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Objective: To compare the real‐world effectiveness and tolerability of calcitonin gene‐related peptide (CGRP) monoclonal antibodies (mAbs) and onabotulinumtoxinA in chronic migraine (CM) patients. Methods: This multicenter study involved retrospective analysis of prospectively collected data of CM patients treated with CGRP mAbs or onabotulinumtoxinA, including difficult‐to‐treat (DTT) patients (i.e., ≥3 preventive failures). Treatment outcomes were determined at 6 months based on prospective headache diaries and Migraine Disability Assessment (MIDAS). Results: The study included 316 (55 M/261F, mean age 44.4 ± 13.5 years) and 333 (61 M/272F, mean age 47.9 ± 13.4 years) CM patients treated with CGRP mAbs or onabotulinbumtoxinA, respectively. At 6 months, CGRP mAb treatment was associated with a greater decrease in monthly migraine days (MMDs) (−13.0 vs. −8.7 days/month, p < 0.001) and a higher ≥50% responder rate (RR) (74.7% vs. 50.7%, p < 0.001) compared with onabotulinumtoxinA injections. The findings were consistent in DTT patients (−13.0 vs. −9.1 MMDs, p < 0.001; ≥50% RR: 73.9% vs. 50.3%, p < 0.001) or those with medication‐overuse headache (MOH) (−13.3 vs. −9.0 MMDs, p < 0.001; ≥50% RR: 79.0% vs. 51.6%, p < 0.001). Besides, patients receiving CGRP mAbs had greater improvement (−42.2 vs. −11.8, p < 0.001) and a higher ≥50% RR (62.0% vs. 40.0%, p = 0.001) in MIDAS scores and a lower rate of adverse events (AEs) (6.0% vs. 21.0%, p < 0.001). However, none of the patients discontinued treatment due to AEs. Conclusions: In this multicenter, real‐world study, CGRP mAbs were more effective than onabotulinumtoxinA in CM patients, even in DTT or MOH patients. All of these injectables were well tolerated. Further prospective studies are needed to verify these findings. [ABSTRACT FROM AUTHOR]

This paper proposes a broadband eight-antenna array design suitable for Fifth Generation New Radio (5G NR) smartphone applications. To cover the 5G NR bands n77/n78/n79 (3300–5000 MHz) and 5G NR-U n46 band (5150–5925 MHz), the single antenna array unit applied is a modified loop antenna element (MLAE) that can generate three different loop modes. To yield good multi-input multi-output (MIMO) performances, the designed MLAE is further arranged as an eight-antenna array, and the experimental results show that the overlapping 6 dB bandwidth can cover the bands-of-interest (3300–5925 MHz) with good isolation and total efficiency of >10 dB and 51–84%, respectively. Finally, good MIMO performances, such as an envelope correlation coefficient (ECC) of lower than 0.1 and desirable channel capacity (CC) of 37–40 bps/Hz, were calculated across the bands-of-interest. [ABSTRACT FROM AUTHOR]

Carotid blowout syndrome (CBS) is a rare yet life-threatening complication that occurs after radiation therapy (RT). This study aimed to determine the incidence of CBS in patients with head and neck cancer (HNC) undergoing contemporary RT and to explore potential discrepancies in the risk of CBS between nasopharyngeal cancer (NPC) and non-NPC patients. A total of 1084 patients with HNC who underwent RT between 2013 and 2023 were included in the study. All patients were under regular follow-ups at the radio-oncology department, and underwent annual contrast-enhanced computed tomography and/or magnetic resonance imaging for cancer recurrence surveillance. Experienced neuroradiologists and vascular neurologists reviewed the recruited patients' images. Patients were further referred to the neurology department for radiation vasculopathy evaluation. The primary outcome of this study was CBS. Patients were categorized into NPC and non-NPC groups and survival analysis was employed to compare the CBS risk between the two groups. A review of the literature on CBS incidence was also conducted. Among the enrolled patients, the incidence of CBS in the HNC, NPC, and non-NPC groups was 0.8%, 0.9%, and 0.7%, respectively. Kaplan–Meier analysis revealed no significant difference between the NPC and non-NPC groups (p = 0.34). Combining the findings for our cohort with those of previous studies revealed that the cumulative incidence of CBS in patients with HNC is 5% (95% CI = 3–7%) after both surgery and RT, 4% (95% CI = 2–6%) after surgery alone, and 5% (95% CI = 3–7%) after RT alone. Our findings indicate a low incidence of CBS in patients with HNC undergoing contemporary RT. Patients with NPC may have a CBS risk close to that of non-NPC patients. However, the low incidence of CBS could be a potentially cause of selection bias and underestimation bias. [ABSTRACT FROM AUTHOR]

