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Abstract: Organic carbon in seawater plays a significant role in the global carbon cycle. The concentration and composition of dissolved organic carbon reflect the activity of the biological community and chemical reactions that occur in seawater. From 2016 to 2019, we repeatedly sampled the oligotrophic northwest Sargasso Sea in the vicinity of the Bermuda Atlantic Time‐series Study site (BATS) to quantitatively follow known compounds within the pool of dissolved organic matter in the upper 1000 m of the water column. Most metabolites showed surface enrichment, and 83% of the metabolites had significantly lower concentrations with increasing depth. Dissolved metabolite concentrations most notably revealed temporal variability. Fourteen metabolites displayed seasonality that was repeated in each of the 4 yr sampled. Concentrations of vitamins, including pantothenic acid (vitamin B5) and riboflavin (vitamin B2), increased annually during winter periods when mixed layer depths were deepest. During diel sampling, light‐sensitive riboflavin decreased significantly during daylight hours. The temporal variability in metabolites at BATS was less than the spatial variability in metabolites from a previous sample set collected over a broad latitudinal range in the western Atlantic Ocean. The metabolites examined in this study are all components of central carbon metabolism. By examining these metabolites at finer resolution and in a time‐series, we begin to provide insights into the chemical compounds that may be exchanged by microorganisms in marine systems, data which are fundamental to understanding the chemical response of marine systems to future changes in climate.

Background: Determining the presence of bacteria in the shoulder prior to shoulder arthroplasty can be challenging especially in the case of revision arthroplasty. An open biopsy provides an opportunity to obtain tissue samples with minimal patient morbidity. The purpose of this study was to characterize the diagnostic utility of an open shoulder biopsy. Methods: A retrospective cohort study was performed at an academic medical center. All patients that underwent an open shoulder biopsy using a small proximal deltopectoral incision between 2008 and 2021 were included. Demographics, surgical history, culture results, and development of subsequent infection were recorded. Subsequent infection was defined as the development of a sinus tract, purulent drainage, or revision surgery with greater than or equal to two tissues specimens with growth of the same bacterial species. Sensitivity and negative predictive value (NPV) of an open biopsy were calculated based on the development of subsequent infection. As culture positive patients were treated for their infection, positive predictive value and specificity could not be determined. Results: We identified 55 patients that underwent 75 open biopsies. Most patients had a shoulder arthroplasty in place at the time of biopsy (69.1%), while 23.6% had an antibiotic spacer, and 7.3% had a native shoulder. Patients with a history of infection were more likely to have a spacer in place at the time of biopsy (65% vs. 0%; P

Abstract Background Black men consistently have higher rates of prostate cancer (PCA)- related mortality. Advances in PCA treatment, screening, and hereditary cancer assessment center around germline testing (GT). Of concern is the significant under-engagement of Black males in PCA GT, limiting the benefit of precision therapy and tailored cancer screening despite longstanding awareness of these disparities. To address these critical disparities, the Socioecological Model (SEM) was employed to develop comprehensive recommendations to overcome barriers and implement equitable strategies to engage Black males in PCA GT. Methods Clinical/research experts, national organization leaders, and community stakeholders spanning multiple regions in US and Africa participated in developing a framework for equity in PCA GT grounded in the SEM. A novel mixed-methods approach was employed to generate key areas to be addressed and informed statements for consensus consideration utilizing the modified Delphi model. Statements achieving strong consensus (> =75% agreement) were included in final equity frameworks addressing clinical/community engagement and research engagement. Results All societal levels of the SEM (interpersonal, institutional, community, and policy/advocacy) must deliver information about PCA GT to Black males that address benefits/limitations, clinical impact, hereditary cancer implications, with acknowledgment of mistrust (mean scores [MS] 4.57-5.00). Interpersonal strategies for information delivery included engagement of family/friends/peers/Black role models to improve education/awareness and overcome mistrust (MS 4.65-5.00). Institutional strategies included diversifying clinical, research, and educational programs and integrating community liaisons into healthcare institutions (MS 4.57-5.00). Community strategies included partnerships with healthcare institutions and visibility of healthcare providers/researchers at community events (MS 4.65–4.91). Policy/advocacy included improving partnerships between advocacy and healthcare/community organizations while protecting patient benefits (MS 4.57-5.00). Media strategies were endorsed for the first time at every level (MS 4.56-5.00). Conclusion The SEM-based equity frameworks proposed provide the first multidisciplinary strategies dedicated to increase engagement of Black males in PCA GT, which are critical to reduce disparities in PCA-mortality through informing tailored screening, targeted therapy, and cascade testing in families.

