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Aims: High uric acid (HUA)plays a significant role in the pathophysiology of cardiovascular disease. Studies have indicated that elevated uric acid levels can adversely affect cardiovascular health. Nevertheless, the impact of hyperuricemia on cardiomyopathy remains uncertain. Further research is needed to elucidate the relationship between HUA and cardiomyopathy, shedding light on its potential implications for heart health., Results: We demonstrated that Uox-KO mice accelerated the development of cardiomyopathy, causing significantly impaired cardiac function and myocardial fibrosis.Meanwhile, the mitochondrial morphology was destroyed, the lipid peroxidation products increased in number and the antioxidant function was weakened. In addition, we evaluated the effects of ferrostatin-1 (Fer-1), the ferroptosis inhibitor. Myocardial damage can be reversed by the Fer-1 treatment caused by HUA combined with DOX treatment. Benzbromarone, a uric acid-lowering drug, decreases myocardial fibrosis and ferroptosis by alleviating hyperuricemia in Uox-KO mice by DOX administration. In vitro, we observed that the activity of cardiomyocytes treated with HUA combined with DOX decreased significantly, and lipid reactive oxygen species (ROS) increased significantly. Afterward, we demonstrated that HUA could promote oxidative stress in DOX, characterized by increased mitochondrial ROS, and down-regulate protein levels of glutathione peroxidase 4 (GPX4). N-acetyl-L-cysteine, an antioxidant, inhibits the process by which HUA promotes DOX-induced ferroptosis by increasing the GPX4 expression., Innovation: We verified that HUA can exacerbate myocardial damage. This has clinical implications for the treatment of cardiac damage in patients with hyperuricemia., Conclusions: Our data suggested that HUA promotes cardiomyopathy. HUA promotes DOX-induced ferroptosis by increasing oxidative stress and down-regulating GPX4.

Background: Combining morphological and physiological evaluations might improve the risk stratification of patients who undergo percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) culprit lesions., Aims: We aimed to investigate the clinical utility of morphofunctional evaluation after PCI for identifying ACS patients with increased risk of subsequent clinical events., Methods: We retrospectively studied 298 consecutive ACS patients who had undergone optical coherence tomography (OCT)-guided PCI. We performed OCT-based morphological analysis and quantitative flow ratio (QFR)-based physiological assessment immediately after PCI. The non-culprit segment (NCS) was defined as the most stenotic untreated segment in the culprit vessel. The primary outcome was target vessel failure (TVF), a composite of cardiac death, target vessel-related myocardial infarction, and ischaemia-driven target vessel revascularisation., Results: During a median follow-up period of 990 days, 42 patients experienced TVF. Cox regression analysis revealed that the presence of thin-cap fibroatheroma (TCFA) in the NCS and a low post-PCI QFR, or the presence of TCFA in the NCS and a high ΔQFR in the NCS (QFR NCS ), were independently associated with TVF. The subgroup with TCFA in the NCS and a low post-PCI QFR had a significantly higher incidence of TVF (75%) than the other subgroups, and those with TCFA in the NCS and a high ΔQFR NCS had a significantly higher incidence of TVF (86%) than the other subgroups. The integration of TCFA in NCS, post-PCI QFR, and ΔQFR NCS with traditional risk factors significantly enhanced the identification of subsequent TVF cases., Conclusions: Combining post-PCI OCT and QFR evaluation may enhance risk stratification for ACS patients after successful PCI, particularly in predicting subsequent TVF.

Application of physical forces, ranging from ultrasound to electric fields, is recommended in various clinical practice guidelines, including those for treating cancers and bone fractures. However, the mechanistic details of such treatments are often inadequately understood, primarily due to the absence of comprehensive study models. In this study, we demonstrate that an alternating magnetic field (AMF) inherently possesses a direct anti-cancer effect by enhancing oxidative phosphorylation (OXPHOS) and thereby inducing metabolic reprogramming. We observed that the proliferation of human glioblastoma multiforme (GBM) cells (U87 and LN229) was inhibited upon exposure to AMF within a specific narrow frequency range, including around 227 kHz. In contrast, this exposure did not affect normal human astrocytes (NHA). Additionally, in mouse models implanted with human GBM cells in the brain, daily exposure to AMF for 30 min over 21 days significantly suppressed tumor growth and prolonged overall survival. This effect was associated with heightened reactive oxygen species (ROS) production and increased manganese superoxide dismutase (MnSOD) expression. The anti-cancer efficacy of AMF was diminished by either a mitochondrial complex IV inhibitor or a ROS scavenger. Along with these observations, there was a decrease in the extracellular acidification rate (ECAR) and an increase in the oxygen consumption rate (OCR). This suggests that AMF-induced metabolic reprogramming occurs in GBM cells but not in normal cells. Our results suggest that AMF exposure may offer a straightforward strategy to inhibit cancer cell growth by leveraging oxidative stress through metabolic reprogramming., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Murray law-based quantitative flow ratio (μQFR) is a novel computational method that enables accurate estimation of fractional flow reserve (FFR) using a single angiographic projection. However, its diagnostic value in patients with severe aortic stenosis (AS) remains unclear., Method: We included 25 consecutive patients who underwent transcatheter aortic valve replacement (TAVR) for severe AS with intermediate or greater (30-90%) coronary artery disease (CAD). Pre- and post-TAVR μQFR, QFR, instantaneous flow reserve (iFR), and post-TAVR invasive FFR values were measured. We evaluated the diagnostic performance of pre-TAVR μQFR, QFR, and iFR using post-TAVR FFR ≤ 0.80 as a reference standard of ischemia., Result: Pre-TAVR μQFR was significantly correlated with post-TAVR FFR (r = 0.73, p < 0.0001). The area under the curve of pre-TAVR μQFR on post-TAVR FFR ≤ 0.8 was 0.91 (95% confidence interval [CI] 0.77-0.98), comparable to that of pre-TAVR iFR (0.86 [95% CI 0.71-0.98], p = 0.97). The accuracy, sensitivity, specificity, and positive and negative predictive values of pre-TAVR μQFR on post-TAVR FFR ≤ 0.8 were 84.2% (95% CI 68.7-93.4), 61.6% (95% CI 31.6-86.1), 96.0% (95% CI 79.6-99.9), 88.9% (95% CI 52.9-98.3), and 82.8% (95% CI 70.6-90.6), respectively. For pre-TAVR iFR, these values were 76.5% (95% CI 58.8-89.3), 90.9% (95% CI 58.7-99.8), 69.6% (95% CI 47.1-86.8), 58.8% (95% CI 42.8-73.1), and 94.1% (95% CI 70.8-99.1), respectively., Conclusion: μQFR could be useful for the physiological evaluation of patients with severe AS with concomitant CAD., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Background: We investigate whether Intensive uric acid (UA)-lowering therapy (ULT) provides increased renal protection compared with standard therapy in chronic kidney disease (CKD) patients., Methods: This was a multicenter randomized controlled trial. Only CKD patients with hyperuricemia were included in this study. The participants were randomly assigned to either the Intensive therapy group (target serum UA level ≥ 4.0 mg/dL and < 5.0 mg/dL) or the standard therapy group (serum UA level ≥ 6.0 mg/dL and < 7.0 mg/dL). ULT was performed using topiroxostat, a non-purine-type selective xanthine oxidase inhibitor. The primary endpoint was change in the logarithmic value of urine albumin to the creatinine ratio (ACR) between baseline and week 52 of the treatment., Results: Three hundred fifty-two patients were included in the full analysis set. In the Standard therapy group, mean serum UA was 8.23 mg/dL at baseline and 6.13 mg/dL at 52 weeks. In the Intensive therapy group, mean serum UA was 8.15 mg/dL at baseline and 5.25 mg/dL at 52 weeks. There was no significant difference in changes in log ACR at 52 weeks between the Intensive therapy and the Standard therapy groups., Conclusion: This study did not reveal the benefit of Intensive ULT to improve albuminuria levels. (UMIN000026741 and jRCTs051180146)., (© 2024. The Author(s).)

