Functional antibody and T-cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study (NCT03226886) integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2-positive, 94 were symptomatic and 2 patients died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies, 82% had neutralizing antibodies against WT, whereas neutralizing antibody titers (NAbT) against the Alpha, Beta, and Delta variants were substantially reduced. Whereas S1-reactive antibody levels decreased in 13% of patients, NAbT remained stable up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment-specific, but presented compensatory cellular responses, further supported by clinical. Overall, these findings advance the understanding of the nature and duration of immune response to SARS-CoV-2 in patients with cancer

ATP-binding cassette (ABC) transporters in normal and pathological lung

ATP-binding cassette (ABC) transporters are a family of transmembrane proteins that can transport a wide variety of substrates across biological membranes in an energy-dependent manner. Many ABC transporters such as P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP) are highly expressed in bronchial epithelium. This review aims to give new insights in the possible functions of ABC molecules in the lung in view of their expression in different cell types. Furthermore, their role in protection against noxious compounds, e.g. air pollutants and cigarette smoke components, will be discussed as well as the (mal)function in normal and pathological lung. Several pulmonary drugs are substrates for ABC transporters and therefore, the delivery of these drugs to the site of action may be highly dependent on the presence and activity of many ABC transporters in several cell types. Three ABC transporters are known to play an important role in lung functioning. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene can cause cystic fibrosis, and mutations in ABCA1 and ABCA3 are responsible for respectively Tangier disease and fatal surfactant deficiency. The role of altered function of ABC transporters in highly prevalent pulmonary diseases such as asthma or chronic obstructive pulmonary disease (COPD) have hardly been investigated so far. We especially focused on polymorphisms, knock-out mice models and in vitro results of pulmonary research. Insight in the function of ABC transporters in the lung may open new ways to facilitate treatment of lung diseases

Aguas del Iténez o Guaporé

Bolivia y Brasil comparten una de las cuencas más atractivas y preservadas de la te-giuri amazônica: la cuenca del rio llénez o Guaporé, que escurre tanto sobre el lecho rocoso del Escudo Precámbrico Brasilefto como sobre las Hanuras del Beni. Estas influencias hacen que la cuenca del iténez tenga una elevada heterogeneidad de habitats, una fauna acuálica peculiar y un alto valor de conservation. Este patrimo­nio binacional posée un potencial importante para la conservación de la diversidad regional y cl dcsar rollo sostcniblc participativo de las comunidades locales. El libro contiene un resumen del conotimìento de la cuenca y sus recursos, generado en los últimos 10 anos por un equipo de investigadores bolivianos, brasilefios y de otras nacionalidades. Se presenta una descripeión del medio fisico, así como resultados relevantes sobre la biodiversidad acuática, con énfasis en algas, peces, reptiles y mamíferos. El aporte más notable del libro, adernas de la descripeión ecológica del ecosistema, son las lecciones aprendidas que surgieron de experiências locales sobre la élaboration participativa de herramientas para la gestion de los recursos hidrobiológicos.A Bolívia e o Brasil compartilham uma das bacias hidrográficas mais atrativas e preservadas da região amazônica: a bacia do Rio Iténez ou Guaporé. A combinação das influências do escudo pré-cambriano brasileiro e da planícies do Beni é uma das razões pela qual existem na região elevada heterogeneidade de habitats, fauna aquática peculiar e alto grau valor dc conservação. Eslc patrimônio binacional possui potencial significativo para a conservação da diversidade regional e desenvolvimento sustentável participativo das comunidades locais. O livro contém um resumo do conhecimento da bacia e seus recursos, gerado nos últimos dez anos por uma equipe de pesquisadores bolivianos, brasileiros e de outras nacionalidades. Apresentamos uma descrição do meio físico, bem como resultados relevantes da biodiversidade aquática, com ênfase em algas, peixes, répteis e mamíferos. A contribuição mais notável do livro, além da descrição ecológica do ecossistema, é a descrição das lições aprendidas que surgiram a partir de experiências locais sobre elaboração participativa de ferramentas para a gestão dos recursos aquáticos presentes nesta bacia

Ablating adult neurogenesis does not affect fear conditioning.

