tbuckley/cabot-search huggingface dataset:
Deep learning for automatic organ and tumor segmentation in nanomedicine pharmacokinetics
Authors: Alex Dhaliwal, Jun Ma, Mark Zheng, Qing Lyu, Maneesha A. Rajora, Shihao Ma, Laura Oliva, Anthony Ku, Michael Valic, Bo Wang, Gang Zheng
Journal: Theranostics (2024)

Rationale: Multimodal imaging provides important pharmacokinetic and dosimetry information during nanomedicine development and optimization.However, accurate quantitation is time-consuming, resource intensive, and requires anatomical expertise.Methods: We present NanoMASK: a 3D U-Net adapted deep learning tool capable of rapid, automatic organ segmentation of multimodal imaging data that can output key clinical dosimetry metrics without manual intervention.This model was trained on 355 manually-contoured PET/CT data volumes of mice injected with a variety of nanomaterials and imaged over 48 hours.Results: NanoMASK produced 3-dimensional contours of the heart, lungs, liver, spleen, kidneys, and tumor with high volumetric accuracy (pan-organ average %DSC of 92.5).Pharmacokinetic metrics including %ID/cc, %ID, and SUVmax achieved correlation coefficients exceeding R = 0.987 and relative mean errors below 0.2%.NanoMASK was applied to novel datasets of lipid nanoparticles and antibody-drug conjugates with a minimal drop in accuracy, illustrating its generalizability to different classes of nanomedicines.Furthermore, 20 additional auto-segmentation models were developed using training data subsets based on image modality, experimental imaging timepoint, and tumor status.These were used to explore the fundamental biases and dependencies of auto-segmentation models built on a 3D U-Net architecture, revealing significant differential impacts on organ segmentation accuracy.Conclusions: NanoMASK is an easy-to-use, adaptable tool for improving accuracy and throughput in imaging-based pharmacokinetic studies of nanomedicine.It has been made publicly available to all readers for automatic segmentation and pharmacokinetic analysis across a diverse array of nanoparticles, expediting agent development.
Misinterpretations and Omissions: A Critical Response to Goodwin and Colleagues’ Commentary on Psilocybin-Assisted Therapy
Authors: Kelley C. O’Donnell, Brian T. Anderson, Frederick S. Barrett, Michael P. Bogenschutz, Charles S. Grob, Peter S. Hendricks, Benjamin Kelmendi, Sandeep M. Nayak, Christopher R. Nicholas, Casey A. Paleos, Christopher S. Stauffer, Natalie Gukasyan
Journal: American Journal of Psychiatry (2024)
SGK3 promotes vascular calcification via Pit-1 in chronic kidney disease
Authors: Qing-Qing Dong, Yu-Chi Tu, Pan Gao, Qian-Qian Liao, Peng Zhou, Hui Zhang, Hua-Pan Shu, Lu-Lu Sun, Li Feng, Li-Jun Yao
Journal: Theranostics (2024)

Rationale: Vascular calcification (VC) is a life-threatening complication in patients with chronic kidney disease (CKD) caused mainly by hyperphosphatemia.However, the regulation of VC remains unclear despite extensive research.Although serum-and glucocorticoid-induced kinase 3 (SGK3) regulate the sodium-dependent phosphate cotransporters in the intestine and kidney, its effect on VC in CKD remains unknown.Additionally, type III sodium-dependent phosphate cotransporter-1 (Pit-1) plays a significant role in VC development induced by high phosphate in vascular smooth muscle cells (VSMCs).However, it remains unclear whether SGK3 regulates Pit-1 and how exactly SGK3 promotes VC in CKD via Pit-1 at the molecular level.Thus, we investigated the role of SGK3 in the certified outflow vein of arteriovenous fistulas (AVF) and aortas of uremic mice.Methods and Results: In our study, using uremic mice, we observed a significant upregulation of SGK3 and calcium deposition in certified outflow veins of the AVF and aortas, and the increase expression of SGK3 was positively correlated with calcium deposition in uremic aortas.In vitro, the downregulation of SGK3 reversed VSMCs calcification and phenotype switching induced by high phosphate.Mechanistically, SGK3 activation enhanced the mRNA transcription of Pit-1 through NF-κB, downregulated the ubiquitin-proteasome mediated degradation of Pit-1 via inhibiting the activity of neural precursor cells expressing developmentally downregulated protein 4 subtype 2 (Nedd4-2), an E3 ubiquitin ligase.Moreover, under high phosphate stimulation, the enhanced phosphate uptake induced by SGK3 activation was independent of the increased protein expression of Pit-1.Our co-immunoprecipitation and in vitro kinase assays confirmed that SGK3 interacts with Pit-1 through Thr468 in loop7, leading to enhanced phosphate uptake.Conclusion: Thus, it is justifiable to conclude that SGK3 promotes VC in CKD by enhancing the expression and activities of Pit-1, which indicate that SGK3 could be a therapeutic target for VC in CKD.
Annotation of CD8<sup>+</sup> T-cell function via ICAM-1 imaging identifies FAK inhibition as an adjuvant to augment the antitumor immunity of radiotherapy
Authors: Ting Zhang, Yining Zhang, Yang Zhao, Rui Song, Yanpu Wang, Kui Li, Haoyi Zhou, Feng Wang, Shixin Zhou, Meixin Zhao, Hua Zhu, Weifang Zhang, Zhi Yang, Zhaofei Liu
Journal: Theranostics (2024)

