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BACKGROUND: Atrial fibrillation (AF) that occurs as a frequent complication of myocardial infarction (MI) is associated with a poor clinical outcome. It nonetheless remains uncertain whether AF that occurs transiently during MI is associated with a subsequent increased risk of the development of AF and ischemic stroke. METHODS: We retrospectively studied the impact of transient AF on the long-term risk of the occurrence of AF, ischemic stroke, and mortality in 431 consecutive patients (mean [+/- SEM] age, 64 +/- 1 years; 75% men). All patients had experienced an acute inferior ST-segment-elevation MI and had preserved left ventricular ejection fraction (LVEF) [> 45%]. RESULTS: All patients were in sinus rhythm on hospital admission, and transient AF was observed in 59 patients (13.7%) during their hospitalization for MI. On hospital discharge, all patients were in sinus rhythm and had been prescribed antiplatelet agents alone as antithrombotic therapy. Patients in whom transient AF developed during MI were older (mean age, 70 +/- 1.4 vs 64 +/- 0.7 years, respectively; p < 0.01) and more likely to be women (37% vs 23%, respectively; p < 0.02) compared with those without AF. At 1-year follow-up, the incidence of AF (22.0% vs 1.3%, respectively; p < 0.01) and ischemic stroke (10.2% vs 1.8%, respectively; p < 0.01) was higher in patients with transient AF than in those without transient AF. The total mortality rate was nonetheless similar (5.6% vs 6.8%, respectively; p = 0.73); Cox regression analysis demonstrated that age > 65 years and transient AF during MI were independent predictors of the subsequent occurrence of AF and the development of ischemic stroke. CONCLUSION: Transient AF complicating acute inferior MI is associated with an increased future risk of AF occurrence and ischemic stroke in patients with preserved LVEF, despite the use of antiplatelet therapy. [ABSTRACT FROM AUTHOR]

Screening measures to identify very young children at risk for autism spectrum disorders include the Modified Checklist for Autism in Toddlers (M-CHAT) and the Social Communication Questionnaire (SCQ). To examine the validity of these written questionnaires, parents completed them prior to their child's diagnostic assessment at a tertiary autism clinic. The M-CHAT was given to 84 parents of 2 to 3-year-olds and the SCQ to 94 parents of 4 to 6-year olds. On both measures sensitivity was higher than specificity with positive predictive values 0.63-0.68. False negatives, or children with autism who were missed by screening, were somewhat higher functioning than true positives. Results were better for parents who spoke English as a second language, contrary to expectations. At this stage of development these tools would be recommended as part of more comprehensive surveillance programmes to identify children in need of further assessment but not to 'screen out' the possibility of autism. [ABSTRACT FROM AUTHOR]

Forty-nine 2 years olds with social and language characteristics suggestive of autism were identified by community professionals and screening tools, then given a diagnostic assessment and reexamined at age 4 1/2. Agreement between autism clinic and screenings was high, with 88% receiving a diagnosis on the autism spectrum. The children were lower functioning relative to the autism population, thus more likely to be identified early. Reliability of diagnoses from 2 1/2 to 4 1/2 was high with 79% staying in the same diagnostic category, but more so for clear autism than for PDDNOS. About a third improved over 20 IQ points and similar number similarly declined. Changes were not related to amount or type of intervention but were related to the children's characteristics. Higher functioning children with milder autism were the most improved. [ABSTRACT FROM AUTHOR]

Background: Active case finding could effectively detect tuberculosis (TB) patients, but it can be costly. Therefore, a feasible, cost-saving, and efficient algorithm for community-based TB screening is needed., Methods: The study population was based on a previous TB prevalence survey conducted in the Zambia/South Africa Tuberculosis and HIV/AIDS Reduction trial. We developed predictive scoring models for HIV-positive and HIV-negative/unknown populations for practical purposes. We compared the cost-effectiveness of our models with that of WHO tools through average cost-effectiveness ratio (ACER) and incremental cost-effectiveness ratio., Results: The prediction model for HIV-positive population presented higher area under the curve (AUC) = 0.652, 95% confidence interval (CI) = 0.602-0.701) than WHO-recommended four-symptom screen (AUC = 0.568, 95% CI = 0.524-0.612) among South African participants. The AUC of the model for HIV-negative/unknown population was 0.673 (95% CI = 0.648-0.697), which was higher than that of the WHO tools as well. The ACER of our model can range from 246 to 1670 USD per TB case detected in the South African communities., Conclusions: The scoring system for active TB case finding presented a better performance and showed cost-effectiveness, which can provide new strategies for active TB case finding with multiple options under budget considerations., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Background: Unmanned aerial vehicles (UAVs) are increasingly used in precision agriculture, particularly for pesticide application in rice cultivation. One challenge is off-target pesticide drift, which raises environmental concerns and reduces pesticide efficiency. Lecithin adjuvants have been suggested to enhance droplet stability, reduce drift, and improve control efficacy. This study aims to evaluate the efficiency of lecithin adjuvants in reducing pesticide drift and improving deposition during UAV-based pesticide application under various paddy field conditions., Results: The addition of 1% lecithin adjuvants in 75% dosage of tricyclazole and ferimzone dual active ingredient formulations reduced off-target drift by 2.62 to 3.16 times compared to the 100% and 75% dosage of standard formulations, with deposition efficiency along the spray path increasing by up to 155%. Wind direction and speed were found to be the primary environmental factor affecting deposition efficiency and drift rate. The control efficacy against leaf blast disease was significantly improved, with a maximum efficacy of 73.7% observed in the adjuvant-treated group. Initial pesticide residues on rice plants were the highest in treatments with adjuvants, but their harvest products, brown rice and dried straw, were still within safe limits for human consumption., Conclusion: Lecithin adjuvants significantly reduce off-target drift and enhance pesticide deposition during UAV-based application. This method allowed for lower pesticide dosages without compromising control efficacy, contributing to more sustainable agricultural practices. These findings highlight the potential of adjuvants to improve UAV pesticide application and reduce the environmental impact of pesticide use. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Proteolysis-targeting chimeras (PROTACs) have emerged as a promising technology for inducing targeted protein degradation by leveraging the intrinsic ubiquitin-proteasome system (UPS). While the potential druggability of PROTACs toward undruggable proteins has accelerated their rapid development and the wide-range of applications across diverse disease contexts, off-tissue effects and side-effects of PROTACs have recently received attentions to improve their efficacy. To address these issues, spatial or temporal target protein degradation by PROTACs has been spotlighted. In this review, we explore chemical strategies for modulating protein degradation in a cell type-specific (spatio-) and time-specific (temporal-) manner, thereby offering insights for expanding PROTAC applications to overcome the current limitations of target protein degradation strategy., (© 2024 The Author(s). ChemMedChem published by Wiley-VCH GmbH.)

