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Oncohematological patients show a low immune response against SARS-CoV-2, both to natural infection and after vaccination. Most studies are focused on the analysis of the humoral response; therefore, the information available about the cellular immune response is limited. In this study, we analyzed the humoral and cellular immune responses in nine individuals who received chemotherapy for their oncohematological diseases, as well as consolidation with autologous stem cell transplantation (ASCT), after being naturally infected with SARS-CoV-2. All individuals had asymptomatic or mild COVID-19 and were not vaccinated against SARS-CoV-2. These results were compared with matched healthy individuals who also had mild COVID-19. The humoral response against SARS-CoV-2 was not detected in 6 of 9 oncohematological individuals prior to ASCT. The levels of antibodies and their neutralization capacity decreased after ASCT. Conversely, an enhanced cytotoxic activity against SARS-CoV-2-infected cells was observed after chemotherapy plus ASCT, mostly based on high levels of NK, NKT, and CD8+TCRγδ+ cell populations that were able to produce IFNγ and TNFα. These results highlight the importance of performing analyses not only to evaluate the levels of IgGs against SARS-CoV-2, but also to determine the quality of the cellular immune response developed during the immune reconstitution after ASCT. This work was supported by the Coordinated Research Activities at the Centro Nacional de Microbiología (CNM, Instituto de Salud Carlos III) (COV20_00679) to promote an integrated response against SARS-CoV-2 in Spain (Spanish Ministry of Science and Innovation) that is coordinated by Dr Inmaculada Casas (WHO National Influenza Center of the CNM), the Spanish Ministry of Science and Innovation (PID2019-110275RB-I00), and AES 2021 grant from Instituto de Salud Carlos III (PI21/00877). The work of Sara Rodríguez-Mora is financed by NIH grant R01AI143567. The work of Montserrat Torres is supported by Instituto de Salud Carlos III (COV20_00679). The work of Lorena Vigón is supported by a pre-doctoral grant from Instituto de Salud Carlos III (FIS PI16CIII/00034-ISCIII-FEDER). Sí

El 'Atlas of Cancer Mortality in Portugal and Spain 2003–2012', muestra la distribución espacial de la mortalidad municipal por distintos tipos cáncer para el periodo 2003-2012. Ha sido desarrollado por la Unidad de Epidemiología del Cáncer y Ambiental del Centro Nacional de Epidemiología del ISCIII, que forma parte del CIBERESP, y por el Departamento de Epidemiología del Instituto Nacional De Saúde Doutor Ricardo Jorge de Portugal. El estudio de la distribución geográfica del riesgo de fallecer por cáncer es una de las herramientas que se usan en epidemiología para generar hipótesis sobre la posible implicación de factores ambientales en el origen de los tumores. This project is partially supported by research grant from the Spanish Health Research Fund (FIS) of the National Institute of Health Carlos III (ISCIII), Spain (Project PI17CIII/00040: “Spatial distribution of municipal cancer mortality in Spain (SICAMSA)” (“Distribución Espacial de la Mortalidad municipal por CÁncer en ESpaña (DEMOCAES)”). Introduction. Methods. Results: Oesophagus (ICD-10 C15) Stomach (ICD-10 C16) Colorectal (ICD-10 C18–C21) Pancreas (ICD-10 C25) Larynx (ICD-10 C32) Lung (ICD-10 C33–C34) Female Breast (ICD-10 C50) Prostate (ICD-10 C61) Bladder (ICD-10 C67) Leukaemia (ICD-10 C91–C95) References. Annexes: Annex I and Annex II No

The High Road to Economic Prosperity offers a macro analysis of the California Workforce Development Board’s (CWDB) High Road Training Partnership (HRTP) initiative. The report defines the HRTP model and evaluates the successes and challenges of adopting the high road approach, including recommendations on how to strengthen the HRTP framework and model as the initiative expands. The report finds that HRTPs offer a more inclusive definition of industry leadership and build collective power. HRTPs bring together employers, labor, and community actors to look at their industries from a bird’s eye view and use their collective expertise to find mutually beneficial industry solutions. This values-based approach prioritizes underlying systemic issues like racial inequality. HRTPs move beyond diversity initiatives by identifying racial inequalities and creating tailored workforce development interventions, including sustainable long term policies that can be widely adopted to address the needs of disadvantaged communities. The initiative offers an innovative model for public programs that are responsive to change. HRTPs are continuously experimenting, learning, and refining their interventions, which allows them to respond to external shifts, such as economic downturns and climate change, in real time and work toward solutions that meet the needs of firms, workers, and communities. The HRTP approach advances a shift in measuring workforce development success. Traditional workforce development metrics often measure success by the number — not quality — of job placements. HRTPs also associate success with promoting worker voice and power, systems change, culture shifts, and other qualitatively measured indicators of high road success.

