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Protein engineering approach enables effective immobilisation of thermostable affinity proteins onto polystyrene materials.

To investigate the value of using the Gesell Development Diagnosis Scale (GDDS) to predict developmental outcomes in very young children who undergo simultaneous bilateral cochlear implantation.In this prospective cohort study, a repeated-measures investigation was conducted in a tertiary referral hospital. A total of 62 children receiving simultaneous bilateral cochlear implantations were enrolled from April 2017 to August 2018. They were divided into 2 groups depending on the operative age: "Infants" group (6 to 12 months, N = 38) or "Children" group (12 to 36 months, N = 24). Data on the surgical outcomes, auditory development, speech production, and developmental indicators were collected until 2 years after the initial fitting. The primary outcome measure was the GDDS, a neuropsychological development examination. Secondary outcomes included the following: complication rate, aided pure-tone average, Infant-Toddler Meaningful Auditory Integration Scale, Categories of Auditory Performance-II, Meaningful Use of Speech Scale, Speech Intelligibility Rating, and the LittlEARS Auditory Questionnaire.The mean ages at implantation in infants and children groups were 9.2 ± 1.17 and 16.6 ± 3.60 months, respectively. Significant differences were found in the social skills (p = 0.001) and adaptability (p = 0.031) domains of GDDS. The younger the age of bilateral cochlear implants surgery, the higher developmental quotient of language, social skills, and adaptability the child could achieve after 2 years. The complication rates in the infants and children groups were 0% versus 2.1% (p = 0.57). There was no surgical complication in the infants group. In the children group, 1 case with enlarged vestibular aqueduct and Mondini malformation had a receiver-implant misplacement on the right side (2%, 1/48). In the two groups, auditory performance and speech production had improved similarly. In the infants group, social skills developmental quotient at baseline had a significant positive relationship with Meaningful Use of Speech Scale after 2 years.Simultaneous bilateral cochlear implantation in younger children improves adaptability and social skills. GDDS is a sensitive tool of evaluating short-term effect of bilateral cochlear implants in neuropsychological development and constitutes a reliable predictor of speech production for the very younger pediatric cochlear implant users.

The trace element selenium, which is found in selenoproteins, plays an antioxidant role in preventing muscle tissue injury. A positive association between selenium concentrations and hand grip strength has been reported in older adults; however, the evidence of this association is scarce in general adults. In this study, we aimed to evaluate the association between blood selenium concentrations and low hand grip strength using the data from the National Health and Nutrition Examination Survey 2011–2012 and 2013–2014 in the United States (US). Logistic regression was used to calculate the odds ratio (OR) of low hand grip strength, with blood selenium level adjusted for potential confounders. Among 8158 adults (women: 51.59%) with a mean age of 47 (range: 18–80) years, women and non-Hispanic Blacks tended to have low blood selenium concentrations. Notably, participants with high blood selenium concentrations (range, 178.1–192.5 µg/L) were more likely to have a low risk of low hand grip strength after adjusting for the potential covariates (OR: 0.60, 95% confidence interval (CI): 0.38–0.95) than those with low blood selenium concentrations. After excluding participants with chronic diseases, high blood selenium concentrations were found to be associated with a low risk of low hand grip strength (OR: 0.30, 95% CI: 0.14–0.65). A J-shaped relationship was found between selenium concentrations and low hand grip strength ( P for nonlinear trend

