Search

The public health and social measures (PHSMs) for mitigation/control of COVID-19 pandemic influenced the transmission dynamics of many other infectious diseases, including respiratory syncytial virus (RSV) infection, and hand, foot and mouth disease (HFMD) and their disease-burden. This study aimed to infer the transmission dynamics of these respiratory viruses and assess the impact of COVID-19 PHSMs on their community activity. We developed a compartmental framework to infer the transmission dynamics of RSV and HFMD in Hong Kong and South Korea from January 2014 to May 2024. We assessed the impact of PHSMs by comparing the change in virus transmissibility, reproduction number and population susceptibility before, during, and after the COVID-19 pandemic period. A significant reduction in RSV and HFMD activity was observed starting in January 2020, with a resurgence since late 2021. Transmissibility of both diseases decreased by 46 % - 95 % during the lull, while population susceptibility was estimated to increase by maximum of 19 %. On relaxation of the PHSMs, the transmissibility were recovered up to 70 % in Hong Kong and nearly 100 % in South Korea in 2023 with significant epidemics for these viruses. Strict implementation of COVID-19 PHSMs led to low RSV and HFMD activity, but the absence of community infection resulted in reductions in population immunity, and slightly larger epidemics when these diseases re-emerged following the COVID-19 pandemic., Competing Interests: Declaration of Competing Interest BJC received honoraria from AstraZeneca, Fosun Pharma, GSK, Haleon, Moderna, Novavax, Pfizer, Roche, and Sanofi. The authors report no other potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The anomalous Hall effect (AHE), significantly enhanced by the extrinsic mechanism, has attracted attention for its almost unlimited Hall response, which exceeds the upper limit of the Berry curvature mechanism. However, due to the high conductivity in the clean regime and weak skew scattering, it is a great challenge to obtain large anomalous Hall conductivities and large anomalous Hall angles at the same time. Here, we unveil a new magnetic metal system, EuAl 2 Si 2 , which hosts both colossal anomalous Hall conductivity ( σ Axy ≥ 10 4 Ω -1 cm -1 ) and large anomalous Hall angle (AHA >10%). The scaling relation suggests that the skew scattering mechanism is dominant in the colossal anomalous Hall response and gives rise to a large skew scattering constant. The large effective SOC and large magnetic moment may account for this anomaly. Our results indicate that EuAl 2 Si 2 is a good platform to study the extrinsic AHE mechanism.

Cavity optomechanical systems have enabled precision sensing of magnetic fields, by leveraging the optical resonance-enhanced readout and mechanical resonance-enhanced response. Previous studies have successfully achieved mass-produced and reproducible microcavity optomechanical magnetometry (MCOM) by incorporating Terfenol-D thin films into high-quality (Q) factor whispering gallery mode (WGM) microcavities. However, the sensitivity was limited to 585 pT Hz -1/2 , over 20 times inferior to those using Terfenol-D particles. In this work, we propose and demonstrate a high-sensitivity and mass-produced MCOM approach by sputtering a FeGaB thin film onto a high-Q SiO 2 WGM microdisk. Theoretical studies are conducted to explore the magnetic actuation constant and noise-limited sensitivity by varying the parameters of the FeGaB film and SiO 2 microdisk. Multiple magnetometers with different radii are fabricated and characterized. By utilizing a microdisk with a radius of 355 μm and a thickness of 1 μm, along with a FeGaB film with a radius of 330 μm and a thickness of 1.3 μm, we have achieved a remarkable peak sensitivity of 1.68 pT Hz -1/2 at 9.52 MHz. This represents a significant improvement of over two orders of magnitude compared with previous studies employing sputtered Terfenol-D film. Notably, the magnetometer operates without a bias magnetic field, thanks to the remarkable soft magnetic properties of the FeGaB film. Furthermore, as a proof of concept, we have demonstrated the real-time measurement of a pulsed magnetic field simulating the corona current in a high-voltage transmission line using our developed magnetometer. These high-sensitivity magnetometers hold great potential for various applications, such as magnetic induction tomography and corona current monitoring., (© 2024. The Author(s).)

The hepatitis delta virus (HDV) is a unique pathogen with significant global health implications, affecting individuals who are coinfected with the hepatitis B virus (HBV). HDV infection has profound clinical consequences, manifesting either as coinfection with HBV, resulting in acute hepatitis and potential liver failure, or as superinfection in chronic HBV cases, substantially increasing the risk of cirrhosis and hepatocellular carcinoma. Given the complex dynamics of HDV infection and the urgent need for advanced research tools, this article introduces vHDvDB 2.0, a comprehensive HDV full-length sequence database. This innovative platform integrates data preprocessing, secondary structure prediction, and epidemiological research tools. The primary goal of vHDvDB 2.0 is to consolidate HDV sequence data into a user-friendly repository, thereby facilitating access for researchers and enhancing the broader scientific understanding of HDV. The significance of this database lies in its potential to streamline HDV research by providing a centralized resource for analyzing viral sequences and exploring genotype-specific characteristics. It will also enable more in-depth research within the HDV sequence domains.