There are few well-established risk factors for childhood leukemias. While the frequency of childhood leukemias might be partially attributable to some diseases (accounting for a small fraction of cases) or ionizing radiation, the role of heavy metals has not been assessed. The objective of our study was to assess the potential association between levels of cadmium (Cd) and lead (PB) in soil and childhood leukemias incidence. We conducted a population-based case-control study of childhood leukaemia in Spain, covering 2897 incident cases gathered from the Spanish Registry of Childhood Tumours and including 14 Spanish Regions with a total population of 5,307,433 children (period 1996-2015). Cd and Pb bioavailable levels at every children's home address were estimated using data from the Geochemical Atlas of Spain. We used logistic regression to estimate odds ratios (ORs) and their 95% confidence intervals (95%CIs); we included as covariates: sex, rurality, employment rate and socioeconomic status. Metal levels were analysed according to two definitions: as continuous variable assuming linearity and as categorical variables to explore a potentially nonlinear association (quantiles). Increases in both Cd and Pb topsoil levels were associated with increased probability of childhood leukemias incidence. The results for the models with the continuous variables showed that a unit increase on the topsoil level was associated with an OR of 1.11 for Cd (95%CI 1.00-1.24) and an OR of 1.10 for Pb (95%CI 0.99-1.21). Our study may point towards a possible link between residential Cd and Pb topsoil levels and the probability of childhood leukemias incidence. Residing in a location with the highest concentrations of these heavy metals compared to those locations with the lowest could increase the risk around a 20%, for both Cd and Pb.

Table S1. Intermolecular interactions between the V3 tips and CCR5.

Figure S3. Structure and dynamics of free V3 from the MVC-Sens (grey) or MVC-Res (black) isolates. (A) Time series of root mean square deviation (RMSD) values for all atoms of the V3 loops, using as reference the average coordinates computed from the five independent simulations. (B) The phi and psi angular fluctuations were calculated and averaged by residue for every 25 ps segment of the five molecular dynamics trajectories. Standard deviations are reported for phi (top) and psi (bottom) backbone torsion angles. (C) The average RMS fluctuations (RMSF) were calculated for the carbon alpha atoms of the V3 loop residues from the ensemble of structures after superimposition of residues 296 to 330 (complete V3 loop, plain lines) or superimposition of residues 308 to 315 (V3 tip, dotted lines).

Figure S4. Western blot analysis of gp120 and Gag p24 expression on MVC-Sens, MVC-Res, MVC-Sens(V3R) and MVC-Res(V3S) viral particles. Three hundred ng Gag p24 of the different viral isolates were solubilized in lysis buffer (100 mM (NH4)2SO4, 20 mM Tris-HCl (pH 7.5), 10 % glycerol, and 1% Triton X-100) and then loaded onto Biorad CriterionTM XT 4-12% Bis-Tris Gels under reducing conditions. Virus-associated gp120 and p24 were visualized using a sheep anti-HIV-1 gp120 polyclonal antibody (AALTO Bio Reagents LTD.) and a mouse anti-HIV-1 p24 monoclonal antibody (clone 183-H12-5C) (NIH AIDS Reagent Program), respectively, and then with the appropriate HRP-conjugated secondary antibodies (VECTOR). Bands were developed by enhanced chemiluminescence (Thermo Scientific) and were quantified using a LAS-1000 CCD camera (Image Gauge Software, Fuji Film Co., Tokyo, Japan). The figure shows that the viral isolates have gp120/p24 ratios R that are in the same range (R = 1, 1.15, 1.24 and 0.81 for MVC-Sens, MVC-Res, MVC-Sens(V3R) and MVC-Res(V3S), respectively). A representative experiment out of two is shown.

Figure S5. Molecular modeling of the complex between CCR5 and MVC-Sens V3. The graphic shows time series of RMSD values of the complex using as reference the input coordinates. The table indicates which constraints or restraints were imposed on the system during the simulation. bb : backbone atoms, all : all atoms, sc : side chains.

Supplemental text (related to Figure 7 and additional file 4).

Figure S6. Molecular modeling of the complex between MVC-bound CCR5 and MVC-Res V3. The graphic shows time series of RMSD values of the complex using as reference the input coordinates. The table indicates which constraints or restraints were imposed on the system during the simulation. bb : backbone atoms, all : all atoms, sc : side chains.