Locoregional Recurrence in Adenoid Cystic Carcinoma of the Breast: A Retrospective, Multicenter Study (KROG 22-14).

Purpose: This study aims to evaluate the treatment approaches and locoregional patterns for Adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data. Materials and Methods: A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). The recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed. Results: Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with 5 of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in 5 patients (5.4%) and 4 cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in 2 patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS. Conclusion: BCS followed by PORT was the predominant treatment approach for ACC of the breast and local recurrence mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC.

Prognostic Value of Preoperative N Subcategories in Patients with Stage IIIA N2 Non-Small Cell Lung Cancer.

Purpose To evaluate the preoperative risk factors in patients with pathologic IIIA N2 non-small cell lung cancer (NSCLC) who underwent upfront surgery and to evaluate the prognostic value of new N subcategories. Materials and Methods Patients with pathologic stage IIIA N2 NSCLC who underwent upfront surgery in a single tertiary center from January 2015 to April 2021 were retrospectively reviewed. Each patient's clinical N (cN) was assigned to one of six subcategories (cN0, cN1a, cN1b, cN2a1, cN2a2, and cN2b) based on recently proposed N descriptors. Cox regression analysis was used to identify the significant prognostic factors for recurrence-free survival (RFS) and overall survival (OS). Results A total of 366 patients (mean age ± SD, 62.0 years ± 10.1; 202 male patients [55%]) were analyzed. The recurrence rate was 55% (203 of 366 patients) over a median follow-up of 37.3 months. Multivariable analysis demonstrated that cN (hazard ratios [HRs] for cN1 and cN2b compared with cN0, 1.66 [95% CI: 1.11, 2.48] and 2.11 [95% CI: 1.32, 3.38], respectively) and maximum lymph node (LN) size at N1 station (≥12 mm; HR, 1.62 [95% CI: 1.15, 2.29]), in addition to clinical T category (HR, 1.51 [95% CI: 1.14, 1.99]), were independent prognostic factors for RFS. For OS, clinical N subcategories (cN1, cN2a2, and cN2b vs cN0; HRs, 1.91 [95% CI: 1.11, 3.27], 1.89 [95% CI: 1.13, 2.18], and 2.02 [95% CI: 1.07, 3.80], respectively) and LN size at N1 station (HR, 1.75 [95% CI: 1.12, 2.71]) were independent prognostic factors. For clinical N1, OS was further stratified according to LN size (log-rank test, P < .001). Conclusion Assessing the proposed N subcategories by reporting single versus multistation involvement of N2 disease and maximum size of metastatic LN, reflecting metastatic burden, at preoperative CT may offer useful prognostic information for planning optimal treatment strategies. Keywords: CT, Lung, Staging, Non-Small Cell Lung Cancer Supplemental material is available for this article. ©RSNA, 2024.

Balloon-expandable cobalt chromium stent versus self-expandable nitinol stent for the Atherosclerotic Iliac Arterial Disease (SENS-ILIAC Trial) Trial: a randomized controlled trial.

Iliac artery angioplasty with stenting is an effective alternative treatment modality for aortoiliac occlusive diseases. Few randomized controlled trials have compared the efficacy and safety between self-expandable stent (SES) and balloon-expandable stent (BES) in atherosclerotic iliac artery disease. In this randomized, multicenter study, patients with common or external iliac artery occlusive disease were randomly assigned in a 1:1 ratio to either BES or SES. The primary end point was the 1-year clinical patency, defined as freedom from any surgical or percutaneous intervention due to restenosis of the target lesion after the index procedure. The secondary end point was a composite event from major adverse clinical events at 1 year. A total of 201 patients were enrolled from 17 major cardiovascular intervention centers in South Korea. The mean age of the enrolled patients was 66.8 ± 8.5 years and 86.2% of the participants were male. The frequency of critical limb ischemia was 15.4%, and the most common target lesion was in the common iliac artery (75.1%). As the primary end point, the 1-year clinical patency as primary end point was 99% in the BES group and 99% in the SES group (p > 0.99). The rate of repeat revascularization at 1 year was 7.8% in the BES group and 7.0% in the SES group (p = 0.985; confidence interval, 1.011 [0.341-2.995]). In our randomized study, the treatment of iliac artery occlusive disease with self-expandable versus balloon-expandable stent was comparable in 12-month clinical outcomes without differences in the procedural success or geographic miss rate regardless of the deployment method in the distal aortoiliac occlusive lesion (ClinicalTrials.gov, NCT01834495).

