tbuckley/cabot-search huggingface dataset:
Matrix‐Bound Hyaluronan Molecular Weight as a Regulator of Dendritic Cell Immune Potency
Authors: Brian Chesney Quartey, Jiranuwat Sapudom, Mei ElGindi, Aseel Alatoom, Jeremy Teo
Journal: Advanced Healthcare Materials (2023)

Abstract Hyaluronic acid (HA) is a glycosaminoglycan in the extracellular matrix with immunoregulatory properties depending on its molecular weight (MW). However, the impact of matrix‐bound HA on dendritic cells (DCs) remains unclear due to varying distribution of HA MW under different physiological conditions. To investigate DCs in defined biosystems, 3D collagen matrices modified with HA of specific MW with similar microstructure and HA levels are used. It is found that HA MW influences cytokine binding to matrix, suggesting modulation of cytokine availability by the different HA MWs. These studies on DC immune potency reveal that low MW HA (8–15 kDa) enhances immature DC differentiation and antigen uptake, while medium (MMW‐HA; 500–750 kDa) and high MW HA (HMW‐HA; 1250–1500 kDa) increase cytokine secretion in mature DCs. The effect on DC phenotype and cytokine secretion by different MWs of HA is independent of CD44. However, blocking the CD44 receptor reveals its potential role in regulating acute inflammation through increased secretion of CCL2, CXCL8, and IL‐6. Additionally, MMW‐ and HMW‐HA matrices reduce migratory capacity of DCs, dependent on CD44. Overall, these findings provide insights into MW‐dependent effects of matrix‐bound HA on DCs, opening avenues for the design of DC‐modulating materials to enhance DC‐based therapy.
Heterogeneous associations of gut microbiota with Crohn’s disease activity
Authors: Susanne Pinto, Elisa Benincà, Gianluca Galazzo, Daisy Jonkers, John Penders, Johannes A. Bogaards
Journal: Gut Microbes (2023)

The multi-factorial involvement of gut microbiota with Crohn's disease (CD) necessitates robust analysis to uncover possible associations with particular microbes. CD has been linked to specific bacteria, but reported associations vary widely across studies. This inconsistency may result from heterogeneous associations across individual patients, resulting in no apparent or only weak relationships with the means of bacterial abundances. We investigated the relationship between bacterial relative abundances and disease activity in a longitudinal cohort of CD patients (n = 57) and healthy controls (n = 15). We applied quantile regression, a statistical technique that allows investigation of possible relationships outside the mean response. We found several significant and mostly negative associations with CD, especially in lower quantiles of relative abundance on family or genus level. Associations found by quantile regression deviated from the mean response in relative abundances of Coriobacteriaceae, Pasteurellaceae, Peptostreptococcaceae, Prevotellaceae, and Ruminococcaceae. For the family Streptococcaceae we found a significant elevation in relative abundance for patients experiencing an exacerbation relative to those who remained without self-reported symptoms or measurable inflammation. Our analysis suggests that specific bacterial families are related to CD and exacerbation, but associations vary between patients due to heterogeneity in disease course, medication history, therapy response, gut microbiota composition and historical contingency. Our study underscores that microbial diversity is reduced in the gut of CD patients, but suggests that the process of diversity loss is rather irregular with respect to specific taxonomic groups. This novel insight may advance our ecological understanding of this complex disease.
Luteal phase support in assisted reproductive technology
Authors: Akanksha Garg, Agata P. Zielinska, Arthur C. Yeung, Rebecca Abdelmalak, Runzhi Chen, Aleena Hossain, Alisha Israni, Scott M. Nelson, Andy V. Babwah, Waljit S. Dhillo, Ali Abbara
Journal: Nature Reviews Endocrinology (2023)
Targeting S100A9 protein affects mTOR-ER stress signaling and increases venetoclax sensitivity in Acute Myeloid Leukemia
Authors: Rong Fan, Hatice Satilmis, Niels Vandewalle, Emma Verheye, Elke De Bruyne, Eline Menu, Nathan De Beule, Ann De Becker, Gamze Ates, Ann Massie, Tessa Kerre, Marie Törngren, Helena Eriksson, Karin Vanderkerken, Karine Breckpot, Ken Maes, Kim De Veirman
Journal: Blood Cancer Journal (2023)

