Effect of biologic therapies on quality of life in severe asthma: Findings from the PRISM study.

Background: Anti-type 2 (T2) biologic therapies (biologics) improve exacerbation rates, lung function, and asthma-related quality of life (QoL) in patients with severe T2 asthma. However, studies comparing different biologics are lacking. We evaluated the QoL in patients with severe asthma comprehensively and compare the efficacy of different T2-directed biologics using QoL questionnaires. Methods: We compared the QoL between severe and mild-to-moderate asthma and between severe asthma with and without biologics treatment. Data of mild-to-moderate were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea, and data of severe asthma were collected from the Precision Medicine Intervention in Severe Asthma. We included 183 patients with severe asthma treated with T2 biologics or conventional therapy between April 2020 and May 2021 and assessed QoL of them using the Questionnaire for Adult Korean Asthmatics (QLQAKA), Severe Asthma Questionnaire (SAQ), and EuroQoL-5Dimensions (EQ-5D) at baseline and 6 months. Results: The EQ-5D index (0.803) of severe asthma was lower than that of other chronic diseases representing a worse QoL. The scores for all questions of QLQAKA, except "cough," were lower (less control) in the severe asthma group than in the mild-to-moderate asthma group at baseline and 6 months (P < 0.05). The total scores and subscores of all domains of the QLQAKA, SAQ, and EQ-5D improved significantly 6 months after biologic therapy but not after conventional therapy. The total QLQAKA, SAQ, and EQ-5D scores improved after 6 months in the anti-IL-5 (P < 0.05) and anti-IL-4/IL-13 (P < 0.05) treatment groups with no significant difference between groups (P > 0.05). Conclusion: QoL was worse in severe asthma than in mild-to-moderate asthma and other chronic diseases. T2 biologics equally improved QoL in patients with severe asthma.

Laser-responsive erastin-loaded chondroitin sulfate nanomedicine targeting CD44 and system xc- in liver cancer: A non-ferroptotic approach.

Erastin, a ferroptosis-inducing system xc- inhibitor, faces clinical challenges due to suboptimal physicochemical and pharmacokinetic properties, as well as relatively low potency and off-target toxicity. Addressing these, we developed ECINs, a novel laser-responsive erastin-loaded nanomedicine utilizing indocyanine green (ICG)-grafted chondroitin sulfate A (CSA) derivatives. Our aim was to improve erastin's tumor targeting via CSA-CD44 interactions and enhance its antitumor efficacy through ICG's photothermal and photodynamic effects in the laser-on state while minimizing off-target effects in the laser-off state. ECINs, with their nanoscale size of 186.7 ± 1.1 nm and high erastin encapsulation efficiency of 93.0 ± 0.8%, showed excellent colloidal stability and sustained drug release up to 120 h. In vitro, ECINs demonstrated a mechanism of cancer cell inhibition via G1-phase cell cycle arrest, indicating a non-ferroptotic action. In vivo biodistribution studies in SK-HEP-1 xenograft mice revealed that ECINs significantly enhanced tumor distribution of erastin (1.9-fold greater than free erastin) while substantially reducing off-target accumulation in the lungs and spleen by 203-fold and 19.1-fold, respectively. Combined with laser irradiation, ECINs significantly decreased tumor size (2.6-fold, compared to free erastin; 2.4-fold, compared to ECINs without laser irradiation) with minimal systemic toxicity. This study highlights ECINs as a dual-modality approach for liver cancer treatment, demonstrating significant efficacy against tumors overexpressing CD44 and system xc-.

The prognostic value of lymphovascular invasion for stage I lung adenocarcinoma based on the presence of ground-glass opacity.

