tbuckley/cabot-search huggingface dataset:
Distributional reinforcement learning in prefrontal cortex
Authors: Timothy H. Muller, James L. Butler, Sebastijan Veselic, Bruno Miranda, Joni D. Wallis, Peter Dayan, Timothy E. J. Behrens, Zeb Kurth-Nelson, Steven W. Kennerley
Journal: Nature Neuroscience (2024)

Abstract The prefrontal cortex is crucial for learning and decision-making. Classic reinforcement learning (RL) theories center on learning the expectation of potential rewarding outcomes and explain a wealth of neural data in the prefrontal cortex. Distributional RL, on the other hand, learns the full distribution of rewarding outcomes and better explains dopamine responses. In the present study, we show that distributional RL also better explains macaque anterior cingulate cortex neuronal responses, suggesting that it is a common mechanism for reward-guided learning.
Organoids derived from patients provide a new opportunity for research and individualized treatment of malignant peritoneal mesothelioma
Authors: XiaoChang Fang, Lin Shu, TianLiang Chen, XiaoLe Zhao, LiuCui Yang, Tingting Dou, Lijie Yang, Xuanfei Li, Maohui Feng
Journal: Molecular Cancer (2024)

Abstract Background Malignant peritoneal mesothelioma (MPM) is an extremely rare and highly invasive tumor. Due to the lack of accurate models that reflect the biological characteristics of primary tumors, studying MPM remains challenging and is associated with an exceedingly unfavorable prognosis. This study was aimed to establish a new potential preclinical model for MPM using patient-derived MPM organoids (MPMOs) and to comprehensively evaluate the practicality of this model in medical research and its feasibility in guiding individualized patient treatment. Methods MPMOs were constructed using tumor tissue from MPM patients. Histopathological analysis and whole genome sequencing (WGS) were employed to determine the ability of MPMOs to replicate the original tumor's genetic and histological characteristics. The subcutaneous and orthotopic xenograft models were employed to assess the feasibility of establishing an in vivo model of MPM. MPMOs were also used to conduct drug screening and compare the results with retrospective analysis of patients after treatment, in order to evaluate the potential of MPMOs in predicting the effectiveness of drugs in MPM patients. Results We successfully established a culture method for human MPM organoids using tumor tissue from MPM patients and provided a comprehensive description of the necessary medium components for MPMOs. Pathological examination and WGS revealed that MPMOs accurately represented the histological characteristics and genomic heterogeneity of the original tumors. In terms of application, the success rate of creating subcutaneous and orthotopic xenograft models using MPMOs was 88% and 100% respectively. Drug sensitivity assays demonstrated that MPMOs have different medication responses, and these differences were compatible with the real situation of the patients. Conclusion This study presents a method for generating human MPM organoids, which can serve as a valuable research tool and contribute to the advancement of MPM research. Additionally, these organoids can be utilized as a means to evaluate the effectiveness of drug treatments for MPM patients, offering a model for personalized treatment approaches.
Passenger Gene Coamplifications Create Collateral Therapeutic Vulnerabilities in Cancer
Authors: Yi Bei, Luca Bramé, Marieluise Kirchner, Raphaela Fritsche-Guenther, Severine Kunz, Animesh Bhattacharya, Mara-Camelia Rusu, Dennis Gürgen, Frank P.B. Dubios, Julia K.C. Köppke, Jutta Proba, Nadine Wittstruck, Olga Alexandra Sidorova, Rocío Chamorro González, Heathcliff Dorado Garcia, Lotte Brückner, Robin Xu, Mădălina Giurgiu, Elias Rodriguez-Fos, Qinghao Yu, Bastiaan Spanjaard, Richard P. Koche, Clemens A. Schmitt, Johannes H. Schulte, Angelika Eggert, Kerstin Haase, Jennifer Kirwan, Anja I.H. Hagemann, Philipp Mertins, Jan R. Dörr, Anton G. Henssen
Journal: Cancer Discovery (2024)

