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Je-Yang Jau,1 Terry BJ Kuo,1– 3 Lieber PH Li,1,4– 6 Tien-Yu Chen,1,7 Ying-Shuo Hsu,1,8,9 Chun-Ting Lai,1,2 Weng-Cheu Yue,10 Pin-Hsuan Huang,11 Cheryl CH Yang1,2,4,12,13 1Institute of Brain Science, National Yang-Ming Chiao-Tung University, Taipei, Taiwan; 2Sleep Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan; 3Tsoutun Psychiatric Center, Ministry of Health and Welfare, Nantou, Taiwan; 4Department of Otolaryngology, Cheng Hsin General Hospital, Taipei, Taiwan; 5Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; 6Department of Speech Language Pathology and Audiology, College of Health Technology, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan; 7Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; 8Department of Otolaryngology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 9School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; 10DP Dental, Singapore; 11Department of Health Promotion and Health Education, National Taiwan Normal University, Taipei, Taiwan; 12Department of Education and Research, Taipei City Hospital, Taipei, Taiwan; 13Brain Research Center, National Yang Ming Chiao Tung University, Taipei, TaiwanCorrespondence: Cheryl CH Yang, Institute of Brain Science, National Yang-Ming Chiao-Tung University, No. 155, Sec. 2, Li-Nong St., Beitou, Taipei, 11221, Taiwan, Tel +886-2-28267058, Fax +886-2-28273123, Email cchyang@ym.edu.tw Lieber PH Li, Department of Otolaryngology, Cheng Hsin General Hospital, No. 45, Cheng Hsin St., Beitou, Taipei, 11221, Taiwan, Tel +886-2-28264400, Email lieber.chgh@gmail.comPurpose: This study aimed to investigate (1) the role of mouth puffing phenomenon and upper airway features in obstructive sleep apnea (OSA) and (2) whether mouth-taping during sleep alleviated the severity of OSA.Participants and Methods: Seventy-one participants underwent a two-night home sleep test (the first day sleeping normally; the second day sleeping with their mouths being taped); their oximetry desaturation index (ODI) and mouth puffing signals (non-mouth puffing, complete mouth puffing, intermittent mouth puffing (IMP), and side mouth puffing) were detected by a validated fingertip pulse oximeter and a mouth puffing detector. The participants were grouped into the ODI-improved group and the ODI-not-improved group according to their sleeping test results. The radiograph was taken by cone-beam computed tomography and cephalometries. Upper airway features including airways, soft tissues, and oral cavity variables were measured.Results: Participants with severe OSA showed a higher IMP percentage compared with those with normal, mild, and moderate OSA (severe: 33.78%, moderate: 22.38%, mild: 14.55%, normal: 0.31%, p < 0.001). In all participants, the ODI and the percentage of SpO2 under 90 (T90) were positively related to body mass index (BMI) (r = 0.310 and 0.333, respectively), while ODI and T90 were negatively correlated with the minimum width of the airway (r = − 0.473 and − 0.474, respectively); all mentioned relationships were significant (p < 0.05).Conclusion: IMP proportions were found to be higher in the half of participants whose ODI did not improve after mouth-taping and in those with severe OSA. Moreover, OSA patients with higher ODI, higher T90, and higher proportions of IMP were more likely to have a narrower upper airway.Keywords: mouth breathing, mouth puffing, sleep phenomena, oximeter, sleep apnea, accelerometer

Feng-Hsiang Chiu,1,2 Yi Chang,3 Wen-Wei Liao,3 Yu-Ling Yeh,3 Chia-Mo Lin,4– 6 Ofer Jacobowitz,7 Ying-Shuo Hsu8,9 1Department of Otolaryngology, Head and Neck Surgery, Tri-service General Hospital, Taipei, Taiwan; 2National Defense Medical Center, Taipei City, Taiwan; 3Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 4Division of Chest Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 5Department of Chemistry, Fu-Jen Catholic University, New Taipei City, Taiwan; 6Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City, Taiwan; 7ENT & Allergy Associates, New York, NY, USA; 8Department of Otolaryngology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 9School of Medicine, Fu Jen Catholic University, New Taipei City, TaiwanCorrespondence: Ofer JacobowitzENT & Allergy Associates, New York, NY, USATel +1 646 868-4300Email ojacobowitz@entandallergy.comYing-Shuo HsuDepartment of Otolaryngology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, TaiwanTel +1-886-2-28332211 ext.2551Email sulisky@gmail.comIntroduction: The findings of drug-induced sleep endoscopy (DISE) are not always correlated with the outcome of upper airway surgery for obstructive sleep apnea (OSA), and whether multilevel surgery is truly required in treating multilevel obstruction identified in preoperative DISE remains an issue. We attempted to compare DISE findings before and after palatopharyngoplasty in patients with OSA because changes in DISE may be beneficial to better understand polysomnographic and anatomical outcomes.Methods: This was a prospective cohort study for 34 patients with moderate to severe OSA who underwent palatopharyngoplasty at a tertiary care center from 2016 to 2018. We recorded the patients’ demographic characteristics, procedures, and surgical outcomes and compared the preoperative and postoperative DISE staging patterns.Results: The apnea-hypopnea index (AHI) values of 34 adults improved significantly after surgery (40.6 ± 23.3 versus 25.6 ± 20.6, P < 0.001). The majority of patients, 26/34, had preoperative complete concentric collapse at the velum, and for most (20/26, 77%) there was a change of the collapse pattern into anteroposterior collapse postoperatively. Patients with postoperative velar collapse had higher follow-up AHI values than those who without (27.8 ± 21.9 versus 15.2 ± 7.7, P = 0.023). Patients with preoperative complete tongue base collapse had higher follow-up AHI values than did those with no or partial collapse (40.6 ± 21.0 versus 21.0 ± 18.6, P = 0.017). Patients with postoperative complete tongue base collapse also had higher follow-up AHI values than the others (42.7 ± 22.1 versus 18.5 ± 15.4, P = 0.001).Conclusion: Palatopharyngoplasty could change the collapse pattern at the velum in most patients. Preoperative and postoperative complete tongue base collapse and postoperative velar collapse identified in TCI-DISE were associated with relatively poor outcomes.Keywords: obstructive sleep apnea, drug-induced sleep endoscopy, palatopharyngoplasty, postoperative, complete concentric collapse, tongue base collapse

