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Background: Left atrial epicardial adipose tissue (LA-EAT) is associated with the recurrence of atrial tachyarrhythmias (AF/AT) after catheter ablation for atrial fibrillation (AF). However, no previous studies have assessed the predictive value of segment-specific LA-EAT volumes for AF/AT recurrence. This study aimed to assess the relationship between segmental LA-EAT volume and AF/AT recurrence., Methods: This study included 350 consecutive patients who underwent initial AF ablation (53.7 % paroxysmal AF (PAF)). Preoperative multidetector row computed tomography assessed LA-EAT, categorized into three segments: anterior-EAT, posterior-EAT, and interatrial septal adipose tissue (IAS-AT)., Results: During a mean follow-up period of 351 ± 109 days, 56 patients (16.0 %) experienced AF/AT recurrence. The mean LA-EAT volume was 20.7 ± 11.1 ml and LA-EAT ≥26.8 ml was an independent risk factor for AF/AT recurrence (HR 2.21, 95 % confidence interval (CI): 1.24-3.93, P = 0.007). Receiver operating characteristic analyses revealed the area under the curve for IAS-AT was 0.669 (95 % CI: 0.596-0.743) with an optimal cut-off point of 1.3 ml (sensitivity 76.8 %; specificity 50.0 %), significantly outperforming the anterior- and posterior-EAT in predicting recurrent AF/AT. Multivariate analysis indicated IAS-AT was an independent predictor of AF/AT recurrence in patients with persistent AF (PeAF) (HR 3.52, 95 % CI: 1.52-8.13, P = 0.003), but not in patients with PAF., Conclusions: LA-EAT predicts AF/AT recurrence after AF ablation, with IAS-AT proving significantly more effective than other LA-EAT segments in predicting recurrence. Notably, IAS-AT emerged as an independent predictor of AF/AT recurrence in patients with PeAF but not in those with PAF., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Atrial fibrillation (AF) is a prevalent multifactorial arrhythmia associated with specific single-nucleotide polymorphisms (SNPs). Pulmonary vein (PV) isolation is an established treatment for AF; however, recurrence risk remains caused by AF triggers beyond the PVs. Understanding the embryological origins of these triggers could improve treatment outcomes., Objectives: This study aimed to investigate the association between embryologically categorized AF triggers, clinical and genetic backgrounds, and postablation prognosis., Methods: In cohort 1, comprising 3,067 patients with AF undergoing PV isolation, the clinical characteristics and outcomes were analyzed. Among them, 815 patients underwent genetic analysis using AF-associated SNPs (cohort 2). Patients were delineated based on the developmental origin of the AF triggers: common PV, sinus venosus (SV), and primitive atrium (PA)., Results: SV-origin extra-PV AF triggers occurred in 20.3% (n = 622) of patients, whereas PA-origin triggers occurred in 11.9% (n = 365) of patients in cohort 1. Multivariate analysis of cohort 2 revealed that female sex, lower body mass index, absence of hypertension, rs2634073 near PITX2, and rs6584555 in NEURL1 were associated with SV-AF, whereas nonparoxysmal AF and rs2634073 near PITX2 were predictors of PA-AF. The PA group had a significantly higher arrhythmia recurrence rate after repeated procedures than the common PV (HR: 1.75; 95% CI: 1.34-2.29; P < 0.001) and SV-AF (HR: 1.31; 95% CI: 1.19-1.45; P < 0.001) groups with more de novo AF triggers. However, the incidence of adverse events did not differ significantly among the 3 groups., Conclusions: SV-derived AF triggers may have hereditary factors with a favorable postablation prognosis, whereas PA-derived triggers are linked to AF persistence and poor ablation response. Variants near PITX2 may play a pivotal role in extra-PV triggers., Competing Interests: Funding Support and Author Disclosures This research received financial support from the Tailor-made Medical Treatment Program (grant number 1K157), Grant-in-Aid (Grant No. 26293052) bestowed by the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan, and the Practical Research Project for Life-Style Related Diseases Including Cardiovascular Diseases and Diabetes Mellitus, courtesy of the Japan Agency for Medical and Development (AMED) under Project Code 15656344. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Very high-power short-duration (vHPSD) ablation creates shallower lesions, potentially reducing efficacy. This study aims to identify factors leading to insufficient lesions during pulmonary vein antral isolation (PVAI) with vHPSD-ablation and to develop an optimized PVAI strategy using this technology., Methods: PVAI was performed on 41 atrial fibrillation patients using vHPSD-ablation (90 W/4 s). Lesion parameters were recorded and analyzed to identify predictors of insufficient lesions. An optimized PVAI strategy, based on these predictors, was tested in subsequent 42 patients., Results: In total, 3099 RF-applications, including 103(3.3%) insufficient lesions, were analyzed. First-pass PVAI was achieved in 19/40(47.5%) right PVs and 24/41(58.5%) left PVs. Multivariate analysis identified significant predictors of insufficient lesions: local largest bipolar voltage (Bi-V), average contact force, baseline impedance, impedance drop, temperature rise, inter-lesion distance (ILD), and anatomical location (carina or not). An ILD:4-6 mm increased the risk of insufficient lesions 2.2-fold, and lesions at the carina increased it 3.6-fold for both ILD < 4 mm and ILD:4-6 mm. Local largest Bi-V was the strongest predictor for insufficient lesions. The optimized PVAI approach, utilizing vHPSD-ablation with an ILD < 4 mm in non-carinal areas with Bi-V < 4 mV, and high-power ablation-index guided ablation (HPAI, 50 W, ablation-index:450-550) in remaining areas, achieved first-pass PVAI in 92.7% of right PVs and 88.1% of left PVs, using vHPSD-ablation in approximately 65% of total RF-applications. The optimized PVAI achieved significantly higher first-pass PVI rate (p < .0001) with shorter ablation time (p = .04)., Conclusion: Appropriate use of vHPSD and HPAI, based on local largest Bi-V and anatomical information, may achieve high first-pass PVAI rates in shorter ablation time with minimal energy delivery., (© 2024 Wiley Periodicals LLC.)