Label-free detection of glutathione and glutathione disulfide in biological fluid by using an alpha-hederin nanopore.

Glutathione (GSH) is indispensable for maintaining redox homeostasis in biological fluids and serves as a key component in cellular defense mechanisms. Accurate assessment of GSH relative to its oxidized counterpart, glutathione disulfide (GSSG), is critical for the early diagnosis and understanding of conditions related to oxidative stress. Despite existing methods for their quantification, the label-free and simultaneous measurement of GSH and GSSG in biological fluid presents significant challenges. Herein, we report the use of an alpha-hederin (Ah) nanopore for the direct measurement of the GSH:GSSG ratio in simulated biological fluid, containing fetal bovine serum (FBS). This system hinges on detecting characteristic relative ion blockades (ΔI/Io) as GSH and GSSG molecules pass through the Ah nanopore under an applied electric field. The distinct current blockage signals derived from the translocation of GSH and GSSG enabled us to determine the molar ratio of GSH and its oxidized form. Notably, the interactions between the hydroxyl groups of the sugar moiety lining the nanopore's inner surface and the sulfhydryl group of GSH significantly influence the translocation dynamics, resulting in a longer translocation time for GSH compared to GSSG. The Ah nanopore technology proposed in this study offers a promising approach for real-time, single molecule-level monitoring of glutathione redox status in biological fluids, eliminating the need for labeling or extensive sample preparation.

An Effective Catholyte for Sulfide-Based All-Solid-State Batteries Utilizing Gas Absorbents.

All-solid-state batteries (ASSBs) possess the advantage of ensuring safety while simultaneously maximizing energy density, making them suitable for next-generation battery models. In particular, sulfide solid electrolytes (SSEs) are viewed as promising candidates for ASSB electrolytes due to their excellent ionic conductivity. However, a limitation exists in the form of interfacial side reactions occurring between the SSEs and cathode active materials (CAMs), as well as the generation of sulfide-based gases within the SSE. These issues lead to a reduction in the capacity of CAMs and an increase in internal resistance within the cell. To address these challenges, cathode composite materials incorporating zinc oxide (ZnO) are fabricated, effectively reducing various side reactions occurring in CAMs. Acting as a semiconductor, ZnO helps mitigate the rapid oxidation of the solid electrolyte facilitated by an electronic pathway, thereby minimizing side reactions, while maintaining electron pathways to the active material. Additionally, it absorbs sulfide-based gases, thus protecting the lithium ions within CAMs. In this study, the mass spectrometer is employed to observe gas generation phenomena within the ASSB cell. Furthermore, a clear elucidation of the side reactions occurring at the cathode and the causes of capacity reduction in ASSB are provided through density functional theory calculations.

Metabolic stress induces a double-positive feedback loop between AMPK and SQSTM1/p62 conferring dual activation of AMPK and NFE2L2/NRF2 to synergize antioxidant defense.

