Toward integrated conservation of North America's crop wild relatives

North America harbors a rich native flora of crop wild relatives—the progenitors and closely related species of domesticated plants—as well as a range of culturally significant wild utilized plants. Despite their current and potential future value, they are rarely prioritized for conservation efforts; thus many species are threatened in their natural habitats, and most are underrepresented in plant genebanks and botanical gardens. Further coordination of efforts among land management, botanical, and agricultural science organizations will improve conservation and general public awareness with regard to these species. We present examples of productive collaborations focused on wild cranberries (Vaccinium macrocarpon and Vaccinium oxycoccos) and chile peppers (Capsicum annuum var. glabriusculum). We then discuss five shared priorities for further action: (1) understand and document North America's crop wild relatives and wild utilized plants, (2) protect threatened species in their natural habitats, (3) collect and conserve ex situ the diversity of prioritized species, (4) make this diversity accessible and attractive for plant breeding, research, and education, and (5) raise public awareness of their value and the threats to their persistence

People pollinating partnerships: harnessing collaborations between botanic gardens and agricultural research organizations on crop diversity

The world's botanic gardens are repositories of plant diversity but are seldom considered to be major contributors to conservation and research of crops. Thus, botanic gardens and agricultural research organizations have had somewhat limited interactions historically. An unprecedented three-year collaboration between the American Society of Agronomy, Crop Science Society of America, Soil Science Society of America, the American Public Gardens Association, and the World Food Prize Foundation brought together experts from botanic gardens and the agricultural research community, culminating in a Symposium in April 2019 in Des Moines, Iowa. Funded by a grant from the United States Department of Agriculture – National Institute of Food and Agriculture (USDA – NIFA), one of the major outcomes of this collaboration was the development of a shared Road Map for conservation, use, and public engagement around North America’s crop wild relatives and wild utilized plants – species of interest to both communities. Key takeaways from this collaboration are discussed

The First Provenance Challenge

The first Provenance Challenge was set up in order to provide a forum for the community to help understand the capabilities of different provenance systems and the expressiveness of their provenance representations. To this end, a Functional Magnetic Resonance Imaging workflow was defined, which participants had to either simulate or run in order to produce some provenance representation, from which a set of identified queries had to be implemented and executed. Sixteen teams responded to the challenge, and submitted their inputs. In this paper, we present the challenge workflow and queries, and summarise the participants contributions

An inventory of crop wild relatives and wild-utilized plants in Canada

In the face of global pressures of change and biodiversity loss, crop wild relatives (CWR) and wild-utilized species (WUS) urgently require conservation attention. To advance conservation, we assembled a national inventory of CWR and WUS in Canada. To assess current ex situ conservation of these plant species, we gathered a virtual metacollection of accession data from botanical gardens and national genebanks. The inventory includes 779 CWR and WUS taxa (658 distinct species), with 263 (222 distinct species) that are related to food crops of national and global importance such as blueberry (Vaccinium corymbosum L.), apple (Malus domestica (Suckow) Borkh.), sunflower (Helianthus annuus L.), and saskatoon (Amelanchier spp.). Sixty-one food crop relatives are prioritized for breeding potential, and sixteen due to conservation threats. Although most food crop CWR are represented in ex situ collections (91% of species), representation of within-species diversity is low (median = 5% of Canadian ecogeographic types represented per species). Poor representation of within-species diversity demands an integrative conservation strategy that emphasizes in situ protection, especially focusing on wild populations in Canada's southern ecoregions where diversity is concentrated. While genebank collections represent higher accession counts per species, botanical gardens include living collections of fruit crop relatives and other woody perennials that are well situated to raise broader awareness of CWR and WUS. To promote further conservation action, we present a web application that enables conservation planners and practitioners to identify local CWR and WUS and to identify within-species ecogeographic types that are underrepresented in ex situ conservation systems

Berries as a case study for crop wild relative conservation, use, and public engagement in Canada

Conservation of plant biodiversity, in particular crop wild relatives including those tended and cultivated by Indigenous Peoples, is critical to food security and agricul ture. Building on the 2019 road map for crop wild relatives, we examine berries as a case study for crop wild relative conservation, use, and public engagement. We focus on berries due not only to their economic, cultural, and nutritional importance but also because they are consumed fresh, providing a unique opportunity for individuals and communities to connect with plants. We outline health benefits, geographic dis tribution, and species at risk for Canadian berries. We describe practices, strategies, and approaches used by Indigenous Peoples to steward berries and emphasize the importance of traditional knowledge. We highlight opportunities for in situ and ex situ berry conservation and use of berries in plant breeding and Indigenous foodways. Our aim is to lay the groundwork for future collaborative efforts in these areas and to showcase berries as a useful case study for conservation of food plant biodiversity and public engagement

Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX.