Combining microbial products with different mechanisms of action can produce synergistic insecticidal effects and slow down the development of resistance. This study evaluated the insecticidal activity of mixtures containing the commercial Photorhabdus luminescens (Pl) strain ATCC 29,999, the local isolate Pl 2103-UV, and the commercial Bacillus thuringiensis subsp. kurstaki (Bt) ABTS-351 against Spodoptera frugiperda. As the proportion of Bt increased in the mixtures, insecticidal activity increased, with the synergistic ratios reaching 1.98 for ATCC 29,999 and 5.29 for 2103-UV at a1:5 Pl:Bt ratio, representing approximately twofold and fivefold reductions, respectively, in the Bt dosage required for mortality. Hemolymph analysis revealed the highest Pl bacterial loads in the 1:5 treatments within the S. frugiperda hemocoel. Histopathology also showed exacerbated midgut vacuolation in the 1:5 ATCC 29,999:Bt treatment. Whole-genome analysis showed that 2103-UV produced more porins, potentially contributing to its higher insecticidal activity. This study demonstrated that Bt assists the invasion of Pl into the hemocoel and enhances synergistic insecticidal efficiency. The findings provide a reference for integrating Pl with other microbial products to sustainably manage significant and severe lepidopteran pests. [ABSTRACT FROM AUTHOR]

The Developmental Origins of Health and Disease (DOHaD) concept has gained prominence in maternal and child health (MCH), emphasizing how early-life factors impact later-life non-communicable diseases. However, a knowledge–practice gap exists in applying DOHaD principles among healthcare professionals. Healthy Early Life Moments in Singapore (HELMS) introduced webinars to bridge this gap and empower healthcare professionals. We aimed to conduct a preliminary assessment to gain early insights into the outreach and effectiveness of the educational initiative offered with the HELMS webinars. We employed a pragmatic serial cross-sectional study approach and targeted healthcare professionals involved in MCH care. We also collected and analyzed data on webinar registration and attendance, participants' profession and organizational affiliations, and post-webinar survey responses. The median webinar attendance rate was 59.6 % (25th–75th percentile: 58.4–60.8 %). Nurses represented 68.6 % of attendees (n=2,589 out of 3,774). Post-webinar surveys revealed over 75 % of the participants providing positive responses to 14 out of 15 survey questions concerning content, delivery, applicability to work, and organization. Assessment of the HELMS webinars provided insight into the outreach and early effectiveness in enhancing healthcare professionals' knowledge and confidence in delivering DOHaD education. Bridging the knowledge–practice gap remains a crucial goal. [ABSTRACT FROM AUTHOR]

Neurons in sensory and motor cortices tend to aggregate in clusters with similar functional properties. Within the primate dorsal ("where") pathway, an important interface between three-dimensional (3-D) visual processing and motor-related functions consists of two hierarchically organized areas: V3A and the caudal intraparietal (CIP) area. In these areas, 3-D visual information, choice-related activity, and saccade-related activity converge, often at the single-neuron level. Characterizing the clustering of functional properties in areas with mixed selectivity, such as these, may help reveal organizational principles that support sensorimotor transformations. Here we quantified the clustering of visual feature selectivity, choice-related activity, and saccade-related activity by performing correlational and parametric comparisons of the responses of well-isolated, simultaneously recorded neurons in macaque monkeys. Each functional domain showed statistically significant clustering in both areas. However, there were also domain-specific differences in the strength of clustering across the areas. Visual feature selectivity and saccade-related activity were more strongly clustered in V3A than in CIP. In contrast, choice-related activity was more strongly clustered in CIP than in V3A. These differences in clustering may reflect the areas' roles in sensorimotor processing. Stronger clustering of visual and saccade-related activity in V3A may reflect a greater role in within-domain processing, as opposed to cross-domain synthesis. In contrast, stronger clustering of choice-related activity in CIP may reflect a greater role in synthesizing information across functional domains to bridge perception and action. NEW & NOTEWORTHY: The occipital and parietal cortices of macaque monkeys are bridged by hierarchically organized areas V3A and CIP. These areas support 3-D visual transformations, carry choice-related activity during 3-D perceptual tasks, and possess saccade-related activity. This study quantifies the functional clustering of neuronal response properties within V3A and CIP for each of these domains. The findings reveal domain-specific cross-area differences in clustering that may reflect the areas' roles in sensorimotor processing. [ABSTRACT FROM AUTHOR]

