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Summary Objectives A whole body vibration platform using vertical oscillation has been shown to be efficacious in reducing vocal fatigue in adults. This study aimed to investigate whether this platform-generated whole body vibration was unique in reducing vocal fatigue by comparing it with self-generated whole body vibration. Methods Twenty-four female adults (mean age = 23.96 years) were randomly assigned to one of the following three groups: a machine-generated whole body vibration group (N = 8), a self-generated whole body vibration group (N = 8), and a placebo vocal resting group (N = 8). All participants performed a karaoke singing task for at least 95 minutes. Each participant received 10 minutes of platform-generated vibration, self-vibration, or sham localised vibration (placebo group with basically voice rest only), according to their group allocation. Vocal function ability, measured by the highest fundamental frequency produced, and a self-reported vocal fatigue score were evaluated at three time points: baseline (prefatigue), after the singing task (post-fatigue) and post-vibration. Results The study revealed that machine-generated whole body vibration was significantly better at improving vocal fatigue than self-generated whole body vibration or voice rest. Conclusion The findings support previous research that machine-generated whole body vibration is effective in reducing vocal fatigue. The non-significant results of self-generated whole body vibration in terms of relieving vocal fatigue suggest that inadequate vibration frequency or amplitude together with leg muscle fatigue may have been the main factor of ineffectiveness.

IEEE 802.11ax is the standard for the new generation WiFi networks. In this paper, we formulate the problem of joint access point (AP) placement and power-channel-resource unit assignment for 802.11ax-based dense WiFi. The objective is to minimize the number of APs. Two quality-of-service (QoS) requirements are to be fulfilled: (1) a two-tier throughput requirement which ensures that the throughput of each station is good enough, and (2) a fault tolerance requirement which ensures that the stations could still use WiFi even when some APs fail. We prove that this problem is NP-hard. To tackle this problem, we first develop an analytic model to derive the throughput of each station under the OFDMA mechanism and a widely used interference model. We then design a heuristic algorithm to find high-quality solutions with polynomial time complexity. Simulation results under both fixed-user and mobile-user cases show that: (1) when the area is small (50 x 50 m2), our algorithm gives the optimal solutions; when the area is larger (80 x 60 m2), our algorithm can reduce the number of APs by 34.9-87.7% as compared to the Random and Greedy algorithms. (2) Our algorithm can always get feasible solutions that fulfill the QoS requirements.

We propose a strategy for magnetic navigation of collective stem cell microrobots in blood environments under ultrasound Doppler imaging. The cell microrobots are fabricated through a coculture process of stem cells and iron microparticles, they have spheroidal structures and are actuated under external magnetic fields. The collective cell microrobots can be reversibly gathered and spread by adjusting the magnetic interaction, and these microrobots are able to exhibit collective motion in whole blood under rotating magnetic fields. Simulation results indicate that the induced blood flow around the collective pattern affects the motion of red blood cells, and experimental results show that Doppler signals are observed when emitting ultrasound waves to the microrobots. Due to the induced three-dimensional blood flow, Doppler signals can also be observed when the imaging plane is above the collective microrobots, which enables indirect localization when performing navigation on uneven surfaces. Moreover, collective patterns of different numbers of microrobots are formed in flowing conditions, and these collective biohybrid agents are actively navigated against flowing blood with a flow rate up to 4.5 mL/min (mean velocity: 5.97 mm/s). Our study investigates a strategy for pattern formation and navigation of collective microrobots under ultrasound Doppler imaging, demonstrating the integration of collective control approach and medical imaging holds great potential for real-time active delivery tasks.

Existing transfer learning methods that focus on problems in stationary environments are not usually applicable to dynamic environments, where concept drift may occur. To the best of our knowledge, the concept drift-tolerant transfer learning (CDTL), whose major challenge is the need to adapt the target model and knowledge of source domains to the changing environments, has yet to be well explored in the literature. This article, therefore, proposes a hybrid ensemble approach to deal with the CDTL problem provided that data in the target domain are generated in a streaming chunk-by-chunk manner from nonstationary environments. At each time step, a class-wise weighted ensemble is presented to adapt the model of target domains to new environments. It assigns a weight vector for each classifier generated from the previous data chunks to allow each class of the current data leveraging historical knowledge independently. Then, a domain-wise weighted ensemble is introduced to combine the source and target models to select useful knowledge of each domain. The source models are updated with the source instances performed by the proposed adaptive weighted CORrelation ALignment (AW-CORAL). AW-CORAL iteratively minimizes domain discrepancy meanwhile decreases the effect of unrelated source instances. In this way, positive knowledge of source domains can be potentially promoted while negative knowledge is reduced. Empirical studies on synthetic and real benchmark data sets demonstrate the effectiveness of the proposed algorithm.

Research Question To investigate the effect of adding an anti-spasmodic to an existing ultrasound-guided manual vacuum aspiration (USG-MVA) protocol to alleviate immediate post-procedure abdominal cramping pain in women treated for early pregnancy loss. Design : Double-blind, placebo-controlled, randomised control trial conducted between February 2018 and January 2020 in a university-affiliated tertiary hospital. 111 women were assigned to receive a 1ml intravenous injection containing either a 20mg hyoscine butylbromide (HBB) (n = 55) or saline (n =56) as a control immediately before the USG-MVA procedure. The primary outcome was whether adding a 20mg dose HBB to the current pain control regimen reduced abdominal pain. Secondary outcomes were vaginal pain, complications and side effects, women's pre- and post-procedure's psychological state, physiological stress (saliva alpha-amylase (sAA) and procedure pain control satisfaction. Two-way mixed ANOVA was used to evaluate for main effects and interactions. Results VAS abdominal pain scores in the HBB group were 16% lower immediately and 21% lower two hours postoperatively, though not statistically significant. Two-way ANOVA indicated that time (F (1,108) =83.41,p Conclusions Anti-spasmodics can be helpful in the reduction of USG-MVA associated abdominal cramping pain, though our results showed HBB produced an insignificant decrease in abdominal pain score. Further studies with longer-acting or larger doses of anti-spasmodics are warranted.

