Search

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.)

Objectives: This study explores the connection between chronic stress and tinnitus, a phantom auditory perception, using an animal model., Methods: Rats were subjected to 2 h of daily restraint stress for 10 days. Tinnitus was assessed on the last day of stress exposure using the gap response of pre-pulse inhibition acoustic reflex, measured at 60 dB background sound level at 8, 16, and 20 kHz. Chronic stress-exposed rats were categorized into two groups: tinnitus (RTG) and non-tinnitus (RNTG). Various tests, including hearing assessments (distortion product otoacoustic emissions and auditory brainstem response), behavioral evaluations (elevated plus maze test and forced swimming test), and immunohistochemical studies in the auditory and limbic brain regions, were conducted to understand the relationship between chronic stress, tinnitus, and behavioral changes., Results: Following chronic restraint stress, 64.3% of the rats exhibited tinnitus with no audiometric changes. EPM and FST indicated an increase of anxiety- and depression-related behavior in RTG. Immunohistochemical analyses identified specific alterations in the expression of neurotransmitter receptors within brain regions implicated in tinnitus. Specifically, we observed a decrease in γ-aminobutyric acid A receptor α1 expression and an increase in glutamate receptor (N-methyl-D-aspartate receptor subunit 1 and receptor subunit 2B) expression in specific brain region. These changes suggest a reorganization of neural circuits associated with the tinnitus generation and behavioral changes of the rats after chronic stress exposure., Conclusion: Chronic stress alone can be a causal factor for the generation of tinnitus and behavioral changes through altered neural activities in tinnitus-related brain networks., Level of Evidence: NA Laryngoscope, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: The molecular mechanisms by which stress leads to the development of tinnitus are not yet well understood. This study aimed to identify brain changes in a stress-induced tinnitus (ST) animal model through transcriptome analysis of the prefrontal lobe and hippocampus., Methods: Twenty Sprague-Dawley rats were subjected to restraint stress for 2 h. Following the gap prepulse inhibition of the acoustic startle (GPIAS) reflex test to assess tinnitus development, the prefrontal lobes and hippocampi of the brains were harvested from 15 rats: five with evident tinnitus (ST), five with noticeable non-tinnitus (stress-induced non-tinnitus; SNT), and five without stress (control group). Comparative RNA-seq analysis was conducted to examine gene expression profiles., Results: In comparison to the control group, the ST group exhibited 971 and 463 differentially expressed genes (DEGs) in the prefrontal lobe and hippocampus, respectively (FDR < 0.05). The SNT group showed a largely similar gene expression to the control group. Enrichment analysis of the prefrontal lobe revealed the downregulation of gene sets associated with neurotransmitter and synapse-related functions and the upregulation of cell cycle-related gene sets in the ST group. In the hippocampus, there were significantly downregulated gene sets associated with steroid production and upregulated gene sets related to the extracellular matrix in the ST group. Immune-related gene sets were upregulated in both the prefrontal lobe and hippocampus., Conclusion: Our research presents evidence that differences in genetic expression in the prefrontal lobe and hippocampus after exposure to stress play a significant role in the development of tinnitus., Level of Evidence: NA Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Koenigia alpina (All.) T.M.Schust. & Reveal (alpine knotweed) is a perennial herb belonging to the Polygonaceae family. Several studies have examined Polygonaceae species' potential applications as cosmeceutical materials; however, the potential of K. alpina as a cosmeceutical has not yet been studied., Materials and Methods: Hydrogen peroxide (H 2 O 2 ) and lipopolysaccharide were used to induce an inflammatory response in RAW 264.7 cells. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radicals and H 2 O 2 were used to evaluate the free-radical scavenging activity of K. alpina extract and its protective effect against reactive oxygen species (ROS)-induced cell damage. The whitening, antiaging, and cell proliferation/migration effects of the extracts were evaluated via tyrosinase inhibition, collagenase/elastase inhibition, and wound healing assays, respectively. The anti-inflammatory effect was confirmed by evaluating nitric oxide (NO) production in RAW 264.7 cells. High-performance liquid chromatography (HPLC), UV, and MS/MS were used to determine the main components of the extract and fractions., Results: The ethyl acetate (EA) fraction and its aglycone fraction showed very high free-radical scavenging activities (47.5 and 47.1 µg/mL, respectively). The extract/fractions also showed significant tyrosinase inhibition (IC 50 = 0.38 mg/mL in EA fraction), collagenase inhibition (IC 50 = 0.21 mg/mL in EA fraction), and elastase inhibition (IC 50 = 0.57 mg/mL in aglycone fraction). NO production in lipopolysaccharide-induced RAW 264.7 cells was inhibited by the extract/fractions. The extract also promoted the closure of scratch wounds in HaCaT cells. The K. alpina extract/fractions contained cardamonin, quercetin, and quercitrin., Conclusion: K. alpina extracts/fractions showed antioxidant, antiaging, whitening, and anti-inflammatory activities, suggesting they may have potential as antiaging cosmeceuticals., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Objectives: Vitamin D deficiency as a risk factor of tinnitus has not been well known. We tried to evaluate the association between the serum 25-(OH) vitamin D levels and tinnitus among the Korean population to propose the possible role of serum vitamin D in patients with tinnitus., Methods: This cross-sectional study investigated the potential risk factors of tinnitus in relation to serum 25(OH)D levels within the Korean population. It encompassed a health interview, nutrition assessment, and a health examination. Data was sourced from the KNHANES V (2010-2012), conducted by the Division of Health and Nutritional Survey under the Korean Centers for Disease Control and Prevention (KCDCP). Participants were chosen from various sampling units categorized by geography, gender, and age group. The selection was facilitated through household registries using a stratified, multistage, clustered probability sampling approach., Results: Data of 16 408 subjects were collected in this study. There were significant differences in gender, economic status, educational level, and sun exposure duration between the tinnitus and non-tinnitus groups. Serum 25(OH) vitamin D level between hearing loss and normal hearing was also significantly different. The logistic regression models with serum 25(OH) vitamin D quartile and tinnitus as the dependent variable, which were controlled for age, sex, smoking status, BMI, diabetes, hypertension, sun exposure, regular exercise, income, and education, eventually demonstrated that serum vitamin D deficiency and low sun exposure duration significantly increased the risk of tinnitus development., Conclusion: This study demonstrated a significant association between serum vitamin D levels and tinnitus, driven by large epidemiological data. The results of our study provide baseline data for further research to investigate the role of vitamin D in the pathogenesis and management of tinnitus., 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.