Like other tropical and subtropical regions, influenza viruses can circulate year-round in Hong Kong. However, during the COVID-19 pandemic, there was a significant decrease in influenza activity. The objective of this study was to retrospectively forecast influenza activity during the year 2020 and assess the impact of COVID-19 public health social measures (PHSMs) on influenza activity and hospital admissions in Hong Kong. Using weekly surveillance data on influenza virus activity in Hong Kong from 2010 to 2019, we developed a statistical modeling framework to forecast influenza virus activity and associated hospital admissions. We conducted short-term forecasts (1-4 weeks ahead) and medium-term forecasts (1-13 weeks ahead) for the year 2020, assuming no PHSMs were implemented against COVID-19. We estimated the reduction in transmissibility, peak magnitude, attack rates, and influenza-associated hospitalization rate resulting from these PHSMs. For short-term forecasts, mean ambient ozone concentration and school holidays were found to contribute to better prediction performance, while absolute humidity and ozone concentration improved the accuracy of medium-term forecasts. We observed a maximum reduction of 44.6% (95% CI: 38.6% - 51.9%) in transmissibility, 75.5% (95% CI: 73.0% - 77.6%) in attack rate, 41.5% (95% CI: 13.9% - 55.7%) in peak magnitude, and 63.1% (95% CI: 59.3% - 66.3%) in cumulative influenza-associated hospitalizations during the winter-spring period of the 2019/2020 season in Hong Kong. The implementation of PHSMs to control COVID-19 had a substantial impact on influenza transmission and associated burden in Hong Kong. Incorporating information on factors influencing influenza transmission improved the accuracy of our predictions., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: BJC received honoraria from AstraZeneca, Fosun Pharma, GSK, Haleon, Moderna, Novavax, Pfizer, Roche, and Sanofi. The authors report no other potential conflicts of interest., (Copyright: © 2024 Lau et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The serial interval distribution is used to approximate the generation time distribution, an essential parameter to infer the transmissibility (${R}_t$) of an epidemic. However, serial interval distributions may change as an epidemic progresses. We examined detailed contact tracing data on laboratory-confirmed cases of COVID-19 in Hong Kong during the five waves from January 2020 to July 2022. We reconstructed the transmission pairs and estimated time-varying effective serial interval distributions and factors associated with longer or shorter intervals. Finally, we assessed the biases in estimating transmissibility using constant serial interval distributions. We found clear temporal changes in mean serial interval estimates within each epidemic wave studied and across waves, with mean serial intervals ranged from 5.5 days (95% CrI: 4.4, 6.6) to 2.7 (95% CrI: 2.2, 3.2) days. The mean serial intervals shortened or lengthened over time, which were found to be closely associated with the temporal variation in COVID-19 case profiles and public health and social measures and could lead to the biases in predicting ${R}_t$. Accounting for the impact of these factors, the time-varying quantification of serial interval distributions could lead to improved estimation of ${R}_t$, and provide additional insights into the impact of public health measures on transmission., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Varied seasonal patterns of respiratory syncytial virus (RSV) have been reported worldwide. We conducted a systematic review on articles identified in PubMed reporting RSV seasonality based on data collected before 1 January 2020. RSV seasonal patterns were examined by geographic location, calendar month, analytic method, and meteorological factors including temperature and absolute humidity. Correlation and regression analyses were conducted to explore the relationship between RSV seasonality and study methods and characteristics of study locations. RSV seasons were reported in 209 articles published in 1973-2023 for 317 locations in 77 countries. Regular RSV seasons were similarly reported in countries in temperate regions, with highly variable seasons identified in subtropical and tropical countries. Longer durations of RSV seasons were associated with a higher daily average mean temperature and daily average mean absolute humidity. The global seasonal patterns of RSV provided important information for optimizing interventions against RSV infection., Competing Interests: Potential conflicts of interest. J. N. was previously employed by and owns shares in Sanofi. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Screen printing is one of the most used techniques for developing printed electronics. It stands out for its simplicity, scalability, and effectivity. Specifically, the manufacturing of hybrid integrated circuits has promoted the development of the technique, and the photovoltaic industry has enhanced the printing process by developing high-performance metallization pastes and high-end screens. In recent years, fine lines of 50 μm or smaller are about to be adopted in mass production, and screen printing has to compete with digital printing techniques such as inkjet printing, which can reach narrower lines. In this sense, this work is focused on testing the printing resolution of a high-performance stainless-steel screen with commercial conductive inks and functional lab-made inks based on reduced graphene oxide using an interdigitated structure. We achieved electrically conductive functional patterns with a minimum printing resolution of 40 μm for all inks., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Aims: The high negative predictive value of post-chemoradiation (CRT) positron emission tomography-computed tomography (PET-CT) is well established in head and neck squamous cell cancers (HNSCC). The positive predictive value (PPV) remains under scrutiny, with increasing evidence that it is affected by several factors. The aim of this study was to assess the PPV of post-treatment PET-CT for residual nodal disease when stratified by treatment modality and tumour human papillomavirus (HPV) status., Materials and Methods: This was a retrospective cohort study in a tertiary oncology centre carried out between January 2013 and December 2019. Patients were radically treated with radiotherapy only/CRT for node-positive HNSCC. PET-CT nodal responses were categorised as complete, equivocal (EQR) or incomplete (ICR), and outcomes extracted from electronic records., Results: In total, 480 patients were evaluated, all had a minimum potential follow-up of 2 years, with a median of 39.2 months. The PPV of 12-week PET-CT was significantly different between HPV-positive (22.5%) and HPV-unrelated (52.7%) disease, P < 0.001. It was also significantly different between the CRT (24.8%) and radiotherapy-only (51.1%) groups, P = 0.001. The PPV of an EQR was significantly less than an ICR, irrespective of HPV status and primary treatment modality. In HPV-positive disease, the PPV of an EQR was 9.0% for the CRT group compared with 21.4% for radiotherapy only, P = 0.278. The PPV in those who achieved an ICR was 34.2% in the CRT group, significantly lower than 70.0% in the radiotherapy-only group, P = 0.03., Conclusion: The PPV of 12-week PET-CT is significantly lower for HPV-positive compared with HPV-unrelated HNSCC. It is poorer in patients with HPV-positive disease treated with CRT compared with radiotherapy alone., (Copyright © 2023. Published by Elsevier Ltd.)

In this letter, by measuring resistivity and magnetization with magnetic field H rotated in ab plane and current I along c axis, we studied the magnetic and electronic structure symmetry of frustrated topological bilayer Kagome ferromagnet Fe 3 Sn 2 . We observed that the curves of the resistivity and magnetization both showed broken two-fold symmetry from 5 K to 380 K. The further analysis indicates that there is a close causality between the spin arrangement and the electronic states in Fe 3 Sn 2 even above room temperature. These phenomena are closely related to the change in spin-orbit coupling (SOC) under the magnetic field. Our experimental results suggest that Fe 3 Sn 2 is an ideal platform to study the influence of spin arrangement on electronic state in topological materials and can also be used to design next generation magnetic devices by modulating SOC at external magnetic field., (© 2023 IOP Publishing Ltd.)

Copper potentially provides a cost-effective replacement for silver in printed electronic circuitry with diverse applications in healthcare, solar energy, IOT devices and automotive applications. The primary challenge facing copper is that it readily oxidizes to its non-conductive state during the sintering process. Photonic sintering offers a means of overcoming the oxidation by which rapid conversion from discrete nano-micro particles to fully or partially sintered products occurs. An experimental study of flash lamp sintering of mixed nano copper and mixed nano/ micro copper thick film screen printed structures on FTO coated glass was carried out. It shows that there may be multiple energy windows which can successfully sinter the thick film copper print preventing detrimental copper oxidation. Under optimum conditions, the conductivities achieved in under 1 s was (3.11-4.3 × 10 -7 Ω m) matched those achieved in 90 min at 250 °C under reducing gas conditions, offering a significant improvement in productivity and reduced energy demand. Also present a good film stability of a 14% increase in line resistance of 100 N material, around 10% for the 50N50M ink and only around 2% for the 20N80M., (© 2023. The Author(s).)

Androgen receptor variant 7 (AR-V7), an AR isoform with a truncated ligand-binding domain, functions as a transcription factor in an androgen-independent manner. AR-V7 is expressed in a subpopulation of hepatocellular carcinoma (HCC), however, its role(s) in this cancer is undefined. In this study, we investigated the potential roles of AR-V7 in hepatocarcinogenesis in vivo in a c-MYC-driven mouse HCC model generated by the hydrodynamic tail-vein injection system. The impacts of AR-V7 on gene expression in mouse HCC were elucidated by RNA-seq transcriptome and ontology analyses. The results showed that AR-V7 significantly exacerbated the c-MYC-mediated oncogenesis in the livers of both sexes. The transcriptome and bioinformatics analyses revealed that AR-V7 and c-MYC synergistically altered the gene sets involved in various cancer-related biological processes, particularly in lipid and steroid/sterol metabolisms. Importantly, AR-V7 suppressed a tumor suppressor Claudin 7 expression, upregulated by c-MYC overexpression via the p53 signaling pathway. Claudin 7 overexpression significantly suppressed the c-MYC-driven HCC development under p53-deficient conditions. Our results suggest that the AR-V7 exacerbates the c-MYC-driven hepatocarcinogenesis by potentiating the oncogenic roles and minimizing the anti-oncogenic functions of c-MYC. Since AR-V7 is expressed in a subpopulation of HCC cases, it could contribute to the inter- and intra-heterogeneity of HCC., (© 2023. The Author(s).)