Ordinal attribute has all the common characteristics of a nominal one but it differs from the nominal one by having naturally ordered possible values (also called categories interchangeably). In clustering analysis tasks, categorical data composed of both ordinal and nominal attributes (also called mixed-categorical data interchangeably) are common. Under this circumstance, existing distance and similarity measures suffer from at least one of the following two drawbacks: 1) directly treat ordinal attributes as nominal ones, and thus ignore the order information from them and 2) suppose all the attributes are independent of each other, measure the distance between two categories from a target attribute without considering the valuable information provided by the other attributes that correlate with the target one. These two drawbacks may twist the natural distances of attributes and further lead to unsatisfactory clustering results. This article, therefore, presents an entropy-based distance metric that quantifies the distance between categories by exploiting the information provided by different attributes that correlate with the target one. It also preserves the order relationship among ordinal categories during the distance measurement. Since attributes are usually correlated in different degrees, we also define the interdependence between different types of attributes to weight their contributions in forming distances. The proposed metric overcomes the two above-mentioned drawbacks for mixed-categorical data clustering. More important, it conceptually unifies the distances of ordinal and nominal attributes to avoid information loss during clustering. Moreover, it is parameter free, and will not bring extra computational cost compared to the existing state-of-the-art counterparts. Extensive experiments show the superiority of the proposed distance metric.

The aim of this randomized controlled trial was to compare the skeletal stability between sagittal split ramus osteotomy (SSRO) and intraoral vertical ramus osteotomy (IVRO) in the treatment of mandibular prognathism. Patients presenting with mandibular prognathism and scheduled for orthognathic surgery were randomized into either the SSRO group or the IVRO group. Changes at B-point were assessed by serial tracing of lateral cephalograms, which were taken preoperatively, and at 2 weeks, 6 months, 1 year, and 2 years postoperatively. Ninety-eight patients were recruited, with 49 patients in each group. Between 2 weeks and 6 months postoperatively, there was significantly more surgical relapse in the horizontal direction (anterior movement) in the SSRO group when compared with the IVRO group (1.83 mm (SD 2.91 mm) vs 0.49 mm (SD 2.32 mm); p = 0.019). At 2 years, there was more surgical relapse in the horizontal direction in the SSRO group than in the IVRO group (0.27 mm (SD 0.34 mm) vs 0.10 mm (SD 0.29 mm); p = 0.014). There were also more absolute changes (irrespective of direction) at B-point in the SSRO group than in the IVRO group at postoperative 6 months, 1 year, and 2 years (p = 0.016, 0.049, and 0.045, respectively). The amounts of change at B-point as percentages of total mandibular setback were 1.3% and 3.5% in the IVRO group and SSRO group, respectively. There were no differences in vertical changes between the two groups at any time points. In conclusion, the horizontal stability at B-point was shown to be superior in the IVRO group compared with the SSRO group in the correction of mandibular prognathism during the 2-year follow-up. Although the exact clinical importance of this difference is unknown at this time, this possible benefit may be an important key factor when deciding which osteotomy technique to employ for mandibular setback.

Ship detection plays a significant role in the high-resolution remote sensing (HRRS) community, but it is a challenging task due to the complex contents within HRRS images and the diverse orientation of ships. Recently, with the development of deep learning, the performance of the HRRS ship detection model has been improved greatly. Most of them employ deep networks and complicate anchor mechanism to get well ship detection results. Nevertheless, this kind of combination limits the detection efficiency. To address this problem, a new approach named accurate and real-time rotational ship detector (AR²Det) is proposed in this article to detect ships without the anchor mechanism. Based on the extracted features by the feature extraction module (FEM) and the central information of ships, AR²Det adopts two simple modules, ship detector (SDet) and center detector (CDet), to generate and improve the detection results, respectively. AR²Det is efficient due to the simple postprocessing and the lightweight network. Also, AR²Det performs satisfactorily due to the effective generation and enhancement strategy of bounding boxes. The extensive experiments are conducted on a public HRRS image ship detection dataset HRSC2016. The promising results show that our method outperforms the state-of-the-art approaches in terms of both accuracy and speed.

The COVID-19 pandemic is the third outbreak this century of a zoonotic disease caused by a coronavirus, following the emergence of severe acute respiratory syndrome (SARS) in 20031 and Middle East respiratory syndrome (MERS) in 20122. Treatment options for coronaviruses are limited. Here we show that clofazimine-an anti-leprosy drug with a favourable safety profile3-possesses inhibitory activity against several coronaviruses, and can antagonize the replication of SARS-CoV-2 and MERS-CoV in a range of in vitro systems. We found that this molecule, which has been approved by the US Food and Drug Administration, inhibits cell fusion mediated by the viral spike glycoprotein, as well as activity of the viral helicase. Prophylactic or therapeutic administration of clofazimine in a hamster model of SARS-CoV-2 pathogenesis led to reduced viral loads in the lung and viral shedding in faeces, and also alleviated the inflammation associated with viral infection. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Clofazimine, which is orally bioavailable and comparatively cheap to manufacture, is an attractive clinical candidate for the treatment of outpatients and-when combined with remdesivir-in therapy for hospitalized patients with COVID-19, particularly in contexts in which costs are an important factor or specialized medical facilities are limited. Our data provide evidence that clofazimine may have a role in the control of the current pandemic of COVID-19 and-possibly more importantly-in dealing with coronavirus diseases that may emerge in the future.

Background Hepatocellular carcinoma (HCC) ranks many tasks in clinical oncology due to possibly develop general tumor in men and, usually lead to malignant to death within years. Researches had reported about major factors for being HCC was male sex and HCC associated with cirrhosis in childhood was found more common in males than females. In certain mouse strains as studied, breeding with testosterone significantly increases the development of HCC. Furthermore, castration of male mice diminished the frequency of the development of liver tumors. Meanwhile Male hepatitis B virus transgenic mice have greater occurrence of HCC than females. Methods We apply degenerate priming PCR to observe the expression of various steroid receptors in livers. Yeast-two hybrid screening to search a novel RNA fragment helps to find a new full-length gene by RACE experiment. RT-PCR is applied to detect various of expression in tissues and cell lines. In situ hybridization detects DNA in Chromosome mapping. GFP-constructs transfection proves the gene localization in cells. Immunoprecipitation pulldown assay verifies protein interaction. Gene transfection followed with luciferase assay demonstrates interaction of genes within cellular signaling. Genomic alignment analysis for observing sequences data perform from NCBI database website (http://www.ncbi.nim.nih.gov/genebank/). Results The androgen receptor (AR) expression level is found at the highest level among the steroid receptors families detected in liver tumors. By yeast-two hybrid screening, we cloned an ARCAP (Androgen Receptor Complex Associated Protein), of 95 Kd in molecular weight and its cDNA. ARCAP locates at Chromosome 1. Our findings indicate ARCAP highly expresses in hepatoma cell lines and liver tumors and their adjacent tumors as observed. Yeast two-hybrid assay and in vitro immunoprecipitation assays demonstrated an interaction between AR and ARCAP. Conclusion Our aim is to search for different types and levels of steroid receptors expressed within human hepatocellular carcinomas and in the adjacent liver tissues. To verify possible molecular mechanisms by which AR might affect hepatoma cells, we had characterized a novel protein ARCAP which functions as a coregulator to interact with AR within liver. The ligand-dependent AR with its cofactor, ARCAP, can induce a signal cascade by transactivation.