Learning in asynchronous online environments has gained importance over the last several decades, and educational environment shifts from the COVID-19 pandemic appear to have increased this need. Science educators and students need information about which approaches work in the asynchronous environment where informal feedback tends to be reduced, compared to other teaching modalities. In this study, we asynchronously implemented a learning module across 5 institutions that guided students (N = 199) from prescriptive data analysis through guided inquiry and eventually to open inquiry. The module focuses on the science behind climate change. Students work with the same authentic data sets used by professional scientists to examine geologic history and causes of climate change. By analyzing contemporary atmospheric carbon dioxide and temperature data and then using the 800,000-year record available from the Vostok ice core proxy record of atmospheric properties, students identify the causes of climate change and discover the unprecedented nature of recent atmospheric changes. Using a pre/post-module assessment, we demonstrate improvement in students' understanding of climate change processes and statistical methods used to analyze data. However, there was no evidence that the module develops students' scientific reasoning about the relationship between causation and correlation. Students maintained that correlation is not causation, even when a robust causal mechanism (i.e., the greenhouse effect) explains the link between atmospheric carbon dioxide and temperature. Finally, our analysis indicated that generally, anxiety about climate change was reduced during the module, such that students become less anxious about the climate change the more they learn about it. However, science-denying students experienced much higher anxiety about climate change than students who accepted the scientific consensus about climate change. Climate science-dissenting students were so few in this study that a statistical comparison was not possible, but this intriguing finding warrants further investigation of the role of anxiety in science denial. Mainly, this study demonstrates how asynchronous online learning environments can indeed support the achievement of learning objectives related to conducting authentic science, such as increasing understanding of climate change and statistical concepts, all while not provoking anxiety about climate change.

Approximately half of the annual carbon fixation on Earth occurs in the surface ocean through the photosynthetic activities of phytoplankton such as the ubiquitous picocyanobacterium Prochlorococcus. Ecologically distinct subpopulations (or ecotypes) of Prochlorococcus are central conduits of organic substrates into the ocean microbiome, thus playing important roles in surface ocean production. We measured the chemical profile of three cultured ecotype strains, observing striking differences among them that have implications for the likely chemical impact of Prochlorococcus subpopulations on their surroundings in the wild. Subpopulations differ in abundance along gradients of temperature, light, and nutrient concentrations, suggesting that these chemical differences could affect carbon cycling in different ocean strata and should be considered in models of Prochlorococcus physiology and marine carbon dynamics.

As coral reef ecosystems experience unprecedented change, effective monitoring of reef features supports management, conservation, and intervention efforts. Omic techniques show promise in quantifying key components of reef ecosystems including dissolved metabolites and microorganisms that may serve as invisible sensors for reef ecosystem dynamics. Dissolved metabolites are released by reef organisms and transferred among microorganisms, acting as chemical currencies and contributing to nutrient cycling and signaling on reefs. Here, we applied four omic techniques (taxonomic microbiome via amplicon sequencing, functional microbiome via shotgun metagenomics, targeted metabolomics, and untargeted metabolomics) to waters overlying Floridas Coral Reef, as well as microbiome profiling on individual coral colonies from these reefs to understand how microbes and dissolved metabolites reflect biogeographical, benthic, and nutrient properties of this 500-km barrier reef. We show that the microbial and metabolite omic approaches each differentiated reef habitats based on geographic zone. Further, seawater microbiome profiling and targeted metabolomics were significantly related to more reef habitat characteristics, such as amount of hard and soft coral, compared to metagenomic sequencing and untargeted metabolomics. Across five coral species, microbiomes were also significantly related to reef zone, followed by species and disease status, suggesting that the geographic water circulation patterns in Florida also impact the microbiomes of reef builders. A combination of differential abundance and indicator species analyses revealed metabolite and microbial signatures of specific reef zones, which demonstrates the utility of these techniques to provide new insights into reef microbial and metabolite features that reflect broader ecosystem processes.

