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Context. High-mass young stellar objects gain most of their mass in short intense bursts of accretion. Maser emission is an invaluable tool in discovering and probing these accretion bursts. Aims. Our aim was to observe the 22 GHz water maser response induced by the accretion burst in NGC6334I-MM1B and to identify the underlying maser variability mechanisms. Methods. We report seven epochs of very long baseline interferometry (VLBI) observations of 22 GHz water masers in NGC6334I with the VLBI Exploration of Radio Astrometry (VERA) array, from 2014 to 2016, spanning the onset of the accretion burst in 2015.1. We also report 2019 Atacama Large Millimeter/submillimeter Array (ALMA) observations of 321 GHz water masers and 22 GHz single-dish maser monitoring by the Hartebeesthoek Radio Astronomical Observatory (HartRAO). We analysed long-term variability patterns and used proper motions with the 22 GHz to 321 GHz line ratio to distinguish between masers in non-dissociative C-shocks and dissociative J-shocks. We also calculated the burst-to-quiescent variance ratio of the single-dish time series. Results. We detected a water maser distribution resembling a bipolar outflow morphology. The constant mean proper motion before and after the burst indicates that maser variability is due to excitation effects from variable radiation rather than jet ejecta. For the whole region, we find that the flux density variance ratio in the single-dish time series can identify maser efficiency variations in 22 GHz masers. The northern region, CM2-W2, is excited in C-shocks and showed long-term flaring with velocity-dependent excitation of new maser features after the onset of the burst. We propose that radiative heating of H2 due to high-energy radiation from the accretion burst be the main mechanism for the flaring in CM2-W2. The southern regions are excited by J-shocks, which have shown short-term flaring and dampening of water masers. We attribute the diverse variability patterns in the southern regions to the radiative transfer of the burst energy in the complex source geometry. Conclusions. Our results indicate that the effects of source geometry, shock type, and incident radiation spectrum are fundamental factors affecting 22 GHz maser variability. Investigating water masers in irradiated shocks will improve their use as a diagnostic in time-variable radiation environments, such as accretion bursting sources. [ABSTRACT FROM AUTHOR]

Background: On-pump beating coronary artery bypass grafting (CABG) is a procedure that uses cardiopulmonary bypass to maintain circulation and it is a useful technique for CABG in patients with severely impaired cardiac function. Here, we report a case of left atrial rupture that occurred during CABG. Reports of left atrial injury are rare, and there have been no previous reports of such cases associated with on-pump beating CABG., Case Presentation: An 80-year-old man with a history of myocardial infarction was admitted to another hospital for acute heart failure. Coronary angiography revealed triple-vessel disease, and echocardiography showed reduced left ventricular function and moderate mitral regurgitation. He was transferred to our hospital for coronary artery bypass grafting and the operation was scheduled. Surgery was started with the intention of off-pump CABG, but due to circulatory instability, the patient was converted to on-pump beating CABG. While the heart was being dislocated and anastomosis was being performed, sudden bleeding from the left atrium occurred. To achieve hemostasis, we needed to arrest the patient's heart. A 5-cm laceration along the posterior mitral annulus was found in the left atrium and repaired with a bovine pericardial patch. Mitral annuloplasty with a flexible ring was performed simultaneously. He recovered uneventfully., Conclusions: The left atrial rupture during on-pump beating coronary artery bypass grafting is extremely rare. The wall of the atrium is thought to have been damaged by the stress applied during the displacement of the heart and the impact of the enlarged mitral regurgitant jet. Repair under cardiac arrest is necessary, and in some cases, mitral annuloplasty may be additionally required., Competing Interests: Declarations. Ethics approval and consent to participate: This report was approved by Kumamoto University Hospital Medical Practice Review Committee on July 17, 2024 (Case Report No.4). Consent for publication: Written informed consent of the patient was obtained. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

