Computational single-cell RNA-seq (scRNA-seq) methods have been successfully applied to experiments representing a single condition, technology, or species to discover and define cellular phenotypes. However, identifying subpopulations of cells that are present across multiple data sets remains challenging. Here, we introduce an analytical strategy for integrating scRNA-seq data sets based on common sources of variation, enabling the identification of shared populations across data sets and downstream comparative analysis. We apply this approach, implemented in our R toolkit Seurat (http://satijalab.org/seurat/), to align scRNA-seq data sets of peripheral blood mononuclear cells under resting and stimulated conditions, hematopoietic progenitors sequenced using two profiling technologies, and pancreatic cell 'atlases' generated from human and mouse islets. In each case, we learn distinct or transitional cell states jointly across data sets, while boosting statistical power through integrated analysis. Our approach facilitates general comparisons of scRNA-seq data sets, potentially deepening our understanding of how distinct cell states respond to perturbation, disease, and evolution.

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Integrating single-cell transcriptomic data across different conditions, technologies, and species.

The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

To combat infection, the fruit fly Drosophila melanogaster relies on multiple innate defense reactions, many of which are shared with higher organisms. These reactions include the use of physical barriers together with local and systemic immune responses. First, epithelia, such as those beneath the cuticle, in the alimentary tract, and in tracheae, act both as a physical barrier and local defense against pathogens by producing antimicrobial peptides and reactive oxygen species. Second, specialized hemocytes participate in phagocytosis and encapsulation of foreign intruders in the hemolymph. Finally, the fat body, a functional equivalent of the mammalian liver, produces humoral response molecules including antimicrobial peptides. Here we review our current knowledge of the molecular mechanisms underlying Drosophila defense reactions together with strategies evolved by pathogens to evade them.

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The Host Defense of Drosophila melanogaster

Aspergillus species have emerged as an important cause of life-threatening infections in immunocompromised patients. This expanding population is composed of patients with prolonged neutropenia, advanced HIV infection, and inherited immunodeficiency and patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT) and/or lung transplantation. This document constitutes the guidelines of the Infectious Diseases Society of America for treatment of aspergillosis and replaces the practice guidelines for Aspergillus published in 2000 [1]. The objective of these guidelines is to summarize the current evidence for treatment of different forms of aspergillosis. The quality of evidence for treatment is scored according to a standard system used in other Infectious Diseases Society of America guidelines. This document reviews guidelines for management of the 3 major forms of aspergillosis: invasive aspergillosis, chronic (and saprophytic) forms of aspergillosis, and allergic forms of aspergillosis. Given the public health importance of invasive aspergillosis, emphasis is placed on the diagnosis, treatment, and prevention of the different forms of invasive aspergillosis, including invasive pulmonary aspergillosis, sinus aspergillosis, disseminated aspergillosis, and several types of single-organ invasive aspergillosis. There are few randomized trials on the treatment of invasive aspergillosis. The largest randomized controlled trial demonstrates that voriconazole is superior to deoxycholate amphotericin B (D-AMB) as primary treatment for invasive aspergillosis. Voriconazole is recommended for the primary treatment of invasive aspergillosis in most patients (A-I). Although invasive pulmonary aspergillosis accounts for the preponderance of cases treated with voriconazole, voriconazole has been used in enough cases of extrapulmonary and disseminated infection to allow one to infer that voriconazole is effective in these cases. A randomized trial comparing 2 doses of liposomal amphotericin B (L-AMB) showed similar efficacy in both arms, suggesting that liposomal therapy could be considered as alternative primary therapy in some patients (A-I). For salvage therapy, agents include lipid formulations of amphotericin (LFAB; A-II), posaconazole (B-II), itraconazole (B-II), caspofungin (B-II), or micafungin (B-II). Salvage therapy for invasive aspergillosis poses important challenges with significant gaps in knowledge. In patients whose aspergillosis is refractory to voriconazole, a paucity of data exist to guide management. Therapeutic options include a change of class using an amphotericin B (AMB) formulation or an echinocandin, such as caspofungin (B-II); further use of azoles should take into account host factors and pharmacokinetic considerations. Refractory infection may respond to a change to another drug class (B-II) or to a combination of agents (B-II). The role of combination therapy in the treatment of invasive aspergillosis as primary or salvage therapy is uncertain and warrants a prospective, controlled clinical trial. Assessment of patients with refractory aspergillosis may be difficult. In evaluating such patients, the diagnosis of invasive aspergillosis should be established if it was previously uncertain and should be confirmed if it was previously known. The drug dosage should be considered. Management options include a change to intravenous (IV) therapy, therapeutic monitoring of drug levels, change of drug class, and/or combination therapy. Antifungal prophylaxis with posaconazole can be recommended in the subgroup of HSCT recipients with graft-versus-host disease (GVHD) who are at high risk for invasive aspergillosis and in neutropenic patients with acute myelogenous leukemia or myelodysplastic syndrome who are at high risk for invasive aspergillosis (A-I). Management of breakthrough invasive aspergillosis in the context of mould-active azole prophylaxis is not defined by clinical trial data. The approach to such patients should be individualized on the basis of clinical criteria, including host immunosuppression, underlying disease, and site of infection, as well as consideration of antifungal dosing, therapeutic monitoring of drug levels, a switch to IV therapy, and/or a switch to another drug class (B-III). Certain conditions of invasive aspergillosis warrant consideration for surgical resection of the infected focus. These include but are not limited to pulmonary lesions contiguous with the heart or great vessels, invasion of the chest wall, osteomyelitis, pericardial infection, and endocarditis (B-III). Restoration of impaired host defenses is critical for improved outcome of invasive aspergillosis (A-III). Recovery from neutropenia in a persistently neutropenic host or reduction of corticosteroids in a patient receiving high-dose glucocorticosteroids is paramount for improved outcome in invasive aspergillosis. A special consideration is made concerning recommendations for therapy of aspergillosis in uncommon sites, such as osteomyelitis and endocarditis. There are very limited data on these infections, and most involve D-AMB as primary therapy simply because of its long-standing availability. Based on the strength of the randomized study, the panel recommends voriconazole for primary treatment of these very uncommon manifestations of invasive aspergillosis (B-III). Management of the chronic or saprophytic forms of aspergillosis varies depending on the condition. Single pulmonary aspergillomas may be best managed by surgical resection (B-III), whereas chronic cavitary and chronic necrotizing pulmonary aspergillosis require long-term medical therapy (B-III). The management of allergic forms of aspergillosis involves a combination of medical and anti-inflammatory therapy. For example, management of allergic bronchopulmonary aspergillosis (ABPA) involves the administration of itraconazole and corticosteroids (A-I). © 2008 by the Infectious Diseases Society of America. All rights reserved.