DNA amplifications in cancer do not only harbor oncogenes. We sought to determine whether passenger coamplifications could create collateral therapeutic vulnerabilities. Through an analysis of >3,000 cancer genomes followed by the interrogation of CRISPR-Cas9 loss-of-function screens across >700 cancer cell lines, we determined that passenger coamplifications are accompanied by distinct dependency profiles. In a proof-of-principle study, we demonstrate that the coamplification of the bona fide passenger gene DEAD-Box Helicase 1 (DDX1) creates an increased dependency on the mTOR pathway. Interaction proteomics identified tricarboxylic acid (TCA) cycle components as previously unrecognized DDX1 interaction partners. Live-cell metabolomics highlighted that this interaction could impair TCA activity, which in turn resulted in enhanced mTORC1 activity. Consequently, genetic and pharmacologic disruption of mTORC1 resulted in pronounced cell death in vitro and in vivo. Thus, structurally linked coamplification of a passenger gene and an oncogene can result in collateral vulnerabilities. We demonstrate that coamplification of passenger genes, which were largely neglected in cancer biology in the past, can create distinct cancer dependencies. Because passenger coamplifications are frequent in cancer, this principle has the potential to expand target discovery in oncology. This article is featured in Selected Articles from This Issue, p. 384.
Experts Call for Data, Deep Breath, on CARs
Journal: Cancer Discovery (2024)

Despite an FDA alert in late November about a possible link between chimeric antigen receptor (CAR) T-cell therapy and the development of secondary hematologic malignancies, as well as the first published report of a patient case and a change in the boxed warning on one CAR product in December, experts in cellular and gene therapies and immunology suggest no changes in clinical practice in a commentary.
Micronuclei and Cancer
Authors: Melody Di Bona, Samuel F. Bakhoum
Journal: Cancer Discovery (2024)

Chromosome-containing micronuclei are a feature of human cancer. Micronuclei arise from chromosome mis-segregation and characterize tumors with elevated rates of chromosomal instability. Although their association with cancer has been long recognized, only recently have we broadened our understanding of the mechanisms that govern micronuclei formation and their role in tumor progression. In this review, we provide a brief historical account of micronuclei, depict the mechanisms underpinning their creation, and illuminate their capacity to propel tumor evolution through genetic, epigenetic, and transcriptional transformations. We also posit the prospect of leveraging micronuclei as biomarkers and therapeutic targets in chromosomally unstable cancers. Micronuclei in chromosomally unstable cancer cells serve as pivotal catalysts for cancer progression, instigating transformative genomic, epigenetic, and transcriptional alterations. This comprehensive review not only synthesizes our present comprehension but also outlines a framework for translating this knowledge into pioneering biomarkers and therapeutics, thereby illuminating novel paths for personalized cancer management.
In Search of a Timely, Safe, and Effective Alternative to Hospitalization for Heart Failure
Authors: Shanshan E. Gustafson, Steven A. Hamilton, Andrew P. Ambrosy
Journal: JAMA Network Open (2024)

Peter S. Pang, MD, MS; David A. Berger, MD; Simon A. Mahler, MD, MS; Xiaochun Li, PhD; Susan J. Pressler, PhD, RN; Kathleen A. Lane, MS; Jason J. Bischof, MD; Douglas Char, MD; Deborah Diercks, MD; Alan E. Jones, MD; Erik P. Hess, MD; Phillip Levy, MD; Joseph B. Miller, MD; Arvind Venkat, MD; Nicholas E. Harrison, MD; Sean P. Collins, MD, MSc
Publisher Correction: Transcriptional and epigenetic decoding of the microglial aging process
Authors: Xiaoyu Li, Yuxin Li, Yuxiao Jin, Yuheng Zhang, Jingchuan Wu, Zhen Xu, Yubin Huang, Lin Cai, Shuai Gao, Taohui Liu, Fanzhuo Zeng, Yafei Wang, Wenxu Wang, Ti-Fei Yuan, Hengli Tian, Yousheng Shu, Feifan Guo, Wei Lu, Ying Mao, Xifan Mei, Yanxia Rao, Bo Peng
Journal: Nature Aging (2024)
US Veterans Affairs and Department of Defense 2023 Clinical Guideline for PTSD—Devolving Not Evolving
Authors: Charles W. Hoge, Kathleen M. Chard, Rachel Yehuda
Journal: JAMA Psychiatry (2024)

