Despite strides in characterizing human history from genetic polymorphism data, progress in identifying genetic signatures of recent demography has been limited. Here we identify very recent fine-scale population structure in North America from a network of over 500 million genetic (identity-by-descent, IBD) connections among 770,000 genotyped individuals of US origin. We detect densely connected clusters within the network and annotate these clusters using a database of over 20 million genealogical records. Recent population patterns captured by IBD clustering include immigrants such as Scandinavians and French Canadians; groups with continental admixture such as Puerto Ricans; settlers such as the Amish and Appalachians who experienced geographic or cultural isolation; and broad historical trends, including reduced north-south gene flow. Our results yield a detailed historical portrait of North America after European settlement and support substantial genetic heterogeneity in the United States beyond that uncovered by previous studies.
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http://dx.doi.org/10.1038/ncomms14238 | DOI Listing |
J Clin Invest
January 2025
Department of Laboratory Medicine, Division of Translational Cancer Researc, Lund University Cancer Centre, Lund University, Lund, Sweden.
The biology centered around the TGF-beta type I receptor Activin Receptor-Like Kinase (ALK)1 (encoded by ACVRL1) has been almost exclusively based on its reported endothelial expression pattern since its first functional characterization more than two decades ago. Here, in efforts to better define the therapeutic context in which to use ALK1 inhibitors, we uncover a population of tumor-associated macrophages (TAMs) that, by virtue of their unanticipated Acvrl1 expression, are effector targets for adjuvant anti-angiogenic immunotherapy in mouse models of metastatic breast cancer. The combinatorial benefit depended on ALK1-mediated modulation of the differentiation potential of bone marrow-derived granulocyte-macrophage progenitors, the release of CD14+ monocytes into circulation, and their eventual extravasation.
View Article and Find Full Text PDFJAMA Netw Open
January 2025
Division of Population Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts.
Importance: Adolescent and young adult (AYA) patients with advanced cancer often die in hospital settings. Data characterizing the degree to which this pattern of care is concordant with patient goals are sparse.
Objective: To evaluate the extent of concordance between the preferred and actual location of death among AYA patients with cancer.
JAMA Netw Open
January 2025
Division of Intramural Research, National Institute on Minority Health and Health Disparities, Bethesda, Maryland.
Importance: Cigarette companies have been introducing synthetic cooling agent menthol-mimicking cigarettes into the US marketplace as menthol cigarette bans are implemented. These cigarettes may reduce the public health benefits of menthol cigarette bans.
Objective: To examine the epidemiology of the use of synthetic cooling agent menthol-mimicking cigarettes among adults in the US.
JAMA Netw Open
January 2025
Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital, Boston, Massachusetts.
Importance: Nearly all Medicare Advantage (MA) plans offer dental, vision, and hearing benefits not covered by traditional Medicare (TM). However, little is known about MA enrollees' use of those benefits or how much they cost MA insurers or enrollees.
Objective: To estimate use, out-of-pocket (OOP) spending, and insurer payments for dental, hearing, and vision services among Medicare beneficiaries.
Aging Clin Exp Res
January 2025
Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054, Shaanxi, China.
Objective: This study aims to analyze adverse drug events (ADE) related to romosozumab from the second quarter of 2019 to the third quarter of 2023 from FAERS database.
Methods: The ADE data related to romosozumab from 2019 Q2 to 2023 Q3 were collected. After data normalization, four signal strength quantification algorithms were used: ROR (Reporting Odds Ratios), PRR (Proportional Reporting Ratios), BCPNN (Bayesian Confidence Propagation Neural Network), and EBGM (Empirical Bayesian Geometric Mean).
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