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Abstract Using a self‐administered questionnaire (the five‐item Brief Symptom Rating Scale, BSRS‐5), determine the prevalence of suicide ideation (SI), psychiatric morbidity (PM), and the factors associated with these conditions in a general hospital in Taiwan. All individuals aged 12 years or older, who were admitted to a Medical University Hospital between August 2014 and December 2016, were asked to fill out the BSRS‐5 at admission. The study was conducted in a medical inpatient setting, excluding Intensive Care Units and the Emergency Service Department. The 93,129 participants were recruited for analysis. Pearson's correlation, regression analysis and path analysis were performed to test the association between SI and each item of psychopathology and to determine the discrimination validity of individual BSRS‐5 items for predicting SI. The prevalence rate was 2.3% for SI and 2.0% for PM among all participants. PM was more prevalent in females and those aged 25–54 years. Individuals with PM had a significantly higher rate of SI (44.6%) than did others (1.4%). The prevalence of PM was varied by department, e.g., Psychiatry (44.3%), Rehabilitation Medicine (7.9%), and Nephrology (5.2%). The regression analysis and path analysis with structural equation model indicated that depression, hostility, anxiety, and inferiority were significant independent predictors of SI. The BSRS‐5 is an efficient and useful screening tool to identify psychological distress and SI among inpatients in a general hospital. Its integration into the electronic medical chart facilitates identifying patients at risk.

Abstract Introduction Ropeginterferon alfa-2b is a novel mono-pegylated proline-interferon. This clinical study aimed to evaluate its antiviral efficacy of ropeginterferon alfa-2b against SARS-CoV-2 infection. Methods This is a multicenter, randomized, open-label study. Adult patients with confirmed SARS-CoV-2 infection with initial cycle threshold (Ct) value

Large-scale forest inventory at the individual tree level is critical for natural resource management decision making. Terrestrial Laser Scanning (TLS) has been used for individual tree level inventory at plot scale However, due to the inflexibility of TLS and the complex scene of natural forests, it is still challenging to localize and measure every tree at large scale. In this paper, we present a framework to conduct large-scale natural forest inventory at the individual tree level by taking advantage of deep learning models and Mobile Laser Scanning (MLS) systems. First, a deep learning model, ForestSPG, was developed to perform large-scale semantic segmentation on MLS LiDAR data in natural forests. Then, the forest segmentation results were used for individual stem mapping. Finally, Diameter at Breast Height (DBH) was measured for each individual stem. Two natural forests mapped with backpack and Unmanned Aerial Vehicle (UAV) LiDAR systems were tested. The results showed that the proposed ForestSPG is able to segment large-scale forest LiDAR data into multiple ecologically meaningful classes. The proposed framework was able to localize and measure all 5838 stems at individual tree level in a 20 ha natural forest in less than 20 min using UAV LiDAR. DBH measurement results on trees’ DBH larger than 38.1 cm (15 in) showed that backpack LiDAR was able to achieve 1.82 cm of Root Mean Square Error (RMSE) and UAV LiDAR was able to achieve 3.13 cm of RMSE. The proposed framework can not only segment complex forest components with LiDAR data from different platforms but also demonstrate good performance on stem mapping and DBH measurement. Our research provides and automatic and scalable solution for large-scale natural forest inventory at individual tree level, which can be the basis for large-scale estimation of wood volume and biomass.

Background: Recent studies have demonstrated a global decline in the age at menarche. Our study aimed to determine the age at menarche of Taiwanese women born between 1943 and 1989. Methods: Data were obtained from the Taiwan Biobank. To view the trends in age at menarche, we analyzed data from 74,799 women. The mean, standard deviation, and annual percentage change in age at menarche were calculated for birth-year cohorts. Results: The mean age at menarche of Taiwanese women born in 1943 was 14.85 years. The age at menarche decreased to 12.20 years for those born in 1989. The mean age at menarche declined by 2.65 years across the 47-year study period; hence, the reduction rate was 0.56 years per decade. This study demonstrated a downward secular trend in the age at menarche of Taiwanese women born between 1943 and 1989. This trend occurred in three stages of decline: fast (1943–1953), slow (1953–1965), and moderate (1965–1989). Conclusion: The age at menarche decreased by 2.65 years among Taiwanese women born in 1943 compared with those born in 1989. This decline occurred in three stages: fast (1943–1953), slow (1953–1965), and moderate (1965–1989). This significant downward secular trend in age at menarche reflects Taiwan's socioeconomic development.