Feng-Hsiang Chiu,1,2 Chih-Yu Chen,1,2 Jih-Chin Lee,1,2 Ying-Shuo Hsu3,4 1Department of Otolaryngology, Head and Neck Surgery, Tri-Service General Hospital, Taipei, Taiwan; 2National Defense Medical Center, Taipei City, Taiwan; 3Department of Otolaryngology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 4School of Medicine, Fu Jen Catholic University, New Taipei City, TaiwanCorrespondence: Jih-Chin LeeDepartment of Otolaryngology, Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei City, TaiwanTel +886-2-87927192Fax +886-2-87927193Email doc30450@mail.ndmctsgh.edu.twYing-Shuo HsuDepartment of Otolaryngology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei City, TaiwanTel +886-2-28332211 ext.2551Email sulisky@gmail.comObjective: Uvulopalatopharyngoplasty (UPPP) is a common procedure for the treatment of obstructive sleep apnea (OSA) and is usually initiated with the resection of palatine tonsils. Because tonsillectomy potentially contributes to complications, minimally invasive upper airway surgeries have been proposed for OSA therapy. Whether tonsillectomy is always essential for UPPP remains unclear, particularly for patients with small tonsils. The purpose of this study was to present the effect of modified UPPP without tonsillectomy (UPsT) on patients with OSA and attempt to select the candidates for this procedure.Methods: This is a retrospective cohort study of patients with OSA, with tonsil size of grade 0– 2, and with only retropalatal obstruction in drug-induced sleep endoscopy (DISE). The patients underwent UPsT at a tertiary center from November 2017 to December 2019. The sleep study was performed before and at least 3 months after surgery. The demographics, surgical outcomes, and staging patterns of preoperative DISE were recorded. The correlation between surgical outcome and DISE was also established.Results: A total of 22 adults with an average age of 46.5 years [interquartile range: 40 to 60 years] completed the follow-up study. Their apnea–hypopnea index (AHI) and Epworth sleepiness scale values improved significantly after surgery. Of the 17 patients with partial collapse and complete anteroposterior collapse (APC) at the velum, 16 presented good responses to UPsT. However, among the five patients with complete concentric collapse (CCC), only two (2/5, 40%) satisfied the criteria for surgical success. Furthermore, their follow-up AHI values were significantly higher than those of patients without CCC in DISE.Conclusion: UPsT was demonstrated to be an effective therapy for patients with OSA who had small tonsils and retropalatal obstruction in DISE. CCC in sleep endoscopy indicates a poorer surgical outcome than does complete APC and partial collapse at the velum.Keywords: tonsillectomy, uvulopalatopharyngoplasty, suspension palatoplasty, lateral pharyngoplasty, obstructive sleep apnea, drug-induced sleep endoscopy, complete concentric collapse

Kuo YH, Liu TJ, Chiu FH, et al. Nat Sci Sleep. 2021;13:2087–2099. The authors have advised that the funding statement on page 2098 is incorrect. The text “This study was supported by a grant from Shin Kong Wu- Ho-Su memorial Hospital (2018SKHADR018)” should read “This study was supported by a grant from Shin Kong Wu-Ho-Su memorial Hospital (2019SKHADR027)”. The authors apologize for this error. Read the original article

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Objective: Obstructive sleep apnea (OSA) is a prevalent disorder, with oral breathing influencing its severity. Expiratory velopharyngeal obstruction (EVO), observed during drug-induced sleep endoscopy (DISE), may contribute to oral breathing in OSA patients. EVO results in obstruction between the pharynx and nasal cavity during expiration. This study aims to identify factors associated with positive EVO during DISE., Study Design: Case series., Setting: Tertiary Medical Center., Methods: Seventy-two OSA patients underwent clinical evaluation, polysomnography, and DISE, utilizing interventions like intraoral negative airway pressure (iNAP), mouth closure, and oral appliances (OAs) in supine positions with head rotation. The findings, classified under velopharynx, oropharynx, tongue base, epiglottis, included the presence of EVO., Results: The results demonstrated that interventions including mouth closure and iNAP were associated with increased observation of EVO (43.1% and 34.7%) compared to OA (20.1%). However, head rotation was associated with decreased presence of EVO during DISE compare to supine (26% vs 35.8%). Noticeably, per 1 year increase of age was associated with an increased odds of EVO (odds ratio: 1.03, 95% confidence interval: 1.01-1.06). However, no other baseline characteristics were significantly associated the odds of EVO., Conclusion: Our study reveals the effectiveness of head rotation and OA in reducing EVO and improving mouth breathing in OSA patients, offering valuable insights for future treatment strategies., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Chimeric antigen receptor (CAR)-based therapies have pioneered synthetic cellular immunity but remain limited in their long-term efficacy. Emerging data suggest that dysregulated CAR-driven T cell activation causes T cell dysfunction and therapeutic failure. To re-engage the precision of the endogenous T cell response, we designed MHC-independent T cell receptors (miTCRs) by linking antibody variable domains to TCR constant chains. Using predictive modeling, we observed that this standard "cut and paste" approach to synthetic protein design resulted in myriad biochemical conflicts at the hybrid variable-constant domain interface. Through iterative modeling and sequence modifications we developed structure-enhanced miTCRs which significantly improved receptor-driven T cell function across multiple tumor models. We found that 41BB costimulation specifically prolonged miTCR T cell persistence and enabled improved leukemic control in vivo compared to classic CAR T cells. Collectively, we have identified core features of hybrid receptor structure responsible for regulating function.

While polymer fabrics are integral to a wide range of applications, their vulnerability to mechanical damage limits their sustainability and practicality. Addressing this challenge, our study introduces a versatile strategy to develop photohealable fabrics, utilizing a composite of polystyrene (PS) and an azobenzene-containing polymer (PAzo). This combination leverages the structural stability of PS to compensate for the mechanical weaknesses of PAzo, forming the fiber structures. Key to our approach is the reversible trans - cis photoisomerization of azobenzene groups within the PAzo under UV light exposure, enabling controlled morphological alterations in the PS/PAzo blend fibers. The transition of PAzo sections from a solid to a liquid state at a low glass transition temperature ( T g ∼ 13.7 °C) is followed by solidification under visible light, thus stabilizing the altered fiber structures. In this study, we explore various PS/PAzo blend ratios to optimize surface roughness and mechanical properties. Additionally, we demonstrate the capability of these fibers for photoinduced self-healing. When damaged fabrics are clamped and subjected to UV irradiation for 20 min and pressed for 24 h, the mobility of the cis -form PAzo sections facilitates healing while retaining the overall fabric structure. This innovative approach not only addresses the critical issue of durability in polymer fabrics but also offers a sustainable and practical solution, paving the way for its application in smart clothing and advanced fabric-based materials.

The rates of many electrocatalytic reactions can be strongly affected by the structure and dynamics of the electrochemical double layer, which in turn can be tuned by the concentration and identity of the supporting electrolyte's cation. The effect of cations on an electrocatalytic process depends on a complex interplay between electrolyte components, electrode material and surface structure, applied electrode potential, and reaction intermediates. Although cation effects remain insufficiently understood, the principal mechanisms underlying cation-dependent reactivity and selectivity are beginning to emerge. In this Perspective, we summarize and critically examine recent advances in this area in the context of the hydrogen evolution reaction (HER) and CO2-to-CO conversion, which are among the most intensively studied and promising electrocatalytic reactions for the sustainable production of commodity chemicals and fuels. Improving the kinetics of the HER in base and enabling energetically efficient and selective CO2 reduction at low pH are key challenges in electrocatalysis. The physical insights from the recent literature illustrate how cation effects can be utilized to help achieve these goals and to steer other electrocatalytic processes of technological relevance., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Immune checkpoint inhibition has shown success in treating metastatic cutaneous melanoma but has limited efficacy against metastatic uveal melanoma, a rare variant arising from the immune privileged eye. To better understand this resistance, we comprehensively profile 100 human uveal melanoma metastases using clinicogenomics, transcriptomics, and tumor infiltrating lymphocyte potency assessment. We find that over half of these metastases harbor tumor infiltrating lymphocytes with potent autologous tumor specificity, despite low mutational burden and resistance to prior immunotherapies. However, we observe strikingly low intratumoral T cell receptor clonality within the tumor microenvironment even after prior immunotherapies. To harness these quiescent tumor infiltrating lymphocytes, we develop a transcriptomic biomarker to enable in vivo identification and ex vivo liberation to counter their growth suppression. Finally, we demonstrate that adoptive transfer of these transcriptomically selected tumor infiltrating lymphocytes can promote tumor immunity in patients with metastatic uveal melanoma when other immunotherapies are incapable., (© 2024. The Author(s).)

