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The European Observatory of Wildlife EOW, as part of the ENETWILD project, represents a collaborative network that has been operating since 2021 to develop and implement standardized protocols to obtain harmonized data on distribution and density of target mammal species. In so doing, the EOW aims at contributing to improving the quality of data that are available for wildlife management and risk assessment on a European scale. This report describes the activities carried out during the 2023 EOW campaign, which was joined by a total of 30 organizations who committed to collect data in 44 sites across 22 different countries. We present data on the distribution and density of three species – wild boar (Sus scrofa), European roe deer (Capreolus capreolus), and red fox (Vulpes vulpes) – obtained by implementing a camera trapping protocol and by fitting the random encounter model (REM) for density estimation. Camera‐trap images were processed using the Agouti platform and some of its tools specifically designed for the management of camera trapping projects. This includes the use of photogrammetry to obtain parameters for the REM directly from the sequences of images. A total of 24 EOW sites were monitored in past years as well, providing multiannual density estimates and population trends and highlighting an improvement in the precision of the estimates, related to the improved study design and protocol implementation. We also describe the activities of the 2024 campaign, carried out as part of ENETWILD 2.0, where big efforts were made to expand the network, focusing on sites at risk of African Swine Fever, with wild boar/pig interactions and containing wetlands, as potential hubs for Avian Influenza. This effort resulted in the engagement of 40 participants monitoring 64 study sites (27 countries), including 28 study sites located either in infected areas or < 100km from the ASF frontline, and 25 sites with wetland habitats. Furthermore, in at least 20 sites pig farming is practised either intensively, extensively or as backyard farming. Finally, synergies were established with other international initiatives related to wildlife monitoring and disease prevention, with the aim of sharing experiences and sustaining a transnational data collection and harmonization. [ABSTRACT FROM AUTHOR]

ENETWILD consortium with the collaboration of the MammalNet project2 has promoted some informatic tools to improve the data collection of wildlife distribution and abundance: iMammalia; MammalWeb and Agouti. Here we update the activities in relation to (i) the new languages implemented; (ii) new functionalities, (iii) and the improvement and testing of the artificial intelligence module to identify species in Agouti. The iMammalia app is now available in 17 languages with at least two more to be added soon. MammalWeb is available in six languages with more to be added soon. Agouti is available in seven languages. iMammalia automates data transfer to the global database GBIF, and MammalWeb will consider a similar approach in the near future. Technical improvements were made to meet the needs of iMammalia as a carcass reporting app for wild boar, which will favour early awareness in case of ASF outbreak. As for density estimation through camera trapping, processing of big number of images by hand is tedious, and to facilitate the annotation process Agouti offers and has continuously improved automatic species recognition using Artificial Intelligence (AI). We summarize several topics for the further development of Agouti. [ABSTRACT FROM AUTHOR]

It is essential to provide tools to wildlife professionals and researchers in order to facilitate data collection on wildlife density estimation following standardized protocols in the field. This is relevant for efficient harmonized data management systems, from the field to final reporting. Our main objective was to facilitate the collection of information in the field using established density estimation protocols. The specific objectives were (i) to evaluate and use already existing data registration IT tools for collecting and storing the data in the field; (ii) to make these data available in real time (cloud‐based solution), and (iii) being flexible enough to incorporate new protocols and species, as methods (such as camera trap‐based) and needs continuously evolves. We improved an already existing tool, Spatial Monitoring and Reporting Tool (SMART; https://smartconservationtools.org/). It is an open source software, which allows easily collect, visualize, store, analyze, report and act on a wide range of field data relevant for wildlife monitoring. The integration of SMART tools on EOW was successfully done for (i) distance sampling, (ii) hunting data and (iii) camera trap protocols. ENETWILD, therefore, made now available new IT functionalities to wildlife professionals and researchers to facilitate and harmonize wildlife data collection systems. [ABSTRACT FROM AUTHOR]

During summer 2022, the European Wildlife Observatory (EOW2), involving 50 study areas in at least 30 European countries, has applied similar camera‐trapping‐based population estimation protocols and data collection standards to facilitate harmonization and interoperability. For this purpose, continuous training of the network of wildlife professionals in Europe is a key activity of the EOW. In this context, in May 2022 the ENETWILD consortium organized a first online training course to update information on methodology to process with next steps in the field. The course here reported took place in two different dates, 28th September, and 21st November 2022, online. The first part of the course (28th September) presented the progress of the EOW and focused on the analytical tools incorporated to Agouti app, on the use of information technology tools and artificial intelligence to process and analyse photo‐trappings to finally obtain a standardized database, ready for analysis. The main objective of the course offered on 21st November was providing detailed instructions on running the random encounter model (REM) on camera trap data packages from Agouti and incorporating some recommendations to improve the calibration of images for distance estimation. We also presented SMART app adapted to the EOW, which facilitates the collection of information in the field using stablished density estimation protocols to make these data available in the destock in real time (cloud‐based solution). SMART is flexible enough to incorporate new protocols and species, as methods (such as camera traps‐based) and needs continuously evolve. The integration of SMART tools on EOW was successfully done for (i) distance sampling, (ii) hunting data and (iii) camera trap protocols. This course was successfully attended by 46 wildlife biologists, animal health professionals and wildlife experts from national hunting and forestry authorities. Detailed explanations, protocols, and examples for applying such protocols were provided. [ABSTRACT FROM AUTHOR]

The International Symposium on Wild Boar and Other Suids (IWBS 2022), which took place in Montseny Biosphere Reserve (Catalonia, Spain) in September 2022, provided to ENETWILD with the opportunity to meet in‐person for the first time after 2.5 years, and meet the international scientific community with expertise on wild suids and other ungulates. Twelve members of ENETWILD consortium representing 6 partners were present. Bringing together international experts, stakeholders and ENETWILD collaborators was a perfect occasion to present the European Observatory of Wildlife (EOW). Two hundred and twenty‐five wildlife experts from 25 countries were present at symposium, and at presentation of the EOW. Overall, 3 'Plenary Talks' and 118 presentations (62 oral and 56 posters) were made. The meeting has gone through all the possible topics regarding wild suids, from genetics to monitoring and management. This was the optimal context to introduce the EOW to an ideal target audience, both in terms of interest and in terms of potential new member of the Network. From our presentation, it emerged the importance of comparable data on geographical distribution and abundance of wildlife hosts in Europe, fundamental to develop the best management policies and to perform effective risk assessments for shared emergent diseases. The adoption of a common and effective protocol adopted throughout the continent would ensure such comparability. Moreover, the discussion highlighted the need of extending the network to as many European countries as possible and, when feasible, of having multiple sites within each country. A number of participants manifested their interest to join the EOW during the 2023 campaign. Such a capillary distribution of observation points would provide solid and comparable density estimates as well as effective feedback about the field protocol implemented by the EOW. A number of questions were raised by the audience during the presentation of the EOW. [ABSTRACT FROM AUTHOR]

This report presents the results of field activities in relation to the generation of reliable wild boar density values by camera trapping (CT) in 19 areas in Europe, mainly in East Europe. Random Encounter Model (REM) densities ranged from 0.35±0.24 to 15.25±2.41 (SE) individuals/km2. No statistical differences in density among bioregions were found. The number of contacts was the component of the trapping rate that determined the coefficient of variation (CV) the most. The daily range (DR) significantly varied as a function of management; the higher values were detected in hunting grounds compared to protected areas, indicating that movement parameters are population specific, and confirming the potential role of hunting activities in increasing wild boar movement and contact rates among individual or groups. The results presented in this report illustrate that a harmonized approach to actual wildlife density estimation (namely for terrestrial mammals) is possible at a European scale, sharing the same protocols, collaboratively designing the study, processing, and analysing the data. This report adds reliable wild boar density values that have the potential to be used for wild boar abundance spatial modelling, both directly or to calibrate outputs of model based on abundance (such as hunting bags) or occurrence data. Future REM developments should focus on improving the precision of estimates (probably through increased survey effort). Next steps require an exhaustive and representative design of a monitoring network to estimate reliable trends of wild boar populations as a function of different factors in Europe. In this regard, the newly created European Observatory of Wildlife will be a network of observation points provided by collaborators from all European countries capable to monitor wildlife population at European level. [ABSTRACT FROM AUTHOR]