In bacteria, the ankyrin-like protein AnkB helps overcome stress by regulating catalase activity when expressed under stressful conditions. As the structural properties of AnkB are largely unexplored, our understanding of various AnkB-mediated functions in bacteria remains limited. In the present study, we describe the structure of AnkB from Acinetobacter baumannii, hereafter referred to as "AbAnkB," which has a unique tertiary configuration compared with that of other ankyrin domain-containing proteins. Structural analysis revealed that AbAnkB has a relatively long loop between AKR3 and AKR4 and an oppositely positioned α 8 helix. Based on amino acid conservation and protein surface analyses, we identified a hydrophobic patch that might be critical for the function of AbAnkB. To the best of our knowledge, our study is the first to report the structure of a bacterial AnkB protein; our findings will markedly enhance our understanding of its functions in bacteria., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The fall armyworm (FAW), Spodoptera frugiperda is a cold-sensitive species that overwinters in temperate climates without diapause. Overwintering in insects involves rapid cold hardening (RCH), supported by trehalose (TRE), which serves as an intermediate between glycogen (GLY) and glucose (GLU). However, both GLU and TRE help maintain homeostasis under stress. TRE is hydrolyzed by the enzyme trehalase (Treh) into GLU. This study retrieved Sf-Treh1a, Sf-Treh1b, and Sf-Treh2 from the FAW transcriptome analysis. RNA interference (RNAi) targeting these three Treh genes resulted in significant downregulation of mRNA levels and altered survival rates in RNAi-treated FAW larvae following RCH treatment. High-pressure liquid chromatography (HPLC) quantification of TRE and GLU in treated groups suggests that GLU is an essential component of the hemolymph for survival adaptation to cold conditions in S. frugiperda. This study reveals limited cold adaptability of FAW, as evidenced by lower glucose concentration levels. We found that FAW requires alternative molecules, in conjunction with glucose and trehalose for freeze tolerance and survivability. Our study aims to discover the molecular mechanisms that contribute to freeze tolerance in FAW by exploring the roles of trehalose, glucose, and glycogen., (© 2024. The Author(s).)

DNA methylation is a molecular process that mediates gene-environment interactions. Epigenome-wide association studies (EWAS) using the Illumina Human Methylation BeadChip are powerful tools for quantifying the relationship between DNA methylation and phenotypes. Recently, the Illumina Methylation EPICv2 BeadChip (EPICv2) was released, which includes new features, such as duplicated probes and changed probe names. Several published algorithms have been updated to address these features in EPICv2. However, appropriate EPICv2 preprocessing and integration with previous microarray versions remain complex. Therefore, MethylCallR, an open-source R package designed to provide standard procedures for performing EWAS using Illumina methylation microarrays including EPICv2, was developed. MethylCallR can be used to control duplicated probes in EPICv2, by using pre-set data implemented in MethylCallR or new customized data. MethylCallR includes a straightforward conversion function between different types of Illumina Human Methylation BeadChips. Using MethylCallR, potential outlier sample detection and statistical power estimation were conducted and used to select meaningful probes. Publicly available data was analyzed using MethylCallR and the findings were compared to that of a previous study., (© 2024. The Author(s).)

Background: This study aims to investigate the association between serum calcium levels and acute coronary syndrome (ACS) risk, examining whether this relationship differs by sex, given the known differences in calcium metabolism and hormonal influences between males and females. Methods: Utilizing the Korean Genome Epidemiology Study (KoGES) prospective cohort data, our primary exposure variables were serum calcium level and sex. The incidence of ACS served as the main outcome of interest. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression analysis. An interaction analysis was conducted to assess the interaction effect of calcium level and sex on ACS incidence. Results: After adjusting for confounding variables, high calcium intake did not significantly increase ACS incidence, with a hazard ratio (HR) of 1.07 (95% CI: 0.90-1.26). There was also no significant difference in ACS risk between females and males (HR: 0.81, 95% CI: 0.61-1.04). However, interaction effect analysis revealed that higher calcium levels were associated with an increased risk of ACS only in females (HR: 1.24, 95% CI: 1.07-1.58), whereas the association in males was not statistically significant (HR: 0.90, 95% CI: 0.71-1.15). Conclusion: Our study results indicate that elevated serum calcium levels alone did not independently increase the risk of ACS; however, high serum calcium levels were associated with an increased risk of ACS in females but not in males, underscoring the importance of sex-specific factors in assessing and managing ACS risk and highlighting the necessity for personalized medical approaches to improve cardiovascular health outcomes for women., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Microrobots possessing multifunctional integration are desired for therapeutics and biomedicine applications. However, existing microrobots with desired functionalities need to be fabricated through complex procedures due to their constrained volume, limited manufacturing processes, and lack of effective in vivo observation methods. Inspired by bubbles exhibiting various abilities, we report magnetic air bubble microrobots with simpler structures to simultaneously integrate multiple functions, including microcargo delivery, multimode locomotion, imaging, and biosensing. Contributed by buoyancy and magnetic actuation to overcome obstacles, flexible three-dimensional locomotion is implemented, guaranteeing the integrity of micro-objects adsorbed on the surface of the air bubble microrobot. Introducing air microbubbles enhances the ultrasound imaging capability of microrobots in the vascular system of mice in vivo , facilitating ample medical applications. Moreover, air-liquid reactions endow microrobots with rapid pH biosensing. This work provides a unique strategy to utilize relatively simple air bubbles to achieve the complex functions of microrobots for biomedical applications.

Energy harvesting from ubiquitous natural water vapor based on moisture electric generator (MEG) technology holds great potential to power portable electronics, the Internet of Things, and wireless transmission. However, most devices still encounter challenges of low output, and a single MEG complemented with another form of energy harvesting for achieving high power has seldom been demonstrated. Herein, we report a flexible and efficient hybrid generator capable of harvesting moisture and tribo energies simultaneously, both from the source of water droplets. The moisture electric and triboelectric layers are based on a water-absorbent citric acid (CA)-mediated polyglutamic acid (PGA) hydrogel and porous electret expanded polytetrafluoroethylene (E-PTFE), respectively. Such a waterproof E-PTFE film not only enables efficient triboelectrification with water droplets' contact but also facilitates water vapor to be transferred into the hydrogel layer for moisture electricity generation. A single hybrid generator under water droplets' impact delivers a DC voltage of 0.55 V and a peak current density of 120 μA cm -2 from the MEG, together with a simultaneous AC output voltage of 300 V and a current of 400 μA from the complementary water-based triboelectric generator (TEG) side. Such a hybrid generator can work even under harsh wild environments with 5 °C cold and saltwater impacts. Significantly, an optical alarm and wireless communication system for wild, complex, and emergency scenarios is demonstrated with power from the hybrid generators. This work expands the applications of water-based electricity generation technologies and provides insight into harvesting multiple potential energies in the natural environment with high output.