The generation time distribution, reflecting the time between successive infections in transmission chains, is a key epidemiological parameter for describing COVID-19 transmission dynamics. However, because exact infection times are rarely known, it is often approximated by the serial interval distribution. This approximation holds under the assumption that infectors and infectees share the same incubation period distribution, which may not always be true. We estimated incubation period and serial interval distributions using 629 transmission pairs reconstructed by investigating 2989 confirmed cases in China in January-February 2020, and developed an inferential framework to estimate the generation time distribution that accounts for variation over time due to changes in epidemiology, sampling biases and public health and social measures. We identified substantial reductions over time in the serial interval and generation time distributions. Our proposed method provides more reliable estimation of the temporal variation in the generation time distribution, improving assessment of transmission dynamics., (© 2022. The Author(s).)

The transport behavior of Mn 3 SnC and Mn 3 SnC 0.8 compounds was investigated. Positive magnetoresistance (MR) and an anomalous Hall effect (AHE) are observed for each compound near respective Curie temperature, T C . The positive MR is reversed during cooling from T C but is reentrant at low temperature. A 20% carbon deficiency of Mn 3 SnC 0.8 enlarges the positive MR at T C and shifts the temperatures for MR reversals. Ferromagnetic (FM) resonance measurements reveal that the MR reversals are related to the competition between FM and antiferromagnetic components of Mn atoms in each compound. A sign change of the Hall resistivity is observed during cooling of Mn 3 SnC but not for Mn 3 SnC 0.8 . A scaling analysis suggests that the AHE in each compound is mostly due to an intrinsic contribution and that the intrinsic contribution is decreased by the carbon deficiency in Mn 3 SnC 0.8 ., (© 2022 IOP Publishing Ltd.)

Background: The transmission dynamics of influenza were affected by public health and social measures (PHSMs) implemented globally since early 2020 to mitigate the COVID-19 pandemic. We aimed to assess the effect of COVID-19 PHSMs on the transmissibility of influenza viruses and to predict upcoming influenza epidemics., Methods: For this modelling study, we used surveillance data on influenza virus activity for 11 different locations and countries in 2017-22. We implemented a data-driven mechanistic predictive modelling framework to predict future influenza seasons on the basis of pre-COVID-19 dynamics and the effect of PHSMs during the COVID-19 pandemic. We simulated the potential excess burden of upcoming influenza epidemics in terms of fold rise in peak magnitude and epidemic size compared with pre-COVID-19 levels. We also examined how a proactive influenza vaccination programme could mitigate this effect., Findings: We estimated that COVID-19 PHSMs reduced influenza transmissibility by a maximum of 17·3% (95% CI 13·3-21·4) to 40·6% (35·2-45·9) and attack rate by 5·1% (1·5-7·2) to 24·8% (20·8-27·5) in the 2019-20 influenza season. We estimated a 10-60% increase in the population susceptibility for influenza, which might lead to a maximum of 1-5-fold rise in peak magnitude and 1-4-fold rise in epidemic size for the upcoming 2022-23 influenza season across locations, with a significantly higher fold rise in Singapore and Taiwan. The infection burden could be mitigated by additional proactive one-off influenza vaccination programmes., Interpretation: Our results suggest the potential for substantial increases in infection burden in upcoming influenza seasons across the globe. Strengthening influenza vaccination programmes is the best preventive measure to reduce the effect of influenza virus infections in the community., Funding: Health and Medical Research Fund, Hong Kong., Competing Interests: Declaration of interests BJC reports honoraria from AstraZeneca, Fosun Pharma, GSK, Moderna, Pfizer, Roche, and Sanofi. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To determine an optimal setting for functional contouring and quantification of prostate cancer lesions with minimal variation by evaluating metabolic parameters on 18F-PSMA-1007 PET/CT measured by threshold-based and gradient-based methods under the influence of varying uptake time., Methods and Materials: Dual time point PET/CT was chosen to mimic varying uptake time in clinical setting. Positive lesions of patients who presented with newly diagnosed disease or biochemical recurrence after total prostatectomy were reviewed retrospectively. Gradient-based and threshold-based tools at 40%, 50% and 60% of lesion SUVmax (MIM 6.9) were used to create contours on PET. Contouring was considered completed if the target lesion, with its hottest voxel, was delineated from background tissues and nearby lesions under criteria specific to their operations. The changes in functional tumour volume (FTV) and metabolic tumour burden (MTB, defined as the product of SUVmean and FTV) were analysed. Lesion uptake patterns (increase/decrease/stable) were determined by the percentage change in tumour SUVmax at ±10% limit., Results: A total of 275 lesions (135 intra-prostatic lesions, 65 lymph nodes, 45 bone lesions and 30 soft tissue lesions in pelvic region) in 68 patients were included. Mean uptake time of early and delayed imaging were 94 and 144 minutes respectively. Threshold-based method using 40% to 60% delineated only 85 (31%), 110 (40%) and 137 (50%) of lesions which all were contoured by gradient-based method. Although the overall percentage change using threshold at 50% was the smallest among other threshold levels in FTV measurement, it was still larger than gradient-based method (median: 50%=-7.6% vs gradient=0%). The overall percentage increase in MTB of gradient-based method (median: 6.3%) was compatible with the increase in tumour SUVmax. Only a small proportion of intra-prostatic lesions (<2%), LN (<4%), bone lesions (0%) and soft tissue lesions (<4%) demonstrated decrease uptake patterns., Conclusions: With a high completion rate, gradient-based method is reliable for prostate cancer lesion contouring on 18F-PSMA-1007 PET/CT. Under the influence of varying uptake time, it has smaller variation than threshold-based method for measuring volumetric parameters. Therefore, gradient-based method is recommended for tumour delineation and quantification on 18F-PSMA-1007 PET/CT., 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 Lau, Chen, Ho and Cai.)

" Differences of Sexual Development (DSD )," individuals with rearranged Y chromosome breaks in their 46,XY cells are reported with male and female gender phenotypes and differences in germ cell tumour (GCT) risk. This raised the question of whether male or female gender and GCT risk depends on the site of the break and/or rearrangement of the individual´s Y chromosome. In this paper, we report molecular mapping of the breakpoint on the aberrant Y chromosome of 22 DSD individuals with a 45,X/46,XY karyotype reared with a different gender. Their Y chromosome breaks are found at different sites on the long and short Y arms. Our data indicate that gender rearing is, neither dependent on the site of Y breakage, nor on the amount of 45,X0 cells in the individuals' leukocytes. Most prominent are secondary rearrangements of the Y chromosome breaks forming di-centric Y-structures ("dic-Y"). Duplications of the short Y arm and the proximal part of the long Y arm are the results. A putative GCT risk has been analysed with immunohistochemical experiments on some dysgenetic gonadal tissue sections. With specific antibodies for OCT3/4 expression, we marked the pluripotent germ cell fraction being potential tumour precursor cells. With specific antibodies for DDX3Y, TSPY, and UTY we analyzed their putative Gonadoblastoma Y (GBY) tumour susceptibility function in the same specimen. We conclude GBY expression is only diagnostic for GCT development in the aberrant germ cells of these DSD individuals when strong OCT3/4 expression has marked their pluripotency.