Competing Interests: Declaration of competing interest The authors declare they have no financial interests.

The human malaria parasite Plasmodium falciparum causes the most severe form of malaria in endemic regions and is transmitted via mosquito bites. To better understand the biology of this deadly pathogen, a variety of P. falciparum reporter lines have been generated using transgenic approaches to express reporter proteins, such as fluorescent proteins and luciferases. This review discusses the advances in recently generated P. falciparum transgenic reporter lines, which will aid in the investigation of parasite physiology and the discovery of novel antimalarial drugs. Future prospects for the generation of new and superior human malaria parasite reporter lines are also discussed, and unresolved questions in malaria biology are highlighted to help boost support for the development and implementation of malaria treatments., Competing Interests: Declaration of interests Shinya Miyazaki declares grant/research funding from Shionogi & Co., Ltd., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Megalin, a type I transmembrane protein, serves as a multi-ligand endocytic receptor in the apical membrane of proximal tubules. Its ectodomain and full-length forms are excreted into human urine, with the former being more abundant. We previously developed two types of sandwich enzyme-linked immunosorbent assays (ELISAs) utilizing monoclonal antibodies that target the amino-terminal ligand-binding domain-I and the carboxyl-terminal cytoplasmic region of human megalin, respectively. The former, termed "A-megalin" ELISA, primarily identifies ectodomains of megalin, whereas the latter, "C-megalin" ELISA, specifically recognizes full-length megalin originating from urinary extracellular vesicles. This study developed novel sandwich ELISAs to assess mouse urinary A-megalin and C-megalin, thereby facilitating studies involving these biomarkers in mouse disease models. Immunoblotting and immunohistochemistry of monoclonal antibodies against human megalin were performed to assess their compatibility with mouse megalin in novel sandwich ELISAs, which were constructed and validated using human assay protocols. Immunoblot analysis of megalin in urinary extracellular vesicles and supernatant was performed to investigate the ratio of ectodomain to full-length forms in mouse urine. Stable measurements having a precision and accuracy within 15 % were achieved in the measurement of quality control samples. A-megalin and C-megalin were detectable in the urine of C57BL/6 mice, whereas most urine samples from kidney-specific conditional megalin-knockout mice were below detection limits. Ectodomain forms of megalin were at least approximately 70 times more abundant than the full-length form, even in mouse urine. In conclusion, we successfully developed sandwich ELISAs for assessing mouse urinary A-megalin and C-megalin to evaluate primarily ectodomain and full-length forms of megalin, respectively., Competing Interests: Declaration of competing interest A.S. received research grants from Denka Co., Ltd., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Typical atrial flutter (AFL) is a macroreentrant tachycardia in which intracardiac conduction rotates counterclockwise around the tricuspid annulus. Typical AFL has specific electrocardiographic characteristics, including a negative sawtooth-like wave in the inferior lead and a positive F wave in lead V1. This study aimed to analyze the origin of the positive F wave in lead V1, which has not been completely understood., Methods: This study enrolled 10 patients who underwent radiofrequency catheter ablation for a typical AFL. Electroanatomical mapping was performed both during typical AFL and entrainment from the right atrial appendage (RAA). The 12-lead electrocardiogram (ECG) and three-dimensional (3D) electroanatomical maps were analyzed., Results: The positive F wave in lead V1 changed during entrainment from the RAA in all the cases. The 3D map during entrainment from the RAA revealed an area of antidromic capture around the RAA, which collided with the orthodromic wave in the anterior right atrium. This area of antidromic capture around the RAA was the only difference from the 3D electroanatomical map of AFL and is considered the cause of the change in the F wave in lead V1 during entrainment., Conclusion: The analysis of the differences in the 12-lead ECG and 3D maps between tachycardia and entrainment from the RAA clearly demonstrated that activation around the RAA is responsible for the generation of the positive F wave in lead V1 of typical AFL., (© 2024 Wiley Periodicals LLC.)

