwards Life Science, Medtronic, and Abbott Vascular. H.S. reports receiving personal fees from Abbott Vascular, Boston Scientific, and Daiichi Sankyo. T.M reports receiving lecturer fees from Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Kyocera, Novartis, and Toray and manuscript fees from Bristol-Myers Squibb and Kowa, as well as being on the advisory board for Sanofi. T. Kimura reports being on the advisory board for Abbott Vascular and receiving grants from Edwards Lifescience, Daiichi Sankyo, Takeda Pharmaceutical, Bayer, Otsuka Parmaceutical, Boehringer Ingelheim, Mitsubishi Tanabe Pharma, Sumitomo Dainippon Pharma, Kowa, Abiomed, Japan Academic Research Forum, NIPRO, W.L. Gore & Associates G.K., RPM Co., Ltd., CSL Behring, Pfizer R&D Japan G.K., and EP- CRSU Co., Ltd; and honoraria from MSD, Eisai, Edwards Lifescience, Ono Pharmaceutical, Tsumura, Medical Review, Kowa, Sanofi, Pharmaceuticals and Medical Devices Agency, Bristol-Myers Squibb, Boston Scientific, Lifescience, Toray, Astellas Amgen Biopharma, Astellas, AstraZeneca, OrbusNeich, MSD Life Science Foundation, Public Health Research Foundation, Chugai Pharmaceutical, Japan Society for the Promotion of Science, Interscience, Philips, Kowa Pharmaceutical, Mitsubishi Tanabe Pharma, Terumo, Novartis Pharma, HeartFlow Japan G.K., and CROSSCO Co. The remaining authors have no conflicts of interest to disclose. IRB information: The present study was approved by Kyoto University Graduate School and Faculty of Medicine Ethics Committee, Reference number: R1501., (© 2024. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

The integrative multi-kingdom interaction of the gut microbiome in ulcerative colitis (UC) and Crohn's disease (CD) remains underinvestigated. Here, we perform shotgun metagenomic sequencing of feces from patients with UC and CD, and healthy controls in the Japanese 4D cohort, profiling bacterial taxa, gene functions, and antibacterial genes, bacteriophages, and fungi. External metagenomic datasets from the US, Spain, the Netherlands, and China were analyzed to validate our multi-biome findings. We found that Enterococcus faecium and Bifidobacterium spp. were enriched in both diseases. Enriched Escherichia coli was characteristic of CD and was linked to numerous antibiotic resistance genes involved in efflux pumps and adherent-invasive Escherichia coli virulence factors. Virome changes correlated with shifts in the bacteriome, including increased abundances of phages encoding pathogenic genes. Saccharomyces paradoxus and Saccharomyces cerevisiae were enriched in UC and CD, respectively. Saccharomyces cerevisiae and Escherichia coli had negative associations with short-chain fatty acid (SCFA)-producing bacteria in CD. Multi-biome signatures and their interactions in UC and CD showed high similarities between Japan and other countries. Since bacteria, phages, and fungi formed multiple hubs of intra- or trans-kingdom networks with SCFA producers and pathobionts in UC and CD, an approach targeting the interaction network may hold therapeutic promise., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Data on concomitant mitral regurgitation (MR) in patients with severe aortic stenosis (AS) are scarce., Methods and results: We investigated the risk of concomitant MR in patients with severe AS in the CURRENT AS Registry-2 according to initial treatment strategy (transcatheter aortic valve implantation [TAVI], surgical aortic valve replacement [SAVR], or conservative). Among 3,365 patients with severe AS, 384 (11.4%) had moderate/severe MR (TAVI: n=126/1,148; SAVR: n=68/591; conservative: n=190/1,626). The cumulative 3-year incidence for death or heart failure (HF) hospitalization was significantly higher in the moderate/severe than no/mild MR group in the entire population (54.6% vs. 34.3%, respectively; P<0.001) and for each treatment strategy (TAVI: 45.0% vs. 31.8% [P=0.006]; SAVR: 31.9% vs. 18.7% [P<0.001]; conservative: 67.8% vs. 41.6% [P<0.001]). The higher adjusted risk of moderate/severe MR relative to no/mild MR for death or HF hospitalization was not significant in the entire population (hazard ratio [HR] 1.15; 95% confidence interval [CI] 0.95-1.39; P=0.15); however, the risk was significant in the SAVR (HR 1.92; 95% CI 1.04-3.56; P=0.04) and conservative (HR 1.30; 95% CI 1.02-1.67; P=0.04) groups, but not in the TAVI group (HR 1.03; 95% CI 0.70-1.52; P=0.86), despite no significant interaction (P interaction =0.37)., Conclusions: Moderate/severe MR was associated with a higher risk for death or HF hospitalization in the initial SAVR and conservative strategies, while the association was less pronounced in the initial TAVI strategy.

Nonadiabatic ab initio molecular dynamics simulations were performed to explore the photoisomerization pathway from isoxazole (iso-OXA) to oxazole (OXA), considering four electronic states. The XMS-CASPT2 and SA4-CASSCF theories were employed to describe these electronic structures, which were caused by 12 electrons in 11 orbitals with the cc-pVDZ + sp diffuse basis set; the Gaussian s- and p-type diffuse functions were extracted from Dunning's aug-cc-pVDZ function. The potential energy and its gradient at each time step were computed on-the-fly at these levels in the time evolution of the classical trajectory. When the two electronic states were close to each other, the trajectory surface hopping (TSH) judgment between the two adjacent states was carried out by the anteater procedure based on the Zhu-Nakamura formula (ZN-TSH). The two different excited state lifetimes were found to exist in the first electronic state (S 1 ), estimated at 10.77 and 119.81 fs. Upon photoexcitation, the N-O bond breaks and energetically relaxes to the ground state (S 0 ). In the pathway leading to the main product, azirine formation, the 5-membered ring retains a planar structure while undergoing a non-adiabatic transition with an increasing N-O bond distance. Furthermore, it was verified that a 1,2-shift takes place in the pathway that results in the production of ketenimine, causing a nonadiabatic transition.

