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Background and Aims: Queer femme Latinx men, trans, and gender variant individuals live in a complex fabric of intersecting structures of oppression including, but not limited to, racism, sexism, homophobia, transphobia, poverty, citizenship status, internalized homophobia, internalized racism and linguistic hierarchy. Consequently, queer femme Latinx individuals navigate complex identities that are often not understood or adequately researched. While empirical research highlights how minoritized identities may negatively impact psychosocial functioning, mental health, and well-being, we still do not have a clear understanding of how individual queer femme Latinx navigate their identities in relation to these structures of oppression. This project seeks to understand how queer femme Latinx individuals subjectively understand their lived experiences.Methods: This phenomenological study is theoretically grounded in intersectionality. Individual semi-structured in-depth interviews with open-ended questions were conducted via Zoom with participants who reside in the state of California, were 18 to 30, self-identify as queer femme men, trans, or gender variant and as Latinx. Recruitment was conducted via a purposive sampling method initiated with a recruitment email sent to LGBTQ+ and Latinx resource centers and university-level academic departments across California.Results: 10 interviews were conducted. The analysis revealed four major themes: (1) “there is no particular way of existing; (2) “safety isn’t guaranteed;” (3) “the different personas you create”; and (4) “reminding myself I’m worth it.” Participants shared a common understanding of feeling a sense of limitlessness and freedom in their identities. They understood safety isn’t guaranteed and discussed the need to create different personas as an adaptive behavior, while, being able to remind themselves they are worth it and practice selflove. Finally, participants were able to use community resources, knowledge building, and peer/family support to strengthen their own identity understanding.Conclusion and Implications: This study provides an inclusive and intersectional understanding of the queer femme Latinx individual experience. Implications for social work practice include developing culturally-based and contextually situated interventions that support well-being and identity management. Particularly, this study shows queer femme Latinx individuals have a strong awareness of their own worth and are able to practice selflove. Social work practitioners could assist queer femme Latinx individuals understand the role of their adaptive behaviors while promoting selflove. Additionally, enhancing relationships with service-providing agencies to building a cohesive community of support to help normalize queer femme Latinx individuals’ experiences could support queer femme Latinx individual’s well-being and identity management.

[ES] Los efectos en salud de la exposición a factores medio ambientales son un problema difícil de estudiar, pero la mayor disponibilidad de datos, el desarrollo de métodos estadísticos de análisis espacial y de sistemas de información geográfica (SIG) han permitido avanzar en esta dirección. En el caso de los datos, la disponibilidad de registros públicos permite identificar focos emisores. El cáncer infantil es la primera causa de mortalidad infantil por enfermedad en España, donde cada año se diagnostican más de 1.100 casos en niños/as de entre 0 y 14 años. Las causas de estas patologías son muy poco conocidas y el papel de la exposición a factores de riesgo medioambientales es una de las hipótesis más estudiadas en la actualidad. El objetivo de este trabajo es la presentación del protocolo de un estudio de investigación diseñado para identificar factores de riesgo medioambientales en cáncer infantil usando herramientas de análisis espacial y de SIG, e información ambiental de bases de datos de acceso público. Los factores medioambientales estudiados son: contaminación industrial, contaminación urbana, contaminación por tráfico, cercanía a cultivos susceptibles de ser tratados con pesticidas, índice socio-económico y cercanía a espacios verdes urbanos.[EN] The health effects associated to exposure to environmental factors are difficult to study, nonetheless the greater availability of data, the development of statistical methods of spatial analysis and geographic information systems (GIS) have allowed to progress in this direction. As regards of data, the availability of public records and data bases make it possible to identify emission sources.Childhood cancer is the leading cause of infant mortality due to disease in Spain, where more than 1,100 cases are diagnosed each year in children between 0 and 14 years of age. The causes of these pathologies are mostly unknown and the role of exposure to environmental risk factors is one of the most studied hypotheses at present. The objective of this work is the presentation of a protocol for a research study designed to identify environmental risk factors in childhood cancer using spatial analysis and GIS tools, and environmental information from public access databases. The environmental factors studied are: industrial pollution, urban pollution, traffic pollution, proximity to crops that can be treated with pesticides, socio-economic index and proximity to urban green spaces.