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Treatment of Aspergillosis: Clinical Practice Guidelines of the Infectious Diseases Society of America

Natural killer cell deficiencies and severe varicella infection.

L’hyponatremie est un desordre hydro-electrolytique frequemment observe chez la personne âgee. La connaissance des mecanismes physiopathologiques elementaires est indispensable pour en assurer une prise en charge therapeutique optimale.L’hyponatremie ne doit pas etre systematiquement associee a une diminution du capital sode et donc ne doit pas etre automatiquement corrigee par l’administration d’une solution salee.La premiere etape de la demarche diagnostique doit s’assurer de l’authenticite d’une hyperhydratation intracellulaire devant la decouverte d’une hyponatremie (hyponatremie hypotonique).L’appreciation clinico-biologique de l’etat d’hydratation extracellulaire est la deuxieme etape qui permet de caracteriser les trois types d’hyponatremie hypotonique: hypovolemique, hypervolemique et euvolemique.La prise en charge therapeutique est avant tout etiologique.La restriction hydrique reste la pierre angulaire de la prise en charge therapeutique des hyponatremies hypotoniques asymptomatiques ou pauci-symptomatiques, en s’assurant d’une vitesse de correction moderee, surtout devant une hyponatremie chronique.L’utilisation des antagonistes des recepteurs de l’ADH est une avancee therapeutique interessante, mais son rapport benefice /risque doit etre evalue plus precisement chez le sujet âge.

Hyponatrémie chez la personne âgée : orientation diagnostique et prise en charge thérapeutique

Introduction: The objective was to study the association of frailty status in hospitalized elderly patients with risk of fall in an acute geriatric unit and to characterize elderly “fallers” using a comprehensive gerontological assessment. Patients and Methods: A cross-sectional study was conducted in patients over 65 years of age and hospitalized in an acute geriatric unit. This work was carried out in the Acute Geriatric Medicine Unit, Saint-Julien Hospital, Center Hospitalier Universitaire de Rouen from 1 June 2016 to 15 August 2016. Results: 172 patients were included during the collection period, with a female predominance of 115 patients (66.9%). The average age of the sample was 79.37 years old (65–85). The average CHARLSON score was 6.93 (3–16). Patients came from home in 81.4% of cases (i.e., 140 patients), and from a nursing home in 18.6% of cases (i.e., 32 patients). The risk of falling, as assessed by the Monopodal Support Test, returned as abnormal for 127 patients. In our series, there was a statistically strong link between the risk of falling and the presence of a dementia pathology (p = 0.009), the presence of a vitamin D deficiency (p = 0.03), the presence of frailty, as assessed by the three scales (modified SEGA scale, Fried scale and CFS/7 (<0.001), a high comorbidity score (p = 0.04), and a disturbed autonomy assessment according to IADL (p = 1.02 × 10−5) and according to ADL (p = 6.4 × 10−8). There was a statistically strong link between the risk of falling and the occurrence of death (p = 0.01). Conclusion: The consequences of the fall in terms of morbidity and mortality and the frequency of this event with advancing age and its impact on the quality of life as well as on health expenditure justify a systematic identification of the risk of falling in the elderly population. It is therefore important to have sensitive, specific, and reproducible tools available for identifying elderly people at high risk of falling.

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Association of Frailty Status with Risk of Fall among Hospitalized Elderly Patients: A Cross-Sectional Study in an Acute Geriatric Unit

Monitoring patients with heart failure, atrial fibrillation and under anticoagulant agent by using telemedicine systems is a potential means for optimizing the management of these patients. The HOCAS project is developing an “intelligent” communicative platform enabling the home monitoring Original Research Article Andrès et al.; BJAST, 11(3): 1-7, 2015; Article no.BJAST.19746 2 of patients with heart failure, arrhythmias and anticoagulation drugs using non-invasive sensors, electronic pillbox to promote therapy adherence, a questionnaire to monitor patients’ hygiene and diet, a questionnaire to monitor patients’ therapy adherence together with additional contextual information and patients’ profile. As a result, this platform will assist health care professionals by providing an automated processing of these sensors’ transmitted data in order to detect and report signs of cardiac decompensation early or wrong adherence to therapy.

Emmanuel Andrès

Papers

Natural killer cell deficiencies and severe varicella infection.

Hyponatrémie chez la personne âgée : orientation diagnostique et prise en charge thérapeutique

Association of Frailty Status with Risk of Fall among Hospitalized Elderly Patients: A Cross-Sectional Study in an Acute Geriatric Unit

Home Care Security (HOCAS): A Telemedicine Project to Monitor Patients with Heart Failure and Atrial Fibrillation under Anticoagulation at Home

Anticorps anti-pseudo-PCNA de type 1 (anti-SG2NA) : cherchez un cancer, pas le lupus ☆