Purpose: To evaluate the long-term efficacy and safety of ripasudil-brimonidine fixed-dose combination (RBFC), a new intraocular pressure (IOP)-lowering medication for glaucoma and ocular hypertension (OHT)., Methods: This prospective, multicentre (23 sites in Japan), open-label study enrolled patients with primary open-angle glaucoma (POAG), OHT or exfoliative glaucoma and assigned them to one of four combination therapy cohorts, based on previous treatment(s) received: prostaglandin (PG) analogue (Cohort 1); PG analogue and beta-adrenoceptor blocker (β-blocker) (Cohort 2); PG analogue, β-blocker and carbonic anhydrase inhibitor (Cohort 3); or other/no treatment (Cohort 4). After a ≥ 4-week screening period, eligible patients received twice-daily RBFC for 52 weeks in addition to the treatments they were already receiving. Efficacy was assessed by change in IOP from baseline through week 52. Adverse events and adverse drug reactions (ADRs) were monitored throughout., Results: In total, 179 patients from Cohort 1 (n = 48), Cohort 2 (n = 44), Cohort 3 (n = 41) and Cohort 4 (n = 46) entered the RBFC treatment period. For all cohorts, mean IOP was significantly reduced at 11:00 (2 h after instillation of RBFC) through week 52 with the changes from baseline at week 52 of - 2.7 to - 4.1 mmHg across cohorts; all p < 0.001. Common ADRs were conjunctival hyperaemia (58%), allergic conjunctivitis (18%) and blepharitis (17%), most of which were mild in severity., Conclusion: These data demonstrated the long-term efficacy and safety of RBFC, both alone and in combination with other anti-glaucoma agents. RBFC may offer a new treatment option for the long-term management of glaucoma and OHT., Trial Registration: Japan Registry of Clinical Trials Identifier: jRCT2080225063., Date of Registration: 17 February 2020., (© 2024. The Author(s).)

The objectives of this study were to evaluate the reliability of cartilage T2 relaxation time measurements and to identify focal changes in T2 relaxation on the affected knee from 6 to 24 months after anatomic anterior cruciate ligament reconstruction (ACLR). Data from 41 patients who received anatomic ACLR were analyzed. A bilateral 3.0-T MRI was acquired 6 and 24 months after ACLR. T2 relaxation time was measured in subregions of the femoral condyle and the tibial plateau. The root-mean-square coefficient of variation (RMS CV ) was calculated to evaluate the reliability of T2 relaxation time in the contralateral knee. Subregion changes in the affected knee T2 relaxation time were identified using the contralateral knee as a reference. The superficial and full thickness layers of the central and inner regions showed good reliability. Conversely, the outer regions on the femoral side and regions in the deep layers showed poor reliability. T2 relaxation time increased in only 3 regions on the affected knee when controlling for changes in the contralateral knee, while changes in T2 relaxation time were identified in 14 regions when not using the contralateral knee as a reference. In conclusion, evaluation of cartilage degeneration by T2 relaxation time after ACLR is most reliable for central and inner cartilage regions. Cartilage degeneration occurs in the central and outer regions of the lateral femoral condyle from 6 to 24 months after anatomic ACLR., (© 2024 The Author(s). Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Background: Electronic gambling machines (EGMs) in gambling venues cause gambling-related harm and are a public health concern. This study focused on pachinko parlours as gambling venues and income-generating crimes as gambling-related harm. We aimed to verify whether income-generating crime rates increase in proximity to pachinko parlours and during the opening and post-closing periods of pachinko parlours relative to the pre-opening periods., Methods: We used crime records spanning 6.5 years, including data on the opening and closing days of pachinko parlours for 6.5 years. We also sampled the addresses of convenience stores, bowling alleys, and households with official land prices all over Japan. The dependent variable was the daily income-generating crime incidence rate. Areas within 0.5 km, 0.5-1 km, 1-5 km, and 5-10 km radii of the pachinko parlours were the independent variables. The pre-, opening-, and post-closing periods of the pachinko parlours were also independent variables. The covariates included the number of convenience stores and always open pachinko parlours near pachinko parlours. Data were analysed using an analysis of variance (ANOVA) and covariance (ANCOVA). We also used differences-in-differences analysis (DD) to reveal the increase in income-generating crime rates in neighbourhoods exposed to the opening or closing of pachinko parlours., Results: The daily income-generating crime incidence rate was significantly higher in areas within 0.5-1 km and 1-5 km radii of pachinko parlours than in those within 0.5 km and 5-10 km radii of them. The daily income-generating crime incidence rate was also significantly higher during the opening and post-closing periods than during the pre-opening period, even when controlling for the number of convenience stores and always open pachinko parlours. In particular, fraud crime rates increased with the opening and closing of pachinko parlours., Conclusions: The highest income-generating crime incidence rate was observed within a 0.5-1 km and 1-5 km radius of pachinko parlours. The opening of pachinko parlours also increased income-generating crime incidence rates, which increased after closing. Pachinko parlours are considered to be creating public harm because the corporate activities of these parlours make the youth in their neighbourhood perpetrators of fraud and older adults its victims. Future research should examine the current findings using official crime records., (© 2024. The Author(s).)

This study evaluated the reliability and validity of the Japanese version of the Body Talk Scale (BTS), designed to measure negative fat talk, negative muscle talk, and positive body talk. The study also explored the longitudinal associations between each body talk category and body dissatisfaction. We conducted two separate studies among university students in Japan. Separate confirmatory factor analyses for female and male data indicated that the initially proposed three-factor model demonstrated an acceptable fit, whereas the bi-factor model provided a better fit. The Japanese BTS showed good construct validity, acceptable to adequate internal consistency, and test-retest reliability within 2 weeks. A four-week longitudinal study involving 386 women and 216 men (mean age = 19.22 and 19.62, respectively) revealed that negative fat talk predicted an increase in the discrepancy between the thin ideal body image and the actual body image among women. In contrast, positive body talk was linked to reduced body dissatisfaction and body image discrepancy in women. There were no such significant associations in men. These findings support the use of the Japanese BTS as a valuable instrument for future research on the intrapersonal and interpersonal effects of various types of body talk., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Virtual reality self-counseling (VR-SC) is considered an effective approach for addressing mental health problems. Previous studies have shown the effectiveness of VR-SC using Sigmund Freud's avatar as the counselor. However, considering that virtual reality (VR) enables embodied perspective-taking of another person, VR-SC using the avatar of a person who cares about the participant (an intimate person), such as a family member or friend, is considered effective because it could create warm attitudes toward the participants themselves. In this study, 60 undergraduate and graduate students were split into three conditions: VR-SC with intimate persons, VR-SC with Freud, and a control group. The intervention effects were then compared. The results showed that VR-SC with an intimate person was the most effective in improving anxiety symptoms. These results may be attributed to accepting and affirming oneself from the perspective of the intimate person's avatar and counseling oneself. This study is significant in that it is the first to conduct VR-SC with the avatar of an intimate person and compare the effects with Freud's avatar. More importantly, it showed that the same VR-SC method could have different effects depending on the avatar of the counseling partner., (© 2024. The Author(s).)

Background and Objectives: The influence of the age at which complete corpus callosotomy (CC) surgery is performed on seizure outcomes remains unclear. This study aimed to evaluate the age-dependent aspects of long-term seizure outcomes after complete CC., Methods: We reviewed 41 patients who underwent one-stage complete CC. Seizure outcomes were analyzed for age at epilepsy onset and at complete CC, focal MRI abnormality, and etiology., Results: The median age was 7 months at epilepsy onset and 93 months at complete CC. The median follow-up duration was 67 months. Sixteen patients had focal MRI lesions and 4 had only general atrophy. Etiology was identified in 20 patients. For overall seizure outcomes (N = 41), complete seizure freedom was achieved in 5 patients, excellent seizure reduction (>80%) in 11, good (50%-80%) in 5, and poor (<50%) in 20. Freedom was correlated with younger age at complete CC and unknown etiology (P ≤ .05). Freedom was only achieved in patients aged younger than 7 years. Worthwhile (≥50%, freedom, excellent, and good) and not worthwhile (<50%, poor) overall seizure reduction showed no statistical difference in age at complete CC. No related factor was found for worthwhile overall seizure reduction. For drop attack outcomes (N = 31), freedom was achieved in 22 cases, excellent in 5, and poor in 4. Freedom was correlated with younger age at complete CC (P < .05) although freedom was achieved in 4 of 7 patients older than 20 years. Age at complete CC showed no statistical difference between worthwhile (≥50%) and not worthwhile (<50%) drop attack reduction. Worthwhile drop attack reduction was correlated with unknown etiology (P < .05). Complications were mild and transient., Conclusion: Complete CC is an excellent surgical option based on favorable seizure outcomes and acceptable complications in our present study., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