Rice straw is used as livestock feed and compost. Ferimzone and tricyclazole, common fungicides for rice blast control, can be found in high concentrations in rice straw after unmanned aerial vehicle (UAV) spraying, potentially affecting livestock and human health through pesticide residues. In this study, an optimized method for the analysis of the two fungicides in rice straw was developed using the improved QuEChERS method. After the optimization of water and solvent volume, extraction conditions including ethyl acetate (EtOAc), acetonitrile (MeCN), a mixed solvent, and MeCN containing 1% acetic acid were compared. Different salts, including unbuffered sodium chloride, citrate, and acetate buffer salts, were compared for partitioning. Among the preparation methods, the MeCN/EtOAc mixture with unbuffered salts showed the highest recovery rates (88.1-97.9%, RSD ≤ 5.1%). To address the severe matrix effect (%ME) of rice straw, which is characterized by low moisture content and cellulose-based complex matrices, samples were purified using 25 mg each of primary-secondary amine (PSA) and octadecylsilane (C 18 ), without pesticide loss. The developed method was validated with a limit of quantification (LOQ) of 0.005 mg/kg for target pesticides, and recovery rates at levels of 0.01, 0.1, and 2 mg/kg met the permissible range (82.3-98.9%, RSD ≤ 8.3%). The %ME ranged from -17.6% to -0.3%, indicating a negligible effect. This optimized method was subsequently applied to residue studies following multi-rotor spraying. Fungicides from all fields and treatment groups during harvest season did not exceed the maximum residue limits (MRLs) for livestock feed. This confirms that UAV spraying can be safely managed without causing excessive residues.

Specific bacterial species induce algal blooms by producing growth-promoting substances, such as siderophores, under iron-limited conditions. However, the molecular mechanisms underlying these effects remain poorly understood. This study investigates the interactions between the harmful dinoflagellate Alexandrium pacificum (Group IV) and siderophore-producing bacteria, with a focus on iron acquisition facilitated by bacterial siderophores. During algal bloom seasons in the South Sea of Korea, Photobacterium sp. TY1-4 was isolated, which enhances A. pacificum cell density under iron-deficient conditions, TY1-4 can use the sterile exudates from A. pacificum as the sole source of carbon, suggesting a mutualistic relationship. Transcriptomic and genomic analyses revealed siderophore-mediated redox-based signaling and non-reductive pathways enhancing iron bioavailability. Photobacterium sp. TY1-4 initiates siderophore production through quorum sensing, whereas A. pacificum utilizes specific receptors and transporters for hydroxamate-type siderophores (ApFHUA and ApFHUC) to uptake iron. Three redox key iron-uptake genes were also identified in A. pacificum: membrane-bound ferroxidase ApFET3, high-affinity iron permease ApFTR1, and ferric-chelate reductases/oxidoreductases ApFRE1, with transcription levels inversely related to bioavailable iron. Increased iron bioavailability mediated by siderophores alleviates iron stress in A. pacificum, supporting its growth in iron-scarce environments. Additionally, A. pacificum co-cultured with Photobacterium sp. TY1-4 synthesized high-toxicity STXs, including GTX4, GTX2, and STX. These findings highlight the critical role of bacterial siderophores in iron binding and their potential impact on harmful algal bloom dynamics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: There is a high possibility of trauma patients being referred to an unsuitable medical institution for their rehabilitation treatment since the decision is made by them. This study sought to develop a standardized scale to evaluate the need for specialized rehabilitation in patients with multiple traumas and evaluate the effectiveness of the developed scale., Methods: This study employed a systematic review of existing literature to inform the development of a specialized rehabilitation evaluation scale. An expert panel consisting of trauma surgeons, orthopedic surgeons, and rehabilitation medicine physicians collaborated to create a discharge-planning checklist by assessing the need for specialized rehabilitation. The checklist was validated using retrospective data from trauma patients treated at Seoul National University Hospital., Results: We identified 12 studies, providing factors influencing the discharge location and rehabilitation needs of trauma patients. The checklist was developed through expert consensus and comprised 3 criteria: discharge feasibility to specialized rehabilitation facilities, diagnostic eligibility for specialized rehabilitation, and functional assessment. Validation of the checklist demonstrated that the percentage agreement, likelihood ratio of a positive test, and Cohen's kappa value were 82.1%, 5.21, and 0.375, respectively when comparing whether the checklist was met and the actual discharge location, indicating its effectiveness., Conclusion: This study established standardized criteria for assessing the need for specialized rehabilitation in trauma patients, offering a practical tool for clinical use. Implementation of this assessment scale has the potential to improve the trajectory of trauma survivors by facilitating access to appropriate rehabilitation services., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2024, the Korean Surgical Society.)