In recent years, hafnium oxide (HfO 2 ) has gained increasing interest because of its high dielectric constant, excellent thermal stability, and high band gap. Although HfO 2 bulk and film materials have been prepared and well-studied, HfO 2 fibers, especially hollow fibers, have been less investigated. In this study, we present a facile preparation method for HfO 2 hollow fibers through a unique integration of the sol-gel process and electrospinning technique. Initially, polystyrene (PS) fibers are fabricated by using electrospinning, followed by dipping in a HfO 2 precursor solution, resulting in HfO 2 -coated PS fibers. Subsequent thermal treatment at 800 °C ensures the selective pyrolysis of the PS fibers and complete condensation of the HfO 2 precursors, forming HfO 2 hollow fibers. Scanning electron microscopy (SEM) characterizations reveal HfO 2 hollow fibers with rough surfaces and diminished diameters, a transformation attributed to the removal of the PS fibers and the condensation of the HfO 2 precursors. Our study also delves into the influence of precursor solution molar ratios, showcasing the ability to achieve smaller HfO 2 fiber diameters with reduced precursor quantities. Validation of the material composition is achieved through thermogravimetric analysis (TGA) and energy-dispersive spectroscopy (EDS) mapping. Additionally, X-ray diffraction (XRD) analysis provides insights into the crystallinity of the HfO 2 hollow fibers, highlighting a higher crystallinity in fibers annealed at 800 °C compared with those treated at 400 °C. Notably, the HfO 2 hollow fibers demonstrate a water contact angle (WCA) of 38.70 ± 5.24°, underscoring the transformation from hydrophobic to hydrophilic properties after the removal of the PS fibers. Looking forward, this work paves the way for extensive research on the surface properties and potential applications of HfO 2 hollow fibers in areas such as filtration, energy storage, and memory devices.

Objective: In patients with obstructive sleep apnea (OSA), epiglottic collapse (EC) constitutes a major factor in the failure of continuous positive airway pressure therapy and uvulopalatopharyngoplasty. This study explored treatments that can improve EC in patients with OSA through drug-induced sleep endoscopy with target-controlled infusion (TCI-DISE)., Study Design: Retrospective cohort study., Setting: Tertiary center., Methods: This study screened 352 OSA patients who underwent TCI-DISE between 2016 and 2022. Fifty-four patients with EC were included in the final analysis. EC severity was assessed multiple times through TCI-DISE with different interventions., Results: The application of these interventions in patients with anteroposterior epiglottic collapse (apEC) led to a significant decrease in apEC severity from total to partial or no obstruction in 60.0% of patients by head rotation, in 53.6% by mouth closure, in 47.4% who received oral appliances (OA), and in 28.0% who received intermittent negative airway pressure (iNAP). With simultaneous head rotation, apEC severity decreased more significantly from total to partial or no obstruction in 77.8% of patients by mouth closure, in 70.3% who received OA, and in 68.0% who received iNAP. Lateral epiglottic collapse (latEC) severity decreased in 53.8% of patients after OA use and in 61.5% of patients with OA use and head rotation., Conclusion: This study identified head rotation with mouth closure as the most effective treatment for apEC through TCI-DISE. Patients with latEC had higher weight, apnea-hypopnea index, and body mass index compared with patients with apEC. OA use with head rotation appeared more effective in latEC through TCI-DISE., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

This study proposes a three-lens design with a short lens length and explores the curved imaging plane and performs a relative illumination analysis. There are two ways to reduce the lens length: shortening the back focal and lens group lengths. We derived the relevant parameter relationships of three lenses using the first-order geometric optics theory. The optical lens length can be controlled within 2 mm. The shorter the lens length, the larger the angle of the chief ray in the image space, resulting in an increase in the field curvature and astigmatism. Third-order Seidel aberrations can be effectively reduced by a curved image plane. We also derived the equations for relative illuminance, solid angle, surface transmittance, and internal transmittance for the short three-lens design. The optical lens design uses a curved image plane to shorten the distance from the off-axis beam image space to the image plane and reduce the incident angle of the chief ray on the image plane. The formula and design results verified by Code V software (version 11.2) show that both the solid angle and relative contrast of the lens can be increased. For the proposed three-lens design with a short lens length, the semi-field angle is 32°, F/# is 2.7, the effective focal length is 1.984 mm, the image plane area is 2.16 mm × 1.22 mm, and the curvature radius of the concave image plane is 3.726 mm. Moroever, the MTF (100 lp/mm) is larger than 52%, the lateral color aberration is less than 2.12 μm, the optical distortion is less than 2.00%, and the relative illumination is greater than 68%.

Objective: To identify the value of head rotation in the supine position and oral appliance (OA) use in drug-induced sleep endoscopy (DISE)., Study Design: Eighty-three sleep apnea adults undergoing target-controlled infusion-DISE (TCI-DISE) were recruited from a tertiary academic medical center., Setting: During DISE, 4 positions were utilized: supine position (position 1), head rotation (position 2), mandibular advancement using an OA (position 3), and head rotation with an OA (position 4)., Methods: Polysomnography (PSG) data and anthropometric variables during DISE were analyzed., Results: Eighty-three patients (65 men and 18 women; mean [standard deviation, SD], 48.5 [11.0] years) who underwent PSG and TCI-DISE were included. The mean (SD) apnea-hypopnea index (AHI) was 35.5 (22.4) events/h. Twenty-three patients had persistent complete concentric velopharyngeal collapse in the supine position, even with concurrent head rotation and OA (position 4). Their mean (SD) AHI was 54.7 (24.6) events/h, significantly higher than that of the 60 patients without such collapse in position 4 (p < .001). Their mean (SD) body mass index (BMI) was 29.0 (4.1) kg/m 2 , also significantly higher (p = .005). After adjustment for age, BMI, tonsil size, and tongue position, the degree of velum and tongue base obstruction was significantly associated with sleep apnea severity in positions 2, 3, and 4., Conclusion: We showed the feasibility, safety, and usefulness of using simple edge-to-edge, reusable OA in DISE. Patients who are not responsive to head rotation and OA during TCI-DISE may need upper airway surgery and/or weight control., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