Significance: The initiation of goal-directed actions is a complex process involving the medial prefrontal cortex and dopaminergic inputs through the mesocortical pathway. However, it is unclear what information the mesocortical pathway conveys and how it impacts action initiation. In this study, we unveiled the indispensable role of mesocortical axon terminals in encoding the execution of movements in self-initiated actions., Aim: To investigate the role of mesocortical axon terminals in encoding the execution of movements in self-initiated actions., Approach: We designed a lever-press task in which mice internally determine the timing of the press, receiving a larger reward for longer waiting periods., Results: Our study revealed that self-initiated actions depend on dopaminergic signaling mediated by D2 receptors, whereas sensory-triggered lever-press actions do not involve D2 signaling. Microprism-mediated two-photon calcium imaging further demonstrated ramping activity in mesocortical axon terminals approximately 0.5 s before the self-initiated lever press. Remarkably, the ramping patterns remained consistent whether the mice responded to cues immediately for a smaller reward or held their response for a larger reward., Conclusions: We conclude that mesocortical dopamine axon terminals encode the timing of self-initiated actions, shedding light on a crucial aspect of the intricate neural mechanisms governing goal-directed behavior., (© 2024 The Authors.)

Failure of anterior cruciate ligament reconstruction (ACLR) is a common yet devastating complication due to inferior clinical outcomes associated with revision ACLR. Identifying the cause and associated risk factors for failure is the most important consideration during preoperative planning. Special attention to tunnel quality, concomitant injuries, and modifiable risk factors will help determine the optimal approach and staging for revision ACLR. Additional procedures including lateral extra-articular tenodesis and osteotomy may be considered for at-risk populations. The purpose of this review is to explore causes of ACLR failure, clinical indications and appropriate patient evaluation, and technical considerations when performing revision ACLR., Competing Interests: Conflict of interest No Disclosure: S. Dadoo, N. Benvegnu, Z.J. Herman, T. Yamamoto, J.D. Hughes. V. Musahl. Education: Smith & Nephew, Arthrex, DePuy Synthes, Conmed. Consulting: Smith & Nephew, Newclip, Ostesys. Royalties: Springer. Shareholder: Ostesys. Board Member: ACL Study Group, AOSSM, ISAKOS, KSSTA (Deputy Editor-in-chief). Codeveloper of iPad app (Serial No. 61/566,761). NIH Grant Support: U01AR076144, W81XWH-16-PRORP-ICTA., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Aneurysms located in the distal middle cerebral artery (DMCA) are relatively rare and lack an established treatment strategy. For DMCA aneurysms, we performed a one-stage combined procedure of endovascular parent artery occlusion (PAO) with coils and superficial temporal artery to middle cerebral artery (STA-MCA) bypass in a hybrid operating room (HOR). The aim of this study was to evaluate the safety and efficacy of this procedure., Methods: Cases of unruptured DMCA aneurysms treated with the one-stage combined PAO and STA-MCA bypass in HOR were retrospectively examined, and patients' and aneurysmal backgrounds, surgical procedures, and treatment outcomes were analyzed., Results: Six patients were included in the study. The average maximum diameter of the aneurysms was 14.4 mm. One aneurysm was located at M2 and five at M3. All aneurysms had a fusiform shape. No cases were associated with infection, trauma, or malignant tumors. In all 6 cases, the combined PAO and STA-MCA bypass was successfully completed. No postoperative hemorrhagic complications occurred. A symptomatic ischemic complication occurred in 1 case whose symptom disappeared in a week. Three months after surgery, complete obliteration of the aneurysm and patency of the bypass was confirmed in all cases., Conclusions: The one-stage combined PAO and STA-MCA bypass in the HOR is safe and effective for DMCA aneurysms, potentially serving as a treatment option for this complex aneurysm., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Poly(vinyl chloride) (PVC) is one of the most widely used plastics. However, a major challenge in recycling PVC is that there is no economical method to separate and remove its toxic phthalate plasticizers. This research made a breakthrough by extracting PVC with liquefied dimethyl ether (DME) and successfully separating the plasticizer components. Nearly all (97.1 %) of the di(2-ethylhexyl) phthalate plasticizer was extracted within 30 min by passing liquefied DME (285 g) through PVC at 25 °C. The compatibility of PVC with organic solvents, including liquefied DME, was derived theoretically from their Hansen solubility parameters (HSP), and actual dissolution experiments were conducted to determine the optimal PVC solvents. A liquefied DME mixture was used to dissolve PVC, and the extract was diluted with ethanol to precipitate the dissolved PVC. We demonstrated that liquefied DME is a promising method for producing high quality recycled products and that the process retains the fundamental properties of plasticizers and PVC without inducing degradation or depolymerization. Because of its low boiling point, DME can be easily separated from the solute after extraction, allowing for efficient reuse of the solvent, extracted plasticizer, and PVC. DME does not require heat and produces little harmful wastewater, which significantly reduces the energy consumption of the plasticizer additive separation process., 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: The increasing prevalence of heated tobacco products (HTPs) has heightened concerns regarding their potential health risks. Previous studies have demonstrated the toxicity of cigarette smoke extract (CSE) from traditional tobacco's mainstream smoke, even after the removal of nicotine and tar. Our study aimed to investigate the cytotoxicity of CSE derived from HTPs and traditional tobacco, with a particular focus on the role of reactive oxygen species (ROS) and intracellular Ca 2+ ., Methods: A human oral squamous cell carcinoma (OSCC) cell line, HSC-3 was utilized. To prepare CSE, aerosols from HTPs (IQOS) and traditional tobacco products (1R6F reference cigarette) were collected into cell culture media. A cell viability assay, apoptosis assay, western blotting, and Fluo-4 assay were conducted. Changes in ROS levels were measured using electron spin resonance spectroscopy and the high-sensitivity 2',7'-dichlorofluorescein diacetate assay. We performed a knockdown of calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) by shRNA lentivirus in OSCC cells., Results: CSE from both HTPs and traditional tobacco exhibited cytotoxic effects in OSCC cells. Exposure to CSE from both sources led to an increase in intracellular Ca 2+ concentration and induced p38 phosphorylation. Additionally, these extracts prompted cell apoptosis and heightened ROS levels. N-acetylcysteine (NAC) mitigated the cytotoxic effects and p38 phosphorylation. Furthermore, the knockdown of CaMKK2 in HSC-3 cells reduced cytotoxicity, ROS production, and p38 phosphorylation in response to CSE., Conclusion: Our findings suggest that the CSE from both HTPs and traditional tobacco induce cytotoxicity. This toxicity is mediated by ROS, which are regulated through Ca 2+ signaling and CaMKK2 pathways., (© 2024. The Author(s).)

Whether in ant-aphid mutualism the ants exert evolutionary selection pressure on aphid morphology has not yet been fully tested. Here, we tested whether the long proboscises of Stomaphis yanonis (Aphididae Lachninae) aphids confer an advantage in preventing predation by the tending ants. Specifically, we tested the hypothesis that aphids with a shorter proboscis would excrete less honeydew, making them more likely to be preyed upon by ants. Our results showed that aphid individuals with a shorter proboscis took up less phloem sap and excreted less honeydew than individuals with a longer proboscis. In addition, among aphids with a similar body size, those with a shorter proboscis were more susceptible to predation by ants than those with a longer proboscis. These results suggest that predation by tending ants, by exerting selection pressure on aphid proboscis morphology, has caused the aphids to evolve longer proboscises., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Porous hybrid microparticles are characterized by their densities and porosities. Consequently, the evaluation for density and porosity of porous hybrid microparticles in liquids is crucial for predicting the transport of particles in the atmosphere, human body, and industrial processes. However, direct measurement of the density and porosity of porous hybrid microparticles in liquids remains a challenge. In this study, we investigated the centrifugal sedimentation of polystyrene-silica hybrid microparticles with and without gas-containing closed pores. A centrifugal liquid sedimentation-dynamic light scattering combined analytical method was employed to determine the apparent densities of hybrid microparticles with and without gas-containing closed pores. The porosity of the hybrid microparticles with gas-containing closed pores was elucidated based on the inner buoyancy, which is a centrifugal force generated by the presence of low-density gas inside numerous closed pores. Further, the inner gas buoyancy was analyzed to estimate the particle porosity in liquids. The results obtained in this study confirmed the feasibility of utilizing the proposed method to determine the apparent density and porosity of porous hybrid microparticles in liquids., (© 2024. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