Background and objective Few head-to-head evaluations of immune responses to different vaccines have been reported. Methods Surrogate virus neutralization test (sVNT) antibody levels of adults receiving either two doses of BNT162b2 (n = 366) or CoronaVac (n = 360) vaccines in Hong Kong were determined. An age-matched subgroup (BNT162b2 [n = 49] vs. CoronaVac [n = 49]) was tested for plaque reduction neutralization (PRNT) and spike-binding antibody and T-cell reactivity in peripheral blood mononuclear cells. Results One month after the second dose of vaccine, BNT162b2 elicited significantly higher PRNT50 , PRNT90 , sVNT, spike receptor binding, spike N-terminal domain binding, spike S2 domain binding, spike FcR binding and antibody avidity levels than CoronaVac. The geometric mean PRNT50 titres in those vaccinated with BNT162b2 and CoronaVac vaccines were 251.6 and 69.45, while PRNT90 titres were 98.91 and 16.57, respectively. All of those vaccinated with BNT162b2 and 45 (91.8%) of 49 vaccinated with CoronaVac achieved the 50% protection threshold for PRNT90. Allowing for an expected seven-fold waning of antibody titres over 6 months for those receiving CoronaVac, only 16.3% would meet the 50% protection threshold versus 79.6% of BNT162b2 vaccinees. Age was negatively correlated with PRNT90 antibody titres. Both vaccines induced SARS-CoV-2-specific CD4+ and CD8+ T-cell responses at 1 month post-vaccination but CoronaVac elicited significantly higher structural protein-specific CD4+ and CD8+ T-cell responses. Conclusion Vaccination with BNT162b2 induces stronger humoral responses than CoronaVac. CoronaVac induces higher CD4+ and CD8+ T-cell responses to the structural protein than BNT162b2.

Femoral facial syndrome (FFS) is a rare condition which may present with hypoplasia or aplasia of the femora and unusual facies characterized by long philtrum, thin upper lip and micrognathia. We present the case of a ten-month old infant with FFS who had retroglossal obstruction and who was treated with a pre-epiglottic baton plate. The pre-epiglottic baton plate can be a simple, non-invasive and effective tool for the clinical management of syndromic patients with mild-to-moderate upper airway obstruction due to micrognathia.

The purpose of this study was to examine 1) the relationship between apathy and leisure activity participation in nursing home residents with Alzheimer disease (AD) and 2) the moderator effect of the severity of dementia on this relationship. Data were collected from 290 residents with AD using the Apathy Evaluation Scale-informant version (AES-I), Leisure Activities Questionnaire (LAQ), and Clinical Dementia Rating scale (CDR). The multiple linear regression model showed that leisure activity participation (β=-0.452, p0.001) was negatively associated with apathy, while the severity of dementia (β=0.515, p0.001) was positively associated with apathy. The severity of dementia moderated the effect of leisure activity participation on apathy (β=-0.108, p=0.015). The results indicate that the effects of leisure activity participation on apathy diminish with the aggravation of AD. The severity of dementia should be considered when designing and delivering leisure activity interventions to manage apathy in nursing home residents with AD.

Introduction Agitation and impaired cognitive functioning are common symptoms of dementia, which require costly medication regimens that are associated with adverse effects. This study investigates the effects of dance interventions on agitation and cognitive function in people living with dementia in institutional care facilities. Methods Five electronic databases were searched for eligible studies on dance interventions for people living with dementia published between 2002 and 2021. Standard deviation and post mean values were extracted. Within-group Hedges’ g was computed for individual studies. Results Six randomised controlled trials and three non-randomised studies of satisfactory quality, with a total of 610 participants, were included. Statistical analysis found significant improvements in agitation and cognitive functioning with dance interventions. Discussion This review provided favourable evidence on the effects of dance interventions on agitation and cognitive functions in people with dementia. However, given the limited evidence, more studies are needed to confirm the effects.

Neural machine translation technologies are having increasing applications in clinical and healthcare settings. In multicultural countries, automatic translation tools provide critical support to medical and health professionals in their interaction and exchange of health messages with migrant patients with limited or non-English proficiency. While research has mainly explored the usability and limitations of state-of-the-art machine translation tools in the detection and diagnosis of physical diseases and conditions, there is a persistent lack of evidence-based studies on the applicability of machine translation tools in the delivery of mental healthcare services for vulnerable populations. Our study developed Bayesian machine learning algorithms using relevance vector machine to support frontline health workers and medical professionals to make better informed decisions between risks and convenience of using online translation tools when delivering mental healthcare services to Spanish-speaking minority populations living in English-speaking countries. Major strengths of the machine learning classifier that we developed include scalability, interpretability, and adaptability of the classifier for diverse mental healthcare settings. In this paper, we report on the process of the Bayesian machine learning classifier development through automatic feature optimisation and the interpretation of the classifier-enabled assessment of the suitability of original English mental health information for automatic online translation. We elaborate on the interpretation of the assessment results in clinical settings using statistical tools such as positive likelihood ratios and negative likelihood ratios.

This HR-pQCT study was conducted to examine bone properties of the distal tibia post-stroke and to identify clinical outcomes that were associated with these properties at this site. It was found that spasticity and gait speed were independently associated with estimated failure load in individuals with chronic stroke. Purpose (1) To examine the influence of stroke on distal tibia bone properties and (2) the association between these properties and clinical outcomes in people with chronic stroke. Methods Sixty-four people with stroke (age, 60.8 ± 7.7 years; time since stroke, 5.7 ± 3.9 years) and 64 controls (age: 59.4 ± 7.8 years) participated in this study. High-resolution peripheral quantitative computed tomography (HR-pQCT) was used to scan the bilateral distal tibia, and estimated failure load was calculated by automated finite element analysis. Echo intensity of the medial gastrocnemius muscle and blood flow of the popliteal artery were assessed with ultrasound. The 10-m walk test (10MWT), Fugl-Meyer Motor Assessment (FMA), and Composite Spasticity Scale (CSS) were also administered. Results The percent side-to-side difference (%SSD) in estimated failure load, cortical area, thickness, and volumetric bone mineral density (vBMD), and trabecular and total vBMD were significantly greater in the stroke group than their control counterparts (Cohen's d = 0.48-1.51). Isometric peak torque and echo intensity also showed significant within- and between-groups differences (p ≤ 0.01). Among HR-pQCT variables, the %SSD in estimated failure load was empirically chosen as one example of the strong discriminators between the stroke group and control group, after accounting for other relevant factors. The 10MWT and CSS subscale for ankle clonus remained significantly associated with the %SSD in estimated failure load after adjusting for other relevant factors (p ≤ 0.05). Conclusion The paretic distal tibia showed more compromised vBMD, cortical area, cortical thickness, and estimated failure load than the non-paretic tibia. Gait speed and spasticity were independently associated with estimated failure load. As treatment programs focusing on these potentially modifiable stroke-related impairments are feasible to administer, future studies are needed to determine the efficacy of such intervention strategies for improving bone strength in individuals with chronic stroke.