The aim of this study is to compare long-term health outcomes between IVF-conceived children and non-IVF-conceived children in Japan, in the context of strong recommendation for single embryo transfer. Using data from a nationwide birth cohort linked with perinatal database, this study analyzed 2140 children born in Japan in May 2010. It compared child health and development outcomes up to 9 years of age between IVF-conceived and non-IVF-conceived children (binary exposure). A Poisson regression with robust variance to estimate the risk ratios for the association between IVF and various long-term child health and developmental outcomes. After adjusting for confounding factors, no significant differences were observed between IVF-conceived and naturally conceived children for most outcomes, including hospitalization, obesity, and developmental milestones. IVF-conceived children showed a slightly lower risk of attention problems at 8 years (adjusted Risk Ratio [aRR]: 0.73, 95% CI: 0.53-1.00). In subgroup analyses, IVF-conceived term children and singletons demonstrated reduced risk of cognitive delays at 5.5 years (aRR: 0.31, 95% CI: 0.10-0.96 and aRR: 0.37, 95% CI: 0.14-0.98, respectively).Conclusion: In this Japanese cohort, IVF conception was not associated with adverse long-term health or developmental outcomes. These findings provide reassurance about the safety of IVF, particularly in the context of single embryo transfer policies. Further research is needed to explore specific IVF protocols and subgroups., Competing Interests: Declarations Ethics approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Review Board of the Graduate School of Biomedical Sciences, Okayama University (No. 2310–018), and the Clinical Research Management and Review Committee of the Japan Society of Obstetrics and Gynecology (No. 150). Consent to participate Patient consent was waived for this study as it utilized secondary data from national surveys and databases managed by relevant authorities and obstetrics and gynecology societies. All data used were anonymized and collected in accordance with applicable ethical guidelines and regulations. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Completion of DNA replication before chromosome segregation is essential for the stable maintenance of the genome. Under replication stress, DNA synthesis may persist beyond S phase, especially in genomic regions that are difficult to proceed with the replication processes. Incomplete replication in mitosis emerges as non-disjoined segment in mitotic chromosomes leading to anaphase bridges. The resulting chromosome rearrangements are not well characterized, however. Here, we report that incomplete replication due to SMC5/6 deficiency impairs sister chromatid disjunction at difficult-to-replicate regions, including common fragile sites. These non-disjoined regions manifest as cytologically defined symmetric gaps, causing anaphase bridges. These bridges break at the gaps, leading to telomere loss, micronucleation, and fragmentation. Subsequently, fusions between telomere-deficient chromosomes generate complex chromosomal rearrangements, including dicentric chromosomes, suggesting the occurrence of breakage-fusion-bridge cycle. Additionally, chromosomes in micronuclei were pulverized, indicative of chromothripsis. Our findings suggest that incomplete replication facilitates complex chromosomal rearrangements, which may contribute to genomic instability in human cancers., (© 2024 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

Objectives: The aim of this article is to update evidence on the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) and provide information to the taskforce for the 2024 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis (RA)., Methods: We searched various databases for randomised controlled trials on RA published until June 2022, with no language restriction. For each of the 15 clinical questions, two independent reviewers screened the articles, evaluated the core outcomes, and performed meta-analyses., Results: Subcutaneous injection of methotrexate (MTX) showed similar efficacy to oral MTX in MTX-naïve RA patients. Ozoralizumab combined with MTX improved drug efficacy compared to the placebo in RA patients with inadequate response (IR) to conventional synthetic DMARD (csDMARD). Rituximab with and without concomitant csDMARDs showed similar efficacy to other biological DMARDs (bDMARDs) in bDMARD-IR RA patients. Combined Janus kinase inhibitors and MTX achieved similar clinical responses and equal safety during a 4-year period compared to tumour necrosis factor inhibitors in MTX-IR RA patients. Biosimilars showed efficacy equivalent to that of the original bDMARDs in csDMARD-IR and bDMARD-IR RA patients., Conclusions: This systematic review provides latest evidence for the 2024 update of the Japan College of Rheumatology clinical practice guidelines for RA management., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Background: Posaconazole (PCZ) plays a crucial role in the prophylaxis and treatment of invasive fungal infections in hematologic malignancies. PCZ concentrations reportedly vary among patients receiving delayed-release tablets (DRT). However, the factors influencing these concentrations remain insufficiently elucidated. Therefore, this study aimed to evaluate the factors influencing PCZ concentrations and their effect on the probability of target attainment (PTA) using a population pharmacokinetic (PPK) approach. We also explored the relationship between PCZ exposure and hepatotoxicity., Methods: This retrospective study included adult patients with hematologic malignancies who received PCZ DRT. A PPK model was developed based on observational data for 130 concentrations in 28 patients. Simulation analyses were performed to assess the PTA at standard doses of 0.7 and 1.0 mg/L for prophylaxis and treatment, respectively. Estimated concentrations were used to evaluate the correlation between PCZ exposure and hepatotoxicity., Results: Significant factors influencing PCZ concentrations included body weight, serum total protein levels, and diarrhea. Diarrhea correlated with decreased PCZ concentrations resulting in up to 26% lower PTA compared with that without diarrhea. Moreover, PTA declined markedly as the total protein levels decreased from 6.6 g/dL to 4.4 g/dL. The incidence of hepatotoxicity was 17.4% (4/23); no significant relationship could be established between the PCZ concentrations and hepatotoxicity ( P = 0.188)., Conclusions: We identified the factors affecting PCZ exposure, which could not be detected by PPK analysis using data from clinical trials. Our results suggest that the generally recommended dose of PCZ causes underexposure in patients with hematologic malignancies characterized by high body weight, hypoproteinemia, or concurrent diarrhea. Therapeutic drug monitoring for DRT may be recommended, especially in patients with these risk factors., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: It has been reported that circadian clock components, Brain and Muscle ARNT-Like 1 (BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK), are uniquely essential for glioblastoma (GBM) stem cell (GSC) biology and survival. Consequently, we developed a novel Cryptochrome (CRY) activator SHP1705, which inhibits BMAL1-CLOCK transcriptional activity., Methods: We analyzed buffy coats isolated from Phase 1 clinical trial subjects' blood to assess any changes to circadian, housekeeping, and blood transcriptome-based biomarkers following SHP1705 treatment. We utilized GlioVis to determine which circadian genes are differentially expressed in non-tumor versus GBM tissues. We employed in vitro and in vivo methods to test the efficacy of SHP1705 against patient-derived GSCs and xenografts in comparison to earlier CRY activator scaffolds. Additionally, we applied a novel-REV-ERB agonist SR29065, which inhibits BMAL1 transcription, to determine whether targeting both negative limbs of the circadian transcription-translation feedback loop (TTFL) would yield synergistic effects against various GBM cells., Results: SHP1705 is safe and well-tolerated in Phase I clinical trials. SHP1705 has increased selectivity for the CRY2 isoform and potency against GSC viability compared to previously published CRY activators. SHP1705 prolonged survival in mice bearing GBM tumors established with GSCs. When combined with the novel REV-ERB agonist SR29065, SHP1705 displayed synergy against multiple GSC lines and differentiated GSCs (DGCs)., Conclusions: These demonstrate the efficacy of SHP1705 against GSCs, which pose for GBM patient outcomes. They highlight the potential of novel circadian clock compounds in targeting GBM as single agents or in combination with each other or current standard-of-care., Key Points: SHP1705 is a novel CRY2 activator that has shown success in Phase 1 safety trialsSHP1705 has a significantly improved efficacy against GSCs and GBM PDX tumorsNovel REV-ERB agonist SR29065 and SHP1705 display synergistic effects against GSCs., Importance of the Study: CRY2 is decreased in GBM tissues compared to CRY1 suggesting that promoting CRY2 activity will be an efficacious GBM treatment paradigm. SHP1705, a CRY2 activator that has shown success in Phase 1 safety trials, has significantly improved preclinical efficacy. Novel REV-ERB agonist SR29065 displays synergistic effects against diverse GBM cells.

