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We report the observation of an electric field in twisted-bilayer molybdenum disulfide (MoS 2 ) and elucidate its correlation with local polar domains using four-dimensional scanning transmission electron microscopy (4D-STEM) and first-principles calculations. We reveal the emergence of in-plane topological vortices within the periodic moiré patterns for both commensurate structures at small twist angles and the incommensurate quasicrystal structure that occurs at a 30° twist. The large-angle twist leads to mosaic chiral vortex patterns with tunable characteristics. A twisted quasicrystal bilayer, characterized by its 12-fold rotational symmetry, hosts complex vortex patterns and can be manipulated by picometer-scale interlayer displacement. Our findings highlight that twisting 2D bilayers is a versatile strategy for tailoring local electric polar vortices.

Macroautophagy (hereafter autophagy) is essential for cells to respond to nutrient stress by delivering cytosolic contents to vacuoles for degradation via the formation of a multi-layer vesicle named autophagosome. A set of autophagy-related (ATG) regulators are recruited to the phagophore assembly site for the initiation of phagophore, as well as its expansion and closure and subsequent delivery into the vacuole. However, it remains elusive that how the phagophore assembly is regulated under different stress conditions. Here, we described an unknown Arabidopsis (Arabidopsis thaliana) cytosolic ATG8-interaction protein family (ERC1/2), that binds ATG8 and NBR1 to promote autophagy. ERC1 proteins translocate to the phagophore membrane and develop into classical ring-like autophagosomes upon autophagic induction. However, ERC1 proteins form large droplets together with ATG8e proteins when in the absence of ATG8 lipidation activity. We described the property of these structures as phase-separated membraneless condensates by solving the in vivo organization with spatial and temporal resolution. Moreover, ERC1 condensates elicits a strong recruitment of the autophagic receptor NBR1. Loss of ERC1 suppressed NBR1 turnover and attenuated plant tolerance to heat stress condition. This work provides novel insights into the mechanical principle of phagophore initiation via an unreported ERC1-mediated biomolecular condensation for heat tolerance in Arabidopsis .

Reactive oxygen species (ROS) including the superoxide anion (O 2 •- ) are typically studied in cell cultures using fluorescent dyes, which provide only discrete single-point measurements. These methods lack the capabilities for assessing O 2 •- kinetics and release in a quantitative manner over long monitoring times. Herein, we present the fabrication and application of an electrochemical biosensor that enables real-time continuous monitoring of O 2 •- release in cell cultures for extended periods (> 8 h) using an O 2 •- specific microelectrode. To achieve the sensitivity and selectivity requirements for cellular sensing, we developed a biohybrid system consisting of superoxide dismutase (SOD) and Ti 3 C 2 T x MXenes, deposited on a gold microwire electrode (AuME) as O 2 •- specific materials with catalytic amplification through the synergistic action of the enzyme and the biomimetic MXenes-based structure. The biosensor demonstrated a sensitivity of 18.35 nA/μM with a linear range from 147 to 930 nM in a cell culture medium. To demonstrate its robustness and practicality, we applied the biosensor to monitor O 2 •- levels in human leukemia monocytic THP-1 cells upon stimulation with lipopolysaccharide (LPS). Using this strategy, we successfully monitored LPS-induced O 2 •- in THP-1 cells, as well as the quenching effect induced by the ROS scavenger N-acetyl-L-cysteine (NAC). The biosensor is generally useful for exploring the role of oxidative stress and longitudinally monitoring O 2 •- release in cell cultures, enabling studies of biochemical processes and associated oxidative stress mechanisms in cellular and other biological environments., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

While family functioning is crucial to adolescent developmental outcomes, the mediating role of spirituality in the relationship between family functioning and academic-related outcomes of adolescents has been sparsely explored, particularly in non-Western contexts. To address this gap, based on a short-term longitudinal study, we examined the influence of family functioning on the academic values and academic anxiety of 4,981 Chinese adolescents in Sichuan, China, with spirituality as the mediator. We gathered data from students aged 11 and above at Wave 1 and at six months later (Wave 2). Analysis utilizing structural equation modeling indicated that prior family functioning positively and negatively predicted subsequent academic values and academic anxiety respectively, with spirituality as a significant mediator. Theoretically, this study helps to build up a conceptual model on how family functioning and spirituality of adolescents shape academic values and academic anxiety of adolescents. Practically, the present findings highlight the significance of enhancing family functioning and adolescent spirituality to help adolescents strive for academic success., Competing Interests: The authors declare that the study was performed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shek, Leung, Li, Dou and Zhu.)

In Hong Kong, newly diagnosed multiple myeloma (NDMM) receives bortezomib-based triplet induction. Upfront autologous stem cell transplant (ASCT) is offered to transplant eligible (TE) patients (NDMM ≤ 65 years of age), unless medically unfit (TE-unfit) or refused (TE-refused). Data was retrieved for 448 patients to assess outcomes. For the entire cohort, multivariate analysis showed that male gender (p = 0.006), international staging system (ISS) 3 (p = 0.003), high lactate dehydrogenase (LDH) (p = 7.6 × 10 -7 ) were adverse predictors for overall survival (OS), while complete response/ near complete response (CR/nCR) post-induction (p = 2.7 × 10 -5 ) and ASCT (p = 4.8 × 10 -4 ) were favorable factors for OS. In TE group, upfront ASCT was conducted in 252 (76.1%). Failure to undergo ASCT in TE patients rendered an inferior OS (TE-unfit p = 1.06 × 10 -8 , TE-refused p = 0.002) and event free survival (EFS) (TE-unfit p = 0.00013, TE-refused p = 0.002). Among TE patients with ASCT, multivariate analysis showed that age ≥ 60 (p = 8.9 × 10 -4 ), ISS 3 (p = 0.019) and high LDH (p = 2.6 × 10 -4 ) were adverse factors for OS. In those with high-risk features (HR cytogenetics, ISS 3, R-ISS 3), ASCT appeared to mitigate their adverse impact. Our data reaffirmed the importance of ASCT. The poor survival inherent with refusal of ASCT should be recognized by clinicians. Finally, improved outcome with ASCT in those with high-risk features warrant further studies., (© 2024. The Author(s).)

Emerging non-noble metal 2D catalysts, such as molybdenum disulfide (MoS 2 ), hold great promise in hydrogen evolution reactions. The sulfur vacancy is recognized as a key defect type that can activate the inert basal plane to improve the catalytic performance. Unfortunately, the method of introducing sulfur vacancies is limited and requires costly post-treatment processes. Here, a novel salt-assisted chemical vapor deposition (CVD) method is demonstrated for synthesizing ultrahigh-density vacancy-rich 2H-MoS 2 , with a controllable sulfur vacancy density of up to 3.35 × 10 14  cm -2 . This approach involves a pre-sprayed potassium chloridepromoter on the growth substrate. The generation of such defects is closely related to ion adsorption in the growth process, the unstable MoS 2 -K-H 2 O triggers the formation of sulfur vacancies during the subsequent transfer process, and it is more controllable and nondestructive when compared to traditional post-treatment methods. The vacancy-rich monolayer MoS 2 exhibits exceptional catalytic activity based on the microcell measurements, with an overpotential of ≈158.8 mV (100 mA cm -2 ) and a Tafel slope of 54.3 mV dec -1 in 0.5 m H 2 SO 4 electrolyte. These results indicate a promising opportunity for modulating sulfur vacancy defects in MoS 2 using salt-assisted CVD growth. This approach represents a significant leap toward achieving better control over the catalytic performances of 2D materials., (© 2023 Wiley‐VCH GmbH.)

