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FLEX: 30K Full Transcriptome, Real-World Evidence Database for Early-Stage Breast Cancer, and Investigator-Initiated Protocols BACKGROUND: Genomic signatures, such as the 70-gene MammaPrint, provide additional prognostic information for early-stage breast cancer (EBC), such as tumor metastatic potential, and expand the available information clinicians and patients require for shared treatment decision making beyond the standard clinicopathologic factors. EBC tumors are further stratified into clinically actionable subtypes by molecular assays such as the 80-gene molecular profiling assay BluePrint, improving pathological complete response rates (pCR) and outcomes as evidenced by a number of recent trials. The ongoing FLEX Study (NCT03053193) is designed to expand the genomic information available for EBC cases, and to increase the speed of data generation for rare and underserved research areas. To date, FLEX is the largest international multicenter real-world evidence (RWE) EBC registry, with more than 10,000 patients enrolled in fewer than five years since opening. FLEX pairs full genome data with more than 800 clinical data points collected over 10 years of follow up to provide the most comprehensive big data database available for early-stage breast cancer. The FLEX enrollment has a goal of a minimum of 30,000 patients within 10 years. METHODS: The FLEX study is a multicenter, prospective, observational trial for patients ≥18 years old with histologically proven stage I-III invasive breast cancer that is node negative or positive (up to three nodes) who receive MammaPrint, with or without BluePrint as standard of care management. Patients consent to the collection of clinically annotated full transcriptome data. Additionally, this study protocol allows physicians to investigate targeted populations or clinical trial investigator-initiated studies (IIS) upon approval by a peer-driven Scientific Review Committee. As patients enrolled in the FLEX study meet all eligibility criteria for inclusion no additional consent is required. The FLEX enrollment has already surpassed 1/3 of set target goal. As of April 2022, the trial has surpassed 10,000 patients enrolled at nearly 100 trial sites across the US and Europe, Middle East and Africa (EMEA). To date, there have been 36 publications in international scientific congresses with 39 FLEX IIS and in progress. With over 250 active and collaborating physicians leveraging the shared infrastructure, the IIS have enabled the ability to address disparities in treatment to underrepresented populations, rare subtypes, age, and patient centered specific topics. Current and future questions investigated via this platform will continue to strive to improve outcomes for early-stage breast cancer patients. Citation Format: Alejandra Perez, Hannah Linden, Nathalie Johnson, Sami Diab, Chirag Jani, Chelsea D. Gawryletz, Richard Fine, Laura Lawson, Megan Baker, Victoria Poillucci, Lisa E. Blumencranz, William Audeh. FLEX: 30K Full Transcriptome, Real-World Evidence Database for Early-Stage Breast Cancer, and Investigator-Initiated Protocols [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-05-01.

Seafloor sediment flows (turbidity currents) form some of the largest sediment accumulations on Earth, carry globally significant volumes of organic carbon, and can damage critical seafloor infrastructure. These fast and destructive events are notoriously challenging to measure in action, as they often damage any instruments anchored within the flow. We present the first direct evidence that turbidity currents generate seismic signals which can be remotely sensed (~1-3 km away), revealing the internal structure and remarkably prolonged duration of the longest runout sediment flows on Earth. Passive Ocean Bottom Seismograph (OBS) sensors, located on terraces of the Congo Canyon, offshore West Africa, recorded thirteen turbidity currents over an 8-month period. The occurrence and timing of these turbidity currents was confirmed by nearby moorings with acoustic Doppler current profilers.Results show that turbidity currents travelling over ~1.5 m/s produce a seismic signal concentrated below 10 Hz with a sudden onset and more gentle decay. Comparison of the seismic signals with information on flow velocities from the acoustic Doppler current profilers demonstrates that the seismic signal is generated by the fast-moving front of the flow (frontal cell), which contains higher sediment concentrations compared to the slower-moving body. Long runout flows travelling >1000 km have a fast (3.7-7.6 m s-1) frontal cell, which can be 14 hours, and ~350 km long, with individual flows lasting >3 weeks. Flows travelling >1000 km eroded >1300 Mt of sediment in one year, yet had near-constant front speeds, contrary to past theory. The seismic dataset allows us to propose a fundamental new model for how turbidity currents self-sustain, where sediment fluxes into and from a dense frontal layer are near-balanced.Seismic monitoring of turbidity currents provides a new method to record these hazardous submarine flows, safely, over large areas, continuously for years yet at sub-second temporal resolution. Monitoring these processes from land would considerably ease deployment efforts and costs. Thus, work is underway investigating if terrestrial seismic stations can record submarine seafloor processes in Bute Inlet, a fjord in western Canada where independent measurement of delta-lip failures and turbidity currents can be compared to a passive seismic dataset.