Background: While mastoid obliteration techniques have received much attention in decreasing the disadvantages associated with the resultant mastoid cavity from canal wall down procedures, techniques for an anatomically normal looking ear canal reconstruction to increase the feasibility of hearing aid fitting are less commonly discussed as an alternative., Methods: Our mastoidoplasty technique basically utilises an inferiorly based periosteal flap with or without temporalis muscles and fascia to obliterate the epitympanum and reconstruct the external auditory canal (EAC). Stay sutures are used to keep them in place. For larger cavities, demineralized bone matrix (DBM) is used to obliterate the mastoid cavity and support the neo-EAC., Conclusions: The concept of our mastoidoplasty potentially provides a very useful alternative in recreating a near normal ear canal anatomy avoiding cavity problems as well as facilitating hearing aid fitting with canal type hearing aids after canal wall down mastoidectomy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Middle ear myoclonic tinnitus (MEMT) is a disease caused by myoclonus or abnormal contractive movement of middle ear muscles (MEMs). This translational study was conducted to propose intratympanic botulinum toxin (IT-BTX) injection as a new therapeutic modality to treat MEMT., Study Design: Animal experiment and nonrandomized controlled clinical trial., Setting: Laboratory and medical center of an academic tertiary medical institution., Methods: For the animal study, male Sprague-Dawley rats were divided into 4 subgroups according to the sacrificing day after IT-BTX injection. After initial hearing tests, randomly assigned experimental ears were intratympanically injected with 1 unit/100 μL of BTX-A, whereas control ears were injected with normal saline. Changes in the hearing thresholds, morphometry of the cochleae, electron microscopy study, and immunofluorescence analysis of MEMs were evaluated. For the human study, 10 intractable MEMT patients were enrolled. The hearing thresholds and the degree of tinnitus distress were observed for changes after IT-BTX injection. All patients were followed up for 3 months., Results: As for the animal study, there were no significant changes in hearing thresholds and cochlear morphologies in all 4 subgroups of the rats. Significant MEM degenerations and immuno-detection of cleaved synaptosome-associated protein of 25 kDa (cSNAP-25) indicated the efficacy of IT-BTX. MEMT patients enrolled for the pilot clinical trial showed statistically significant improvement in tinnitus after IT-BTX injection. No major complications were noted., Conclusion: The new therapeutic modality of IT-BTX injection for the treatment of MEMT seems highly promising with an excellent result., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Objectives: To analyze the sizes of the stapedius and tensor tympani (TT) muscles using a temporal bone CT (TBCT) scan in patients with middle ear myoclonic tinnitus (MEMT) and investigate their value for the diagnosis of this rare cause of tinnitus., Methods: Medical records and TBCT of patients with MEMT or vascular tinnitus (VT) at Seoul St. Mary's Hospital from January 2012 to December 2022 were reviewed. The stapedius and TT muscles were analyzed., Results: Thirty-eight patients with unilateral MEMT and 39 patients with VT were included. More males were in the MEMT group compared to the VT group (MEMT: n  = 24, VT: n  = 8, p  = .001). The mean age of the MEMT group was younger compared to the VT group (MEMT: 35 ± 12 years, VT: 44 ± 14.3 years, p  = .005). The mean BMI for the MEMT group was less than the VT group (MEMT: 22.3 ± 2.5, VT: 24.8 ± 4.36, p  = .010). The mean length and width of the stapedius in the MEMT group were larger than those of the VT group ( Length MEMT: 1.47 ± 0.60 mm, VT: 0.98 ± 0.24 mm, p  = .001; Width MEMT: 0.89 ± 0.32 mm, VT: 0.72 ± 0.19 mm, p  = .009). The mean length and width of the TT in the MEMT group were larger than that of the VT group ( Length MEMT: 3.10 ± 0.50 mm, VT: 2.27 ± 0.42, p  = .001; Width MEMT: 2.02 ± 0.36, VT: 1.75 ± 0.26 p  = .001)., Conclusion: The mean length and width of the stapedius and TT muscles measured in the MEMT group were longer and wider than the VT group. This suggests the use TBCT scan as a diagnostic tool for MEMT. Further studies with a larger study group to validate the results of this study are recommended.Level of Evidence: 4., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Purpose: This study is descriptive research aiming to identify factors influencing the stigma experienced by college students with coronavirus disease 2019 (COVID-19), focusing on COVID-19 pandemic stress, depression, and fear of negative evaluation as the main variables., Methods: An online survey was administered to 175 college students who had been diagnosed with COVID-19 from January to May 2022 and were enrolled in universities in Seoul, Cheongju, and Daegu, South Korea. The survey collected data on pandemic stress, depression, fear of negative evaluation, and stigma. The data were analyzed using the t-test, ANOVA, the Scheffé test, Pearson's correlation coefficients, and stepwise multiple regression in SPSS/WIN 26.0., Results: We analyzed differences in stigma scores based on general characteristics of the college students and found significant differences in stigma scores by age, major satisfaction, interpersonal satisfaction, date of COVID-19 confirmation, treatment modality, and recent subjective health condition. Factors influencing stigmatization were identified as COVID-19 pandemic stress, depression, date of COVID-19 confirmation, treatment modality, recent subjective health condition, and major satisfaction, with an overall explanatory power of 37.6%., Conclusion: This study is significant as it identifies emotional changes across various aspects of pandemic stress, depression, fear of negative evaluation, and stigma among college students who have been diagnosed with COVID-19. The findings of this study suggest the development of programs to reduce psychological distress and enhance mental health management skills among these students.

Fusobacterium nucleatum (Fn), a bacterium present in the human oral cavity and rarely found in the lower gastrointestinal tract of healthy individuals 1 , is enriched in human colorectal cancer (CRC) tumours 2-5 . High intratumoural Fn loads are associated with recurrence, metastases and poorer patient prognosis 5-8 . Here, to delineate Fn genetic factors facilitating tumour colonization, we generated closed genomes for 135 Fn strains; 80 oral strains from individuals without cancer and 55 unique cancer strains cultured from tumours from 51 patients with CRC. Pangenomic analyses identified 483 CRC-enriched genetic factors. Tumour-isolated strains predominantly belong to Fn subspecies animalis (Fna). However, genomic analyses reveal that Fna, considered a single subspecies, is instead composed of two distinct clades (Fna C1 and Fna C2). Of these, only Fna C2 dominates the CRC tumour niche. Inter-Fna analyses identified 195 Fna C2-associated genetic factors consistent with increased metabolic potential and colonization of the gastrointestinal tract. In support of this, Fna C2-treated mice had an increased number of intestinal adenomas and altered metabolites. Microbiome analysis of human tumour tissue from 116 patients with CRC demonstrated Fna C2 enrichment. Comparison of 62 paired specimens showed that only Fna C2 is tumour enriched compared to normal adjacent tissue. This was further supported by metagenomic analysis of stool samples from 627 patients with CRC and 619 healthy individuals. Collectively, our results identify the Fna clade bifurcation, show that specifically Fna C2 drives the reported Fn enrichment in human CRC and reveal the genetic underpinnings of pathoadaptation of Fna C2 to the CRC niche., (© 2024. The Author(s).)

Background: Hearing rehabilitation with auditory training (AT) is necessary to improve speech perception ability in patients with hearing loss. However, face-to-face AT has not been widely implemented due to its high cost and personnel requirements. Therefore, there is a need for the development of a patient-friendly, mobile-based AT program., Objective: In this study, we evaluated the effectiveness of hearing rehabilitation with our chat-based mobile AT (CMAT) program for speech perception performance among experienced hearing aid (HA) users., Methods: A total of 42 adult patients with hearing loss who had worn bilateral HAs for more than 3 months were enrolled and randomly allocated to the AT or control group. In the AT group, CMAT was performed for 30 minutes a day for 2 months, while no intervention was provided in the control group. During the study, 2 patients from the AT group and 1 patient from the control group dropped out. At 0-, 1- and 2-month visits, results of hearing tests and speech perception tests, compliance, and questionnaires were prospectively collected and compared in the 2 groups., Results: The AT group (n=19) showed better improvement in word and sentence perception tests compared to the control group (n=20; P=.04 and P=.03, respectively), while no significant difference was observed in phoneme and consonant perception tests (both P>.05). All participants were able to use CMAT without any difficulties, and 85% (17/20) of the AT group completed required training sessions. There were no changes in time or completion rate between the first and the second month of AT. No significant difference was observed between the 2 groups in questionnaire surveys., Conclusions: After using the CMAT program, word and sentence perception performance was significantly improved in experienced HA users. In addition, CMAT showed high compliance and adherence over the 2-month study period. Further investigations are needed to validate long-term efficacy in a larger population., Trial Registration: Clinical Research Information Service (CRiS) KCT0006509; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22110&search&#95;page=L., (© Jae Sang Han, Ji Hyung Lim, Yeonji Kim, Aynur Aliyeva, Jae-Hyun Seo, Jaehyuk Lee, Shi Nae Park. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org).)