Automatic detection and characterization of cancer are important clinical needs to optimize early treatment. We developed a deep, semisupervised transfer learning approach for fully automated, whole-body tumor segmentation and prognosis on PET/CT. Methods: This retrospective study consisted of 611 18 F-FDG PET/CT scans of patients with lung cancer, melanoma, lymphoma, head and neck cancer, and breast cancer and 408 prostate-specific membrane antigen (PSMA) PET/CT scans of patients with prostate cancer. The approach had a nnU-net backbone and learned the segmentation task on 18 F-FDG and PSMA PET/CT images using limited annotations and radiomics analysis. True-positive rate and Dice similarity coefficient were assessed to evaluate segmentation performance. Prognostic models were developed using imaging measures extracted from predicted segmentations to perform risk stratification of prostate cancer based on follow-up prostate-specific antigen levels, survival estimation of head and neck cancer by the Kaplan-Meier method and Cox regression analysis, and pathologic complete response prediction of breast cancer after neoadjuvant chemotherapy. Overall accuracy and area under the receiver-operating-characteristic (AUC) curve were assessed. Results: Our approach yielded median true-positive rates of 0.75, 0.85, 0.87, and 0.75 and median Dice similarity coefficients of 0.81, 0.76, 0.83, and 0.73 for patients with lung cancer, melanoma, lymphoma, and prostate cancer, respectively, on the tumor segmentation task. The risk model for prostate cancer yielded an overall accuracy of 0.83 and an AUC of 0.86. Patients classified as low- to intermediate- and high-risk had mean follow-up prostate-specific antigen levels of 18.61 and 727.46 ng/mL, respectively ( P < 0.05). The risk score for head and neck cancer was significantly associated with overall survival by univariable and multivariable Cox regression analyses ( P < 0.05). Predictive models for breast cancer predicted pathologic complete response using only pretherapy imaging measures and both pre- and posttherapy measures with accuracies of 0.72 and 0.84 and AUCs of 0.72 and 0.76, respectively. Conclusion: The proposed approach demonstrated accurate tumor segmentation and prognosis in patients across 6 cancer types on 18 F-FDG and PSMA PET/CT scans., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

The emergence of SARS-CoV-2 mutations poses significant challenges to diagnostic tests, as these mutations can reduce the sensitivity of commonly used RT-PCR assays. Therefore, there is a need to design diagnostic assays with multiple targets to enhance sensitivity. In this study, we identified a novel diagnostic target, the nsp10 gene, using nanopore sequencing. Firstly, we determined the analytical sensitivity and specificity of our COVID-19-nsp10 assay. The COVID-19-nsp10 assay had a limit of detection of 74 copies/mL (95% confidence interval: 48-299 copies/mL) and did not show cross-reactivity with other respiratory viruses. Next, we determined the diagnostic performance of the COVID-19-nsp10 assay using 261 respiratory specimens, including 147 SARS-CoV-2-positive specimens belonging to the ancestral strain and Alpha, Beta, Gamma, Delta, Mu, Eta, Kappa, Theta and Omicron lineages. Using a LightMix E-gene RT-PCR assay as the reference method, the diagnostic sensitivity and specificity of the COVID-19-nsp10 assay were found to be 100%. The median Cp values for the LightMix E-gene RT-PCR and our COVID-19-nsp10 RT-PCR were 22.48 (range: 12.95-36.60) and 25.94 (range 16.37-36.87), respectively. The Cp values of the COVID-19-nsp10 RT-PCR assay correlated well with those of the LightMix E-gene RT-PCR assay (Spearman's ρ = 0.968; p < 0.0001). In conclusion, nsp10 is a suitable target for a SARS-CoV-2 RT-PCR assay.

Regarding the assessment of family functioning in Chinese people, there are several research gaps. First, although there are some instruments in the field, there are very few validated instruments. Second, while some translated measures have been developed, there are very few assessment tools based on indigenous Chinese concepts. Third, compared to Hong Kong, research on family assessment is relatively inactive in mainland China. Fourth, there are very few family assessment tools to assess perceived family functioning in older children and early adolescents. Fifth, few studies used large samples to validate family assessment tools. Sixth, researchers seldom utilized longitudinal data to examine the psychometric properties of family assessment tools. Finally, few studies have examined factorial validity across samples and time to demonstrate the stability of Chinese family assessment measures. In Hong Kong, based on focus group data (i.e., indigenous concepts of family functioning) and an integration with the family science literature, we have developed the Chinese Family Assessment Instrument (C-FAI) to assess perceived family functioning according to the perception of adolescents. Results showed that the C-FAI possessed good reliability and validity. Specifically, five dimensions of the measure (mutuality, communication, conflict, parental concern and parental control) were supported via exploratory factor analysis and confirmatory factor analysis. Convergent validity and reliability of the C-FAI were illustrated. To understand the psychometric properties of the C-FAI in mainland China, we collected three waves of data from students in the period of preadolescence and early adolescence in mainland China ( N  = 3,732). Based on the data, we examined the psychometric properties of the measure, particularly factor invariance in different samples and at different times. Confirmatory factor analysis provided support for the five dimensions in C-FAI, including factorial invariance in terms of configuration, factor loading, intercepts, and over time. There was evidence for convergent validity and discriminant validity of the measure. Finally, reliability analyses showed that the total C-FAI scale and its subscales are internally consistent. The present findings suggest that family researchers and practitioners can use the C-FAI to objectively assess perceived family functioning in preadolescence and early adolescence in different Chinese communities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shek, Leung, Li and Dou.)

This study presents novel and compelling evidence of the disparities in factors influencing the beliefs and aspirations for higher education among mainstream and immigrant youth in Hong Kong, particularly those who are underprivileged. We developed and validated a psychometric questionnaire, known as the Post-Secondary Education Pursuit Instrument (PSEPi), which was administered to 4,850 students aged between 15 and 18 years old from 23 secondary schools. The objective of this study was to explore the factors that impact students' choices and plans for higher education. The results of the one-way Multivariate Analysis of Variance (MANOVA) analysis deepen our understanding of the differential effects of success and obstacle factors on students' higher education pursuits across various cultural groups. The underprivileged mainstream, Chinese immigrant, and ethnic minority South Asian youth reported a perceived glass ceiling effect associated with their ethnic backgrounds, as well as financial aid barriers, while pursuing higher education, in contrast to their average Hong Kong mainstream counterparts (mean Cohen's d = 0.40). The direct effects and multiple mediation analyses demonstrated that significant others' influence, particularly the influence of parents, and locus of control are prime determinants of the perceived usefulness of higher education for all student groups. The implications are that educational policies should be implemented to level the playing field in higher education admissions for both privileged and underprivileged youth in Hong Kong and other international countries. Overall, this study provides robust empirical evidence that can be utilized to enhance educational policies and practices to bridge the gap between mainstream and underprivileged immigrant youth in their pursuit of higher education., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yuen, Cheung and Leung.)

Cytokine dynamics in patients with coronavirus disease 2019 (COVID-19) have been studied in blood but seldomly in respiratory specimens. We studied different cell markers and cytokines in fresh nasopharyngeal swab specimens for the diagnosis and for stratifying the severity of COVID-19. This was a retrospective case-control study comparing Myeloperoxidase (MPO), Adenosine deaminase (ADA), C-C motif chemokine ligand 22 (CCL22), Tumour necrosis factor alpha (TNFα) and Interleukin-6 (IL-6) mRNA expression in 490 (327 patients and 163 control) nasopharyngeal specimens from 317 (154 COVID-19 and 163 control) hospitalized patients. Of the 154 COVID-19 cases, 46 died. Both total and normalized MPO, ADA, CCL22, TNFα, and IL-6 mRNA expression levels were significantly higher in the nasopharyngeal specimens of infected patients when compared with controls, with ADA showing better performance (OR 5.703, 95% CI 3.424-9.500, p  < 0.001). Receiver operating characteristics (ROC) curve showed that the cut-off value of normalized ADA mRNA level at 2.37 × 10 -3 had a sensitivity of 81.8% and specificity of 83.4%. While patients with severe COVID-19 had more respiratory symptoms, and elevated lactate dehydrogenase, multivariate analysis showed that severe COVID-19 patients had lower CCL22 mRNA (OR 0.211, 95% CI 0.060-0.746, p  = 0.016) in nasopharyngeal specimens, while lymphocyte count, C-reactive protein, and viral load in nasopharyngeal specimens did not correlate with disease severity. In summary, ADA appears to be a better biomarker to differentiate between infected and uninfected patients, while CCL22 has the potential in stratifying the severity of COVID-19.