Anionic boron clusters, such as [B 12 X 12 ] 2- (X = Cl, Br, I), have attracted attention in pharmaceuticals due to their unique superchaotropic properties. In particular, [B 12 Br 12 ] 2- ( 1 ) has demonstrated strong interactions with biomolecules, facilitating cargo translocation across plasma membranes. In this study, we investigated the effect of covalently attaching chlorinated dodecaborate moiety [B 12 Cl 11 O-] 2- to 6-carboxyfluorescein (6-FAM) ( 3 ) via a PEG3 linker to form conjugate ( 4 ). We compared the membrane permeability of this covalent conjugate with that of non-covalent interactions between 6-FAM ( 3 ) and [B 12 Cl 12 ] 2- ( 2 ). Live-cell fluorescence imaging revealed that the covalent conjugate exhibited enhanced membrane permeability and water solubility while maintaining low cytotoxicity. These results highlight the potential of covalent conjugation with boron clusters for improving the cellular uptake of hydrophilic cargos.

Background/objectives: This study investigated the hitherto unclear association of body mass index (BMI) with age at overall, disability, and disability-free survival in older adults with and without frailty., Methods: This prospective cohort study enroled 10232 Japanese adults aged ≥65 years, who underwent follow-up for adverse events, from the Kyoto-Kameoka Study conducted from 2011-2016. BMI, calculated based on self-reported height and body weight, was classified into five categories: <18.5, 18.5-21.4, 21.5-24.9, 25.0-27.4, and ≥27.5 kg/m 2 . Frailty was assessed using the validated Kihon Checklist. The relationships between BMI and disability and mortality were analysed using multivariate Cox proportional hazards models and Laplace regression., Results: During the 5.3-year median follow-up period (45472 person-years), 2348 (22.9%) incidences of disabilities occurred. After adjusting for confounders, including medical history and lifestyle, individuals in the lowest and highest BMI categories had a higher hazard ratio (HR) of disability [<18.5 kg/m 2 : HR: 1.31, confidence interval (CI): 1.16-1.49; ≥27.5 kg/m 2 : HR: 1.27, 95% CI: 1.08-1.49, p for non-linearity <0.001] compared with that of those with BMI = 21.5-24.9 kg/m 2 . In the 50th percentile differences in age at overall and disability-free survival, participants with BMI < 18.5 kg/m 2 were more likely to die before disability incidence [survival with disability (overall survival - disability-free survival): -10.2 months]; those with BMI ≥ 27.5 kg/m 2 had longer survival with disability (12.5 months). These relationships were more marked in the frailty-stratified model, where in the BMI ≥ 27.5 kg/m 2 group, individuals with frailty survived longer with disability (27.2 months) than did individuals without frailty (6.2 months)., Conclusion: Higher BMI is associated with a longer duration of survival with disability among older adults, especially in those with frailty. Therefore, reversing frailty should be prioritised because individuals with frailty have a shorter probability of disability-free survival than do individuals without frailty, regardless of BMI., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

MID1-COMPLEMENTING ACTIVITY (MCA) is a land plant-specific, plasma membrane protein and Ca2+ signaling component that responds to exogenous mechanical stimuli, such as touch, gravity, and hypotonic-osmotic stress, in various plant species. MCA is essential for cell proliferation and differentiation during growth and development in rice (Oryza sativa) and maize (Zea mays). However, the mechanism by which MCA mediates cell proliferation and differentiation via Ca2+ signaling remains unknown. Here, we address this question using the liverwort Marchantia polymorpha. We show that the M. polymorpha MCA ortholog, MpMCA, is highly expressed in actively dividing regions, such as apical notches in the thalli and developing gametangiophores, and that MpMCA is a plasma membrane protein. In vivo Ca2+ imaging using a Ca2+ sensor (yellow cameleon) revealed that MpMCA is required for maintaining proper [Ca2+]cyt levels in the apical notch region, egg cells, and antheridium cells. Mpmca mutant plants showed severe cell proliferation and differentiation defects in the thalli, gametangiophores, and gametangia, resulting in abnormal development and unsuccessful fertilization. Furthermore, expression of the Arabidopsis MCA1 gene complemented most of the defects in the growth and development of the Mpmca mutant plants. Our findings indicate that MpMCA is an evolutionarily conserved Ca2+-signaling component that regulates cell proliferation and development across the life cycle of land plants., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

