tbuckley/cabot-search huggingface dataset:
Substances as a core domain
Authors: Susan J Hespos, Lance J Rips
Journal: Behavioral and Brain Sciences (2024)

Abstract Central to What Babies Know (Spelke, 2022) is the thesis that infants' understanding is divided into independent modules of core knowledge. As a test case, we consider adding a new domain: core knowledge of substances. Experiments show that infants' understanding of substances meets some criteria of core knowledge, and they raise questions about the relations that hold between core domains.
Divisive language
Authors: Moira R Dillon
Journal: Behavioral and Brain Sciences (2024)

Abstract What language devises, it might divide. By exploring the relations among the core geometries of the physical world, the abstract geometry of Euclid, and language, I give new insight into both the persistence of core knowledge into adulthood and our access to it through language. My extension of Spelke's language argument has implications for pedagogy, philosophy, and artificial intelligence.
Investigating infant knowledge with representational similarity analysis
Authors: Cameron T Ellis
Journal: Behavioral and Brain Sciences (2024)

Abstract Decades of research have pushed us closer to understanding what babies know. However, a powerful approach – representational similarity analysis (RSA) – is underused in developmental research. I discuss the strengths of this approach and what it can tell us about infant conceptual knowledge. As a case study, I focus on numerosity as a domain where RSA can make unique progress.
Ketogenic diet-induced bile acids protect against obesity through reduced calorie absorption
Authors: Xiao Li, Jie Yang, Xiaofeng Zhou, Chen Dai, Mengmeng Kong, Linshan Xie, Chenglin Liu, Yilian Liu, Dandan Li, Xiaonan Ma, Yuxiang Dai, Yan Sun, Zhijie Jian, Xiaohuan Guo, Xu Lin, Yixue Li, Liang Sun, Xin Liu, Li Jin, Huiru Tang, Yan Zheng, Shangyu Hong
Journal: Nature Metabolism (2024)
Clinical implementation of artificial-intelligence-assisted detection of breast cancer metastases in sentinel lymph nodes: the CONFIDENT-B single-center, non-randomized clinical trial
Authors: C. van Dooijeweert, R. N. Flach, N. D. ter Hoeve, C. P. H. Vreuls, R. Goldschmeding, J. E. Freund, P. Pham, T. Q. Nguyen, E. van der Wall, G. W. J. Frederix, N. Stathonikos, P. J. van Diest
Journal: Nature Cancer (2024)

Abstract Pathologists’ assessment of sentinel lymph nodes (SNs) for breast cancer (BC) metastases is a treatment-guiding yet labor-intensive and costly task because of the performance of immunohistochemistry (IHC) in morphologically negative cases. This non-randomized, single-center clinical trial (International Standard Randomized Controlled Trial Number:14323711) assessed the efficacy of an artificial intelligence (AI)-assisted workflow for detecting BC metastases in SNs while maintaining diagnostic safety standards. From September 2022 to May 2023, 190 SN specimens were consecutively enrolled and allocated biweekly to the intervention arm ( n = 100) or control arm ( n = 90). In both arms, digital whole-slide images of hematoxylin–eosin sections of SN specimens were assessed by an expert pathologist, who was assisted by the ‘Metastasis Detection’ app (Visiopharm) in the intervention arm. Our primary endpoint showed a significantly reduced adjusted relative risk of IHC use (0.680, 95% confidence interval: 0.347–0.878) for AI-assisted pathologists, with subsequent cost savings of ~3,000 €. Secondary endpoints showed significant time reductions and up to 30% improved sensitivity for AI-assisted pathologists. This trial demonstrates the safety and potential for cost and time savings of AI assistance.
Serum small RNAs in metastatic colorectal cancer predict response to chemotherapy and characterize high-risk patients
Authors: Robin Mjelle, Are K Kristensen, None Tora S Solheim, Ganna S Westvik, Hege Elvebakken, Eva Hofsli
Journal: Molecular Cancer (2024)