Pancreatic neuroendocrine tumors (PanNETs) are generally hypervascular and readily detectable on imaging tests. However, hypovascular PanNETs are clinically problematic, requiring multiple imaging tests and tissue analyses to differentiate them from pancreatic ductal cancers. A 41 year-old man presented with Whipple's triad; 72 h fasting test followed by glucagon challenge test suggested insulinoma. However, contrast-enhanced computed tomography image showed a 17 mm tumor with poor enhancement and unclear borders in the tail of the pancreas . Abdominal magnetic resonance imaging and contrast-enhanced endoscopic ultrasonography (EUS) indicated cystic degeneration and necrosis at the same site; EUS-guided fine-needle aspiration cytology indicated a PanNET Grade 1 tumor. Although the imaging was inconclusive, diazoxide treatment ameliorated the hypoglycemia-related symptoms and insulinoma was deemed likely; following tail pancreatectomy and splenectomy, the symptoms disappeared. Pathological examination revealed a tumor positive for insulin and classed as PanNET Grade 1 according to the 2019 WHO classification. The microvessel density (MVD) of the tumor was found to be as low as 3.9%, which may partly account for the inconclusive images. The present case was difficult to diagnose preoperatively due to hypovascularity on imaging because of reduced MVD. It is clinically important to evaluate MVD in cases of hypovascular PanNETs by multiple preoperative imaging studies to differentiate them from pancreatic cancers and to validate the findings by postoperative pathological analysis., Competing Interests: Conflicts of interestDY has received consulting/lecture fees from Novo Nordisk Pharma Ltd., Nippon Boehringer Ingelheim, Eli Lilly Japan K.K., and Kyowa Kirin Co., Ltd. DY also received grants from Arkray Inc., Novo Nordisk Pharma Ltd., Nippon Boehringer Ingelheim, Taisho Pharmaceutical Co. Ltd., and Terumo Corporation. YH has received lecture fees from Sumitomo Pharma Co. Ltd. RI, MS, TK, SO, SK, YL, YT, KT, MM, TH, TM, TK, TK, and TM declare that they have no conflict of interest. All authors declare that they have no competing interests relevant to this study., (© The Japan Diabetes Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Maintenance of ploidy depends on the mitotic kinase Aurora B, the catalytic subunit of the chromosomal passenger complex (CPC) whose proficient activity is supported by HP1 enriched at inner centromeres. HP1 is known to associate with INCENP of the CPC in a manner that depends on the PVI motif conserved across HP1 interactors. Here, we found that the interaction of INCENP with HP1 requires not only the PVI motif but also its C-terminally juxtaposed domain. Remarkably, these domains conditionally fold the β-strand (PVI motif) and the α-helix from a disordered sequence upon HP1 binding and render INCENP with high affinity to HP1. This bipartite binding domain termed SSH domain (Structure composed of Strand and Helix) is necessary and sufficient to attain a predominant interaction of HP1 with INCENP. These results identify a unique HP1-binding module in INCENP that ensures enrichment of HP1 at inner centromeres, Aurora B activity, and thereby mitotic fidelity., (© 2024 Sako et al.)

