tbuckley/cabot-search huggingface dataset:
Impact of Propofol Exposure on Neurocognitive Outcomes in Children With High-Risk B ALL: A Children's Oncology Group Study
Authors: Sarah Alexander, John A. Kairalla, Sumit Gupta, Emily Hibbitts, Hannah Weisman, Doralina Anghelescu, Naomi J. Winick, Kevin R. Krull, Wanda L. Salzer, Michael J. Burke, Lia Gore, Meenakshi Devidas, Leanne Embry, Elizabeth A. Raetz, Stephen P. Hunger, Mignon L. Loh, Kristina K. Hardy
Journal: Journal of Clinical Oncology (2024)

PURPOSE Many children treated for ALL develop long-term neurocognitive impairments. Increased risk of these impairments is associated with treatment and demographic factors. Exposure to anesthesia is an additional possible risk factor. This study evaluated the impact of cumulative exposure to anesthesia on neurocognitive outcomes among a multicenter cohort of children with ALL. METHODS This study was embedded in AALL1131, a Children's Oncology Group phase III trial for patients with high-risk B-ALL. In consenting patients age 6-12 years, prospective uniform assessments of neurocognitive function were performed during and at 1 year after completion of therapy. Exposure to all episodes of anesthetic agents was abstracted. Multivariable linear regression models determined associations of cumulative anesthetic agents with the primary neurocognitive outcome reaction time/processing speed (age-normed) at 1 year off therapy, adjusting for baseline neurocognitive score, age, sex, race/ethnicity, insurance status (as a proxy for socioeconomic status), and leukemia risk group. RESULTS One hundred and forty-four children, 76 (52.8%) males, mean age of 9.1 (min-max, 6.0-12.0) years at diagnosis, underwent a median of 27 anesthetic episodes (min-max, 1-37). Almost all patients were exposed to propofol (140/144, 97.2%), with a mean cumulative dose of 112.3 mg/kg. One year after therapy, the proportion of children with impairment ( Z-score ≤–1.5) was significantly higher compared with a normative sample. In covariate-adjusted multivariable analysis, cumulative exposure to propofol was associated with a 0.05 Z-score decrease in reaction time/processing speed per each 10 mg/kg propofol exposure ( P = .03). CONCLUSION In a multicenter and uniformly treated cohort of children with B-ALL, cumulative exposure to propofol was an independent risk factor for impairment in reaction time/processing speed 1 year after therapy. Anesthesia exposure is a modifiable risk, and opportunities to minimize propofol use should be considered.
Mitoxantrone Versus Liposomal Daunorubicin in Induction of Pediatric AML With Risk Stratification Based on Flow Cytometry Measurement of Residual Disease
Authors: Anne Tierens, Nira Arad-Cohen, Daniel Cheuk, Barbara De Moerloose, Jose Maria Fernandez Navarro, Henrik Hasle, Kirsi Jahnukainen, Kristian Løvvik Juul-Dam, Gertjan Kaspers, Zanna Kovalova, Birgitte Lausen, Ulrika Norén-Nyström, Josefine Palle, Ramune Pasauliene, Cornelis Jan Pronk, Kadri Saks, Bernward Zeller, Jonas Abrahamsson
Journal: Journal of Clinical Oncology (2024)

Measurable residual disease (MRD) by using flow cytometry after induction therapy is strongly prognostic in pediatric AML, and hematopoietic stem-cell transplant (hSCT) may counteract a poor response. We designed a phase III study with intensified response-guided induction and MRD-based risk stratification and treated poor induction response with hSCT. The efficacy of liposomal daunorubicin (DNX) in induction was compared with mitoxantrone.
Increasing power in screening trials by testing control-arm specimens: application to multicancer detection screening
Authors: Hormuzd A Katki, Philip C Prorok, Philip E Castle, Lori M Minasian, Paul F Pinsky
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background Cancer screening trials have required large sample sizes and long time-horizons to demonstrate cancer mortality reductions, the primary goal of cancer screening. We examine assumptions and potential power gains from exploiting information from testing control-arm specimens, which we call the “intended effect” (IE) analysis that we explain in detail herein. The IE analysis is particularly suited to tests that can be conducted on stored specimens in the control arm, such as stored blood for multicancer detection (MCD) tests. Methods We simulated hypothetical MCD screening trials to compare power and sample size for the standard vs IE analysis. Under two assumptions that we detail herein, we projected the IE analysis for 3 existing screening trials (National Lung Screening Trial [NLST], Minnesota Colon Cancer Control Study [MINN-FOBT-A], and Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial—colorectal component [PLCO-CRC]). Results Compared with the standard analysis for the 3 existing trials, the IE design could have reduced cancer-specific mortality P values 5-fold (NLST), 33-fold (MINN-FOBT-A), or 14 160-fold (PLCO-CRC) or, alternately, reduced sample size (90% power) by 26% (NLST), 48% (MINN-FOBT-A), or 59% (PLCO-CRC). For potential MCD trial designs requiring 100 000 subjects per arm to achieve 90% power for multicancer mortality for the standard analysis, the IE analysis achieves 90% power for only 37 500-50 000 per arm, depending on assumptions concerning control-arm test-positives. Conclusions Testing stored specimens in the control arm of screening trials to conduct the IE analysis could substantially increase power to reduce sample size or accelerate trials and could provide particularly strong power gains for MCD tests.
Single cell lineage tracing reveals clonal dynamics of anti-EGFR therapy resistance in triple negative breast cancer
Authors: Simona Pellecchia, Melania Franchini, Gaetano Viscido, Riccardo Arnese, Gennaro Gambardella
Journal: Genome Medicine (2024)