This Viewpoint discusses the updated 2023 clinical practice guidelines issued by the US Department of Veterans Affairs and the US Department of Defense regarding treatment approaches for posttraumatic stress disorder.
Inositol phosphatase INPP4B sustains ILC1s and intratumoral NK cells through an AKT-driven pathway
Authors: Vincent Peng, Tihana Trsan, Raki Sudan, Bishan Bhattarai, Victor S. Cortez, Martina Molgora, Jean Vacher, Marco Colonna
Journal: The Journal of Experimental Medicine (2024)

Innate lymphoid cells (ILCs) are a heterogeneous population of lymphocytes that coordinate early immune responses and maintain tissue homeostasis. Type 1 innate immune responses are mediated by natural killer (NK) cells and group 1 ILCs (ILC1s). Despite their shared features, NK cells and ILC1s display profound differences among various tissue microenvironments. Here, we identify the inositol polyphosphatase INPP4B as a hallmark feature of tissue-resident ILC1s and intratumoral NK cells using an scRNA-seq atlas of tissue-associated and circulating NK/ILC1s. Conditional deletion of Inpp4b in ILC1s and NK cells reveals that it is necessary for the homeostasis of tissue-resident ILC1s but not circulating NK cells at steady-state. Inpp4b-deficient cells display increased rates of apoptosis and reduced activation of the prosurvival molecule AKT. Furthermore, expression of Inpp4b by NK/ILC1s is necessary for their presence in the intratumoral environment, and lack of Inpp4b impairs antitumor immunity. These findings highlight INPP4B as a novel regulator of tissue residency and antitumor function in ILC1s and NK cells.
A New Twist on a Classic: Enhancing Radioiodine Uptake in Advanced Thyroid Cancer
Authors: Melissa G. Lechner, Gregory A. Brent
Journal: Clinical Cancer Research (2024)

Summary Advanced differentiated thyroid cancer that is resistant to radioactive iodine therapy may become responsive with a unique treatment combination of chloroquine and vorinostat. This treatment was demonstrated in cellular and animal models of thyroid cancer to inhibit endocytosis of the plasma membrane–bound iodine transporter, NIS, and restore iodine uptake. See related article by Read et al., p. 1352
Trans-regulatory variant network contributes to missing heritability
Authors: Vanessa Pereira, Elena Kuzmin
Journal: Cell Genomics (2024)

In a recent Cell Genomics article, Tsouris et al.1 analyze the transcriptomes of a large diallel panel of hybrids from Saccharomyces cerevisiae natural isolates to study cis- and trans-regulatory changes underlying gene expression variation. Vanessa Pereira and Elena Kuzmin discuss the authors' findings and the wider context in missing heritability research in this preview.
Population-Based Validation of the MIA and MSKCC Tools for Predicting Sentinel Lymph Node Status
Authors: Roger Olofsson Bagge, Rasmus Mikiver, Michael A. Marchetti, Serigne N. Lo, Alexander C. J. van Akkooi, Daniel G. Coit, Christian Ingvar, Karolin Isaksson, Richard A. Scolyer, John F. Thompson, Alexander H. R. Varey, Sandra L. Wong, Johan Lyth, Edmund K. Bartlett
Journal: JAMA Surgery (2024)

