tbuckley/cabot-search huggingface dataset:
Examining Excess Mortality Associated With the COVID-19 Pandemic for Renters Threatened With Eviction
Authors: Nick Graetz, Peter Hepburn, Carl Gershenson, Sonya R. Porter, Danielle H. Sandler, Emily Lemmerman, Matthew Desmond
Journal: JAMA (2024)

Importance Residential evictions may have increased excess mortality associated with the COVID-19 pandemic. Objective To estimate excess mortality associated with the COVID-19 pandemic for renters who received eviction filings ( threatened renters ). Design, Setting, and Participants This retrospective cohort study used an excess mortality framework. Mortality based on linked eviction and death records from 2020 through 2021 was compared with projected mortality estimated from similar records from 2010 through 2016. Data from court records between January 1, 2020, and August 31, 2021, were collected via the Eviction Lab’s Eviction Tracking System. Similar data from court records between January 1, 2010, and December 31, 2016, also collected by the Eviction Lab, were used to estimate projected mortality during the pandemic. We also constructed 2 comparison groups: all individuals living in the study area and a subsample of those individuals living in high-poverty, high-filing tracts. Exposures Eviction filing. Main Outcomes and Measures All-cause mortality in a given month. The difference between observed mortality and projected mortality was used as a measure of excess mortality associated with the pandemic. Results The cohort of threatened renters during the pandemic period consisted of 282 000 individuals (median age, 36 years [IQR, 28-47]). Eviction filings were 44.7% lower than expected during the study period. The composition of threatened renters by race, ethnicity, sex, and socioeconomic characteristics during the pandemic was comparable with the prepandemic composition. Expected cumulative age-standardized mortality among threatened renters during this 20-month period of the pandemic was 116.5 (95% CI, 104.0-130.3) per 100 000 person-months, and observed mortality was 238.6 (95% CI, 230.8-246.3) per 100 000 person-months or 106% higher than expected. In contrast, expected mortality for the population living in similar neighborhoods was 114.6 (95% CI, 112.1-116.8) per 100 000 person-months, and observed mortality was 142.8 (95% CI, 140.2-145.3) per 100 000 person-months or 25% higher than expected. In the general population across the study area, expected mortality was 83.5 (95% CI, 83.3-83.8) per 100 000 person-months, and observed mortality was 91.6 (95% CI, 91.4-91.8) per 100 000 person-months or 9% higher than expected. The pandemic produced positive excess mortality ratios across all age groups among threatened renters. Conclusions and Relevance Renters who received eviction filings experienced substantial excess mortality associated with the COVID-19 pandemic.
A High-Quality Blue Whale Genome, Segmental Duplications, and Historical Demography
Authors: Yury V Bukhman, Phillip A Morin, Susanne Meyer, Li-Fang Chu, Jeff K Jacobsen, Jessica Antosiewicz-Bourget, Daniel Mamott, Maylie Gonzales, Cara Argus, Jennifer Bolin, Mark E Berres, Olivier Fedrigo, John Steill, Scott A Swanson, Peng Jiang, Arang Rhie, Giulio Formenti, Adam M Phillippy, Robert S Harris, Jonathan M D Wood, Kerstin Howe, Bogdan M Kirilenko, Chetan Munegowda, Michael Hiller, Aashish Jain, Daisuke Kihara, J Spencer Johnston, Alexander Ionkov, Kalpana Raja, Huishi Toh, Aimee Lang, Magnus Wolf, Erich D Jarvis, James A Thomson, Mark J P Chaisson, Ron Stewart
Journal: Molecular Biology and Evolution (2024)

Abstract The blue whale, Balaenoptera musculus, is the largest animal known to have ever existed, making it an important case study in longevity and resistance to cancer. To further this and other blue whale-related research, we report a reference-quality, long-read-based genome assembly of this fascinating species. We assembled the genome from PacBio long reads and utilized Illumina/10×, optical maps, and Hi-C data for scaffolding, polishing, and manual curation. We also provided long read RNA-seq data to facilitate the annotation of the assembly by NCBI and Ensembl. Additionally, we annotated both haplotypes using TOGA and measured the genome size by flow cytometry. We then compared the blue whale genome with other cetaceans and artiodactyls, including vaquita (Phocoena sinus), the world's smallest cetacean, to investigate blue whale's unique biological traits. We found a dramatic amplification of several genes in the blue whale genome resulting from a recent burst in segmental duplications, though the possible connection between this amplification and giant body size requires further study. We also discovered sites in the insulin-like growth factor-1 gene correlated with body size in cetaceans. Finally, using our assembly to examine the heterozygosity and historical demography of Pacific and Atlantic blue whale populations, we found that the genomes of both populations are highly heterozygous and that their genetic isolation dates to the last interglacial period. Taken together, these results indicate how a high-quality, annotated blue whale genome will serve as an important resource for biology, evolution, and conservation research.
DNA satellite and chromatin organization at mouse centromeres and pericentromeres
Authors: Jenika Packiaraj, Jitendra Thakur
Journal: Genome biology (2024)