Background: Radiotherapy (RT) may trigger systemic antitumor immunity, manifesting as regression of non-irradiated lesions (abscopal effect).Intracellular adhesion molecule-1 (ICAM-1) is a key molecule involved in the abscopal effect of RT.However, the specific function of ICAM-1 in CD8 + T cells during antitumor immune responses remains unclear.Herein, we investigated whether noninvasive imaging of ICAM-1 can be used to annotate CD8 + T-cell function, thereby better selecting combinational therapy to enhance the antitumor immunity induced by RT.Methods: Using knockout mouse models, we investigated the role of ICAM-1 expressed on CD8 + T cells in the antitumor immunity of RT and conducted drug screening guided by ICAM-1-targeted noninvasive imaging. Results:The systemic antitumor effect of RT relies on the expression of ICAM-1 on CD8 + T cells.ICAM-1 expression is essential for CD8 + T-cell activation, proliferation, and effector function.Noninvasive annotation of the proliferation and effector function of CD8 + T cells by ICAM-1-targeted imaging identified VS-6063, a focal adhesion kinase inhibitor, as a new adjuvant to augment systemic antitumor immunity of RT in an immunologically "cold" tumor model.Mechanistically, VS-6063 overcomes the physical barriers in tumors and promotes the migration and infiltration of CD8 + T cells primed by RT into distant tumors.Conclusion: Our findings highlight that molecular imaging of ICAM-1 levels provides a dynamic readout of the proliferation and effector function of tumor-infiltrating CD8 + T cells, which facilitates the high-throughput exploitation of new combinational drugs to maximize the systemic antitumor effect of RT.
Human organoids-on-chips for biomedical research and applications
Authors: Hui Wang, Xiufan Ning, Feng Zhao, Hui Zhao, Dong Li
Journal: Theranostics (2024)

Human organoids-on-chips (OrgOCs) are the synergism of human organoids (HOs) technology and microfluidic organs-on-chips (OOCs).OOCs can mimic extrinsic characteristics of organs, such as environmental clues of living tissue, while HOs are more amenable to biological analysis and genetic manipulation.By spatial cooperation, OrgOCs served as 3D organotypic living models allowing them to recapitulate critical tissue-specific properties and forecast human responses and outcomes.It represents a giant leap forward from the regular 2D cell monolayers and animal models in the improved human ecological niche modeling.In recent years, OrgOCs have offered potential promises for clinical studies and advanced the preclinical-to-clinical translation in medical and industrial fields.In this review, we highlight the cutting-edge achievements in OrgOCs, introduce the key features of OrgOCs architectures, and share the revolutionary applications in basic biology, disease modeling, preclinical assay and precision medicine.Furthermore, we discuss how to combine a wide range of disciplines with OrgOCs and accelerate translational applications, as well as the challenges and opportunities of OrgOCs in biomedical research and applications.
Macroscale pseudo-spheroids fabricated using methacrylated collagen-coated cells
Authors: SooJung Chae, Hyeongjin Lee, Dongryeol Ryu, GeunHyung Kim
Journal: Theranostics (2024)