Neoadjuvant chemotherapy combined with bevacizumab is used to treat colorectal cancer (CRC) patients by targeting tumor and vascular cells. However, it is known that other cells in the tumor microenvironment (TME) also change in response to this treatment. To investigate the changes in TME subpopulations in response to neoadjuvant FOLFOX6 plus bevacizumab, we studied pre- and post-treatment CRC tissues in four patients using single-cell RNA sequencing (scRNA-seq). This analysis classified nine cell types, including epithelial, vascular, immune cells, and fibroblasts. The cellular responses were widespread across the cell types, but there were specific subpopulations that altered, especially in vascular, immune, and fibroblast cells. In vascular subpopulations, CDH13-endothelial, arteriole, and CA4 capillary cells were selectively reduced. In immune cells, CD4+, CD8+ T cells, conventional dendritic cell type 1 (cDC1), and CCL19-expressing migrating DC (migDC-1) increased, while Th17, Th22, and tumor-associated macrophage (TAM) cells decreased, indicating that the treatment might be immunostimulatory. In fibroblasts, two major cancer-associated fibroblasts (matrix CAF (mCAF) and inflammatory CAF (iCAF)) increased, while conventional fibroblasts decreased, suggesting that the treatment remodeled the reparative/inflammatory processes, which might lead to reduced aggressiveness from the cancer-associated fibroblasts. In summary, our study reveals that neoadjuvant FOLFOX6 plus bevacizumab leads to alterations in particular subpopulations of vascular, immune, and reparative/inflammatory cells in the TME of CRCs. These alterations include vascular reduction, immunologic stimulation, and reduction of cancer-associated fibroblasts, which may underlie the responsiveness to the therapy in CRC. Our results may provide insights into the mechanisms of responsiveness/resistance to neoadjuvant FOLFOX6 plus bevacizumab therapy in CRCs., Competing Interests: Declaration of Competing Interest There is no conflict of interest for the authors., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Ubiquitous moisture is of particular interest for sustainable power generation and self-powered electronics. However, current moisture electric generators (MEGs) can only harvest moisture energy in the air, which tremendously limits the energy harvesting efficiency and practical application scenarios. Herein, the operationality of MEG from air to underwater environment, through a sandwiched engineered-hydrogel device with an additional waterproof breathable membrane layer allowing water vapor exchange while preventing liquid water penetration, is expanded. Underwater environment, the device can spontaneously deliver a voltage of 0.55 V and a current density of 130 µA cm -2 due to the efficient ion separation assisted by negative ions confinement in hydrogel networks. The output can be maintained even under harsh underwater environment with 10% salt concentration, 1 m s -1 disturbing flow, as well as >40 kPa hydraulic pressure. The engineered hydrogel used for MEG also exhibits excellent self-healing ability, flexibility, and biocompatibility. As the first demonstration of practical applications in self-powered underwater electronics, the MEG device is successfully powering a wireless emitter for remote communication in water. This new type of MEG offers an innovative route for harvesting moisture energy underwater and holds promise in the creation of a new range of innovative electronic devices for marine Internet-of-Things., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objectives: Oral biofilms, including pathogens such as Porphyromonas gingivalis, are involved in the initiation and progression of various periodontal diseases. However, the treatment of these diseases is hindered by the limited efficacy of many antimicrobial materials in removing biofilms under the harsh conditions of the oral cavity. Our objective is to develop a gel-type antimicrobial agent with optimal physicochemical properties, strong tissue adhesion, prolonged antimicrobial activity, and biocompatibility to serve as an adjunctive treatment for periodontal diseases., Methods: Phenylboronic acid-conjugated alginate (Alg-PBA) was synthesized using a carbodiimide coupling agent. Alg-PBA was then combined with tannic acid (TA) to create an Alg-PBA/TA hydrogel. The composition of the hydrogel was optimized to enhance its mechanical strength and tissue adhesiveness. Additionally, the hydrogel's self-healing ability, erosion and release profile, biocompatibility, and antimicrobial activity against P. gingivalis were thoroughly characterized., Results: The Alg-PBA/TA hydrogels, with a final concentration of 5 wt% TA, exhibited both mechanical properties comparable to conventional Minocycline gel and strong tissue adhesiveness. In contrast, the Minocycline gel demonstrated negligible tissue adhesion. The Alg-PBA/TA hydrogel also retained its rheological properties under repeated 5 kPa stress owing to its self-healing capability, whereas the Minocycline gel showed irreversible changes in rheology after just one stress cycle. Additionally, Alg-PBA/TA hydrogels displayed a sustained erosion and TA release profile with minimal impact on the surrounding pH. Additionally, the hydrogels exhibited potent antimicrobial activity against P. gingivalis, effectively eliminating its biofilm without compromising the viability of MG-63 cells., Significance: The Alg-PBA/TA hydrogel demonstrates an optimal combination of mechanical strength, self-healing ability, tissue adhesiveness, excellent biocompatibility, and sustained antimicrobial activity against P. gingivalis. These attributes make it superior to conventional Minocycline gel. Thus, the Alg-PBA/TA hydrogel is a promising antiseptic candidate for adjunctive treatment of various periodontal diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

MltG, a membrane-bound lytic transglycosylase, has roles in terminating glycan polymerization in peptidoglycan and incorporating glycan chains into the cell wall, making it significant in bacterial cell-wall biosynthesis and remodeling. This study provides the first reported MltG structure from Mycobacterium abscessus (maMltG), a superbug that has high antibiotic resistance. Our structural and biochemical analyses revealed that MltG has a flexible peptidoglycan-binding domain and exists as a monomer in solution. Further, the putative active site of maMltG was disclosed using structural analysis and sequence comparison. Overall, this study contributes to our understanding of the transglycosylation reaction of the MltG family, aiding the design of next-generation antibiotics targeting M. abscessus., (open access.)