Aim: Frailty results from age‐associated declines in physiological reserve and function and is prevalent in older people. Our aim is to examine the association of the Hospital Frailty Risk Score (HFRS) with adverse events in older patients hospitalized with community‐acquired pneumonia (CAP) and hypothesise that frailty is a comparable predictor of outcomes in CAP versus traditional severity indices such as CURB‐65. Methods: Retrospective review of electronic medical records in patients ≥65 years with CAP admitted to a tertiary hospital from 1 January to 30 April 2021. Patients were identified using ICD codes for CAP and categorized as high risk (>15), intermediate risk (5–15) and low risk (<5) of frailty using the HFRS. Results: Of 429 patients with CAP, 53.8% male, mean age of 82.9 years, older patients (85 vs. 79.7 years, P < 0.001) were at higher risk of frailty. Using the HFRS, 47.6% were deemed at high risk, 35.9% at intermediate risk, and 16.6% at low risk of frailty. Multivariate logistic regression shows that HFRS was more strongly associated (≥7 days, OR 1.042, CI 1.017–1.069) than CURB‐65 (OR 0.995, CI 0.810–1.222) with long hospital length of stay (LOS), while CURB‐65 (Confusion, Urea >7mmol/L, Respiratory rate >30, Blood pressure, age => 65 years old) was more strongly associated with mortality at 30, 90 and 365 days, compared with the HFRS. Comparing the values for the area under the receiver operator characteristic curve, the HFRS was found to be a better predictor of long LOS, while CURB‐65 remains a better predictor of mortality. Conclusions: Patients with high risk of frailty have higher healthcare utilization and HFRS is a better predictor of long LOS than CURB‐65 but CURB‐65 was a better predictor of mortality. Geriatr Gerontol Int 2024; 24: 135–141. [ABSTRACT FROM AUTHOR]

Introduction: Frailty has an important impact on the health outcomes of older patients, and frailty screening is recommended as part of perioperative evaluation. The Hospital Frailty Risk Score (HFRS) is a validated tool that highlights frailty risk using 109 International Classification of Diseases, 10th revision (ICD-10) codes. In this study, we aim to compare HFRS to the Charlson Comorbidity Index (CCI) and validate HFRS as a predictor of adverse outcomes in Asian patients admitted to surgical services. Method: A retrospective study of electronic health records (EHR) was undertaken in patients aged 65 years and above who were discharged from surgical services between 1 April 2022 to 31 July 2022. Patients were stratified into low (HFRS <5), intermediate (HFRS 5--15) and high (HFRS >15) risk of frailty. Results: Those at high risk of frailty were older and more likely to be men. They were also likely to have more comorbidities and a higher CCI than those at low risk of frailty. High HFRS scores were associated with an increased risk of adverse outcomes, such as mortality, hospital length of stay (LOS) and 30-day readmission. When used in combination with CCI, there was better prediction of mortality at 90 and 270 days, and 30-day readmission. Conclusion: To our knowledge, this is the first validation of HFRS in Singapore in surgical patients and confirms that high-risk HFRS predicts long LOS (≥7days), increased unplanned hospital readmissions (both 30-day and 270-day) and increased mortality (inpatient, 10-day, 30-day, 90-day, 270-day) compared with those at low risk of frailty. [ABSTRACT FROM AUTHOR]

The impact of vitamin D supplementation on 25-hydroxyvitamin D (25OHD) levels, metabolic status, and pregnancy outcomes in pregnant women with overweight and obesity (OW/OB) is uncertain. This study aimed to examine whether administrating 800 IU of vitamin D3 orally would improve maternal serum 25OHD levels, lipid profile, and pregnancy outcomes compared to 400 IU. This was a two-arm, parallel, non-blinded randomised controlled trial involving 274 pregnant women recruited from KK Women's and Children's Hospital, with a body mass index of ≥25 kg/m2 within 16 weeks gestation. The participants were randomly assigned to receive 800 IU/day (intervention group) or 400 IU/day (control group) of oral vitamin D3 supplements. The primary outcomes were maternal serum 25OHD and lipid levels at 24–28 weeks gestation. The secondary outcomes included maternal and birth outcomes. Compared with controls (n = 119), the intervention group (n = 112) exhibited higher 25OHD levels at 24–28 weeks gestation (adjusted mean difference 6.52 nmol/L; 95% confidence interval 2.74, 10.31). More women in the intervention group achieved sufficient 25OHD levels (77.7% vs. 55.5%; p < 0.001). No differences were observed in lipid profiles or maternal or birth outcomes between the groups. An additional 400 IU of oral vitamin D3 supplementation increased serum 25OHD levels but did not impact lipid profiles or pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Improving technological innovation (TI) capabilities is an integral component of government policies aimed at improving the competitiveness of small and medium enterprises (SMEs). This study aims to address implementation challenges arising from the use of Qualitative Forecasting Method (QFM) in new product development programs and proposes a novel method to aid decision makers (DMs) in their decision-making process. To tackle this issue, a hybrid method is proposed, incorporating Fuzzy Delphi method (FDM), Fuzzy Analytic Hierarchy Process (FAHP), Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS), and Multi-Choice Goal Programming with utility function (MCGP-U), while introducing prospect theory as a novel approach. is proposed. The proposed method offers several advantages, including effective early planning, accurate identification of key success factors (KSFs), selection of the most suitable project leader, and estimation of the most reasonable resource investment, all of which are critical factors for success in TI for enterprises. The research results show that (1) the proposed method reduces project execution time by 20% compared to the original manual planning, (2) it facilitates the acquisition of KSFs using a rational approach to ensure project success, and (3) it increases the financial returns of the company by 17% compared to the company's forecast. In summary, this paper makes a significant contribution to practical applications and additionally contributes to decision-making field by introducing prospect theory into the proposed hybrid method. [ABSTRACT FROM AUTHOR]