Background: Advances in vertical take-off and landing (VTOL) technologies may enable drone-like crewed air ambulances to rapidly respond to out-of-hospital cardiac arrest (OHCA) in urban areas. We estimated the impact of incorporating VTOL air ambulances on OHCA response intervals in two large urban centres in France and Canada., Methods: We included adult OHCAs occurring between Jan. 2017-Dec. 2018 within Greater Paris in France and Metro Vancouver in Canada. Both regions utilize tiered OHCA response with basic (BLS)- and advanced life support (ALS)-capable units. We simulated incorporating 1-2 ALS-capable VTOL air ambulances dedicated to OHCA response in each study region, and computed time intervals from call reception by emergency medical services (EMS) to arrival of the: (1) first ALS unit ("call-to-ALS arrival interval"); and (2) first EMS unit ("call-to-first EMS arrival interval")., Results: There were 6,217 OHCAs included during the study period (3,760 in Greater Paris and 2,457 in Metro Vancouver). Historical median call-to-ALS arrival intervals were 21 min [IQR 16-29] in Greater Paris and 12 min [IQR 9-17] in Metro Vancouver, while median call-to-first EMS arrival intervals were 11 min [IQR 8-14] and 7 min [IQR 5-8] respectively. Incorporating 1-2 VTOL air ambulances improved median call-to-ALS arrival intervals to 7-9 min and call-to-first EMS arrival intervals to 6-8 min in both study regions (all P < 0.001)., Conclusion: VTOL air ambulances dedicated to OHCA response may improve EMS response intervals, with substantial improvements in ALS response metrics., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Prof. Alain Cariou is a member of the Resuscitation’s editorial board. All authors declare no conflict of interest with any of the two VTOL companies cited in this work (Urban Aero or Volocopter).]., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background The lipid hypothesis postulates that lower blood cholesterol is associated with reduced coronary heart disease (CHD) risk, which has been challenged by reports of a U-shaped relation between cholesterol and death in recent studies. We sought to examine whether the U-shaped relationship is true and to assess the impact of age on this association. Method and Results We conducted a prospective cohort study of 4 467 942 veterans aged >18 years, with baseline outpatient visits from 2002 to 2007 and follow-up to December 30, 2018, in the Veterans Health Administration electronic health record system. We observed a J-shaped relation between total cholesterol (TC) and CHD mortality after a comprehensive adjustment of confounding factors: flat for TC <180 mg/dL, and greater risk was present at higher cholesterol levels. Compared with veterans with TC between 180 and 199 mg/dL, the multiadjusted hazard ratios (HRs) for CHD death were 1.03 (95% CI, 1.02-1.04), 1.07 (95% CI, 1.06-1.09), 1.15 (95% CI, 1.13-1.18), 1.25 (95% CI, 1.22-1.28), and 1.45 (95% CI, 1.42-1.49) times greater among veterans with TC (mg/dL) of 200 to 219, 220 to 239, 140 to 259, 260 to 279 and ≥280, respectively. Similar J-shaped TC-CHD mortality patterns were observed among veterans with and without statin use at or before baseline. Conclusions The cholesterol paradox, for example, higher CHD death in patients with a low cholesterol level, was a reflection of reverse causality, especially among older participants. Our results support the lipid hypothesis that lower blood cholesterol is associated with reduced CHD. Furthermore, the hypothesis remained true when TC was low due to use of statins or other lipid-lowering medication.

Introduction: Although no case of COVID-19 transmission through transfusion has been reported, blood transfusion service (BTS) continues to implement pre-donation and post-donation measures to minimise the risk. In year 2022, when local healthcare system was badly impacted by a major outbreak, it opened an opportunity to re-examine the viraemia risk in these asymptomatic donors., Materials and Methods: Records were retrieved from blood donors who reported COVID-19 after donation and follow-up was also made for recipients who received their blood. Blood samples at donation were tested for SARS-CoV-2 viraemia by single-tube nested real-time RT-PCR assay designed to detect most SARS-CoV-2 variants including the prevailing delta and omicron variants., Results: From 1 January to 15 August 2022, the city with 7.4 M inhabitants recorded 1 187 844 COVID-19 positive cases and 125 936 successful blood donations were received. 781 donors reported to the BTS after donation with 701 being COVID-19 related (including close contact and symptoms respiratory tract infection). 525 COVID-19 were positive at the time of call back or follow-up. Of the 701 donations, they were processed into 1480 components with 1073 discarded upon donors' call back. For remaining 407 components, no recipient was found to have adverse event or COVID-19 positive. 510 samples from the above 525 COVID-19 positive donors were available and all tested negative for SARS-CoV-2 RNA., Discussion: With the negative SARS-CoV-2 RNA in blood donation samples and follow up data in transfusion recipients, the risk of transfusion transmitted COVID-19 appears negligible. However, current measures remains important in securing blood safety with ongoing surveillance of their effectiveness., (© 2023 British Blood Transfusion Society.)

The scalable 2D device fabrication and integration demand either the large-area synthesis or the post-synthesis transfer of 2D layers. While the direct synthesis of 2D materials on most targeted surfaces remains challenging, the transfer approach from the growth substrate onto the targeted surfaces offers an alternative pathway for applications and integrations. However, the current transfer techniques for 2D materials predominantly involve polymers and organic solvents, which are liable to contaminate or deform the ultrasensitive atomic layers. Here, novel ice-aided transfer and ice-stamp transfer methods are developed, in which water (ice) is the only medium in the entire process. In practice, the adhesion between various 2D materials and ice can be well controlled by temperature. Through such controlled adhesion of ice, it is shown that the new transfer methods can yield ultrahigh quality and exceptional cleanliness in transferred 2D flakes and continuous 2D films, and are applicable for a wide range of substrates. Furthermore, beyond transfer, ice can also be used for cleaning the surfaces of 2D materials at higher temperatures. These novel techniques can enable unprecedented ultraclean 2D materials surfaces and performances, and will contribute to the upcoming technological revolutions associated with 2D materials., (© 2023 Wiley-VCH GmbH.)

Objective: To determine the prevalence of mitochondrial diseases (MD) in Hong Kong (HK) and to evaluate the clinical characteristics and genetic landscape of MD patients in the region., Methods: This study retrospectively reviewed the phenotypic and molecular characteristics of MD patients from participating public hospitals in HK between January 1985 to October 2020. Molecularly and/or enzymatically confirmed MD cases of any age were recruited via the Clinical Analysis and Reporting System (CDARS) using relevant keywords and/or International Classification of Disease (ICD) codes under the HK Hospital Authority or through the personal recollection of treating clinicians among the investigators., Results: A total of 119 MD patients were recruited and analyzed in the study. The point prevalence of MD in HK was 1.02 in 100,000 people (95% confidence interval 0.81-1.28 in 100,000). 110 patients had molecularly proven MD and the other nine were diagnosed by OXPHOS enzymology analysis or mitochondrial DNA depletion analysis with unknown molecular basis. Pathogenic variants in the mitochondrial genome (72 patients) were more prevalent than those in the nuclear genome (38 patients) in our cohort. The most commonly involved organ system at disease onset was the neurological system, in which developmental delay, seizures or epilepsy, and stroke-like episodes were the most frequently reported presentations. The mortality rate in our cohort was 37%., Conclusion: This study is a territory-wide overview of the clinical and genetic characteristics of MD patients in a Chinese population, providing the first available prevalence rate of MD in Hong Kong. The findings of this study aim to facilitate future in-depth evaluation of MD and lay the foundation to establish a local MD registry., (© 2023. The Author(s).)

