Anti-epileptic drug use and subsequent degenerative dementia occurrence.

INTRODUCTION: The use of anti-epileptic drugs (AEDs) in degenerative dementia (DD) remains uncertain. We aimed to evaluate the association of early AED administration with subsequent DD occurrence. METHODS: Using a large nationwide database, we enrolled patients newly diagnosed with epilepsy from 2014 to 2019 (n = 104,225), and using propensity score matching, we divided them into treatment (those prescribed AEDs in 2014) and control groups. The primary outcome was subsequent DD occurrence in 2019. RESULTS: Overall, 4489 pairs of patients (2156 women) were matched. The odds ratio (treatment/control) for DD occurrence was 0.533 (95% confidence interval: 0.459-0.617). The DD proportions significantly differed between the treatment (340/4489 = 0.076) and control (577/4489 = 0.129) groups. DISCUSSION: Among patients newly diagnosed with epilepsy, compared to non-use, early AED use was associated with a lower occurrence of subsequent DD. Further investigations into and optimization of early intervention for epilepsy in DD are warranted. Highlights: Anti-epileptic drug (AED) use before epilepsy diagnosis was linked with a lower subsequent degenerative dementia (DD) occurrence.Identifying the epileptic phenotype was crucial for justifying early AED use in DD.AED use with an epilepsy diagnosis did not pose an additional risk of DD.The potential contribution of combination drug therapy to the strategy was noted.

Spontaneous termination of ventricular tachycardia in the human heart.

INTRODUCTION: Understanding the spatiotemporal location of the spontaneous termination of ventricular tachycardia (VT) may provide new insights for ablation. To test the hypothesis that spontaneous VT termination most frequently occurs at the VT exit due to source-sink mismatch and to characterize electrophysiological properties of the sites termination during VT and with extra-stimulus technique. METHODS: Retrospective analysis of intraoperative mapping studies of nine patients with ischemic cardiopathy or repaired tetralogy of Fallot. Simultaneous endocardial and epicardial mapping was performed in both ventricles using a custom mapping array during VT. Electrogram (EGM) characteristics before and at the moment of termination were analyzed including: cycle length oscillations, EGM heterogeneity and a variation in the systolic/diastolic path. The decrements to extra stimulus were analysed for termination sites and other diastolic sites. RESULTS: Nine VTs in seven patients demonstrated spontaneous VT termination. Seven VTs (77.8%) spontaneously terminated in the final third of the systolic interval, one (11.1%) in early diastole and one (11.1%) in mid diastole. Cycle length oscillations (prolongation, shortening, and no change) were seen in equal frequency. Four VTs (44.4%) showed alternans in the local EGM at the site of termination and this was more prevalent than alternans at other sites in the diastolic pathway (p < .001). Only one-third of VTs showed a change in activation pattern before termination. There was no difference based on etiology. During substrate characterization with extra-stimulus pacing, sites of spontaneous termination showed greater decrement than other sites of the VT circuit during pacing (43.5 ± 14.5 ms vs. 31.2 ± 31.2 ms; p = .003). CONCLUSION: The entrance zone rather than the exit is the commonest site for the spontaneous termination of VT in the human heart. These sites tend to demonstrate EGM alternans during VT and greater decrement during extrastimulus pacing. These findings may help guide future studies into improving the success of VT ablation.

Ultra sensor based on color and UV-excited fluorescence images for predicting quality attributes of Shine-Muscat grape bunches at different maturity stages.

Fruit maturity at harvest is a major factor in determining its quality. In this study, external skin color of grape has been utilized to predict their chemical content and, in turn, the maturity of the fruit. Measurements of the chemical content such as Brix and acidity were made on ten bunches of "Shine Muscat" grapes at three different harvest periods (immature, mature, and overmature). Using a machine vision system, color and UV-excited fluorescence images of grape berries and bunches were taken during the respective harvest stages. Acquired images were processed using ImageJ to obtain RGB values. Rratio and a*/b* are strongly related to Brix and sugar-to-acid ratio of grape fruit, with regression coefficients of 0.5626 and 0.5180, repectively. It was found that a* color index was the best predictor of grape bunch maturity. Furthermore, discriminant analysis has shown that color images of grape berries perform better than 365 nm fluorescence images.