Amyloid-beta peptide (Aβ) is a neurotoxic constituent of senile plaques in the brains of Alzheimer’s disease (AD) patients. The detailed mechanisms by which protein kinase C-delta (PKCδ) contributes to Aβ toxicity is not yet entirely understood. Using fully differentiated primary rat cortical neurons, we found that inhibition of Aβ25-35-induced PKCδ increased cell viability with restoration of neuronal morphology. Using cyclin D1, proliferating cell nuclear antigen (PCNA), and histone H3 phosphorylated at Ser-10 (p-Histone H3) as the respective markers for the G1-, S-, and G2/M-phases, PKCδ inhibition mitigated cell cycle reentry (CCR) and subsequent caspase-3 cleavage induced by both Aβ25-35 and Aβ1-42 in the post-mitotic cortical neurons. Upstream of PKCδ, signal transducers and activators of transcription (STAT)-3 mediated PKCδ induction, CCR, and caspase-3 cleavage upon Aβ exposure. Downstream of PKCδ, aberrant neuronal CCR was triggered by overactivating cyclin-dependent kinase-5 (CDK5) via calpain2-dependent p35 cleavage into p25. Finally, PKCδ and CDK5 also contributed to Aβ25-35 induction of p53-upregulated modulator of apoptosis (PUMA) in cortical neurons. Together, we demonstrated that, in the post-mitotic neurons exposed to Aβs, STAT3-dependent PKCδ expression triggers calpain2-mediated p35 cleavage into p25 to overactivate CDK5, thus leading to aberrant CCR, PUMA induction, caspase-3 cleavage, and ultimately apoptosis.

Abstract Objective Early diagnosis and treatment of nasopharyngeal carcinoma (NPC) are vital for a better prognosis. Still, because of obscure anatomical sites and insidious symptoms, nearly 80% of patients with NPC are diagnosed at a late stage. This study aimed to validate a machine learning (ML) model utilizing symptom‐related diagnoses and procedures in medical records to predict nasopharyngeal carcinoma (NPC) occurrence and reduce the prediagnostic period. Materials and Methods Data from a population‐based health insurance database (2001–2008) were analyzed, comparing adults with and without newly diagnosed NPC. Medical records from 90 to 360 days before diagnosis were examined. Five ML algorithms (Light Gradient Boosting Machine [LGB], eXtreme Gradient Boosting [XGB], Multivariate Adaptive Regression Splines [MARS], Random Forest [RF], and Logistics Regression [LG]) were evaluated for optimal early NPC detection. We further use a real‐world data of 1 million individuals randomly selected for testing the final model. Model performance was assessed using AUROC. Shapley values identified significant contributing variables. Results LGB showed maximum predictive power using 14 features and 90 days before diagnosis. The LGB models achieved AUROC, specificity, and sensitivity were 0.83, 0.81, and 0.64 for the test dataset, respectively. The LGB‐driven NPC predictive tool effectively differentiated patients into high‐risk and low‐risk groups (hazard ratio: 5.85; 95% CI: 4.75–7.21). The model‐layering effect is valid. Conclusions ML approaches using electronic medical records accurately predicted NPC occurrence. The risk prediction model serves as a low‐cost digital screening tool, offering rapid medical decision support to shorten prediagnostic periods. Timely referral is crucial for high‐risk patients identified by the model.

The amyloid-beta peptide (Aβ) is the neurotoxic component in senile plaques of Alzheimer’s disease (AD) brains. Previously we have reported that Aβ toxicity is mediated by the induction of sonic hedgehog (SHH) to trigger cell cycle re-entry (CCR) and apoptosis in post-mitotic neurons. Basella alba is a vegetable whose polysaccharides carry immunomodulatory and anti-cancer actions, but their protective effects against neurodegeneration have never been reported. Herein, we tested whether polysaccharides derived from Basella alba (PPV-6) may inhibit Aβ toxicity and explored its underlying mechanisms. In differentiated rat cortical neurons, Aβ25-35 reduced cell viability, damaged neuronal structure, and compromised mitochondrial bioenergetic functions, all of which were recovered by PPV-6. Immunocytochemistry and western blotting revealed that Aβ25-35-mediated induction of cell cycle markers including cyclin D1, proliferating cell nuclear antigen (PCNA), and histone H3 phosphorylated at Ser-10 (p-Histone H3) in differentiated neurons was all suppressed by PPV-6, along with mitigation of caspase-3 cleavage. Further studies revealed that PPV-6 inhibited Aβ25-35 induction of SHH; indeed, PPV-6 was capable of suppressing neuronal CCR and apoptosis triggered by the exogenous N-terminal fragment of sonic hedgehog (SHH-N). Our findings demonstrated that, in the fully differentiated neurons, PPV-6 exerts protective actions against Aβ neurotoxicity via the downregulation of SHH to suppress neuronal CCR and apoptosis.

The nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) protein plays an essential role in the cisplatin (CDDP)-induced generation of reactive oxygen species (ROS). In this study, we evaluated the suitability of ultrasound-mediated lysozyme microbubble (USMB) cavitation to enhance NOX4 siRNA transfection in vitro and ex vivo. Lysozyme-shelled microbubbles (LyzMBs) were constructed and designed for siNOX4 loading as siNOX4/LyzMBs. We investigated different siNOX4-based cell transfection approaches, including naked siNOX4, LyzMB-mixed siNOX4, and siNOX4-loaded LyzMBs, and compared their silencing effects in CDDP-treated HEI-OC1 cells and mouse organ of Corti explants. Transfection efficiencies were evaluated by quantifying the cellular uptake of cyanine 3 (Cy3) fluorescein-labeled siRNA. In vitro experiments showed that the high transfection efficacy (48.18%) of siNOX4 to HEI-OC1 cells mediated by US and siNOX4-loaded LyzMBs significantly inhibited CDDP-induced ROS generation to almost the basal level. The ex vivo CDDP-treated organ of Corti explants of mice showed an even more robust silencing effect of the NOX4 gene in the siNOX4/LyzMB groups treated with US sonication than without US sonication, with a marked abolition of CDDP-induced ROS generation and cytotoxicity. Loading of siNOX4 on LyzMBs can stabilize siNOX4 and prevent its degradation, thereby enhancing the transfection and silencing effects when combined with US sonication. This USMB-derived therapy modality for alleviating CDDP-induced ototoxicity may be suitable for future clinical applications.

The synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) are the most vulnerable structures in the noise-exposed cochlea. Cochlear synaptopathy results from the disruption of these synapses following noise exposure and is considered the main cause of poor speech understanding in noisy environments, even when audiogram results are normal. Cochlear synaptopathy leads to the degeneration of SGNs if damaged IHC-SGN synapses are not promptly recovered. Oxidative stress plays a central role in the pathogenesis of cochlear synaptopathy. C-Phycocyanin (C-PC) has antioxidant and anti-inflammatory activities and is widely utilized in the food and drug industry. However, the effect of the C-PC on noise-induced cochlear damage is unknown. We first investigated the therapeutic effect of C-PC on noise-induced cochlear synaptopathy. In vitro experiments revealed that C-PC reduced the H2O2-induced generation of reactive oxygen species in HEI-OC1 auditory cells. H2O2-induced cytotoxicity in HEI-OC1 cells was reduced with C-PC treatment. After white noise exposure for 3 h at a sound pressure of 118 dB, the guinea pigs intratympanically administered 5 μg/mL C-PC exhibited greater wave I amplitudes in the auditory brainstem response, more IHC synaptic ribbons and more IHC-SGN synapses according to microscopic analysis than the saline-treated guinea pigs. Furthermore, the group treated with C-PC had less intense 4-hydroxynonenal and intercellular adhesion molecule-1 staining in the cochlea compared with the saline group. Our results suggest that C-PC improves cochlear synaptopathy by inhibiting noise-induced oxidative stress and the inflammatory response in the cochlea.

Shigellosis appears to increase in certain at-risk populations in developed countries. Based on the nationwide surveillance, the annual incidence of shigellosis in Taiwan (1999-2019) was 0.38-5.77 cases per 100,000 people. Indigenous shigellosis has mostly affected men who have sex with men (MSM) and people living with HIV (PLWH) since 2015. In this retrospective study, compared with those diagnosed before 2015, indigenous cases diagnosed during 2015–2019 mostly occurred in male adults (96.0% vs 47.1%, P