Purpose: Single-sided deafness (SSD) presents significant challenges for patients, including compromised sound localization, reduced speech recognition, and often, tinnitus. These issues are typically addressed using interventions such as cochlear implantation (CI) and bone conduction implant (BCI). However, evidence regarding the efficacy of BCI in reducing tinnitus in SSD patients remains limited. This study explored the ability of a novel active transcutaneous BCI (Bonebridge BCI602) to alleviate tinnitus in SSD patients., Study Design: Prospective cohort multicenter study., Setting: Tertiary referral hospitals., Methods: A prospective multicenter study of 30 SSD patients was conducted. The patients were divided into two groups: those with (n = 19) and without (n = 11) tinnitus. Audiometric assessments, subjective questionnaires including the Abbreviated Profile of Hearing Aid Benefit (APHAB) and the Bern Benefit in Single-Sided Deafness (BBSS), and tinnitus evaluations with the Tinnitus Handicap Inventory (THI) and tinnitogram were conducted before and after BCI surgery., Results: THI scores after surgery were significantly reduced in SSD patients with tinnitus. Subjective satisfaction improved in both the tinnitus and non-tinnitus groups; however, the former group exhibited a significantly greater improvement in the APHAB questionnaire score. According to tinnitograms, the loudness of tinnitus decreased, particularly in patients with ipsilateral tinnitus. Patients with residual hearing had greater reductions in their THI scores. However, three patients without residual hearing had a relative worsening of tinnitus after surgery., Conclusion: The Bonebridge BCI602 effectively reduced tinnitus in SSD patients, particularly in those with residual hearing. Subjective satisfaction improved in both the tinnitus and non-tinnitus groups. These findings demonstrate the therapeutic potential of BCI for managing SSD and associated tinnitus., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Laryngopharyngeal reflux disease (LPRD) is mainly treated with proton pump inhibitors (PPI) such as esomeprazole, which have shortcomings like delayed absorption and increased osteoporosis. Fexuprazan is a novel potent potassium-competitive acid blocker that inhibits gastric acid secretion with rapid onset and long duration of action. To assess the efficacy and safety of fexuprazan compared to esomeprazole in patients with LPRD., Methods: This prospective, randomized, double-blinded, multicenter, active-controlled trial was conducted in nine otolaryngologic clinics. Patients with reflux symptom index (RSI) ≥ 13 and reflux finding score (RFS) ≥ 7 were randomly assigned to the fexuprazan or esomeprazole groups, and received fexuprazan 40-mg or esomeprazole 40-mg once daily for 8 weeks. The outcomes were (1) mean change, change rate, and valid rate in RSI, RFS, and LPR-related questionnaires; and (2) adverse events., Results: A total of 136 patients (fexuprazan n = 68, esomeprazole n = 68) were followed up for ≥ 1 month. Each parameter significantly improved after 4 and 8 weeks in each group, with no significant differences between the two groups. For those with severe symptoms (RSI ≥ 18), the fexuprazan group (n = 32) showed more improvement in the mean change and change rate in the RSI than esomeprazole group (n = 31) after 4 weeks (p = .036 and .045, respectively). This phenomenon was especially observed in hoarseness and troublesome cough., Conclusion: Fexuprazan improved symptoms and signs without no serious adverse events in patients with LPRD. In patients with severe symptoms, fexuprazan resulted in a faster symptom improvement than PPI., Trial Registration: KCT0007251, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22100 ., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study demonstrates the developments of self-assembled optical metasurfaces to overcome inherent limitations in polarization density (P) and high refractive indices (n) within naturally occurring materials. The Maxwellian macroscopic description establishes a link between P and n, revealing a static limit in natural materials, restricting n to ≈4.0 at optical frequencies. Previously, it is accepted that self-assembly enables the creation of nanogaps between metallic nanoparticles (NPs), boosting capacitive enhancement of P and resultant exceptionally high n at optical frequencies. The work focuses on assembling gold (Au) NPs into a closely packed monolayer by rationally designing the polymeric ligand to balance attractive and repulsive forces, in that polymeric brush-mediated self-assembly of the close-packed Au NP monolayer is robustly achieved over a large-area. The resulting monolayer of Au nanospheres (NSs), nanooctahedras (NOs), and nanocubes (NCs) exhibits high macroscopic integrity and crystallinity, sufficiently enough for pushing n to record-high regimes. The systematic comparisons between each differently shaped Au NP monolayers elucidate the significance of capacitive coupling in achieving an unnaturally high n. The achieved n of 10.12 at optical frequencies stands as a benchmark, highlighting the potential of polyhedral Au NPs in advancing optical metasurfaces., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Telmisartan is an angiotensin receptor blocker (ARB) approved by the Food and Drug Administration of the US for the treatment of hypertension. It possesses unique pharmacologic properties, including the longest half-life among all ARBs; this leads to a 24-h sustained reduction of blood pressure. Besides well-known antihypertensive and cardioprotective effects, there is also strong clinical evidence that telmisartan confers renoprotection. Aryl hydrocarbon receptor (AhR) belongs to the steroid receptor family. 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) is an endogenous ligand of AhR. Cytochrome P450 (CYP) 1A1 is an AhR-target gene. In this article, we demonstrated that telmisartan (2.5-60 μM) enhanced CYP1A1 promoter activity and expressions of mRNA and protein. Telmisartan-induced CYP1A1 expression was blocked by the AhR antagonist CH-223191 in liver cell lines and was negligible in the AhR signaling-deficient mutant cells. In addition, telmisartan induced transcriptional activity mediated by aryl hydrocarbon response element in both human and mouse cells, and was able to induce AhR translocation into the nucleus. Accordingly, telmisartan is an AhR agonist. It also acted synergistically with ITE to further enhance the expression of CYP1A1 mRNA and protein. This synergistic effect was more pronounced in cells with AhR overexpression compared to those without. AhR activity has strong association with the progression of chronic renal disease. Our study demonstrated that telmisartan is an AhR agonist and has synergistic effect with ITE, an indole derivative, to potentiate the effect on AhR. This finding may provide additional clues about the mechanism of the protective effect of telmisartan on the kidney., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Balloon dilation of Eustachian tube (BDET) has been widely used as a minimally invasive treatment for obstructive Eustachian tube dysfunction (ETD). We used a Delphi consensus methodology to explore recommendations for clinical management of BDET in obstructive ETD., Procedure: A Delphi panel of 26 expert physicians of otology participated in two rounds of anonymous, iterative questionnaires. Consensus is defined as ≥ 70% of panelists agree with recommendation and disagreement as < 70% agree. The responses from the Delphi study were analyzed using both the content validity ratio and Kendall's coefficient of concordance., Results: The panel finally evaluated 26 topics, agreed 9 and did not reach consensus on 17 topics after 2 rounds. Although no consensus was reached on the postoperative follow-up period, a period of 12 months was most adopted. The Valsalva maneuver and questionnaire responses showed the highest agreement as postoperative assessment tools after BDET., Conclusion: Consensus was reached on some of the recommendations for the management of BEDT in obstructive ETD. The resultant agreement will provide directions for future research to describe standard postoperative management of BDET.

Background: Emerging evidence has underscored the harmful effects of air pollution on the upper airway. We investigated the relationship between ambient particulate matter (PM) level and the frequency of outpatient visits for chronic rhinosinusitis (CRS)., Methods: We conducted an ecological cohort study of US adults enrolled in The Merative MarketScan outpatient database from 2007 to 2020. For each geographical subunit (core-based statistical area [CBSA]), we calculated the annual rate of CRS-related outpatient visits per 1000 well-patient checkup visits (CRS-OV). Using data from the Environmental Protection Agency's Air Quality System, we mapped the rolling statistical average of daily PM 2.5 and PM 10 over the preceding year onto each CBSA × year combination. We employed multivariable negative binomial regression modeling to estimate the association between PM levels and subsequent CRS-OV., Results: Across 3933 observations (CBSA × year combinations), encompassing ∼4 billion visits, the median CRS-OV was 164 (interquartile range 110-267). The mean PM 2.5 level was 8.9 µg/m 3 (SD 2.6) and the mean PM 10 level was 20.2 µg/m 3 (SD 7.2). Adjusting for patient demographics and respiratory comorbidities, a compounded rise in subsequent CRS-OV was observed with increasing PM levels. Each µg/m 3 rise in PM 2.5 independently predicted a 10% increase in CRS-OV (adjusted incidence rate ratio [aIRR]) 1.10, 95% confidence interval [CI] 1.08-1.13) and each µg/m 3 rise in PM 10 independently predicted a 3% increase in CRS-OV (aIRR 1.03, 95% CI 1.02-1.04)., Conclusion: Elevated ambient PM 2.5 and PM 10 levels are associated with a subsequent compounded increase in the frequency of CRS-OV, with PM 2.5 predicting a more pronounced rise compared to PM 10 ., (© 2024 ARS‐AAOA, LLC.)

