tbuckley/cabot-search huggingface dataset:
Obesity and Outcomes of Kawasaki Disease and COVID-19–Related Multisystem Inflammatory Syndrome in Children
Authors: Michael Khoury, Ashraf S. Harahsheh, Geetha Raghuveer, Nagib Dahdah, Simon Lee, Marianna Fabi, Elif Seda Selamet Tierney, Michael A. Portman, Nadine F. Choueiter, Matthew Elias, Deepika Thacker, Frédéric Dallaire, William B. Orr, Tyler H. Harris, Kambiz Norozi, Dongngan T. Truong, Manaswitha Khare, Jacqueline R. Szmuszkovicz, Joseph J. Pagano, Cedric Manlhiot, Pedrom Farid, Brian W. McCrindle, Mahmoud Alsalehi, Jean A. Ballweg, Benjamin T. Barnes, Elizabeth Braunlin, Ashley Buffone, Juan Carlos Bustamante-Ogando, Arthur J. Chang, Paul Dancey, Sarah D. De Ferranti, Catherine Dimes, Audrey Dionne, Mona El Ganzoury, Nora El Samman, Elisa Fernández Cooke, Luis Martin Garrido-Garcia, Therese M. Giglia, Guillermo Larios Goldenberg, Kevin C. Harris, Mark D. Hicar, Nicolas M. Hidalgo Corral, Supriya S. Jain, Pei-Ni Jone, Hidemi Kajimoto, Shelby Kutty, Marcello Lanari, Robert W. Lowndes, Victoria Maksymiuk, Daniel Mauriello, Kimberly E. McHugh, Shae A. Merves, Nilanjana Misra, Sindhu Mohandas, Tapas Mondal, Todd T. Nowlen, Deepa Prasad, Prasad Ravi, Arash A. Sabati, Anupam Sehgal, Ashish Shah, Balasubramanian Sundaram, Belén Toral Vázquez, Adriana H. Tremoulet, Aishwarya Venkataraman, Marco Antonio Yamazaki-Naksahimada, Anji T. Yetman, Varsha Zadokar
Journal: JAMA Network Open (2023)

Obesity may affect the clinical course of Kawasaki disease (KD) in children and multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19.
Uncovering the Role of Kidney Disease and Its Care in the US Maternal Health Equity Crisis
Authors: Dinushika Mohottige, L. Ebony Boulware
Journal: JAMA Network Open (2023)

Lauren M. Kucirka, MD, PhD; Ana M. Angarita, MD; Tracy A. Manuck, MD, MS; Kim A. Boggess, MD, MS; Vimal K. Derebail, MD, MPH; Mollie E. Wood, PhD; Michelle L. Meyer, PhD, MPH; Dorry L. Segev, MD, PhD; Monica L. Reynolds, MD, MSCR
To Quiesce or Senesce, That Is the Question for Dedifferentiated Liposarcoma
Authors: Mia C. Weiss, Vanessa Eulo, Brian A. Van Tine
Journal: Clinical Cancer Research (2023)

Summary Dedifferentiated liposarcoma (DDLPS) has an appealing therapeutic target due to its CDK4 amplification on chromosome 12q. The understanding of geroconversion from quiescent cells to senescent cells defines a patient's response to CDK4 inhibitors. This new observation will inform not only the ongoing phase III clinical trial of abemaciclib, but all future clinical trials in DDLPS. See related article by Gleason et al., p. 703
Prosocial Interventions and Health Outcomes
Authors: Margaret Byrne, Rayner Kay Jin Tan, Dan Wu, Gifty Marley, Takhona Grace Hlatshwako, Yusha Tao, Jennifer Bissram, Sophie Nachman, Weiming Tang, Rohit Ramaswamy, Joseph D. Tucker
Journal: JAMA Network Open (2023)

Prosocial interventions encourage voluntary actions that benefit others. Community solidarity in response to the COVID-19 pandemic, expanding mutual aid programs, and health workforce issues have accelerated prosocial health interventions.
Sex and Race Differences in Obesity-Related Genetic Susceptibility and Risk of Cardiometabolic Disease in Older US Adults
Authors: Hairui Yu, Nicole Armstrong, Greg Pavela, Kathryn Kaiser
Journal: JAMA Network Open (2023)

