Candidate Genes for Expansion and Transformation of Hematopoietic Stem Cells by NUP98-HOX Fusion Genes

BACKGROUND: Hox genes are implicated in hematopoietic stem cell (HSC) regulation as well as in leukemia development through translocation with the nucleoporin gene NUP98. Interestingly, an engineered NUP98-HOXA10 (NA10) fusion can induce a several hundred-fold expansion of HSCs in vitro and NA10 and the AML-associated fusion gene NUP98-HOXD13 (ND13) have a virtually indistinguishable ability to transform myeloid progenitor cells in vitro and to induce leukemia in collaboration with MEIS1 in vivo. METHODOLOGY/PRINCIPAL FINDINGS: These findings provided a potentially powerful approach to identify key pathways mediating Hox-induced expansion and transformation of HSCs by identifying gene expression changes commonly induced by ND13 and NA10 but not by a NUP98-Hox fusion with a non-DNA binding homedomain mutation (N51S). The gene expression repertoire of purified murine bone marrow Sca-1+Lin- cells transduced with retroviral vectors encoding for these genes was established using the Affymetrix GeneChip MOE430A. Approximately seventy genes were differentially expressed in ND13 and NA10 cells that were significantly changed by both compared to the ND13(N51S) mutant. Intriguingly, several of these potential Hox target genes have been implicated in HSC expansion and self-renewal, including the tyrosine kinase receptor Flt3, the prion protein, Prnp, hepatic leukemia factor, Hlf and Jagged-2, Jag2. Consistent with these results, FLT3, HLF and JAG2 expression correlated with HOX A cluster gene expression in human leukemia samples. CONCLUSIONS: In conclusion this study has identified several novel Hox downstream target genes and provides important new leads to key regulators of the expansion and transformation of hematopoietic stem cells by Hox

MAMMALS IN PORTUGAL : A data set of terrestrial, volant, and marine mammal occurrences in P ortugal

Mammals are threatened worldwide, with 26% of all species being includedin the IUCN threatened categories. This overall pattern is primarily associatedwith habitat loss or degradation, and human persecution for terrestrial mam-mals, and pollution, open net fishing, climate change, and prey depletion formarine mammals. Mammals play a key role in maintaining ecosystems func-tionality and resilience, and therefore information on their distribution is cru-cial to delineate and support conservation actions. MAMMALS INPORTUGAL is a publicly available data set compiling unpublishedgeoreferenced occurrence records of 92 terrestrial, volant, and marine mam-mals in mainland Portugal and archipelagos of the Azores and Madeira thatincludes 105,026 data entries between 1873 and 2021 (72% of the data occur-ring in 2000 and 2021). The methods used to collect the data were: live obser-vations/captures (43%), sign surveys (35%), camera trapping (16%),bioacoustics surveys (4%) and radiotracking, and inquiries that represent lessthan 1% of the records. The data set includes 13 types of records: (1) burrowsjsoil moundsjtunnel, (2) capture, (3) colony, (4) dead animaljhairjskullsjjaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8),observation in shelters, (9) photo trappingjvideo, (10) predators dietjpelletsjpine cones/nuts, (11) scatjtrackjditch, (12) telemetry and (13) vocalizationjecholocation. The spatial uncertainty of most records ranges between 0 and100 m (76%). Rodentia (n=31,573) has the highest number of records followedby Chiroptera (n=18,857), Carnivora (n=18,594), Lagomorpha (n=17,496),Cetartiodactyla (n=11,568) and Eulipotyphla (n=7008). The data setincludes records of species classified by the IUCN as threatened(e.g.,Oryctolagus cuniculus[n=12,159],Monachus monachus[n=1,512],andLynx pardinus[n=197]). We believe that this data set may stimulate thepublication of other European countries data sets that would certainly contrib-ute to ecology and conservation-related research, and therefore assisting onthe development of more accurate and tailored conservation managementstrategies for each species. There are no copyright restrictions; please cite thisdata paper when the data are used in publications.info:eu-repo/semantics/publishedVersio

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Mammals in Portugal: a data set of terrestrial, volant, and marine mammal occurrences in Portugal

Mammals are threatened worldwide, with ~26% of all species being included in the IUCN threatened categories. This overall pattern is primarily associated with habitat loss or degradation, and human persecution for terrestrial mammals, and pollution, open net fishing, climate change, and prey depletion for marine mammals. Mammals play a key role in maintaining ecosystems functionality and resilience, and therefore information on their distribution is crucial to delineate and support conservation actions. MAMMALS IN PORTUGAL is a publicly available data set compiling unpublished georeferenced occurrence records of 92 terrestrial, volant, and marine mammals in mainland Portugal and archipelagos of the Azores and Madeira that includes 105,026 data entries between 1873 and 2021 (72% of the data occurring in 2000 and 2021). The methods used to collect the data were: live observations/captures (43%), sign surveys (35%), camera trapping (16%), bioacoustics surveys (4%) and radiotracking, and inquiries that represent less than 1% of the records. The data set includes 13 types of records: (1) burrows | soil mounds | tunnel, (2) capture, (3) colony, (4) dead animal | hair | skulls | jaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8), observation in shelters, (9) photo trapping | video, (10) predators diet | pellets | pine cones/nuts, (11) scat | track | ditch, (12) telemetry and (13) vocalization | echolocation. The spatial uncertainty of most records ranges between 0 and 100 m (76%). Rodentia (n =31,573) has the highest number of records followed by Chiroptera (n = 18,857), Carnivora (n = 18,594), Lagomorpha (n = 17,496), Cetartiodactyla (n = 11,568) and Eulipotyphla (n = 7008). The data set includes records of species classified by the IUCN as threatened (e.g., Oryctolagus cuniculus [n = 12,159], Monachus monachus [n = 1,512], and Lynx pardinus [n = 197]). We believe that this data set may stimulate the publication of other European countries data sets that would certainly contribute to ecology and conservation-related research, and therefore assisting on the development of more accurate and tailored conservation management strategies for each species. There are no copyright restrictions; please cite this data paper when the data are used in publications

Bayesian networks for feature selection and patient pre-screening for depressive symptomatology:a prototype

Background: Identifying individuals with depressive symptomatology (DS) promptly and effectively is of paramount importance for providing timely treatment. Machine learning models have shown promise in this area, yet studies often fall short in demonstrating the practical benefits of utilizing these models and fail to provide tangible real-world applications. Objective: The objectives of this study were: 1) to establish a novel methodology for identifying individuals likely to exhibit DS; 2) to identify the most influential features in a more explainable way via probabilistic measures; 3) to propose tools that can be used in real-world applications. Methods: Three datasets were utilized in this study: the PROACTIVE dataset, along with the Brazilian National Health Survey (PNS) datasets from 2013 and 2019, comprising socio-demographic and health-related features. A Bayesian Network was used for feature selection. Selected features were then employed to train machine learning models to predict DS, operationalized as a score of 10 or higher on the 9-item Patient Health Questionnaire (PHQ-9). Furthermore, an analysis was conducted to evaluate the influence of different sensitivities on the reduction in number of screening interviews achieved through the utilization of the model compared with a random approach.Results: The methodology allows the end-user to make an informed trade-off between sensitivity, specificity and a reduction in the number of interviews. At the thresholds of 0.444, 0.412, and 0.472, determined by maximizing Youden's index, the models achieved sensitivities of 0.717, 0.741, and 0.718, and specificities of 0.644, 0.737, and 0.766 for PROACTIVE, PNS 2013, and PNS 2019, respectively. The area under the receiver operating characteristic curve (AUC) was 0.736, 0.801, and 0.809 for these three datasets respectively. For the PROACTIVE dataset, the most influential features identified were postural balance, shortness of breath, and how old people feel they are. In the PNS 2013 dataset, the features were: the ability to do usual activities, chest pain, sleep problems, and chronic back problems. The PNS 2019 dataset shared three of the most influential features with the PNS 2013 dataset. However, the difference was the replacement of chronic back problems with verbal abuse. It is important to note that the features contained in the PNS datasets differ from those found in the PROACTIVE dataset. An empirical analysis demonstrated that utilizing the proposed model led to a potential reduction in screening interviews of up to 52% while maintaining a sensitivity of 0.80.Conclusion: This study developed a novel methodology for identifying individuals with DS by demonstrating the practical benefits of employing Bayesian networks to identify the most significant features to be used in a machine learning model for the prediction of DS in three general health and socio-economic datasets. Moreover, simulations indicated that the utilization of this approach has the potential to substantially reduce the screening interviews for identifying people with DS while maintaining a high sensitivity. These findings pave the way for improved early identification and intervention strategies for individuals experiencing depressive symptomatology

“Does it matter how old I feel?” The role of subjective age in a psychosocial intervention for improving depressive symptomatology among older adults in Brazil (PROACTIVE)

