Worldwide experience with biosimilar development

Limited access for high-quality biologics due to cost of treatment constitutes an unmet medical need in the US and other regions of the world. The term “biosimilar” is used to designate a follow-on biologic that meets extremely high standards for comparability or similarity to the originator biologic drug that is approved for use in the same indications. Use of biosimilar products has already decreased the cost of treatment in many regions of the world and now a regulatory pathway for approval of these products has been established in the US. The Food and Drug Administration (FDA) led the world with the regulatory concept of comparability and the European Medicines Agency (EMA) was the first to apply this to biosimilars. Patents on the more complex biologics, especially monoclonal antibodies, are now beginning to expire and biosimilar versions of these important medicines are in development. The new Biologics Price Competition and Innovation Act (BPCIA) allows the FDA to approve biosimilars and allows the FDA to lead on the formal designation of interchangeability of biosimilars with their reference products. The FDA's approval of biosimilars is critical to facilitating patient access to high-quality biologic medicines and will allow society to afford the truly innovative molecules currently in the global biopharmaceutical industry's pipeline

Unravelling the Stability of Nightingale Song Over Time and Space Using Open, Citizen Science and Shared Data

Open science approaches enable and facilitate the investigation of many scientific questions in bioacoustics, such as studies on the temporal and spatial evolution of song, as in vocal dialects. In contrast to previous dialect studies, which mostly focused on songbird species with a small repertoire, here we studied the common nightingale (Luscinia megarhynchos), a bird species with a complex and large repertoire. To study dialects on the population level in this species, we used recordings from four datasets: an open museum archive, a citizen science platform, a citizen science project, and shared recordings from academic researchers. We conducted the to date largest temporal and geographic dialect study of birdsong including recordings from 1930 to 2019 and from 13 European countries, with a geographical coverage of 2,652 km of linear distance. To examine temporal stability and spatial dialects, a catalog of 1,868 song types of common nightingales was created. Instead of dialects, we found a high degree of stability over time and space in both, the sub-categories of song and in the occurrence of song types. For example, the second most common song type in our datasets occurred over nine decades and across Europe. In our case study, open and citizen science data proved to be equivalent, and in some cases even better, than data shared by an academic research group. Based on our results, we conclude that the combination of diverse and open datasets was particularly useful to study the evolution of song in a bird species with a large repertoire

Study of T Cell subsets and IL-7 protein expression in HIV-1-infected patients after 7 years HAART

<p>Abstract</p> <p>Objective</p> <p>To study the changes in T cell subsets and IL-7 in HIV-1-infected patients after seven years of highly active antiretroviral therapy (HAART).</p> <p>Methods</p> <p>Seventy-five individuals were included in this study (25 with effective HAART, 18 with ineffective HAART, 17 untreated HIV+ patients, and 15 volunteers in the HIV negative control group). The counts of CD4⁺, CD8⁺, CD8/CD38⁺, and CD8/HLADR⁺T cells as well as the IL-7 protein expression was measured at 5 time points during a period of seven years in patients starting HAART (baseline) and in the HIV negative control group. The expression of CD127 on CD3⁺T cells was measured by flow cytometry at a single time point (after 7 years) in patients with HAART and was compared with untreated HIV+ patients and the HIV negative control group.</p> <p>Results</p> <p>At baseline CD4⁺T cell counts of HIV-1-infected patients were lower than that in the control group (p < 0.01), whereas the CD8⁺, CD8/HLADR⁺and CD8/CD38⁺T cell counts were higher than those in the control group (<it>p <</it>0.01). After seven years of effective HAART, the CD4⁺T cell counts had increased and the CD8⁺T cell count had decreased, although not to the normal levels (<it>p </it>< 0.05). Both the CD8/HLADR⁺and CD8/CD38⁺T cell counts had gradually approached those of the control group (<it>p </it>> 0.05). In the ineffective HAART group, the CD8/CD38⁺T cell count had not decreased significantly, and CD8/HLADR⁺T cell count gradually decreased. Before treatment, IL-7 serum levels of patients were significantly higher than that in the control group (<it>p </it>< 0.01). After seven years of effective HAART, IL-7 levels had gradually decreased, but were still higher than in the control group (<it>p </it>< 0.01). The CD127 expression on CD3⁺CD8⁺T cells in effective HAART patients was higher than in untreated HIV+ patients (<it>p </it>< 0.05), but was lower than that in the control group (<it>p </it>< 0.05). CD127 expression on CD3⁺CD4+ T cells was not significantly different among the control group, untreated HIV+ patients and effective HAART group.</p> <p>Conclusion</p> <p><it>After seven years of </it>effective HAART, the quantity and capacity of T cell subsets and IL-7 in HIV-1-infected patients had been partially restored, and the abnormal immune activation has significantly diminished.</p

Impaired Cross-Talk between Mesolimbic Food Reward Processing and Metabolic Signaling Predicts Body Mass Index

