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The covalent immobilization of synthetic or natural macromolecular compounds containing amino groups onto polystyrene (PS) solid surfaces is of great interest in diagnostic applications. A sensitive assay allowing the determination of reactive end groups is therefore a powerful tool for predicting the performance of the active surface. Recently, we reported the use of the Coomassie brilliant blue (CBB) colorimetric reagent to quantify protonated groups (N) in linear and dendritic structures in solution (Coussot et al., Polym Int 58(5):511-518, ). In this work, a simple method using CBB dye for the characterization of PS aminated solid surfaces is developed. The proposed amino density estimation by colorimetric assay (ADECA) method is based on the reversible complexation of the dye with the N groups on solid surfaces. The assay measures the released dye thanks to the use of a unique sodium carbonate-methanol buffer. Thereby, for the first time, the same surface can be used for characterization and for further coupling applications. A surface density of four N groups per square nanometer can be measured in PS microwell format, the whole characterization being done within 30 min. Performances of this new colorimetric-based method are detailed. The ADECA method is further demonstrated to be useful for the characterization of aminated polypropylene and glass materials with various sizes and shapes. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Development of gene transfer strategies will necessitate improved efficiency and control of transduction and transgene expression. We here provide evidence that targeting expression of the GFP reporter gene to the B-lymphoid progeny of genetically modified human hematopoietic progenitor cells can be achieved through the insertion of regulatory sequences from the human CD19 gene promoter into a lentiviral vector. Based on a bioinformatics approach, three human CD19-derived sequences were designed and inserted into a self-inactivated lentiviral vector backbone upstream of the GFP gene: S.CD19 (230 bp), M.CD19 (464 bp), and L.CD19 (1274 bp). These new lentiviral vectors efficiently transduced cord blood CD34+ cells. The M.CD19 and especially L.CD19 sequences preferentially targeted GFP expression to in vitro and in vivo differentiated CD19+ progeny; moreover, transgene expression was detected from the CD34+ pro/pre-B cell to the mature peripheral IgM+ B cell stage. In contrast, GFP expression was weak or absent in primary T-lymphoid and uncommitted progenitor cells or in erythroid, natural killer, or myeloid differentiated cells. Such B-lineage-specific lentiviral vectors may be useful for correcting inherited disorders that affect B-lymphoid cells or for deciphering the transcriptional program that controls B cell commitment and differentiation. [Copyright &y& Elsevier]

This corrects the article DOI: 10.1038/ncomms11208 [ABSTRACT FROM AUTHOR]

The article presents questions and answers related to ovarian cancer screening, including the prevalence of ovarian cancer in the U.S., the role of American Cancer Society (ACS) in the promotion of ovarian cancer screening, and symptoms of the disease.

The article discusses the importance of gluten-free diet. It mentions that many Americans suffer from celiac disease (CD), gluten sensitivity or wheat allergy, therefore, a gluten-free diet is important for CD, gluten sensitivity and its related disorders. Gluten is found in all products containing wheat, rye, and barley which are found in many foods in Western nations; people should carefully read the ingredients written on prepared food packets so that they can adhere to a gluten-free diet.

The article discusses the current guidelines for diagnosing and treating rheumatoid arthritis (RA) which is crucial for physician assistants (PAs) for its management. Several drugs have been developed which target the specific steps in the autoimmune cascade in RA. An updated clinical classification system issued by the American College of Rheumatology and the European League against Rheumatism (ACR/EULAR) is stated. The primary care PAs play vital role in team management of patients with RA.

The article discusses the management of patients with heart failure (HF). It notes that the management of HF must retard the onset of refractory, end-stage disease, avert acute decompensated heart failure and reduce the incidence of sudden cardiac death (SCD). Also, it mentions that three beta-blockers such as bisoprolol, carvedilol and metoprolol succinate have shown to be effective in reducing mortality from HF.

The article focuses on the screening and early intervention of childhood obesity. It states that almost 20% of children aged two to 19 years in the U.S. are affected by childhood obesity. It mentions that the U.S. Preventive Services Task Force recommends that assessment of body mass index (BMI) must begin at six years of age. It adds that primary care can perform an essential role for treating overweight and obesity in children. INSET: TAKE-HOME POINTS.

The article offers information on the use and misuse of performance-enhancing drugs. According to the American Academy of Pediatrics, performance enhancers benefit sports performance by increasing strength, power, speed, or endurance and improve performance by causing changes in behavior, arousal level, and perception of pain. It emphasizes that physician's assistants (PAs) need to know about performance-enhancing practices to help patients manage abuse.

Background: COVID-19 may be more frequent and more severe in cancer patients than in other individuals. Our aims were to assess the rate of COVID-19 in hospitalized cancer patients, to describe their demographic characteristics, clinical features and care trajectories, and to assess the mortality rate., Methods: This multicenter cohort study was based on the Electronic Health Records of the Assistance Publique-Hôpitaux de Paris (AP-HP). Cancer patients with a diagnosis of COVID-19 between 3 March and 19 May 2020 were included. Main outcome was all-cause mortality within 30 days of COVID-19 diagnosis., Results: A total of 29,141 cancer patients were identified and 7791 (27%) were tested for SARS-CoV-2. Of these, 1359 (17%) were COVID-19-positive and 1148 (84%) were hospitalized; 217 (19%) were admitted to an intensive care unit. The mortality rate was 33% (383 deaths). In multivariate analysis, mortality-related factors were male sex (aHR = 1.39 [95% CI: 1.07-1.81]), advanced age (78-86 y: aHR = 2.83 [95% CI: 1.78-4.51] vs. <66 y; 86-103 y: aHR = 2.61 [95% CI: 1.56-4.35] vs. <66 y), more than two comorbidities (aHR = 2.32 [95% CI: 1.41-3.83]) and C-reactive protein >20 ng/mL (aHR = 2.20 [95% CI: 1.70-2.86]). Primary brains tumors (aHR = 2.19 [95% CI: 1.08-4.44]) and lung cancer (aHR = 1.66 [95% CI: 1.02-2.70]) were associated with higher mortality. Risk of dying was lower among patients with metabolic comorbidities (aHR = 0.65 [95% CI: 0.50-0.84])., Conclusions: In a hospital-based setting, cancer patients with COVID-19 had a high mortality rate. This mortality was mainly driven by age, sex, number of comorbidities and presence of inflammation. This is the first cohort of cancer patients in which metabolic comorbidities were associated with a better outcome.