Transient receptor potential (TRP) ion channels have a crucial role as cellular sensors, mediating diverse physical and chemical stimuli. The formation of heteromeric structures expands the functionality of TRP channels; however, their molecular architecture remains largely unknown. Here we present the cryo-electron microscopy structures of the human TRPC1/TRPC4 heteromer in the apo and antagonist-bound states, both consisting of one TRPC1 subunit and three TRPC4 subunits. The heteromer structure reveals a distinct ion-conduction pathway, including an asymmetrically constricted selectivity filter and an asymmetric lower gate, primarily attributed to the incorporation of TRPC1. Through a structure-guided electrophysiological assay, we show that both the selectivity filter and the lower part of the S6 helix participate in deciding overall preference for permeating monovalent cations. Moreover, we reveal that the introduction of one lysine residue of TRPC1 into the tetrameric central cavity is enough to render one of the most important functional consequences of TRPC heteromerization: reduced calcium permeability. Our results establish a framework for addressing the structure-function relationship of the heteromeric TRP channels., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Magnetic resonance-guided focused ultrasound (MRgFUS) capsulotomy is a promising treatment for refractory obsessive-compulsive disorder (OCD); however, long-term clinical outcome studies are lacking. We aimed to investigate the long-term efficacy and safety of MRgFUS capsulotomy in patients with refractory OCD. Ten of the eleven patients who underwent MRgFUS capsulotomy for treatment-resistant OCD between 2013 and 2014 were included in this study. Clinical outcomes were assessed after 10 years of follow-up post-MRgFUS capsulotomy using tools such as neuropsychological test, the Frontal Systems Behavior Scale (FrSBe), and a locally developed MRgFUS-patient-centered outcomes questionnaire. After 10 years of follow-up, there was a mean improvement of 52.3% in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score. Seven out of the ten participants responded fully (Y-BOCS reduction ≥35% + CGI-I 1 or 2) to the procedure, two of whom achieved remission (Y-BOCS score ≤12 and CGI-S 1 or 2). Obsessive-compulsive symptoms and overall functioning significantly reduced and improved, respectively (Y-BOCS = 20.7 after 2 years vs. 16.4 after 10 years, p = 0.012; Global Assessment of Functioning = 57.4 after 2 years vs. 69.0 after 10 years, p = 0.011). The patients experienced significantly improved frontal lobe-related functions (FrSBe Sum before 91.0 ± 17.6 vs. after 78.6 ± 17.7, p < 0.05). No adverse effects, including cases of suicide and neurological deficits, were reported. The majority of the respondents were generally satisfied with MRgFUS capsulotomy. MRgFUS capsulotomy is an effective and safe treatment option for the treatment of severe refractory OCD with sustained efficacy even after 10 years., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Connexin 36 (Cx36) forms interneuronal gap junctions, establishing electrical synapses for rapid synaptic transmission. In disease conditions, inhibiting Cx36 gap junction channels (GJCs) is beneficial, as it prevents abnormal synchronous neuronal firing and apoptotic signal propagation, mitigating seizures and progressive cell death. Here, we present cryo-electron microscopy structures of human Cx36 GJC in complex with known channel inhibitors, such as mefloquine, arachidonic acid, and 1-hexanol. Notably, these inhibitors competitively bind to the binding pocket of the N-terminal helices (NTH), inducing a conformational shift from the pore-lining NTH (PLN) state to the flexible NTH (FN) state. This leads to the obstruction of the channel pore by flat double-layer densities of lipids. These studies elucidate the molecular mechanisms of how Cx36 GJC can be modulated by inhibitors, providing valuable insights into potential therapeutic applications., (© 2024. The Author(s).)

Background: Cancer is the leading cause of disease-related mortality in children. Causes of leukemia, the most common form, are largely unknown. Growing evidence points to an origin in-utero, when global redistribution of DNA methylation occurs driving tissue differentiation., Methods: Epigenome-wide DNA methylation was profiled in surrogate (blood) and target (bone marrow) tissues at birth, diagnosis, remission and relapse of pediatric pre-B acute lymphoblastic leukemia (pre-B ALL) patients. Double-blinded analyses was performed between prospective cohorts extending from birth to diagnosis and retrospective studies backtracking from clinical disease to birth. Validation was carried out using independent technologies and populations., Results: The imprinted and immuno-modulating VTRNA2-1 was hypermethylated (FDR<0.05) at birth in nested cases relative to controls in all tested populations (totaling 317 cases and 483 controls), including European and Hispanic ancestries. VTRNA2-1 methylation was stable over follow-up years after birth and across surrogate, target and other tissues (n=5,023 tissues; 30 types). When profiled in leukemic tissues from two clinical cohorts (totaling 644 cases), VTRNA2-1 methylation exhibited higher levels at diagnosis relative to controls, it reset back to normal levels at remission, and then re-increased to above control levels at relapse. Hypermethylation was significantly associated with worse pre-B ALL patient survival and with reduced VTRNA2-1 expression (n=2,294 tissues; 26 types), supporting a functional and translational role for VTRNA2-1 methylation., Conclusion: This study provides proof-of-concept to detect at birth epigenetic precursors of pediatric pre-B ALL. These alterations were reproducible with different technologies, in three continents and in two ethnicities, and can offer biomarkers for early detection and prognosis as well as actionable targets for therapy., (© 2024. The Author(s).)

Semimetal electrodes for 2D semiconductors have been extensively studied; however, research on p-type semimetals has been limited due to the scarcity of materials that satisfy both high work functions and low resistances. In response, we investigated the behavior of NiSe 2 as an electrode. Utilizing a novel co-evaporation method that suppresses oxidation and contamination, we synthesized NiSe 2 demonstrating a high work function of 5.53 eV, a low resistance of 5.81 × 10 -5 Ω cm, and a record hole concentration exceeding 10 23 cm -3 . We confirmed that when WSe 2 comes into contact with NiSe 2 , the Fermi level of WSe 2 falls below the work function of NiSe 2 , leading to complete hole degeneration of the channel. This unusual Fermi level alignment correlates with the high hole concentration in NiSe 2 and the maximum energy level of its hole pockets. Our research provides new insights into how an electrode's hole concentration affects channel behavior.

