An HMM–ensemble approach to predict severity progression of ICU treatment for hospitalized Covid–19 patients

COVID–19–related pneumonia requires different modalities of Intensive Care Unit (ICU) interventions at different times to facilitate breathing, depending on severity progression. The ability for clinical staff to predict how patients admitted to hospital will require more or less ICU treatment on a daily basis is critical to ICU management. For real datasets that are sparse and incomplete and where the most important state transitions (dismissal, death) are rare, a standard Hidden Markov Model (HMM) approach is insufficient, as it is prone to overfitting. In this paper we propose a more sophisticated ensemble-based approach that involves training multiple HMMs, each specialized in a subset of the state transitions, and then selecting the more plausible predictions either by selecting or combining the models. We have validated the approach on a live dataset of about 1,000 patients from a partner hospital. Our results show that rare events, as well as the transitions to the most severe treatments outperform state of the art approaches

New theropod dinosaur from the Upper Cretaceous of Patagonia sheds light on the paravian radiation in Gondwana

The fossil record of basal paravians in Gondwana is still poorly known, being limited to the Cretaceous unenlagiids from South America and the problematic Rahonavis from Madagascar. Here we report on a new paravian from the Cenomanian-Turonian (Late Cretaceous) of Río Negro province, NW Patagonia, Argentina. The new taxon exhibits a derived bird-like morphology of the forelimbs (e.g., robust ulna with prominent, anteriorly oriented, and proximally saddle-shaped radial cotyle and wide medial flange on metacarpal I) and a plesiomorphic foot with a raptorial pedal digit II. Phylogenetic analysis recovers the new taxon in a monophyletic clade with Rahonavis, being the sister group of the remaining Avialae and more derived than other non-avian dinosaurs. Both exhibit derived forelimb traits in opposition with their plesiomorphic hind limbs. The position of the new taxon and Rahonavis as stem avialans indicates that Gondwanan basal paravians are represented by two different clades, at least. The new taxon probably constitutes a previously unknown grade in the avian-line theropods in which some flight-related adaptations of the forelimbs are present in cursorial taxa. The present discovery sheds light on the acquisition of flight-related traits in non-avian dinosaurs and on the still poorly known paravian radiation in Gondwana.Fil: Motta, Matias Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Agnolin, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; Argentina. Fundación de Historia Natural Félix de Azara; ArgentinaFil: Brissón Egli, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Novas, Fernando Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; Argentin

Data-Driven, AI-Based Clinical Practice:Experiences, Challenges, and Research Directions

Clinical practice is evolving rapidly, away from the traditional but inefficient detect-and-cure approach, and towards a Preventive, Predictive, Personalised and Participative (P4) vision that focuses on extending people's wellness state. This vision is increasingly data-driven, AI-based, and is underpinned by many forms of "Big Health Data" including periodic clinical assessments and electronic health records, but also using new forms of self-assessment, such as mobile-based questionnaires and personal wearable devices. Over the last few years, we have been conducting a fruitful research collaboration with the Infectious Disease Clinic of the University Hospital of Modena having the main aim of exploring specific opportunities offered by data-driven AI-based approaches to support diagnosis, hospital organization and clinical research. Drawing from this experience, in this paper we provide an overview of the main research challenges that need to be addressed to design and implement data-driven healthcare applications. We present concrete instantiations of these challenges in three real-world use cases and summarise the specific solutions we devised to address them and, finally, we propose a research agenda that outlines the future of research in this field.</p

Data-driven, AI-based clinical practice: experiences, challenges, and research directions

Clinical practice is evolving rapidly, away from the traditional but inefficient detect-and-cure approach, and towards a Preventive, Predictive, Personalised and Participative (P4) vision that focuses on extending people’s wellness state. This vision is increasingly data-driven, AI-based, and is underpinned by many forms of "Big Health Data" including periodic clinical assessments and electronic health records, but also using new forms of self-assessment, such as mobile-based questionnaires and personal wearable devices. Over the last few years, we have been conducting a fruitful research collaboration with the Infectious Disease Clinic of the University Hospital of Modena having the main aim of exploring specific opportunities offered by data-driven AI-based approaches to support diagnosis, hospital organization and clinical research. Drawing from this experience, in this paper we provide an overview of the main research challenges that need to be addressed to design and implement data-driven healthcare applications. We present concrete instantiations of these challenges in three real-world use cases and summarise the specific solutions we devised to address them and, finally, we propose a research agenda that outlines the future of research in this field