Background: Tinnitus is a bothersome condition associated with various symptoms. However, the mechanisms of tinnitus are still uncertain, and a standardized assessment of the diagnostic criteria for tinnitus is required. We aimed to reach a consensus on diagnosing tinnitus with professional experts by conducting a Delphi study with systematic review of the literature., Methods: Twenty-six experts in managing tinnitus in Korea were recruited, and a two-round modified Delphi study was performed online. The experts evaluated the level of agreement of potential criteria for tinnitus using a scale of 1-9. After the survey, a consensus meeting was held to establish agreement on the results obtained from the Delphi process. Consensus was defined when over 70% of the participants scored 7-9 (agreement) and fewer than 15% scored 1-3 (disagreement). To analyze the responses of the Delphi survey, the content validity ratio and Kendall's coefficient of concordance were evaluated., Results: Consensus was reached for 22 of the 38 statements. For the definition of tinnitus, 10 out of 17 statements reached consensus, with three statements achieving complete agreement including; 1) Tinnitus is a conscious perception of an auditory sensation in the absence of a corresponding external stimulus, 2) Tinnitus can affect one's quality of life, and 3) Tinnitus can be associated with hearing disorders including sensorineural hearing loss, vestibular schwannoma, Meniere's disease, otosclerosis, and others. For the classification of tinnitus, 11 out of 18 statements reached consensus. The participants highly agreed with statements such as; 1) Vascular origin is expected in pulse-synchronous tinnitus, and 2) Tinnitus can be divided into acute or chronic tinnitus. Among three statements on the diagnostic tests for tinnitus only Statement 3, "There are no reliable biomarkers for sensory or emotional factors of tinnitus." reached consensus. All participants agreed to perform pure-tone audiometry and tinnitus questionnaires, including the Tinnitus Handicap Inventory and Tinnitus Questionnaire., Conclusion: We used a modified Delphi method to establish a consensus-based definition, a classification, and diagnostic tests for tinnitus. The expert panel reached agreement for several statements, with a high level of consensus. This may provide practical information for clinicians in managing tinnitus., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Objective: To investigate the safety and efficacy of a novel active transcutaneous bone conduction implant (BCI) device for patients with single-sided deafness (SSD)., Study Design: Prospective cohort study., Setting: Tertiary referral hospitals., Methods: This prospective multicenter study was conducted at 15 institutions nationwide. Thirty adult (aged ≥19 years) SSD patients were recruited. They underwent implantation of an active transcutaneous BCI device (Bonebridge BCI602). Objective outcomes included aided pure-tone thresholds, aided speech discrimination scores (SDSs), and the Hearing in Noise Test (HINT) and sound localization test results. The Bern Benefit in Single-Sided Deafness (BBSS) questionnaire, the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire, and the Tinnitus Handicap Inventory (THI) were used to measure subjective benefits., Results: The mean aided pure-tone threshold was 34.2 (11.3), mean (SD), dB HL at 500 to 4000 Hz. The mean total BBSS score was 27.5 (13.8). All APHAB questionnaire domain scores showed significant improvements: ease of communication, 33.6 (23.2) versus 22.6 (21.3), P = .025; reverberation, 44.8 (16.6) versus 32.8 (15.9), P = .002; background noise, 55.5 (23.6) versus 35.2 (18.1), P < .001; and aversiveness, 36.7 (22.8) versus 25.8 (21.4), P = .028. Moreover, the THI scores were significantly reduced [47.4 (30.1) versus 31.1 (27.0), P = .003]. Congenital SSD was a significant factor of subjective benefit (-11.643; 95% confidence interval: -21.946 to -1.340)., Conclusion: The BCI602 active transcutaneous BCI device can provide functional hearing gain without any adverse effects and is a feasible option for acquired SSD patients with long-term deafness., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Background: The upright head roll test (UHRT) is a recently introduced diagnostic maneuver for lateral semicircular canal benign paroxysmal positional vertigo (LSC-BPPV)., Objective: This study aimed to evaluate the reliability and validity of the UHRT., Methods: Two separate studies were conducted. Study 1 analyzed 827 results of videonystagmography (VNG) to assess UHRT reliability, and Study 2 analyzed 130 LSC-BPPV cases to evaluate UHRT validity., Results: The inter-test reliability between UHRT and the supine head roll test (SHRT) showed substantial agreement (Cohen's kappa = 0.753) in direction-changing positional nystagmus (DCPN) and almost perfect agreement (Cohen's kappa = 0.836) in distinguishing the direction of DCPN. The validity assessment of UHRT showed high accuracy in diagnosing LSC-BPPV (80.0%) and in differentiating the variant types (74.6%). UHRT was highly accurate in diagnosing the canalolithiasis type in LSC-BPPV patients (Cohen's kappa = 0.835); however, it showed only moderate accuracy in diagnosing the cupulolithiasis type (Cohen's kappa = 0.415). The intensity of nystagmus in UHRT was relatively weaker than that in SHRT (P < 0.05)., Conclusion: UHRT is a reliable test for diagnosing LSC-BPPV and distinguishing subtypes. However, UHRT has a limitation in discriminating the affected side owing to a weaker intensity of nystagmus than SHRT.

Introduction: Lazertinib, a third-generation mutant-selective EGFR tyrosine kinase inhibitor, improved progression-free survival compared with gefitinib in the phase 3 LASER301 study (ClinicalTrials.gov Identifier: NCT04248829). Here, we report the efficacy of lazertinib and gefitinib in patients with baseline central nervous system (CNS) metastases., Methods: Treatment-naive patients with EGFR-mutated advanced NSCLC were randomized one-to-one to lazertinib (240 mg/d) or gefitinib (250 mg/d). Patients with asymptomatic or stable CNS metastases were included if any planned radiation, surgery, or steroids were completed more than 2 weeks before randomization. For patients with CNS metastases confirmed at screening or subsequently suspected, CNS imaging was performed every 6 weeks for 18 months, then every 12 weeks. End points assessed by blinded independent central review and Response Evaluation Criteria in Solid Tumors version 1.1 included intracranial progression-free survival, intracranial objective response rate, and intracranial duration of response., Results: Of the 393 patients enrolled in LASER301, 86 (lazertinib, n = 45; gefitinib, n = 41) had measurable and or non-measurable baseline CNS metastases. The median intracranial progression-free survival in the lazertinib group was 28.2 months (95% confidence interval [CI]: 14.8-28.2) versus 8.4 months (95% CI: 6.7-not reached [NR]) in the gefitinib group (hazard ratio = 0.42, 95% CI: 0.20-0.89, p = 0.02). Among patients with measurable CNS lesions, the intracranial objective response rate was numerically higher with lazertinib (94%; n = 17) versus gefitinib (73%; n = 11, p = 0.124). The median intracranial duration of response with lazertinib was NR (8.3-NR) versus 6.3 months (2.8-NR) with gefitinib. Tolerability was similar to the overall LASER301 population., Conclusions: In patients with CNS metastases, lazertinib significantly improved intracranial progression-free survival compared with gefitinib, with more durable responses., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Objective: Review of a sigmoid sinus diverticuli (SSDi) variants surgically managed with a novel technique using an inferior periosteal flap., Study Design: Case series., Setting: Tertiary referral center., Patients: Patients presenting with pulsatile tinnitus to a tertiary referral center between January 1, 2015, and June 31, 2021, who were diagnosed with SSDi variants on CT temporal bone and who received surgical management for these SSDi variants., Interventions: Obliteration of SSDi variants using a novel technique with an inferiorly based periosteal flap., Main Outcome Measures: Pure-tone audiometry, Tinnitus Handicap Inventory score, and visual analogue scale score for tinnitus severity (loudness, awareness, annoyance, and effect on life)., Results: Include statistical measures as appropriate., Conclusions: We would like to propose the use of an inferiorly based periosteal flap as an option for obliteration and concomitant hemostasis of more sizeable or complex (e.g., bifid) SSDi. Further study of this technique with a long-term follow-up will be needed to evaluate its long-term safety and efficacy., Competing Interests: Conflict of interest statement: The authors disclose no conflicts of interest., (Copyright © 2023, Otology & Neurotology, Inc.)

Background: The risk of disasters and infectious diseases continues to persist in modern times. Children are a vulnerable group in disaster prevention and management due to their limited ability to cope on their own. Hence, the role and disaster preparedness capacity of early childhood teachers (ECTs) is vital for children's protection., Objectives: This study aims to explore how ECTs can improve their personal resilience to adapt to and overcome disasters as part of early childhood education and care (ECEC). To this end, this study examined the effects of ECTs' self-efficacy, resilience, disaster awareness, COVID-19 stress, and work-related stress on their disaster preparedness., Results: According to the outcomes of disaster preparedness of ECTs based on their general and job characteristics, full-time employees and principals scored significantly higher in work-related disaster preparedness (WrDP) compared to part-time workers and general and assistant teachers, respectively. Resilience and WrDP were identified as influencing factors of general disaster preparedness (GdP), with an explanatory power of 26.4%. GdP and self-efficacy were identified as influencing factors of WrDP, with an explanatory power of 25.7%., Discussion: According to the findings, ECTs' self-efficacy and GdP must be improved, followed by developing strategies to strengthen their resilience and WrDP. Doing so would ensure the safety and disaster preparedness of ECTs and infants who have low self-care capacity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lee, Park, Lee and Nam.)

Objectives: Sigmoid sinus resurfacing (SS-R) is one of the most effective surgical treatments for patients with pulsatile tinnitus (PT) originating from anatomical variants of the vascular walls in the temporal bone. This study aimed to provide updated information on the clinical outcomes of SS-R and evaluate the efficacy of the water occlusion test (WOT) as an additional diagnostic modality., Methods: We retrospectively reviewed medical records including tinnitus questionnaires, temporal bone computed tomography (TBCT) scans, audiologic tests, and preoperative WOT., Results: from patients who underwent SS-R., Results: In total, 26 patients were included in the study. The mean age was 44 years, and the mean symptom duration was 3 months. Fourteen patients (53.8%) were completely cured, seven (26.9%) significantly improved, and five (19.2%) remained stable. The mean visual analog scale loudness score decreased from 5.26 to 1.34 (P<0.001) and the mean Tinnitus Handicap Inventory score also improved from 50.23 to 5.5 (P<0.001) after SS-R surgery. In 10 patients with discrepancies between the preoperative TBCT and intraoperative findings, WOT showed a significant additive effect in predicting surgical outcomes. No patients experienced severe intraoperative or postoperative complications during the entire follow-up period., Conclusion: SS-R provides significant symptom improvement in patients with sigmoid sinus dehiscence who had a positive WOT without other sigmoid sinus variants. A combined diagnostic approach with TBCT, WOT, and intraoperative findings is crucial for achieving better surgical outcomes in patients with PT caused by sigmoid sinus variants.

Objectives: The aim of this study was to determine the most effective treatment approach by comparing the impacts of various otolith reduction techniques in patients with apogeotropic lateral semicircular canal benign paroxysmal positional vertigo (LC-BPPV)., Methods: We performed a multicenter randomized prospective study from January to December 2015, involving 72 consecutive patients with apogeotropic LC-BPPV. The patients were divided into three treatment groups: therapeutic head-shaking (group A), the Gufoni-Appiani maneuver (group B), and the cupulolith repositioning maneuver (CuRM; group C). Each group underwent evaluation and treatment up to the fourth week. Treatment success was defined as the disappearance of positional vertigo and nystagmus., Results: This study included 72 patients (49 male and 23 female), with a mean (±standard deviation) age of 55.4±13.5 years. The mean duration of vertigo experienced prior to treatment was 3.9±4.4 days. The mean latency and duration of nystagmus were 2.7±3.0 seconds and 47.9±15.8 seconds, respectively. The overall treatment frequency was 2.0±0.9. The number of treatments differed significantly among the three groups (P<0.05). After 4 weeks, the success rates for groups A, B, and C were 90.5%, 92.3%, and 100%, respectively. No significant difference was observed in the success rate across treatment., Methods: and periods (P>0.05). However, CuRM was the only method with a 100% treatment success rate., Conclusion: While no clear difference was observed among the three treatments for LC-BPPV, CuRM was found to be superior to the other approaches in the long term.

We present an integrating hemisphere-based (i.e., a variant of integrating spheres) implementation of the indirect illumination method for absolute photoluminescence quantum yield measurements, which is a recommended method in the international standard IEC 62607-3-1:2014. We rigorously formulated a mathematical model and a measurement procedure for the absolute photoluminescence quantum yield measurement in the integrating hemisphere-based system. The measurement system was calibrated using an Hg-Ar discharge lamp and spectral irradiance standard lamps for wavelength and relative spectral radiant flux scales, respectively. Furthermore, we identified and evaluated uncertainty components involved in the photoluminescence quantum yield (PLQY) measurement. To validate our measurement system, we applied it to the two de facto standard dyes: quinine bisulfate (QBS) and fluorescein (FLS). Consequently, their PLQY values were determined to be 0.563±0.024 ( k =2) and 0.876±0.032 ( k =2) for, respectively, QBS and FLS, which are consistent with previous reports.

The purposes of this study were to examine the compositional changes in the salivary microbiota according to the severity of periodontal disease and to verify whether the distribution of specific bacterial species in saliva can distinguish the severity of disease. Saliva samples were collected from 8 periodontally healthy controls, 16 patients with gingivitis, 19 patients with moderate periodontitis, and 29 patients with severe periodontitis. The V3 and V4 regions of the 16S rRNA gene in the samples were sequenced, and the levels of 9 bacterial species showing significant differences among the groups by sequencing analysis were identified using quantitative real-time PCR (qPCR). The predictive performance of each bacterial species in distinguishing the severity of disease was evaluated using a receiver operating characteristic curve. Twenty-nine species, including Porphyromonas gingivalis, increased as the severity of disease increased, whereas 6 species, including Rothia denticola, decreased. The relative abundances of P. gingivalis, Tannerella forsythia, Filifactor alocis, and Prevotella intermedia determined by qPCR were significantly different among the groups. The three bacterial species P. gingivalis, T. forsythia, and F. alocis were positively correlated with the sum of the full-mouth probing depth and were moderately accurate at distinguishing the severity of periodontal disease. In conclusion, the salivary microbiota showed gradual compositional changes according to the severity of periodontitis, and the levels of P. gingivalis, T. forsythia , and F. alocis in mouth rinse saliva had the ability to distinguish the severity of periodontal disease. IMPORTANCE Periodontal disease is one of the most widespread medical conditions and the leading cause of tooth loss, imposing high economic costs and an increasing burden worldwide as life expectancy increases. Changes in the subgingival bacterial community during the progression of periodontal disease can affect the entire oral ecosystem, and bacteria in saliva can reflect the degree of bacterial imbalance in the oral cavity. This study explored whether the specific bacterial species in saliva can distinguish the severity of periodontal disease by analyzing the salivary microbiota and suggested P. gingivalis, T. forsythia , and F. alocis as biomarkers for distinguishing the severity of periodontal disease in saliva., Competing Interests: The authors declare a conflict of interest. All authors are co-applicants on patent application 10-2021-0138897 entitled “Composition for diagnosing periodontal disease using microbiome in saliva and use thereof”.

Competing Interests: The authors disclose no conflicts of interest.

One of the bottlenecks to building semiconductor chips is the increasing cost required to develop chemical plasma processes that form the transistors and memory storage cells 1,2 . These processes are still developed manually using highly trained engineers searching for a combination of tool parameters that produces an acceptable result on the silicon wafer 3 . The challenge for computer algorithms is the availability of limited experimental data owing to the high cost of acquisition, making it difficult to form a predictive model with accuracy to the atomic scale. Here we study Bayesian optimization algorithms to investigate how artificial intelligence (AI) might decrease the cost of developing complex semiconductor chip processes. In particular, we create a controlled virtual process game to systematically benchmark the performance of humans and computers for the design of a semiconductor fabrication process. We find that human engineers excel in the early stages of development, whereas the algorithms are far more cost-efficient near the tight tolerances of the target. Furthermore, we show that a strategy using both human designers with high expertise and algorithms in a human first-computer last strategy can reduce the cost-to-target by half compared with only human designers. Finally, we highlight cultural challenges in partnering humans with computers that need to be addressed when introducing artificial intelligence in developing semiconductor processes., (© 2023. The Author(s).)

Purpose: We developed a virtual reality (VR) program for use in pediatric nursing practicums to help nursing students learn to measure vital signs in children., Methods: The analysis, design, development, implementation, and evaluation model was employed between July 2021 and December 2021 at a university in South Korea. In the analysis phase, in-depth interviews were conducted with four nursing students, two nursing school graduates, and four experts. The topic and contents of the VR program were settled in the design phase. The VR program was developed and subsequently used and evaluated by 20 nursing students and four experts., Results: The contents of the VR program for pediatric nursing practicums included the measurement of vital signs in a newborn baby and a young child, as well as an evaluation system. The mean score for the nursing students' satisfaction with practice was 4.02 out of 5 points. The mean scores for overall satisfaction with the VR program were 4.15 and 4.79 out of 5 points for nursing students and experts, respectively., Conclusion: The VR program developed in this study allows nursing students to practice measuring vital signs in children, thus improving the students' clinical performance in pediatric nursing.

Objectives: The impacts of ventilation tube (VT) type and effusion composition on the VT extrusion rate and complications in children with otitis media remain unclear. This part II study evaluated the factors affecting the extrusion rate, recurrence rate, and complications of VT insertion., Methods: A prospective study was conducted between June 2014 and December 2016 (the EVENT study [analysis of the effectiveness of ventilation tube insertion in pediatric patients with chronic otitis media]), with follow-up data collected until the end of 2017. Patients aged <15 years diagnosed with otitis media with effusion who received VT insertion were recruited at 15 tertiary hospitals. The primary outcomes were time to extrusion of VT, time to effusion recurrence, and complications., Results: Data from 401 patients were analyzed. After excluding the., Results: of long-lasting tubes (Paparella type II and T-tubes), silicone tubes (Paparella type I) exhibited a significantly longer extended time to extrusion (mean, 400 days) than titanium tubes (collar-button-type 1.0 mm: mean, 312 days; P<0.001). VT material (hazard ratio [HR], 2.117, 95% confidence interval [CI], 1.254-3.572; P=0.005), age (HR, 3.949; 95% CI, 1.239-12.590; P=0.02), and effusion composition (P=0.005) were significantly associated with the time to recurrence of middle ear effusion. Ears with purulent (mean, 567 days) and glue-like (mean, 588 days) effusions exhibited a shorter time to recurrence than ears with serous (mean, 846 days) or mucoid (mean, 925 days) effusions. The revision VT rates during follow-up were 3.5%, 15.5%, 10.4%, and 38.9% in ears with serous, mucoid, glue-like, and purulent effusions, respectively (P<0.001). The revision surgery rates were higher among patients aged <7 years than among those aged ≥7 years., Conclusion: Silicone tubes (Paparella type I) were less prone to early extrusion than titanium 1.0 mm tubes. VT type, patient age, and effusion composition affected the time to recurrence of effusion.

The safety and efficacy of intratympanic (IT) histamine (HIS) injection as an adjuvant to increase the inner ear penetration of dexamethasone (DEX) was investigated in this study. IT injections of DEX-only, 1% HIS+DEX and 4% HIS+DEX were performed in mice with noise-induced hearing loss. An inflammatory reaction in the middle ear was observed only in the 4% HIS+DEX group although no serious cytotoxic effects on the organ of Corti (OC) were observed at that concentration. Compared with the DEX-only group, the perilymphatic concentration of DEX was approximately two times higher in the 1% HIS+DEX group and approximately five times higher in the 4% HIS+DEX group. The expression of the DEX receptor in the cochlea was significantly increased in the 4%-HIS+DEX group. HIS appeared to induce transient damage the microstructure of the RWM with recovery observed within 3 weeks. The 1 and 4% HIS + DEX groups showed a significant recovery of the OC compared with the control group and they also achieved significantly better hearing restoration at 8 kHz in the DPOAE hearing test (P < .05) when compared to the DEX-only group. IT HIS temporarily disrupts the structure of the RWM and middle ear mucosa and significantly enhances the inner ear penetration of DEX. Therefore, IT HIS injection could be a simple and effective adjuvant therapy to increase perilymph concentration of DEX and achieve OC recovery after cochlear damage., (Copyright © 2022. Published by Elsevier B.V.)

Objectives: This study was performed to evaluate the effectiveness of our novel group vestibular rehabilitation therapy (G-VRT) and to analyze the factors affecting outcomes., Study Design: Retrospective case series., Setting: Tertiary referral center., Patients: Patients with chronic dizziness who received G-VRT between December 2019 and July 2020., Intervention: The G-VRT program consisted of a 1-hour physical therapy session by an otologist in a small group setting., Main Outcome Measures: Dizziness Handicap Inventory, visual analog scale, functional level scales, and video head impulse test, as well as the compliance to the program, were evaluated., Results: All scores of dizziness questionnaires were significantly improved after G-VRT ( p < 0.001). The overall vestibule-ocular reflex gain calculated by video head impulse test increased compared to the initial scores, whereas the average PR scores of all three semicircular canals significantly decreased from the initial scores, indicating enhanced vestibular compensation ( p < 0.05). Enrolled patients showed high compliance to the program., Conclusion: G-VRT program is a cost-effective and efficient way to provide relief for chronic dizzy patients. Further case-control studies in a larger group, as well as comparative studies with generic or customized vestibular exercise, will be needed to validate the clinical value of G-VRT., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

Alpha-lipoic acid (ALA) is an antioxidant with oto-protective effects. In the present study, the safety and effectiveness of ALA therapy after noise-induced hearing loss was confirmed based on the administration method. The safety of intratympanic ALA (IT-ALA) was evaluated with oto-endoscopy and middle ear mucosa morphologic study. Perilymph ALA concentrations according to the administration routes were compared, and the efficacy of ALA was investigated through hearing tests and cochlear histological studies. The middle ear mucosa was swollen 1 week after IT-ALA but completely recovered within 3 weeks. ALA concentration in the perilymph was significantly higher in the IT-ALA group. Recovery of organ of Corti morphology and hearing levels were predominant in the IT-ALA group compared with the intraperitoneal injection group (IP-ALA) and showed similar rescue effects in the IT-dexamethasone group (IT-DEX). Interleukin-1 beta and nuclear factor-kappa B expression was significantly downregulated in the IT-ALA group. IT-ALA showed better cochlear recovery from acoustic trauma with higher inner ear penetration rate than IP-ALA. The rescue effect of IT-ALA after noise-induced hearing loss was similar to IT-DEX; however, the ALA and DEX mechanisms are different. IT-ALA appears to be another safe and effective treatment modality after acoustic trauma and comparable to IT-DEX.

