tbuckley/cabot-search huggingface dataset:
Organoids: development and applications in disease models, drug discovery, precision medicine, and regenerative medicine
Authors: Qigu Yao, Sheng Cheng, Qiaoling Pan, Jiong Yu, Guoqiang Cao, Lanjuan Li, Hongcui Cao
Journal: MedComm (2024)

Organoids are miniature, highly accurate representations of organs that capture the structure and unique functions of specific organs. Although the field of organoids has experienced exponential growth, driven by advances in artificial intelligence, gene editing, and bioinstrumentation, a comprehensive and accurate overview of organoid applications remains necessary. This review offers a detailed exploration of the historical origins and characteristics of various organoid types, their applications-including disease modeling, drug toxicity and efficacy assessments, precision medicine, and regenerative medicine-as well as the current challenges and future directions of organoid research. Organoids have proven instrumental in elucidating genetic cell fate in hereditary diseases, infectious diseases, metabolic disorders, and malignancies, as well as in the study of processes such as embryonic development, molecular mechanisms, and host-microbe interactions. Furthermore, the integration of organoid technology with artificial intelligence and microfluidics has significantly advanced large-scale, rapid, and cost-effective drug toxicity and efficacy assessments, thereby propelling progress in precision medicine. Finally, with the advent of high-performance materials, three-dimensional printing technology, and gene editing, organoids are also gaining prominence in the field of regenerative medicine. Our insights and predictions aim to provide valuable guidance to current researchers and to support the continued advancement of this rapidly developing field.
Intricate relationship between cancer stemness, metastasis, and drug resistance
Authors: Tikam Chand Dakal, Ravi Bhushan, Caiming Xu, Bhana Ram Gadi, Swaranjit Singh Cameotra, Vikas Yadav, Jarek Maciaczyk, Ingo G. H. Schmidt‐Wolf, Abhishek Kumar, Amit Sharma
Journal: MedComm (2024)

Cancer stem cells (CSCs) are widely acknowledged as the drivers of tumor initiation, epithelial-mesenchymal transition (EMT) progression, and metastasis. Originating from both hematologic and solid malignancies, CSCs exhibit quiescence, pluripotency, and self-renewal akin to normal stem cells, thus orchestrating tumor heterogeneity and growth. Through a dynamic interplay with the tumor microenvironment (TME) and intricate signaling cascades, CSCs undergo transitions from differentiated cancer cells, culminating in therapy resistance and disease recurrence. This review undertakes an in-depth analysis of the multifaceted mechanisms underlying cancer stemness and CSC-mediated resistance to therapy. Intrinsic factors encompassing the TME, hypoxic conditions, and oxidative stress, alongside extrinsic processes such as drug efflux mechanisms, collectively contribute to therapeutic resistance. An exploration into key signaling pathways, including JAK/STAT, WNT, NOTCH, and HEDGEHOG, sheds light on their pivotal roles in sustaining CSCs phenotypes. Insights gleaned from preclinical and clinical studies hold promise in refining drug discovery efforts and optimizing therapeutic interventions, especially chimeric antigen receptor (CAR)-T cell therapy, cytokine-induced killer (CIK) cell therapy, natural killer (NK) cell-mediated CSC-targeting and others. Ultimately use of cell sorting and single cell sequencing approaches for elucidating the fundamental characteristics and resistance mechanisms inherent in CSCs will enhance our comprehension of CSC and intratumor heterogeneity, which ultimately would inform about tailored and personalized interventions.
Sonographic Skin Features and Shear Wave Elastography in Distinguishing Active from Inactive Morphea Lesions: A Case-control Study
Authors: Ifa Etesami, Narges Azizi, Reyhaneh Sabrinejad, Sahar Montazeri, Kambiz Kamyab, Maryam Nasimi, Hamidreza Mahmoudi, Faezeh Khorasanizadeh, Ximena Wortsman
Journal: Journal of the American Academy of Dermatology (2024)
L‐PRF in extra‐oral wound care
Authors: Nelson Pinto, Jize Yu, Sushil Koirala, Carlos Fernando Mourão, Catherine Andrade, Enrico Rescigno, Yelka Zamora, Diego Pinto, Marc Quirynen
Journal: Periodontology 2000 (2024)

