ASSESSING THE NUTRITIONAL CONDITION OF PREGNANT WOMEN IN THE CITY OF SANTO ANDRÉ THROUGH ROSSO’S GRAPH

A falta de vigilancia da condição nutricional da gestante durante o exame pré-natal tem dificultado intervenções adequadas no sentido de prevenir a ocorrência do baixo peso ao nascimento (BP). Foram avaliadas, prospectivamente, 95 gestantes de baixo nível sócio-econômico do Município de Santo André, para realização de exame pré-natal, utilizando-se a curva de Rosso para sua classificação nutricional. O percentual de mãe com baixo peso foi de 36,8%. As mães com mais de duas gestações apresentaram maior ocorrência de sobrepeso ou obesidade e as com menos de duas gestações, percentual significativamente maior de baixo peso. A anemia também se associou de maneira significativa às gestantes de baixo peso. O presente trabalho ressalta a importancia da implantação de instrumento na rede básica de saúde para controlar o ganho de peso da gestante, bem como da vigilancia de outros fatores de risco no intuito de reduzir os elevados percentuais de recém-nascidos com BP.The lack of monitoring ofthenutritional condition of pregnamtwomen during theprenatal exammat^lon has made it difficult for interventions aimir g at the prevention of low weight at birth (BP). 45 pregnmt women of low socio-economic levei registered m the posts of the FOUNDATION for ASSISTANCE to INFANCY (FAISA - Santo André, São Paulo) were evaluated, for accomplishment of prenatal exammation, using Rosso’s Graph for its nutritional classification. The achieved percentage of pregnantwomenwi^th low weightwas 36,8%. Mo^therswi^thmore thamtwo ges^tations and wi^th less than two presented greater occurrence of overweight obesi^ty amd low weight, respectively. Higher percentage of amemia in the pregmant women with low weight was verified. Therefore, it is evident that this instrument should be implemented as routine in ^the prenatal examinabon

PD-1 blockade in recurrent or metastatic cervical cancer: Data from cemiplimab phase I expansion cohorts and characterization of PD-L1 expression in cervical cancer

Objectives: To characterize the safety, tolerability, and anti-tumor activity of cemiplimab as monotherapy or in combination with hypofractionated radiation therapy (hfRT) in patients with recurrent or metastatic cervical cancer. To determine the association between histology and programmed death-ligand 1 (PD-L1) expression. Methods: In non-randomized phase I expansion cohorts, patients (squamous or non-squamous histology) received cemiplimab 3 mg/kg intravenously every 2 weeks for 48 weeks, either alone (monotherapy cohort) or with hfRT during week 2 (combination cohort). Due to insufficient tissue material, PD-L1 protein expression was evaluated in commercially purchased samples and mRNA expression levels were analyzed from The Cancer Genome Atlas (TCGA). Results: Twenty patients enrolled in both cohorts in total; 10 had squamous histology. The most common adverse events of any grade were diarrhea, fatigue, and hypokalemia, occurring in 35%, 25%, and 25%, respectively. Objective response rate was 10% in each cohort; responders had squamous histology. Duration of response was 11.2 months and 6.4 months for the responder in the monotherapy and combination cohort, respectively. Irradiated lesions were not included in the response assessments. In separate archived specimens (N = 155), PD-L1 protein expression in tumor and immune cells was negative (<1%) more commonly in adenocarcinoma than in squamous tumors. PD-L1 mRNA levels were lower in adenocarcinoma than squamous cell tumors (1.2 vs 5.0 mean transcripts per million, respectively) in TCGA. Conclusions: Cemiplimab has activity in cervical squamous cell carcinoma. The phase I results, combined with results from other anti-PD-1 trials in cervical cancer and our biomarker analyses have informed the design of the ongoing phase III trial, with the primary overall survival hierarchical analyses being done first in patients with squamous histology