Importance The fat mass and obesity–associated gene ( FTO ) is associated with obesity phenotypes, but the association is inconsistent across populations. Within-population differences may explain some of the variability observed. Objective To investigate sex differences in the association between FTO single-nucleotide variants (SNVs) and obesity traits among self-identified non-Hispanic Black and non-Hispanic White US adults, to examine whether the SNVs were associated with cardiometabolic diseases, and to evaluate whether obesity mediated the association between FTO SNVs and cardiometabolic diseases. Design, Setting, and Participants This cross-sectional study used data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a US population-based cohort study with available genetic data (assayed in 2018) and phenotypic data at baseline (enrolled 2003-2007). Participants were aged 45 to 98 years at baseline. Data were analyzed from October 2021 to October 2022. Exposures Eleven SNVs in the FTO gene present among both Black and White participants. Main Outcomes and Measures Objectively measured obesity indicators (body mass index and waist-to-height ratio), objectively measured and/or self-reported cardiometabolic diseases (hypertension, stroke history, heart disease, and diabetes), and self-reported social-economic and psychosocial status. Results A total of 10 447 participants (mean [SD] age, 64.4 [9.7] years; 5276 [55.8%] women; 8743 [83.7%] Black and 1704 [16.3%] White) were included. In the White group, 11 FTO SNVs were significantly associated with obesity, hypertension, and diabetes using linear models (eg, body mass index: β = 0.536; 95% CI, 0.197-0.875), but none of the FTO SNVs were associated with obesity traits in the Black group. White males had a higher risk of obesity while White females had a higher risk of hypertension and diabetes. However, 1 FTO SNV (rs1121980) was associated with a direct increase in the risk of heart disease in Black participants not mediated by obesity (c′ = 0.145 [SE, 0.0517]; P = .01). Conclusions and Relevance In this cross-sectional study of obesity phenotypes and their association with cardiometabolic diseases, the tested FTO SNVs reflected sex differences in White participants. Different patterns of associations were observed among self-identified Black participants. Therefore, these results could inform future work discovering risk alleles or risk scores unique to Black individuals or further investigating genetic risk in all US residents.
Biomimetic Hydrogel Containing Copper Sulfide Nanoparticles and Deferoxamine for Photothermal Therapy of Infected Diabetic Wounds
Authors: Haijun Shen, Chun Zhang, Ye Meng, Yi Qiao, Yane Ma, Jialing Chen, Xiaona Wang, Lei Pan
Journal: Advanced Healthcare Materials (2023)

Abstract Inducing cell migration from the edges to the center of a wound, promoting angiogenesis, and controlling bacterial infection are very important for diabetic wound healing. Incorporating growth factors and antibiotics into hydrogels for wound dressing is considered a potential strategy to meet these requirements. However, some present drawbacks greatly slow down their development toward application, such as the short half‐life and high price of growth factors, low antibiotic efficiency against drug‐resistant bacteria, insufficient ability of hydrogels to promote cell migration, etc. Deferoxamine (DFO) can upregulate the expression of HIF‐1α, thus stimulating the secretion of angiogenesis‐related endogenous growth factors. Copper sulfide (CuS) nanoparticles possess excellent antibacterial performance combined with photothermal therapy (PTT). Herein, DFO and CuS nanoparticles are incorporated into a biomimetic hydrogel, which mimics the structure and function of the extracellular matrix (ECM), abbreviated as DFO/CuS‐ECMgel. This biomimetic hydrogel is expected to be able to promote cell adhesion and migration, be degraded by cell‐secreted matrix metalloproteinases (MMPs), and then release DFO and CuS nanoparticles at the wound site to exert their therapeutic effects. As a result, the three crucial requirements for diabetic wound healing, “beneficial for cell adhesion and migration, promoting angiogenesis, effectively killing drug‐resistant bacteria,” can be achieved simultaneously.
Urban Living Environment and Myopia in Children
Authors: Xiaotong Li, Lihua Li, Wen Qin, Qing Cao, Xin Mu, Tiange Liu, Zhen Li, Wei Zhang
Journal: JAMA Network Open (2023)

Importance The global prevalence of myopia has shown a steady increase over recent decades, with urban areas seemingly experiencing a more significant impact. Objective To assess the association between urbanization and the prevalence, incidence, progression, and severity of myopia. Design, Setting, and Participants This cohort study included students in grades 1 to 6 in Tianjin, China, who underwent 3 vision examinations conducted over a 2-year period, from March 1, 2021, to March 31, 2023. Participants from grades 1 to 4 completed the 2-year follow-up. Exposures Urban living environment Main Outcomes and Measures The association of urbanization with the incidence, progression, prevalence, and severity of myopia. To quantify urbanization, an urban score was constructed using satellite data and an iterative exploratory factor analysis. Results Of 177 894 students (51.7% male; mean [SD] age, 10.27 [1.75] years) included in the study, 137 087 students (52.3% male; mean [SD] age, 8.97 [1.21] years) were followed up for 2 years. A positive association was identified between myopia incidence and urbanization. Specifically, each 1-unit increment in the urban score was associated with an increased risk of myopia over a 1-year period (odds ratio [OR], 1.09; 95% CI, 1.01-1.15; P = .02) and a 2-year period (OR, 1.53; 95% CI, 1.50-1.57; P &amp;amp;lt; .001). Conversely, each 1-unit increase in the urban score was associated with a significant decrease in myopia progression at 1 year (OR, 0.84; 95% CI, 0.82-0.86; P &amp;amp;lt; .001) and 2 years (OR, 0.73; 95% CI, 0.70-0.75, P &amp;amp;lt; .001). In a cross-sectional data analysis, the urban score was positively associated with myopia prevalence (OR, 1.62; 95% CI, 1.08-2.42; P = .02) and negatively associated with myopia severity, as indicated by spherical equivalent refraction (OR, 1.46; 95% CI, 1.07-1.99; P = .02). Conclusions and Relevance This study exploring urban living environments and myopia revealed dual associations of urban living with both the incidence and the progression of myopia. The observed patterns emphasize the urgency of promptly implementing myopia control strategies in less urbanized regions, where myopia progression may be accentuated.
Avatrombopag for adults with early versus chronic immune thrombocytopenia
Authors: Zain M. Virk, Rebecca K. Leaf, David J. Kuter, Katayoon Goodarzi, Nathan T. Connell, Jean M. Connors, Hanny Al‐Samkari
Journal: American Journal of Hematology (2023)

Abstract Avatrombopag is a newer thrombopoietin receptor agonist (TPO‐RA) currently approved to treat chronic ITP (duration &gt;12 months). No studies have yet evaluated the safety and effectiveness of avatrombopag in newly diagnosed ITP (duration &lt;3 months) or persistent ITP (duration 3–12 months), and so its use in these populations is presently off‐label worldwide. We hypothesize that avatrombopag has similar safety and effectiveness irrespective of ITP disease phase. To evaluate this, we performed a multicenter observational cohort study of adults with ITP treated with avatrombopag, comparing patient outcomes by disease phase (newly diagnosed/persistent versus chronic). Seventy‐five patients were included, 23 with newly diagnosed/persistent ITP (17.7 patient‐years of avatrombopag treatment) and 52 with chronic ITP (65.3 patient‐years of avatrombopag treatment). On avatrombopag, 91% of newly diagnosed/persistent patients versus 96% of chronic patients ( p = .58) achieved a platelet response (≥50 × 10 9 /L) and 86% versus 81% of patients ( p = .78) achieved a complete response (≥100 × 10 9 /L). Median platelet counts on avatrombopag were similar between the two groups (165 × 10 9 /L vs. 129 × 10 9 /L, p = .57). Response durability was high and similar in both groups. No patients in the newly diagnosed/persistent group had a major bleeding event, thromboembolic event or avatrombopag discontinuation for adverse events, compared with 4, 1, and 2, respectively, in the chronic group. Thrombocytosis (platelets ≥400 × 10 9 /L) incidence was similar in the two groups. No other drug‐related adverse events occurred in either group. Avatrombopag was safe and effective in patients with newly diagnosed and persistent ITP, with outcomes numerically, statistically, and clinically similar to patients receiving avatrombopag for chronic ITP.
US County–Level Variation in Preterm Birth Rates, 2007-2019
Authors: Sadiya S. Khan, Adam S. Vaughan, Katharine Harrington, Laura Seegmiller, Xiaoning Huang, Lindsay R. Pool, Matthew M. Davis, Norrina B. Allen, Simon Capewell, Martin O’Flaherty, Gregory E. Miller, Roxana Mehran, Birgit Vogel, Kiarri N. Kershaw, Donald M. Lloyd-Jones, William A. Grobman
Journal: JAMA Network Open (2023)

Importance Preterm birth is a leading cause of preventable neonatal morbidity and mortality. Preterm birth rates at the national level may mask important geographic variation in rates and trends at the county level. Objective To estimate age-standardized preterm birth rates by US county from 2007 to 2019. Design, Setting, and Participants This serial cross-sectional study used data from the National Center for Health Statistics composed of all live births in the US between 2007 and 2019. Data analyses were performed between March 22, 2022, and September 29, 2022. Main Outcomes and Measures Age-standardized preterm birth (&amp;amp;lt;37 weeks’ gestation) and secondarily early preterm birth (&amp;amp;lt;34 weeks’ gestation) rates by county and year calculated with a validated small area estimation model (hierarchical bayesian spatiotemporal model) and percent change in preterm birth rates using log-linear regression models. Results Between 2007 and 2019, there were 51 044 482 live births in 2383 counties. In 2007, the national age-standardized preterm birth rate was 12.6 (95% CI, 12.6-12.7) per 100 live births. Preterm birth rates varied significantly among counties, with an absolute difference between the 90th and 10th percentile counties of 6.4 (95% CI, 6.2-6.7). The gap between the highest and lowest counties for preterm births was 20.7 per 100 live births in 2007. Several counties in the Southeast consistently had the highest preterm birth rates compared with counties in California and New England, which had the lowest preterm birth rates. Although there was no statistically significant change in preterm birth rates between 2007 and 2019 at the national level (percent change, −5.0%; 95% CI, −10.7% to 0.9%), increases occurred in 15.4% (95% CI, 14.1%-16.9%) of counties. The absolute and relative geographic inequalities were similar across all maternal age groups. Higher quartile of the Social Vulnerability Index was associated with higher preterm birth rates (quartile 4 vs quartile 1 risk ratio, 1.34; 95% CI, 1.31-1.36), which persisted across the study period. Similar patterns were observed for early preterm birth rates. Conclusions and Relevance In this serial cross-sectional study of county-level preterm and early preterm birth rates, substantial geographic disparities were observed, which were associated with place-based social disadvantage. Stability in aggregated rates of preterm birth at the national level masked increases in nearly 1 in 6 counties between 2007 and 2019.
Relevance of Obesity in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children Associated With COVID-19
Authors: Kirsten Dummer, Jane C. Burns
Journal: JAMA Network Open (2023)