Connexin hemichannels were identified as the first members of the eukaryotic large-pore channel family that mediate permeation of both atomic ions and small molecules between the intracellular and extracellular environments. The conventional view is that their pore is a large passive conduit through which both ions and molecules diffuse in a similar manner. In stark contrast to this notion, we demonstrate that the permeation of ions and of molecules in connexin hemichannels can be uncoupled and differentially regulated. We find that human connexin mutations that produce pathologies and were previously thought to be loss-of-function mutations due to the lack of ionic currents are still capable of mediating the passive transport of molecules with kinetics close to those of wild-type channels. This molecular transport displays saturability in the micromolar range, selectivity, and competitive inhibition, properties that are tuned by specific interactions between the permeating molecules and the N-terminal domain that lies within the pore--a general feature of large-pore channels. We propose that connexin hemichannels and, likely, other large-pore channels, are hybrid channel/transporter-like proteins that might switch between these two modes to promote selective ion conduction or autocrine/paracrine molecular signaling in health and disease processes. [ABSTRACT FROM AUTHOR]

Background/Purpose: Based on the fundamental of the S3-level clinical practice guideline (CPG) for treating stage I-III periodontitis developed by the European Federation of Periodontology (EFP), this consensus report aimed to develop treatment recommendations for treating periodontitis in the Taiwanese population. Methods: The report was constructed by experts from the Taiwan Academy of Periodontology. The following topics were reviewed: (a) the prevalence of periodontitis in Asia and current status of treatment in Taiwan; (b) specific anatomical considerations for treating periodontitis in Asians; (d) educational and preventive interventions and supragingival plaque control; (d) subgingival instrumentation and adjunctive treatment; (e) surgical periodontal therapy; and (f) maintenance and supportive periodontal care. Recommendations were made according to the evidences from the EFP CPG, the published literature and clinical studies in Asians, and the expert opinions. Results: The treatment recommendations for the Taiwanese population were generally in parallel with the EFP CPG, and extra cautions during treatment and maintenance phases were advised due to the anatomical variations, such as shorter root trunk, higher prevalence of supernumerary distolingual root and lingual bony concavity in mandibular posteriors, and thinner anterior labial plate, of the Asian population. Conclusion: The EFP CPG could be adopted for treating periodontitis and maintaining periodontal health of the Taiwanese population, and anatomical variations should be cautious when the treatment is delivered.

Emerging mobile LiDAR mapping systems exhibit great potential as an alternative for mapping urban environments. Such systems can acquire high-quality, dense point clouds that capture detailed information over an area of interest through efficient field surveys. However, automatically recognizing and semantically segmenting different components from the point clouds with efficiency and high accuracy remains a challenge. Towards this end, this study proposes a semantic segmentation framework to simultaneously classify bridge components and road infrastructure using mobile LiDAR point clouds while providing the following contributions: 1) a deep learning approach exploiting graph convolutions is adopted for point cloud semantic segmentation; 2) cross-labeling and transfer learning techniques are developed to reduce the need for manual annotation; and 3) geometric quality control strategies are proposed to refine the semantic segmentation results. The proposed framework is evaluated using data from two mobile mapping systems along an interstate highway with 27 highway bridges. With the help of the proposed cross-labeling and transfer learning strategies, the deep learning model achieves an overall accuracy of 84% using limited training data. Moreover, the effectiveness of the proposed framework is verified through test covering approximately 42 miles along the interstate highway, where substantial improvement after quality control can be observed.