Metastatic colorectal cancer (mCRC) presents significant challenges in clinical management due to its heterogeneity and variable response to treatment. In this study, we conducted comprehensive small RNA (sRNA) sequencing analyses to identify sRNA biomarkers associated with survival and treatment response in mCRC patients. We measured serum sRNAs before and after chemotherapy treatment in a discovery cohort of 189 mCRC patients. Our analysis revealed 25 microRNAs (miRNA) as significantly associated with overall survival at baseline. We found that 11 of the 25 significant miRNAs were also significant in an independent validation cohort of 20 mCRC patients, including the top five miRNAs from the discovery cohort. Importantly, all but four of the 25 significant miRNAs from the discovery cohort had hazard ratios in the same direction in the validation cohort. Among the 25 significant miRNAs, we identified the miR-320 family of miRNAs as the strongest independent prognostic marker, with high baseline levels correlating with poor survival outcomes. Furthermore, post-treatment levels of the same miRNAs were even more predictive of overall survival, emphasizing the prognostic value of serum changes in miRNA levels before and after treatment. Moreover, we observed significant changes in serum miRNAs and other sRNAs when comparing samples before and after chemotherapy, with distinct expression patterns between responders and non-responders. Leveraging these differential expression patterns, we established a serum sRNA signature that accurately predicts response to chemotherapy with an area under the curve (AUC) of 0.8. In summary, our study highlights the prognostic and predictive potential of sRNA biomarkers in mCRC, offering valuable insights into patient stratification and personalized treatment approaches.
A common flanking variant is associated with enhanced stability of the FGF14-SCA27B repeat locus
Authors: David Pellerin, Giulia F. Del Gobbo, Madeline Couse, Egor Dolzhenko, Sathiji K. Nageshwaran, Warren A. Cheung, Isaac R. L. Xu, Marie-Josée Dicaire, Guinevere Spurdens, Gabriel Matos-Rodrigues, Igor Stevanovski, Carolin K. Scriba, Adriana Rebelo, Virginie Roth, Marion Wandzel, Céline Bonnet, Catherine Ashton, Aman Agarwal, Cyril Peter, Dan Hasson, Nadejda M. Tsankova, Ken Dewar, Phillipa J. Lamont, Nigel G. Laing, Mathilde Renaud, Henry Houlden, Matthis Synofzik, Karen Usdin, Andre Nussenzweig, Marek Napierala, Zhao Chen, Hong Jiang, Ira W. Deveson, Gianina Ravenscroft, Schahram Akbarian, Michael A. Eberle, Kym M. Boycott, Tomi Pastinen, Emily Bateman, Chelsea Berngruber, Fabio Cunial, Colleen P. Davis, Huyen Dinh, Harsha Doddapaneni, Kim Doheny, Shannon Dugan-Perez, Tara Dutka, Evan E. Eichler, Philip Empey, Sarah Fazal, Chris Frazar, Kiran Garimella, Jessica Gearhart, Richard Gibbs, Jane Grimwood, Namrata Gupta, Salina K. Hall, Yi Han, William T. Harvey, Jess Hosea, PingHsun Hsieh, Jianhong Hu, Yongqing Huang, James Hwang, Michal Izydorczyk, Hyeonsoo Jeong, Ziad Khan, Sarah Kirkpatrick, Michelle Kokosinski, Sam Kovaka, Edibe Nehir Kurtas, Rebecca Lakatos, Emily LaPlante, Samuel K. Lee, Niall Lennon, Shawn Levy, Qiuhui Li, Lee Lichtenstein, Glennis A. Logsdon, Chris Lord, Ryan Lorig-Roach, Medhat Madmoud, Anant Maheshwari, Beth Marosy, Heer Mehta, Ginger Metcalf, David Mohr, Carolina Montano, Luke Morina, Yulia Mostovoy, Anjene Musick, Donna Muzny, Shane Neph, Justin Paschall, Karynne Patterson, Arianna Pionzio, David Porubsky, Nripesh Prasad, Allison N. Rozanski, Alba Sanchis-Juan, Michael C. Schatz, Sophie Schwartz, Alan Scott, Adriana Sedeno-Cortes, Fritz Sedlazeck, Tristan Shaffer, Hua Shen, Beri Shifaw, Joshua D. Smith, Natthapon Soisangwan, Andrew Stergachis, Hang Su, Michael Talkowski, Winston Timp, Vanesa Vee, Evie Wan, Yuanyuan Wang, George Weissenberger, Julie Wertz, Marsha Wheeler, Christopher Whelan, DongAhn Yoo, Shadi Zaheri, Xinchang Zheng, Yiming Zhu, Michelle Zilka, Bernard Brais, Stephan Zuchner, Matt C. Danzi
Journal: Nature Genetics (2024)
T cell-mediated microglial activation triggers myelin pathology in a mouse model of amyloidosis
Authors: Shreeya Kedia, Hao Ji, Ruoqing Feng, Peter Androvic, Lena Spieth, Lu Liu, Jonas Franz, Hanna Zdiarstek, Katrin Perez Anderson, Cem Kaboglu, Qian Liu, Nicola Mattugini, Fatma Cherif, Danilo Prtvar, Ludovico Cantuti-Castelvetri, Arthur Liesz, Martina Schifferer, Christine Stadelmann, Sabina Tahirovic, Ozgun Gokce, Mikael Simons
Journal: Nature Neuroscience (2024)