Michael Khoury, MD; Ashraf S. Harahsheh, MD; Geetha Raghuveer, MD; Nagib Dahdah, MD, MBA; Simon Lee, MD; Marianna Fabi, MD, PhD; Elif Seda Selamet Tierney, MD; Michael A. Portman, MD; Nadine F. Choueiter, MD; Matthew Elias, MD; Deepika Thacker, MD; Frédéric Dallaire, MD, PhD; William B. Orr, MD; Tyler H. Harris, MD; Kambiz Norozi, MD, PhD; Dongngan T. Truong, MD, MS; Manaswitha Khare, MD; Jacqueline R. Szmuszkovicz, MD; Joseph J. Pagano, MD, PhD; Cedric Manlhiot, PhD; Pedrom Farid, BMSc; Brian W. McCrindle, MD, MPH; International Kawasaki Disease Registry; Mahmoud Alsalehi; Jean A. Ballweg; Benjamin T. Barnes; Elizabeth Braunlin; Ashley Buffone; Juan Carlos Bustamante-Ogando; Arthur J. Chang; Paul Dancey; Sarah D. De Ferranti; Catherine Dimes; Audrey Dionne; Mona El Ganzoury; Nora El Samman; Elisa Fernández Cooke; Luis Martin Garrido-Garcia; Therese M. Giglia; Guillermo Larios Goldenberg; Kevin C. Harris; Mark D. Hicar; Nicolas M. Hidalgo Corral; Supriya S. Jain; Pei-Ni Jone; Hidemi Kajimoto; Shelby Kutty; Marcello Lanari; Robert W. Lowndes; Victoria Maksymiuk; Daniel Mauriello; Kimberly E. McHugh; Shae A. Merves; Nilanjana Misra; Sindhu Mohandas; Tapas Mondal; Todd T. Nowlen; Deepa Prasad; Prasad Ravi; Arash A. Sabati; Anupam Sehgal; Ashish Shah; Balasubramanian Sundaram; Belén Toral Vázquez; Adriana H. Tremoulet; Aishwarya Venkataraman; Marco Antonio Yamazaki-Naksahimada; Anji T. Yetman; Varsha Zadokar
Spatial Transcriptomics Resolve an Emphysema-specific Lymphoid Follicle B Cell Signature in COPD
Authors: Joselyn Rojas-Quintero, Scott A Ochsner, Felicia New, Prajan Divakar, Chen Xi Yang, Tianshi David Wu, Jerid Robinson, Darshan Shimoga Chandrashekar, Nicholas E Banovich, Ivan O. Rosas, Maor Sauler, Farrah Kheradmand, Amit Gaggar, Camilla Margaroli, Raul San Jose Estepar, Neil J McKenna, Francesca Polverino
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Within chronic obstructive pulmonary disease (COPD), emphysema is characterized by a significant yet partially understood B cell immune component.
Re: William Morello, Esra Baskin, Augustina Jankauskiene, et al. Antibiotic Prophylaxis in Infants with Grade III, IV, or V Vesicoureteral Reflux. N Engl J Med 2023;389:987–97
Authors: Andrew T. Gabrielson, Logan Galansky, Heather N. Di Carlo
Journal: European Urology (2023)
Microwave-responsive gadolinium metal-organic frameworks nanosystem for MRI-guided cancer thermotherapy and synergistic immunotherapy
Authors: Hao Cui, Yu-Yue Zhao, Qiong Wu, Yan You, Zhou Lan, Ke-Long Zou, Guo-Wang Cheng, Hao Chen, Yan-Hua Han, Yan Chen, Xiang-Dong Qi, Xian-Wei Meng, Li-Min Ma, Guang-Tao Yu
Journal: Bioactive Materials (2023)

The clinical application of cancer immunotherapy is unsatisfied due to low response rates and systemic immune-related adverse events. Microwave hyperthermia can be used as a synergistic immunotherapy to amplify the antitumor effect. Herein, we designed a Gd-based metal-organic framework (Gd-MOF) nanosystem for MRI-guided thermotherapy and synergistic immunotherapy, which featured high performance in drug loading and tumor tissue penetration. The PD-1 inhibitor (aPD-1) was initially loaded in the porous Gd-MOF (Gd/M) nanosystem. Then, the phase change material (PCM) and the cancer cell membrane were further sequentially modified on the surface of Gd/MP to obtain Gd-MOF@aPD-1@CM (Gd/MPC). When entering the tumor microenvironment (TME), Gd/MPC induces immunogenic death of tumor cells through microwave thermal responsiveness, improves tumor suppressive immune microenvironment and further enhances anti-tumor ability of T cells by releasing aPD-1. Meanwhile, Gd/MPC can be used for contrast-enhanced MRI. Transcriptomics data revealed that the downregulation of MSK2 in cancer cells leads to the downregulation of c-fos and c-jun, and ultimately leads to the apoptosis of cancer cells after treatment. In general, Gd/MPC nanosystem not only solves the problem of system side effect, but also achieves the controlled drug release via PCM, providing a promising theranostic nanoplatform for development of cancer combination immunotherapy.
Reactive oxygen species (ROS)-mediated M1 macrophage-dependent nanomedicine remodels inflammatory microenvironment for osteoarthritis recession
Authors: Chunchun Xue, Jia Tian, Zepeng Cui, Yang Liu, Dawei Sun, Mengting Xiong, Nanxing Yi, Kaiqiang Wang, Xiaofeng Li, Yongjun Wang, Hao Xu, Weian Zhang, Qianqian Liang
Journal: Bioactive Materials (2023)