Quiescent cancer stem cells (CSC) play important roles in tumorigenesis, relapse, and resistance to chemoradiotherapy. However, the determinants of CSC quiescence and how they sustain themselves to generate tumors and relapse beyond resistance to chemoradiotherapy remains unclear. Here, we found that SET domain–containing protein 4 (SETD4) epigenetically controls breast CSC (BCSC) quiescence by facilitating heterochromatin formation via H4K20me3 catalysis. H4K20me3 localized to the promoter regions and regulated the expression of a set of genes in quiescent BCSCs (qBCSC). SETD4-defined qBCSCs were resistant to chemoradiotherapy and promoted tumor relapse in a mouse model. Upon activation, a SETD4-defined qBCSC sustained itself in a quiescent state by asymmetric division and concurrently produced an active daughter cell that proliferated to produce a cancer cell population. Single-cell sequence analysis indicated that SETD4+ qBCSCs clustered together as a distinct cell type within the heterogeneous BCSC population. SETD4-defined quiescent CSCs were present in multiple cancer types including gastric, cervical, ovarian, liver, and lung cancers and were resistant to chemotherapy. SETD4-defined qBCSCs had a high tumorigenesis potential and correlated with malignancy and chemotherapy resistance in clinical breast cancer patients. Taken together, the results from our previous study and current study on six cancer types reveal an evolutionarily conserved mechanism of cellular quiescence epigenetically controlled by SETD4. Our findings provide insights into the mechanism of tumorigenesis and relapse promoted by SETD4-defined quiescent CSCs and have broad implications for clinical therapies.Significance:These findings advance our knowledge on the epigenetic determinants of quiescence in cancer stem cell populations and pave the way for future pharmacologic developments aimed at targeting drug-resistant quiescent stem cells.

Supplementary Table S1 and Supplementary Figure S1 to S11

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.

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.

_ The objective of this paper is to predict the noise radiated from submarine propellers with different control surface types (the cross- and X-type). When the propellers are free from cavitation, such as those of submarines at a diving depth, the radiated noise dominate, due to unsteady propeller forces. A well-known submarine model (DARPA SUBOFF) is taken as the computing sample. Simulations for hydrodynamics, including stern wakes and unsteady propeller forces, are carried out by using CFD (Computational Fluid Dynamics) technology, and the results are compared with the experimental data. The accuracy of the predicted noise depends on the CFD results. Comparisons between the CFD results and the experimental data are in good agreement. The CFD results are treated as dipole strengths in the linear wave theory to predict the radiated noise caused by the unsteady forces of the propeller. It is found that, when the control surface is of the X-type, the propeller inflow is more uniform, and the radiated noise can be decreased by about 5 dB compared to the cruciform control surface. Introduction When submarines are at diving depth, the noise generated by unsteady propeller forces (i.e., dipole strengths) will dominate. Because the juncture vortex caused by the sail makes the propeller inflow more nonuniform, the dipole strength will be enhanced and the radiated noise will be more noticeable. The uniformity of the wake field at the stern should be controlled well in order to restrain the radiated noise.

Rapid diagnostic tests (RDTs) have shown to be instrumental in healthcare and disease control. However, they have been plagued by many inefficiencies in the laborious empirical development and optimization process for the attainment of clinically relevant sensitivity. While various studies have sought to model paper-based RDTs, most have relied on continuum-based models that are not necessarily applicable to all operation regimes, and have solely focused on predicting the specific interactions between the antigen and binders. It is also unclear how the model predictions may be utilized for optimizing assay performance. Here, we propose a streamlined and simplified model-based framework, only relying on calibration with a minimal experimental dataset, for the acceleration of assay optimization. We show that our models are capable of recapitulating experimental data across different formats and antigen-binder-matrix combinations. By predicting signals due to both specific and background interactions, our facile approach enables the estimation of several pertinent assay performance metrics such as limit-of-detection, sensitivity, signal-to-noise ratio and difference. We believe that our proposed workflow would be a valuable addition to the toolset of any assay developer, regardless of the amount of resources they have in their arsenal, and aid assay optimization at any stage in their assay development process.

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 ortholog 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 (H2 O2 ), 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 signaling 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. This article is protected by copyright. All rights reserved.