Recent philosophy has witnessed a renewed interest in the works and ideas of Henri Bergson (1859-1941). But while contemporary scholarship has sought to rehabilitate Bergson's insights on time, memory, consciousness, and human freedom, comparatively little attention has been paid to Bergson's relationship to pantheism. By revisiting the 'pantheism' controversy surrounding Bergsonian philosophy during Bergson's lifetime, this article argues that the panentheistic notion of 'being-in-God' can serve as an illuminating framework for the interpretation of Bergson's philosophy. By examining the 'pantheist' readings of Bergson and comparing and contrasting Bergson's philosophy of life with Spinoza's panentheistic metaphysics, this paper shows that an account of 'being-in-Life' is key to Bergson's metaphysical outlook as well as his account of philosophy as a practice of 'intuitive' thinking. In so doing, this paper highlights some of the implicit religious motifs not only in Bergson's metaphysical outlook but also in his conception of the task of philosophy., (© The Author(s) 2022.)

Background: Accurate classification of sites of interest on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) images is an important diagnostic requirement for the differentiation of prostate cancer (PCa) from foci of physiologic uptake. We developed a deep learning and radiomics framework to perform lesion-level and patient-level classification on PSMA PET images of patients with PCa., Methods: This was an IRB-approved, HIPAA-compliant, retrospective study. Lesions on [ 18 F]DCFPyL PET/CT scans were assigned to PSMA reporting and data system (PSMA-RADS) categories and randomly partitioned into training, validation, and test sets. The framework extracted image features, radiomic features, and tissue type information from a cropped PET image slice containing a lesion and performed PSMA-RADS and PCa classification. Performance was evaluated by assessing the area under the receiver operating characteristic curve (AUROC). A t-distributed stochastic neighbor embedding (t-SNE) analysis was performed. Confidence and probability scores were measured. Statistical significance was determined using a two-tailed t test., Results: PSMA PET scans from 267 men with PCa had 3794 lesions assigned to PSMA-RADS categories. The framework yielded AUROC values of 0.87 and 0.90 for lesion-level and patient-level PSMA-RADS classification, respectively, on the test set. The framework yielded AUROC values of 0.92 and 0.85 for lesion-level and patient-level PCa classification, respectively, on the test set. A t-SNE analysis revealed learned relationships between the PSMA-RADS categories and disease findings. Mean confidence scores reflected the expected accuracy and were significantly higher for correct predictions than for incorrect predictions (P < 0.05). Measured probability scores reflected the likelihood of PCa consistent with the PSMA-RADS framework., Conclusion: The framework provided lesion-level and patient-level PSMA-RADS and PCa classification on PSMA PET images. The framework was interpretable and provided confidence and probability scores that may assist physicians in making more informed clinical decisions., (© 2022. The Author(s).)

Accurate and simple diagnostic tests for coronavirus disease 2019 (COVID-19) are essential components of the pandemic response. In this study, we evaluated a one-tube reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay coupled with clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein-mediated endpoint detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in clinical samples. RT-LAMP-CRISPR is fast and affordable, does not require bulky thermocyclers, and minimizes carryover contamination risk. Results can be read either visually or with a fluorometer. RT-LAMP-CRISPR assays using primers targeting a highly expressed nsp8 gene and previously described nucleocapsid (N) gene primers were designed. The analytical characteristics and diagnostic performance of RT-LAMP-CRISPR assays were compared to those of a commercial real-time RT-PCR E gene assay. The limits of detection (LODs) of the nsp8 and N RT-LAMP-CRISPR assays were 750 and 2,000 copies/mL, which were higher than that of the commercial real-time RT-PCR assay (31.3 copies/mL). Despite the higher LOD, RT-LAMP-CRISPR assays showed diagnostic sensitivity and specificity of 98.6% and 100%, respectively, equivalent to those of the real-time RT-PCR assay ( P  = 0.5). The median fluorescence reading from the nsp8 assay (378.3 raw fluorescence unit [RFU] [range, 215.6 to 592.6]) was significantly higher than that of the N gene assay (342.0 RFU [range, 143.0 to 576.6]) ( P  < 0.0001). In conclusion, we demonstrate that RT-LAMP-CRISPR assays using primers rationally designed from highly expressed gene targets are highly sensitive, specific, and easy to perform. Such assays are a valuable asset in resource-limited settings. IMPORTANCE Accurate tests for the diagnosis of SARS-CoV-2, the virus causing coronavirus disease 2019 (COVID-19), are important for timely treatment and infection control decisions. Conventional tests such as real-time reverse transcription-PCR (RT-PCR) require specialized equipment and are expensive. On the other hand, rapid antigen tests suffer from a lack of sensitivity. In this study, we describe a novel assay format for the diagnosis of COVID-19 that is based on principles of loop-mediated isothermal amplification (LAMP) and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas chemistry. A major advantage of this assay format is that it does not require expensive equipment to perform, and results can be read visually. This method proved to be fast, easy to perform, and inexpensive. The test compared well against an RT-PCR assay in terms of the ability to detect SARS-CoV-2 RNA in clinical samples. No false-positive test results were observed. The new assay format is ideal for SARS-CoV-2 diagnosis in resource-limited settings.

Osteoporosis is a systemic skeletal disease where there is low bone mass and deterioration of bone microarchitecture, leading to an increased risk of a fragility fracture. The aim of this clinical guideline from Fragility Fracture Network Hong Kong SAR, is to provide evidence-based recommendations on the post-acute treatment of the osteoporotic fracture patient that presents for clinical care at the Fracture Liaison Service (FLS). It is now well established that the incidence of a second fracture is especially high after the first 2 years of the initial osteoporotic fracture. Therefore, the recent osteoporotic fracture should be categorized as "very-high" re-fracture risk. Due to the significant number of silent vertebral fractures in the elderly population, it is also recommended that vertebral fracture assessment (VFA) should be incorporated into FLS. This would have diagnostic and treatment implications for the osteoporotic fracture patient. The use of a potent anti-osteoporotic agent, and preferably an anabolic followed by an anti-resorptive agent should be considered, as larger improvements in BMD is strongly associated with a reduction in fractures. Managing other risk factors including falls and sarcopenia are imperative during rehabilitation and prevention of another fracture. Although of low incidence, one should remain vigilant of the atypical femoral fracture. The aging population is increasing worldwide, and it is expected that the treatment of osteoporotic fractures will be routine. The recommendations are anticipated to aid in the daily clinical practice for clinicians., The Translational Potential of This Article: Fragility fractures have become a common encounter in clinical practise in the hospital setting. This article provides recommendations on the post-acute management of fragility fracture patients at the FLS., Competing Interests: The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. Author names: Ronald Man Yeung Wong, Sheung Wai Law, Simon Kwoon Ho Chow, Wilson Li, Albert Yung Chak Hsu, Raymond Wai Kit Ng, Angela Wing Hang Ho, Shing Hing Choi, Christian Xinshuo Fang, Chun Fung Chan, Ka Hei Leung, Kwok Keung Chu, Timothy Chi Yui Kwok, Minghui Yang, Maoyi Tian, Wing Hoi Cheung., (© 2022 The Authors.)

Although adolescent materialism and egocentrism are growing problems in Chinese societies, there are very few studies investigating their predictors and related mediators. Longitudinal studies in this area are also sparse. Based on a short-term longitudinal study (n = 4981), we assessed the impact of family functioning on materialism and egocentrism of Chinese adolescents, with positive youth development attributes as a hypothesized mediating factor. Results showed that family functioning positively predicted positive youth development attributes but negatively predicted adolescent materialism and egocentrism; positive youth development attributes also negatively predicted adolescent materialism and egocentrism. Mediational analyses showed that positive youth development attributes mediated the impact of family functioning on adolescent materialism and egocentrism. The theoretical and methodological advances of the study are discussed.

