A Methodology for the Assessment and Prioritization of Genetic Biocontainment Technologies for Engineered Microbes.

Introduction: Organisms engineered with synthetic genes and genomes have the potential to play critical roles to address important issues in the environment, human health, and manufacturing. Engineered genetic biocontainment technologies are needed to manage the risks of unintended consequences when deploying these biological systems in consultation with the biosafety and biosecurity communities. Metrics measuring genetic biocontainment and a methodology to apply them are required to determine which genetic biocontainment technologies warrant further development for real-world applications. In this study, we develop and apply a systems analysis of the current technical landscape using expert opinion and a metric-based scoring system resulting in a semiquantitative comparative assessment of genetic biocontainment technologies in microorganisms. Methods: Genetic biocontainment technologies were evaluated according to multiple metrics, falling into two broad classes: feasibility and applicability. Specific genetic biocontainment example scenarios and generalized categories were scored with these metrics. Gap analysis was carried out, indicating particular areas where genetic biocontainment can be improved. Results: Metric analysis scoring of feasibility and applicability enabled prioritization of genetic biocontainment technologies for real-world applications. Gap analysis showed that technology readiness and containment stability scored low for a number of scenarios and categories, indicating a general need for further development before they can be ready for deployment. Conclusion: Developing an assessment framework with defined metrics produced a straightforward system for evaluating genetic biocontainment strategies intended for various real-world applications. Use of the methodology also provided insights into existing gaps in genetic biocontainment strategies, and by altering the metrics, can be applied to other biotechnologies.

Informing the public about chemical mixtures in the local environment: Currently applied indicators in the Netherlands and ways forward.

The current use of chemicals puts pressure on human and ecological health. Based on the Aarhus Convention, citizens have the right to have access to information on substances in their local environment. Providing this information is a major challenge, especially considering complex mixtures, as the current substance-by-substance risk assessment may not adequately address the risk of co-exposure to multiple substances. Here, we provide an overview of the currently available indicators in the Netherlands to explore current scientific possibilities to indicate the impacts of complex chemical mixtures in the environment on human health and ecology at the local scale. This is limited to impact estimates on freshwater species for 701 substances, impact estimates of four metals on soil organisms, and impacts on human health for particulate matter (PM10) and nitrogen dioxide (NO2) in air. The main limiting factors in developing and expanding these indicators to cover more compartments and substances are the availability of emission and concentration data of substances and dose-response relationships at the population (human health) or community (ecology) level. As ways forward, we propose; 1) developing cumulative assessment groups (CAGs) for substances on the European Pollutant Transfer and Release Register and Water Framework Directive substance lists, to enable the development of mixture indicators based on mixture risk assessment and concentration addition principles; 2) to gain insight into local mixtures by also applying these CAGs to emission data, which is available for soil and air for more substances than concentrations data; 3) the application of analytical non-target screening methods as well as effect-based methods for whole-mixture assessment.

Research priorities for diagnosis, prognosis, and rehabilitation following concussion: results from a national survey of Australian health professionals.

PURPOSE: Recently, the Concussion James Lind Alliance Priority Setting Partnership (JLAPSP) (Canada) identified serious research gaps regarding diagnosis, management, and access to effective rehabilitation for concussion/mild traumatic brain injury (mTBI). Our aim was to determine if the same research priorities are important to Australian health professionals working in the concussion/mTBI field. MATERIALS AND METHODS: A survey was distributed via professional networks, social media, professional group listservs, a research project noticeboard, and at conferences. It comprised of 25 of the highest ranked concussion research questions from the JLAPSP. We examined how professionals ranked the research questions and analyzed variation in ranking by clinical role and concussion/mTBI work experience. RESULTS: Our sample of 187 participants included medical and allied health professionals. Most participants were occupational therapists (22%), physiotherapists (18%), neuropsychologists (17%), and worked in Victoria (47%), New South Whales (18%), or Queensland (15%) in metropolitan areas. Health professionals ranked three research questions highest: identifying methods to predict prolonged recovery; effectiveness of early referral and treatment by a specialized concussion/mTBI team; and implementation studies on upskilling healthcare workers. CONCLUSIONS: The research priorities identified can guide research efforts to improve the assessment, management, and rehabilitation of individuals with concussion/mTBI in Australia.