<p><b>A</b> Freezing behavior of GCV-treated wild type (n = 7) and GFAP-TK (n = 10) rats during 60 s preceding a tone previously paired with a shock (Pre Tone) and during the first 20 s of tone presentation (Tone). Data represent % time spent freezing during each time period (± sem). <b>B</b> Freezing behavior of GCV-treated wild type (n = 7) and GFAP-TK (n = 10) rats in a context previously associated with shock presentation. Data represent % time freezing during 4 minutes (60 s time bins; ± sem). *p<0.05 tone significantly different from pre-tone. Wild type data are represented by an open circle connected by an interrupted line, GFAP-TK data are represented by filled squares and a solid line.</p

Ablating adult neurogenesis does not affect spatial working memory in the radial maze.

<p><b>A</b> Arm configuration for radial maze task. <b>B</b> Mean number (± sem) of correct arm entries made during a maximum of 6 entries per trial, by GCV-treated wild type (n = 13) and GFAP-TK (n = 13) rats. <b>C</b> Number of arm entries made before all 6 arms had been visited in a trial, by GCV-treated wild type (n = 13) and GFAP-TK (n = 11) rats. The mean score (± sem) is shown for four sessions (4 trials per session). <b>D</b> Rats made 3 initial arm choices, followed by a 1, 20 or 60 minute delay, followed by 3 final arm choices. Data show the number of errors made during the final 3 arm choices, by GCV-treated WT (n = 13) and GFAP-TK (n = 11) rats. Each data point represents the mean score (± sem) for 3 trials for each rat. <b>E</b> Number of errors made per trial into the single arm, pair of arms and arm trio, by GCV-treated wild type (n = 13) and GFAP-TK (n = 11) rats. Data are adjusted according to the number of arms in each group (e.g. total number of arm entries into the trio was divided by 3). Each data point represents the mean score (± sem) per trial. <b>F</b> Arm configuration for the binary choice delayed non-matching to place radial maze task. <b>G</b> The percentage of trials (± sem) in which the novel arm was correctly chosen, by GCV-treated wild type (n = 11) and GFAP-TK (n = 9) rats in the delayed non-matching to place task. Wild type data are represented by an open circle connected by an interrupted line, GFAP-TK data are represented by filled squares and a solid line. The interrupted horizontal line represents chance levels of performance.</p

Ganciclovir administration ablates neurogenesis in the dentate gyrus of the GFAP-TK rat.

<p><b>A</b>, Schematic of the <i>Tk</i>-pA-FRTneo^rFRT genetic construct and position of insertion to replace the start codon of the rat <i>Gfap</i> gene within a Bacterial Artificial Chromosome (BAC). <b>B</b>, Number of doublecortin (DCX) positive (+) cells in the dentate gyrus of untreated 7-week old wild type (n = 5) and GFAP-TK (n = 5) rats. Data expressed as mean DCX+ cell counts (± s.e.m), generated from four 40 µm coronal sections taken from a ‘1 in 8’ series, starting at −2.5 mm from Bregma, along the dorsal/ventral extent of the hippocampus <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Paxinos1" target="_blank">[73]</a>. <b>C</b>, Number of DCX+ cells in the dentate gyrus of GFAP-TK rats dosed for 28 days with vehicle (saline, n = 2), or Ganciclovir (GCV) at 2 mg/kg/day (n = 2), 4 mg/kg/day (n = 2), 8 mg/kg/day (n = 2), or 10 mg/kg/day (n = 2). Data expressed as mean DCX+ cells as a percentage of vehicle control, generated from eight 40 µm coronal sections taken from a ‘1 in 12’ series from −2.5 mm from Bregma. <b>D</b>, Example of a DCX-stained dentate gyrus section from a wild type and GFAP-TK rat chronically treated with GCV (28 days, 10 mg/kg/day). Scale bar represents 200 µm.</p

Meta-analysis of adult neurogenesis literature.