Abstract Age-related myelin damage induces inflammatory responses, yet its involvement in Alzheimer’s disease remains uncertain, despite age being a major risk factor. Using a mouse model of Alzheimer’s disease, we found that amyloidosis itself triggers age-related oligodendrocyte and myelin damage. Mechanistically, CD8 + T cells promote the progressive accumulation of abnormally interferon-activated microglia that display myelin-damaging activity. Thus, our data suggest that immune responses against myelinating oligodendrocytes may contribute to neurodegenerative diseases with amyloidosis.
4-1BB-encoding CAR causes cell death via sequestration of the ubiquitin-modifying enzyme A20
Authors: Zhangqi Dou, Thomas Raphael Bonacci, Peishun Shou, Elisa Landoni, Mark G. Woodcock, Chuang Sun, Barbara Savoldo, Laura E. Herring, Michael J. Emanuele, Feifei Song, Albert S. Baldwin, Yisong Wan, Gianpietro Dotti, Xin Zhou
Journal: Cellular and Molecular Immunology (2024)

Abstract CD28 and 4-1BB costimulatory endodomains included in chimeric antigen receptor (CAR) molecules play a critical role in promoting sustained antitumor activity of CAR-T cells. However, the molecular events associated with the ectopic and constitutive display of either CD28 or 4-1BB in CAR-T cells have been only partially explored. In the current study, we demonstrated that 4-1BB incorporated within the CAR leads to cell cluster formation and cell death in the forms of both apoptosis and necroptosis in the absence of CAR tonic signaling. Mechanistic studies illustrate that 4-1BB sequesters A20 to the cell membrane in a TRAF-dependent manner causing A20 functional deficiency that in turn leads to NF-κB hyperactivity, cell aggregation via ICAM-1 overexpression, and cell death including necroptosis via RIPK1/RIPK3/MLKL pathway. Genetic modulations obtained by either overexpressing A20 or releasing A20 from 4-1BB by deleting the TRAF-binding motifs of 4-1BB rescue cell cluster formation and cell death and enhance the antitumor ability of 4-1BB-costimulated CAR-T cells.
Effects of an Intervention to Improve Evidence-Based Care for People With Diabetes and Cardiovascular Disease Across Sex, Race, and Ethnicity Subgroups: Insights From the COORDINATE-Diabetes Trial
Authors: Manasi Tannu, Lisa Kaltenbach, Neha J. Pagidipati, Darren K. McGuire, Vanita R. Aroda, Rodica Pop-Busui, Nitin Kondamudi, Hussein R. Al-Khalidi, Renato D. Lopes, Matthew A. Cavender, Adam J. Nelson, Julienne Kirk, Ildiko Lingvay, Melissa Magwire, Caroline Regina Richardson, Laura Webb, Monica Leyva, Ambarish Pandey, Alana Washington, Jonathan Pak, Tanya Gaynor, Waqar Khan, Patrick Weston, Christopher B. Granger, Jennifer Green
Journal: Circulation (2024)