Aims: A fourth heart sound (S4) was reported to be almost never present in patients with amyloid light-chain cardiomyopathy. There have been no reports on S4 in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). This study aimed to clarify the clinical implications of S4 in patients with ATTRwt-CM., Methods and Results: Seventy-six patients with ATTRwt-CM (mean age: 80.4 ± 5.4 years, 68 males) who had undergone phonocardiography (PCG) were retrospectively assessed. We measured S4 amplitude on digitally recorded PCG. S4 was considered to be present when its amplitude was 1.0 mm or greater on the PCG. Distinct S4 was defined as S4 with an amplitude of 2.0 mm or greater, which is usually recognizable by auscultation. According to the rhythm and presence or absence of S4, the patients were divided into three groups, namely, sinus rhythm (SR) with S4, SR without S4, and non-SR. Non-SR consisted of atrial fibrillation, atrial flutter, and atrial tachycardia. Thirty-six patients were in SR and the remaining 40 patients were in non-SR. In the 36 patients in SR, S4 was shown by PCG to be present in 17 patients (47%), and distinct S4 was recognized in 7 patients (19%) by auscultation. In patients who were in SR, those with S4 had higher systolic blood pressure (124 ± 15 vs. 99 ± 8 mmHg, P < 0.001), lower level of plasma B-type natriuretic peptide (308 [interquartile range (IQR): 165, 354] vs. 508 [389, 765] pg/mL, P = 0.034) and lower level of high-sensitivity cardiac troponin T (0.068 [0.046, 0.089] vs. 0.109 [0.063, 0.148] ng/mL, P = 0.042) than those without S4. There was no significant difference in left atrium (LA) volume index or LA reservoir strain between patients with S4 and without S4. Patients with S4 had more preserved LA systolic function than those without S4 (peak atrial filling velocity: 53 ± 25 vs. 34 ± 9 cm/s, P = 0.033; LA contractile strain: 4.1 ± 2.1 vs. 1.6 ± 2.0%, P = 0.012). Patients in SR without S4 had worse short-term prognosis compared with the other two groups (generalized Wilcoxon test, P = 0.033)., Conclusions: S4 was present in 47% of the patients in SR with ATTRwt-CM. Patients in SR without S4 had more impaired LA systolic function than those in SR with S4. The absence of S4 portends a poor short-term prognosis in patients with ATTRwt-CM., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Probiotic-fermented milk is commonly used to maintain intestinal health. However, the effects of heat-treated fermented milk, which does not contain live microorganisms, on intestinal function are not yet fully understood. This study aimed to investigate whether heat-treated Lactobacillus helveticus CP790-fermented milk affects fecal microbiota and gut health as a "postbiotic". A randomized, double-blind, placebo-controlled trial was conducted in healthy Japanese individuals aged 20-59 years with a tendency toward constipation. Participants consumed 100 mL of either the test beverage ( n = 60) or placebo beverage ( n = 60) for four weeks. The test beverages were prepared with heat-treated CP790-fermented milk, while the placebo beverages were prepared with nonfermented milk flavored with lactic acid. Fecal samples were analyzed using 16S rRNA gene sequencing. Constipation symptoms were assessed using defecation logs and the Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire. Mood state was also assessed using the Profile of Mood States 2 (POMS2) questionnaire to explore its potential as a "psychobiotic". Desulfobacterota were significantly decreased by CP790-fermented milk intake. PICRUSt2 analysis predicted a decrease in the proportion of genes involved in the sulfate reduction pathway following the consumption of CP790-fermented milk. The CP790-fermented milk intervention significantly improved stool consistency and straining during defecation. These improvements were correlated with a decrease in Desulfobacterota . After the intervention, overall mood, expressed as total mood disturbance, and depression-dejection were significantly better in the CP790 group than in the placebo group. These results suggest that the intake of CP790-fermented milk could be effective in modulating gut microbiota and improving constipation symptoms and mood states.

Letermovir is a newly developed antiviral agent used for the prophylaxis of human cytomegalovirus infections in patients undergoing allogeneic hematopoietic cell transplantation. This novel anti-cytomegalovirus drug, used for the prophylaxis of cytomegalovirus reactivation until approximately 200 days after transplantation, effectively reduces the risk of clinically significant cytomegalovirus infection. No human counterpart exists for the terminase complex; letermovir is virus specific and lacks some toxicities previously observed with other anti-cytomegalovirus drugs, such as cytopenia and nephrotoxicity. The absolute bioavailability of letermovir in healthy individuals is estimated to be 94% based on a population-pharmacokinetic analysis. In contrast, oral administration of letermovir to patients undergoing hematopoietic cell transplantation results in lower exposure than that in healthy individuals. Renal or hepatic impairment does not influence the intrinsic clearance of letermovir. Co-administration of letermovir may alter the plasma concentrations of other drugs, including itself, as it acts as a substrate and inhibitor/inducer of several drug-metabolizing enzymes and transporters. In particular, attention should be paid to the drug-drug interactions between letermovir and calcineurin inhibitors or azole antifungal agents, which are commonly used in patients undergoing hematopoietic cell transplantation. This article reviews and summarizes the clinical pharmacokinetics and pharmacodynamics of letermovir, focusing on patients undergoing hematopoietic cell transplantation, healthy individuals, and specific patient subsets., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Lactononadecapeptide (LNDP; NIPPLTQTPVVVPPFLQPE), a casein-derived peptide comprising 19 residues, is known for its capacity to enhance cognitive function. This study aimed to explore the transepithelial transport and stability of LNDP. Results showed that LNDP retained over 90% stability after 2 h of treatment with gastrointestinal enzymes. The stability of LNDP on Caco-2 cell monolayers ranged from 93.4% ± 0.9% to 101.1% ± 1.2% over a period of 15-60 min, with no significant differences at each time point. The permeability of LNDP across an artificial lipid membrane was very low with the effective permeability of 3.6 × 10 -11 cm/s. The Caco-2 assay demonstrated that LNDP could traverse the intestinal epithelium, with an apparent permeability of 1.22 × 10 -6 cm/s. Its transport was significantly inhibited to 67.9% ± 5.0% of the control by Gly-Pro, a competitor of peptide transporter 1 (PEPT1). Furthermore, PEPT1 knockdown using siRNA significantly inhibited LNDP transport by 77.6% ± 1.9% in Caco-2 cell monolayers. The LNDP uptake in PEPT1-expressing HEK293 cells was significantly higher (54.5% ± 14.6%) than that in mock cells. These findings suggest that PEPT1 plays a crucial role in LNDP transport, and LNDP exhibits good resistance to gastrointestinal enzymes.