Co-occurring mutations in KEAP1 in STK11/LKB1-mutant NSCLC activate NFE2L2/NRF2 to compensate for the loss of STK11-AMPK activity during metabolic adaptation. Characterizing the regulatory crosstalk between the STK11-AMPK and KEAP1-NFE2L2 pathways during metabolic stress is crucial for understanding the implications of co-occurring mutations. Here, we found that metabolic stress increased the expression and phosphorylation of SQSTM1/p62, which is essential for the activation of NFE2L2 and AMPK, synergizing antioxidant defense and tumor growth. The SQSTM1-driven dual activation of NFE2L2 and AMPK was achieved by inducing macroautophagic/autophagic degradation of KEAP1 and facilitating the AXIN-STK11-AMPK complex formation on the lysosomal membrane, respectively. In contrast, the STK11-AMPK activity was also required for metabolic stress-induced expression and phosphorylation of SQSTM1, suggesting a double-positive feedback loop between AMPK and SQSTM1. Mechanistically, SQSTM1 expression was increased by the PPP2/PP2A-dependent dephosphorylation of TFEB and TFE3, which was induced by the lysosomal deacidification caused by low glucose metabolism and AMPK-dependent proton reduction. Furthermore, SQSTM1 phosphorylation was increased by MAP3K7/TAK1, which was activated by ROS and pH-dependent secretion of lysosomal Ca2+. Importantly, phosphorylation of SQSTM1 at S24 and S226 was critical for the activation of AMPK and NFE2L2. Notably, the effects caused by metabolic stress were abrogated by the protons provided by lactic acid. Collectively, our data reveal a novel double-positive feedback loop between AMPK and SQSTM1 leading to the dual activation of AMPK and NFE2L2, potentially explaining why co-occurring mutations in STK11 and KEAP1 happen and providing promising therapeutic strategies for lung cancer.Abbreviations: AMPK: AMP-activated protein kinase; BAF1: bafilomycin A1; ConA: concanamycin A; DOX: doxycycline; IP: immunoprecipitation; KEAP1: kelch like ECH associated protein 1; LN: low nutrient; MAP3K7/TAK1: mitogen-activated protein kinase kinase kinase 7; MCOLN1/TRPML1: mucolipin TRP cation channel 1; MEFs: mouse embryonic fibroblasts; MTORC1: mechanistic target of rapamycin kinase complex 1; NAC: N-acetylcysteine; NFE2L2/NRF2: NFE2 like bZIP transcription factor 2; NSCLC: non-small cell lung cancer; PRKAA/AMPKα: protein kinase AMP-activated catalytic subunit alpha; PPP2/PP2A: protein phosphatase 2; ROS: reactive oxygen species; PPP3/calcineurin: protein phosphatase 3; RPS6KB1/p70S6K: ribosomal protein S6 kinase B1; SQSTM1/p62: sequestosome 1; STK11/LKB1: serine/threonine kinase 11; TCL: total cell lysate; TFEB: transcription factor EB; TFE3: transcription factor binding to IGHM enhancer 3; V-ATPase: vacuolar-type H+-translocating ATPase.

Population pharmacokinetic modeling of sufentanil in adult Korean patients undergoing cardiopulmonary bypass surgery.

Sufentanil is frequently used as an anesthetic agent in cardiac surgery owing to its cardiovascular safety and favorable pharmacokinetics. However, the pharmacokinetics profiles of sufentanil in patients undergoing cardiopulmonary bypass (CPB) surgery remain less understood, which is crucial for achieving the desired level of anesthesia and mitigating surgical complications. Therefore, this study aimed to develop a population pharmacokinetic model of sufentanil in patients undergoing CPB surgery and elucidate the clinical factors affecting its pharmacokinetic profile. Adult patients who underwent cardiac surgery with CPB and were administered sufentanil for anesthesia were enrolled. Arterial blood samples were collected to quantify plasma concentrations of sufentanil and clinical laboratory parameters, including inflammatory cytokines. A population pharmacokinetic model was established using nonlinear mixed-effects modeling. Simulations were performed using the pharmacokinetic parameters of the final model. Overall, 20 patients were included in the final analysis. Sufentanil pharmacokinetics were modeled using a two-compartment model, accounting for CPB effects. Sufentanil clearance increased 2.80-fold during CPB and warming phases, while the central compartment volume increased 2.74-fold during CPB. CPB was a significant covariate affecting drug clearance and distribution volume. No other significant covariates were identified despite increased levels of the inflammatory cytokines, including IL-6, IL-8, and TNF-α during CPB. The simulation indicated a 30 µg loading dose and 40 µg/h maintenance infusion for target-controlled infusion. Additionally, a bolus dose of 60 µg was added at CPB initiation to adjust for exposure changes during this phase. Considering the target sufentanil concentrations, a uniform dosing regimen was acceptable for effective analgesia.

Digital technology revolutionizing mandibular fracture treatment: a comparative analysis of patient-specific plates and conventional titanium plates.