Comparing Injection Site Reactions of Aprepitant and Fosaprepitant in Gynecologic Cancer Chemotherapy.

BACKGROUND/AIM: The frequency rate of injection site reactions (ISR) due to fosaprepitant meglumine (Fos APR) has been shown to vary depending on the types of combined anticancer drug. This study aimed to elucidate the impact of Fos APR on ISR in patients receiving paclitaxel and carboplatin, with and without bevacizumab therapy (TC±Bev). PATIENTS AND METHODS: This study focused on patients with gynecologic cancer (n=93) who received TC±Bev administration at Fujita Health University Hospital from March 2016 to February 2020, and monitored up to six cycles. The patients were randomly assigned to the Fos APR group (n=47) and the Aprepitant (APR) group (n=46). Using Visual Infusion Phlebitis (VIP) scores, ISR was evaluated by comparing the VIP scores of all cycles using a linear mixed model. The risk factors that contribute to the occurrence of vascular pain throughout all cycles were also examined. RESULTS: The VIP scores of all cycles showed a near significant intergroup difference (p=0.071). Factors that affected the development of vascular pain included Fos APR and age (p=0.027 and 0.049, respectively). Regarding age, patients aged <65 years had a higher risk. Four patients underwent a switch from the originally assigned neurokinin-1 receptor antagonist; in all of these cases, Fos APR was changed to APR for vascular pain. CONCLUSION: Fos APR may increase the risk for ISR associated with TC±Bev therapy for gynecological cancer.

Tunable elastic wave transmission and resonance in a periodically aligned tube-block structure.

A tube-block structure is proposed to realize tunable elastic wave transmission and resonance, consisting of periodically aligned circular tubes sandwiched and joined by two blocks. Finite element simulations for a unit structure are carried out to reveal the frequency dependence of the transmission behavior for the normal incidence of longitudinal and transverse waves in the tube-block structure. As a result, the transmission ratios are found to take multiple local maxima at different peak frequencies. Eigenfrequency analysis shows that the local resonances of the tube and the block surfaces occur at the peak frequencies in the transmission ratios. The peak frequencies originating from the local resonance of the tube depend on its radius and thickness, while those from the resonance on the block surfaces are in good agreement with the theoretical relation between the interval of the periodically aligned tubes and the wavelength of the Rayleigh wave. Furthermore, when the tube-block structure is subjected to compressive loading, the deformation shifts the peak frequencies of the transmission ratio corresponding to the local resonance of the tube. This result implies that the proposed structure has the potential to serve as a tunable meta-interface between solid blocks.

Long-read sequencing identifies an SVA_D retrotransposon insertion deep within the intron of ATP7A as a novel cause of occipital horn syndrome.

BACKGROUND: SINE-VNTR-Alu (SVA) retrotransposons move from one genomic location to another in a 'copy-and-paste' manner. They continue to move actively and cause monogenic diseases through various mechanisms. Currently, disease-causing SVA retrotransposons are classified into human-specific young SVA_E or SVA_F subfamilies. In this study, we identified an evolutionarily old SVA_D retrotransposon as a novel cause of occipital horn syndrome (OHS). OHS is an X-linked, copper metabolism disorder caused by dysfunction of the copper transporter, ATP7A. METHODS: We investigated a 16-year-old boy with OHS whose pathogenic variant could not be detected via routine molecular genetic analyses. RESULTS: A 2.8 kb insertion was detected deep within the intron of the patient's ATP7A gene. This insertion caused aberrant mRNA splicing activated by a new donor splice site located within it. Long-read circular consensus sequencing enabled us to accurately read the entire insertion sequence, which contained highly repetitive and GC-rich segments. Consequently, the insertion was identified as an SVA_D retrotransposon. Antisense oligonucleotides (AOs) targeting the new splice site restored the expression of normal transcripts and functional ATP7A proteins. AO treatment alleviated excessive accumulation of copper in patient fibroblasts in a dose-dependent manner. Pedigree analysis revealed that the retrotransposon had moved into the OHS-causing position two generations ago. CONCLUSION: This is the first report of a human monogenic disease caused by the SVA_D retrotransposon. The fact that the evolutionarily old SVA_D is still actively transposed, leading to increased copy numbers may make a notable impact on rare genetic disease research.

