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Background Despite the regional and global effects of biomass burning at national and pantropical scales, little effort has focused on determining the influence of climate and socioeconomic conditions on fire regimes in tropical regions. Aims We explored the climate and human factors that explain remotely sensed burnt area and fire abundance in Mexico. Methods We used MCD64A1 data and climate and socioeconomic metrics to understand factors explaining the variation in number of fires and burned area. Key results The largest burned area (41.9% of the total) occurred in temperate forests, grasslands and hydrophilic vegetation, with numerous fire events of medium relative size. The next most extensive burned area (38%) was observed in croplands, with numerous small-size fires. The third group (17.8%) occurred in tropical forests, which had the smallest and most frequent fires. Finally, a fourth group (11.9%) was composed of shrublands, which showed the largest fire sizes and lowest-frequency events. The variability of burned area was related to variations in temperature and precipitation, poverty index, altitude, and distance to water bodies. Conclusions and Implications Our analysis suggests that an assessment integrating climate, human and topographic metrics predicts burned area and may improve fire forecasting in Mexico landscapes.

Resumen La transversalidad y la continuidad asistencial, mediante la comunicación interniveles son la base para mejorar la atención a los pacientes. La Atención Primaria constituye el principio y el final de todo proceso asistencial. La consulta de la Unidad de CMA debe procurar establecerse como de alta resolución y debe incluir la valoración de cirugía, anestesia y enfermería. En ella se debe confirmar el diagnóstico y la indicación quirúrgica, así como aplicar los criterios de selección de pacientes y procedimientos, el consentimiento informado. Igualmente se debe dar al paciente y familiar toda la información acerca del proceso ambulatorio y, en lo posible, la fecha aproximada de la intervención. El control postoperatorio inmediato y tardío es factible realizarlo desde la Atención Primaria.

Global burned area has declined by nearly one quarter between 1998 and 2015. Drylands contain a large proportion of these global fires but there are important differences within the drylands, for example, savannas and tropical dry forests (TDF). Savannas, a biome fire-prone and fire-adapted, have reduced the burned area, while the fire in the TDF is one of the most critical factors impacting biodiversity and carbon emissions. Moreover, under climate change scenarios TDF is expected to increase its current extent and raise the risk of fires. Despite regional and global scale effects, and the influence of this ecosystem on the global carbon cycle, little effort has been dedicated to studying the influence of climate (seasonality and extreme events) and socioeconomic conditions of fire regimen in TDF. Here we use the Global Fire Emissions Database and, climate and socioeconomic metrics to better understand long-term factors explaining the variation in burned area and biomass in TDF at Pantropical scale. On average, fires affected 1.4% of the total TDF' area (60,208 kmEl área global quemada se redujo en casi una cuarta parte entre 1998 y 2015. Los bosques secos contienen una gran proporción de esos incendios globales, pero existen diferencias importantes dentro de ellos, por ejemplo, las sabanas y los bosques secos tropicales (SBC). Las sabanas, son un bioma propenso y adaptado al fuego, y que en los últimos años han reducido su área quemada. Mientras que el fuego en la SBC es uno de los factores más críticos que impactan la biodiversidad y las emisiones de carbono. Además, bajo escenarios de cambio climático, se espera que la SBC aumente su extensión actual y aumente el riesgo de incendios. A pesar de los efectos a escala regional y global, y la influencia de este ecosistema en el ciclo global del carbono, se le ha dedicado poco esfuerzo a estudiar la influencia del clima (estacionalidad y eventos extremos) y las condiciones socioeconómicas del régimen de incendios. Aquí usamos la base de datos global de emisiones de incendios y métricas climáticas y socioeconómicas para comprender mejor los factores a largo plazo que explican la variación en el área quemada y la biomasa a escala Pantropical. En promedio, los incendios afectaron el 1,4% del área total de la SBC (60 208 km