Context: Diabetes is reported as a risk factor for severe coronavirus disease 2019 (COVID-19), but whether this risk is similar in all categories of age remains unclear., Objective: To investigate the risk of severe COVID-19 outcomes in hospitalized patients with and without diabetes according to age categories., Design Setting and Participants: We conducted a retrospective observational cohort study of 6314 consecutive patients hospitalized for COVID-19 between February and 30 June 2020 in the Paris metropolitan area, France; follow-up was recorded until 30 September 2020., Main Outcome Measure(s): The main outcome was a composite outcome of mortality and orotracheal intubation in subjects with diabetes compared with subjects without diabetes, after adjustment for confounding variables and according to age categories., Results: Diabetes was recorded in 39% of subjects. Main outcome was higher in patients with diabetes, independently of confounding variables (hazard ratio [HR] 1.13 [1.03-1.24]) and increased with age in individuals without diabetes, from 23% for those <50 to 35% for those >80 years but reached a plateau after 70 years in those with diabetes. In direct comparison between patients with and without diabetes, diabetes-associated risk was inversely proportional to age, highest in <50 years and similar after 70 years. Similarly, mortality was higher in patients with diabetes (26%) than in those without diabetes (22%, P < 0.001), but adjusted HR for diabetes was significant only in patients younger than age 50 years (HR 1.81 [1.14-2.87])., Conclusions: Diabetes should be considered as an independent risk factor for the severity of COVID-19 in young adults more so than in older adults, especially for individuals younger than 70 years., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We leveraged the largely untapped resource of electronic health record data to address critical clinical and epidemiological questions about Coronavirus Disease 2019 (COVID-19). To do this, we formed an international consortium (4CE) of 96 hospitals across five countries (www.covidclinical.net). Contributors utilized the Informatics for Integrating Biology and the Bedside (i2b2) or Observational Medical Outcomes Partnership (OMOP) platforms to map to a common data model. The group focused on temporal changes in key laboratory test values. Harmonized data were analyzed locally and converted to a shared aggregate form for rapid analysis and visualization of regional differences and global commonalities. Data covered 27,584 COVID-19 cases with 187,802 laboratory tests. Case counts and laboratory trajectories were concordant with existing literature. Laboratory tests at the time of diagnosis showed hospital-level differences equivalent to country-level variation across the consortium partners. Despite the limitations of decentralized data generation, we established a framework to capture the trajectory of COVID-19 disease in patients and their response to interventions., Competing Interests: Competing interestsR.B. and A.M. are shareholders of Biomeris s.r.l., (© The Author(s) 2020.)

The analysis of the Nystagmus waveforms from eye-tracking records is crucial for the clinical interpretation of this pathological movement. A major issue to automatize this analysis is the presence of natural eye movements and eye blink artefacts that are mixed with the signal of interest. We propose a method based on Convolutional Dictionary Learning that is able to automatically highlight the Nystagmus waveforms, separating the natural motion from the pathological movements. We show on simulated signals that our method can indeed improve the pattern recovery rate and provide clinical examples to illustrate how this algorithm performs.

Platelet transfusions are a key treatment option for a range of life threatening conditions including cancer, chemotherapy and surgery. Efficient ex vivo systems to generate donor independent platelets in clinically relevant numbers could provide a useful substitute. Large quantities of megakaryocytes (MKs) can be produced from human pluripotent stem cells, but in 2D culture the ratio of platelets harvested from MK cells has been limited and restricts production rate. The development of biomaterial cell supports that replicate vital hematopoietic micro-environment cues are one strategy that may increase in vitro platelet production rates from iPS derived Megakaryocyte cells. In this paper, we present the results obtained generating, simulating and using a novel structurally-graded collagen scaffold within a flow bioreactor system seeded with programmed stem cells. Theoretical analysis of porosity using micro-computed tomography analysis and synthetic micro-particle filtration provided a predictive tool to tailor cell distribution throughout the material. When used with MK programmed stem cells the graded scaffolds influenced cell location while maintaining the ability to continuously release metabolically active CD41  +  CD42  +  functional platelets. This scaffold design and novel fabrication technique offers a significant advance in understanding the influence of scaffold architectures on cell seeding, retention and platelet production., (Copyright © 2018. Published by Elsevier Ltd.)

The differentiation of megakaryocytes from human pluripotent stem cells in vitro offers intriguing new perspectives for research and transfusion medicine. However, applications have been hampered by the low efficiency of cytokine driven differentiation protocols leading to poor megakaryocyte purity and yield. Here we describe a novel forward programming approach relying on the combined ectopic expression of the three transcription factors GATA1, FLI1, and TAL1 in human pluripotent stem cells for large scale production of mature megakaryocytes using chemically defined culture and minimum cytokines.