Objectives: A nurse duty roster is usually prepared monthly in a hospital ward. It is common for nurses to make duty shift requests prior to scheduling. A ward manager normally spends more than a working day to manually prepare and subsequently to optimally adjust the schedule upon staff requests and hospital policies. This study aimed to develop an automatic nurse roster scheduling system with the use of open-source operational research tools by taking into account the hospital standards and the constraints from nurses., Methods: Artificial intelligence and end user tools operational research tools were used to develop the code for the nurse duty roster scheduling system. To compare with previous research on various heuristics in employee scheduling, the current system was developed on open architecture and adopted with real shift duty requirements in a hospital ward., Results: The schedule can be generated within 1 min under both hard and soft constraint optimization. All hard constraints are fulfilled and most nurse soft constraints could be met. Compared with those schedules prepared manually, the computer-generated schedules were more optimally adjusted as real time interaction among nurses and management personnel. The generated schedules were flexible to cope with daily and hourly duty changes by redeploying ward staff in order to maintain safe staffing levels., Conclusions: An economical but yet highly efficient and user friendly solution to nurse roster scheduling system has been developed and adopted using open-source operational research methodology. The open-source platform is found to perform satisfactorily in scheduling application. The system can be implemented to different wards in hospitals and be regularly updated with new hospital polices and nurse manpower by hospital information personnel with training in artificial intelligence., (© 2022 The Authors.)

In the early stages of the coronavirus disease 2019 (COVID-19) pandemic, national lockdowns and stay-at-home orders were implemented by many countries to curb the rate of infection. An extended stay-at-home period can frustrate people's need for relatedness, with many turning to social media to interact with others in the outside world. However, social media use may be maladaptive due to its associations with social media addiction and psychosocial problems. Our study was set at this special context to examine the associations among social media addiction, two aspects of relatedness needs (i.e., satisfaction and frustration), and two prominent psychosocial problems (i.e., depressive symptoms and loneliness). The participants were 1048 residents of the U.K. or U.S. (46% men, mean age = 44.10 years, SD = 12.59, age range: 18-65). The results indicated significant positive associations between relatedness need frustration and social media addiction as well as significant positive associations between social media addiction and the two types of psychosocial problems. More importantly, both of these significant associations were strong enough to partially explain the significant positive associations between relatedness need frustration and the two types of psychosocial problems. These findings provided some support for relatedness need frustration as a motivation of social media addiction.

Hemophilic arthropathy causes the damage of synovium, cartilage, and subchondral bone. The present study evaluated the safety and the effect of extracorporeal shockwave therapy (ESWT), a safe treatment widely used in musculoskeletal conditions in patients with hemophilic arthropathy. Between 1 August 2019 and 31 July 2020, seven hemophilia A patients were enrolled and treated with medium-energy ESWT on the knee joint in the first two months after prophylactic coagulation factor administration. At the beginning of the study and at 1-, 2-, 3-, and 6-month follow-ups, the Hemophilia Joint Health Score (HJHS), visual analog scale score (VAS), and Hemophilia Early Arthropathy Detection with Ultrasound score (HEAD-US) were evaluated for therapeutic effectiveness and safety, while serum bone morphogenetic protein 2 (BMP-2) and von Willebrand factor (vWF) levels were analyzed for assessing chondroprotection and bone healing. Magnetic resonance imaging (MRI) of the knee was performed at the beginning of the study and the 6-month follow-ups. As a result, a non-significant decrease in VAS scores ( p = 0.151) but not HJHS after treatment was noticed. At the 3-month follow-up, there was a non-significant increase in BMP2 levels ( p = 0.171) but not vWF. Ultrasonography showed no disease activity score elevation in five patients and no further disease damage in all patients. Repeated MRI examinations in three patients showed no structural progression during the 6-month follow-up. As to adverse events, redness, local heat, and mild swelling were noted in five patients without breakthrough bleeding. We concluded that medium-energy ESWT might be safe for hemophilic arthropathy once prophylactic coagulation factors are administered.

Background: Coronavirus disease 2019 (COVID-19) has caused a heavy disease burden globally. The impact of process and timing of data collection on the accuracy of estimation of key epidemiological distributions are unclear. Because infection times are typically unobserved, there are relatively few estimates of generation time distribution., Methods: We developed a statistical framework to jointly estimate generation time and incubation period from human-to-human transmission pairs, accounting for sampling biases. We applied the framework on 80 laboratory-confirmed human-to-human transmission pairs in China. We further inferred the infectiousness profile, serial interval distribution, proportions of presymptomatic transmission, and basic reproduction number (R0) for COVID-19., Results: The estimated mean incubation period was 4.8 days (95% confidence interval [CI], 4.1-5.6), and mean generation time was 5.7 days (95% CI, 4.8-6.5). The estimated R0 based on the estimated generation time was 2.2 (95% CI, 1.9-2.4). A simulation study suggested that our approach could provide unbiased estimates, insensitive to the width of exposure windows., Conclusions: Properly accounting for the timing and process of data collection is critical to have correct estimates of generation time and incubation period. R0 can be biased when it is derived based on serial interval as the proxy of generation time., (© 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.)

COVID-19 is caused by a novel virus with an unknown aetiology. People across the globe are dealing with not only a health crisis but also an 'infodemic', a term coined by the World Health Organization to refer to the avalanche of contradictory information that is arousing widespread confusion and anxiety. This study aimed to examine the prevalence of anxiety and sleep disturbance at the early stage of the pandemic, and unveil the information coping process underlying differential susceptibility to COVID-19 infection anxiety and sleep disturbance. The participants were 1,270 adults (47% men, M age  = 42.82) from the UK and US who completed initial (Time 1) and follow-up (Time 2) surveys from 16 to 22 March and 18 to 24 May 2020, respectively. The prevalence of probable clinically relevant anxiety was 61% and 45% at the first and second time points, and more than half of the participants in this anxiety group also reported mild to severe sleep disturbance. Moreover, 41% of the participants perceived themselves as not having enough COVID-19-related information and reported higher levels of COVID-19 infection anxiety and sleep disturbance over time than those who perceived themselves as having enough of such information. Moderated mediation analysis identified two groups who were more vulnerable to both psychological problems: high blunters who sought COVID-19-related information online more frequently and high monitors who sought such information offline less frequently. These findings highlight the importance of a good match between information coping style and strategy deployment in dealing with an infodemic surrounding a novel disease., (© 2020 European Sleep Research Society.)