In this study, we investigated the effect of the stacking order of metal precursors on the formation of volume defects, such as blisters and nanopores, in CZTSSe thin-film solar cells. We fabricated CZTSSe thin films using three types of metal-precursor combinations, namely, Zn/Cu/Sn/Mo, Cu/Zn/Sn/Mo, and Sn/Cu/Zn/Mo, and studied the blister formation. The blister-formation mechanism was based on the delamination model, taking into consideration the compressive stress and adhesion properties. A compressive stress could be induced during the preferential formation of a ZnSSe shell. Under this stress, the adhesion between the ZnSSe film and the Mo substrate could be maintained by the surface tension of a metallic liquid phase with good wettability, or by the functioning of ZnSSe pillars as anchors, depending on the type of metal precursor used. Additionally, the nanopore formation near the back-contact side was found to be induced by the columnar microstructure of the metal precursor with the Cu/Zn/Mo stacking order and its dezincification. Based on the two volume-defect-formation mechanisms proposed herein, further development of volume-defect-formation suppression technology is expected to be made.

This study compared the accuracy of a new MALDI-TOF mass spectrometry system, ASTA MicroIDSys system, with that of MALDI Biotyper system for the identification of reference and clinical bacterial and yeast strains. The identification accuracy of the 2 systems was compared using a total of 406 strains comprising 142 aerobic and 180 anaerobic bacterial strains and 84 yeast strains. The genus and species identification rates were 98.0% and 89.4% using MicroIDSys and 96.1% and 89.4% using Biotyper, respectively. The species identification rates of MicroIDSys and Biotyper for aerobic bacteria were 93.0% and 97.2%, respectively, and those for anaerobic bacteria were 85.6% and 81.7%, respectively. The accuracy of yeast identification at the species level was 91.7% using MicroIDSys and 92.9% using Biotyper. These findings indicate that MicroIDSys could be useful for the accurate identification of bacteria and yeast in clinical microbiology laboratories., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: Despite sufficient hearing gains, many patients with hearing loss have difficulty using hearing aids due to poor word recognition ability. This study was performed to introduce our hearing rehabilitation therapy (HRT) program for hearing aid users and to evaluate its effect on hearing improvement., Methods: In this prospective randomized case-control study, 37 participants with moderate or moderate-severe sensorineural hearing loss who had used bilateral hearing aids for more than 3 months with sufficient functional hearing gain were enrolled in this study. Nineteen participants were randomly assigned to the control group (CG) and 18 patients were assigned to participate in our HRT program once a week for 8 consecutive weeks (hearing rehabilitation therapy group [HRTG]). Their hearing results and questionnaire scores for hearing handicap and hearing aid outcomes were prospectively collected and compared between the two groups., Results: After completing 8 weeks of the HRT program, the HRTG showed a significantly greater improvement in scores for consonant-only and consonant-vowel sound perception than the CG (P<0.05). In addition, the HRTG showed a significant improvement in hearing ability as measured by two questionnaires (p<0.05), while no differences were observed in the CG. However, word and sentence recognition test results did not show significant differences between the two groups., Conclusion: Even after short-term HRT, patients had subjectively better hearing outcomes and improved phoneme perception ability; this provides scientific evidence regarding a possible positive role for HRT programs in hearing aid users. Further validation in a larger population through a long-term follow-up study is needed.

Objectives: This study was conducted to evaluate the user satisfaction, efficacy, and safety of round window (RW) vibroplasty using the Vibrant Soundbridge (VSB) in patients with persistent mixed hearing loss after mastoidectomy., Methods: The study included 27 patients (mean age, 58.7 years; age range, 28-76 years; 11 men and 16 women) with mixed hearing loss after mastoidectomy from 15 tertiary referral centers in Korea. The VSB was implanted at the RW. The Korean translation of the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire and the Korean version of the International Outcome Inventory for Hearing Aids (K-IOI-HA) questionnaire were used to evaluate user satisfaction as the primary outcome. The secondary outcome measures were audiological test results and complication rates., Results: The mean scores for ease of communication (61.3% to 29.7% to 30.2%), reverberation (62.1% to 43.1% to 37.4%), and background noise (63.3% to 37.7% to 34.3%) subscales of the APHAB questionnaire significantly decreased after VSB surgery. The mean K-IOI-HA scores at 3 and 6 months after surgery were significantly higher than the mean preoperative score (18.6 to 27.2 to 28.1). The postoperative VSB-aided thresholds were significantly lower than the preoperative unaided and hearing aid (HA)-aided thresholds. There was no significant difference between preoperative unaided, preoperative HA-aided, and postoperative VSB-aided maximum phonetically balanced word-recognition scores. None of the 27 patients experienced a change in postoperative bone conduction pure tone average. One patient developed temporary facial palsy and two developed surgical wound infections., Conclusion: RW vibroplasty resulted in improved satisfaction and audiological test results in patients with mixed hearing loss after mastoidectomy, and the complication rate was tolerable.

Objectives: The aims of this study were to investigate the test-retest reliability of measurements of loudness discomfort levels (LDLs), to suggest cut-off values for diagnosing patients with hyperacusis, and to evaluate the clinical value of-LDL measurements as a test for monitoring hyperacusis., Methods: For the test-retest reliability of LDL measurements (study 1), a total of 68 patients who sought consultations at our clinic were subcategorized into four groups: patients with tinnitus (group 1), tinnitus and hearing loss (group 2), hyperacusis (group 3), and normal controls (group 4). Inter-hour and inter-day test-retest reliability values using different stimuli were investigated. For study 2, the clinical value of LDL measurements using pure tone stimuli was analyzed by comparing changes after sound generator use in patients with hyperacusis., Results: In study 1, the group 3 patients showed significantly lower LDLs than the other groups. High test-retest reliability of LDL tests was demonstrated, regardless of the type of stimulus used. The cut-off values for screening patients with hyperacusis were 90 dB HL using pure tone stimuli and 62 dB HL using white-band noise stimuli. In study 2, significantly increased LDLs were correlated with improved symptoms and improved scores on tinnitus questionnaires after sound generator use, indicating that LDL measurement is a reliable test for monitoring hyperacusis during an intervention., Conclusion: LDL measurement is a reliable diagnostic tool to reflect the condition of hyperacusis, especially during the course of treatment.