Abstract Background Centromeres are essential for faithful chromosome segregation during mitosis and meiosis. However, the organization of satellite DNA and chromatin at mouse centromeres and pericentromeres is poorly understood due to the challenges of assembling repetitive genomic regions. Results Using recently available PacBio long-read sequencing data from the C57BL/6 strain, we find that contrary to the previous reports of their homogeneous nature, both centromeric minor satellites and pericentromeric major satellites exhibit a high degree of variation in sequence and organization within and between arrays. While most arrays are continuous, a significant fraction is interspersed with non-satellite sequences, including transposable elements. Using chromatin immunoprecipitation sequencing (ChIP-seq), we find that the occupancy of CENP-A and H3K9me3 chromatin at centromeric and pericentric regions, respectively, is associated with increased sequence enrichment and homogeneity at these regions. The transposable elements at centromeric regions are not part of functional centromeres as they lack significant CENP-A enrichment. Furthermore, both CENP-A and H3K9me3 nucleosomes occupy minor and major satellites spanning centromeric-pericentric junctions and a low yet significant amount of CENP-A spreads locally at centromere junctions on both pericentric and telocentric sides. Finally, while H3K9me3 nucleosomes display a well-phased organization on major satellite arrays, CENP-A nucleosomes on minor satellite arrays are poorly phased. Interestingly, the homogeneous class of major satellites also phase CENP-A and H3K27me3 nucleosomes, indicating that the nucleosome phasing is an inherent property of homogeneous major satellites. Conclusions Our findings reveal that mouse centromeres and pericentromeres display a high diversity in satellite sequence, organization, and chromatin structure.
Prevalence and predictive factors of colorectal sessile serrated lesions in younger individuals
Authors: Jen-Hao Yeh, Chih-Wen Lin, Po-Jen Hsiao, Daw-Shyong Perng, Jen-Chieh Chen, Kuo-Tung Hung, Chia-Chang Hsu, Chia-Chi Chen, Yu-Peng Liu, Yi-Chia Lee, Jaw-Yuan Wang
Journal: Endoscopy (2024)

Abstract Background Sessile serrated lesions (SSLs) are obscured lesions predominantly in the right-sided colon and associated with interval colorectal cancer; however, their prevalence and risk factors among younger individuals remain unclear. Methods This retrospective study enrolled individuals who underwent index colonoscopy. The primary outcome was the SSL prevalence in the younger (&lt;50 years) and older (≥50 years) age groups, while the secondary outcomes included clinically significant serrated polyps (CSSPs). Multivariable logistic regression was employed to identify predictors. Results Of the 9854 eligible individuals, 4712 (47.8%) were categorized into the younger age group. Individuals in the younger age group exhibited lower prevalences of adenomas (22.6% vs. 46.2%; P&lt;0.001) and right-sided adenomas (11.2% vs. 27.2%; P&lt;0.001) compared with their older counterparts. However, both groups exhibited a similar prevalence of SSLs (7.2% vs. 6.5%; P=0.16) and CSSPs (10.3% vs. 10.3%;P=0.96). Multivariable analysis revealed that age 40–49 years (odds ratio [OR] 1.81, 95%CI 1.01–3.23), longer withdrawal time (OR 1.17, 95%CI 1.14–1.20, per minute increment), and endoscopist performance (OR 3.35, 95%CI 2.44–4.58) were independent predictors of SSL detection in the younger age group. No significant correlation was observed between adenoma and SSL detection rates among endoscopists. Conclusion SSLs are not uncommon among younger individuals. Moreover, diligent effort and expertise are of paramount importance in SSL detection. Future studies should explore the clinical significance of SSLs in individuals of younger age.
Disparities in Sodium–Glucose Cotransporter 2 (SGLT2) Inhibitor Prescription and Dispensing in the Israeli Population—A Retrospective Cohort Study
Authors: Yaara Leibovici Weissman, Bronislava Calvarysky, Tzippy Shochat, Zoya Korotkov, Alon Grossman, Leonard Leibovici, Adi Turjeman
Journal: Diabetes Care (2024)