Abstract Background Most primary Triple Negative Breast Cancers (TNBCs) show amplification of the Epidermal Growth Factor Receptor (EGFR) gene, leading to increased protein expression. However, unlike other EGFR-driven cancers, targeting this receptor in TNBC yields inconsistent therapeutic responses. Methods To elucidate the underlying mechanisms of this variability, we employ cellular barcoding and single-cell transcriptomics to reconstruct the subclonal dynamics of EGFR-amplified TNBC cells in response to afatinib, a tyrosine kinase inhibitor (TKI) that irreversibly inhibits EGFR. Results Integrated lineage tracing analysis revealed a rare pre-existing subpopulation of cells with distinct biological signature, including elevated expression levels of Insulin-Like Growth Factor Binding Protein 2 (IGFBP2). We show that IGFBP2 overexpression is sufficient to render TNBC cells tolerant to afatinib treatment by activating the compensatory insulin-like growth factor I receptor (IGF1-R) signalling pathway. Finally, based on reconstructed mechanisms of resistance, we employ deep learning techniques to predict the afatinib sensitivity of TNBC cells. Conclusions Our strategy proved effective in reconstructing the complex signalling network driving EGFR-targeted therapy resistance, offering new insights for the development of individualized treatment strategies in TNBC.
The Budding Neuroscience of Ant Social Behavior
Authors: Dominic D. Frank, Daniel J.C. Kronauer
Journal: Annual Review of Neuroscience (2024)

Ant physiology has been fashioned by 100 million years of social evolution. Ants perform many sophisticated social and collective behaviors yet possess nervous systems similar in schematic and scale to that of the fruit fly Drosophila melanogaster, a popular solitary model organism. Ants are thus attractive complementary subjects to investigate adaptations pertaining to complex social behaviors that are absent in flies. Despite research interest in ant behavior and the neurobiological foundations of sociality more broadly, our understanding of the ant nervous system is incomplete. Recent technical advances have enabled cutting-edge investigations of the nervous system in a fashion that is less dependent on model choice, opening the door for mechanistic social insect neuroscience. In this review, we revisit important aspects of what is known about the ant nervous system and behavior, and we look forward to how functional circuit neuroscience in ants will help us understand what distinguishes solitary animals from highly social ones.
Author Correction: Potent suppression of neuroendocrine tumors and gastrointestinal cancers by CDH17CAR T cells without toxicity to normal tissues
Authors: Zijie Feng, Xin He, Xuyao Zhang, Yuan Wu, Bowen Xing, Alison Knowles, Qiaonan Shan, Samuel Miller, Taylor Hojnacki, Jian Ma, Bryson W. Katona, Terence P. F. Gade, Don L. Siegel, Jörg Schrader, David C. Metz, Carl H. June, Xianxin Hua
Journal: Nature Cancer (2024)
In Memoriam of William Lloyd Henrich, MD, MACP
Authors: Kumar Sharma, Jochen Reiser, Orson W. Moe, W. Brian Reeves
Journal: Journal of the American Society of Nephrology (2024)