OBJECTIVES: The treatment of fractures prioritizes the restoration of functionality through the realignment of fractured segments. Conventional methods, such as titanium plates, have been employed for this purpose; however, certain limitations have been observed, leading to the development of patient-specific plates. Furthermore, recent advancements in digital technology in dentistry enable the creation of virtual models and simulations of surgical procedures. The aim was to assess the clinical effectiveness of patient-specific plates utilizing digital technology in treating mandibular fractures compared to conventional titanium plates. MATERIALS AND METHODS: Twenty patients diagnosed with mandibular fractures were included and randomly assigned to either the study or control groups. The surgical procedure comprised reduction and internal fixation utilizing patient-specific plates generated through virtual surgery planning with digital models for the study group, while the control group underwent the same procedure with conventional titanium plates. Assessment criteria included the presence of malunion, infection, sensory disturbance, subjective occlusal disturbance and occlusal force in functional maximum intercuspation (MICP). Statistical analysis involved using the Chi-square test and one-way repeated measures analysis of variance. RESULTS: All parameters showed no statistically significant differences between the study and control groups, except for the enhancement in occlusal force in functional MICP, where a statistically significant difference was observed (p = 0.000). CONCLUSION: Using patient-specific plates using digital technology has demonstrated clinical effectiveness in treating mandibular fractures, offering advantages of time efficiency and benefits for less experienced surgeons. CLINICAL RELEVANCE: Patient-specific plates combined with digital technology can be clinically effective in mandibular fracture treatment.

Safety and efficacy of selumetinib in pediatric and adult patients with neurofibromatosis type 1 and plexiform neurofibroma.

BACKGROUND: The MEK inhibitor, selumetinib, reduces plexiform neurofibroma (PN) in pediatric patients with neurofibromatosis type 1 (NF1). Its safety and efficacy in adults with PN and effectiveness in other NF1manifestations (e.g., neurocognitive function, growth reduction, and café-au-lait spots) are unknown. METHODS: This open-label, phase 2 trial enrolled 90 pediatric or adult NF1 patients with inoperable, symptomatic, or potentially morbid, measurable PN (≥ 3 cm). Selumetinib was administered at doses of 20 or 25 mg/m2 or 50 mg q 12 hrs for 2 years. Pharmacokinetics, PN volume, growth parameters, neurocognitive function, café-au-lait spots, and quality of life (QoL) were evaluated. RESULTS: Fifty-nine children and 30 adults (median age, 16 years; range, 3-47) received an average of 22±5 (4-26) cycles of selumetinib. Eighty-eight (98.9%) out of 89 per-protocol patients showed volume reduction in the target PN (median, 40.8%; 4.2%-92.2%), and 81 (91%) patients showed partial response (≥ 20% volume reduction). The response lasted until cycle 26. Scores of neurocognitive functions (verbal comprehension, perceptual reasoning, processing speed, and full-scale IQ) significantly improved in both pediatric and adult patients (P <0.05). Prepubertal patients showed increases in height score and growth velocity (P <0.05). Café-au-lait spot intensity decreased significantly (P <0.05). Improvements in QoL and pain scores were observed in both children and adults. All adverse events were CTCAE grade 1 or 2 and were successfully managed without drug discontinuation. CONCLUSION: Selumetinib decrease PN volume in the majority of pediatric and adult NF1 patients while also showing efficacy in non-malignant diverse NF1 manifestations.

CT Quantification of Interstitial Lung Abnormality and Interstitial Lung Disease: From Technical Challenges to Future Directions.

ABSTRACT: Interstitial lung disease (ILD) encompasses a variety of lung disorders with varying degrees of inflammation or fibrosis, requiring a combination of clinical, imaging, and pathologic data for evaluation. Imaging is essential for the noninvasive diagnosis of the disease, as well as for assessing disease severity, monitoring its progression, and evaluating treatment response. However, traditional visual assessments of ILD with computed tomography (CT) suffer from reader variability. Automated quantitative CT offers a more objective approach by using computer-based analysis to consistently evaluate and measure ILD. Advancements in technology have significantly improved the accuracy and reliability of these measurements. Recently, interstitial lung abnormalities (ILAs), which represent potential preclinical ILD incidentally found on CT scans and are characterized by abnormalities in over 5% of any lung zone, have gained attention and clinical importance. The challenge lies in the accurate and consistent identification of ILA, given that its definition relies on a subjective threshold, making quantitative tools crucial for precise ILA evaluation. This review highlights the state of CT quantification of ILD and ILA, addressing clinical and research disparities while emphasizing how machine learning or deep learning in quantitative imaging can improve diagnosis and management by providing more accurate assessments, and finally, suggests the future directions of quantitative CT in this area.