Abstract Leukocyte‐ and platelet‐rich fibrin (L‐PRF), a by‐product of centrifuged autologous whole blood, contains high concentrations of platelets, leukocytes, and fibrin (the latter spontaneously creating a strong 3‐D network (a membrane)). L‐PRF membranes possess several characteristics essential in wound healing, including a barrier function, an antibacterial and analgesic activity, and the release of growth factors enhancing tissue regeneration and neo‐vasculogenesis. This review investigated the role of L‐PRF in treating non‐responding chronic wounds such as diabetic foot, venous leg ulcers, pressure ulcers, complex wounds, leprosy ulcers (Hansen's Disease), and other demanding wounds. Chronic wounds affect millions worldwide, negatively impacting their quality of life, productivity, and life expectancy while incurring high treatment costs for themselves and private and public health systems. L‐PRF has demonstrated clear adjunctive advantages in treating chronic skin wounds, shortening the time to complete wound closure, and improving patient‐reported outcome measures (including reducing pain and minimizing the need for analgesics). Also, in other demanding wounds, L‐PRF facilitates healing. To help clinicians, this article also proposes recommendations for the use of L‐PRF in the treatment of extra‐oral wounds.
Health impact, budget impact, and price threshold for cost-effectiveness of lenacapavir for HIV pre-exposure prophylaxis in eastern and southern Africa: a modelling analysis
Authors: Linxuan Wu, David Kaftan, Rachel Wittenauer, Cory Arrouzet, Nishali Patel, Arden L Saravis, Brian Pfau, Edinah Mudimu, Anna Bershteyn, Monisha Sharma
Journal: The Lancet HIV (2024)
Sequential and parallel testing for microbiological confirmation of tuberculosis disease in children in five low-income and middle-income countries: a secondary analysis of the RaPaed-TB study
Authors: Laura Olbrich, Zoe Franckling-Smith, Leyla Larsson, Issa Sabi, Nyanda Elias Ntinginya, Celso Khosa, Denise Banze, Marriott Nliwasa, Elizabeth Lucy Corbett, Robina Semphere, Valsan Philip Verghese, Joy Sarojini Michael, Marilyn Mary Ninan, Elmar Saathoff, Timothy Daniel McHugh, Alia Razid, Stephen Michael Graham, Rinn Song, Pamela Nabeta, Andre Trollip, Mark Patrick Nicol, Michael Hoelscher, Christof Geldmacher, Norbert Heinrich, Heather Joy Zar
Journal: The Lancet Infectious Diseases (2024)
Venetoclax plus decitabine as a bridge to allogeneic haematopoietic stem-cell transplantation in older patients with acute myeloid leukaemia (VEN-DEC GITMO): final report of a multicentre, single-arm, phase 2 trial
Authors: Domenico Russo, Nicola Polverelli, Simona Bernardi, Stella Santarone, Mirko Farina, Erika Borlenghi, Francesco Onida, Luca Castagna, Stefania Bramanti, Angelo Michele Carella, Roberto Sorasio, Massimo Martino, Caterina Alati, Attilio Olivieri, Germana Beltrami, Antonio Curti, Calogero Vetro, Salvatore Leotta, Valentina Mancini, Elisabetta Terruzzi, Massimo Bernardi, Piero Galieni, Pellegrino Musto, Raffaella Cerretti, Luisa Giaccone, Cristina Skert, Vera Radici, Marika Vezzoli, Stefano Calza, Alessandro Leoni, Luca Garuffo, Cristian Bonvicini, Simone Pellizzeri, Michele Malagola, Fabio Ciceri
Journal: The Lancet Haematology (2024)
Blood microRNA testing in participants with suspicious low-dose CT findings: follow-up of the BioMILD lung cancer screening trial
Authors: Mattia Boeri, Federica Sabia, Roberta E Ledda, Maurizio Balbi, Paola Suatoni, Miriam Segale, Anna Zanghì, Anna Cantarutti, Luigi Rolli, Camilla Valsecchi, Giovanni Corrao, Alfonso Marchianò, Ugo Pastorino, Gabriella Sozzi
Journal: The Lancet Regional Health - Europe (2024)
GCN2 inhibition reduces mutant SOD1 clustering and toxicity and delays disease progression in an amyotrophic lateral sclerosis mouse model
Authors: Didio Alberto Ortiz, Nuria Peregrín, Miguel Valencia, Rodrigo Vinueza-Gavilanes, Elisa Marín-Ordovas, Roberto Ferrero, María Jesús Nicolás, Gloria González-Aseguinolaza, Montserrat Arrasate, Tomás Aragón
Journal: Translational Neurodegeneration (2024)
Lipid profiling identifies modifiable signatures of cardiometabolic risk in children and adolescents with obesity
Authors: Yun Huang, Karolina Sulek, Sara E Stinson, Louise Aas Holm, Min Kim, Kajetan Trost, Kourosh Hooshmand, Morten Asp Vonsild Lund, Cilius E Fonvig, Helene Bæk Juel, Trine Nielsen, Lars Ängquist, Peter Rossing, Maja Thiele, Aleksander Krag, Jens-Christian Holm, Cristina Legido-Quigley, Torben Hansen
Journal: Nature Medicine (2024)

Pediatric obesity is a progressive, chronic disease that can lead to serious cardiometabolic complications. Here we investigated the peripheral lipidome in 958 children and adolescents with overweight or obesity and 373 with normal weight, in a cross-sectional study. We also implemented a family-based, personalized program to assess the effects of obesity management on 186 children and adolescents in a clinical setting. Using mass spectrometry-based lipidomics, we report an increase in ceramides, alongside a decrease in lysophospholipids and omega-3 fatty acids with obesity metabolism. Ceramides, phosphatidylethanolamines and phosphatidylinositols were associated with insulin resistance and cardiometabolic risk, whereas sphingomyelins showed inverse associations. Additionally, a panel of three lipids predicted hepatic steatosis as effectively as liver enzymes. Lipids partially mediated the association between obesity and cardiometabolic traits. The nonpharmacological management reduced levels of ceramides, phospholipids and triglycerides, indicating that lowering the degree of obesity could partially restore a healthy lipid profile in children and adolescents.
Privacy-preserving large language models for structured medical information retrieval
Authors: Isabella Catharina Wiest, Dyke Ferber, Jiefu Zhu, Marko van Treeck, Sonja K Meyer, Radhika Juglan, Zunamys I Carrero, Daniel Paech, Jens Kleesiek, Matthias P Ebert, Daniel Truhn, Jakob Nikolas Kather
Journal: npj Digital Medicine (2024)

Most clinical information is encoded as free text, not accessible for quantitative analysis. This study presents an open-source pipeline using the local large language model (LLM) "Llama 2" to extract quantitative information from clinical text and evaluates its performance in identifying features of decompensated liver cirrhosis. The LLM identified five key clinical features in a zero- and one-shot manner from 500 patient medical histories in the MIMIC IV dataset. We compared LLMs of three sizes and various prompt engineering approaches, with predictions compared against ground truth from three blinded medical experts. Our pipeline achieved high accuracy, detecting liver cirrhosis with 100% sensitivity and 96% specificity. High sensitivities and specificities were also yielded for detecting ascites (95%, 95%), confusion (76%, 94%), abdominal pain (84%, 97%), and shortness of breath (87%, 97%) using the 70 billion parameter model, which outperformed smaller versions. Our study successfully demonstrates the capability of locally deployed LLMs to extract clinical information from free text with low hardware requirements.
How large language models can reshape collective intelligence
Authors: Jason W Burton, Ezequiel Lopez-Lopez, Shahar Hechtlinger, Zoe Rahwan, Samuel Aeschbach, Michiel A Bakker, Joshua A Becker, Aleks Berditchevskaia, Julian Berger, Levin Brinkmann, Lucie Flek, Stefan M Herzog, Saffron Huang, Sayash Kapoor, Arvind Narayanan, Anne-Marie Nussberger, Taha Yasseri, Pietro Nickl, Abdullah Almaatouq, Ulrike Hahn, Ralf H J M Kurvers, Susan Leavy, Iyad Rahwan, Divya Siddarth, Alice Siu, Anita W Woolley, Dirk U Wulff, Ralph Hertwig
Journal: Nature Human Behaviour (2024)
Spatial analysis reveals targetable macrophage-mediated mechanisms of immune evasion in hepatocellular carcinoma minimal residual disease
Authors: Lea Lemaitre, Nia Adeniji, Akanksha Suresh, Reshma Reguram, Josephine Zhang, Jangho Park, Amit Reddy, Alexandro E Trevino, Aaron T Mayer, Anja Deutzmann, Aida S Hansen, Ling Tong, Vinodhini Arjunan, Neeraja Kambham, Brendan C Visser, Monica M Dua, C Andrew Bonham, Nishita Kothary, H Blaize D'Angio, Ryan Preska, Yanay Rosen, James Zou, Vivek Charu, Dean W Felsher, Renumathy Dhanasekaran
Journal: Nature Cancer (2024)
Developmental interplay between transcriptional alterations and a targetable cytokine signaling dependency in pediatric ETO2::GLIS2 leukemia
Authors: Verónica Alonso-Pérez, Klaudia Galant, Fabien Boudia, Elie Robert, Zakia Aid, Laurent Renou, Vilma Barroca, Saryiami Devanand, Loélia Babin, Virginie Rouiller-Fabre, Delphine Moison, Didier Busso, Guillaume Piton, Christophe Metereau, Nassera Abermil, Paola Ballerini, Pierre Hirsch, Rima Haddad, Jelena Martinovic, Arnaud Petit, Hélène Lapillonne, Erika Brunet, Thomas Mercher, Françoise Pflumio
Journal: Molecular Cancer (2024)

Several fusion oncogenes showing a higher incidence in pediatric acute myeloid leukemia (AML) are associated with heterogeneous megakaryoblastic and other myeloid features. Here we addressed how developmental mechanisms influence human leukemogenesis by ETO2::GLIS2, associated with dismal prognosis.
Meta-analysis of the make-up and properties of in vitro models of the healthy and diseased blood–brain barrier
Authors: James G Shamul, Zhiyuan Wang, Hyeyeon Gong, Wenquan Ou, Alisa M White, Diogo P Moniz-Garcia, Shuo Gu, Alisa Morss Clyne, Alfredo Quiñones-Hinojosa, Xiaoming He
Journal: Nature Biomedical Engineering (2024)
Effectiveness of janus kinase inhibitors compared with biologic disease modifying anti‐rheumatic drugs on pain reduction in rheumatoid arthritis
Authors: Anna Eberhard, Daniela Di Giuseppe, Johan Askling, Stefan Bergman, Hannah Bower, Katerina Chatzidionysiou, Helena Forsblad‐d'Elia, Alf Kastbom, Tor Olofsson, Thomas Frisell, Carl Turesson
Journal: Arthritis & Rheumatology (2024)

To compare the effectiveness of Janus kinase inhibitors (JAKis) and biologic disease-modifying anti-rheumatic drugs (bDMARDs) on pain in patients with rheumatoid arthritis (RA).
The Immune-Related 27-Gene Signature DetermaIO Predicts Response to Neoadjuvant Atezolizumab plus Chemotherapy in Triple-Negative Breast Cancer
Authors: Matteo Dugo, Chiun-Sheng Huang, Daniel Egle, Begoña Bermejo, Claudio Zamagni, Robert S. Seitz, Tyler J. Nielsen, Marc Thill, Antonio Antón-Torres, Stefania Russo, Eva Maria Ciruelos, Brock L. Schweitzer, Douglas T. Ross, Barbara Galbardi, Richard Greil, Vladimir Semiglazov, Balázs Gyorffy, Marco Colleoni, Catherine M. Kelly, Gabriella Mariani, Lucia Del Mastro, Olivia Blasi, Maurizio Callari, Lajos Pusztai, Pinuccia Valagussa, Giuseppe Viale, Luca Gianni, Giampaolo Bianchini
Journal: Clinical Cancer Research (2024)

We assessed the 27-gene RT-qPCR-based DetermaIO assay and the same score calculated from RNA sequencing (RNA-seq) data as predictors of sensitivity to immune checkpoint therapy in the neoTRIPaPDL1 randomized trial that compared neoadjuvant carboplatin/nab-paclitaxel chemotherapy (CT) plus atezolizumab with CT alone in stage II/III triple-negative breast cancer. We also assessed the predictive function of the immuno-oncology (IO) score in expression data of patients treated with pembrolizumab plus paclitaxel (N = 29) or CT alone (N = 56) in the I-SPY2 trial.
The cutting‐edge progress in bioprinting for biomedicine: principles, applications, and future perspectives
Authors: Shuge Liu, Yating Chen, Zhiyao Wang, Minggao Liu, Yundi Zhao, Yushuo Tan, Zhan Qu, Liping Du, Chunsheng Wu
Journal: MedComm (2024)

Bioprinting is a highly promising application area of additive manufacturing technology that has been widely used in various fields, including tissue engineering, drug screening, organ regeneration, and biosensing. Its primary goal is to produce biomedical products such as artificial implant scaffolds, tissues and organs, and medical assistive devices through software-layered discrete and numerical control molding. Despite its immense potential, bioprinting technology still faces several challenges. It requires concerted efforts from researchers, engineers, regulatory bodies, and industry stakeholders are principal to overcome these challenges and unlock the full potential of bioprinting. This review systematically discusses bioprinting principles, applications, and future perspectives while also providing a topical overview of research progress in bioprinting over the past two decades. The most recent advancements in bioprinting are comprehensively reviewed here. First, printing techniques and methods are summarized along with advancements related to bioinks and supporting structures. Second, interesting and representative cases regarding the applications of bioprinting in tissue engineering, drug screening, organ regeneration, and biosensing are introduced in detail. Finally, the remaining challenges and suggestions for future directions of bioprinting technology are proposed and discussed. Bioprinting is one of the most promising application areas of additive manufacturing technology that has been widely used in various fields. It aims to produce biomedical products such as artificial implant scaffolds, tissues and organs, and medical assistive devices. This review systematically discusses bioprinting principles, applications, and future perspectives, which provides a topical description of the research progress of bioprinting.
Feeder cell training shapes the phenotype and function of in vitro expanded natural killer cells
Authors: Fei Gao, Mauricio Campos Mora, Michael Constantinides, Loïs Coënon, Caroline Multrier, Loïc Vaillant, Julien Peyroux, Tianxiang Zhang, Martin Villalba
Journal: MedComm (2024)

Abstract Natural killer (NK) cells are candidates for adoptive cell therapy, and the protocols for their activation and expansion profoundly influence their function and fate. The complexity of NK cell origin and feeder cell cues impacts the heterogeneity of expanded NK (eNK) cells. To explore this, we compared the phenotype and function of peripheral blood‐derived NK (PB‐NK) and umbilical cord blood‐derived NK (UCB‐NK) cells activated by common feeder cell lines, including K562, PLH, and 221.AEH. After first encounter, most PB‐NK cells showed degranulation independently of cytokines production. Meanwhile, most UCB‐NK cells did both. We observed that each feeder cell line uniquely influenced the activation, expansion, and ultimate fate of PB eNK and UCB eNK cells, determining whether they became cytokine producers or killer cells. In addition, they also affected the functional performance of NK cell subsets after expansion, that is, expanded conventional NK (ecNK) and expanded FcRγ – NK (eg‐NK) cells. Hence, the regulation of eNK cell function largely depends on the NK cell source and the chosen expansion system. These results underscore the significance of selecting feeder cells for NK cell expansion from various sources, notably for customized adoptive cell therapies to yield cytokine‐producing or cytotoxic eNK cells.
Pulmonary fibrosis: pathogenesis and therapeutic strategies
Authors: Jianhai Wang, Kuan Li, De Hao, Xue Li, Yu Zhu, Hongzhi Yu, Huaiyong Chen
Journal: MedComm (2024)