OBJECTIVES: There is still a debate regarding the prognostic implication of lymphovascular invasion (LVI) in stage I lung adenocarcinoma. Ground-glass opacity (GGO) on CT is known to correlate with a less invasive or lepidic component in adenocarcinoma, which may influence the strength of prognostic factors. This study aimed to explore the prognostic value of LVI in stage I lung adenocarcinoma based on the presence of GGO. MATERIALS AND METHODS: Stage I lung adenocarcinoma patients receiving lobectomy between 2010 and 2019 were retrospectively categorized as GGO-positive or GGO-negative (solid adenocarcinoma) on CT. Multivariable Cox regression analyses were performed for disease-free survival (DFS) and overall survival (OS) to evaluate the prognostic significance of pathologic LVI based on the presence of GGO. RESULTS: Of 924 patients included (mean age, 62.5 ± 9.2 years; 505 women), 525 (56.8%) exhibited GGO-positive adenocarcinoma and 116 (12.6%) were diagnosed with LVI. LVI was significantly more frequent in solid than GGO-positive adenocarcinoma (20.1% vs. 6.9%, p < 0.001). Multivariable analysis identified LVI and visceral pleural invasion (VPI) as significant prognostic factors for shorter DFS among solid adenocarcinoma patients (LVI, hazard ratio (HR): 1.89, p = 0.004; VPI, HR: 1.65, p = 0.003) but not GGO-positive patients (p = 0.76 and p = 0.87). In contrast, LVI was not a significant prognostic factor for OS in either group (p > 0.05). CONCLUSION: In stage I lung adenocarcinoma, pathologic LVI was associated with DFS only in patients with solid lung adenocarcinoma. CLINICAL RELEVANCE STATEMENT: Lymphovascular invasion (LVI) significantly affects disease-free survival in solid-stage I lung adenocarcinoma patients, but not those with ground-glass opacity (GGO) adenocarcinoma. Risk stratification considering both GGO on CT and LVI may identify patients benefiting from increased surveillance. KEY POINTS: The presence of ground-glass opacity portends different prognoses for lung adenocarcinoma. In stage I lung adenocarcinoma, lymphovascular invasion (LVI) was significantly more frequent in solid adenocarcinomas than in ground-glass opacity (GGO)-positive adenocarcinomas. LVI was not associated with overall survival in patients with either solid adenocarcinomas or GGO adenocarcinomas.

Hybrid CMOS-Memristor synapse circuits for implementing Ca ion-based plasticity model.

Neuromorphic computing research is being actively pursued to address the challenges posed by the need for energy-efficient processing of big data. One of the promising approaches to tackle the challenges is the hardware implementation of spiking neural networks (SNNs) with bio-plausible learning rules. Numerous research works have been done to implement the SNN hardware with different synaptic plasticity rules to emulate human brain operations. While a standard spike-timing-dependent-plasticity (STDP) rule is emulated in many SNN hardware, the various STDP rules found in the biological brain have rarely been implemented in hardware. This study proposes a CMOS-memristor hybrid synapse circuit for the hardware implementation of a Ca ion-based plasticity model to emulate the various STDP curves. The memristor was adopted as a memory device in the CMOS synapse circuit because memristors have been identified as promising candidates for analog non-volatile memory devices in terms of energy efficiency and scalability. The circuit design was divided into four sub-blocks based on biological behavior, exploiting the non-volatile and analog state properties of memristors. The circuit was designed to vary weights using an H-bridge circuit structure and PWM modulation. The various STDP curves have been emulated in one CMOS-memristor hybrid circuit, and furthermore a simple neural network operation was demonstrated for associative learning such as Pavlovian conditioning. The proposed circuit is expected to facilitate large-scale operations for neuromorphic computing through its scale-up.

Medication burden reduction and early clinical benefit through aripiprazole once monthly in schizophrenia patients with polypharmacy.

Antipsychotic polypharmacy is commonly used in clinical settings, with a growing trend in using long-acting injections to mitigate many side effects of polypharmacy. A previous study demonstrated that long-acting aripiprazole once-monthly (AOM) injection increased treatment adherence, restored functionality, and improved symptoms. However, there is insufficient evidence to demonstrate the therapeutic effects of AOM in polypharmacy practice. This observational study aimed to investigate the real-world clinical benefits and effectiveness of AOM by assessing changes in drug dosage, the number of drugs, clinical functioning, psychotic symptoms, and the duration of drug efficacy. Study participants were recruited from eight study sites, with the baseline visit marking the initiation of drug treatment. Clinical and demographic data were collected from medical records at screening, baseline, and months 1, 3, 6, 9, and 12. Over 12 months, we analyzed changes in drug dosage, the number of drugs, and scores of the Positive and Negative Syndrome Scale-6 (PANSS-6), Global Assessment of Functioning (GAF), and Clinical Global Impression-Severity (CGIS). Data from 139 participants were analyzed. Total 12-month antipsychotic doses calculated in chlorpromazine equivalents (CPE) were reduced by 32.6%. A comparison of total monthly antipsychotic doses in CPE between the first and last months showed a 24.6% reduction in the dose. Additionally, the quantity of benzodiazepine tablets/capsules, total benzodiazepine doses calculated in lorazepam equivalents, and quantity of tablets/capsules of mood stabilizers, anticholinergics, and beta blockers were significantly reduced. GAF scores increased by 14.1% over 12 months, and PANSS-6 total scores reduced by 17.3% over 12 months, with significant differences observed from month 1 and baseline, respectively. The scores steadily improved until month 9 compared to those of the previous months, continuing to improve through month 12. The CGI-S score reduced by 14.3% over 12 months, showing a significant decrease from month 1 and a steady improvement until month 6, maintaining this improvement until month 12. In conclusion, this study demonstrated the early effectiveness of AOM in treating Korean patients with schizophrenia on polypharmacy. AOM improved function and clinical symptoms in patients with schizophrenia from treatment onset and caused a decrease in the quantity and dosage of drugs taken by the patients.

