Publications by authors named "Huan Jia"

72 Publications

A rapid simple point-of-care assay for the detection of SARS-CoV-2 neutralizing antibodies.

Commun Med (Lond) 2021 11;1:46. Epub 2021 Nov 11.

Antimicrobial Resistance Interdisciplinary Research Group (AMR-IRG), Singapore-MIT Alliance in Research and Technology (SMART), #03-10/11 Innovation Wing, 1 CREATE way, Singapore, 138602 Singapore.

Background: Neutralizing antibodies (NAbs) prevent pathogens from infecting host cells. Detection of SARS-CoV-2 NAbs is critical to evaluate herd immunity and monitor vaccine efficacy against SARS-CoV-2, the virus that causes COVID-19. All currently available NAb tests are lab-based and time-intensive.

Method: We develop a 10 min cellulose pull-down test to detect NAbs against SARS-CoV-2 from human plasma. The test evaluates the ability of antibodies to disrupt ACE2 receptor-RBD complex formation. The simple, portable, and rapid testing process relies on two key technologies: (i) the vertical-flow paper-based assay format and (ii) the rapid interaction of cellulose binding domain to cellulose paper.

Results: Here we show the construction of a cellulose-based vertical-flow test. The developed test gives above 80% sensitivity and specificity and up to 93% accuracy as compared to two current lab-based methods using COVID-19 convalescent plasma.

Conclusions: A rapid 10 min cellulose based test has been developed for detection of NAb against SARS-CoV-2. The test demonstrates comparable performance to the lab-based tests and can be used at Point-of-Care. Importantly, the approach used for this test can be easily extended to test RBD variants or to evaluate NAbs against other pathogens.
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http://dx.doi.org/10.1038/s43856-021-00045-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9053278PMC
November 2021

Finger stick blood test to assess postvaccination SARS-CoV-2 neutralizing antibody response against variants.

Bioeng Transl Med 2022 May 10;7(2):e10293. Epub 2022 Feb 10.

Antimicrobial Resistance Interdisciplinary Research Group (AMR-IRG) Singapore-MIT Alliance in Research and Technology (SMART) Singapore.

There is clinical need for a quantifiable point-of-care (PoC) SARS-CoV-2 neutralizing antibody (nAb) test that is adaptable with the pandemic's changing landscape. Here, we present a rapid and semi-quantitative nAb test that uses finger stick or venous blood to assess the nAb response of vaccinated population against wild-type (WT), alpha, beta, gamma, and delta variant RBDs. It captures a clinically relevant range of nAb levels, and effectively differentiates prevaccination, post first dose, and post second dose vaccination samples within 10 min. The data observed against alpha, beta, gamma, and delta variants agrees with published results evaluated in established serology tests. Finally, our test revealed a substantial reduction in nAb level for beta, gamma, and delta variants between early BNT162b2 vaccination group (within 3 months) and later vaccination group (post 3 months). This test is highly suited for PoC settings and provides an insightful nAb response in a postvaccinated population.
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http://dx.doi.org/10.1002/btm2.10293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9115707PMC
May 2022

Generation of Thermally Stable Affinity Pairs for Sensitive, Specific Immunoassays.

Methods Mol Biol 2022 ;2491:417-469

Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

Many point-of-care diagnostic tests rely on a pair of monoclonal antibodies that bind to two distinct epitopes of a molecule of interest. This protocol describes the identification and generation of such affinity pairs based on an easily produced small protein scaffold rcSso7d which can substitute monoclonal antibodies. These strong binding variants are identified from a large yeast display library. The approach described can be significantly faster than antibody generation and epitope binning, yielding affinity pairs synthesized in common bacterial protein synthesis strains, enabling the rapid generation of novel diagnostic tools.
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http://dx.doi.org/10.1007/978-1-0716-2285-8_21DOI Listing
January 2022

Candidacy for Cochlear Implantation in Prelingual Profoundly Deaf Adult Patients.

J Clin Med 2022 Mar 28;11(7). Epub 2022 Mar 28.

Unité Fonctionnelle Implants Auditifs, Département d'Oto-Rhino-Laryngologie, Groupe Hospitalo-Universitaire Pitié-Salpêtrière, APHP Sorbonne Université, 75013 Paris, France.

Cochlear implantation is usually not recommended for prelingual profoundly deaf adults, although some of these patients might benefit from it. This study aims to define the candidates for cochlear implantation in this population. This retrospective study reviewed 34 prelingual profoundly deaf patients who had received a cochlear implant at 32 ± 1.7 years old (16-55), with at least 1 year of follow-up. Speech perception and quality of life were assessed before and 3, 6, and 12 months after cochlear implantation, then every year thereafter. According to the word speech intelligibility in quiet (WSI) 1 year after implantation, two groups were identified: good performer (GP) with WSI ≥ 50% ( = 15), and poor performer (PP) with WSI ≤ 40% ( = 19). At the 1 year mark, mean WSI improved by 28 ± 4.6% (-20-100) ( < 0.0001). In GP, the intelligibility for words and sentences, communication and quality of life scales improved. In PP, the communication scale improved, but not auditory performance or quality of life. GP and PP differed pre-operatively in speech production, communication abilities, and WSI in best-aided conditions. In prelingual profoundly deaf adults, a dramatic auditory performance benefit could be expected after cochlear implantation if the patients have some degree of speech intelligibility in aided conditions and have developed oral communication and speech production.
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http://dx.doi.org/10.3390/jcm11071874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8999851PMC
March 2022

Development and translation of a paper-based top readout vertical flow assay for SARS-CoV-2 surveillance.

Lab Chip 2022 03 29;22(7):1321-1332. Epub 2022 Mar 29.

Antimicrobial Resistance Interdisciplinary Research Group (AMR-IRG), Singapore-MIT Alliance in Research and Technology (SMART), 1 CREATE Way, 138602 Singapore.

Surveillance of SARS-CoV-2 infection is critical for controlling the current pandemic. Antigen rapid tests (ARTs) provide a means for surveillance. Available lateral flow assay format ARTs rely heavily on nitrocellulose paper, raising challenges in supply shortage. Vertical flow assay (VFA) with cellulose paper as test material attracts much attention as a complementary test approach. However, current reported VFAs are facing challenges in reading the test signal from the bottom face of the test cassette, complicating the test workflow and hindering translation into rapid test application. Here, we address this gap with an enhanced VFA against SARS-CoV-2 N protein that adapts a cellulose pull-down test format allowing (1) one-step sample application at the top of the test cassette and (2) readout of the test signal from the top. We also demonstrate the feasibility of translating the enhanced VFA into a point-of-care application that can help in SARS-CoV-2 surveillance.
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http://dx.doi.org/10.1039/d2lc00073cDOI Listing
March 2022

Genetic findings of Sanger and nanopore single-molecule sequencing in patients with X-linked hearing loss and incomplete partition type III.