Background: The relationships between electrocardiography (ECG) findings and echocardiographic profiles in patients with hypertrophic cardiomyopathy (HCM) are not fully understood., Methods: One hundred forty patients (mean age: 62.9 ± 15.3 years, 96 men) with HCM were studied. We assessed the associations between ECG findings and echocardiographic findings including maximum left ventricular wall thickness, HCM subtypes and distribution of left ventricular hypertrophy (LVH): the LV was divided into basal, mid, and apical segments by dividing it into thirds along the long axis., Results: In ECG, LVH by voltage criteria, abnormal Q wave, negative T wave, and giant negative T wave (GNT) were observed in 74 (53 %), 30 (21 %), 132 (94 %), and 25 (18 %) of the patients, respectively. In two groups with and without an LVH pattern according to voltage criteria in ECG, there were no significant differences in maximum LV wall thickness, subtype of HCM, and distribution of LVH. Regarding an abnormal Q wave, the proportion of patients with LVH in the basal segment was significantly higher in patients with an abnormal Q wave than in patients without an abnormal Q wave (87 % vs 61 %, p = 0.008). An abnormal Q wave was not observed in patients with LVH confined to the apex. Patients with a GNT included patients with LVH located at only the apex (apical HCM), LVH from the mid segment to apex, and LVH from the base to apex. No GNT was found in patients with hypertrophy located in the upper region from the base to mid segment of the LV., Conclusions: In patients with HCM, there was no significant correlation between the presence of LVH by voltage criteria in ECG and echocardiographic findings. An abnormal Q wave was associated with disproportionate hypertrophy of the basal wall and a GNT reflected the presence of LVH in the apical segment., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Cardiac surgery-associated (CSA) acute kidney injury (AKI) is a severe postoperative complication in patients undergoing off-pump coronary artery bypass grafting (OPCAB). Early detection of postoperative CSA-AKI may be key to improving patient outcomes. This study explored the use of renal biomarkers measured immediately after surgery for the early detection of CSA-AKI in patients undergoing OPCAB., Methods and results: In all, 111 patients who underwent OPCAB at Kumamoto University Hospital between June 2020 and October 2022 were included in this study. Urinary neutrophil gelatinase-associated lipocalin, liver-type fatty acid-binding protein, and N-acetyl-β-D-glucosaminidase (NAG) were measured upon arrival in the intensive care unit (ICU) after surgery. AKI was diagnosed using KDIGO criteria. Of the 111 patients, 32 (28.8%) developed postoperative AKI. Regarding AKI staging, 19 (59.4%), 11 (34.4%), and 2 (6.3%) patients had Stage 1, 2, and 3 AKI, respectively. There were significant differences in chronic kidney disease, preoperative estimated glomerular filtration rate (eGFR), and NAG between the AKI and non-AKI groups. Multivariate analysis showed that preoperative eGFR (odds ratio [OR] for 5-mL/min/1.73 m 2 increase in eGFR 0.75; 95% confidence interval [CI] 0.63-0.89) and increasing urinary NAG concentrations at ICU admission (OR 2.44; 95% CI 1.30-4.60) were significant risk factors for CSA-AKI in OPCAB patients., Conclusions: NAG and eGFR may be valuable biomarkers for the early detection of CSA-AKI in patients undergoing OPCAB.