Acute Myeloid Leukemia (AML) is a heterogeneous disease with limited treatment options and a high demand for novel targeted therapies. Since myeloid-related protein S100A9 is abundantly expressed in AML, we aimed to unravel the therapeutic impact and underlying mechanisms of targeting both intracellular and extracellular S100A9 protein in AML cell lines and primary patient samples. S100A9 silencing in AML cell lines resulted in increased apoptosis and reduced AML cell viability and proliferation. These therapeutic effects were associated with a decrease in mTOR and endoplasmic reticulum stress signaling. Comparable results on AML cell proliferation and mTOR signaling could be observed using the clinically available S100A9 inhibitor tasquinimod. Interestingly, while siRNA-mediated targeting of S100A9 affected both extracellular acidification and mitochondrial metabolism, tasquinimod only affected the mitochondrial function of AML cells. Finally, we found that S100A9-targeting approaches could significantly increase venetoclax sensitivity in AML cells, which was associated with a downregulation of BCL-2 and c-MYC in the combination group compared to single agent therapy. This study identifies S100A9 as a novel molecular target to treat AML and supports the therapeutic evaluation of tasquinimod in venetoclax-based regimens for AML patients.
Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis
Authors: Anja Meyer, Stephanie R. Zack, Wes Nijim, Adel Burgos, Vishwa Patel, Brian Zanotti, Michael V. Volin, M. Asif Amin, Myles J. Lewis, Costantino Pitzalis, Shiva Arami, Joseph A. Karam, Nadera J. Sweiss, Shiva Shahrara
Journal: Cellular and Molecular Immunology (2023)
Addressing the disparities: the approach to the African American patient with multiple myeloma
Authors: Manisha Bhutani, Brandon J. Blue, Craig Cole, Ashraf Z. Badros, Saad Z. Usmani, Ajay K. Nooka, Leon Bernal-Mizrachi, Joseph Mikhael
Journal: Blood Cancer Journal (2023)

Abstract There are significant disparities with regards to incidence, timely diagnosis, access to treatment, clinical trial participation and health care utilization that negatively impact outcomes for African American patients with multiple myeloma. Health care providers have a role in ameliorating these disparities with thoughtful consideration of historical, sociocultural, individual and disease characteristics that influence the care provided to African American patient population. This review by a group of experts committed to health disparity in multiple myeloma provides a snapshot of disparities at both biologic and non-biologic levels, barriers to clinical care, and best practices to ensure that African American patients receive the best care available.
Young duplicate genes show developmental stage- and cell type-specific expression and function in Caenorhabditis elegans
Authors: Fuqiang Ma, Chun Yin Lau, Chaogu Zheng
Journal: Cell Genomics (2023)

Gene duplication produces the material that fuels evolutionary innovation. The "out-of-testis" hypothesis suggests that sperm competition creates selective pressure encouraging the emergence of new genes in male germline, but the somatic expression and function of the newly evolved genes are not well understood. We systematically mapped the expression of young duplicate genes throughout development in Caenorhabditis elegans using both whole-organism and single-cell transcriptomic data. Based on the expression dynamics across developmental stages, young duplicate genes fall into three clusters that are preferentially expressed in early embryos, mid-stage embryos, and late-stage larvae. Early embryonic genes are involved in protein degradation and develop essentiality comparable to the genomic average. In mid-to-late embryos and L4-stage larvae, young genes are enriched in intestine, epidermal cells, coelomocytes, and amphid chemosensory neurons. Their molecular functions and inducible expression indicate potential roles in innate immune response and chemosensory perceptions, which may contribute to adaptation outside of the sperm.
Alchemy
Authors: Bonnie Salomon
Journal: Annals of Internal Medicine (2023)