ABSTRACT The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has substantially affected human health globally. Spike-specific antibody response plays a major role in protection against SARS-CoV-2 infection. Here, we examined serological anti-spike antibody and memory B cell responses in adults with acute SARS-CoV-2 infection. Twenty-five adult patients were enrolled between January and September 2020, and 21 (84%) had a detectable spike-binding antibody response in serum on day 21 ± 8 (6 to 33) after the onset of illness. Among those with positive spike-binding antibody response, 19 (90%) had a positive hemagglutination titer and 15 (71%) had angiotensin-converting enzyme 2 (ACE2)-blocking serological activities. Follow-up serum samples collected 11 ± 1 (7 to 15) months after infection exhibited an average of 2.6 ± 1.0 (1.0 to 3.5)-fold reduction in the spike-binding antibody response. Moreover, convalescent and follow-up serum samples showed 83 ± 82 (15 to 306)- and 165 ± 167 (12 to 456)-fold reductions in the neutralization activity against the Omicron variant, respectively. Upon acute infection, spike-specific memory B cell responses were elicited, with an average frequency of 1.3% ± 1.2% of peripheral B cells on day 19 ± 7 (6 to 33) after the onset of illness. IgM memory B cells were predominantly induced. Patients with fever and pneumonia showed significantly stronger spike-binding, ACE2-blocking antibody, and memory B cell responses. In conclusion, spike-specific antibody response elicited upon acute SARS-CoV-2 infection may wane over time and be compromised by the emergence of viral variants. IMPORTANCE As spike protein-specific antibody responses play a major role in protection against SARS-CoV-2, we examined spike-binding and ACE2-blocking antibody responses in SARS-CoV-2 infection at different time points. We found robust responses following acute infection, which waned approximately 11 months after infection. Patients with fever and pneumonia showed significantly stronger spike-binding, ACE2-blocking antibody, and memory B cell responses. In particular, spike-specific antibody response in the convalescent and follow-up serum samples was substantially affected by emerging variants, especially Beta and Omicron variants. These results warrant continued surveillance of spike-specific antibody responses to natural infections and highlight the importance of maintaining functional anti-spike antibodies through immunization.

Abstract Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

Mechanosensitive Piezo1 channels transduce mechanical stimuli into electrochemical signals. Jiang et al. show that due to the bending rigidity of the membrane, the overlap of neighboring Piezo1 footprints produces a flattening of the Piezo1 footprints and a cation-selective conducting pore. This study suggests that the clustering of Piezo1 channels may tune its sensitivity to applied force.

Abstract The risk of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in primary Sjogren syndrome (pSS) has rarely been explored. To explore the association between BRONJ and pSS, we conducted a population-based propensity-score-matched cohort study using Taiwan’s National Health Insurance Research Database, including pSS patients receiving antiosteoporotic therapy and patients without pSS receiving antiosteoporotic therapy. A 1:4 matched-pair cohort based on propensity score was created. The stratified Cox proportional hazards model compared the risk of BRONJ in the pSS and non-pSS groups. In the study, 23,280 pSS patients and 28,712,152 controls were enrolled. After matching, 348 patients with pSS receiving antiosteoporotic drugs and 50,145 without pSS receiving antiosteoporotic drugs were included for analysis. The risk of developing BRONJ was 1.96 times higher in pSS patients compared with non-pSS patients after adjustment for age, sex, and comorbidities. No dose–response effect was observed in the bisphosphonate-treated pSS cohorts, documented as the cumulative defined daily doses of either

Our previous study first investigated feasibility of applying ultrasound (US) and microbubbles (MBs) via external auditory canal to facilitate drug delivery into inner ear. However, most drugs are in aqueous formulae and eliminated via Eustachian tubes after drug application. In this study, feasibility of sustained release of thermosensitive poloxamer 407 (P407)-based MB gel for US mediation-enhanced inner ear drug (dexamethasone, DEX) delivery was investigated. The sol-to-gel transition temperature showed that mixture of DEX and only 10% and 12.5% P407 in MBs can be used for in vitro and in vivo drug delivery experiments. In in vitro Franz diffusion experiments, the release rates of 12.5% P407-MBs + US groups in the model using DEX as the delivered reagent at 3 h resulted in values 1.52 times greater than those of 12.5% P407-MBs groups. In guinea pigs, by filling tympanic bulla with DEX in 12.5% P407-MBs (DEX-P407-MBs), USMB applied at post-treatment days 1 and 7 induced 109.13% and 66.67% increases in DEX delivery efficiencies, respectively, compared to the group without US. On the 28th day after US-mediated P407-MB treatment, the safety assessment showed no significant changes in the hearing thresholds and no damage to the integrity of cochlea or middle ear. These are the first results to demonstrate feasibility of US-modified liquid form DEX-P407-MB cavitation for enhancing permeability of round window membrane. Then, a gel form of DEX-P407-MBs was generated and thus prolonged the release of DEX in middle ear to maintain the therapeutic DEX level in inner ear for at least 7 days.