The increasing plastic pollution of the world’s oceans represents a serious threat to marine ecosystems and has become a well-known topic garnering growing public attention. The global input of plastic waste into the oceans is estimated to be approximately 10 million tons per year and predicted to rise by one order of magnitude by 2025. More than 90% of the plastic that enters the oceans is thought to end up on the seafloor, and seafloor sediment samples show that plastics are concentrated in confined morphologies and sedimentary environments such as submarine canyons. These canyons are occasionally flushed by powerful gravity-driven sediment flows called turbidity currents, which transport vast volumes of sediment to the deep sea and deposit sediment in deep-sea fans. As such, turbidity currents may also transport plastics present in the canyon and bury plastics in deep-sea fans. These fans may therefore act as sinks for seafloor plastics. Here we present a comprehensive dataset showing the spatial distribution of microplastics in seafloor sediments from the Congo Canyon, offshore West Africa. Multicores taken from 16 locations along the canyon, sampled different sedimentary sub-environments including the canyon thalweg, canyon terraces, and distal lobe. Microplastics were extracted from the sediments by density separation and the polymer type, size, and shape of all individual microplastic particles were analysed using laser-direct infrared-spectroscopy (LDIR). Microplastic number concentrations in the sediments of the distal lobe are significantly higher than in the canyon, indicating that the Congo Canyon system is a highly efficient conduit for microplastic transport to the deep sea. Moreover, microplastic concentrations of >20,000 particles per kg of dry sediment were recorded in the lobe, which represent some of the highest ever recorded microplastic number concentrations in seafloor sediments. This shows that deep-sea fans can serve as hotspots and potential terminal sinks for seafloor microplastics.

Sediment gravity flows exhibit a large range of flow behaviours, making their flow dynamics hard to predict and the resulting deposits a challenge to interpret. Cohesive sediment gravity flows containing clay are particularly complex, as their behaviour is controlled by the balance of turbulent and cohesive forces. A first set of laboratory lock-exchange experiments investigated the effect of adding 25% very fine sand by volume to high-density cohesive sediment gravity flows with strongly suppressed turbulence. This caused these mixed clay–sand flows to become more cohesive, have shorter runout distances, and have lower head velocities than the original pure-clay flows, despite the increase in density difference and the non-cohesive properties of the sand. Yield stress measurements confirmed that adding the non-cohesive very fine sand increases the cohesive strength of dense clay suspensions. This higher cohesive strength outcompetes the enhanced density difference and reduces the flow mobility. A second set of experiments across a larger range of clay concentrations showed that, for low-density cohesive sediment gravity flows dominated by turbulent mixing, the addition of 25% very fine sand increased the head velocities because of the enhanced density difference and weak cohesive forces. Thus, the addition of very fine sand may increase or decrease the mobility of cohesive sediment gravity flows, depending on the initial type of flow and the balance between turbulent and cohesive forces. In the natural environment, this study proposes that very fine sand can only increase the cohesive strength and reduce the flow mobility of cohesive sediment gravity flows that have a sufficiently strong matrix strength to fully support the sand particles. The contribution of very fine sand to the cohesive strength of high-density cohesive sediment gravity flows may have important implications for flow transformation on submarine fans, especially in distal regions where transient–turbulent, cohesive flows are particularly common.

In a recent exhibit, the Choctaw Nation of Oklahoma, Musée du quai Branly-Jacques Chirac, and Bibliothèque Municipale de Versailles worked together to learn more about the museum’s royal Americas collection which features items from numerous Indigenous communities. Collected by French explorers during the eighteenth century and later displayed in royal curiosity cabinets, these items have not been seen by Choctaw communities since they left the continent. This collaboration has culminated in the “La Curiosité d’un Prince” exhibit, which features a room curated by Choctaw Nation. This article shows how a joint initiative to study the collection gave voice to the relationships and material histories inherent in the items. Reflecting on this less-known historical period, this collaboration has reinvigorated Choctaw-French relations and allowed Choctaw Nation to showcase the richness and complexity of its sovereignty—which is often narrowly understood through its relationship with the United States. By providing an example of true collaboration that has spurred new research and writing on both the cultural and political knowledge contained in the objects held in France, we demonstrate the potential for relationships and knowledge inherent in museum collections to act as a platform for new expressions of Indigenous sovereignty.