Abstract TREK-1 is a mechanosensitive channel activated by polyunsaturated fatty acids (PUFAs). Its activation is supposed to be linked to changes in membrane tension following PUFAs insertion. Here, we compared the effect of 11 fatty acids and ML402 on TREK-1 channel activation using the whole cell and the inside-out configurations of the patch-clamp technique. Firstly, TREK-1 activation by PUFAs is variable and related to the variable constitutive activity of TREK-1. We observed no correlation between TREK-1 activation and acyl chain length or number of double bonds suggesting that the bilayer-couple hypothesis cannot explain by itself the activation of TREK-1 by PUFAs. The membrane fluidity measurement is not modified by PUFAs at 10 µM. The spectral shift analysis in TREK-1-enriched microsomes indicates a KD,TREK1 at 44 µM of C22:6 n-3. PUFAs display the same activation and reversible kinetics than the direct activator ML402 and activate TREK-1 in both whole-cell and inside-out configurations of patch-clamp suggesting that the binding site of PUFAs is accessible from both sides of the membrane, as for ML402. Finally, we proposed a two steps mechanism: first, insertion into the membrane, with no fluidity or curvature modifications at 10 µM, and then interaction with TREK-1 channel to open it.

Background: A social justice framework can be used to inform healthy equity-focused research, and operationalizing social justice can inform strategic planning for research and practice models. This study aimed to develop a working definition of social justice based on input from a diverse group of collaborators to better inform the work conducted within the Center for Research, Health, and Social Justice. Methods: A concept mapping study was conducted from March to May 2022. A prompt designed to elicit social justice themes was developed (phase 1). At a study website, participants brainstormed statements that represented their definition of social justice (phase 2). Participants then sorted statements based on similarity and rated statements on importance (phase 3). Multidimensional scaling and hierarchical cluster analysis were used to identify nonoverlapping thematic clusters of statements (phase 4). Models were reviewed for best fit, and clusters were assigned names based on theme (phase 5). Results: Participants (n = 49) generated 52 unique statements that were sorted into 5 clusters describing social justice themes. Clusters included (1) Empathy, Awareness, and Understanding (n = 11); (2) Education and Systems Change (n = 10); (3) Policy Design and Implementation (n = 9); (4) Equity and Leveling the Playing Field (n = 11); and (5) Access to Services and Fair Living Standard (n = 11). High mean cluster ratings ranging from 5.22 to 6.02 out of 7 indicated all clusters were rated as being very important aspects of social justice. Conclusions: These data can guide the restructuring of research ecosystems that help eliminate race- and place-based health disparities.

Pseudoaneurysm development is a well-recognized consequence of arterial injury, frequently observed in procedures involving arterial groin access. Breast emergencies are infrequent but need prompt attention. We present a notable case of breast pseudoaneurysm postcore needle biopsy, incidentally, identified through subsequent magnetic resonance imaging. Remarkably, the patient's lactating status emerged as a unique risk factor. Our report thoroughly explores the pathogenesis, etiology, preventive measures, and treatment strategies specific to breast pseudoaneurysms. A comprehensive understanding of this phenomenon is essential for radiologists at large, with particular importance for specialists in breast imaging.

PURPOSEThis study aims to describe genomic characteristics of patients with metastatic prostate cancer (mPC).PATIENTS AND METHODSThis study is a retrospective, multicenter cohort study of patients with mPC and reports on genomic testing. Patients were included from 12 academic centers in five countries.RESULTSA total of 349 patients with PC were included in this study. Most patients (209, 59.9%) were de novo metastatic. Genomic analysis was performed in 233 (66.6%) patients in the metastatic castration-resistant prostate cancer (mCRPC) setting, and only 115 (32.8%) patients had a tumor evaluation in the metastatic hormone sensitive prostate cancer scenario. The evaluation of somatic and/or germline mutations was performed through multigene panel analyses in 290 (83.09%) patients, and next-generation sequencing of BRCA1 and BRCA2 genes was performed in 59 (16.91%) patients. Analyzing the mCRPC subgroup, with a median follow-up of 15.6 months (IQR, 14-19.06), the median progression-free survival (PFS) was not reached (NR) and the PFS at 16 months was 58.7% (95% CI, 50.8 to 67.8). When comparing patients with BRCA mutations with those who are not BRCA-mutated in the mCRPC scenario, the median PFS was NR (95% CI, 14 to NR) and 26.3 months (95% CI, 16.7 to 36.5; P = .2), respectively. Two of six patients with BRCA mutations were treated with targeted therapies (poly-ADP-ribose polymerase inhibitors).CONCLUSIONOur study, to the best of our knowledge, represents one of the larger data sets for somatic testing in patients with PC in Latin America (LATAM). It adds valuable information to the growing body of knowledge about the genomic landscape of advanced PC in real-world daily practice scenarios in LATAM countries, which are not always well-represented in large-scale randomized clinical trials.