Various all-atom molecular dynamics (MD) simulation methods have been developed to compute free energies and crossing rates of ions and small molecules through ion channels. However, a systemic comparison across different methods is scarce. Using a carbon nanotube as a model of small conductance ion channel, we computed the single-channel permeability for potassium ion using umbrella sampling, Markovian milestoning, and steady-state flux under applied voltage. We show that a slightly modified inhomogeneous solubility-diffusion equation yields a single-channel permeability consistent with the mean first passage time (MFPT) based method. For milestoning, applying cylindrical and spherical bulk boundary conditions yield consistent MFPT if factoring in the effective bulk concentration. The sensitivity of the MFPT to the output frequency of collective variables is highlighted using the convergence and symmetricity of the inward and outward MFPT profiles. The consistent transport kinetic results from all three methods demonstrated the robustness of MD-based methods in computing ion channel permeation. The advantages and disadvantages of each technique are discussed, focusing on the future applications of milestoning in more complex systems.

By the request of the Minister of Health and Welfare, NHRI Biobank was assigned to establish a COVID-19 biobank in early Feb, 2020 to collect COVID-19 patients’ blood samples for Taiwan researchers and industries in an emergent way. It was set up in less than 3 weeks and quickly opened for application. By August 5, 2020, this COVID-19 biobank has collected 165 blood samples of 110 patients from more than 10 hospitals across north, middle and south part of Taiwan, including both COVID-19 (+) and (-) pneumonia patients. This biobank can provide applicants with biosamples, such as serum, DNA and RNA, and also the clinical and genomic data, so as to accelerate the COVID-19 treatment and prevention research in Taiwan. This COID-19 biobank already received 15 applications. It has become the most important research resource for the COVID-19 pandemic in Taiwan, including new screening reagents, disease mechanism, the variable human responses and epidemic preventions. Since it is publicly available for both academic and industrial applicants.

An increase of Ct values was 0.9 per day in 2 cases of COVID-19 treated with lopinavir/ritonavir (LPV/r), an increase was 1.0 per day in 3 cases without LPV/r through illness day 1–10, indicating that LPV/r did not shorten the duration of SARS CoV-2 shedding.

ABSTRACTThis multicenter, retrospective study included 346 serum samples from 74 patients with coronavirus disease 2019 (COVID-19) and 194 serum samples from non-COVID-19 patients to evaluate the performance of five anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests, i.e. two chemiluminescence immunoassays (CLIAs): Roche Elecsys® Anti-SARS-CoV-2 Test (Roche Test) and Abbott SARS-CoV-2 IgG (Abbott Test), and three lateral flow immunoassays (LFIAs): Wondfo SARS-CoV-2 Antibody Test (Wondfo Test), ASK COVID-19 IgG/IgM Rapid Test (ASK Test), and Dynamiker 2019-nCoV IgG/IgM Rapid Test (Dynamiker Test). We found high diagnostic sensitivities (%, 95% confidence interval [CI]) for the Roche Test (97.4%, 93.4–99.0%), Abbott Test (94.0%, 89.1–96.8%), Wondfo Test (91.4%, 85.8–94.9%), ASK Test (97.4%, 93.4–99.0%), and Dynamiker Test (90.1%, 84.3–94.0%) after >21 days of symptom onset. Meanwhile, the diagnostic specificity was 99.0% (95% CI, 96.3–99.7%) for the Roche Test, 97.9% (95% CI, 94.8–99.2%) for the Abbott Test, and 100.0% (95% CI, 98.1–100.0%) for the three LFIAs. Cross-reactivity was observed in sera containing anti-cytomegalovirus (CMV) IgG/IgM antibodies and autoantibodies. No difference was observed in the time to seroconversion detection of the five serological tests. Specimens from patients with COVID-19 pneumonia demonstrated a shorter seroconversion time and higher chemiluminescent signal than those without pneumonia. Our data suggested that understanding the dynamic antibody response after COVID-19 infection and performance characteristics of different serological test are crucial for the appropriate interpretation of serological test result for the diagnosis and risk assessment of patient with COVID-19 infection.

Objective: Lower serum low-density lipoprotein cholesterol (LDL-C) levels are associated with increased intracerebral hemorrhage (ICH) risk. However, reverse causality and residual confounding has not attracted public attention. Therefore, we assessed whether people with LDL-C have increased risk of mortality adjusting for potential confounders using two large Taiwan cohorts.Methods: The Mei-Jhao (MJ) cohort has 414,372 adults participating in a medical screening program with 378 ICH deaths within 15 years of follow-up (1994–2008). Cox proportional hazards regressions estimated hazard death ratios according to LDL-C levels. We identified 4,606 ICH patients from the Taiwan Stroke Registry (TSR) and analyzed the impact of LDL-C on 3-month mortality.Results: Low cholesterol (LDL-C