Risk factors for residual liver recurrence of colorectal cancer after resection of liver metastases and significance of adjuvant chemotherapy.

OBJECTIVE: The risk factors for residual liver recurrence after resection of colorectal cancer liver metastases were analyzed separately for synchronous and metachronous metastases. METHODS: This retrospective study included 236 patients (139 with synchronous and 97 with metachronous lesions) who underwent initial surgery for colorectal cancer liver metastases from April 2010 to December 2021 at the Fujita Health University Hospital. We performed univariate and multivariate analyses of risk factors for recurrence based on clinical background. RESULTS: Univariate analysis of synchronous liver metastases identified three risk factors: positive lymph nodes (p = 0.018, HR = 2.067), ≥3 liver metastases (p < 0.001, HR = 2.382), and use of adjuvant chemotherapy (p = 0.013, HR = 0.560). Multivariate analysis identified the same three factors. For metachronous liver metastases, univariate and multivariate analysis identified ≥3 liver metastases as a risk factor (p = 0.002, HR = 2.988); however, use of adjuvant chemotherapy after hepatic resection was not associated with a lower risk of recurrence for metachronous lesions. Inverse probability of treatment weighting analysis of patients with these lesions with or without adjuvant chemotherapy after primary resection showed that patients with metachronous liver metastases who did not receive this treatment had fewer recurrences when adjuvant therapy was administered after subsequent liver resection, although the difference was not significant. Patients who received adjuvant chemotherapy after hepatic resection had less recurrence but less benefit from this treatment. CONCLUSION: Risk factors for liver recurrence after resection of synchronous liver metastases were positive lymph nodes, ≥3 liver metastases, and no postoperative adjuvant chemotherapy. Adjuvant chemotherapy is recommended after hepatic resection of synchronous liver metastases.

Influence of Previous Therapy for Neutropenia Caused by Combination Therapy of Ramucirumab and Docetaxel.

In the present study, the influence of previous immune checkpoint inhibitor (ICI) therapy with ramucirumab (RAM) + docetaxel (DTX) therapy on the occurrence of severe neutropenia in patients with non-small cell lung cancer (NSCLC) was evaluated, taking into account the influences of cytotoxic chemotherapy used in pretreatment. The study participants included patients who received a combination therapy of RAM and DTX as cancer chemotherapy for NSCLC. The influences of previous ICI treatment and pretreatment with cytotoxic anticancer agents on the development of grade ≥ 3 neutropenia were analysed. A total of 89 patients, including 50 with and 39 without a history of ICI treatment, were analysed. Kaplan-Meier curves showed a significant difference in the influence of previous ICI treatment on the development of grade ≥ 3 neutropenia (p = 0.006). Moreover, Cox regression analysis identified a history of ICI treatment and prophylactic administration of G-CSF as factors associated with the development of grade ≥ 3 neutropenia (p = 0.018 and p < 0.001, respectively). This study found that previous treatment with ICIs reduced the incidence of grade ≥ 3 neutropenia after RAM + DTX therapy in patients with NSCLC, regardless of the influences of pretreatment with cytotoxic anticancer agents.

Size-dependent reactivity of Rh cationic clusters to reduce NO by CO in the gas phase at high temperatures.