Orphanet J Rare Dis 2022 02 21;17(1):65. Epub 2022 Feb 21.

Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.

Background: POU3F4 is the causative gene for X-linked deafness-2 (DFNX2), characterized by incomplete partition type III (IP-III) malformation of the inner ear. The purpose of this study was to investigate the clinical characteristics and molecular findings in IP-III patients by Sanger or nanopore single-molecule sequencing.

Methods: Diagnosis of IP-III was mainly based on clinical characteristics including radiological and audiological findings. Sanger sequencing of POU3F4 was carried out for these IP-III patients. For those patients with negative results for POU3F4 Sanger sequencing, nanopore long-read single-molecule sequencing was used to identify the possible pathogenic variants. Hearing intervention outcomes of hearing aids (HAs) fitting and cochlear implantation (CI) were also analyzed. Aided pure tone average (PTA) was further compared between two groups of patients according to their different locations of POU3F4 variants: in the exon region or in the upstream region.

Results: In total, 18 male patients from 14 unrelated families were diagnosed with IP-III. 10 variants were identified in POU3F4 by Sanger sequencing and 6 of these were reported for the first time (p.Gln181*, p.Val215Gly, p.Arg282Gln, p.Gln316*, c.903_912 delins TGCCA and p.Arg205del). Four different deletions that varied from 80 to 486 kb were identified 876-1503 kb upstream of POU3F4 by nanopore long-read single-molecule sequencing. De novo genetic mutations occurred in 21.4% (3/14) of patients with POU3F4 mutations. Among these 18 patients, 7 had bilateral HAs and 10 patients received unilateral CI. The mean aided PTA for HAs and CI users were 41.1 ± 5.18 and 40.3 ± 7.59 dB HL respectively. The mean PTAs for patients with the variants located in the exon and upstream regions were 39.6 ± 6.31 versus 43.0 ± 7.10 dB HL, which presented no significant difference (p = 0.342).

Conclusions: Among 14 unrelated IP-III patients, 28.6% (4/14) had no definite mutation in exon region of POU3F4. However, possible pathogenic deletions were identified in upstream region of this gene. De novo genetic mutations occurred in 21.4% (3/14) of patients with POU3F4 mutation. There was no significant difference of hearing intervention outcomes between the IP-III patients with variants located in the exon region and in the upstream region.
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http://dx.doi.org/10.1186/s13023-022-02235-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8862311PMC
February 2022

Origins of biallelic inactivation of NF2 in neurofibromatosis type 2.

Neuro Oncol 2022 06;24(6):903-913

Department of Otolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Elucidating the mechanism by which biallelic inactivation evolved could provide a mechanistic understanding for NF2 tumorigenesis and also a rationale for clinical management.

Methods: A cohort of 60 NF2 patients was recruited. Next-generation sequencing of tumor and paired control samples was used to explore how NF2 mutations evolve in determining the clinical phenotypes.

Results: In total, 60 blood samples (one from each patient) and 61 (from 35 patients) NF2-associated tumors were collected. Next-generation sequencing of the blood samples detected "first hit" NF2 mutation in 35/60 donors (58.3%), 82.9% of which (29/35) bear heterozygous germline mutations, and 17.1% (6/35) of which are mosaics with variable allelic frequency (VAF). While a number of NF2 patients were found without germline mutation, most (57/61, 93.4%) NF2-associated tumors were identified with NF2 somatic mutation. We calculated the correlation between the onset latency of mosaic and germline NF2 allele carriers with the mosaicism VAF. The mosaicism VAF is negatively and linearly correlated to clinical symptom onset latency (R2 = 0.3677, P = .00351), suggesting biallelic inactivation probability is a linear function of "first hit" prevalence in the body. The second NF2 somatic mutation occurrence time positively correlates with the onset of clinical symptoms (R2 = 0.4151, P = .02633), suggesting tumor growth is linearly proportional to the time after biallelic inactivation.

Conclusions: Our results suggested that biallelic inactivation of NF2 evolved through neutral drift and preexisting first hit NF2 allele determines certain aspects of the clinical symptoms. Genetic diagnosis should be included in the diagnostic criteria and treatment consideration of NF2.
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http://dx.doi.org/10.1093/neuonc/noab287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9159453PMC
June 2022

Hearing Protection Outcomes of Analog Electrode Arrays Coated with Different Drug-Eluting Polymer Films Implanted into Guinea Pig Cochleae.

Drug Des Devel Ther 2021 11;15:3443-3450. Epub 2021 Aug 11.

Department of Otorhinolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People's Republic of China.

Objective: To investigate the hearing protection outcomes of different drug-eluting analog electrode arrays implanted into guinea pig cochleae.

Methods: Sixty guinea pigs were randomly divided into a negative control group and five experimental groups implanted separately with blank (drug carrier), dexamethasone (DXM), aracytine (Ara-C), Ara-C+DXM, and nicotinamide adenine dinucleotide (NAD+) eluting analog electrode arrays. Micro CT was used to supervise the surgical procedure. Auditory brainstem response (ABR) thresholds of the guinea pigs were measured and analyzed.

Results And Conclusions: Compared with the negative control, all other groups showed a significant increase in ABR threshold (p<0.001) after surgery. Among them, there was no obvious difference between the blank (0 vs 90 days: 59.70±10.57 vs 64.60±9.47 dB SPL) and the NAD+ group (0 vs 90 days: 59.90±9.87 vs 64.70±8.65 dB SPL). On the other hand, the ABR thresholds in the DXM (0 days: 58.10±10.73 dB SPL; 90 days: 51.70±9.07 dB SPL) and the Ara-C group (0 days: 59.00±10.05 dB SPL; 90 days: 51.60±8.48 dB SPL) decreased significantly compared with the former two groups (p<0.001). However, the Ara-C+DXM group showed no further benefit (p>0.05). In addition, a significantly higher survival rate of spiral ganglion neurons in cochleae was observed in the Ara-C and/or DXM groups.
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http://dx.doi.org/10.2147/DDDT.S318117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370035PMC
January 2022

ProfKin: A comprehensive web server for structure-based kinase profiling.

Eur J Med Chem 2021 Dec 14;225:113772. Epub 2021 Aug 14.

Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, Shanghai, 200237, China. Electronic address:

Protein kinases are central mediators of signal-transduction cascades and attractive drug targets for therapeutic intervention. Since kinases are structurally and mechanistically related to each other, kinase inhibitor selectivity is often investigated by kinase profiling and considered as an important index for drug discovery. We here describe a versatile web server termed ProfKin for structure-based kinase profiling, which is based on a kinase-ligand focused database (KinLigDB). It provides all ready-to-use 3D structure coordinates of 4219 kinase-ligand complex structures covering 297 human kinases and the associated information, particularly including binding site type, binding ligand type, interaction fingerprints, downstream molecules and related human diseases. The web server works via predicting possible binding modes for the query molecule, prioritizing the binding modes guided by an interaction fingerprint analysis method, and giving a list of ranked kinases by a comprehensive index. Users can freely select entire or part of the KinLigDB database, e.g. via subfamily and binding site type, to customize the profiling contents. The superimpositions of the predicted binding poses of the query molecule with reference binding modes can be visually inspected on the website. The additional classification attributes and phylogenetic tree are also given for each top-ranked kinase.
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http://dx.doi.org/10.1016/j.ejmech.2021.113772DOI Listing
December 2021

Developing a SARS-CoV-2 Antigen Test Using Engineered Affinity Proteins.

ACS Appl Mater Interfaces 2021 Aug 11;13(33):38990-39002. Epub 2021 Aug 11.

Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

The ongoing COVID-19 pandemic has clearly established how vital rapid, widely accessible diagnostic tests are in controlling infectious diseases and how difficult and slow it is to scale existing technologies. Here, we demonstrate the use of the rapid affinity pair identification via directed selection (RAPIDS) method to discover multiple affinity pairs for SARS-CoV-2 nucleocapsid protein (N-protein), a biomarker of COVID-19, from in vitro libraries in 10 weeks. The pair with the highest biomarker sensitivity was then integrated into a 10 min, vertical-flow cellulose paper test. Notably, the as-identified affinity proteins were compatible with a roll-to-roll printing process for large-scale manufacturing of tests. The test achieved 40 and 80 pM limits of detection in 1× phosphate-buffered saline (mock swab) and saliva matrices spiked with cell-culture-generated SARS-CoV-2 viruses and is also capable of detection of N-protein from characterized clinical swab samples. Hence, this work paves the way toward the mass production of cellulose paper-based assays which can address the shortages faced due to dependence on nitrocellulose and current manufacturing techniques. Further, the results reported herein indicate the promise of RAPIDS and engineered binder proteins for the timely and flexible development of clinically relevant diagnostic tests in response to emerging infectious diseases.
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http://dx.doi.org/10.1021/acsami.1c08174DOI Listing
August 2021

Robot-Assisted Electrode Array Insertion Becomes Available in Pediatric Cochlear Implant Recipients: First Report and an Intra-Individual Study.

Front Surg 2021 7;8:695728. Epub 2021 Jul 7.

Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

As an advanced surgical technique to reduce trauma to the inner ear, robot-assisted electrode array (EA) insertion has been applied in adult cochlear implantation (CI) and was approved as a safe surgical procedure that could result in better outcomes. As the mastoid and temporal bones are generally smaller in children, which would increase the difficulty for robot-assisted manipulation, the clinical application of these systems for CI in children has not been reported. Given that the pediatric candidate is the main population, we aim to investigate the safety and reliability of robot-assisted techniques in pediatric cochlear implantation. Retrospective cohort study at a referral center in Shanghai including all patients of simultaneous bilateral CI with robotic assistance on one side (RobOtol® system, Collin ORL, Bagneux, France), and manual insertion on the other (same brand of EA and CI in both side), from December 2019 to June 2020. The surgical outcomes, radiological measurements (EA positioning, EA insertion depth, mastoidectomy size), and audiological outcomes (Behavior pure-tone audiometry) were evaluated. Five infants (17.8 ± 13.5 months, ranging from 10 to 42 months) and an adult (39 years old) were enrolled in this study. Both perimodiolar and lateral wall EAs were included. The robot-assisted EA insertion was successfully performed in all cases, although the surgical zone in infants was about half the size in adults, and no difference was observed in mastoidectomy size between robot-assisted and manual insertion sides ( = 0.219). The insertion depths of EA with two techniques were similar ( = 0.583). The robot-assisted technique showed no scalar deviation, but scalar deviation occurred for one manually inserted pre-curved EA (16%). Early auditory performance was similar to both techniques. Robot-assisted technique for EA insertion is approved to be used safely and reliably in children, which is possible and potential for better scalar positioning and might improve long-term auditory outcome. Standard mastoidectomy size was enough for robot-assisted technique. This first study marks the arrival of the era of robotic CI for all ages.
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http://dx.doi.org/10.3389/fsurg.2021.695728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294934PMC
July 2021

Thermal Safety of Endoscopic Usage in Robot-Assisted Middle Ear Surgery: An Experimental Study.

Front Surg 2021 14;8:659688. Epub 2021 May 14.

Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The widespread application of endoscopic ear surgery (EES), performed through the external auditory canal, has revealed the limitations of the one-handed technique. The RobOtol® (Collin ORL, Bagneux, France) otological robotic system has been introduced to enable two-handed procedures; however, the thermal properties of dedicated endoscopes, which are usually used in neurosurgery, called "neuro-endoscopes," have not yet been clarified for the robotic systems. In this study, we aimed to profile the thermal characteristics of two dedicated neuro-endoscopes, as compared to endoscopes used routinely in manual EES, called "oto-endoscopes," and defined by a smaller diameter and shorter length, and to discuss the safe application of robotic assistance in EES. Two neuro-endoscopes (3.3 mm, 25 cm, 0°/30°) were studied using two routine light sources (LED/xenon), and two routine oto-endoscopes (3 mm, 14 cm, 0°/30°) were initially measured to provide a comprehensive comparison. Light intensities and temperatures were measured at different power settings. The thermal distributions were measured in an open environment and a human temporal bone model of EES. The cooling measures were also studied. Light intensity was correlated with stabilized tip temperatures ( < 0.01, = 0.8719). Under 100% xenon power, the stabilized temperatures at the tips of 0°, 30° neuro-endoscopes, and 0°, 30° oto-endoscopes were 96.1, 60.1, 67.8, and 56.4°C, respectively. With 100% LED power, the temperatures decreased by about 10°C, respectively. For the 0° neuro-endoscope, the illuminated area far away 1cm from the tip was below 37°C when using more than 50% both power, while this distance for 30° neuro-endoscope was 0.5 cm. In the EES temporal bone model, the round window area could reach 59.3°C with the 0° neuro-endoscope under 100% xenon power. Suction resulted in a ~1-2°C temperature drop, while a 10 mL saline rinse gave a baseline temperature which lasted for 2.5 min. Neuro-endoscope causes higher thermal releasing in the surgical cavity of ESS, which should be especially cautious in the robotic system usage. Applying submaximal light intensity, a LED source and intermittent rinsing should be considered for the safer robot-assisted EES using a neuro-endoscope that allows a two-handed surgical procedure.
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http://dx.doi.org/10.3389/fsurg.2021.659688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160440PMC
May 2021

Developing a SARS-CoV-2 Antigen Test Using Engineered Affinity Proteins.

