Biomarker discovery with quantum neural networks: a case-study in CTLA4-activation pathways.

BACKGROUND: Biomarker discovery is a challenging task due to the massive search space. Quantum computing and quantum Artificial Intelligence (quantum AI) can be used to address the computational problem of biomarker discovery from genetic data. METHOD: We propose a Quantum Neural Networks architecture to discover genetic biomarkers for input activation pathways. The Maximum Relevance-Minimum Redundancy criteria score biomarker candidate sets. Our proposed model is economical since the neural solution can be delivered on constrained hardware. RESULTS: We demonstrate the proof of concept on four activation pathways associated with CTLA4, including (1) CTLA4-activation stand-alone, (2) CTLA4-CD8A-CD8B co-activation, (3) CTLA4-CD2 co-activation, and (4) CTLA4-CD2-CD48-CD53-CD58-CD84 co-activation. CONCLUSION: The model indicates new genetic biomarkers associated with the mutational activation of CLTA4-associated pathways, including 20 genes: CLIC4, CPE, ETS2, FAM107A, GPR116, HYOU1, LCN2, MACF1, MT1G, NAPA, NDUFS5, PAK1, PFN1, PGAP3, PPM1G, PSMD8, RNF213, SLC25A3, UBA1, and WLS. We open source the implementation at: https://github.com/namnguyen0510/Biomarker-Discovery-with-Quantum-Neural-Networks .

Annona glabra L. Seeds: An Agricultural Waste Biosorbent for the Eco-Friendly Removal of Methylene Blue.

The seeds of Annona glabra L., an invasive plant in Vietnam, were first employed as a new biosorbent for the adsorption of methylene blue (MB) from aqueous media. The characterizations of the material using FT-IR, SEM, nitrogen adsorption-desorption analysis, and point of zero charge reveals that it possesses a rough and irregular surface, various polar functional groups, and pHpzc of 5.5. Certain adsorption conditions including adsorbent dose, solution pH, contact time, and initial concentration of MB were found to affect adsorption efficiency. The kinetic data are well fitted with pseudo-second-order model with the adsorption rate of 0.002 g mg-1 min-1 and initial rate of 4.46 mg g-1 min-1. For the adsorption isotherm, three nonlinear models were used to analyze the experiment data, including Langmuir, Freundlich, and Temkin. The results indicate that the Langmuir model best describes the adsorption of Annona glabra L. seeds powder (AGSP) with a maximum adsorption capacity of 98.0 mg g-1. The investigation underpins the adsorption mechanism, whereby the electrostatic attraction between positively charged MB and negatively charged surface of AGSP is expected to be the predominant mechanism, together with hydrogen bonding and pi-pi interaction. These results make AGSP an interesting biosorbent concerning its environmental friendliness, cost-effectiveness, and relatively high dye adsorption capacity.

A global research agenda on public health and social measures during emergencies.

The importance of strong coordination for research on public health and social measures was highlighted at the Seventy-fourth World Health Assembly in 2021. This article describes efforts undertaken by the World Health Organization (WHO) to develop a global research agenda on the use of public health and social measures during health emergencies. This work includes a multistep process that started with a global technical consultation convened by WHO in September 2021. The consultation included experts from around the world and from a wide range of disciplines, such as public health, education, tourism, finance and social sciences, and aimed to identify research and implementation approaches based on lessons learnt during the coronavirus disease 2019 pandemic. To prepare for future epidemics and pandemics, it is essential to adopt a more robust, comparable and systematic research approach to public health and social measures. Such comprehensive approach will better inform agile, balanced and context-specific implementation decisions during future emergencies. This article describes the methods used to develop global research priorities for public health and social measures and the next steps needed.