The reactivity of the reduction of NO pre-adsorbed on Rh2-9+ clusters by CO was investigated using a combination of an alternate on-off gas injection method and thermal desorption spectrometry. The reduction of RhnNxOy+ clusters by CO was evaluated by varying the CO concentration at T = 903 K. Among the RhnNxOx+ clusters, the Rh3N2O2+ cluster exhibited the highest reduction activity, whereas the other clusters, Rh2,4-9NxOx+, showed lower reactivity. Density functional theory (DFT) calculations for Rh3+ and Rh6+ revealed that the rate-determining step for NO reduction in the presence of CO was NO bond dissociation through the kinetics analysis using the RRKM theory. The reduction of Rh3N2O2+ is kinetically preferable to that of Rh6N2O2+. The DFT results were in qualitative agreement with the experimental results.

Impacts of Febuxostat on Cerebral and Cardiovascular Events in Elderly Patients with Hyperuricemia: Post Hoc Analysis of a Randomized Controlled Trial.

A recent meta-analysis found no benefit of uric acid-lowering therapy including febuxostat on death, cardiovascular events, or renal impairment. However, there may be populations that benefit from febuxostat in reducing mortality and cerebral and cardiovascular events. The aim of the present study was to examine the clinical benefit of febuxostat in elderly patients stratified by age using Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy (FREED) data. FREED was a randomized study involving patients aged 65 years or older with hyperuricemia and risk factors for cerebral, cardiovascular, or renal diseases. A total of 1,070 patients were included in this post hoc analysis, divided into 2 age groups: 65-74 years and ≥ 75 years. Patients were randomized into febuxostat and non-febuxostat groups, with uric acid levels monitored for 36 months. The primary composite end point included cerebral, cardiovascular, and renal events. In patients aged between 65 and 74 years, febuxostat significantly reduced the risk of future cerebral and cardiorenovascular events. However, no effects of febuxostat were found in the older population aged ≥ 75 years. Heterogeneity in potential interactions between the age and febuxostat treatment was particularly observed in non-fatal cerebral and cardiovascular events and all-cause death. Patients aged ≥ 75 years exhibited more pre-existing factors associated with cerebral and cardiorenovascular events than those aged 65-74 years. The effectiveness of febuxostat varies by age group, with potential benefits for patients aged 65-74 years. The effects of febuxostat are complex and it is important to consider patient characteristics in its clinical use.

Factors associated with physical activity following total knee arthroplasty for knee osteoarthritis: a longitudinal study.

BACKGROUND: After total knee arthroplasty (TKA), patients' physical activity (PA) levels at 6 months are lower than those of healthy subjects. Few studies have investigated the factors associated with PA at 6 months after TKA by objectively measuring preoperative and postoperative PA intensity using an accelerometer and knee function using a goniometer and dynamometer. The purpose of this study was to determine the factors associated with PA levels at 6 months after TKA based on objective data. METHODS: Eighty-two patients (mean [SD] age 74.5 [6.4] years) with moderate-to-severe knee osteoarthritis (OA) who were scheduled for TKA at the Nagoya Orthopaedic and Joint Replacement Clinic from July 2018 to July 2019 were enrolled in this longitudinal study. All patients underwent evaluations of knee function, including range-of-motion and knee-extension muscle strength; knee pain; performance in the timed up-and-go test; and accelerometer-measured PA both preoperatively and 6 months postoperatively. Factors associated with PA at 6 months after TKA were assessed using a hierarchical multiple linear regression analysis adjusted for age, sex, body mass index, and presence of diabetes mellitus. RESULTS: A higher average daily step count at 6 months after TKA was significantly associated with greater preoperative knee-extension muscle strength on the operated side (ß = 0.155, p = 0.028) as well as a higher preoperative average daily step count (ß = 0.834, p < 0.001). Furthermore, average daily time spent in moderate-to-vigorous-intensity PA postoperatively was significantly associated only with time spent in moderate-to-vigorous-intensity PA preoperatively (ß = 0.723, p < 0.001). CONCLUSION: These findings indicate that a higher preoperative daily step count and greater preoperative knee-extension muscle strength on the operated side may be associated with a higher daily step count at 6 months after TKA. Factors associated with PA differed by the PA intensity level. Rehabilitation and interventions for psychosocial factors before TKA beginning when mild knee OA first occurs are expected to lead to increased PA in TKA patients.