We administered severe acute respiratory syndrome coronavirus-2 viral-specific T cells (VSTs) under emergency investigational new drug applications to 6 immunocompromised patients with persistent coronavirus disease 2019 (COVID-19) and characterized clinical and virologic responses. Three patients had partial responses after failing other therapies but then died. Two patients completely recovered, but the role of VSTs in recovery was unclear due to concomitant use of other antivirals. One patient had not responded to 2 courses of remdesivir and experienced sustained recovery after VST administration. The use of VSTs in immunocompromised patients with persistent COVID-19 requires further study., Competing Interests: Potential conflicts of interest. G. H. reports research grants from AlloVir, Inc, Karius, the National Institutes of Health, and AstraZeneca; consulting fees for serving on the advisory boards of Karius and AstraZeneca; and honoraria from MDOutlook. Y. S. H. is supported by the Hillman Fellowship for Innovative Cancer Research. F. P. S. reports research grants from Ansun, Regeneron, and Merck and serves on the advisory boards for Takeda and Eurofins Viracor. A. M. L. is a cofounder and equity holder in AlloVir, Inc, and Marker Therapeutics and a consultant for AlloVir, Inc. W. L. M. and E. A. are former employees and current stockholders of AlloVir, Inc. M. M. and B. P. are current employees of AlloVir, Inc. J. W. M. is a consultant to Gilead Sciences, Inc; reports grant funding from Gilead Sciences, Inc, to the University of Pittsburgh and compensation from Abound Bio, Inc (unrelated to the current work); and has share options in Infectious Disease Connect, Inc, and Galapagos, NV (unrelated to the current work). All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Esophageal squamous cell carcinoma (ESCC), one of the most lethal cancers, has become a global health issue. Stearoyl-coA desaturase 1 (SCD1) has been demonstrated to play a crucial role in human cancers. However, pan-cancer analysis has revealed little evidence to date. In the current study, we systematically inspected the expression patterns and potential clinical outcomes of SCD1 in multiple human cancers. SCD1 was dysregulated in several types of cancers, and its aberrant expression acted as a diagnostic biomarker, indicating that SCD1 may play a role in tumorigenesis. We used ESCC as an example to demonstrate that SCD1 was dramatically upregulated in tumor tissues of ESCC and was associated with clinicopathological characteristics in ESCC patients. Furthermore, Kaplan-Meier analysis showed that high SCD1 expression was correlated with poor progression-free survival (PFS) and disease-free survival (DFS) in ESCC patients. The protein-protein interaction (PPI) network and module analysis by PINA database and Gephi were performed to identify the hub targets. Meanwhile, the functional annotation analysis of these hubs was constructed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Functionally, the gain-of-function of SCD1 in ESCC cells promoted cell proliferation, migration, and invasion; in contrast, loss-of-function of SCD1 in ESCC cells had opposite effects. Bioinformatic, QPCR, Western blotting and luciferase assays indicated that SCD1 was a direct target of miR-181a-5p in ESCC cells. In addition, gain-of-function of miR-181a-5p in ESCC cells reduced the cell growth, migratory, and invasive abilities. Conversely, inhibition of miR-181a-5p expression by its inhibitor in ESCC cells had opposite biological effects. Importantly, reinforced SCD1 in miR-181a-5p mimic ESCC transfectants reversed miR-181a-5p mimic-prevented malignant phenotypes of ESCC cells. Taken together, these results indicate that SCD1 expression influences tumor progression in a variety of cancers, and the miR-181a-5p/SCD1 axis may be a potential therapeutic target for ESCC treatment., Competing Interests: 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., (© 2023 The Authors.)

T cells engineered to express chimeric antigen receptors (CARs) targeting CD19 have demonstrated impressive activity against relapsed or refractory B-cell cancers yet fail to induce durable remissions for nearly half of all patients treated. Enhancing the efficacy of this therapy requires detailed understanding of the molecular circuitry that restrains CAR-driven antitumor T-cell function. We developed and validated an in vitro model that drives T-cell dysfunction through chronic CAR activation and interrogated how CAR costimulatory domains, central components of CAR structure and function, contribute to T-cell failure. We found that chronic activation of CD28-based CARs results in activation of classical T-cell exhaustion programs and development of dysfunctional cells that bear the hallmarks of exhaustion. In contrast, 41BB-based CARs activate a divergent molecular program and direct differentiation of T cells into a novel cell state. Interrogation using CAR T cells from a patient with progressive lymphoma confirmed the activation of this novel program in a failing clinical product. Furthermore, we demonstrate that 41BB-dependent activation of the transcription factor FOXO3 is directly responsible for impairing CAR T-cell function. These findings identify that costimulatory domains are critical regulators of CAR-driven T-cell failure and that targeted interventions are required to overcome costimulation-dependent dysfunctional programs., (© 2023 by The American Society of Hematology.)

Background Aims: Regulatory (or "tolerogenic") dendritic cells (DCregs) are a highly promising, innovative cell therapy for the induction or restoration of antigen-specific tolerance in immune-mediated inflammatory disorders. These conditions include organ allograft rejection, graft-versus-host disease following bone marrow transplantation and various autoimmune disorders. DCregs generated for adoptive transfer have potential to reduce patients' dependence on non-specific immunosuppressive drugs that can induce serious side effects and enhance the risk of infection and certain types of cancer. Here, our aim was to provide a detailed account of our experience manufacturing and validating comparatively large numbers of Good Manufacturing Practice-grade DCregs for systemic (intravenous) infusion into 28 organ (liver) transplant recipients and to discuss factors that influence the satisfaction of release criteria and attainment of target cell numbers., Results: DCregs were generated in granulocyte-macrophage colony stimulating factor and interleukin (IL)-4 from elutriated monocyte fractions isolated from non-mobilized leukapheresis products of consenting healthy adult prospective liver transplant donors. Vitamin D3 was added on day 0 and 4 and IL-10 on day 4 during the 7-day culture period. Release and post-release criteria included cell viability, purity, phenotype, sterility and functional assessment. The overall conversion rate of monocytes to DCregs was 28 ± 8.2%, with 94 ± 5.1% product viability. The mean cell surface T-cell co-inhibitory to co-stimulatory molecule (programmed death ligand-1:CD86) mean fluorescence intensity ratio was 3.9 ± 2.2, and the mean ratio of anti-inflammatory:pro-inflammatory cytokine product (IL-10:IL-12p70) secreted upon CD40 ligation was 60 ± 63 (median = 40). The mean total number of DCregs generated from a single leukapheresis product (n = 25 donors) and from two leukapheresis products (n = 3 donors) was 489 ± 223 × 10 6 (n = 28). The mean total number of DCregs infused was 5.9 ± 2.8 × 10 6 per kg body weight. DCreg numbers within a target cell range of 2.5-10 × 10 6 /kg were achieved for 25 of 27 (92.6%) of products generated., Conclusions: High-purity DCregs meeting a range of quality criteria were readily generated from circulating blood monocytes under Good Manufacturing Practice conditions to meet target cell numbers for infusion into prospective organ transplant recipients., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Burkholderia sp. SP4, isolated from agricultural soils, has a high capability of degrading di-2-ethylhexyl-phthalate (DEHP). It degrades up to 99% of DEHP (300 mg l -1 ) in minimal salt (MS) media within 48 h without adding additionally auxiliary carbon source. The optimal conditions for SP4 to degrade DEHP are determined to be at 35 °C and pH 6.0. Supplementation of glucose (3.0 g l -1 ), sodium dodecyl sulfate (SDS) (0.2%), peptone (0.5 g l -1 ), or non-ionic surfactant Brij 35 (0.2%, 0.5% or 1%) in MS-DEHP media increases the DEHP degradation activity. Furthermore, kinetic analyses for DEHP degradation by SP4 reveals that it is a first-order reaction, and the half-life analyses also demonstrates that SP4 has a better degradative activity compared to other previously identified microbes. By means of HPLC-ESI-QTOF-MS, the metabolic intermediates of DEHP are identified for SP4, which include mono-2-ethylhexylphthalate (MEHP), mono-butyl phthalate (MBP), phthalic acid (PA), salicylic acid (SA), and 4-oxo-hexanoic acid. The presence of SA indicates that SP4 can consume DEHP using a dual biodegradation pathway diverged from the isomeric products of benzoate. Taken together, our study identifies a resilient DEHP-degradable bacterium and characterizes a novel degradation pathway for DEHP biodegradation. We plan to build on this finding in the context of removing DEHP from various environments., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Both higher- and lower-affinity self-reactive CD4 + T cells are expanded in autoimmunity; however, their individual contribution to disease remains unclear. We addressed this question using peptide-MHCII chimeric antigen receptor (pMHCII-CAR) T cells to specifically deplete peptide-reactive T cells in mice. Integration of improvements in CAR engineering with TCR repertoire analysis was critical for interrogating in vivo the role of TCR affinity in autoimmunity. Our original MOG 35-55 pMHCII-CAR, which targeted only higher-affinity TCRs, could prevent the induction of experimental autoimmune encephalomyelitis (EAE). However, pMHCII-CAR enhancements to pMHCII stability, as well as increased survivability via overexpression of a dominant-negative Fas, were required to target lower-affinity MOG-specific T cells and reverse ongoing clinical EAE. Thus, these data suggest a model in which higher-affinity autoreactive T cells are required to provide the "activation energy" for initiating neuroinflammatory injury, but lower-affinity cells are sufficient to maintain ongoing disease.