In the cyber era, people interact with others not only face-to-face but also through social media platforms such as Facebook and Instagram. Social media addiction has emerged as a problem of global concern, with researchers all over the world conducting studies to evaluate how pervasive the problem is. However, the prevalence rates of social media addiction reported in the literature vary dramatically. The present meta-analysis aimed to systematically synthesize the extant research on social media addiction prevalence. Subgroup analysis and meta-regression were conducted to investigate whether the prevalence rates would differ by classification schemes, cultural values, and demographic factors. The meta-analysis involved 63 independent samples with 34,798 respondents from 32 nations spanning seven world regions. The random-effects meta-analytic findings revealed variations in prevalence among studies adopting distinct classification schemes. The pooled prevalence estimate was 5% (95% CI: 3%-7%) for studies adopting monothetic or strict monothetic classifications. A higher pooled prevalence estimate (13%; 95% CI: 8%-19%) was found for studies adopting a cutoff for severe level or strict polythetic classifications, and that estimate was even higher (25%; 95% CI: 21%-29%) for studies adopting a cutoff for moderate level or polythetic classifications. Moreover, cross-cultural comparisons revealed the pooled prevalence estimate obtained in collectivist nations (31%; 95% CI: 26%-36%) to be twofold higher than that obtained in individualist nations (14%; 95% CI: 9%-19%). This meta-analysis indicates that both the classification scheme used and cultural factors should be considered when interpreting the prevalence findings on social media addiction., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: This pilot study aimed to evaluate the congruency in consensus molecular subtypes (CMS) of primary colorectal cancer and corresponding hepatic metastasis (HM)., Materials & Methods: RNA was extracted from both primary colorectal cancer and HM from ten patients, sequenced to establish gene-expression profiles and classified into CMS. Clinical data were collected retrospectively., Results: Of the ten patients recruited, nine had primary tumors that were classifiable: seven were CMS2, one was CMS3 and one was CMS4. Five had incongruent classification in the corresponding HM. Three out of the five patients with incongruent classification had received adjuvant chemotherapy prior to hepatic resection., Conclusion: A change in CMS type between matched primary and metastatic colorectal tumors is common and may be attributable to chemotherapy., Competing Interests: Financial & competing interests disclosure YC Lau: Richard Stewart Scholarship from the University of Otago; R Purcell: Maurice and Phyllis Paykel Trust; Gut Cancer Foundation (NZ), with support from the Hugh Green Foundation; Colorectal Surgical Society of Australia and New Zealand (CSSANZ); The Health Research Council of New Zealand. The funding bodies had no role in the design of the study or collection, analysis and interpretation of data or in writing the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript., (© 2021 The Authors.)

Objective: To report survival, functional, and quality-of-life (QoL) outcomes after extended radical resection for advanced pelvic tumors with en bloc sciatic or femoral nerve resection., Background: Advanced pelvic tumors involving the sciatic or femoral nerve have traditionally been considered inoperable. Small studies have suggested acceptable functional outcomes can be achieved after pelvic exenteration with en bloc sciatic nerve resection., Method: Consecutive patients who underwent extended radical pelvic surgery with en bloc resection of the sciatic or femoral nerves at a single center were included., Results: Of 713 radical pelvic resections, 68 patients (9.5%) had en bloc sciatic or femoral nerve resection. Complete sciatic, partial sciatic, and complete femoral nerve resection was performed in 26 (38%), 38 (56%), and 4 patients (6%), respectively. Overall and major postoperative complication rates were 63% and 40%, respectively. R0 resection was achieved in 65% of patients, which translated to 55% and 76% overall and local recurrence-free 5-year survival in those with colorectal cancer. Twenty-two (96%) and 25 (92%) patients could mobilize independently after complete and partial sciatic nerve resection, respectively. Physical QoL was significantly lower at 6 months after surgery compared with baseline (P = 0.041), but returned to baseline at 12 months (P = 0.163). There was no difference in mental or overall QoL at 6 or 12 months compared with baseline., Conclusion: En bloc sciatic and femoral nerve resection can be performed during extended radical pelvic resections with morbidity and survival outcomes comparable with existing exenteration literature, including in patients with recurrent rectal cancer. Physical QoL may be impaired after surgery, but returns to baseline by 12 months., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Atrial fibrillation (AF) is associated with increased risk of stroke and thromboembolism. Patients with AF have a higher incidence of renal impairment, which may influence the risks of systemic thromboembolism or bleeding. We determined how different oral anticoagulants affect plasma clot properties and whether progressive renal dysfunction affects plasma clot properties in patients on warfarin., Materials and Methods: We studied 257 patients with AF receiving oral anticoagulants. Furthermore, we recruited 192 separate patients with AF on warfarin and divided them in 4 groups based on estimated glomerular filtration rate (eGFR). Platelet poor plasma was prepared and clot formation and fibrinolysis was monitored kinetically up to 1 h., Results: Rate of clot formation was significantly slower with dabigatran and rivaroxaban. Time between 50% clotting and 50% lysis was prolonged in patients receiving warfarin compared to NOACs. Time to 50% lysis from maximum absorbance was significantly shorter in patients receiving rivaroxaban. Time between 50% clotting and 50% lysis became significantly prolonged with worsening eGFR. Time to 50% lysis from maximum absorbance was prolonged as renal function worsened., Conclusions: Compared to warfarin, NOACs differently modulate coagulation and fibrinolysis under ex vivo conditions. Worsening renal function in AF patients on warfarin prolongs fibrinolysis, potentially increasing the risk of thrombosis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: COVID-19 has spread like wildfire across the globe, prompting many governments to impose unprecedented stay-at-home orders to limit its transmission. During an extended stay-at-home period, individuals may engage in more online leisure activities. Internet use is a double-edged sword that may have both desirable and undesirable effects on psychological well-being, and this study sought to disentangle adaptive from maladaptive internet use amidst this unusual health crisis., Objective: The objectives of this study were to assess the prevalence of probable depression during the COVID-19 stay-at-home period and to test three hypothesized risk reduction or risk elevation mechanisms, namely social capital-accrual, escape-from-self, and time-displacement effects., Methods: This study took place from March to May 2020 at the early stage of the pandemic. The study adopted a prospective design, with an online survey administered to 573 UK and 474 US adult residents at two assessment points 2 months apart., Results: The prevalence of moderate to severe depression was 36% (bootstrap bias-corrected and accelerated [BCa] 95% CI 33%-39%) at Time 1 (ie, initial time point) and 27% (bootstrap BCa 95% CI 25%-30%) at Time 2 (ie, follow-up time point). The results supported the social capital-accrual hypothesis by showing that the approach coping style was inversely associated with Time 2 depression through its positive associations with both social networking and perceived family support. The results also supported the escape-from-self hypothesis by revealing that the avoidant coping style was positively associated with Time 2 depression through its positive associations with both gaming and cyberbullying victimization, but the serial mediation model was no longer significant after Time 1 depression and some demographic risk factors had been controlled for. Finally, the results supported the time-displacement hypothesis by showing that gaming was positively associated with Time 2 depression through its inverse associations with social networking and perceived family support., Conclusions: During the extended stay-at-home period in the early stages of the COVID-19 pandemic, the prevalence of probable depression during the 2-month study period was high among the UK and US residents. Individuals with distinct coping styles may engage in different types of online leisure activities and perceive varying levels of social support, which are associated with risks of probable depression., (©Cecilia Cheng, Yan-Ching Lau, Jeremy W Luk. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 24.12.2020.)