Effect of Liver Dysfunction on S-1 Therapy Induced Adverse Effects: A Retrospective Cohort Study.

BACKGROUND/AIM: Renal dysfunction necessitates S-1 dose reduction. However, decreased dihydropyrimidine dehydrogenase (DPD) activity may lead to adverse events due to 5-FU. The guidelines provided by pharmaceutical companies state that total bilirubin (T-Bil) should be ≤upper limit of normal (ULN)×1.5 as a reference value for safely taking S-1. Nevertheless, the relationship between the degree of liver dysfunction and S-1 dose reduction has not been clearly established. PATIENTS AND METHODS: This study focused on patients who received S-1 monotherapy for various types of cancer. The primary outcome was defined as the variation between blood sampling results on the test day and the subsequent test. The variation data were categorized based on the difference in T-Bil: Low T-Bil group (≤2.25) and High T-Bil group (>2.25). RESULTS: The number of patients that underwent S-1 monotherapy was 883 and the running number was 7,511; Low T-Bil group included 7,245 and High T-Bil group included 266. Examination of the effect of the T-Bil Group on clinical outcomes revealed a correlation with red blood cell (RBC) count, platelet (PLT) count, and T-Bil level. When the impact of the interaction between the T-Bil Group and any of the clinical outcomes, such as the RBC count, PLT count, and T-Bil level, was determined, each outcome showed a significant decrease in the High T-Bil group compared with the Low T-Bil group. CONCLUSION: S-1 administration in patients with liver dysfunction accompanied by elevated T-Bil levels may cause thrombocytopenia.

Appetite and family and friends network among community-dwelling older adults: A cross-sectional study.

OBJECTIVES: The aim of this study was to investigate the stronger correlate of appetite-family or friend networks-in community-dwelling older adults, given that undernutrition can impair physical function, increase mortality, and be influenced by social networks. METHODS: A cross-sectional study was conducted in Kasugai City, Aichi Prefecture, and Nara City, Nara Prefecture, Japan, between August 2019 and March 2023. The analysis included 119 participants (women: 79%, mean age: 76.5 ± 5.6 y). A multiple regression analysis was performed, using the scores from the Japanese version of the Simplified Nutritional Appetite Questionnaire (SNAQ-J) as the dependent variable and family network and friend network as the independent variables. The analysis included social participation, living alone status, sex, age, body mass index, skeletal muscle mass index, grip strength, walking speed, and the Japanese version of the 15 Geriatric Depression Scale score as covariates to examine their relationship with appetite. RESULTS: The mean value of the SNAQ-J score of the participants was 15.4 ± 1.2. Seven participants (6%) had a loss of appetite. Family network was significantly associated with appetite (B = 0.121, ß = 0.266, P <0.05; 95% condidence interval [CI], 0.030-0.212). In the single regression analysis, the friend network was significantly associated with the total score of the SNAQ-J (B = 0.115, P <0.001; 95% CI, 0.052-0.177); however, this association was not observed in the multiple regression analysis (B = 0.002, ß = 0.006, P = 0.954; 95% CI, -0.074-0.078). CONCLUSION: Appetite was associated with family networks. Among social networks, focusing on family networks may help prevent the loss of appetite in older adults in Japan.

Exploration of useful clinical laboratory values as diagnostic criteria for eosinophilic gastroenteritis.