Introduction: Targeted protein degradation (TPD) has emerged as an innovative therapeutic strategy through selective degradation of specific proteins by harnessing the cellular ubiquitin-proteasome system (UPS), which involves over 600 E3 ubiquitin ligases. Recent proteome profiling reported tumor-specific E3 ligases in human. Development of those tumor-specific E3 ligase ligands would provide a solution for tumor-specific TPD for effective cancer treatment., Areas Covered: This review provides a comprehensive list of E3 ligases found only in specific types of tumor from public databases and highlights examples of their ligands discovered through fragment-based approaches. It details their discovery process and potential applications for precise TPD and effective cancer treatments., Expert Opinion: Current TPD strategies using proteolysis-targeting chimeras (PROTACs) primarily utilize general E3 ligases, such as CRBN and VHL. Since these E3 ligases demonstrate effective protein degradation activity in most human cell types, CRBN and VHL-based PROTACs can exhibit undesired TPD in off-target tissues, which often leads to the side effects. Therefore, developing tumor-specific E3 ligase ligands can be crucial for effective cancer treatments. Fragment-based ligand discovery (FBLD) approaches would accelerate the identification of these tumor-specific E3 ligase ligands and associated PROTACs, thereby advancing the field of targeted cancer therapies.

Off-target pesticide drift in paddy fields following unmanned aerial vehicle (UAV) spraying was evaluated using cellulose deposition samplers (CDSs). An analytical method for quantifying ferimzone Z and E isomers deposited on CDSs was developed using LC-MS/MS. The suitability of the CDS method was confirmed by comparing deposition patterns on CDSs with residue levels in rice plant samples. To assess pesticide deposition in paddy fields, CDSs were strategically placed at varying distances from target areas, followed by UAV spraying. The fungicide agrochemicals were applied with and without adjuvants, and wind direction affected the drift trajectory for all treatment groups. Adjuvants, particularly soy lecithin as the major component, significantly enhanced pesticide deposition within the spray pathway while reducing drift rates relatively by 47.9-68.0 %. Higher wind speeds were found to exacerbate drift, but adjuvant-treated sprays showed less variability in deposition patterns under these conditions. Pesticide residues in harvested brown rice were found to be below the maximum residue limits (MRLs), ensuring safety for consumption. These findings highlight the importance of selecting appropriate adjuvants in UAV-based pesticide applications to optimize deposition efficiency and minimize environmental contamination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Penicillin-binding protein 2 (PBP2), a vital protein involved in bacterial cell-wall synthesis, serves a target for β-lactam antibiotics. Acinetobacter baumannii is a pathogen notorious for multidrug resistance; therefore, exploration of PBPs is pivotal in the development of new antimicrobial strategies. In this study, the tertiary structure of PBP2 from A. baumannii (abPBP2) was elucidated using X-ray crystallography. The structural analysis demonstrated notable movement in the head domain, potentially critical for its glycosyltransferase function, suggesting that abPBP2 assumes a fully closed conformation. Our findings offer valuable information for developing novel antimicrobial agents targeting abPBP2 that are applicable in combating multidrug-resistant infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The pragmatic role of dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) needs to be evaluated and compared across distinct lymphatic disorders. We aimed to evaluate the performance of DCMRL for identifying the underlying causes of lymphatic disorders and to define the potential benefit of DCMRL for planning lymphatic interventions., Methods: Patients who underwent DCMRL between August 2017 and July 2022 were included in this retrospective analysis. DCMRL was performed with intranodal injection of a gadolinium-based contrast medium through inguinal lymph nodes under local anesthesia. Technical success of DCMRL and feasibility of percutaneous embolization were assessed based on the lymphatic anatomy visualized by DCMRL. Based on the underlying causes, clinical outcomes were evaluated and compared., Results: Seventy consecutive patients were included. The indications were traumatic chylothorax (n = 42), traumatic chylous ascites (n = 11), and nontraumatic lymphatic leak (n = 17). The technical success rate of DCMRL was the highest in association with nontraumatic lymphatic disorders (94.1% [16/17]), followed by traumatic chylothorax (92.9% [39/42]) and traumatic chylous ascites (81.8% [9/11]). Thirty-one (47.7%) patients among 65 patients who underwent technically successful DCMRL had feasible anatomy for intervention. Clinical success was achieved in 90.3% (28/31) of patients with feasible anatomy for radiologic intervention, while 62.5% (10/16) of patients with anatomical challenges showed improvement. Most patients with traumatic chylothorax showed improvement (92.9% [39/42]), whereas only 23.5% (4/17) of patients with nontraumatic lymphatic disorders showed clinical improvement., Conclusion: DCMRL can help identify the underlying causes of lymphatic disorders. The performance of DCMRL and clinical outcomes vary based on the underlying cause. The feasibility of lymphatic intervention can be determined using DCMRL, which can help in predicting clinical outcomes., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Aramid copolymers have garnered significant interest due to their potential applications in extreme environments such as the aerospace, defense, and automotive industries. Recent developments in aramid copolymers have moved beyond their traditional use in high-strength, high-temperature resistant fibers. There is now a demand for new polymers that can easily be processed into thin films for applications such as electrical insulation films and membranes, utilizing the inherent properties of aramid copolymers. In this work, we demonstrate two novel aramid copolymers that are capable of polymerizing in polar organic solvents with a high degree of polymerization, achieved by incorporating flexible bis(4-aminophenoxy) benzene moieties into the chain backbone. The synthesized MBAB-aramid and PBAB-aramid have enabled the fabrication of exceptionally thin, clear films, with an average molecular weight exceeding 150 kDa and a thickness ranging from 3 to 10 μm. The dynamic mechanical analysis (DMA) and thermogravimetric analysis (TGA) reveal that the thin films of MBAB-aramid and PBAB-aramid exhibited glass transition temperatures of 270.1 °C and 292.7 °C, respectively, and thermal decomposition temperatures of 449.6 °C and 465.5 °C, respectively. The mechanical tensile analysis of the 5 μm thick films confirmed that the tensile strengths, with elongation at break, are 107.1 MPa (50.7%) for MBAB-aramid and 113.5 MPa (58.4%) for PBAB-aramid, respectively. The thermal and mechanical properties consistently differ between the two polymers, which is attributed to variations in the linearity of the polymer structures and the resulting differences in the density of intermolecular hydrogen bonding and pi-pi interactions. The resulting high-strength, ultra-thin aramid materials offer numerous potential applications in thin films, membranes, and functional coatings across various industries.

