Cross-species oncogenomics offers insight into human muscle-invasive bladder cancer.

BACKGROUND: In humans, muscle-invasive bladder cancer (MIBC) is highly aggressive and associated with a poor prognosis. With a high mutation load and large number of altered genes, strategies to delineate key driver events are necessary. Dogs and cats develop urothelial carcinoma (UC) with histological and clinical similarities to human MIBC. Cattle that graze on bracken fern also develop UC, associated with exposure to the carcinogen ptaquiloside. These species may represent relevant animal models of spontaneous and carcinogen-induced UC that can provide insight into human MIBC. RESULTS: Whole-exome sequencing of domestic canine (n = 87) and feline (n = 23) UC, and comparative analysis with human MIBC reveals a lower mutation rate in animal cases and the absence of APOBEC mutational signatures. A convergence of driver genes (ARID1A, KDM6A, TP53, FAT1, and NRAS) is discovered, along with common focally amplified and deleted genes involved in regulation of the cell cycle and chromatin remodelling. We identify mismatch repair deficiency in a subset of canine and feline UCs with biallelic inactivation of MSH2. Bovine UC (n = 8) is distinctly different; we identify novel mutational signatures which are recapitulated in vitro in human urinary bladder UC cells treated with bracken fern extracts or purified ptaquiloside. CONCLUSION: Canine and feline urinary bladder UC represent relevant models of MIBC in humans, and cross-species analysis can identify evolutionarily conserved driver genes. We characterize mutational signatures in bovine UC associated with bracken fern and ptaquiloside exposure, a human-linked cancer exposure. Our work demonstrates the relevance of cross-species comparative analysis in understanding both human and animal UC.

Machine learning enhances prediction of plants as potential sources of antimalarials.

Plants are a rich source of bioactive compounds and a number of plant-derived antiplasmodial compounds have been developed into pharmaceutical drugs for the prevention and treatment of malaria, a major public health challenge. However, identifying plants with antiplasmodial potential can be time-consuming and costly. One approach for selecting plants to investigate is based on ethnobotanical knowledge which, though having provided some major successes, is restricted to a relatively small group of plant species. Machine learning, incorporating ethnobotanical and plant trait data, provides a promising approach to improve the identification of antiplasmodial plants and accelerate the search for new plant-derived antiplasmodial compounds. In this paper we present a novel dataset on antiplasmodial activity for three flowering plant families - Apocynaceae, Loganiaceae and Rubiaceae (together comprising c. 21,100 species) - and demonstrate the ability of machine learning algorithms to predict the antiplasmodial potential of plant species. We evaluate the predictive capability of a variety of algorithms - Support Vector Machines, Logistic Regression, Gradient Boosted Trees and Bayesian Neural Networks - and compare these to two ethnobotanical selection approaches - based on usage as an antimalarial and general usage as a medicine. We evaluate the approaches using the given data and when the given samples are reweighted to correct for sampling biases. In both evaluation settings each of the machine learning models have a higher precision than the ethnobotanical approaches. In the bias-corrected scenario, the Support Vector classifier performs best - attaining a mean precision of 0.67 compared to the best performing ethnobotanical approach with a mean precision of 0.46. We also use the bias correction method and the Support Vector classifier to estimate the potential of plants to provide novel antiplasmodial compounds. We estimate that 7677 species in Apocynaceae, Loganiaceae and Rubiaceae warrant further investigation and that at least 1300 active antiplasmodial species are highly unlikely to be investigated by conventional approaches. While traditional and Indigenous knowledge remains vital to our understanding of people-plant relationships and an invaluable source of information, these results indicate a vast and relatively untapped source in the search for new plant-derived antiplasmodial compounds.

Evaluation of 43 species of Congolese medicinal plants used traditionally for the treatment of schistosomiasis leading to the isolation of an anti-schistosomal phaeophytin from Pseudolachnostylis maprouneifolia Pax.