BACKGROUND: Eosinophilic gastroenteritis (EGE) is a rare eosinophilic infiltrative disorder. In Japan, EGE is diagnosed using clinical symptoms as well as microscopic, haematologic and histopathological findings. In this study, we examined the usefulness of laboratory data in the diagnosis of EGE. METHODS: Patients who were diagnosed with EGE at Fujita Health University Bantane Hospital between April 2015 and December 2020 were enrolled in this study and their data was retrospectively analysed. We evaluated their medical history, laboratory data including leukocyte count, eosinophil count, immunoglobulin (Ig) E, thymus and activation-regulated chemokine (TARC), C-reactive protein (CRP), etc. and histopathological data were collected from the electronic medical records. RESULTS: One hundred twelve of 168 patients who were treated for EGE could be analysed. The peripheral eosinophil count was correlated with the duodenal or ascending colon eosinophil count; moreover, the blood lymphocyte count and the TARC were correlated with the transverse colon eosinophil count. Multivariate regression analysis showed correlations only in the oesophagus, stomach and duodenum. Specifically, correlations were noted between blood eosinophils and gastric eosinophils, blood eosinophils and duodenal eosinophils, blood lymphocytes and gastric eosinophils, blood IgE and oesophageal, gastric and duodenal eosinophils and CRP and oesophageal eosinophils. CONCLUSION: The extent of blood eosinophil count, lymphocyte count, IgE and CRP elevation together with clinical features and pathology can be incorporated into a diagnostic scoring criteria system to improve the accuracy of diagnosing this uncommon condition in the future.

Longitudinal association between oral function and underweight onset among community-dwelling older adults: Role of regular self-weighing.

AIMS: Regular self-weighing is effective in weight management and may help to mitigate the risk of underweight among older adults. We examined which factors of oral function are associated with a risk for underweight among community-dwelling older adults and whether regular self-weighing can mitigate that risk. METHODS: This was a cohort study. Self-administered questionnaires were mailed to 7665 older adults in March 2019 (response rate 74.3%) and 7591 in March 2020 (response rate 74.7%). Among those who responded to both surveys, 3594 older adults who were not underweight in March 2019 were included (follow-up rate: 59.2%). We examined the association between dysphagia, poor masticatory function, and dry mouth and the development of underweight, and whether regular self-weighing reduced the risk for underweight. RESULTS: The average age ± standard deviation of participants was 71.1 ± 3.4 years. There was a significant association between swallowing difficulty and the occurrence of underweight (odds ratio = 1.65, p = .012). However, this relationship did not differ significantly with regular self-weighing (p = .477). CONCLUSIONS: These study findings suggest that to prevent underweight among community-dwelling older adults, it is important to focus on those with poor swallowing function.

Sodium-Glucose Cotransporter-2 Inhibitors Stabilize Coronary Plaques in Acute Coronary Syndrome With Diabetes Mellitus.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are widely used in cardiology and are effective in treating acute coronary syndrome (ACS). Their effects on unstable plaque in patients with ACS remains unclear. This study aimed to examine the effectiveness of SGLT2is in coronary plaque based on optical coherence tomography (OCT) images and the prognosis of ACS with type 2 diabetes mellitus. This retrospective study included 109 patients in the total cohort and 29 patients in the OCT cohort. Based on SGLT2i administration after ACS, the total cohort was categorized into non-SGLT2i (n = 69) and SGLT2i (n = 40) groups. The OCT cohort had 15 and 14 patients in the non-SGLT2i and SGLT2i groups, respectively. The OCT images of unstable plaque were analyzed in nonstented lesions during ACS catheterization and at the 6-month follow-up. The total cohort was assessed after 1 year for major adverse cardiovascular events, including all-cause mortality, revascularization, cerebrovascular disease, and heart failure hospitalization. SGLT2is improved unstable lesions with a significantly thicker fibrous cap (48 ± 15 µm vs 26 ± 24 µm, p = 0.005), reduced lipid arc (-29 ± 12° vs -18 ± 14°, p = 0.028), higher % decrease in total lipid arc (-35 ± 13% vs -19 ± 18%, p = 0.01), and lower major adverse cardiovascular event incidence (log-rank p = 0.023, hazard ratio 4.72 [1.08 to 20.63]) and revascularization rate (adjusted hazard ratio 6.77 [1.08 to 42.52]) than the non-SGLT2i group. In conclusion, SGLT2is can improve the markers of plaque stability and may improve the prognosis in patients with type 2 diabetes mellitus.

Phase Angle as a Nutritional Assessment Method in Patients with Hip Fractures: A Cross-Sectional Study.