Background: Hepatitis E virus (HEV) variants belonging to Orthohepevirus species A (HEV-A) are the primary cause of human hepatitis E. However, we previously reported that Orthohepevirus species C genotype 1 (HEV-C1), a divergent HEV variant commonly found in rats, also causes hepatitis in humans. Here, we present a clinical-epidemiological investigation of human HEV-C1 infections detected in Hong Kong, with an emphasis on outcomes in immunocompromised individuals., Methods: A surveillance system for detecting human HEV-C1 infections was established in Hong Kong. Epidemiological and clinical characteristics of HEV-C1 cases identified via this system between 1 August 2019 and 31 December 2020 were retrieved. Phylogenetic analysis of HEV-C1 strain sequences was performed. Infection outcomes of immunocompromised individuals with HEV-A and HEV-C1 infections were analyzed., Results: HEV-C1 accounted for 8 of 53 (15.1%) reverse-transcription polymerase chain reaction (RT-PCR)-confirmed HEV infections in Hong Kong during the study period, raising the total number of HEV-C1 infections detected in the city to 16. Two distinct HEV-C1 strain groups caused human infections. Patients were elderly and/or immunocompromised; half tested negative for HEV immunoglobulin M. Cumulatively, HEV-C1 accounted for 9 of 21 (42.9%) cases of hepatitis E recorded in immunocompromised patients in Hong Kong. Immunocompromised HEV-C1 patients progressed to persistent hepatitis at similar rates (7/9 [77.8%]) as HEV-A patients (10/12 [75%]). HEV-C1 patients responded to oral ribavirin, although response to first course was sometimes poor or delayed., Conclusions: Dedicated RT-PCR-based surveillance detected human HEV-C1 cases that evade conventional hepatitis E diagnostic testing. Immunosuppressed HEV-C1-infected patients frequently progress to persistent HEV-C1 infection, for which ribavirin is a suitable treatment option., Competing Interests: Potential conflicts of interest. S. S. has received speaker’s honoraria from Abbott Laboratories Ltd. All other authors report no potential conflicts of interest. The authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect human and other mammals, including hamsters. Syrian (Mesocricetus auratus) and dwarf (Phodopus sp.) hamsters are susceptible to SARS-CoV-2 infection in the laboratory setting. However, pet shop-related Coronavirus Disease 2019 (COVID-19) outbreaks have not been reported., Methods: We conducted an investigation of a pet shop-related COVID-19 outbreak due to Delta variant AY.127 involving at least 3 patients in Hong Kong. We tested samples collected from the patients, environment, and hamsters linked to this outbreak and performed whole genome sequencing analysis of the reverse transcription polymerase chain reaction (RT-PCR)-positive samples., Results: The patients included a pet shop keeper (Patient 1), a female customer of the pet shop (Patient 2), and the husband of Patient 2 (Patient 3). Investigation showed that 17.2% (5/29) and 25.5% (13/51) environmental specimens collected from the pet shop and its related warehouse, respectively, tested positive for SARS-CoV-2 RNA by RT-PCR. Among euthanized hamsters randomly collected from the storehouse, 3% (3/100) tested positive for SARS-CoV-2 RNA by RT-PCR and seropositive for anti-SARS-CoV-2 antibody by enzyme immunoassay. Whole genome analysis showed that although all genomes from the outbreak belonged to the Delta variant AY.127, there were at least 3 nucleotide differences among the genomes from different patients and the hamster cages. Genomic analysis suggests that multiple strains have emerged within the hamster population, and these different strains have likely transmitted to human either via direct contact or via the environment., Conclusions: Our study demonstrated probable hamster-to-human transmission of SARS-CoV-2. As pet trading is common around the world, this can represent a route of international spread of this pandemic virus., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

While machine learning (ML) methods may significantly improve image quality for SPECT imaging for the diagnosis and monitoring of Parkinson's disease (PD), they require a large amount of data for training. It is often difficult to collect a large population of patient data to support the ML research, and the ground truth of lesion is also unknown. This paper leverages a generative adversarial network (GAN) to generate digital brain phantoms for training ML-based PD SPECT algorithms. A total of 594 PET 3D brain models from 155 patients (113 male and 42 female) were reviewed and 1597 2D slices containing the full or a portion of the striatum were selected. Corresponding attenuation maps were also generated based on these images. The data were then used to develop a GAN for generating 2D brain phantoms, where each phantom consisted of a radioactivity image and the corresponding attenuation map. Statistical methods including histogram, Fréchet distance, and structural similarity were used to evaluate the generator based on 10,000 generated phantoms. When the generated phantoms and training dataset were both passed to the discriminator, similar normal distributions were obtained, which indicated the discriminator was unable to distinguish the generated phantoms from the training datasets. The generated digital phantoms can be used for 2D SPECT simulation and serve as the ground truth to develop ML-based reconstruction algorithms. The cumulated experience from this work also laid the foundation for building a 3D GAN for the same application.

Project GIFT is a pioneer research-based gifted education program which has been found to be effective in fostering holistic development of students in Hong Kong. Nevertheless, little is known whether the Project is beneficial to teachers. To investigate the changes in teachers after participating in the Project, we adopted a quasi-experimental design with pretest and posttest data collected from experimental and control groups in this study. A total of 2031 primary and secondary school teachers participated in the professional development program of the Project. They completed validated measures on teachers' knowledge of and attitudes toward gifted education, teaching behaviors, characteristics and competencies, in addition to well-being before and after participating in the program. Results of one-way ANCOVA showed that the program could promote teachers' knowledge of gifted education and specific teaching strategies to gifted learners. This study provides preliminary support for the program in promoting holistic professional development of participating teachers in gifted education. The theoretical and practical implications of the findings are discussed.

The thrombopoietin mimetic eltrombopag (EPAG) is efficacious in clinical trials of newly diagnosed moderate (M), severe (S) and very severe (vS) aplastic anaemia (AA). Its use in routine practice and resource-constrained settings is not well described. Twenty-five men and 38 women at a median age of 54 (18-86) years with newly diagnosed AA treated consecutively in a 7-year period with EPAG (N = 6), EPAG/cyclosporine (CsA) (N = 33) and EPAG/CsA/anti-thymocyte globulin (ATG) (N = 24) were analyzed. Because EPAG was not reimbursed, peak doses ranged from 25 to 200 mg/day depending on affordability. EPAG/CsA-treated patients were older (median age: 61 years) with less severe AA (MAA, N = 15; SAA, N = 14; vSAA, N = 4), whereas EPAG/CsA/ATG-treated patients were younger (median age: 44 years) with more severe AA (MAA, N = 2; SAA, N = 12, vSAA, N = 10). The overall/trilineage response rates were 83%/50% for EPAG-treated patients; 79%/42% for EPAG/CsA-treated patients and 75%/63% for EPAG/CsA/ATG-treated patients. Adverse events included grade 1 liver derangement (N = 7) and grade 1 dyspepsia (N = 3). The 5-year overall survivals/failure-free survivals were 62%/80% for the entire cohort; 55%/75% for EPAG/CsA-treated patients and 82%/78% for EPAG/CsA/ATG-treated patients. EPAG showed robust efficacy in AA in routine practice. However, EPAG dosage and combinations remain to be optimized for AA of different severities., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Airborne transmission of SARS-CoV-2 has been increasingly recognized in the outbreak of COVID-19, especially with the Omicron variant. We investigated an outbreak due to Omicron variant in a restaurant. Besides epidemiological and phylogenetic analyses, the secondary attack rates of customers of restaurant-related COVID-19 outbreak before (Outbreak R1) and after enhancement of indoor air dilution (Outbreak R2) were compared. On 27th December 2021, an index case stayed in restaurant R2 for 98 min. Except for 1 sitting in the same table, six other secondary cases sat in 3 corners at 3 different zones, which were served by different staff. The median exposure time was 34 min (range: 19-98 min). All 7 secondary cases were phylogenetically related to the index. Smoke test demonstrated that the airflow direction may explain the distribution of secondary cases. Compared with an earlier COVID-19 outbreak in another restaurant R1 (19th February 2021), which occurred prior to the mandatory enhancement of indoor air dilution, the secondary attack rate among customers in R2 was significantly lower than that in R1 (3.4%, 7/207 vs 28.9%, 22/76, p<0.001). Enhancement of indoor air dilution through ventilation and installation of air purifier could minimize the risk of SARS-CoV-2 transmission in the restaurants., (Copyright © 2022 Elsevier B.V. All rights reserved.)