Objectives:Depression is a prevalent mental health condition that also often affects older adults. The PROACTIVE psychosocial intervention was developed to reduce depressive symptomatology among older adults within primary care settings in Brazil. An important psychological marker that affects individuals’ aging experience relates to how old people feel. Known as subjective age, this marker has been shown to be a risk factor for experiencing greater depressive symptoms if individuals report feeling older than their (chronological) age. In this study, we perform secondary analyses of the PROACTIVE cluster-randomized controlled trial to examine the role of subjective age.Method:The sample included 715 Brazilian older adults (74% female, Mage 68.6, SD = 6.9, age range: 60–94 years) randomized to intervention (n = 360, 74% female, Mage 68.4, SD = 6.6, age range: 60–89 years) or control (n = 355, 74% female, Mage 68.9, SD = 7.2, age range: 60–94 years) arms. Here our primary outcome was depressive symptoms at the 8-month follow-up assessed with the 9-item Patient Health Questionnaire (PHQ-9) as a continuous variable. Our previous analyses demonstrated improved recovery from depression at follow-up in the intervention compared with the control arm.Results:Relevant main effects and interactions in regression models for PHQ-9 presented here found that those reporting older subjective age had worse depressive symptoms at follow-up but that they benefitted more from the intervention when initial levels of depression were high. For participants who reported younger subjective ages the intervention showed positive effects that were independent of initial levels of depression.Conclusion:Our findings emphasize the importance of investigating possible underlying mechanisms that can help clarify the impact of mental health interventions

A PRÁTICA CLÍNICA DO FARMACÊUTICO NO NÚCLEO DE APOIO À SAÚDE A FAMÍLIA

Resumo Este estudo teve como objetivo compreender os elementos essenciais do processo de sistematização da prática clínica de uma farmacêutica da atenção primária à saúde com base no referencial teórico-metodológico da atenção farmacêutica, que subsidia o serviço clínico de gerenciamento da terapia medicamentosa. Tratou-se de pesquisa qualitativa autoetnográfica, construída de forma colaborativa entre os autores, de outubro de 2014 a outubro de 2015, nos Centros de Saúde da Prefeitura Municipal de Belo Horizonte, onde uma das autoras trabalha. Os dados foram produzidos por meio de observação participante, diários de campo, reflexões e entrevistas semiestruturadas com farmacêuticos que desenvolviam prática clínica na atenção primária à saúde. Os resultados evidenciaram que os principais elementos para sistematização da prática clínica passam pela ‘construção de uma nova identidade profissional na equipe multiprofissional’ e pela ‘incorporação de novas atividades na rotina de trabalho’ que, combinadas, resultam em uma ‘proposta de integração de um serviço de gerenciamento da terapia medicamentosa nos fluxos das unidades de saúde’. Dessa forma, para que o farmacêutico possa legitimar o seu papel no cuidado do paciente, é preciso mudar, transformar, reorganizar e reconstruir a sua prática

Estimation of Secondary Household Attack Rates for Emergent Spike L452R Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants Detected by Genomic Surveillance at a Community-Based Testing Site in San Francisco.

BackgroundSequencing of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral genome from patient samples is an important epidemiological tool for monitoring and responding to the pandemic, including the emergence of new mutations in specific communities.MethodsSARS-CoV-2 genomic sequences were generated from positive samples collected, along with epidemiological metadata, at a walk-up, rapid testing site in the Mission District of San Francisco, California during 22 November to 1 December, 2020, and 10-29 January 2021. Secondary household attack rates and mean sample viral load were estimated and compared across observed variants.ResultsA total of 12 124 tests were performed yielding 1099 positives. From these, 928 high-quality genomes were generated. Certain viral lineages bearing spike mutations, defined in part by L452R, S13I, and W152C, comprised 54.4% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to the "California" or "West Coast" variants (B.1.427 and B.1.429) were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, risk ratio [RR] = 1.28; 95% confidence interval [CI]: 1.00-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020. Viral loads were similar among persons infected with West Coast versus non-West Coast strains, as was the proportion of individuals with symptoms (60.9% vs 64.3%).ConclusionsThe increase in prevalence, relative household attack rates, and reproductive number are consistent with a modest transmissibility increase of the West Coast variants. Summary: We observed a growing prevalence and modestly elevated attack rate for "West Coast" severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in a community testing setting in San Francisco during January 2021, suggesting its modestly higher transmissibility