An 85-year-old woman with a history of diabetes mellitus became aware of motor weakness of the left lower extremity. Magnetic resonance imaging showed multiple small cerebral infarctions in the right corona radiata. Angiography revealed persistent primitive trigeminal artery (PPTA) originating from the right internal carotid artery (ICA) and connecting to basilar artery, and the right ICA occluded distal to PPTA. Collateral blood circulation had developed, and sufficient collateral blood flow was expected. From these findings, the right ICA was considered to show stenosis due to atherosclerotic changes before occlusion. Conservative treatment was conducted with the transoral administration of rivaroxaban. It is important to correctly diagnose the anatomy and existence of an anomalous vessel in a stroke patient, not only when endovascular treatment is planned, but also for conservative medical treatment. Rapid and accurate radiological examinations facilitate safe and effective treatment., Competing Interests: Conflict of Interest None declared., (Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: Cadaver biomechanical testing suggests that the morphology of articulating bones contributes to the stability of the joints and determines their kinematics; however, there are no studies examining the correlation between bone morphology and kinematics of the subtalar joint. The purpose of this study was to investigate the influence of talar and calcaneal morphology on subtalar kinematics during walking in healthy individuals., Methods: Forty ankles (20 healthy subjects, 10 women/10 men) were included. Participants walked at a self-selected pace while synchronized biplane radiographs of the hindfoot were acquired at 100 images per second during stance. Motion of the talus and calcaneus was tracked using a validated volumetric model-based tracking process, and subtalar kinematics were calculated. Talar and calcaneal morphology were evaluated using statistical shape modeling. Pearson correlation coefficients were used to assess the relationship between subtalar kinematics and the morphology features of the talus and calcaneus., Results: This study found that a shallower posterior facet of the talus was correlated with the subtalar joint being in more dorsiflexion, more inversion, and more internal rotation, and higher curvature in the posterior facet was correlated with more inversion and eversion range of motion during stance. In the calcaneus, a gentler slope of the middle facet was correlated with greater subtalar inversion., Conclusion: The morphology of the posterior facet of the talus was found to a primary factor driving multiplanar subtalar joint kinematics during the stance phase of gait., Clinical Relevance: This new knowledge relating form and function in the hindfoot may assist in identifying individuals susceptible to subtalar instability and in improving implant design to achieve desired kinematics after surgery., 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. Disclosure forms for all authors are available online.

To examine changes in individuals' psychosocial variables (e.g., psychological distress, social isolation, and alcohol use) during the prolonged COVID-19 pandemic, a two-year longitudinal survey was conducted at approximately one-year intervals between May 2020 and May 2022, after the first COVID-19-related state of emergency was announced in Japan. The online survey was conducted on May 11-12, 2020 (Phase 1), June 14-20, 2021 (Phase 2), and May 13-30, 2022 (Phase 3). The survey in Phase 1 was conducted during the first emergency declaration period, the survey in Phase 2 was conducted during the third emergency declaration period, and the survey in Phase 3 was conducted at a time when there was no state of emergency but many COVID-19 positive cases. Notably, 3,892 participants responded to all three surveys. In addition to psychosocial inventories often used worldwide, survey items included lifestyle and stress management indicators related to COVID-19 and various sociodemographic items including occupation (e.g., healthcare workers) or income, history of medical treatment for mental problems, severe physical illnesses, and COVID-19., (© 2024. The Author(s).)

Background: Various antigen-presenting cells and tumor cells-expressing PD-L1 inhibits antitumor immune responses in the tumor microenvironment. Recently, numerous studies have shown that tumor cell intrinsic PD-L1 also plays important roles in tumor growth and progression. On the other hand, oral squamous cell carcinoma (OSCC) cells overexpress epidermal growth factor receptor (EGFR) and EGFR signal pathway exacerbates tumor progression. Therefore, this study assessed whether tumor-intrinsic PD-L1 facilitates malignant potential of OSCC cells through regulation of EGFR signaling., Methods: Two OSCC cell lines, SAS and HSC-3, were transfected with PD-L1 and EGFR-specific small interfering RNA (siRNA). Influences of PD-L1 knockdown on malignant potentials of OSCC cells were examined by Cell Counting kit-8 assay, transwell assay, sphere formation assay, flow cytometry, and Western blot. Effects of PD-L1 and EGFR knockdown on each expression were examined by quantitative real-time PCR (qRT-PCR), Western blot, and flow cytometry., Results: Transfection of an PD-L1-siRNA into OSCC cells decreased the abilities of proliferation, stemness, and mobility of these cells significantly. PD-L1 knockdown also decreased EGFR expression through the promotion of proteasome- and lysosome-mediated degradation and following activation of the EGFR/protekin kinase B (AKT) signal pathway. Meanwhile, EGFR knockdown did not influence PD-L1 expression in SAS and HSC-3 cells, but treatment with a recombinant human EGF induced its expression. Treatment with erlotinib and cetuximab suppressed rhEGF-induced PD-L1 expression and localization in the cellular membrane of both OSCC cells., Conclusion: OSCC cells-expressing PD-L1 induced by EGF stimulation may promote malignancy intrinsically via the activation of the EGFR/AKT signaling cascade., (© 2024 The Authors. Journal of Oral Pathology & Medicine published by John Wiley & Sons Ltd.)

Photodynamic therapy (PDT) is useful for various cancers such as high-grade glioma and cancers of other organs. However, the mechanism of tumor-specific accumulation of porphyrin is not clear. The authors previously reported that heme carrier protein 1 (HCP1) contributes to the transport of porphyrins; specifically, we showed that the production of cancer-specific reactive oxygen species from mitochondria (mitROS) leads in turn to enhanced HCP1 expression. Indomethacin (IND), a non-steroidal anti-inflammatory drug, increases ROS production by affecting mitochondrial electron transfer system. In the present work, the authors investigated the effect of pretreatment with IND on cancer-specific porphyrin accumulation, using both a glioma cell line and a rat brain tumor model. This work demonstrated that exposure of a rat glioma cell to IND results in increased generation of cancer-specific mitROS and accumulation of HCP1 expression and porphyrin concentration. Additionally, systemic dosing of a brain tumor animal model with IND resulted in elevated cellular accumulation of porphyrin in tumor cell. This is an effect not seen with normal brain tissue. Thus, the administration of IND increases intracellular porphyrin concentrations in tumor cell without exerting harmful effects on normal brain tissue, and increased porphyrin concentration in tumor cell may lead to improved PDT effect., Competing Interests: EI received scholarship funds from Eisai Co., Ltd., (Copyright © 2024 JCBN.)

This article describes the concept and technical aspects of the occipital transtentorial approach(OTA)for tumor extraction in the pineal region, based on the author's experience and literature review. Awareness of the successful completion of each surgical step is essential. Preoperative preparation and imaging evaluations, with particular attention to the veins and venous sinuses, are especially important. It is also helpful to perform a complete dura incision and inversion up to the edge of confluence, superior sagittal sinus, and transverse sinus. Subsequently, it is necessary to understand the usefulness of adequate dissection in the vicinity of the corpus callosum and internal occipital vein(IOV)so that the occipital lobe can be moved without difficulty. Furthermore, development of the IOV with adequate tentoriotomy facilitates contralateral work. Finally, complete understanding of each step during the bilateral, ambient cistern and cerebellomesencephalic fissure dissection process, where the cerebellar vermis can be moved without difficulty, is necessary for a safe OTA to pineal region tumor extraction.