Introduction: Subjective cognitive decline (SCD) is a self-reported cognitive decline without objective cognitive impairment. The relationship between audiometric hearing loss (HL) and cognitive function has not been reported in SCD. The purpose of this study was to investigate whether HL affects cognition-related indexes in SCD individuals., Methods: This is a cross-sectional study that used the baseline data of a multicenter cohort study that monitors clinical progression from SCD to dementia. Individuals aged ≥60 years who reported cognitive decline but had no objective cognitive impairment on comprehensive neuropsychological tests were recruited. Participants were grouped into the normal-hearing (NH) and bilateral HL groups. The demographics, clinical characteristics, dementia biomarkers, global cognition, questionnaire scores, neuropsychological test scores, and segmental brain volumes from MRI were compared between the groups., Results: Of a total of 120 participants, one hundred and two had NH (n = 57) or bilateral HL (n = 45). There were no group differences in the demographic and clinical data except the age. The biomarkers, global cognition, and questionnaire scores were not different between the groups. The HL group performed worse (the z-score of -0.06) in the Stroop Color Word Test than the NH group (0.27) (p = 0.025). Brain volumetric analysis revealed that the HL group had reduced gray matter volumes in four brain subregions: left temporal pole, left caudal middle frontal gyrus, left hippocampus, and right isthmus of the cingulate gyrus., Conclusion: In SCD, HL exerted an adverse effect on cognitive function, primarily frontal executive function tested in the Stroop task. HL was also related to gray matter volume reductions in brain subregions, although causality needs further investigation. This study may provide evidence for a potential link between hearing and cognition in SCD, an emerging clinical entity., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

This study describes temperature and precipitation trends in the two National Parks located in the two highest mountain ranges on the Iberian Peninsula: the Sierra Nevada (Sierra Nevada National Park, SN) and the Pyrenees (Aigüestortes i Sant Maurici National Park, ASM). Special focus is placed on analysing disparities between the lowlands and the highlands, as well as the agreement between observational data and grid data (IBERIA01 and E‐OBS). For this purpose, a quality‐controlled and homogeneity‐adjusted database of the daily maximum temperature, minimum temperature and precipitation (SMADS database) has been generated. Regional trends in mean temperature indicate that warming in ASM (0.17°C·decade−1) was greater than in the Sierra Nevada (SN) (0.13°C·decade−1) in the longest joint period, 1930–2020. For annual precipitation, the trends over the past nine decades were negative, although not significantly. Only the summer in SN showed a significant negative trend, which has intensified in recent decades to −13.4%·decade−1 for 1975–2020. A parallel evolution was observed in the annual mean temperature of the highlands (>1500 m) and lowlands (<1500 m) of ASM, with a common trend of 0.17°C·decade−1, while in SN negative elevation‐dependent warming was detected. Differences between lowlands and highlands were also noted in precipitation trends in both mountain ranges: a positive trend in precipitation was found in the lowlands while in the highlands practically null trends (ASM) or decreasing precipitation trends (SN) were detected. The comparison of the Spanish Mountain Adjusted Daily Series (SMADS) results with the IBERIA01 and E‐OBS grid series yielded differences no greater than ±0.2°C·decade−1. No notable differences were detected between the regional trends calculated with observational series or with grid series. These results worsened when the differences in the trends detected in the individual observed temperature series were compared against the corresponding grid series. [ABSTRACT FROM AUTHOR]

High grade serous ovarian carcinoma (HGSOC) is the most common and aggressive ovarian malignancy. Accumulating evidence indicates that HGSOC may originate from human fallopian tube epithelial cells (FTECs), although the exact pathogen(s) and/or molecular mechanism underlying the malignant transformation of FTECs is unclear. Here we show that human papillomavirus (HPV), which could reach FTECs via retrograde menstruation or sperm-carrying, interacts with the yes-associated protein 1 (YAP1) to drive the malignant transformation of FTECs. HPV prevents FTECs from natural replicative and YAP1-induced senescence, thereby promoting YAP1-induced malignant transformation of FTECs. HPV also stimulates proliferation and drives metastasis of YAP1-transformed FTECs. YAP1, in turn, stimulates the expression of the putative HPV receptors and suppresses the innate immune system to facilitate HPV acquisition. These findings provide critical clues for developing new strategies to prevent and treat HGSOC., (© 2024. The Author(s).)

Purpose: Sigmoid sinus anomalies such as dehiscence or diverticula may present with pulsatile tinnitus (PT) and low-frequency hearing loss. Occasionally, these symptoms are severe, necessitating resurfacing of the affected area to restore a normal-appearing sinus wall. This study describes three cases wherein we managed PT attributed to sigmoid sinus anomalies using polymethylmethacrylate (PMMA) bone cement, a novel material., Methods: Three patients with PT without any history of illnesses initially underwent cortical mastoidectomy to expose the affected area and resurface the sinus wall. Subsequently, PMMA bone cement was used to reconstruct any bony defects causing PT symptoms. Viscosity of the bone cement was altered based on specific characteristics and causes of the affected area. Additionally, we performed the water occlusion test (WOT), audiological assessment, the Tinnitus Handicap Inventory score (THI), and temporal computed tomography, both pre- and postoperatively, to assess the extent of PT., Results: Preoperatively, all three patients had tinnitus that dissipated with pressure on the neck and the water occlusion test (WOT), with no reported vertigo, trauma, or ear infections. Moreover, all three cases had a severe handicap according to the THI. In contrast, all cases had reduced PT and a significantly decreased THI score postoperatively, as well as no recurrence or complications and no instances of increased intracranial hypertension at the 12-month follow-up., Conclusion: All cases showed promising results, emphasizing the sustained benefits of this novel intervention for the management of PT., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Congenital cholesteatoma is a rare, non-neoplastic lesion that causes conductive hearing loss in children. It is underrecognized and often diagnosed only when there is an established hearing deficit. In the pediatric population, hearing deficiency is particularly detrimental because it can impede speech and language development and, in turn, the social and academic well-being of affected children. Delayed diagnosis leads to advanced disease that requires more extensive surgery and a greater chance of recurrence. A need to promote awareness and recognition of this condition has been advocated by clinicians and surgeons, but no comprehensive imaging review dedicated to this entity has been performed. This review aims to discuss the diagnostic utility of high-resolution computed tomography and magnetic resonance imaging in preoperative and postoperative settings in congenital cholesteatoma. Detailed emphasis is placed on the essential preoperative computed tomography findings that facilitate individualized surgical management and prognosis in the pediatric population., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To emphasize the surgical importance of addressing dehiscence over diverticulum in resolving pulsatile tinnitus (PT) in patients with sigmoid sinus wall anomalies (SSWAs) and investigate anatomical differences., Study Design: Retrospective data analysis., Setting: Multi-institutional tertiary university medical centers., Patients: Fifty participants (dehiscence/diverticulum, 29:21 cases) with SSWA-associated PT were included in the study. All 21 diverticulum participants underwent surgical intervention., Interventions: 1) Surgical intervention with novel techniques monitored by intraoperative microphone. 2) Radiologic and ophthalmologic imaging methods., Main Outcome Measures: Quantitative and qualitative preoperative and postoperative alterations of PT and anatomical differences between dehiscence and diverticulum., Results: Addressing dehiscence overlying diverticulum and sigmoid sinus wall dehiscences significantly reduced visual analog score and Tinnitus Handicap Inventory ( p < 0.01). Sinus wall reconstruction led to substantial PT sound intensity reduction in the frequency range of 20 to 1000 Hz and 20 to 500 Hz (paired-sample t test, p < 0.01). Diploic vein analysis showed a significant positive correlation in 85.7% of the diverticulum cohort compared with the dehiscence cohort ( p < 0.01). Eight percent of the participants exhibited papilledema, which was limited to the dehiscence cohort., Conclusion: 1) Effective reduction of PT can be achieved by addressing all dehiscences, including those overlying the diverticulum, without the need to exclude the diverticulum. 2) Diploic vein may involve in the formation of diverticulum, and loss of dura mater and vascular wall thickness are observed at the SSWA locations., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2023, Otology & Neurotology, Inc.)