The peptidoglycan recognition protein (PGRP), an important pattern recognition receptor of insects, is significant for reducing innate immunity and effective pest control. We cloned four PGRP genes (LsPGRP-LB, LsPGRP-LB1, LsPGRP-LE, and LsPGRP-SC2) from the cigarette beetle, Lasioderma serricorne (Fabricius), which encoded proteins of 216, 197, 317, and 190 amino acids, respectively. Three LsPGRPs were predominantly expressed in the larval and pupal stages, whereas LsPGRP-LE displayed high expression in adults. All the four LsPGRPs genes were highly expressed in the midgut and integument. Pathogen inoculation revealed that the four LsPGRPs actively responded to Escherichia coli and its peptidoglycan. The transcription levels of LsPGRP-LE and LsPGRP-SC2 increased significantly after Staphylococcus aureus stimulation. RNA interference-mediated knockdown of the four LsPGRPs led to increased larval mortality when challenged by E. coli, and the expression of four antimicrobial peptide genes (LsCole, LsAtt2, LsDef1 and LsDef2) had a significant decrease. Higher mortality and lower AMP expression were also observed in L. serricorne under S. aureus infection after silencing LsPGRP-LE and LsPGRP-SC2. Our results suggest that the four LsPGRP genes play important and distinct regulatory roles in the antibacterial defense response of L. serricorne.

With the continuous strengthening of application requirements, neutron sources are becoming more and more compact, integrated and mobile. There are challenges in two aspects. The first is to achieve high transmission efficiency of high beam current physically, the second is to achieve integration and miniaturization technically. The coupling of RFQ and DTL is a feasible way. A preliminary study on the key physical problems in the RFQ-DTL coupled cavity has been accomplished. For the beam dynamics, the compact matching of RFQ and DTL was studied for the coupled cavity. Taking the compact physical design of the RFQ-DTL for deuterium ion beam of 30 mA with the energy of 11 MeV without MEBT as an example, we studied the smooth transition of the phase advance per unit length, the ability of RFQ transition cell to rotate beam in the transverse phase space, the transverse and longitudinal acceptance optimization of DTL. The RFQ and DTL can be matched transversely and longitudinally after removing MEBT, and the transmission efficiency is 98.7%. For direct coupling of four-vane RFQ and CH-DTL, we studied the realization of the coupling, the factors affecting the field amplitude ratio, the tuning of the cavity, and the influence of the superimposed field on the beam transmission. The field amplitude ratio between RFQ and CH-DTL is from 16.5 to 36.2. Under the influence of the superimposed field, the difference in normalized RMS emittance is less than 1%. We have designed, constructed and cold-test the 750 MHz model cavity. The normalized electric field coefficients measured and simulated are basically in agreement.

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.

Treatment of neurofibromatosis type 2 (NF2) associated vestibular schwannomas (VS) can prove challenging because of the various choices, from observation to surgery and radiosurgery with medical treatment opportunities, sometimes within clinical trials. Some factors direct the treatment decision tree such as size of VS and hearing level. Others factors have to be considered such as patient clinical status, inherited situation, and contralateral VS characteristics. All these factors are detailed, discussed, and weighted in this review. Another essential part of the clinical management of patients with NF2 includes the hearing rehabilitation process using either cochlear or auditory brainstem implants. The management of VS in patients with NF2 has become difficult, owing to a multitude of solution options, and should be performed in reference NF2 centers.

Cardiac injury upon myocardial infarction (MI) is the leading cause of heart failure. The present study aims to investigate the role of EndoA2 in ischemia-induced cardiomyocyte apoptosis and cardiac injury. In vivo, we established an MI mouse model by ligating the left anterior descending (LAD) coronary artery, and intramyocardial injection of adenoviral EndoA2 (Ad-EndoA2) was used to overexpress EndoA2. In vitro, we used the siRNA and Ad-EndoA2 transfection strategies. Here, we reported that EndoA2 expression was remarkably elevated in the infarct border zone of MI mouse hearts and neonatal rat cardiomyocytes (NRCMs) stimulated with oxygen and glucose deprivation (OGD) which mimicked ischemia. We showed that intramyocardial injection of Ad-EndoA2 attenuated cardiomyocyte apoptosis and reduced endoplasmic reticulum (ER) stress in response to MI injury. Using siRNA for knockdown and Ad-EndoA2 for overexpression, we validated that knockdown of EndoA2 in NRCMs exacerbated OGD-induced NRCM apoptosis, whereas overexpression of EndoA2 attenuates OGD-induced cardiomyocyte apoptosis. Mechanistically, knockdown of EndoA2 activated ER stress response, which increases ER oxidoreductase 1α (ERO1α) and inositol 1, 4, 5-trisphosphate receptor (IP3R) activity, thus led to increased intracellular Ca2+ accumulation, followed by elevated calcineurin activity and nuclear factor of activated T-cells (NFAT) dephosphorylation. Pretreatment with the IP3R inhibitor 2-Aminoethoxydiphenylborate (2-APB) attenuated intracellular Ca2+ accumulation, and pretreatment with the Ca2+ chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) or the calcineurin inhibitor Cyclosporin A (CsA) inhibited EndoA2-knockdown-induced NRCM apoptosis. Overexpression of EndoA2 led to the opposite effects by suppressing ER-stress-mediated ERO1α/IP3R signaling pathway. This study demonstrated that EndoA2 protected cardiac function in response to MI via attenuating ER-stress-mediated ERO1α/IP3R signaling pathway. Targeting EndoA2 is a potential therapeutic strategy for the prevention of postinfarction-induced cardiac injury and heart failure.