Failure of immunotherapy after applying checkpoint inhibitors or CAR-T cells is linked to T cell exhaustion. Here, we explored the T cell landscape in chronic lymphocytic leukemia (CLL) by single-cell omics analyses of blood, bone marrow and lymph node samples of patients and spleen samples of a CLL mouse model. By single-cell RNA-sequencing, mass cytometry (CyTOF), and multiplex image analysis of tissue microarrays, we defined the spectrum of phenotypes and transcriptional programs of T cells and and their differentiation state trajectories. We identified disease-specific accumulation of distinct regulatory T cell subsets and T cells harboring an exhausted phenotype exclusively in the CLL lymph node tissue. Integration of TCR data revealed a clonal expansion of CD8+precursor exhausted T cells, suggesting their reactivity for CLL cells. Interactome analyses identified the TIM3 ligand Galectin-9 as novel immunoregulatory molecule in CLL. Blocking of Galectin-9 in CLL-bearing mice slowed down disease development and reduced the number of TIM3 expressing T cells. Galectin-9 expression correlated with shorter survival of CLL patients. Thus, Galectin-9 contributes to immune escape in CLL and represents a novel target for immunotherapy.

This chapter traces the conceptual genealogies of religious space and place in the modern study of religion. It describes the spatial turn in the field inaugurated by Mircea Eliade and the Chicago History of Religions School, which provoked a revisionist trend, led by Jonathan Z. Smith. Although this turn relied upon the appropriation of ancient and indigenous constructions of spatial significance, its dialectical relationship between scholarly and native epistemologies of space countered earlier colonial discourses that displaced spatial ways of thought and action in favor of temporal ones. A parallel spatial turn in the social sciences and humanities led by Lefebvre, Harvey, Foucault and others—also a critical reaction to this displacement—emphasized modern and postmodern spacialities, but largely neglected religious ones. Nevertheless, it inspired the revitalization of the study of religious space by a new generation of scholars, leading to a second turn in the field of religious studies.

In this paper, we propose a dengue transmission model of SIR(S)-SI type that accounts for two sex-structured mosquito populations: the wild mosquitoes (males and females that are Wolbachia-free), and those deliberately infected with either wMel or wMelPop strain of Wolbachia. This epidemiological model has four possible outcomes: with or without Wolbachia and with or without dengue. To reach the desired outcome, with Wolbachia and without dengue, we employ the dynamic optimization approach and then design optimal programs for releasing Wolbachia-carrying male and female mosquitoes. Our discussion is focused on advantages and drawbacks of two Wolbachia strains, wMelPop and wMel, that are recommended for dengue prevention and control. On the one hand, the wMel strain guarantees a faster population replacement, ensures durable Wolbachia persistence in the wild mosquito population, and requiters fewer releases. On the other hand, the wMelPop strain displays better results for averting dengue infections in the human population.

International audience; Sleep is essential for human health. Bad sleep and sleepdisorders have been increasingly prevalent and are graduallybecoming a social problem that cannot be ignored. The currentgold standard in sleep monitoring is polysomnography (PSG)allowing nearly complete approach. Unfortunately, this wealthof information is obtained at the cost of invasive system, onlyusable in hospital environment under the control of sleepexperts. Therefore, we develop a wireless body networks forhome sleep monitoring with effort on non-intrusiveness,portability and autonomy. In this paper, we present our globalarchitecture from sensors to user display with a focus on mainfunctions and hardware. Then, we introduce the chosenindicators for sleep monitoring and the algorithms developedfor sleep stages classification. Finally we show the evaluationof our approach compared to PSG. We illustrate the sleep stageclassification during one night in the sleep unit of ToulouseUniversity Hospital and highlight correlation between bodytemperature on extremities and Periodic Limb Movementduring Sleep. Results are promising but need to be reinforcedwith new tests in hospital with several volunteers