In the POLLUX study, daratumumab plus lenalidomide/dexamethasone significantly reduced risk of progression/death versus lenalidomide/dexamethasone alone in relapsed/refractory multiple myeloma. We provide one additional year of follow up and include the effect on minimal residual disease and in clinically relevant subgroups. After 25.4 months of follow up, daratumumab plus lenalidomide/dexamethasone prolonged progression-free survival versus lenalidomide/dexamethasone alone (median not reached vs 17.5 months; hazard ratio, 0.41; 95% confidence interval, 0.31-0.53; P<0.0001). The overall response rate was 92.9% versus 76.4%, and 51.2% versus 21.0% achieved a complete response or better, respectively (both P<0.0001). At the 10-5 sensitivity threshold, 26.2% versus 6.4% were minimal residual disease-negative, respectively (P<0.0001). Post hoc analyses of clinically relevant patient subgroups demonstrated that progression-free survival was significantly prolonged for daratumumab plus lenalidomide/dexamethasone versus lenalidomide/dexamethasone regardless of number of prior lines of therapy. Patients previously treated with lenalidomide or thalidomide and those refractory to bortezomib received similar benefits (all P<0.01). Treatment benefit with daratumumab plus lenalidomide/dexamethasone was maintained in high-risk patients (median progression-free survival 22.6 vs 10.2 months; hazard ratio, 0.53; 95% confidence interval, 0.25-1.13; P=0.0921) and patients with treatment-free intervals of >12 and ≤12 months and >6 and ≤6 months. No new safety signals were observed. In relapsed/refractory multiple myeloma patients, daratumumab plus lenalidomide/dexamethasone continued to improve progression-free survival and deepen responses versus lenalidomide/dexamethasone. Trial Registration: clinicaltrials.gov identifier: 02076009

IL-13 is a driver of COVID-19 severity

Immune dysregulation is characteristic of the more severe stages of SARS-CoV-2 infection. Understanding the mechanisms by which the immune system contributes to COVID-19 severity may open new avenues to treatment. Here, we report that elevated IL-13 was associated with the need for mechanical ventilation in 2 independent patient cohorts. In addition, patients who acquired COVID-19 while prescribed Dupilumab, a mAb that blocks IL-13 and IL-4 signaling, had less severe disease. In SARS-CoV-2–infected mice, IL-13 neutralization reduced death and disease severity without affecting viral load, demonstrating an immunopathogenic role for this cytokine. Following anti–IL-13 treatment in infected mice, hyaluronan synthase 1 (Has1) was the most downregulated gene, and accumulation of the hyaluronan (HA) polysaccharide was decreased in the lung. In patients with COVID-19, HA was increased in the lungs and plasma. Blockade of the HA receptor, CD44, reduced mortality in infected mice, supporting the importance of HA as a pathogenic mediator. Finally, HA was directly induced in the lungs of mice by administration of IL-13, indicating a new role for IL-13 in lung disease. Understanding the role of IL-13 and HA has important implications for therapy of COVID-19 and, potentially, other pulmonary diseases. IL-13 levels were elevated in patients with severe COVID-19. In a mouse model of the disease, IL-13 neutralization reduced the disease and decreased lung HA deposition. Administration of IL-13–induced HA in the lung. Blockade of the HA receptor CD44 prevented mortality, highlighting a potentially novel mechanism for IL-13–mediated HA synthesis in pulmonary pathology

Daratumumab, lenalidomide, and dexamethasone in relapsed/refractory myeloma: a cytogenetic subgroup analysis of POLLUX