Citizen science (CS) has been increasingly used in wildlife disease surveillance since it can facilitate the detection and recovery of carcasses of target species used as sentinels of infection. This report updates on the improvement of an app adapted from iMammalia (MammalNet project) for early reporting carcasses of wild boar with a warning system. This app has a great potential for improving wildlife disease surveillance (carcass reporting), such as for ASF. The app has been expanded in the context of ENETWILD project during the second part of 2021 to several countries in their respective languages: Italy, Greece, Serbia, Montenegro, Kosovo, Bosnia‐Herzegovina, North Macedonia, Albania, and the latest to incorporate, Portugal. The ENETWILD project has generated alliance with FAO to promote the use of iMammalia in the Balkans to collect data in gap areas about the distribution of wild boar, to document the presence of carcasses of dead animals. The technical improvements that have been made to meet the needs of iMammalia to report the presence of wild boar carcasses correspond to the possibility of recording different parameters, such as sex, age, whether the dead animal has been hunted or not, or the degree of decomposition observed. The possibility of generating warnings to notify these records in real time to wildlife and/or sanitary services will be implemented in 2022. To date, iMammalia collected 14,393 mammal observations all over Europe, 797 of which corresponds to wild boar. A total of 1,270 observations correspond to animals found dead (5.53%), 30 out of which are wild boar, which, in some cases, were later diagnosed as ASF positive (e.g. in Serbia). We finally summarize the next step of ENETWILD in relation to iMammalia promotion, including an online workshop to provide an overview of disease surveillance systems in Europe, and to propose changes, including the promotion of CS. [ABSTRACT FROM AUTHOR]

The 2nd ENETWILD Annual General Meeting took place on 5‐6th October 2021, bringing together experts, stakeholders and ENETWILD collaborators in online workshop discussions. First, workshop discussions contributed to the analysis and proposal of approaches for a harmonized European‐wide wildlife monitoring framework able of sustaining coordinated decision‐making. Secondly, participants identified the key challenges that managers face in making decisions for wildlife in Europe and data needs for policies. Finally, we illustrated these challenges with the case of wild boar as a model species widely distributed across Europe. Inputs from the participants were collated into a plan of proposed steps and objectives for the mid‐term (5‐year time frame) to achieve progress on harmonised, coordinated, and integrated wildlife monitoring at the European level, which requires the contribution of experts from the early stages.. Specific proposed actions include the creation of a trans‐disciplinary authority at the European level, effective points of reference for data collection and sharing at different administrative levels and countries, a standing committee to coordinate and exchange experience and capacities on data collection between countries, and expert groups for problem solving, with proper EU financial support, establishing regular policy meetings.. To provide useful results, wildlife monitoring must ensure proper design and data analysis for subsequent science‐based management and best allocation of management resources. The 'Observatory' approach (a representative network of intensively monitored sites) can provide long‐term systematic and representative insights, normally more feasible for comparative studies, providing less biases and support for decision‐making. For international decision‐making by wildlife managers and politicians based on scientific knowledge and interdisciplinary research, experts should define the foundations of a common European wildlife decision‐making framework (inter‐institutional and inter‐sectorial). The development of a European legislation on wildlife management may represent an opportunity for addressing the abovementioned steps, identifying data priorities matching the needs of the various European Directorates, Agencies, and monitoring frameworks. [ABSTRACT FROM AUTHOR]

The ENETWILD consortium (www.enetwild.com) aims at progressively defining the spatial interface between wild ungulates and livestock in Europe, which is essential to evaluate the risk for shared diseases. This is to provide preliminary risk maps of possible wild‐domestic interfaces at European scale using relatively similar sized regions by compiling, for the first time, comprehensive data for both groups, wild and domestic ungulates in the continent. We spatially represented (i) the richness of species (livestock and wild ungulates), (ii) their specific occupancy and abundance (the latter for livestock), and finally, (iii) their spatial overlapping over Europe. Species richness in animal communities, including wildlife and domestic hosts, may moderate pathogen transmission and disease outcome.. As a first step, we should characterize the diverse assemblages of animal communities at large scale to better understand possible scenarios for further assessment of shared infection dynamics. About 90% of Europe land area hosts from one to five species of wild native ungulates. Therefore, the interface between livestock and wildlife is wide spread over the European continent. Native wild boar, roe deer and reed deer are widely distributed species, present in most possible assemblages of wild/domestic communities over Europe. The richness of ungulate species is high in Central Europe, from West to East, from the Alps (where the presence of mountain ungulates adds richness), extending to countries with important big game tradition and presence of introduced species, and finally, to Eastern Europe (where also typically northern species such as bisons appear)... To sum, we described by pair of species a wide diversity of potential interfaces, which had variable distribution areas.. While the analysis presented herein is purely spatial and at administrative level, the interface between wild and domestic ungulates is influenced by livestock husbandry (e.g., enclosed, herded or free‐ranging, level of biosecurity), landscape and land uses, and wildlife management practices, among other factors, operating locally. Therefore, there is need for a more detailed picture of the interface at European scale. [ABSTRACT FROM AUTHOR]