OBJECTIVE To describe disparities in prescribing and dispensing sodium–glucose cotransporter 2 inhibitors (SGLT2i) in Israel. RESEARCH DESIGN AND METHODS This was a population-based retrospective cohort study of adults with type 2 diabetes eligible for SGLT2i treatment from 2017 to 2023. The primary outcome was the time between initial eligibility and the first prescription of SGLT2i. RESULTS Among 32,742 eligible patients, only 53% were prescribed SGLT2i. Multivariable analyses, adjusting for death as a competing risk, revealed delays in prescription were associated with older age, Arab or Bedouin ethnicity, neoplasms, acute kidney failure, falls, previous hospitalization, urinary tract infections, and dementia. Factors associated with shorter time intervals to prescription were sex (men), medium/high socioeconomic status, and residing in an intermediate or central area of Israel. CONCLUSIONS Disparities in drug prescription exist, even in a country with universal health coverage. Addressing these disparities requires improvements in health care systems, education, and alert systems to overcome barriers to evidence-based interventions.
Histone lysine acetyltransferase inhibitors: an emerging class of drugs for cancer therapy
Authors: Jeffrey White, Frederick A. Derheimer, Kristen Jensen-Pergakes, Shawn O’Connell, Shikhar Sharma, Noah Spiegel, Thomas A. Paul
Journal: Trends in Pharmacological Sciences (2024)

Lysine acetyltransferases (KATs) are a family of epigenetic enzymes involved in the regulation of gene expression; they represent a promising class of emerging drug targets. The frequent molecular dysregulation of these enzymes, as well as their mechanistic links to biological functions that are crucial to cancer, have led to exploration around the development of small-molecule inhibitors against KATs. Despite early challenges, recent advances have led to the development of potent and selective enzymatic and bromodomain (BRD) KAT inhibitors. In this review we discuss the discovery and development of new KAT inhibitors and their application as oncology therapeutics. Additionally, new chemically induced proximity approaches are presented, offering opportunities for unique target selectivity profiles and tissue-specific targeting of KATs. Emerging clinical data for CREB binding protein (CREBBP)/EP300 BRD inhibitors and KAT6 catalytic inhibitors indicate the promise of this target class in cancer therapeutics.
LNK/SH2B3 loss of function increases susceptibility to murine and human atrial fibrillation
Authors: Matthew B Murphy, Zhenjiang Yang, Tuerdi Subati, Eric Farber-Eger, Kyungsoo Kim, Daniel J Blackwell, Matthew R Fleming, Joshua M Stark, Joseph C Van Amburg, Kaylen K Woodall, Justin P Van Beusecum, Vineet Agrawal, Charles D Smart, Ashley Pitzer, James B Atkinson, Agnes B Fogo, Julie A Bastarache, Annet Kirabo, Quinn S Wells, Meena S Madhur, Joey V Barnett, Katherine T Murray
Journal: Cardiovascular Research (2024)

Abstract Aims The lymphocyte adaptor protein (LNK) is a negative regulator of cytokine and growth factor signalling. The rs3184504 variant in SH2B3 reduces LNK function and is linked to cardiovascular, inflammatory, and haematologic disorders, including stroke. In mice, deletion of Lnk causes inflammation and oxidative stress. We hypothesized that Lnk−/− mice are susceptible to atrial fibrillation (AF) and that rs3184504 is associated with AF and AF-related stroke in humans. During inflammation, reactive lipid dicarbonyls are the major components of oxidative injury, and we further hypothesized that these mediators are critical drivers of the AF substrate in Lnk−/− mice. Methods and results Lnk−/− or wild-type (WT) mice were treated with vehicle or 2-hydroxybenzylamine (2-HOBA), a dicarbonyl scavenger, for 3 months. Compared with WT, Lnk−/− mice displayed increased AF duration that was prevented by 2-HOBA. In the Lnk−/− atria, action potentials were prolonged with reduced transient outward K+ current, increased late Na+ current, and reduced peak Na+ current, pro-arrhythmic effects that were inhibited by 2-HOBA. Mitochondrial dysfunction, especially for Complex I, was evident in Lnk−/− atria, while scavenging lipid dicarbonyls prevented this abnormality. Tumour necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1β) were elevated in Lnk−/− plasma and atrial tissue, respectively, both of which caused electrical and bioenergetic remodelling in vitro. Inhibition of soluble TNF-α prevented electrical remodelling and AF susceptibility, while IL-1β inhibition improved mitochondrial respiration but had no effect on AF susceptibility. In a large database of genotyped patients, rs3184504 was associated with AF, as well as AF-related stroke. Conclusion These findings identify a novel role for LNK in the pathophysiology of AF in both experimental mice and humans. Moreover, reactive lipid dicarbonyls are critical to the inflammatory AF substrate in Lnk−/− mice and mediate the pro-arrhythmic effects of pro-inflammatory cytokines, primarily through electrical remodelling.
18F-FDG PET/CT in a Case of Clear Cell Sarcoma of the Kidney
Authors: Hongfu Jin, Yafu Yin, Hui Wang, Weiwei Cheng
Journal: Clinical Nuclear Medicine (2024)