Background/aims: Although certain allergic diseases have been reported to be associated with the prevalence of functional dyspepsia (FD) and irritable bowel syndrome (IBS), it is unclear whether the presence of multiple allergic diseases further increases the prevalence of FD and IBS. The aim of this study is to determine this issue in young people., Methods: A cohort of 8923 Japanese university students was enrolled and diagnoses of FD and IBS were confirmed using Rome III criteria. Allergic disorders diagnosed at medical institutions were obtained by means of a self-administered questionnaire., Results: The prevalence of FD, IBS, and their overlap was found to be 1.9%, 6.5%, and 1.1%, respectively. Pollen allergy was independently positively correlated with FD, IBS, and overlap of FD and IBS. Allergic rhinitis was positively linked to IBS. Drug allergy was positively associated with FD. The presence of multiple allergic diseases was positively correlated with FD and IBS (FD: adjusted OR for 2 allergic diseases: 1.95 [95% CI, 1.24-2.98], P for trend = 0.003; and IBS: adjusted OR for 1 allergic disease: 1.40 [95% CI, 1.15-1.69], 2 allergic diseases 1.47 [95% CI, 1.12-1.91], and 3 or more allergic diseases: 2.22 [95% CI, 1.45-3.28], P for trend = 0.001). Additionally, the concomitant existence of multiple allergic diseases was also demonstrated to have a trend that correlated with the overlap of FD and IBS ( P for trend = 0.018)., Conclusion: Allergic disease multimorbidity is positively correlated with the prevalence of FD and IBS in a young population.

Background: Takotsubo cardiomyopathy (TC) is a well-known complication of subarachnoid haemorrhage (SAH), often accompanied by neurogenic myocardial dysfunction. Although TC has been reported to be associated with higher morbidity and mortality among patients with aneurysmal SAH (aSAH), some patients have been reported to recover, the profiles and follow-up outcomes of these survivors remain unclear., Materials and Methods: To characterize the profiles of patients with aSAH complicated by TC who experienced favourable outcomes using long-term follow-up data, a consecutive series of patients with aSAH were enrolled and TC diagnosis was based on the revised version of the Mayo Clinic criteria. Clinical outcomes were assessed at 6 months according to modified Rankin Scale scores., Results: Among 165 consecutive patients with aSAH, 15 cases were complicated by TC, corresponding to an occurrence rate of 9.0%. Five patients with aSAH complicated by TC (33.3%) experienced a favourable outcome, and the mean value of systolic blood pressure on arrival was significantly lower than in those who experienced an unfavourable outcome ( p  = 0.032)., Conclusion: According to analysis, it is possible cardiac dysfunction with decreased cerebral perfusion pressure and catecholamine toxicity transiently worsens conscious disturbance in aSAH complicated by TC. Therefore, it is important to carefully screen patients with aSAH to identify those complicated by TC, and for close collaboration of the multidisciplinary team to design appropriate treatment strategies.

This study aimed to characterize ankle and hindfoot kinematics of healthy men and women during overground running using biplane radiography, and to compare these data to those previously obtained in the same cohort during overground walking. Participants ran across an elevated platform at a self-selected pace while synchronized biplane radiographs of their ankle and hindfoot were acquired. Motion of the tibia, talus, and calcaneus was tracked using a validated volumetric model-based tracking process. Tibiotalar and subtalar 6DOF kinematics were obtained. Absolute side-to-side differences in ROM and kinematics waveforms were calculated. Side-to-side and sex-specific differences were evaluated at 10 % increments of stance phase with mixed model analysis. Pearson correlation coefficients were used to assess the relationship between stance-phase running and walking kinematics. 20 participants comprised the study cohort (10 men, mean age 30.8 ± 6.3 years, mean BMI 24.1 ± 3.1). Average absolute side-to-side differences in running kinematics waveforms were 5.6°/2.0 mm or less at the tibiotalar joint and 5.2°/3.2 mm or less at the subtalar joint. No differences in running kinematics waveforms between sides or between men and women were detected. Correlations were stronger at the tibiotalar joint (42/66 [64 %] of correlations were p < 0.05), than at the tibiotalar joint (38/66 [58 %] of correlations were p < 0.05). These results provide a normative reference for evaluating native ankle and hindfoot kinematics which may be informative in surgical or rehabilitation contexts. Sex-specific differences in ankle kinematics during overground running are likely not clinically or etiologically significant. Associations seen between walking and running kinematics suggest one could be used to predict the other., Competing Interests: Declaration of competing interest JCS, PFP, TY, SY and WA have no professional or financial affiliations to report. MVH serves on the editorial board for AAOS, AOFAS, and BOS., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction Preoperative embolization can potentially facilitate surgical resection of challenging tumors in the intracranial and facial regions; however, its clinical efficacy remains controversial, mainly due to potential morbidity risks. We explored negative factors of the combined treatment of preoperative embolization and tumor resection that affect neurological prognosis. Method This retrospective study used clinical data from 132 consecutive tumors that underwent combined treatment at multiple facilities between January 2016 and May 2021. Basic patient information, tumor characteristics, and treatment details were assessed to identify predictors of deterioration as measured using the modified Rankin scale (mRS) score at three months post-treatment. Results Among the 126 eligible combined treatments, a deterioration in the postoperative mRS score was observed in 19/126 (15.1%). Complications related to embolization and tumor resection occurred in 8/126 (6.3%) and 19/125 (15.2%) of procedures, respectively. Multivariate analyses indicated significant associations between migration of embolic material (adjusted odds ratio 13.80; 95% confidence interval 1.25-152.52; p=0.03), elevated intraoperative blood loss (p=0.04), and deterioration of postoperative mRS score. Embolic material migration was identified as the primary prognostic factor for the deterioration of score. An analysis of 192 procedures, excluding those that exclusively used coils, identified embolization targeting the accessory meningeal artery (p=0.046) and the third segment of the internal maxillary artery (p=0.03) as a risk factor for embolic material migration. Conclusions Embolic material migration is the predominant factor associated with declining neurological outcome that persists into the chronic phase after combined treatment. Given that preoperative embolization is a supplementary treatment option, a thorough understanding of vascular anatomy and striving safe procedure are critical., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Suzuki et al.)

Background: Fractional flow reserve-computed tomography (FFR CT ) has not been validated in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) for coronary artery disease due to theoretical difficulties in using nitroglycerin for such patients., Methods and results: In this single-center study, we prospectively enrolled 21 patients (34 vessels) and performed pre-TAVR FFR CT without nitroglycerin, pre-TAVR invasive instantaneous wave-free ratio (iFR) measurements, and post-TAVR FFR measurements using a pressure wire. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of pre-TAVR FFR CT ≤0.80 to predict post-TAVR invasive FFR ≤0.80 were 82%, 83%, 82%, 71%, and 90%, respectively. A receiver operating characteristic analysis demonstrated an optimal cutoff of 0.78 for pre-TAVR FFR CT to indicate post-TAVR FFR ≤0.80, with an area under the curve (AUC) of 0.84, and the counterpart cutoff of pre-TAVR iFR was 0.89 with an AUC of 0.86., Conclusions: FFR CT without nitroglycerin could be a useful non-invasive imaging modality for assessing the severity of coronary artery lesions in patients with severe AS.

Objectives: In Japan, caudal block with 1% lidocaine is commonly used for transrectal prostate biopsy. Although 10 mL of 1% lidocaine is commonly used, the appropriate dosage of 1% lidocaine has not been studied. Our hospital routinely uses two different doses (5 or 10 mL) of 1% lidocaine for caudal block for transrectal prostate biopsy. Herein, we retrospectively evaluated the efficacy and safety of both doses of 1% lidocaine., Methods: This retrospective study included 869 patients who underwent transrectal prostate biopsy with caudal block at our hospital. The amount of 1% lidocaine was determined by the day of the week on which the biopsy was performed, and the patient voluntarily chose the day of the biopsy, unaware of the dose of 1% lidocaine used on that day. Pain, anal sphincter tonus, cancer diagnosis rate, and early complications were compared., Results: In total, 466 and 403 patients received 5 and 10 mL of 1% lidocaine for a caudal block, respectively. After propensity-score matching for patient characteristics, each group contained 395 patients. The pain score, anal sphincter tonus score, or prostate cancer diagnosis rate were not significantly different between the two groups. However, rectal bleeding was significantly more frequent and severe in the 10-mL than the 5-mL group ( p =0.018 and p =0.0036, respectively). The incidence of other complications was not significantly different between the groups., Conclusions: Our results suggest that 5 mL of 1% lidocaine may be more suitable than 10 mL for caudal block during transrectal prostate biopsy., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Norichika Ueda et al.)