Introduction: The novel cryoballoon with 28 mm or 31 mm adjustable diameters, aims to achieve a wide antral pulmonary vein isolation (PVI). However, the distribution of antral lesions and their variations based on left atrial (LA) remodeling require further clarification., Methods: We evaluated 22 patients (67 [59.5-74.8] years, 19 males) who underwent PVI of atrial fibrillation (AF) (13 paroxysmal AF [PAF] and 9 non-PAF) using size-adjustable cryoballoons. LA electro-anatomical mapping was performed post-PVI with three-dimensional mapping systems. We assessed the shapes of the LA and pulmonary veins (PVs) and the distribution of isolated areas (IAs), comparing the results between PAF and non-PAF patients., Results: In the left PVs (LPVs), the distance between the PV orifice and IA edge (PVos-IA) was larger on the roof and posterior segments (~15 mm) but relatively smaller on the anterior segment near the PV ridge (<10 mm). For the right PVs (RPVs), it was more extensive in the posterior segment (10-15 mm). Comparing PAF and non-PAF, there were no significant differences in the PVos-IA except for the right posterior-carina segment, antrum IA (LPVs: 5.9 ± 1.6 vs. 5.8 ± 0.8 cm², p = .81; RPVs: 4.8 ± 2.3 vs. 4.8 ± 1.2 cm², p = .81), distances between the right and left IAs on the LA posterior wall (LAPW), and un-isolated LAPW area (9.0 ± 4.9 vs. 9.9 ± 2.5 cm², p = .62). No individual PVIs were observed in either group. Two patients exhibited overlapping IAs on the roof, and one patient who underwent 31 mm balloon applications for all PVs exhibited an LAPW isolation., Conclusion: The size-adjustable cryoballoon achieved a wide antral PVI even in non-PAF patients., (© 2024 Wiley Periodicals LLC.)

Background: Safety data of the latest radiofrequency (RF) technologies during atrial fibrillation (AF) ablation in real-world clinical practice are limited., Objectives: We sought to evaluate the acute procedural safety of the four latest ablation catheters commonly used for AF ablation., Methods: A total of 3957 AF ablation procedures performed between January 2022 and December 2023 at 20 centers with either the THERMOCOOL SMARTTOUCH SF (STSF), TactiCath (TC), QDOT Micro (QDM), or TactiFlex (TF) were retrospectively analyzed., Results: In total, QDM, STSF, TF, and TC were used in 343 (8.7%), 1793 (45.3%), 1121 (28.4%), and 700(17.7%) procedures. Among 2406 index procedures, electrical pulmonary vein isolations were successfully achieved in 99.5%. Despite similar total procedure times in the four groups, the total fluoroscopic time was significantly shorter for QDM/STSF with CARTO than TF/TC with EnSite (18.7 ± 14 vs. 27.6 ± 20.6 min, p < .001) and longest in the TF group. The incidence of cardiac tamponade was 0.7% (0.5% and 0.9% during index and redo procedures, 0.8% and 0.3% for paroxysmal and non-paroxysmal AF) and was significantly lower for QDM/STSF than TF/TC (0.2% vs. 1.1%, p = .008) and highest in the TF group. The incidence of cardiac tamponade was higher for TF than TC and STSF than QDM. In the multivariate analysis, TF/TC with EnSite was a significant independent predictor of cardiac tamponade during both the index (odds ratio [OR] = 4.8, 95% confidence interval [CI] = 1.3-17.5, p = .02) and all procedures (OR = 3.0, 95% CI = 1.3-7.2, p = .01)., Conclusions: The incidence of cardiac tamponade and the fluoroscopic time during AF ablation significantly differed among the latest RF catheters and mapping systems in real-world clinical practice., (© 2024 Wiley Periodicals LLC.)