Abstract 18 F-FDG PET/CT was performed in a 1-year-old girl who had a heterogeneous mass in the right abdominal cavity revealed by abdominal ultrasound. A heterogeneous mass with internal necrosis, cystic changes, and hemorrhage in the right kidney, accompanied by a slight increase of FDG uptake, was observed in FDG PET/CT. Malignant renal tumor was considered, and Wilms tumor was preferentially suspected. However, the mass was demonstrated as clear cell sarcoma of the kidney by histopathological examination.
Hemangioma of the Ilium Simulating Bone Metastasis on 18F-PSMA-1007 PET/CT
Authors: Aisheng Dong, Shensheng Nian, Yushu Bai, Changjing Zuo
Journal: Clinical Nuclear Medicine (2024)

Abstract A 64-year-old man was referred for 18 F-PSMA-1007 PET/CT scan for initial staging of biopsy-proved prostate adenocarcinoma. 18 F-PSMA-1007 PET/CT showed focal intense 18 F-PSMA-1007 of the prostate adenocarcinoma and a focal intense activity with SUV max of 10.5 in the left ilium. The 18 F-PSMA-1007–avid iliac bone lesion corresponded to a hemangioma, which was initially detected on pelvic MRI 13 months ago and remained stable in size. This case indicates that hemangioma should be included in the differential diagnosis of PSMA-avid iliac bone lesions.
Uptake of 99mTc-DTPA in Bone Metastases From Follicular Thyroid Carcinoma
Authors: Zhiying Liang, Wei Li
Journal: Clinical Nuclear Medicine (2024)

Abstract A 53-year-old man with follicular thyroid carcinoma (FTC) was referred for renal scintigraphy using 99m Tc-DTPA to assess the kidney function. Unexpectedly, the images showed an abnormal uptake of radiotracer in the right pelvic region. It corresponded to the site of metastasis in the right ilium revealed on 131 I SPECT/CT images. The biopsy pathology of the ilium lesion demonstrated follicular thyroid cancer.
FDG PET/CT in a Case of Isolated Gastric Metastasis From Pancreatic Ductal Adenocarcinoma
Authors: Xia Ji, Aisheng Dong, Yang Wang
Journal: Clinical Nuclear Medicine (2024)

Abstract Hematogenous gastric metastasis from pancreatic cancer is extremely rare. We describe FDG PET/CT findings in a case of isolated hematogenous gastric metastasis from pancreatic cancer with significantly elevated serum carbohydrate antigen 19-9 level. The gastric metastasis showed intense focal FDG uptake mimicking a primary tumor. The elevation of serum carbohydrate antigen 19-9 level may be useful as an aid in the differential diagnosis.
Lifetime Duration of Breastfeeding and Cardiovascular Risk in Women With Type 2 Diabetes or a History of Gestational Diabetes: Findings From Two Large Prospective Cohorts
Authors: Anna Birukov, Marta Guasch-Ferré, Sylvia H. Ley, Deirdre K. Tobias, Fenglei Wang, Clemens Wittenbecher, Jiaxi Yang, JoAnn E. Manson, Jorge E. Chavarro, Frank B. Hu, Cuilin Zhang
Journal: Diabetes Care (2024)