ETHNOPHARMACOLOGICAL RELEVANCE: Schistosomiasis (bilharzia) is an important, prevalent and neglected tropical disease for which new treatments are urgently required. In the DR Congo and other sub- and tropical countries, traditional medicines are widely used for the control of schistosomiasis. AIM OF STUDY: To evaluate 43 Congolese plant species used traditionally for the treatment of urogenital schistosomiasis against Schistosoma mansoni. MATERIALS AND METHODS: Methanolic extracts were screened against S. mansoni newly transformed schistosomula (NTS). Three of the most active extracts were evaluated for acute oral toxicity in guinea pigs and activity guided fractionation of the least toxic was carried out using S. mansoni NTS and adult stages. An isolated compound was identified by means of spectroscopic techniques. RESULTS: Thirty-nine of 62 extracts killed S. mansoni NTS at 100 µg/mL and 7 extracts were active at ≥ 90% at 25 µg/mL; 3 extracts were selected for acute oral toxicity evaluation; the least toxic of these, Pseudolachnostylis maprouneifolia leaf was then subjected to activity-guided fractionation. 173-ethoxyphaeophorbide a (1) was isolated as an active compound with 56% activity against NTS at 50 µg/mL and 22.5% activity against adult S. mansoni at 100 µg/mL but these activities are significantly less than those of the parent fractions suggesting that other active compounds are also present and/or that synergistic interactions are taking place. CONCLUSION: This study has identified 39 plant extracts with activity against S. mansoni NTS lending support to their traditional use in the treatment of schistosomiasis for which new treatments are urgently needed. P. maprouneifolia leaf extract was found to have potent anti-schistosomal activity and low in vivo oral toxicity in guinea pigs; activity-guided fractionation resulted in the isolation of an active compound, 173-ethoxyphaeophorbide a. Phaeophorbides may merit exploration as potential anti-schistosomal agents and further work on plant species shown to have potent activity against S. mansoni NTS in this study would be worthwhile.

Pharmacists as members of an interdisciplinary pulmonary embolism response team.

Introduction: Pulmonary embolism response teams (PERTs) were developed to assist with diagnosis, risk stratification, and management of intermediate and high-risk pulmonary embolism (PE) and have been shown to reduce 90-day mortality. The pharmacist's role on the PERT is not well defined. Objectives: Describe the pharmacist's role as a PERT member and determine if pharmacists can improve time to anticoagulation and promote use of low molecular weight heparin (LMWH) instead of unfractionated heparin (UFH). Methods: A retrospective, observational study of adult patients with massive or submassive PE between January 2014 and May 2020. Patient demographics, clinical variables, anticoagulation treatment/timing, and pharmacist activities during PERT response were evaluated. Patients were divided into three groups for comparisons (pre-PERT vs post-PERT with a pharmacist vs post-PERT without a pharmacist). Wilcoxon rank-sum or Kruskal-Wallis test and chi-squared analysis were used for continuous and categorical data, respectively. Results: A total of 573 patients were included (mean age 63.2 ± 15.6 years, 54% male, 78% submassive PE); 137 in the pre-PERT and 436 in the post-PERT groups. Within the post-PERT group, 305 patients (70%) had a pharmacist as a member of the PERT, of which 222 (73%) had a documented pharmacotherapy-related intervention/activity. Most (n = 178, 58%) involved a pharmacist facilitating ordering/administration of an anticoagulant/thrombolytic. Median time from diagnosis to anticoagulation was significantly reduced in the post-PERT groups (pre-PERT: 104 minutes [IQR 124.5], post-PERT with a pharmacist: 63 minutes [IQR 84], post-PERT without a pharmacist: 75.5 minutes [IQR 113], P = .0001). More patients in the post-PERT groups received LMWH compared to UFH when a pharmacist was involved vs without a pharmacist (69.5% vs 53.3%, P = .0019) and major bleeding events were reduced (pre-PERT: 14.6%, post-PERT with a pharmacist: 4.6%, and post-PERT without a pharmacist: 9.9%, P = .0013). Conclusion: Pharmacists have an active role on the PERT and their involvement was associated with a shorter diagnosis to anticoagulation time, increased LMWH use, and fewer major bleeding events.

Semi-Synthetic Analogues of Cryptolepine as a Potential Source of Sustainable Drugs for the Treatment of Malaria, Human African Trypanosomiasis, and Cancer.