Trivalent europium (Eu(III)) complexes emit narrow-band luminescence as a result of energy transfer following the photoexcitation of antenna ligands. Bidentate β-diketonates are typically used as antenna ligands; however, their entire energy transfer mechanism to Eu(III) remains unknown. We used time-resolved photoluminescence spectroscopy and femtosecond transient absorption spectroscopy to map the complete intramolecular energy transfer process in the [Eu(hfa) 3 (TPPO) 2 ] (hfa = hexafluoroacetylacetonate, TPPO = triphenylphosphine oxide) complex; hfa is a β-diketonate antenna ligand. Our analysis provides a "full picture" of energy transfer, tracing each step from initial photoexcitation to final relaxation: intersystem crossing in the ligands, energy transfer from the ligands to the metal center, and multiple internal conversion of Eu(III). We demonstrated that the direct bonds of the bidentate ligands enabled a quick and near-unity-efficiency energy transfer from the triplet state of the ligand to the 5 D 2 state of Eu(III). We also revealed that the loss of the ligand-centered intersystem crossing process reduces the overall sensitization efficiency. Our findings provide a foundation for the rational design of advanced luminescent materials, paving the way for advances in lanthanide-based luminescence research.

Background: Understanding the gait pattern of patients eligible for total hip arthroplasty (THA) due to hip osteoarthritis (OA) offers valuable information for improving locomotive syndrome (LS). This study aims to measure the gait patterns of THA-eligible patients using an optical motion capture system and to analyze these patterns using principal component analysis (PCA). Additionally, this study examines the relationship between THA-induced gait patterns and LS., Methods: This before-after study included 237 patients who underwent unilateral primary THA due to hip OA. The primary outcome measures were spatiotemporal gait parameters. Secondary outcome measures included three LS risk tests: a stand-up test, a two-step test, a 25-question Geriatric Locomotive Function Scale (GLFS-25), and total clinical decision limits stages. PCA was performed using 16 spatiotemporal gait parameters collected before and three months after THA. Principal components (PC) were selected to achieve a cumulative contribution rate of 90% (0.9) or higher. Each summarized PC was compared using a paired t -test before and three months after THA. Furthermore, multiple regression analysis was conducted to determine how changes in each PC between before and three months after THA related to changes in the four LS evaluation items., Results: PCA identified three principal components (PC1, PC2, PC3) that accounted for a cumulative contribution rate of 0.910 using 16 spatiotemporal gait parameters. When comparing before and three months after THA for all three PCs, significant differences were observed in each PC ( p  < 0.001), with overall walking ability and stance phase being higher three months after THA than before THA, while the asymmetry of support time was lower three months after THA. The results of multiple regression analysis revealed that PC1, PC2, and PC3 were the most influential factors in total clinical decision limits stage. For each LS risk test, the factors related to the stand-up test were identified as PC1, PC2, and PC3, while the factors related to the two-step test were identified as PC1 and PC2. The factors related to the GLFS-25 were also identified as PC1 and PC2., Conclusions: The most important findings of this study indicate that the three PCs represent over 90% of the 16 spatiotemporal gait parameters, which are associated with total clinical decision limits stage and LS risk tests. The present results suggest that PC1 represents overall walking ability, PC2 represents the stance phase, and PC3 represents asymmetry of support time. Gait pattern characteristics, such as overall walking ability, stance phase, and asymmetry of support time, were clearly defined by these PCs. Regarding the relationship between PC and LS, all three PCs are related to total clinical decision limits stage. In addition, PC1 and PC2 related to all three LS risk tests, and PC3 related only to the stand-up test., Competing Interests: The authors declare there are no competing interests., (©2024 Miyazaki et al.)