ChemRxiv 2021 Apr 19. Epub 2021 Apr 19.

Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

The ongoing COVID-19 pandemic has clearly established how vital rapid, widely accessible diagnostic tests are in controlling infectious diseases and how difficult and slow it is to scale existing technologies. Here, we demonstrate the use of the rapid affinity pair identification via directed selection (RAPIDS) method to discover multiple affinity pairs for SARS-CoV-2 nucleocapsid protein (N-protein), a biomarker of COVID-19, from in vitro libraries in 10 weeks. The pair with the highest biomarker sensitivity was then integrated into a 10-minute, vertical-flow cellulose paper test. Notably, the as-identified affinity proteins were compatible with a roll-to-roll printing process for large-scale manufacturing of tests. The test achieved 40 pM and 80 pM limits of detection in 1×PBS (mock swab) and saliva matrices spiked with cell-culture generated SARS-CoV-2 viruses and is also capable of detection of N-protein from characterized clinical swab samples. Hence, this work paves the way towards the mass production of cellulose paper-based assays which can address the shortages faced due to dependence on nitrocellulose and current manufacturing techniques. Further, the results reported herein indicate the promise of RAPIDS and engineered binder proteins for the timely and flexible development of clinically relevant diagnostic tests in response to emerging infectious diseases.
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http://dx.doi.org/10.26434/chemrxiv.14442785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132241PMC
April 2021

MAP kinase Hog1 mediates a cytochrome P450 oxidoreductase to promote the Sporisorium scitamineum cell survival under oxidative stress.

Environ Microbiol 2021 06 19;23(6):3306-3317. Epub 2021 May 19.

College of Plant Protection, South China Agricultural University, Guangzhou, Guangdong, 510642, China.

The MAP kinase high osmolarity glycerol 1 (Hog1) plays a central role in responding to external oxidative stress in budding yeast Saccchromyces cerevisiae. However, the downstream responsive elements regulated by Hog1 remain poorly understood. In this study, we report that a Sporisorium scitamineum orthologue of Hog1, named as SsHog1, induced transcriptional expression of a putative cytochrome P450 oxidoreductase encoding gene SsCPR1, to antagonize oxidative stress. We found that upon exposure to hydrogen peroxide (H O ), SsHog1 underwent strikingly phosphorylation, which was proved to be critical for transcriptional induction of SsCPR1. Loss of SsCPR1 led to hypersensitive to oxidative stress similar as the sshog1Δ mutant did, but was resistant to osmotic stress, which is different from the sshog1Δ mutant. On the other hand, overexpression of SsCPR1 in the sshog1Δ mutant could partially restore its ability of oxidative stress tolerance, which indicated that the Hog1 MAP kinase regulates the oxidative stress response specifically through cytochrome P450 (SsCpr1) pathway. Overall, our findings highlight a novel MAPK signalling pathway mediated by Hog1 in regulation of the oxidative stress response via the cytochrome P450 system, which plays an important role in host-fungus interaction.
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http://dx.doi.org/10.1111/1462-2920.15565DOI Listing
June 2021

Intraoperative facial nerve electromyography parameters to optimize postoperative facial nerve outcome in patients with large unilateral vestibular schwannoma.

Acta Neurochir (Wien) 2021 08 7;163(8):2209-2217. Epub 2021 Apr 7.

Department of Otology, Auditory Implants and Skull Base Surgery, Sorbonne Université-APHP6, Groupe Hospitalier Pitié-Salpêtrière, 75013, Paris, France.

Background: Decision-making for large sporadic vestibular schwannomas (VS) resection guided by the intraoperative change in supramaximal facial nerve (FN) amplitude and latency response to optimize post-operative FN outcome.

Methods: Prospectively study of 43 patients, from January to December 2018, of large sporadic VS with preoperative normal FN function at our center. Tumors were removed through retrosigmoid (81%) or translabyrinthine (19%) approaches with FN monitoring. Intraoperative pre- and post-VS resection supramaximal (2 mA) amplitude and latency responses at the proximal FN root were recorded.

Results: Total, near-/subtotal VS resections (TR, NTR, STR) were achieved in 51%, 38%, and 11% of tumors, respectively, guided by no more than 40% decrease in supramaximal amplitude. Pre- and post-resection supramaximal amplitude and latency responses were lower and longer, respectively, in NTR+STR than in TR. At day 8, FN function was grade I-II in 77% of patients and grade III-V in 23%, and after 6 months, it was in grade I-II in 95% and grade III in 5%, and there was no significant difference between TR and NTR+STR. Facial palsy occurred in older patients and in the case of severe FN adhesion. At day 8, pre- and post-resection supramaximal amplitude but not latency responses were different between FN grade III-V and grade I-II. Serviceable hearing was preserved in 28% of large VS.

Conclusions: Intraoperative FN monitoring guided VS resection in large VS so that 49% retained some residual tumor. Accordingly, 95% good postoperative FN function and significant hearing preservation were achieved after 6 months.
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http://dx.doi.org/10.1007/s00701-021-04814-2DOI Listing
August 2021

Vertical Flow Cellulose-Based Assays for SARS-CoV-2 Antibody Detection in Human Serum.

ACS Sens 2021 05 6;6(5):1891-1898. Epub 2021 Apr 6.

Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

Rapid and inexpensive serological tests for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies are essential to conduct large-scale seroprevalence surveys and can potentially complement nucleic acid or antigen tests at the point of care. During the COVID-19 pandemic, extreme demand for traditional lateral flow tests has stressed manufacturing capacity and supply chains. Motivated by this limitation, we developed a SARS-CoV-2 antibody test using cellulose, an alternative membrane material, and a double-antigen sandwich format. Functionalized SARS-CoV-2 antigens were used as both capture and reporter binders, replacing the anti-human antibodies currently used in lateral flow tests. The test could provide enhanced sensitivity because it labels only antibodies against SARS-CoV-2 and the signal intensity is not diminished due to other human antibodies in serum. Three-dimensional channels in the assay were designed to have consistent flow rates and be easily manufactured by folding wax-printed paper. We demonstrated that this simple, vertical flow, cellulose-based assay could detect SARS-CoV-2 antibodies in clinical samples within 15 min, and the results were consistent with those from a laboratory, bead-based chemiluminescence immunoassay that was granted emergency use approval by the US FDA.
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http://dx.doi.org/10.1021/acssensors.1c00235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043201PMC
May 2021

HflX is a GTPase that controls hypoxia-induced replication arrest in slow-growing mycobacteria.

