Schistosomiasis Drug Discovery in the Era of Automation and Artificial Intelligence.

Schistosomiasis is a parasitic disease caused by trematode worms of the genus Schistosoma and affects over 200 million people worldwide. The control and treatment of this neglected tropical disease is based on a single drug, praziquantel, which raises concerns about the development of drug resistance. This, and the lack of efficacy of praziquantel against juvenile worms, highlights the urgency for new antischistosomal therapies. In this review we focus on innovative approaches to the identification of antischistosomal drug candidates, including the use of automated assays, fragment-based screening, computer-aided and artificial intelligence-based computational methods. We highlight the current developments that may contribute to optimizing research outputs and lead to more effective drugs for this highly prevalent disease, in a more cost-effective drug discovery endeavor

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases

Background In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy. Main body As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care. Conclusion In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.Peer reviewe

Rainfall, not soil temperature, will limit the seed germination of dry forest species with climate change

Drylands are predicted to become more arid and saline due to increasing global temperature and drought. Although species from the Caatinga, a Brazilian tropical dry forest, are tolerant to these conditions, the capacity for germination to withstand extreme soil temperature and water deficit associated with climate change remains to be quantified. We aimed to evaluate how germination will be affected under future climate change scenarios of limited water and increased temperature. Seeds of three species were germinated at different temperatures and osmotic potentials. Thermal time and hydrotime model parameters were established and thresholds for germination calculated. Germination performance in 2055 was predicted, by combining temperature and osmotic/salt stress thresholds, considering soil temperature and moisture following rainfall events. The most pessimistic climate scenario predicts an increase of 3.9 °C in soil temperature and 30% decrease in rainfall. Under this scenario, soil temperature is never lower than the minimum and seldomly higher than maximum temperature thresholds for germination. As long as the soil moisture (0.139 cm3 cm3) requirements are met, germination can be achieved in 1 day. According to the base water potential and soil characteristics, the minimum weekly rainfall for germination is estimated to be 17.5 mm. Currently, the required minimum rainfall occurs in 14 weeks of the year but will be reduced to 4 weeks by 2055. This may not be sufficient for seedling recruitment of some species in the natural environment. Thus, in future climate scenarios, rainfall rather than temperature will be extremely limiting for seed germination

The negative effect of a vertically-transmitted fungal endophyte on seed longevity is stronger than that of ozone transgenerational effect

Seed morphology underpins many critical biological and ecological processes, such as seed dormancy and germination, dispersal, and persistence. It is also a valuable taxonomic trait that can provide information about plant evolution and adaptations to different ecological niches. This study characterised and compared various seed morphological traits, i.e., seed and pod shape, seed colour and size, embryo size, and air volume for six orchid species; and explored whether taxonomy, biogeographical origin, or growth habit are important determinants of seed morphology. We investigated this on two tropical epiphytic orchid species from Indonesia (Dendrobium strebloceras and D. lineale), and four temperate species from New Zealand, terrestrial Gastrodia cunnninghamii, Pterostylis banksii and Thelymitra nervosa, and epiphytic D. cunninghamii. Our results show some similarities among related species in their pod shape and colour, and seed colouration. All the species studied have scobiform or fusiform seeds and prolate-spheroid embryos. Specifically, D. strebloceras, G. cunninghamii, and P. banksii have an elongated seed shape, while T. nervosa has truncated seeds. Interestingly, we observed high variability in the micro-morphological seed characteristics of these orchid species, unrelated to their taxonomy, biogeographical origin, or growth habit, suggesting different ecological adaptations possibly reflecting their modes of dispersal