Background: Very high power and short duration (vHPSD) ablation is recently used for pulmonary vein isolation. However, low first-pass isolation rates have been reported, possibly because of shallow lesion formation, necessitating deeper lesions to improve treatment outcomes., Objective: This study aimed to confirm the safety and efficacy of double radiofrequency applications of vHPSD ablation in an in vivo beating swine heart model., Methods: Eighteen swine were anesthetized and underwent vHPSD ablation using the QDOT-MICRO catheter at 90 W for 4 seconds, targeting a contact force of 10 g. Radiofrequency applications were performed as single application (SA) and double applications (DA) with 4-8 seconds rest intervals. Lesion surface area and volume were measured postablation., Results: A total of 337 atrial lesions and 74 ventricular lesions were created. Both 4-6 seconds DA and 7-8 seconds DA produced significantly larger and deeper lesions than did SA, with atrial surface lengths averaging 9.0 mm for 4-6 seconds DA, 9.2 mm for 7-8 seconds DA, and 8.0 mm for SA. Transmurality was observed at 100% for 4-6 seconds and 7-8 seconds DAs, while it was 94% for SA (P = .002). Ventricular lesion metrics followed similar trends. Except for 1 event of tiny char formation during 4 seconds DA in the ventricle, neither steam pops nor char formation was observed in either the atrium or the ventricle., Conclusion: In an in vivo swine heart model, DA with 4-6 seconds and 7-8 seconds intervals create deeper and wider lesions than does SA, suggesting its potential for clinical application in areas with thicker myocardial walls. However, DA with very short intervals may still pose a risk of excessive tissue heating., Competing Interests: Disclosures Drs Goto, Takigawa, and Miyazaki received endowments from Medtronic Japan, Boston Scientific, Japan Lifeline, and Win International. No other authors have conflict of interest to declare., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

The Kirsten rat sarcoma (KRAS) oncogene was considered "undruggable" until the development of sotorasib, a KRAS G12C selective inhibitor that shows favorable effects against lung cancers. MRTX1133, a novel KRAS G12D inhibitor, has shown promising results in basic research, although its effects against pancreatic cancer are limited when used alone. Therefore, there is an urgent need to identify effective drugs that can be used in combination with KRAS inhibitors. In this study, we found that administration of the KRAS inhibitors sotorasib or MRTX1133 upregulated STAT3 phosphorylation and reactivated ERK through a feedback reaction. The addition of the MEK inhibitor trametinib and the JAK2 inhibitor fedratinib successfully reversed this effect and resulted in significant growth inhibition in vitro and in vivo. Analyses of sotorasib- and MRTX1133-resistant cells showed that trametinib plus fedratinib reversed the resistance to sotorasib or MRTX1133. These findings suggest that the JAK2-mediated pathway and reactivation of the MAPK pathway may play key roles in resistance to KRAS inhibitors in pancreatic cancers. Accordingly, simultaneous inhibition of KRAS, MEK, and JAK2 could be an innovative therapeutic strategy against KRAS-mutant pancreatic cancer., (© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Preoperative left ventricular (LV) ejection fraction (LVEF) and LV end-systolic dimension (LVESD) are established predictors of LV dysfunction (LVD) after mitral valve repair (MVr) for mitral regurgitation (MR). Although elevated estimated right ventricular systolic pressure (eRVSP) indicating pulmonary hypertension is the best proposed additional predictor, we hypothesized that transthoracic echocardiography (TTE) parameters more directly reflecting left atrial pressure (LAP) would more accurately predict LVD than eRVSP. Furthermore, predictors of a significant decline in LVEF remain unknown. We retrospectively studied 622 patients, aged 20-87 years, who underwent MVr for severe chronic primary MR. As previously reported predictors of postoperative LVD, we collected seven preoperative TTE parameters, including LVESD, LVEF, eRVSP, LV end-diastolic dimension, left atrial volume index (LAVI), early transmitral annular (e') velocity, and atrial fibrillation. Furthermore, as LAP-related TTE parameters, we collected left atrial dimension, E-wave velocity, and E/e' ratio, in addition to eRVSP and LAVI. Using multivariate logistic regression and receiver operating characteristic curve analyses, we explored predictors of early postoperative LVD, defined as LVEF < 50% measured on postoperative day 7. We further explored predictors of a significant decline in LVEF, defined as an absolute decline in LVEF of > 12 percentage points, the third quintile of the data. Incidences of postoperative LVD and a significant LVEF decline were 12.9% and 23.2%, respectively. In addition to LVESD and LVEF, E-wave velocity, but not eRVSP, remained a significant predictor of postoperative LVD. E-wave velocity, LVESD, and LVEF had additive effects in risk prediction. Furthermore, E-wave velocity was the strongest predictor of a significant LVEF decline. E-wave velocities > 121.5 cm/s and > 101.5 cm/s were associated with increased risks of postoperative LVD (odds ratio [OR], 2.896; 95% confidence interval [95%CI], 1.792-4.681; p < 0.001) and a significant LVEF decline (OR, 6.345; 95%CI, 3.707-10.86; p < 0.001), respectively. After adjustment for multiple TTE parameters, E-wave velocity, but not eRVSP, remained significant predictors of postoperative LVD and a significant LVEF decline after MVr. These results were reproducible in 461 patients who underwent follow-up TTE at 1 year, suggesting an important role of E-wave velocity in risk prediction., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Background: Extremely low uric acid (UA) levels or increased urinary UA (Uua) excretion might be risk factors for kidney disease in renal hypouricemia (RHU) patients, but their relationship with kidney dysfunction is unclear. This study investigated time-dependent changes in eGFR in RHU patients., Methods: This multicenter retrospective study assessed UA metabolism and changes in eGFR (median 5.5 years) in 13 RHU patients. We then compared eGFR change in 7 of 13 RHU patients whose eGFR could be measured for 4 years with those in normouricemic group (n = 31). In addition, 7 RHU patients were divided into two groups based on URAT1 gene mutations: homozygote and compound heterozygote mutations (Homo/Com group, n = 3), and wild-type and heterogeneous mutations (WT/Hetero group, n = 4)., Results: In 13 RHU patients, the median and mean serum UA (SUA) were 0.8 (0.4-2.5) and 1.1 ± 0.7 mg/dL. The median and mean Uua were 44.3 (12.7-141.1) and 49.7 ± 36.2 mg/dL. The median and mean urinary urate clearance (Cua/Ccr) were 46.8 (11.3-73.6) and 43.3 ± 19.7%. Over 4 years, eGFR did not change in the RHU group but declined in the normouricemic group. Annual mean eGFR decline and change rate in the RHU group were the same as those in the normouricemic group (- 1.09 ± 1.11 vs. - 1.09 ± 1.92 mL/min/1.73 m 2 /year, p = 0.996) (- 1.74 ± 1.96 vs. - 1.36 ± 2.10%, p = 0.664). And no significant difference was found in eGFR decline or change rate between Homo/Com and WT/Hetero groups (- 0.33 ± 1.03 vs. - 1.67 ± 0.85 mL/min/1.73 m 2 /year, p = 0.116) (- 0.61 ± 1.62 vs. - 2.59 ± 1.91%, p = 0.210)., Conclusion: RHU from URAT1 genetic mutation may not show eGFR decline over 4 consecutive years., (© 2024. The Author(s).)

Most tortoise beetles, belonging to the subfamily Cassidinae (Coleoptera: Chrysomelidae), possess distinctive explanate margins, comprising elongations of the pronotum and elytra outer margins. These margins flatten against the ground, serving as a unique defensive mechanism against predators. To understand the developmental and evolutionary origins of explanate margins, we examined the development of the pronotal part of these structures in two tortoise beetle species: Thlaspida biramosa (Boheman) (tribe Cassidini) and Laccoptera nepalensis (Boheman) (tribe Aspidimorphini). Although final (fifth) instar larvae of both species exhibited no external prothoracic structures associated with explanate margins, pupae possessed a plate-shaped structure projecting anterolaterally on their pronotum. This plate-shaped structure was identified as the pupal primordium of the pronotal explanate margin, as the explanate margin emerged from inside the structure during eclosion. In prepupae of T. biramosa , the primordial tissue exhibited three region-specific folding and furrowing patterns, beneath larval cuticles. These epithelial structures expanded within minutes at the onset of pupation, resulting in pupal primordial formation. Thus, pronotal explanate margins originate from pronotal epithelia, with the furrowing and folding patterns of the epithelia shaping pupal and even adult pronotal explanate margins. The presence of morphologically similar pupal pronotal projections in various Cassidinae suggests that the development of pronotal explanate margins is likely common in these beetles.