With the rapid development of Internet, network management and monitoring face a number of challenges, one of which is traffic classification. Meanwhile, SSL/TLS protocols are extensively used to encrypt the communication payloads, which makes traditional rule-based classification methods not applicable. Without fingerprints of sufficient distinguishing power, other existing methods cannot achieve satisfactory performances on encrypted traffic classification. In this paper, we focus on SSL/TLS encrypted traffic, and propose the Adaptive Fingerprint with Multi-level Attributes (AFMA) to classify them. AFMA combines field-level and sequence-level attributes to tackle encrypted traffic classification problem. Specifically, the distribution of server-to-client ciphersuites on applications is first imported to characterize application preferences. Moreover, besides message type sequences, length block sequences are especially designed to highlight the differences in application fingerprints. In addition, AFMA can adaptively learn the distributions for constructing the fingerprint by analyzing the overall statistics of the applications. The performance of AFMA was verified on a real-world dataset of a campus network (with 956,000+ SSL/TLS traffic flows for 18 popular applications). Our experiments show that AFMA could achieve a true positive rate of up to 99.46% and a false positive rate as low as 0.03%, which outperforms the state-of-the-art methods and our previous method.

Asparaginase is an important drug to treat childhood haematological malignancies. Data on the association between human leukocyte antigens (HLA) and asparaginase hypersensitivity among Chinese are lacking. We conducted a retrospective study to identify HLA alleles associated with asparaginase hypersensitivity among Chinese children with acute lymphoblastic leukaemia (ALL), mixed phenotype leukaemia and non-Hodgkin lymphoma (NHL), who received asparaginases with HLA typing performed between 2009 and 2019. 107 Chinese patients were analysed. 66.3% (71/107) developed hypersensitivity to at least one of the asparaginases. HLA-B*46:01 (OR 3.8, 95% CI 1.4–10.1, p p l-asparaginase hypersensitivities, which remained significant after adjustment for age, gender and B cell ALL [HLA-B*46:01 (adjusted OR 3.5, 95% 1.3–10.5, p = 0.02) and DRB1*09:01 (OR 4.4, 95% CI 1.6–13.3, p

Tibial stress fracture, anteromedial bone pain, and early subsidence could occur after unicondylar knee arthroplasty (UKA). The change in metaphyseal tibial bone density (MTBD) in the coronal and sagittal planes after UKA might be a contributing factor, but this has rarely been investigated. The aim of this study was to assess the regional and temporal change in MTBD in the coronal and sagittal planes in the first 2 years after UKA.Patients with fixed-bearing medial UKA were recruited. The change in MTBD in the first 24 months after UKA using digital radiological densitometry (DRD) was measured. Potential predictors and clinical correlations were analyzed.Eighty-four cases (female 60%) were selected for review. The follow up time was 63 (±17) months. Anterior and medial regions had the largest proportion of cases with MTBD reduction (90-97%, P 0.05). Reduction was largest at anterior and medial regions (21-29%, P 0.05) and smallest at posterior and lateral regions (5-15%, P 0.05). Maximal reduction occurred at 12 months for the medial region and 24 months for the anterior region. MTBDs of both regions were not significantly influenced by any confounding factors. Significant correlation was found between medial MTBD and Function Score at 6 months.Bone loss in a zonal pattern occurs in the first 2 years after UKA with the largest loss in the anterior region below the tibial tray. It is not affected by body mass index, perioperative alignment, or angle of correction. This suggests a physiological response to trauma other than a mechanical response to the change in bone strain.

Background The BNT162b2 mRNA vaccine has been shown to be effective at preventing serious COVID-19 events in clinical trials. There is less evidence on effectiveness in real-world settings, especially for older people. Here, we aimed to estimate vaccine effectiveness in the context of the rapid NHS mass-vaccination programme in England, exploiting age-based vaccination eligibility thresholds to minimise and correct for selection bias. Methods We studied 170,226 individuals between the ages of 80 and 83 years from community settings outside care homes who received one dose of BNT162b2 mRNA between the 15 and 20 December 2020 and were scheduled a second dose 21 days later. We matched these vaccine recipients to slightly younger (aged 76–79 years) persons not yet eligible to receive the vaccine on gender, area of residence, area deprivation, health status, living arrangements, acute illness, and history of seasonal flu vaccination. We compared their rates of COVID-19 positivity and hospitalisation in the subsequent 45 days. We adjusted for the increasing concentration of COVID-19 positivity in the control population caused by the requirement to have no COVID-19 symptoms prior to vaccination. Results Emergency hospital admissions were 51.0% (95% confidence interval 19.9 to 69.5%) lower and positive COVID-19 tests were 55.2% (40.8 to 66.8%) lower for vaccinated individuals compared to matched controls 21 to 27 days after first vaccination. Emergency admissions were 75.6% (52.8 to 87.6%) lower, and positive COVID-19 tests were 70.1% (55.1 to 80.1%) lower 35 to 41 days after first vaccination when 79% of participants had received a second dose within 26 days of their first dose. Conclusions Receipt of the BNT162b2 mRNA vaccine is effective at reducing COVID-19 hospitalisations and infections. The nationwide vaccination of older adults in England with the BNT162b2 mRNA vaccine reduced the burden of COVID-19.

Preparing large amounts of training data is the key to the success of machine learning. Due to the public’s concern about individual privacy, different techniques are proposed to achieve privacy preserving machine learning. Homomorphic encryption enables calculation on encrypted data in the cloud. However, current schemes either focus on single key or a specific algorithm. Cooperation between different institutions is quite common in this era of big data. Encrypting data from different institutions under one single key is a risk to data privacy. Moreover, constructing secure scheme for a specific machine learning algorithm lacks universality. Based on an additively homomorphic encryption supporting one multiplication, we propose a general multikey computing framework to execute common arithmetic operations on encrypted data such as addition, multiplication, comparison, sorting, division and etc. Our scheme can be used to run different machine learning algorithms. Our scheme is proven to be secure against semi-honest attackers and the experimental evaluations demonstrate the practicality of our computing framework.