Radiological and clinical outcomes after Attune primary total knee arthroplasty using Stemmable Tibia: A two-year follow-up prospective bi-center study.

This prospective bi-center study aimed to analyze the outcomes of primary total knee arthroplasty using the Stemmable Tibia Attune system. A total of 100 patients who underwent primary total knee arthroplasty with Stemmable Tibia from January 2019 to December 2021 were enrolled in the study. Radiological outcomes (hip-knee-ankle axis and medial proximal tibial angle) were assessed preoperatively and postoperatively. Clinical outcomes (visual analog scale score, Hospital for Special Surgery score, Knee Society function score, Knee Society knee score, flexion contracture, further flexion, and range of motion) were analyzed preoperatively and at 6 weeks, 3 months, 6 months, 1 year, and 2 years postoperatively. Complications (periprosthetic joint infection and aseptic loosening) were examined. The hip-knee-ankle axis decreased (preoperative: 9.5° ± 6.3°, postoperative: 1.1° ± 2.7°), whereas the medial proximal tibial angle increased (preoperative: 84.6° ± 4.1°, postoperative: 89.8° ± 1.9°). The visual analog scale score, Hospital for Special Surgery score, Knee Society knee score, and Knee Society function score increased postoperatively. The Knee Society knee score indicated above good outcomes (100.0% and 99.0% at 1 and 2 years postoperatively, respectively). The Knee Society function score also showed above good results (98.0% and 93.0% at 1 and 2 years postoperatively, respectively). The range of motion significantly improved (p < 0.001): flexion contracture decreased from 9.10° ± 7.23° to 2.15° ± 2.87°, whereas further flexion increased from 136.05° ± 14.78° to 139.80° ± 10.02°. One patient developed periprosthetic joint infection; no early loosening was observed. In conclusion, Attune primary total knee arthroplasty with Stemmable Tibia not only is safe and effective but also leads to radiological and clinical improvements.

Photobleaching-mediated charge-convertible cyclodextrin nanoparticles achieve deep tumour penetration for rectal cancer theranostics.

Although charge-converting nanoparticles (NPs) potentially penetrate tumours deeply, conventional charge conversion strategies possess limitations, including low selectivity and slow, inconsistent conversion rate within the tumour microenvironment. In this study, we synthesized a zwitterionic near-infrared cyclodextrin derivative of heptamethine cyanine and complexed it with pheophorbide-conjugated ferrocene to produce multifunctional theranostic nanotherapeutics. Our NPs demonstrated enhanced tumour-targeting ability, enabling the highly specific imaging of rectal tumours, with tumour-to-rectum signal ratios reaching up to 7.8. The zwitterionic surface charge of the NPs was rapidly converted to a cationic charge within the tumours on 880 nm near-infrared laser irradiation, promoting the tumoural penetration of NPs via transcytosis. After penetration, photodynamic/chemodynamic therapy was initiated using a 660 nm laser. Our NPs eradicated clinically relevant-sized heterotopic tumours (~250 mm3) and orthotopic rectal tumours, displaying their potential as theranostic nanoplatforms for targeting rectal cancer.

Allergy Wheal and Erythema Segmentation Using Attention U-Net.

The skin prick test (SPT) is a key tool for identifying sensitized allergens associated with immunoglobulin E-mediated allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, urticaria, angioedema, and anaphylaxis. However, the SPT is labor-intensive and time-consuming due to the necessity of measuring the sizes of the erythema and wheals induced by allergens on the skin. In this study, we used an image preprocessing method and a deep learning model to segment wheals and erythema in SPT images captured by a smartphone camera. Subsequently, we assessed the deep learning model's performance by comparing the results with ground-truth data. Using contrast-limited adaptive histogram equalization (CLAHE), an image preprocessing technique designed to enhance image contrast, we augmented the chromatic contrast in 46 SPT images from 33 participants. We established a deep learning model for wheal and erythema segmentation using 144 and 150 training datasets, respectively. The wheal segmentation model achieved an accuracy of 0.9985, a sensitivity of 0.5621, a specificity of 0.9995, and a Dice similarity coefficient of 0.7079, whereas the erythema segmentation model achieved an accuracy of 0.9660, a sensitivity of 0.5787, a specificity of 0.97977, and a Dice similarity coefficient of 0.6636. The use of image preprocessing and deep learning technology in SPT is expected to have a significant positive impact on medical practice by ensuring the accurate segmentation of wheals and erythema, producing consistent evaluation results, and simplifying diagnostic processes.