Background: Pharmacists should be aware of their thought processes in dispensing work, including differences in the dispensing complexities owing to different drug positions in the left, center, and right areas. Dispensing errors associated with "same-name drugs (a pair of drugs with the same name but a different ingredient quantity)" are prevalent and often negatively affect patients. In this study, using five pairs of comparative models, the gaze movements of pharmacists in dispensing work were analyzed using an eye-tracking method to elucidate their thought processes., Methods: We prepared verification slides and displayed them on a prescription monitor and three drug rack monitors. The dispensing information (drug name, drug usage, location display, and total amount) was displayed on a prescription monitor. A total of 180 drugs including five target drugs were displayed on the three drug rack monitors. Total gaze points in the prescription area, those in the drug rack area, total vertical movements between the two areas, and time required to dispense drugs were measured as the four classifications Gaze 1, Gaze 2, Passage, and Time, respectively. First, we defined the two types of location displays as "numeral combination" and "color/symbol combination." Next, we defined two pairs of models A 1 -A 2 (numerals) and B 1 -B 2 (color/symbol) to compare differences between the left and right areas. Moreover, three pairs of models C 1 -C 2 (left), D 1 -D 2 (center), and E 1 -E 2 (right) were established to compare differences between "numeral combination" and "color/symbol combination.", Results: Significant differences in the complexities of dispensing work were observed in Gaze 2, Passage, and Time between the models A 1 -A 2 (A 1 2 ), in Gaze 2 between the models B 1 -B 2 (B 1 >B 2 ), and in Gaze 2 and Time between the models C 1 -C 2 , D 1 -D 2 , and E 1 -E 2 (C 1 >C 2 , D 1 >D 2 , and E 1 >E 2 , respectively)., Conclusions: Using the current dispensing rules, pharmacists are not good at dispensing drugs located in the right area. An effective measure for reducing the dispensing complexity is to introduce visual information in the prescription content; the utilization of the right brain facilitates reducing the complexity in the right dispensing area., (© 2024. The Author(s).)

Background: There is insufficient information regarding the bleeding sites and surgical strategies of cardiac tamponade during catheter ablation for atrial fibrillation (AF)., Case Presentation: Of the five patients with cardiac tamponade, three required surgical intervention and two required pericardiocentesis. In the first case of three cardiac tamponades requiring surgical intervention, considering that the peripheral route was used, the catecholamines did not reach the heart, and due to unstable vital signs, venoarterial extracorporeal membrane oxygenation (VA-ECMO) was inserted. No bleeding point was identified, but a thrombus had spread around the left atrium (LA) with diverticulum. Hemostasis was achieved with adhesives placed around the LA under on-pump beating. In the second case, pericardiocentesis was performed, but the patient showed heavy bleeding and unstable vital signs. Thus, VA-ECMO was inserted. Heavy bleeding was expected, and safety was enhanced by attaching a reservoir to the VA-ECMO. The bleeding point was found between the left upper pulmonary artery and LA under cardiac arrest to obtain a good surgical view for suturing repair. In the third case, the LA diverticulum was damaged. Pericardiocentesis resulted in stable vitals, but sustained bleeding was present. A bleeding point was found at the LA diverticulum, and suture repair under on-pump beating was performed., Conclusions: When cardiac tamponade occured in any patient with LA diverticulum, treatment could not be completed with pericardiocentesis alone, and thoracotomy was likely to be necessary. If the bleeding point could be confirmed, suturing technique is a more reliable surgical strategy than adhesive alone that leads to pseudoaneurysm. If the bleeding point is unclear, it is important to confirm the occurrence of LA diverticulum using a preoperative CT, and if confirmed, cover it with adhesive due to a high possibility of diverticulum bleeding. The necessity of CPB should be determined based on whether these operations can be completed while maintaining vital stability., (© 2024. The Author(s).)

Three-dimensional printing of cell constructs with high-cell density, shape fidelity, and heterogeneous cell populations is an important tool for investigating cell sociology in living tissues but remains challenging. Herein, we propose an artificial intercellular adhesion method using a photoresponsive chemical cue between a thiol-bearing polymer and a methacrylate-bearing cell membrane. This process provided cell fabrication containing 10 8 cells/mL, embedded multiple cell populations in one structure, and enabled millimeter-sized scaleup. Our approach allows for the artificial cell construction of complex structures and is a promising bioprinting strategy for engineering tissues that are structurally and physiologically relevant.

Objective: There is heterogeneity in the pathophysiology of chronic rhinosinusitis (CRS). Obtaining a detailed understanding of patient profiles in specific regions can provide valuable information not only for clinical practice but also future research plans. The aim of this study was to investigate the characteristics of patients who underwent endoscopic sinus surgery (ESS) for CRS., Methods: This retrospective, single-center study examined the features of 453 patients with CRS who underwent ESS in the Tokyo area of Japan. The study evaluated various factors in patients with CRS including sex and age, the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) score, the recurrence rate of CRS, comorbidities of asthma and/or allergic diseases, and IgE sensitization to 12 inhaled allergens., Results: Age-related declines in the sensitization rate to inhaled allergens were observed, and the most notable age-related decrease in specific IgE antibodies was observed for house dust mites (HDM) (p = 8.3 × 10 -7 ). Sensitization to HDM, cat dander, and various types of fungi, including Aspergillus, was frequently observed in the CRS with asthma group, with rates of 54%, 17%, and 17%, respectively. We found that 23% of the patients had recurrence. In the recurrence group, the positive rates of specific IgE antibodies for birch and cat dander were significantly higher than in the no recurrence group. Bronchial asthma was identified as an important factor for recurrence. Among male patients, the recurrence group was younger than the no-recurrence group (p = 0.0032). Severe eosinophilic CRS (ECRS) showed early recurrence after surgery, with over the half of the patients experiencing at least one recurrence within 2 years post-surgery. Among patients with ECRS, the recurrence rate for females was 1.92 times higher than for males., Conclusion: Our study revealed the influences of age and sex on various clinical phenotypes of CRS patients undergoing ESS. There was a high sensitization rate to cat dander in both the recurrence and asthma groups. Further research on diverse disease etiologies is necessary to improve therapeutic strategies for patients with CRS., Competing Interests: Declaration of Competing Interest This work was supported in part by a Research Grant from the Jikei University School of Medicine. Tsuguhisa Nakayama reports lecture fees from Sanofi. Mayumi Tamari reports lecture fees from Sanofi, Astra Zeneca UCB Japan, and KYORIN Pharmaceutical Co., Ltd. Mamoru Yoshikawa reports lecture fees from Sanofi and contracted research expenses from Kissei Pharmaceutical. These sources had no role in the design, conduct, preparation, or writing of this manuscript and the rest of the study authors have no conflicts of interest to disclose. The authors have no actual or potential conflict of interest to declare., (Copyright © 2023. Published by Elsevier B.V.)