The evolution of science has given rise to many technologies that have changed the world. The upcoming Six-Generation (6G) mobile network indicates a fundamental transformation in wireless technologies, enhancing connectivity and data transmission rates. In this circumstance, Mobile Edge Computing (MEC) is a paradigm technology that emerges as a key major supporter of enhancing mobility awareness. Edge computing offers improved efficiency for service migration from the edge node to the user. However, mobility management in MEC is a complex challenge as seamless handovers between edge nodes must be efficiently executed to ensure uninterrupted service for mobile devices, demanding intricate coordination and low-latency decision-making. To the best of the author's knowledge, there has been no comprehensive work on the most recent developments in mobility awareness using mobile edge computing in 6G. However, this paper aims to present a general overview of the intersection between mobility awareness and MEC over 6G networks. The general concept of MEC in 6G mobile networks is comprehensively introduced. This will highlight the integration between MEC and 6G for bringing more efficient network and service migration to the edge, reducing latency, and enhancing the user experience. Meanwhile, this survey discusses augmented reality with MEC applications. This survey discusses the integration of mobility awareness and mobile edge computing in upcoming mobile applications and emphasizes the need for 6G networks. This integration results in providing seamless communication during handovers between the serving base station and the target base station. This study contributes to understanding the upcoming trends that will enable the operation of mobility awareness and MEC operation in the 6G mobile communication. Furthermore, we delve into a comprehensive overview of the challenges and future research directions for mobility management with MEC in 6G mobile networks, underlining the complexities and potentials of integrating mobility awareness and mobile edge computing.

We evaluated the in vitro effects of lyophilization for 2 vesicular stomatitis virus–based vaccines by using 3 stabilizing formulations and demonstrated protective immunity of lyophilized/reconstituted vaccine in guinea pigs. Lyophilization increased stability of the vaccines, but specific vesicular stomatitis virus–based vaccines will each require extensive analysis to optimize stabilizing formulations.

Abstract Ebola virus (EBOV) is able to persist and actively replicate in the reproductive tract of male disease survivors months or years after recovery from Ebola virus disease (EVD)1. Persistent EBOV infections are usually asymptomatic and can be transmitted sexually, but the host and viral factors that mediate these infections have not been characterized2,3. We investigated the interaction between host and viral factors during EBOV infection of the blood testis barrier (BTB), with a focus on Sertoli cells as a potential reservoir for viral persistence. We assessed viral replication kinetics and host responses of mouse testicular Leydig cells and Sertoli cells infected with EBOV Makona (i.e. infectious EBOV) and collected samples up to 28 days post-infection. Viral replication was apparent in both cell lines, but intracellular early viral loads were much higher in Leydig cells compared to Sertoli cells. We used RNAseq analysis to characterize transcriptomic responses of Leydig cells and Sertoli cells to EBOV infection over time. Further investigation of early interactions between host cells and EBOV was performed using virus-like particles (EBOV trVLP) and assays of phosphorylation-based cell signaling. Our findings indicate that virus-treated Sertoli cells responded more rapidly and robustly than Leydig cells, and with a particular emphasis on detection of, and response to, external stimuli. We discuss how the roles played by Sertoli cells in immune privilege and spermatogenesis may affect their initial and continued response to EBOV infection in a manner that could facilitate asymptomatic persistence.