Association of changes in predicted body composition with subsequent risk of dementia.

OBJECTIVE: The effect of body composition change on the risk of dementia is not clear. This study analyzed the associations of changes in predicted lean body mass index (pLBMI), predicted appendicular skeletal muscle mass index (pASMI), and predicted body fat mass index (pBFMI) with the risk of dementia. METHODS: In this nationwide cohort study, data were obtained from the Korean National Health Insurance Service database. The exposure was defined as changes in pLBMI, pASMI, and pBFMI derived from validated prediction equations. The outcome was dementia, defined based on the dementia diagnosis with prescription of anti-dementia medication. Cox proportional hazards regression analyses were performed to obtain the hazard ratio with a 95% confidence interval for risk of dementia according to changes in predicted body composition. RESULTS: A total of 13,215,208 individuals with no prior record of dementia who underwent health screenings twice between 2009-2010 and 2011-2012 were included. A 1-kg/m2 increase in pLBMI and pASMI had an association with reduced risk of dementia (aHR: 0.85, 95% CI 0.84-0.87; aHR: 0.70, 95% CI 0.69-0.72, respectively for men, and aHR: 0.69, 95% CI 0.67-0.71; aHR: 0.59, 95% CI 0.57-0.61, respectively for women). A 1-kg/m2 increase in pBFMI had an association with a raised risk of dementia (aHR: 1.19, 95% CI 1.17-1.21 for men and aHR: 1.53, 95% CI 1.48-1.57 for women). These results remained consistent regardless of sex or weight change. INTERPRETATION: Increase in pLBMI or pASMI, or reduction in pBFMI was linked to lower risk of dementia.

Ferroelectric Stochasticity in 2D CuInP2S6 and Its Application for True Random Number Generator.

True random number generators (TRNGs), which create cryptographically secure random bitstreams, hold great promise in addressing security concerns regarding hardware, communication, and authentication in the Internet of Things (IoT) realm. Recently, TRNGs based on nanoscale materials have gained considerable attention for avoiding conventional and predictable hardware circuitry designs that can be vulnerable to machine learning (ML) attacks. In this article, a low-power and low-cost TRNG developed by exploiting stochastic ferroelectric polarization switching in 2D ferroelectric CuInP2S6 (CIPS)-based capacitive structures, is reported. The stochasticity arises from the probabilistic switching of independent electrical dipoles. The TRNG exhibits enhanced stochastic variability with near-ideal entropy, uniformity, uniqueness, Hamming distance, and independence from autocorrelation variations. Its unclonability is systematically examined using device-to-device variations. The generated cryptographic bitstreams pass the National Institute of Standards and Technology (NIST) randomness tests. This nanoscale CIPS-based TRNG is circuit-integrable and exhibits potential for hardware security in edge devices with advanced data encryption.

Risk of pulmonary embolism and deep vein thrombosis following COVID-19: a nationwide cohort study.

Recent studies elucidate that coronavirus disease 2019 (COVID-19) patients may face a higher risk of cardiovascular complications. This study aimed to evaluate association of COVID-19 with the risk of pulmonary embolism (PE) or deep vein thrombosis (DVT). This nationwide population-based retrospective cohort study included Korean adult citizens between January 2021 and March 2022 from the Korea Disease Control and Prevention Agency COVID-19 National Health Insurance Service cohort. The Fine and Gray's regression with all-cause death as a competing event was adopted to evaluate PE and DVT risks after COVID-19. This study included a total of 1,601,835 COVID-19 patients and 14,011,285 matched individuals without COVID-19. The risk of PE (adjusted hazard ratio [aHR], 6.25; 95% confidence interval [CI], 3.67-10.66; p < 0.001) and DVT (aHR, 3.05; 95% CI, 1.75-5.29; p < 0.001) was higher in COVID-19 group in individuals without complete COVID-19 vaccination. In addition, individuals with complete COVID-19 vaccination still had a higher risk of COVID-19-related PE (aHR, 1.48; 95% CI, 1.15-1.88; p < 0.001). However, COVID-19 was not a significant risk factor for DVT among those with complete COVID-19 vaccination. COVID-19 was identified as an independent factor that elevated PE and DVT risks, especially for individuals without complete COVID-19 vaccination.