The Bulge Metallicity Distribution from the APOGEE Survey

The Apache Point Observatory Galactic Evolution Experiment (APOGEE) provides spectroscopic information of regions of the inner Milky Way, which are inaccessible to optical surveys. We present the first large study of the metallicity distribution of the innermost Galactic regions based on high-quality measurements for 7545 red giant stars within 4.5 kpc of the Galactic center, with the goal to shed light on the structure and origin of the Galactic bulge. Stellar metallicities are found, through multiple Gaussian decompositions, to be distributed in several components, which is indicative of the presence of various stellar populations such as the bar or the thin and the thick disks. Super-solar ([Fe/H] = +0.32) and solar ([Fe/H] = +0.00) metallicity components, tentatively associated with the thin disk and the Galactic bar, respectively, seem to be major contributors near the midplane. A solar-metallicity component extends outwards in the midplane but is not observed in the innermost regions. The central regions (within 3 kpc of the Galactic center) reveal, on the other hand, the presence of a significant metal-poor population ([Fe/H] = −0.46), tentatively associated with the thick disk, which becomes the dominant component far from the midplane ($| Z| \geqslant +0.75$ kpc). Varying contributions from these different components produce a transition region at +0.5 kpc $\leqslant \,| Z| \,\leqslant \ +1.0\,\mathrm{kpc}$, characterized by a significant vertical metallicity gradient

Final Targeting Strategy for the SDSS-IV APOGEE-2N Survey

APOGEE-2 is a dual-hemisphere, near-infrared (NIR), spectroscopic survey with the goal of producing a chemo-dynamical mapping of the Milky Way Galaxy. The targeting for APOGEE-2 is complex and has evolved with time. In this paper, we present the updates and additions to the initial targeting strategy for APOGEE-2N presented in Zasowski et al. (2017). These modifications come in two implementation modes: (i) "Ancillary Science Programs" competitively awarded to SDSS-IV PIs through proposal calls in 2015 and 2017 for the pursuit of new scientific avenues outside the main survey, and (ii) an effective 1.5-year expansion of the survey, known as the Bright Time Extension, made possible through accrued efficiency gains over the first years of the APOGEE-2N project. For the 23 distinct ancillary programs, we provide descriptions of the scientific aims, target selection, and how to identify these targets within the APOGEE-2 sample. The Bright Time Extension permitted changes to the main survey strategy, the inclusion of new programs in response to scientific discoveries or to exploit major new datasets not available at the outset of the survey design, and expansions of existing programs to enhance their scientific success and reach. After describing the motivations, implementation, and assessment of these programs, we also leave a summary of lessons learned from nearly a decade of APOGEE-1 and APOGEE-2 survey operations. A companion paper, Santana et al. (submitted), provides a complementary presentation of targeting modifications relevant to APOGEE-2 operations in the Southern Hemisphere.Comment: 59 pages; 11 Figures; 7 Tables; 2 Appendices; Submitted to Journal and Under Review; Posting to accompany papers using the SDSS-IV/APOGEE-2 Data Release 17 scheduled for December 202

Single-Cell Transcriptional Analysis of Normal, Aberrant, and Malignant Hematopoiesis in Zebrafish

Hematopoiesis culminates in the production of functionally heterogeneous blood cell types. In zebrafish, the lack of cell surface antibodies has compelled researchers to use fluorescent transgenic reporter lines to label specific blood cell fractions. However, these approaches are limited by the availability of transgenic lines and fluorescent protein combinations that can be distinguished. Here, we have transcriptionally profiled single hematopoietic cells from zebrafish to define erythroid, myeloid, B, and T cell lineages. We also used our approach to identify hematopoietic stem and progenitor cells and a novel NK-lysin 4+ cell type, representing a putative cytotoxic T/NK cell. Our platform also quantified hematopoietic defects in rag2E450fs mutant fish and showed that these fish have reduced T cells with a subsequent expansion of NK-lysin 4+ cells and myeloid cells. These data suggest compensatory regulation of the innate immune system in rag2E450fs mutant zebrafish. Finally, analysis of Myc-induced T cell acute lymphoblastic leukemia showed that cells are arrested at the CD4+/CD8+ cortical thymocyte stage and that a subset of leukemia cells inappropriately reexpress stem cell genes, including bmi1 and cmyb. In total, our experiments provide new tools and biological insights into single-cell heterogeneity found in zebrafish blood and leukemia

Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals

Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common (ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV (PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors

PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma

BACKGROUNDNo systemic therapies have been approved for the treatment of advanced cutaneous squamous-cell carcinoma. This cancer may be responsive to immune therapy, because the mutation burden of the tumor is high and the disease risk is strongly associated with immunosuppression. In the dose-escalation portion of the phase 1 study of cemiplimab, a deep and durable response was observed in a patient with metastatic cutaneous squamous-cell carcinoma.METHODSWe report the results of the phase 1 study of cemiplimab for expansion cohorts of patients with locally advanced or metastatic cutaneous squamous-cell carcinoma, as well as the results of the pivotal phase 2 study for a cohort of patients with metastatic disease (metastatic-disease cohort). In both studies, the patients received an intravenous dose of cemiplimab (3 mg per kilogram of body weight) every 2 weeks and were assessed for a response every 8 weeks. In the phase 2 study, the primary end point was the response rate, as assessed by independent central review.RESULTSIn the expansion cohorts of the phase 1 study, a response to cemiplimab was observed in 13 of 26 patients (50%; 95% confidence interval [CI], 30 to 70). In the metastatic-disease cohort of the phase 2 study, a response was observed in 28 of 59 patients (47%; 95% CI, 34 to 61). The median follow-up was 7.9 months in the metastatic-disease cohort of the phase 2 study. Among the 28 patients who had a response, the duration of response exceeded 6 months in 57%, and 82% continued to have a response and to receive cemiplimab at the time of data cutoff. Adverse events that occurred in at least 15% of the patients in the metastatic-disease cohort of the phase 2 study were diarrhea, fatigue, nausea, constipation, and rash; 7% of the patients discontinued treatment because of an adverse event.CONCLUSIONSAmong patients with advanced cutaneous squamous-cell carcinoma, cemiplimab induced a response in approximately half the patients and was associated with adverse events that usually occur with immune checkpoint inhibitors

Genome-Wide Association Study of White Blood Cell Count in 16,388 African Americans: the Continental Origins and Genetic Epidemiology Network (COGENT)

Total white blood cell (WBC) and neutrophil counts are lower among individuals of African descent due to the common African-derived “null” variant of the Duffy Antigen Receptor for Chemokines (DARC) gene. Additional common genetic polymorphisms were recently associated with total WBC and WBC sub-type levels in European and Japanese populations. No additional loci that account for WBC variability have been identified in African Americans. In order to address this, we performed a large genome-wide association study (GWAS) of total WBC and cell subtype counts in 16,388 African-American participants from 7 population-based cohorts available in the Continental Origins and Genetic Epidemiology Network. In addition to the DARC locus on chromosome 1q23, we identified two other regions (chromosomes 4q13 and 16q22) associated with WBC in African Americans (P<2.5×10−8). The lead SNP (rs9131) on chromosome 4q13 is located in the CXCL2 gene, which encodes a chemotactic cytokine for polymorphonuclear leukocytes. Independent evidence of the novel CXCL2 association with WBC was present in 3,551 Hispanic Americans, 14,767 Japanese, and 19,509 European Americans. The index SNP (rs12149261) on chromosome 16q22 associated with WBC count is located in a large inter-chromosomal segmental duplication encompassing part of the hydrocephalus inducing homolog (HYDIN) gene. We demonstrate that the chromosome 16q22 association finding is most likely due to a genotyping artifact as a consequence of sequence similarity between duplicated regions on chromosomes 16q22 and 1q21. Among the WBC loci recently identified in European or Japanese populations, replication was observed in our African-American meta-analysis for rs445 of CDK6 on chromosome 7q21 and rs4065321 of PSMD3-CSF3 region on chromosome 17q21. In summary, the CXCL2, CDK6, and PSMD3-CSF3 regions are associated with WBC count in African American and other populations. We also demonstrate that large inter-chromosomal duplications can result in false positive associations in GWAS

Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms

Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. Video Abstract [Figure presented] Keywords: type 2 diabetes (T2D); genetics; disease mechanism; SLC16A11; MCT11; solute carrier (SLC); monocarboxylates; fatty acid metabolism; lipid metabolism; precision medicin

Apophis planetary defense campaign

We describe results of a planetary defense exercise conducted during the close approach to Earth by the near-Earth asteroid (99942) Apophis during 2020 December–2021 March. The planetary defense community has been conducting observational campaigns since 2017 to test the operational readiness of the global planetary defense capabilities. These community-led global exercises were carried out with the support of NASA's Planetary Defense Coordination Office and the International Asteroid Warning Network. The Apophis campaign is the third in our series of planetary defense exercises. The goal of this campaign was to recover, track, and characterize Apophis as a potential impactor to exercise the planetary defense system including observations, hypothetical risk assessment and risk prediction, and hazard communication. Based on the campaign results, we present lessons learned about our ability to observe and model a potential impactor. Data products derived from astrometric observations were available for inclusion in our risk assessment model almost immediately, allowing real-time updates to the impact probability calculation and possible impact locations. An early NEOWISE diameter measurement provided a significant improvement in the uncertainty on the range of hypothetical impact outcomes. The availability of different characterization methods such as photometry, spectroscopy, and radar provided robustness to our ability to assess the potential impact risk