Subcritical Water Extraction of Undaria pinnatifida: Comparative Study of the Chemical Properties and Biological Activities across Different Parts.

The subcritical water extraction of Undaria pinnatifida (blade, sporophyll, and root) was evaluated to determine its chemical properties and biological activities. The extraction was conducted at 180 °C and 3 MPa. Root extracts exhibited the highest phenolic content (43.32 ± 0.19 mg phloroglucinol/g) and flavonoid content (31.54 ± 1.63 mg quercetin/g). Sporophyll extracts had the highest total sugar, reducing sugar, and protein content, with 97.35 ± 4.23 mg glucose/g, 56.44 ± 3.10 mg glucose/g, and 84.93 ± 2.82 mg bovine serum albumin (BSA)/g, respectively. The sporophyll contained the highest fucose (41.99%) and mannose (10.37%), whereas the blade had the highest galactose (48.57%) and glucose (17.27%) content. Sporophyll had the highest sulfate content (7.76%). Key compounds included sorbitol, glycerol, L-fucose, and palmitic acid. Root extracts contained the highest antioxidant activity, with IC50 values of 1.51 mg/mL (DPPH), 3.31 mg/mL (ABTS+), and 2.23 mg/mL (FRAP). The root extract exhibited significant α-glucosidase inhibitory activity with an IC50 of 5.07 mg/mL, indicating strong antidiabetic potential. The blade extract showed notable antihypertensive activity with an IC50 of 0.62 mg/mL. Hence, subcritical water extraction to obtain bioactive compounds from U. pinnatifida, supporting their use in functional foods, cosmetics, and pharmaceuticals is highlighted. This study uniquely demonstrates the variation in bioactive compound composition and bioactivities across different parts of U. pinnatifida, providing deeper insights. Significant correlations between chemical properties and biological activities emphasize the use of U. pinnatifida extracts for chronic conditions.

Lipids Extracted from Aptocyclus ventricosus Eggs Possess Immunoregulatory Effects on RAW264.7 Cells by Activating the MAPK and NF-κB Signaling Pathways.

This study was conducted to evaluate the potential anti-inflammatory and immune-enhancement properties of lipids derived from Aptocyclus ventricosus eggs on RAW264.7 cells. Firstly, we determined the fatty acid compositions of A. ventricosus lipids by performing gas chromatography analysis. The results showed that A. ventricosus lipids contained saturated fatty acids (24.37%), monounsaturated fatty acids (20.90%), and polyunsaturated fatty acids (54.73%). They also contained notably high levels of DHA (25.91%) and EPA (22.05%) among the total fatty acids. Our results for the immune-associated biomarkers showed that A. ventricosus lipids had immune-enhancing effects on RAW264.7 cells. At the maximum dose of 300 µg/mL, A. ventricosus lipids generated NO (119.53%) and showed greater phagocytosis (63.69%) ability as compared with untreated cells. A. ventricosus lipids also upregulated the expression of iNOS, IL-1ß, IL-6, and TNF-α genes and effectively upregulated the phosphorylation of MAPK (JNK, p38, and ERK) and NF-κB p65, indicating that these lipids could activate the MAPK and NF-κB pathways to stimulate macrophages in the immune system. Besides their immune-enhancing abilities, A. ventricosus lipids significantly inhibited LPS-induced RAW264.7 inflammatory responses via the NF-κB and MAPK pathways. The results indicated that these lipids significantly reduced LPS-induced NO production, showing a decrease from 86.95% to 38.89%. Additionally, these lipids downregulated the expression of genes associated with the immune response and strongly suppressed the CD86 molecule on the cell surface, which reduced from 39.25% to 33.80%. Collectively, these findings imply that lipids extracted from A. ventricosus eggs might have biological immunoregulatory effects. Thus, they might be considered promising immunomodulatory drugs and functional foods.

Can Pre-Transplant Psychometric Testing Predict Tacrolimus Intrapatient Variability After Living Kidney Transplantation?