Results from the COORDINATE-Diabetes trial (Coordinating Cardiology Clinics Randomized Trial of Interventions to Improve Outcomes - Diabetes) demonstrated that a multifaceted, clinic-based intervention increased prescription of evidence-based medical therapies to participants with type 2 diabetes and atherosclerotic cardiovascular disease. This secondary analysis assessed whether intervention success was consistent across sex, race, and ethnicity.
Associations of Urban Blue and Green Spaces With Coronary Artery Calcification in Black Individuals and Disadvantaged Neighborhoods
Authors: Kyeezu Kim, Brian T. Joyce, Yinan Zheng, Drew R. Nannini, Jun Wang, Penny Gordon-Larsen, Ankeet S. Bhatt, Kelley P. Gabriel, James M. Shikany, Ming Hu, Aimin Chen, Orna Reges, Mercedes R. Carnethon, Donald M. Lloyd-Jones, Kai Zhang, Lifang Hou
Journal: Circulation (2024)

Proximity to urban blue and green spaces has been associated with improved cardiovascular health; however, few studies have examined the role of race and socioeconomic status in these associations.
NOTCH1 fusions in pediatric T‐cell lymphoblastic lymphoma: A high‐risk subgroup with CCL17 (TARC) levels as diagnostic biomarker
Authors: Emma Kroeze, Michelle M. Kleisman, Lennart A. Kester, Marijn A. Scheijde‐Vermeulen, Edwin Sonneveld, Jessica G. C. Buijs‐Gladdines, Melanie M. Hagleitner, Friederike A. G. Meyer‐Wentrup, Margreet A. Veening, Auke Beishuizen, Jules P. P. Meijerink, Jan L. C. Loeffen, Roland P. Kuiper
Journal: HemaSphere (2024)

Twenty percent of children with T-cell lymphoblastic lymphoma (T-LBL) will relapse and have an extremely poor outcome. Currently, we can identify a genetically low-risk subgroup in pediatric T-LBL, yet these high-risk patients who need intensified or alternative treatment options remain undetected. Therefore, there is an urgent need to recognize these high-risk T-LBL patients through identification of molecular characteristics and biomarkers. By using RNA sequencing which was performed in 29/49 T-LBL patients who were diagnosed in the Princess Maxima Center for Pediatric Oncology between 2018 and 2023, we discovered a previously unknown high-risk biological subgroup of children with T-LBL. This subgroup is characterized by
Improving Outcomes After Post–Cardiac Arrest Brain Injury: A Scientific Statement From the International Liaison Committee on Resuscitation
Authors: Gavin D. Perkins, Robert Neumar, Cindy H. Hsu, Karen G. Hirsch, Anders Aneman, Lance B. Becker, Keith Couper, Clifton W. Callaway, Cornelia W.E. Hoedemaekers, Shir Lynn Lim, William Meurer, Theresa Olasveengen, Mypinder S. Sekhon, Markus Skrifvars, Jasmeet Soar, Min-Shan Tsai, Bhuma Vengamma, Jerry P. Nolan
Journal: Circulation (2024)

This scientific statement presents a conceptual framework for the pathophysiology of post–cardiac arrest brain injury, explores reasons for previous failure to translate preclinical data to clinical practice, and outlines potential paths forward. Post–cardiac arrest brain injury is characterized by 4 distinct but overlapping phases: ischemic depolarization, reperfusion repolarization, dysregulation, and recovery and repair. Previous research has been challenging because of the limitations of laboratory models; heterogeneity in the patient populations enrolled; overoptimistic estimation of treatment effects leading to suboptimal sample sizes; timing and route of intervention delivery; limited or absent evidence that the intervention has engaged the mechanistic target; and heterogeneity in postresuscitation care, prognostication, and withdrawal of life-sustaining treatments. Future trials must tailor their interventions to the subset of patients most likely to benefit and deliver this intervention at the appropriate time, through the appropriate route, and at the appropriate dose. The complexity of post–cardiac arrest brain injury suggests that monotherapies are unlikely to be as successful as multimodal neuroprotective therapies. Biomarkers should be developed to identify patients with the targeted mechanism of injury, to quantify its severity, and to measure the response to therapy. Studies need to be adequately powered to detect effect sizes that are realistic and meaningful to patients, their families, and clinicians. Study designs should be optimized to accelerate the evaluation of the most promising interventions. Multidisciplinary and international collaboration will be essential to realize the goal of developing effective therapies for post–cardiac arrest brain injury.
Efficacy and safety of bendamustine‐containing bridging therapy in R/R LBCL patients receiving CD19 CAR T‐cells
Authors: Gloria Iacoboni, Mario A. Sánchez‐Salinas, Kai Rejeski, Ana Á. Martín‐López, Mi Kwon, Víctor Navarro, Katarzyna A. Jalowiec, Rafael Hernani, Juan L. Reguera‐Ortega, Laura Gallur, Viktoria Blumenberg, María Herrero‐García, Claire Roddie, Ana Benzaquén, Javier Delgado‐Serrano, Rebeca Bailén, Cecilia Carpio, Paula Amat, Lucia López‐Corral, Lourdes Martín‐Martín, Mariana Bastos, Marion Subklewe, Maeve O'Reilly, Pere Barba
Journal: HemaSphere (2024)