Health professionals with experience in the assessment and rehabilitation of adults with concussions overwhelmingly agree that there is a need for further research to understand the prognosis and the effectiveness of specialized rehabilitation clinics.The role of healthcare providers in supporting recovery and the long-term health implications of suffering a concussion was identified as a priority.Both pre-clinical and clinical research are identified priorities to determine the effectiveness of biomarkers for concussion and return to activity.Health professionals also call for clinical trials testing management protocols, and implementation trials to support translation of clinical guidelines into practice to understand the role of healthcare providers in rehabilitation.

Comparative analysis of RUSLE and SWPT for sub-watershed conservation prioritization in the Ayu watershed, Abay basin, Ethiopia.

Ethiopia is currently facing a major environmental problem caused by soil erosion. In order to tackle this problem, it is essential to implement a comprehensive watershed management approach and give priority to conservation efforts depending on the level of severity. Therefore, the objective of this research is to evaluate the mean annual soil erosion and rank the sub-watersheds for conservations in the Ayu watershed, utilizing the Revised Universal Soil Loss Equation (RUSLE) model and the Sub-Watershed Prioritization Tool (SWPT). RUSLE was utilized to predict the annual average soil erosion rate, while SWPT was applied to conduct Weighted Sum Analysis (WSA) for ranking sub-watersheds. Support Vector Machine (SVM) was employed for classifying land use and land cover. The Relative importance of morphometric and topo-hydrologic features in the SWPT was analyzed using a Random Forest model. The Bland-Altman plot and Wilcoxon Signed Rank Test were employed to assess the agreement in prioritizing watersheds between RUSLE results and the SWPT. Furthermore, field observations were conducted to validate the land use classification by collecting ground data. In addition, the study was enhanced with local viewpoints by conducting focus group discussions with agricultural experts and farmers to obtain qualitative insights and validation of resuts. The findings showed that soil loss varied from 0 to 110 t/ha/yr, with an average of 8.95 t/ha/yr, resulting in a total loss of 384365.3 tons annually. The comparison of RUSLE and SWPT showed a moderate positive relationship (r = 0.59). The results of the Bland-Altman plot indicate a consistent agreement between the two methods. However, there is inconsistency among the five sub watersheds. This study enhances the knowledge of soil erosion patterns and offers useful guidance for watershed conservation techniques. It can be also used as a beneficial framework for managing watersheds, with possible uses outside of the Ayu watershed.

Development of a Prioritization Framework to Aid Healthcare Funding Decision Making in Health Technology Assessment in Australia: Application of Multicriteria Decision Analysis.

OBJECTIVES: This study develops a prioritization framework to aid healthcare funding decision making in health technology assessment (HTA) in Australia using a multiple criteria decision analysis (MCDA) approach. METHODS: MCDA frameworks for HTAs were reviewed through literature survey to identify the initial criteria and levels within each criterion. Key stakeholders and experts were consulted to confirm these criteria and levels. A conjoint analysis using 1000Minds was undertaken with policy makers from the Department of Health to establish ranking criteria and weighting scores. Monte Carlo simulations were used to examine the sensitivity of findings to factors affecting the ranking and weighting scores. The MCDA was then applied to 6 examples of chronic care models or technologies projects to demonstrate the performance of this approach. RESULTS: Five criteria (clinical efficacy/effectiveness, safety and tolerability, severity of the condition, quality/uncertainty, and direct impact on healthcare costs) were consistently ranked highest by healthcare decision makers. Among the criteria, patient-level health outcomes were considered the most important, followed by social and ethical values. The analyses were robust to inform the uncertainty in the parameter. CONCLUSIONS: This study has developed an MCDA tool that effectively integrates key priorities for HTA reviews, reflecting the values and preferences of healthcare stakeholders in Australia. Although this tool aims to align the assessment process more closely with health benefits, it also highlights the importance of considering other criteria.

Optimizing restoration: A holistic spatial approach to deliver Nature's Contributions to People with minimal tradeoffs and maximal equity.