Rationale: Cell spheroids have shown great promise as tools for creating effective three-dimensional (3D) tissue models, facilitating tissue reconstruction and organoid development, due to their high cell density and efficient cellular interactions.However, a significant challenge persists in creating large-scale tissue structures with a 3D geometrical architecture using spheroids, due to the continual condensation and reorganization of cells and their environments.Methods: The spherical cell aggregates (pseudo-cell spheroids) or macroscale cell aggregates were obtained by coating each adipose-derived stem cell (hASC) with methacrylated collagen (Col-Ma).Subsequently, the coated cells were printed into an alginate supporting bath and photocrosslinked through exposure to UV light.To assess the effectiveness of this procedure on regenerative potential, the generated cell aggregates were compared with conventional cell spheroids and bioprinted cell constructs using immunofluorescent staining and quantification of myogenic-related gene expressions.Moreover, the bioconstructs were implanted into a mouse model with volumetric muscle loss to further elucidate their regenerative and functional recovery properties.Results: The use of Col-Ma as a cell-coating material enables the rapid and physical aggregation of cells within several hours, regardless of the cell type.Furthermore, Col-Ma-coated cell aggregates can provide relatively lower hypoxic conditions than cell spheroids fabricated using the hanging drop method owing to the thin porous Col-Ma layer coated on the cells.In addition, the resulting structures maintain their geometrical architecture following cell fusion and possess the potential for efficient scale-up and 3D complex shape formation, making them more suitable for clinical applications than conventional cell spheroids.Finally, the feasibility of the Col-Ma-coated cylindrical human adipose-derived stem cells aggregates was assessed through implantation in a mouse volumetric muscle loss model, showing a significantly higher regenerative ability of muscle tissue than the normally bioprinted cell construct.Conclusion: Our newly proposed method has meaningful potential for various tissue engineering applications, supported by the improved cellular activities and efficient muscle regeneration observed in both in vitro and in vivo studies, and organ-chip models.
NRF2 promotes radiation resistance by cooperating with TOPBP1 to activate the ATR-CHK1 signaling pathway
Authors: Xiaohui Sun, Mingxin Dong, Jiale Li, Yuxiao Sun, Yu Gao, Yan Wang, Liqing Du, Yang Liu, Kaihua Ji, Ningning He, Jinhan Wang, Manman Zhang, Huijuan Song, Chang Xu, Qiang Liu
Journal: Theranostics (2024)

Radiation resistance is the main limitation of the application of radiotherapy. Ionizing radiation (IR) kills cancer cells mainly by causing DNA damage, particularly double-strand breaks (DSBs). Radioresistant cancer cells have developed the robust capability of DNA damage repair to survive IR. Nuclear factor erythroid 2-related factor 2 (NRF2) has been correlated with radiation resistance. We previously reported a novel function of NRF2 as an ATR activator in response to DSBs. However, little is known about the mechanism that how NRF2 regulates DNA damage repair and radiation resistance.
Bioengineered hydrogels enhance ex vivo preservation of patient-derived tumor explants for drug evaluation
Authors: Christabella Adine, Kanishka Fernando, Nicholas Ching Wei Ho, Hong Sheng Quah, Samantha Shu Wen Ho, Kenny Zhuoran Wu, Karen Wei Weng Teng, Camille Arcinas, Ling Li, Kelly Ha, Joey Wei Ling Chew, Chenhui Wang, Nathaniel Sheng Hua Too, Joe Poh Sheng Yeong, Daniel Shao Weng Tan, Iain Bee Huat Tan, Rahul Nagadia, Claramae Shulyn Chia, Dominique Macalinao, Hariraman Bhuvaneswari, N Gopalakrishna Iyer, Eliza Li Shan Fong
Journal: Biomaterials (2024)
Biology-driven therapy advances in high-grade serous ovarian cancer
Authors: Yinu Wang, Alexander James Duval, Mazhar Adli, Daniela Matei
Journal: Journal of Clinical Investigation (2024)