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

HIV-1 infects CD4 T lymphocytes (CD4TL) through binding the chemokine receptors CCR5 or CXCR4. CXCR4-using viruses are considered more pathogenic, linked to accelerated depletion of CD4TL and progression to AIDS. However, counterexamples to this paradigm are common, suggesting heterogeneity in the virulence of CXCR4-using viruses. Here, we investigated the role of the CXCR4 chemokine CXCL12 as a driving force behind virus virulence. In vitro, CXCL12 prevents HIV-1 from binding CXCR4 and entering CD4TL, but its role in HIV-1 transmission and propagation remains speculative. Through analysis of thirty envelope glycoproteins (Envs) from patients at different stages of infection, mostly treatment-naïve, we first interrogated whether sensitivity of viruses to inhibition by CXCL12 varies over time in infection. Results show that Envs resistant (RES) to CXCL12 are frequent in patients experiencing low CD4TL levels, most often late in infection, only rarely at the time of primary infection. Sensitivity assays to soluble CD4 or broadly neutralizing antibodies further showed that RES Envs adopt a more closed conformation with distinct antigenicity, compared to CXCL12-sensitive (SENS) Envs. At the level of the host cell, our results suggest that resistance is not due to improved fusion or binding to CD4, but owes to viruses using particular CXCR4 molecules weakly accessible to CXCL12. We finally asked whether the low CD4TL levels in patients are related to increased pathogenicity of RES viruses. Resistance actually provides viruses with an enhanced capacity to enter naive CD4TL when surrounded by CXCL12, which mirrors their situation in lymphoid organs, and to deplete bystander activated effector memory cells. Therefore, RES viruses seem more likely to deregulate CD4TL homeostasis. This work improves our understanding of the pathophysiology and the transmission of HIV-1 and suggests that RES viruses’ receptors could represent new therapeutic targets to help prevent CD4TL depletion in HIV+ patients on cART., Author summary HIV-1 infects immune cells by binding CD4 and a coreceptor, CCR5 or CXCR4. CXCR4-using viruses are thought to accelerate depletion of CD4 T lymphocytes (CD4TL) and AIDS development. This paradigm, while often true, is however not seen in all patients, suggesting heterogeneity in the virulence of viruses. Here, we show that CXCR4-using viruses can be discriminated on the basis of their resistance to the anti-HIV-1 effect of the CXCR4 chemokine CXCL12. Resistant (RES) viruses are found in patients with low CD4TL levels. They are featured by unique properties of their envelope glycoprotein and the way they use CXCR4. Our data also indicate that RES viruses could contribute to CD4TL depletion. They more effectively kill bystander activated effector memory CD4TL, a subset of CD4TL enriched in HIV+ patients, and enter CD4TL subsets surrounded by CXCL12. Resistance could therefore enhance the ability of viruses to target naive cells and their precursors in lymphoid organs where CXCL12 is present, further hindering CD4TL renewal. Beyond presenting a novel view of CXCR4-using HIV-1 pathogenesis, this work also opens new therapeutic perspectives and increases our knowledge of the still debated role of CXCL12 in HIV-1 transmission.

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.