Two lineages of influenza B virus currently co-circulate and have distinct antigenicity, termed Victoria and Yamagata after the B/Victoria/2/87 and B/Yamagata/16/88 strains, respectively. We analyzed antibody titer dynamics following PCR-confirmed influenza B virus infection in a longitudinal community-based cohort study conducted in Hong Kong from 2009-2014 to assess patterns in changes in antibody titers to B/Victoria and B/Yamagata viruses following infections with each lineage. Among 62 PCR-confirmed cases, almost half had undetectable hemagglutination inhibition (HAI) antibody titers to the lineage of infection both pre-infection and post-infection. Among those infected with influenza B/Victoria who showed an HAI titer response after infection, we found strong rises to the lineage of infection, positive but smaller cross-lineage HAI titer boosts, a small dependence of HAI titer boosts on pre-infection titers, and a shorter half-life of HAI titers in adults. Our study is limited by the low HAI sensitivity for non-ether-treated IBV antigen and the incapacity of performing other assays with higher sensitivity, as well as the mismatch between the B/Yamagata lineage circulating strain and the assay strain in one of the study seasons., Competing Interests: BJC has received honoraria from Roche and Sanofi. The authors report no other potential conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Aims: To evaluate the implementation of 18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) surveillance after (chemo)radiotherapy, to compare outcomes for those who achieved a complete (CR), equivocal (EQR) and incomplete (ICR) nodal response on 12-week PET-CT according to their human papillomavirus (HPV) status, and to assess the safety of ongoing surveillance beyond 12 weeks in the HPV-positive EQR group., Materials and Methods: All patients with node-positive head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy between January 2013 and September 2017 were identified. PET-CT responses were classified as CR, ICR or EQR. Patient outcomes were obtained from electronic records., Results: In total, 236 patients with a minimum of 2 years of follow-up were identified. The mean age was 59 years; 79.3% had N2 disease; 77.1% of patients had oropharyngeal cancer and 10.1% had squamous cell carcinoma of unknown primary, of whom 82.0% (169) were HPV positive; 78.0% received chemoradiotherapy. The median time from the end of radiotherapy to PET-CT was 91 days. Of the HPV-related HNSCC, 60.4% achieved CR, 29.0% EQR and 10.6% ICR. With a median follow-up of 41.7 months, there was no difference in survival between patients with HPV-related HNSCC achieving CR and EQR (median overall survival not reached for both, P = 0.67) despite the omission of immediate neck dissection in 98.0% of the EQR group., Conclusion: Patients with HPV-positive HNSCC who have achieved EQR have comparable survival outcomes to those who achieved a CR despite the omission of immediate neck dissections; this shows the safety of ongoing surveillance beyond 12 weeks in this group of patients., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Sex differences are prevalent in normal development, physiology and disease pathogeneses. Recent studies have demonstrated that mosaic loss of Y chromosome and aberrant activation of its genes could modify the disease processes in male biased manners. This mini review discusses the nature of the genes on the human Y chromosome and identifies two general categories of genes: those sharing dosage-sensitivity functions with their X homologues and those with testis-specific expression and functions. Mosaic loss of the former disrupts the homeostasis important for the maintenance of health while aberrant activation of the latter promotes pathogenesis in non-gonadal tissues, thereby contributing to genetic predispositions to diseases in men., Competing Interests: Competing interestsThe author declare no competing interests., (© The Author(s) 2020.)

Hepatocellular carcinoma (HCC) is a highly heterogeneous liver cancer with significant male biases in incidence, disease progression, and outcomes. Previous studies have suggested that genes on the Y chromosome could be expressed and exert various male-specific functions in the oncogenic processes. In particular, the RNA-binding motif on the Y chromosome (RBMY) gene is frequently activated in HCC and postulated to promote hepatic oncogenesis in patients and animal models. In the present study, immunohistochemical analyses of HCC specimens and data mining of The Cancer Genome Atlas (TCGA) database revealed that high-level RBMY expression is associated with poor prognosis and survival of the patients, suggesting that RBMY could possess oncogenic properties in HCC. To examine the immediate effect(s) of the RBMY overexpression in liver cancer cells, cell proliferation was analyzed on HuH-7 and HepG2 cells. The results unexpectedly showed that RBMY overexpression inhibited cell proliferation in both cell lines as its immediate effect, which led to vast cell death in HuH-7 cells. Transcriptome analysis showed that genes involved in various cell proliferative pathways, such as the RAS/RAF/MAP and PIP3/AKT signaling pathways, were downregulated by RBMY overexpression in HuH-7 cells. Furthermore, in vivo analyses in a mouse liver cancer model using hydrodynamic tail vein injection of constitutively active AKT and RAS oncogenes showed that RBMY abolished HCC development. These findings support the notion that Y-linked RBMY could serve dual tumor-suppressing and tumor-promoting functions, depending on the spatiotemporal and magnitude of its expression during oncogenic processes, thereby contributing to sexual dimorphisms in liver cancer., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

We report temporal patterns of viral shedding in 94 patients with laboratory-confirmed COVID-19 and modeled COVID-19 infectiousness profiles from a separate sample of 77 infector-infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% (95% confidence interval, 25-69%) of secondary cases were infected during the index cases' presymptomatic stage, in settings with substantial household clustering, active case finding and quarantine outside the home. Disease control measures should be adjusted to account for probable substantial presymptomatic transmission.

We have studied the charge to spin conversion in Bi 1- x Sb x /CoFeB heterostructures. The spin Hall conductivity (SHC) of the sputter-deposited heterostructures exhibits a high plateau at Bi-rich compositions, corresponding to the topological insulator phase, followed by a decrease of SHC for Sb-richer alloys, in agreement with the calculated intrinsic spin Hall effect of Bi 1- x Sb x . The SHC increases with increasing Bi 1- x Sb x thickness before it saturates, indicating that it is the bulk of the alloy that predominantly contributes to the generation of spin current; the topological surface states, if present, play little role. Unexpectedly, the SHC is found to increase with increasing temperature, following the trend of carrier density. These results suggest that the large SHC at room temperature, with a spin Hall efficiency exceeding 1 and an extremely large spin current mobility, is due to increased number of thermally excited Dirac-like electrons in the L valley of the narrow gap Bi 1- x Sb x alloy., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Purpose: To assess the outcome of ligation of intersphincteric fistula tract (LIFT) and bioprosthetic graft (BioLIFT) in the management of transsphincteric perianal fistula., Methods: A single-institution retrospective analysis of all patients undergoing LIFT and BioLIFT from January 2009 to June 2018 was performed. Only patients who had LIFTs and BioLIFT performed as their primary sphincter-preserving procedure was included. Primary outcome measured was primary healing. Secondary outcomes measured were secondary healing, morbidity, time to recurrence, and pre- and post-operative anorectal manometry. Chi-square analysis was used to determine predictive factors., Results: A total of 116 patients were identified. One hundred five had LIFT and 11 had BioLIFT. The total primary healing rate was 60.3% (62.9% and 34.9% for LIFT and BioLIFT respectively). The overall secondary healing rate was 80.2% (80.0% and 81.9% for LIFT and BioLIFT respectively). There was no inpatient morbidity or post-procedural faecal incontinence reported. There was no significant change in the pre- and post-operative manometries in either group (P = 0.417 and P = 0.834 for LIFT and BioLIFT respectively). The only predictor for primary failure identified was anteriorly located fistula., Conclusion: LIFT and BioLIFT compare favourably with other sphincter-preserving procedures. LIFT and BioLIFT can be performed safely, with minimal morbidity and with no reported loss of sphincteric function.