According to the positive youth development (PYD) approach, PYD attributes such as psychosocial competencies are developmental assets which can promote the holistic development of adolescents, such as increase in thriving and decrease in risk behavior. Although there are research findings supporting this theoretical proposition, there are several weaknesses in this literature. These include a lack of studies examining family antecedents of PYD attributes and the mediating role of PYD attributes in the relationship between family functioning and adolescent delinquency. There are also few longitudinal studies utilizing large samples and validated measures of family functioning and PYD attributes in the scientific literature. In this study, we examined the predictive effect of family functioning on adolescent delinquency and the mediating role of PYD attributes. Using a short-term longitudinal study in Sichuan, China, we collected two waves of data from 4,981 adolescents aged 11 and above, with 6 months between the two waves. Analyses using structural equation modeling showed that family functioning at Wave 1 negatively predicted the level of and change in delinquent behavior at Wave 2, with PYD attributes at Wave 2 as a mediating factor. The present study enriches the conceptual framework on the role of family functioning and PYD attributes in adolescent delinquent behavior. The findings also suggest that strengthening family functioning and PYD attributes would protect adolescents from engaging in delinquent acts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shek, Leung, Dou and Zhu.)

Introduction: Bortezomib has been reported to favourably impact the outcomes of t (4;14) and del(17p) in multiple myeloma (MM), but its impact on gain 1q (+1q) is unknown., Methods: To address this, 250 patients treated with bortezomib-based induction were analysed. All myeloma samples had fluorescence in situ hybridization (FISH) performed on CD138-sorted bone marrow aspirate, and plasma cells were analysed using DNA probes specific for the following chromosomal aberrations: del(13q14), del(17p), t (14;16), t (4;14), and +1q. Presence of +1q was defined as the presence of at least three copies of 1q21 at the cut off level of 20% of bone marrow plasma cells., Results: +1q identified in 167 (66.8%) and associated with t (4;14) and high lactate dehydrogenase (LDH). +1q was not associated with response rate but shorter event-free survival (EFS) (median EFS 35 vs 55 months, p  = 0.05) and overall survival (OS) (median OS 74 vs 168 months, p  = 0.00025). Copy number and clone size did not impact survival. Multivariate analysis showed +1q was an independent adverse factor for OS together with International Staging System (ISS)3, high LDH, del(17p) and t (4;14). When a risk score of 1 was assigned to each independent adverse factor, OS was shortened incrementally by a risk score from 0 to 4. Post-relapse/progression survival was inferior in those with +1q (median 60 vs 118 months, p  = 0.000316). Autologous stem cell transplantation (ASCT) improved OS for those with +1q (median OS 96 vs 49 months, p  = 0.000069)., Conclusion: +1q is an adverse factor for OS in MM uniformly treated with bortezomib-based induction but was partially mitigated by ASCT. A risk scoring system comprising +1q, LDH, high-risk FISH, and ISS is a potential tool for risk stratification in MM., Competing Interests: Conflict of interest statement: The authors declared no potential conflict of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

In this study, we used a quasi-experimental research design with pretest and post-test data collected from an experimental group and a control group to investigate changes in students after participating in a school-based gifted education program (Project GIFT) in Hong Kong. There were 3207 successfully matched students (3rd to 9th graders) joining the Level 1 program (for all students) alone or both the Level 1 program and Level 2 program (for gifted students). Participants of the experimental and control groups completed validated measures on creativity, multiple intelligences, gifted characteristics, self-efficacy, psychological well-being, and satisfaction with life before and after participating in the program(s). One-way ANCOVA results revealed that students in the experimental groups showed positive changes after joining the program(s), with a greater impact for students joining both Level 1 and Level 2 programs. Students participating in both Level 1 and Level 2 programs displayed significant improvement in creativity, academic performance, logical-mathematical intelligence, intrapersonal intelligence, self-efficacy, autonomy, environmental mastery, and personal growth compared to the control counterparts. This study illustrates the benefits of the Level 1 and Level 2 programs in promoting the holistic development of the program participants.

Objectives: Sensitive molecular diagnostic assays are essential for COVID-19 diagnosis. We evaluated the Hecin Scientific SARS-CoV-2 nucleic acid test kit, a dual-target real-time RT-PCR assay targeting the SARS-CoV-2 N and ORF1ab genes., Methods: The Hecin test kit's diagnostic performance in detecting SARS-CoV-2 RNA was compared to the LightMix Modular SARS and Wuhan CoV E-gene kit (TIB Molbiol) and an in-house single-tube nested real-time RT-PCR using 296 clinical specimens, 11 proficiency testing samples, and 30 low-positive deep throat saliva and nasopharyngeal swab (NPS) samples pooled into negative samples in ratios of 1:5, 1:10, and 1:30., Results: The limit-of-detection of the Hecin test kit was around 500 dC/mL for the N and ORF1ab targets. Sensitivity and specificity of the Hecin test kit were 98.1% (95% CI: 93.4-99.8%) and 100% (98.1-100%), respectively, when measured against the reference method. The Hecin test kit showed fair sensitivity (80%) in low-positive NPS samples pooled in ratios of 1:5 and 1:10. Its performance in pooled samples could be dramatically improved by adjusting the assay Ct cutoff., Conclusion: The Hecin test kit enables sensitive and specific detection of SARS-CoV-2 in clinical samples and pooled samples.

Background: Diagnosis of Parkinson's disease (PD) is informed by the presence of progressive motor and non-motor symptoms and by imaging dopamine transporter with [ 123 I]ioflupane (DaTscan). Deep learning and ensemble methods have recently shown promise in medical image analysis. Therefore, this study aimed to develop a three-stage, deep learning, ensemble approach for prognosis in patients with PD., Methods: Retrospective data of 198 patients with PD were retrieved from the Parkinson's Progression Markers Initiative database and randomly partitioned into the training, validation, and test sets with 118, 40, and 40 patients, respectively. The first and second stages of the approach extracted features from DaTscan and clinical measures of motor symptoms, respectively. The third stage trained an ensemble of deep neural networks on different subsets of the extracted features to predict patient outcome 4 years after initial baseline screening. The approach was evaluated by assessing mean absolute percentage error (MAPE), mean absolute error (MAE), Pearson's correlation coefficient, and bias between the predicted and observed motor outcome scores. The approach was compared to individual networks given different data subsets as inputs., Results: The ensemble approach yielded a MAPE of 18.36%, MAE of 4.70, a Pearson's correlation coefficient of 0.84, and had no significant bias indicating accurate outcome prediction. The approach outperformed individual networks not given DaTscan imaging or clinical measures of motor symptoms as inputs, respectively., Conclusion: The approach showed promise for longitudinal prognostication in PD and demonstrated the synergy of imaging and non-imaging information for the prediction task.