The prospect of eradicating malaria continues to be challenging in the face of increasing parasite resistance to antimalarial drugs so that novel antimalarials active against asexual, sexual, and liver-stage malaria parasites are urgently needed. In addition, new antimalarials need to be affordable and available to those most in need and, bearing in mind climate change, should ideally be sustainable. The West African climbing shrub Cryptolepis sanguinolenta is used traditionally for the treatment of malaria; its principal alkaloid, cryptolepine (1), has been shown to have antimalarial properties, and the synthetic analogue 2,7-dibromocryptolepine (2) is of interest as a lead toward new antimalarial agents. Cryptolepine (1) was isolated using a two-step Soxhlet extraction of C. sanguinolenta roots, followed by crystallization (yield 0.8% calculated as a base with respect to the dried roots). Semi-synthetic 7-bromo- (3), 7, 9-dibromo- (4), 7-iodo- (5), and 7, 9-dibromocryptolepine (6) were obtained in excellent yields by reaction of 1 with N-bromo- or N-iodosuccinimide in trifluoroacetic acid as a solvent. All compounds were active against Plasmodia in vitro, but 6 showed the most selective profile with respect to Hep G2 cells: P. falciparum (chloroquine-resistant strain K1), IC50 = 0.25 µM, SI = 113; late stage, gametocytes, IC50 = 2.2 µM, SI = 13; liver stage, P. berghei sporozoites IC50 = 6.13 µM, SI = 4.6. Compounds 3-6 were also active against the emerging zoonotic species P. knowlesi with 5 being the most potent (IC50 = 0.11 µM). In addition, 3-6 potently inhibited T. brucei in vitro at nM concentrations and good selectivity with 6 again being the most selective (IC50 = 59 nM, SI = 478). These compounds were also cytotoxic to wild-type ovarian cancer cells as well as adriamycin-resistant and, except for 5, cisplatin-resistant ovarian cancer cells. In an acute oral toxicity test in mice, 3-6 did not exhibit toxic effects at doses of up to 100 mg/kg/dose × 3 consecutive days. This study demonstrates that C. sanguinolenta may be utilized as a sustainable source of novel compounds that may lead to the development of novel agents for the treatment of malaria, African trypanosomiasis, and cancer.

A methanolic extract of Zanthoxylum bungeanum modulates secondary metabolism regulator genes in Aspergillus flavus and shuts down aflatoxin production.

Aflatoxin B1 (AFB1) is a food-borne toxin produced by Aspergillus flavus and a few similar fungi. Natural anti-aflatoxigenic compounds are used as alternatives to chemical fungicides to prevent AFB1 accumulation. We found that a methanolic extract of the food additive Zanthoxylum bungeanum shuts down AFB1 production in A. flavus. A methanol sub-fraction (M20) showed the highest total phenolic/flavonoid content and the most potent antioxidant activity. Mass spectrometry analyses identified four flavonoids in M20: quercetin, epicatechin, kaempferol-3-O-rhamnoside, and hyperoside. The anti-aflatoxigenic potency of M20 (IC50: 2-4 µg/mL) was significantly higher than its anti-proliferation potency (IC50: 1800-1900 µg/mL). RNA-seq data indicated that M20 triggers significant transcriptional changes in 18 of 56 secondary metabolite pathways in A. flavus, including repression of the AFB1 biosynthesis pathway. Expression of aflR, the specific activator of the AFB1 pathway, was not changed by M20 treatment, suggesting that repression of the pathway is mediated by global regulators. Consistent with this, the Velvet complex, a prominent regulator of secondary metabolism and fungal development, was downregulated. Decreased expression of the conidial development regulators brlA and Medusa, genes that orchestrate redox responses, and GPCR/oxylipin-based signal transduction further suggests a broad cellular response to M20. Z. bungeanum extracts may facilitate the development of safe AFB1 control strategies.

The safety and efficacy of systemic versus catheter-based therapies: application of a prognostic model by a pulmonary embolism response team.