La soixante-quatorzième Assemblée mondiale de la Santé en 2021 a souligné l'importance d'une coordination solide pour la recherche sur la santé publique et les mesures sociales. Le présent article décrit les efforts entrepris par l'Organisation mondiale de la santé (OMS) pour élaborer un programme de recherche mondial sur l'utilisation des mesures de santé publique et des mesures sociales lors de situations d'urgence sanitaire. Ce travail comprend un processus en plusieurs étapes qui a commencé par une consultation technique mondiale organisée par l'OMS en septembre 2021. La consultation a réuni des experts du monde entier issus d'un large éventail de disciplines telles que la santé publique, l'éducation, le tourisme, la finance et les sciences sociales. Elle visait à identifier des approches de recherche et de mise en œuvre fondées sur les enseignements tirés de la pandémie de maladie à coronavirus de 2019. Pour se préparer aux futures épidémies et pandémies, il est essentiel d'adopter une approche de recherche plus solide, comparable et systématique en matière de santé publique et de mesures sociales. Cette approche globale permettra de mieux éclairer les décisions de mise en œuvre agiles, équilibrées et adaptées au contexte lors des futures situations d'urgence. Le présent article décrit les méthodes appliquées pour définir les priorités mondiales de recherche en matière de santé publique et de mesures sociales, ainsi que les prochaines étapes à franchir.

En la 74.ª Asamblea Mundial de la Salud, celebrada en 2021, se destacó la importancia de una sólida coordinación en la investigación sobre salud pública y medidas sociales. Este artículo describe los esfuerzos que ha emprendido la Organización Mundial de la Salud (OMS) para desarrollar un programa mundial de investigación sobre el uso de medidas sociales y de salud pública durante las emergencias sanitarias. Este trabajo incluye un proceso de varios pasos que comenzó con una consulta técnica mundial que convocó la OMS en septiembre de 2021. La consulta incluyó a expertos de todo el mundo y de una gran variedad de disciplinas, como la salud pública, la educación, el turismo, las finanzas y las ciencias sociales, y tuvo como objetivo identificar enfoques de investigación y aplicación basados en las lecciones aprendidas durante la pandemia de la enfermedad por coronavirus de 2019. Para prepararse ante futuras epidemias y pandemias, es esencial adoptar un enfoque de investigación más sólido, comparable y sistemático en materia de salud pública y medidas sociales. Este enfoque integral informará mejor las decisiones de aplicación ágiles, equilibradas y adaptadas al contexto durante futuras emergencias. En este artículo se describen los métodos utilizados para elaborar las prioridades mundiales de investigación sobre salud pública y medidas sociales, así como los próximos pasos necesarios.

Mapping the international health regulations monitoring and evaluation framework: an expert consultation, triangulation crosswalk and quantitative analysis.

The International Health Regulations Monitoring and Evaluation Framework (IHRMEF) includes four components regularly conducted by States Parties to measure the current status of International Health Regulations (IHR) 2005 core capacities and provide recommendations for strengthening these capacities. However, the four components are conducted independently of one another and have no systematic referral to each other before, during or after each process, despite being largely conducted by the same team, country and support organisations. This analysis sets out to identify ways in which IHRMEF components could work more synergistically to effectively measure the status of IHR core capacities, taking into account the country's priority risks. We developed a methodology to allow these independent components to communicate with each other, including expert consultation, a qualitative crosswalk analysis and a country-level quantitative analysis. The demonstrated results act as a proof of concept and illustrate a methodology to provide benefits across all four components before, during and after implementation.

WHO's Investigations and Studies, Unity Studies: A global initiative creating equitable opportunities for enhanced surveillance, operational research, capacity building, and global knowledge sharing.

The World Health Organization's Unity Studies global initiative provides a generic preparedness and readiness framework for conducting detailed investigations and epidemiological studies critical for the early and ongoing assessment of emerging respiratory pathogens of pandemic potential. During the COVID-19 pandemic, the initiative produced standardized investigation protocols and supported Member States to generate robust and comparable data to inform public health decision making. The subsequent iteration of the initiative is being implemented to develop revised and new investigation protocols, implementation toolkits and work to build a sustainable global network of sites, enabling the global community to be better prepared for the next emerging respiratory pathogen with epidemic or pandemic potential.

Preparing for the next respiratory pathogen pandemic: using tabletop simulation exercises to strengthen national planning in Cook Islands, Costa Rica, Lebanon and Mongolia.