During vesicular acidification, chloride (Cl - ), as the counterion, provides the electrical shunt for proton pumping by the vacuolar H + ATPase. Intracellular CLC transporters mediate Cl - influx to the endolysosomes through their 2Cl - /H + exchange activity. However, whole-endolysosomal patch-clamp recording also revealed a mysterious conductance releasing Cl - from the lumen. It remains unknown whether CLCs or other Cl - channels are responsible for this activity. Here, we show that the newly identified proton-activated Cl - (PAC) channel traffics from the plasma membrane to endosomes via the classical YxxL motif. PAC deletion abolishes the endosomal Cl - conductance, raises luminal Cl - level, lowers luminal pH, and increases transferrin receptor-mediated endocytosis. PAC overexpression generates a large endosomal Cl - current with properties similar to those of endogenous conductance, hypo-acidifies endosomal pH, and reduces transferrin uptake. We propose that the endosomal Cl - PAC channel functions as a low pH sensor and prevents hyper-acidification by releasing Cl - from the lumen., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Hepatitis E virus (HEV) variants causing human infection predominantly belong to HEV species A (HEV-A). HEV species C genotype 1 (HEV-C1) circulates in rats and is highly divergent from HEV-A. It was previously considered unable to infect humans, but the first case of human HEV-C1 infection was recently discovered in Hong Kong. The aim of this study is to further describe the features of this zoonosis in Hong Kong., Approach and Results: We conducted a territory-wide prospective screening study for HEV-C1 infection over a 31-month period. Blood samples from 2,860 patients with abnormal liver function (n = 2,201) or immunosuppressive conditions (n = 659) were screened for HEV-C1 RNA. In addition, 186 captured commensal rats were screened for HEV-C1 RNA. Sequences of human-derived and rat-derived HEV-C1 isolates were compared. Epidemiological and clinical features of HEV-C1 infection were analyzed. HEV-C1 RNA was detected in 6/2,201 (0.27%) patients with hepatitis and 1/659 (0.15%) immunocompromised persons. Including the previously reported case, eight HEV-C1 infections were identified, including five in patients who were immunosuppressed. Three patients had acute hepatitis, four had persistent hepatitis, and one had subclinical infection without hepatitis. One patient died of meningoencephalitis, and HEV-C1 was detected in cerebrospinal fluid. HEV-C1 hepatitis was generally milder than HEV-A hepatitis. HEV-C1 RNA was detected in 7/186 (3.76%) rats. One HEV-C1 isolate obtained from a rat captured near the residences of patients was closely related to the major outbreak strain., Conclusions: HEV-C1 is a cause of hepatitis E in humans in Hong Kong. Immunosuppressed individuals are susceptible to persistent HEV-C1 infection and extrahepatic manifestations. Subclinical HEV-C1 infection threatens blood safety. Tests for HEV-C1 are required in clinical laboratories., (© 2020 by the American Association for the Study of Liver Diseases.)

An important need exists for reliable positron emission tomography (PET) tumor-segmentation methods for tasks such as PET-based radiation-therapy planning and reliable quantification of volumetric and radiomic features. To address this need, we propose an automated physics-guided deep-learning-based three-module framework to segment PET images on a per-slice basis. The framework is designed to help address the challenges of limited spatial resolution and lack of clinical training data with known ground-truth tumor boundaries in PET. The first module generates PET images containing highly realistic tumors with known ground-truth using a new stochastic and physics-based approach, addressing lack of training data. The second module trains a modified U-net using these images, helping it learn the tumor-segmentation task. The third module fine-tunes this network using a small-sized clinical dataset with radiologist-defined delineations as surrogate ground-truth, helping the framework learn features potentially missed in simulated tumors. The framework was evaluated in the context of segmenting primary tumors in 18 F-fluorodeoxyglucose (FDG)-PET images of patients with lung cancer. The framework's accuracy, generalizability to different scanners, sensitivity to partial volume effects (PVEs) and efficacy in reducing the number of training images were quantitatively evaluated using Dice similarity coefficient (DSC) and several other metrics. The framework yielded reliable performance in both simulated (DSC: 0.87 (95% confidence interval (CI): 0.86, 0.88)) and patient images (DSC: 0.73 (95% CI: 0.71, 0.76)), outperformed several widely used semi-automated approaches, accurately segmented relatively small tumors (smallest segmented cross-section was 1.83 cm 2 ), generalized across five PET scanners (DSC: 0.74 (95% CI: 0.71, 0.76)), was relatively unaffected by PVEs, and required low training data (training with data from even 30 patients yielded DSC of 0.70 (95% CI: 0.68, 0.71)). In conclusion, the proposed automated physics-guided deep-learning-based PET-segmentation framework yielded reliable performance in delineating tumors in FDG-PET images of patients with lung cancer.

Objectives: Accurate assays for hepatitis C virus (HCV) quantitation and genotyping are important for the management of HCV infection. In this study, we evaluated the performance of cobas HCV and cobas HCV GT assays (Roche) for HCV quantitation and genotyping on the cobas 4800 System., Methods: We compared the performance of the cobas HCV assays with another commercial system (Abbott m 2000) using a panel of well-characterized patient samples and proficiency testing samples., Results: The limit-of-detection of the cobas HCV assay in our center was higher (15 IU/mL) than the manufacturer claim (9.2 IU/mL). The assay showed high analytical specificity, accuracy, precision, and linearity. Performance was congruent with the RealTi m e HCV assay (Abbott). For genotyping, the cobas HCV GT assay only showed moderate agreement with the RealTi m e HCV Genotype II assay (kappa = 0.550). The cobas assay outperformed the RealTi m e assay for typing HCV genotypes 1b and 6 (p = 0.033)., Conclusion: Our results confirm that the cobas 4800 System is a reliable platform for HCV quantitation and genotyping. The cobas HCV GT assay is a good choice for genotype 1b/6 endemic areas in east Asia, clearly outperforming the RealTi m e HCV Genotype II assay.

Optical trapping of molecules with long coherence times is crucial for many protocols in quantum information and metrology. However, the factors that limit the lifetimes of the trapped molecules remain elusive and require improved understanding of the underlying molecular structure. Here we show that measurements of vibronic line strengths in weakly and deeply bound ^{88}Sr&#95;{2} molecules, combined with ab initio calculations, allow for unambiguous identification of vibrational quantum numbers. This, in turn, enables the construction of refined excited potential energy curves, informing the selection of magic wavelengths that facilitate long vibrational coherence. We demonstrate Rabi oscillations between far-separated vibrational states that persist for nearly 100 ms.