Exacerbation of cognitive, motor and nonmotor symptoms have been described in critically ill COVID-19 patients, indicating that, like prior pandemics, neurodegenerative sequelae may mark the aftermath of this viral infection. Moreover, SARS-CoV-2, the causative agent of COVID-19 disease, was associated with hyperferritinemia and unfavorable prognosis in older individuals, suggesting virus-induced ferrosenescence. We have previously defined ferrosenescence as an iron-associated disruption of both the human genome and its repair mechanisms, leading to premature cellular senescence and neurodegeneration. As viruses replicate more efficiently in iron-rich senescent cells, they may have developed the ability to induce this phenotype in host tissues, predisposing to both immune dysfunction and neurodegenerative disorders. In this mini-review, we summarize what is known about the SARS-CoV-2-induced cellular senescence and iron dysmetabolism. We also take a closer look at immunotherapy with natural killer cells, angiotensin II receptor blockers (“sartans”), iron chelators and dipeptidyl peptidase 4 inhibitors (“gliptins”) as adjunct treatments for both COVID-19 and its neurodegenerative complications., Graphical abstract SARS-CoV-2 exploitation of ACE-4, DPP4 and furin augment host intracellular iron, inflicting DNA and p53 damage, causing NK cells ferrosenescence. (CD147-induced mitochondrial damage and iron release are not shown). Disabled NKCs fail to clear senescent, virus-infected cells and α-synuclein, predisposing COVID-19 critical illness and neurodegenerative disorders.Unlabelled Image, Highlights • To proliferate in host cells, the SARS-CoV-2 virus requires iron. • To acquire iron and lower host immunity, the virus inflicts mitochondrial damage. • Iron-linked DNA, mtDNA and p53 disruption triggers ferrosenescence in NK cells. • Dysfunctional NK cells are incapable of eliminating senescent cells, leading to neurodegeneration. • Immunotherapy with NK cells and ferrosenescence-lowering drugs may facilitate the clearance of aged cells.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in the late 2019 and spread rapidly throughout the world, becoming a pandemic in March 2020. It became obvious early that the prognosis of this illness is highly variable, ranging from few mild symptoms to severe complications and death, indicating that aside from the pathogen virulence, host factors contribute significantly to the overall outcome. Like SARS-CoV and Human Coronavirus NL63 (HCoV-NL63-NL63), SARS-CoV-2 enters host cells via several receptors among which angiotensin converting enzyme-2 (ACE-2) are the most studied. As this protein is widely expressed in the lungs, blood vessels, brain, kidney, testes and ovaries, the effects of this virus are widespread, affecting many body tissues and organs. Viral attachment to ACE-2 downregulates this protein, disrupting angiotensin II (ANG II) hydrolysis that in return contributes to the unchecked accumulation of this peptide. ANG II toxicity is the result of excessive activation of ANG II type 1 receptors (AT-1Rs) and N-methyl-D-aspartate NMDA receptors (NMDARs). Overstimulation of these proteins, along with the loss of angiotensin (1–7) (ANG 1–7), upregulates reactive oxygen species (ROS), inflicting end-organ damage (hit 1). However, a preexistent redox impairment may be necessary for the development of SARS-CoV-2 critical illness (hit 2). Here we propose a two-hit paradigm in which COVID-19 critical illness develops primarily in individuals with preexistent antioxidant dysfunction. Several observational studies are in line with the two hit model as they have associated poor COVID-19 prognosis with the hereditary antioxidant defects. Moreover, the SARS-CoV-2 interactome reveals that viral antigen NSP5 directly inhibits the synthesis of glutathione peroxidase (GPX), an antioxidant enzyme that along with glucose-6-phosphate dehydrogenase (G6PD) protect the body from oxidative damage. Indeed, individuals with G6PD deficiency have less favorable COVID-19 outcomes compared to the general population.

International audience; Objectives BackgroundSocial isolation is probably one of the most affected health outcomes in the elderly people, particularly those living alone, due to the COVID-19 pandemic. Therefore, we try to identify it by detecting changes in the elderly such as malnutrition and lack of mobility.Material and methodsThe system consists of two types of sensors installed at various locations in the user's home: Passive infrared (PIR) sensors and reed switch sensors. It was implemented for 15 days in the home of a 26-year-old student living alone, as a first step to later be deployed in the home of elderly people.ResultsOur study showed strong similarities between the activities detected by the algorithm and the real activity pattern of the interviewed individual. In addition, the system was able to identify two daily patterns (weekday and weekend) of the person as he is a student and is present in class during the week.ConclusionA system composed of low-cost, unobtrusive, non-intrusive and miniaturized sensors is able to detect meal-taking activity and mobility. These results are an intermediate step in assessing the potential risk of social isolation in older people living alone based on these ADLs.