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.

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.

Rheumatoid arthritis (RA) is a chronic and refractory autoimmune disease characterized by synovial inflammation with unknown aetiology. Immune system dysfunction mediated by CD4In this study, the levels of peripheral CD4Serum OPN levels in both patients with active RA and patients with refractory RA were higher than those in healthy controls (HCs). Compared with HCs, the absolute numbers of Th2 cells increased in patients with active RA, while the absolute counts of Th1 and TFewer T

For the guarantee of the long-distance transport of the bunches of China Initiative Accelerator Driven System (CIADS), a new scheme is proposed that extra magnetic field is used in the accelerator-target coupling section before the windowless target to minimize the self-modulation (SM) mechanism. Particle-in-cell simulations are carried out to study the influence of the solenoidal magnetic field on the self-modulation mechanism when long proton bunches move in the background plasmas. The long proton bunches used in the simulations are similar to these in the linear accelerator of CIADS. It is found that the presence of the solenoidal magnetic field will significantly inhibit the self-modulation process. For the strong magnetic field, the longitudinal separation and transverse focusing of the long bunches disappear. We attribute these phenomena to the reason that the strong solenoidal magnetic field restricts the transverse movement of plasma electrons. Thus, there are not enough electrons around the bunch to compensate the space charge effect. Moreover, without transverse current, the longitudinal pinched effect disappears, and the long bunch can not be separated into small pulses anymore.

Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) cause severe respiratory diseases in infants and elderly adults1. 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 activities2,3. 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 A2 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. A cryo-electron microscopy reconstruction shows the ring-shaped structure of the polymerase and capping domains of the L protein bound to a tetramer of phosphoprotein P of the human metapneumovirus.

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. 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. 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. 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. In response to infections, the human body produces proteins called antibodies. Neutralizing antibodies (NAbs) are one type of such proteins that are capable of inactivating the target, such as the SARS-CoV-2 virus that causes COVID-19. Monitoring levels of NAb allows us to understand levels of protective immunity. However, current methods to measure NAb are laboratory-based and are not necessarily suitable for large scale NAb monitoring in a large population. We develop a rapid test to detect SARS-CoV-2 NAb in 10 min that can be operated outside a laboratory. Our test provides results that are comparable to lab-based tests, which require between 1 h and up to 2 days to get a result. Our test may be useful for large-scale monitoring of immunity, for example in populations that do not have routine access to a lab. Kongsuphol et al. develop a paper-based, vertical flow assay to detect SARS-CoV-2 neutralizing antibodies. The point-of-care assay has comparable performance to lab-based tests and provides results in 10 min.

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. Ministry of Health (MOH) National Medical Research Council (NMRC) National Research Foundation (NRF) Published version This study is supported by National Health Innovation Singapore (NHIC) grant # NHIC-COVID19-2005004, National Research Foundation via CREATE Share grant #R571-002-021-592 and the Anti-microbial Resistance Interdisciplinary Research Group (AMR-IRG) of Singapore-MIT Alliance in Research and Technology (SMART). All samples acquired from National Centre for Infectious Diseases (NCID) were supported by Singapore Ministry of Health's National Medical Research Council COVID-19 Research Fund: COVID19RF-0008.