Following a period of slow progress, the completion of genome sequencing and the paradigm shift relative to the cell of origin for high grade serous ovarian cancer (HGSOC) led to a new perspective on the biology and therapeutic solutions for this deadly cancer. Experimental models were revisited to address old questions, and improved tools were generated. Additional pathways emerging as drivers of ovarian tumorigenesis and key dependencies for therapeutic targeting, in particular, VEGF-driven angiogenesis and homologous recombination deficiency, were discovered. Molecular profiling of histological subtypes of ovarian cancer defined distinct genetic events for each entity, enabling the first attempts toward personalized treatment. Armed with this knowledge, HGSOC treatment was revised to include new agents. Among them, PARP inhibitors (PARPis) were shown to induce unprecedented improvement in clinical benefit for selected subsets of patients. Research on mechanisms of resistance to PARPis is beginning to discover vulnerabilities and point to new treatment possibilities. This Review highlights these advances, the remaining challenges, and unsolved problems in the field.
Immune mechanisms of granuloma formation in sarcoidosis and tuberculosis
Authors: Praveen Weeratunga, David R. Moller, Ling-Pei Ho
Journal: Journal of Clinical Investigation (2024)

Sarcoidosis is a complex immune-mediated disease characterized by clusters of immune cells called granulomas. Despite major steps in understanding the cause of this disease, many questions remain. In this Review, we perform a mechanistic interrogation of the immune activities that contribute to granuloma formation in sarcoidosis and compare these processes with its closest mimic, tuberculosis, highlighting shared and divergent immune activities. We examine how Mycobacterium tuberculosis is sensed by the immune system; how the granuloma is initiated, formed, and perpetuated in tuberculosis compared with sarcoidosis; and the role of major innate and adaptive immune cells in shaping these processes. Finally, we draw these findings together around several recent high-resolution studies of the granuloma in situ that utilized the latest advances in single-cell technology combined with spatial methods to analyze plausible disease mechanisms. We conclude with an overall view of granuloma formation in sarcoidosis.
In vivo gene editing of CAMKIID: out with the bad and in with the good
Authors: John E. Smith, Henk Granzier
Journal: Journal of Clinical Investigation (2024)

The ability to change an organism's DNA through gene editing is of great importance for the prevention and treatment of genetic and acquired diseases. Rapid progress has been made during the last decade due to the discovery and refinement of CRISPR/Cas9 as an accurate, fast, and reliable genome editing technique. In this issue of the JCI, Lebek et al. present the culmination from a line of work in the Olson laboratory focused on in vivo gene editing of CAMK2D. The paper presents a combined state-of-the-art gene therapy approach that demonstrates how gene therapy can yield cardioprotection in a mouse model and takes notable steps toward potential applicability in patients.
Extreme Heat and Occupational Health Risks
Authors: Kathryn Gibb, Stella Beckman, Ximena P. Vergara, Amy Heinzerling, Robert Harrison
Journal: Annual Review of Public Health (2024)

Climate change poses a significant occupational health hazard. Rising temperatures and more frequent heat waves are expected to cause increasing heat-related morbidity and mortality for workers across the globe. Agricultural, construction, military, firefighting, mining, and manufacturing workers are at particularly high risk for heat-related illness (HRI). Various factors, including ambient temperatures, personal protective equipment, work arrangements, physical exertion, and work with heavy equipment may put workers at higher risk for HRI. While extreme heat will impact workers across the world, workers in low- and middle-income countries will be disproportionately affected. Tracking occupational HRI will be critical to informing prevention and mitigation strategies. Renewed investment in these strategies, including workplace heat prevention programs and regulatory standards for indoor and outdoor workers, will be needed. Additional research is needed to evaluate the effectiveness of interventions in order to successfully reduce the risk of HRI in the workplace.
Climate Change, Landscape Fires, and Human Health: A Global Perspective
Authors: Fay H. Johnston, Grant Williamson, Nicolas Borchers-Arriagada, Sarah B. Henderson, David M.J.S. Bowman
Journal: Annual Review of Public Health (2024)

Landscape fires are an integral component of the Earth system and a feature of prehistoric, subsistence, and industrial economies. Specific spatiotemporal patterns of landscape fire occur in different locations around the world, shaped by the interactions between environmental and human drivers of fire activity. Seven distinct types of landscape fire emerge from these interactions: remote area fires, wildfire disasters, savanna fires, Indigenous burning, prescribed burning, agricultural burning, and deforestation fires. All can have substantial impacts on human health and well-being directly and indirectly through (a) exposure to heat flux (e.g., injuries and destructive impacts), (b) emissions (e.g., smoke-related health impacts), and (c) altered ecosystem functioning (e.g., biodiversity, amenity, water quality, and climate impacts). Minimizing the adverse effects of landscape fires on population health requires understanding how human and environmental influences on fire impacts can be modified through interventions targeted at individual, community, and regional levels.
Warning Labels as a Public Health Intervention: Effects and Challenges for Tobacco, Cannabis, and Opioid Medications
Authors: Lucy Popova, Zachary B. Massey, Nicholas A. Giordano
Journal: Annual Review of Public Health (2024)