Ad LibitumDecember 2023AlchemyBonnie Salomon, MDBonnie Salomon, MDNorthwestern Medicine Lake Forest HospitalLake Forest, IllinoisSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M23-1747 Audio Reading - “Alchemy” Supplement. Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads “Alchemy” by Bonnie Salomon, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail When you said the IV was infusingBlue Jell-OI smiled and nodded my head.Who was I to denyThat elixir dripped inWasn’t magical potion instead?How delicious—blue Jell-O, if there was such a thing,Fading tumors to shadows, then gone.So turn chemo to Jell-O, change hope into goldGlitter so bright it can blind.But it wasn’t blue Jell-O and there was no goldAnd the tumors remained, solidIn your beautiful, blighted,gelatinous brain.Already the details begin to recedeOf blood tests and scans that robbed years.Yet the needs remain, as they always doSince the fears, outlived, came true. Author, Article, and Disclosure InformationAuthors: Bonnie Salomon, MDAffiliations: Northwestern Medicine Lake Forest HospitalLake Forest, IllinoisCorresponding Author: Bonnie Salomon, MD; e-mail, BonSalomon@aol.com. PreviousarticleNextarticle Advertisement Audio Reading - “Alchemy” Supplement. Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads “Alchemy” by Bonnie Salomon, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics Current Issue December 2023Volume 176, Issue 12 Page: 1679 ePublished: 19 December 2023 Issue Published: December 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Contemporary Public Health Finance: Varied Definitions, Patterns, and Implications
Authors: Jason M. Orr, Jonathon P. Leider, Rachel Hogg-Graham, J. Mac McCullough, Aaron Alford, David Bishai, Glen P. Mays
Journal: Annual Review of Public Health (2023)

The financing of public health systems and services relies on a complex and fragmented web of partners and funding priorities. Both underfunding and “dys-funding” contribute to preventable mortality, increases in disease frequency and severity, and hindered social and economic growth. These issues were both illuminated and magnified by the COVID-19 pandemic and associated responses. Further complicating issues is the difficulty in constructing adequate estimates of current public health resources and necessary resources. Each of these challenges inhibits the delivery of necessary services, leads to inequitable access and resourcing, contributes to resource volatility, and presents other deleterious outcomes. However, actions may be taken to defragment complex funding paradigms toward more flexible spending, to modernize and standardize data systems, and to assure equitable and sustainable public health investments.
More than a Nuisance: Implications of Food Marketing for Public Health Efforts to Curb Childhood Obesity
Authors: Jennifer L. Harris, Lindsey Smith Taillie
Journal: Annual Review of Public Health (2023)

Fifteen years ago, public health experts urged industry, governments, and advocates to take action to dramatically improve the unhealthy food-marketing environment surrounding children in order to address the global childhood obesity crisis. Since then, research has confirmed that food marketing to children has far-reaching negative effects on their diets and health, takes advantage of adolescent vulnerabilities, and contributes to health disparities. In addition, digital marketing has profoundly changed young people's engagement with brands. Moreover, reliance on industry self-regulation as a solution has proven ineffective. Government-led policies have been more successful, but they remain limited in scope and challenging to adopt and implement. New approaches are necessary to increase public and policy maker awareness that food marketing is more than a nuisance, that it threatens the long-term health of children and adolescents worldwide, and that meaningful governmental action is urgently required to curtail industry's negative impact on young people's well-being.
Test and Treat for Prediabetes: A Review of the Health Effects of Prediabetes and the Role of Screening and Prevention
Authors: Rosette J. Chakkalakal, Karla I. Galaviz, Sathish Thirunavukkarasu, Megha K. Shah, K.M. Venkat Narayan
Journal: Annual Review of Public Health (2023)

The term prediabetes describes blood glucose levels above the normal range but below the threshold to diagnose type 2 diabetes. Several population health initiatives encourage a test and treat approach for prediabetes. In this approach, screening and identification of individuals with prediabetes should be followed by prompt referral to structured lifestyle modification programs or pharmacologic interventions that have been shown to prevent or delay the progression to type 2 diabetes in clinical trials. Here we provide a critical review of evidence for this test and treat approach by examining health outcomes associated with prediabetes and the availability and effectiveness of lifestyle modification approaches that target prediabetes. We also describe current limitations to the reach and uptake of evidence-based treatment options for prediabetes. Finally, we highlight lessons learned from identifying and labeling other preconditions to consider challenges and opportunities that may arise with increasing awareness of prediabetes as part of routine preventive care.
Long-Term Follow-Up of Rituximab Maintenance in Young Patients With Mantle-Cell Lymphoma Included in the LYMA Trial: A LYSA Study
Authors: Clémentine Sarkozy, Catherine Thieblemont, Lucie Oberic, Anne Moreau, Krimo Bouabdallah, Gandhi Damaj, Thomas Gastinne, Benoit Tessoulin, Vincent Ribrag, Olivier Casasnovas, Corinne Haioun, Roch Houot, Fabrice Jardin, Eric Van Den Neste, Morgane Cheminant, Franck Morschhauser, Mary Callanan, Violaine Safar, Remy Gressin, Olivier Hermine, Steven Le Gouill
Journal: Journal of Clinical Oncology (2023)