This study aimed at investigating the surface morphology and nanotopography of normal enamel (NE) and developmentally hypomineralised enamel (HE) when subjected to various pretreatment protocols under scanning electron microscopy (SEM) and atomic force microscopy (AFM). Sixteen NE, 16 creamy/white (CW) HE and 16 yellow/brown (YB) HE specimens sectioned from extracted hypomineralised first permanent molars (FPMs) were included in this study. They were randomly distributed into 12 experimental groups (n = 4). Each group involved the following: (1) deproteinisation with Papacarie Duo® gel or no deproteinisation, and (2) the use of Scotchbond™ Universal Adhesive (Scotchbond) in self-etch (SE) mode or 37% phosphoric acid etchant. Subsequently, the surface morphology and nanotopography of pretreated enamel specimens were evaluated under SEM and AFM, respectively. SEM observation showed that deproteinisation with Papacarie Duo® gel before phosphoric acid etching led to favourable etching patterns. This was consistent across all groups irrespective of the type of enamel specimen and the severity of hypomineralisation. In contrast, AFM results identified three factors that influenced surface parameters: (1) type of enamel specimen, (2) severity of hypomineralisation and (3) etching mode. YB HE recorded higher surface roughness values than CW HE and NE when subjected to the same pretreatment protocol. Deproteinisation and the application of Scotchbond in SE mode led to minimal topographic changes; however, acid etching was associated with an increase in surface roughness. Deproteinisation with Papacarie Duo® gel followed by acid etching contributed to improved etching patterns on HE.

In recent years, research has found that people have stable predispositions to engage in certain behavioural patterns to work safely or unsafely, which vary among individuals as a function of their personality features. In this regard, an innovative machine learning model has been recently developed to predict workers’ behavioural tendency based on personality factors. This paper presents an empirical evaluation of the model’s prediction performance (i.e. the degree to which the model can generate similar results compared to reality) to address the issue of the model’s usability before it is implemented in real situations. As virtual reality allows a good grip on fidelity resembling real-world situations, it can stimulate more natural behaviour responses from participants to increase ecological validity of experimental results. Thus, we implemented a virtual reality experimentation environment to assess workers’ safety behaviour. The model’s prediction capability was then evaluated by comparing the model prediction results and workers’ safety behaviour as assessed in virtual reality. The comparison results showed that the model predictions on two dimensions of workers’ safety behaviour (i.e. task and contextual performance) were in good agreement with the virtual reality experimental results, with Spearman correlation coefficients of 79.7% and 87.8%, respectively. The machine learning model thus proved to have good prediction capability, which allows the model to help identify vulnerable workers who are prone to undertake unsafe behaviours. The findings also suggest that virtual reality is a promising method for measuring workers’ safety behaviour as it can provide a realistic and safe environment for experimentation.

In a proxy re-signature scheme, a semi-trusted proxy can convert Alice's (also called as delegatee's) signature into Bob's (also called as delegator's) signature on the same message. However, the proxy itself cannot produce any signatures on behalf of either Alice or Bob. There exists some unidirectional one-use and multi-use (a message can be re-signed a polynomial number of times) proxy re-signature schemes. In some scenarios of big data, it is required to design unidirectional infinite-use (a message can be re-signed infinite number of times) proxy re-signature schemes. In this paper, we propose the first unidirectional infinite-use proxy re-signature scheme and identity-based unidirectional infinite-use proxy re-signature scheme with private re-signature keys based on lattice and prove that they are secure in the random oracle model.

Increased serum uric acid (SUA) is common in type 2 diabetes mellitus (T2DM) and is associated with left ventricular (LV) myocardial dysfunction. Nonetheless the association of SUA with right ventricular (RV) function in T2DM has not been studied. This study aimed to investigate the association of SUA with biventricular myocardial function in patients with T2DM.A total of 560 patients with T2DM were enrolled and divided into four groups according to sex-specific quartiles of SUA. Transthoracic echocardiography was performed and two-dimensional speckle tracking was used to measure biventricular myocardial strain, including LV global longitudinal strain (GLS), circumferential strain (CS), radial strain (RS), and RV free wall longitudinal strain (RV-FWLS). The absolute value of all biventricular strain parameters showed a stepwise decrease across SUA quartiles (all P 0.01). In particular, LV assessment by GLS, CS and RS demonstrated that those in the 4th quartile were impaired compared with the other quartiles (all P 0.05). Similarly, RV-FWLS of the 4th quartile was significantly impaired compared with the 1st and 2nd quartiles (all P 0.05). The same reduction in biventricular strain across SUA quartiles was observed in patients with estimated glomerular filtration rate or ≥60 ml/min/1.73 mSUA was independently associated with biventricular myocardial dysfunction in asymptomatic T2DM patients, regardless of renal function or diabetic control.

Objectives To systematically assess the current literature on soft tissue response associated with osseous movement following orthognathic surgery in patients with facial asymmetry. Methods Six electronic databases (PubMed, EMBASE (via Ovid), Medline (via Ovid), Cochrane Library, Scopus, and Web of Science) were searched for studies evaluating hard and soft tissue response 3-dimensionally after orthognathic surgery and gray literature using MeSH terms and keywords. The methodological quality and level of evidence of the included studies were analyzed using EPHPP and GRADE, respectively. Results The primary search yielded 125 articles, and 10 articles that satisfied the predefined inclusion criteria were finally included. All the included articles evaluated soft tissue response, whereas six of them additionally investigated the magnitude of the soft tissue response. Soft tissues move with hard tissues horizontally and anteroposteriorly; however, soft tissue movement is less than hard tissue movement. In addition, soft tissue movement is more pronounced in the lower facial central region. Six articles were judged as having “strong” methodological quality, and the evidence was found to be of “low” quality for the soft tissue response and magnitude of the response. Conclusion Despite a low level of evidence, the present review substantiates a favorable 3dimensional soft tissue response following osseous surgery. The soft tissue response is more pronounced horizontally, antero-posteriorly and in the lower central facial region. Nevertheless, well-designed prospective studies with a higher level of evidence are needed.