Background: Glioblastoma (GBM), a primary malignant brain tumor, has a poor prognosis, even with standard treatments such as radiotherapy and chemotherapy. In this study, we explored the anticancer effects of the synergistic combination of perphenazine (PER), a dopamine receptor D2/3 (DRD2/3) antagonist, and temozolomide (TMZ), a standard treatment for GBM, in patient-derived human GBM tumorspheres (TSs)., Methods: The biological effects of the combination of PER and TMZ in GBM TSs were assessed by measuring cell viability, ATP, stemness, invasiveness, and apoptosis. Changes in protein and mRNA expression were analyzed using western blotting and RNA sequencing. Co-administration of PER and TMZ was evaluated in vivo using a mouse orthotopic xenograft model., Results: The Severance dataset showed that DRD2 and DRD3 expression was higher in tumor tissues than in the tumor-free cortex of patients with GBM. DRD2/3 knockout by CRISPR/Cas9 in patient-derived human GBM TSs inhibited cell growth and ATP production. The combined treatment with PER and TMZ resulted in superior effects on cell viability and ATP assays compared to those in single treatment groups. Flow cytometry, western blotting, and RNA sequencing confirmed elevated apoptosis in GBM TSs following combination treatment. Additionally, the combination of PER and TMZ downregulated the expression of protein and mRNA associated with stemness and invasiveness. In vivo evaluation showed that combining PER and TMZ extended the survival period of the mouse orthotopic xenograft model., Conclusions: The synergistic combination of PER and TMZ has potential as a novel combination treatment strategy for GBM., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Objective: Computed tomography (CT) imaging of the temporal bone constitutes an integral element in the diagnostic workup of superior canal dehiscence (SCD). This study explores the utility of a clinically efficient method of manually estimating SCD size on CT imaging in predicting surgical outcomes., Study Design: Cohort study., Setting: Tertiary center., Methods: Consecutive middle fossa repairs of SCD between 2011 and 2022 were included. Measurements of approximate dehiscence area (ADA), a previously established estimation method, on temporal bone CT imaging were performed by trained raters blind to clinical information. Surgical outcomes, evaluated with symptom resolution and audiometric improvement following repair, were assessed in multivariable regression models with ADA as the primary predictor and patient demographics and other history factors as covariates., Results: Among 311 cases included, mean ADA was 2.68 mm 2 , and 71% of cases achieved overall symptom improvement (OSI). Every 1 mm 2 rise in ADA predicted on average 3 dB greater narrowing of low-frequency air-bone gap (β 95% confidence interval, CI [-5.4, -0.7]) but 50% lower odds of OSI (adjusted odds ratio: 95% CI [0.32, 0.78]) among unilateral SCD cases. A model incorporating ADA, patient demographics, and history factors predicted OSI with a sensitivity, specificity combination as high as 85%, 73% and a positive predictive value, negative predictive value combination as high as 85%, 82% (area under the curve: 95% CI: 0.76-0.93)., Conclusion: Increased ADA predicts more pronounced audiometric improvement but poorer symptomatic response among unilateral SCD cases. ADA is an efficient and practical method of estimating SCD size and demonstrated clinical utility in accurately predicting surgical outcomes., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Objective: To investigate the state and trajectory of gender, racial, and academic authorship diversity in the otolaryngology clinical trial literature over the past 2 decades., Study Design: Bibliometric analysis., Setting: Otolaryngology clinical trial literature., Methods: Clinical trials published in the 9 major otolaryngology journals between 2000 and 2020 were included. The gender, race, and academic seniority of the first, senior, and corresponding authors were recorded for each trial. Multivariable regression models assessed the temporal trajectory of authorship diversity over time and the disparity in citations across author characteristics. Models adjusted for relevant confounders pertaining to publication environment and study design., Results: Among 2117 trials, first, senior, and corresponding authors have been predominantly White (60%-64%), male (76%-80%), and attending physicians (63%-69%). Trials led by Black (<1%) and Hispanic (<5%) authors were severely underrepresented. Over time, the representation of female (adj. β 0.8%, 95% CI [0.5%, 1.1%] per year), Asian (1.0% [0.7%, 1.3%] per year), and MD resident (0.4% [0.1%, 0.7%] per year) first authorship increased, but representation of female (0.2% [-0.1%, 0.5%] per year), Black (0% [-0.03%, 0.02%] per year), Hispanic (-0.2% [-0.33%, -0.02%] per year) senior authorship remained persistently low. Asian-led trials were cited significantly less compared to White-led trials even after adjusting for study design and publication year (aIRR 0.82 [0.73, 0.92])., Conclusions: Despite promising signs of improving authorship diversity over time, persistent underrepresentation of female, Black, Hispanic senior authorship underscore the need for additional efforts to diversify the otolaryngology clinical science workforce., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background: We compared and analyzed the surgical results of fat myringoplasty between elderly and young adult patients with chronic otitis media. We also investigated whether underlying diseases and other factors impact the surgical outcome., Methods: We retrospectively reviewed the data of 141 patients who underwent fat myringoplasty for chronic otitis media for five years. They were compared by age, sex, underlying disease, perforation size, pre- and postoperative pure tone audiometry, postoperative otorrhea, postoperative re-perforation, and cause of re-perforation., Result: Postoperative re-perforation was more common in the elderly group, albeit with no significant difference (p = 0.072). The factors affecting re-perforation were insufficient fat graft (44.4%), postoperative infection (33.3%), and nasal blowing (22.2%). Our findings revealed no significant association between preoperative perforation size and re-perforation (p = 0.391). Additionally, we found no significant relationship between hypertension and re-perforation (p > 0.99), nor between age group and postoperative infection (p = 0.488). Diabetes was also not significant (p = 0.640). Following surgery, both groups exhibited a significant improvement in hearing., Conclusion: Although age and underlying conditions play significant roles in the healing process, our results suggest that external factors such as infection, nasal blowing, cough, and insufficient grafted fat tissue have a similarly significant impact on surgical outcomes in elderly patients with COM as they do in adults. In conclusion, the decision to perform surgery in elderly patients with COM should be based on a comprehensive assessment of the patient's overall health status, hearing, use of hearing aids, and the indications for surgery., (© 2024. The Author(s).)