Background: Passive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19 for which evidence from controlled clinical trials is lacking. Methods: We conducted a multi-center, randomized clinical trial in patients hospitalized for COVID-19. All patients received standard of care treatment, including off-label use of marketed medicines, and were randomized 1:1 to receive one dose (250-300 mL) of CP from donors with IgG anti-SARS-CoV-2. The primary endpoint was the proportion of patients in categories 5, 6 or 7 of the COVID-19 ordinal scale at day 15. Results: The trial was stopped after first interim analysis due to the fall in recruitment related to pandemic control. With 81 patients randomized, there were no patients progressing to mechanical ventilation or death among the 38 patients assigned to receive plasma (0%) versus 6 out of 43 patients (14%) progressing in control arm. Mortality rates were 0% vs 9.3% at days 15 and 29 for the active and control groups, respectively. No significant differences were found in secondary endpoints. At inclusion, patients had a median time of 8 days (IQR, 6-9) of symptoms and 49,4% of them were positive for anti-SARS-CoV-2 IgG antibodies. Conclusions: Convalescent plasma could be superior to standard of care in avoiding progression to mechanical ventilation or death in hospitalized patients with COVID-19. The strong dependence of results on a limited number of events in the control group prevents drawing firm conclusions about CP efficacy from this trial. (Funded by Instituto de Salud Carlos III; NCT04345523). This research is funded by the Government of Spain, Ministry of Science and Innovation, Instituto de Salud Carlos III, grant number COV20/00072 (Royal Decree-Law 8/2020, of 17 March, on urgent extraordinary measures to deal with the economic and social impact of COVID-19), co-financed by the European Regional Development Fund (FEDER) ‘‘A way to make Europe’’ and supported by SCReN (Spanish Clinical Research Network), ISCIII, project PT17/0017/0009. Clinical trial insurance coverage was kindly donated by MARCH RS Correduría de Seguros y Reaseguros. Mikel Mancheño-Losa holds a "Río Hortega" research contract (expte. CM19/00226 No

CCR5 plays immune functions and is the coreceptor for R5 HIV-1 strains. It exists in diverse conformations and oligomerization states. We interrogated the significance of the CCR5 structural diversity on HIV-1 infection. We show that envelope glycoproteins (gp120s) from different HIV-1 strains exhibit divergent binding levels to CCR5 on cell lines and primary cells, but not to CD4 or the CD4i monoclonal antibody E51. This owed to differential binding of the gp120s to different CCR5 populations, which exist in varying quantities at the cell surface and are differentially expressed between different cell types. Some, but not all, of these populations are antigenically distinct conformations of the coreceptor. The different binding levels of gp120s also correspond to differences in their capacity to bind CCR5 dimers/oligomers. Mutating the CCR5 dimerization interface changed conformation of the CCR5 homodimers and modulated differentially the binding of distinct gp120s. Env-pseudotyped viruses also use particular CCR5 conformations for entry, which may differ between different viruses and represent a subset of those binding gp120s. In particular, even if gp120s can bind both CCR5 monomers and oligomers, impairment of CCR5 oligomerization improved viral entry, suggesting that HIV-1 prefers monomers for entry. From a functional standpoint, we illustrate that the nature of the CCR5 molecules to which gp120/HIV-1 binds shapes sensitivity to inhibition by CCR5 ligands and cellular tropism. Differences exist in the CCR5 populations between T-cells and macrophages, and this is associated with differential capacity to bind gp120s and to support viral entry. In macrophages, CCR5 structural plasticity is critical for entry of blood-derived R5 isolates, which, in contrast to prototypical M-tropic strains from brain tissues, cannot benefit from enhanced affinity for CD4. Collectively, our results support a role for CCR5 heterogeneity in diversifying the phenotypic properties of HIV-1 isolates and provide new clues for development of CCR5-targeting drugs., Author summary CCR5 regulates host immune responses against pathogens. It also serves as an anchor for R5-tropic strains of HIV-1 to infect immune cells, hence contributing to development of AIDS. CCR5 exists in different forms (e.g. conformations, oligomerization states), but the mechanisms that govern this diversity and its consequences on the physio-/pathophysio-logical functions of the receptor remain unclear. Because genetically diverse viral isolates populate HIV-1 infected individuals, we asked whether divergent viruses differ in the nature of the CCR5 molecules they use, and if so, whether this accounts for differences in their biological properties. Here we answered in the positive to both questions. We also identified CCR5 oligomerization as a key process regulating the receptor conformational diversity, the extent to which HIV-1 envelope glycoproteins bind to target cells and viral entry efficacy. From a functional standpoint, the nature/quantity of the receptor populations that are used by HIV-1 isolates regulates the type of cells they can infect and their ability to escape inhibition by CCR5 ligands. This study thus represents a step forward toward understanding of the mechanisms that regulate CCR5 diversity and its implications on the virus biological properties while opening new avenues for the development of drugs targeting CCR5.

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.