Paravian phylogeny and the dinosaur-bird transition: An overview

Recent years witnessed the discovery of a great diversity of early birds as well as closely related non-avian theropods, which modified previous conceptions about the origin of birds and their flight. We here present a review of the taxonomic composition and main anatomical characteristics of those theropod families closely related with early birds, with the aim of analyzing and discussing the main competing hypotheses pertaining to avian origins. We reject the postulated troodontid affinities of anchiornithines, and the dromaeosaurid affinities of microraptorians and unenlagiids, and instead place these groups as successive sister taxa to Avialae. Aiming to evaluate previous phylogenetic analyses, we recoded unenlagiids in the traditional TWiG data matrix, which resulted in a large polytomy at the base of Pennaraptora. This indicates that the TWiG phylogenetic scheme needs a deep revision. Regarding character evolution, we found that: (1) the presence of an ossified sternum goes hand in hand with that of ossified uncinate processes; (2) the presence of foldable forelimbs in basal archosaurs indicates widespread distribution of this trait among reptiles, contradicting previous proposals that forelimb folding driven by propatagial and associated tendons was exclusive to the avian lineage; (3) in basal paravians and avialans (e.g., Archaeopteryx, Anchiornis) the wings are relatively large and wide, with relatively short rectricial feathers, a rounded alar contour, and a convex leading margin. These taxa exhibit restricted forelimb folding capability with respect to more derived birds, their hands being preserved at angles of flexion (with respect to the radius/ulna) of no less than 90°. In more derived birds, however, the rectrices are notably elongate and the angle between the hand and forearm is much less than 90°, indicating not only increased forelimb folding capability but also an increased variety of wingbeat movements during flight. Because of the strong similarities in pectoral girdle configuration between ratites and basal avialans and paravians, it is possible to infer that the main forelimb movements were similar in all these taxa, lacking the complex dorsoventral wing excursion characteristic of living neognathans.Fil: Agnolin, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; Argentina. Fundación de Historia Natural Félix de Azara; ArgentinaFil: Motta, Matias Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Brissón Egli, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Lo Coco, Gastón Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Novas, Fernando Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; Argentin

Real-world data mining meets clinical practice: Research challenges and perspective

As Big Data Analysis meets healthcare applications, domain-specific challenges and opportunities materialize in all aspects of data science. Advanced statistical methods and Artificial Intelligence (AI) on Electronic Health Records (EHRs) are used both for knowledge discovery purposes and clinical decision support. Such techniques enable the emerging Predictive, Preventative, Personalized, and Participatory Medicine (P4M) paradigm. Working with the Infectious Disease Clinic of the University Hospital of Modena, Italy, we have developed a range of Data-Driven (DD) approaches to solve critical clinical applications using statistics, Machine Learning (ML) and Big Data Analytics on real-world EHRs. Here, we describe our perspective on the challenges we encountered. Some are connected to medical data and their sparse, scarce, and unbalanced nature. Others are bound to the application environment, as medical AI tools can affect people's health and life. For each of these problems, we report some available techniques to tackle them, present examples drawn from our experience, and propose which approaches, in our opinion, could lead to successful real-world, end-to-end implementations. DESY report number: DESY-22-153

Comments on the morphology of basal paravian shoulder girdle: New data based on unenlagiid Theropods and Paleognath birds

In 1976 John Ostrom published an enlightening paper about the anatomical transformations in the shoulder girdle and forelimb elements along the origin of birds. Most of his ideas were based on comparing Archaeopteryx lithographica with the extant New World vulture Cathartes aura. Ostrom offered innovative ideas about range of movements and function of wing elements in the basal bird Archaeopteryx. Further, he explored anatomical transformations that may have occurred at early stages of the evolution of flight and established several hypothetical steps toward the acquisition of flapping flight in modern birds. Since then, however, our understanding of paravian diversity and anatomy has increased dramatically. Based on novel information derived from recent experiments, and currently available anatomical evidence of basal paravians, the present paper aims to review some important topics on pectoral girdle anatomy related to flight origins. Further, a brief analysis of pectoral girdle osteology and myology of the extant paleognath Rhea americana is also included with the aim to test whether Ostrom?s ideas still remain valid under this new context, based on available phylogenetic and anatomical frameworks.Fil: Novas, Fernando Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Motta, Matias Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Agnolin, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; Argentina. Universidad Maimónides; ArgentinaFil: Rozadilla, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Lo Coco, Gastón Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Brissón Egli, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; Argentin