Abstract Bridging therapy (BT) after leukapheresis is required in most relapsed/refractory (R/R) large B‐cell lymphoma (LBCL) patients receiving chimeric antigen receptor (CAR) T cells. Bendamustine‐containing regimens are a potential BT option. We aimed to assess if this agent had a negative impact on CAR‐T outcomes when it was administered as BT. We included R/R LBCL patients from six centers who received systemic BT after leukapheresis from February 2019 to September 2022; patients who only received steroids or had pre‐apheresis bendamustine exposure were excluded. Patients were divided into two BT groups, with and without bendamustine. Separate safety and efficacy analyses were carried out for axi‐cel and tisa‐cel. Of 243 patients who received BT, bendamustine (benda) was included in 62 (26%). There was a higher rate of BT progressors in the non‐benda group (62% vs. 45%, p = 0.02). Concerning CAR‐T efficacy, complete responses were comparable for benda versus non‐benda BT cohorts with axi‐cel (70% vs. 53%, p = 0.12) and tisa‐cel (44% vs. 36%, p = 0.70). Also, 12‐month progression‐free and overall survival were not significantly different between BT groups with axi‐cel (56% vs. 43% and 71% vs. 63%) and tisa‐cel (25% vs. 26% and 52% vs. 48%); there were no differences when BT response was considered. CAR T‐cell expansion for each construct was similar between BT groups. Regarding safety, CRS G ≥3 (6% vs. 6%, p = 0.79), ICANS G ≥3 (15% vs. 17%, p = 0.68), severe infections, and neutropenia post‐infusion were comparable among BT regimens. BT with bendamustine‐containing regimens is safe for patients requiring disease control during CAR T‐cell manufacturing.
PANX1-mediated ATP release confers FAM3A’s suppression effects on hepatic gluconeogenesis and lipogenesis
Authors: Cheng-Qing Hu, Tao Hou, Rui Xiang, Xin Li, Jing Li, Tian-Tian Wang, Wen-Jun Liu, Song Hou, Di Wang, Qing-He Zhao, Xiao-Xing Yu, Ming Xu, Xing-Kai Liu, Yu-Jing Chi, Ji-Chun Yang
Journal: Military Medical Research (2024)