Background: Traditional nomograms can inform the presence of extraprostatic extension (EPE) but not laterality, which remains important for surgical planning, and have not fully incorporated multiparametric MRI data. We evaluated predictors of side-specific EPE on surgical pathology including MRI characteristics and developed side-specific EPE risk calculators., Methods: This was a retrospective cohort of patients evaluated with mpMRI prior to radical prostatectomy (RP) in our eleven hospital healthcare system from July 2018-November 2022. The dominant side was defined pre-operatively using a tiered system based on laterality of highest biopsy Gleason Grade Group (GG), highest PIRADS lesion, number of lesions, and cancer volume. Univariable and multivariable logistic regression were performed for overall EPE, dominant side EPE, and non-dominant side EPE. Internal validation with leave one out and calibration curves were completed., Results: EPE was identified in 53% (317/601) of patients at RP. Side-specific factors (PIRADS, GG, abutment) were only associated with EPE on their respective side. Final variables in the model associated with EPE on the dominant and non-dominant sides included age, log PSA density (PSAD), side-specific PIRADS 5, side-specific GG3-5, and percentage positivity of systematic cores. AUCs for dominant and non-dominant side EPE were 0.77 (95% CI 0.73-0.80) and 0.79 (95% CI 0.74-0.84), respectively. MRI-identified abutment and prostate health index (PHI) did not improve model discrimination. Risk calculators available online at https://rossnm1.shinyapps.io/PredictionOfEPELaterality/ ., Conclusions: PSA, side-specific PIRADS, side-specific GG, and percentage positivity of systematic cores were associated with side-specific EPE at RP and incorporated into a risk calculator to assist in surgical planning and nerve-sparing decisions at time of RP., Competing Interests: Competing interests: AER is engaged in consulting with American Society of Clinical Oncology (ASCO), Astellas, Bayer HealthCare Pharmaceuticals, Blue Earth Diagnostics, Janssen Biotech, Lantheus Medical Imaging, Myovant Sciences, NCCN, Pfizer, Tempus Health, and Veracyte. EMS is engaged in consulting with Astellas, Lantheus Medical Imaging, Pfizer. The other contributing authors have no conflicts of interest to declare. Ethics approval and consent to participate: The study was reviewed under IRB STU00214996 issued by Northwestern University. The study was performed in accordance with the Declaration of Helsinki., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The representation of wildlife-livestock interface (WLI) at an accurate spatial resolution poses several challenges. Furthermore, there is a lack of published material providing detailed descriptions of geospatial techniques for the purpose of producing visual results that are interpretable and contrastable for epidemiological analysis., Objectives: Our aim is to develop a standardized, applicable, and scalable methodological framework for describing and characterizing the WLI across a large spatial extent. Subsequently, we aim to employ this framework to depict specific WLI based on different epidemiological scenarios determined by the abundance of wild boar (Sus scrofa) and domestic ungulates as an illustrative case, specifically focusing on mainland Spain., Methods: To establish a methodological framework, we merged data from both wild and domestic sources into a hexagonal grid. We utilized data on wild boar hunting and the locations of pig, cattle, sheep, and goat farms in mainland Spain. New variables were derived from this combined dataset to illustrate the overlapping abundance between wild boar and domestic species. Finally, a cluster analysis of the generated variables was carried out, with the aim of distinguishing and characterizing various scenarios of the wild boar-domestic ungulate interface in mainland Spain., Results: The hexagonal grid proved appropriate to represent and evaluate the WLI at fine spatial resolution over such broad extent. Despite the inability to ascribe a dominant livestock type and production system to a specific region, we were able to identify fifteen main areas of interest in terms of overlap. As for extensive livestock, normally at the highest risk of interaction with wild boar, the primary regions in Spain were those with dehesa agroecosystem and the Atlantic areas. Certain scenarios were particularly relevant in terms of risk for interaction and subsequent transmission of disease, namely, the case of extensive pig production in south western Spain (dehesa agroecosystem), which is especially concerned about the potential introduction of African Swine fever (ASF) in the Country. DISCUSSION AND CONCLUSIONS: We provide a basis for visualizing and understanding of different WLI scenarios, which is extensible to other regions and interfaces, and automatable where precise source of data from wildlife and livestock are available. This spatial statistics framework enables the utilization of high-resolution data, ensuring consistency on uniform grids. This aligns with the needs of high-resolution disease dissemination models based on wildlife behaviour. Such aspects are crucial for developing risk assessment and improving strategies for the prevention, control, and eradication of shared priority emerging diseases at national and international levels, such as ASF., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: This study aimed to evaluate the association of dynamic contrast enhancement (DCE) with clinically significant prostate cancer (csPCa, Gleason Grade Group ≥2) and compare biparametric magnetic resonance imaging (bpMRI) and multiparametric MRI (mpMRI) nomograms., Subjects/patients and Methods: We identified a retrospective cohort of biopsy naïve patients who underwent pre-biopsy MRI separated by individual MRI series from 2018 to 2022. csPCa detection rates were calculated for patients with peripheral zone (PZ) lesions scored 3-5 on diffusion weighted imaging (DWI) with available DCE (annotated as - or +). bpMRI Prostate Imaging Reporting and Data System (PIRADS) (3 = 3-, 3+; 4 = 4-, 4+; 5 = 5-, 5+) and mpMRI PIRADS (3 = 3-; 4 = 3+, 4-, 4+; 5 = 5-, 5+) approaches were compared in multivariable logistic regression models. Nomograms for detection of csPCa and ≥GG3 PCa incorporating all biopsy naïve patients who underwent prostate MRI were generated based on available serum biomarkers [PHI, % free prostate-specific antigen (PSA), or total PSA] and validated with an independent cohort., Results: Patients ( n = 1010) with highest PIRADS lesion in PZ were included in initial analysis with 127 (12.6%) classified as PIRADS 3+ (PIRADS 3 on bpMRI but PIRADS 4 on mpMRI). On multivariable analysis, PIRADS 3+ lesions were associated with higher csPCa rates compared to PIRADS 3- (3+ vs. 3-: OR 1.86, p  = 0.024), but lower csPCa rates compared to PIRADS DWI 4 lesions (4 vs. 3+: OR 2.39, p  < 0.001). csPCa rates were 19% (3-), 31% (3+), 41.5% (4-), 65.9% (4+), 62.5% (5-), and 92.3% (5+). bpMRI nomograms were non-inferior to mpMRI nomograms in the development ( n  = 1410) and independent validation ( n  = 353) cohorts. Risk calculators available at: https://rossnm1.shinyapps.io/MynMRIskCalculator/., Conclusion: While DCE positivity by itself was associated with csPCa among patients with highest PIRADS lesions in the PZ, nomogram comparisons suggest that there is no significant difference in performance of bpMRI and mpMRI. bpMRI may be considered as an alternative to mpMRI for prostate cancer evaluation in many situations., Competing Interests: EMS is a consultant for Atria Academy of Science and Medicine, Early Medical, Lantheus, Pfizer, and PinnacleCare Health Advisors. AER is a consultant for Astellas, Astra Zeneca, Bayer HealthCare Pharmaceuticals, BillionToOne, Janssen Biotech, Lantheus, Myovant, Novartis, Pfizer, and Veracyte. These relationships are not related to the contents of this manuscript., (© 2024 The Author(s). BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Malaria is a public health problem and the cases diagnosed in the capital of Roraima, Brazil, show potential to characterize the burden of the disease in the state. This study aimed to describe the epidemiological, clinical, and laboratory aspects of malaria cases diagnosed in Boa Vista. For this purpose, a descriptive, cross-sectional study was conducted in two health units in the city, with individuals diagnosed and who agreed to respond the questionnaire. Of the total of 206 participants, characterized as men, mixed-race, and young, 96% (198) reported participating in illegal mining activity. Among the group of miners, 66% (131) came from other states of Brazil or other countries. The mines were mainly located in the Yanomami territory in Roraima. Plasmodium vivax infection occurred in 74% (153) of participants. In the miner's group, hospitalizations for severe malaria, previous malaria attacks, and delays in treatment after the onset of symptoms were reported. Although 73% (145) of miners reported knowing how malaria was transmitted, only 54% (107) used mosquito nets or repellents. The use of Artecom and chloroquine by miners is not for the complete treatment but only to relieve symptoms for returning to gold mines, highlighting the importance of molecular surveillance to antimalarial resistance. Indigenous peoples are considered vulnerable to malaria and miners promotes the increase of malaria in Roraima Indigenous Lands. Therefore, access to diagnosis and treatment in Indigenous areas invaded by miners is imperative to confront this disease that ravages Indigenous communities and threatens public health on a large scale to achieve the goal of eliminating malaria in the state.

The immune system plays a central role in controlling acute hepatitis B infection and in patients resolving chronic hepatitis B (CHB). Given that 221 million (75%) of CHB patients reside in low- and middle-income countries, the development of a vaccine with therapeutic properties represents a rational and cost-effective approach more than a romantic endeavor. This review systematically analyzes the key variables related to the safety, efficacy, and effectiveness of CHB treatments. HeberNasvac experience is revisited for addressing the challenges and potentialities of therapeutic vaccines, as well as the current roadblocks in research and development, registration, and large-scale implementation., How to Cite This Article: Aguilar JC, Akbar SMF, Al-Mahtab M, et al. HeberNasvac: Development and Application in the Context of Chronic Hepatitis B. Euroasian J Hepato-Gastroenterol 2024;14(2):221-237., Competing Interests: Source of support: Nil Conflict of interest: Dr. Sheikh MF Akbar is associated as Editor-in-Chief of this journal and this manuscript was subjected to this journal's standard review procedures, with this peer review handled independently of the Editor-in-Chief and his research group.Conflict of interest: Dr. Sheikh MF Akbar is associated as Editor-in-Chief of this journal and this manuscript was subjected to this journal's standard review procedures, with this peer review handled independently of the Editor-in-Chief and his research group., (Copyright © 2024; The Author(s).)