The Preparedness and Resilience for Emerging Threats (PRET) initiative takes an innovative mode-of-transmission approach to pandemic planning by advocating for integrated preparedness and response systems and capacities for groups of pathogens with common transmission pathways. The World Health Organization (WHO) launched this initiative in 2023 with the publication of PRET Module 1 addressing respiratory pathogens. Exercise PanPRET-1 is a customizable tabletop simulation exercise (TTX) package developed to complement PRET Module 1. The exercise scenario focuses on strengthening capacities for multisectoral coordination, risk communication and community engagement, and the triggers for operational decision-making. This article reports on the experiences of the first four countries to implement Exercise PanPRET-1: Cook Islands, Costa Rica, Lebanon and Mongolia. Exercise outcomes demonstrated that PanPRET-1 can be an effective tool for testing pandemic plans in a multisectoral forum and identifying opportunities to improve preparedness and response in key domains. In quantitative evaluations in Cook Islands, Costa Rica and Mongolia, high proportions of exercise participants indicated that multiple aspects of the exercise were well-designed and were beneficial for improving health emergency preparedness. Exercise participants in Lebanon provided qualitative feedback indicating that they found the exercise to be beneficial. Conducting a TTX and monitoring the implementation of action plans based on exercise findings facilitates a country-owned whole-of-society vision for pandemic planning. Countries are encouraged to incorporate TTX such as Exercise PanPRET-1 into a continuous cycle of activity to improve pandemic preparedness.

Mitochondrial DNA damage is sensitive to exogenous H(2)O(2) but independent of cellular ROS production in prostate cancer cells.

Intrinsic oxidative stress through enhanced production of reactive oxygen species (ROS) in prostate and other cancers may contribute to cancer progression due to its stimulating effect on cancer growth. In this study, we investigate differential responses to exogenous oxidative stimuli between aggressive prostate cancer and normal cell lines and explore potential mechanisms through interactions between cytotoxicity, cellular ROS production and oxidative DNA damage. The circular, multi-copy mitochondrial DNA (mtDNA) is used as a sensitive surrogate to oxidative DNA damage. We demonstrate that exogenous H(2)O(2) induces preferential cytotoxicity in aggressive prostate cancer than normal cells; a cascade production of cellular ROS, composed mainly of superoxide (O(2)(-)), is shown to be a critical determinant of H(2)O(2)-induced selective toxicity in cancer cells. In contrast, mtDNA damage and copy number depletion, as measured by a novel two-phase strategy of the supercoiling-sensitive qPCR method, are very sensitive to exogenous H(2)O(2) exposure in both cancer and normal cell lines. Moreover, we demonstrate for the first time that the sensitive mtDNA damage response to exogenous H(2)O(2) is independent of secondary cellular ROS production triggered by several ROS modulators regardless of cell phenotypes. These new findings suggest different mechanisms underpinning cytotoxicity and DNA damage induced by oxidative stress and a susceptible phenotype to oxidative injury associated with aggressive prostate cancer cells in vitro.

PIPDeploy: Development and implementation of a gamified table top simulation exercise to strengthen national pandemic vaccine preparedness and readiness.

Successful emergency vaccination campaigns rely on effective deployment and vaccination plans. This applies to localised outbreaks as well as for pandemics. In the wake of the 2009 H1N1 influenza pandemic, analysis of the global Vaccine Deployment Initiative, through which the World Health Organization (WHO) donated pandemic influenza vaccines to countries in need, revealed that an absence of vaccine deployment plans in many countries significantly hindered vaccine deployment. Through the Pandemic Influenza Preparedness Framework adopted by the World Health Assembly in 2011, WHO is engaging in several capacity building activities to improve pandemic influenza preparedness and response and make provisions for access to vaccines and sharing of other benefits. The Framework calls for the development and exercise of operational plans for deployment of influenza vaccines to enhance pandemic preparedness. To this end, WHO has supported the development of PIPDeploy, an interactive, in-person table top simulation exercise to facilitate learning for emergency preparedness. It employs various game design elements including a game board, time pressure, leaderboards and teams to enhance participants' motivation. PIPDeploy formed part of five WHO Pandemic Influenza Vaccine Deployment Workshops attended by national-level managers responsible for pandemic influenza vaccine response predominantly in non-producing countries. The purpose of this study was to describe the features and application of PIPDeploy, and present findings of the evaluation of participants' experiences during the simulation involving a "hot wash" discussion and collection of quantitative data. The simulation's instructional approach was widely accepted by participants, who reported that the format was novel and engaging. They reflected on its utility for identifying gaps in their own vaccine deployment plans and regulatory frameworks for importation of vaccine products. All participants found the simulation relevant to their professional objectives. A range of other potential applications were suggested, including PIPDeploy's adaptation to sub-national contexts and to other epidemic diseases.

Viet Nam's mandatory motorcycle helmet law and its impact on children.

