An International Collaborative Consensus Statement on En Bloc Resection of Bladder Tumour Incorporating Two Systematic Reviews, a Two-round Delphi Survey and a Consensus Meeting

Funding/Support and role of the sponsor: This study was supported by the General Research Fund/Early Career Scheme of the Research Grants Council, Hong Kong, China (reference no. 24116518).Peer reviewedPostprin

Novel venom-derived inhibitors of the human EAG channel, a putative antiepileptic drug target

Recently, we and other groups revealed that gain-of-function mutations in the human ether à go-go voltage-gated potassium channel hEAG1 (K10.1) lead to developmental disorders with associated infantile-onset epilepsy. However, the physiological role of hEAG1 in the central nervous system remains elusive. Potent and selective antagonists of hEAG1 are therefore much sought after, both as pharmacological tools for studying the (patho)physiological functions of this enigmatic channel and as potential leads for development of anti-epileptic drugs. Since animal venoms are a rich source of potent ion channel modifiers that have been finely tuned by millions of year of evolution, we screened 108 arachnid venoms for hEAG1 inhibitors using electrophysiology. Two hit peptides (Aa1a and Ap1a) were isolated, sequenced, and chemically synthesised for structure-function studies. Both of these hEAG1 inhibitors are C-terminally amidated peptides containing an inhibitor cystine knot motif, which provides them with exceptional stability in both plasma and cerebrospinal fluid. Aa1a and Ap1a are the most potent peptidic inhibitors of hEAG1 reported to date, and they present a novel mode of action by targeting both the activation and inactivation gating of the channel. These peptides should be useful pharmacological tools for probing hEAG1 function as well as informative leads for the development of novel anti-epileptic drugs

Training immunophenotyping deep learning models with the same-section ground truth cell label derivation method improves virtual staining accuracy

IntroductionDeep learning (DL) models predicting biomarker expression in images of hematoxylin and eosin (H&E)-stained tissues can improve access to multi-marker immunophenotyping, crucial for therapeutic monitoring, biomarker discovery, and personalized treatment development. Conventionally, these models are trained on ground truth cell labels derived from IHC-stained tissue sections adjacent to H&E-stained ones, which might be less accurate than labels from the same section. Although many such DL models have been developed, the impact of ground truth cell label derivation methods on their performance has not been studied.MethodologyIn this study, we assess the impact of cell label derivation on H&E model performance, with CD3+ T-cells in lung cancer tissues as a proof-of-concept. We compare two Pix2Pix generative adversarial network (P2P-GAN)-based virtual staining models: one trained with cell labels obtained from the same tissue section as the H&E-stained section (the ‘same-section’ model) and one trained on cell labels from an adjacent tissue section (the ‘serial-section’ model).ResultsWe show that the same-section model exhibited significantly improved prediction performance compared to the ‘serial-section’ model. Furthermore, the same-section model outperformed the serial-section model in stratifying lung cancer patients within a public lung cancer cohort based on survival outcomes, demonstrating its potential clinical utility.DiscussionCollectively, our findings suggest that employing ground truth cell labels obtained through the same-section approach boosts immunophenotyping DL solutions

Seasonal effects of influenza on mortality in a subtropical city

<p>Abstract</p> <p>Background</p> <p>Influenza has been associated with a heavy burden of mortality. In tropical or subtropical regions where influenza viruses circulate in the community most of the year, it is possible that there are seasonal variations in the effects of influenza on mortality, because of periodic changes in environment and host factors as well as the frequent emergence of new antigenically drifted virus strains. In this paper we explored this seasonal effect of influenza.</p> <p>Methods</p> <p>A time-varying coefficient Poisson regression model was fitted to the weekly numbers of mortality of Hong Kong from 1996 to 2002. Excess risks associated with influenza were calculated to assess the seasonal effects of influenza.</p> <p>Results</p> <p>We demonstrated that the effects of influenza were higher in winter and late spring/early summer than other seasons. The two-peak pattern of seasonal effects of influenza was found for cardio-respiratory disease and sub-categories pneumonia and influenza, chronic obstructive pulmonary disease, cerebrovascular diseases and ischemic heart disease as well as for all-cause deaths.</p> <p>Conclusion</p> <p>The results provide insight into the possibility that seasonal factors may have impact on virulence of influenza besides their effects on virus transmission. The results warrant further studies into the mechanisms behind the seasonal effect of influenza.</p