Purpose Thyroid dysfunction, including thyroiditis, is well recognized in COVID-19 patients. We evaluated thyroid ultrasonographic features among COVID-19 survivors, which are less well known. Methods Adult COVID-19 survivors without known thyroid disorders who attended dedicated COVID-19 clinic underwent thyroid ultrasonography and assessment of thyroid function and autoimmunity. Adults admitted for acute non-thyroidal surgical problems and negative for COVID-19 were recruited as control. SARS-CoV-2 viral load (VL) was presented as the inverse of cycle threshold values from the real-time reverse transcription-polymerase chain reaction of the respiratory specimen on admission. Results In total, 79 COVID-19 patients and 44 non-COVID-19 controls were included. All abnormal thyroid function tests during acute COVID-19 recovered upon follow-up. Thyroid ultrasonography was performed at a median of 67 days after acute COVID-19. The median thyroid volume was 9.73 mL (IQR: 7.87–13.70). In multivariable linear regression, SARS-CoV-2 VL on presentation (standardized beta −0.206, p = 0.042) inversely correlated with thyroid volume, in addition to body mass index at the time of ultrasonography (p

Objective Long COVID (LC) is an emerging global health issue. Fatigue is a common feature. Whether thyroid function and autoimmunity play a role is uncertain. We aimed to evaluate the prevalence and predictors of LC and the potential role of thyroid function and autoimmunity in LC. Methods We included consecutive adults without known thyroid disorder, admitted to a major COVID-19 centre for confirmed COVID-19 from July to December 2020 who had thyroid function tests (TFTs) and anti-thyroid antibodies measured on admission and at follow-up. LC was defined by the presence or persistence of symptoms upon follow-up. Results In total, 204 patients (median age: 55.0 years; 46.6% men) were reassessed at a median of 89 days (IQR: 69–99) after acute COVID-19. Forty-one (20.1%) had LC. Female (adjusted odds ratio [aOR] 2.48, p=0.018) and SARS-CoV-2 PCR cycle threshold value, Long COVID is common among COVID-19 survivors, with female and those with higher viral load in acute COVID-19 particularly vulnerable. Our observation of incident anti-TPO positivity among COVID-19 survivors warrants further follow-up for thyroid dysfunction. Whether anti-TPO plays a protective role in long COVID remains to be elucidated.

Background Around 15% of the Hong Kong population was found to suffer from overactive bladder (OAB), but the current available treatments, such as medication, behavioral therapy and physical therapy are unsatisfactory. Previous studies have suggested that acupuncture may have promising effect for OAB, but some limitations on the study design render the evidence questionable. This study aimed to evaluate the effectiveness and safety of acupuncture treatment for patients with OAB in Hong Kong. Methods One hundred patients with OAB were enrolled. The patients were randomized to receive either active acupuncture or sham needle intervention twice a week for 8 consecutive weeks, and had a follow-up consultation 12 weeks after the completion of acupuncture intervention. The primary outcome assessment was the 3-Day Voiding Diary, which records daytime and night-time urinary frequency and symptoms, at the baseline, the end of the 8-week intervention and 12 weeks after acupuncture intervention. Secondary outcomes included Urine NGF level, Incontinence Impact Questionnaire (IIQ-7) and Urogenital Distress Inventory (UDI-6), as well as Overactive Bladder Symptom Score (OABSS). Results After 16 sessions of treatment, when compared with the baseline, both active and sham acupuncture significantly reduced the frequency of urgency urinary incontinence (UUI), daytime and night-time urinary frequency as well as the scores of IIQ-7, UDI-6 and OABSS. Moreover, the treatment effects could last for at least 3 months. However, no significant difference in frequency of UUI and daytime urinary frequency was found between the active and sham acupuncture groups. On the other hand, the night-time urinary frequency decreased more significantly during the treatment and follow-up in the active acupuncture group than in the sham control group after controlling baseline night-time urinary frequency. Urine NGF level could not be detected by ELISA method in our experiments. Conclusion This study suggests a beneficial effect of acupuncture on improving OAB symptoms. Both active and sham acupuncture treatment were able to improve the symptoms of frequency of urgency urinary incontinence, and the daytime and night-time urinary frequency, while only mild adverse effects were found. This project was unable to establish the specific effect of acupuncture for OAB. Trial registration Chinese Clinical Trial Registry, ChiCTR-INR-16010048. Registered on 29 Nov 2016.

In January 2020, Novel Coronavirus Disease 2019 (COVID-19) resulted in a global pandemic, creating uncertainty towards the management of Liver Transplantation (LT) programmes. Lombardy has been the most affected region in Italy: The current mortality rate of COVID-19 patients is 18,3% (10022 deaths) (April 10th) with hospitals in Lombardy having to expand the total number of ICU beds from 724 to 1381 to accommodate infected patients. There has been a drastic decrease in liver donors. From February 23rd until April 10th, 17 LTs were performed in Lombardy. Mean donor age was 49 years (range 18-74) whereas mean recipient age was 55 (13-69); mean MELD Score was 12 (6-24). All donors underwent screening for SARS CoV-2 prior to LT. Two patients tested positive after LT, and one patient died for COVID on POD 30. 16 patients are alive after an average of 30 days post LT (range 3-46). 10 patients have been discharged. This study has found no specific reason concerning the safety of recipients, to stop liver transplantation programmes. Several Key-lessons from our experience are reported. However, due to the complex circumstances which surround the viral outbreak, the cessation or a reduction in LT activity is a pragmatic requirement.

We assessed right ventricular (RV)–pulmonary arterial (PA) coupling in patients with repaired tetralogy of Fallot (TOF). Sixty patients (34 males) aged 18.6 ± 8.3 years at 14.8 ± 7.4 years after repair and 60 controls were studied. Two-dimensional, tissue Doppler and speckle tracking echocardiography and colour flow mapping were performed to assess RV end-systolic (ESA) and -diastolic areas, tricuspid valve Doppler and myocardial velocities, left ventricular (LV) and RV deformation and pulmonary (PR), tricuspid regurgitation (TR), respectively. The ratios of RV area change to ESA and peak tricuspid annular systolic (s) velocity to RV ESA indexed to body surface area reflected RV–PA coupling. Patients had greater RV areas and reduced tricuspid annular and myocardial velocities, LV and RV myocardial mechanics compared to controls (all p

We demonstrate the potential for machine learning systems to predict three-dimensional (3D)-relevant NMR properties beyond traditional 1 H- and 13 C-based data, with comparable accuracy to density functional theory (DFT) (but orders of magnitude faster). Predictions of DFT-calculated 15 N chemical shifts for 3D molecular structures can be achieved using a machine learning system-IMPRESSION (Intelligent Machine PREdiction of Shift and Scalar information Of Nuclei), with an accuracy of 6.12-ppm mean absolute error (∼1% of the δ15 N chemical shift range) and an error of less than 20 ppm for 95% of the chemical shifts. It provides less accurate raw predictions of experimental chemical shifts, due to the limited size and chemical space diversity of the training dataset used in its creation, coupled with the limitations of the underlying DFT methodology in reproducing experiment.