Background: Perivascular inflammation contributes to the development of atherosclerosis and microcirculatory dysfunction. Pericoronary adipose tissue (PCAT) attenuation, measured by coronary computed tomography angiography, is a potential indicator of coronary inflammation. However, the relationship between PCAT attenuation, microcirculatory dysfunction, and periprocedural myocardial injury (PMI) remains unclear., Methods and Results: Patients with chronic coronary syndrome who underwent coronary computed tomography angiography before percutaneous coronary intervention were retrospectively identified. PCAT attenuation and adverse plaque characteristics were assessed using coronary computed tomography angiography. The extent of microcirculatory dysfunction was evaluated using the angio-based index of microcirculatory resistance before and after percutaneous coronary intervention. Overall, 125 consecutive patients were included, with 50 experiencing PMI (PMI group) and 75 without PMI (non-PMI group). Multivariable analysis showed that older age, higher angio-based index of microcirculatory resistance, presence of adverse plaque characteristics, and higher lesion-based PCAT attenuation were independently associated with PMI occurrence (odds ratio [OR], 1.07 [95% CI, 1.01-1.13]; P =0.02; OR, 1.06 [95% CI, 1.00-1.12]; P =0.04; OR, 6.62 [95% CI, 2.13-20.6]; P =0.001; and OR, 2.89 [95% CI, 1.63-5.11]; P <0.001, respectively). High PCAT attenuation was correlated with microcirculatory dysfunction before and after percutaneous coronary intervention and its exacerbation during percutaneous coronary intervention. Adding lesion-based PCAT attenuation to the presence of adverse plaque characteristics improved the discriminatory and reclassification ability in predicting PMI., Conclusions: Adding PCAT attenuation at the culprit lesion level to coronary computed tomography angiography-derived adverse plaque characteristics may provide incremental benefit in identifying patients at risk of PMI. Our results highlight the importance of microcirculatory dysfunction in PMI development, particularly in the presence of lesions with high PCAT attenuation., Registration: URL: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr&#95;view.cgi?recptno=R000057722; Unique identifier: UMIN000050662.

Study Design: Systematic review and meta-analysis., Objective: Using a network meta-analysis (NMA), this study aimed to compare the risks of C5 palsy after three different procedures of anterior cervical decompression., Summary of Background Data: C5 palsy is a well-known complication affecting the quality of life after anterior procedures. Due to the limited evidence on the various procedures available, we evaluate the basis for selection to prevent palsy and achieve maximal decompression in cases spanning 3-6 levels., Materials and Methods: We conducted a comprehensive search for C5 palsy and complications after 3representative procedures, including anterior cervical discectomy and fusion (ACDF), anterior cervical corpectomy and fusion (ACCF), and their combination (hybrid), involving 3 to 6 intervertebral levels. The incidence of C5 palsy was compared using a NMA., Results: We identified 1655 patients in 11 studies who met inclusion criteria. Sixty-nine patients (4.2%) developed delayed C5 palsies. The incidences among ACDF, ACCF, and hybrid cases were 2.3% (16/684, 95% CI: 1.4% to 3.8%), 6.4% (39/613, 95% CI: 4.7% to 8.6%), and 3.9% (14/358, 95% CI: 2.3% to 6.5%), respectively ( P < 0.01). A NMA was performed for 15 pairwise comparisons across the 3 procedure arms: ACDF versus hybrid, 7/232 (3.0%) versus 11/234 (4.7%); hybrid versus ACCF, 14/301 (4.3%) versus 18/224 (8.0%); ACCF versus ACDF, 38/523 (7.8%) versus 16/619 (2.6%). Compared with ACDF, the risk of C5 palsy was significantly higher in ACCF (odds ratio: 2.72, 95% CI: 1.47 to 5.01), whereas ACDF versus hybrid did not significantly differ in risk (odds ratio: 1.56, 95% CI: 0.68 to 3.60)., Conclusion: We determined that ACCF was associated with a higher risk of postoperative C5 palsy than ACDF in cases spanning 3 to 6 intervertebral levels. If practicable, ACDF surgery may be an appropriate choice for cases requiring anterior decompression of 3 to 6 levels., Level of Evidence: Level III., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Polymeric nanoparticles are primarily synthesized through emulsion polymerization, where surfactants are necessary to maintain dispersion stability. However, surfactants cause significant environmental pollution. The soap-free emulsion polymerization of styrene in melamine foam (MF) using a three-dimensional micronetwork structure as a reactor has been used to synthesize polymer nanoparticles, resulting in an extremely low polymer yield. To address this problem, the temperature of MF was reduced to prevent the diffusion of the monomer, which was driven by the difference of temperature between the bottom and top of MF. Furthermore, ultraviolet irradiation was applied to perform radical polymerization using an azo initiator, 4,4'-azobis(4-cyanovaleric acid). The resulting polymer yield was over 80%, although the reaction temperature was reduced from 70 to 40 °C. However, at an MF porosity of 0.60, the average polystyrene particle size was 49.2 nm with a polymer yield of 89.7%. The pore sizes in the MF were made homogeneous by pressing the MF to reduce the porosity, resulting in uniform nanoparticles., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Introduction This study aimed to determine the optimal timing for surgical intervention and the prognostic factors of cerebrospinal fluid (CSF) leakage. Methods We identified 25 patients with probable CSF leaks from 472 consecutive patients with head trauma. In addition to baseline characteristics and findings on admission, injury severity score (ISS), abbreviated injury score (AIS), and other factors related to CSF leakage were considered. We analyzed the prognostic factors after setting the primary endpoint as the modified Rankin Scale (mRS) at the time of discharge to determine the appropriate timing for surgical intervention. Results Univariate analysis revealed significantly poorer prognoses for elderly patients (p<0.001) and cases with low Glasgow Coma Scale (GCS) levels (p=0.039) and high D-dimer levels (p=0.028), which was consistent with findings from the analyses of all patients with head trauma. We found that multiple traumas (AIS≥3 at two or more sites, p=0.047) and high lactate levels (p=0.043) were poor prognostic factors specific to CSF leakage cases, while a longer time to CSF leakage cessation was also associated with a poorer prognosis (median, six days versus 13 days, p=0.014). An evaluation of the time to closure found that spontaneous cessation occurred within 14 days in most cases. Conclusions Conservative medical treatment is the first choice for most cases of traumatic CSF leakage. Surgical intervention should be considered if leakage does not cease after 14 days post injury. Furthermore, severe multiple injuries and high lactate levels were poor prognostic factors specific to patients with CSF leakage., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Shizawa et al.)

Purpose: The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors uses an integrated approach involving histopathology and molecular profiling. Because majority of adult malignant brain tumors are gliomas and primary CNS lymphomas (PCNSL), rapid differentiation of these diseases is required for therapeutic decisions. In addition, diffuse gliomas require molecular information on single-nucleotide variants (SNV), such as IDH1/2. Here, we report an intraoperative integrated diagnostic (i-ID) system to classify CNS malignant tumors, which updates legacy frozen-section (FS) diagnosis through incorporation of a qPCR-based genotyping assay., Experimental Design: FS evaluation, including GFAP and CD20 rapid IHC, was performed on adult malignant CNS tumors. PCNSL was diagnosed through positive CD20 and negative GFAP immunostaining. For suspected glioma, genotyping for IDH1/2, TERT SNV, and CDKN2A copy-number alteration was routinely performed, whereas H3F3A and BRAF SNV were assessed for selected cases. i-ID was determined on the basis of the 2021 WHO classification and compared with the permanent integrated diagnosis (p-ID) to assess its reliability., Results: After retrospectively analyzing 153 cases, 101 cases were prospectively examined using the i-ID system. Assessment of IDH1/2, TERT, H3F3AK27M, BRAFV600E, and CDKN2A alterations with i-ID and permanent genomic analysis was concordant in 100%, 100%, 100%, 100%, and 96.4%, respectively. Combination with FS and intraoperative genotyping assay improved diagnostic accuracy in gliomas. Overall, i-ID matched with p-ID in 80/82 (97.6%) patients with glioma and 18/19 (94.7%) with PCNSL., Conclusions: The i-ID system provides reliable integrated diagnosis of adult malignant CNS tumors., (©2023 American Association for Cancer Research.)