Current dogma dictates that during adulthood, endothelial cells (ECs) are locked in an immutable stable homeostatic state. By contrast, herein we show that maintenance of EC fate and function are linked and active processes, which depend on the constitutive cooperativity of only two ETS-transcription factors (TFs) ERG and Fli1. While deletion of either Fli1 or ERG manifest subtle vascular dysfunction, their combined genetic deletion in adult EC results in acute vasculopathy and multiorgan failure, due to loss of EC fate and integrity, hyperinflammation, and spontaneous thrombosis, leading to death. ERG and Fli1 co-deficiency cause rapid transcriptional silencing of pan- and organotypic vascular core genes, with dysregulation of inflammation and coagulation pathways. Vascular hyperinflammation leads to impaired hematopoiesis with myeloid skewing. Accordingly, enforced ERG and FLI1 expression in adult human mesenchymal stromal cells activates vascular programs and functionality enabling engraftment of perfusable vascular network. GWAS-analysis identified vascular diseases are associated with FLI1/Erg mutations. Constitutive expression of ERG and Fli1 uphold EC fate, physiological function, and resilience in adult vasculature; while their functional loss can contribute to systemic human diseases., Competing Interests: Competing Interest Statement: Shahin Rafii is the co-founder and non-paid consultant to Angiocrine Bioscience, CA.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and deadliest cancer worldwide. The primary reasons for this are the lack of early detection methods and targeted therapy. Emerging evidence highlights the metabolic addiction of cancer cells as a potential target to combat PDAC. Oncogenic mutations of KRAS are the most common triggers that drive glucose uptake and utilization via metabolic reprogramming to support PDAC growth. Conversely, high glucose levels in the pancreatic microenvironment trigger genome instability and de novo mutations, including KRAS G12D , in pancreatic cells through metabolic reprogramming. Here, we review convergent and diverse metabolic networks related to oncogenic KRAS mutations between PDAC initiation and progression, emphasizing the interplay among oncogenic mutations, glucose metabolic reprogramming, and the tumor microenvironment. Recognizing cancer-related glucose metabolism will provide a better strategy to prevent and treat the high risk PDAC population., (© 2022. The Author(s).)

Preserving the marginal bone level (MBL) is essential for the long-term success of dental implant therapy, and bone remodeling around dental implants is considered to vary with time. Numerous studies comparing the platform-switching (PS) and platform-matching (PM) dental implants have indicated that PS dental implants showed a lesser reduction for the MBL, and the majority of them had a relatively short period. This study aimed to evaluate vertical and horizontal bone defects by using digital periapical radiographs to examine the changes in MBL around PM and PS dental implants over 5 years after functional loading. The vertical MBL (vMBL) was measured from the implant-abutment junction to the first bone-to-implant contact. The horizontal MBL (hMBL) was measured from the implant-abutment junction to the bone crest. All data were presented as means ± standard errors. Paired and independent t -tests with Welch's correction were used to analyze the data. A total of 61 dental implants in 38 patients after 5 years of functional loading were evaluated. Over time, PS dental implants were more likely to gain bone; by contrast, PM dental implants were more likely to lose bone during the observation time. Changes in vMBL for PS dental implants were significantly less than those for PM dental implants at 1-year ( p = 0.045), 3-year ( p = 0.021), and 5-year ( p = 0.010) loading. Likewise, changes in hMBL for PS dental implants were significantly smaller than in those for PM dental implants at 3-year ( p = 0.021) and 5-year ( p = 0.006) loading; however, the changes were minimal in both approaches. PS dental implants had a significant increment in the percentage of bone integration, whereas that for PM dental implants dropped over time, with no significance. In PS dental implants that occlude with natural teeth, vertical and horizontal bone gain was observed, and it was significant at 3 years ( p = 0.023). A significant horizontal bone gain was observed in the opposing natural teeth at 3-year ( p = 0.002) and 5-year loading ( p = 0.002). The PS concept appears to preserve more MBL around dental implants by stabilizing the vMBL and hMBL over a 5-year period. A minimal marginal bone change was detected in both concepts. The opposing natural teeth at PS dental implants showed a favorable effect on marginal bone tissues.