The decision by pulmonary embolism response teams (PERTs) to utilize anticoagulation (AC) with or without systemic thrombolysis (ST) or catheter-directed therapies (CDT) for pulmonary embolism (PE) is a balance between the desire for a positive outcome and safety. Our primary aim was to develop a predictive model of in-hospital mortality for patients with high- or intermediate-risk PE managed by PERT while externally validating this model. Our secondary aim was to compare the relative safety and efficacy of ST and CDT in this cohort. Consecutive patients hospitalized between June 2014 and January 2020 at the Cleveland Clinic Foundation and The University of Rochester with acute high- or intermediate-risk PE managed by PERT were retrospectively evaluated. Groups were stratified by treatment strategy. The primary outcome was in-hospital mortality, and secondary outcome was major bleeding. A logistic regression model to predict the primary outcome was built using the derivation cohort, with 100-fold bootstrapping for internal validation. External validation was performed and the area under the receiver operating curve (AUC) was calculated. Of 549 included patients, 421 received AC alone, 71 received ST, and 64 received CDT. Predictors of major bleeding include ESC risk category, PESI score, hypoxia, hemodynamic instability, and serum lactate. CDT trended towards lower mortality but with an increased risk of bleeding relative to ST (OR = 0.42; 95% CI [0.15, 1.17] and OR = 2.14; 95% CI [0.9, 5.06] respectively). In the multivariable logistic regression model in the derivation institution cohort, predictors of in-hospital mortality were age, cancer, hemodynamic instability requiring vasopressors, and elevated NT-proBNP (AUC = 0.86). This model was validated using the validation institution cohort (AUC = 0.88). We report an externally-validated model for predicting in-hospital mortality in patients with PE managed by PERT. The decision by PERT to initiate CDT or ST for these patients had no impact on mortality or major bleeding, yet the long-term efficacy of these interventions needs to be elucidated.

Effect of a Multidisciplinary Pulmonary Embolism Response Team on Patient Mortality.

Multidisciplinary Pulmonary Embolism Response Teams (PERTs) may improve the care of patients with a high risk of pulmonary embolism (PE). The impact of a PERT on long-term mortality has never been evaluated. An observational analysis was conducted of 137 patients before PERT implementation (between 2014 and 2015) and 231 patients after PERT implementation (between 2016 and 2019), presenting to the emergency department of an academic medical center with submassive and massive PE. The primary outcome was 6-month mortality, evaluated by univariate and multivariate analyses. PERT was associated with a sustained reduction in mortality through 6 months (6-month mortality rates of 14% post-PERT vs 24% pre-PERT, unadjusted hazard ratio of 0.57, Relative Risk Reduction of 43%, p = 0.025). There was a reduced length of stay following PERT implementation (9.1 vs 6.5 days, p = 0.007). Time from triage to a diagnosis of PE was independently predictive of mortality, and the risk of mortality was reduced by 5% for each hour earlier that the diagnosis was made. In conclusion, this study is the first to demonstrate an association between PERT implementation and a sustained reduction in 6-month mortality for patients with high-risk PE.

Review of the Phytochemistry and Biological Activity of Cissus incisa Leaves.

BACKGROUND: Cissus incisa is a Vitaceae with a pantropical distribution. In northern Mexico, its leaves have traditionally been used to treat skin infections, abscesses and tumors. Despite its medicinal uses, few studies have been reported. OBJECTIVE: The objective of this study is to summarize the phytochemical and biological studies carried out so far on the leaves of C. incisa, since this part of the plant is the one frequently used, and awaken scientific interest towards the plant. METHODS: Since C. incisa was an undocumented species, most of the information comes from reports of our research group. Databases, books, and websites were also consulted. The information collected was organized and presented in a synthesized way. Plant name was checked with the database "The Plant List". RESULTS: 171, 260, and 114 metabolites were identified by UHPLC-QFTOF-MS in the hexane, chloroform/ methanol, and aqueous extracts, respectively. Fatty acyls, sphingolipids, sterols, glycerolipids, prenol lipids, and terpenes are common metabolites found in these extracts. 2-(2´-hydroxydecanoyl amino)-1,3,4-hexadecanotriol-8-ene, 2,3-dihydroxypropyl tetracosanoate, ß-sitosterol, ß-sitosterol-D-glucopyranoside, α-amyrin-3-O-ß-D-glucopyranoside were also isolated and characterized. Extracts, phytocompounds and semi-synthetic derivatives showed antimicrobial activity against multi-drug resistant bacteria and various cancer cell lines. Results from Perturbation- Theory-Machine Learning-Information-Fusion model (PTMLIF), molecular docking, and vesicular contents assay identified potential targets on the cell membrane, suggesting an antibacterial mechanism of action for ceramides from C. incisa leaves. CONCLUSION: This review reports the efforts of the scientific community in authenticating species used in traditional medicine. Moreover, it gives a compendium of phytochemistry and the biological activities of the components from C. incisa leaves.