1UT Health Science Center San Antonio, San Antonio, TX, [email protected] 2University of Texas Medical Branch Office of University Advancement: The University of Texas Medical Branch at Galveston Development Office 3UT Southwestern: The University of Texas Southwestern Medical Center 4The University of Texas Health Science Center at San Antonio
Influence of Temperature and Precipitation on the Effectiveness of Water, Sanitation, and Handwashing Interventions against Childhood Diarrheal Disease in Rural Bangladesh: A Reanalysis of the WASH Benefits Bangladesh Trial
Authors: Anna T. Nguyen, Jessica A. Grembi, Marie Riviere, Gabriella Barratt Heitmann, William D. Hutson, Tejas S. Athni, Arusha Patil, Ayse Ercumen, Audrie Lin, Yoshika Crider, Andrew Mertens, Leanne Unicomb, Mahbubur Rahman, Stephen P. Luby, Benjamin F. Arnold, Jade Benjamin-Chung
Journal: Environmental Health Perspectives (2024)

Diarrheal disease is a leading cause of childhood morbidity and mortality globally. Household water, sanitation, and handwashing (WASH) interventions can reduce exposure to diarrhea-causing pathogens, but meteorological factors may impact their effectiveness. Information about effect heterogeneity under different weather conditions is critical to refining these targeted interventions.
Spontaneous Preterm Birth Phenotyping Based on Cervical Length and Immune-Mediated Factors
Authors: Paolo Ivo Cavoretto, Massimo Candiani, Antonio Farina
Journal: JAMA Network Open (2024)

Tianchen Wu, PhD; Shuang Li, MD; Xiaoli Gong, MD; Jiaxin Li, MD; Xuening Li, PhD; Yujia Zhai, PhD; Jiaqi Huang, MD; Xiaona Li, PhD; Luyao Li, MD; Jing Yang, MD; Xueju Wang, MD; Huifeng Shi, PhD; Pengbo Yuan, MD; Yangyu Zhao, MD; Yuan Wei, MD
User Information Sharing and Hospital Website Privacy Policies
Authors: Matthew S. McCoy, Angela Wu, Sam Burdyl, Yungjee Kim, Noell Kristen Smith, Rachel Gonzales, Ari B. Friedman
Journal: JAMA Network Open (2024)

Importance Hospital websites frequently use tracking technologies that transfer user information to third parties. It is not known whether hospital websites include privacy policies that disclose relevant details regarding tracking. Objective To determine whether hospital websites have accessible privacy policies and whether those policies contain key information related to third-party tracking. Design, Setting, and Participants In this cross-sectional content analysis of website privacy policies of a nationally representative sample of nonfederal acute care hospitals, hospital websites were first measured to determine whether they included tracking technologies that transferred user information to third parties. Hospital website privacy policies were then identified using standardized searches. Policies were assessed for length and readability. Policy content was analyzed using a data abstraction form. Tracking measurement and privacy policy retrieval and analysis took place from November 2023 to January 2024. The prevalence of privacy policy characteristics was analyzed using standard descriptive statistics. Main Outcomes and Measures The primary study outcome was the availability of a website privacy policy. Secondary outcomes were the length and readability of privacy policies and the inclusion of privacy policy content addressing user information collected by the website, potential uses of user information, third-party recipients of user information, and user rights regarding tracking and information collection. Results Of 100 hospital websites, 96 (96.0%; 95% CI, 90.1%-98.9%) transferred user information to third parties. Privacy policies were found on 71 websites (71.0%; 95% CI, 61.6%-79.4%). Policies were a mean length of 2527 words (95% CI, 2058-2997 words) and were written at a mean grade level of 13.7 (95% CI, 13.4-14.1). Among 71 privacy policies, 69 (97.2%; 95% CI, 91.4%-99.5%) addressed types of user information automatically collected by the website, 70 (98.6%; 95% CI, 93.8%-99.9%) addressed how collected information would be used, 66 (93.0%; 95% CI, 85.3%-97.5%) addressed categories of third-party recipients of user information, and 40 (56.3%; 95% CI, 44.5%-67.7%) named specific third-party companies or services receiving user information. Conclusions and Relevance In this cross-sectional study of hospital website privacy policies, a substantial number of hospital websites did not present users with adequate information about the privacy implications of website use, either because they lacked a privacy policy or had a privacy policy that contained limited content about third-party recipients of user information.
State Medicaid Coverage for Tobacco Cessation Treatments and Barriers to Accessing Treatments — United States, 2018–2022
Authors: Anne DiGiulio, Michael A. Tynan, Anna Schecter, Kisha-Ann S. Williams, Brenna VanFrank
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