In odontoblasts, intracellular Ca 2+ signaling plays key roles in reactionary dentin formation and generation of dentinal pain. Odontoblasts also express several G s protein-coupled receptors that promote production of cyclic AMP (cAMP). However, the crosstalk between intracellular cAMP and Ca 2+ signaling, as well as the role of cAMP in the cellular functions of odontoblasts, remains unclear. In this study, we measured intracellular cAMP levels and intracellular free Ca 2+ concentration ([Ca 2+ ] i ). We also investigated the effect of intracellular cAMP on mineralization by the odontoblasts. In the presence of extracellular Ca 2+ , the application of forskolin (adenylyl cyclase activator) or isoproterenol (G s protein-coupled beta-2 adrenergic receptor agonist) increased intracellular cAMP levels and [Ca 2+ ] i in odontoblasts. The [Ca 2+ ] i increases could not be observed by removing extracellular Ca 2+ , indicating that cAMP is capable to activate Ca 2+ entry. Forskolin-induced [Ca 2+ ] i increase was inhibited by a protein kinase A inhibitor in odontoblasts. The [Ca 2+ ] i increase was sensitive to Gd 3+ , 2APB, or Zn 2+ but not verapamil, ML218, or La 3+ . In immunofluorescence analyses, odontoblasts were immunopositive for calcium homeostasis modulator 1 (CALHM1), which was found close to ionotropic ATP receptor subtype, P2X 3 receptors. When CALHM1 was knocked down, forskolin-induced [Ca 2+ ] i increase was suppressed. Alizarin red and von Kossa staining showed that forskolin decreased mineralization. These findings suggest that activation of adenylyl cyclase elicited increases in the intracellular cAMP level and Ca 2+ influx via protein kinase A activation in odontoblasts. Subsequent cAMP-dependent Ca 2+ influx was mediated by CALHM1 in odontoblasts. In addition, the intracellular cAMP signaling pathway in odontoblasts negatively mediated dentinogenesis., Competing Interests: Declarations Ethical approval Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Ventricular assist device (VAD) infections are frequent causes of hospital readmission. The risk factors and optimal preventive strategies for such, including chronic suppressive antibiotics (CSA), remain uncertain. We performed a single-center, retrospective, observational cohort study assessing continuous flow VAD recipients who underwent implantation between 2008 and 2018 in Japan. From primary VAD infection (VADI), we followed the patients for recurrent infection, defined as relapsing VAD-specific (e.g., localized infections) or VAD-related (e.g., bacteremia) infections requiring hospital readmission. CSA was defined as the use of oral antimicrobial agents continued beyond initial antibiotic use until transplantation, VAD withdrawal, VADI recurrence, or death. Survival analysis was performed to identify risk factors for recurrent infection accounting for competing risks (e.g., deaths and transplants). Among 163 eligible patients, 76 patients had VADIs. The main causative organism in primary VADI was Staphylococcus aureus (63%, 48/76). Among them, 41 had recurrent infections, whereas 35 had none during the follow-up period (median, 335 days). Thirty-six patients received CSA for a median of 478 days. Although CSA was associated with a decreased risk of recurrent infection [adjusted sub-distribution hazard ratio (SHR), 0.40; 95% confidence interval (CI), 0.18-0.89; P = 0.03], this protective effect was observed only after primary VAD-specific infection (SHR, 0.28; 95% CI, 0.12-0.64; P < 0.01) but not after VAD-related infection. Surgical procedures during primary VADI were associated with an increased risk (SHR, 2.00; 95% CI, 1.10-3.66; P = 0.02). One patient had an adverse drug reaction. CSA may be an effective approach to limit relapsing VADIs following a primary VAD-specific infection with minimal adverse events., Importance: Ventricular assist device infections (VADIs) are a significant complication leading to hospital readmissions. However, the risk factors and optimal preventive strategies for VADI remain unclear. This study investigated the effectiveness of chronic suppressive antibiotic therapy in patients with VADI. We found that the use of chronic suppressive antibiotic therapy was associated with a reduction in the risk of VADI recurrence with few adverse reactions. Our findings suggest the potential benefit of chronic suppressive antibiotics in preventing infections in selected cases. Our findings are relevant for the management of patients with ventricular assist devices awaiting heart transplantation, providing valuable insights for clinical practice., Competing Interests: H.K. reports receiving consultation fees from Mitsubishi-Tanabe Pharma Corporation, and EPS Corporation, and a speaker fee from Chugai Pharmaceutical Co., Ltd. He is affiliated with the Department of Health Quality Assessment at the University of Tokyo, a social collaboration department supported by the National Clinical Database, Johnson & Johnson K.K., Nipro Corporation, and Intuitive Surgical Sàrl. S.H. has received grants or contracts from Shinogi & Company Ltd., and received payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational activities from Shinogi & Co., Ltd., MSD, Daiichi Sankyo, and Nissui Pharmaceutical. No other competing financial interests declared.

Silica polymorphs occur under various pressures and temperature conditions, and their characteristics can be used to better understand the complex metamorphic history of planetary materials. Here, we conducted isothermal heating experiments of silica polymorphs in basaltic eucrites to assess their formation and stability. We revealed that each silica polymorph exhibits different metamorphic responses: (1) Quartz recrystallizes into cristobalite when heated at ≥ 1040 °C. (2) Monoclinic (MC) tridymite recrystallizes into no other polymorphs when heated at ≤ 1070 °C. (3) Silica glass recrystallizes into quartz when heated at 900-1010 °C, and recrystallize into cristobalite when heated at ≥ 1040 °C. These results suggest that MC tridymite in eucrites does not recrystallize into other polymorphs during the reheating events, nor does it recrystallize from other silica phases below the solidus temperature of eucrite (~ 1060 °C). Additionally, we found that pseudo-orthorhombic (PO) tridymite crystallizes from quenched melts in the samples heated at ≥ 1070 °C. Previously, cristobalite has been considered as the initial silica phase, which crystallizes from eucritic magma. Our findings suggest that the first crystallizing silica minerals may not always be cristobalite. These require a reconsideration of the formation process of silica minerals in eucrites., (© 2024. The Author(s).)

Interleukin-33 (IL-33) is an alarmin released upon epithelial tissue damage. It functions as a nuclear factor for regulating gene expression. We hypothesised that IL-33 is involved in the formation of decubitus ulcers through damaged epidermis. Therefore, this study aimed to clarify the mechanism of IL-33 action in decubitus ulcer formation. IL-33 knockout (KO), soluble stimulation-2 (ST2) transgenic, and wild-type (WT) mice were used to construct an ischemia-reperfusion (I/R) injury as a decubitus model. The ulcer area was significantly reduced in IL-33 KO mice compared to WT mice but was not reduced in ST2 transgenic mice. Anti-IL-33 receptor (transmembrane ST2) antibodies effectively prevented ulcer formation; however, an anti-IL-33 neutralising antibody was ineffective. The number of infiltrating macrophages was higher, while that of neutrophils and mast cells was lower in IL-33 KO mice than in WT mice. The number of M2 macrophages increased in IL-33 KO mice. Characterisation of gene expression levels revealed significantly reduced interleukin-1 beta (IL-1β) and increased C-C motif chemokine ligand 17 expression in IL-33 KO mice. Macrophages isolated from ulcers in WT or IL-33 KO mice stimulated with exogenous IL-33 produced comparable amounts of IL-1β. In conclusion, our study indicates that IL-33 is released in response to I/R injury in the skin, contributing to inflammatory macrophage and mast cell infiltration and stimulation, resulting in IL-1β production and the massive infiltration of effector cells, including neutrophils, which finally induces decubitus ulcer formation. These results suggest that suppressing IL-33 expression could be beneficial for treating early-phase decubitus ulcers., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background/aim: Cancer-associated systemic inflammatory response is a pivotal indicator of tumor progression and prognosis in various cancers. "Lymphocyte × albumin (LA)" is a prognostic inflammatory marker in rectal cancer. This study examined the correlation between LA, complete adjuvant chemotherapy (ACT), and prognosis in patients with gastric cancer (GC) who underwent radical gastrectomy., Patients and Methods: We retrospectively evaluated 108 patients with stage II/III GC who underwent radical gastrectomy at our institute between January 2015 and December 2021. Survival was assessed using Kaplan-Meier and Cox regression analyses. Factors associated with complete ACT were identified using logistic regression analysis., Results: Of the 108 patients with GC, 60 (55.6%) and 41 (38.0%) initiated and completed ACT, respectively. In multivariate analysis, the pre-operative LA was an independent factor for complete ACT [hazard ratio (HR)=0.35, 95% confidence interval (CI)=0.121-0.995; p=0.049]. In addition, age, pre-operative creatinine clearance, neutrophil-to-lymphocyte ratio, modified Glasgow prognostic score, and poor overall survival were significantly associated with low LA (<7,474). LA was an independent prognostic factor for overall survival in univariate analysis (HR=2.29, 95%CI=1.020-5.145; p=0.045) but not in multivariate analysis (HR=2.00, 95%CI=0.882-4.552; p=0.097)., Conclusion: Pre-operative LA is a useful marker for predicting complete ACT and prognosis of patients with GC following radical gastrectomy., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: Patient education is crucial for preventing chronic kidney disease (CKD) progression, but adequate educational time is not always available in standard nephrology outpatient clinics. However, usefulness of educational materials provided by healthcare providers in educational settings has been reported. This study aimed to compare the efficacy of pamphlet and video materials in increasing CKD knowledge at a nephrology clinic using waiting time., Materials and Methods: 44 CKD stage 3 - 5 patients were randomly assigned to either pamphlet or video education group, receiving a single session during an outpatient visit. We evaluated the objective CKD knowledge score, perceived kidney disease knowledge score, self-care scores, and amount of estimated salt intake before and after the educational intervention., Results: In both groups, the educational intervention significantly increased objective and perceived CKD knowledge scores (p < 0.001). No significant differences in increase in total knowledge scores between both groups were observed; however, different educational effects were observed in several individual knowledge items such as urinary protein and CKD stages. In both groups, self-care scores and amount of estimated salt intake did not change significantly before and after the intervention, but amount of estimated salt intake significantly decreased in patients with a history of dietary guidance (p = 0.044)., Conclusion: A single educational session with simple materials during outpatient waiting time at the nephrology clinic visit significantly improved patients' CKD knowledge, and suitable educational methods may differ according to knowledge items. Furthermore, patients who receive dietary guidance with specific instructions might exhibit salt reduction behavior through the use of educational materials.