Background: The maintenance of marginal bone levels around dental implants is an important criterion for evaluating the success of implants. Although computer-aided design/computer-aided manufacturing (CAD/CAM) customized abutments (CAs) provide more flexible solutions, compared with the original preformed stock abutments (PAs), there are dimensional tolerances and underlying drawbacks in the production of CAD/CAM CAs, which may change the tightness and seamless connection between fixtures and abutments set by the manufacturer and then affect the long-term stability of the abutments. This study aimed to examine the change in both mesial and distal bone levels using digital periapical radiographs to evaluate the difference between CAD/CAM CAs and original PAs.Material and methods: Radiographs were taken before delivery; after functional loading for 1 month; and after 3, 6, and 12 months; and the vertical marginal bone levels (vMBLs) of both the mesial and distal surrounding implant bones were measured. All data are presented as means ± standard errors and were analyzed using Student’s t-test. A p-value < 0.05 was judged to represent a significant difference. Results: A total of 57 implants in 50 patients were divided into 22 CAD/CAM CAs and 35 original stock abutments. The PAs appeared to have a more stable bone level. By contrast, the amount of bone level change in the CAs was higher than that in the PAs. The change in the vMBL of the CAs was significantly more than that of the PAs after functional loading for 1 month (p = 0.006), 3 months (p = 0.013), 6 months (p = 0.014), and 12 months (p = 0.002). In contrast, the distal marginal bone level was lower than the mesial marginal bone level in any period. Nevertheless, the bone levels of the CAs and PAs in any period were comparable with no significant difference. Conclusions: Significant differences were found between the mesial and distal bone levels in the PAs. The CAD/CAM CAs showed a significantly greater bone level change than the original stock abutments after functional loading.

While chimeric antigen receptor (CAR) T cells targeting CD19 can cure a subset of patients with B cell malignancies, most patients treated will not achieve durable remission. Identification of the mechanisms leading to failure is essential to broadening the efficacy of this promising platform. Several studies have demonstrated that disruption of CD19 genes and transcripts can lead to disease relapse after initial response; however, few other tumor-intrinsic drivers of CAR T cell failure have been reported. Here we identify expression of the Golgi-resident intramembrane protease Signal peptide peptidase-like 3 (SPPL3) in malignant B cells as a potent regulator of resistance to CAR therapy. Loss of SPPL3 results in hyperglycosylation of CD19, an alteration that directly inhibits CAR T cell effector function and suppresses anti-tumor cytotoxicity. Alternatively, over-expression of SPPL3 drives loss of CD19 protein, also enabling resistance. In this pre-clinical model these findings identify post-translational modification of CD19 as a mechanism of antigen escape from CAR T cell therapy., (© 2022. The Author(s).)

Background: In Taiwan, the vaccination program started in March 2021, with ChAdOx1-S being the first available WHO-approved COVID-19 vaccine, followed by Moderna vaccine. This study aimed to investigate the immunogenicity and safety of homologous and heterologous prime-boost regimens with ChAdOx1-S and mRNA-1273., Methods: From March to November 2021, homologous or heterologous regimens with ChAdOx1-S and mRNA-1273 vaccination (ChAdOx1-S/ChAdOx1-S, mRNA-1273/mRNA-1273, ChAdOx1-S/mRNA-1273) were given to 945 healthy participants. Serum samples were collected at designated time points. The anti-RBD/S1 antibody titers and neutralizing ability were measured by three different immunoassays: Elecsys® Anti-SARS-CoV-2 S (Roche Diagnostics, Mannheim, Germany), AdviseDx SARS-CoV-2 IgG II (Abbott Diagnostics Division, Sligo, Ireland), and cPass™ SARS-CoV-2 Neutralization Antibody Detection Kit (GenScript, New Jersey, USA)., Results: We found that heterologous vaccination with ChAdOx1-S/mRNA-1273 had an acceptable safety profile and induced higher total anti-RBD/S1 antibody production (p < 0.0001), yet lower anti-RBD/S1 IgG titer (p < 0.0001) and neutralizing ability (p = 0.0101) than mRNA-1273/mRNA-1273 group. Both regimens showed higher antibody titers and superior neutralizing abilities than ChAdOx1-S/ChAdOx1-S. An age-dependent antibody response to ChAdOx1-S/mRNA-1273 was shown after both the priming and the booster doses. Younger age was associated with higher antibody production and neutralizing ability., Conclusions: Heterologous ChAdOx1-S/mRNA-1273 vaccination regimen is generally safe and induces a robust humoral immune response that is non-inferior to that of mRNA-1273/mRNA-1273., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aberrant sugar metabolism is linked to an increased risk of pancreatic cancer. Previously, we found that high glucose induces genome instability and de novo oncogenic KRAS mutation preferentially in pancreatic cells through dysregulation of O-GlcNAcylation. Increasing O-GlcNAcylation by extrinsically supplying N-acetyl-D-glucosamine (GlcNAc) causes genome instability in all kinds of cell types regardless of pancreatic origin. Since many people consume excessive amount of sugar (glucose, fructose, and sucrose) in daily life, whether high sugar consumption directly causes genome instability in animals remains to be elucidated. In this communication, we show that excess sugar in the daily drink increases DNA damage and protein O-GlcNAcylation preferentially in pancreatic tissue but not in other kinds of tissue of mice. The effect of high sugar on the pancreatic tissue may be attributed to the intrinsic ratio of GFAT and PFK activity, a limiting factor that dictates UDP-GlcNAc levels. On the other hand, GlcNAc universally induces DNA damage in all six organs examined. Either inhibiting O-GlcNAcylation or supplementing dNTP pool diminishes the induced DNA damage in these organs, indicating that the mechanism of action is similar to that of high glucose treatment in pancreatic cells. Taken together, these results suggest the potential hazards of high sugar drinks and high glucosamine intake to genomic instability and possibly cancer initiation., Competing Interests: None., (AJCR Copyright © 2022.)

Background: Unproven cellular therapies are being offered to patients for a variety of conditions and diseases for which other treatments have failed. The use of untested cellular therapies is a worldwide problem. Practitioners (e.g., physicians, scientists, QA/QI facility managers, and policy advocates) are perhaps unaware of the risks involved with such therapies. Therefore, a critical need exists to bring attention to the potential limitations and adverse effects of these therapies to inform and limit misinformation., Study Design and Methods: We describe the extent of the unproven cellular therapy problem through a search of scientific literature and social media coverage. We also describe the regulatory framework that can be used by the practitioner to review and evaluate both proven and unproven cellular therapies., Results: We report on the current state of unproven cellular therapies across the globe. A workflow to facilitate an understanding of the regulatory processes involved in the approval of cellular therapies is provided as well as a list of warnings required by regulatory agencies on various products. It is hoped that this article will serve as a tool kit to educate the practitioner on navigating the field of unproven cellular therapy products., Discussion: Increasing awareness of the issues associated with unproven therapies through education is important to help in reducing misinformation and risks to patients., (© 2022 AABB.)

This study aims to identify research trends of scaffolding in the field of science education. To this end, both descriptive analysis and co-word analysis were conducted to examine the selected articles published in the Social Science Citation Index journals from 2000 to 2019. A total of 637 papers were retrieved as research samples through rounds of searching in Web of Science database. Overall, this study reveals a growing trend of science educators' academic publications about scaffolding in the recent two decades. In these sample papers, from 1,487 non-repeated keywords, we extracted 286 author-defined keywords shared by at least two studies as a benchmark dictionary. A series of co-word analyses were then conducted based on the dictionary to reveal the underlying co-occurring relationships of the words in title and abstract of the sample papers. Results showed that "scaffolding," "support," and "design" were the top three most frequently used keywords during 2000 and 2019. Visualization of co-word networks in each 5-year period further helps clarify both educators' common research foci and relevant research trends. Derived discussion and potential research directions are also provided., 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 © 2022 Lin, Tang, Lin, Changlai and Hsu.)