Evaluation of Gamma Aminobutyric Acid and Sodium Butyrate in Juvenile Red Seabream (Pagrus major) Diets Containing Graded Levels of Fish Meal and Soy Protein Concentrate.

The experiment was conducted to evaluate the supplementary effects of gamma aminobutyric acid (GABA) and sodium butyrate (SB) when a graded level of fish meal (FM) was replaced with soy protein concentrate (SPC) in diets for juvenile red seabream (Pagrus major). A control diet was designed to contain 60% FM (F60). Two other diets were formulated by reducing FM levels to 40% and 20% with SPC (F40 and F20). Six more diets were formulated by adding 0.02% GABA or 0.2% SB to each F60, F40 and F20 diets (F60G, F60S, F40G, F40S, F20G and F20S). Each diet was randomly assigned to a triplicate group of fish (5.52 g/fish) and provided for eight weeks. Final body weight, weight gain and specific growth rate of fish fed F60G, F60S, F40G and F40S diets were comparable and significantly higher (p < 0.05) than other groups. The growth of fish fed SB-containing diets was significantly increased (p < 0.05) compared to fish fed the respective control diets. The feed efficiency and protein efficiency ratios were significantly higher (p < 0.05) in the fish fed all diets containing 60% and 40% FM compared to F20 and F20G groups. The F40S diet resulted in the highest feed utilization values. The F20S group exhibited significantly higher (p < 0.05) feed utilization than the F20 and F20G groups. Serum lysozyme activity was significantly higher (p < 0.05) in fish fed the GABA- and SB-containing diets compared to the F20 group. The F60S group exhibited the highest lysozyme activity which was significantly higher (p < 0.05) than in the F20 and F40 groups. Therefore, the growth performance, feed utilization and innate immunity of red seabream can be enhanced by dietary supplementation with GABA or SB in low-FM diets containing SPC. The FM level in the juvenile red seabream diet can be reduced to 40% with SPC and GABA or SB while maintaining performance better than a diet containing 60% FM.

Lactitol Alleviates Loperamide-Induced Constipation in Sprague Dawley Rats by Regulating Serotonin, Short-Chain Fatty Acids, and Gut Microbiota.

The objective of this study was to examine the impact of lactitol on constipation caused by loperamide in Sprague Dawley rats, with a particular emphasis on its underlying mechanisms and potential health advantages. The lactitol effectively improved fecal parameters, intestinal tissue structure, and the expression of constipation-related gene expression and proteins. Lactitol alleviated fecal weight and water content altered by loperamide and enhanced gastrointestinal transit. The administration also restored mucosal and muscular layer thickness. Mechanistically, lactitol upregulated the mRNA expression and/or protein levels of mucins (MUC2 and MUC4), occludin, claudin-1, and zonula occludens, indicating improved intestinal barrier function. Lactitol positively regulated the composition of cecal microbiota, leading to an increased relative abundance of Bifidobacterium, Lactobacillus, and Romboutsia. Conversely, lactitol decreased the relative abundance of Prevotella, Aerococcus, Muribaculum, Blautia, and Ruminococcus. This study demonstrated the potential of lactitol to relieve constipation by modulating the gut microbiota. These findings suggest that lactitol is an alternative to traditional laxatives and has potential as a health-promoting food sweetener.

High gain quasi-omnidirectional dipole array fed by radial power divider for millimeter-wave IoT sensing.

This article presents the design and implementation of a dipole array antenna based on a radial waveguide power divider for millimeter-wave IoT sensing applications. The dipole array and radial waveguide power divider techniques are used in tandem to achieve high gain with omnidirectional radiation properties. The proposed antenna is comprised of eight non-uniform array dipole structures, a circular radiating loop, and shorting vias. The one-to-eight power divider is created with the shorting vias to feed the circularly arranged eight non-uniform dipole arrays simultaneously. The proposed antenna is simulated and manufactured on Rogers-RO3003C substrate with a thickness of 8 mils. Both simulated and tested results confirm that the proposed method enables the antenna to offer a quasi-omnidirectional pattern with a high peak gain of 5.42 dBi. The antenna offers an impedance bandwidth (S11 < ‒ 10 dB) of more than 1 GHz ranging from 27.93 to 29.13 GHz. Moreover, by optimizing the parameters of the power divider network the proposed antenna can be tuned between a wide bandwidth range of 14.53 GHz as the designed dipole array offering the operating bandwidth from 25.56 to 40.09 GHz. Due to its comprehensive set of performance attributes, particularly for the quasi-omnidirectional radiation characteristics, the presented antenna is a viable candidate for the 5G millimeter wave wireless IoT sensing applications. Additionally, this work will accommodate other researchers to explore the proposed method for developing high-gain omnidirectional antennas for millimeter-wave applications.

