A spatially resolved single-cell lung atlas integrated with clinical and blood signatures distinguishes COVID-19 disease trajectories.

COVID-19 is characterized by a broad range of symptoms and disease trajectories. Understanding the correlation between clinical biomarkers and lung pathology during acute COVID-19 is necessary to understand its diverse pathogenesis and inform more effective treatments. Here, we present an integrated analysis of longitudinal clinical parameters, peripheral blood markers, and lung pathology in 142 Brazilian patients hospitalized with COVID-19.

Host cell maturation modulates parasite invasion and sexual differentiation in .

Malaria remains a global health problem causing more than 400,000 deaths annually. parasites, the causative agents of malaria, replicate asexually in red blood cells (RBCs) of their vertebrate host, while a subset differentiates into sexual stages (gametocytes) for mosquito transmission. Parasite replication and gametocyte maturation in the erythropoietic niches of the bone marrow and spleen contribute to pathogenesis and drive transmission, but the mechanisms underlying this organ enrichment remain unknown.

Lung Ultrasound to Monitor Disease Severity and Aid Prognostication in COVID-19 Pneumonia: A Retrospective Analysis of Serial Lung Ultrasound Assessments.

The aim of this retrospective analysis was to assess if serial lung ultrasound assessments in patients with COVID-19 pneumonia, including a novel simplified scoring system, correlate with PaO:FiO ratio, as a marker of disease severity, and patient outcomes. : Patients treated for COVID-19 pneumonia in a tertiary intensive care unit who had a lung ultrasound assessment were included. Standardised assessments of anterior and lateral lung regions were prospectively recorded.

Raman spectroscopic analysis of skin as a diagnostic tool for Human African Trypanosomiasis.

Human African Trypanosomiasis (HAT) has been responsible for several deadly epidemics throughout the 20th century, but a renewed commitment to disease control has significantly reduced new cases and motivated a target for the elimination of Trypanosoma brucei gambiense-HAT by 2030. However, the recent identification of latent human infections, and the detection of trypanosomes in extravascular tissues hidden from current diagnostic tools, such as the skin, has added new complexity to identifying infected individuals. New and improved diagnostic tests to detect Trypanosoma brucei infection by interrogating the skin are therefore needed.

The hepatic compensatory response to elevated systemic sulfide promotes diabetes.

Impaired hepatic glucose and lipid metabolism are hallmarks of type 2 diabetes. Increased sulfide production or sulfide donor compounds may beneficially regulate hepatic metabolism. Disposal of sulfide through the sulfide oxidation pathway (SOP) is critical for maintaining sulfide within a safe physiological range.

Inferior T cell immunogenicity of a Plasmodium berghei model liver stage antigen expressed throughout pre-erythrocytic maturation.

Sporozoite antigens are the basis of a number of malaria vaccines being tested, but the contribution of antigens expressed during subsequent liver stage development to pre-erythrocytic stage immunity is poorly understood. We previously showed that, following immunisation with radiation attenuated sporozoites (RAS), a model epitope embedded in a sporozoite surface protein elicited robust CD8 T cell responses, whilst the same epitope in a liver stage antigen induced inferior responses. Since RAS arrest early in their development in host hepatocytes, we hypothesised that extending parasite maturation in the liver could considerably improve the epitope-specific CD8 T cell response.

Low immunogenicity of malaria pre-erythrocytic stages can be overcome by vaccination.

Immunogenicity is considered one important criterion for progression of candidate vaccines to further clinical evaluation. We tested this assumption in an infection and vaccination model for malaria pre-erythrocytic stages. We engineered Plasmodium berghei parasites that harbour a well-characterised epitope for stimulation of CD8 T cells, either as an antigen in the sporozoite surface-expressed circumsporozoite protein or the parasitophorous vacuole membrane associated protein upregulated in sporozoites 4 (UIS4) expressed in exo-erythrocytic forms (EEFs).

Comparison of leucocyte profiles between healthy children and those with asymptomatic and symptomatic Plasmodium falciparum infections.

Background: The immune mechanisms that determine whether a Plasmodium falciparum infection would be symptomatic or asymptomatic are not fully understood. Several studies have been carried out to characterize the associations between disease outcomes and leucocyte numbers. However, the majority of these studies have been conducted in adults with acute uncomplicated malaria, despite children being the most vulnerable group.

Importance of the Immunodominant CD8 T Cell Epitope of Plasmodium berghei Circumsporozoite Protein in Parasite- and Vaccine-Induced Protection.

The circumsporozoite protein (CSP) builds up the surface coat of sporozoites and is the leading malaria pre-erythrocytic-stage vaccine candidate. CSP has been shown to induce robust CD8 T cell responses that are capable of eliminating developing parasites in hepatocytes, resulting in protective immunity. In this study, we characterized the importance of the immunodominant CSP-derived epitope SYIPSAEKI of in both sporozoite- and vaccine-induced protection in murine infection models.

Plasmodium falciparum Gametocyte Density and Infectivity in Peripheral Blood and Skin Tissue of Naturally Infected Parasite Carriers in Burkina Faso.

Background: Plasmodium falciparum transmission depends on mature gametocytes that can be ingested by mosquitoes taking a blood meal on human skin. Although gametocyte skin sequestration has long been hypothesized as important contributor to efficient malaria transmission, this has never been formally tested.

Methods: In naturally infected gametocyte carriers from Burkina Faso, we assessed infectivity to mosquitoes by direct skin feeding and membrane feeding.

New Insights into Malaria Pathogenesis.

Malaria remains a major public health threat in tropical and subtropical regions across the world. Even though less than 1% of malaria infections are fatal, this leads to about 430,000 deaths per year, predominantly in young children in sub-Saharan Africa. Therefore, it is imperative to understand why a subset of infected individuals develop severe syndromes and some of them die and what differentiates these cases from the majority that recovers.

Prevalence, Determinants, and Clinical Associations of High-Sensitivity Cardiac Troponin in Patients Attending Emergency Departments.

Background: High-sensitivity cardiac troponin assays may improve the diagnosis of myocardial infarction but increase the detection of elevated cardiac troponin in patients without acute coronary syndrome.

Methods: In a prospective cohort study, we evaluated the prevalence, determinants, and outcome of patients with elevated cardiac troponin attending the emergency department without suspected acute coronary syndrome. We measured high-sensitivity cardiac troponin in 918 consecutive patients attending the emergency department without suspected acute coronary syndrome who had blood sampling performed by the attending clinician.

Corrigendum: Genetic identification of thiosulfate sulfurtransferase as an adipocyte-expressed antidiabetic target in mice selected for leanness.

This corrects the article DOI: 10.1038/nm.4115.

Genetic identification of thiosulfate sulfurtransferase as an adipocyte-expressed antidiabetic target in mice selected for leanness.

The discovery of genetic mechanisms for resistance to obesity and diabetes may illuminate new therapeutic strategies for the treatment of this global health challenge. We used the polygenic 'lean' mouse model, which has been selected for low adiposity over 60 generations, to identify mitochondrial thiosulfate sulfurtransferase (Tst; also known as rhodanese) as a candidate obesity-resistance gene with selectively increased expression in adipocytes. Elevated adipose Tst expression correlated with indices of metabolic health across diverse mouse strains.