OBJECTIVE: Tacrolimus intrapatient variability (Tac IPV) has been considered a marker for post-graft risk. We investigated pre-transplant psychometric testing to predict Tac IPV after living kidney transplantation. METHODS: Minnesota Multiphasic Personality Inventory-2 (MMPI-2) examined during pre-transplant evaluation by 102 recipients were analyzed. Subjects were divided into two groups, low IPV (L-IPV) and high IPV (H-IPV), by cutoffs of Tac IPV: median of 24 and value of 30. T-scores of MMPI-2 scales were used to analyze difference between L-IPV and H-IPV using independent t-tests. Stepwise multiple logistic regression was used to test whether MMPI-2 scales affected Tac IPV. Confusion matrix of logistic regression was used to explain statistical power. Cutoff values of significant scales for H-IPV were analyzed by constructing receiver operating characteristic curves. RESULTS: Hysteria (Hy) and depression (D) scale scores and Tac IPV were associated in IPV 24 (odds ratio [OR]: 1.08, p<0.01 for Hy; OR: 0.93, p<0.01 for D) and IPV 30 models (OR: 1.09, p<0.01 for Hy; OR: 0.92, p<0.01 for D). Paranoia (Pa) scale scores were associated with Tac IPV in IPV 24 model (OR=1.10, p<0.01) and were significantly higher in H-IPV 24 (p<0.01). F1 scores of confusion matrix in IPV 24 and 30 models were 0.70 and 0.71, respectively. Cutoffs of Hy, D, and Pa scales were 51, 57, and 47, respectively. CONCLUSION: MMPI-2 profile is suggested as a predictor for high Tac IPV after living kidney transplantation.

Causal inference analysis of the radiologic progression in the chronic obstructive pulmonary disease.

There is limited evidence regarding the causal inference of emphysema and functional small airway disease in the subsequent progression of chronic obstructive pulmonary disease (COPD). Patients consisting of two independent cohorts diagnosed with COPD and underwent two serial chest CT scans were included. Total percent emphysema (PRMEmph) and fSAD (PRMfSAD) was quantified via PRM. To investigate the progression of emphysema, we divided COPD patients with PRMEmph < 10% into low and high PRMfSADgroup, matched with similar baseline characteristics, and conducted nonparametric hypothesis tests based on randomization inference using Wilcoxon signed rank test and Huber's M statistics. In patients with baseline PRMEmph < 10%, there were 26 and 16 patients in the low PRMfSA group and 52 and 64 patients in the high PRMfSA in the derivation and validation cohorts, respectively. In the both low and high PRMfSAD groups, there were 0.11 and 1.43 percentage point increases (Huber's M statistic p = 0.016) and 0.58 and 2.09 percentage point increases (p = 0.038) in the proportion of emphysema in the derivation and validation cohorts, respectively. On the contrary, among patients with baseline PRMfSAD < 20%, there was no significant differences in the interval changes of PRMfSAD between the low and high PRMEmph groups in both cohorts. In COPD patients with low emphysema, group with baseline high PRMfSAD showed greater change of PRMEmph than those with low PRMfSAD in both the derivation and validation cohorts. Imaging-based longitudinal quantitative analysis may provide important evidence that small airway disease precedes emphysema in CT-based early COPD patients.

Development of a Standardized Suicide Prevention Program for Gatekeeper Intervention in Korea (Suicide CARE Version 2.0) to Prevent Adolescent Suicide: Version for Teachers.

OBJECTIVE: The increasing concern over adolescent suicide necessitates suicide prevention training for school teachers, as students spend a significant portion of their time at school. This study's objective is to develop a suicide prevention program tailored for teachers. METHODS: The program was developed by a multidisciplinary research team, drawing on a review of both domestic and international suicide prevention programs, related scholarly articles, and Korean psychological autopsy interviews of adolescents. This was complemented by a survey of teachers to assess the program's practicality and usability. RESULTS: The developed program comprises three parts, consistent with other versions: Careful Observation, Active Listening, and Risk Evaluation and Expert Referral. Careful Observation focuses on training teachers to recognize verbal, behavioral, and situational warning signs of suicidal ideation in students; Active Listening involves strategies for encouraging students to express their suicidal thoughts and techniques for being an empathetic and attentive listener; Risk Evaluation and Expert Referral provides instruction on how to assess suicide risk and assist students safely. CONCLUSION: It is anticipated that this program will equip teachers with valuable knowledge and skills, contributing to a reduction in adolescents suicide rates.

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.

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.

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.

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.

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.