Ecosystem restoration is inherently a complex activity with inevitable tradeoffs in environmental and societal outcomes. These tradeoffs can potentially be large when policies and practices are focused on single outcomes versus joint achievement of multiple outcomes. Few studies have assessed the tradeoffs in Nature's Contributions to People (NCP) and the distributional equity of NCP from forest restoration strategies. Here, we optimized a defined forest restoration area across India with systematic conservation planning to assess the tradeoffs between three NCP: i) climate change mitigation NCP, ii) biodiversity value NCP (habitat created for forest-dependent mammals), and iii) societal NCP (human direct use of restored forests for livelihoods, housing construction material, and energy). We show that restoration plans aimed at a single-NCP tend not to deliver other NCP outcomes efficiently. In contrast, integrated spatial forest restoration plans aimed at achievement of multiple outcomes deliver on average 83.3% (43.2 to 100%) of climate change mitigation NCP, 89.9% (63.8 to 100%) of biodiversity value NCP, and 93.9% (64.5 to 100%) of societal NCP delivered by single-objective plans. Integrated plans deliver NCP more evenly across the restoration area when compared to other plans that identify certain regions such as the Western Ghats and north-eastern India. Last, 38 to 41% of the people impacted by integrated spatial plans belong to socioeconomically disadvantaged groups, greater than their overall representation in India's population. Moving ahead, effective policy design and evaluation integrating ecosystem protection and restoration strategies can benefit from the blueprint we provide in this study for India.

Spatiotemporal variations and priority ranking of emerging contaminants in nanwan reservoir: A case study from the agricultural region in huaihe river basin in China.

The presence of emerging contaminants (ECs) in drinking water sources is an increasing concern, yet limited data exists on their occurrence and risk in the upper Huaihe River Basin, an important agricultural region in Central China. This study investigated 70 ECs, including pesticide and antibiotics in surface water from drinking water source areas in Nanwan Reservoir along the upper reaches of the Huaihe River Basin to prioritize the ECs based on ecological risk and health risk assessment. A total of 66 ECs were detected in the surface water at least once at the selected 38 sampling sites, with concentrations ranging from 0.04 to 2508 ng/L. Ecological risk assessment using the risk quotient (RQ) method revealed high risks (RQ > 1) from 7 ECs in the dry season and 15 ECs in the wet season, with triazine pesticides as the main contributors. Non-carcinogenic risks were below negligible levels, but carcinogenic risks from neonicotinoid and carbamate pesticides and macrolide antibiotics were concerning for teenagers. Ciprofloxacin exhibited a high level of resistance risk during the wet season. A multi-indicator prioritization approach integrating occurrence, risk, and chemical property data ranked 6 pesticides and 3 antibiotics as priority pollutants. The results highlight EC contamination of drinking water sources in this agriculturally-intensive region and the need for targeted monitoring and management to protect water quality.

Neglecting biodiversity baselines in longitudinal river connectivity restoration impacts priority setting.

River habitats are fragmented by barriers which impede the movement and dispersal of aquatic organisms. Restoring habitat connectivity is a primary objective of nature conservation plans with multiple efforts to strategically restore connectivity at local, regional, and global scales. However, current approaches to prioritize connectivity restoration do not typically consider how barriers spatially fragment species' populations. Additionally, we lack knowledge on biodiversity baselines to predict which species would find suitable habitat after restoring connectivity. In this paper, we asked how neglecting these biodiversity baselines in river barrier removals impacts priority setting for conservation planning. We applied a novel modelling approach combining predictions of species distributions with network connectivity models to prioritize conservation actions in rivers of the Rhine-Aare system in Switzerland. Our results show that the high number and density of barriers has reduced structural and functional connectivity across representative catchments within the system. We show that fragmentation decreases habitat suitability for species and that using expected distributions as biodiversity baselines significantly affects priority settings for connectivity restorations compared to species-agnostic metrics based on river length. This indicates that priorities for barrier removals are ranked higher within the expected distributions of species to maximize functional connectivity while barriers in unsuitable regions are given lower importance scores. Our work highlights that the joint consideration of existing barriers and species past and current distributions are critical for restoration plans to ensure the recovery and persistence of riverine fish diversity.