Background: Multiparametric prostate MRI (mpMRI) is being increasingly adopted for work-up of prostate cancer. For patients selected to omit biopsy, we identified factors associated with repeat MRI, eventual prostate biopsy, and subsequent detection of clinically significant prostate cancer (csPCa, Grade Group ≥2)., Methods: We identified biopsy-naïve men presenting with PSA 2-20 ng/mL (March 2018-June 2021) undergoing initial mpMRI with PIRADS 1-3 lesions who were not selected for biopsy with ≥6 months follow-up. We examined factors associated with repeat mpMRI, progression to biopsy, and subsequent detection of csPCa with univariable and multivariable logistic regression., Results: Of 1494 men, 31% (463/1494) did not pursue biopsy. PSA density (PSAD) ≤ 0.1, prostate health index (PHI) < 55, and PIRADS 1-2 were associated with omission of prostate biopsy. csPCa diagnosis-free survival was 97.6% (326/334) with median follow up of 23.1 months (IQR 15.1-34.6 months). Black race, PSA, PHI, PSA density, and PSA and PHI velocity were significant predictors of undergoing repeat mpMRI (15.6%, 52/334) and subsequent biopsy (8.4%, 28/334). 8 men were subsequently diagnosed with csPCa (N = 7 on prostate biopsy; N = 1 incidentally on holmium enucleation of prostate). All patients diagnosed with csPCa had PIRADS 4-5 on repeat mpMRI., Conclusions: The subsequent detection rate of csPCa among patients not initially biopsied after mpMRI was low at 2.4%. Decisions to omit biopsy after initial reassuring PHI, PSAD, and mpMRI appear safe with subsequent reassuring serum biomarkers and for cause mpMRI during follow-up., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

We sought to assess erectile dysfunction (ED) medication use among males aged 18-40. Between June and July 2023, a cross-sectional survey on Qualtrics (Provo, UT) was disseminated via Research Match. Among 210 respondents, ED prevalence was 57.1% with 39.0% reporting prior ED medication use. Black or African American race (OR = 3.54, p < 0.001), Hispanic or Latino ethnicity (OR = 3.32, p = 0.01), and Medicare or Medicaid insurance status (OR = 6.07, p < 0.001) were associated with increased medication utilization. Income >$200,000 was associated with decreased medication usage (OR 0.23, p = 0.04). ED severity significantly correlated with higher medication usage. Primary care providers were the most common source of acquisition (47.6%), followed by online direct to consumer (DTC) platforms (31.7%) and personal connections (19.5%). Privacy (n = 51, 62.2%) and cost (n = 45, 54.9%) were key considerations in obtaining medications. Despite 73.2% of individuals receiving counseling regarding risks/benefits and 84.1% receiving instructions for proper use, only 28.0% correctly identified essential aspects of proper/appropriate use. Overall, we found a high ED prevalence and medication utilization rate. The preference for privacy in procuring medications suggests ongoing stigma around men's sexual health. Despite extensive counseling, a significant knowledge gap remains indicating a pressing need for enhanced patient education., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) provides appropriate use criteria (AUC) for prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) which include guidance on imaging in newly diagnosed prostate cancer and in patients with biochemically recurrent (BCR) disease. This study aims to examine trends in PSMA implementation and the prevalence and outcomes of scans ordered in scenarios deemed rarely appropriate or not meeting SNMMI AUC., Methods: We retrospectively identified patients who were diagnosed with presumptive National Comprehensive Cancer Network unfavorable intermediate, high, or very high risk prostate cancer, patients who underwent staging for BCR, and all patients staged with PSMA between July 2021 and March 2023. Positivity was validated by adherence to a predetermined reference standard., Results: The frequency of PSMA use increased in initial staging from 24% to 80% and work-up of BCR from 91% to 99% over our study period. In addition, 5% (17/340) of PSMA scans ordered for initial staging did not meet AUC and 3% (15/557) of posttreatment scans were deemed rarely appropriate. Initial staging orders not meeting SNMMI AUC resulted in no positivity (0/17), while rarely appropriate posttreatment scans were falsely positive in 75% (3/4) of cases. Urologists (53%, 17/32) comprised the largest ordering specialty in rarely appropriate use., Conclusion: The frequency of PSMA use rose across the study period. A significant minority of patients received PSMA PET/CT in rarely appropriate scenarios yielding no positivity in initial staging and significant false positivity post-therapy. Further education of providers and electronic medical record-based interventions could help limit the rarely appropriate use of PET imaging., (© 2024 The Authors. The Prostate published by Wiley Periodicals LLC.)

P2X7 is an ATP-activated purinergic receptor implicated in pro-inflammatory responses. It is associated with the development of several diseases, including inflammatory and neurodegenerative conditions. Although several P2X7 receptor antagonists have recently been reported in the literature, none of them is approved for clinical use. However, the structure of the known antagonists can serve as a scaffold for discovering effective compounds in clinical therapy. This study aimed to propose an improved virtual screening methodology for the identification of novel potential P2X7 receptor antagonists from natural products through the combination of shape-based and docking approaches. First, a shape-based screening was performed based on the structure of JNJ-47965567, a P2X7 antagonist, using two natural product compound databases, MEGx (~5.8 × 10 3 compounds) and NATx (~32 × 10 3 compounds). Then, the compounds selected by the proposed shape-based model, with Shape-Tanimoto score values ranging between 0.624 and 0.799, were filtered for drug-like properties. Finally, the compounds that met the drug-like filter criteria were docked into the P2X7 allosteric binding site, using the docking programs GOLD and DockThor . The docking poses with the best score values were submitted to careful visual inspection of the P2X7 allosteric binding site. Based on our established visual inspection criteria, four compounds from the MEGx database and four from the NATx database were finally selected as potential P2X7 receptor antagonists. The selected compounds are structurally different from known P2X7 antagonists, have drug-like properties, and are predicted to interact with key P2X7 allosteric binding pocket residues, including F88, F92, F95, F103, M105, F108, Y295, Y298, and I310. Therefore, the combination of shape-based screening and docking approaches proposed in our study has proven useful in selecting potential novel P2X7 antagonist candidates from natural-product-derived compounds databases. This approach could also be useful for selecting potential inhibitors/antagonists of other receptors and/or biological targets.

Social media (SoMe) offers great potential to expand access to health information, but a significant proportion of users consume its content instead of consulting a physician. We sought to quantify the volume and characterize the accuracy of men's health-related content on TikTok and Instagram. We searched TikTok and Instagram for the terms: testosterone, erectile dysfunction, male infertility, semen retention, Peyronie's disease, and vasectomy. The top 10 hashtags for each term were used to estimate the total impressions for each term on each platform, and posts were then characterized by creator type, content type, and accuracy (1 to 5 scale). TikTok had 2,312,407,100 impressions and Instagram had 3,107,300 posts across all topics. Semen retention had the most impressions on TikTok (1,216,074,000) and posts on Instagram (1,077,000). Physicians created only a small portion of total TikTok and Instagram posts (10.3% and 12.9%, respectively). Across all topics, the accuracy of content was poor (2.6 ± 1.7), however, physician posts were more accurate than non-physician posts (mean 4.2 ± 1.2 vs 2.3 ± 1.6, p < 0.001, respectively). Men's health content is popular on TikTok and Instagram but is not accurate. We recommend that physicians actively engage in SoMe to address misinformation., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Buprenorphine is used to treat opioid use disorder (OUD). Weekly and monthly subcutaneous long-acting buprenorphine injections (CAM2038) provide more stable buprenorphine plasma levels and reduce the treatment burden, misuse, and diversion associated with sublingual transmucosal buprenorphine formulations. To characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship, a maximum inhibition (I max ) model was developed relating CAM2038 buprenorphine plasma concentration to drug liking maximum effect (E max ) visual analog scale (VAS; bipolar) score after intramuscular hydromorphone administration. Data included time-matched observations of buprenorphine plasma concentration and drug liking E max VAS score after hydromorphone 18 mg administration in 47 non-treatment-seeking adults with moderate to severe OUD in a phase 2 study. Analysis used non-‍linear mixed-effects modeling (NONMEM ® ). The final I max model adequately described the PK/PD relationship between buprenorphine plasma concentration and drug liking E max VAS score. Simulations showed drug liking was effectively blocked at low buprenorphine plasma concentrations (0.4 ng/mL) where the upper 95% confidence interval of the drug liking E max VAS score was below the pre-defined 11-point complete blockade threshold. The buprenorphine plasma concentration required to achieve 90% of the maximal effect (IC 90 ) of drug liking was 0.675 ng/mL. Interindividual variability in responses to buprenorphine was observed; some participants experienced fluctuating responses, and a few did not achieve drug liking blockade even with higher buprenorphine plasma concentrations. This affirms the need to individualize treatment and titrate doses for optimal treatment outcomes. PK/PD models were also developed for desire to use VAS and Clinical Opiate Withdrawal Scale (COWS) scores, with results aligned to those for drug liking., (© 2024. The Author(s).)