The absence of trace amounts of natural bioactive compounds with important biological activities in traditional dietary models for global farm animals, coupled with an incomplete theoretical system for animal nutrition, has led to unbalanced and inadequate animal nutrition. This deficiency has adversely impacted animal health and the ecological environment, presenting formidable challenges to the advancement of the swine breeding industry in various countries around the world toward high-quality development. Recently, due to the ban of antibiotics for growth promotion in swine diets, botanical active compounds have been extensively investigated as feed additives. Polyphenols represent a broad group of plant secondary metabolites. They are natural, non-toxic, pollution-free, and highly reproducible compounds that have a wide range of physiological functions, such as antioxidant, anti-inflammatory, immunomodulatory, antiviral, antibacterial, and metabolic activities. Accordingly, polyphenols have been widely studied and used as feed additives in swine production. This review summarizes the structural characteristics, classification, current application situation, general properties of polyphenols, and the latest research advances on their use in swine production. Additionally, the research and application bottlenecks and future development of plant polyphenols in the animal feed industry are reviewed and prospected. This review aims to stimulate the in-depth study of natural plant polyphenols and the research and development of related products in order to promote the green, healthy, and high-quality development of swine production, while also providing ideas for the innovation and development in the theoretical system of animal nutrition. [ABSTRACT FROM AUTHOR]

Background: Given the characteristics of the rehabilitation therapy specialty and the drawback of the traditional didactic teaching approach, we developed the innovative teaching approach from the students' perspective using the person–environment–occupation (PEO) model. The new model was developed from the original PEO model to be applied in pedagogical contexts and tailored to the characteristics of an application-oriented specialty, such as rehabilitation therapy. The present study aimed to examine the perceived effectiveness of the PEO innovative teaching model applied to rehabilitation therapy students. Methods: A pre–post descriptive study was conducted to compare the perceived effectiveness of the PEO innovative teaching model for two consecutive student cohorts. A purposive sampling method was used to recruit students from two cohorts of junior medical students majoring in rehabilitation therapy in the spring semesters of 2020 and 2021. A questionnaire was developed to evaluate the perceived effectiveness of the PEO innovative teaching model. SPSS version 26.0 was used to perform data analysis. Results: A total of 112 students were included in the study and completed both pre- and post-tests. Of 112 received questionnaires, 101 were considered as valid questionnaires after the quality check (effective rate 90.18%). In the 2020 and 2021 cohorts, students rated the PEO innovative teaching model significantly higher than the didactic teaching approach in the following aspects: the teaching content is highly professional and valuable; the course is extensively expounded; the clinical reasoning is strengthened; problem-solving ability is developed; communication skills are improved; and teamwork skills are developed. Conclusion: The PEO innovative teaching model was perceived to be an effective teaching strategy to enhance students' academic performance. In addition, three core skills including clinical reasoning, problem-solving ability, and communication skills were improved by the PEO innovative teaching model. [ABSTRACT FROM AUTHOR]

Purpose: Hybrid simulation has emerged to increase the practicality of simulation training by combining simulators and standardized patient (SP) that implement realistic clinical environments at a high level. This study aimed to develop a hybrid simulation program focused on case of pediatric cardiac catheterization and to evaluate its effectiveness. Methods: The hybrid simulation program was developed according to the Analyze, Design, Develop, Implement, and Evaluate (ADDIE) model. And deep learning-based analysis program was used to analyze non-verbal communication with SP and applied it for debriefing sessions. To verify the effect of the program, a quasi-experimental study using a random assignment design was conducted. In total, 48 nursing students (n=24 in the experimental group; n=24 in the control group) participated in the study. Results: Knowledge (F=3.53, p=.038), confidence in clinical performance (F=9.73, p<.001), and communication self-efficacy (F=5.20, p=.007) showed a significant difference in both groups and interaction between time points, and the communication ability of the experimental group increased significantly (t=3.32, p=.003). Conclusion: Hybrid simulation program developed in this study has been proven effective, it can be implemented in child nursing education. Future research should focus on developing and incorporating various hybrid simulation programs using SP into the nursing curriculum and evaluating their effectiveness. [ABSTRACT FROM AUTHOR]

Objective: To analyze medical device reports (MDR) submitted to the Food and Drug Administration's (FDA) Manufacturer and User Device Facility Experience (MAUDE) database to identify adverse events (AEs) in patients implanted with novel active bone conduction hearing implants (BCIs). Methods: We conducted a search of the FDA MAUDE database on the newest generation of BCIs. Data were collected concerning device malfunctions, patient injuries, factors triggering these incidents, and the subsequent actions taken. Results: In total, 93 (16.7%) device malfunctions and 465 (83.3%) patient injuries with 358 subsequent interventions were identified, resulting in 558 AEs. Although the absolute AE number per device cannot be identified, the following trends were detected: Among the 494 AEs associated with OSI200, 55 (11.1%) reported device malfunctions and 454 (88.9%) cited patient injuries. Out of the 64 AEs linked to BCI602, 28 (59.4%) were associated with malfunctions, whereas 26 (40.6%) involved patient injuries. The most frequently reported particular AEs for the OSI200 were infection (n = 171, 34.6%), extrusion of the device (n = 107, 21.7%), and pain (n = 51, 10.3%). Conversely, no device output (n = 20, 31.3%) and loss of osseointegration (n = 7, 10.9%) were the most reported AEs for the BCI602. Various AEs led to 214 explanations and 77 revision surgeries. Sixty‐seven AEs reported conservative treatment. Conclusion: The current study provides an overview of the most commonly reported complications with new active BCIs. Although providing an overview, given the limitations of the FDA MAUDE database, our results have to be interpreted with caution. Level of Evidence: 4. [ABSTRACT FROM AUTHOR]

Bioprinting is a highly promising application area of additive manufacturing technology that has been widely used in various fields, including tissue engineering, drug screening, organ regeneration, and biosensing. Its primary goal is to produce biomedical products such as artificial implant scaffolds, tissues and organs, and medical assistive devices through software‐layered discrete and numerical control molding. Despite its immense potential, bioprinting technology still faces several challenges. It requires concerted efforts from researchers, engineers, regulatory bodies, and industry stakeholders are principal to overcome these challenges and unlock the full potential of bioprinting. This review systematically discusses bioprinting principles, applications, and future perspectives while also providing a topical overview of research progress in bioprinting over the past two decades. The most recent advancements in bioprinting are comprehensively reviewed here. First, printing techniques and methods are summarized along with advancements related to bioinks and supporting structures. Second, interesting and representative cases regarding the applications of bioprinting in tissue engineering, drug screening, organ regeneration, and biosensing are introduced in detail. Finally, the remaining challenges and suggestions for future directions of bioprinting technology are proposed and discussed. Bioprinting is one of the most promising application areas of additive manufacturing technology that has been widely used in various fields. It aims to produce biomedical products such as artificial implant scaffolds, tissues and organs, and medical assistive devices. This review systematically discusses bioprinting principles, applications, and future perspectives, which provides a topical description of the research progress of bioprinting. [ABSTRACT FROM AUTHOR]