Effect driven prioritization of contaminants in wastewater treatment plants across China: A data mining-based toxicity screening approach.

A diversity of contaminants of emerging concern (CECs) are present in wastewater effluent, posing potential threats to receiving waters. It is urgent for a holistic assessment of the occurrence and risk of CECs related to wastewater treatment plants (WWTP) on national and regional scales. A data mining-based risk prioritization method was developed to collect the reported contaminants and their respective concentrations in municipal and industrial WWTPs and their receiving waters across China over the past 20 years. A total of 10,781 chemicals were reported in 8336 publications, of which 1037 contaminants were reported with environmental concentrations. While contaminant categories varied across WWTP types (municipal vs. industrial) and regions, pharmaceuticals and cyclic hydrocarbons were the most studied CECs. Contaminant composition in receiving water was closer to that in municipal than industrial WWTPs. Publications on legacy pesticides and polycyclic aromatic hydrocarbons in WWTP decreased recently compared to the past, while pharmaceuticals and perfluorochemicals have received increasing attention, showing a changing concern over time. Detection frequency, concentration, removal efficiency, and toxicity data were integrated for assessing potential risks and prioritizing CECs on national and regional scales using an environmental health prioritization index (EHPi) approach. Among 666 contaminants in municipal WWTP effluent, trichlorfon and perfluorooctanesulfonic acid were with the highest EHPi scores, while 17ɑ-ethinylestradiol and bisphenol A had the highest EHPi scores among 304 contaminants in industrial WWTPs. The prioritized contaminants varied across regions, suggesting a need for tailoring regional measures of wastewater treatment and control.

"I was afraid to go to the hospital": A qualitative analysis and ethical implications of the impacts of COVID-19 on the health and medical care of older adults in Ethiopia.

Objective: The COVID-19 pandemic has brought severe health consequences among older adults and posed ethical challenges. The aim of this study was to explore the impacts of COVID-19 on the health and medical care of older adults in Ethiopia and associated ethical implications, regardless of older adults' COVID-19 infection status. Methods: In this qualitative study, we followed an inductive exploratory approach based on reflexive thematic analysis. We conducted semistructured interviews between March 2021 and November 2021 with 20 older adults and 26 health professionals who were selected from healthcare facilities and communities in Ethiopia using purposive and snowball sampling techniques. We audio-recorded, transcribed, translated, and inductively analyzed the interviews using thematic analysis. Results: Participants reported that the pandemic compromised the accessibility and quality of both COVID and non-COVID healthcare services for older adults, which negatively impacted older adults' health conditions and medical care. Moreover, participants elaborated on the health conditions and care of older patients with COVID-19 and highlighted that older COVID-19 patients often have severe health conditions, do not get adequate COVID-19 care, and may receive lower priority for admission to intensive care units compared to younger patients when resources are limited. Conclusions: Results of this study showed that practices of COVID-19 care and measures may have led to adverse consequences such as limited availability and access to aged care in Ethiopia, which could have further health consequences on older patients. Our results contribute to a better understanding of ethical issues such as distributive justice and prioritization arising in the healthcare of older patients in times of global pandemic. It is imperative for local and international health policymakers and ethicists to further analyze and address the challenges that compromise the accessibility and continuity of quality care for older persons during a public healthcare crisis.

Occurrence and risks of pharmaceuticals, personal care products, and endocrine-disrupting compounds in Chinese surface waters.

The continuous and rapid increase of chemical pollution in surface waters has become a pressing and widely recognized global concern. As emerging contaminants (ECs) in surface waters, pharmaceutical and personal care products (PPCPs), and endocrine-disrupting compounds (EDCs) have attracted considerable attention due to their wide occurrence and potential threat to human health. Therefore, a comprehensive understanding of the occurrence and risks of ECs in Chinese surface waters is urgently required. This study summarizes and assesses the environmental occurrence concentrations and ecological risks of 42 pharmaceuticals, 15 personal care products (PCPs), and 20 EDCs frequently detected in Chinese surface waters. The ECs were primarily detected in China's densely populated and highly industrialized regions. Most detected PPCPs and EDCs had concentrations between ng/L to µg/L, whereas norfloxacin, caffeine, and erythromycin had relatively high contamination levels, even exceeding 2000 ng/L. Risk evaluation based on the risk quotient method revealed that 34 PPCPs and EDCs in Chinese surface waters did not pose a significant risk, whereas 4-nonylphenol, 4-tert-octylphenol, 17α-ethinyl estradiol, 17ß-estradiol, and triclocarban did. This review provides a comprehensive summary of the occurrence and associated hazards of typical PPCPs and EDCs in Chinese surface waters over the past decade, and will aid in the regulation and control of these ECs in Chinese surface waters.