Anthelmintic activity and non-cytotoxicity of phaeophorbide-a isolated from the leaf of Spondias mombin L.

ETHNOPHARMACOLOGICAL RELEVANCE: Helminthosis (worm infection) is a disease of grazing livestock, with significant economic implications. Increasing resistance to existing synthetic anthelmintics used to control helminthosis and the unwanted presence of residues of the anthelmintics reported in meat and dairy products present a serious global health challenge. These challenges have necessitated the development of novel anthelmintics that could combat drug resistance and exhibit better safety profiles. Spondias mombin L. (Anacardiaceae) is a plant that has been used traditionally as a worm expeller. AIM OF STUDY: The aim of the work reported herein was to isolate and characterise anthelmintic compound(s) from S. mombin leaf, establishing their bioactivity and safety profile. MATERIALS AND METHODS: Adult Haemonchus placei motility assay was used to assess anthelmintic bioactivity. Bioassay-guided chromatographic fractionation of acetone extract of S. mombin leaf was carried out on a silica gel stationary phase. The structure of the compound was elucidated using spectroscopy (1H and 13C NMR) and Liquid Chromatography-Mass Spectrometry (LC-ESI-MS). Screening to exclude potential cytotoxicity against mammalian cells (H460, Caco-2, MC3T3-E1) was done using alamar blue (AB) and CellTitreGlo (CTG) viability reagents. RESULTS: The acetone extract yielded an active fraction 8 (Ethyl acetate: methanol 90:10; anthelmintic LC50: 3.97 mg/mL), which yielded an active sub-fraction (Ethyl acetate: Methanol 95:5; anthelmintic LC50: 53.8 µg/mL), from which active compound 1 was isolated and identified as phaeophorbide-a (LC50: 23.0 µg/mL or 38.8 µM). The compound was not toxic below 200 µM but weakly cytotoxic at 200 µM. CONCLUSIONS: Phaeophorbide-a (1) isolated from S. mombin leaf extract and reported in the plant for the first time in this species demonstrated anthelmintic activity. No significant toxicity to mammalian cells was observed. It therefore represents a novel anthelmintic pharmacophore as a potential lead for the development of novel anthelmintics.

An Efficient Method for the Isolation of Toxins from Pteridium aquilinum and Evaluation of Ptaquiloside Against Cancer and Non-cancer Cells.

The common fern, bracken (Pteridium aquilinum), is well known for its toxic effects on livestock due principally to the carcinogenic constituent ptaquiloside ( 1: ), although other toxins are present including the cyanogenic glycoside, prunasin ( 2: ). Here, we report an improved and relatively "green" process for the isolation of 1: and 2: from fresh bracken fronds and the evaluation of 1: for cytotoxicity against several cancer cell lines. The results indicate that 1: displays selective toxicity against cancer cells relative to noncancer retinal epithelial cells, and the improved method for the isolation of 1: is expected to facilitate further exploration of its pharmacological properties.

Recent Advances in the Chemistry and Pharmacology of Cryptolepine.