JCO
Understanding Homelessness Among Young People to Improve Outcomes
Authors: Norweeta G. Milburn, Eric Rice, Laura Petry
Journal: Annual Review of Clinical Psychology (2023)

In the United States, an estimated 4.2 million young people experience homelessness during critical stages in their development—adolescence and emerging adulthood. While research on youth homelessness often emphasizes risk and vulnerability, the field must situate these issues within the developmental trajectories of adolescence and emerging adulthood to effectively prevent and end youth homelessness. This review uses the Risk Amplification and Abatement Model (RAAM) as a conceptual framework for contextualizing the landscape of youth homelessness research in the United States since 2010. An extension of ecological models of risk-taking, RAAM emphasizes both risk and resilience, positing that negative as well as positive socialization processes across interactions with family, peers, social services, and formal institutions affect key housing, health, and behavioral outcomes for youth experiencing homelessness. This review applies RAAM to our understanding of the causes and consequences of youth homelessness, recent interventions, and recommendations for future directions.
Correction to: Lessons learned from phase 3 trials of immunotherapy for glioblastoma: Time for longitudinal sampling?
Journal: Neuro-Oncology (2023)

the DCVax-L group exhibited a mOS of 19.3 months, almost 4 months lower than the one reported previouslyThe correct version should state:In this manuscript, the data were reanalyzed and now the DCVax-L group exhibited a mOS of 19.3 months from randomization and 22.4 months from surgery.This error has been corrected online.
68Ga-Oxine–Labeled Erythrocytes as a New PET Tracer for the Localization of Gastrointestinal Bleeding
Authors: Theresa Leder, Christian Kühnel, Sebastian Gröber, Robert Drescher, Martin Freesmeyer
Journal: Clinical Nuclear Medicine (2023)

Abstract A 69-year-old man presented with recurring drops in hemoglobin levels and suspected gastrointestinal bleeding. Endoscopy did not show a site of bleeding so further examinations became necessary. Scintigraphy and SPECT/CT with 99m TcO 4 − –labeled red blood cells were performed without evidence of a hemorrhage. Based on an established protocol for splenic PET/CT, autologous erythrocytes can be labeled with 68 Ga-oxine and used as a tracer for the localization of active bleeding sites. In the patient, PET/CT with 68 Ga-oxine–labeled undamaged erythrocytes was performed successfully and revealed a hemorrhage of the gastric corpus that was confirmed and treated by endoscopy.
Tumor-Specific Activity of Precision Medicines in the NCI-MATCH Trial
Authors: Ivvone Zhou, Deborah Plana, Adam C. Palmer
Journal: Clinical Cancer Research (2023)

Abstract Purpose: National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) is a precision medicine basket trial designed to test the effectiveness of treating cancers based on specific genetic changes in patients’ tumors, regardless of cancer type. Multiple subprotocols have each tested different targeted therapies matched to specific genetic aberrations. Most subprotocols exhibited low rates of tumor shrinkage as evaluated across all tumor types enrolled. We hypothesized that these results may arise because these precision cancer therapies have tumor type-specific efficacy, as is common among other cancer therapies. Experimental Design: To test the hypothesis that certain tumor types are more sensitive to specific therapies than other tumor types, we applied permutation testing to tumor volume change and progression-free survival data from 10 published NCI-MATCH subprotocols (together n = 435 patients). FDR was controlled by the Benjamini–Hochberg procedure. Results: Six of ten subprotocols exhibited statistically significant evidence of tumor-specific drug sensitivity, four of which were previously considered negative based on response rate across all tumors. This signal-finding analysis highlights potential uses of FGFR tyrosine kinase inhibition in urothelial carcinomas with actionable FGFR aberrations and MEK inhibition in lung cancers with BRAF non-V600E mutations. In addition, it identifies low-grade serious ovarian carcinoma with BRAF v600E mutation as especially sensitive to BRAF and MEK co-inhibition (dabrafenib plus trametinib), a treatment that received accelerated FDA approval for advanced solid tumors with BRAF v600E mutation. Conclusions: These findings support the value of basket trials because even when precision medicines do not have tumor-agnostic activity, basket trials can identify tumor-specific activity for future study.
Preterm Birth and Metal Mixture Exposure among Pregnant Women from the Navajo Birth Cohort Study
Authors: Joseph H. Hoover, Eric S. Coker, Esther Erdei, Li Luo, David Begay, Debra MacKenzie, Johnnye Lewis
Journal: Environmental Health Perspectives (2023)