A novel digital PCR assay for detection and comprehensive characterization of Molluscum contagiosum virus genotypes MOCV1, MOCV2, and MOCV3 and recombinant lineages.

Molluscum contagiosum virus (MOCV) is an important human pathogen causing a high disease burden worldwide. It is the last exclusively human-infecting poxvirus still circulating in its natural reservoir-a valuable model of poxviral evolution. Unfortunately, MOCV remains neglected, and little is known about its evolutionary history and circulating genomic variants, especially in non-privileged countries. The design weaknesses of available MOCV detection/genotyping assays surfaced with recent accumulation of abundant sequence information: all existing MOCV assays fail at accurate genotyping and capturing sub-genotype level diversity. Because complete MOCV genome characterization is an expensive and labor-intensive task, it makes sense to prioritize samples for whole-genome sequencing by diversity triage screening. To meet this demand, we developed a novel assay for accurate MOCV detection and genotyping, and comprehensive sub-genotype qualification to the level of phylogenetic groups (PGs). The assay included a novel set of oligonucleotide primers and probes, and it was implemented using digital polymerase chain reaction (dPCR). It offers sensitive, specific, and accurate detection, genotyping (MOCV1-MOCV3), and PG qualification (PG1-6) of MOCV DNA from clinical samples. The novel dPCR assay is suitable for MOCV diversity triage screening and prioritization of samples for complete MOCV genome characterization.

Admission prioritization of heart failure patients with multiple comorbidities.

The primary objective of this study was to enhance the operational efficiency of the current healthcare system by proposing a quicker and more effective approach for healthcare providers to deliver services to individuals facing acute heart failure (HF) and concurrent medical conditions. The aim was to support healthcare staff in providing urgent services more efficiently by developing an automated decision-support Patient Prioritization (PP) Tool that utilizes a tailored machine learning (ML) model to prioritize HF patients with chronic heart conditions and concurrent comorbidities during Urgent Care Unit admission. The study applies key ML models to the PhysioNet dataset, encompassing hospital admissions and mortality records of heart failure patients at Zigong Fourth People's Hospital in Sichuan, China, between 2016 and 2019. In addition, the model outcomes for the PhysioNet dataset are compared with the Healthcare Cost and Utilization Project (HCUP) Maryland (MD) State Inpatient Data (SID) for 2014, a secondary dataset containing heart failure patients, to assess the generalizability of results across diverse healthcare settings and patient demographics. The ML models in this project demonstrate efficiencies surpassing 97.8% and specificities exceeding 95% in identifying HF patients at a higher risk and ranking them based on their mortality risk level. Utilizing this machine learning for the PP approach underscores risk assessment, supporting healthcare professionals in managing HF patients more effectively and allocating resources to those in immediate need, whether in hospital or telehealth settings.

Using economic analysis to inform health resource allocation: lessons from Malawi.

Despite making remarkable strides in improving health outcomes, Malawi faces concerns about sustaining the progress achieved due to limited fiscal space and donor dependency. The imperative for efficient health spending becomes evident, necessitating strategic allocation of resources to areas with the greatest impact on mortality and morbidity. Health benefits packages hold promise in supporting efficient resource allocation. However, despite defining these packages over the last two decades, their development and implementation have posed significant challenges for Malawi. In response, the Malawian government, in collaboration with the Thanzi la Onse Programme, has developed a set of tools and frameworks, primarily based on cost-effectiveness analysis, to guide the design of health benefits packages likely to achieve national health objectives. This review provides an overview of these tools and frameworks, accompanied by other related analyses, aiming to better align health financing with health benefits package prioritization. The paper is organized around five key policy questions facing decision-makers: (i) What interventions should the health system deliver? (ii) How should resources be allocated geographically? (iii) How should investments in health system inputs be prioritized? (iv) How should equity considerations be incorporated into resource allocation decisions? and (v) How should evidence generation be prioritized to support resource allocation decisions (guiding research)? The tools and frameworks presented here are intended to be compatible for use in diverse and often complex healthcare systems across Africa, supporting the health resource allocation process as countries pursue Universal Health Coverage.