Shining a Light on Venom-Peptide Receptors: Venom Peptides as Targeted Agents for In Vivo Molecular Imaging

Molecular imaging has revolutionised the field of biomedical research by providing a non-invasive means to visualise and understand biochemical processes within living organisms. Optical fluorescent imaging in particular allows researchers to gain valuable insights into the dynamic behaviour of a target of interest in real time. Ion channels play a fundamental role in cellular signalling, and they are implicated in diverse pathological conditions, making them an attractive target in the field of molecular imaging. Many venom peptides exhibit exquisite selectivity and potency towards ion channels, rendering them ideal agents for molecular imaging applications. In this review, we illustrate the use of fluorescently-labelled venom peptides for disease diagnostics and intraoperative imaging of brain tumours and peripheral nerves. Finally, we address challenges for the development and clinical translation of venom peptides as nerve-targeted imaging agents

The Effect of Conduction Exercise and Self-Acupressure in Treatment of Parkinson’s Disease: A Pilot Study

Introduction. Parkinson’s disease cannot be well treated by conventional medication. Acupuncture and Tai Chi are proven to be effective in relieving symptoms of Parkinson’s disease. Traditional Chinese medicine exercises may prove to be an effective complementary therapy. Objective. To evaluate the efficacy and safety of conduction exercise and self-acupressure in treating Parkinson’s disease. Method. This study is an accessor- and data analyzer-blind, add-on, randomized, controlled, pilot clinical study. In the treatment group, they were taught to practice conduction exercise and self-acupressure for 8 weeks. No additional treatment was given in the control group. Assessments were done at week 4 and week 8 of the treatment period. The primary outcomes are the total score and domain scores of the Chinese version of 39-item Parkinson’s Disease Questionnaire. The secondary outcomes are the total score and domain scores of a custom-designed questionnaire, which is a short form of Nonmotor Symptom Scale. Results. 22 patients in the treatment group and 14 in the control group continued to the treatment phase. Patients in the treatment group displayed improvement trends in primary and secondary outcomes. Improvements were significant in two areas of a custom-designed questionnaire: total score (p=0.014) and domain score of gastrointestinal tract (p=0.004). No severe adverse events were reported. Conclusion. Conduction exercise and self-acupressure were well accepted by and feasible for Parkinson’s disease patients. The data generated can be used for the planning of future studies. The exercise regime can be promoted as a home-based, self-practice therapy for Parkinson’s disease patients, due to its safety, low cost, and convenience in implementation. This study is registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-17011987, on 14 July 2017)

Cardiac health knowledge and misconceptions among nursing students: implications for nursing curriculum design

Abstract Background Cardiac misconceptions are common among healthcare professionals. The development of professional knowledge is considered an essential component of nursing education. Nurses, regardless of their grade, skills, and experience, should be updated with information so as to be able to rectify their misconceptions, as these could affect patient health outcomes. As the literature evaluating the cardiac knowledge and misconceptions of nursing students is sparse, a study of the subject seems warranted. Methods A cross-sectional sample survey was used to study the cardiac knowledge and cardiac misconceptions of nursing students in Hong Kong. The study sample included 385 senior nursing students from three universities. Their level of knowledge of cardiac disease was assessed using the modified Coronary Heart Disease Knowledge Test. The York Cardiac Beliefs Questionnaire (YCBQv1) was used to examine cardiac misconceptions. Results The scores for the nursing students’ level of knowledge were diverse. Their mean score in the Cardiac Knowledge Test was 12.27 out of 18 (SD 2.38), with a range of 2–17. For cardiac misconceptions, their mean score in the YCBQv1 was 6.98 out of 20 (SD 2.84), with a range of 0–14. A negative correlation, r = −0.33 was found among students with more knowledge and fewer misconceptions. (p < 0.001). The Chi-square tests found some associations between the students’ experiences of caring for cardiac patients and misconceptions about stress and physiology. Conclusions The results of our analyses indicate a diversity in levels of knowledge among the nursing students. Students with higher scores in cardiac knowledge did not necessarily have fewer misconceptions. There were associations between the students’ misbeliefs and their caregiving experiences with cardiac patients. This study presents a framework for designing the contents of cardiac nursing programmes and is a starting point for promoting research on misconceptions held by undergraduate nursing students. A new paradigm of teaching should include inputs from both perspectives to help students to make critical use of theoretical knowledge to rectify their misconceptions and pursue excellence in the working world