Introduction: Clinicians may offer patients with positive lymph nodes (pN1) and undetectable PSA following surgery for prostate cancer either observation or adjuvant therapy based on AUA, EAU, and NCCN guidelines considering standard PSA detection thresholds of <0.1ng/ml. Here we sought to investigate the outcomes of pN1 patients in the era of ultrasensitive PSA testing., Methods: We queried the Northwestern Electronic Data Warehouse for patients with prostate cancer who were pN1 at radical prostatectomy and followed with ultrasensitive PSA. Patients receiving neoadjuvant treatment were excluded. We compared clinical characteristics including age, race, pre-operative PSA, Gleason grade, tumor stage, surgical margins, and nodal specimens to identify factors associated with achievement and maintenance of an undetectable PSA (defined as <0.01 ng/mL). Statistics were performed using t-test, Mann-Whitney U test, chi-squared analysis, and logistic regression with significance defined as p<0.05., Results: From 2018-2023, 188 patients were included. Subsequently, 39 (20.7%) had a PSA decline to undetectable levels (<0.01 ng/mL) post-operatively at a median time of 63 days. Seven percent of these men (3/39) were treated with adjuvant RT + ADT with undetectable PSA levels. 13/39 (33.3%) had eventual rises in PSA to ≥0.01 ng/mL for which they underwent salvage RT with ADT. Overall, 23/39 (59%) patients achieved and maintained undetectable PSA levels without subsequent therapy at median follow-up of 24.2 mo. Compared to patients with PSA persistence after surgery or elevations to detectable levels (≥0.01 ng/mL), patients who achieved and maintained undetectable levels had lower Gleason grades (p=0.03), lower tumor stage (p<0.001), fewer positive margins (p=0.02), and fewer involved lymph nodes (p=0.02). On multivariable analysis, only primary tumor (pT) stage was associated with achieving and maintaining an undetectable PSA; pT3b disease was associated with a 6.6-fold increased chance of developing a detectable PSA (p=0.03)., Conclusion: Ultrasensitive PSA can aid initiation of early salvage therapy for lymph node positive patients after radical prostatectomy while avoiding overtreatment in a significant subset. 20% of patients achieved an undetectable PSA and over half of this subset remained undetectable after 2 years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Aguiar, Li, Ho, Bennett, Li, Neill, Schaeffer, Patel and Ross.)

Surface superconductivity, wherein electron pairing occurs at material surfaces or interfaces, has attracted a remarkable amount of attention since its discovery. Recent theoretical predictions have unveiled increased critical temperatures, especially at the surfaces of certain compounds and/or structures. The notion of "surface ordering" has been advanced to elucidate this phenomenon. Employing the framework of self-consistent Bogoliubov-de Gennes equations and a model incorporating correlated disorder, our study demonstrates the persistence of the surface ordering effect in the presence of weak to moderate bulk disorder. Intriguingly, our findings indicate that under moderate disorder conditions the surface critical temperature can be further increased, depending on the intensity and correlation of the disorder.

(1) Background: Malaria remains a significant global public health issue. Since parasites quickly became resistant to most of the available antimalarial drugs, treatment effectiveness must be constantly monitored. In Brazil, up to 10% of cases of vivax malaria resistant to chloroquine (CQ) have been registered. Unlike P. falciparum , there are no definitive molecular markers for the chemoresistance of P. vivax to CQ. This work aimed to investigate whether polymorphisms in the pvcrt-o and pvmdr1 genes could be used as markers for assessing its resistance to CQ. (2) Methods: A total of 130 samples from P. vivax malaria cases with no clinical and/or parasitological evidence of CQ resistance were studied through polymerase chain reaction for gene amplification followed by target DNA sequencing. (3) Results: In the pvcrt-o exons, the K10 insert was present in 14% of the isolates. Regarding pvmdr1 , T958 M and F1076 L haplotypes showed frequencies of 95% and 3%, respectively, while the SNP Y976 F was not detected. (4) Conclusions: Since K10- pvcrt-o and F1076 L /T958 M - pvmdr1 polymorphisms were detected in samples from patients who responded well to CQ treatment, it can be concluded that mutations in these genes do not seem to have a potential for association with the phenotype of CQ resistance.

Rationale: Despite its increasingly widespread use, little is known about the impact of cannabis smoking on the response to viral infections like influenza A virus (IAV). Many assume that cannabis smoking will disrupt antiviral responses in a manner similar to cigarette smoking; however, since cannabinoids exhibit anti-inflammatory effects, cannabis smoke exposure may impact viral infection in distinct ways., Methods: Male and female BALB/c mice were exposed daily to cannabis smoke and concurrently intranasally instilled with IAV. Viral burden, inflammatory mediator levels (multiplex ELISA), lung immune cells populations (flow cytometry) and gene expression patterns (RNA sequencing) were assessed in the lungs. Plasma IAV-specific antibodies were measured via ELISA., Results: We found that cannabis smoke exposure increased pulmonary viral burden while decreasing total leukocytes, including macrophages, monocytes and dendritic cell populations in the lungs. Furthermore, infection-induced upregulation of certain inflammatory mediators (interferon-γ and C-C motif chemokine ligand 5) was blunted by cannabis smoke exposure, which in females was linked to the transcriptional downregulation of pathways involved in innate and adaptive immune responses. Finally, plasma levels of IAV-specific IgM and IgG1 were significantly decreased in cannabis smoke-exposed, infected mice compared to infected controls, only in female mice., Conclusions: Overall, cannabis smoke exposure disrupted host-defence processes, leading to increased viral burden and dampened inflammatory signalling. These results suggest that cannabis smoking is detrimental to the maintenance of pulmonary homeostasis during viral infection and highlight the need for data regarding the impact on immune competency in humans., Competing Interests: Conflict of interest: All authors have nothing to disclose., (Copyright ©The authors 2023.)