The prevalence of cigarette smoking among U.S. adults enrolled in Medicaid is higher than among adults with private insurance; more than one in five adults enrolled in Medicaid smokes cigarettes.Smoking cessation reduces the risk for smoking-related disease and death.Effective treatments for smoking cessation are available, and comprehensive, barrierfree insurance coverage of these treatments can increase cessation.However, Medicaid treatment coverage and treatment access barriers vary by state.The American Lung Association collected and analyzed state-level information regarding coverage for nine tobacco cessation treatments and seven access barriers for standard Medicaid enrollees.As of December 31, 2022, a total of 20 state Medicaid programs provided comprehensive coverage (all nine treatments), an increase from 15 as of December 31, 2018.Only three states had zero access barriers, an increase from two; all three also had comprehensive coverage.Although states continue to improve smoking cessation treatment coverage and decrease access barriers for standard Medicaid enrollees, coverage gaps and access barriers remain in many states.State Medicaid programs can improve the health of enrollees who smoke and potentially reduce health care expenditures by providing barrier-free coverage of all evidence-based cessation treatments and by promoting this coverage to enrollees and providers.
<i>Notes from the Field:</i> Neonatal Salmonellosis Associated with Backyard Poultry — Oregon, November 2023
Authors: Stephen G. Ladd-Wilson, Karen Yeargain, Samuel P. Myoda, Mansour Samadpour, Karim Morey, Paul R. Cieslak
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Outbreaks of salmonellosis (infection with non-typhoidal Salmonella) involving young children associated with keeping backyard poultry,* including descriptions of high-risk practices such as keeping poultry inside households and kissing birds, have been well documented (1).During 2023 (as of October 19), backyard poultry-associated salmonellosis outbreaks were reported to CDC from 48 States and Puerto Rico; these outbreaks accounted for 1,072 cases of illness, including 247 hospitalizations (2).Several of these outbreaks involved multiple states and included serotypes Braenderup, Enteritidis, Indiana, Infantis, Mbandaka, and Typhimurium (3).During a salmonellosis outbreak investigation across multiple states (A.Lodato, CDC, unpublished data, 2023), the Oregon Health Authority, in collaboration with a local health department, investigated a case of salmonellosis in a newborn whose parents had kept backyard poultry.This activity was deemed to be routine public health surveillance by the Public Health Division of the Oregon Health Authority and did not require human subjects review.
Synthetic biology approaches for improving the specificity and efficacy of cancer immunotherapy
Authors: Bo Zhu, Hang Yin, Di Zhang, Meiling Zhang, Xiaojuan Chao, Luca Scimeca, Ming-Ru Wu
Journal: Cellular and Molecular Immunology (2024)

Abstract Immunotherapy has shown robust efficacy in treating a broad spectrum of hematological and solid cancers. Despite the transformative impact of immunotherapy on cancer treatment, several outstanding challenges remain. These challenges include on-target off-tumor toxicity, systemic toxicity, and the complexity of achieving potent and sustainable therapeutic efficacy. Synthetic biology has emerged as a promising approach to overcome these obstacles, offering innovative tools for engineering living cells with customized functions. This review provides an overview of the current landscape and future prospects of cancer immunotherapy, particularly emphasizing the role of synthetic biology in augmenting its specificity, controllability, and efficacy. We delineate and discuss two principal synthetic biology strategies: those targeting tumor surface antigens with engineered immune cells and those detecting intratumoral disease signatures with engineered gene circuits. This review concludes with a forward-looking perspective on the enduring challenges in cancer immunotherapy and the potential breakthroughs that synthetic biology may contribute to the field.
The orientation of CpG conjugation on aluminum oxyhydroxide nanoparticles determines the immunostimulatory effects of combination adjuvants
Authors: Zhihui Liang, Hang Bao, Zhiying Yao, Min Li, Chen Chen, Lei Zhang, Huiyang Wang, Yiyang Guo, Yubin Ma, Xuecheng Yang, Ge Yu, Jiancheng Zhang, Changying Xue, Bingbing Sun, Chuanbin Mao
Journal: Biomaterials (2024)
Effectiveness of Conventional Digital Fundus Photography-Based Teleretinal Screening for Diabetic Retinopathy and Diabetic Macular Edema
Authors: Christina Y. Weng, Maureen G. Maguire, Christina J. Flaxel, Nieraj Jain, Stephen J. Kim, Shriji Patel, Justine R. Smith, Leo A. Kim, Steven Yeh
Journal: Ophthalmology (2024)
Evaluating <scp>ChatGPT</scp> as an educational resource for patients with multiple myeloma: <scp>A</scp> preliminary investigation
Authors: Ludovic Saba, Chieh‐Lin Fu, Jack Khouri, Beth Faiman, Faiz Anwer, Chakra P. Chaulagain
Journal: American Journal of Hematology (2024)