OBJECTIVE Breastfeeding duration is inversely associated with risks of cardiovascular disease (CVD) and type 2 diabetes in parous women. However, the association among women at high risk, including women with type 2 diabetes or gestational diabetes mellitus (GDM) is unclear. RESEARCH DESIGN AND METHODS We included 15,146 parous women with type 2 diabetes from the Nurses’ Health Study I and II (NHS, NHS II) and 4,537 women with a history of GDM from NHS II. Participants reported history of breastfeeding via follow-up questionnaires. Incident CVD by 2017 comprised stroke or coronary heart disease (CHD) (myocardial infarction, coronary revascularization). Adjusted hazard ratios (aHRs) and 95% CIs were estimated using Cox models. RESULTS We documented 1,159 incident CVD cases among women with type 2 diabetes in both cohorts during 188,874 person-years of follow-up and 132 incident CVD cases among women with a GDM history during 100,218 person-years of follow-up. Longer lifetime duration of breastfeeding was significantly associated with lower CVD risk among women with type 2 diabetes, with pooled aHR of 0.68 (95% CI 0.54–0.85) for &amp;gt;18 months versus 0 months and 0.94 (0.91–0.98) per 6-month increment in breastfeeding. Similar associations were observed with CHD (pooled aHR 0.93 [0.88–0.97]) but not with stroke (0.96 [0.91–1.02]) per 6-month increment in breastfeeding. Among women with GDM history, &amp;gt;18 months versus 0 months of breastfeeding was associated with an aHR of 0.49 (0.28–0.86) for total CVD. CONCLUSIONS Longer duration of breastfeeding was associated with lower risk of CVD in women with type 2 diabetes or GDM.
Cardiovascular Health Care in Low- and Middle-Income Countries
Authors: Ana Olga Mocumbi
Journal: Circulation (2024)

ardiovascular disease (CVD) accounts for ≈18 million deaths annually worldwide, 1 with major disparities between low-and middle-income countries (LMICs) and high-income countries.LMICs contribute a greater share to the global burden of CVDs, with these conditions being responsible for 80% of all cardiovascular deaths worldwide. 1A greater reason for concern is the fact that premature deaths correspond to around half of all deaths in developing countries.Between 2008 and 2017, high-income countries contributed 81.1% of the global CVD research output and accounted for 8.1% and 8.5% of global CVD disability-adjusted life-year losses and death rates, respectively. 2In the same period, LMICs contributed 2.8% of the research output and accounted for 59.5% and 57.1% of global CVD disability-adjusted life-year losses and death rates, respectively. 2VD burden is determined by diverse conditions, ranging from hypertension and ischemic heart disease to persisting infection-related diseases (eg, rheumatic heart disease, Chagas disease, HIV-related cardiopathy) that affect the fragile economy and health systems in LMICs.Increase in life expectancy and exposure to cardiometabolic risk factors lead to growing trends in incidence and mortality related to ischemic heart disease and stroke.Outdoor air pollution and indoor exposure to biomass fuel smoke potentially contribute to right heart failure, particularly in women and nonsmokers.Poor health literacy, low access to health facilities, shortage of trained health providers, and weak health care and research infrastructure hamper prevention, early diagno-The American Heart Association celebrates its 100th anniversary in 2024.
Highlights From the <i>Circulation</i> Family of Journals
Authors: Melissa Middeldorp, Roopinder Sandhu, Jessica Mao, Baris Gencer, Jacqueline Danik, Vinayaga Moorthy, Nancy Cook, Christine Albert, Kui Deng, Deepak Gupta, Xiao-Ou Shu, Loren Lipworth, Wei Zheng, Victoria Thomas, Hui Cai, Qiuyin Cai, Thomas Wang, Danxia Yu, Gregg Fonarow, Leo Akioyamen, Husam Abdel-Qadir, Lu Han, Maneesh Sud, Nikhil Mistry, David Alter, Clare Atzema, Peter Austin, ; Sacha Bhatia, Gillian Booth, Irfan Dhalla, Andrew Ha, Cynthia Jackevicius, Moira Kapral, Harlan Krumholz, Douglas Lee, Candace Mcnaughton, Idan Roifman, Michael Schull, Atul Sivaswamy, Karen Tu, Jacob Udell, Harindra Wijeysundera, Dennis Ko, Mayooran Namasivayam, Philippe Bertrand, Samuel Bernard, Timothy Churchill, Shaan Khurshid, Frank Marcus, Luisa Mestroni, Jeffrey Saffitz, Jeffrey Towbin, Wojciech Zareba, Michael Picard, Danita Sanborn, Woochan Kwon, Myung Lee, ; Kyeong, Ho Yun, ; Ki, Hong Choi, Seung-Jae Lee, Jong-Young Lee, ; Sang, Yeub Lee, Min Kim, Jae Cho, ; Chan, Joon Kim, Hyo-Suk Ahn, Chang-Wook Nam, Jun Yoon, Yong Park, ; Wang, Soo Lee, Jin-Ok Jeong, ; Pil, Sang Song, Joon-Hyung Doh
Journal: Circulation (2024)

The December highlights from the Circulation