Objectives: Some studies reported a relationship between life-space mobility (LSM) and frailty assessed by physical aspects; however, a more comprehensive discussion of frailty is underdeveloped. In addition, previous studies have focused only on older Euro-American people. Therefore, we aimed to examine LSM-frailty relationships in community-dwelling older Japanese persons using physical and comprehensive frailty indices., Design: A cross-sectional study., Setting and Participants: We used the data of 8898 older adults from a baseline survey of the Kyoto-Kameoka Study in Japan., Methods: The validated life-space assessment (LSA) was used to evaluate LSM and categorized it into quartiles. Two validated indices were used to evaluate frailty: the Kihon Checklist (KCL) and the simple Frailty Screening Index (FSI). Multivariable logistic regression was used to determine the relationships between LSM scores and frailty., Results: The mean age (SD) of the participants was 73.4 (6.3) years, and 53.3% were women. The mean LSM score of the study participants was 53.0. The prevalence of frailty by KCL and FSI was 40.7% and 16.8%, respectively. Significant differences between LSM score and frailty prevalence were observed [KCL: Q1, reference; Q2, odds ratio (OR) 0.53, 95% CI 0.45-0.62; Q3, OR 0.30, 95% CI 0.25-0.35; Q4: OR 0.22, 95% CI 0.18-0.26, P for trend <.001; FSI: Q1, reference; Q2, OR 0.57, 95% CI 0.48-0.68; Q3: OR 0.38, 95% CI 0.31-0.46; Q4: OR 0.35, 95% CI 0.28-0.42, P for trend <.001]. Similar results were observed when LSM scores were examined at 10-point intervals, with LSM and frailty exhibiting an L-shaped relationship. The LSM score dose-response curve at which the OR for frailty plateaued among older individuals was approximately 81-90 score., Conclusions and Implications: LSM score and frailty prevalence exhibited L-shaped relationships in community-dwelling older persons. This study's findings provide useful data for setting LSM targets for preventing frailty in community-dwelling older persons., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to identify anatomical and clinical factors associated with limb-based patency (LBP) loss, major adverse limb events (MALEs), and poor amputation-free survival (AFS) after an infrapopliteal arterial bypass (IAB) surgery according to the Global Limb Anatomic Staging System. A retrospective analysis of patients undergoing IAB surgery between January 2010 and December 2021 at a single institution was performed. Two-year AFS, freedom from LBP loss, and freedom from MALEs were assessed using the Kaplan-Meier method. Anatomical and clinical predictors were assessed using multivariate analysis. The total number of risk factors was used to calculate risk scores for subsequent categorization into low-, moderate-, and high-risk groups. IABs were performed on 103 patients. The rates of two-year freedom from LBP loss, freedom from MALEs, and AFS were 71.3%, 76.1%, and 77.0%, respectively. The multivariate analysis showed that poor run-off beyond the ankle and a bypass vein caliber of < 3 mm were significantly associated with LBP loss and MALEs. Moreover, end-stage renal disease, non-ambulatory status, and a body mass index of < 18.5 were significantly associated with poor AFS. The rates of freedom from LBP loss and MALEs and the AFS rate were significantly lower in the high-risk group than in the other two groups (12-month low-risk rates: 92.2%, 94.8%, and 94.4%, respectively; 12-month moderate-risk rates: 58.6%, 84.6%, and 78.3%, respectively; 12-month high-risk rates: 11.1%, 17.6%, and 56.2%, respectively; p < 0.001, p < 0.001, and p < 0.001, respectively). IAB is associated with poor clinical outcomes in terms of LBP, MALEs, and AFS in high-risk patients. Risk stratification based on these predictors is useful for long-term prognosis., (© 2024. The Author(s).)