Introduction To evaluate the performance of the Vesical Imaging-Reporting and Data System (VIRADS) in differentiating muscle-invasive and non-muscle-invasive bladder cancer and whether this reporting system improves inter-reader agreement. Methods Sixty-four cases of multiparametric 3 tesla bladder MRI from January 2014 to May 2020 were reviewed retrospectively. T2-weighted, diffusion and post-contrast images were reviewed. All magnetic resonance images were reported by a radiologist with 15 years' experience (Reader 1) and a final year radiology trainee with a special interest in urogenital imaging with 3 years of experience (Reader 2). Both readers were blinded to clinical history and histopathology results when scoring each lesion. Results The sensitivity and specificity for differentiating MIBC and NMIBC were 91% and 68%, respectively, for Reader 1 and 91% and 63%, respectively, for Reader 2. The inter-reader agreement for assigning VIRADS scores was 0.79. The area under the receiver operator curve for Reader 1 and 2 were not significantly different (Reader 1 = 0.79, Reader 2 = 0.77, P = 0.83). Conclusions Staging of bladder cancer prior to treatment can be accurately and reliably diagnosed using VIRADS, a novel, standardised reporting system for bladder MRI.

BACKGROUND Although metastatic adenocarcinoma of the ileum is not uncommon, solitary metastasis to the seminal vesicle has not been reported. We report a patient with recurrent hematospermia diagnosed with metastasis to the seminal vesicle following ileal adenocarcinoma resection, his subsequent management and outcome. CASE SUMMARY A 46-year-old man presented with recurrent episodes of painless hematospermia. This was not associated with any lower urinary tract symptoms. He had a past medical history of ileal tumor at the terminal ileum with solitary mesenteric lymph node metastasis on presentation, and underwent partial ileectomy and lymphadenectomy 4 years ago. Subsequent investigations included positron-emission tomography and computed tomography imaging confirmed the very unusual diagnosis of a solitary tumor at the left seminal vesicle. Laparoscopic left-sided vesiculectomy was carried out. Histological analysis with immunohistochemistry showed that CDX-2 was positive and CK7 was negative, and the appearance was consistent with the diagnosis of recurrent metastatic adenocarcinoma of his previously treated intestine primary. The patient had an uneventful post-operative recovery. He received adjuvant chemoradiotherapy following surgery. He remained asymptomatic until he developed multiple bone and pulmonary metastases one year after surgery. CONCLUSION Clinicians should be aware of hematospermia as the first symptom of metastatic recurrence in patients with a history of ileal adenocarcinoma.

To assess the effect from individual component in combinations of steroid, ascorbic acid, and thiamine on outcomes in adults with sepsis and septic shock with component network meta-analysis (NMA). We searched PubMed, EMBASE, and the Cochrane Library Central Register of Controlled Trials from 1980 to March 2021 for randomized controlled trials (RCT) that studied the use of glucocorticoid, fludrocortisone, ascorbic acid, and thiamine in patients with sepsis and septic shock. Citations screening, study selection, data extraction, and risk of bias assessment were independently performed by two authors. The primary outcome was short-term mortality. Secondary outcomes were longer-term mortality, time to resolution of shock and duration of mechanical ventilation. Thirty-three RCTs including 9898 patients presented on short-term mortality. In additive component NMA, patients on ascorbic acid alone (RR 0.74, 95% CI 0.57–0.97) or the combination of glucocorticoid and fludrocortisone (RR 0.89, 95% CI 0.80–0.99) had lower short-term mortality, but only the latter was associated with improved long-term mortality (RR 0.89, 95% CI 0.82–0.98). The use of glucocorticoid or the combination of glucocorticoid, ascorbic acid and thiamine hastened resolution of shock. Component NMA showed glucocorticoid (MD − 0.96, 95% CI − 1.61 to − 0.30) but not ascorbic acid or thiamine shortened the time to resolution of shock. Glucocorticoid shortened the duration of mechanical ventilation (MD − 1.48, 95% CI − 2.43 to − 0.52). In adults with sepsis and septic shock, the combination of glucocorticoid and fludrocortisone improved short-term and longer-term mortality. Glucocorticoid shortened the time to resolution of shock and duration of mechanical ventilation. There was no strong evidence supporting the routine use of thiamine and ascorbic acid, but they were associated with minimal adverse effects.

Indirect excess morbidity in the COVID-19 pandemic may arise from public health risk-mitigation efforts such as stay-at-home orders and re-purposing of healthcare services1 . Increased mental health disorders and shortfalls in the care of long-term conditions are described.

Aberrant morphological changes in lumbar multifidus muscle (LMM) are prevalent among patients with low back pain (LBP). Motor control exercise (MCE) aims to improve the activation and coordination of deep trunk muscles (eg, LMM), which may restore normal LMM morphology and reduce LBP. However, its effects on LMM morphology have not been summarized. This review aimed to summarize evidence regarding the (1) effectiveness of MCE in altering LMM morphometry and decreasing LBP; and (2) relations between post-MCE changes in LMM morphometry and LBP/LBP-related disability. Cumulative Index to Nursing and Allied Health Literature, MEDLINE, Cochrane Central Register of Controlled Trials, the Physiotherapy Evidence Database, EMBASE and SPORTDiscus were searched from inception to 30 September 2020 to identify relevant randomized controlled trials. Two reviewers independently screened articles, extracted data, and evaluated risk of bias and quality of evidence. Four hundred and fifty-one participants across 9 trials were included in the review. Very low-quality evidence supported that 36 sessions of MCE were better than general physiotherapy in causing minimal detectable increases in LMM cross-sectional areas of patients with chronic LBP. Very low- to low-quality evidence suggested that MCE was similar to other interventions in increasing resting LMM thickness in patients with chronic LBP. Low-quality evidence substantiated that MCE was significantly better than McKenzie exercise or analgesics in increasing contracted LMM thickness in patients with chronic LBP. Low-quality evidence corroborated that MCE was not significantly better than other exercises in treating people with acute/chronic LBP. Low-quality evidence suggested no relation between post-MCE changes in LMM morphometry and LBP/LBP-related disability. Collectively, while MCE may increase LMM dimensions in patients with chronic LBP, such changes may be unrelated to clinical outcomes. This raises the question regarding the role of LMM in LBP development/progression.

Cross-modal retrieval has received increasing attentions for efficient retrieval across different modalities, and hashing technique has made significant progress recently due to its low storage cost and high query speed. However, most existing cross-modal hashing works still face the challenges of narrowing down the semantic gap between different modalities and training with imbalanced multi-modal data. This article presents an efficient Adversarial Tri-Fusion Hashing Network (ATFH-N) for cross-modal retrieval, which lies among the early attempts to incorporate adversarial learning for working with imbalanced multi-modal data. Specifically, a triple fusion network associated with zero padding operation is proposed to adapt either balanced or imbalanced multi-modal training data. At the same time, an adversarial training mechanism is leveraged to maximally bridge the semantic gap of the common representations between balanced and imbalanced data. Further, a label prediction network is utilized to guide the feature learning process and promote hash code learning, while additionally embedding the manifold structure to preserve both inter-modal and intra-modal similarities. Through the joint exploitation of the above, the underlying semantic structure of multimedia data can be well preserved in Hamming space, which can benefit various cross-modal retrieval tasks. Extensive experiments on three benchmark datasets show that the proposed ATFH-N method yields the comparable performance in balanced scenario and brings substantial improvements over the state-of-the-art methods in imbalanced scenarios.