Monoclonal Antibodies for Non-Hodgkin's Lymphoma: State of the Art and Perspectives

Monoclonal antibodies have been the most successful therapeutics ever brought to cancer treatment by immune technologies. The use of monoclonal antibodies in B-cell Non-Hodgkin's lymphomas (NHL) represents the greatest example of these advances, as the introduction of the anti-CD20 antibody rituximab has had a dramatic impact on how we treat this group of diseases today. Despite this success, several questions about how to optimize the use of monoclonal antibodies in NHL remain open. The best administration schedules, as well as the optimal duration of rituximab treatment, have yet to be determined. A deeper knowledge of the mechanisms underlying resistance to rituximab is also necessary in order to improve the activity of this and of similar therapeutics. Finally, new antibodies and biological agents are entering the scene and their advantages over rituximab will have to be assessed. We will discuss these issues and present an overview of the most significant clinical studies with monoclonal antibodies for NHL treatment carried out to date

Rare Case of Abdominal Aortic and Multiple Visceral Aneurysms in a Pediatric Patient With PIK3CA Mutation and Vasculitis

Abdominal aortic aneurysms (AAA) are most commonly observed in elderly male patients and are particularly rare in children. Among the pediatric population, they are usually diagnosed in the context of connective tissue disorders, genetic mutations, or vasculitis. The same is true of visceral arteries aneurysms. This case report describes the staged management of an 11-year-old patient presenting PIK3CA mutation and a 5.8 cm infrarenal AAA associated with bilateral common iliac arteries and multiple visceral aneurysms, the largest observed in the superior mesenteric artery (SMA = 3.2 cm). After careful evaluation, decision was made to first approach the most life-threatening lesion (the infrarenal AAA due to the large diameter) and the remaining aneurysms in secondary procedures, with special attention to the SMA aneurysm. The patient underwent a staged repair, with the first phase consisting of an aortobi-iliac graft with the distal anastomosis made at the left common iliac artery and right external iliac artery. The right hypogastric artery was ligated. The second procedure consisted of SMA aneurysm repair with a plication technique, as 7 branches were visualized coming off the aneurysm sac. Postoperative pathology analysis of the aortic and SMA aneurysms sac revealed vasculitis with a mixed inflammatory pattern and a COL3A1 gene heterozygote variant. He is currently in his 18th month after the last surgical intervention, receiving immunomodulatory therapy, with a planned follow-up by the interdisciplinary team to monitor the medications’ side effects and the diameter of the remaining visceral aneurysms

Regenerated silk fibroin membranes as separators for transparent microbial fuel cells

Abstract In recent years novel applications of bioelectrochemical systems are exemplified by phototrophic biocathodes, biocompatible enzymatic fuel cells and biodegradable microbial fuel cells (MFCs). Herein, transparent silk fibroin membranes (SFM) with various fibroin content (2%, 4% and 8%) were synthesised and employed as separators in MFCs and compared with standard cation exchange membranes (CEM) as a control. The highest real-time power performance of thin-film SFM was reached by 2%-SFM separators: 25.7 ± 7.4 μW, which corresponds to 68% of the performance of the CEM separators (37.7 ± 3.1 μW). Similarly, 2%-SFM revealed the highest coulombic efficiency of 6.65 ± 1.90%, 74% of the CEM efficiency. Current for 2%-SFM reached 0.25 ± 0.03 mA (86% of CEM control). Decrease of power output was observed after 23 days for 8% and 4% and was a consequence of deterioration of SFMs, determined by physical, chemical and biological studies. This is the first time that economical and transparent silk fibroin polymers were successfully employed in MFCs