Warning labels help consumers understand product risks, enabling informed decisions. Since the 1966 introduction of cigarette warning labels in the United States, research has determined the most effective message content (health effects information) and format (brand-free packaging with pictures). However, new challenges have emerged. This article reviews the current state of tobacco warning labels in the United States, where legal battles have stalled pictorial cigarette warnings and new products such as electronic cigarettes and synthetic nicotine products pose unknown health risks. This article describes the emerging research on cannabis warnings; as more places legalize recreational cannabis, they are adopting lessons from tobacco warnings. However, its uncertain legal status and widespread underestimation of harms impede strict warning standards. The article also reviews opioid medication warning labels, suggesting that lessons from tobacco could help in the development of effective and culturally appropriate FDA-compliant opioid warning labels that promote safe medication use and increased co-dispensing of naloxone.
Leveraging Implementation Science to Advance Environmental Justice Research and Achieve Health Equity through Neighborhood and Policy Interventions
Authors: Laura Ellen Ashcraft, Keven I. Cabrera, Meghan B. Lane-Fall, Eugenia C. South
Journal: Annual Review of Public Health (2024)

Environmental justice research is increasingly focused on community-engaged, participatory investigations that test interventions to improve health. Such research is primed for the use of implementation science–informed approaches to optimize the uptake and use of interventions proven to be effective. This review identifies synergies between implementation science and environmental justice with the goal of advancing both disciplines. Specifically, the article synthesizes the literature on neighborhood-, community-, and policy-level interventions in environmental health that address underlying structural determinants (e.g., structural racism) and social determinants of health. Opportunities to facilitate and scale the equitable implementation of evidence-based environmental health interventions are highlighted, using urban greening as an illustrative example. An environmental justice–focused version of the implementation science subway is provided, which highlights these principles: Remember and Reflect, Restore and Reclaim, and Reinvest. The review concludes with existing gaps and future directions to advance the science of implementation to promote environmental justice.
Challenges and Opportunities for Paving the Road to Global Health Equity Through Implementation Science
Authors: Prajakta Adsul, Rachel C. Shelton, April Oh, Nathalie Moise, Juliet Iwelunmor, Derek M. Griffith
Journal: Annual Review of Public Health (2024)

Implementation science focuses on enhancing the widespread uptake of evidence-based interventions into routine practice to improve population health. However, optimizing implementation science to promote health equity in domestic and global resource-limited settings requires considering historical and sociopolitical processes (e.g., colonization, structural racism) and centering in local sociocultural and indigenous cultures and values. This review weaves together principles of decolonization and antiracism to inform critical and reflexive perspectives on partnerships that incorporate a focus on implementation science, with the goal of making progress toward global health equity. From an implementation science perspective, wesynthesize examples of public health evidence-based interventions, strategies, and outcomes applied in global settings that are promising for health equity, alongside a critical examination of partnerships, context, and frameworks operationalized in these studies. We conclude with key future directions to optimize the application of implementation science with a justice orientation to promote global health equity.
Evidence for Policies and Practices to Address Global Food Insecurity
Authors: Lora Iannotti, Eliza Kleban, Patrizia Fracassi, Stineke Oenema, Chessa Lutter
Journal: Annual Review of Public Health (2024)

Food insecurity affects an estimated 691–783 million people globally and is disproportionately high in Africa and Asia. It arises from poverty, armed conflict, and climate change, among other demographic and globalization forces. This review summarizes evidence for policies and practices across five elements of the agrifood system framework and identifies gaps that inform an agenda for future research. Under availability, imbalanced agriculture policies protect primarily staple food producers, and there is limited evidence on food security impacts for smallholder and women food producers. Evidence supports the use of cash transfers and food aid for affordability and school feeding for multiple benefits. Food-based dietary guidelines can improve the nutritional quality of dietary patterns, yet they may not reflect the latest evidence or food supplies. Evidence from the newer food environment elements, promotion and sustainability, while relatively minimal, provides insight into achieving long-term impacts. To eliminate hunger, our global community should embrace integrated approaches and bring evidence-based policies and practices to scale.