Atopic dermatitis has a substantial impact on work and activity impairment according to studies from Western communities. Prospective studies of work productivity and activity impairment in Asian patients with atopic dermatitis are lacking. The aims of this study were to investigate the impacts of atopic dermatitis on work productivity and activity impairment among Taiwanese patients, and to stratify the analyses by disease severity. One-third of employed participants reported missing work (absenteeism) in the preceding week due to atopic dermatitis, while 88.5% of the remaining two-thirds reported impaired work effectiveness (presenteeism). In addition, 92.5% of all participants reported impaired daily activities. Overall work impairment (aggregate productivity loss from absenteeism and presenteeism) was 1.8- and 2.6-fold greater in subjects with moderate and severe atopic dermatitis, respectively, compared with those with mild atopic dermatitis. Presenteeism, but not absenteeism, contributes to the majority of total work impairment in this cohort. Daily activity impairment was 1.5-fold greater in moderate atopic dermatitis, and 2.0-fold greater in severe atopic dermatitis, compared with mild atopic dermatitis. Both work and activity impairment showed significant positive correlations with atopic dermatitis severity scores (SCORing Atopic Dermatitis; SCORAD). In conclusion, work productivity and activity impairment is significantly correlated with disease severity in this Taiwanese atopic dermatitis cohort. In order to obtain a full picture of disease burden to patients and caregivers, patients with atopic dermatitis should be monitored for disease activity as well as corresponding impacts on quality of life.

Light Detection and Ranging (LiDAR) data collected by mobile mapping systems (MMS) have been utilized to detect lane markings through intensity-based approaches. As LiDAR data continue to be used for lane marking extraction, greater emphasis is being placed on enhancing the utility of the intensity values. Typically, intensity correction/normalization approaches are conducted prior to lane marking extraction. The goal of intensity correction is to adjust the intensity values of a LiDAR unit using geometric scanning parameters (i.e., range or incidence angle). Intensity normalization aims at adjusting the intensity readings of a LiDAR unit based on the assumption that intensity values across laser beams/LiDAR units/MMS should be similar for the same object. As MMS technology develops, correcting/normalizing intensity values across different LiDAR units on the same system and/or different MMS is necessary for lane marking extraction. This study proposes a generalized correction/normalization approach for handling single-beam/multi-beam LiDAR scanners onboard single or multiple MMS. The generalized approach is developed while considering the intensity values of asphalt and concrete pavement. For a performance evaluation of the proposed approach, geometric/morphological and deep/transfer-learning-based lane marking extraction with and without intensity correction/normalization is conducted. The evaluation shows that the proposed approach improves the performance of lane marking extraction (e.g., the F1-score of a U-net model can change from 0.1% to 86.2%).

LiDAR data acquired by various platforms provide unprecedented data for forest inventory and management. Among its applications, individual tree detection and segmentation are critical and prerequisite steps for deriving forest structural metrics, especially at the stand level. Although there are various tree detection and localization approaches, a comparative analysis of their performance on LiDAR data with different characteristics remains to be explored. In this study, a new trunk-based tree detection and localization approach (namely, height-difference-based) is proposed and compared to two state-of-the-art strategies—DBSCAN-based and height/density-based approaches. Leaf-off LiDAR data from two unmanned aerial vehicles (UAVs) and Geiger mode system with different point densities, geometric accuracies, and environmental complexities were used to evaluate the performance of these approaches in a forest plantation. The results from the UAV datasets suggest that DBSCAN-based and height/density-based approaches perform well in tree detection (F1 score > 0.99) and localization (with an accuracy of 0.1 m for point clouds with high geometric accuracy) after fine-tuning the model thresholds; however, the processing time of the latter is much shorter. Even though our new height-difference-based approach introduces more false positives, it obtains a high tree detection rate from UAV datasets without fine-tuning model thresholds. However, due to the limitations of the algorithm, the tree localization accuracy is worse than that of the other two approaches. On the other hand, the results from the Geiger mode dataset with low point density show that the performance of all approaches dramatically deteriorates. Among them, the proposed height-difference-based approach results in the greatest number of true positives and highest F1 score, making it the most suitable approach for low-density point clouds without the need for parameter/threshold fine-tuning.