This study analyzed the seasonal variation, sources, and source-specific health risks of PM

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.

In the present study, the borate anions intercalated MgAl-layered double hydroxides (B-LDHs) microsphere and its calcinated product (B-LDOs) have been prepared by precursor method and characterized by the XRD, FT-IR, XPS, TG-DSC, SEM and TEM. This microsphere with hierarchical porous nanostructure was assembled by nanosheets. The B-LDHs and B-LDOs samples have high specific surface area of 138.6 m2 g −1 and 123.0 m2 g−1 measured by N2 adsorption−desorption, respectively. They were used as adsorbents to remove Congo red (CR) dye in an aqueous solution, exhibiting excellent adsorption performance with maximum adsorption capacities of 166 and 273 mg g −1 for CR respectively, which outperform most of the reported adsorbents in literatures. The adsorption processes nicely fitted with the kinetic pseudo-second-order rate equation and Langmuir adsorption model. The effects of B-LDOs sample dosage, pH and temperature of CR solution on adsorption were investigated. The possible adsorption mechanisms were also proposed. It can be expected that both samples, especially B-LDOs sample with higher adsorption efficiency and good reusability, could be considered as promising candidates for wastewater treatment.

An end plate propeller (ENDP) shaped by a diffused endplate bent to the pressure side is proposed in the paper. The ENDP differs from a contracted and loaded tip (CLT) propeller, and possess remarkable performance in terms of cavitation, efficiency, vibration, and noise comparing with that of CLT and conventional propeller, particularly operating at inclined shaft condition. According to experiments conducted in the cavitation tunnel of National Taiwan Ocean University, it is observed that the diffused endplate can effectively restrain tip vortex cavitation, and eliminate tip-plate cavitation typically found on the outer surface of the tip-plate of a CLT propeller. The optimal diameter of the ENDP is smaller than that of a conventional propeller; thus, the ENDP is more suitable for ships with small stern space. Besides, the thrust of the ENDP is contributed much more from its pressure side, therefore, the cavitation on the back is reduced, and the efficiency is increased. Sea trials using a yacht with the ENDP were carried out and the results show that vibrations due to the sheet cavitation at blade-rate frequencies by the ENDP are significantly decreased in comparison with those of conventional propeller, and overall broad-band amplitude caused by the tip vortex cavitation by the ENDP at high frequencies are nearly disappeared.

Borate is a kind of green and environmental protective flame-retardant, which has been used in fiber, resin and wood and the like. To solve this bottleneck problem of prepared larger particles for borate flame-retardant which makes its poor flame retardant in the research and application, we prepared the calcium borate 2CaO•5B2O3•5H2O nanoplate and micro/nanosheet under hydrothermal conditions by adjusting pH of solution and reaction temperature, which were characterized by the XRD, FTIR, TGA, FESEM and TEM. The flame retardant properties of the prepared 2CaO•5B2O3•5H2O samples were investigated by using multiple thermochemical strategies (including TGA, DSC and non-isothermal decomposition kinetics), and further verified by limited oxygen index method. The nanoplate sample has the less TG mass loss and heat release for DSC, as well as the bigger LOI value, and apparent activation energy E a. These show that the flame retardant property of prepared 2CaO•5B2O3•5H2O nanoplate sample is stronger than that of micro/nanosheet sample. The possible flame retarding mechanism has been proposed. In addition, the horizontal comparison shows that the flame retardant property of prepared 2CaO•5B2O3•5H2O nanoplate is also better than that of 2CaO•B2O3•H2O nanosheet. This research indicated that 2CaO•5B2O3•5H2O nanoplate could be a potential utility-type flame retardant.

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.

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

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. 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. 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. 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.

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.