Proc Natl Acad Sci U S A 2021 03;118(12)

Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 117456 Singapore;

GTPase high requency of ysogenization X (HflX) is highly conserved in prokaryotes and acts as a ribosome-splitting factor as part of the heat shock response in Here we report that HflX produced by slow-growing bacillus Calmette-Guérin (BCG) is a GTPase that plays a critical role in the pathogen's transition to a nonreplicating, drug-tolerant state in response to hypoxia. Indeed, HflX-deficient BCG (KO) replicated markedly faster in the microaerophilic phase of a hypoxia model that resulted in premature entry into dormancy. The KO mutant displayed hallmarks of nonreplicating mycobacteria, including phenotypic drug resistance, altered morphology, low intracellular ATP levels, and overexpression of Dormancy (Dos) regulon proteins. Mice nasally infected with HflX KO mutant displayed increased bacterial burden in the lungs, spleen, and lymph nodes during the chronic phase of infection, consistent with the higher replication rate observed in vitro in microaerophilic conditions. Unlike fast growing mycobacteria, BCG HlfX was not involved in antibiotic resistance under aerobic growth. Proteomics, pull-down, and ribo-sequencing approaches supported that mycobacterial HflX is a ribosome-binding protein that controls translational activity of the cell. With HflX fully conserved between BCG and , our work provides further insights into the molecular mechanisms deployed by pathogenic mycobacteria to adapt to their hypoxic microenvironment.
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http://dx.doi.org/10.1073/pnas.2006717118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000101PMC
March 2021

Radiological and Audiological Outcomes of the LISTENT LCI-20PI Cochlear Implant Device.

Otol Neurotol 2021 04;42(4):524-531

Department of Otolaryngology Head and Neck Surgery, Sino-French Joint Clinic Research Center on Otology and Neuro-Otology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University.

Objective: To study the surgical results, intracochlear position of the electrode array (EA) and auditory performance of the LISTENT LCI-20PI cochlear implant device, and daily use status at 3 years.

Study Design: A retrospective study.

Setting: A single-tertiary referral center.

Patients: Between January and December 2016, 20 patients underwent cochlear implantation using the LISTENT LCI-20PI (lateral wall EA).

Intervention: Cochlear implantation.

Main Outcome Measures: Measurement of cochlear size, extent of posterior tympanotomy, and insertion depth. Scalar position of the EA evaluated by 3D reconstruction. Auditory outcomes 1 year after implantation and daily use status at 3 years.

Results: EAs were completely inserted in all cases with an insertion depth of 288 ± 36.8 degrees. One year later, the average sentence recognition score (SRS) was 90 ± 21.7%. EA scalar location was analyzed in 18 patients. Thirteen EAs (72.2%) were fully inserted into the scala tympani (ST) and 5 (27.8%) had shifted from the ST to the scala vestibuli (SV). There was no statistically significant difference in cochlear size, extent of posterior tympanotomy, or insertion depth between these two groups. EAs inserted by cochleostomy had a higher chance of scalar shift than those inserted via the round window (60% vs 15.4%, p = 0.099). SRS at 1 year with full ST insertion was significantly better than in those with scalar shift (99 ± 1.3% vs 83 ± 16.5%, p = 0.002). Three years after implantation, 92% of patients were daily users and 46% were telephone users.

Conclusions: The LISTENT LCI-20PI provided accredited hearing rehabilitation with a short insertion depth. Full insertion into the ST was associated with better cochlear implantation outcomes.
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http://dx.doi.org/10.1097/MAO.0000000000002963DOI Listing
April 2021

Cochlear Duct Length Calculation: Comparison Between Using Otoplan and Curved Multiplanar Reconstruction in Nonmalformed Cochlea.

Otol Neurotol 2021 08;42(7):e875-e880

Department of Otolaryngology-Head and Neck Surgery, Ninth People's Hospital.

Objective: To describe a new method to measure the cochlear parameters using Otoplan software, and to compare it with the traditional method using curved multiplanar reconstruction (cMPR).

Study Design: Retrospective analysis using internal consistency reliability and paired sample t test.

Setting: Tertiary referral center.

Patients: Thirty-four patients including 68 ears from a clinical trial were retrospectively reviewed.

Main Outcome Measures: The length, width, height (distances A, B, H), and cochlear duct length of each cochlea were measured independently using two modalities: Otoplan and cMPR. Internal consistency reliability of the two modalities was analyzed. The time spent on each measurement was also recorded.

Results: Otoplan software was compatible with all radiological data in this series. Distances A, B, and H showed no significant differences between Otoplan (9.33 ± 0.365, 6.61 ± 0.359, and 2.91 ± 0.312 mm) and cMPR (9.32 ± 0.314, 6.59 ± 0.342, and 2.93 ± 0.250 mm). The average cochlear duct length calculated by Otoplan was 34.37 ± 1.481 mm, which was not significantly different from that calculated by cMPR (34.55 ± 1.903mm, p = 0.215). The measurements with Otoplan had better internal consistency reliability compared with those by cMPR, and measurements with a higher peak kilovoltage (140 kVp) CT scan showed further higher internal consistency reliability. Time spent on each cochlea by Otoplan was 5.9 ± 0.69 min, significantly shorter than that by cMPR (9.3 ± 0.72 min).

Conclusion: Otoplan provides more rapid and reliable measurement of the cochlea than cMPR. Furthermore, it can be easily used in the laptop computer.
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http://dx.doi.org/10.1097/MAO.0000000000003119DOI Listing
August 2021

A microscope-assisted endoscopic transcanal transpromontorial approach for vestibular schwannoma resection: a preliminary report.

Eur Arch Otorhinolaryngol 2022 Jan 1;279(1):75-82. Epub 2021 Feb 1.

Department of Otolaryngology-Head and Neck Surgery, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.

Objective: To evaluate the feasibility of a microscope-assisted endoscopic transcanal transpromontorial approach (METTA) for the removal of small vestibular schwannomas (VS) limited to the internal auditory canal (IAC), and introduce a modification without external auditory canal (EAC) closure.

Methods: Between August 2018 and February 2019, seven patients with intrameatal VS underwent surgery in our center, endoscopic transcanal transpromontorial approach was applied in the first 2 patients and the rest 5 patients were operated via METTA. Treatment outcomes including efficacy of tumor resection, facial nerve outcome, operation time and post-operative course were recorded and analyzed.

Results: All seven patients were pathologically confirmed to have intrameatal VS. Total tumor removal was achieved in all cases. Two patients experienced cerebrospinal fluid leakage which resolved spontaneously within 5 days. The average operation time was 161.41 ± 18.42 min. All patients presented normal facial nerve function 1 month after surgery.

Conclusion: The METTA was effective in the removal of intrameatal VS. It can be an alternative surgical option for intrameatal VS with no serviceable hearing.
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http://dx.doi.org/10.1007/s00405-021-06612-zDOI Listing
January 2022

Bimodal Stimulation in Children With Bilateral Profound Sensorineural Hearing Loss: A Suitable Intervention Model for Children at the Early Developmental Stage.