Abstract Background Extracellular adenosine triphosphate (ATP) is an important signal molecule. In previous studies, intensive research had revealed the crucial roles of family with sequence similarity 3 member A (FAM3A) in controlling hepatic glucolipid metabolism, islet β cell function, adipocyte differentiation, blood pressure, and other biological and pathophysiological processes. Although mitochondrial protein FAM3A plays crucial roles in the regulation of glucolipid metabolism via stimulating ATP release to activate P2 receptor pathways, its mechanism in promoting ATP release in hepatocytes remains unrevealed. Methods db/db , high-fat diet (HFD)-fed, and global pannexin 1 ( PANX1 ) knockout mice, as well as liver sections of individuals, were used in this study. Adenoviruses and adeno-associated viruses were utilized for in vivo gene overexpression or inhibition. To evaluate the metabolic status in mice, oral glucose tolerance test (OGTT), pyruvate tolerance test (PTT), insulin tolerance test (ITT), and magnetic resonance imaging (MRI) were conducted. Protein–protein interactions were determined by coimmunoprecipitation with mass spectrometry (MS) assays. Results In livers of individuals and mice with steatosis, the expression of ATP-permeable channel PANX1 was increased ( P &lt; 0.01). Hepatic PANX1 overexpression ameliorated the dysregulated glucolipid metabolism in obese mice. Mice with hepatic PANX1 knockdown or global PANX1 knockout exhibited disturbed glucolipid metabolism. Restoration of hepatic PANX1 rescued the metabolic disorders of PANX1-deficient mice ( P &lt; 0.05). Mechanistically, ATP release is mediated by the PANX1-activated protein kinase B-forkhead box protein O1 (Akt-FOXO1) pathway to inhibit gluconeogenesis via P2Y receptors in hepatocytes. PANX1-mediated ATP release also activated calmodulin (CaM) ( P &lt; 0.01), which interacted with c-Jun N-terminal kinase (JNK) to inhibit its activity, thereby deactivating the transcription factor activator protein-1 (AP1) and repressing fatty acid synthase (FAS) expression and lipid synthesis ( P &lt; 0.05). FAM3A stimulated the expression of PANX1 via heat shock factor 1 (HSF1) in hepatocytes ( P &lt; 0.05). Notably, FAM3A overexpression failed to promote ATP release, inhibit the expression of gluconeogenic and lipogenic genes, and suppress gluconeogenesis and lipid deposition in PANX1-deficient hepatocytes and livers. Conclusions PANX1-mediated release of ATP plays a crucial role in maintaining hepatic glucolipid homeostasis, and it confers FAM3A’s suppressive effects on hepatic gluconeogenesis and lipogenesis.
Effectiveness and safety of molnupiravir in the intended-use population: an observational cohort study
Authors: Wiessam Abu Ahmad, Ronen Arbel, Yael Wolff Sagy, Erez Battat, Ruslan Sergienko, Michael Friger, Shlomit Yaron, Danielle Serby, Roy Zucker, Ariel Hammerman, Hadar Duskin Bitan, Alon Peretz, Gil Lavie, Doron Netzer
Journal: Clinical Microbiology and Infection (2024)
Airway epithelial‐derived exosomes induce acute asthma exacerbation after respiratory syncytial virus infection
Authors: Ye Yao, Yu Yang, Ming Ji, Qingwu Qin, Kun Xu, Zhenkun Xia, Huijun Liu, Lin Yuan, Yunchang Yuan, Ling Qin, Xizi Du, Leyuan Wang, Kai Zhou, Xinyu Wu, Weijie Wang, Bei Qing, Yang Xiang, Xiangping Qu, Ming Yang, Xiaoqun Qin, Chi Liu
Journal: MedComm (2024)

Abstract Acute asthma exacerbation refers to the progressive deterioration of asthma symptoms that is always triggered by virus infection represented by respiratory syncytial virus (RSV). After RSV infection, exaggerated Th2‐mediated pulmonary inflammation is the critical pathological response of asthmatic patients with acute exacerbation. Significantly, airway epithelial cells, being the primary targets of RSV infection, play a crucial role in controlling the pulmonary inflammatory response by releasing airway epithelial cell‐derived exosomes (AEC‐Exos), which potentially influence the development of asthma. However, the specific role of AEC‐Exos in acute asthma exacerbation after RSV infection remains obscure. The purpose of this study was to determine the distinct function of AEC‐Exos in exacerbating acute asthma following RSV infection. Blockade of exosomes by GW reduce the enhanced pulmonary inflammation significantly. Specifically, the enhanced Th2 inflammation was induced by AEC‐Exos thorough transportation of hsa‐miR‐155‐5p–Sirtuin 1 (SIRT1) pathway during acute asthma exacerbation. Targeted inhibition of hsa‐miR‐155‐5p blocks the exaggerated Th2 inflammation effectively in mice with acute asthma exacerbation. In summary, our study showed that during acute asthma exacerbation after RSV infection, AEC‐Exos promote the enhanced Th2 inflammation through transportation of increased hsa‐miR‐155‐5p, which was mediated partly through SIRT1‐mediated pathway. hsa‐miR‐155‐5p is a potential biomarker for early prediction of acute asthma exacerbation.