Purpose: To develop nomograms that predict the detection of clinically significant prostate cancer (csPCa, defined as ≥GG2 [Grade Group 2]) at diagnostic biopsy based on multiparametric prostate MRI (mpMRI), serum biomarkers, and patient clinicodemographic features., Materials and Methods: Nomograms were developed from a cohort of biopsy-naïve men presenting to our 11-hospital system with prostate specific antigen (PSA) of 2-20 ng/mL who underwent pre-biopsy mpMRI from March 2018-June 2021 (n = 1494). The outcomes were the presence of csPCa and high-grade prostate cancer (defined as ≥GG3 prostate cancer). Using significant variables on multivariable logistic regression, individual nomograms were developed for men with total PSA, % free PSA, or prostate health index (PHI) when available. The nomograms were both internally validated and evaluated in an independent cohort of 366 men presenting to our hospital system from July 2021-February 2022., Results: 1031 of 1494 men (69%) underwent biopsy after initial evaluation with mpMRI, 493 (47.8%) of whom were found to have ≥GG2 PCa, and 271 (26.3%) were found to have ≥GG3 PCa. Age, race, highest PIRADS score, prostate health index when available, % free PSA when available, and PSA density were significant predictors of ≥GG2 and ≥GG3 PCa on multivariable analysis and were used for nomogram generation. Accuracy of nomograms in both the training cohort and independent cohort were high, with areas under the curves (AUC) of ≥0.885 in the training cohort and ≥0.896 in the independent validation cohort. In our independent validation cohort, our model for ≥GG2 prostate cancer with PHI saved 39.1% of biopsies (143/366) while only missing 0.8% of csPCa (1/124) with a biopsy threshold of 20% probability of csPCa., Conclusions: Here we developed nomograms combining serum testing and mpMRI to help clinicians risk stratify patients with elevated PSA of 2-20 ng/mL who are being considered for biopsy. Our nomograms are available at https://rossnm1.shinyapps.io/MynMRIskCalculator/ to aid with biopsy decisions., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Main Results: Technology transfer can take place at large events, as long as safety protocols are strictly enforced. It is important to disseminate, at these events, the concepts of the Responsible Research and Innovation (RRI). Implications for services: Face-to-face training course is fundamental for training public health professionals. Technology transfer between research institutions and health services results in updating and improving health system performance., Perspectives: Based on the success of the reported technology transfer, a new module will be incorporated into the next edition of VEME (Panama 2022), entitled Virus Evolution to Public Health Policy Makers. The objective of this report was to describe the first face-to-face course aimed at training public health professionals in performing real-time genomic surveillance during the pandemic period. Experience report on a theoretical-practical course focusing on genomic research and surveillance, including mobile sequencing technologies, bioinformatics, phylogenetics and epidemiological modeling. There were 162 participants in the event and it was the first major face-to-face training course conducted during the COVID-19 epidemic in Brazil. No cases of SARS-CoV-2 infection was detected among the participants at the end of the event, suggesting the safety and effectiveness of all safety measures adopted. The results of this experience suggest that it is possible to conduct professional training safely during pandemics, as long as all safety protocols are followed.

HeberNasvac is a recently developed therapeutic vaccine for chronic hepatitis B (CHB) administered by intranasal (IN) and subcutaneous (SC) routes in a 14 days/10 doses schedule. To compare different schedules and routes of immunizations, a group of patients received four different vaccination regimens in a placebo-controlled factorial study. Subsequently, patients were followed for a minimum time of 48 weeks. Samples collected at the end of the follow-up were compared with initial samples. Groups I and II received the product by IN/SC routes, every 14 and 7 days, respectively. Groups III and IV were treated by SC route alone following a 14 and 7 days schedule. A group of 21 CHB patients received the vaccine in four different schedules and eight patients received placebo for a total of 29 patients enrolled. The 61.9% of vaccinees reduced their VL ≥2Log compared with baseline levels and 25% in placebo group. The 47.6% of vaccines reduced HBV levels to undetectable, 25% in placebo. HBeAg loss and seroconversion to anti-HBeAg was only achieved in vaccinees, 4 out of 9 (44.4%), and 40% (8 out of 20) developed anti-HBs response, none in placebo group. Reduction of HBsAg level in ≥1Log was achieved in the 35.0% of vaccinees and in none of the placebo-treated patients. Considering the individual and factorial analysis, significant HBV DNA reduction was detected in groups I and II, immunized by IN/SC routes. A significantly higher proportion of patients reducing VL to ≥2Log was also detected grouping the patients treated by IN/SC routes (G I + II) and grouping those inoculated every 14 days (G I + III), with 72.7% and 63.6%, respectively, compared with the placebo group (25.0%). The patients immunized every 14 days (G I + G III) also reduced the HBsAg levels compared with baseline. In conclusion, after more than 48 weeks of treatment-free follow-up, HeberNasvac-treated patients demonstrated superior responses compared with the placebo group in terms of antiviral and serological responses. The factorial analysis evidenced that the schedule combining the IN route of immunization and the frequency of 14 days resulted in the stronger antiviral and serological responses. Present results support the study of IN-only immunization schedules in future and was consistent with previous results. Long-lasting follow-ups were done to explore histological variables and the progression of serological variables in order to detect late responders., How to Cite This Article: Freyre FM, Aguiar JA, Cinza Z, et al . Impact of the Route and Schedule of Immunization on the Serological and Virological Response of Chronic Hepatitis B Patients Treated with HeberNasvac. Euroasian J Hepato-Gastroenterol 2023;13(2):73-78., Competing Interests: Source of support: Ministry of Public Health of Cuba; CIGB. Conflict of interest: Dr Eduardo Penton, Dr Mamun Al Mahtab, Dr Sheikh Mohammad Fazle Akbar, and Dr Julio Cesar Aguilar are associated as the Editorial board members of this journal and this manuscript was subjected to this journal's standard review procedures, with this peer review handled independently of these Editorial board members and their research group. Consent for publishing: Publication of these results has been approved by all coauthors and our institutional authorities., (Copyright © 2023; The Author(s).)

Using the tight-binding Bogoliubov-de Gennes formalism, we describe the influence of the surface potential on the superconducting critical temperature at the surface. Surface details are taken into account within the framework of the self-consistent Lang-Kohn effective potential. The regimes of strong and weak coupling of superconducting correlations are considered. Our study reveals that, although the enhancement of the surface critical temperature, originating from the enhancement of the localized correlation due to the constructive interference between quasiparticle bulk orbits, can be sufficiently affected by the surface potential, this influence, nonetheless, strongly depends on the bulk material parameters, such as the effective electron density parameter and Fermi energy, and is likely to be negligible for some materials, in particular for narrow-band metals. Thus, superconducting properties of a surface can be controlled by the surface/interface potential properties, which offer an additional tuning knob for the superconducting state at the surface/interface.

The aim of this study was to externally validate the predictive performance of published population pharmacokinetic models of gentamicin in all paediatric age groups, from preterm newborns to adolescents. We first selected published population pharmacokinetic models of gentamicin developed in the paediatric population with a wide age range. The parameters of the literature models were then re-estimated using the PRIOR subroutine in NONMEM ® . The predictive ability of the literature and the tweaked models was evaluated. Retrospectively collected data from a routine clinical practice (512 concentrations from 308 patients) were used for validation. The models with covariates characterising developmental changes in clearance and volume of distribution had better predictive performance, which improved further after re-estimation. The tweaked model by Wang 2019 performed best, with suitable accuracy and precision across the complete paediatric population. For patients treated in the intensive care unit, a lower proportion of patients would be expected to reach the target trough concentration at standard dosing. The selected model could be used for model-informed precision dosing in clinical settings where the entire paediatric population is treated. However, for use in clinical practice, the next step should include additional analysis of the impact of intensive care treatment on gentamicin pharmacokinetics, followed by prospective validation., (© 2023 Mateja Črček et al., published by Sciendo.)

Background: The utilization of MRI to risk stratify elevated PSA prior to prostate biopsy has been inconsistently adopted and varies considerably by practice setting. This study aims to evaluate the usage and performance of MRI as an advanced risk stratification tool of elevated PSA prior to biopsy and identify factors associated with differential utilization of MRI at a large academic setting with ready access to 3T multiparametric MRI of the prostate., Methods: A retrospective single-center study of 2900 men presenting with elevated PSA 2-20 ng/mL from 2018 through 2021 was conducted. We analyzed trends in MRI utilization and outcomes of prostate biopsy by MRI usage. Univariate and multivariate logistic regressions were performed to calculate odds ratios to identify patient- and provider-level predictors of MRI usage., Results: Rates of prebiopsy MRI utilization increased from 56% in 2018 to 89% in 2021 (p < 0.001). Prebiopsy MRI led to biopsy avoidance in 31% of men. MRI usage enhanced detection of clinically significant prostate cancer by 13% and reduced identification of Gleason Grade Group 1 disease by 3% and negative biopsies by 10% (p < 0.001). Men who received MRI were more likely to be younger than 75 years in age and have private or Medicare insurance, PSA >4 ng/mL, and PHI >27. In both univariate and multivariate analysis, black race and Medicaid insurance were associated with reduced MRI utilization (all p < 0.001). Urologic provider was an independent predictor of MRI usage (p < 0.001)., Conclusions: Use of MRI as a risk stratification tool for elevated PSA rose during this 4-year study period. Men who self-identify as black or men with Medicaid coverage have diminished rates of MRI usage. Considerable provider-level variability in MRI use was observed. Future research aimed at identifying factors affecting implementation of MRI as a routine risk assessment tool is warranted., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