Few studies have compared marginal bone loss (MBL) around implant-retaining overdentures (IODs) vs. implant-supported fixed prostheses (FPs). This study evaluated the mean MBL and radiographic bone-implant interface contact (r-BIIC) around IODs and implant-supported FPs. We also investigated osseointegration and MBL around non-submerged dental implants. We measured the changes between the MBL in the mesial and distal sites immediately after prosthetic delivery and after one year. The mean MBL and its changes in the IOD group were significantly higher. The mean percentage of r-BIIC was significantly higher in the FP group. MBL and its changes in males were significantly higher in the IOD group. The percentage of r-BIIC was significantly higher in the FP group. MBL in the lower site in the IOD group was significantly higher. Regarding MBL, the location of the implant was the only significant factor in the IOD group, while gender was the only significant predictor in the FP group. Regarding the r-BIIC percentage, gender was a significant factor in the FP group. We concluded that non-submerged dental implants restored with FPs and IODs maintained stable bone remodeling one year after prosthetic delivery.

Background: competition in the healthcare market is becoming increasingly intense. Health technology continues to evolve, so hospitals and clinics need to strengthen hospital management techniques and also adopt a more patient-centered approach in order to provide high-quality healthcare services, including a more simplified process and shorter waiting times for examinations. The Lean and Six Sigma methodologies and smart technology were introduced and implemented into the integrated perioperative management (PERIO) processes for the purpose of decreasing pre-admission management waiting time, as well as increasing the completion rate and quality of pre-admission management for surgical patients in a 1576-bed medical center in central Taiwan., Methods: in order to improve hospital admission procedures for surgical patients by shortening process waiting times, simplifying admission processes, emphasizing a patient-centered approach, and providing the most efficient service process, the present study applied the DMAIC architecture of the Lean Six Sigma. This approach allowed the patients to save time on the hospital admission process. The current workflow used value flow mapping to identify wasted time caused by unnecessary walking and waiting during the hospital admission process. Therefore, we improved the process cycle for each patient by simultaneously selecting and controlling the process for the purpose of saving time., Results: the experimental results show that the percentage of Process Cycle Efficiency (PCE) increased from 35.42% to 42.47%, Value Added was reduced from 34 to 31 min, and Non-Value Added was reduced from 62 to 42 min. The satisfaction score of the 97 pre-implementation patients was 4.29 compared with 4.40 among the 328 post-implementation patients ( p < 0.05). The LOS (Length of Stay) of 2660 pre-implementation patients was 2.49~3.31 days and for 304 after-implementation patients it was 1.16~1.57 days., Conclusions: by integrating different units and establishing standard perioperative management (PERIO) procedures, together with the support of the information systems, the time spent by patients on hospital admission procedures was shortened. These changes also improved the comprehensiveness of the preoperative preparations and the surgical safety of patients, thereby facilitating the provisions necessary for high-quality healthcare services. This in turn reduced the average length of hospital stays and increased the turnover of patients, benefiting the overall operations of the hospital.

Obstructive sleep apnoea (OSA) is a global health concern, and polysomnography (PSG) is the gold standard for assessing OSA severity. However, the sleep parameters of home-based and in-laboratory PSG vary because of environmental factors, and the magnitude of these discrepancies remains unclear. We enrolled 125 Taiwanese patients who underwent PSG while wearing a single-lead electrocardiogram patch (RootiRx). After the PSG, all participants were instructed to continue wearing the RootiRx over three subsequent nights. Scores on OSA indices-namely, the apnoea-hypopnea index, chest effort index (CEI), cyclic variation of heart rate index (CVHRI), and combined CVHRI and CEI (Rx index), were determined. The patients were divided into three groups based on PSG-determined OSA severity. The variables (various severity groups and environmental measurements) were subjected to mean comparisons, and their correlations were examined by Pearson's correlation coefficient. The hospital-based CVHRI, CEI, and Rx index differed significantly among the severity groups. All three groups exhibited a significantly lower percentage of supine sleep time in the home-based assessment, compared with the hospital-based assessment. The percentage of supine sleep time (∆Supine%) exhibited a significant but weak to moderate positive correlation with each of the OSA indices. A significant but weak-to-moderate correlation between the ∆Supine% and ∆Rx index was still observed among the patients with high sleep efficiency (≥80%), who could reduce the effect of short sleep duration, leading to underestimation of the patients' OSA severity. The high supine percentage of sleep may cause OSA indices' overestimation in the hospital-based examination. Sleep recording at home with patch-type wearable devices may aid in accurate OSA diagnosis.

Purpose: No study to date has described the overall landscape of sleep disorders management and training in otolaryngology departments of different countries. The aim of our study was to investigate and compare settings, diagnostic and therapeutic approaches and training programmes., Methods: An international online survey was developed with the collaboration of the YO-IFOS (Young Otolaryngologists-International Federation of Otorhinolaryngological Societies) to assess the current practice of otolaryngologists in the management of sleep disorders. The survey also included a session dedicated to training., Results: A total of 126 otolaryngologists completed the survey. The larger part of responses was collected from Central/South America and Europe. The majority of responders from South/Central America (97%) declared to be certified as sleep specialist while 49% of Europeans stated the opposite. Of responders 83% perform a drug-induced sleep endoscopy (DISE) before planning a possible surgical intervention. Soft palate and base of tongue interventions were the most common procedure, respectively performed in 94% and 79% of the cases. Residents were allowed to perform soft palate surgery in 77% of the cases. Upper airway stimulation (26% vs 10%), trans-oral robotic surgery (36% vs 11%) and radiofrequency of the base of the tongue (58% vs 25%) were preferred more frequently by European responders. The highest caseloads of soft palate surgery and bi-maxillary advancement were registered in the academic institutions., Conclusion: Significant concordance and few interesting divergences in diagnosis and treatment of sleep disorders were observed between nationalities and types of institution. Economic resources might have played a significant role in the therapeutic choice. Trainees' lack of exposure to certain interventions and to a sufficient caseload appeared to be the main burden to overcome., (© 2020. Springer Nature Switzerland AG.)