Background: A cruise ship is a closed-off environment that simulates the basic functioning of a city in terms of living conditions and interpersonal interactions. Thus, the Diamond Princess cruise ship, which was quarantined because of an onboard outbreak of COVID-19 in February, 2020, provides an opportunity to define the shedding pattern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patient antibody responses before and after the onset of symptoms., Methods: We recruited adult (≥18 years) passengers from Hong Kong who had been on board the Diamond Princess cruise ship docked in Yokohama, Japan in February, 2020. All participants had been found to be negative for SARS-CoV-2 by RT-PCR 4 days before disembarking and were transferred to further quarantine in a public estate in Hong Kong, where they were recruited. Participants were prospectively screened by quantitative RT-PCR (RT-qPCR) of nasopharyngeal and throat swabs, and serum IgG and IgM against internal nucleoprotein and the surface spike receptor-binding protein (RBD) of SARS-CoV-2 at baseline (upon entering quarantine) and on days 4, 8, and 12 of quarantine., Findings: On Feb 22, 2020, 215 adults were recruited, of whom nine (4%; 95% CI 2-8) were positive for SARS-CoV-2 by RT-qPCR or serology and were hospitalised. Of these nine patients, nasopharyngeal swab RT-qPCR was positive in eight patients (89%; 57-99) at baseline. All nine patients were positive for anti-RBD IgG by day 8. Eight (89%; 57-99) were simultaneously positive for nasopharyngeal swab RT-PCR and anti-RBD IgG. One patient who was positive for anti-RBD IgG and had a negative viral load had multifocal peripheral ground-glass changes on high-resolution CT that were typical of COVID-19. Five patients (56%; 27-81) with ground-glass changes on high-resolution CT were found to have higher anti-nucleoprotein-IgG OD values on day 8 and 12 and anti-RBD IgG OD value on day 12 than patients without ground-glass changes. Six (67%; 35-88) patients remained asymptomatic throughout the 14-day quarantine period., Interpretation: Patients with COVID-19 can develop asymptomatic lung infection with viral shedding and those with evidence of pneumonia on imaging tend to have an increased antibody response. Positive IgG or IgM confirmed infection of COVID-19 in both symptomatic and asymptomatic patients. A combination of RT-PCR and serology should be implemented for case finding and contact tracing to facilitate early diagnosis, prompt isolation, and treatment., Funding: Shaw Foundation Hong Kong; Sanming-Project of Medicine (Shenzhen); High Level-Hospital Program (Guangdong Health Commission)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The phenotypic instability of adult tissue-derived Schwann cell-like cells (SCLCs) as revealed upon withdrawal of glia-inducing culture supplements limits their clinical utility for cell therapy and disease modelling. We previously overcame this limitation by co-culturing bone marrow-derived SCLCs with neurons purified from developing rat and subsequently human sensory neurons such that direct contact between cell types accomplished the cell-intrinsic switch to the Schwann cell fate. Here, our search for juxtacrine instructive signals found both Notch ligands and neuregulin-1 type III localized on the surface of DRG neurons via live cell immunocytochemistry. Bypassing ligand-induced release of the Notch intracellular domain (NICD) by transient transfection of SCLCs with the pAdlox/V5-His-NICD construct was shown to upregulate ErbB2/3. Interaction of ErbB2/3 with neuregulin-1 type III (NRG1 type III) as presented on neurons then mediated the switch to the Schwann cell fate as demonstrated by expression of S100β/p75/ Sox10/Krox20. In contrast, treatment of cocultures with γ-secretase inhibitor perturbed Notch signalling in SCLCs and consequently deterred both upregulation of ErbB2/3 and the transition to the Schwann cell fate. Taken together, juxtacrine signalling via Notch is key to the upregulation of ErbB receptors for neuregulin-driven commitment of SCLCs to the Schwann cell fate., (© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Sensitive molecular assays are critical for coronavirus disease 2019 (COVID-19) diagnosis. Here, we designed and evaluated two single-tube nested (STN) real-time RT-PCR assays, targeting SARS-CoV-2 RdRp/Hel and N genes. Both STN assays had a low limit of detection and did not cross react with other human coronaviruses and respiratory viruses. Using 213 initial respiratory specimens from suspected COVID-19 patients, the sensitivity of both the STN COVID-19-RdRp/Hel and the STN COVID-19-N assays was 100% (99/99), while that of the comparator non-nested N assay was 95% (94/99). Among 108 follow-up specimens from confirmed COVID-19 patients who tested negative by the non-nested COVID-19-RdRp/Hel assay, 28 (25.9%) were positive for SARS-CoV-2 by the STN COVID-19-RdRp/Hel or the STN COVID-19-N assay. To evaluate the performance of our novel STN assays in pooled specimens, we created four sample pools, with each pool consisting of one low positive specimen and 49 negative specimens. While the non-nested COVID-19-RdRp/Hel assay was positive in only one of four sample pools (25%), both of the STN assays were positive in two of four samples pools (50%). In conclusion, the STN assays are highly sensitive and specific for SARS-CoV-2 detection. Their boosted sensitivity offers advantages in non-traditional COVID-19 testing algorithms such as saliva screening and pooled sample screening during massive screening.

Background: Rapid and sensitive diagnostic assays for SARS-CoV-2 detection are required for prompt patient management and infection control. The analytical and clinical performances of LightMix® Modular SARS and Wuhan CoV E-gene kit, a widely used commercial assay for SARS-CoV-2 detection, have not been well studied., Objective: To evaluate the performance characteristics of the LightMix® E-gene kit in comparison with well-validated in-house developed COVID-19 RT-PCR assays., Study Design: Serial dilutions of SARS-CoV-2 culture isolate extracts were used for analytical sensitivity evaluation. A total of 289 clinical specimens from 186 patients with suspected COVID-19 and 8 proficiency testing (PT) samples were used to evaluate the diagnostic performance of the LightMix® E-gene kit against in-house developed COVID-19-RdRp/Hel and COVID-19-N RT-PCR assays., Results: The LightMix® E-gene kit had a limit of detection of 1.8 × 10 -1 TCID 50 /mL, which was one log 10 lower than those of the two in-house RT-PCR assays. The LightMix® E-gene kit (149/289 [51.6%]) had similar sensitivity as the in-house assays (144/289 [49.8%] for RdRp/Hel and 146/289 [50.5%] for N). All three assays gave correct results for all the PT samples. Cycle threshold (Cp) values of the LightMix® E-gene kit and in-house assays showed excellent correlation. Reproducibility of the Cp values was satisfactory with intra- and inter-assay coefficient of variation values <5%. Importantly, the LightMix® E-gene kit, when used as a stand-alone assay, was equally sensitive as testing algorithms using multiple COVID-19 RT-PCR assays., Conclusions: The LightMix® E-gene kit is a rapid and sensitive assay for SARS-CoV-2 detection. It has fewer verification requirements compared to laboratory-developed tests., Competing Interests: Declaration of Competing Interest J.F.-W.C. has received travel grants from Pfizer Corporation Hong Kong and Astellas Pharma Hong Kong Corporation Limited, and was an invited speaker for Gilead Sciences Hong Kong Limited and Luminex Corporation. S.S. has received speaker’s honoraria from Abbott Laboratories Limited. The other authors declared no conflict of interests. The funding sources had no role in study design, data collection, analysis or interpretation or writing of the report., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background & Aims: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which has been characterized by fever, respiratory, and gastrointestinal symptoms as well as shedding of virus RNA into feces. We performed a systematic review and meta-analysis of published gastrointestinal symptoms and detection of virus in stool and also summarized data from a cohort of patients with COVID-19 in Hong Kong., Methods: We collected data from the cohort of patients with COVID-19 in Hong Kong (N = 59; diagnosis from February 2 through February 29, 2020),and searched PubMed, Embase, Cochrane, and 3 Chinese databases through March 11, 2020, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We analyzed pooled data on the prevalence of overall and individual gastrointestinal symptoms (loss of appetite, nausea, vomiting, diarrhea, and abdominal pain or discomfort) using a random effects model., Results: Among the 59 patients with COVID-19 in Hong Kong, 15 patients (25.4%) had gastrointestinal symptoms, and 9 patients (15.3%) had stool that tested positive for virus RNA. Stool viral RNA was detected in 38.5% and 8.7% among those with and without diarrhea, respectively (P = .02). The median fecal viral load was 5.1 log 10 copies per milliliter in patients with diarrhea vs 3.9 log 10 copies per milliliter in patients without diarrhea (P = .06). In a meta-analysis of 60 studies comprising 4243 patients, the pooled prevalence of all gastrointestinal symptoms was 17.6% (95% confidence interval [CI], 12.3-24.5); 11.8% of patients with nonsevere COVID-19 had gastrointestinal symptoms (95% CI, 4.1-29.1), and 17.1% of patients with severe COVID-19 had gastrointestinal symptoms (95% CI, 6.9-36.7). In the meta-analysis, the pooled prevalence of stool samples that were positive for virus RNA was 48.1% (95% CI, 38.3-57.9); of these samples, 70.3% of those collected after loss of virus from respiratory specimens tested positive for the virus (95% CI, 49.6-85.1)., Conclusions: In an analysis of data from the Hong Kong cohort of patients with COVID-19 and a meta-analysis of findings from publications, we found that 17.6% of patients with COVID-19 had gastrointestinal symptoms. Virus RNA was detected in stool samples from 48.1% patients, even in stool collected after respiratory samples had negative test results. Health care workers should therefore exercise caution in collecting fecal samples or performing endoscopic procedures in patients with COVID-19, even during patient recovery., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)