(1) Background: Malaria is a public health problem worldwide. Despite global efforts to control it, antimalarial drug resistance remains a great challenge. In 2009, our team identified, for the first time in Brazil, chloroquine (CQ)-susceptible Plasmodium falciparum parasites in isolates from the Brazilian Amazon. The present study extends those observations to include survey samples from 2010 to 2018 from the Amazonas and Acre states for the purpose of tracking pfcrt molecular changes in P. falciparum parasites. (2) Objective: to investigate SNPs in the P. falciparum gene associated with chemoresistance to CQ ( pfcrt) . (3) Methods: Sixty-six P. falciparum samples from the Amazonas and Acre states were collected from 2010 to 2018 in patients diagnosed at the Reference Research Center for Treatment and Diagnosis of Malaria (CPD-Mal/Fiocruz), FMT-HVD and Acre Health Units. These samples were subjected to PCR and DNA Sanger sequencing to identify mutations in pfcrt (C72 S , M74 I , N75 E , and K76 T ). (4) Results: Of the 66 P. falciparum samples genotyped for pfcrt , 94% carried CQ-resistant genotypes and only 4 showed a CQ pfcrt sensitive-wild type genotype, i.e., 1 from Barcelos and 3 from Manaus. (5) Conclusion: CQ-resistant P. falciparum populations are fixed, and thus, CQ cannot be reintroduced in malaria falciparum therapy.

Background: Genetic evaluation of men with advanced prostate cancer is recognized as imperative both to guide treatment decisions and to trigger cascade genetic testing of family members. Here we investigate utilization patterns of genetic testing among a contemporary cohort of men with advanced prostate cancer at our institution., Methods: We queried the Northwestern Electronic Data Warehouse from January 2021 to present for all men diagnosed with National Comprehensive Cancer Network high-risk/very high-risk, regional, or metastatic prostate cancer. Patients were excluded from analyses if treated at an outside institution and/or presented for a second opinion evaluation. Statistics were performed using t-test, Chi-squared test, and univariable and multivariable logistic regression with significance defined as p < 0.05., Results: Atotal of 320 men (52.5%) had local/regional disease and 290 (47.5%) had metastatic disease, 53 (18.3%) of whom had castrate resistant prostate cancer. Rates of germline genetic testing rate were low in patients with localized disease (9.4%) and metastatic disease (34.1%). Only 19 (35.8%) men diagnosed with metastatic castrate resistant prostate cancer underwent germline genetic evaluation. Germline testing was most frequently discussed or ordered by medical oncologists (52%) followed by urologists (20%). Men who underwent germline testing were younger (p < 0.001), more likely to have Medicaid or private insurance (p = 0.002), and more likely to have metastatic disease (p < 0.001). There were no statistically significant differences in baseline PSA, ethnicity, race, or castration sensitivity status. Age (odds ratio [OR]: 0.94, 95% confidence interval [CI]: 0.91-0.97, p < 0.001) and metastatic disease (OR: 5.71, 95% CI: 3.63-9.22, p < 0.001) were significant independent predictors of genetic testing on multivariable logistic regression., Conclusions: Here we report that utilization of genetic testing is associated with metastatic disease and inversely associated with age. Overall, utilization rates of genetic testing remain low in all patient groups, including in the metastatic castrate resistant setting, where genetic testing can identify patients with homologous recombination repair deficiency who may benefit from use of targeted therapeutics such as PARP inhibitors. Genetic testing in men with aggressive prostate cancer is critical and barriers to routine implementation of testing require further study to develop strategies to improve utilization rates., (© 2022 Wiley Periodicals LLC.)

The growth of advanced energy technologies for power generation is enabled by the design, development, and integration of structural materials that can withstand extreme environments, such as high temperatures, radiation damage, and corrosion. High-entropy alloys (HEAs) are a class of structural materials in which suitable chemical elements in four or more numbers are mixed to typically produce single-phase concentrated solid solution alloys (CSAs). Many of these alloys exhibit good radiation tolerance like limited void swelling and hardening up to relatively medium radiation doses (tens of displacements per atom (dpa)); however, at higher radiation damage levels (>50 dpa), some HEAs suffer from considerable void swelling limiting their near-term acceptance for advanced nuclear reactor concepts. In this study, we developed a HEA containing a high density of Cu-rich nanoprecipitates distributed in the HEA matrix. The Cu-added HEA, NiCoFeCrCu 0.12 , shows excellent void swelling resistance and negligible radiation-induced hardening upon irradiation up to high radiation doses (i.e., higher than 100 dpa). The void swelling resistance of the alloy is measured to be significantly better than NiCoFeCr CSA and austenitic stainless steels. Density functional theory simulations predict lower vacancy and interstitial formation energies at the coherent interfaces between Cu-rich nanoprecipitates and the HEA matrix. The alloy maintained a high sink strength achieved via nanoprecipitates and the coherent interface with the matrix at a high radiation dose (∼50 dpa). From our experiments and simulations, the effective recombination of radiation-produced vacancies and interstitials at the coherent interfaces of the nanoprecipitates is suggested to be the critical mechanism responsible for the radiation tolerance of the alloy. The materials design strategy based on incorporating a high density of interfaces can be applied to high-entropy alloy systems to improve their radiation tolerance.

Nasvac (HeberNasvac ® ) is a novel therapeutic vaccine for chronic hepatitis B (CHB). This product is a formulation of the core (HBcAg) and surface (HBsAg) antigens of the hepatitis B virus (HBV), administered by nasal and subcutaneous routes, in a distinctive schedule of immunizations. In the present review article, we discuss the action mechanisms of HeberNasvac, considering the immunological properties of the product and their antigens. Specifically, we discuss the capacity of HBcAg to activate different pathways of innate immunity and the signal transduction after a multi-TLR agonist effect, and we review the results of recent clinical trials and in vitro studies. Aimed at understanding the clinical results of Nasvac and other therapeutic vaccines under development, we discuss the rationale of administering a therapeutic vaccine through the nasal route and also the current alternatives to combine therapeutic vaccines and antivirals (NUCs). We also disclose potential applications of this product in novel fields of immunotherapy.