Most elements of filamentous fungi seen in human tissue by pathologists are hyphae, and encountering other elements may interfere with diagnosis. Sporangia and chlamydospores are such elements that have been described in only a few case reports. We present an autopsy case with the extremely rare coexistence of Mucorales sporangia and chlamydospores in the lung. These fungal elements must be recognized and identified accurately because they can easily be mistaken for other fungi, microorganisms, or degenerated tissue structures., (© 2024 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Invasive aspergillosis (IA) is a rare but fatal disease among liver transplant recipients (LiTRs). We performed a multicenter 1:2 case-control study comparing LiTRs diagnosed with proven/probable IA and controls with no invasive fungal infection. We included 62 IA cases and 124 matched controls. Disseminated infection occurred only in 8 cases (13%). Twelve-week all-cause mortality of IA was 37%. In multivariate analyses, systemic antibiotic usage (adjusted odds ratio [aOR], 4.74; P = .03) and history of pneumonia (aOR, 48.7; P = .01) were identified as independent risk factors associated with the occurrence of IA. Moreover, reoperation (aOR, 5.99; P = .01), systemic antibiotic usage (aOR, 5.03; P = .04), and antimold prophylaxis (aOR, 11.9; P = .02) were identified as independent risk factors associated with the occurrence of early IA. Among IA cases, Aspergillus colonization (adjusted hazard ratio [aHR], 86.9; P < .001), intensive care unit stay (aHR, 3.67; P = .02), disseminated IA (aHR, 8.98; P < .001), and dialysis (aHR, 2.93; P = .001) were identified as independent risk factors associated with 12-week all-cause mortality, while recent receipt of tacrolimus (aHR, 0.11; P = .001) was protective. Mortality among LiTRs with IA remains high in the current era. The identified risk factors and protective factors may be useful for establishing robust targeted antimold prophylactic and appropriate treatment strategies against IA., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. J. Hand reports research grant funding from Pfizer, Janssen, Scynexis, and GlaxoSmithKline. D. Neofytos has received research support from MSD and Pfizer and consulting fees from MSD, Pfizer, Basilea, and Gilead. N.J. Mueller is on the scientific advisory board of Takeda MSD, and Pfizer and has received travel support from Biotest. M. Luong is on the Scientific Advisory Board of Takeda and Merck. S. Husain reports grant funding from Merck, Astellas, ScynexisInc, Pulmocide, Ltd, and Gilead Sciences Inc, outside the submitted work. All other authors have no potential conflicts., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To explore the frequency and positions of genetic mutations in CYP1B1 and FOXC1 in a Japanese population., Study Design: Molecular genetic analysis., Methods: Genomic DNA was extracted from 31 Japanese patients with childhood glaucoma (CG) from 29 families. We examined the CYP1B, FOXC1, and MYOC genes using Sanger sequencing and whole-exome sequencing (WES)., Results: For CYP1B1, we identified 9 families that harbored novel mutations, p.A202T, p.D274E, p.Q340*, and p.V420G; the remaining mutations had been previously reported. When mapped to the CYP1B1 protein structure, all mutations appeared to influence the enzymatic activity of CYP1B1 by provoking structural deformity. Five patients were homozygotes or compound heterozygotes, supporting the recessive inheritance of the CYP1B1 mutations in CG. In contrast, four patients were heterozygous for the CYP1B1 mutation, suggesting the presence of regulatory region mutations or strong modifiers. For the FOXC1 gene, we identified 3 novel mutations, p.Q23fs, p.Q70R, and p.E163*, all of which were identified in a heterozygous state. No mutation was found in the MYOC gene in these CG patients. All individuals with CYP1B1 and FOXC1 mutations were severely affected by early-onset CG. In the CYP1B1-, FOXC1-, and MYOC-negative families, we also searched for variants in the other candidate genes reported for CG through WES, but could not find any mutations in these genes., Conclusions: Our analyses of 29 CG families revealed 9 families with point mutations in the CYP1B1 gene, and four of those patients appeared to be heterozygotes, suggesting the presence of complex pathogenic mechanisms. FOXC1 appears to be another major causal gene of CG, indicating that panel sequencing of CYP1B1 and FOXC1 will be useful for diagnosis of CG in Japanese individuals., Competing Interests: Declarations. Conflict of interest: N. Fuse, None; M. Kimura, None; A. Shimizu, None; S. Koshiba, None; T. Hamanaka, None; M. Nakamura, None; N. Ishida, None; H. Sakai, None; Y. Ikeda, None; K. Mori, None; A. Endo, None; M. Nagasaki, None; F. Katsuoka, None; J. Yasuda, None; Y. Matsubara, None; T. Nakazawa, None; M. Yamamoto, None., (© 2024. The Author(s).)

Background: T-SPOT.TB ® , one of the screening tests for latent tuberculosis infection (LTBI), yields invalid results in human T-cell leukemia virus type 1 (HTLV-1)-positive patients with rheumatoid arthritis. However, the detailed mechanisms behind this invalidation are unclear. Additionally, it remains unclear whether T-SPOT.TB ® or QuantiFERON-TB (QFT) is more useful in HTLV-1-positive patients with rheumatic disease (RD)., Method: Among all of the HTLV-1-positive RD patients who visited our department between August 2012 and December 2022, 44 patients who were screened using T-SPOT.TB® were included in the analysis. QFT testing was performed in 33 of the 44 patients, and the results were compared with that of T-SPOT.TB®. Furthermore, we performed a culture experiment mimicking T-SPOT.TB® using peripheral blood mononuclear cells (PBMCs) obtained from HTLV-1-positive patients with RD. Additionally, T-cell subsets with autonomous product IFN-γ were analyzed using a flow cytometer., Results: Of the included patients, 13 (29.5%) were invalid for T-SPOT.TB® because of the increased number of negative control spots. The median HTLV-1 proviral load in the invalid group was higher than that in the valid group (2.45 vs. 0.49 copies/100 PBMCs, respectively, p = 0.002). QFT was performed in all 33 patients, including 13 patients who were invalid in T-SPOT.TB®. The main source of IFN-γ production was CD8+ T-cells in the T-SPOT.TB® mimic experiment. Furthermore, Tax-expressing CD4+ T-cells and Tax-specific cytotoxic CD8+ T-cells were more frequently observed in patients with invalid results than in patients with valid results. CD4+ T-cell depletion in the T-SPOT.TB® mimic experiment reduced the population of IFN-γ producing CD8+ T cells., Conclusion: T-SPOT.TB® may be invalidated by the interaction between Tax-expressing CD4+ T-cells and cytotoxic CD8+ T-cells. Moreover, HTLV-1-associated immune reactions due to contact between these cells may be unlikely to occur in QFT using whole blood. Therefore, our results reveal the superiority of QFT over T-SPOT.TB® as a screening test for LTBI in HTLV-1-positive patients with RD., Competing Interests: TH received honoraria for lectures from AbbVie GK, Eli Lilly Japan K.K., Pfizer Japan Inc., Asahi Kasei Pharma Corp., Bristol-Myers K.K., Chugai Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K.,Taisho Pharma Co., Ltdand Eisai Co. K. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kimura, Umekita, Iwao, Kawano, Hashikura, Hashiba, Hidaka, Sugata, Satou and Miyazaki.)