Streptococcus pyogenes (group A Streptococcus) is a clinically important microbial pathogen that requires iron in order to proliferate. During infections, S. pyogenes uses the surface displayed Shr receptor to capture human hemoglobin (Hb) and acquires its iron-laden heme molecules. Through a poorly understood mechanism, Shr engages Hb via two structurally unique N-terminal Hb-interacting domains (HID1 and HID2) which facilitate heme transfer to proximal NEAr Transporter (NEAT) domains. Based on the results of X-ray crystallography, small angle X-ray scattering, NMR spectroscopy, native mass spectrometry, and heme transfer experiments, we propose that Shr utilizes a "cap and release" mechanism to gather heme from Hb. In the mechanism, Shr uses the HID1 and HID2 modules to preferentially recognize only heme-loaded forms of Hb by contacting the edges of its protoporphyrin rings. Heme transfer is enabled by significant receptor dynamics within the Shr-Hb complex which function to transiently uncap HID1 from the heme bound to Hb's β subunit, enabling the gated release of its relatively weakly bound heme molecule and subsequent capture by Shr's NEAT domains. These dynamics may maximize the efficiency of heme scavenging by S. pyogenes, enabling it to preferentially recognize and remove heme from only heme-loaded forms of Hb that contain iron.

Electronic nicotine products (ENPs) are the most prevalent form of tobacco use among U.S. young adults. Research is needed to investigate how to communicate new risks from ENPs to the public. In this study, we tested the comparative persuasiveness of ENP explosion and lung injury graphic warnings. We recruited a sample of 343 young adults (18 to 28 years; 146 male, 197 female), including both ENP users and nonusers, via Amazon Mechanical Turk in October 2020. We randomly assigned participants to one of six exposure conditions: two images of lung injuries with prevalence statistics, two images of battery explosion injuries with prevalence statistics, and two images of ENPs with messages about chemicals or nicotine/addiction. We measured perceptions and intention to use ENPs before and after exposure. Linear regression models examined whether exposure conditions were associated with post-exposure perceived susceptibility and severity of ENP lung injuries and explosion injuries, perceived intensity, fear, and intention to use, adjusting for baseline values and potential confounders. Compared to the chemicals/nicotine messages, explosion and lung injury stimuli were perceived to be more intense (p < .001) and evoked greater fear (p < .001). Both explosion injury images were associated with increased perceived susceptibility (p < .01) and severity (p < .001). One lung injury image was associated with increased perceived susceptibility (p < .01) and reduced intention to use ENPs (p < .05). Our results show that ENP graphic warnings can increase threat perceptions about ENP lung and explosion injuries among young adults. Similar graphic warnings may be effective for other harms associated with ENPs.

Ocean sciences in the U.S. remains a field with one of the lowest rates of diversity, having disproportionately low representation from marginalized groups, including Black, Asian, LatinX, Indigenous, and other people of color; LGBTQIA+ individuals; disabled persons; women; those with neurological differences; and those from low-income groups. With equity and inclusion in mind, recent efforts have been made to increase the number of ocean science professionals from marginalized groups through multiple entry points, including internships. However, there still exists a large gap between the diversity found in the general population and the diversity within ocean sciences. Perhaps one reason why this field continues to have lower diversity owes to the unique component of many oceanographic careers, which continues to present an especially high barrier for marginalized groups: participating in sea-going research expeditions. Herein, we have synthesized possible ways to prioritize the physical and emotional safety of marginalized ocean science professionals participating in a research expedition, including guidance on preparation, implementation, and providing support post-cruise. These suggestions are intended to be useful for the broader oceanographic research community to consider the safety and well-being of individuals from marginalized groups at sea, since the field of ocean sciences - like all fields - would greatly benefit from increased representation and diversity.

IntroductionTBI incidence and distribution are largely overrepresented in low- to middle-income countries (LMICs), such as South Africa (SA), with substantial associated human and financial costs. However, access to rehabilitation for the public is severely limited and not standard practice in SA. Given this background, studies demonstrating the successful implementation of neuropsychological rehabilitation in a LMIC setting are important. Published studies of this nature are generally lacking in this context. Further, there is a need to evaluate interventions that can be implemented at a low cost. To this end, we report on a neuropsychological rehabilitation program for an individual with severe TBI in a LMIC context, aimed at improving his capacity for activities of daily living.MethodA 33-year-old, South African male who sustained a severe traumatic brain injury (TBI) partook in a neuropsychological intervention aimed at remediating functional deficits and enhancing independent functioning. The intervention utilised principles of Goal Management Training and external memory aids, with reliance on procedural memory and errorless learning, to target the participant's impairments in executive functioning and memory through the use of assistive technology—namely smart device applications.ResultsData collected pre- and post-intervention on formal neuropsychological measures demonstrated no significant change in cognition. However, observational data and qualitative feedback from the participant's family indicated notable improvement in performance on everyday tasks with reduced number of errors and reduced need for external prompting whilst completing intervention tasks across sessions.DiscussionIn the context of severe TBI, neuropsychological rehabilitation can facilitate gains in independent functioning. This study provides support for the value of neurorehabilitation especially for interventions that can be rolled out at low cost and should serve as impetus for further such research in South Africa, where neuropsychological rehabilitation infrastructure and services are lacking.