Cryptolepine, the principal constituent of the West African climbing shrub Cryptolepis sanguinolenta, continues to be of interest as a lead to new therapeutic agents, especially for the treatment of protozoal infections and cancer. This contribution reviews the research published in the last decade, highlighting new synthesis routes to cryptolepine and to analogs of this alkaloid, as well as their pharmacology. Studies relating to the use of C. sanguinolenta as an herbal medicine for the treatment of malaria are discussed, as well as the development of analogs of cryptolepine as leads to new agents for the treatment of malaria, trypanosomiasis, and cancer with an emphasis on the pharmacological mechanisms involved. Other potential therapeutic applications include antimicrobial, antidiabetic, and anti-inflammatory activities; the pharmacokinetics and toxicity of cryptolepine are also reviewed.

Lacan on Trauma and Causality: A Psychoanalytic Critique of Post-Traumatic Stress/Growth.

This article makes the case for the largely unacknowledged relevance of the thought of the French psychoanalyst, Jacques Lacan, for the emerging field of the medical and/or health humanities. From the 1930s all the way through to the late 1970s, Lacan was deeply concerned with the ethical and political consequences of then-dominant conceptions of the human in the 'psy' disciplines. His attempt to 'humanise' these disciplines involved an emphasis on humans as symbolic beings, inevitably entangled in the structures of speech and the 'logic of the signifier.' This article explores the implications of Lacan's linguistic framework for his understanding of trauma. It argues that the Lacanian concept of trauma offers a timely antidote to dominant psychiatric notions of trauma today, linked as they are to the questionable politics of 'Post-Traumatic Stress Disorder' and, more recently, of 'Post-Traumatic Growth.'

Effect of platelet inhibitors on thrombus burden in patients with acute pulmonary embolism.

Venous thromboembolism (VTE) whether provoked or not can be life-threatening due to an acute increase in load on the right ventricle (RV) from obstruction of the pulmonary artery (PA). Treatment for and prevention of VTE involves anti-thrombotic agents; more specifically, medications targeting the anticoagulation cascade. In spite of the widespread acceptance of anticoagulants in the treatment of VTE, there appears to be an ongoing belief that platelet reactivity contributes to thrombus burden in patients with acute pulmonary embolism (PE). This investigation of 398 patients presenting with acute PE evaluated whether anti-platelet medication use, which consisted mostly of aspirin therapy, at the time of presentation, affects PA thrombus burden, RV load, or short-term patient outcomes. We conclude that platelets may have been erroneously incriminated as direct thrombotic mediators in patients with acute PE since aspirin neither decreased PA thrombus burden, nor did aspirin improve short-term mortality following acute PE.

Bioactivity and cytotoxicity profiling of vincosamide and strictosamide, anthelmintic epimers from Sarcocephalus latifolius (Smith) Bruce leaf.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaf of Sarcocephalus latifolius is known to be used traditionally by the Fulanis in Nigeria to deworm animals. As helminthosis remains a major constraint to profitable livestock production worldwide, a precarious situation aggravated by the advent of resistant parasites, the discovery of new anthelmintics is a priority, necessitating exploration of medicinal plants for their anthelmintic principles. AIM OF THE STUDY: To identify and characterise compounds with anthelmintic activity from the leaf of Sarcocephalus latifolius. MATERIALS AND METHODS: Powdered S. latifolius leaves were extracted by successive maceration with n-hexane, chloroform and acetone. The dried extracts were evaluated for anthelmintic activity against Haemonchus placei adult worms, and the most active extract was subjected to bioassay-guided chromatographic separations. The isolated compounds were evaluated for cytotoxicity against the mammalian HeLa and MC3T3-E1 cell lines, using alamar blue and CellTitreGloTM to quantify cell viability. LC50 values were computed from the in vitro anthelmintic activity data by fitting to a non-linear regression equation (variable slope). Isolated compounds were characterized using spectroscopic and mass spectrometric analyses. RESULTS: Anthelmintic activity LC50 values for n-hexane, chloroform and acetone extracts were 47.85, 35.76 and 5.72 (mg/mL), respectively. Chromatographic separation of acetone extract afforded two bioactive epimers, identified as vincosamide (LC50 14.7 mg/mL) and strictosamide (LC50 12.8 mg/mL). Cytotoxicity evaluation showed that, below 200 µg/mL (400 µM), neither compound was toxic to the HeLa or MC3T3-E1 cells. CONCLUSION: Vincosamide and strictosamide could serve as novel scaffolds for the development of anthelmintic derivatives with improved potency and helminth selectivity.