Background: Co-infection with Klebsiella pneumoniae presents a significant concern in hospitalized patients with coronavirus disease (COVID-19), increasing the risk of severe disease progression. Hypervirulent (hv) and hypermucoviscous (hm) K. pneumoniae (Kp) has gained prominence in Asia due to its capacity to cause invasive community-acquired infections. However, recognition of hvKp/hmKp co-infections in the context of COVID-19 remains limited. We report a severe case of rapidly progressing co-infection with hmKp exhibiting "difficult-to-diagnose" phenotypes in a hospitalized patient with COVID-19., Case Presentation: A 61-year-old woman with COVID-19 initially exhibited mild symptoms resembling the common cold. However, her condition rapidly deteriorated over 7 days, leading to hospital admission with the development of dyspnea. The patient required supplemental oxygen, antibiotic treatment, and mechanical ventilation. Gram-negative bacteria with atypical phenotypes were isolated from alveolar lavage fluid and blood cultures. Both strains formed small, glossy, non-lactose-fermenting colonies on clinically relevant media and were susceptible to ampicillin. Conventional biochemical tests failed to identify the Enterobacteriales strains owing to the urease-negative phenotype. Consequently, the identification of K. pneumoniae was difficult until matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis was performed. A positive string test indicated mucoviscosity, but with variability in the material used for stretching colonies. Whole-genome sequencing performed on the MiSeq and GridION platforms revealed the blood-derived strain JARB-RN-0063 as belonging to serotype K1 and sequence type (ST) 82. The hvKp-associated genes rmpA and iroCD were located on a 5.0-Mb chromosome, and iucABCD-iutA was identified on a 217.9-kb IncFIB(K)/IncR-type plasmid. Therefore, JARB-RN-0063 was genetically classified as hvKp with a Kleborate virulence score of 3. The intrinsic penicillinase gene bla SHV was defective owing to an IS1F element insertion, resulting in the strain being atypically susceptible to ampicillin., Conclusions: This is the first case of severe COVID-19-associated co-infection with a difficult-to-diagnose K. penummoniae strain. Notably, co-infection by the hmKp K1-ST82 clone exhibited atypical phenotypes, including stunted growth, non-lactose fermentation, urease-negative reaction, ampicillin susceptibility, and abnormal mucoviscosity, posing diagnostic challenges for clinical laboratories and impedes the identification of hvKp/hmKp. Delayed identification may worsen patient outcomes, highlighting the need for increased clinical awareness of such difficult-to-diagnose clones to prevent deterioration., (© 2024. The Author(s).)

Background: Segmental absence of intestinal musculature (SAIM) is a partial defect of intestinal muscularis propria without diverticulum. Many reports indicate that the increase in intestinal pressure caused by enemas or endoscopic examinations leads to bowel perforation, but there are few reports involving malignant tumors. Moreover, few reports have had good outcomes after performing one-stage intestinal anastomosis., Case Presentation: A 60-year-old male came to the office with right-side abdominal pain, and was diagnosed with acute generalized peritonitis caused by ascending colon perforation. Emergency laparotomy was performed, and oval and smooth perforation at the ascending colon was observed, which caused ascites with feces. In addition, there was a tumor on the distal side. The terminal ileum was not dilated, so the cause of the perforation was more likely the SAIM-related thin intestinal wall rather than increased internal intestinal pressure due to obstruction of the tumor. Therefore, a right hemicolectomy with functional end-to-end anastomosis (FEEA) between the ascending colon and ileum was performed, rather than creating a stoma. On pathological examination, the resected bowel segments had a partial defect of intestinal muscularis propria around the perforation, leading to the diagnosis of SAIM. The patient had a favorable postoperative course without anastomotic issues and was discharged safely., Conclusions: This case implies that initial intestinal anastomosis can be performed without creating a stoma when SAIM is suspected from the shape of the perforation and proximal intestine. This case report suggests surgeons should keep SAIM in mind during operations for colon perforations., (© 2024. The Author(s).)

Background: Dexamethasone is currently administered for Coronavirus disease 2019(COVID-19); however, there are concerns about its effect on specific antibodies' production. The aim of this study was to evaluate whether specific antibodies were affected by COVID-19 severity and corticosteroid treatment., Methods: Of 251 confirmed COVID-19 patients admitted to our hospital between January 26 and August 10, 2020, the early period of the pandemic, 75 patients with sera within 1 month of onset and 1 month or longer were included in the research. A total of 253 serum samples from these patients were collected. The levels of specific antibodies for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), immunoglobulin G (IgG) and M (IgM), were measured retrospectively. The results were compared separately of each COVID-19 severity, and with or without corticosteroid treatment., Results: Among the 75 patients, 47, 18, and 10 had mild, moderate, and severe disease, respectively. The median age was 53.0 years and 22 (29%) were women. The most common comorbidities were hypertension and dyslipidemia. Corticosteroids were administered to 20 (27%) and 10 (53%), patients with moderate and severe disease, respectively. The positivity rates IgM increased first, and IgG was almost always positive after day 16, regardless of the severity of COVID-19. On days 6-10, both IgG and IgM positivity rates were higher in patients with moderate disease than in those with mild or severe disease. In patients with moderate disease, IgG positivity was similar over time, regardless of corticosteroid treatment., Conclusions: In COVID-19 patients, specific IgG is positive and maintained for a long period of time, even after corticosteroid treatment. The effect of corticosteroid treatment in a COVID-19 epidemiological study using specific IgG antibodies was considered minor. COVID-19 patients were more likely to receive oxygen if IgM was positive 1 week after onset, but not mechanical ventilation. IgM measurement 1 week after onset may predict COVID-19 severity., (© 2024. The Author(s).)