OBJECTIVE: To measure the use of motorcycle helmets in children and to determine the reasons why children wear helmets less often than adults. METHODS: The frequency of helmet wearing among adults and children was ascertained by trained roadside observers, and randomized road user surveys were completed in four major centres in Viet Nam: Hanoi, Ho Chi Minh City, Can Tho and Da Nang. Survey data on key questions were cross tabulated, and chi2 was calculated for significant differences between parents and non-parents (0.05). FINDINGS: The frequency of helmet use in the four study locations ranged from 90-99% among adults, from 15-53% among children 7 but

Early detection of clinically significant prostate cancer at diagnosis: a prospective study using a novel panel of TMPRSS2:ETS fusion gene markers.

We explore noninvasive clinical applications of multiple disease-specific fusion markers recently discovered in prostate cancer to predict the risk of cancer occurrence and aggressiveness at diagnosis. A total of 92 men who were prostate-specific antigen (PSA) screened and scheduled for diagnostic biopsy were enrolled for this study. Prospectively collected urine was blind coded for laboratory tests. RNA from urine sediments was analyzed using a panel of 6 TMPRSS2:ETS fusion markers with a sensitive quantitative PCR platform. The pathology reported 39 biopsy-positive cases from 92 patients (42.4%). In urine test, 10 unique combinations of fusion types were detected in 32 of 92 (34.8%) prebiopsy samples. A novel combination of fusion markers, termed Fx (III, IV, ETS), was identified with a sensitivity of 51.3% and an odds ratio of 10.1 in detecting cancer on biopsy. Incorporating a categorical variable of Fx (III, IV, ETS) with urine PCA3 and serum PSA, a regression model was developed to predict biopsy outcomes with an overall accuracy of 77%. Moreover, the overexpression of Fx (III, IV, or ETS) was shown to be an independent predictor to the high-grade cancer, with a predictive accuracy of 80% when coupled with PSA density. The individualized risk scores further stratified a high-risk group that is composed of 92% high-grade cancers and a low-risk group that harbors mainly clinically insignificant cancers. In conclusion, we have identified a novel combination of fusion types very specific to the clinically significant prostate cancer and developed effective regression models to predict biopsy outcomes and aggressive cancers at diagnosis.

A panel of TMPRSS2:ERG fusion transcript markers for urine-based prostate cancer detection with high specificity and sensitivity.

BACKGROUND: The TMPRSS2:ERG fusion is both prevalent and unique to prostate cancer (PCa) and has great potential for noninvasive diagnosis of PCa in bodily fluids. OBJECTIVES: To evaluate the specificity and sensitivity of the TMPRSS2:ERG fusion in urine from diverse clinical contexts and to explore potential clinical applications. DESIGN, SETTING, AND PARTICIPANTS: A total of 101 subjects were enrolled in 2008 from urologic oncology clinics to form three study groups: 44 PCa free, 46 confirmed PCa, and 11 negative prostate biopsies. The PCa-free group included females, healthy young men, and post-radical prostatectomy (RP) patients. The confirmed PCa group was composed of patients under active surveillance, scheduled for treatment, or with metastatic disease. MEASUREMENTS: Urine was collected after attentive digital rectal exam (DRE) and coded to blind group allocation for laboratory test. RNA from urine sediments was analyzed using a panel of four TMPRSS2:ERG fusion markers with quantitative polymerase chain reaction (qPCR). RESULTS AND LIMITATIONS: Our fusion markers demonstrated very high technical specificity and sensitivity for detecting a single fusion-positive cancer cell (VCaP) in the presence of at least 3000 cells in urine sediments. In clinical analysis, there were no fusion-positive samples in the PCa-free group (0 of 44 samples), while there were 16 of 46 (34.8%) fusion-positive samples in the confirmed PCa group. The fusion incidence varied significantly among the three PCa subgroups. The clinical sensitivity increased to 45.4% in cancer patients prior to treatments. The fusion markers were detected in 2 of 11 (18.2%) biopsy-negative patients, suggesting potentially false negative biopsies. This study is not prospective and is limited in sample sizes. CONCLUSIONS: Our novel panel of TMPRSS2:ERG fusion markers provided a very specific and sensitive tool for urine-based detection of PCa. Theses markers can potentially be used to diagnose patients with PCa who have negative biopsies.