The purpose of this study is to determine how home visits conducted by teachers from a diverse, urban high school impacted student success and relationships between parents and teachers. Participants were high school teachers who were invited to conduct home visits for rising ninth graders and the students visited at home. In this mixed methods design, attendance and graduation data were collected for students participating in home visits, surveys were administered to eligible teachers and staff, and semi-structured interviews were subsequently conducted with seven home visiting teachers. Data over five years reveals the chronic absenteeism rate was lower for students visited at home (4%) compared to the whole cohort. The graduation rate for students visited at home at this site was also higher (3.7%) than the rate for the whole graduating class. Surveys and interviews indicate teachers who visited students at home were more likely than non-home visiting teachers to report positive relationships with and support from parents. Home visiting teachers also met with parents more in person, and, more than non-home visiting teachers, they believed parents welcome home visits.

Pathogenic Staphylococcus aureus actively acquires iron from human hemoglobin (Hb) using the IsdH surface receptor. Heme extraction is mediated by a tri-domain unit within the receptor that contains its second (N2) and third (N3) NEAT domains joined by a helical linker domain. Extraction occurs within a dynamic complex, in which receptors engage each globin chain; the N2 domain tightly binds to Hb, while substantial inter-domain motions within the receptor enable its N3 domain to transiently distort the globin's heme pocket. Using molecular simulations coupled with Markov modeling, along with stopped-flow experiments to quantitatively measure heme transfer kinetics, we show that directed inter-domain motions within the receptor play a critical role in the extraction process. The directionality of N3 domain motion and the rate of heme extraction is controlled by amino acids within a short, flexible inter-domain tether that connects the N2 and linker domains. In the wild-type receptor directed motions originating from the tether enable the N3 domain to populate configurations capable of distorting Hb's pocket, whereas mutant receptors containing altered tethers are less able to adopt these conformers and capture heme slowly via indirect processes in which Hb first releases heme into the solvent. Thus, our results show inter-domain motions within the IsdH receptor play a critical role in its ability to extract heme from Hb and highlight the importance of directed motions by the short, unstructured, amino acid sequence connecting the domains in controlling the directionality and magnitude of these functionally important motions.

Inequity in cancer care access among LATAM countries is huge. Experience with gastrointestinal tumors in Latin America has shown care disparities can be reduced by equalizing access to high-quality medical knowledge in a context of a multidisciplinary environment for medical discussions.Here, we describe our experience of working with virtual genitourinary multidisciplinary tumor boards (vGUMDT), including how the virtual board has helped with clinical decision-making.We describe vGUMDT ́s experience and the importance of basing clinical decision-making in the consultant’s own center, reducing the need for referrals.In total, 345 cases were presented. The majority were prostate cancer cases, and the median age of patients was 64 years. Five participating centers were in Buenos Aires, 7 were in other cities in Argentina (Neuquén, Mendoza, Formosa, Salta, Santa Fé, Entre Ríos, Córdoba), and 3 centers were located in other countries in South America (Perú, Colombia, and Paraguay). Median distance from treating center to vGUMDT headquarters was 1289.8 km. A few patients (n = 60, 17.3%) were referred to the Alexander Fleming Cancer Institute or tertiary health care centers for surgery or systemic therapy, and a minority of cases were referred for radiotherapy. Multidisciplinary virtual experiences, such as vGUMDT, should be carefully addressed by health care decision-makers, given their popularity and their demonstrated cost-effectiveness.