Autism Spectrum Disorder (ASD) is a developmental disorder characterized by impaired social communication and repetitive behaviors. In recent years, a pharmacological mouse model of ASD involving maternal administration of valproic acid (VPA) has become widely used. Newborn pups in this model show an abnormal balance between excitatory and inhibitory (E/I) signaling in neurons and exhibit ASD-like behavior. However, the molecular basis of this model and its implications for the pathogenesis of ASD in humans remain unknown. Using quantitative secretome analysis, we found that the level of leucine-rich repeat and immunoglobulin domain-containing protein 2 (Lingo2) was upregulated in the conditioned medium of VPA model neurons. This upregulation was associated with excitatory synaptic organizer activity. The secreted form of the extracellular domain of Lingo2 (sLingo2) is produced by the transmembrane metalloprotease ADAM10 through proteolytic processing. sLingo2 was found to induce the formation of excitatory synapses in both mouse and human neurons, and treatment with sLingo2 resulted in an increased frequency of miniature excitatory postsynaptic currents in human neurons. These findings suggest that sLingo2 is an excitatory synapse organizer involved in ASD, and further understanding of the mechanisms by which sLingo2 induces excitatory synaptogenesis is expected to advance our understanding of the pathogenesis of ASD., (© 2024. The Author(s).)

Probiotics, particularly those native to the gut microbiota, have a profound influence on the gut environment. In this study, we conducted a randomized placebo-controlled, double-blind, parallel-group comparison trial to investigate the effects of Bifidobacterium longum BB536 ( B. longum BB536) on the fecal microbiota and metabolite compositions in healthy individuals. We compared the effects of fermented milk produced solely with Streptococcus thermophiles and Lactobacillus bulgaricus (placebo group) and fermented milk supplemented with B. longum BB536 (BY group). Our findings revealed a significantly greater relative abundance of Faecalibacterium in the BY group than in the placebo group by the 3rd day, a trend that persisted until the end of the trial on the 17th day. Additionally, the BY group presented significantly increased concentrations of tryptophan (Trp), Indole-3-lactic acid, and Indole-3-aldehyde on the 17th day. A significant positive correlation was observed between the relative abundance of Faecalibacterium and the number of viable B. longum BB536 bacteria in the feces. The concentrations of Trp and Indole-3-acetic acid were also significantly correlated with the number of viable B. longum BB536 bacteria in the feces. Our results suggest that B. longum BB536 intake can modulate the gut microbiota and metabolite profiles, which are general indicators for monitoring the gut environment, potentially conferring health benefits to the host.

Conotruncal heart defects are severe congenital malformations of the outflow tract, including truncus arteriosus (TA) and double-outlet right ventricle (DORV). TA is a severe congenital heart disease (CHD) in which the main arterial outflow tract of the heart fails to separate. We recently reported TMEM260 (NM&#95;017799.4), c.1617del (p.Trp539Cysfs*9), as a major cause of TA in the Japanese population (TMEM260 Keio-Tohoku variant) comparable to the prevalence of the 22q11.2 deletion syndrome, which accounts for 12%-35% of TA. However, no other major causes of TA have not been identified. Here, we report a family that included a TA patient and a DORV patient, harboring the compound heterozygous variants of TMEM260, a 7066-bp deletion encompassing exons 6-7 and c.1393C > T, p.(Gln465*). The allele frequency of the 7066-bp deletion was particularly high in the Japanese population (0.17%). Based on the allele frequency of this deletion and c.1617del (0.36%) in the Japanese population, TMEM260 variants might be associated with more than half of the Japanese patients with TA. This study showed that TMEM260 pathogenic variants might be the most common cause of TA in the Japanese population and could explain the wide spectrum of phenotypes associated with TMEM260-related CHD, including DORV, demonstrating the usefulness of genetic testing in Japanese patients with TA., (© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

The fetal liver is a hematopoietic organ, hosting a diverse and evolving progenitor population. While human liver organoids derived from pluripotent stem cells (PSCs) mimic aspects of embryonic and fetal development, they typically lack the complex hematopoietic niche and the interaction between hepatic and hematopoietic development. We describe the generation of human Fetal Liver-like Organoids (FLOs), that model human hepato-hematopoietic interactions previously characterized in mouse models. Developing FLOs first integrate a yolk sac-like hemogenic endothelium into hepatic endoderm and mesoderm specification. As the hepatic and hematopoietic lineages differentiate, the FLO culture model establishes an autonomous niche capable of driving subsequent progenitor differentiation without exogenous factors. Consistent with yolk sac-derived waves, hematopoietic progenitor cells (HPCs) within FLOs exhibit multipotency with a preference for myeloid lineage commitment, while retaining fetal B and T cell differentiation potential. We reconstruct in FLOs the embryonic monocyte-to-macrophage and granulocyte immune trajectories within the FLO microenvironment and assess their functional responses in the liver niche. In vivo, FLOs demonstrate a liver engraftment bias of hematopoietic cells, recapitulating a key phenomenon of human hematopoietic ontogeny. Our findings highlight the intrinsic capacity of liver organoids to support hematopoietic development, establishing FLOs as a platform for modeling and manipulating human blood-liver niche interactions during critical stages of development and disease.

Background : Many studies have reported on the relationship between cognitive and masticatory functions. However, it remains unclear how the mandibular movements change during chewing in facility residents as dementia progresses. This study aimed to investigate the relationship between a kinematic analysis of mandibular movement during mastication and cognitive function in facility residents. Methods: Sixty-three participants were included from two long-term care facilities. The primary outcome variable was the kinematic data of mandibular movement during mastication. The participants chewed rice crackers, and their faces were recorded during this motion. The partial correlation coefficient between kinematic data and cognitive function was calculated. Furthermore, group comparisons were performed after dividing the participants into three groups based on their cognitive function. Results: Circular motion frequency was significantly correlated with the ABC dementia scale, even after adjusting for the appendicular skeletal muscle index, Eichner index, and short-form mini-nutritional assessment. The cycle and circular motion frequencies were markedly lower in the severe dementia group than in the mild dementia group. Conclusions: With declining cognitive function, mandibular movements during mastication decrease in circular motion and increase in linear motion. Additionally, our results suggested that residents with severe cognitive impairment had more linear mandibular motions during mastication than those with mild cognitive impairment. This may make it more difficult for residents with cognitive decline to ingest normal solid foods.