Pesticides in wastewater treatment plant effluents in the Yeongsan River Basin, Korea: Occurrence and environmental risk assessment.

Pesticides are among the main drivers posing risks to aquatic environments, with effluents from wastewater treatment plants (WWTPs) serving as a major source. This study aimed to identify the primary pesticides for which there was a risk of release into aquatic environments through WWTP effluents, thereby enabling more effective contamination management in public water bodies. In this study, monitoring, risk assessment, and risk-based prioritization of 87 pesticides in effluents from three WWTPs in the Yeongsan River Basin, Korea, were conducted. A total of 59 pesticides were detected at concentrations from 0.852 ng/L to 82.044 µg/L and exhibited variable patterns across different WWTP locations. An environmental risk assessment based on the risk quotient (RQ) of individual pesticides identified 13 substances implicated in significant ecotoxicological risks, as they exceeded RQ values of 1 at least once. An optimized risk (RQf)-based prioritization, considering the frequency of the measured environmental concentration (MEC) exceeding the predicted environmental concentration (PNEC), was conducted to identify pesticides that potentially posed risks and thus should be managed as a priority. Four pesticides had an RQf value >1; metribuzin exhibited the highest RQf value of 4.951, followed by 3-phenoxybenzoic acid, atrazin-2-hydroxy, and atrazine. Additionally, five pesticides (terbuthylazine, methabenzthiazuron, diuron, thiacloprid, and fipronil) and another four pesticides (propazine, imidacloprid, hexaconazole, and hexazione) had RQf values >0.1 and > 0.01, respectively. By calculating the contributions of individual pesticides to the RQf of these mixtures (RQf, mix) based on the concentration addition model, it was determined that >95 % of the sum of RQf, mix was driven by the top seven pesticides. These findings highlight the importance of prioritizing pesticides for effective management of contamination sources.

Unraveling the mechanism of semantic object-based attention: The role of top-down search strategies.

There is an ongoing debate between the sensory enhancement account and the attentional prioritization account concerning the mechanism underlying object-based attention. This debate remains unresolved because of the predominant use of geometric objects in previous studies, which made it difficult to experimentally dissociate the two accounts due to the prominent boundaries of these objects. The current study investigated the mechanism underlying semantic object-based attention by utilizing Chinese two-character words with different word frequencies and the event-related potentials (ERPs) technique to elucidate the ongoing debate. The behavioral results showed that the semantic object effect was observed only in the high-frequency condition. The ERP results revealed the following: (1) the N1 component was larger for the high-frequency condition compared with the low-frequency condition. However, there was no significant difference in amplitude between the N1 component elicited by invalid same object locations and invalid different object locations, irrespective of whether it occurred in high- or low-frequency conditions. (2) The P3 component elicited by invalid same object locations was larger than that elicited by invalid different object locations only in the high-frequency condition. (3) The N400 amplitude elicited by invalid same object locations was smaller than that elicited by invalid different object locations only in the high-frequency condition. These results suggest that in the absence of obvious object boundaries, the production of object-based attention is primarily driven by search strategies. Attentional prioritization, rather than sensory enhancement, is the dominant mechanism underlying object-based attention.

pVACview: an interactive visualization tool for efficient neoantigen prioritization and selection.