Background: Disturbance of mucociliary clearance is an important factor in the pathogenesis of asthma. We hypothesized that common variants in genes responsible for ciliary function may contribute to the development of asthma with certain phenotypes., Methods: Three independent adult Japanese populations (including a total of 1,158 patients with asthma and 2,203 non-asthmatic healthy participants) were studied. First, based on the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/), we selected 12 common single-nucleotide polymorphisms (SNPs) with molecular consequences (missense, nonsense, and 3'-untranslated region mutation) in 5 primary ciliary dyskinesia (PCD)-related genes and calculated a PCD-genetic risk score (GRS) as a cumulative effect of these PCD-related genes. Second, we performed a two-step cluster analysis using 3 variables, including PCD-GRS, forced expiratory volume in 1 second (%predicted FEV1), and age of asthma onset., Results: Compared to adult asthma clusters with an average PCD-GRS, clusters with high and low PCD-GRS had similar overall characteristics: adult-onset, female predominance, preserved lung function, and fewer features of type 2 immunity as determined by IgE reactivity and blood eosinophil counts. The allele frequency of rs1530496, a SNP representing an expression quantitative trait locus (eQTL) of DNAH5 in the lung, showed the largest statistically significant difference between the PCD-GRS-High and PCD-GRS-Low asthma clusters (p = 1.4 x 10-15)., Conclusion: Genes associated with PCD, particularly the common SNPs associated with abnormal expression of DNAH5, may have a certain influence on the development of adult-onset asthma, perhaps through impaired mucociliary clearance., Competing Interests: NH has received lecture fees and/or research funding from AstraZeneca, Boehringer Ingelheim, KYORIN Pharmaceutical, GlaxoSmithKline, Novartis, and Sanofi. The rest of the authors have no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Shigemasa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: This study was performed to investigate the effectiveness of hydrodissection during computed tomography-guided renal cryoablation by evaluation of the fluid distribution based on the retroperitoneal anatomy with the interfascial plane., Materials and Methods: Between March 2014 and March 2021, 52 renal tumors were treated by cryoablation with hydrodissection (36 men; mean age 72.5 years). The hydrodissection needle was located in perirenal space. The spreading fluid space based on the retroperitoneal anatomy with the interfascial plane was retrospectively evaluated. The fluid space that most effectively separated the tumor from the adjacent organs was defined. The relationship of the needle tip position in the perirenal space (renal capsule or fascia side) and the most effective fluid space was also evaluated., Results: Cryoablation was successfully completed in all cases with no major complications. Hydrodissection was effective in all cases. The distance between the tumors and the adjacent organs was significantly longer after hydrodissection (from 7.50 ± 7.43 to 22.6 ± 9.86 mm) (P < 0.0001). Although fluid spreading through multiple retroperitoneal spaces was frequently observed, the retromesenteric plane was observed more frequently as the most effective fluid space (67.3%) than the perirenal space (21.2%) (P < 0.0001). Regardless of the needle tip position, the most effective fluid space was also commonly the retromesenteric plane., Conclusions: The retromesenteric plane could be the most effective fluid space to separate the tumor from the adjacent organ, regardless of where the hydrodissection needle tip is positioned in the perirenal space., Level of Evidence: 3b., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Background: Acute aortic dissection (AAD) has high morbidity and a high fatality rate for a cardiovascular disease. Recent studies suggested that the incidence of AAD is increasing. However, the actual incidence and mortality rates of AAD are not well known. This study investigated the current epidemiology of AAD within the Yatsushiro medical jurisdictional area., Methods and results: A population-based review of patients with AAD was performed in a geographically well-defined area. Data were collected retrospectively from January 2011 to December 2020 for a total of 196 patients with AAD (Stanford Type A, n=126 [64.3%]; Stanford Type B, n=70 [35.7%]). The mean patient age was 74.3 years, and 55.6% (109/196) were women. The crude and age-standardized incidence rates of AAD in our medical jurisdictional area were 13.6 and 11.4 per 100,000 inhabitants per year, respectively. The crude and age-standardized 30-day mortality rates of AAD were 4.9 and 4.0 per 100,000 inhabitants per year, respectively. There were upward tendencies for both the incidence and 30-day mortality rate of AAD with age, with both being significantly higher in patients aged ≥85 years (P<0.001)., Conclusions: This population-based study detected a higher incidence of AAD than previous studies, but reported a lower incidence of AAD in men than in women. Increasing age was associated with an increased incidence and mortality rate of AAD.