BACKGROUND: Phase angle, which is associated with cellular health, has attracted attention as a noninvasive and objective method for nutritional assessment. However, the association between malnutrition and phase angle in older inpatients with hip fractures has not been reported. Therefore, this study investigated this association in older inpatients (aged ≥65 years) with hip fractures and determined the cutoff phase angle for determining malnutrition. METHODS: This cross-sectional study retrospectively analyzed the data of 96 inpatients with hip fractures who were hospitalized in rehabilitation units after surgery (male, 29.4%; mean age, 82.4±6.2 years). Nutritional status was assessed using the Geriatric Nutritional Risk Index (GNRI), with malnutrition defined as a GNRI ≥98. Bioelectrical impedance analysis was used to measure phase angles. RESULTS: The phase angle was associated with malnutrition (B=-1.173; odds ratio=0.310; 95% confidence interval 0.58-0.83; p=0.015). The area under the receiver operating characteristic curve was 0.71. The cutoff phase angle for malnutrition was 3.96° (sensitivity=0.85, specificity=0.63). CONCLUSION: Phase angle could be an indicator of malnutrition in older inpatients with hip fractures. Our findings will help formulate rehabilitation strategies for these patients.

Intraoperative Integrated Diagnostic System for Malignant Central Nervous System Tumors.

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.

High-level phenol bioproduction by engineered Pichia pastoris in glycerol fed-batch fermentation using an efficient pertraction system.

This study aimed to establish a high-level phenol bioproduction system from glycerol through metabolic engineering of the yeast Pichia pastoris (Komagataella phaffii). Introducing tyrosine phenol-lyase to P. pastoris led to a production of 59 mg/L of phenol in flask culture. By employing a strain of P. pastoris that overproduces tyrosine-a precursor to phenol-we achieved a phenol production of 1052 mg/L in glycerol fed-batch fermentation. However, phenol concentrations exceeding 1000 mg/L inhibited P. pastoris growth. A phenol pertraction system utilizing a hollow fiber membrane contactor and tributyrin as the organic solvent was developed to reduce phenol concentration in the culture medium. Integrating this system with glycerol fed-batch fermentation resulted in a 214 % increase in phenol titer (3304 mg/L) compared to glycerol fed-batch fermentation alone. These approaches offer a significant framework for the microbial production of chemicals and materials that are highly toxic to microorganisms.

Difference in tissue temperature change between two cryoballoons.

BACKGROUND: Cryoballoon ablation, especially Arctic Front Advance Pro (AFA-Pro) (Medtronic, Minneapolis, Minnesota, USA), has been widely recognised as a standard approach to atrial fibrillation (AF). Recently, Boston Scientific has released a novel cryoballoon system (POLARx). Despite comparable acute clinical outcomes of these two cryoballoons, the recent study reported a higher complication rate, especially for phrenic nerve palsy, with POLARx. However, their impact on biological tissue remains unclear. OBJECTIVE: The purpose of our study is to evaluate temperature change of biological tissue during cryoablation of each cryoballoon using a porcine experimental model. METHOD: A tissue-based pulmonary vein model was constructed from porcine myocardial tissue and placed on a stage designed to simulate pulmonary vein anatomy and venous flow. Controlled cryoablations of AFA-Pro and POLARx were performed in this model to evaluate the tissue temperature. A temperature sensor was set behind the muscle and cryoballoon ablation was performed after confirming the occlusion of pulmonary vein with cryoballoon. RESULTS: The mean tissue nadir temperature during cryoablation with AFA-Pro was -41.5°C±4.9°C, while the mean tissue nadir temperature during cryoablation with POLARx was -58.4°C±5.9°C (p<0.001). The mean balloon nadir temperature during cryoablation with AFA-Pro was -54.6°C±2.6°C and the mean balloon nadir temperature during cryoablation with POLARx was -64.7°C±3.8°C (p<0.001). CONCLUSION: POLARx could freeze the biological tissue more strongly than AFA-Pro.