Background: Whether muscle mass and muscle quality affect the prognosis of elderly patients with aspiration pneumonia is unclear. This study aimed to evaluate the relationship between erector spinae muscle mass and muscle quality on the 30-day prognosis of elderly patients with aspiration pneumonia., Methods: Two hundred fifty-eight patients who were diagnosed with aspiration pneumonia and admitted to Sanuki Municipal Hospital for pulmonary rehabilitation intervention were included. The cross-sectional area (ESM CSA /BSA) and CT values (ESM CT ) of the erector spinae muscles at the 12th thoracic vertebra were measured on chest CT images to represent muscle mass and quality, respectively. The primary outcome was defined as 30-day survival., Results: Twenty-six patients died within 30 days after hospitalization. The ESM CSA /BSA ratio was significantly greater in the survival group than in the nonsurvival group (p = 0.001). The cutoff values for 30-day survival were calculated as follows: the ESM CSA /BSA was 11.046 cm 2 /m 2 in male patients and 9.600 cm 2 /m 2 in female patients; the ESM CT was 26.85 HU in male patients and 8.00 HU in female patients. A higher ESM CSA /BSA significantly improved 30-day survival, while ESM CT did not show a significant difference. Cox proportional hazards regression analysis revealed that the ESM CSA /BSA was independently associated with 30-day short-term prognosis (hazard ratio 0.34, p = 0.034)., Conclusion: The short-term prognosis of elderly patients with aspiration pneumonia may be more strongly influenced by muscle mass than by the muscle quality of the erector spinae muscles., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Previous studies have emphasized the necessity of surveillance and control measures for hepatitis E virus (HEV) infection in wild boars, an important reservoir of HEV. To assess the current situation of HEV infection in wild boars in Japan, this study investigated the prevalence and genetic diversity of HEV among wild boars captured in 16 prefectures of Japan during 2018-2023. Serum samples from 968 wild boars were examined for anti-HEV IgG antibodies and HEV RNA. The prevalence of anti-HEV IgG varied geographically from 0 % to 35.0 %. HEV RNA was detected in 3.6 % of boars, with prevalence varying by prefecture from 0 % to 22.2 %. Genotype 3 was the most prevalent genotype (91.9 %), followed by genotype 4 (5.4 %), with one strain closely related to genotype 6. The prevalence of HEV infection among wild boars decreased from 2018/2019 to 2022/2023 with significant declines in levels of anti-HEV IgG antibodies (14.5 % vs. 6.2 %, P < 0.0001) and HEV RNA (7.6 % vs. 1.5 %, P < 0.0001). Regional analysis showed varying trends, with no HEV RNA-positive boars found in several regions in recent years. A plausible factor contributing to the decline in HEV infection is the application of countermeasures, including installing fences to prevent intrusion into pig farms, implemented in response to the emergence of classical swine fever virus (CSFV) infection in wild boars and domestic pigs, with incidents reported annually since 2018. Further investigation is warranted to explore the association between countermeasures to CSFV infection and the decrease in HEV infection among wild boars., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

We report herein the design and discovery of novel allosteric HIV-1 integrase inhibitors. Our design concept utilized the spirocyclic moiety to restrain the flexibility of the conformation of the lipophilic part of the inhibitor. Compound 5 showed antiviral activity by binding to the nuclear lens epithelium-derived growth factor (LEDGF/p75) binding site of HIV-1 integrase (IN). The introduction of a lipophilic amide substituent into the central benzene ring resulted in a significant increase in antiviral activity against HIV-1 WT X-ray crystallography of compound 15 in complex with the integrase revealed the presence of a hydrogen bond between the oxygen atom of the amide of compound 15 and the hydroxyl group of the T125 side chain. Chiral compound 17 showed high antiviral activity, good bioavailability, and low clearance in rats., 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.)