High cytogenetic risk abnormalities confer poor outcomes in multiple myeloma patients. In POLLUX, daratumumab/lenalidomide/dexamethasone (D-Rd) demonstrated significant clinical benefit versus lenalidomide/dexamethasone (Rd) in relapsed/refractory multiple myeloma (RRMM) patients. We report an updated subgroup analysis of POLLUX based on cytogenetic risk. The cytogenetic risk was determined using fluorescence in situ hybridization/karyotyping; patients with high cytogenetic risk had t(4;14), t(14;16), or del17p abnormalities. Minimal residual disease (MRD; 10–5) was assessed via the clonoSEQ® assay V2.0. 569 patients were randomized (D-Rd, n = 286; Rd, n = 283); 35 (12%) patients per group had high cytogenetic risk. After a median follow-up of 44.3 months, D-Rd prolonged progression-free survival (PFS) versus Rd in standard cytogenetic risk (median: not estimable vs 18.6 months; hazard ratio [HR], 0.43; P < 0.0001) and high cytogenetic risk (median: 26.8 vs 8.3 months; HR, 0.34; P = 0.0035) patients. Responses with D-Rd were deep, including higher MRD negativity and sustained MRD-negativity rates versus Rd, regardless of cytogenetic risk. PFS on subsequent line of therapy was improved with D-Rd versus Rd in both cytogenetic risk subgroups. The safety profile of D-Rd by cytogenetic risk was consistent with the overall population. These findings demonstrate the improved efficacy of daratumumab plus standard of care versus standard of care in RRMM, regardless of cytogenetic risk

Subcutaneous daratumumab in patients with relapsed or refractory multiple myeloma: Part 2 of the open-label, multicenter, dose-escalation phase 1b study (PAVO)

Intravenous daratumumab is approved for the treatment of multiple myeloma. In Part 1 of the PAVO study, a mix-and-deliver subcutaneous formulation of daratumumab with recombinant human hyaluronidase PH20 (rHuPH20) was well tolerated, with low rates of infusion-related reactions and similar efficacy to intravenous daratumumab. Part 2 of PAVO evaluated a concentrated, pre-mixed co-formulation of daratumumab and rHuPH20 (DARA SC). Patients with ≥2 prior lines of therapy, including a proteasome inhibitor and immunomodulatory drug, received daratumumab (1800 mg) and rHuPH20 (30,000 U) in 15 mL subcutaneously over 3-5 minutes per the approved intravenous monotherapy dosing schedule. Primary endpoints were daratumumab trough concentration at the end of weekly dosing (just prior to the Cycle 3 Day 1 dose) and safety. Twenty-five patients were enrolled in PAVO Part 2. DARA SC achieved daratumumab trough concentrations similar to or greater than intravenous daratumumab 16 mg/kg. The adverse event profile of DARA SC was consistent with intravenous daratumumab, with no new safety concerns and a lower infusion-related reaction rate. At a median follow-up of 14.2 months, the overall response rate was 52%, median duration of response was 15.7 months, and median progression-free survival was 12.0 months. DARA SC 1800 mg was well tolerated in relapsed/refractory multiple myeloma, with a low infusion-related reaction rate and reduced administration time. Daratumumab serum concentrations following DARA SC were consistent with intravenous dosing, and deep and durable responses were observed. Based on these results, ongoing studies are investigating DARA SC in multiple myeloma and other conditions. (ClinicalTrials.gov identifier: 02519452)

Covichem: A biochemical severity risk score of COVID-19 upon hospital admission

Clinical and laboratory predictors of COVID-19 severity are now well described and combined to propose mortality or severity scores. However, they all necessitate saturable equipment such as scanners, or procedures difficult to implement such as blood gas measures. To provide an easy and fast COVID-19 severity risk score upon hospital admission, and keeping in mind the above limits, we sought for a scoring system needing limited invasive data such as a simple blood test and co-morbidity assessment by anamnesis. A retrospective study of 303 patients (203 from Bordeaux University hospital and an external independent cohort of 100 patients from Paris Pitié-Salpêtrière hospital) collected clinical and biochemical parameters at admission. Using stepwise model selection by Akaike Information Criterion (AIC), we built the severity score Covichem. Among 26 tested variables, 7: obesity, cardiovascular conditions, plasma sodium, albumin, ferritin, LDH and CK were the independent predictors of severity used in Covichem (accuracy 0.87, AUROC 0.91). Accuracy was 0.92 in the external validation cohort (89% sensitivity and 95% specificity). Covichem score could be useful as a rapid, costless and easy to implement severity assessment tool during acute COVID-19 pandemic waves