Comparison of biportal endoscopic and microscopic tubular paraspinal approach for foraminal and extraforaminal lumbar disc herniation.

OBJECTIVE: Foraminal and extraforaminal lumbar disc herniation (FELDH) is an important pathological condition that can lead to lumbar radiculopathy. The paraspinal muscle-splitting approach introduced by Reulen and Wiltse is a reasonable surgical technique. Minimally invasive procedures using a tubular retractor system have also been introduced. However, surgical treatment is considered more challenging for FELDH than for central or subarticular lumbar disc herniations (LDHs). Some researchers have proposed uniportal extraforaminal endoscopic lumbar discectomy through a posterolateral approach as an alternative for FELDH, but heterogeneous clinical results have been reported. Recently, the biportal endoscopic (BE) paraspinal approach has been suggested as an alternative. The aim of this study was to compare the clinical outcomes of BE and microscopic tubular (MT) paraspinal approaches for decompressive foraminotomy and lumbar discectomy (paraLD) in patients with FELDH. METHODS: Ninety-one consecutive patients with unilateral lumbar radiculopathy and FELDH underwent paraLD. Demographic and perioperative data were collected. Clinical outcomes were evaluated using the visual analog scale (VAS) for back and leg pain, the Oswestry Disability Index (ODI) for spinal disability, and the modified Macnab criteria for patient satisfaction. Postoperative complications and reoperation rates were also evaluated. RESULTS: In total, 76 patients were included in the final analysis. Among them, 43 underwent BE paraLD (group A) and the remaining 33 underwent MT paraLD (group B). The demographic and preoperative data were not statistically different between the groups. All patients showed significant improvements in VAS back, VAS leg, and ODI scores compared with baseline values (p < 0.05). The improvement in VAS back scores was significantly better in group A than in group B on postoperative day 2 (p < 0.001). However, all clinical parameters were comparable between the two groups after postoperative year 1 (p > 0.05). According to the modified Macnab criteria, 86.1% and 72.7% of the patients had excellent or good outcomes in groups A and B, respectively. No intergroup differences were observed (p = 0.367). In addition, there were no differences in the total operation time or amount of surgical drainage. Postoperative complications were not significantly different between the two groups (p = 0.301); however, reoperation rates were significantly higher in group B (p = 0.035). CONCLUSIONS: BE paraLD is an effective treatment for FELDH and is an alternative to MT paraLD. In particular, BE paraLD has advantages of early improvement in postoperative back pain and low reoperation rates.

Chronic rapid eye movement sleep deprivation aggravates the pathogenesis of Alzheimer's disease by decreasing brain O-GlcNAc cycling in mice.

This study investigated the role of O-GlcNAc cycling in Alzheimer's disease-related changes in brain pathophysiology induced by chronic REM sleep deprivation (CSD) in mice. CSD increased amyloid beta (Aß) and p-Tau accumulation and impaired learning and memory (L/M) function. CSD decreased dendritic length and spine density. CSD also increased the intensity of postsynaptic density protein-95 (PSD-95) staining. All of these Alzheimer's disease (AD) pathogenic changes were effectively reversed through glucosamine (GlcN) treatment by enhancing O-GlcNAcylation. Interestingly, the lelvel of O-GlcNAcylated-Tau (O-Tau) exhibited an opposite trend compared to p-Tau, as it was elevated by CSD and suppressed by GlcN treatment. CSD increased neuroinflammation, as indicated by elevated levels of glial fibrillary acidic protein and IBA-1-positive glial cells in the brain, which were suppressed by GlcN treatment. CSD promoted the phosphorylation of GSK3ß and led to an upregulation in the expression of endoplasmic reticulum (ER) stress regulatory proteins and genes. These alterations were effectively suppressed by GlcN treatment. Minocycline not only suppressed neuroinflammation induced by CSD, but it also rescued the decrease in O-GlcNAc levels caused by CSD. Minocycline also reduced AD neuropathy without affecting CSD-induced ER stress. Notably, overexpressing O-GlcNAc transferase in the dentate gyrus region of the mouse brain rescued CSD-induced cognitive dysfunction, neuropathy, neuroinflammation, and ER stress responses. Collectively, our findings reveal that dysregulation of O-GlcNAc cycling underlies CSD-induced AD pathology and demonstrate that restoration of OGlcNAcylation protects against CSD-induced neurodegeneration.