The anticipation of the pleasure derived from food intake drives the motivation to eat, and hence facilitate overconsumption of food which ultimately results in obesity. Brain imaging studies provide evidence that mesolimbic brain regions underlie both general as well as food related anticipatory reward processing. In light of this knowledge, the present study examined the neural responsiveness of the ventral striatum in participants with a broad BMI spectrum. The study differentiated between general (i.e. monetary) and food related anticipatory reward processing. We recruited a sample of volunteers with greatly varying body weights, ranging from a low BMI (below 20 kg/m²) over a normal (20 to 25 kg/m²) and overweight (25 to 30 kg/m²) BMI, to class I (30 to 35 kg/m² ) and class II (35 to 40 kg/m²) obesity. A total of 24 participants underwent functional magnetic resonance imaging whilst performing both a food and monetary incentive delay task, which allows to measure neural activation during the anticipation of rewards. After the presentation of a cue indicating the amount of food or money to be won, participants had to react correctly in order to earn snack points or money coins which could then be exchanged for real food or money, respectively, at the end of the experiment. During the anticipation of both types of rewards, participants displayed activity in the ventral striatum, a region that plays a pivotal role in the anticipation of rewards. Additionally, we observed that specifically anticipatory food reward processing predicted the individual BMI (current and maximum lifetime). This relation was found to be mediated by impaired hormonal satiety signaling, i.e. increased leptin levels and insulin resistance. These findings suggest that heightened food reward motivation contributes to obesity through impaired metabolic signaling

Community engagement and data quality: best practices and lessons learned from a citizen science project on birdsong

Citizen Science (CS) is a research approach that has become popular in recent years and offers innovative potential for dialect research in ornithology. As the scepticism about CS data is still widespread, we analysed the development of a 3-year CS project based on the song of the Common Nightingale (Luscinia megarhynchos) to share best practices and lessons learned. We focused on the data scope, individual engagement, spatial distribution and species misidentifications from recordings generated before (2018, 2019) and during the COVID-19 outbreak (2020) with a smartphone using the ‘Naturblick’ app. The number of nightingale song recordings and individual engagement increased steadily and peaked in the season during the pandemic. 13,991 nightingale song recordings were generated by anonymous (64%) and non-anonymous participants (36%). As the project developed, the spatial distribution of recordings expanded (from Berlin based to nationwide). The rates of species misidentifications were low, decreased in the course of the project (10–1%) and were mainly affected by vocal similarities with other bird species. This study further showed that community engagement and data quality were not directly affected by dissemination activities, but that the former was influenced by external factors and the latter benefited from the app. We conclude that CS projects using smartphone apps with an integrated pattern recognition algorithm are well suited to support bioacoustic research in ornithology. Based on our findings, we recommend setting up CS projects over the long term to build an engaged community which generates high data quality for robust scientific conclusions.Gesellschaftliches Engagement und Datenqualität: Bewährte Praktiken und Erfahrungen aus einem bürgerwissenschaftlichen Projekt zum Vogelgesang Citizen Science (CS) ist eine Forschungsmethode, die in den letzten Jahren an Bedeutung gewonnen hat und innovatives Potenzial für die Dialektforschung in der Ornithologie bietet. Da die Vorbehalte gegenüber CS-Daten immer noch weit verbreitet sind, haben wir die Entwicklung eines dreijährigen CS-Projekts zum Gesang der Nachtigall (Luscinia megarhynchos) analysiert, um bewährte Praktiken und gewonnene Erfahrungen darzustellen. Wir fokussierten uns auf den Datenumfang, das individuelle Engagement von Teilnehmenden, die räumliche Verteilung und die Fehlbestimmungen von Arten aus Aufnahmen, die vor (2018, 2019) und während des COVID-19-Ausbruchs (2020) mit einem Smartphone unter Verwendung der "Naturblick" App erstellt wurden. Die Anzahl der Aufnahmen von Nachtigallgesängen und das individuelle Engagement stiegen stetig an und erreichten ihren Höhepunkt in der Saison während der Pandemie. 13.991 Aufnahmen von Nachtigallgesängen wurden von anonymen (64%) und nicht-anonymen Teilnehmenden (36%) erstellt. Im Laufe des Projekts weitete sich die räumliche Verteilung der Aufnahmen aus (von Berlin auf bundesweit). Die Rate der Fehlbestimmungen war gering, ging im Laufe des Projekts zurück (von 10% auf 1%) und wurde hauptsächlich von gesanglichen Ähnlichkeiten mit anderen Vogelarten beeinflusst. Unsere Studie zeigte außerdem, dass das gesellschaftliche Engagement und die Datenqualität nicht direkt von den durchgeführten Disseminationsaktivitäten beeinflusst wurden, sondern dass erstere von externen Faktoren abhingen und letztere von der App profitierte. Wir schließen daraus, dass CS-Projekte, die Smartphone-Apps mit einem integrierten Mustererkennungsalgorithmus verwenden, gut geeignet sind, um die bioakustische Forschung in der Ornithologie zu unterstützen. Auf der Grundlage unserer Ergebnisse empfehlen wir, CS-Projekte langfristig zu etablieren, um eine aktive Teilnehmergemeinschaft (Community) aufzubauen, die qualitativ hochwertige Daten für fundierte wissenschaftliche Schlussfolgerungen generiert

CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE.

BACKGROUND: Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load. METHODS AND FINDINGS: Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger), we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements 500 copies/µl, the first of two consecutive measurements between 50-500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI) of: 0.35 (0.30-0.40) for counts <200 cells/µl, 0.81 (0.71-0.92) for counts 200 to <350 cells/µl, 0.74 (0.66-0.83) for counts 350 to <500 cells/µl, and 0.96 (0.92-0.99) for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl. CONCLUSIONS: Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl