tbuckley/cabot-search huggingface dataset:
Tumoroid‐On‐a‐Plate (ToP): Physiologically Relevant Cancer Model Generation and Therapeutic Screening
Authors: Amir Seyfoori, Kaiwen Liu, Hector J. Caruncho, Patrick B. Walter, Mohsen Akbari
Journal: Advanced Healthcare Materials (2024)

Abstract Employing three‐dimensional (3D) in vitro models, including tumor organoids and spheroids, stands pivotal in enhancing cancer therapy. These models bridge the gap between two‐dimensional (2D) cell cultures and complex in vivo environments and offer versatile tools for comprehensive studies into cancer progression, drug responses, and tailored therapies. This study introduces the Tumoroid‐on‐a‐Plate (ToP) device, an innovative ope‐surface microfluidic platform designed to create predictive 3D models of solid tumors. The ToP device combines tumor mass, stromal cells, and extracellular matrix (ECM) components, to closely replicate the microenvironment of glioblastoma (GBM) and pancreatic adenocarcinoma (PDAC). Using the advanced ToP model and testing various GBM ECM compositions such as collagen and Rreelin within the model, we can assess how specific elements affect GBM invasiveness. The ToP in vitro model also enables screening chemotherapeutics such as temozolomide and iron‐chelators in a single and binary treatment setting on the complex ECM‐embedded tumoroids to evaluate their toxicity on GBM and PDAC models viability and apoptosis. Furthermore, co‐culturing PDAC tumoroids with human‐derived fibroblasts reveals the pro‐invasive influence of stromal elements on tumor growth and drug response. This research underscores the value of advanced 3D models like ToP in advancing the understanding of cancer complexity and therapy responses.
Immune dynamics shaping pre-metastatic and metastatic niches in liver metastases: from molecular mechanisms to therapeutic strategies
Authors: Chang Zhu, Jing-Yu Liao, Yi-Yang Liu, Ze-Yu Chen, Rui-Zhi Chang, Xiao-Ping Chen, Bi-Xiang Zhang, Jun-Nan Liang
Journal: Molecular Cancer (2024)

Liver metastases are commonly detected in the advanced stages of various malignant tumors, representing a significant clinical challenge. Throughout the process of liver metastases formation, immune cells play a pivotal role, particularly in the pre-metastatic and metastatic niches within the liver. Immune cells establish extensive and intricate interactions with tumor cells and other components in the liver, collectively promoting and sustaining the growth of liver metastases. Despite the limited efficacy of existing therapeutic modalities against some advanced liver metastases, novel immune-based treatment approaches are continuously being explored and validated. Building on the systematic elucidation of the immunosuppressive characteristics of liver metastases, we explored the potential of novel immunotherapies applicable to patients with liver metastases from multiple dimensions.
Lactic acid bacteria derived extracellular vesicles: emerging bioactive nanoparticles in modulating host health
Authors: Mohan Li, Bingyong Mao, Xin Tang, Qiuxiang Zhang, Jianxin Zhao, Wei Chen, Shumao Cui
Journal: Gut Microbes (2024)

Lactic acid bacteria derived extracellular vesicles (LAB-EVs) are nano-sized and carry a variety of biological cargoes. LAB-EVs have proven to be potential mediators of intercellular communication, serving not only the parental bacteria but also the host cell in both physiology and pathology. LAB-EVs are therapeutically beneficial in various diseases through a cell-free strategy. Particularly, EVs secreted from probiotics can exert health-promoting effects on humans. Additionally, the excitement around LAB-EVs has extended to their use as nano-sized drug carriers, since they can traverse biological barriers. Nevertheless, significant challenges in terms of isolation, characterization, and safety must be addressed to ensure the clinical application of LAB-EVs. Therefore, this review emphasizes the isolation and purification methods of LAB-EVs. We also introduce the biogenesis, cargo sorting, and functions of LAB-EVs. The biological regulatory factors of LAB-EVs are summarized and discussed. Special attention is given to the interaction between LAB-EVs and the host, their ability to maintain intestinal homeostasis, and the immunity and inflammation they induce in diverse diseases. Furthermore, we summarize the characterization of LAB-EV cargoes by advanced analytical methods such as proteomics. Finally, we discuss the challenges and opportunities of LAB-EVs as a means of diagnosis and treatment in clinical translation. In conclusion, this review scrutinizes current knowledge and provides guidelines for proposing new perspectives for future research in the field of LAB-EVs.
Estimates of resource use in the public-sector health-care system and the effect of strengthening health-care services in Malawi during 2015–19: a modelling study (Thanzi La Onse)
Authors: Timothy B Hallett, Tara D Mangal, Asif U Tamuri, Nimalan Arinaminpathy, Valentina Cambiano, Martin Chalkley, Joseph H Collins, Jonathan Cooper, Matthew S Gillman, Mosè Giordano, Matthew M Graham, William Graham, Iwona Hawryluk, Eva Janoušková, Britta L Jewell, Ines Li Lin, Robert Manning Smith, Gerald Manthalu, Emmanuel Mnjowe, Sakshi Mohan, Margherita Molaro, Wingston Ng'ambi, Dominic Nkhoma, Stefan Piatek, Paul Revill, Alison Rodger, Dimitra Salmanidou, Bingling She, Mikaela Smit, Pakwanja D Twea, Tim Colbourn, Joseph Mfutso-Bengo, Andrew N Phillips
Journal: The Lancet Global Health (2024)

In all health-care systems, decisions need to be made regarding allocation of available resources. Evidence is needed for these decisions, especially in low-income countries. We aimed to estimate how health-care resources provided by the public sector were used in Malawi during 2015-19 and to estimate the effects of strengthening health-care services.
Clinical remission attainment, definitions, and correlates among patients with severe asthma treated with biologics: a systematic review and meta-analysis
Authors: Amy Shackleford, Liam G Heaney, Charlene Redmond, P Jane McDowell, John Busby
Journal: The Lancet Respiratory Medicine (2024)

Clinical remission has emerged as an important treatment goal in severe asthma; however, studies have reported variable attainment due to differences in study populations, definitions, and methods. We aimed to perform a systematic review and meta-analysis of clinical remission attainment, definitions, and correlates among patients with severe asthma who have been treated with biologics.
Hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer (CHIPOR): a randomised, open-label, phase 3 trial
Authors: Jean-Marc Classe, Pierre Meeus, Delphine Hudry, Romuald Wernert, François Quenet, Frédéric Marchal, Gilles Houvenaeghel, Anne-Sophie Bats, Fabrice Lecuru, Gwenaël Ferron, Cécile Brigand, Dominique Berton, Laurence Gladieff, Florence Joly, Isabelle Ray-Coquard, Sylvaine Durand-Fontanier, Gabriel Liberale, Marc Pocard, Constantin Georgeac, Sébastien Gouy, Jean-Marc Guilloit, Frédéric Guyon, Cristina Costan, Jean-Marc Rousselet, Lara de Guerké, Naoual Bakrin, Emilie Brument, Elodie Martin, Bernard Asselain, Loïc Campion, Olivier Glehen
Journal: The Lancet Oncology (2024)
Global vaccination against hepatitis E virus: position paper from the ESGVH-ESCMID
Authors: Susanne Dudman, Arjana Zerja, İmran Hasanoğlu, Simona Ruta, Berend van Welzen, Laura Ambra Nicolini, Paul Yonga, Joakim Øverbø, Sumit Rawat, Selma Habibovic, Tan Bou Kim, Antonio Rivero-Juarez
Journal: Clinical Microbiology and Infection (2024)

Hepatitis E Virus (HEV) is a significant global health issue, impacting both low- and middle-income countries (LMICs) and industrialized nations. HEV genotypes 1 and 2, primarily transmitted through contaminated water, are endemic in LMICs, while genotypes 3 and 4 are zoonotically transmitted in industrialized regions. Acute HEV infection poses severe risks, particularly to pregnant women and immunocompromised individuals, while chronic HEV infection leads to serious complications in those with pre-existing liver disease and transplant recipients. The development of an HEV vaccine offers new prevention opportunities, though its availability and integration into global immunization programs remain limited.
Complex roles of autophagy in cancer development, immune evasion, and drug resistance
Authors: Xuegang Niu, Qi You, Kaijian Hou, Yu Tian, Penghui Wei, Yang Zhu, Bin Gao, Milad Ashrafizadeh, Amir Reza Aref, Alireza Kalbasi, Israel Cañadas, Gautam Sethi, Vinay Tergaonkar, Lingzhi Wang, Yuanxiang Lin, Dezhi Kang, Daniel J Klionsky
Journal: Drug Resistance Updates (2024)
Clinical Presentations and Treatment Outcomes in Extragenital Lichen Sclerosus: A 34-Year Multi-Institutional Retrospective Review
Authors: Shawn Afvari, Subin Lim, Britney Nguyen, Ruhi Kanwar, Christina Kraus, Neda Shahriari, Avery H LaChance
Journal: Journal of the American Academy of Dermatology (2024)
Bariatric Surgery Reduced Long-Term Mortality in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease and Cirrhosis
Authors: Nicholas A Rouillard, Scott D Barnett, Xinrong Zhang, Leslie Kam, Richie Manikat, Ramsey Cheung, Mindie H Nguyen
Journal: Clinical and Molecular Hepatology (2024)

With the obesity pandemic, metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease and a leading cause of end-stage liver disease and liver-related deaths in the U.S.A. Therefore, we aimed to compare the long-term outcomes of patients with MASLD and cirrhosis with and without bariatric surgery.
Prospect of emerging treatments for HBV functional cure
Authors: Rex Wan-Hin Hui, Lung-Yi Mak, James Fung, Wai-Kay Seto, Man-Fung Yuen
Journal: Clinical and Molecular Hepatology (2024)

Functional cure, defined as sustained hepatitis B surface antigen (HBsAg) seroclearance with unquantifiable hepatitis B virus (HBV) DNA at 24 weeks off treatment, is a favorable treatment endpoint in chronic hepatitis B (CHB). Nonetheless, functional cure is rarely attained with the current treatment modalities of nucleos(t)ide analogues (NUCs) and pegylated interferon alpha (Peg-IFNα). Multiple novel virus-targeting agents and immunomodulators are under development for HBV with functional cure as the treatment goal. Among virus-targeting agents, antisense oligonucleotides (ASOs) and small-interfering RNA (siRNAs) are the most advanced in the developmental pipeline, and can induce potent and sustainable HBsAg suppression. The other virus-targeting agents have varying effects on HBsAg and HBV DNA, depending on the drug mechanism. In contrast, immunomodulators have modest effects on HBsAg and have limited roles in monotherapy. Multiple combination regimens incorporating RNA interference agents with immunomodulators have been studied through many ongoing clinical trials. These combination strategies demonstrate synergistic effects in inducing functional cure, and will likely be the future direction of development. Despite the promising results, research is warranted to optimize treatment protocols and to establish criteria for NUC withdrawal after novel therapies. Functional cure is now an attainable target in CHB, and the emerging novel therapeutics will revolutionize CHB management.
FRONTIER-2: A phase 2b, long-term extension, dose-ranging study of oral JNJ-77242113 for the treatment of moderate-to-severe plaque psoriasis
Authors: Laura K Ferris, Jerry Bagel, Yu-Huei Huang, Andrew E Pink, Stephen K Tyring, Georgios Kokolakis, Amy M DeLozier, Shu Li, Yaung-Kaung Shen, Charles Iaconangelo, Takayuki Ota, Robert Bissonnette
Journal: Journal of the American Academy of Dermatology (2024)
Cutaneous Adverse Events of Osimertinib in Diverse Patient Populations with EGFR-mutated Non-Small Cell Lung Cancer: A Retrospective Cohort Analysis
Authors: Daniel S Alicea, Emily Miao, Peter Ch'en, Steven W Tuckman, Nitin Ohri, Balazs Halmos, Haiying Cheng, Matthew Lee, Beth N McLellan
Journal: Journal of the American Academy of Dermatology (2024)
Ferroptosis regulates hemolysis in stored murine and human red blood cells
Authors: Angelo D'Alessandro, Gregory R Keele, Ariel M Hay, Travis Nemkov, Eric J Earley, Daniel Stephenson, Matthew Vincent, Xutao Deng, Mars Stone, Monika Dzieciatkowska, Kirk C Hansen, Steven H Kleinman, Steven L Spitalnik, Nareg H Roubinian, Philip J Norris, Michael P Busch, Grier P Page, Brent Stockwell, Gary A Churchill, James C Zimring
Journal: Blood (2024)
Representational spaces in orbitofrontal and ventromedial prefrontal cortex: task states, values, and beyond
Authors: Nir Moneta, Shany Grossman, Nicolas W Schuck
Journal: Trends in Neurosciences (2024)

The orbitofrontal cortex (OFC) and ventromedial-prefrontal cortex (vmPFC) play a key role in decision-making and encode task states in addition to expected value. We review evidence suggesting a connection between value and state representations and argue that OFC / vmPFC integrate stimulus, context, and outcome information. Comparable encoding principles emerge in late layers of deep reinforcement learning (RL) models, where single nodes exhibit similar forms of mixed-selectivity, which enables flexible readout of relevant variables by downstream neurons. Based on these lines of evidence, we suggest that outcome-maximization leads to complex representational spaces that are insufficiently characterized by linear value signals that have been the focus of most prior research on the topic. Major outstanding questions concern the role of OFC/ vmPFC in learning across tasks, in encoding of task-irrelevant aspects, and the role of hippocampus-PFC interactions.
Identification and outcomes of acute kidney disease in patients presenting in Bolivia, Brazil, South Africa, and Nepal
Authors: Rhys D. R. Evans, Sanjib K. Sharma, Rolando Claure-Del Granado, Brett Cullis, Emmanuel A. Burdmann, FOS Franca, Junio Aguiar, Martyn Fredlund, Kelly Hendricks, Maria F. Iturricha-Caceres, Mamit Rai, Bhupendra Shah, Shyam Kafle, David C. Harris, Mike V. Rocco
Journal: PLoS Medicine (2024)

Background The International Society of Nephrology proposes an acute kidney disease (AKD) management strategy that includes a risk score to aid AKD identification in low- and low-middle-income countries (LLMICs). We investigated the performance of the risk score and determined kidney and patient outcomes from AKD at multiple LLMIC sites. Methods and findings Adult patients presenting to healthcare facilities in Bolivia, Brazil, South Africa, and Nepal were screened using a symptom-based risk score and clinical judgment. Those at AKD risk underwent serum creatinine testing, predominantly with a point-of-care (POC) device. Clinical data were collected prospectively between September 2018 and November 2020. We analyzed risk score performance and determined AKD outcomes at discharge and over follow-up of 90 days. A total of 4,311 patients were at increased risk of AKD, and 2,922 (67.8%) had AKD confirmed. AKD prevalence was 80.2% in patients enrolled based on the risk score and 32.5% when enrolled on clinical judgment alone ( p &lt; 0.0001). The area under the receiver operating characteristic curve was 0.73 for the risk score to detect AKD. Death during admission occurred in 84 (2.9%) patients with AKD and 3 (0.2%) patients without kidney disease ( p &lt; 0.0001). Death after discharge occurred in 206 (9.7%) AKD patients, and 1865 AKD patients underwent reassessment of kidney function after discharge; 902 (48.4%) patients had persistent kidney disease including 740 (39.7%) patients reclassified with de novo or previously undiagnosed chronic kidney disease (CKD). The study was pragmatically designed to assess outcomes as part of routine healthcare, and there was heterogeneity in clinical practice and outcomes between sites, in addition to selection bias during cohort identification. Conclusions The use of a risk score can aid AKD identification in LLMICs. High rates of persistent kidney disease and mortality after discharge highlight the importance of AKD follow-up in low-resource settings.
Moderate-Intensity Statin Plus Ezetimibe: Time to Rethink it as an Optimal Initial Lipid-Lowering Strategy
Authors: Sha Li, Hui-Hui Liu, Jian-Jun Li
Journal: Drugs (2024)

Achievement of low-density lipoprotein cholesterol (LDL-C) targets is crucial for the prevention of cardiovascular disease (CVD) in individuals with dyslipidaemia who are at high risk. Current guidelines recommend high-intensity statins at the highest tolerated dose as initial treatment to achieve LDL-C goals. However, the real-world situation is dismal: high-intensity statins are underused and achievement of LDL-C goals is suboptimal. Various challenges exist in the implementation of the recommended initial treatment strategy, including hesitancy to use high-intensity statins, non-adherence, and side effects, and the response to high-intensity statins varies across individuals. Emerging studies have shown another line of lipid-lowering, moderate-intensity statins in combination with ezetimibe, presenting considerable efficacy/effectiveness, along with better safety and adherence compared to statin intensification alone. Here we review the clinical evidence, treatment guidelines and challenges associated with high-intensity statins, and summarise the evidence on the combination therapy, moderate-intensity statin plus ezetimibe, which is the core strategy recommended by the 2023 Chinese Guideline for Lipid Management, as a possible primary treatment to achieve the LDL-C targets across several populations. The upfront use of a moderate-intensity statin plus ezetimibe may improve LDL-C control and lead to the prevention of CVD in real-world settings.
Psoriatic arthritis phenotype clusters and their association with treatment response: a real-world longitudinal cohort study from the psoriatic arthritis research consortium
Authors: Paras Karmacharya, Leslie J Crofford, Daniel W Byrne, Alisa Stephens-Shields, M Elaine Husni, Jose U Scher, Ethan Craig, Robert Fitzsimmons, Soumya M Reddy, Marina N Magrey, Jessica A Walsh, Alexis Ogdie
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Objectives</h3> To identify phenotype clusters and their trajectories in psoriatic arthritis (PsA) and examine the association of the clusters with treatment response in a real-world setting. <h3>Methods</h3> In the multicentre PsA Research Consortium (PARC) study, we applied factor analysis of mixed data to reduce dimensionality and collinearity, followed by hierarchical clustering on principal components. We then evaluated the transition of PsA clusters and their response to new immunomodulatory therapy and tumour necrosis factor inhibitor (TNFi). <h3>Results</h3> Among 627 patients with PsA, three clusters were identified: mild PsA and psoriasis only (PsO) (Cluster 1, 47.4%), severe PsA and mild PsO (Cluster 2, 34.3%) and severe PsA and severe PsO (Cluster 3, 18.3%). Among 339 patients starting or changing, significant differences in response were observed (mean follow-up of 0.7 years, SD 0.8), with Cluster 3 showing the largest improvements in cDAPSA and PsAID. No differences were found among those starting TNFi (n=218). cDAPSA remission and PsAID patient acceptable symptom state were achieved in 10% and 54%, respectively. Clusters remained stable over time despite treatment changes, though some transitions occurred, notably from Cluster 3 to milder clusters. <h3>Conclusion</h3> Data-driven clusters with distinct therapy responses identified in this real-world study highlight the extensive heterogeneity in PsA and the central role of psoriasis and musculoskeletal severity in treatment outcomes. Concurrently, these findings underscore the need for better outcome measures, particularly for individuals with lower disease activity.
Asking Why Is Necessary to Address Health Disparities: A Critical Approach for Solution-Oriented Environmental Epidemiological Research
Authors: Tamarra James-Todd, Kathryn S. Tomsho, Symielle A. Gaston, Kevin C. Elliott, Chandra L. Jackson
Journal: Environmental Health Perspectives (2024)