Threshold of somatic mosaicism leading to brain dysfunction with focal epilepsy.

Somatic mosaicism in a fraction of brain cells causes neurodevelopmental disorders, including childhood intractable epilepsy. However, the threshold for somatic mosaicism leading to brain dysfunction is unknown. In this study, we induced various mosaic burdens in focal cortical dysplasia type II (FCD II) mice, featuring mTOR somatic mosaicism and spontaneous behavioral seizures. The mosaic burdens ranged from approximately 1,000 to 40,000 neurons expressing the mTOR mutant in the somatosensory (SSC) or medial prefrontal (PFC) cortex. Surprisingly, approximately 8,000 to 9,000 neurons expressing the MTOR mutant, which are extrapolated to constitute 0.08-0.09% of total cells or roughly 0.04% of variant allele frequency (VAF) in the mouse hemicortex, were sufficient to trigger epileptic seizures. The mutational burden was correlated with seizure frequency and onset, with a higher tendency for electrographic inter-ictal spikes and beta- and gamma-frequency oscillations in FCD II mice exceeding the threshold. Moreover, mutation-negative FCD II patients in deep sequencing of their bulky brain tissues revealed somatic mosaicism of the mTOR pathway genes as low as 0.07% in resected brain tissues through ultra-deep targeted sequencing (up to 20 million reads). Thus, our study suggests that extremely low levels of somatic mosaicism can contribute to brain dysfunction.

Assessment of Treatment Response in Patients With Severe Asthma Using Visual and Quantitative Analysis of Chest CT.

OBJECTIVE: To evaluate the role of visual and quantitative chest CT parameters in assessing treatment response in patients with severe asthma. MATERIALS AND METHODS: Korean participants enrolled in a prospective multicenter study, named the Precision Medicine Intervention in Severe Asthma study, from May 2020 to August 2021, underwent baseline and follow-up chest CT scans (inspiration/expiration) 10-12 months apart, before and after biologic treatment. Two radiologists scored bronchiectasis severity and mucus plugging extent. Quantitative parameters were obtained from each CT scan as follows: normal lung area (normal), air trapping without emphysema (AT without emph), air trapping with emphysema (AT with emph), and airway (total branch count, Pi10). Clinical parameters, including pulmonary function tests (forced expiratory volume in 1 s [FEV1] and FEV1/forced vital capacity [FVC]), sputum and blood eosinophil count, were assessed at initial and follow-up stages. Changes in CT parameters were correlated with changes in clinical parameters using Pearson or Spearman correlation. RESULTS: Thirty-four participants (female:male, 20:14; median age, 50.5 years) diagnosed with severe asthma from three centers were included. Changes in the bronchiectasis and mucus plugging extent scores were negatively correlated with changes in FEV1 and FEV1/FVC (ρ = from -0.544 to -0.368, all P < 0.05). Changes in quantitative CT parameters were correlated with changes in FEV1 (normal, r = 0.373 [P = 0.030], AT without emph, r = -0.351 [P = 0.042]), FEV1/FVC (normal, r = 0.390 [P = 0.022], AT without emph, r = -0.370 [P = 0.031]). Changes in total branch count were positively correlated with changes in FEV1 (r = 0.349 [P = 0.043]). There was no correlation between changes in Pi10 and the clinical parameters (P > 0.05). CONCLUSION: Visual and quantitative CT parameters of normal, AT without emph, and total branch count may be effective for evaluating treatment response in patients with severe asthma.