Purpose: Given the risks of long-term benzodiazepine use, safer alternatives like orexin receptor antagonists (ORAs) are needed for insomnia treatment. This study aims to compare suvorexant and lemborexant, focusing on early-stage sleep duration as an efficacy measure and fall incidence as a safety measure., Methods: We included patients admitted to our hospital between April 1, 2022 and December 31, 2022, who were newly prescribed suvorexant or lemborexant, excluding patients taking other concomitant sleep medications or antipsychotics. Primary and secondary endpoints were sleep duration during the first three days after taking the medications and the incidence of falls, respectively., Results: We analyzed data from 48 and 57 patients taking suvorexant and lemborexant, respectively. When compared with that in the pre-treatment period, sleep duration was significantly longer on days 2 and 3 in the suvorexant group, and on all three days in the lemborexant group. On day 1 of drug administration, the lemborexant group had a significantly longer sleep duration than the suvorexant group (5.10 ± 1.84 vs. 5.93 ± 1.90 h, respectively; P = 0.017). Zero (0.0%) and three (5.3%) falls occurred in the suvorexant and lemborexant groups, respectively (P = 0.248)., Conclusions: Lemborexant exerted a potent inhibitory effect on orexin 2 receptors, which could explain the longer sleep duration experienced by patients taking this drug on the first day of treatment., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board of Ogaki Municipal Hospital, Ogaki, Japan issued approval 20230427-10. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mori et al.)

Treating disseminated cryptococcosis in people with human immunodeficiency virus (HIV) is challenging due to the limited availability of effective antifungals. Although isavuconazole has antifungal activity against Cryptococcus neoformans, clinical evidence is sparse because this new drug has not been approved for the treatment of cryptococcosis in the US or Europe. Here, we report a case of HIV-associated cryptococcal meningitis that relapsed during maintenance therapy with fluconazole. A Japanese man in his 20s was diagnosed with HIV-1 infection and cryptococcal meningitis. The patient was intolerant to flucytosine and was treated with liposomal amphotericin B monotherapy for 2 weeks as induction therapy, followed by fluconazole (400 mg/day) for 3 months as consolidation therapy. Four months after starting maintenance therapy with fluconazole (200 mg/day), the patient presented with fever and cough, leading to readmission to our hospital. Biopsies of a nodule in the left lung and a left cervical lymph node led to the diagnosis of disseminated cryptococcosis (pulmonary cryptococcosis and cryptococcal lymphadenitis). Although a combination of fluconazole and liposomal amphotericin B was ineffective, the patient was successfully treated with an induction therapy combining isavuconazole and liposomal amphotericin B, followed by a maintenance therapy with isavuconazole. The patient received isavuconazole orally except for loading doses, achieving stable blood concentration levels. Moreover, we observed that blood levels of amphotericin B increased gradually with repeated administration. Therefore, isavuconazole may have a potential role in the treatment of cryptococcosis, and clinical trials involving larger numbers of cases are needed to confirm its efficacy and safety., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Purpose: Blood flow signals (BFSs) through the bone cortex on ultrasonography (US) and bone marrow lesions (BMLs) detected on magnetic resonance imaging (MRI) can be used to assess bone lesions; however, no studies have reported their relationship. Therefore, this study aimed to assess whether BFSs through the bone cortex on US can serve as a screening test for detecting BMLs on MRI in patients with early knee osteoarthritis (OA)., Methods: This study enrolled patients with knee joint pain who were diagnosed with early knee OA between January 2018 and January 2024. We targeted 77 patients who underwent MRI and in whom the presence or absence of BFSs through the bone cortex was confirmed on US. The association between BFSs and BMLs was evaluated using the chi-square test, and the sensitivity and specificity of BFSs for detecting BMLs on MRI were calculated., Results: The chi-square test showed that BFSs and BMLs were significantly associated in the femur and tibia (femur: χ 2 [1] = 52.9, p < 0.001; Tibia: χ 2 [1] = 44.8, p < 0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of BFSs for detecting BMLs on MRI were 85.0%, 96.5%, 89.5%, and 94.8%, respectively, for the femur, and 84.0%, 92.3%, 84.0%, and 92.3%, respectively, for the tibia., Conclusion: BFSs through the bone cortex on US can be used as a screening test for detecting BMLs on MRI in patients with early knee OA., (© 2024. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

A compact, multi-channel ionic liquid-gated graphene field-effect transistor (FET) has been proposed and developed in our work for on-field continuous monitoring of nitrate nitrogen and other nitrogen fertilizers to achieve sustainable and efficient farming practices in agriculture. However, fabricating graphene FETs with easy filling of ionic liquids, minimal graphene defects, and high process yields remains challenging, given the sensitivity of these devices to processing conditions and environmental factors. In this work, two approaches for the fabrication of our graphene FETs were presented, evaluated, and compared for high yields and easy filling of ionic liquids. The process difficulties, major obstacles, and improvements are discussed herein in detail. Both devices, those fabricated using a 3 μm-thick CYTOP ® layer for position restriction and volume control of the ionic liquid and those using a ~20 nm-thick photosensitive hydrophobic layer for the same purpose, exhibited typical FET characteristics and were applicable to various application environments. The research findings and experiences presented in this paper will provide important references to related societies for the design, fabrication, and application of liquid-gated graphene FETs.

Background: Pulmonary vein isolation (PVI) employing cryoballoon (CB) or contact force-guided radiofrequency (CF-RF) catheter ablation has been established as an effective strategy for managing atrial fibrillation (AF). However, its efficacy in hypertrophic cardiomyopathy (HCM) remains to be further explored., Methods: This retrospective study analyzed 60 consecutive AF patients with HCM (average age 67 ± 10 years; 41 men) who were consecutively admitted to our hospital from January 2014 to December 2022 and underwent initial PVI., Results: The patients were treated with CB (26 patients) or CF-RF (34 patients). Successful PVI was achieved in both groups without significant complications. In the CF-RF group, additional ablations were performed on the cavotricuspid isthmus (14.7% of patients) and the anterior line (2.9%). The CB group benefited from reduced procedural times (93 ± 31 vs. 165 ± 60 min, p < 0.05) and decreased saline irrigation requirements (77.5 ± 31.4 vs. 870 ± 281.9 mL, p < 0.0001). Using a contrast medium was exclusive to the CB group (33.8 ± 4.2 mL). In a 12-month follow-up, the atrial tachyarrhythmia recurrence-free rates in the CB and CF-RF groups were comparable (77% and 76%, respectively; p = 0.63 according to the log-rank test). Notably, pulmonary vein reconnection was prevalent in most (7 out of 8) patients requiring a secondary ablation procedure., Conclusion: PVI is feasible as a strategy for AF in patients with HCM employing either CB or CF-RF techniques. While the recurrence-free rates were comparable in both groups, differences were noted in procedure duration, saline usage, and the need for a contrast medium., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)