Background: Neoantigen targeting therapies including personalized vaccines have shown promise in the treatment of cancers, particularly when used in combination with checkpoint blockade therapy. At least 100 clinical trials involving these therapies are underway globally. Accurate identification and prioritization of neoantigens is highly relevant to designing these trials, predicting treatment response, and understanding mechanisms of resistance. With the advent of massively parallel DNA and RNA sequencing technologies, it is now possible to computationally predict neoantigens based on patient-specific variant information. However, numerous factors must be considered when prioritizing neoantigens for use in personalized therapies. Complexities such as alternative transcript annotations, various binding, presentation and immunogenicity prediction algorithms, and variable peptide lengths/registers all potentially impact the neoantigen selection process. There has been a rapid development of computational tools that attempt to account for these complexities. While these tools generate numerous algorithmic predictions for neoantigen characterization, results from these pipelines are difficult to navigate and require extensive knowledge of the underlying tools for accurate interpretation. This often leads to over-simplification of pipeline outputs to make them tractable, for example limiting prediction to a single RNA isoform or only summarizing the top ranked of many possible peptide candidates. In addition to variant detection, gene expression and predicted peptide binding affinities, recent studies have also demonstrated the importance of mutation location, allele-specific anchor locations, and variation of T-cell response to long versus short peptides. Due to the intricate nature and number of salient neoantigen features, presenting all relevant information to facilitate candidate selection for downstream applications is a difficult challenge that current tools fail to address. Results: We have created pVACview, the first interactive tool designed to aid in the prioritization and selection of neoantigen candidates for personalized neoantigen therapies including cancer vaccines. pVACview has a user-friendly and intuitive interface where users can upload, explore, select and export their neoantigen candidates. The tool allows users to visualize candidates across three different levels, including variant, transcript and peptide information. Conclusions: pVACview will allow researchers to analyze and prioritize neoantigen candidates with greater efficiency and accuracy in basic and translational settings The application is available as part of the pVACtools pipeline at pvactools.org and as an online server at pvacview.org.

Target repositioning using multi-layer networks and machine learning: The case of prostate cancer.

The discovery of novel therapeutic targets, defined as proteins which drugs can interact with to induce therapeutic benefits, typically represent the first and most important step of drug discovery. One solution for target discovery is target repositioning, a strategy which relies on the repurposing of known targets for new diseases, leading to new treatments, less side effects and potential drug synergies. Biological networks have emerged as powerful tools for integrating heterogeneous data and facilitating the prediction of biological or therapeutic properties. Consequently, they are widely employed to predict new therapeutic targets by characterizing potential candidates, often based on their interactions within a Protein-Protein Interaction (PPI) network, and their proximity to genes associated with the disease. However, over-reliance on PPI networks and the assumption that potential targets are necessarily near known genes can introduce biases that may limit the effectiveness of these methods. This study addresses these limitations in two ways. First, by exploiting a multi-layer network which incorporates additional information such as gene regulation, metabolite interactions, metabolic pathways, and several disease signatures such as Differentially Expressed Genes, mutated genes, Copy Number Alteration, and structural variants. Second, by extracting relevant features from the network using several approaches including proximity to disease-associated genes, but also unbiased approaches such as propagation-based methods, topological metrics, and module detection algorithms. Using prostate cancer as a case study, the best features were identified and utilized to train machine learning algorithms to predict 5 novel promising therapeutic targets for prostate cancer: IGF2R, C5AR, RAB7, SETD2 and NPBWR1.

Incorporation of human-wildlife interactions in ecosystem-based management to enhance conservation of endangered guitarfish.

Growing human use of the marine environment increases the proximity of humans to marine wildlife and thus likely increases human-wildlife interactions. Such interactions influence perceptions of nature and promote or undermine conservation. Despite their importance, human-wildlife interactions are rarely considered in ecosystem-based marine spatial planning (MSP). Ideally, these interactions should be identified and considered in ecosystem-based management (EBM), which is often purported to be the basis for MSP. We used Marxan software and data from a citizen science project documenting location, species, age, sex, and activity type to identify regions along Israel's coast with a high probability of encounters between people and 2 species of guitarfish. We considered the geographic distribution of these encounters and the various activities undertaken by the reporting observers. We ran 4 scenarios in Marxan. Two had conservation goals of 30% and 50% guitarfish habitat protection. In the third and fourth scenarios, we added a 50% conservation goal of human leisure activities to each guitarfish conservation goal. We also conducted a gap analysis between our guitarfish conservation goals and the Israel Nature and Parks Authority's master plan for marine protected areas. We found the park authority was close to meeting the 30% goal but was far from meeting the conservation goal of 50% of guitarfish habitat conservation. Different human uses were more likely to interact with different life stages of guitarfish, and different recreational activities occurred in different areas. Identifying areas of specific human use showed which activities should be addressed in conservation management decisions. Our addition of certain recreational uses to the model of habitat conservation showed how enhancing human dimensions in conservation planning can lead to more holistic ecosystem-based conservation necessary for effective marine planning.