Abstract Background SUMOylation, as part of the epigenetic regulation of transcription, has been intensively studied in lower eukaryotes that contain only a single SUMO protein; however, the functions of SUMOylation during mammalian epigenetic transcriptional regulation are largely uncharacterized. Mammals express three major SUMO paralogues: SUMO-1, SUMO-2, and SUMO-3 (normally referred to as SUMO-1 and SUMO-2/3). Herpesviruses, including Kaposi’s sarcoma associated herpesvirus (KSHV), seem to have evolved mechanisms that directly or indirectly modulate the SUMO machinery in order to evade host immune surveillance, thus advancing their survival. Interestingly, KSHV encodes a SUMO E3 ligase, K-bZIP, with specificity toward SUMO-2/3 and is an excellent model for investigating the global functional differences between SUMO paralogues. Results We investigated the effect of experimental herpesvirus reactivation in a KSHV infected B lymphoma cell line on genomic SUMO-1 and SUMO-2/3 binding profiles together with the potential role of chromatin SUMOylation in transcription regulation. This was carried out via high-throughput sequencing analysis. Interestingly, chromatin immunoprecipitation sequencing (ChIP-seq) experiments showed that KSHV reactivation is accompanied by a significant increase in SUMO-2/3 modification around promoter regions, but SUMO-1 enrichment was absent. Expression profiling revealed that the SUMO-2/3 targeted genes are primarily highly transcribed genes that show no expression changes during viral reactivation. Gene ontology analysis further showed that these genes are involved in cellular immune responses and cytokine signaling. High-throughput annotation of SUMO occupancy of transcription factor binding sites (TFBS) pinpointed the presence of three master regulators of immune responses, IRF-1, IRF-2, and IRF-7, as potential SUMO-2/3 targeted transcriptional factors after KSHV reactivation. Conclusion Our study is the first to identify differential genome-wide SUMO modifications between SUMO paralogues during herpesvirus reactivation. Our findings indicate that SUMO-2/3 modification near protein-coding gene promoters occurs in order to maintain host immune-related gene unaltered during viral reactivation.

The accumulation of the uremic toxin indoxyl sulfate (IS) is a key pathological feature of chronic kidney disease (CKD). The effect of IS on ferroptosis and the role of IS-related ferroptosis in CKD are not well understood. We used a renal tubular cell model and an adenine-induced CKD mouse model to explore whether IS induces ferroptosis and injury and affects iron metabolism in the renal cells and the kidneys. Our results showed that exposure to IS induced several characteristics for ferroptosis, including iron accumulation, an impaired antioxidant system, elevated reactive oxygen species (ROS) levels, and lipid peroxidation. Exposure to IS triggered intracellular iron accumulation by upregulating transferrin and transferrin receptors, which are involved in cellular iron uptake. We also observed increased levels of the iron storage protein ferritin. The effects of IS-induced ROS generation, lipid peroxidation, ferroptosis, senescence, ER stress, and injury/fibrosis were effectively alleviated by treatments with an iron chelator deferoxamine (DFO) in vitro and the adsorbent charcoal AST-120 (scavenging the IS precursor) in vivo. Our findings suggest that IS triggers intracellular iron accumulation and ROS generation, leading to the induction of ferroptosis, senescence, ER stress, and injury/fibrosis in CKD kidneys. AST-120 administration may serve as a potential therapeutic strategy. [ABSTRACT FROM AUTHOR]