We investigated the effects of low-level Er:YAG laser irradiation on proliferation and alternations in early gene expression of gingival fibroblasts. Mice primary gingival fibroblasts were irradiated with an Er:YAG laser (1.8, 3.9, and 5.8 J/cm 2 ). Irradiation at 3.9 J/cm 2 promoted cell proliferation without significant changes in lactate dehydrogenase or Hspa1a expression. Three hours after irradiation at 3.9 J/cm 2 , the Fn1 expression level was significantly increased. RNA-seq identified 15 differentially expressed genes between irradiated and non-irradiated cells, some of which belonged to immediate early genes (IEGs). Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated MAPK pathway enhancement, and gene set enrichment analysis showed enrichment in the TGF-β signaling gene set. Enhanced proliferation via laser irradiation disappeared upon inhibition of Dusp4, Dusp5, and Tgfr1 expression. Low-level Er:YAG laser irradiation, especially at 3.9 J/cm 2 without a major temperature elevation, enhanced fibroblast proliferation, via TGF-β and the MAPK signaling pathway following IEG expression., (© 2023 Wiley-VCH GmbH.)

Introduction: Statins are HMG-CoA reductase inhibitors that primarily lower plasma cholesterol levels. It has been suggested that the myotoxic response is a direct result of hydroxymethylglutaryl-CoA reductase inhibition and dose-dependent. Therefore, an accurate understanding of the combination of drugs that inhibit statin metabolism and factors that cause interindividual variability in the pharmacokinetics of statin is important to avoid serious side effects of statins. Relevant articles included in this review were identified through a PubMed search (through May 2023)., Areas Covered: This review provides an overview of hepatic and intestinal metabolism of statins, followed by a discussion of drug-drug interactions and interindividual variables that influence statin pharmacokinetics: gut bacteria, disease, and pharmacokinetics-related genetic polymorphisms., Expert Opinion: Drug-drug interactions have a strong influence on statin pharmacokinetics, and gut microbiota, disease, and genetic polymorphisms all contribute significantly to interindividual variation in statin pharmacokinetics. Individual optimization of statin treatment requires studies that consider the progression of the disease and associated changes in concomitant medications.

An 11-year-old female Persian cat underwent ovariohysterectomy due to dilation of the uterine cavity with irregular thickening of the wall. Macroscopically, the middle and distal regions of the left uterine horn were swollen and the uterine wall was irregularly thickened due to the development of multiple coalescent, variably sized nodules. Microscopically, the nodules had originated in the endometrium and were composed of round to polygonal neoplastic cells arranged in dense sheets or ill-defined fascicles. The neoplastic cells had locally invaded the myometrium and reached the subserosa, with lymphovascular invasion. Immunohistochemically, the neoplastic cell population was partially positive for CD10, an established marker of endometrial stromal sarcoma (ESS) in humans, with focal and diffuse nuclear immunopositivity for oestrogen and progesterone receptors and immunonegativity for desmin and α-smooth muscle actin. Based on these findings, the uterine tumour was diagnosed as ESS and was considered to correspond morphologically to high-grade ESS in humans., Competing Interests: Declaration of competing interests The authors declared no conflicts of interest in relation to the research, authorship or publication of this article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Hypomagnesemia is a characteristic adverse event of cetuximab in patients with head and neck cancer (HNC). However, there is limited information about its prevalence, risk factors, and preventive strategies. This study aimed to investigate the risk factors of hypomagnesemia and examine the preventive effects of prophylactic magnesium (Mg) administration. We initially investigated HNC patients treated with cetuximab between 2013 and 2019. Our institute started prophylactic Mg treatment (20-mEq Mg sulfate administration before cetuximab) in practice during this period. We retrospectively assess the preventive efficacy by comparing patients before and after its implementation. In total, 109 patients were included. In 60 patients without prophylaxis, all-grade and grade ≥2 hypomagnesemia at 3 months occurred in 61.7 and 15.0% of patients. The incidence of hypomagnesemia was not affected by regimens and concomitant medications. In 49 patients treated with prophylactic Mg treatment, there was no significant decrease in the cumulative incidence of hypomagnesemia. However, the preventive Mg treatment eliminated the need for additional Mg repletion to maintain Mg levels in patients treated with paclitaxel + cetuximab. A risk factor in patients without prophylaxis was a low Mg level at pre-treatment (≤2.0 mg/dL) (odds ratio: 6.03, 95% confidence interval: 1.78-20.4, p = 0.004), whereas that in patients with prophylaxis was the number of cetuximab doses (≥10) (odds ratio: 5.50, 95% confidence interval: 1.52-19.87, p = 0.009). In conclusion, a low pre-treatment Mg level was the only risk factor that could be avoided by prophylactic Mg administration. This preventive intervention is recommended for managing cetuximab-induced hypomagnesemia.