This corrects the article DOI: 10.1038/leu.2017.177., info:eu-repo/semantics/published

Robust protocols and automation now enable large-scale single-cell RNA and ATAC sequencing experiments and their application on biobank and clinical cohorts. However, technical biases introduced during sample acquisition can hinder solid, reproducible results and a systematic benchmarking is required before entering large-scale data production. Here, we report the existence and extent of gene expression and chromatin accessibility artifacts introduced during sampling and identify experimental and computational solutions for their prevention.

Aedes aegypti females mosquitoes are the principal transmitters of dengue and other arboviral infections. In recent years, it was disclosed that, when deliberately infected with Wolbachia symbiont, this mosquito species loses its vectorial competence and becomes less capable of transmitting the virus to human hosts. Thanks to this important discovery, Wolbachia-based biocontrol is now accepted as an ecologically friendly and potentially cost-effective method for prevention and control of dengue and other arboviral infections. In this paper, we propose a dengue transmission model that accounts for the presence of wild Aedes aegypti females and those deliberately infected with wMelPop Wolbachia strain, which is regarded as the best blocker of dengue and other arboviral infections. However, wMelPop strain of Wolbachia considerably reduces the individual fitness of mosquitoes, what makes rather challenging to achieve the gradual extrusion of wild mosquitoes and ensure their posterior replacement by Wolbachia-carriers. Nonetheless, this obstacle have been overcome by employing the optimal control approach for design of specific intervention programs based on daily releases of Wolbachia-carrying mosquitoes. The resulting optimal release programs ensure the population replacement and eventual local extinction of wild mosquitoes in the finite time and also entail a significant reduction in the number of expected dengue infections among human hosts under the long-term settings.

BACKGROUND Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by progressive surfactant accumulation and hypoxemia. It is caused by disruption of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, which pulmonary alveolar macrophages require to clear surfactant. Recently, inhaled GM-CSF was shown to improve the partial pressure of arterial oxygen in patients with aPAP. METHODS In a double-blind, placebo-controlled, three-group trial, we randomly assigned patients with aPAP to receive the recombinant GM-CSF molgramostim (300 μg once daily by inhalation), either continuously or intermittently (every other week), or matching placebo. The 24-week intervention period was followed by an open-label treatment-extension period. The primary end point was the change from baseline in the alveolar-arterial difference in oxygen concentration (A-aDo2) at week 24. RESULTS In total, 138 patients underwent randomization; 46 were assigned to receive continuous molgramostim, 45 to receive intermittent molgramostim, and 47 to receive placebo. Invalid A-aDo2 data for 4 patients (1 in each molgramostim group and 2 in the placebo group) who received nasal oxygen therapy during arterial blood gas measurement were replaced by means of imputation. For the primary end point - the change from baseline in the A-aDo2 at week 24 - improvement was greater among patients receiving continuous molgramostim than among those receiving placebo (-12.8 mm Hg vs. -6.6 mm Hg; estimated treatment difference, -6.2 mm Hg; P = 0.03 by comparison of least-squares means). Patients receiving continuous molgramostim also had greater improvement than those receiving placebo for secondary end points, including the change from baseline in the St. George's Respiratory Questionnaire total score at week 24 (-12.4 points vs. -5.1 points; estimated treatment difference, -7.4 points; P = 0.01 by comparison of least-squares means). For multiple end points, improvement was greater with continuous molgramostim than with intermittent molgramostim. The percentages of patients with adverse events and serious adverse events were similar in the three groups, except for the percentage of patients with chest pain, which was higher in the continuous-molgramostim group. CONCLUSIONS In patients with aPAP, daily administration of inhaled molgramostim resulted in greater improvements in pulmonary gas transfer and functional health status than placebo, with similar rates of adverse events. (Funded by Savara Pharmaceuticals; IMPALA ClinicalTrials.gov number, NCT02702180.). Copyright © 2020 Massachusetts Medical Society.