In environmental epidemiology, we use an array of tools from various, related disciplines to answer key questions about environmental exposures in relation to health outcomes. Typically, we ask questions related to what, who, where, when, and how. We value these questions because they contribute to novel scientific discovery and our understanding of disease etiology linked to environmental exposures. In addition, these questions help us better understand who might be at highest risk of exposure and subsequent risk of disease. Although necessary for the goals of environmental epidemiology, these questions are insufficient for addressing environmental health disparities. Specifically, these questions may be able to help us describe exposure-health outcome associations but are limited in their ability to move beyond identification to intervening on observed disparities to achieve environmental health equity.
Cohesin distribution alone predicts chromatin organization in yeast via conserved-current loop extrusion
Authors: Tianyu Yuan, Hao Yan, Kevin C Li, Ivan Surovtsev, Megan C King, Simon G J Mochrie
Journal: Genome biology (2024)

Abstract Background Inhomogeneous patterns of chromatin-chromatin contacts within 10–100-kb-sized regions of the genome are a generic feature of chromatin spatial organization. These features, termed topologically associating domains (TADs), have led to the loop extrusion factor (LEF) model. Currently, our ability to model TADs relies on the observation that in vertebrates TAD boundaries are correlated with DNA sequences that bind CTCF, which therefore is inferred to block loop extrusion. However, although TADs feature prominently in their Hi-C maps, non-vertebrate eukaryotes either do not express CTCF or show few TAD boundaries that correlate with CTCF sites. In all of these organisms, the counterparts of CTCF remain unknown, frustrating comparisons between Hi-C data and simulations. Results To extend the LEF model across the tree of life, here, we propose the conserved-current loop extrusion (CCLE) model that interprets loop-extruding cohesin as a nearly conserved probability current. From cohesin ChIP-seq data alone, we derive a position-dependent loop extrusion rate, allowing for a modified paradigm for loop extrusion, that goes beyond solely localized barriers to also include loop extrusion rates that vary continuously. We show that CCLE accurately predicts the TAD-scale Hi-C maps of interphase Schizosaccharomyces pombe , as well as those of meiotic and mitotic Saccharomyces cerevisiae , demonstrating its utility in organisms lacking CTCF. Conclusions The success of CCLE in yeasts suggests that loop extrusion by cohesin is indeed the primary mechanism underlying TADs in these systems. CCLE allows us to obtain loop extrusion parameters such as the LEF density and processivity, which compare well to independent estimates.
Altered sphingolipid biosynthetic flux and lipoprotein trafficking contribute to trans-fat-induced atherosclerosis
Authors: Jivani M Gengatharan, Michal K Handzlik, Zoya Y Chih, Maureen L Ruchhoeft, Patrick Secrest, Ethan L Ashley, Courtney R Green, Martina Wallace, Philip L S M Gordts, Christian M Metallo
Journal: Cell Metabolism (2024)