Importance Patients with melanoma are selected for sentinel lymph node biopsy (SLNB) based on their risk of a positive SLN. To improve selection, the Memorial Sloan Kettering Cancer Center (MSKCC) and Melanoma Institute Australia (MIA) developed predictive models, but the utility of these models remains to be tested. Objective To determine the clinical utility of the MIA and MSKCC models. Design, Setting, and Participants This was a population-based comparative effectiveness research study including 10 089 consecutive patients with cutaneous melanoma undergoing SLNB from the Swedish Melanoma Registry from January 2007 to December 2021. Data were analyzed from May to August 2023. Main Outcomes and Measures, The predicted probability of SLN positivity was calculated using the MSKCC model and a limited MIA model (using mitotic rate as absent/present instead of count/mm 2 and excluding the optional variable lymphovascular invasion) for each patient. The operating characteristics of the models were assessed and compared. The clinical utility of each model was assessed using decision curve analysis and compared with a strategy of performing SLNB on all patients. Results Among 10 089 included patients, the median (IQR) age was 64.0 (52.0-73.0) years, and 5340 (52.9%) were male. The median Breslow thickness was 1.8 mm, and 1802 patients (17.9%) had a positive SLN. Both models were well calibrated across the full range of predicted probabilities and had similar external area under the receiver operating characteristic curves (AUC; MSKCC: 70.8%; 95% CI, 69.5-72.1 and limited MIA: 69.7%; 95% CI, 68.4-71.1). At a risk threshold of 5%, decision curve analysis indicated no added net benefit for either model compared to performing SLNB for all patients. At risk thresholds of 10% or higher, both models added net benefit compared to SLNB for all patients. The greatest benefit was observed in patients with T2 melanomas using a threshold of 10%; in that setting, the use of the nomograms led to a net reduction of 8 avoidable SLNBs per 100 patients for the MSKCC nomogram and 7 per 100 patients for the limited MIA nomogram compared to a strategy of SLNB for all. Conclusions and Relevance This study confirmed the statistical performance of both the MSKCC and limited MIA models in a large, nationally representative data set. However, decision curve analysis demonstrated that using the models only improved selection for SLNB compared to biopsy in all patients when a risk threshold of at least 7% was used, with the greatest benefit seen for T2 melanomas at a threshold of 10%. Care should be taken when using these nomograms to guide selection for SLNB at the lowest thresholds.
Optimal Timing of Cholecystectomy for Severe Acute Pancreatitis and Understanding Complications and Comorbidities—Reply
Authors: Marcello Di Martino, Benedetto Ielpo, Mauro Podda
Journal: JAMA Surgery (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Combinatorial expression motifs in signaling pathways
Authors: Alejandro A. Granados, Nivedita Kanrar, Michael B. Elowitz
Journal: Cell Genomics (2024)

In animal cells, molecular pathways often comprise families of variant components, such as ligands or receptors. These pathway components are differentially expressed by different cell types, potentially tailoring pathway function to cell context. However, it has remained unclear how pathway expression profiles are distributed across cell types and whether similar profiles can occur in dissimilar cell types. Here, using single-cell gene expression datasets, we identified pathway expression motifs, defined as recurrent expression profiles that are broadly distributed across diverse cell types. Motifs appeared in core pathways, including TGF-β, Notch, Wnt, and the SRSF splice factors, and involved combinatorial co-expression of multiple components. Motif usage was weakly correlated between pathways in adult cell types and during dynamic developmental transitions. Together, these results suggest a mosaic view of cell type organization, in which different cell types operate many of the same pathways in distinct modes.
Moving Beyond the NYU Algorithm for Emergency Department Visit Appropriateness
Authors: Jeremiah D. Schuur
Journal: JAMA Network Open (2024)

In response to overcrowding of local emergency departments (EDs), often by patients with seemingly minor concerns, a team led by John Billings, JD, of New York University (NYU) reviewed 6000 ED records from hospitals in the Bronx, New York, from 1994 and 1998 to determine how much of this ED use was avoidable, particularly with better primary care. 1 The year was 1999.A quarter-century later, despite numerous publications evaluating what was dubbed the NYU algorithm, this important work is still being misused.The NYU researchers pointed out in their original publications that "the algorithm is not intended as a triage tool or a mechanism to determine whether ED use is appropriate for required reimbursement by a managed care plan." 1 Yet variations on this algorithm have been used for these purposes over the last 25 years, including by health care payers looking to deny payment for avoidable ED visits. 2 Unsurprisingly, multiple studies have shown the weaknesses of misapplying the NYU algorithm to classify the appropriateness of individual visits.
Funding for Refugee Health Research From the National Institutes of Health Between 2000 and 2020
Authors: Mehak Kaur, Lana Bridi, Dahlia Kaki, Behnan Albahsahli, Nissma Bencheikh, Altaf Saadi, Gretchen Bandoli, Cheryl A.M. Anderson, Alissa Bernstein Sideman, Tala Al-Rousan
Journal: JAMA Network Open (2024)