Mitochondrial diseases are a broad, genetically heterogeneous class of metabolic disorders characterized by deficits in oxidative phosphorylation (OXPHOS). Primary mitochondrial disease (PMD) defines pathologies resulting from mutation of mitochondrial DNA (mtDNA) or nuclear genes affecting either mtDNA expression or the biogenesis and function of the respiratory chain. Secondary mitochondrial disease (SMD) arises due to mutation of nuclear-encoded genes independent of, or indirectly influencing OXPHOS assembly and operation. Despite instances of novel SMD increasing year-on-year, PMD is much more widely discussed in the literature. Indeed, since the implementation of next generation sequencing (NGS) techniques in 2010, many novel mitochondrial disease genes have been identified, approximately half of which are linked to SMD. This review will consolidate existing knowledge of SMDs and outline discrete categories within which to better understand the diversity of SMD phenotypes. By providing context to the biochemical and molecular pathways perturbed in SMD, we hope to further demonstrate the intricacies of SMD pathologies outside of their indirect contribution to mitochondrial energy generation.

Submarine canyons and channels include the largest sediment transport systems on our planet. They are an important transport pathway for sediment, organic carbon, nutrients and pollutants to the deep sea. However, it is challenging to study these submarine locations, especially larger systems on the deep seafloor, and they remain poorly understood. Here we use the first extensive time-lapse bathymetric surveys of the Congo Submarine Fan (offshore West Africa), one of the largest submarine fans in the world. Channel-modifying processes (such as landslides, avulsions and knickpoints) are identified by comparing new high-resolution bathymetric data from 2019 to lower-resolution bathymetric data collected between 1992 and 1998, along a 475 km section of the Congo submarine system. These channel-modifying processes leave a specific fingerprint in morphometric characteristics (e.g., bed slope, width, cross-sectional flow area, sinuosity, levee slope and height) that are automatically extracted with a Matlab script from the bathymetric data. This work has the important implication that the identification of channel-modifying processes can be based on a single bathymetric survey, and does not require repeated surveys. In the upstream part of the Congo Canyon, a re-analysis of bathymetric data collected between 1992 and 1998 reveals a previously unnoticed channel-blocking landslide, which is of similar magnitude to a more recent landslide observed from the repeated surveys with a volume of ~0.4 km³. This observation of additional landslides supports the concept that the upstream canyon is morphologically defined by flank collapses, which can locally block the channel and store material for extended periods of time. In the intermediate channel part of the Congo Fan, avulsions already identified in previous work are demonstrated to leave a specific fingerprint within the morphometric characteristics such as a change in levee slope. In the most distal and youngest part of the Congo submarine channel, upstream migrating knickpoints are dominant and are shown to also leave a specific fingerprint in morphometric characteristics. These findings can underpin efficient searches for submarine canyon and channel processes in other systems, and provide new insights into how turbidity currents flush sediment into the deep-sea.

Here we document for the first time how major rivers connect directly to the deep-sea, by analysing the longest runout sediment flows (of any type) yet measured in action. These seafloor turbidity currents originated from the Congo River-mouth, with one flow travelling >1,130 km whilst accelerating from 5.2 to 8.0 m/s. In one year, these turbidity currents eroded 1-2 km3 of sediment from just one submarine canyon, equivalent to 14-28% of the annual global-flux from rivers. It was known earthquakes trigger canyon-flushing flows. We show major river-floods also generate canyon-flushing flows, primed by rapid sediment-accumulation at the river-mouth, but triggered by spring tides weeks to months after the flood. This is also the first field-confirmation that turbidity currents which erode can self-accelerate, thereby travelling much further. These observations explain highly-efficient organic carbon transfer, and have important implications for hazards to seabed cables, or how terrestrial climate change impacts the deep-sea.