Abstract Pulmonary fibrosis (PF) is a chronic and progressive lung disease characterized by extensive alterations of cellular fate and function and excessive accumulation of extracellular matrix, leading to lung tissue scarring and impaired respiratory function. Although our understanding of its pathogenesis has increased, effective treatments remain scarce, and fibrotic progression is a major cause of mortality. Recent research has identified various etiological factors, including genetic predispositions, environmental exposures, and lifestyle factors, which contribute to the onset and progression of PF. Nonetheless, the precise mechanisms by which these factors interact to drive fibrosis are not yet fully elucidated. This review thoroughly examines the diverse etiological factors, cellular and molecular mechanisms, and key signaling pathways involved in PF, such as TGF‐β, WNT/β‐catenin, and PI3K/Akt/mTOR. It also discusses current therapeutic strategies, including antifibrotic agents like pirfenidone and nintedanib, and explores emerging treatments targeting fibrosis and cellular senescence. Emphasizing the need for omni‐target approaches to overcome the limitations of current therapies, this review integrates recent findings to enhance our understanding of PF and contribute to the development of more effective prevention and management strategies, ultimately improving patient outcomes.
Heterogeneous effects of Medicaid coverage on cardiovascular risk factors: secondary analysis of randomized controlled trial
Authors: Kosuke Inoue, Susan Athey, Katherine Baicker, Yusuke Tsugawa
Journal: BMJ (2024)

Abstract Objectives To investigate whether health insurance generated improvements in cardiovascular risk factors (blood pressure and hemoglobin A 1c (HbA 1c ) levels) for identifiable subpopulations, and using machine learning to identify characteristics of people predicted to benefit highly. Design Secondary analysis of randomized controlled trial. Setting Medicaid insurance coverage in 2008 for adults on low incomes (defined as lower than the federal-defined poverty line) in Oregon who were uninsured. Participants 12 134 participants from the Oregon Health Insurance Experiment with in-person data for health outcomes for both treatment and control groups. Interventions Health insurance (Medicaid) coverage. Main outcomes measures The conditional local average treatment effects of Medicaid coverage on systolic blood pressure and HbA 1c using a machine learning causal forest algorithm (with instrumental variables). Characteristics of individuals with positive predicted benefits of Medicaid coverage based on the algorithm were compared with the characteristics of others. The effect of Medicaid coverage was calculated on blood pressure and HbA 1c among individuals with high predicted benefits. Results In the in-person interview survey, mean systolic blood pressure was 119 (standard deviation 17) mm Hg and mean HbA 1c concentrations was 5.3% (standard deviation 0.6%). Our causal forest model showed heterogeneity in the effect of Medicaid coverage on systolic blood pressure and HbA 1c . Individuals with lower baseline healthcare charges, for example, had higher predicted benefits from gaining Medicaid coverage. Medicaid coverage significantly lowered systolic blood pressure (−4.96 mm Hg (95% confidence interval −7.80 to −2.48)) for people predicted to benefit highly. HbA 1c was also significantly reduced by Medicaid coverage for people with high predicted benefits, but the size was not clinically meaningful (−0.12% (−0.25% to −0.01%)). Conclusions Although Medicaid coverage did not improve cardiovascular risk factors on average, substantial heterogeneity was noted in the effects within that population. Individuals with high predicted benefits were more likely to have no or low prior healthcare charges, for example. Our findings suggest that Medicaid coverage leads to improved cardiovascular risk factors for some, particularly for blood pressure, although those benefits may be diluted by individuals who did not experience benefits.