Incorporación de las interacciones humano­fauna dentro de la gestión basada en el ecosistema para mejorar la conservación del pez guitarra en peligro Resumen El uso creciente que el humano le da al mar incrementa la cercanía de las personas con la fauna marina, lo que probablemente incrementa las interacciones humano­fauna. Dichas interacciones influyen sobre las percepciones que se tienen de la naturaleza y promueven debilitan la conservación. A pesar de su importancia, pocas veces se consideran las relaciones humano­fauna dentro de la planeación espacial basada en ecosistemas marinos (PEM). Lo ideal debería ser la identificación y consideración de estas interacciones dentro de la gestión basada en el ecosistema (GBE), la cual con frecuencia se considera como la base de la PEM. Usamos software Marxan y datos de un proyecto de ciencia ciudadana que documenta la ubicación, especie, edad, sexo y tipo de actividad para identificar las regiones de la costa de Israel con una alta probabilidad de encuentros entre las personas y dos especies de pez guitarra. Consideramos la distribución geográfica de estos encuentros y las diferentes actividades que realizan los observadores. En Marxan corrimos cuatro escenarios. Dos de los escenarios contaban objetivos de conservación del 30% y 50% de la protección del hábitat del pez guitarra. En los otros dos escenarios, añadimos un objetivo de conservación de 50% de las actividades humanas de recreación a los objetivos uno y dos. También realizamos un análisis de brecha entre los objetivos de conservación del pez guitarra y el plan maestro para las áreas marinas protegidas de la Autoridad de Parques y Naturaleza de Israel. Descubrimos que esta autoridad estaba cerca de lograr el objetivo del 30% pero lejos del de 50% de la conservación del hábitat del pez guitarra. Fue más probable que los diferentes usos humanos interactuaran con diferentes estadios de vida del pez guitarra y las diversas actividades recreativas ocurrieron en áreas distintas. La identificación de las áreas con un uso humano específico mostró cuáles actividades deberían abordarse en las decisiones de gestión de la conservación. La suma de ciertos usos recreativos al modelo de conservación del hábitat mostró cómo aumentar las dimensiones humanas en la planeación de la conservación puede derivar en una conservación basada en el ecosistema más holística, necesaria para la planeación marina eficiente.

What does "urgency" mean when prioritizing cancer treatment? Results from a qualitative study with German oncologists and other experts during the COVID-19 pandemic.

PURPOSE: Cancer care in Germany during the COVID-19 pandemic was affected by resource scarcity and the necessity to prioritize medical measures. This study explores ethical criteria for prioritization and their application in cancer practices from the perspective of German oncologists and other experts. METHODS: We conducted fourteen semi-structured interviews with German oncologists between February and July 2021 and fed findings of interviews and additional data on prioritizing cancer care into four structured group discussions, in January and February 2022, with 22 experts from medicine, nursing, law, ethics, health services research and health insurance. Interviews and group discussions were digitally recorded, transcribed verbatim and analyzed using qualitative content analysis. RESULTS: Narratives of the participants focus on "urgency" as most acceptable criterion for prioritization in cancer care. Patients who are considered curable and those with a high level of suffering, were given a high degree of "urgency." However, further analysis indicates that the "urgency" criterion needs to be further distinguished according to at least three different dimensions: "urgency" to (1) prevent imminent harm to life, (2) prevent future harm to life and (3) alleviate suffering. In addition, "urgency" is modulated by the "success," which can be reached by means of an intervention, and the "likelihood" of reaching that success. CONCLUSION: Our analysis indicates that while "urgency" is a well-established criterion, its operationalization in the context of oncology is challenging. We argue that combined conceptual and clinical analyses are necessary for a sound application of the "urgency" criterion to prioritization in cancer care.