Background: Human influenza virus infections cause a considerable burden of morbidity and mortality worldwide each year. Understanding regional influenza-associated outpatient burden is crucial for formulating control strategies against influenza viruses., Methods: We extracted the national sentinel surveillance data on outpatient visits due to influenza-like-illness (ILI) and virological confirmation of sentinel specimens from 30 provinces of China from 2006 to 2015. Generalized additive regression models were fitted to estimate influenza-associated excess ILI outpatient burden for each individual province, accounting for seasonal baselines and meteorological factors., Results: Influenza was associated with an average of 2.5 excess ILI consultations per 1000 person-years (py) in 30 provinces of China each year from 2006 to 2015. Influenza A(H1N1)pdm09 led to a higher number of influenza-associated ILI consultations in 2009 across all provinces compared with other years. The excess ILI burden was 4.5 per 1000 py among children aged below 15 years old, substantially higher than that in adults., Conclusions: Human influenza viruses caused considerable impact on population morbidity, with a consequent healthcare and economic burden. This study provided the evidence for planning of vaccination programs in China and a framework to estimate burden of influenza-associated outpatient consultations., (© 2019 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

There have been significant advances in the surgical management of locally advanced and recurrent rectal cancer in recent decades. Patient with advanced pelvic tumours involving adjacent organs and neurovascular structures, beyond the traditional mesorectal planes, who would have traditionally been considered irresectable at many centres, now undergo surgery routinely at specialised units. While high rates of morbidity and mortality were reported by the pioneers of pelvic exenteration (PE) in early literature, this is now considered historical data. In 2019, patients who undergo PE for advanced or recurrent rectal cancer can expect reasonable rates of long-term survival (up to 60% at 5 years) and acceptable morbidity and quality of life. This article describes the surgical techniques that have been developed for radical multivisceral pelvic resections and reviews contemporary outcomes., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Journal of Gastrointestinal Oncology. All rights reserved.)

Background: Post-surgical staging is the mainstay of prognostic stratification for colorectal cancer (CRC). Here, we compare TNM staging to consensus molecular subtyping (CMS) and assess the value of subtyping in addition to stratification by TNM., Methods: Three hundred and eight treatment-naïve colorectal tumours were accessed from our institutional tissue bank. CMS typing was carried out using tumour gene-expression data. Post-surgical TNM-staging and CMS were analysed with respect to clinicopathologic variables and patient outcome., Results: CMS alone was not associated with survival, while TNM stage significantly explained mortality. Addition of CMS to TNM-stratified tumours showed a prognostic effect in stage 2 tumours; CMS3 tumours had a significantly lower overall survival (P = 0.006). Stage 2 patients with a good prognosis showed immune activation and up-regulation of tumour suppressor genes., Conclusions: Although stratification using CMS does not outperform TNM staging as a prognostic indicator, gene-expression based subtyping shows promise for improved prognostication in stage 2 CRC.

Background: The estimation of influenza-associated excess mortality in countries can help to improve estimates of the global mortality burden attributable to influenza virus infections. We did a study to estimate the influenza-associated excess respiratory mortality in mainland China for the 2010-11 through 2014-15 seasons., Methods: We obtained provincial weekly influenza surveillance data and population mortality data for 161 disease surveillance points in 31 provinces in mainland China from the Chinese Center for Disease Control and Prevention for the years 2005-15. Disease surveillance points with an annual average mortality rate of less than 0·4% between 2005 and 2015 or an annual mortality rate of less than 0·3% in any given years were excluded. We extracted data for respiratory deaths based on codes J00-J99 under the tenth edition of the International Classification of Diseases. Data on respiratory mortality and population were stratified by age group (age <60 years and ≥60 years) and aggregated by province. The overall annual population data of each province and national annual respiratory mortality data were compiled from the China Statistical Yearbook. Influenza surveillance data on weekly proportion of samples testing positive for influenza virus by type or subtype for 31 provinces were extracted from the National Sentinel Hospital-based Influenza Surveillance Network. We estimated influenza-associated excess respiratory mortality rates between the 2010-11 and 2014-15 seasons for 22 provinces with valid data in the country using linear regression models. Extrapolation of excess respiratory mortality rates was done using random-effect meta-regression models for nine provinces without valid data for a direct estimation of the rates., Findings: We fitted the linear regression model with the data from 22 of 31 provinces in mainland China, representing 83·0% of the total population. We estimated that an annual mean of 88 100 (95% CI 84 200-92 000) influenza-associated excess respiratory deaths occurred in China in the 5 years studied, corresponding to 8·2% (95% CI 7·9-8·6) of respiratory deaths. The mean excess respiratory mortality rates per 100 000 person-seasons for influenza A(H1N1)pdm09, A(H3N2), and B viruses were 1·6 (95% CI 1·5-1·7), 2·6 (2·4-2·8), and 2·3 (2·1-2·5), respectively. Estimated excess respiratory mortality rates per 100 000 person-seasons were 1·5 (95% CI 1·1-1·9) for individuals younger than 60 years and 38·5 (36·8-40·2) for individuals aged 60 years or older. Approximately 71 000 (95% CI 67 800-74 100) influenza-associated excess respiratory deaths occurred in individuals aged 60 years or older, corresponding to 80% of such deaths., Interpretation: Influenza was associated with substantial excess respiratory mortality in China between 2010-11 and 2014-15 seasons, especially in older adults aged at least 60 years. Continuous and high-quality surveillance data across China are needed to improve the estimation of the disease burden attributable to influenza and the best public health interventions are needed to curb this burden., Funding: National Science Fund for Distinguished Young Scholars, National Science and Technology Major Project of China, National Institute of Health Research, the Harvard Center for Communicable Disease Dynamics from the National Institute of General Medical Sciences, and the China-US Collaborative Program on Emerging and Re-emerging Infectious Disease., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The Dzyaloshinskii-Moriya (DM) interaction is an antisymmetric exchange interaction that is responsible for the emergence of chiral magnetism. The origin of the DM interaction, however, remains to be identified albeit the large number of studies reported on related effects. It has been recently suggested that the DM interaction is equivalent to an equilibrium spin current density originating from spin-orbit coupling, an effect referred to as the spin Doppler effect. The model predicts that the DM interaction can be controlled by spin current injected externally. Here we show that the DM exchange constant (D) in W/CoFeB-based heterostructures can be modulated with external current passed along the film plane. At higher current, D decreases with increasing current, which we infer is partly due to the adiabatic spin transfer torque. At lower current, D increases linearly with current regardless of the polarity of current flow. The rate of increase in D with the current density agrees with that predicted by the model based on the spin Doppler effect. These results imply that the DM interaction at the heavy-metal-ferromagnetic-metal interface partly originates from an equilibrium interface spin (polarized) current which can be modulated externally.

The Y-located testis-specific protein Y-encoded (TSPY) and its X-homologue TSPX originated from the same ancestral gene, but act as a proto-oncogene and a tumor suppressor gene, respectively. TSPY has specialized in male-specific functions, while TSPX has assumed the functions of the ancestral gene. Both TSPY and TSPX harbor a conserved SET/NAP domain, but are divergent at flanking structures. Specifically, TSPX contains a C-terminal acidic domain, absent in TSPY. They possess contrasting properties, in which TSPY and TSPX, respectively, accelerate and arrest cell proliferation, stimulate and inhibit cyclin B-CDK1 phosphorylation activities, have no effect and promote proteosomal degradation of the viral HBx oncoprotein, and exacerbate and repress androgen receptor (AR) and constitutively active AR variant, such as AR-V7, gene transactivation. The inhibitory domain has been mapped to the carboxyl acidic domain in TSPX, truncation of which results in an abbreviated TSPX exerting positive actions as TSPY. Transposition of the acidic domain to the C-terminus of TSPY results in an inhibitory protein as intact TSPX. Hence, genomic mutations/aberrant splicing events could generate TSPX proteins with truncated acidic domain and oncogenic properties as those for TSPY. Further, TSPY is upregulated by AR and AR-V7 in ligand-dependent and ligand-independent manners, respectively, suggesting the existence of a positive feedback loop between a Y-located proto-oncogene and male sex hormone/receptors, thereby amplifying the respective male oncogenic actions in human cancers and diseases. TSPX counteracts such positive feedback loop. Hence, TSPY and TSPX are homologues on the sex chromosomes that function at the two extremes of the human oncogenic spectrum.