Aim: Microscopic bowel inflammation is present in up to 60% of all patients with spondyloarthritis (SpA) and appears to be associated with more severe joint disease and a higher risk of developing inflammatory bowel disease (IBD). This study aimed to determine the utility of fecal calprotectin (fCAL) in evaluating endoscopic and histological bowel inflammation in SpA patients., Methods: Ileocolonoscopies with biopsies and fCAL measurements were performed in 65 patients with SpA., Results: In 47 (72.3%) patients, the fCAL levels were higher than 50 μg/g, whereas in 20 (30.7%), these levels were greater than 250 μg/g. A total of 38 (58.5%) patients presented with microscopic bowel inflammation, and 13 (20%) presented with signs of endoscopic inflammation. fCAL levels were significantly higher in patients with microscopic bowel inflammation than in those without inflammatory findings (P < .001); additionally, these levels were slightly higher in patients with endoscopic signs of bowel inflammation (P = .053). A fCAL cutoff value of 96 μg/g predicted histological bowel inflammation with 73% sensitivity and 67% specificity. No statistically significant difference was observed in the fCAL levels between patients who had been treated or not treated with nonsteroidal anti-inflammatory drugs (NSAIDs)., Conclusion: Our findings confirm a high prevalence of microscopic bowel inflammation in SpA patients, regardless of the use of NSAIDs. The evaluation of fCAL levels proved to be useful in the identification of microscopic inflammation and could help in the more judicious indication of ileocolonoscopy. These results support the use of fCAL for the evaluation of microscopic bowel inflammation in SpA patients., (© 2022 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objective: This study evaluated the effects of aluminum (Al) intake on endochondral ossification during the neonatal phase., Method: Twelve male newborn Gerbils (Meriones unguiculatus) were randomly divided into control (C) and aluminum (Al) groups (n = 6 animals/group). From the 1st to 15th day of life, gerbils received an AlCl 3 solution (10 mg/kg/day) via gavage. The control group received only the saline solution. On the 16th day, their tibias were processed for paraffin embedding and were submitted to histomorphometric, histochemical, and immunohistochemical analyses., Results: In the epiphyseal cartilage Al did not affect the proteoglycan content or cell proliferation; however, it increased matrix metalloprotease-2 (MMP-2) immunostaining and the hypertrophic layer thickness. In bone, Al decreased trabeculae number, trabecular width, cortical bone width, and proliferation. Furthermore, the relative frequency of bone matrix and fibrillar collagen decreased 3.9% and 16.2%, respectively. The number of osteoclasts and osteocalcin digital optical density (D.O.D) remained the same., Conclusion: The results suggest that Al intake during the neonatal period impairs endochondral ossification by affecting epiphyseal cartilage and bone architecture., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Multi-input multi-output (MIMO) transmission schemes have become the techniques of choice for increasing spectral efficiency in bandwidth-congested areas. However, the design of cost-effective receivers for MIMO channels remains a challenging task. The maximum likelihood detector can achieve excellent performance-usually, the best performance-but its computational complexity is a limiting factor in practical implementation. In the present work, a novel MIMO scheme using a practically feasible decoding algorithm based on the phase transmittance radial basis function (PTRBF) neural network is proposed. For some practical scenarios, the proposed scheme achieves improved receiver performance with lower computational complexity relative to the maximum likelihood decoding, thus substantially increasing the applicability of the algorithm. Simulation results are presented for MIMO-OFDM under 5G wireless Rayleigh channels so that a fair performance comparison with other reference techniques can be established.

Introduction: Over 300 million people in the world live with asthma, resulting in 500,000 annual global deaths with future increases expected. It is estimated that around 50-80% of asthma exacerbations are due to viral infections. Currently, a combination of long-acting beta agonists (LABA) for bronchodilation and glucocorticoids (GCS) to control lung inflammation represent the dominant strategy for the management of asthma, however, it is still sub-optimal in 35-50% of moderate-severe asthmatics resulting in persistent lung inflammation, impairment of lung function, and risk of mortality. Mechanistically, LABA/GCS combination therapy results in synergistic efficacy mediated by intracellular cyclic adenosine monophosphate (cAMP)., Hypothesis: Increasing intracellular cAMP during LABA/GCS combination therapy via inhibiting phosphodiesterase 4 (PDE4) and/or blocking the export of cAMP by ATP Binding Cassette Transporter C4 (ABCC4), will potentiate anti-inflammatory responses of mainstay LABA/GCS therapy., Methods: Expression and localization experiments were performed using in situ hybridization and immunohistochemistry in human lung tissue from healthy subjects, while confirmatory transcript and protein expression analyses were performed in primary human airway epithelial cells and cell lines. Intervention experiments were performed on the human airway epithelial cell line, HBEC-6KT, by pre-treatment with combinations of LABA/GCS with PDE4 and/or ABCC4 inhibitors followed by Poly I:C or imiquimod challenge as a model for viral stimuli. Cytokine readouts for IL-6, IL-8, CXCL10/IP-10, and CCL5/RANTES were quantified by ELISA., Results: Using archived human lung and human airway epithelial cells, ABCC4 gene and protein expression were confirmed in vitro and in situ. LABA/GCS attenuation of Poly I:C or imiquimod-induced IL-6 and IL-8 were potentiated with ABCC4 and PDE4 inhibition, which was greater when ABCC4 and PDE4 inhibition was combined. Modulation of cAMP levels had no impact on LABA/GCS modulation of Poly I:C-induced CXCL10/IP-10 or CCL5/RANTES., Conclusion: Modulation of intracellular cAMP levels by PDE4 or ABCC4 inhibition potentiates LABA/GCS efficacy in human airway epithelial cells challenged with viral stimuli. The data suggest further exploration of the value of adding cAMP modulators to mainstay LABA/GCS therapy in asthma for potentiated anti-inflammatory efficacy., (© 2021. The Author(s).)

Acute cholangitis presents with a wide severity spectrum and can rapidly deteriorate from local infection to multiorgan failure and fatal sepsis. The pathophysiology, diagnosis, and general management principles will be discussed in this review article. The focus of this article will be on the role of biliary drainage performed by interventional radiology to manage acute cholangitis. There are specific scenarios where percutaneous drainage should be preferred over endoscopic drainage. Percutaneous transhepatic and transjejunal biliary drainage are both options available to interventional radiology. Additionally, interventional radiology is now able to manage these patients beyond providing acute biliary drainage including cholangioplasty, stenting, and percutaneous cholangioscopy/biopsy., (Thieme. All rights reserved.)

The hepatobiliary system is known to have high anatomic variability, as studies have shown variant rates of over 40% among individuals. This review will describe biliary anatomy and the most common anatomic variants, knowledge of which is critical to ensuring safe and effective biliary interventions., (Thieme. All rights reserved.)

NK cells are central to anti-tumor immunity and recently showed efficacy for treating hematologic malignancies. However, their dysfunction in the hostile tumor microenvironment remains a pivotal barrier for cancer immunotherapies against solid tumors. Using cancer patient samples and proteomics, we found that human NK cell dysfunction in the tumor microenvironment is due to suppression of glucose metabolism via lipid peroxidation-associated oxidative stress. Activation of the Nrf2 antioxidant pathway restored NK cell metabolism and function and resulted in greater anti-tumor activity in vivo. Strikingly, expanded NK cells reprogrammed with complete metabolic substrate flexibility not only sustained metabolic fitness but paradoxically augmented their tumor killing in the tumor microenvironment and in response to nutrient deprivation. Our results uncover that metabolic flexibility enables a cytotoxic immune cell to exploit the metabolic hostility of tumors for their advantage, addressing a critical hurdle for cancer immunotherapy., Competing Interests: Declaration of interests S.M.P. and A.A.A. are inventors on a pending Canadian Provisional Patent application for the use of metabolic profiling and reprogramming for NK cell immunotherapy. The authors declare no other competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Type I interferons (IFNs) are our first line of defense against virus infection. Recent studies have suggested the ability of SARS-CoV-2 proteins to inhibit IFN responses. Emerging data also suggest that timing and extent of IFN production is associated with manifestation of COVID-19 severity. In spite of progress in understanding how SARS-CoV-2 activates antiviral responses, mechanistic studies into wild-type SARS-CoV-2-mediated induction and inhibition of human type I IFN responses are scarce. Here we demonstrate that SARS-CoV-2 infection induces a type I IFN response in vitro and in moderate cases of COVID-19. In vitro stimulation of type I IFN expression and signaling in human airway epithelial cells is associated with activation of canonical transcriptions factors, and SARS-CoV-2 is unable to inhibit exogenous induction of these responses. Furthermore, we show that physiological levels of IFNα detected in patients with moderate COVID-19 is sufficient to suppress SARS-CoV-2 replication in human airway cells., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Cluster formation is a focus of interdisciplinary research in both chemistry and physics. Here we discuss the exotic example of this phenomenon in the vortex matter of a thin superconductor. In superconducting films, the clustering takes place because of particular properties of the vortex interactions in the crossover or intertype regime between superconductivity types I and II. These interactions are controlled by the two parameters that are responsible for the crossover, Ginzburg-Landau parameter κ, which specifies the superconducting material of the film, and film thickness d , which controls effects due to stray magnetic fields outside the sample. We demonstrate that their competition gives rise to a complex spatial dependence of the interaction potential between vortices, favoring the formation of chainlike vortex clusters.