Otol Neurotol 2020 12;41(10):1357-1362

Department of Otolaryngology-Head and Neck Surgery, Ninth People's Hospital.

Objective: To evaluate the auditory and speech benefit of bimodal stimulation for prelingual deafened cochlear implantation recipients.

Study Design: Retrospective and comparative study.

Setting: Tertiary referral center.

Patients: Fifty-six children with bilateral prelingual profound sensorineural hearing loss were enrolled, including 28 consecutive children with unilateral cochlear implantation (CI group), and 28 consecutive children with bimodal stimulation (BI group) who used an additional hearing aid (HA) in the contralateral ear.

Main Outcome Measures: Hearing assessments included the Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) and Categories of Auditory Performance (CAP). Speech evaluations included the Meaningful Use of Speech Scale (MUSS), and Speech Intelligibility Rating (SIR). These measurements were evaluated at the first mapping of cochlear implants and 0.5, 1, 3, 6, 12, 18, 24 months after. Data were analyzed by repeated measures analysis.

Results: The mean ages of BI and CI groups were similar (17.6 ± 6.87 vs 19.0 ± 8.10 months, p = 0.497). The initial scores for hearing and speech assessments showed no differences between the two groups, apart from IT-MAIS (2.46 ± 0.631 in BI group vs 0.50 ± 0.279 in CI group, p = 0.004). The auditory and speech development over time were different in the two groups as seen in IT-MAIS (p < 0.001), CAP (p = 0.029), MUSS (p < 0.001), and SIR (p < 0.001). A continuing but stable difference was observed in CAP, MUSS, and SIR at 3, 18, and 12 months after the first mapping, respectively. In addition, the BI group had better IT-MAIS scores at 3 and 6 months compared with the CI group; however, the difference was not significant after 12 months.

Conclusion: Bimodal stimulation is beneficial for prelingually deafened CI recipients who have minimal contralateral residual hearing when bilateral CIs are not available. Hearing aid use in the contralateral ear might be recommended for children after unilateral cochlear implantation to facilitate the development of auditory and speech skills.
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http://dx.doi.org/10.1097/MAO.0000000000002812DOI Listing
December 2020

IVORY Guidelines (Instructional Videos in Otorhinolaryngology by YO-IFOS): A Consensus on Surgical Videos in Ear, Nose, and Throat.

Laryngoscope 2021 03 17;131(3):E732-E737. Epub 2020 Aug 17.

Department of Oto-Rhino-Laryngology-Head and Neck Surgery, Aix Marseille University, APHM, Language and Speech Laboratory, La Conception University Hospital, Marseille, France.

Objectives/hypothesis: Otolaryngology instructional videos available online are often of poor quality. The objective of this article was to establish international consensus recommendations for the production of educational surgical videos in otolaryngology.

Study Design: DELPHI survey.

Methods: Twenty-seven international respondents participated in this study from 12 countries. Consensus was reached after three rounds of questionnaires following the Delphi methodology. The proposals having reached the 80% agreement threshold in the third round were retained.

Results: The main recommendations are as follows: 1) Ethics: patients must be anonymized and unrecognizable (apart from plastic surgery if necessary). A signed authorization must be obtained if the person is recognizable. 2) Technical aspects: videos should be edited and in high-definition (HD) quality if possible. Narration or subtitles and didactic illustrations are recommended. 3) Case presentation: name of pathology and procedure must be specified; the case should be presented with relevant workup. 4) Surgery: surgical procedures should be divided into several distinct stages and include tips and pitfalls. Pathology should be shown if relevant. Key points should be detailed at the end of the procedure. 5) Organ-specific: type of approach and bilateral audiometry should be specified in otology. Coronal plane computed tomography scans should be shown in endonasal surgery. It is recommended to show pre- and postoperative videos in voice surgery and preoperative drawings and photos of scars in plastic surgery, as well as the ventilation method in airway surgery.

Conclusions: International recommendations have been determined to assist in the creation and standardization of educational surgical videos in otolaryngology and head and neck surgery.

Level Of Evidence: 5 Laryngoscope, 131:E732-E737, 2021.
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http://dx.doi.org/10.1002/lary.29020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891442PMC
March 2021

[Distribution of juvenile laryngeal papilloma in different stages].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2020 Dec;34(12):1088-1092

Department of Otolaryngology Head and Neck Surgery,Shanghai Ninth People's Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai,200011,China.

To study the anatomical distribution and tumor extent of juvenile laryngeal papilloma(JLP), and to sum up the similarity and difference in distribution between initiatial and recurrent tumor. Data of 65 patients with JLP who were admitted to the Ear Institute, School of Medicine, Shanghai Jiao Tong University from January 2011 to December 2018 were retrospectively analyzed. The RRP tumor assessment method proposed by Derkay et al. was referred to, in which larynx was divided in to 11 anatomical sites. 2.9±1.3 Laryngeal anatomical sites were involved in patients with initial tumor, while that was 3.1±1.5 in patients with recurrent tumor. The most common sites were true vocal fords, anterior commissure and false vocal fords in both group; and the least ones were subglottis, posterior glottis and ary-epiglottic fold. However, subglottis(=0.038) and trachea(=0.007) were more likely to be involved in recurrent tumor, with statistical differences. There were differences in distribution of JLP between initial and recurrent tumor, which might be the result of suitable areas for HPV survival or micro-lesion of residual tumor.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2020.12.008DOI Listing
December 2020

Management of Laryngopharyngeal Reflux Around the World: An International Study.

Laryngoscope 2021 05 17;131(5):E1589-E1597. Epub 2020 Nov 17.

Laryngopharyngeal Reflux Study Group of Young-Otolaryngologists of the International Federations of Oto-rhino-laryngological Societies (YO-IFOS), Paris, France.

Objective: To investigate worldwide practices of otolaryngologists in the management of laryngopharyngeal reflux (LPR).

Methods: An online survey was sent on the management of LPR to members of many otolaryngological societies. The following aspects were evaluated: LPR definition, prevalence, clinical presentation, diagnosis, and treatment.

Results: A total of 824 otolaryngologists participated, spread over 65 countries. The symptoms most usually attributed to LPR are cough after lying down/meal, throat clearing and globus sensation while LPR-related findings are arytenoid erythema and posterior commissure hypertrophy. Irrespective to geography, otolaryngologists indicate lack of familiarity with impedance pH monitoring, which they attribute to lack of knowledge in result interpretation. The most common therapeutic regimens significantly vary between world regions, with a higher use of H2 blocker in North America and a lower use of alginate in South America. The duration of treatment also significantly varies between different regions, with West Asia/Africa and East Asia/Oceania otolaryngologists prescribing medication for a shorter period than the others. Only 21.1% of respondents are aware about the existence of nonacid LPR. Overall, only 43.2% of otolaryngologists believe themselves sufficiently knowledgeable about LPR.

Conclusions: LPR knowledge and management significantly vary across the world. International guidelines on LPR definition, diagnosis, and treatment are needed to improve knowledge and management around the world.

Level Of Evidence: N.A. Laryngoscope, 131:E1589-E1597, 2021.
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http://dx.doi.org/10.1002/lary.29270DOI Listing
May 2021

Management and Outcomes of Sporadic Vestibular Schwannoma: A Longitudinal Study Over 12 Years.

Laryngoscope 2021 03 25;131(3):E970-E976. Epub 2020 Jul 25.

APHP, Groupe Hospitalo-Universitaire Pitié Salpêtrière, Otorhinolaryngology Department, Unit of Otology, Auditory Implants and Skull Base Surgery, Sorbonne Université, Paris, France.

Objectives: To evaluate the management of sporadic vestibular schwannomas (VS) with a 12-year follow-up.

Study Design: Retrospective study of all VS patients initially treated in 2005 in a tertiary referent center.

Methods: Initial decision making for microsurgical resection (MSR) or wait-and-scan (WaS) was according to VS size and hearing; subsequently, MSR or stereotactic radiosurgery (SRS) was proposed dependent on VS growth and size, hearing, and patient's age or willingness.

Results: Two hundred and one sporadic VS were included. The first management apportionment was 120 WaS (61.5%), 72 MSR (37%), three SRS (1.5%), and six others refused MSR and were lost to follow-up (LFU). Within 1 year, 95 (47%) VS were surgically removed; 17 (8.5%) were treated by SRS; and 35 (17.5%) were LFU. The proportions for SRS and LFU were virtually unchanged for the following years, and the proportion under MSR increased slightly within 3 years and then remained stable. Finally, at 12 years, 104 (51.5%) cases had been operated on, 21 (10.5%) treated by SRS, 23 (11.5%) still under WaS, and 53 (26.5%) LFU, which were mainly intracanalicular. The initially and subsequently operated cases presented similar hearing preservation rates and good facial nerve function outcomes.

Conclusion: This longitudinal study of a large number of VS, which were diagnosed over a short period of time and followed for 12 years, provides new information on both the natural history of these benign tumors and individual patient concerns. This study recommends use of the WaS policy for small and mid-sized VS before active therapeutic decision making.

Level Of Evidence: 3 Laryngoscope, 131:E970-E976, 2021.
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http://dx.doi.org/10.1002/lary.28888DOI Listing
March 2021

Management of Laryngopharyngeal Reflux in Asia.

Clin Exp Otorhinolaryngol 2020 Aug 12;13(3):299-307. Epub 2020 May 12.

Laryngopharyngeal Reflux Study Group of Young Otolaryngologists of the International Federation of Oto-rhino-laryngological Societies, Paris, France.

Objectives: This study was conducted to investigate the current practices of Asian otolaryngologists for laryngopharyngeal reflux (LPR).

Methods: An online survey about LPR was sent to 2,000 members of Asian otolaryngological societies, and a subgroup analysis was performed between Western and Eastern Asian otolaryngologists. The survey was conducted by the Laryngopharyngeal Reflux Study Group of Young Otolaryngologists of the International Federation of Oto-rhino-laryngological Societies.

Results: Among approximately 1,600 Asian otolaryngologists, 146 completed the survey (62 from Western Asian countries, 84 from Eastern Asian countries). A substantial majority (73.3%) of the otolaryngologists considered LPR and gastroesophageal reflux disease to be different diseases. The symptoms thought to be closely related to LPR were coughing after lying down, throat clearing, and globus sensation. The findings thought to be closely related to LPR were posterior commissure granulations and hypertrophy, arytenoids, and laryngeal erythema. The respondents indicated that they mostly diagnosed LPR (70%) after an empirical therapeutic trial of proton pump inhibitors (PPIs). Although multichannel intraluminal impedance-pH (MII-pH) monitoring is a useful tool for diagnosing nonacid or mixed LPR, 78% of Asian otolaryngologists never or very rarely used MII-pH. Eastern Asian otolaryngologists more frequently used once-daily PPIs (64.3% vs. 45.2%, P=0.021), whereas Western Asian otolaryngologists preferred to use twice-daily PPIs (58.1% vs. 39.3%, P=0.025). The poor dietary habits of patients were considered to be the main reason for therapeutic failure by Asian otolaryngologists (53.8%). Only 48.6% of Asian otolaryngologists considered themselves to be adequately knowledgeable and skilled regarding LPR.

Conclusion: Significant differences exist between Western and Eastern Asian otolaryngologists in the diagnosis and treatment of LPR. Future consensus statements are needed to establish diagnostic criteria and therapeutic regimens.
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http://dx.doi.org/10.21053/ceo.2019.01669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435427PMC
August 2020

Development of a rapidly made, easily personalized drug-eluting polymer film on the electrode array of a cochlear implant during surgery.

Biochem Biophys Res Commun 2020 05 24;526(2):328-333. Epub 2020 Mar 24.

Department of Otorhinolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China; Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases (14DZ2260300), Shanghai, 200125, China; Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, China. Electronic address:

Objective: To develop a drug-eluting polymer film which can be easily personalized and rapidly made on the electrode array of a cochlear implant during surgery.

Methods: A precursor solution was prepared with poly lactic-co-glycolic acid (PLGA) and trichloromethane. Using a dip-coating method, the silicone electrode array (HiFocus 1J, Advanced Bionics) was coated in polymer film produced from the precursor solution containing one of three drugs: dexamethasone sodium phosphate (DSP), cytosine arabinoside hydrochloride (Ara-C), or nicotinamide adenine dinucleotide (NAD), and the release of these drugs from the polymer film was studied. The drug-eluting film on the electrode array was analyzed by environmental scanning electron microscopy (ESEM). The water contact angle and the impedance of the electrode array were measured before and after coating. Drug release kinetics was evaluated in a quasi-stationary release model, using high performance liquid chromatography every 24 h for 15 days.

Results: Five electrode arrays were tested with each of the three drugs in the polymer film coating. Before and after coating, ESEM studies revealed that the drug-loaded PLGA coating yielded a smooth covering with an average thickness of 1.02 ± 0.05 μm. The mass of the coated electrode increased by 1.00 ± 0.03 mg. The water contact angle decreased after coating (102 ± 0.6° vs 77 ± 1.6°, p < 0.01) but there was no significant change in the average impedance of the electrodes after coating (0.9 ± 0.22 kΩ vs 1.0 ± 0.18 kΩ, p > 0.05). An in vitro drug kinetics study revealed a faster release in the first 24 h (63.4 ± 0.6%) and a sustained release over the following 15 days (78.3 ± 1.7% in 2 days, 95.6 ± 1.0% in 7 days and 99.1 ± 0.4% in 14 days). The release rate was not affected by the drug, dose or the thickness of the coating.

Conclusion: The dip-coating method is feasible for rapid casting of a drug-eluting PLGA film on an electrode array during CI surgery. The coated electrode array maintained its original morphology and became more hydrophilic. The loaded drug is released in a sustained manner and is easily regulated, and so the method might represent a potential application for clinical use in cochlear implantation.
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http://dx.doi.org/10.1016/j.bbrc.2020.02.171DOI Listing
May 2020

Structure of the human metapneumovirus polymerase phosphoprotein complex.

Nature 2020 01 7;577(7789):275-279. Epub 2019 Nov 7.

School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.

Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) cause severe respiratory diseases in infants and elderly adults. No vaccine or effective antiviral therapy currently exists to control RSV or HMPV infections. During viral genome replication and transcription, the tetrameric phosphoprotein P serves as a crucial adaptor between the ribonucleoprotein template and the L protein, which has RNA-dependent RNA polymerase (RdRp), GDP polyribonucleotidyltransferase and cap-specific methyltransferase activities. How P interacts with L and mediates the association with the free form of N and with the ribonucleoprotein is not clear for HMPV or other major human pathogens, including the viruses that cause measles, Ebola and rabies. Here we report a cryo-electron microscopy reconstruction that shows the ring-shaped structure of the polymerase and capping domains of HMPV-L bound to a tetramer of P. The connector and methyltransferase domains of L are mobile with respect to the core. The putative priming loop that is important for the initiation of RNA synthesis is fully retracted, which leaves space in the active-site cavity for RNA elongation. P interacts extensively with the N-terminal region of L, burying more than 4,016 Å of the molecular surface area in the interface. Two of the four helices that form the coiled-coil tetramerization domain of P, and long C-terminal extensions projecting from these two helices, wrap around the L protein in a manner similar to tentacles. The structural versatility of the four P protomers-which are largely disordered in their free state-demonstrates an example of a 'folding-upon-partner-binding' mechanism for carrying out P adaptor functions. The structure shows that P has the potential to modulate multiple functions of L and these results should accelerate the design of specific antiviral drugs.
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http://dx.doi.org/10.1038/s41586-019-1759-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949429PMC
January 2020

Management of sporadic vestibular schwannoma with contralateral nonserviceable hearing.

Laryngoscope 2020 06 23;130(6):E407-E415. Epub 2019 Oct 23.

Otorhinolaryngology Department, Unit of Otology, Auditory Implants and Skull Base Surgery, Greater paris university hospitals, Pitié-Salpêtrière University Group Hospital, Paris, France.

Objectives/hypothesis: To outline a possible decision-making process for sporadic vestibular schwannoma (VS) with contralateral nonserviceable hearing at diagnosis.

Study Design: Retrospective case series.

Methods: Diagnosed VS was studied in a tertiary referral center from 1995 to 2013.

Results: Twenty-eight patients were included, with a mean follow-up of 6.9 years (range = 0.5-20 years). Ten were stage 1, 10 were stage 2, five were stage 3, and three were stage 4. Ipsilateral hearing levels were A (n = 3), B (n = 10), C (n = 7) and D (n = 8) American Academy of Otolaryngology-Head and Neck Surgery classification. Contralateral hearing levels were C (n = 11) and D (n = 17). Initial VS management included surveillance (n = 12) or surgery (n = 16), and four patients were later treated with surgery (n = 3) or stereotactic irradiation (n = 1). Hearing was improved by hearing aids and/or etiological treatment (n = 8), restored by contralateral (n = 15) or ipsilateral (n = 4) cochlear implants (CIs), or ipsilateral auditory brainstem implants (ABIs) (n = 3). Finally, 18 CIs were active daily; 14 of them presented high or moderate benefit with mean open-set dissyllabic word scores (WRS) of 58.1% and sentence recognition scores (SRS) of 69.7%, but only one ABI was still active (WRS of 70% and SRS of 87% with lip reading).

Conclusions: When early removal of VS was not necessary, contralateral CI or etiological treatment for hearing loss might be recommended initially. Ipsilateral CI is proposed, whereas VS should be operated on if previous hearing restoration was not successful. ABI should be reserved for the rare cases where a contralateral CI could not be implanted or the cochlear nerve was sectioned during VS removal.

Level Of Evidence: 3 Laryngoscope, 130:E407-E415, 2020.
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June 2020

NF2-Related Intravestibular Schwannomas: Long-Term Outcomes of Cochlear Implantation.

Otol Neurotol 2020 01;41(1):94-99

APHP, GH Pitié-Salpêtrière, Department of Otology, Auditory Implants and Skull Base Surgery, Ile-de-France Reference Center of Cochlear Implant and Auditory Brainstem Implant; Rare Diseases Center of Genetic deafness for adult.

Objective: Intravestibular schwannomas (IVS) are uncommon tumors in Neurofibromatosis type 2 (NF2) and are mainly associated with multiple internal auditory meatus (IAM) and cerebellopontine angle (CPA) tumors. They usually induce profound hearing loss which can be rehabilitated by cochlear implantation (CI). The aim of this study was to analyze the long-term outcomes of CI during the unpredictable evolution of NF2 disease.

Study Design: Retrospective case review.

Setting: Tertiary referral center.

Patients: Three adults with neurofibromatosis type 2 and intravestibular schwannomas, and who were cochlear implant recipients.

Interventions: Periodic radiologic follow-up, tumor resection, and hearing rehabilitation.

Main Outcome Measures: Audiological evolution, tumor evolution, surgical outcome, cochlear implant outcome.

Results: Three NF2 patients (mean age at diagnosis, 26.3 ± 3.2 yr) were identified with IVS in the period between 2000 and 2017. IVS were first observed by serial MRI and profound hearing loss occurred in this ear after 4 ± 1.5 years of follow-up. IVS were removed via a translabyrinthine approach, and ipsilateral cochlear implantations were simultaneously performed. In two patients, large contralateral CPA tumors had previously been removed without hearing preservation, whereas in the third patient, a small, growing contralateral VS was excised via a retrosigmoid approach 6 months after IVS removal/cochlear implantation with serviceable hearing preservation. In all cases, CI provided good hearing outcomes. In two cases, hearing outcomes were even better for more than 5 years when ipsilateral intracanalicular vestibular schwannomas were removed in either the same or subsequent procedures.

Conclusions: Rehabilitation of hearing with CI provides a favorable long-term outcome in patients with NF2-related IVS which could be altered by the occurrence of other intracanalicular and/or CPA NF2-related tumors.
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http://dx.doi.org/10.1097/MAO.0000000000002431DOI Listing
January 2020
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