Background: In intermittent negative airway pressure (iNAP) therapy, soft tissues are reshaped into a forward-resting position, thus reducing airway obstruction during sleep. This study investigated the effect of iNAP therapy that was administered during drug-induced sleep endoscopy with target-controlled infusion (TCI-DISE) in patients with obstructive sleep apnea (OSA) intolerant of continuous positive airway pressure (CPAP) therapy., Methods: This prospective case series study included 92 patients with polysomnography (PSG)-confirmed OSA who underwent TCI-DISE with iNAP from January 2018 to February 2020 at a tertiary referral hospital. Upper airway obstruction was evaluated and scored using the velum, oropharynx, tongue base, and epiglottis (VOTE) classification. Obstruction severity was assessed multiple times with the patient in the supine position with or without lateral rotation of the head and the application of iNAP therapy, respectively., Results: After the application of iNAP therapy in the supine position, obstruction severity decreased significantly: from complete or partial obstruction to partial or no obstruction in 37, 12, and 36 patients (40.2%, 13%, and 39%, respectively) with velar obstruction, oropharyngeal, and tongue base obstruction, respectively. After simultaneously applying iNAP therapy with head rotation, obstruction severity decreased in 47, 43, and 19 patients (51%, 47%, and 21%, respectively) with velar, tongue base, and epiglottic obstruction, respectively., Conclusion: In TCI-DISE, we found that iNAP therapy relieved velar, oropharyngeal, and tongue base obstruction in the supine position in some patients. Moreover, iNAP therapy can be combined with positional therapy to alleviate velar, tongue base, and epiglottic obstruction in some patients. TCI-DISE can also be used to screen the possible responders for iNAP therapy because it is less time consuming than PSG., Competing Interests: Ofer Jacobowitz reports grants and personal fees from Livanova and personal fees from Nyxoah Medical, outside the submitted work. The authors report no other potential conflicts of interest for this work., (© 2021 Kuo et al.)

Background: The objective of this study was to evaluate the effects of opposite tooth conditions on change in marginal bone level (MBL) around submerged dental implants., Materials and Methods: The study included healthy patients with one or two implants. Structures opposite implants were either natural teeth (NT) or fixed restorations (FRs). MBLs were measured on digital periapical radiographs at the mesial and distal aspects of each implant., Results: Sixty implants were inserted by the 3-year follow-up. Mean MBLs for NT were 0.21 ± 0.33 mm before prosthetic loading and 0.30 ± 0.41 mm 3 years later ( p = 0.001). Mean MBLs with FRs were 0.36 ± 0.45 mm before loading and 0.53 ± 0.50 mm 3 years later ( p < 0.001). Changes in mean MBL from the 6-month follow-up to the 1- and 3-year follow-ups were statistically significant ( p < 0.01) for implants opposite NT. However, changes in mean MBL from the 6-month follow-up to the 1-year ( p = 0.161) and 3-year follow-ups ( p = 1.000) were not significant for implants opposite FRs. Between baseline and the 3-year follow-up, MBL change was relatively small and did not differ regarding NT and FRs., Conclusion: Bone loss was greater if submerged dental implants were opposed by FRs. MBLs around submerged implants continued to change after 3 years if NT opposed implants.

Absorbable porcine collagen membrane with a bovine bone graft can be considered for regenerative treatment in periodontal class II furcation defects. We evaluated the clinical efficacy of guided tissue regeneration (GTR) treatment with bovine bone xenograft and a porcine collagen membrane in molars with class II furcations. Probing depth (PD), clinical attachment level (CAL), and bone level (BL) were recorded at baseline and at 3, 6, and 9 months postoperatively. Thirty class II furcation defects from the lower and upper molars were assessed. Significant improvements in PD and CAL were observed from baseline to 9 months in all groups ( p < 0.01). BL improved in all groups except group A in the upper molars in radiographic assessment ( p < 0.05). The lower and upper molars showed PD reduction of 50.5% ± 7.44% and 46.2% ± 11.2%, respectively, at 9 months ( p = 0.044). In furcations of 1-3 mm, the lower and upper molars showed PD reductions of 51.2% ± 4.49% and 36.5% ± 16.14%, respectively ( p = 0.035). The lower and upper molars showed a CAL gain of 51.1% ± 4.64% and 33.6% ± 18.8%, respectively ( p = 0.037). Thus, GTR with bovine bone graft and porcine collagen membrane yielded good results in class II furcations, with better results in the lower than in the upper molars.

Background: Coronavirus disease 2019 (COVID-19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes infectious symptoms including fever, cough, respiratory and gastrointestinal symptoms, and even loss of smell/taste and to date had caused 489 000 people to be infected with 32 000 deaths. This article aims to develop some strategies in dealing with the COVID-19 epidemic to prevent nosocomial infection and ensure the safety of healthcare workforce and employees., Methods: This is a prospectively registered and retrospective descriptive study investigating the clinical characteristics, results of diagnostic tests, and patients' disposition from February 1, 2020, to April 30, 2020, at a tertiary medical center in Northern Taiwan., Results: There is no nosocomial spreading of SARS-CoV-2 in our facility. The following strategies were followed: information transparency; epidemic prevention resources planning by authorities; multidisciplinary cooperation; informative technologies; immigration quarantine policies; travel restrictions; management of diversion/subdivision; self-health monitoring; social distancing; screening of travel, occupation, contact, and cluster (TOCC) history; traffic control bundling (TCB); training of using personal protective equipment; real-name visiting management; and employee care. The patients' basic characteristics and diagnostic results were gathered. Of the 3832 cases, about 25.9% had travel history. Most of them were traveling to Asia (419 people/time, 10.9%) and from China (256 people/time, 6.7%). Meanwhile, healthcare personnel accounted for 316 people/time (8.3%) and cleaning personnel, 6 people/time (0.16%). The 36 cases who care or have contact with confirmed cases have negative results from the COVID-19 test. The most frequent symptoms were fever and upper respiratory infection followed by gastrointestinal symptoms., Conclusion: The above strategies were followed. Patients were stratified based on the risk of TOCC history assessment to ensure the safety of healthcare personnel and patients' appropriate and timely medical services., Competing Interests: Conflicts of Interest: The authors declared no conflict of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)

Objectives/hypothesis: To evaluate associations between sleep surgery and CRP (C-reactive protein) levels in adults with obstructive sleep apnea (OSA)., Study Design: Meta-analysis., Methods: Two authors independently searched PubMed, Medline, EMBASE, and Cochrane review databases until July 2019. The keywords used were sleep apnea, OSA, sleep apnea syndromes, surgery, C-reactive protein (CRP), and inflammatory markers. The effects of sleep surgery on CRP levels were examined using a random-effects model., Results: Nine studies with 277 patients were analyzed (mean age: 46.5 years; 92% men; mean sample size: 30.8 patients). The mean change in the apnea-hypopnea index (AHI) after surgery was significantly reduced by -21.1 (95% confidence interval [CI], -28.4 to -13.7) events/hr. Overall, sleep surgery resulted in a significant reduction of CRP levels in patients with OSA (standardized mean difference [SMD] = -0.39, 95% CI, -0.67 to -0.11). Patients with postoperative AHI reduction >20 events/hr achieved a greater reduction in CRP than those with AHI reduction <20 events/hr (SMD: -0.72 vs. -0.14, P for heterogeneity = .007). According to subgroup analysis, differences in the CRP levels after surgery were nonsignificant in the different countries (i.e., United States vs. other countries), CRP types (i.e., CRP vs. high-sensitivity CRP), surgical procedures (i.e., pharyngeal surgery vs. other surgical procedures), and follow-up period (i.e., <6 vs. >6 months)., Conclusions: Sleep surgery for OSA resulted in a significant reduction of CRP levels in adults. The beneficial effect of surgery on CRP levels is greater in patients with large improvement in OSA (i.e., AHI reduction >20 events/hr) after sleep surgery. Laryngoscope, 131:1180-1187, 2021., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)