Controlled human malaria infection (CHMI) provides a highly informative means to investigate host-pathogen interactions and enable in vivo proof-of-concept efficacy testing of new drugs and vaccines. However, unlike Plasmodium falciparum, well-characterized P. vivax parasites that are safe and suitable for use in modern CHMI models are limited. Here, two healthy malaria-naïve UK adults with universal donor blood group were safely infected with a clone of P. vivax from Thailand by mosquito-bite CHMI. Parasitemia developed in both volunteers and, prior to treatment, each volunteer donated blood to produce a cryopreserved stabilate of infected red blood cells. Following stringent safety screening, the parasite stabilate from one of these donors ("PvW1") was thawed and used to inoculate six healthy malaria-naïve UK adults by blood-stage CHMI, at three different dilutions. Parasitemia developed in all volunteers, who were then successfully drug treated. PvW1 parasite DNA was isolated and sequenced to produce a high quality genome assembly by using a hybrid assembly method. We analysed leading vaccine candidate antigens and multigene families, including the Vivax interspersed repeat (VIR) genes of which we identified 1145 in the PvW1 genome. Our genomic analysis will guide future assessment of candidate vaccines and drugs, as well as experimental medicine studies.

Aims Twitter is a powerful platform for sharing information. Retweets allow users to reach a wider audience quickly. Our aim was to determine what tweet and twitter-account related factors affect the “retweetability” of surgical publications. Methods All papers published (in print) in Annals of Surgery, BJS and JAMASurgery in 2019 were selected. We identified each paper’s first appearance on Twitter and analysed characteristics of the posting twitter account and the tweet itself. The association between such characteristics and the number of retweets was investigated. Results 413 papers were selected. Median number of retweets was 3 (range, 0-121). The first tweet created about a paper was usually from a reader (42%) with only a minority created by the journal (17%) or the authors (20%). Use of visual abstracts (22/413, p Multivariate analysis confirmed visual abstracts (p Conclusions Authors and journals should create the first presence on social media to improve engagement with their papers. Such tweets should use visual abstracts or pictures, relevant hashtags and avoid solely posting the paper title to make their research more widely shared.

Aims Surgical journals have developed social media profiles to increase engagement though it remains unclear as to whether social media attention indices for publications act as a surrogate or predictor of traditional citation metrics. This study used machine learning to determine if there is a relationship between Twitter mentions and number of citations for surgical publications. Methods We identified all original research and review papers published in Annals of Surgery, BJS and JAMA Surgery in 2019. Citations data and Twitter mentions were retrieved and the Spearman rank coefficient was used to determine degree of correlation between the two variables. An unsupervised machine-learning hierarchical clustering algorithm was used to define clusters of outlying papers. Quantitative and qualitative analysis of the clusters was completed. Results 413 papers were selected. Median number of citations was 7 (IQR 3-14), median number of Twitter mentions was 40 (IQR 15-79). No correlation between Twitter mentions and number of citations was observed (Spearman’s rho 0.076 p-value 0.124). Cluster analysis identified one large (cluster 2, 367/413 papers) and six small clusters. Analysis of cluster 2 revealed a weak but significant correlation between citations and Twitter mentions (Spearman’s rho 0.107 p-value 0.041). The remaining six clusters were characterised by an out of proportion number of Twitter mentions compared to citations or vice versa. Conclusions Twitter mentions should not be used as a surrogate or predictor of traditional citation metrics. In our database the relationship between social media attention and citations was skewed by a small number of outlying papers.

Aim Unsurprisingly, much of the medical profession has focussed on treating covid-19 over the past year often to the detriment of other pathologies. Engagement with academic literature may follow a similar trend; this paper used standard social media attention and citations metrices to assess whether the pandemic has affected engagement with surgical literature. Method Twitter Mentions and Mendeley Readers Data were retrieved for all papers published in Annals of Surgery, BJS and JAMASurgery between January 2019 and October 2020. The non-parametric Mann-Whitney U test was used to compare Twitter Mentions and Mendeley Readers for COVID surgical vs non-COVID surgical publications (in 2020) and all surgical papers published before and after the advent of COVID-19. A control database of all papers published in NEJM, BMJ and Lancet over the same period of time was also created. Results There was no difference in Twitter mentions between COVID-19 and non-COVID-19 papers (p-value 0.604); however there were significantly more Mendeley readers of COVID-19 papers than non-COVID-19 papers in 2020 (55 vs 5 median readers, p Analysis of the non-surgical control dataset revealed the opposite trend; papers published in 2020 received significantly more attention than those published in 2019 (39 vs 30 median Twitter citations, p Conclusion Surgical papers published during the COVID-19 pandemic received significantly fewer social media mentions. Such reduced visibility has the potential to affect future citation metrics and dissemination of surgical knowledge