<p>Forest plot showing the results of studies examining the relationship between adult neurogenesis and three tests of learning and memory (contextual and cued fear conditioning, the probe trial of the Morris water maze (MWM)), and two tests of anxiety (total activity in the open-field arena (OF) and time spent in the open-arms of an elevated plus maze (EPM)). The figure shows the standardized mean difference for each study, the associated 95% confidence intervals and the pooled estimate, all based on a random-effects (RE) model and Hedge's estimator. Multiple entries for one publication arise when authors report analyses using different ablation methods (irradiation vs genetic for example) or variation in experimental protocols. On the right of each panel is the reference number for each publication, followed by a number that identifies the data set we extracted from the literature. This number refers to an entry in the supplemental table containing details of each data set and relevant covariates <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Revest1" target="_blank">[8]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Shors1" target="_blank">[11]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Santarelli1" target="_blank">[12]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Saxe1" target="_blank">[13]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Snyder2" target="_blank">[17]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Dupret1" target="_blank">[18]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Deng1" target="_blank">[19]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Zhang1" target="_blank">[20]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Jessberger1" target="_blank">[21]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-HernandezRabaza1" target="_blank">[22]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Meshi1" target="_blank">[23]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Winocur1" target="_blank">[24]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Ko1" target="_blank">[25]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Wojtowicz1" target="_blank">[26]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Kitamura1" target="_blank">[32]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Tronel1" target="_blank">[36]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Scobie1" target="_blank">[37]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Jaholkowski1" target="_blank">[49]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Garthe1" target="_blank">[50]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Rola1" target="_blank">[51]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Zhao1" target="_blank">[52]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Shimazu1" target="_blank">[53]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Bergami1" target="_blank">[54]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Ageta1" target="_blank">[55]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Pollak1" target="_blank">[56]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-WarnerSchmidt1" target="_blank">[57]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Denny1" target="_blank">[58]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Drew1" target="_blank">[59]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-David1" target="_blank">[60]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Goodman1" target="_blank">[61]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Fuss2" target="_blank">[62]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Clark1" target="_blank">[74]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Groves1" target="_blank">[75]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Imayoshi2" target="_blank">[76]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003718#pgen.1003718-Raber1" target="_blank">[77]</a>.</p

Thymidine kinase is expressed in the SVZ and DG, and co-localizes with GFAP positive cells.

<p>Thymidine kinase (TK) positive cells are detected in the subventricular zone (SVZ) and dentate gyrus (DG) of GFAP-TK rats, but not in wild type controls. Panels A and B show controls and panels D and E show GFAP-TK rats, Panel C shows double labeling of TK (red) and glial fibrillary acidic protein (GFAP, green) in the DG of a GFAP-TK rat. Higher magnification of a segment of panel C shows that TK positive (red) cells co-localize with GFAP staining. Scale bar represents 200 µm for panels A, B, D & E.</p

Safety and Treatment Outcomes of Nivolumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Retrospective Multicenter Cohort Study.

Nivolumab is an anti-PD-1 monoclonal antibody currently used as immunotherapy for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) with evidence of disease progression after platinum-based chemotherapy. This study evaluates real-world safety and treatment outcomes of non-trial nivolumab use. A retrospective multicenter cohort study of patients with recurrent/metastatic HNSCC treated with nivolumab between January 2017 and March 2020 was performed. Overall, 123 patients were included. The median age was 64 years, the majority of patients were male (80.5%) and had a smoking history (69.9%). Primary outcomes included overall response rate (ORR) of 19.3%, median progression-free survival (PFS) of 3.9 months, 1-year PFS rate of 16.8%, a median overall survival (OS) of 6.5 months and 1-year OS rate of 28.6%. These results are comparable to the CHECKMATE-141 study. Of 27 patients who had PD-L1 status tested, positive PD-L1 status did not significantly affect PFS ( = 0.86) or OS ( = 0.84). Nivolumab was well tolerated with only 15.1% experiencing immune-related toxicities (IRT) and only 6.7% of patients stopping due to toxicity. The occurrence of IRT appeared to significantly affect PFS ( = 0.01) but not OS ( = 0.07). Nivolumab in recurrent/metastatic HNSCC is well tolerated and may be more efficacious in patients who develop IRT