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 selectivity profiling, which is based on a kinase-ligand focused database (KinLigDB). It provides all ready-to-use 3D structure coordinates of 4,219 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. For each top-ranked kinase, the additional classification attributes and the phylogenetic tree are given simultaneously.

OBJECTIVE: 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. METHOD: 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. RESULT: 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(P=0.038) and trachea(P=0.007) were more likely to be involved in recurrent tumor, with statistical differences. CONCLUSION: 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.

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.

To investigate the outcomes of cochlear implantation in patients with neurofibromatosis type 2 (NF2), and to discuss the current management strategy for NF2 patients. The medical records of NF2 patients who received cochlear implants (CI) at our center between 2012 and 2016 were retrospectively reviewed. Pre-operative hearing status, tumor status, treatment of tumors, and auditory outcomes post-implantation were evaluated. Twelve patients were included in the study. Five were implanted with the tumor in situ; two of them received radiotherapy pre-implantation, and three were implanted without any previous treatment. Four patients were implanted simultaneously with tumor removal. Three patients were implanted as second-stage after failed hearing preservation surgery. The mean pure tone audiometry with the implant was 44 dB (range 25–80 dB) and the mean sentence recognition score (SRS) in a quiet environment without lip reading was 63% (range 0–97%). A poorer objective auditory outcome was identified in one patient who showed no response to electrical promontory stimulation (EPS), but the sound perception was still helpful. In total, 11 of 12 (91%) patients were daily users, and the other patient used the implant as a “sleeper” device due to its interference with contralateral hearing provided by a hearing aid. CI is an effective option in auditory rehabilitation and should be considered primarily for NF2 patients with intact cochlear nerve. EPS might be a predictor for cochlear implant performance. Good contralateral hearing may present a barrier to daily use.

The Institute of Modern Physics (IMP) of the Chinese Academy of Sciences (CAS) is building a compact neutron source using a superconducting linac. The injector RFQ will operate in continuous wave (CW) mode, accelerating a 10-mA deuteron beam from 20 keV/u to 1.5 MeV/u. To minimize the possibility of beam loss in the downstream superconducting linac and maintain high acceleration efficiency, we take the 99.9% longitudinal beam emittance as the key optimization parameter for the beam dynamics design of the RFQ, and include an internal buncher to reduce the longitudinal beam emittance. This paper describes the design procedures, beam dynamics simulations and preliminary beam commissioning results for this RFQ. Simulation results show that 99.9% longitudinal beam emittance at the RFQ exit is optimized to 3.5 pi mm mrad, which is 0.13 times the longitudinal acceptance of the downstream superconducting linac. Beam commissioning results demonstrate that the RFQ can accelerate 7.8 mA H 2 + to 3.11 MeV. The transmission efficiency from a Faraday cup before the RFQ to the beam dump after the RFQ is 97.6%. The measured transmission efficiency agrees well with simulation results at different values for the inter-vane voltage.

To compare the intracochlear trauma induced by optimized robot-based and manual techniques with a straight electrode array prototype inserted at different lengths.Experimental study.Robot-based otologic surgery laboratory.A prototype array was inserted at different insertion lengths (21 and 25 mm) in 20 temporal bones. The manual insertion was performed with a microforceps. The optimized approach consisted of an optimal axis insertion provided by a robot-based arm controlled by a tracking system, with a constant speed of insertion (0.25 mm/s) achieved by a motorized insertion tool. The electrode position was determined at the level of each electrode by stereomicroscopic cochlea section analysis.A higher number of electrodes correctly located in the scala tympani was associated with the optimized approach ( P = .03, 2-way analysis of variance). Regardless of the insertion technique used, the array inserted at 25 mm allowed complete insertion of the active stimulating portion of the array in all cases. Insertion depth was greater when the array was inserted to 25 mm versus 21 mm ( P.001, 2-way analysis of variance). The optimized insertion was associated with less trauma than that from manual insertion regardless the length of the inserted array ( P = .04, 2-way analysis of variance).Compared with a manual insertion, intracochlear trauma could be reduced with array insertion performed on an optimal axis by using motorized insertion and by applying a constant insertion speed.