The findings of this study highlight a 95% accuracy rate in ChatGPT responses, as assessed by five myeloma specialists, underscoring its potential as a reliable educational tool.
Scoary2: rapid association of phenotypic multi-omics data with microbial pan-genomes
Authors: Thomas Roder, Grégory Pimentel, Pascal Fuchsmann, Mireille Tena Stern, Ueli von Ah, Guy Vergères, Stephan Peischl, Ola Brynildsrud, Rémy Bruggmann, Cornelia Bär
Journal: Genome biology (2024)

Abstract Unraveling bacterial gene function drives progress in various areas, such as food production, pharmacology, and ecology. While omics technologies capture high-dimensional phenotypic data, linking them to genomic data is challenging, leaving 40–60% of bacterial genes undescribed. To address this bottleneck, we introduce Scoary2 , an ultra-fast microbial genome-wide association studies (mGWAS) software. With its data exploration app and improved performance, Scoary2 is the first tool to enable the study of large phenotypic datasets using mGWAS. As proof of concept, we explore the metabolome of yogurts, each produced with a different Propionibacterium reichii strain and discover two genes affecting carnitine metabolism.
A call for accessible tools to unlock single-cell immunometabolism research
Authors: Jason Cosgrove, Antoine Marçais, Felix J. Hartmann, Andreas Bergthaler, Ivan Zanoni, Mauro Corrado, Leïla Perié, Nina Cabezas-Wallscheid, Philippe Bousso, Theodore Alexandrov, Tammy Kielian, Nuria Martínez-Martín, Christiane A. Opitz, Costas A. Lyssiotis, Rafael J. Argüello, Jan Van den Bossche
Journal: Nature Metabolism (2024)
Adipose tissue macrophages secrete small extracellular vesicles that mediate rosiglitazone-induced insulin sensitization
Authors: Theresa V. Rohm, Felipe Castellani Gomes Dos Reis, Roi Isaac, Cairo Murphy, Karina Cunha e Rocha, Gautam Bandyopadhyay, Hong Gao, Avraham M. Libster, Rizaldy C. Zapata, Yun Sok Lee, Wei Ying, Charlene Miciano, Allen Wang, Jerrold M. Olefsky
Journal: Nature Metabolism (2024)
A pan-genome of 69 Arabidopsis thaliana accessions reveals a conserved genome structure throughout the global species range
Authors: Qichao Lian, Bruno Huettel, Birgit Walkemeier, Baptiste Mayjonade, Céline Lopez-Roques, Lisa Gil, Fabrice Roux, Korbinian Schneeberger, Raphael Mercier
Journal: Nature Genetics (2024)

Abstract Although originally primarily a system for functional biology, Arabidopsis thaliana has, owing to its broad geographical distribution and adaptation to diverse environments, developed into a powerful model in population genomics. Here we present chromosome-level genome assemblies of 69 accessions from a global species range. We found that genomic colinearity is very conserved, even among geographically and genetically distant accessions. Along chromosome arms, megabase-scale rearrangements are rare and typically present only in a single accession. This indicates that the karyotype is quasi-fixed and that rearrangements in chromosome arms are counter-selected. Centromeric regions display higher structural dynamics, and divergences in core centromeres account for most of the genome size variations. Pan-genome analyses uncovered 32,986 distinct gene families, 60% being present in all accessions and 40% appearing to be dispensable, including 18% private to a single accession, indicating unexplored genic diversity. These 69 new Arabidopsis thaliana genome assemblies will empower future genetic research.
Strategic aspects for the commercialization of nanomedicines
Authors: Eva Hemmrich, Scott McNeil
Journal: Journal of Controlled Release (2024)

The projected growth of the nanomedicine market mirrors the increase in commercial interest and investment in the field. Yet, amidst this optimism, research efforts have often been geared towards developing innovative materials, and less on bringing these innovations to market. In this article, we present a strategic approach of 'commercialization by design' to overcome various challenges related to commercialization. This approach shifts the focus from materials-centric development to one driven by market demands, evaluating nanomedicines considering factors like reimbursement restrictions and unmet medical needs, and aiming to generate robust evidence for regulatory authorities, Health Technology Assessment bodies and Payers alike. We highlight the linkages from the market backwards to the preclinical phase, where nanomedicines are tailored to specific clinician-identified requirements. Transitioning from a technology 'push' model to one with market 'pull' will enhance the commercial success of nanomedicines.