A stratified medicine approach for the treatment of psoriasis promises greater certainty of clinical decision making through prediction of response on the basis of clinical, pharmacological, and -omics data from an individual patient. As yet, there is no predictive model for treatment response in routine clinical use for psoriasis. The Psoriasis Stratification to Optimise Relevant Therapy (PSORT) Consortium is a United Kingdom Medical Research Council‒funded, academic‒industrial stratified medicine consortium established with the objective of discovering the predictors and stratifiers of response of psoriasis to biologic therapies. A showcase meeting was convened and attended by 80 stakeholders at the Royal College of Physicians, London, United Kingdom on 18 November 2019. The purpose was to disseminate the research findings from the PSORT consortium discovered thus far. This report summarizes the presentations made on the day and the significant advances made by PSORT toward a stratified medicine approach to the management of psoriasis.

Introduction: The intra-aortic balloon pump (IABP) and Impella are left ventricular unloading devices with peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) in place and later serve as bridging therapy when VA-ECMO is terminated. We aimed to determine the potential differences in clinical outcomes and rate of complications between the two combinations of mechanical circulatory support. Methods: This was a retrospective, single institutional cohort study conducted in the intensive care unit (ICU) of Queen Elizabeth Hospital, Hong Kong. Inclusion criteria included all patients aged ⩾18 years, who had VA-ECMO support, and who had left ventricular unloading by either IABP or Impella between January 1, 2018 and October 31, 2020. Patients Results: Fifty-two patients with ECMO + IABP and 14 patients with ECMO + Impella were recruited. No statistically significant difference was observed in terms of ECMO duration (2.5 vs 4.6 days, p = 0.147), ICU LOS (7.7 vs 10.8 days, p = 0.367), and hospital LOS (14.8 vs 16.5 days, p = 0.556) between the two groups. No statistically significant difference was observed in the ECMO, ICU, and hospital mortalities between the two groups. Specific complications related to the ECMO and Impella combination were also noted. Conclusions: Impella was not shown to offer a statistically significant clinical benefit compared with IABP in conjunction with ECMO. Clinicians should be aware of the specific complications of using Impella.

Purpose The purpose of this paper is to investigate the literature on resilience factors applied to post-disaster reconstruction projects and to develop a guiding framework to assist in their strategic selection and application. Design/methodology/approach A systematic review was undertaken on the literature’s account in four major bibliographic databases to elicit resilience factors contributing to improving post-disaster reconstruction projects' robustness. Through summative content analysis and open-coding of research outputs over the past decade, the factors identified informed the development of a conceptual framework that can significantly impact the built environment’s resilience development process. Findings The review found 24 resilience factors open-coded into five criteria groups: governance, innovations, reconstruction approaches, resource management and stakeholder expectations. While these factors have influenced reconstruction projects, the recently increased participation of clients and end-users in construction management accentuates their strategic selection and applications. Research limitations/implications The research focused on English language articles; therefore, any claim to a comprehensive resilience factors listing can be amiss. The framework provides a platform for developing clear measurement indicators for allocating project resources and determining resilience deficiencies. Practical implications Results confirm the designs and assessment of a resilient built environment extends beyond the traditional structural characteristics, but includes the ability of the integrated network of buildings and infrastructure to support the continuous delivery of the community’s social and economic services in normal and post-disaster settings. Originality/value The review is very specific as it attempts to develop a novel conceptual framework for guiding developers and practitioners in the application of resiliency to post-disaster reconstruction projects.

There is substantial evidence regarding the association between psoriasis and the elevated risk of cardiovascular (CV) disease. Many patients with psoriasis may also be concerned that their treatments may be associated with a further increase in the risk of CV disease. In this article, we summarize the data regarding the biological role of interleukin (IL)-12/23 in atherogenesis. We performed a literature search for currently known CV safety data from trials and observational studies of treatments targeting IL-12/23 in psoriasis, i.e. the p40 inhibitors ustekinumab and briakinumab, and the p19 inhibitors guselkumab, risankizumab, and tildrakizumab. On balance, extensive evidence supports the CV safety of ustekinumab, with over 14 years of follow-up data in multiple cohort studies and randomized controlled trials (RCTs). One self-controlled study concluded ustekinumab may precipitate short-term raised CV risk, but the study had limitations hindering interpretation. The safety evidence from RCTs on the p19 inhibitors are reassuring thus far, but these studies may not detect rare CV events in real-world patients. We concluded that the overall evidence does not show that ustekinumab is associated with an increase in the risk of CV disease in patients with psoriasis, but further data are awaited to assess the CV safety of p19 inhibitors for the treatment of psoriasis.

Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer. NEPC arises de novo only rarely; the disease predominantly develops from adenocarcinoma in response to drug-induced androgen receptor signalling inhibition, although the mechanisms behind this transdifferentiation are a subject of debate. The survival of patients with NEPC is poor, and few effective treatment options are available. To improve clinical outcomes, understanding of the biology and molecular mechanisms regulating NEPC development is crucial. Various NEPC molecular drivers make temporal contributions during NEPC development, and despite the limited treatment options available, several novel targeted therapeutics are currently under research.

INTRODUCTION: Clinical practice guidelines (CPGs), statements that include recommendations intended to optimise patient care, play a critical role in standardising and improving treatment outcomes based on best evidence. It is currently unclear how many CPGs are available globally to assist clinicians in the management of patients with skin disease.OBJECTIVE: Our aim was to search for and identify CPGs for dermatological conditions with the highest burden globally.METHODS: We adapted a list of 12 dermatological conditions with the highest burden from the Global Burden of Disease (GBD) study 2019. A broad systematic literature search was conducted to identify CPGs published between October 2014 to October 2019. The scoping review was conducted and reported in accordance with the PRISMA framework.RESULTS: A total of 226 CPGs were included. Melanoma had the greatest representation in the CPGs, followed by dermatitis and psoriasis. Skin cancers had the highest CPGs representation overall but with lower GBD disease burden ranking. There was an uneven distribution by geographical region, with resource-poor settings being under-represented. The CPGs' skin disease categories correlated weakly with the GBD disability-adjusted life-years metrics. 89 CPGs did not have funding disclosures and 34 CPGs were behind a paywall.CONCLUSION: The global production of dermatology CPGs showed wide variation in geographical representation, article accessibility and funding reporting. The number of skin disease CPGs were not commensurate with its disease burden. Future work will critically appraise the methodology and quality of dermatology CPGs and lead to the production of an accessible online resource summarising these findings.