Study Question: Which Y genes mapped to the 'Gonadoblastoma Y (GBY)' locus on human Y chromosome are expressed in germ cells of individuals with some Differences of Sexual Development (DSD) and a Y chromosome in their karyotype (DSD-XY groups)?, Summary Answer: The GBY candidate genes DDX3Y and TSPY are expressed in the germ cells of DSD-XY patients from distinct etiologies: patients with mixed gonadal dysgenesis (MGD) and sex chromosome mosaics (45,X0/46,XY; 46,XX/46,XY); patients with complete androgen insensitivity (CAIS), patients with complete gonadal dysgenesis (CGD; e.g. Swyer syndrome)., What Is Known Already: A GBY locus was proposed to be present on the human Y chromosome because only DSD patients with a Y chromosome in their karyotype have a high-although variable-risk (up to 55%) for germ cell tumour development. GBY was mapped to the proximal part of the short and long Y arm. TSPY located in the proximal part of the short Y arm (Yp11.1) was found to be a strong GBY candidate gene. It is expressed in the germ cells of DSD-XY patients with distinct etiologies but also in foetal and pre-meiotic male spermatogonia. However, the GBY region extends to proximal Yq11 and therefore includes probably more than one candidate gene., Study Design, Size, Duration: Protein expression of the putative GBY candidate gene in proximal Yq11, DDX3Y, is compared with that of TSPY in serial gonadal tissue sections of 40 DSD-XY individuals from the three DSD patient groups (MGD, Complete Androgen Insensitivity Syndrome [CAIS], CGD) with and without displaying malignancy. Expression of OCT3/4 in the same tissue samples marks the rate of pluripotent germ cells., Participants/materials, Setting, Method: A total of 145 DSD individuals were analysed for the Y chromosome to select the DSD-XY subgroup. PCR multiplex assays with Y gene specific marker set score for putative microdeletions in GBY Locus. Immunohistochemical experiments with specific antisera mark expression of the GBY candidate proteins, DDX3Y, TSPY, in serial sections of the gonadal tissue samples; OCT3/4 expression analyses in parallel reveal the pluripotent germ cell fraction., Main Results and the Role of Chance: Similar DDX3Y and TSPY protein expression patterns were found in the germ cells of DSD-XY patients from each subgroup, independent of age. In CAIS patients OCT3/4 expression was often found only in a fraction of these germ cells. This suggest that GBY candidate proteins are also expressed in the non-malignant germ cells of DSD-XY individuals like in male spermatogonia., Limitations, Reasons for Caution: Variation of the expression profiles of GBY candidate genes in the germ cells of some DSD-XY individuals suggests distinct transcriptional and translational control mechanisms which are functioning during expression of these Y genes in the DSD-XY germ cells. Their proposed GBY tumour susceptibility function to transform these germ cells to pre-malignant GB/Germ Cell Neoplasia in Situ (GB/GCNIS) cells seems therefore to be limited and depending on their state of pluripotency., Wider Implications of the Findings: These experimental findings are of general importance for each individual identified in the clinic with DSD and a Y chromosome in the karyotype. To judge their risk of germ cell tumour development, OCT3/4 expression analyses on their gonadal tissue section is mandatory to reveal the fraction of germ cells still being pluripotent. Comparative expression analysis of the GBY candidate genes can be helpful to reveal the fraction of germ cells with genetically still activated Y chromosomes contributing to further development of malignancy if at high expression level., Study Funding/competing Interest(s): This research project was supported by a grant (01GM0627) from the BMBF (Bundesministerium für Bildung und Forschung), Germany to P.H.V. and B.B. The authors have no competing interests., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Due to its negligible spontaneous magnetization, high spin polarization and giant perpendicular magnetic anisotropy, Mn 2 Ru x Ga (MRG) is an ideal candidate as an oscillating layer in THz spin-transfer-torque nano-oscillators. Here, the effect of ultrathin Al and Ta diffusion barriers between MRG and MgO in perpendicular magnetic tunnel junctions is investigated and compared to devices with a bare MRG/MgO interface. Both the compensation temperature, T comp , of the electrode and the tunneling magnetoresistance (TMR) of the device are highly sensitive to the choice and thickness of the insertion layer used. High-resolution transmission electron microscopy, as well as analysis of the TMR, its bias dependence, and the resistance-area product allow us to compare the devices from a structural and electrical point of view. Al insertion leads to the formation of thicker effective barriers and gives the highest TMR, at the cost of a reduced T comp . Ta is the superior diffusion barrier which retains T comp , however, it also leads to a much lower TMR on account of the short spin diffusion length which reduces the tunneling spin polarization. The study shows that fine engineering of the Mn 2 Ru x Ga/barrier interface to improve the TMR amplitude is feasible.

Background: Liver cancer is one of the major causes of cancer death worldwide, with significantly higher incidence and mortality among the male patients. Although sex hormones and their receptors could contribute to such sex differences, the story is incomplete. Genes on the male-specific region of the Y chromosome could play a role(s) in this cancer. TSPY is the putative gene for the gonadoblastoma locus on the Y chromosome (GBY) that is ectopically expressed in a subset of male hepatocellular carcinomas (HCCs). Although various studies showed that TSPY expression is associated with poor prognosis in the patients and its overexpression promotes cell proliferation of various cancer cell lines, it remains unclear how TSPY contributes to the clinical outcomes of the HCC patients. Identifying the downstream genes and pathways of TSPY actions would provide novel insights on its contribution(s) to male predominance in this deadly cancer., Results: To determine the effects of TSPY on HCC, a TSPY transgene was introduced to the HCC cell line, HuH-7, and studied with RNA-Seq transcriptome analysis. The results showed that TSPY upregulates various genes associated with cell-cycle and cell-viability, and suppresses cell-death related genes. To correlate the experimental observations with those of clinical specimens, transcriptomes of male HCCs with high TSPY expression were analyzed with reference to those with silent TSPY expression from the Cancer Genome Atlas (TCGA). The comparative analysis identified 49 genes, which showed parallel expression patterns between HuH-7 cells overexpressing TSPY and clinical specimens with high TSPY expression. Among these 49 genes, 16 likely downstream genes could be associated with survival rates in HCC patients. The major upregulated targets were cell-cycle related genes and growth factor receptor genes, including CDC25B and HMMR, whose expression levels are negatively correlated with the patient survival rates. In contrast, PPARGC1A, SLC25A25 and SOCS2 were downregulated with TSPY expression, and possess favorable prognoses for HCC patients., Conclusion: We demonstrate that TSPY could exacerbate the oncogenesis of HCC by differentially upregulate the expression of pro-oncogenic genes and downregulate those of anti-oncogenic genes in male HCC patients, thereby contributing to the male predominance in this deadly cancer.