Importance The US has historically resettled more refugees than any other country, with over 3.5 million refugees since 1980. The National Institutes of Health (NIH) is the largest public funder of biomedical research and development, but its role in mitigating many health disparities refugees experience through its funded research remains unknown. Objective To examine the NIH’s research funding patterns on refugee health research over the last 2 decades. Design, Setting, and Participants Secondary analysis of NIH-funded grants between 2000 and 2020 using a cross-sectional study design. The NIH Research Portfolio Online Reporting Tools database was used to find relevant grants. Data were analyzed from November 2021 to September 2022. Main Outcomes and Measures NIH grants awarded by year, state, grant type, research area, funding institute, grant duration, and amount funded. Results Of 1.7 million NIH grants funded over the 20-year study period, only 78 addressed refugee health. Funded grants were mostly training grants (23 grants [29%]), followed by hypothesis-driven research (R01 grants; 22 grants [28%]), pilot or preliminary investigation proposals (13 grants [17%]), and other types of grants (20 grants [26%]). The most studied research domain was mental health (36 grants [46%]), followed by refugee family dynamics and women’s and children’s health (14 grants [18%]). A total of 26 grants (33%) were funded by the National Institute of Mental Health and 15 (19%) were funded by the National Institute of Child Health and Human Development. Most grants were US-based (60 grants [76%]) and the state of Massachusetts received the greatest amount of funding ($14 825 852 [18%]). In 2020, the NIH allocated about $2.3 million to refugee health research, or less than 0.01% of its $42 billion budget that year. The number of grants funded in each time period did not always reflect changes in the number of refugees resettled in the US over the years. Conclusions and Relevance This cross-sectional study found that there remain significant gaps in the understanding of and interventions in the health research needs of refugees locally and along the migratory route. To close these gaps, the NIH should increase its investments in comprehensive studies assessing the physical, mental, and social well-being of this expanding population. This can be achieved by ensuring that all NIH institutes allocate budgets specifically for refugee health research and extend support for the training of refugee researchers.
Risk of Alopecia Areata After COVID-19
Authors: Jong-Seung Kim, Geon-Jong Lee, Cho-Yun Jeong, Sang-Woo Yeom, Kyung-Hwa Nam, Seok-Kweon Yun, Jin Park
Journal: JAMA Dermatology (2024)

This cohort study examines the incidence, prevalence, and risk of alopecia areata after COVID-19.
Precision Measurement of Telomere Length as a Future Guide to Improve CVD Interventions
Authors: Javier Yu Peng Koh, Shang Li, Angela S. Koh
Journal: JAMA Cardiology (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Post-pandemic memory T cell response to SARS-CoV-2 is durable, broadly targeted, and cross-reactive to the hypermutated BA.2.86 variant
Authors: Rofhiwa Nesamari, Millicent A. Omondi, Richard Baguma, Maxine A. Höft, Amkele Ngomti, Anathi A. Nkayi, Asiphe S. Besethi, Siyabulela F.J. Magugu, Paballo Mosala, Avril Walters, Gesina M. Clark, Mathilda Mennen, Sango Skelem, Marguerite Adriaanse, Alba Grifoni, Alessandro Sette, Roanne S. Keeton, Ntobeko A.B. Ntusi, Catherine Riou, Wendy A. Burgers
Journal: Cell Host & Microbe (2024)

Ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has given rise to recombinant Omicron lineages that dominate globally (XBB.1), as well as the emergence of hypermutated variants (BA.2.86). In this context, durable and cross-reactive T cell immune memory is critical for continued protection against severe COVID-19. We examined T cell responses to SARS-CoV-2 approximately 1.5 years since Omicron first emerged. We describe sustained CD4+ and CD8+ spike-specific T cell memory responses in healthcare workers in South Africa (n = 39) who were vaccinated and experienced at least one SARS-CoV-2 infection. Spike-specific T cells are highly cross-reactive with all Omicron variants tested, including BA.2.86. Abundant nucleocapsid and membrane-specific T cells are detectable in most participants. The bulk of SARS-CoV-2-specific T cell responses have an early-differentiated phenotype, explaining their persistent nature. Overall, hybrid immunity leads to the accumulation of spike and non-spike T cells evident 3.5 years after the start of the pandemic, with preserved recognition of highly mutated SARS-CoV-2 variants.
Dual specific phosphatase 4 suppresses ferroptosis and enhances sorafenib resistance in hepatocellular carcinoma
Authors: Shi-Hui Hao, Xiao-Dan Ma, Li Xu, Jing-Dun Xie, Zi-Hao Feng, Jie-Wei Chen, Ri-Xin Chen, Feng-Wei Wang, Yu-Hao Tang, Dan Xie, Mu-Yan Cai
Journal: Drug Resistance Updates (2024)