There is increasing evidence of the relevant connection and regulation between the gut and skin immune axis. In fact, oral administration of lipoteichoic acid (LTA) from Lactobacillus rhamnosus GG (LGG) prevents the development of UV‐induced skin tumors in chronically exposed mice. Here we aim to evaluate whether this LTA is able to revert UV‐induced immunosuppression as a mechanism involved in its anti‐tumor effect and whether it has an immunotherapeutic effect against cutaneous squamous cell carcinoma. Using a mouse model of contact hypersensitivity, we demonstrate that LTA overcomes UV‐induced skin immunosuppression. This effect was in part achieved by modulating the phenotype of lymph node resident dendritic cells (DC) and the homing of skin migratory DC. Importantly, oral LTA reduced significantly the growth of established skin tumors once UV radiation was discontinued, demonstrating that it has a therapeutic, besides the already demonstrated preventive antitumor effect. The data presented here strongly indicates that oral administration of LTA represents a promising immunotherapeutic approach for different conditions in which the skin immune system is compromised. Fil: Friedrich, Adrián David. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Campo, Valeria Evelyn. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina Fil: Cela, Eliana Maiten. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina Fil: Morelli, Adrian E.. University of Pittsburgh; Estados Unidos Fil: Shufesky, William J.. University of Pittsburgh; Estados Unidos Fil: Tckacheva, Olga A.. University of Pittsburgh; Estados Unidos Fil: Leoni, Juliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Paz, Mariela Laura. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina Fil: Larregina, Adriana T.. University of Pittsburgh; Estados Unidos Fil: Gonzalez Maglio, Daniel Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina

Wolbachia-based biocontrol has recently emerged as a potential method for prevention and control of dengue and other vector-borne diseases. Major vector species, such as Aedes aegypti females, when deliberately infected with Wolbachia become less capable of getting viral infections and transmitting the virus to human hosts. In this paper, we propose an explicit sex-structured population model that describes an interaction of uninfected (wild) male and female mosquitoes and those deliberately infected with wMelPop strain of Wolbachia in the same locality. This particular strain of Wolbachia is regarded as the best blocker of dengue and other arboviral infections. However, wMelPop strain of Wolbachia also causes the loss of individual fitness in Aedes aegypti mosquitoes. Our model allows for natural introduction of the decision (or control) variable, and we apply the optimal control approach to simulate wMelPop Wolbachia infestation of wild Aedes aegypti populations. The control action consists in continuous periodic releases of mosquitoes previously infected with wMelPop strain of Wolbachia in laboratory conditions. The ultimate purpose of control is to find a tradeoff between reaching the population replacement in minimum time and with minimum cost of the control effort. This approach also allows us to estimate the number of Wolbachia-carrying mosquitoes to be released in day-by-day control action. The proposed method of biological control is safe to human health, does not contaminate the environment, does not make harm to non-target species, and preserves their interaction with mosquitoes in the ecosystem.

SOX11 defines two different subtypes of mantle cell lymphoma through transcriptional regulation of BCL6

Background The co-existence at diagnosis of follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) components (FL/DLBCL) has been considered a transformed lymphoma and accordingly treated although clinicobiological information on these patients is scarce. The aim of this study was to analyze the initial features and outcome of FL/DLBCL patients in the rituximab era. Patients and methods All patients consecutively diagnosed at a single institution with FL/DLBCL (n = 40), as well as those with pure FL (n = 328) or de novo DLBCL (n = 510) as controls. Results The proportion of the DLBCL component was highly variable (median 50%). In 29 FL/DLBCL cases analyzed, the cell of origin was GCB in 86%, ABC in 10% and unclassifiable in 4%. NOTCH1-2 was mutated in 10% of these cases. The proportion of DLBCL component did not impact on overall survival (OS). Regarding initial characteristics, patients with FL/DLBCL were closer to FL in terms of primary nodal origin, good performance status and advanced stage, whereas the other features were intermediate between FL and DLBCL. FL/DLBCL patients were treated as DLBCL with no further intensification. Complete response and primary refractory rates were 65% and 20%, respectively, with these figures being similar to DLBCL and worse than FL. Progression-free survival and OS were intermediate between FL and DLBCL (5-year OS: 85%, 73% and 63% for FL, FL/DLBCL and DLBCL, respectively). FL/DLBCL histology did not reach independent prognostic value for OS in the multivariate analyses. Conclusions The outcome of FL/DLBCL patients is not worse than that of de novo DLBCL. These cases should be treated with immunochemotherapy as DLBCL, but intensification with ASCT may not be necessary. The biological insights of FL/DLBCL warrants further genetic and molecular studies.