Osteoarthritis (OA) is a common chronic inflammatory disorder. Effective remodeling of inflammatory microenvironment in the joint is a promising strategy to prevent OA. However, current drugs remain unsatisfactory due to a lack of targeted and effective ways for relieving inflammatory conditions in OA joints. Bortezomib (BTZ), a proteasome inhibitor, could effectively inhibit proinflammatory cytokines but with poor accumulation in the inflammatory tissues. To overcome the shortcomings of BTZ delivery and to improve the efficacy of OA therapy, herein, we designed a novel nanomedicine (denoted as BTZ@PTK) by the co-assembly of BTZ and an amphiphilic copolymer (denoted as PTK) with ROS-cleaved thioketal (TK) linkages. The TK units in BTZ@PTK are first cleaved by the excessive ROS at OA sites, and then triggered the controlled release of BTZ, resulting in the accurate delivery and the inflammatory microenvironment remodeling. Accordingly, BTZ@PTK suppressed ROS generation and proinflammatory cytokines while promoting M1 macrophage apoptosis in lipopolysaccharide (LPS)-activated RAW264.7 macrophages or LPS/IFN-γ-treated primary macrophages, which leads to a better effect than BTZ. In OA mice, BTZ@PTK passively accumulates into inflamed joints to attenuate pain sensitivity and gait abnormality. Importantly, BTZ@PTK treatment successfully ameliorates synovitis with the reduction of synovial hyperplasia and synovitis scores by suppressing M1 macrophage polarization and promoting M1 macrophage apoptosis in the synovium, thereby delaying cartilage damage. Collectively, BTZ@PTK can effectively modulate inflammatory microenvironment for OA recession by activating M1 macrophage apoptosis and inhibiting M1macrophage-mediated inflammatory response.
A case of small-bowel and colon malformation identified during endoscopy in an adult patient
Authors: Chen Wu, Xiangyu Liu, Lingyun Wang
Journal: Endoscopy (2023)

A 57-year-old woman who had never undergone surgery previously was hospitalized due to a 6-month history of intermittent abdominal pain. Computed tomography revealed a communication between a portion of the small intestine and the adjacent segment of the sigmoid colon, with lumen dilatation and localized air and fluid accumulation ([Fig. 1]).
Interchromosomal Colocalization with Parental Genes Is Linked to the Function and Evolution of Mammalian Retrocopies
Authors: Yubin Yan, Yuhan Tian, Zefeng Wu, Kunling Zhang, Ruolin Yang
Journal: Molecular Biology and Evolution (2023)

Retrocopies are gene duplicates arising from reverse transcription of mature mRNA transcripts and their insertion back into the genome. While long being regarded as processed pseudogenes, more and more functional retrocopies have been discovered. How the stripped-down retrocopies recover expression capability and become functional paralogs continually intrigues evolutionary biologists. Here, we investigated the function and evolution of retrocopies in the context of 3D genome organization. By mapping retrocopy-parent pairs onto sequencing-based and imaging-based chromatin contact maps in human and mouse cell lines and onto Hi-C interaction maps in 5 other mammals, we found that retrocopies and their parental genes show a higher-than-expected interchromosomal colocalization frequency. The spatial interactions between retrocopies and parental genes occur frequently at loci in active subcompartments and near nuclear speckles. Accordingly, colocalized retrocopies are more actively transcribed and translated and are more evolutionarily conserved than noncolocalized ones. The active transcription of colocalized retrocopies may result from their permissive epigenetic environment and shared regulatory elements with parental genes. Population genetic analysis of retroposed gene copy number variants in human populations revealed that retrocopy insertions are not entirely random in regard to interchromosomal interactions and that colocalized retroposed gene copy number variants are more likely to reach high frequencies, suggesting that both insertion bias and natural selection contribute to the colocalization of retrocopy-parent pairs. Further dissection implies that reduced selection efficacy, rather than positive selection, contributes to the elevated allele frequency of colocalized retroposed gene copy number variants. Overall, our results hint a role of interchromosomal colocalization in the "resurrection" of initially neutral retrocopies.