Objective: Carotid artery stenting embolic protection devices offer various options, among which distal filter protection is the simplest and easiest to handle. However, compared to balloon protection systems, distal filter protection has more embolic complications. Therefore, we explored the risk factors of distal filter protection, intending to achieve a safer carotid artery stenting. This retrospective study was conducted to identify prognostic factors following carotid artery stenting with only distal filter protection from July 2010 to June 2021., Methods: Information on patient background, procedures and devices, and complications was collected using medical records. The data pertaining to 187 patients were analyzed after excluding the data of patients in whom other protection devices (8 cases) were used. We used FilterWire EZ as the first choice for embolic protection device and SpiderFX when the patients had difficult-to-cross lesions., Results: The patients' mean age was 71.9 ± 6.9 years, and 72 (38.5%) were symptomatic. Symptomatic (odds ratio: 2.02, p = 0.035) and difficult-to-cross lesions (odds ratio: 3.63, p = 0.0013) were factors independently associated with symptomatic complications., Conclusion: This retrospective single-center study established independent prognostic factors for carotid artery stenting with distal filter protection. For patients with symptomatic lesions and severe stenosis or bends that are difficult to pass through, it is necessary to be careful when performing carotid artery stenting with distal filter protection., (©2024 The Japanese Society for Neuroendovascular Therapy.)

Objectives: The superiority and usefulness of liquid material over particles for embolization have been a topic of debate due to differences in materials and techniques. This study aimed to identify the complications and outcomes associated with both embolization materials., Methods: This retrospective multicenter cohort study included 93 patients from an endovascular treatment registry, treated from January 1, 2018 to May 31, 2022. It included patients who underwent preoperative embolization for meningioma, solitary fibrous tumor/hemangiopericytoma, and hemangioblastoma. Data for patient characteristics, procedural factors, complications, and outcomes were collected from medical records., Results: A tortuous access route was the only factor independently associated with complications ( p = 0.020). Although liquid material was more frequently used for embolization in relatively high-risk conditions, complication rates did not differ significantly between the groups ( p = 0.999). In the liquid material group, the tip of the microcatheter could be guided closer to the tumor ( p <0.001) using a distal access catheter and flow-guide microcatheters. The subgroup middle meningeal artery embolization had less operative bleeding in the liquid material group ( p <0.001), whereas the particles group exhibited less intraoperative blood loss than the liquid material group ( p = 0.006)., Conclusion: The vascular tortuosity of the access route was only associated with complications in preoperative tumor embolization. Liquid material and particles showed no difference in complication rates. The use of particles in embolization may reduce intraoperative bleeding, but not in all cases can it be used safely. Therefore, a thorough understanding of the characteristics of both approaches and their relative advantages in clinical practice is essential to opt for the appropriate material according to the case., (©2024 The Japanese Society for Neuroendovascular Therapy.)

Background: An aspiration catheter needs to attach to a thrombus in order to achieve first-pass recanalization by mechanical thrombectomy (MT) for acute ischemic stroke (AIS), particularly that using a direct aspiration first pass technique. The meniscus sign, which is defined as meniscoid contrast opacification indicating the proximal edge of a thrombus, has been suggested to contribute to successful recanalization. In some cases, the meniscus sign is not detected following an injection of contrast medium through a guiding catheter. To precisely identify the location of a thrombus, we use "the microcatheter contrast injection (MCI) technique," which accurately shows the proximal edge of a thrombus. We herein introduce this novel technique and discuss its efficacy in MT. Methods: In cases without the meniscus sign, a microcatheter was advanced to the distal end of contrast opacification, and contrast medium was injected through the microcatheter to detect the meniscus sign. An aspiration catheter was then advanced to the thrombus indicated by the meniscus sign and slowly withdrawn under aspiration. Results: 29 patients underwent MT for AIS using the MCI technique. Even in cases without the meniscus sign on initial angiography, the MCI technique accurately revealed the proximal edge of the thrombus. Moreover, middle cerebral artery occlusion due to atherosclerotic stenosis and displacement of the aspiration catheter and thrombus axis were detected using this technique. Conclusions: The MCI technique may effectively reveal the exact site of a thrombus and increase the success rate of first-pass recanalization., 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.

It is important to understand the dynamics of red blood cells (RBCs) in blood flow. This requires the formulation of coarse-grained RBC models that reproduce the hydrodynamic properties of blood accurately. One of the models that successfully reproduces the rheology and morphology of blood has been proposed by Fedosov et al. [Comput. Methods Appl. Mech. Eng. 199, 1937-1948 (2010)]. The proposed RBC model contains several parameters whose values are determined by either various experiments or physical requirements. In this study, we developed a new method of determining parameter values precisely from the fluctuations of the RBC membrane. Specifically, we studied the relationship between the spectra of the fluctuations and model parameters. Characteristic peaks were observed in the spectra, whose peak frequencies were dependent on the parameter values. In addition, we investigated the spectra of the radius of gyration. We identified the peaks originating from the spring potential and the volume-conserving potential appearing in the spectra. These results lead to the precise experimental determination of the parameters used in the RBC model., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Interoception, which pertains to the physiological state of the body, is associated with subjective emotional experiences. In particular, the accuracy of perceiving interoceptive signals (interoceptive accuracy [IAcc]) is linked to the intensity of emotional arousal, known as arousal focus (AF). IAcc is believed to influence the granularity of emotional experiences. Here, we examined the relationship between IAcc and assessment and verbalisation of one's own or others' emotions. Study I demonstrated that individuals with higher IAcc exhibited significantly greater AF when evaluating their own positive emotions. Furthermore, although no correlation between IAcc and AF was found in free descriptions of emotions, a significant positive correlation was found between IAcc and the number of emotion-related words. Study II showed that individuals with higher IAcc displayed significantly higher AF when assessing the positive emotions of characters in videos. Additionally, in free descriptions of these characters, a significant positive correlation was observed between predicted verbal IQ and the number of emotion-related words. These findings support the notion that interoception is associated with AF during assessment of one's own or others' positive emotions as well as the abundance of emotion-related words. This study demonstrates the relationship between bodily sensations and social aspects of human embodiment., (© 2023. The Author(s).)

Background and Objectives: Insulo-opercular surgery can cause ischemic motor complications. A source of this is the arteries around the superior limiting sulcus (SLS), which reach the corona radiata, but the detailed anatomy remains unclear. To characterize arteries around the SLS including the long insular arteries (LIAs) and long medullary arteries, we classified them and examined their distribution in relation to the SLS, which helps reduce the risk of ischemia., Methods: Twenty adult cadaveric hemispheres were studied. Coronal brain slices were created perpendicular to the SLS representing insular gyri (anterior short, middle short, posterior short, anterior long, and posterior long). The arteries within 10-mm proximity of the SLS that reached the corona radiata were excavated and classified by the entry point., Results: A total of 122 arteries were identified. Sixty-three (52%), 20 (16%), and 39 (32%) arteries penetrated the insula (LIAs), peak of the SLS, and operculum (long medullary arteries), respectively. 100 and six (87%) arteries penetrated within 5 mm of the peak of the SLS. The arteries were distributed in the anterior short gyrus (19%), middle short gyrus (17%), posterior short gyrus (20%), anterior long gyrus (19%), and posterior long gyrus (25%). Seven arteries (5.7%) had anastomoses after they penetrated the parenchyma., Conclusion: Approximately 90% of the arteries that entered the parenchyma and reached the corona radiata were within a 5-mm radius of the SLS in both the insula and operculum side. This suggests that using the SLS as a landmark during insulo-opercular surgery can decrease the chance of ischemia., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Primary central nervous system lymphoma (PCNSL) is a malignant neoplasm of the central nervous system that is refractory to treatment and has extremely poor prognosis. One factor hindering the development of therapeutic options for PCNSL is its molecular heterogeneity and the extreme difficulty in establishing in vitro cell lines that permit intensive research on this disease. In the present study, we developed a method to propagate PCNSL cells in vitro using a contacting transwell cell culture system involving brain vascular pericytes. The co-culture system was found to recapitulate the tumor microenvironment that is influenced by the biological activity of adjacent pericytes, and to sustain the survival and proliferation of PCNSL cells in vitro . We further delineated the underlying molecular mechanisms and found that the HGF-c-Met axis may be involved in the long-term in vitro culture of PCNSL cells. Moreover, the peptidylprolyl isomerase Pin1 was found to play a key role in PCNSL cell survival and it sustained proliferation through interactions with key transcription factors related to B-cell lymphomagenesis. These results suggest that our in vitro co-culture system is well suited to analyzing the biological and molecular characteristics of PCNSL, and may contribute to the discovery of new therapeutic interventions., Competing Interests: Authors YY and YM were employed by Kanto Chemical Co., Inc. 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 © 2023 Nishi, Tateishi, Sundararaj, Ino, Nakai, Hatayama, Yamaoka, Mihana, Miyakawa, Kimura, Kimura, Yamamoto and Ryo.)