Predictors of colony extinction vary by habitat type in social spiders.

Many animal societies are susceptible to mass mortality events and collapse. Elucidating how environmental pressures determine patterns of collapse is important for understanding how such societies function and evolve. Using the social spider Stegodyphus dumicola, we investigated the environmental drivers of colony extinction along two precipitation gradients across southern Africa, using the Namib and Kalahari deserts versus wetter savanna habitats to the north and east. We deployed experimental colonies (n = 242) along two ~ 800-km transects and returned to assess colony success in the field after 2 months. Specifically, we noted colony extinction events after the 2-month duration and collected environmental data on the correlates of those extinction events (e.g., evidence of ant attacks, no. of prey captured). We found that colony extinction events at desert sites were more frequently associated with attacks by predatory ants as compared with savanna sites, while colony extinctions in wetter savannas sites were more tightly associated with fungal outbreaks. Our findings support the hypothesis that environments vary in the selection pressures that they impose on social organisms, which may explain why different social phenotypes are often favored in each habitat.

Spatial proximity and prey vibratory cues influence collective hunting in social spiders.

Social spiders are thought to predominantly receive information about their environment through vibrational cues. Thus, group living introduces the challenge of distinguishing useful vibrational information from the background noise of nestmates. Here we investigate whether spatial proximity between colony-mates may allow social spiders (Stegodyphus dumicola) to reduce background noise that might obstruct vibrational information from prey. To do so, we constructed experimental colonies and measured whether the number of spiders in proximity to one another whilst resting could predict the number of spiders that participated in prey capture. Additionally, we exposed spider colonies to five different simulated vibrational cues mimicking prey to determine which cue types spiders were most responsive to. We found that the number of spiders huddled together prior to foraging trials was positively correlated with the number of spiders participating in collective foraging. Furthermore, colonies responded more quickly to pulsed vibrational cues over other types of vibrational patterns. Together these data reveal that both social interactions and prey cues shape how social sit-and-wait predators experience and respond to their environment.

Right ventricular dysfunction is superior and sufficient for risk stratification by a pulmonary embolism response team.

Several risk stratification tools are available to predict short-term mortality in patients with acute pulmonary embolism (PE). The presence of right ventricular (RV) dysfunction is an independent predictor of mortality and may be a more efficient way to stratify risk for patients assessed by a Pulmonary Embolism Response Team (PERT). We evaluated 571 patients presenting with acute PE, then stratified them by the pulmonary embolism severity index (PESI), by the BOVA score, or categorically as low risk (no RV dysfunction by imaging), intermediate risk/submassive (RV dysfunction by imaging), or high risk/massive PE (RV dysfunction with sustained hypotension). Using imaging data to firstly define the presence of RV strain, and plasma cardiac biomarkers as additional evidence for myocardial dysfunction, we evaluated whether PESI, BOVA, or RV strain by imaging were more appropriate for determining patient risk by a PERT where rapid decision making is important. Cardiac biomarkers poorly distinguished between PESI classes and BOVA stages in patients with acute PE. Cardiac TnT and NT-proBNP easily distinguished low risk from submassive PE with an area under the curve (AUC) of 0.84 (95% CI 0.73-0.95, p < 0.0001), and 0.88 (95% CI 0.79-0.97, p < 0.0001), respectively. Cardiac TnT and NT-proBNP easily distinguished low risk from massive PE with an area under the curve (AUC) of 0.89 (95% CI 0.78-1.00, p < 0.0001), and 0.89 (95% CI 0.82-0.95, p < 0.0001), respectively. In patients with RV dysfunction, the predicted short-term mortality by PESI score or BOVA stage was lower than the observed mortality by a two-fold order of magnitude. The presence of RV dysfunction alone in the context of acute PE is sufficient for the purposes of risk stratification. More complicated risk stratification tools which require the consideration of multiple clinical variables may under-estimate short-term mortality risk.