Preterm birth (PTB), defined as birth before 37 wk gestation, is associated with hypertension, diabetes, inadequate prenatal care, unemployment or poverty, and metal exposure. Indigenous individuals are more likely to have maternal risk factors associated with PTB compared with other populations in the United States; however, the role of environmental metals on PTB among pregnant Indigenous women remains uncertain. Previous research identified associations between PTB and individual metals, but there is limited investigation on metal mixtures and this birth outcome.
State-of-the-Science Data and Methods Need to Guide Place-Based Efforts to Reduce Air Pollution Inequity
Authors: Julia M. Gohlke, Maria H. Harris, Ananya Roy, Tammy M. Thompson, Mindi DePaola, Ramón A. Alvarez, Susan C. Anenberg, Joshua S. Apte, Mary Angelique G. Demetillo, Isabella M. Dressel, Gaige H. Kerr, Julian D. Marshall, Aileen E. Nowlan, Regan F. Patterson, Sally E. Pusede, Veronica A. Southerland, Sarah A. Vogel
Journal: Environmental Health Perspectives (2023)

Recently enacted environmental justice policies in the United States at the state and federal level emphasize addressing place-based inequities, including persistent disparities in air pollution exposure and associated health impacts. Advances in air quality measurement, models, and analytic methods have demonstrated the importance of finer-scale data and analysis in accurately quantifying the extent of inequity in intraurban pollution exposure, although the necessary degree of spatial resolution remains a complex and context-dependent question.The objectives of this commentary were to a) discuss ways to maximize and evaluate the effectiveness of efforts to reduce air pollution disparities, and b) argue that environmental regulators must employ improved methods to project, measure, and track the distributional impacts of new policies at finer geographic and temporal scales.The historic federal investments from the Inflation Reduction Act, the Infrastructure Investment and Jobs Act, and the Biden Administration's commitment to Justice40 present an unprecedented opportunity to advance climate and energy policies that deliver real reductions in pollution-related health inequities. In our opinion, scientists, advocates, policymakers, and implementing agencies must work together to harness critical advances in air quality measurements, models, and analytic methods to ensure success. https://doi.org/10.1289/EHP13063.
Seminar: Scalable Preprocessing Tools for Exposomic Data Analysis
Authors: Stephen K. Grady, Levente Dojcsak, Emily W. Harville, Maeve E. Wallace, Dovile Vilda, Macarius M. Donneyong, Darryl B. Hood, R. Burciaga Valdez, Aramandla Ramesh, Wansoo Im, Patricia Matthews-Juarez, Paul D. Juarez, Michael A. Langston
Journal: Environmental Health Perspectives (2023)

The exposome serves as a popular framework in which to study exposures from chemical and nonchemical stressors across the life course and the differing roles that these exposures can play in human health. As a result, data relevant to the exposome have been used as a resource in the quest to untangle complicated health trajectories and help connect the dots from exposures to adverse outcome pathways.
Nonbinary people: Perceived social support in personal relationships and (virtual) communities
Authors: Teresa Teixeira, Nuno Santos Carneiro, Conceição Nogueira
Journal: International Journal of Transgender Health (2023)

Nonbinary individuals grapple with societal and individual pressures from a pervasive lack of comprehension, acknowledgment, and affirmative social representation. This dearth of a societal conversation recognizing the validity of nonbinary identities leads to instances of discrimination. Social support is recognized as a buffer to these experiences and is positively related to better physical and psychological health.