IntroductionThe 2021 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Prostate Cancer Research in the 21st Century," was held virtually, from June 24-25, 2021.MethodsThe CHPCA Meeting is organized by the Prostate Cancer Foundation as a unique discussion-oriented meeting focusing on critical topics in prostate cancer research envisioned to bridge the next major advances in prostate cancer biology and treatment. The 2021 CHPCA Meeting was virtually attended by 89 investigators and included 31 talks over nine sessions.ResultsMajor topic areas discussed at the meeting included: cancer genomics and sequencing, functional genomic approaches to studying mediators of plasticity, emerging signaling pathways in metastatic castration resistant prostate cancer, Wnt signaling biology and the challenges of targeted therapy, clonal hematopoiesis, neuroendocrine cell plasticity and antitumor immunity, cancer immunotherapy and its synergizers, and imaging the tumor microenvironment and metabolism.DiscussionThis meeting report summarizes the research presented at the 2021 CHPCA Meeting. We hope that publication of this knowledge will accelerate new understandings and the development of new biomarkers and treatments for prostate cancer.

Abstract Recombinant vesicular stomatitis viruses (rVSVs) engineered to express heterologous viral glycoproteins have proven to be remarkably effective vaccines. Indeed, rVSV-EBOV, which expresses the Ebola virus (EBOV) glycoprotein, recently received clinical approval in the United States and Europe for its ability to prevent EBOV disease. Analogous rVSV vaccines expressing glycoproteins of different human-pathogenic filoviruses have also demonstrated efficacy in pre-clinical evaluations, yet these vaccines have not progressed far beyond research laboratories. In the wake of the most recent outbreak of Sudan virus (SUDV) in Uganda, the need for proven countermeasures was made even more acute. Here we demonstrate that an rVSV-based vaccine expressing the SUDV glycoprotein (rVSV-SUDV) generates a potent humoral immune response that protects guinea pigs from SUDV disease and death. Although the cross-protection generated by rVSV vaccines for different filoviruses is thought to be limited, we wondered whether rVSV-EBOV might also provide protection against SUDV, which is closely related to EBOV. Surprisingly, nearly 60% of guinea pigs that were vaccinated with rVSV-EBOV and challenged with SUDV survived, suggesting that rVSV-EBOV offers limited protection against SUDV, at least in the guinea pig model. These results were confirmed by a back-challenge experiment in which animals that had been vaccinated with rVSV-EBOV and survived EBOV challenge were inoculated with SUDV and survived. Whether these data are applicable to efficacy in humans is unknown, and they should therefore be interpreted cautiously. Nevertheless, this study confirms the potency of the rVSV-SUDV vaccine and highlights the potential for rVSV-EBOV to elicit a cross-protective immune response.

Oxygen minimum zones (OMZs) are expanding due to increased sea surface temperatures, subsequent increased oxygen demand through respiration, reduced oxygen solubility, and thermal stratification driven in part by anthropogenic climate change. Devil’s Hole, Bermuda is a model ecosystem to study OMZ microbial biogeochemistry because the formation and subsequent overturn of the suboxic zone occur annually. During thermally driven stratification, suboxic conditions develop, with organic matter and nutrients accumulating at depth. In this study, the bioavailability of the accumulated dissolved organic carbon (DOC) and the microbial community response to reoxygenation of suboxic waters was assessed using a simulated overturn experiment. The surface inoculated prokaryotic community responded to the deep (formerly suboxic) 0.2 μm filtrate with cell densities increasing 2.5-fold over 6 days while removing 5 μmol L−1 of DOC. After 12 days, the surface community began to shift, and DOC quality became less diagenetically altered along with an increase in SAR202, a Chloroflexi that can degrade recalcitrant dissolved organic matter (DOM). Labile DOC production after 12 days coincided with an increase of Nitrosopumilales, a chemoautotrophic ammonia oxidizing archaea (AOA) that converts ammonia to nitrite based on the ammonia monooxygenase (amoA) gene copy number and nutrient data. In comparison, the inoculation of the deep anaerobic prokaryotic community into surface 0.2 μm filtrate demonstrated a die-off of 25.5% of the initial inoculum community followed by a 1.5-fold increase in cell densities over 6 days. Within 2 days, the prokaryotic community shifted from a Chlorobiales dominated assemblage to a surface-like heterotrophic community devoid of Chlorobiales. The DOM quality changed to less diagenetically altered material and coincided with an increase in the ribulose-1,5-bisphosphate carboxylase/oxygenase form I (cbbL) gene number followed by an influx of labile DOM. Upon reoxygenation, the deep DOM that accumulated under suboxic conditions is bioavailable to surface prokaryotes that utilize the accumulated DOC initially before switching to a community that can both produce labile DOM via chemoautotrophy and degrade the more recalcitrant DOM.