In IDH-mutant astrocytoma, IDH2 mutation is quite rare and biological mechanisms underlying tumor progression in IDH2-mutant astrocytoma remain elusive. Here, we report a unique case of IDH2 mutant astrocytoma, CNS WHO grade 3 that developed tumor progression. We performed a comprehensive genomic and epigenomic analysis for primary and recurrent tumors and found that both tumors harbored recurrent IDH2 R172K and TP53 R248W mutation with CDKN2A/B hemizygous deletion. We also found amplifications of CDK4 and MDM2 with PDGFRA gain in the recurrent tumor and upregulated protein expressions of these genes. We further developed, for the first time, a xenograft mouse model of IDH2 R172K and TP53 R248W mutant astrocytoma from the recurrent tumor, but not from the primary tumor. Consistent with parent recurrent tumor cells, amplifications of CDK4 and MDM2 and PDGFRA gain were found, while CDKN2A/B was identified as homozygous deletion in the xenografts, qualifying for integrated diagnosis of astrocytoma, IDH2-mutant, CNS WHO grade 4. Cell viability assay found that CDK4/6 inhibitor and PDGFR inhibitor potently decreased cell viability in recurrent tumor cells, as compared to primary tumor cells. These findings suggest that gene alterations that activate retinoblastoma (RB) signaling pathways and PDGFR may drive tumor progression and xenograft formation in IDH2-mutant astrocytoma, which is equivalent to progressive IDH1-mutant astrocytoma. Also, our findings suggest that these genomic alterations may represent therapeutic targets in IDH2-mutant astrocytoma., (© 2023. The Author(s).)

Motivation facilitates motor performance; however, the neural substrates of the psychological effects on motor performance remain unclear. We conducted a functional magnetic resonance imaging experiment while human subjects performed a ready-set-go task with monetary incentives. Although subjects were only motivated to respond quickly, increasing the incentives improved not only reaction time but also peak grip force. However, the trial-by-trial correlation between reaction time and peak grip force was weak. Extensive areas in the mesocortical system, including the ventral midbrain (VM) and cortical motor-related areas, exhibited motivation-dependent activity in the premovement "Ready" period when the anticipated monetary reward was displayed. This premovement activity in the mesocortical system correlated only with subsequent peak grip force, whereas the activity in motor-related areas alone was associated with subsequent reaction time and peak grip force. These findings suggest that the mesocortical system linking the VM and motor-related regions plays a role in controlling the peak of force generation indirectly associated with incentives but not the initiation of force generation., (© The Author(s) 2023. Published by Oxford University Press.)

Background/objective: Arthroscopic lateral ligament repair (ALLR) for chronic lateral ankle instability (CLAI) has been improving with technical innovations. However, there is a lack of information regarding mid- and/or long-term clinical outcomes after the introduction of ALLR. This study aimed to report mid-term clinical outcomes of ALLR with a knotless anchor., Methods: Thirty-two patients (11 men and 21 women; mean age, 28 ± 14 years) who underwent ALLR with a knotless anchor from December 2015 to October 2020 were included. The mean follow-up period was 31 ± 11 months. The Japanese Society for Surgery of the Foot (JSSF) ankle-hindfoot scale and the Self-Administered Foot Evaluation Questionnaire (SAFE-Q) were used for clinical evaluation preoperatively and at the 2-year follow-up. Surgical complications, particularly knot irritation, were also examined., Results: The JSSF scale scores were significantly improved, from 71.3 ± 13.1 preoperatively to 96.6 ± 5.1 postoperatively (P < 0.05), and the SAFE-Q showed similar improvement in all subscales (P < 0.05). One case had a complication of persistent pain around the lateral portal (3.1%)., Conclusion: ALLR using a knotless anchor provided satisfactory clinical outcomes over 2 years, and no major complications, such as knot irritation, were observed., Case Series: Level of Evidence, 4., Competing Interests: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. ICMJE forms for all authors are available online. The authors received no financial support for the research, authorship, and/or publication of this article., (© 2023 Asia Pacific Knee, Arthroscopy and Sports Medicine Society. Published by Elsevier (Singapore) Pte Ltd.)

Liquid-liquid phase separation (LLPS) has been thought to be the biophysical principle governing the assembly of the multiphase structures of nucleoli, the site of ribosomal biogenesis. Condensates assembled through LLPS increase their sizes to minimize the surface energy as far as their components are available. However, multiple microphases, fibrillar centers (FCs), dispersed in a nucleolus are stable and their sizes do not grow unless the transcription of pre-ribosomal RNA (pre-rRNA) is inhibited. To understand the mechanism of the suppression of the FC growth, we here construct a minimal theoretical model by taking into account nascent pre-rRNAs tethered to FC surfaces by RNA polymerase I. The prediction of this theory was supported by our experiments that quantitatively measure the dependence of the size of FCs on the transcription level. This work sheds light on the role of nascent RNAs in controlling the size of nuclear bodies., (© 2023. The Author(s).)

Purpose: Bony morphology has been proposed as a potential risk factor for anterior cruciate ligament (ACL) injury. The relationship between bony morphology, knee kinematics, and ACL elongation during high-demand activities remains unclear. The purpose of this study was to determine if bone morphology features that have been associated with ACL injury risk and knee kinematics are also predictive of ACL elongation during fast running and double-legged drop jump., Methods: Nineteen healthy athletes performed fast running and double-legged drop jump within a biplane radiography imaging system. Knee kinematics and ACL elongation were measured bilaterally after using a validated registration process to track bone motion in the radiographs and after identifying ACL attachment sites on magnetic resonance imaging (MRI). Bony morphological features of lateral posterior tibial slope (LPTS), medial tibial plateau (MTP) depth, and lateral femoral condyle anteroposterior width (LCAP)/lateral tibial plateau anteroposterior width (TPAP) were measured on MRI. Relationships between bony morphology and knee kinematics or ACL elongation were identified using multiple linear regression analysis., Results: No associations between bony morphology and knee kinematics or ACL elongation were observed during fast running. During double-legged drop jump, a greater range of tibiofemoral rotation was associated with a steeper LPTS (β = 0.382, p = 0.012) and a deeper MTP depth (β = 0.331, p = 0.028), and a greater range of anterior tibial translation was associated with a shallower MTP depth (β = - 0.352, p = 0.018) and a larger LCAP/ TPAP (β = 0.441, p = 0.005); however, greater ACL elongation was only associated with a deeper MTP depth (β = 0.456, p = 0.006) at toe-off., Conclusion: These findings indicate that observed relationships between bony morphology and kinematics should not be extrapolated to imply a relationship also exists between those bone morphology features and ACL elongation during high-demand activities. These new findings deepen our understanding of the relationship between bony morphology and ACL elongation during high-demand activities. This knowledge can help identify high-risk patients for whom additional procedures during ACL reconstruction are most appropriate., (© 2023. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

The goal of this study was to determine how foot type and activity level affect ankle and hindfoot motion. Dynamic biplane radiography and a validated volumetric registration process was used to measure ankle and hindfoot motion of 20 healthy adults during walking and running. The helical axes of motion (HAM) during stance were calculated at the tibiotalar and subtalar joints. The intersection of each HAM and the rotation plane of interest defined the tibiotalar and subtalar centers of rotation (COR). Correlations between foot type and hindfoot kinematics were calculated using Pearson's correlations. The effect of activity, phase of gait, and dominant vs. non-dominant limb on HAM and COR were evaluated using linear mixed effects models. Activity and phase of gait influenced the superior location of the tibiotalar (p < 0.041) and subtalar (p < 0.044) CORs. Activity and gait phase affected tibiotalar (p < 0.049) and subtalar (p < 0.044) HAM direction during gait. Both HAM orientation and COR location changed with activity and phase of gait. These ankle and hindfoot kinematics have implications for total ankle replacement design and musculoskeletal models that estimate force and moment generating capabilities of muscles., 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 © 2023 Elsevier Ltd. All rights reserved.)