We report the case of a patient who had travelled to Japan and who presented mild respiratory symptoms during the COVID-19 outbreak period. There was transient existence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in his oropharynx. The RNA was absent in the six respiratory specimens that were subsequently tested. An anti-SARS-CoV-2 antibody response was absent in the acute and convalescent sera. The reported case indicates that transient colonization of SARS-CoV-2 in the upper respiratory tract is possible without inciting any antibody response against the virus.

Besides mechanical forces, the mechanosensitive channel Piezo1 is activated by the small molecule Yoda1 through an unknown mechanism. Here, using molecular dynamics simulations, calcium imaging and electrophysiology, the authors identify an allosteric Yoda1 binding pocket located in the putative mechanosensory domain.

Abstract Background Weight‐reduction therapies, including bariatric surgery (BS), are standard treatments for severely obese patients with type 2 diabetes; however, the outcomes of these therapies are inconclusive for obese patients with chronic kidney disease (CKD). This study aimed to investigate the effects of BS or non‐surgical interventions on the estimated glomerular filtration rate (eGFR) and to determine whether BS can be recommended for renal function preservation based on body mass index (BMI) and eGFR changes in obese patients with CKD. Methods This study used data from the weight Reduction Intervention on GFR in Obese Patients with Renal Impairment‐Taipei Medical University (TMU) study, which was a large, long‐term, propensity score‐matched cohort study based on clinical data from patients who registered at weight‐reduction centres at TMU and its affiliated hospitals from 2008 to 2016. The patients were stratified according to whether they had undergone BS and into the mild, moderate, and high CKD risk groups using the Kidney Disease: Improving Global Outcomes guidelines. The primary outcome was the eGFR calculated using the Taiwan Chronic Kidney Disease‐Epidemiology Collaboration equation. Cox regression models were used to determine hazard ratios (HRs) for eGFR decreases ≥25%. Results A total of 4332 obese patients were enrolled in this study. After propensity score matching, 1620 patients, including 60.2% women, with a mean age of 36.5 (9.9) years were divided into BS or non‐surgery groups (n = 810 per group). The overall mean eGFRs increased by 4.4 (14) mL/min·1.73 m2 and decreased by 6.4 (16.0) mL/min·1.73 m2 in the BS and non‐surgery groups, respectively. The decrease in BMI in the BS and non‐surgery groups were 2.5 and 1.3 kg/m2, respectively. In the moderate/high CKD risk BS group, a significant correlation was evident between an increased eGFR and a reduced BMI (Spearman's correlation −0.229, P < 0.001). The Cox regression analysis showed that the BS group had a significantly lower risk of an eGFR decline ≥25% at 12 months [adjusted HR (aHR) 0.47, P = 0.03). After BS, obese patients with hypertension or albuminuria had significantly lower risks of eGFR declines ≥25% (aHR 0.37, P = 0.02 and aHR 0.13, P = 0.0018, respectively). Conclusions Bariatric surgery was associated with eGFR preservation in all obese patients and, particularly, in those with moderate‐to‐high CKD risks. A longer term outcome study is warranted to determine the benefits of BS for CKD patients.

Abstract Background Several studies examined headaches as a symptom of brain neoplasms. Nevertheless, very few studies attempted to specifically evaluate the role of headaches as a risk factor. This study aimed to investigate the risk of migraine occurrence in the preceding years among patients diagnosed with brain tumors and unaffected controls. Methods Data were obtained from the Taiwan National Health Insurance Research Database. In total, 11,325 adults with a first-time brain tumor diagnosis were included as cases, together with 11,325 unaffected matched controls. Each individual was traced in the healthcare claims dataset for a prior diagnosis of migraines. Conditional logistic regressions were performed to calculate the odds ratio (OR) and the corresponding 95% confidence interval (CI) to present the association between brain tumors and having previously been diagnosed with migraines. Results We found that among patients with and those without brain tumors, 554 (4.89%) and 235 (2.08%) individuals, respectively, were identified as having a prior migraine diagnosis. Compared to unaffected controls, patients with brain tumors experienced an independent 2.45-fold increased risk of having a prior migraine diagnosis. The risks were even higher among men (odds ratio (OR) = 3.04, 95% confidence interval (CI) = 2.29~ 4.04) and after patients who had received a prior migraine diagnosis within 3 years were excluded (OR = 1.91, 95% CI = 1.59~ 2.29). Conclusions This is the first report demonstrating the occurrence of brain tumors to be associated with a prior migraine history, for both men and women, in a population-based study.