Background Hypouricemia, defined as a serum uric acid (SUA) level ≤2 mg/dL, could be a risk factor for death in hospitalized patients. However, how explanatory variables can explain hypouricemia as an objective variable in a logistic regression analysis remains unknown. Purpose To predict the risk factors for hypouricemia in hospitalized patients using a robust Bayesian logistic (RBL) model. Methods This study retrospectively enrolled patients who visited Yonago Medical Center between April 2020 and March 2021. The association between potential risk factors and hypouricemia was analyzed using the RBL model in Python-modulated PyMC3. The final model was selected based on the lowest Watanabe-Akaike information criterion (WAIC). Results Of the 618 patients, 64 (10.4%) had hypouricemia. Based on the model according to the lowest WAIC, independent risk factors for hypouricemia were febuxostat [odds ratio (OR) 5.46, 95% confidence interval (CI) 2.32-13.4], amino acids in parenteral nutrition (OR 5.19, 95% CI 1.62-15.1), TMP-SMX (OR 4.20, 95% CI 1.66-10.9), emaciation (OR 3.48, 95% CI 1.75-7.21), and serum sodium level (OR 0.90, 95% CI 0.84-0.96). Conclusion The RBL model predicted amino acids in parenteral nutrition, TMP-SMX, emaciation, and low serum sodium levels for hypouricemia, in addition to the authentic risk factor febuxostat.

Background: Pulsed field ablation (PFA), a novel treatment for atrial fibrillation (AF), has yet to be evaluated in a Japanese cohort., Methods: In this sub-analysis of the PULSED AF trial, 12-month outcomes of paroxysmal AF (PAF) and persistent AF (PsAF) patients treated with PFA in four Japan centers were assessed. After a 90-day blanking period, primary efficacy was determined via freedom from a composite endpoint of acute procedural failure, arrhythmia recurrence, or antiarrhythmic drug escalation over 1 year. Patient improvement was evaluated via two quality of life (QoL) surveys (AFEQT and EQ-5D) at baseline and 12 months., Results: The analysis included 32 patients, 16 PAF and 16 PsAF, with PAF patients averaging 61.1 ± 10.6 years and PsAF patients averaging 62.8 ± 11.5 years of age. Females made up 31% of PAF and 25% of PsAF cohorts. Acute pulmonary vein isolation was achieved in 100% of both cohorts. The primary efficacy success rate at 12 months was 75.0% for PAF and 56.3% for PsAF patients. No primary safety events occurred. The mean AFEQT score significantly increased for both PAF (25.9 points, p < 0.0001) and PsAF (13.2 points, p = 0.0002) patients, while the EQ-5D-5L score improved significantly for PAF (0.12 points, p = 0.048) patients but not for PsAF (0.04 points, p = 0.08) patients., Conclusions: Similar to outcomes in the global cohort, ablation with the PulseSelect™ PFA catheter was efficient, effective, and safe in a Japanese population, resulting in improved QoL for PAF and PsAF patients., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04198701., (© 2024. The Author(s).)

Sleep disordered breathing (SDB) is a common comorbidity in patients with atrial fibrillation (AF). Patients undergoing pulmonary vein isolation (PVI) for AF have a high prevalence of SDB. In previous studies, some patients with AF had Cheyne-Stokes respiration (CSR). The aim of the present study was to assess the prevalence of SDB and the correlates of SDB severity and CSR in AF patients who have undergone PVI. The study was conducted using a single-center observational design. All participants underwent a home sleep apnea test (ApneaLink Air, ResMed, Australia), which could determine the severity of SDB as assessed by the apnea-hypopnea index (AHI) and the percentage of CSR (%CSR) pattern. 139 AF patients who underwent PVI were included in the study. Overall, 38 (27.3%) patients had no SDB (AHI < 5), 53 (38.1%) had mild SDB (5 ≤ AHI < 15), 33 (23.7%) had moderate SDB (15 ≤ AHI < 30), and 15 (10.8%) had severe SDB (AHI ≥ 30). Correlates of the increased AHI included male sex (β = 0.23, p = 0.004), age (β = 0.19, p = 0.020), high body mass index (β = 0.31, p < 0.001), and β blockers usage (β = 0.18, p = 0.024). Conversely, correlates with the %CSR rate included male sex (β = 0.18, p = 0.020), age (β = 0.19, p = 0.015), non-paroxysmal AF (β = 0.22, p = 0.008), and high glycohemoglobin A1c (β = 0.36, p < 0.001) and N-terminal pro-brain natriuretic peptide (β = 0.24, p = 0.005) levels. SDB is prevalent in patients with AF who have undergone PVI; predisposing factors for SDB include male sex, older age, and obesity. CSR occurs in patients with AF who have undergone PVI; predisposing factors for CSR include male sex, older age, high left ventricular filling pressure, and abnormal blood glucose level., (© 2024. Springer Nature Japan KK, part of Springer Nature.)